Intermittentpreventivetreatmentinpregnancywithsulphadoxinepyrimethamine (IPTp-SP) hasbeenadoptedaspolicybymanycountriesinsub-SaharanAfrica. However, data o­n the post-implementation effectiveness of this measure are scarce.Methods: Clinical and parasitological parameters were assessed among women delivering atadistricthospitalin ruralsouthernGhanaintheyear2000whenpyrimethaminechemoprophylaxis was recommended(n =839)andin2006(n =226),approximatelyoneyearafterthe implementationofIPTp-SP.Examinationswereperformedinanidenticalmannerin2000 and2006includingthedetectionofplacentalPlasmodiumfalciparuminfection by microscopy, histidine-rich protein 2, and PCR. Results:In2006,77%ofthe womenreported tohavetakenIPTp-SPatleastonce(26%,twice;24%,thrice).In2006ascomparedto 2000,placentalP.falciparuminfectionwasreduced by 43-57%(P <0.0001)and maternal anaemia by 33%(P = 0.0009),and medianbirth weight was 130 g higher (P = 0.02). In 2006, likewise, women who had taken _1 dose ofIPTp-SPrevealedlessinfectionandanaemiaand theirchildrentendedtohavehigherbirth weights as compared to women who had not used IPTp-SP. However, placental P. falciparuminfection wasstillobservedin 11%(microscopy) to 26%(PCR)ofthose women whohadtaken three doses of IPTp-SP.

Conclusions:In southernGhana,placentalmalariaandmaternalanaemiahavedeclinedsubstantiallyand birthweighthasincreasedaftertheimplementationofIPTp-SP.Likely,theseeffectscan furtherbeincreasedbyimprovingIPTp-SPcoverageandadherence.However, the remnant prevalence of infection in women having taken three doses of IPTp-SPsuggests that additional antimalarial measures are needed to prevent malaria in pregnancy inthis region.

Effect of Sulfadoxine-Pyrimethamine Resistance o­n the Efficacy of Intermittent Preventive Therapy for Malaria Control During Pregnancy A Systematic Review. In JAMA, June 20, 2007—Vol 297, No. 23: 2603 By Feiko O. ter Kuile, Annemieke M. van Eijk, Scott J. Filler

Context: In malaria-endemic regions, strategies to control malaria during pregnancy rely o­n case management of malaria illness and anemia, and preventive measures such as insecticide-treated nets and intermittent preventive therapy (IPT). Objective: To determine the effect of increasing resistance to sulfadoxinepyrimethamine o­n the efficacy of IPT during pregnancy in Africa. Data Sources and Study Selection The 6 databases of MEDLINE, EMBASE, SCOPUS, LILACS, Cochrane CENTRAL, and the trial register and bibliographic database of the Malaria in Pregnancy Library were searched for relevant studies regardless of language, published between 1966 and December 2006. The reference lists of all trials identified were searched and researchers were contacted about relevant data. Nine trials of IPT with sulfadoxine-pyrimethamine during pregnancy in Africa were identified and matched by year and location with treatment studies of sulfadoxinepyrimethamine among symptomatic children. Data: Extraction Data o­n the efficacy of IPT with sulfadoxine-pyrimethamine o­n placental and
peripheral malaria, birth weight, and hemoglobin level/anemia were independently abstracted by 2 investigators. Sulfadoxine-pyrimethamine resistance was defined as the proportion of total treatment failures in symptomatic children by day 14. Data Synthesis: Four trials compared 2-dose IPT with sulfadoxine-pyrimethamine to case management or placebo in women during their first or second pregnancy. The IPT reduced placental malaria (relative risk [RR], 0.48; 95% CI, 0.35-0.68), low birth weight (RR, 0.71; 95% CI, 0.55-0.92), and anemia (RR, 0.90; 95% CI, 0.81-0.99). The effect did not vary by sulfadoxine-pyrimethamine resistance levels (range, 19%-26%). Efficacy of IPT with sulfadoxine-pyrimethamine was lower among women using insecticide-treated nets. Three trials compared 2-dose with monthly IPT with sulfadoxine-pyrimethamine during pregnancy. Among HIV-positive women in their first or second pregnancy, monthly IPT resulted in less placental malaria (RR, 0.34; 95% CI, 0.18- 0.64) and higher birth weight (mean difference, 112 g; 95% CI, 19-205 g) over the range of sulfadoxine-pyrimethamine resistance tested (8%-39%). Among HIVnegative women, there was no conclusive additional effect of monthly dosing (2 trials; 24% and 39% resistance).
            Conclusions: In areas in which 1 of 4 treatments with sulfadoxine-pyrimethamine fail in children by day 14, the 2-dose IPT with sulfadoxine-pyrimethamine regimen continues to provide substantial benefit to HIV-negative semi-immune pregnant women. However, more frequent dosing is required in HIV-positive women not using cotrimoxazole prophylaxis for opportunistic infections. 

Effectiveness of intermittent preventive treatment with sulphadoxine-pyrimethamine for control of malaria in pregnancy in western Kenya: a hospital-based study. In Trop Med Int Health. 2004 Mar;9(3):351-60. By van Eijk AM, Ayisi JG, ter Kuile FO, Otieno JA, Misore AO, Odondi JO, Rosen DH, Kager PA, Steketee RW, Nahlen BL. Kenya Medical Research Institute, Centre for Vector Biology and Control Research, Kisumu, Kenya. avaneijk@kisian.mimcom.net

OBJECTIVE: To monitor the effectiveness of intermittent preventive treatment (IPT) with sulphadoxine-pyrimethamine (SP) for the control of malaria in pregnancy at delivery in the Provincial Hospital in Kisumu, Kenya, and to assess the effect of IPT in participants in a cohort study.
          METHODS: Between June 1999 and June 2000, information o­n IPT and birth outcome was collected in 2302 consecutive deliveries. A group of 889 women, who were enrolled in a cohort to assess the interaction between malaria and HIV, were analysed separately because of the enrollment criteria and different access to health care. RESULTS: The prevalence of placental malaria was 13.8% and of low birthweight (LBW) was 12.2%. In multivariable analysis, IPT (> or =1 dose of SP) was associated with a reduction in placental malaria and LBW [adjusted odds ratio (OR) 0.56, 95% confidence interval (CI) 0.39-0.83 and OR 0.65, 95% CI 0.45-0.95, respectively]. An adjusted mean increase in birthweight of 61 g was seen (95% CI 22-101 g) for each increment in number of SP doses (> or =2 doses grouped together). IPT was associated with a reduction in placental malaria in HIV-seronegative women (OR 0.49, 95% CI 0.28-0.86) but this was not significant among HIV-seropositive women (OR 0.45, 95% CI 0.20-1.05). A significant effect o­n birthweight could not be detected among participants in the HIV-cohort.
           CONCLUSIONS: This evaluation confirms that IPT with SP is effective in reducing placental malaria and LBW. It will be important to increase coverage of IPT and to extend IPT to antenatal clinics in peri-urban and rural areas.

Estimation of effectiveness of interventions for malaria control in pregnancy using the screening method.In Int. J. Epidemiol. Advance Access published January 25, 2007 By K Msyamboza, E Senga, E Tetteh-Ashong, P Kazembe and B J Brabin

Background: The evaluation of the effectiveness of antimalarial drugs and bed net use in pregnant women is an important aspect of monitoring and surveillance of malaria control in pregnancy. In principle the screening method for assessing vaccine efficacy can be applied in non-vaccine settings for assessing interventions for malaria control in pregnancy.
           Methods: In this analysis field data o­n the proportion of placental malaria cases treated with two doses of sulphadoxine-pyrimethamine (SP) and the uptake of two doses of SP in the antenatal clinic was used in a case-coverage method to assess the protective effectiveness (PE) of intermittent preventive treatment with SP for malaria control in pregnancy. PE was assessed using placental malaria, low birthweight and maternal anaemia at delivery as outcome variables. The method was also applied to an evaluation of the protective effectiveness of self-reported use of impregnated bed nets (ITNs). Results: Effectiveness was highest for reduction of low birthweight in multigravidae (87.2%, 95% CI, 83.2-91.3%). PE was lower for placental malaria (61.6% primigravidae, 28.5% multigravidae), and maternal anaemia (Hb<8.0 g/dl, 37.8% primigravidae, 29.6% multigravidae). Estimates for PE of self-reported use of ITNs gave values for all three outcome parameters that were much lower than for SP use. For women of all parties effectiveness estimates for reduction of low birthweight were 22% (95% CI, 17.7-26.4), prevention of placental malaria (all types) 7.1% (95% CI, 4.4-9.8), prevention of active placental infection 38.9% (95% CI, 27.4-50.4), and for maternal anaemia 8.8% (95% CI, 0-20.0).
          Conclusions: The case-coverage method could provide a useful and practical approach to routine monitoring and evaluation of drug interventions to control malaria in pregnancy and has potentially wide applications. Effectiveness estimates related to reported ITN use in pregnancy may be less reliable. The method should be further evaluated using currently available data sets.

From evidence to action? Challenges to policy change and programme delivery for malaria in pregnancy. In Lancet Infect Dis. 2007 Feb;7(2):145-55. By Crawley J, Hill J, Yartey J, Robalo M, Serufilira A, Ba-Nguz A, Roman E, Palmer A, Asamoa K, Steketee R. Global Malaria Programme, World Health Organization, Geneva, Switzerland. jane.crawley@gmail.com

This paper discusses the factors that influence whether strategies for preventing and treating malaria in pregnancy are successfully translated into national policy and programme implementation, and identifies key operational research issues. Countries require guidance o­n how to assess the effectiveness of intermittent preventive treatment in pregnancy (IPTp) with sulfadoxine-pyrimethamine in the context of increasing sulfadoxine-pyrimethamine resistance. At the same time, data o­n the safety and efficacy of alternatives to sulfadoxine-pyrimethamine for prevention and treatment are urgently needed. Systematic examination of the cultural and operational constraints to delivery and uptake of IPTp with sulfadoxine-pyrimethamine and use of insecticide-treated nets would provide a rational basis for strategies aimed at improving coverage. Standardised methodology must be used to monitor IPTp coverage and to compare different approaches for scaling-up the delivery of insecticide-treated nets to pregnant women. Adequate budgetary provision for the implementation of policy and for operational research to improve programme delivery should be included in national applications to the Global Fund to Fight AIDS, Tuberculosis and Malaria. The provision of clear policy guidance o­n malaria in pregnancy and its translation into evidence-based guidelines that are made widely available at a country level are central to improving malaria control in this particularly vulnerable group.

Insecticide-Treated Nets for the Prevention of Malaria in Pregnancy: A Systematic Review of Randomised Controlled Trials. In PLoS Medicine, March 2007 | Volume 4 | Issue 3 | e107 By Carol Gamble, Paul J. Ekwaru, Paul Garner, Feiko O. ter Kuile

Background: Protection from malaria with insecticide-treated bednets (ITNs) during pregnancy is widely advocated, but evidence of benefit has been inconsistent. We undertook a systematic review of randomised trials. Methods and Findings: Three cluster-randomised and two individually randomised trials met the inclusion criteria; four from Africa (n¼6,418) and o­ne from Thailand (n¼223). In Africa, ITNs compared to no nets increased mean birth weight by 55 g (95% confidence interval [CI] 21-88), reduced low birth weight by 23% (relative risk [RR] 0.77, 95% CI 0.61-0.98), and reduced miscarriages/stillbirths by 33% (RR 0.67, 0.47-0.97) in the first few pregnancies. Placental parasitaemia was reduced by 23% in all gravidae (RR 0.77, 0.66-0.90). The effects were apparent in the cluster-randomised trials and the o­ne individually randomised trial in Africa. The trial in Thailand, which randomized individuals to ITNs or
untreated nets, showed reductions in anaemia and fetal loss in all gravidae, but not reductions in clinical malaria or low birth weight. Conclusions: ITNs used throughout pregnancy or from midpregnancy o­nwards have a beneficial impact o­n pregnancy outcome in malaria-endemic Africa in the first few pregnancies. The potential impact of ITNs in pregnant women and their newborns in malaria regions outside Africa requires further research.

Intermittent preventive treatment for malaria in pregnancy in Africa: what's new, what's needed? In Malar J. 2007 Feb 16;6:16. By Vallely A, Vallely L, Changalucha J, Greenwood B, Chandramohan D. National institute for Medical Research, Mwanza Centre, PO Box 1462, Mwanza, Tanzania. andrew.vallely@gmail.com

Falciparum malaria is an important cause of maternal, perinatal and neonatal morbidity in high transmission settings in Sub-Saharan Africa. Intermittent preventive treatment with sulphadoxine-pyrimethamine (SP-IPT) has proven efficacious in reducing the burden of pregnancy-associated malaria but increasing levels of parasite resistance mean that the benefits of national SP-IPT programmes may soon be seriously undermined in much of the region. Hence, there is an urgent need to develop alternative drug regimens for IPT in pregnancy. This paper reviews published safety and efficacy data o­n various antimalarials and proposes several candidate combination regimens for assessment in phase II/III clinical trials.

Intermittent preventive treatment for the prevention of malaria during pregnancy in high transmission areas. In Malar J. 2007, 6:160 By Valerie Briand, Gilles Cottrell, Achille Massougbodji, Michel Cot

Malaria in pregnancy is o­ne of the major causes of maternal morbidity and adverse birth outcomes. In high transmission areas, its prevention has recently changed, moving from a weekly or bimonthly chemoprophylaxis to intermittent preventive treatment (IPTp). IPTpconsists in the administration of a single curative dose of an efficacious anti-malarial drug at least twice during pregnancy - regardless of whether the woman is infected or not. The drug is administered under supervision during antenatal care visits. Sulphadoxine-pyrimethamine(SP) is the drug currently recommended by the WHO. While SP-IPTp seems an adequatestrategy, there are many issues still to be explored to optimize it. This paper reviewed data o­nIPTp efficacy and discussed how to improve it. In particular, the determination of both theoptimal number of doses and time of administration of the drug is essential, and this has notyet been done. As both foetal growth and deleterious effects of malaria are maximum in latepregnancy women should particularly be protected during this period. Monitoring of IPTpefficacy should be applied to all women, and not o­nly to primi- and secondigravidae, as it hasnot been definitively established that multigravidae are not at risk for malaria morbidity andmortality. In HIV-positive women, there is an urgent need for specific information o­n drugadministration patterns (need for higher doses, possible interference with sulpha-basedprophylaxis of opportunistic infections). Because of the growing level of resistance ofparasites to SP, alternative drugs for IPTp are urgently needed. Mefloquine is presently o­ne ofthe most attractive options because of its long half life, high efficacy in sub-Saharan Africaand safety during pregnancy. Also, efforts should be made to increase IPTp coverage byimproving the practices of health care workers, the motivation of women and their perceptionof malaria complications in pregnancy. Because IPTp is not applicable in early pregnancy,which is a period when malaria may also be deleterious for women and their offspring, there is a necessity to integrate this strategy with other preventive measures which can be appliedearlier in pregnancy such as insecticide-treated nets.

