Impact of targeted drug administration and intermittent preventive treatment for forest goers using artesunate-pyronaridine to control malaria outbreaks in Cambodia.

INTRODUCTION: The national malaria programme of Cambodia targets the rapid elimination of all human malaria by 2025. As clinical cases decline to near-elimination levels, a key strategy is the rapid identification of malaria outbreaks triggering effective action to interrupt local transmission. We report a comprehensive, multipronged management approach in response to a  2022 Plasmodium falciparum outbreak in Kravanh district, western Cambodia. METHODS: The provincial health department of Pursat in conjunction with the Center for Parasitology, Entomology and Malaria Control (CNM) identified villages where transmission was occurring using clinical records, and initiated various interventions, including the distribution of insecticide-treated bed nets, running awareness campaigns, and implementing fever screening with targeted drug administration. Health stations were set up at forest entry points, and later, targeted drug administrations with artesunate-pyronaridine (Pyramax) and intermittent preventive treatment for forest goers (IPTf) were implemented in specific village foci. Data related to adherence and adverse events from IPTf and TDA were collected. The coverage rates of interventions were calculated, and local malaria infections were monitored. RESULTS: A total of 942 individuals were screened through active fever surveillance in villages where IPTf and TDA were conducted. The study demonstrated high coverage and adherence rates in the targeted villages, with 92% (553/600) coverage in round one and 65% (387/600) in round two. Adherence rate was 99% (551/553) in round one and 98% (377/387) in round two. The study found that forest goers preferred taking Pyramax over repeated testing consistent with the coverage rates: 92% in round one compared to 65% in round two. All individuals reachable through health stations or mobile teams reported complete IPTf uptake. No severe adverse events were reported. Only six individuals reported mild adverse events, such as loss of energy, fever, abdominal pain, diarrhoea, and muscle aches. Two individuals attributed their symptoms to heavy alcohol intake following prophylaxis. CONCLUSIONS: The targeted malaria outbreak response demonstrated high acceptability, safety, and feasibility of the selected interventions. Malaria transmission was rapidly controlled using the available community resources. This experience suggests the effectiveness of the programmatic response for future outbreaks.

Radical cure for Plasmodium vivax malaria after G6PD qualitative testing in four provinces in Cambodia, results from Phase I implementation.

BACKGROUND: Cambodia aims to eliminate all forms of malaria by 2025. In 2020, 90% of all malaria cases were Plasmodium vivax. Thus, preventing P. vivax and relapse malaria is a top priority for elimination. 14-day primaquine, a World Health Organization-recommended radical cure treatment regimen, specifically targets dormant hypnozoites in the liver to prevent relapse. Cambodia introduced P. vivax radical cure with primaquine after glucose-6-phosphate dehydrogenase (G6PD) qualitative testing in 2019. This paper presents Cambodia's radical cure Phase I implementation results and assesses the safety, effectiveness, and feasibility of the programme prior to nationwide scale up. METHODS: Phase I implementation was carried out in 88 select health facilities (HFs) across four provinces. Males over 20kgs with confirmed P. vivax or mixed (P. vivax and Plasmodium falciparum) infections were enrolled. A descriptive analysis evaluated the following: successful referral to health facilities, G6PD testing results, and self-reported 14-day treatment adherence. P. vivax incidence was compared before and after radical cure rollout and a controlled interrupted time series analysis compared the estimated relapse rate between implementation and non-implementation provinces before and after radical cure. RESULTS: In the 4 provinces from November 2019 to December 2020, 3,239 P. vivax/mixed infections were reported, 1,282 patients underwent G6PD deficiency testing, and 959 patients received radical cure, achieving 29.6% radical cure coverage among all P. vivax/mixed cases and 98.8% coverage among G6PD normal patients. Among those who initiated radical cure, 747 patients (78%) completed treatment. Six patients reported side effects. In implementation provinces, an average 31.8 relapse cases per month were estimated signaling a 90% (286 cases) reduction in relapse compared to what would be expected if radical cure was not implemented. CONCLUSIONS: Plasmodium vivax radical cure is a crucial tool for malaria elimination in Cambodia. The high coverage of radical cure initiation and adherence among G6PD normal patients demonstrated the high feasibility of providing radical cure at point of care in Cambodia. Incomplete referral from community to HFs and limited capacity of HF staff to conduct G6PD testing in high burden areas led to lower coverage of G6PD testing. Phase I implementation informed approaches to improve referral completion and patient adherence during the nationwide expansion of radical cure in 2021.

Spatial and temporal epidemiology of clinical malaria in Cambodia 2004-2013.

