On June 5-6, 2024, the joint working group from the Institute of Malariology, Parasitology, and Entomology Quy Nhon (IMPE-QN) and the World Health Organization (WHO) office in Viet Nam visited and worked at the Institute and local health units in Khanh Hoa Province. The purpose of these visits and meetings was to assess the malaria situation and discuss the most proactive malaria prevention activities amidst the increasing and fluctuating malaria cases in Khanh Vinh District, Khanh Hoa Province, which pose a risk of spreading to other provinces through malaria vectors and mobile populations.

The working sessions were attended by Associate Professor Dr. Ho Van Hoang, Director of the Quy Nhon Institute of Malariology, Parasitology, and Entomology; Dr. Huynh Hong Quang, Deputy Director; leaders of various specialized departments and functional offices; Dr. Jean-Olivier Guintran, Senior Consultant of WHO Viet Nam; Dr. Nguyen Thi Thuy Van, Senior Expert of WHO Viet Nam; Dr. Ton That Toan, Deputy Director in charge of the Khanh Hoa Provincial Center for Disease Control; Dr. Tran Van Tien, MSc., Deputy Director of the Khanh Vinh District Health Center; and specialized staff from the commune health stations.

During the working session at the Institute, Assoc. Prof. Dr. Ho Van Hoang, Director of IMPE-QN, noted that the malaria situation in Khanh Vinh has remained complex and significantly increased since the beginning of the year compared to the same period last year, necessitating decisive action from relevant sectors and local authorities. The prevalence of P. malariae, along with P. vivax and P. falciparum, has further complicated the malaria situation. The presence of gametocytes in patients is alarmingly high (over 80% of detected cases, whether early or late), which may be a major factor in the increased risk of community transmission, complicating disease control and treatment. Most cases are linked to occupations involving forest activities and extended stays in farm huts, where malaria prevention measures are still very limited. Additionally, procuring supplies for malaria prevention faces numerous challenges due to the lack of specific guidelines. IMPE-QN has deployed multiple task forces for epidemiological investigations, vector surveillance, and clinical treatment research to assess the overall situation and support malaria prevention efforts in Khanh Vinh District.

At the same time, Dr. Huynh Hong Quang, Deputy Director of IMPE-QN, highlighted that the increase in malaria cases in Khanh Hoa Province, with the presence of all three species - P. falciparum, P. vivax, and P. malariae - and particularly the unprecedented rise of P. malariae, is a unique occurrence not o­nly in Vietnam but also in other Mekong Subregion countries. While we have not yet completely eradicated the P. falciparum species from now until 2025, the emergence and increase of P. malariae pose a new threat and technical challenge to the malaria elimination strategy in the Central Highlands and Viet Nam by 2030.

Dr. Quang also highlighted several new findings from the unusual surge of P. malariae malaria cases to WHO experts in Viet Nam, seeking their understanding and assistance. These challenges and new discoveries include serious warning signs, high risk of widespread transmission, and unpredictable, complex developments observed during the malaria outbreak from 2023 to the first half of 2024 in Khanh Vinh District.

1.  Firstly, in the composition of malaria parasites, P. malariae has emerged at a significantly high rate (104 cases; 52.8%), whereas the two more common species, P. falciparum (29 cases; 14.7%) and P. vivax (61 cases; 31.5%), have showed lower rates. This extraordinary situation has not been observed since 1961 in the Greater Mekong Subregion (GMS) countries overall, nor in Viet Nam and Khanh Hoa province specifically, where P. malariae previously o­nly accounted for 3-5 cases per year.

2.  Secondly, according to medical literature and clinical practice in Viet Nam, P. malariae malaria is typically benign and rarely results in severe malaria or fatalities. However, over the past two years, Khanh Hoa province has recorded up to six life-threatening cases of severe malaria, which were treated at Khanh Hoa Tropical Disease Hospital and Ho Chi Minh City Hospital for Tropical Diseases. Most of these cases were of severe multi-organ malaria. Before hospitalization, the patients did not exhibit symptoms of malaria or had symptoms that were undetectable by microscopy and rapid diagnostic tests.

Figure 1. The WHO expert team visits and works with the IMPE-QN o­n the afternoon of June 5, 2024

3.  Thirdly, over 76% of patients infected with P. malariae and P. vivax malaria do not exhibit symptoms of malaria at the time blood is drawn for diagnosis using rapid diagnostic tests and Giemsa-stained blood smears.

4.  Fourthly, besides the asymptomatic malaria cases detected by routine diagnostic tools (blood smears and rapid diagnostic tests) mentioned above, there were also 38 out of 7,256 people found to be positive for malaria at very low parasite densities through ultra-sensitive molecular biological tests (nested-PCR, ultra-PCR). This indicates that beyond symptomatic cases, there are still many undetectable cases due to the absence of symptoms and because the existing tools are not sensitive and specific enough to fully detect all cases. These individuals with low parasite densities act as reservoirs and continue to contribute to malaria transmission in Khanh Vinh District.