Intermittent preventive treatment of malaria during pregnancy: a qualitative study of knowledge, attitudes and practices of district health managers, antenatal care staff and pregnant women in Korogwe District, North-Eastern Tanzania. In Malar J. 2005 Jul 20;4:31. By Mubyazi G, Bloch P, Kamugisha M, Kitua A, Ijumba J. National Institute for Medical Research, Ubwari Research Station, P.O. Box 81, Muheza, Tanzania.
mubyazig@hotmail.com

BACKGROUND: Intermittent preventive treatment of malaria during pregnancy (IPTp) is a key intervention in the national strategy for malaria control in Tanzania. SP, the current drug of choice, is recommended to be administered in the second and third trimesters of pregnancy during antenatal care (ANC) visits. To allow for a proper design of planned scaling up of IPT services in Tanzania it is useful to understand the IPTp strategy's acceptability to health managers, ANC service providers and pregnant women. This study assesses the knowledge, attitudes and practices of these groups in relation to malaria control with emphasis o­n IPTp services. METHODS: The study was conducted in February 2004, in Korogwe District, Tanzania. It involved in-depth interviews with the district medical officer (DMO), district hospital medical officer in charge and relevant health service staff at two peripheral dispensaries, and separate focus group discussions (FGDs) with district Council Health Management Team members at district level and pregnant women at dispensary and community levels. RESULTS: Knowledge of malaria risks during pregnancy was high among pregnant women although some women did not associate coma and convulsions with malaria. Contacting traditional healers and self-medication with local herbs for malaria management was reported to be common. Pregnant women and ANC staff were generally aware of SP as the drug recommended for IPTp, albeit some nurses and the majority of pregnant women expressed concern about the use of SP during pregnancy. Some pregnant women testified that sometimes ANC staff allow the women to swallow SP tablets at home which gives a room for some women to throw away SP tablets after
leaving the clinic. The DMO was sceptical about health workers' compliance with the direct observed therapy in administering SP for IPTp due to a shortage of clean water and cups at ANC clinics. Intensified sensitization of pregnant women about the benefits of IPTp was suggested by the study participants as an important approach for improving IPTp compliance.

CONCLUSION: The successful implementation of the IPTp strategy in Tanzania depends o­n the proper planning of, and support to, the training of health staff and sustained sensitization of pregnant women at health facility and community levels about the benefits of IPTp for the women and their unborn babies.

Intermittent preventive treatment of malaria during pregnancy in central Mozambique.In Bulletin of the World Health Organization 2007;85:873-879. By Paula E Brentlinger, Martinho Dgedge, Maria Ana Chadreque Correia, Ana Judith Blanco Rojas, Francisco Saúte, Kenneth H Gimbel-Sherr, Benjamin A Stubbs, Mary Anne Mercera & Stephen Gloyda
             New WHO strategies for control of malaria in pregnancy (MiP) recommend intermittent preventive treatment (IPTp), bednet use and improved case management. Approach A pilot MiP programme in Mozambique was designed to determine requirements for scale-up. Local setting The Ministry of Health worked with a nongovernmental organization and an academic institution to establish and monitor a pilot programme in two impoverished malaria-endemic districts. Relevant changes Implementing the pilot programme required provision of additional sulfadoxine-pyrimethamine (SP), materials for directly observed SP administration, bednets and
a modified antenatal card. National-level formulary restrictions o­n SP needed to be waived. The original protocol required modification because imprecision in estimation of gestational age led to missed SP doses. Multiple incompatibilities with other health initiatives (including programmes for control of syphilis, anaemia and HIV) were discovered and overcome. Key outputs and impacts were measured; 92.5% of 7911 women received at least 1 dose of SP, with the mean number of SP doses received being 2.2. At the second antenatal visit, 13.5% of women used bednets. In subgroups (1167 for laboratory analyses; 2600 births), SP use was significantly associated with higher haemoglobin levels (10.9 g/dL if 3 doses, 10.3 if none), less malaria parasitaemia (prevalence 7.5% if 3 doses, 39.3% if none), and fewer low-birth-weight infants (7.3% if 3 doses, 12.5% if none). Lessons learned National-level scale-up will require attention to staffing, supplies, bednet availability, drug policy, gestational-age estimation and harmonization of vertical initiatives.  

Intermittent preventive treatment with sulphadoxine-pyrimethamine is effective in preventing maternal and placental malaria in Ibadan, south-western Nigeria.In Malar J. 2007; 6:88. By Catherine O Falade, Bidemi O Yusuf, Francis F Fadero, Olugbenga A Mokuolu, Davidson H Hamer and Lateef A Salako

Intermittent preventive treatment with sulphadoxine-pyrimethamine (IPT-SP) is currently the recommended regimen for prevention of malaria in pregnancy in endemic areas. This study sets out to evaluate the effectiveness of IPT-SP in the prevention of maternal and placental malaria in parturient mothers in Ibadan, Nigeria, where the risk of malaria is present all year round.
            Method: During a larger study evaluating the epidemiology of congenital malaria, the effect of malaria prophylaxis was examined in 983 parturient mothers. Five hundred and ninety eight mothers (60.8%) received IPT-SP, 214 (21.8%) received pyrimethamine (PYR) and 171 (17.4%) did not take any chemoprophylactic agent (NC). Results: The prevalence of maternal parasitaemia in the IPT-SP, PYR and NC groups was 10.4%, 15.9% and 17% respectively (p = 0.021). The prevalence of placental parasitaemia was 10.5% in the IPT-SP, 16.8% PYR and 17% NC groups, respectively (p = 0.015). The prevalence of maternal anaemia (haematocrit <30%) was 5.7% vs. 8.9% vs. 13.4% among the IPT-SP, PYR and NC groups respectively (p < 0.0001) while that of pre-term delivery (GA <37 weeks) was 10.5%, 19.2% and 25.3% among IPT-SP,
PYR and NC groups respectively (p < 0.0001). Babies born to mothers in the IPT-SP, PYR and NC groups had mean birth weights of 3204 ± 487.16, 3075 ± 513.24 and 3074 ± 505.92 respectively (ρ < 0.0001). There was a trend towards a lower proportion of low birth weight babies in the IPT-SP group (p = 0.095). Conclusion: IPT-SP is effective in preventing maternal and placental malaria as well as improving pregnancy outcomes among parturient women in Ibadan, Nigeria. The implementation of the recently adopted IPT-SP strategy should be pursued with vigour as it holds great promise for reducing the burden of malaria in pregnancy in Nigeria. Malaria Journal 2007, 6:88 doi:10.1186/1475-2875-6-88 Received: 16 May 2007 Accepted: July 2007.

Interpreting household survey data intended to measure insecticide-treated bednet coverage: results from two surveys in Eritrea. In Malar J. 2006 May 5;5:36. By Eisele TP, Macintyre K, Yukich J, Ghebremeskel T. Department of International Health and Development, Tulane University School of Public Health and Tropical Medicine, New Orleans, LA 70115, USA. teisele@tulane.edu

BACKGROUND: As efforts are currently underway to roll-out insecticide-treated bednets (ITNs) to populations within malarious areas in Africa, there is an unprecedented need for data to measure the effectiveness of such programmes in terms of population coverage. This paper examines methodological issues to using household surveys to measure core Roll Back Malaria coverage indicators of ITN possession and use. 
            METHODS: ITN coverage estimates within Anseba and Gash Barka Provinces from the 2002 Eritrean Demographic and Health Survey, implemented just prior to a large-scale ITN distribution programme, are compared to estimates from the same area from a sub-national Bednet Survey implemented 18 months later in 2003 after the roll-out of the ITN programme.
           RESULTS: Measures of bednet possession were dramatically higher in 2003 compared to 2002. In 2003, 82.2% (95% confidence interval (CI) 77.4-87.0) of households in Anseba and Gash Barka possessed at least o­ne ITN. RBM coverage
indicators for ITN use were also dramatically higher in 2003 as compared to 2002, with 76.1% (95% CI 69.9-82.2) of children under five years old and 52.4% (95% CI 38.2-66.6) of pregnant women sleeping under ITNs. The ITN distribution programme resulted in a gross increase in ITN use among children and pregnant women of 68.3% and 48% respectively.
          CONCLUSION: Eritrea has exceeded the Abuja targets of 60% coverage for ITN household possession and use among children under five years old within two malarious provinces. Results point to several important potential sources of bias that must be considered when interpreting data for ITN coverage over time, including: disparate survey universes and target populations that may include non-malarious areas; poor date recall of bednet procurement and treatment; and differences in timing of surveys with respect to malaria season.

Knowledge of malaria influences the use of insecticide treated nets but not intermittent
presumptive treatment by pregnant women in Tanzania. In Malar J. 2004 Nov 12;3:42. By Nganda RY, Drakeley C, Reyburn H, Marchant T. Kilimanjaro Christian Medical Centre, PO Box 3010, Moshi, Tanzania. rhoidanganda@yahoo.com

BACKGROUND: To reduce the intolerable burden of malaria in pregnancy, the Ministry of Health in Tanzania has recently adopted a policy of intermittent presumptive treatment for pregnant women using sulphadoxine-pyrimethamine (IPTp-SP). In addition, there is strong national commitment to increase distribution of insecticide treated nets (ITNs) among pregnant women. This study explores the determinants of uptake for both ITNs and IPTp-SP by pregnant women and the role that individual knowledge and socio-economic status has to play for each. METHODS: 293 women were recruited post-partum at Kibaha District Hospital o­n the East African coast. The haemoglobin level of each woman was measured and a questionnaire administered. RESULTS: Use of both interventions was associated with a reduced risk of severe anaemia (Hb<8 g/dL) compared to women who had used neither intervention (OR 0.31, 95% CI 0.14-0.67). In a logistic regression model it was found that attendance at MCH health education
sessions was the o­nly factor that predicted IPTp-SP use (OR 1.8, 95% CI 1.1-2.9) while high knowledge of malaria predicted use of ITNs (OR 2.3, 95% CI 1.1-4.9). CONCLUSION: Individual knowledge of malaria was an important factor for ITN uptake, but not for IPTp-SP use, which was reliant o­n delivery of information by MCH systems. When both these interventions were used, severe anaemia postpartum was reduced by 69% compared to use of neither, thus providing evidence of effectiveness of these interventions when used in combination.

Lack of inhibition of the anti-malarial action of sulfadoxine-pyrimethamine by folic acid supplementation when used for intermittent preventive treatment in Gambian primigravidae. In Am J Trop Med Hyg. 2006 Jun;74(6):960-4. By Mbaye A, Richardson K, Balajo B, Dunyo S, Shulman C, Milligan P, Greenwood B, Walraven G. Medical Research Council Laboratories, Banjul, The Gambia.

Folic acid is frequently given to pregnant women at the same time as intermittent preventive treatment (IPTp) with sulfadoxine/pyrimethamine (SP), but it is not known if it interferes with the anti-malarial activity of SP. To investigate this concern, 1,035 Gambian primigravidae were randomized to receive either folic acid (500-1,500 microg/day) together with oral iron (522) or oral iron alone (513) for 14 days at the same time as they received IPTp with SP. o­n presentation, 261 women (25%) had Plasmodium falciparum asexual parasitemia. Prevalences of parasitemia o­n day 14 after treatment were similar in both groups: 5.7% (26 of 458) in the iron plus folic acid group and 4.9% (22 of 446) in the iron alone group (risk difference = 0.74%, 95% confidence interval [CI] = -2.2% to 3.7%). Parasitologic cure was observed in 116 (91%) of 128 of women who were parasitemic o­n presentation and who received iron and folic acid and in 122 (92%) of 133 women who received iron alone (difference = 1.1%, 95% CI = -5.6% to 8.0%). Women who received folic acid and iron had a slightly higher mean hemoglobin concentration at day 14 than women who had received iron alone (difference = 0.14 g/dL, 95% CI = 0.01-0.27 g/dL). The results of this study suggest that in an area of low SP resistance, administration of folic acid to pregnant women in a dose of 500-1,500 mug/day will not interfere with the protective effect of SP when used for IPTp.

Malaria Burden Among Pregnant Women Living in the Rural District of Boromo, Burkina Faso. In Am. J. Trop. Med. Hyg., 77(Suppl 6), 2007, pp. 56-60 By Sheick Oumar Coulibaly,* Sabine Gies, and Umberto D’Alessandro Laboratoire National de Santé Publique, Ouagadougou; Institute of Tropical Medicine, Antwerp, Belgium; and UFR Sciences de la Santé, Université de Ouagadougou

In two cross-sectional surveys carried out in the rural health district of Boromo, Burkina Faso, malaria infection was evaluated in 295 pregnant women in May 2003 and 288 pregnant women in December 2003. Malaria prevalence, all P. falciparum infection, was higher in December (32.2%) than in May (11.9%) (P < 0.0001). In both surveys primigravidae had a significantly higher risk of infection than multigravidae (P < 0.0001). Such risk decreased significantly and progressively with gestational age, the highest risk being during the first trimester. Women who had not attended the antenatal clinic had also a significantly higher risk of malaria infection.Despite the high antenatal clinic attendance and the use (or misuse) of chloroquine chemoprophylaxis, malaria remains an important problem for pregnant women living in the rural district of Boromo. This requires a major effort by the health authorities to guarantee all pregnant women have access to and use preventive measures.

Malaria in Pregnancy: Linking Immunity and Pathogenesis to Prevention.In Am. J. Trop. Med. Hyg., 77(Suppl 6), 2007, pp. 14-22 By Stephen J. Rogerson,* Victor Mwapasa, and Steven R. Meshnick, Department of Medicine (RMH/WH), The University of Melbourne, Royal Melbourne Hospital, Australia; Department of Community Health, College of Medicine, University of Malawi, Blantyre, Malawi; Department of Epidemiology, Microbiology and Immunology, University of North Carolina, Chapel Hill, North Carolina

Pregnant women are susceptible to malaria during pregnancy. Plasmodium falciparum, which sequesters in the placenta, causes the greatest disease, contributing significantly to maternal and infant mortality. Parasitized cells in the placenta express unique variant surface antigens (VSA), predominantly the VAR2CSA protein, and lack of immunity to these pregnancy-specific variant surface antigens explains some of the pregnancy-associated malaria susceptibility. Changes in acquired cellular immunity during pregnancy also appear important. Placental inflammatory esponses, particularly monocyte infiltrates, predispose to fetal growth restriction and maternal anemia. Preventing malaria in pregnancy relies o­n insecticide treated bed nets, intermittent preventive treatment with antimalarials such as sulphadoxine-pyrimethamine, and potentially relies o­n the development of effective vaccines. The optimal deployment of each may depend heavily o­n the relationship between the timing of placental malaria infection and its deleterious consequences. Improved understanding of the relationship between pathogenesis, immunity, and pregnancy outcome will allow better targeting of our interventions to prevent the consequences of malaria in pregnancy.

Malaria in pregnancy: pathogenesis and immunity.In The Lancet Infectious Diseases -
Vol. 7, Issue 2, February 2007, Pages 105-117 By Stephen J Rogerson, Lars Hviid, Patrick E Duffy, Rose FG Leke, Diane W Taylor

Understanding of the biological basis for susceptibility to malaria in pregnancy was recently advanced by the discovery that erythrocytes infected with Plasmodium falciparum accumulate in the placenta through adhesion to molecules such as chondroitin sulphate A. Antibody recognition of placental infected erythrocytes is dependent o­n sex and gravidity, and could protect from malaria complications. Moreover, a conserved parasite gene—var2csa—has been associated with placental malaria, suggesting that its product might be an appropriate vaccine candidate. By contrast, our understanding of placental immunopathology and how this contributes to anaemia and low birthweight remains restricted, although inflammatory cytokines produced by T cells, macrophages, and other cells are clearly important. Studies that unravel the role of host response to malaria in pathology and protection in the placenta, and that dissect the relation between timing of infection and outcome, could allow improved targeting of preventive treatments and development of a vaccine for use in pregnant women.

Malaria prevention during pregnancy: assessing the disease burden o­ne year after implementing a program of intermittent preventive treatment in Koupela District, Burkina Faso. In Am J Trop Med Hyg. 2006 Aug;75(2):205-11. By Sirima SB, Cotte AH, Konate A, Moran AC, Asamoa K, Bougouma EC, Diarra A, Ouedraogo A, Parise ME, Newman RD. Centre National de Recherche et de Formation sur le Paludisme, Ministere de la Sante, Ouagadougou, Burkina Faso.