BACKGROUND: Artemisinin-resistant Plasmodium falciparum malaria has recently been identified on the Thailand-Cambodia border and more recently in parts of Thailand, Myanmar and Vietnam. There is concern that if this resistance were to spread, it would severely hamper malaria control and elimination efforts worldwide. Efforts are currently underway to intensify malaria control activities and ultimately eliminate malaria from Cambodia. To support these efforts, it is crucial to have a detailed picture of disease burden and its major determinants over time. METHODS: An analysis of spatial and temporal data on clinical malaria in Cambodia collected by the National Centre for Parasitology, Entomology and Malaria Control (CNM) and the Department of Planning and Health Information, Ministry of Health Cambodia from 2004 to 2013 is presented. RESULTS: There has been a marked decrease of 81% in annual cases due to P. falciparum since 2009 coinciding with a rapid scale-up in village malaria workers (VMWs) and insecticide-treated bed nets (ITNs). Concurrently, the number of cases with Plasmodium vivax has greatly increased. It is estimated that there were around 112,000 total cases in 2012, 2.8 times greater than the WHO estimate for that year, and 68,000 in 2013 (an annual parasite incidence (API) of 4.6/1000). With the scale-up of VMWs, numbers of patients presenting to government facilities did not fall and it appears likely that those who saw VMWs had previously accessed healthcare in the private sector. Malaria mortality has decreased, particularly in areas with VMWs. There has been a marked decrease in cases in parts of western Cambodia, especially in Pailin and Battambang Provinces. In the northeast, the fall in malaria burden has been more modest, this area having the highest API in 2013. CONCLUSION: The clinical burden of falciparum malaria in most areas of Cambodia has greatly decreased from 2009 to 2013, associated with roll-out of ITNs and VMWs. Numbers of cases with P. vivax have increased. Possible reasons for these trends are discussed and areas requiring further study are highlighted. Although malaria surveillance data are prone to collection bias and tend to underestimate disease burden, the finding of similar trends in two independent datasets in this study greatly increased the robustness of the findings.

Evaluation of community-based systems for the surveillance of day three-positive Plasmodium falciparum cases in Western Cambodia.

BACKGROUND: Delayed clearance of Plasmodium falciparum parasites is used as an operational indicator of potential artemisinin resistance. Effective community-based systems to detect P. falciparum cases remaining positive 72 hours after initiating treatment would be valuable for guiding case follow-up in areas of known resistance risk and for detecting areas of emerging resistance. METHODS: Systems incorporating existing networks of village malaria workers (VMWs) to monitor day three-positive P. falciparum cases were piloted in three provinces in western Cambodia. Quantitative and qualitative data were used to evaluate the wider feasibility and sustainability of community-based surveillance of day three-positive P. falciparum cases. RESULTS: Of 294 day-3 blood slides obtained across all sites (from 297 day-0 positives), 63 were positive for P. falciparum, an overall day-3 positivity rate of 21%. There were significant variations in the systems implemented by different partners. Full engagement of VMWs and health centre staff is critical. VMWs are responsible for a range of individual tasks including preparing blood slides on day-0, completing forms, administering directly observed therapy (DOT) on days 0-2, obtaining follow-up slides on day-3 and transporting slides and paperwork to their supervising health centre. When suitably motivated, unsalaried VMWs are willing and able to produce good quality blood smears and achieve very high rates of DOT and day-3 follow-up. CONCLUSIONS: Community-based surveillance of day-3 P. falciparum cases is feasible, but highly intensive, and as such needs strong and continuous support, particularly supervision and training. The purpose and role of community-based day-3 surveillance should be assessed in the light of resource requirements; scaling-up would need to be systematic and targeted, based on clearly defined epidemiological criteria. To be truly comprehensive, the system would need to be extended beyond VMWs to other public and private health providers.

Assessment of disease and infection of lymphatic filariasis in Northeastern Cambodia.

We assessed the filariasis disease burden in four northeastern provinces of Cambodia by using and validating a key-informant questionnaire, consisting of four questions, with pictures of patients with leg elephantiasis and hydrocoele. The questionnaire was distributed and collected through the school, health and administrative systems. Validation surveys included clinical examination, a card test for W. bancrofti (ICT Filariasis card test, AMRAD) and night blood finger prick examination of patients reported with clinical elephantiasis. Only 48.0% of questionnaires were returned. A total of 220 patients were reported, mostly from Stung Treng (36.8%) and Rattanakiri provinces (35.0%). Key-informants reported patients with lymphatic filariasis with a sensitivity of 85.7% for leg and 97.0% for scrotum morbidity, and with a specificity of 95.6%. However, substantial over-reporting resulted in very low positive predictive values for elephantiasis of 19.4% for legs and of 23.7% for the scrotum. As 97.4% of patients with clinical lymphatic filariasis were older than 40 years, the diagnostic performance of the questionnaire would be improved by restricting its use to that age group. About 0.7% of 3490 W. bancrofti card tests were positive; the prevalence was 1.94% (12/618) in Rattanakiri, 0.38% (4/1055) in Stung Treng and 0.22% (2/919) in Preah Vihear. W. bancrofti microfilaria were identified in blood from two patients in Rattanakiri (0.32%) and from one patient in Stung Treng (0.09%). Brugia malayi microfilaria were identified in blood from five patients in Rattanakiri (0.81%) only. No patients with microfilariaemia were identified in Preah Vehear. In Mondulkiri province all investigations (card test, night blood examination, clinical examination) for lymphatic filariasis were negative. Our findings confirm the usefulness of key-informant questionnaire for the identification of filariasis patients provided that high adherence can be achieved. Lymphatic filariasis infection and disease is present in northern Cambodian provinces but the burdens of disease and infection are relatively low. These results are being used in the implementation of the national control programme for lymphatic filariasis.