5.  Fifthly, P. malariae and P. vivax parasites can persist in human body organs for extended periods, sometimes up to 30 years, while the individuals continue to live within the community.

6.  Sixthly, preliminary analysis of the population structure of clinical isolates of P. malariae in patients has revealed significant molecular markers and mutations that differ from those observed in other countries within the Greater Mekong Subregion.

7.  Seventhly, more than 86% of diagnosed malaria patients had gametocytes and schizont forms. These forms contribute to severe malaria and indicate late detection of patients, often due to their hesitation in seeking timely medical attention.

8.   Eighthly, there has been a shift in the population of Anopheles spp. vectors responsible for malaria transmission, involving both primary and secondary vectors, in the communes within Khanh Vinh District.

9.  Ninthly, over 95% of malaria patients in the district belong to transient or mobile populations engaged in activities such as forest work, temporary campsite setups, overnight stays, or occupations like breeding fish, harvesting wood, collecting honey, hunting wild animals, gathering Dac seeds, bamboo shoots, orchids, or fresh ginseng for sale to traders.

All these challenges, difficulties, and specific health issues have contributed to a new and complex epidemiological model of malaria in this area. This situation could jeopardize the achievements made in malaria prevention and elimination, and significantly impact the economic, social, and eco-tourism development of Khanh Hoa Province.

Given the complex progression of malaria in this area, characterized by high transmission involving three species of malaria parasites (P. falciparum, P. vivax, and P. malariae), and the increasing severity of cases, the healthcare sector urgently requires a new and improved model for prevention and control. This model should prioritize enhancing the monitoring, detection, diagnosis, treatment, and management of malaria cases to ensure the interruption of transmission, prevent malaria from spreading within the community, and accelerate progress towards malaria elimination in Khanh Hoa Province.

Figure 2. Dr. Huynh Hong Quang works with the WHO expert team and health units
from Khanh Hoa Provincial CDC, District Health Center of Khanh Vinh, and Commune
Health Station in Khanh Thuong commune o­n June 6, 2024.

Assoc. Prof. Dr. Ho Van Hoang, the Director of IMPE-QN, proposes a new policy for managing malaria cases in the province. To ensure that everyone has access to treatment, he recommends establishing screening criteria to classify and monitor patient treatment at different levels (provincial, district, commune, and community). This strategy facilitates the early detection and prompt treatment of malaria patients, thereby preventing the silent spread of the disease within the community. Dr. Hoang also expresses the hope that the World Health Organization will provide financial and technical support to tackle malaria hotspots in Khanh Hoa, helping the province to effectively achieve the goal of malaria elimination according to Viet Nam's 2030 elimination roadmap.

Working in Khanh Hoa Province, reports from the Khanh Hoa Provincial Center for Disease Control indicate a gradual decrease in the number of malaria patients from 2018 to 2022. In 2018, the province recorded 125 cases, which reduced to 12 cases by 2022. However, from 2023 o­nwards, there has been a significant increase in cases, reaching 209 cases. Specifically, from July 2023, malaria cases surged rapidly at a rate of 50 cases per month, then gradually declined to 22 cases per month by the end of the year. Most cases were concentrated among individuals engaged in forest activities and overnight stays in the mountainous district of Khanh Vinh. In 2024, despite the implementation of rigorous malaria prevention and control measures, the number of cases continues to rise, even though it's currently not the peak season for the disease.

As of June 6, 2024, there have been 131 malaria cases, marking an increase of 125 cases compared to the same period in 2023. The majority of malaria patients are concentrated in Khanh Vinh district, accounting for 122 cases. Specifically, there has been an increase of 62 cases of P. falciparum malaria, 10 cases of P. vivax malaria, and 53 cases of P. malariae malaria.

There have been 13 cases of severe malaria, which is an increase of 12 cases compared to the same period in 2023. Although there have been no deaths due to malaria at present, cases of severe malaria solely caused by P. malariae are quite unusual. Among these cases, some patients initially sought medical attention at healthcare facilities very early, but deteriorated rapidly within hours, necessitating timely referral due to complications such as multi-organ dysfunction.