The World Health Organization recommends that pregnant women in malaria-endemic areas receive >or= 2 doses of intermittent preventive treatment with sulfadoxine-pyrimethamine (IPTp/SP) in the second and third trimesters of pregnancy to prevent maternal anemia, placental parasitemia, and low birth weight (LBW). In 2001, a program evaluation in Koupela District, Burkina Faso demonstrated that despite widespread use of chloroquine chemoprophylaxis, the burden of malaria during pregnancy remained high. In 2003, the Burkina Faso Ministry of Health piloted a program of IPTp/SP (three doses) and accelerated distribution of insecticide-treated nets (ITN) to pregnant women in Koupela District. In 2004, a follow-up program evaluation was conducted. Coverage with >or= 1 doses of IPTp/SP was high among women attending antenatal clinics (ANCs) (96.2%) and delivery units (DUs) (93.5%); ITN ownership was moderately high (ANC = 53.9%, DU = 61.6%). In multivariate analysis, >or= 1 dose of IPTp/SP was associated with a significant reduction in the prevalence of peripheral parasitemia at ANCs (risk ratio [RR] = 0.49, P = 0.008), >or= 2 doses of IPTp/SP were associated with a reduction in the prevalence of placental parasitemia (RR = 0.56, P = 0.02), and three doses of IPTp/SP were associated with a reduced risk of LBW (RR = 0.51, P = 0.04). The proportions of women at ANCs with peripheral parasitemia and anemia were significantly lower in 2004 than in 2001 (RR = 0.53, P = 0.001 and RR = 0.78, P = 0.003, respectively). The proportions of women at DUs with peripheral and placental parasitemia were also significantly lower in 2004 than in 2001 (RR = 0.66, P < 0.0001 and RR = 0.71, P = 0.0002, respectively). These data suggest that a package of IPTp/SP and ITNs is effective in reducing the burden of malaria during pregnancy in Burkina Faso.

Perceptions o­n use of sulfadoxine-pyrimethamine in pregnancy and the policy implications for malaria control in Uganda. In Health Policy. 2006 Aug;77(3):279-89. Epub 2005 Aug 24. By Mbonye AK, Neema S, Magnussen P. Community Health, Ministry of Health, Kampala, Uganda. vpadmn@infocom.co.ug

In malaria endemic areas intermittent treatment with sulfadoxine-pyrimethamine (SP) is recommended for malaria prevention in pregnancy. Yet, data o­n perceptions regarding use of this drug are scarce. An exploratory study was conducted to assess perceptions o­n SP in Mukono district, Uganda. This is an initial step towards a review of the policy aimed at improving access and use of SP in pregnancy, which is currently low. Results show that SP is perceived to be an effective drug that cures malaria quickly. However there are negative perceptions related to its use in pregnancy. SP is believed to be strong and weakens pregnant women, causes abortions and foetal abnormalities. There is also a perception that resorting first to SP for malaria treatment may lead to the development of drug resistance. This perception may limit access to effective treatment of malaria in this community since the policy in Uganda recommends SP in combination with chloroquine as the first-line treatment. The policy implications of these findings include developing a health promotion package to demystify the misconceptions o­n the strength of SP, to explain its benefits and side-effects. This package will involve giving health workers refresher training o­n communication and counselling o­n use of SP in pregnancy targeting special groups like pregnant adolescents. These results provide important lessons to policy makers and programme managers who aim at scaling up access of SP for malaria prevention in pregnancy.

Prevention of anaemia in pregnancy using insecticide-treated bednets and sulfadoxine-pyrimethamine in a highly malarious area of Kenya: a randomized controlled trial. Transactions Of The Royal Society Of Tropical Medicine And Hygiene (2003) 97, 277 282 Abstract By Joseph Kiambo Njagi 1, Pascal Magnussen 2, Benson Estambale 3, John Ouma 1 and Benbolt Mugo

To compare the effects of intermittent treatment with sulfadoxine-pyrimethamine (SP) given during the second and third trimester of pregnancy, the use of insecticide-treated nets (ITN), or the combination of both o­n haemoglobin (Hb) levels during pregnancy, a randomized, placebo-controlled intervention trial was conducted in a malaria-endemic area of western Kenya from July 1997 to September 1999. Primigravidae and secundigravidae were enrolled into the study and randomized into 4 intervention groups: (i) ITNs and SP, (ii) ITNs and placebo SP, (iii) SP alone, and (iv) placebo SP. All groups were offered case management and iron and folic acid supplementation. Seven hundred and fifty-two women were followed until delivery (53.2% were primigravidae and 46.8% seeundigravidae). Among primigravidae in all the groups there was a significant improvement in Hb levels at delivery (107.6 g/L) compared with recruitment (101.9 g/L) (P < 0.006) with the greatest improvement in the combination ITNs + SP group. The protective efficacy of ITNs + SP o­n anaemia was 55.8% (95% CI 30.6:71.8), of SP alone 50.9% (95% CI 22.2-69.0), and oflTNs 41.6% (95% CI 9.8-62.3). Among secundigravidae, Hb levels were slightly lower at delivery compared with recruitment (P = 0.03). It was concluded that malaria is a major cause of anaemia in primigravidae but that other causes play a more significant role in secundigravidae, and that intermittent treatment with SP or use of ITNs benefits primigravidae more than secundigravidae.

Prevention of malaria during pregnancy in West Africa: policy change and the power of subregional action. In Trop Med Int Health. 2006 Apr;11(4):462-9. By Newman RD, Moran AC, Kayentao K, Benga-De E, Yameogo M, Gaye O, Faye O, Lo Y, Moreira PM, Doumbo O, Parise ME, Steketee RW. Malaria Branch, Division of Parasitic Diseases, National Center for Infectious Diseases, Centers for Disease Control and Prevention, Atlanta, GA 30341, USA. rnewman@cdc.gov

BACKGROUND: Despite a broadening consensus about the effectiveness of intermittent preventive treatment (IPTp) in preventing the adverse outcomes of malaria during pregnancy, policy change to IPTp was initially limited to East Africa. In West Africa, where the policy change process for the prevention of malaria during pregnancy started much later, IPTp has been taken up swiftly.

BJECTIVE: To describe the factors that contributed to the rapid adoption of policies to prevent malaria during pregnancy in West Africa.

RESULTS AND CONCLUSION: Several factors appear to have accelerated the process: (1) recognition of the extent of the problem of malaria during pregnancy and its adverse consequences; (2) a clear, evidence-based program strategy strongly articulated by an important multilateral organization (World Health Organization); (3) subregionally generated evidence to support the proposed strategy; (4) a subregional forum for dissemination of data and discussion regarding the proposed policy changes; (5) widespread availability of the proposed intervention drug (sulfadoxine-pyrimethamine); (6) technical support from reputable and respected institutions in drafting new policies and planning for implementation; (7) donor support for pilot experiences in integrating proposed policy change into a package of preventive services; and (8) financial support for scaling up the proposed interventions.

Reaching the Abuja target for intermittent preventive treatment of malaria in pregnancy in African women: a review of progress and operational challenges. In Trop Med Int Health. 2006 Apr;11(4):409-18. By Hill J, Kazembe P. Child and Reproductive Health Group, Liverpool School of Tropical Medicine, Liverpool, UK. j.hill@liv.ac.uk

OBJECTIVE: To review progress with the implementation of intermittent preventive treatment (IPT) for the control of malaria in pregnancy in sub-Saharan Africa (SSA), in order to identify facilitating factors and operational challenges for scaling up IPT delivery.
           METHODS:Information o­n the status of IPT policy, programme and coverage indicators was extracted from published sources. Information o­n country experiences from both published and unpublished literature was supplemented with semi-structured interviews with malaria programme managers.

RESULTS: Whilst countries in SSA have made important progress with IPT implementation, coverage levels remain low. High antenatal clinic (ANC) attendance alone is not sufficient to ensure high IPT coverage. Staff shortages, poor drug supply, poor ANC access and poor health worker practices are some of the operational challenges in delivering IPT.

CONCLUSION: Country experiences show that IPT can be introduced and scaled up relatively quickly and effectively where there is political will, effective integration between malaria and reproductive health programmes, adequate funding and drug supply, high ANC attendance and community receptiveness. There is however urgent need to better document best practices and lessons as a basis for developing simplified guidelines for dissemination to countries embarking o­n IPT implementation.

Reducing the burden of malaria in pregnancy by preventive strategies. In Lancet Infect Diseases - Vol. 7, Issue 2, February 2007, Pages 126-35. By Menendez C, D'Alessandro U, ter Kuile FO. Center for International Health, Hospital Clinic/Barcelona University, Barcelona, Spain. menendez@clinic.ub.es

Malaria is o­ne of the most common and preventable causes of adverse birth outcomes. In Africa, important progress has been made in the past decade with the introduction of a preventive strategy for malaria in pregnancy consisting of intermittent preventive treatment in pregnancy (IPTp) and insecticide-treated nets, yet their coverage is still unacceptably low and malaria continues to demand a huge toll o­n pregnant women and their newborn babies. Increasing the frequency of dosing of IPTp with sulfadoxine-pyrimethamine might provide temporary respite, but increasing resistance to sulfadoxine-pyrimethamine makes research into safe, efficacious, and affordable alternatives for IPTp o­ne of the highest priorities for the control of malaria in pregnancy. A number of promising alternatives are, or will soon be, available that need to be evaluated as IPTp after their safety and pharmacokinetics in pregnancy have first been assessed in parasitaemic women. Little is known about appropriate control strategies in Asia and Latin America for Plasmodium falciparum and Plasmodium vivax malaria in pregnancy, which in most countries rely o­n responsive case management approaches. The role of case management based o­n proactive screening for malaria infection of women attending antenatal care or preventive approaches with insecticide-treated nets or IPTp are urgently needed. To achieve these objectives, multicentre and multidisciplinary approaches are required across the range of malaria transmission settings that include assessment of immunological effect of successful preventions, the perceptions and acceptability of different preventive approaches, and their cost-effectiveness.

Review: Intermittent preventive treatment--a new approach to the prevention of malaria in children in areas with seasonal malaria transmission. In Trop Med Int Health. 2006 Jul;11(7):983-91. By Greenwood B. Department of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, UK. brian.greenwood@lshtm.ac.uk

Intermittent preventive treatment, the administration of a full course of an anti-malarial treatment to a population at risk at specified time points regardless of whether or not they are known to be infected, is now a recommended approach to the prevention of malaria in pregnancy and is being explored as a potential way of preventing malaria in infants. However, in many malaria endemic areas, the main burden of malaria is in older children and increasing use of insecticide treated bednets is likely to increase further the proportion of episodes of malaria that occur in older children. Recently, it has been shown in Senegal and in Mali that intermittent preventive treatment given to older children during the malaria transmission season can be remarkably effective in preventing malaria. This approach to malaria control is likely to be most effective in areas with a high level of malaria transmission concentrated in a short period of the year. However, several issues need to be addressed before intermittent preventive treatment in children can be advocated for use in malaria control programmes. These include: (1) determination of whether intermittent preventive treatment adds to the protection afforded by other control measures such as insecticide-treated bednets; (2) whether an effective and sustainable delivery system can be found; (3) choice of drug to be used; (4) optimum timing of drug administration; (5) the requisite interval between treatments. The potential benefits of intermittent preventive treatment in children are substantial; more research is needed to determine if this is a practical approach to malaria control.

Severe cutaneous reactions to sulfadoxine-pyrimethamine and trimethoprim-sulfamethoxazole in Blantyre District, Malawi. In Am J Trop Med Hyg. 2006 May;74(5):738-43. By Gimnig JE, MacArthur JR, M'bang'ombe M, Kramer MH, Chizani N, Stern RS, Mkandala C, Newman RD, Steketee RW, Campbell CH. Division of Parasitic Diseases, National Center for Infectious Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia 30341, USA. hzg1@cdc.gov

We estimated the frequency of clinically diagnosed Stevens-Johnson syndrome and toxic epidermal necrolysis associated with sulfadoxine-pyrimethamine (SP) and trimethoprim-sulfamethoxazole (CTX) in Blantyre District, Malawi. Cases were detected by passive surveillance at 22 health centers from March 2001 through September 2002. Denominators were estimated from the Malawi national census for Blantyre District and the frequency of SP and CTX use reported in five household surveys. Crude rates of adverse reactions were estimated to be 1.2 per 100,000 exposures for SP and 1.5 per 100,000 exposures for CTX. Rates were higher in adults (1.7 cases per 100,000 SP exposures and 2.6 cases per 100,000 CTX exposures) and in persons positive for human immunodeficiency virus (4.9 cases per 100,000 SP exposures and 8.4 cases per 100,000 CTX exposures). Infrequent treatment doses with SP are associated with a low risk of an adverse cutaneous reaction, and SP can be recommended for treatment of malaria in areas where P. falciparum is susceptible.

The effect of health care worker training o­n the use of intermittent preventive treatment for malaria in pregnancy in rural western Kenya. In Tropical Medicine and International Health, volume 12 no 8 pp 953-961 August 2007 By P. O. Ouma1, A. M. Van Eijk, M. J. Hamel1, E. Sikuku, F. Odhiambo, K. Munguti, J. G. Ayisi, P. A. Kager and L. Slutsker

In 1998, Kenya adopted intermittent preventive treatment (IPTp) with sulphadoxine-pyrimethamine (SP) for malaria prevention during pregnancy. We conducted a survey in 2002 among women who had recently delivered in the rural neighbouring areas Asembo and Gem and reported coverage of 19% of at least o­ne dose and 7% of two or more doses of SP. Health care workers (HCW) in Asembo were retrained o­n IPTp in 2003. Objectives: To evaluate if IPTp coverage increased and if the training in Asembo led to better coverage than in Gem, and to identify barriers to the effective implementation of IPTp. Methods: Community-based cross-sectional survey among a simple random sample of women who had recently delivered in April 2005, interviews with HCW of antenatal clinics (ANC) in Asembo and Gem. Results: Of the 724 women interviewed, 626 (86.5%) attended the ANC o­nce and 516 (71.3%) attended two or more times. Overall IPTp coverage was 41% for at least o­ne dose, and 21% for at least two doses of SP. In Asembo, coverage increased from 19% in 2002 to 61% in 2005 for at least o­ne dose and from 7% to 17% for two doses of SP. In Gem, coverage increased from 17% to 28% and 7% to 11%, respectively. Interviews of HCW in both Asembo and Gem revealed confusion about appropriate timing, and lack of direct observation of IPTp. Conclusion: Training of HCW and useof simplified IPTp messages may be a key strategy in achieving Roll Back Malaria targets for malaria prevention in pregnancy in Kenya.

Use of intermittent preventive treatment for malaria in pregnancy in a rural area of western Kenya with high coverage of insecticide-treated bed nets. In Trop Med Int Health. 2005 Nov;10(11):1134-40. By van Eijk AM, Blokland IE, Slutsker L, Odhiambo F, Ayisi JG, Bles HM, Rosen DH, Adazu K, Lindblade KA. Kenya Medical Research Institute, Centre for Vector Biology and Control Research, Kisumu, Kenya. AMvanEijk@yahoo.com

Kenya established intermittent preventive treatment (IPT) with sulfadoxine-pyrimethamine (SP) for malaria in pregnancy as national policy in 1998. We assessed the coverage of IPT among
women who had recently delivered in a rural area of western Kenya with perennial malaria transmission and high coverage with insecticide treated nets (ITNs) through a cross-sectional, ommunity-based survey in December 2002. Antenatal clinic (ANC) attendance was high (89.9% of the 635 participating women); 77.5% of attendees visited an ANC before the third trimester and 91.9% made more than o­ne visit. Delivery of SP by the ANC was reported by 19.1% of all women but o­nly 6.8% reported receiving more than o­ne dose. Given the high rate of use of ANC services, if SP were given at each visit after the first trimester, the potential coverage of IPT (two doses of SP) would be 80.3% in this study population. ITNs were used by 82.4% of women during pregnancy, and almost all mothers (98.5%) who slept under an ITN shared the nets with their newborns after delivery. Women who thought malaria in pregnancy caused foetal problems were more likely to have used an ITN (adjusted odds ratio [AOR] 1.6, 95% confidence interval [CI] 1.0-2.4), and to have visited ANC more than o­nce (AOR 2.4, 95% CI 1.2-4.7) compared to women who thought malaria in pregnancy was either not a problem or caused problems for the mother o­nly. These findings illustrate the need for improved IPT coverage in this rural area. Identification and removal of the barriers to provision of IPT during ANC visits can help to increase coverage. In this area of Kenya, health messages stressing that foetal complications of malaria in pregnancy may occur in the absence of maternal illness may improve the demand for IPT.

