Search

Background Cambodia has targeted malaria elimination within its territory by 2025 and is developing a model elimination package of strategies and interventions designed to achieve this goal. Methods Cambodia adopted a simplified 1-3-7 surveillance model in the Sampov Loun operational health district in western Cambodia beginning in July 2015. The 1-3-7 approach targets reporting of confirmed cases within one day, investigation of specific cases within three days, and targeted control measures to prevent further transmission within seven days. In Sampov Loun, response measures included reactive case detection (testing of co-travelers, household contacts and family members, and surrounding households with suspected malaria cases), and provision of health education, and insecticide-treated nets. Day 28 follow up microscopy was conducted for all confirmed P. falciparum and P. falciparum-mixed-species malaria cases to assess treatment efficacy. Results The number of confirmed malaria cases in the district fell from 519 in 2015 to 181 in 2017, and the annual parasite incidence (API) in the district fell from 3.21 per 1000 population to 1.06 per 1000 population. The last locally transmitted case of malaria in Sampov Loun was identified in March 2016. In response to the 408 index cases identified, 1377 contacts were screened, resulting in the identification of 14 positive cases. All positive cases occurred among index case co-travelers. Conclusion The experience of the 1-3-7 approach in Sampov Loun indicates that the basic essential malaria elimination package can be feasibly implemented at the operational district level to achieve the goal of malaria elimination in Cambodia and has provided essential information that has led to the refinement of this package.

Background In many endemic areas, Plasmodium vivax malaria is predominantly a disease of young adults and children. International recommendations for radical cure recommend fixed target doses of 0.25 or 0.5 mg/kg/day of primaquine for 14 days in glucose-6-phosphate dehydrogenase normal patients of all ages. However, for many anti-malarial drugs, including primaquine, there is evidence that children have lower exposures than adults for the same weight-adjusted dose. The aim of the study was to develop 14-day weight-based and age-based primaquine regimens against high-frequency relapsing tropical P. vivax. Methods The recommended adult target dose of 0.5 mg/kg/day (30 mg in a 60 kg patient) is highly efficacious against tropical P. vivax and was assumed to produce optimal drug exposure. Primaquine doses were calculated using allometric scaling to derive a weight-based primaquine regimen over a weight range from 5 to 100 kg. Growth curves were constructed from an anthropometric database of 53,467 individuals from the Greater Mekong Subregion (GMS) to define weight-for-age relationships. The median age associated with each weight was used to derive an age-based dosing regimen from the weight-based regimen. Results The proposed weight-based regimen has 5 dosing bands: (i) 5–7 kg, 5 mg, resulting in 0.71–1.0 mg/kg/day; (ii) 8–16 kg, 7.5 mg, 0.47–0.94 mg/kg/day; (iii) 17–40 kg, 15 mg, 0.38–0.88 mg/kg/day; (iv) 41–80 kg, 30 mg, 0.37–0.73 mg/kg/day; and (v) 81–100 kg, 45 mg, 0.45–0.56 mg/kg/day. The corresponding age-based regimen had 4 dosing bands: 6–11 months, 5 mg, 0.43–1.0 mg/kg/day; (ii) 1–5 years, 7.5 mg, 0.35–1.25 mg/kg/day; (iii) 6–14 years, 15 mg, 0.30–1.36 mg/kg/day; and (iv) ≥ 15 years, 30 mg, 0.35–1.07 mg/kg/day. Conclusion The proposed weight-based regimen showed less variability around the primaquine dose within each dosing band compared to the age-based regimen and is preferred. Increased dose accuracy could be achieved by additional dosing bands for both regimens. The age-based regimen might not be applicable to regions outside the GMS, which must be based on local anthropometric data. Pharmacokinetic data in small children are needed urgently to inform the proposed regimens.

International audience; Proposed interventions for eliminating drug-resistant Plasmodium falciparum malaria include the targeting of asymptomatic carriers through screening and treatment. We report on the diagnostic performance of the recently developed ultrasensitive rapid diagnostic test (uRDT) compared with screening with conventional RDTs (cRDT) and polymerase chain reaction (PCR) under field conditions in Cambodia in a total of 2,729 individuals. The P. falciparum positivity by quantitative PCR (qPCR) was 3.8% (26/678) in those screened during active case detection and 0.5% (10/2,051) in the cross-sectional survey. Compared with qPCR, the sensitivity of the uRDTs was 53.8% (95% CI: 33.4-73.4%) when used in active case detection and 60.0% (95% CI: 26.2-87.8%) in the cross-sectional survey. The uRDTs did not show a significant improvement in diagnostic performance over cRDTs when used for active case detection and for a malaria prevalence survey in the context of this low-transmission setting.