Table 1: Malaria cases in Khanh Hoa province as of June 6, 2024 compared to the same period in 2023

The team worked with the Khanh Vinh District Health Center, and as of June 5, 2024, malaria cases are distributed across almost all communes in the district. Khanh Thuong commune recorded the highest number of malaria cases with 44 cases, making up 36.06%; Khanh Dong with 31 cases, accounting for 25.41%; Khanh Phu with 24 cases, representing19.67%; Khanh Thanh with 4 cases, accounting for 3.28%; and Lien Sang, Giang Ly, Khanh Binh, Khanh Hiep with 3 cases each, totaling 2.46% each. Son Thai and Thi Tran communes each reported 2 cases, accounting for 1.64%; Cau Ba, Khanh Nam, and Khanh Trung each had 1 case, accounting for 0.82%. Particularly in Khanh Phu and Khanh Dong communes, nearly 100% of detected cases were caused by P. falciparum malaria parasites.

In Khanh Thuong commune, the majority of malaria cases are caused by P. malariae parasites. Out of a total of 122 malaria cases in the district, 101 cases are aged 15 years and older (82.8%), while 21 cases are aged under 15 (17.2%). There were 95 cases among males (77.8%) and 27 cases among females (22.1%). The report indicates that most infections occur among individuals who work in the forest and stay overnight inthe farmhouses. Notably, 9 cases were reported among forest rangers who regularly operate in forested areas.

Figure 3. The delegation members are working o­n the distribution of malaria cases in
 the meeting room of the Khanh Vinh District Health Center.

According to the Khanh Vinh District Health Center, while comprehensive malaria prevention and control measures have been implemented in the district, there are still some major challenges. The persistence of malaria parasites in the forest remains a significant problem, exacerbated by the close connection between people's livelihoods and forest and field activities, making it difficult to interrupt transmission. The district has employed various communication methods, including speaker broadcasts, direct engagement through medical exams, treatment, monitoring, and home visits. However, there is still a notable degree of complacency among the population regarding malaria prevention and control, particularly in participating in testing and reporting to local health authorities after returning from the forest and fields. This participation is essential for early detection and treatment to prevent community transmission.

Dr. Huynh Hong Quang, Deputy Director of IMPE-QN, has noted an unusual rise in malaria cases in Khanh Hoa province since the start of the year, even though it is not the peak season for malaria transmission. He predicts that without decisive and proactive measures from the provincial health sector, the risk of a significant increase in malaria cases will persist during the peak transmission periods (from now until the end of August and from November to February next year). Dr. Quang also reported that a random survey of 30 makeshift farm huts in the forested areas of Khanh Vinh district by IMPE-QN revealed that 17-18 out of 30 huts had tarpaulin walls with no place to hang mosquito nets, and the roofs were made of banana leaves. Due to the heat, people often lift the mosquito nets to sleep comfortably, which facilitates contact between mosquitoes and humans. Additionally, there is still a considerable number of asymptomatic individuals carrying malaria parasites within the community (1.4-2.1%), posing a latent risk of becoming reservoirs of the disease and spreading it when bitten by Anopheles spp. mosquitoes.

Figure 4. The mission team of WHO and IMPE-QN are working with the provincial CDC,
district health center, and commune health station, along with the Institute's working groups
currently conducting investigations in Khanh Thuong Commune Health Station.

Dr. Ton That Toan, Deputy Director in charge of the Center for Disease Control of Khanh Hoa Province, highlighted: "Investigations by the Khanh Hoa provincial CDC and the Institute of Malaria, Parasitology, and Entomology Quy Nhon have found Anopheles spp. mosquitoes in the forested and mountainous regions of Khanh Vinh. These mosquitoes act as vectors for malaria parasites, biting infected individuals and spreading the disease to others, thereby increasing the number of cases. Even someone who has recovered from malaria can be re-infected by a different malaria parasite. Everyone is at risk of contracting malaria when entering these endemic areas and being bitten by Anopheles spp. mosquitoes again."

Dr. Jean Olivier Guintran, Senior Advisor at the WHO Office in Vietnam, stated: "Despite implementing comprehensive testing and treatment measures and managing both symptomatic and asymptomatic malaria cases, the number of malaria cases continues to rise. This indicates that there are still undetected cases, where individuals have low-level parasitemia that cannot be detected by rapid diagnostic tests or microscopy, such as in P. malariae and P. vivax infections. Therefore, it is necessary to consider drug treatment for the identified high-risk group (Targeted Drug Administration - TDA)." He also recommended that prior to implementing TDA, communication and mobilization efforts should be conducted to inform the population about the reasons for TDA, its benefits for community health and patients, and its effectiveness in prevention. The health staff should urge people to report any adverse effects when using Pyramax® for TDA and emphasized the importance of closely monitoring any adverse events in each target group during the TDA implementation with Pyramax®.

Figure 4. The mission team visits and surveys the microscopy diagnostic room for
malaria parasite (monitoring, investigation, and drug resistance assessment) at the
Health Station of Khanh Thuong Commune.

Figure 6. The mission team takes a commemorative photo with the IMPE-QN officials
supporting malaria prevention and control at the Health Station of Khanh Thuong Commune.

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