Use of intermittent presumptive treatment and insecticide treated bed nets by pregnant women in four Kenyan districts. In Trop Med Int Health. 2004 Feb;9(2):255-61. By Guyatt HL, Noor AM, Ochola SA, Snow RW. Kenya Medical Research Institute/Wellcome Trust Collaborative Programme, Nairobi, Kenya. helenguyatt@yahoo.com

The roll back malaria (RBM) movement promotes the use of insecticide-treated bednets (ITNs) and intermittent presumptive treatment (IPT) of malaria infection as preventive measures against the adverse effects of malaria among pregnant women in Africa. To determine the use of these preventive measures we undertook a community-based survey of recently pregnant women
randomly selected from communities in four districts of Kenya in December 2001. Of the 1814
women surveyed, o­nly 5% had slept under an ITN. More than half of the 13% of women using a bednet (treated or untreated) had bought their nets from shops or markets. Women from rural areas used bednets less than urban women (11% vs. 27%; P < 0.001), and 41% of the bednets used by rural women had been obtained free of charge from a research project in Bondo or a nationwide UNICEF donation through antenatal clinics (ANCs). Despite 96% of ANC providers being aware of IPT with sulphadoxine-pyrimethamine (SP), o­nly 5% of women interviewed had received two or more doses of SP as a presumptive treatment. The coverage of pregnant women with at least o­ne dose of IPT with SP was 14%, though a similar percentage also had received at least a single dose as a curative treatment. The coverage of nationally recommended strategies to prevent malaria during pregnancy during 2001 was low across the diverse malaria ecology of Kenya. Rapid expansion of access to these services is required to meet international and national targets by the year 2005. The scaling up of malaria prevention programmes through ANC services should be possible with 74% of women visiting ANCs at least twice in all four districts. Issues of commodity supply and service costs to clients will be the greatest impediments to reaching RBM targets.

2.Insecticide-Treated Nets (ITNs) and Other Vector Control Measures

Attractiveness of pregnant women to the malaria vector, Anopheles arabiensis, in Sudan. In Ann Trop Med Parasitol. 2004 Sep;98(6):631-3. By Himeidan YE, Elbashir MI, Adam I. Faculty of Agriculture and Natural Resources, University of Kassala, P. O. Box 71, New Halfa, Sudan.

The attractiveness of pregnant women for mosquitoes was investigated in a peri-urban site in New Halfa, eastern Sudan, in September-October 2003. For 20 nights, the mosquitoes feeding o­n nine pregnant and nine non-pregnant women sleeping under untreated bednets were collected.
The women slept outdoors, in the yards of nine houses, each yard holding o­ne pregnant and o­ne
non-pregnant woman. In general, each pregnant woman attracted significantly more Anopheles
arabiensis (the main vector of Plasmodium falciparum in the area) than each non-pregnant women, with mean biting rates of 0.94 and 0.49 bites/woman-night, respectively (P = 0.005). In contrast, the two groups of women attracted similar numbers of the other mosquito species collected, which were all culicine. Impregnated bednets need to be used in the study area, at least by the pregnant women (who appear to be at particularly high risk of acquiring malaria).

Experience of targeting subsidies o­n insecticide-treated nets: what do we know and what are the knowledge gaps? In Trop Med Int Health. 2005 Jan;10(1):19-31. By Worrall E, Hill J, Webster J, Mortimer J. Health Policy Unit, London School of Hygiene and Tropical Medicine, London, UK. eve.worrall@lshtm.ac.uk

Widespread coverage of vulnerable populations with insecticide-treated nets (ITNs) constitutes an important component of the Roll Back Malaria (RBM) strategy to control malaria. The Abuja Targets call for 60% coverage of children under 5 years of age and pregnant women by 2005; but current coverage in Africa is unacceptably low. The RBM 'Strategic Framework for Coordinated National Action in Scaling-up Insecticide-Treated Netting Programmes in Africa' promotes coordinated national action and advocates sustained public provision of targeted subsidies to maximise public health benefits, alongside support and stimulation of the private sector. Several countries have already planned or initiated targeted subsidy schemes either o­n a pilot scale or o­n a national scale, and have valuable experience which can inform future interventions. The WHO RBM 'Workshop o­n mapping models for delivering ITNs through targeted subsidies' held in
Zambia in 2003 provided an opportunity to share and document these country experiences. This paper brings together experiences presented at the workshop with other information o­n experiences of targeting subsidies o­n ITNs, net treatment kits and retreatment services (ITN products) in order to describe alternative approaches, highlight their similarities and differences, outline lessons learnt, and identify gaps in knowledge. We find that while there is a growing body of knowledge o­n different approaches to targeting ITN subsidies, there are significant gaps in knowledge in crucial areas. Key questions regarding how best to target, how much it will cost and what outcomes (levels of coverage) to expect remain unanswered. High quality, well-funded monitoring and evaluation of alternative approaches to targeting ITN subsidies is vital to develop a knowledge base so that countries can design and implement effective strategies to target ITN subsidies.

Insecticide-treated nets. In Adv Parasitol. 2006;61:77-128. By Hill J, Lines J, Rowland M. Child and Reproductive Health Group, Liverpool School of Tropical Medicine, Pembroke Place, Liverpool L3 5QA, UK.

Insecticide-treated nets (ITNs) are the most powerful malaria control tool to be developed since the advent of indoor residual spraying (IRS) and chloroquine in the 1940s, and as such they have been an important component of global and national malaria control policies since the mid-
1990s. Yet a decade later, coverage is still unacceptably low: o­nly 3% of African children are currently sleeping under an ITN, and o­nly about 20% are sleeping under any kind of net.This review charts the scientific, policy and programmatic progress of ITNs over the last 10 years. Available evidence for the range of programmatic delivery mechanisms used at country level is presented alongside the key policy debates that together have contributed to the evolution of ITN delivery strategies over the past decade. There is now global consensus around a strategic framework for scaling up ITN usage in Africa, which recognizes a role for both the public sector (targeting vulnerable groups to promote equity) and the private sector (sustainable supply). So, while progress with increasing coverage to date has been slow, there is now global support for the rapid scale-up of ITNs among vulnerable groups by integrating ITN delivery with maternal and child health programmes (and immunization in particular), at the same time working with the private sector in a complementary and supportive manner to ensure that coverage can be maintained for future generations of African children.

Insecticide-treated nets for preventing malaria in pregnancy. In 62: Cochrane Database Syst Rev. 2006 Apr 19;(2):CD003755. By Gamble C, Ekwaru JP, ter Kuile FO. University of Liverpool, Centre for Medical Statistics and Health Evaluation, Shelley's Cottage, Brownlow Street, Liverpool, UK, L69 3GS. c.gamble@liv.ac.uk

Malaria in pregnancy is associated with adverse consequences for mother and fetus. Protection with insecticide-treated nets (ITNs) during pregnancy is widely advocated, but evidence of their benefit has been inconsistent. OBJECTIVES: To compare the impact of ITNs with no nets or
untreated nets o­n preventing malaria in pregnancy. SEARCH STRATEGY: We searched the
Cochrane Infectious Diseases Group Specialized Register (January 2006), CENTRAL (The
Cochrane Library 2005, Issue 4), MEDLINE (1966 to January 2006), EMBASE (1974 to January 2006), LILACS (1982 to January 2006), and reference lists. We also contacted researchers working in the field. SELECTION CRITERIA: Individual and cluster randomized controlled trials of ITNs in pregnant women. DATA COLLECTION AND ANALYSIS: Three authors independently assessed trials for methodological quality and extracted data. Data were combined using the generic inverse variance method. MAIN RESULTS: Six randomized controlled trials were identified, five of which met the inclusion criteria: four trials from sub-Saharan Africa compared ITNs with no nets, and o­ne trial from Asia compared ITNs with untreated nets. Two trials randomized individual women and three trials randomized communities. In Africa, ITNs, compared with no nets, reduced placental malaria in all pregnancies (relative risk (RR) 0.79, 95% confidence interval (CI) 0.63 to 0.98). They also reduced low birthweight (RR 0.77, 95% CI 0.61 to 0.98) and stillbirths/abortions in the first to
fourth pregnancy (RR 0.67, 95% CI 0.47 to 0.97), but not in women with more than four
previous pregnancies. For anaemia and clinical malaria, results tended to favour ITNs, but the
effects were not significant. In Thailand, o­ne trial randomizing individuals to ITNs or untreated
nets showed a significant reduction in anaemia and stillbirths/abortions in all pregnancies but not
for clinical malaria or low birthweight. AUTHORS' CONCLUSIONS: ITNs have a beneficial
impact o­n pregnancy outcome in malaria-endemic regions of Africa when used by communities
or by individual women. No further trials of ITNs in pregnancy are required in sub-Saharan
Africa. Further evaluation of the potential impact of ITNs is required in areas with less intense
and Plasmodium vivax transmission in Asia and Latin America.

Insecticide-Treated Nets for the Prevention of Malaria in Pregnancy: A Systematic Review
of Randomised Controlled Trials. In PLoS Med. 2007 Mar 27;4(3):e107 [Epub ahead of print] By Gamble C, Ekwaru PJ, Garner P, Ter Kuile FO.

Protection from malaria with insecticide-treated bednets (ITNs) during pregnancy is widely advocated, but evidence of benefit has been inconsistent. We undertook a systematic review of
randomised trials. METHODS AND FINDINGS: Three cluster-randomised and two individually randomised trials met the inclusion criteria; four from Africa (n = 6,418) and o­ne from Thailand
(n = 223). In Africa, ITNs compared to no nets increased mean birth weight by 55 g (95%
confidence interval [CI] 21-88), reduced low birth weight by 23% (relative risk [RR] 0.77, 95%
CI 0.61-0.98), and reduced miscarriages/stillbirths by 33% (RR 0.67, 0.47-0.97) in the first few
pregnancies. Placental parasitaemia was reduced by 23% in all gravidae (RR 0.77, 0.66-0.90).
The effects were apparent in the cluster-randomised trials and the o­ne individually randomised
trial in Africa. The trial in Thailand, which randomised individuals to ITNs or untreated nets,
showed reductions in anaemia and fetal loss in all gravidae, but not reductions in clinical malaria or low birth weight. CONCLUSIONS: ITNs used throughout pregnancy or from mid-pregnancy
onwards have a beneficial impact o­n pregnancy outcome in malaria-endemic Africa in the first
few pregnancies. The potential impact of ITNs in pregnant women and their newborns in malaria regions outside Africa requires further research.

Knowledge of malaria influences the use of insecticide treated nets but not intermittent
presumptive treatment by pregnant women in Tanzania. In Malar J. 2004 Nov 12;3:42.

By Nganda RY, Drakeley C, Reyburn H, Marchant T. Kilimanjaro Christian Medical Centre, PO Box 3010, Moshi, Tanzania. rhoidanganda@yahoo.com

BACKGROUND: To reduce the intolerable burden of malaria in pregnancy, the Ministry of
Health in Tanzania has recently adopted a policy of intermittent presumptive treatment for pregnant women using sulphadoxine-pyrimethamine (IPTp-SP). In addition, there is strong national commitment to increase distribution of insecticide treated nets (ITNs) among pregnant women. This study explores the determinants of uptake for both ITNs and IPTp-SP by pregnant women and the role that individual knowledge and socio-economic status has to play for each.

METHODS: 293 women were recruited post-partum at Kibaha District Hospital o­n the East African coast. The haemoglobin level of each woman was measured and a question naire administered.

RESULTS: Use of both interventions was associated with a reduced risk of severe anaemia (Hb<8 g/dL) compared to women who had used neither intervention (OR 0.31, 95% CI 0.14-0.67). In a logistic regression model it was found that attendance at MCH health education sessions was the o­nly factor that predicted IPTp-SP use (OR 1.8, 95% CI 1.1-2.9) while high knowledge of malaria predicted use of ITNs (OR 2.3, 95% CI 1.1-4.9).

CONCLUSION: Individual knowledge of malaria was an important factor for ITN uptake, but not for IPTp-SP use, which was reliant o­n delivery of information by MCH systems. When both these interventions were used, severe anaemia postpartum was reduced by 69% compared to use of neither, thus providing evidence of effectiveness of these interventions when used in
combination.

Malaria infection among pregnant women attending antenatal clinics in six Rwandan districts. In Trop Med Int Health. 2005 Jul;10(7):681-8.By Van Geertruyden JP, Ntakirutimana D, Erhart A, Rwagacondo C, Kabano A, D'Alessandro U. Department of Parasitology, Prince Leopold Institute of Tropical Medicine, Antwerp, Belgium. jpvangeertruyden@itg.be

OBJECTIVES: The aim of the study was to assess the knowledge, attitude and practices of
pregnant women towards malaria and their association with malaria morbidity.

METHODS: Cross-sectional malaria survey of 1432 pregnant women attending six health centres, each of them situated in a specific health district in Rwanda from September to October 2002.

RESULTS: The overall prevalence of malaria infection was 13.6% and all infections but two
were caused by Plasmodium falciparum. The six health districts were significantly different in terms of malaria prevalence, which varied between 11.5% and 15.4% in four and was <5% in the other two districts. The prevalence of anaemia and splenomegaly mirrored that of malaria infection. In three districts, the prevalence of infection was significantly higher in primigravidae than in secundigravidae and multigravidae (P = 0.01), while in two others it did not vary with parity. Bed net use was low - o­nly 13.1% of the women had at least o­ne bed net at home and 8.3% of them slept under it - and significantly different between districts. Most women knew that malaria might have serious consequences for their pregnancy and that insecticide-treated bed nets are useful for alaria prevention. However, the bed net market price [1525 Rwandan Francs (RFr), approximately 1.6] was much higher than that considered as affordable and acceptable (389 RFr, approximately 0.3).

CONCLUSION: Malaria in pregnancy is a major problem in Rwanda, even in the districts of low transmission. Bed net use among pregnant women is low. The option of providing free insecticide-treated bed nets to pregnant women should be explored and possibly implemented; it could rapidly increase bed net use and earlier attendance to antenatal clinics with clear benefits for the women's health.

Preventing malaria in pregnancy: a study of perceptions and policy implications in Mukono district, Uganda. In Health Policy Plan. 2006 Jan;21(1):17-26. Epub 2005 Nov 29. By Mbonye AK, Neema S, Magnussen P. Reproductive Health Divison, Department of Community Health, Ministry of Health, Kampala, Uganda.

Although the efficacy of insecticide-treated nets (ITNs) in malaria prevention is well documented, the low coverage of ITNs in malaria endemic countries necessitates investigation o­n factors that limit access to this intervention. An exploratory study was conducted in Mukonodistrict, Uganda, to assess perceptions and use of ITNs. Results show that malaria is perceived as a serious illness among pregnant women and children, and there is high awareness o­n the benefits of ITNs. However, ITNs are used by few people, mainly because of their high cost and the perception that the chemicals used to treat them have dangerous effects o­n pregnancy and the foetus. Other factors that influence the use of ITNs include low utilization of antenatal care,husband's lack of interest in malaria prevention and the perception that adolescent girls and primigravidae are at a low risk of getting malaria. The policy implications of these findings include demystifying the negative perceptions o­n the chemicals used to treat nets and subsidizing the cost of ITNs in order to increase access to them. These findings provide important lessons for malaria control programmes that aim at increasing access to ITNs by pregnant women in developing countries.

Public-private delivery of insecticide-treated nets: a voucher scheme in Volta Region, Ghana. In Malar J. 2007 Feb 2;6:14. By Kweku M, Webster J, Taylor I, Burns S, Dedzo M. Ghana Health Service, Volta Regional Health Directorate, P.O. Box HP 72, Ho. Volta Region, Ghana. margaret.kweku@lshtm.ac.uk

Coverage of vulnerable groups with insecticide-treated nets (ITNs) in Ghana, as in the majority of countries of sub-Saharan Africa is currently low. A voucher scheme was introduced in Volta Region as a possible sustainable delivery system for increasing this coverage through scale-up to other regions. Successful scale-up of public health interventions depends upon optimal delivery processes but operational research for delivery processes in large-scale implementation has been inadequate. METHODS: A simple tool was developed to monitor numbers of vouchers given to each health facility, numbers issued to pregnant women by the health staff, and numbers redeemed by the distributors back to the management agent. Three rounds of interviews were undertaken with health facility staff, retailers and pregnant women who had attended antenatal clinic (ANC).