Background Mobile populations and migrant workers are a key population to containing the spread of artemisinin-resistant malaria found in the border areas between Cambodia, Myanmar, and Thailand. Migrants often have limited knowledge of public health, including malaria, services in the area, and many seek care from unregulated, private vendors. Methods Between October 2012 and August 2016, we implemented malaria case finding and treatment in Tanintharyi Region, Kayin State, and Rakhine State of Myanmar through 3 entry points: village malaria workers (VMWs), mobile malaria clinics, and screening points. A total of 1,000 VMWs provided passive case detection and treatment services to residents in malaria-endemic villages. Active case finding through mobile malaria clinics was conducted by staff in 354 remote villages and work sites, where regular monitoring and supervision of VMWs would be difficult to maintain. Malaria screening points were a hybrid combination of active and passive case finding in which screening points were set up at fixed locations in Tanintharyi Region and Kayin State, such as bus stops, ferry docks, or informal border crossing points, and migrants entering into or departing from endemic areas could voluntarily receive malaria testing and treatment. Using routine monitoring data, we assessed and compared the malaria positive rate-the number of positive malaria cases out of those tested-across the 3 approaches as an indication of the programmatic effectiveness in identifying malaria cases in the population. Most testing was conducted with rapid diagnostic tests. Results Mobile teams (169,859) and VMWs (157,048) tested a higher number of community members than screening points (3,676) as they covered a wider geographical area. However, the malaria positive rate was higher among VMWs (7.29%) and screening points (7.10%) than mobile teams (2.64%). VMWs were located in hard-to-access areas that have higher malaria prevalence and are difficult to reach by vehicle while screening points specifically targeted mobile populations and migrant workers. Mobile teams also screened non-fever patients during their visits, which may explain their lower malaria positive rate. Conclusions A combination of malaria testing approaches helps achieve both maximum reach and high case finding as it allows access to a range of migrant communities and provides an opportunity for continuity of service delivery as the migrants travel to their destinations.

Background: Cambodia has a high burden of Tuberculosis (TB) with an incidence rate of 326 per 100,000 population in 2018 and rapidly increasing rates of Diabetes Mellitus (DM) with prevalence rate 9.6% in 2016. The introduction of the first national guidelines for the management of TB/DM co-morbidity in 2014 has resulted in the introduction of coordinated service delivery. Objective: This study aimed to assess the performance and the results of bidirectional TB/DM screening, diagnosis of co-morbidity, and enrollment in treatment in 7 health operational districts in 5 provinces in Cambodia. Methods: The retrospective study reviewed patient records of 6,463 DM patients and 8,403 TB patients who received treatment between July 2016 and February 2019 in 7 referral hospitals and 113 health centers. Results: Forty percent of DM patients were screened for TB, and 55% of TB patients were screened for DM. Of the screened DM patients, 4.6% were diagnosed with TB. Of screened TB patients, 3.7% were diagnosed with DM. All DM patients diagnosed with TB were enrolled in TB treatment and 95% of TB patients diagnosed with DM began receiving treatment for DM. Conclusion: This is the first study examining TB/DM co-morbidity and coordinated service delivery in Cambodia. The gaps in the performance of bidirectional screening suggest areas for further intervention. To increase the rate of bidirectional screening, provider compliance with standards needs to be improved by strengthening providers competencies. Strengthened data collection and reporting systems will also contribute to increasing provider accountability. Secondly, the current structure of TB and DM service delivery with TB services only available from the public sector and public DM services only available at the referral level creates a challenging environment for effective referrals and coordinated care and should be reconsidered. In addition to improved coordination between the public and private sectors, expansion of public DM services to health centers and to the community level warrants exploration. Finally, the increased focus needs to be given to addressing the high levels of pre-diabetes. Cambodia has a limited window of opportunity to build capacity and develop systems to effectively manage TB/DM co-morbidity.

Background The presence of artemisinin-resistant malaria parasites was confirmed in western Cambodia in 2009. In 2013, mutations in the propeller domain of the kelch protein K13 was found to be associated with artemisinin resistance. A cross-sectional study was conducted to determine the prevalence of Day-3 parasitaemia, estimate the frequency of k13 molecular marker and assess their relationship in the context of operational research. Methods Blood smears and filter paper blood spots were collected from febrile patients in Kravanh District, Pursat Province. The blood smears were examined by microscopy, and blood spots by a k13 mutation assay. Results Data from 92 patients were analysed. Only one was positive for Day-3 parasitaemia. Results of the k13 assay were interpretable for 76 of the 92 samples. The findings were: wild type: 9 (12%), C580Y: 64 (84%), Y493H: 3 (4%). Therefore, despite the high prevalence of k13 mutants (67/76: 88%), only 1 of the 92 patients remained blood smear positive for Plasmodium falciparum on Day-3. Conclusions These preliminary findings suggest good potency of artemisinin despite the dominance of k13 mutation in Kravanh, but the result is not necessarily representative of the western part of Cambodia. Further investigation should be made to determine if k13 marker remains useful as a tool for tracking artemisinin resistance and predicting the trend of the efficacy of artemisinin combination therapy once the mutant alleles have been well established in the population.