ESULTS: During the o­ne year pilot 25,926 vouchers were issued to eligible women from clinics, which equates to 50.7% of the 51,658 ANC registrants during this time period. Of the vouchers issued 66.7% were redeemed by distributors back to the management agent. Initially, non-issuing of vouchers to pregnant women was mainly due to eligibility criteria imposed by the midwives; later in the year it was due to decisions of the pregnant women, and supply constraints. These in turn were heavily influenced by factors external to the programme: current household ownership of nets, competing ITN delivery strategies, and competition for the limited number of ITNs available in the country from major urban areas of other regions.

CONCLUSION: Both issuing and redemption of vouchers should be monitored as factors assumed to influence voucher redemption had an influence o­n issuing, and vice versa. More evidence is needed o­n how specific contextual factors influence the success of voucher schemes and other models of delivery of ITNs. Such an evidence base will facilitate optimal strategic decision making so that the delivery model with the best probability of success within a given context is implemented. Rigorous monitoring has an important role to play in the successful scaling-up of delivery of effective public health interventions.

Reduction Of Malaria During Pregnancy By Permethrin-Treated Bed Nets In An Area Of Intense Perennial Malaria Transmission In Western Kenya. In Am. J. Trop. Med. Hyg., 68 (Suppl 4), 2003, pp. 50-60 Feiko O. Ter Kuile, Dianne J. Terlouw, Penelope A. Phillips-Howard, William A. Hawley, Jennifer F. Friedman, Simon K. Kariuki, Ya Ping Shi, Margarette S. Kolczak, Altaf A. Lal, John M. Vulule, And Bernard L. Nahlen

The impact of insecticide (permethrin)-treated bed nets (ITNs) o­n malaria in pregnancy was studied in a rural area in western Kenya with intense perennial malaria transmission. All households in 40 of 79 villages were randomized to receive ITNs by January 1997. The ITNs were distributed in control villages two years later. Complete data o­n birth outcome were available o­n 2,754 (89.6%) of 3,072 deliveries. Women (n _ 780) were followed monthly throughout pregnancy in 19 of 79 illages. Among gravidae 1-4, ITNs were associated with reductions of 38% (95% confidence interval [CI] _ 17-54%) in the incidence of malaria parasitemia and 47% (95% CI _ 6-71%) in the incidence of severe malarial anemia (hemoglobin level < 8 g/dL with parasitemia) during pregnancy. At the time of delivery, mean hemoglobin levels were 0.6 g/dL (95% CI _ 0.01-1.2 g/dL) higher, the prevalence of placental or maternal malaria was reduced by 35% (95% CI_20-47%), and the prevalence of low birth weight was reduced by 28% (95% CI _ 2-47%) in gravidae 1-4 from ITN villages. No beneficial impact was observed in gravidae five or higher. In areas of intense perennial malaria transmission, permethrin-treated bed nets reduce the adverse effect of malaria during the first four pregnancies.

Simultaneous presence of DDT and pyrethroid residues in human breast milk from a malaria endemic area in South Africa. In 16: Environ Pollut. 2006 Dec;144(3):902-17. Epub 2006 Mar 24. By Bouwman H, Sereda B, Meinhardt HM. School for Environmental Sciences and Development, North-West University (Potchefstroom Campus), Private Bag X6001, Potchefstroom 2520, South Africa. drkhb@puk.ac.za

DDT and pyrethroids were determined in 152 breast-milk samples from three towns in KwaZulu-Natal, South Africa, o­ne of which had no need for DDT for malaria control. All compounds were found present in breast milk. Primiparae from o­ne town had the highest mean Sigma DDT whole milk levels (238.23 microg/l), and multiparae from the same town had the highest means for permethrin (14.51 microg/l), cyfluthrin (41.74 microg/l), cypermethrin (4.24 microg/l), deltamethrin (8.39 microg/l), and Sigmapyrethroid (31.5 microg/l), most likely derived from agriculture. The ADI for DDT was o­nly exceeded by infants from o­ne town, but the ADI for pyrethroids was not exceeded. Since the ADI for DDT was recently reduced from 20 to 10 microg/kg/bw, we suggest that this aspect be treated with concern. We therefore raise a concern based o­n toxicant interactions, due to the presence of four different pyrethroids and DDT. Breastfeeding however, remains safe under prevailing conditions.

Use and misuse of a discount voucher scheme as a subsidy for insecticide-treated nets for malaria control in southern Tanzania. In Health Policy Plan. 2006 Jan;21(1):1-9. Epub 2005 Nov 21. By Tami A, Mbati J, Nathan R, Mponda H, Lengeler C, Schellenberg JR. Ifakara Health Research and Development Centre, Tanzania.Adriana.tami@lshtm.ac.uk

Since 1997, discount vouchers for insecticide-treated nets (ITNs) have been used in two rural districts of southern Tanzania as a way to target subsidies to children under 5 years and pregnant women. We assessed appropriate use and misuse of discount vouchers through a follow-up study of 104 randomly selected vouchers. We traced these vouchers from their original issue in mother-and-child health (MCH) clinics through to being redeemed at a sales agent. We found that all vouchers that reached the target population (100%, 56/56) were used to buy an ITN. Moreover, 94% of the ITNs bought with vouchers were used by those intended, women and children under 5 years. However, up to 48% (50/104) of the vouchers had been misused at the clinics that issued them. Nevertheless, large-scale misuse occurred o­nly at three of 21 clinics.

Although most women slept under a net while pregnant, the use of voucher-subsidized ITNs during pregnancy was low despite widespread knowledge of the scheme. Parents had apparently decided to buy the subsidized ITNs o­nce the child was born and not during pregnancy. Importantly, in 20% of households the o­nly existing net had been bought with a voucher. Our findings suggest that vouchers are properly used by the target population, and that to minimize voucher leakage, control measures are needed at MCH clinics and to a certain extent for commercial sales agents. Increased awareness among the whole community o­n the right to receive a discount voucher may also help to control misuse at health facilities.

Use of intermittent presumptive treatment and insecticide treated bed nets by pregnant women in four Kenyan districts. In Trop Med Int Health. 2004 Feb;9(2):255-61. By Guyatt HL, Noor AM, Ochola SA, Snow RW. Kenya Medical Research Institute/Wellcome Trust Collaborative Programme, Nairobi, Kenya. helenguyatt@yahoo.com

The roll back malaria (RBM) movement promotes the use of insecticide-treated bednets (ITNs) and intermittent presumptive treatment (IPT) of malaria infection as preventive measures against the adverse effects of malaria among pregnant women in Africa. To determine the use of these preventive measures we undertook a community-based survey of recently pregnant women randomly selected from communities in four districts of Kenya in December 2001. Of the 1814 women surveyed, o­nly 5% had slept under an ITN. More than half of the 13% of women using a bednet (treated or untreated) had bought their nets from shops or markets. Women from rural areas used bednets less than urban women (11% vs. 27%; P < 0.001), and 41% of the bednets used by rural women had been obtained free of charge from a research project in Bondo or a
nationwide UNICEF donation through antenatal clinics (ANCs). Despite 96% of ANC providers being aware of IPT with sulphadoxine-pyrimethamine (SP), o­nly 5% of women interviewed had received two or more doses of SP as a presumptive treatment. The coverage of pregnant women with at least o­ne dose of IPT with SP was 14%, though a similar percentage also had received at least a single dose as a curative treatment. The coverage of nationally recommended strategies to prevent malaria during pregnancy during 2001 was low across the diverse malaria ecology of Kenya. Rapid expansion of access to these services is required to meet international and national targets by the year 2005. The scaling up of malaria prevention programmes through ANC services should be possible with 74% of women visiting ANCs at least twice in all four districts. Issues of commodity supply and service costs to clients will be the greatest impediments to reaching RBM targets.

Use of intermittent preventive treatment for malaria in pregnancy in a rural area of western Kenya with high coverage of insecticide-treated bed nets. In Trop Med Int Health. 2005 Nov;10(11):1134-40. By van Eijk AM, Blokland IE, Slutsker L, Odhiambo F, Ayisi JG, Bles HM, Rosen DH, Adazu K, Lindblade KA. Kenya Medical Research Institute, Centre for Vector Biology and Control Research, Kisumu, Kenya. AMvanEijk@yahoo.com

Kenya established intermittent preventive treatment (IPT) with sulfadoxine-pyrimethamine (SP) for malaria in pregnancy as national policy in 1998. We assessed the coverage of IPT among women who had recently delivered in a rural area of western Kenya with perennial malaria transmission and high coverage with insecticide treated nets (ITNs) through a cross-sectional, community-based survey in December 2002. Antenatal clinic (ANC) attendance was high (89.9% of the 635 participating women); 77.5% of attendees visited an ANC before the third trimester and 91.9% made more than o­ne visit. Delivery of SP by the ANC was reported by 19.1% of all women but o­nly 6.8% reported receiving more than o­ne dose. Given the high rate of use of ANC services, if SP were given at each visit after the first trimester, the potential coverage of IPT (two doses of SP) would be 80.3% in this study population. ITNs were used by 82.4% of women during pregnancy, and almost all mothers (98.5%) who slept under an ITN shared the nets with their newborns after delivery. Women who thought malaria in pregnancy caused foetal problems were more likely to have used an ITN (adjusted odds ratio [AOR] 1.6, 95% confidence interval [CI] 1.0-2.4), and to have visited ANC more than o­nce (AOR 2.4, 95% CI 1.2-4.7) compared to women who thought malaria in pregnancy was either not a problem or caused problems for the mother o­nly. These findings illustrate the need for improved IPT coverage in this rural area. Identification and removal of the barriers to provision of IPT during ANC visits can help to increase coverage. In this area of Kenya, health messages stressing that foetal complications of malaria in pregnancy may occur in the absence of maternal illness may improve the demand for IPT.

 3.Case Management/Treatment

Artemether in the treatment of falciparum malaria during pregnancy in eastern Sudan. In Trans R Soc Trop Med Hyg. 2004 Sep;98(9):509-13. By Adam I, Elwasila E, Mohammed Ali DA, Elansari E, Elbashir MI. New Halfa Teaching Hospital, P.O. Box 61, New Halfa, Sudan. ishagadam@hotmail.com

This study was carried in New Halfa Hospital, eastern Sudan from October 1997 to February 2001. Twenty-eight pregnant Sudanese women infected with Plasmodium falciparum were treated with intramuscular artemether (six injections, 480 mg) after failure of chloroquine and quinine therapy. The patients were followed-up until delivery; the babies were followed-up until the age of 1 year. Artemether was given to o­ne patient in the tenth week of gestation, to 12 during the second trimester, and to 15 during the third trimester. It was well tolerated, the parasitaemia was cleared and the patients were symptom-free within three days. o­ne patient (3.5%) delivered at 32 weeks and the baby died six hours after delivery. The other 27 (96.5%) delivered full-term live babies. None of the pregnant women died and there was no abortion, stillbirth or congenital abnormalities in the newborn babies.

Artesunate plus sulfadoxine-pyrimethamine in the treatment of uncomplicated Plasmodium falciparum malaria during pregnancy in eastern Sudan. In Trans R Soc Trop Med Hyg. 2006 Jul;100(7):632-5. Epub 2006 Jan 24. By Adam I, Ali DM, Abdalla MA. Faculty of Medicine, University of Khartoum, Khartoum, Sudan. ishagadam@hotmail.com

Malaria during pregnancy is associated with serious adverse effects; these could be avoided with effective treatment. Artesunate plus sulfadoxine-pyrimethamine (AS+SP) is a promising antimalarial combination; however, few data are available o­n its safety during pregnancy. The present study was carried out in New Halfa Hospital, eastern Sudan, between September 2004 and March 2005. Thirty-two pregnant Sudanese women with uncomplicated Plasmodium falciparum malaria were treated with AS+SP at a mean of 29.7 weeks of gestation. The patients were followed-up until delivery and the babies were followed-up until the age of 1 month. The drug was well tolerated, the parasitaemia was cleared and the patients were symptom-free within 2 days. All the patients delivered full-term live babies. o­ne of the babies died o­n the fourth day; none of the women died and there was no miscarriage, stillbirth, or congenital abnormalities in the newborn babies. Thus, this small descriptive study failed to detect unintended effects of AS+SP during pregnancy.

Can amodiaquine be used safely during pregnancy? In Lancet Infect Dis. 2004 Apr;4(4):235-9. Comment in: Lancet Infect Dis. 2004 Dec;4(12):721-2; discussion 722. By Thomas F, Erhart A, D'Alessandro U. Department of Parasitology, Prince Leopold Institut of Tropical Medicine, Antwerp, Belgium.

Several African countries have begun using amodiaquine-containing combinations as first-line antimalarial treatment, with the result that a substantial number of pregnant women are likely to be exposed to amodiaquine. However, little information is available o­n amodiaquine safety and efficacy during pregnancy. Between 1948 and 1990 o­nly six published studies reportedamodiaquine use in pregnancy. o­nly o­ne publication mentioned adverse events, without details. Six additional studies o­n amodiaquine delivered by mass drug administration or medicated salts gave very little information o­n amodiaquine safety. Therefore, there is an urgent need for studies o­n amodiaquine safety and tolerability during pregnancy since current data are not sufficient to recommend its use during pregnancy, particularly as intermittent preventive treatment.

Case Management of Malaria in Pregnancy. In The Lancet Infectious Diseases - Vol. 7, Issue 2, February 2007, Pages 118-125 By François Nosten, Rose McGready, Theonest Mutabingwa

In all malarious areas, infection by any of the main human plasmodial species during pregnancy is detrimental to the mother and the fetus. These potentially fatal infections must be prevented, but when they develop they require prompt diagnosis and treatment. Current tools to detect malaria parasites in pregnant women are often not used and remain too insensitive to detect a low parasitaemia. The kinetics, safety, and efficacy of available antimalarial drugs are poorly
documented because pregnant women are systematically excluded from clinical trials. A considerable effort, involving clinical trials, is urgently required to improve the diagnosis and case management of malaria during pregnancy if the morbidity and mortality of maternal malaria is to be reduced.

Comparative efficacy of chloroquine and sulphadoxine--pyrimethamine in pregnant
women and children: a meta-analysis. In Trop Med Int Health. 2006 May;11(5):569-77. By Kalanda GC, Hill J, Verhoeff FH, Brabin BJ. Child and Reproductive Health Group, Liverpool School of Tropical Medicine, and Royal Liverpool Children's Hospital NHS Trust, UK.

OBJECTIVE: To compare the efficacy of chloroquine and sulphadoxine-pyremethamine against Plasmodium falciparum infection in pregnant women and in children from the same endemic areas of Africa, with the aim of determining the level of correspondence in efficacy determinations in these two risk groups. METHODS: Meta-analysis of nine published and unpublished in vivo antimalarial efficacy studies in pregnant women and in children across five African countries. RESULTS: Pregnant women (all gravidae) were more likely to be sensitive
than children to both chloroquine (odds ratio: 2.07; 95% confidence interval: 1.5, 2.9) and
sulphadoxine-pyrimethamine (odds ratio: 2.66; 95% confidence interval: 11.1, 6.7). Pregnant
women demonstrated an almost uniform increased sensitivity for peripheral parasite clearance at
day 14 compared with children. This finding was consistent across a wide range of drug
sensitivities. Primigravidae at day 14 showed lower clearance to antimalarial drugs than
multigravidae (P<0.05). There was no significant difference between parasite clearance in
primigravidae and in children. CONCLUSION: The greater drug sensitivity in pregnant women
probably indicates differences in host susceptibility rather than parasite resistance. Parasite
sensitivity patterns in children may be a suitable guide to antimalarial policy in pregnant women.

Current issues in the treatment of uncomplicated malaria in Africa. In Br Med Bull. 2004 Dec 13;71:29-43. Print 2004. By Bell D, Winstanley P. Department of Pharmacology and Therapeutics, University of Liverpool, Liverpool L69 3GE, UK. dbell@mlw.medcol.mw

Sub-Saharan Africa is faced with a crisis of rising levels of resistance to antimalarial drugs and few available and affordable alternatives. Combination chemotherapy, using two or more drugs with different mechanisms and sites of action together, is proposed as a mechanism for slowing the process of development of resistance. In Thailand, this approach has resulted in a sustained increase in the cure rate. Whether such an effect would be seen in Africa is not known. This article reviews the rationale behind combination therapy, the drugs available and the available evidence from combination therapy trials in Africa. Treatment of uncomplicated malaria in pregnancy and infants is also discussed.

Effect of self-medication with antimalarial drugs o­n malaria infection in pregnant women in South-Western Nigeria. In Med Princ Pract. 2005 Jan-Feb;14(1):6-9. By Akanbi OM, Odaibo AB, Afolabi KA, Ademowo OG. Department of Environmental Biology and Fisheries, Faculty of Science, Adekunle Ajasin University, Akungba-Akoko, Ondo State, Nigeria.

OBJECTIVE: To determine the effect of self-medication with chloroquine and pyrimethamine o­n malaria infection and anaemia during pregnancy. SUBJECTS AND METHODS: The study involved 210 women who attended Ade Oyo Maternity State Hospital, Ibadan, Nigeria. Of these, 156 were pregnant women while 54 were not pregnant (controls). Of the pregnant women, 66 were primigravidae, while 90 were multigravidae. History of treatment of malaria with
antimalarial drugs was obtained from the subjects. Gravidity and gestation period were also documented. Two millilitres of blood was withdrawn from each subject, for haematological
parameters. Thin and thick films were prepared for malaria parasite identification and quantification. RESULTS: Of the primigravidae and multigravidae 68 and 16.4%, respectively, had taken antimalarial drugs prior to booking. Among primigravidae, o­nly 18% of those with drugs compared with 32% without drugs were malaria-positive. The parasite density was significantly lower among those who took antimalarial drugs than among those who did not (976 +/- 60 versus 2,421 +/- 78, p < 0.05). Similarly, among multigravidae, o­nly 16.4% of those who took antimalarial drugs compared with 34% of those who were not malaria-positive. The parasite density was also significantly lower in multigravidae with drugs than among those without drugs (350 +/- 45 versus 1,000 +/- 65, p < 0.05). The prevalence of anaemia (packed cell volume, PCV < 33) was high, 89% in primigravidae and 70% in multigravidae. Severe anaemia (PCV < 21) was more common in malaria-positive primigravidae and multigravidae than in malaria-negative women. CONCLUSION: The findings indicate that self-medication with chloroquine and pyrimethamine at booking was able to reduce the prevalence of malaria and anaemia in pregnancy.

Effectiveness of quinine monotherapy for the treatment of Plasmodium falciparum infection in pregnant women in Lambarene, Gabon. In Am J Trop Med Hyg. 2005 Aug;73(2):263-6. By Adegnika AA, Breitling LP, Agnandji ST, Chai SK, Schutte D, Oyakhirome S, Schwarz NG, Grobusch MP, Missinou MA, Ramharter M, Issifou S, Kremsner PG. Medical Research Unit, Albert Schweitzer Hospital, Lambarene, Gabon. aadegnika@yahoo.com

Pregnant women participating in a longitudinal immuno-epidemiologic survey in Lambarene, Gabon, and presenting with Plasmodium falciparum parasitemia at monthly blood smear examinations were offered treatment with oral 7-day quinine monotherapy according to national health guidelines. A total of 50 pregnant women were offered 7-day oral quinine sulfate 10
mg/kg thrice daily. Clinical examinations and laboratory tests were performed o­n Days 28 and
56 to assess the effectiveness of this standard regimen. By Day 28, the effectiveness of the 7-day quinine regimen was 60% (95% confidence interval: 46-72%). We conclude that a 7-day course of quinine has a poor effectiveness and that alternative treatment regimens for malaria in pregnant women should be assessed.

Efficacy, safety, and tolerability of amodiaquine plus sulphadoxine-pyrimethamine used alone or in combination for malaria treatment in pregnancy: a randomised trial. In Lancet. 2006 Oct 14;368(9544):1349-56. (with Comment in: Lancet. 2006 Oct 14;368(9544):1306-7.) By Tagbor H, Bruce J, Browne E, Randal A, Greenwood B, Chandramohan D. St Theresa's Hospital, Nkoranza, Ghana. Harry.Tagbor@lshtm.ac.uk

BACKGROUND: The widespread increase in resistance of Plasmodium falciparum to chloroquine and sulphadoxine-pyrimethamine threatens the use of these drugs for malaria reatment in pregnancy. We aimed to assess the safety and efficacy of amodiaquine alone or in combination with sulphadoxine-pyrimethamine as alternative regimens. METHODS: Pregnant women with a gestational age of 16 weeks or more who attended antenatal clinics at a district hospital in Ghana were screened for malaria with OptiMAL dipsticks. 900 pregnant women who had a positive test result and P falciparum asexual stage parasitaemia were enrolled and randomly assigned chloroquine, sulphadoxine-pyrimethamine, amodiaquine, or amodiaquine plus sulphadoxine-pyrimethamine. The primary outcome was parasitological failure by day 28 of treatment. Women were seen o­n days 3, 7, 14, and 28 after the start of treatment to assess the effect of treatment o­n peripheral parasitaemia, haemoglobin concentration, white-blood-cell count, and liver function. Additionally, reports of adverse effects were solicited and monitored during follow-up visits. Analysis was by intention to treat. This trial is registered with the US National Institute of Health clinical trials database number NCT00131703. FINDINGS: PCR-corrected parasitological failure by day 28 was 14%, 11%, 3%, and 0% in the women assigned chloroquine, sulphadoxine-pyrimethamine, amodiaquine, and amodiaquine plus sulphadoxine-pyrimethamine, respectively (p<0.0001). No serious liver toxic effects or white-blood-cell dyscrasias were noted. Minor side-effects were reported more often o­n day 3 by women receiving amodiaquine (86%) or amodiaquine plus sulphadoxine-pyrimethamine (90%) than those receiving sulphadoxine-pyrimethamine (48%) or no antimalarial drugs (34%; p<0.0001 for every comparison). INTERPRETATION: Amodiaquine alone or in combination with sulphadoxine-pyrimethamine, although associated with minor side-effects, is effective when used to treat malaria in pregnancy.

Low-dose quinine for treatment of chloroquine-resistant falciparum malaria in Sudanese pregnant women. In East Mediterr Health J. 2004 Jul-Sep;10(4-5):554-9. By Adam I, Ibrahim MH, A/elbasit IA, Elbashir MI. New Halfa Hospital, New Halfa, Sudan.

Pregnant Sudanese women who presented at a hospital in eastern Sudan with chloroquine-resistant falciparum malaria were randomly allocated to o­ne of two quinine regimens: low-dose (10 mg/kg 2 times/day) (18 patients) or standard (10 mg/kg 3 times/day) (24 patients). Treatment was for 7 days and follow-up for 28 days. Significantly fewer patients in the low-dose group reported vomiting and abdominal pain than the standard regimen group. Hypoglycaemia, preterm labour and recrudescence were slightly but not significantly higher in patients in the standard group than low-dose group. There were no significant differences between the groups in the mean time from admission to remission of fever and parasite clearance. We tentatively advocate the use of quinine 2 times/day to reduce side-effects and improve compliance.

Malaria chemotherapy. In Adv Parasitol. 2006;61:47-76. By Winstanley P, Ward S. Department of Pharmacology & Therapeutics, University of Liverpool, Liverpool L69 3GE, UK.

Most malaria control strategies today depend o­n safe and effective drugs, as they have done for decades. But sensitivity to chloroquine, hitherto the workhorse of malaria chemotherapy, has rapidly declined throughout the tropics since the 1980s, and this drug is now useless in many high-transmission areas. New options for resource-constrained governments are few, and there is growing evidence that the burden from malaria has been increasing, as has malaria mortality in Africa. In this chapter, we have tried to outline the main pharmacological properties of current drugs, and their therapeutic uses and limitations. We have summarised the ways in which these drugs are employed, both in the formal health sector and in self-medication. We have briefly touched o­n the limitations of current drug development, but have tried to pick out a few promising drugs that are under development. Given that Plasmodium falciparum is the organism that kills, and that has developed multi-drug resistance, we have tended to focus upon it. Similarly, given that around 90% of global mortality from malaria occurs in Africa, there is the tendency to dwell o­n this continent. We give no apology for placing our emphasis upon the use of antimalarial drugs in endemic populations rather than their use for prophylaxis in travellers.

Mefloquine in the treatment of falciparum malaria during pregnancy in Eastern Sudan. In Saudi Med J. 2004 Oct;25(10):1400-2. By Adam I, Ali DA, Alwaseila A, Kheir MM, Elbashir MI. Department of Obstetrics and Gynecology, New Halfa Teaching Hospital, New Halfa, Sudan. ishagadam@hotmail.com

OBJECTIVE: To test the efficacy and toxicity of mefloquine therapy both o­n expectant mothers and the outcome of their pregnancies. METHODS: We performed a prospective non-comparative clinical trial in New Halfa Teaching Hospital, Eastern Sudan, during the period October 1998 to June 2001. Pregnant Sudanese women were given mefloquine 25 mg/kg for treatment of falciparum malaria following chloroquine failure. The women were followed every 2 weeks in the antenatal clinic until delivery. The babies were followed until the age of o­ne year. RESULTS: Forty pregnant women were enrolled in the second and third trimesters. Itching which occurred in 17.5% and nausea which occurred in 35% were the cardinal side effects of the patients. Recrudescence or re-infection occurred o­n day 14 in o­ne patient (2.5%). o­ne patient that received mefloquine at 34 weeks gestational age delivered low birth weight (2.1 kg) at 39 weeks gestational age. o­ne child died at the age of 7 months due to unexplained febrile illness. There was no abortion, no stillbirth and no congenital abnormality in the newborn children and no maternal death. CONCLUSION: This relatively small study reported that mefloquine could be used safely for the treatment of malaria in the second and third trimester of pregnancy and a larger study is recommended.

Quinine for chloroquine-resistant falciparum malaria in pregnant Sudanese women in the first trimester. In East Mediterr Health J. 2004 Jul-Sep;10(4-5):560-5. By Adam I, Idris HM, Elbashir MI. New Halfa Hospital, New Halfa, Sudan.

A prospective clinical study in eastern Sudan described the efficacy and toxicity of quinine in early pregnancy in mothers with chloroquine-resistant falciparum malaria. Twenty-six pregnant Sudanese women in their first trimester (mean gestational age 8.5 weeks) were given quinine 10 mg/kg 3 times per day for 7 days and followed up every 2 weeks until delivery. o­ne patient aborted (3.8%) and 2 patients (7.7%) experienced threatened abortion but delivered term babies. Recrudescence or re-infection was observed o­n day 21 in 1 patient. o­ne baby died aged 6 months. There were no detectable congenital malformations, no auditory or visual defects or any other neurological deficits in the remaining infants at birth or 1 year later. Quinine may be safe in the first trimester of pregnancy.

The safety of artemisinins during pregnancy: a pressing question. Malar J. 2007 Feb 14;6:15. By Dellicour S, Hall S, Chandramohan D, Greenwood B. Department of Infectious and Tropical Diseases, London School of Hygiene & Tropical Medicine, 50, Bedford Square, London, WC1B 3DP, UK. stephanie.dellicour@lshtm.ac.uk

An increasing number of countries in sub-Saharan Africa are changing to artemisinins combination therapy (ACT) as first or second line treatment for malaria. There is an urgent need to assess the safety of these drugs in pregnant women who may be inadvertently exposed to or actively treated with ACTs. OBJECTIVES: To examine existing published evidence o­n the relationship between artemisinin compounds and adverse pregnancy outcomes and consider the published evidence with regard to the safety of these compounds when administered during pregnancy. METHODS: Studies o­n ACT use in pregnancy were identified via searches of MEDLINE, EMBASE, Cochrane and Current Contents databases. Data o­n study characteristics, maternal adverse events, pregnancy outcomes and infant follow up were extracted. RESULTS: Fourteen relevant studies (nine descriptive/case reports and five controlled trials) were identified. Numbers of participants in these studies ranged from six to 461. Overall there were reports o­n 945 women exposed to an artemisinin during pregnancy, 123 in the 1st trimester and 822 in 2nd or 3rd trimesters. The primary end points for these studies were drug efficacy and parasite clearance. Secondary endpoints were birth outcomes including low birth weight, pre-term birth, pregnancy loss, congenital anomalies and developmental milestones. While none of the studies found evidence for an association between the use of artemisinin compounds and increased risk of adverse pregnancy outcomes, none were of sufficient size to detect small differences in event rates that could be of public health importance. Heterogeneity between studies in the artemisinin and comparator drugs used, and in definitions of adverse pregnancy outcomes, limited any pooled analysis. CONCLUSION: The limited data available suggest that artemisinins are effective and unlikely to be cause of foetal loss or abnormalities, when used in late pregnancy. However, none of these studies had adequate power to rule out rare serious adverse events, even in 2nd and 3rd trimesters and there is not enough evidence to effectively assess the risk-benefit profile of artemisinin compounds for pregnant women particularly for 1st trimester exposure. Methodologically rigorous, larger studies and post-marketing pharmacovigilance are urgently required.

Therapeutic efficacy of sulphadoxine-pyrimethamine and chloroquine for the treatment of uncomplicated malaria in pregnancy in Burkina Faso. In Malar J. 2006 Jun 15;5:49. By Coulibaly SO, Nezien D, Traore S, Kone B, Magnussen P. Laboratoire National de
Sante Publique, 09 BP 24 Ouagadougou 09, Burkina Faso. sheickoumar2@yahoo.fr

BACKGROUND: A reduction in the therapeutic efficacy of chloroquine (CQ) and sulphadoxine-pyrimethamine (SP) has recently been observed in Burkina Faso. As these two drugs are used in pregnancy, their efficacy in pregnant women was studied to directly assess the level of drug resistance in this specific population, rather than to extrapolate results of studies conducted in children < 5 years of age. METHODS: During the malaria transmission season of 2003 in Ouagadougou, the clinical efficacy of SP and CQ, using the WHO 28-day protocol,was assessed in primigravidae and secundigravidae presenting with uncomplicated malaria.

RESULTS: PCR-corrected results by day 28 showed that among 62 women treated with SP, eight (12.9%) experienced late parasitological failure, but no clinical failures. Among 60 women treated with CQ, the overall failure rate was 46.7% including 1.7% early treatment failures, 5% late clinical failures and 40% late parasitological failures. SP induced a haemoglobin gain of 0.3 g/dL by day 14 and 0.9 g/dL by day 28. Treatment responses were independent of gravidity, gestational age and prior antenatal care visits. CONCLUSION: While CQ should no longer be used, the efficacy of SP is still compatible with use for intermittent preventive treatment (IPT) in pregnancy. However, given the possible spread of resistance, the drug should be restricted in its use.

Treatment-seeking practices for malaria in pregnancy among rural women in Mukono district, Uganda. In J Biosoc Sci. 2006 Mar;38(2):221-37. By Mbonye AK, Neema S, Magnussen P. Ministry of Health, Kampala, Uganda.

Understanding treatment-seeking practices for malaria in pregnancy is necessary in designing effective programmes to address the high malaria morbidity in pregnancy. This study assessed women's perceptions o­n malaria in pregnancy, recognition of early signs of pregnancy and of malaria, and the cultural context in which treatment seeking takes place in Mukono District. Focus group discussions (FGD) and key informant interviews were conducted among pregnant women, non-pregnant women, adolescents and men. The results showed that malaria, locally known as omusujja, was perceived as the most common cause of ill health among pregnant women. Although malaria commonly presents with fever, some pregnant women feel hot in the womb with or without signs of fever and this illness, locally known as nabuguma, may lead to progressive weakness and occasionally to miscarriage and few respondents associated it with malaria. Primigravidae, adolescents and men were not considered at risk of omusujja or nabuguma. Similarly anaemia and low birth weight were not associated with malaria; in fact paleness was described as a normal sign of pregnancy. There are cultural and social pressures o­n married women to get pregnant and this forces them to conceal symptoms like feeling feverishness, backache, nausea, general weakness, loss of appetite and vomiting until they are sure these are due to pregnancy. Most women, however, could not differentiate symptoms of malaria from those of early pregnancy. There is a belief that omusujja is a normal sign of pregnancy and this is coupled with a strong cultural practice of using herbs and clays as a first resort to treat pregnancy ailments including malaria. The cultural beliefs and practices regarding delivery of twin and first births, coupled with the high cost of care, prevent women from delivering and using other services at health units.

4.Epidemiological, Social and Economic Issues in MIP

A survey of knowledge, attitude and practice of malaria management among pregnant women from two health care facilities in Nigeria. In Acta Obstet Gynecol Scand. 2007;86(1):33-6. By Enato EF, Okhamafe AO, Okpere EE. Department of Clinical Pharmacy and Pharmacy Practice, University of Benin, Benin City, 300001, Nigeria. enatoefo@uniben.edu

 BACKGROUND: Malaria remains o­ne of the most important causes of maternal and child morbidity and mortality in sub-Saharan Africa, despite the availability of effective interventions. The objective of this study was to assess the knowledge, attitude and practice of malaria management among pregnant women attending antenatal clinics in Nigeria.

METHODS: A cross-sectional study was undertaken o­n a sample of 867 pregnant women attending antenatal clinics in 2 health care facilities in Edo State, Nigeria, using a self-administered questionnaire.

RESULTS: Of the respondents, 87% said that they had undergone at least 1 episode of malaria during their current pregnancy. Most respondents (89%) attributed malaria to bites from infected mosquitoes, while 75% consider malaria an important health risk during pregnancy. However, knowledge of the consequences of malaria during pregnancy was poor, especially the risk posed to the fetus. Overall, the mean knowledge score o­n a scale of '0-7' was 3.5 (median 4.0). Respondents had poor belief in the effectiveness and use of insecticide-treated bed nets and intermittent preventive therapy, in preventing malaria during pregnancy. CONCLUSIONS: This study has revealed that malaria is perceived as a common health problem among pregnant women attending these 2 health care facilities, and that knowledge, attitude and practice of its management is poor. Efforts should be made to improve anti-malarial intervention during pregnancy, to ensure that the goals of the Roll Back Malaria Initiative are achieved in Nigeria.

Adverse birth outcomes in United Republic of Tanzania--impact and prevention of maternal risk factors. In Bull World Health Organ. 2007 Jan;85(1):9-18. By Watson-Jones D, Weiss HA, Changalucha JM, Todd J, Gumodoka B, Bulmer J, Balira R, Ross D, Mugeye K, Hayes R, Mabey D. Department of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, England.

OBJECTIVE: To determine risk factors for poor birth outcome and their population attributable fractions.

METHODS: 1688 women who attended for antenatal care wererecruited into a prospective study of the effectiveness of syphilis screening and treatment. All women were screened and treated for syphilis and other reproductive tract infections (RTIs) during pregnancy and followed to delivery to measure the incidence of stillbirth, intrauterine growth retardation (IUGR), low birth weight (LBW) and preterm live birth.

FINDINGS: At delivery, 2.7% of 1536 women experienced a stillbirth, 12% of live births were preterm and 8% were LBW. Stillbirth was independently associated with a past history of stillbirth, short maternal stature and anaemia. LBW was associated with short maternal stature, ethnicity, occupation, gravidity and maternal malaria whereas preterm birth was associated with occupation, age of sexual debut, untreated bacterial vaginosis and maternal malaria. IUGR was associated with gravidity, maternal malaria, short stature, and delivering a female infant. In the women who had been screened and treated for syphilis, in between 20 and 34% of women with each outcome was estimated to be attributable to malaria, and 63% of stillbirths were estimated as being attributable to maternal anaemia. Screening and treatment of RTIs was effective and no association was seen between treated RTIs and adverse pregnancy outcomes.

CONCLUSION: Maternal malaria and anaemia continue to be significant causes of adverse pregnancy outcome in sub-Saharan Africa. Providing reproductive health services that include treatment of RTIs and prevention of malaria and maternal anaemia to reduce adverse birth outcomes remains a priority.

An evaluation of the effect of parity and age o­n malaria parasitaemia in pregnancy. In J Obstet Gynaecol. 2006 Nov;26(8):755-8. By Nnaji GA, Okafor CI, Ikechebelu JI. Department of Primary Health Care, Faculty of Medicine, Nnamdi Azikiwe University, Nnewi, Nigeria. godswilln@yahoo.co.uk

A higher prevalence of malaria infection (peripheral or placental) has been reported in the primigravidae and secondigravidae when compared with multigravidae. This study set out to determine the effect of parity and age o­n the prevalence of malaria parasitaemia in pregnancy at the booking antenatal visit at the Nnamdi Azikiwe University Teaching Hospital, Nnewi. Peripheral blood smears were examined in 420 pregnant women at their booking antenatal visit and in 200 control subjects attending the outpatient clinic o­n the same day for malaria parasites. These subjects (pregnant women and controls) met the inclusion criteria of being HIV sero-negative, not sickle-cell positive, did not have a history of recent blood transfusion and had been resident in Nnewi for 1 year. The result showed that there was a statistically significant difference between the prevalence rate of malaria parasitaemia in the primigravidae (87.9%: 109 of 124) and grand multigravidae (63.6%: 28 of 44); and the rates were found to decrease with increasing parity. The primigravidae had a higher mean parasite density (2,155/micro l) when compared with the multigravidae (1,950/micro l). This study also revealed that pregnant women <20 years had the highest prevalence rate of 86.4% (19 of 22). This study demonstrates the higher prevalence of malaria parasitaemia in pregnant women of lower parity, i.e. primigravidae and secondigravidae. Therefore, targeting malaria control efforts to women in their first and second pregnancy will be an important strategy to reach most infected women and minimise resource expenditure. These women should be motivated to use insecticide treated bed nets (ITBN) and other personal malarial control measures during pregnancy.

Associations between mild-to-moderate anaemia in pregnancy and helminth, malaria and HIV infection in Entebbe, Uganda. In Transactions of the Royal Society of Tropical Medicine and Hygiene (2007) By Lawrence Muhangia, Patrick Woodburn, Mildred Omara, Nicholas Omoding, Dennison Kizito, Harriet Mpairwe, Juliet Nabulime, Christine Ameke, Linda A. Morison, Alison M. Elliott

It is suggested that helminths, particularly hookworm and schistosomiasis, may be important causes of anaemia in pregnancy. We assessed the associations between mildto- moderate anaemia (haemoglobin >8.0 g/dl and <11.2 g/dl) and helminths, malaria and HIV among 2507 otherwise healthy pregnant women at enrolment to a trial of deworming in pregnancy in Entebbe, Uganda. The prevalence of anaemia was 39.7%. The prevalence of hookworm was 44.5%, Mansonella perstans 21.3%, Schistosoma mansoni 18.3%, Strongyloides 12.3%, Trichuris 9.1%, Ascaris 2.3%, asymptomatic Plasmodium falciparum parasitaemia 10.9% and HIV 11.9%. Anaemia showed little association with the presence of any helminth, but showed a strong association with malaria (adjusted odds ratio (AOR) 3.22, 95% CI 2.43—4.26) and HIV (AOR 2.46, 95% CI 1.90—3.19). There was a weak association between anaemia and increasing hookworm infection intensity. Thus, although highly prevalent, helminths showed little association with mild-to-moderate anaemia in this population, but HIV and malaria both showed a strong association. This result may relate to relatively good nutrition and low helminth infection intensity. These findings are pertinent to estimating the disease burden of helminths and other infections in pregnancy.

Cytoadhesion of Plasmodium falciparum-infected erythrocytes and the infected placenta: a two-way pathway. In Braz J Med Biol Res. 2006 Dec;39(12):1525-36. By Costa FT, Avril M, Nogueira PA, Gysin J. Departamento de Microbiologia e Imunologia, Instituto de Biologia, Universidade Estadual de Campinas, 13083-862 Campinas, SP, Brazil. costaftm@unicamp.br

Malaria is undoubtedly the world's most devastating parasitic disease, affecting 300 to 500 million people every year. Some cases of Plasmodium falciparum infection progress to the deadly forms of the disease responsible for 1 to 3 million deaths annually. P. falciparum-infected erythrocytes adhere to host receptors in the deep microvasculature of several organs. The cytoadhesion of infected erythrocytes to placental syncytiotrophoblast receptors leads to pregnancy-associated malaria (PAM). This specific maternal-fetal syndrome causes maternal anemia, low birth weight and the death of 62,000 to 363,000 infants per year in sub-Saharan Africa, and thus has a poor outcome for both mother and fetus. However, PAM and non-PAM parasites have been shown to differ antigenically and genetically. After multiple pregnancies, women from different geographical areas develop adhesion-blocking antibodies that protect against placental parasitemia and clinical symptoms of PAM. The recent description of a new parasite ligand encoded by the var2CSA gene as the o­nly gene up-regulated in PAM parasites renders the development of an anti-PAM vaccine more feasible. The search for a vaccine to prevent P. falciparum sequestration in the placenta by eliciting adhesion-blocking antibodies and a cellular immune response, and the development of new methods for evaluating such antibodies should be key priorities in mother-child health programs in areas of endemic malaria. This review summarizes the main molecular, immunological and physiopathological aspects of PAM, including findings related to new targets in the P. falciparum var gene family. Finally, we focus on a new methodology for mimicking cytoadhesion under blood flow conditions in human placental tissue.

Detection and clinical manifestation of placental malaria in southern Ghana. In Malar J. 2006 Dec 13;5:119. By Mockenhaupt FP, Bedu-Addo G, von Gaertner C, Boye R, Fricke K, Hannibal I, Karakaya F, Schaller M, Ulmen U, Acquah PA, Dietz E, Eggelte TA, Bienzle U. Institute of Tropical Medicine and International Health, Charite—University Medicine, Berlin, Germany. frank.mockenhaupt@charite.de

BACKGROUND: Plasmodium falciparum can be detected by microscopy, histidine-rich-protein-2 (HRP2) capture test or PCR but the respective clinical relevance of the thereby diagnosed infections in pregnant women is not well established. METHODS: In a cross-sectional, year-round study among 839 delivering women in Agogo, Ghana, P. falciparum was screened for in both, peripheral and placental blood samples, and associations with maternal anaemia, low birth weight (LBW) and preterm delivery (PD) were analysed.

RESULTS: In peripheral blood, P. falciparum was observed in 19%, 34%, and 53% by microscopy, HRP2 test, and PCR, respectively. For placental samples, these figures were 35%, 41%, and 59%. Irrespective of diagnostic tool, P. falciparum infection increased the risk of anaemia. Positive peripheral blood results of microscopy and PCR were not associated with LBW or PD. In contrast, the HRP2 test performed well in identifying women at increased risk of poor pregnancy outcome, particularly in case of a negative peripheral blood film. Adjusting for age, parity, and antenatal visits, placental HRP2 was the o­nly marker of infection associated with LBW (adjusted odds ratio (aOR), 1.5 (95%CI, 1.0-2.2)) and, at borderline statistical significance, PD (aOR, 1.4 (1.0-2.1)) in addition to anaemia (aOR, 2.3 (1.7-3.2)). Likewise, HRP2 in peripheral blood of seemingly aparasitaemic women was associated with PD (aOR, 1.7 (1.0-2.7)) and anaemia (aOR, 2.1 (1.4-3.2)). CONCLUSION: Peripheral blood film microscopy not o­nly underestimates placental malaria. In this highly endemic setting, it also fails to identify malaria as a cause of foetal impairment. Sub-microscopic infections detected by a HRP2 test in seemingly aparasitaemic women increase the risks of anaemia and PD. These findings indicate that the burden of malaria in pregnancy may be even larger than thought and accentuate the need for effective anti-malarial interventions in pregnancy.

Epidemiology and burden of malaria in pregnancy. In Lancet Infect Dis. 2007 Feb;7(2):93-104. By Desai M, ter Kuile FO, Nosten F, McGready R, Asamoa K, Brabin B, Newman RD. Malaria Branch, Division of Parasitic Diseases, Centers for Disease Control and revention, Atlanta, GA 30341, USA. mdesai@cdc.gov

We reviewed evidence of the clinical implications and burden of malaria in pregnancy. Most studies come from sub-Saharan Africa, where approximately 25 million pregnant women are at risk of Plasmodium falciparum infection every year, and o­ne in four women have evidence of placental infection at the time of delivery. P falciparum infections during pregnancy in Africa rarely result in fever and therefore remain undetected and untreated. Meta-analyses of intervention trials suggest that successful prevention of these infections reduces the risk of severe maternal anaemia by 38%, low birthweight by 43%, and perinatal mortality by 27% among paucigravidae. Low birthweight associated with malaria in pregnancy is estimated to result in 100,000 infant deaths in Africa each year. Although paucigravidae are most affected by malaria, the consequences for infants born to multigravid women in Africa may be greater than previously appreciated. This is because HIV increases the risk of malaria and its adverse effects, particularly in multigravidae, and recent observational studies show that placental infection almost doubles the risk of malaria infection and morbidity in infants born to multigravidae. Outside Africa, malaria infection rates in pregnant women are much lower but are more likely to cause severe disease, preterm births, and fetal loss. Plasmodium vivax is common in Asia and the Americas and, unlike P falciparum, does not cytoadhere in the placenta, yet, is associated with maternal anaemia and low birthweight. The effect of infection in the first trimester, and the longer term effects of malaria beyond infancy, are largely unknown and may be substantial. Better estimates are also needed of the effects of malaria in pregnancy outside Africa, and o­nmaternal morbidity and mortality in Africa. Global risk maps will allow better estimation of potential impact of successful control of malaria in pregnancy.

Health consequences of child marriage in Africa. In Emerg Infect Dis. 2006 Nov;12(11):1644-9. By Nour NM. African Women's Health Center, Department of Maternal-Fetal Medicine, Brigham and Women's Hospital, Boston, Massachussetts 02115, USA. nnour@partners.org

Despite international agreements and national laws, marriage of girls <18 years of age is common worldwide and affects millions. Child marriage is a human rights violation that prevents girls from obtaining an education, enjoying optimal health, bonding with others their own age, maturing, and ultimately choosing their own life partners. Child marriage is driven by poverty and has many effects o­n girls' health: increased risk for sexually transmitted diseases, cervical cancer, malaria, death during childbirth, and obstetric fistulas. Girls' offspring are at increased risk for premature birth and death as neonates, infants, or children. To stop child marriage, policies and programs must educate communities, raise awareness, engage local and religious leaders, involve parents, and empower girls through education and employment.

Hypertension and Maternal-Fetal Conflict during Placental Malaria. In PLoS Medicine, 2006; 3(11): e446 By Atis Muehlenbachs, Theonest K. Mutabingwa1, Sally Edmonds, Michal Fried, Patrick E. Duffy

Malaria and hypertension are major causes of maternal mortality in tropical countries, especially during first pregnancies, but evidence for a relationship between these syndromes is o­ntradictory. Methods and Findings: In a cross-sectional survey of Tanzanian parturients, the rate of hypertension was similar in placental malaria (PM)-positive (11/85 ¼ 13%) and PM-negative (73/602 ¼ 12%) individuals. However, we found that PM was associated with hypertension in first-time mothers aged 18-20 yr but not other mothers. Hypertension was also associated with histologic features of chronic malaria, which is common in first-time mothers. Levels of soluble vascular endothelial growth factor receptor 1 (sVEGFR1), a preeclampsia biomarker, were elevated in first-time mothers with either PM, hypertension, or both, but levels were not elevated in other mothers with these conditions. In first-time mothers with PM, the inflammatory mediator vascular endothelial growth factor (VEGF) was localized to maternal macrophages in the placenta, while sVEGFR1, its soluble inhibitor, was localized to the fetal trophoblast.Conclusions: The data suggest that maternal-fetal conflict involving the VEGF pathway occurs during PM, and that sVEGFR1 may be involved in the relationship between chronic PM and hypertension in first-time mothers. Because placental inflammation causes poor fetal outcomes, we hypothesize that fetal mechanisms that promote sVEGFR1 expression may be under selective pressure during first pregnancies in malaria-endemic areas.

Malaria and helminth interactions in humans: an epidemiological viewpoint. In Ann Trop Med Parasitol. 2006 Oct;100(7):551-70. By Mwangi TW, Bethony JM, Brooker S. Kenya Medical Research Institute, Centre for Geographic Medicine and Research, P.O. Box 230, 80108 Kilifi, Kenya. tmwangi@kilifi.mimcom.net

In the tropics, helminths are among the most common chronic infections of humans and Plasmodium infections the most deadly. As these two groups of parasites have similar geographical distributions, co-infection is commonplace. It has increasingly been speculated that helminth infections may alter susceptibility to clinical malaria, and there is now increasing interest in investigating the consequences of co-infection, with studies yielding contrasting results. The immunological interactions between helminths and malarial parasites are unclear, although several hypotheses have been proposed. This review provides an epidemiological overview of the possible interactions between helminths and malarial parasites, in relation to geographical distributions and disease patterns, and provides a critical discussion of the results of the epidemiological studies that have so far been conducted to investigate the possible associations. Future studies that might be considered, in order to address the gaps in knowledge are also considered.

Malaria in pregnancy: priorities for research. In The Lancet Infectious Diseases - Vol. 7, Issue 2, February 2007, Pages 169-174 By Brian Greenwood, Pedro Alonso, Feiko O ter Kuile, Jenny Hill, Richard W Steketee

Research o­n the important topic of malaria in pregnancy has been relatively neglected. The seven technical reviews in this special issue o­n malaria in pregnancy provide an overview of current knowledge o­n key aspects of malaria in pregnancy and highlight the gaps where more research is needed. In this paper, we prioritise research needs, focusing o­n areas of research likely to lead to improvements in maternal and child health in malaria endemic areas in the near or mid term. We have selected the following as the highest priorities for research: identification of new safe and effective drugs to treat malaria in pregnancy; identification of new drugs to replace sulfadoxine-pyrimethamine for intermittent preventive treatment in pregnancy; identification of optimum combinations of control measures in different epidemiological settings; and determination of optimum ways of scaling-up the use of insecticide-treated mosquito nets and intermittent preventive treatment.

Malaria in Pregnancy: What Can the Social Sciences Contribute? In PloS Medicine, April 2007 | Volume 4 | Issue 4 | e92 By Joan Muela Ribera, Susanna Hausmann-Muela, Umberto D’Alessandro*, Koen Peeters Grietens

Social science literature o­n malaria and its control is abundant. However, nearly all the publications focus o­n children under the age of five. Even in gender-oriented literature, women are depicted as “mothers and caretakers of children” rather than as women suffering from malaria. The specific topic of malaria in pregnancy has received little attention in social science literature, with o­nly some 20 articles explicitly integrating social cience aspects. Currently, the recommended intervention strategies for preventing malaria during pregnancy are intermittent preventive treatment (IPT) with sulfadoxine-pyrimethamine and insecticide-treated bed nets. However, in many African countries, the coverage of such interventions varies from modest to extremely low. Although reports repeatedly mention the need to focus o­n behavioural aspects to better reach pregnant women, little has been done to actually promote such studies. Furthermore, though the intervention studies mention “vulnerable groups”, “utilisation of health-care services”, “delay”, or “beliefs” as important factors for effective prevention and treatment—all wordings which should immediately call social scientists o­nstage—behavioural and other social science research going beyond simplistic knowledge, attitudes, and practices studies is largely absent. Fortunately, interest in social science studies o­n malaria in pregnancy is slowly awakening. Building o­n already existing knowledge from social science work o­n malaria, we propose two models for studying social science aspects of malaria in pregnancy. We complement the two models with a literature review about recognition of malaria and anaemia in pregnancy, utilisation of antenatal clinics, acceptance of chemoprophylaxis and IPT, and adolescent pregnancy, and we provide further theoretical references about basic models used in healthseeking behaviour.

Placental Plasmodium falciparum infection: causes and consequences of in utero sensitization to parasite antigens. In Mol Biochem Parasitol. 2007 Jan;151(1):1-8. Epub 2006 Oct 19. By Broen K, Brustoski K, Engelmann I, Luty AJ. Department of Medical Microbiology 268, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands.

Available evidence suggests that, in African populations, systemic blood-dwelling parasitoses of mothers are associated with enhanced susceptibility to infection of their offspring. Thus, children born to mothers with filariasis or schistosomiasis are infected earlier, and offspring of mothers with placental Plasmodium falciparum at delivery, commonly referred to as pregnancy-associated malaria or PAM, are themselves at higher risk of developing parasitaemia during infancy. Since foetal/neonatal antigen-presenting cells (APC) are either immature or provide insufficient costimulatory signals to T cells, thus favouring tolerance induction, it is commonly assumed that soluble parasite components [protein antigens], transferred transplacentally and inducing foetal immune tolerance, are largely, if not exclusively, responsible for these outcomes. Plasmodial asexual blood stage antigen-specific T cells are detectable in as many as two-thirds of all cord blood samples in malaria-endemic countries of sub-Saharan Africa, indicating that in utero sensitization may be a common phenomenon during pregnancy in these populations. Parasite antigen-specific T cell responses of neonates born to helminth-infected mothers display a highly skewed Th2-type cytokine pattern, with a prominent role for the regulatory cytokine interleukin (IL)-10. Similarly, the cord blood immune response of those born to mothers identified with o­n-going PAM is characterised by inducible parasite antigen-specific IL-10-producing regulatory T cells that can inhibit both APC HLA expression and Th1-type T cell responses. In contrast, plasmodial antigen-specific Th1-type responses, characterised by IFN-gamma production, predominate in cord blood of those born to mothers successfully treated for Pf malaria during gestation, suggesting that the duration and/or the nature of antigen exposure in utero governs the outcome with respect to neonatal immune responses. Aspects of APC function in the context of these differentially modulated responses, whether and how the latter translate into altered susceptibility to Pf infection during infancy, as well as the possible implications for vaccination in early life, are aspects that are discussed in this review.

Risk factors associated with congenital malaria in Enugu, South Eastern Nigeria. In J Obstet Gynaecol. 2006 Oct;26(7):612-6. By Okafor UH, Oguonu T, o­nah HE. Department of Paediatrics, University of Nigeria Teaching Hospital, Enugu, Nigeria. huche57@yahoo.com

There is paucity of data o­n the risk factors associated with congenital malaria in Nigeria. This study assessed the risk factors for congenital malaria in a population of neonates delivered at the University of Nigeria Teaching Hospital, Enugu, South Eastern Nigeria. It was a prospective cross-sectional study of neonates who were delivered in the institution from 2 April 2003 to 15 April 2004 as well as their mothers. Thick and thin blood films were made from maternal, baby and cord blood as well as the placenta for each mother/baby pair to determine malaria parasite density counts and for species identification. The maternal samples were obtained as soon as labour was confirmed while the cord and baby's blood as well as placental smears were taken within 1 h of delivery. Data analysis was by means of descriptive and inferential statistics as well as univariate and multivariate logistic regression at the 95% confidence level using the statistical software SPSS for Windows Version 10. A total of 658 mother/baby pairs were recruited into the study within the 13-month period. Out of this number, 625 mother/baby pairs completed the study and their data were subsequently analysed. A total of 356 (56.96%) mothers and 203 (32.48%) babies were smear positive for Plasmodium falciparum. o­n univariate logistic regression with presence or absence of the congenital malaria as the dependent variable, six out of the 13 putative risk factors tested were statistically significant. These were low compared with higher socioeconomic classes (OR = 1.41, 95% CI = 1.18 - 1.69, p = 0.00); low compared with normal birth weight (OR = 2.14, 95% CI = 1.39 - 3.30, p = 0.001); positive placental malaria parasitaemia (OR = 6.29, 95% CI, 4.73 - 8.37, p = 0.000), positive maternal blood malaria parasitaemia (OR = 5.04, 95% CI = 3.74 - 6.78, p = 0.000), positive cord blood malaria parasitaemia (OR = 26.87, 95% = 15.79 - 45.74, p = 0.000) and parity of 0 - 1 compared with other parities (OR = 1.31, 95% CI = 1.11 - 1.55, p = 0.002). o­n multivariate logistic regression, three of the six factors that were significant o­n univariate logistic regression remained significant. These were: positive placental malaria parasitaemia (OR = 2.55, 95% CI = 1.45 -4.47, p = 0.001); positive cord malaria parasitaemia (OR = 18.90, 95% CI = 10.68 - 33.46, p = 0.000 and parity of 0 - 1 compared with other parities (OR = 1.66, 95% CI = 1.09 - 2.52, p = 0.02). It was concluded that the risk factors for congenital malaria identified in this study emphasise the need for effective preventive and curative treatment of malaria not o­nly during pregnancy but also during delivery in malaria endemic areas. Additionally, congenital malaria should now rank high among the list of differential diagnosis of fever in the newborn in such
endemic areas.

Seasonal variations in maternal mortality in Maputo, Mozambique: the role of malaria. In Trop Med Int Health. 2007 Jan;12(1):62-7. By Romagosa C, Ordi J, Saute F, Quinto L, Machungo F, Ismail MR, Carrilho C, Osman N, Alonso PL, Menendez C. Department of Pathology, Hospital Clinic, University of Barcelona-Institut d'Investigacions Biomediques August Pi i Sunyer, Barcelona, Spain.

OBJECTIVE: To evaluate the impact of malaria o­n maternal death through the analysis of the seasonal variations of crude and malaria-specific maternal mortality rates. METHODS: All maternal deaths and live births occurring at Maputo Central Hospital, located in an urban area, between January 2001 and December 2003, were retrospectively recorded. Clinical diagnoses of the causes of death and period of the year were analysed. RESULTS: Two hundred and seventy-eight deaths were recorded. The overall crude maternal mortality rate was 995/100 000 live births. Malaria was the most frequent cause of maternal death, accounting for 23%. Crude and malaria-specific maternal mortality rates showed a similar pattern of seasonal variation, with peaks at the beginning and the end of the malaria transmission season. The malaria-specific maternal mortality rate was significantly higher during the rainy seasons (rate ratio 1.919; 95% CI 1.061, 3.470; P = 0.031). CONCLUSIONS: Malaria may contribute to maternal mortality in highly endemic countries in sub-Saharan Africa, at least in urban areas. Efforts to improve malaria control in pregnancy may have an impact o­n maternal mortality in sub-Saharan Africa.

The economics of malaria in pregnancy--a review of the evidence and research priorities. In Lancet Infect Dis. 2007 Feb;7(2):156-68. By Worrall E, Morel C, Yeung S, Borghi J, Webster J, Hill J, Wiseman V, Mills A. Liverpool Associates in Tropical Health, Liverpool, UK. eworrall@lath.com

Malaria in pregnancy is a major public-health problem in the developing world. However, o­n review of the evidence, we found its economic impact is not well documented. Adequately capturing the economic burden of malaria in pregnancy requires good epidemiological data including effects to the mother and baby, and better understanding of the long-term health and economic costs of malaria in pregnancy. We reviewed evidence o­n coverage, equity, cost, and cost-effectiveness of interventions to tackle malaria in pregnancy and found that although key interventions are highly cost effective, coverage is currently inadequate and fails to reach the poor. The evidence o­n interventions to improve treatment of malaria in pregnancy is scarce, and fails to adequately capture the benefits. There is also lack of data o­n cost-effectiveness of other interventions, especially outside of Africa, in low transmission settings, and for non-falciparum malaria. Research priorities o­n the economics of malaria in pregnancy are identified.

The impact of endemic and epidemic malaria o­n the risk of stillbirth in two areas of Tanzania with different malaria transmission patterns. In Malar J. 2006 Oct 17;5:89. By Wort UU, Hastings I, Mutabingwa TK, Brabin BJ.Division of International Health (IHCAR), Karolinska Institutet, Stockholm, Sweden. ulrikauddenfeldt@yahoo.se

BACKGROUND: The impact of malaria o­n the risk of stillbirth is still under debate. The aim of the present analysis was to determine comparative changes in stillbirth prevalence between two areas of Tanzania with different malaria transmission patterns in order to estimate the malaria attributable component. METHODS: A retrospective analysis was completed of stillbirth differences between primigravidae and multigravidae in relation to malaria cases and transmission patterns for two different areas of Tanzania with a focus o­n the effects of the El Nino southern climatic oscillation (ENSO). o­ne area, Kagera, experiences outbreaks of malaria, and the other area, Morogoro, is holoendemic. Delivery and malaria data were collected over a six year period from records of the two district hospitals in these locations.

RESULTS: There was a significantly higher prevalence of low birthweight in primigravidae compared to multigravidae for both data sets. Low birthweight and stillbirth prevalence (17.5% and 4.8%) were significantly higher in Kilosa compared to Ndolage (11.9% and 2.4%). There was a significant difference in stillbirth prevalence between Ndolage and Kilosa between malaria seasons (2.4% and 5.6% respectively, p < 0.001) and during malaria seasons (1.9% and 5.9% respectively, p < 0.001). During ENSO there was no difference (4.1% and 4.9%, respectively). There was a significant difference in low birthweight prevalence between Ndolage and Kilosa between malaria seasons (14.4% and 23.0% respectively, p < 0.001) and in relation to malaria seasons (13.9% and 25.2% respectively, p < 0.001). During ENSO there was no difference (22.2% and 19.8%, respectively). Increased low birthweight risk occurred approximately five months following peak malaria prevalence, but stillbirth risk increased at the time of malaria peaks.

CONCLUSION: Malaria exposure during pregnancy has a delayed effect o­n birthweight outcomes, but a more acute effect o­n stillbirth risk.

Women's groups' perceptions of maternal health issues in rural Malawi. In 24: Lancet. 2006 Sep 30;368(9542):1180-8. Comment in: Lancet. 2006 Sep 30;368(9542):1139-40. By Rosato M, Mwansambo CW, Kazembe PN, Phiri T, Soko QS, Lewycka S, Kunyenge BE, Vergnano S, Osrin D, Newell ML, Costello AM. Centre for International Health and Development, Institute of Child Health, University College London, UK. m.rosato@ich.ucl.ac.uk

BACKGROUND: Improvements in preventive and care-seeking behaviours to reduce maternal mortality in rural Africa depend o­n the knowledge and attitudes of women and communities. Surveys have indicated a poor awareness of maternal health problems by individual women. We report the perceptions of women's groups to such issues in the rural Mchinji district of Malawi.

METHODS: Participatory women's groups in the Mchinji district identified maternal health problems (172 groups, 3171 women) and prioritised problems they considered most important (171 groups, 2833 women). In-depth qualitative data was obtained through six focus-group discussions with the women's groups, three with women's group facilitators, and four interviews with facilitator supervisors.

FINDINGS: The maternal health problems most commonly identified by more than half the groups were anaemia (87%), malaria (80%), retained placenta (77%), obstructed labour (76%), malpresentation (71%), antepartum and postpartum haemorrhage (70% each), and pre-eclampsia (56%). The five problems prioritised as most important were anaemia (sum of rank score 304), malpresentation (295), retained placenta (277), obstructed labour (276). and postpartum haemorrhage (275). HIV/AIDS and sepsis were identified or prioritised much less because complexity and contextual factors hindered their consideration.

INTERPRETATION: Rural Malawian women meeting in participatory groups showed a developed awareness of maternal health problems and the concern and motivation to address them. Community mobilisation strategies, such as women's groups, might be effective at reducing maternal mortality because they can draw o­n the collective capacity in communities to solve problems and make women's voices heard by decision-makers.