Malaria poses a significant public health burden in the remote areas of western Cambodia, where access to health services and information is limited. Recognizing the potential of village malaria workers to reach these communities, the US Agency for International Development-funded Malaria Control in Cambodia project used a multipronged approach to strengthen the village malaria workers network. As a result, the proportion of confirmed malaria cases treated by village malaria workers has doubled during the past 2 years, significantly increasing the numbers being properly diagnosed and treated. Key to the program's success has been the integration of village malaria workers with public health facilities, improved patient access to prompt diagnosis and treatment, and resolution of systemic barriers such as logistics for rapid diagnostic tests.

Background Funding for scaling-up antiretroviral treatment (ART) in low-income countries has increased substantially, but the lack of human resources for health (HRH) is increasingly being identified as an important constraint for scaling-up ART. Methods In a clinic run by Médecins Sans Frontières in Siem Reap, Cambodia, we documented the use of doctor-time for ART in September 2004 and in August 2005, for different phases in ART (pre-ART, ART initiation, ART follow-up Year 1, & ART follow-up Year 2). Based on these observations and using a variety of assumptions for survival of patients on ART (between 90 and 95% annually) and for further reductions in doctor-time per patient (between 0 and 10% annually), we estimated the need for doctors for the period 2004 till 2013 in the Siem Reap clinic, and in a hypothetical district in sub-Saharan Africa. Results In the Siem Reap clinic, we found that from 2004 to 2005 the doctor-time needed per patient was reduced by between 14% and 33%, thanks to a reduction in number of visits per patient and shorter consultation times. In 2004, 2.06 full-time equivalent (FTE) doctors were needed for 522 patients on ART, and in 2005 this was slightly reduced to 1.97 FTE doctors for 911 patients on ART. By 2013, Siem Reap clinic will need between 2 and 5 FTE doctors for ART. In a district in sub-Saharan Africa with 200,000 inhabitants and 20% adult HIV prevalence, using a similar doctor-based ART delivery model, between 4 and 11 FTE doctors would be needed to cover 50% of ART needs. Conclusion ART is labour intensive. Important reductions in doctor-time per patient can be realized during scaling-up. The doctor-based ART delivery model analysed seems adequate for Cambodia. However, for many districts in sub-Saharan Africa a doctor-based ART delivery model may be incompatible with their HRH constraints.

After publication of the original article [1], it came to the authors’ attention that there was an error in the PQ pharmacokinetics sub-section of the Background section. The following sentence is affected: “There is no PK interaction between PQ and either artesunate-pyronaridine [76] or mefloquine [69, 77]; no PK interaction data exist for PQ and artemether-lumefantrine (AL).” This sentence should have read as follows: “AS pyronaridine increased PQ exposure by 15% without affecting significantly cPQ exposure [76]. There is no PK interaction between PQ and mefloquine [69, 77]; no PK interaction data exist for PQ and artemether-lumefantrine (AL).”

Background In 2012, the World Health Organization recommended the addition of single low-dose primaquine (SLDPQ, 0.25 mg base/kg body weight) to artemisinin combination therapies to block the transmission of Plasmodium falciparum without testing for glucose-6-phosphate dehydrogenase deficiency. The targeted group was non-pregnant patients aged ≥ 1 year (later changed to ≥ 6 months) with acute uncomplicated falciparum malaria, primarily in countries with artemisinin-resistant P. falciparum (ARPf). No dosing regimen was suggested, leaving malaria control programmes and clinicians in limbo. Therefore, we designed a user-friendly, age-based SLDPQ regimen for Cambodia, the country most affected by ARPf. Methods By reviewing primaquine’s pharmacology, we defined a therapeutic dose range of 0.15–0.38 mg base/kg (9–22.5 mg in a 60-kg adult) for a therapeutic index of 2.5. Primaquine doses (1–20 mg) were tested using a modelled, anthropometric database of 28,138 Cambodian individuals (22,772 healthy, 4119 with malaria and 1247 with other infections); age distributions were: 0.5–4 years (20.0 %, n = 5640), 5–12 years (9.1 %, n = 2559), 13–17 years (9.1 %, n = 2550), and ≥ 18 years (61.8 %, n = 17,389). Optimal age-dosing groups were selected according to calculated mg base/kg doses and proportions of individuals receiving a therapeutic dose. Results Four age-dosing bands were defined: (1) 0.5–4 years, (2) 5–9 years, (3) 10–14 years, and (4) ≥15 years to receive 2.5, 5, 7.5, and 15 mg of primaquine base, resulting in therapeutic doses in 97.4 % (5494/5640), 90.5 % (1511/1669), 97.7 % (1473/1508), and 95.7 % (18,489/19,321) of individuals, respectively. Corresponding median (1st–99th centiles) mg base/kg doses of primaquine were (1) 0.23 (0.15–0.38), (2) 0.29 (0.18–0.45), (3) 0.27 (0.15–0.39), and (4) 0.29 (0.20–0.42). Conclusions This age-based SLDPQ regimen could contribute substantially to malaria elimination and requires urgent evaluation in Cambodia and other countries with similar anthropometric characteristics. It guides primaquine manufacturers on suitable tablet strengths and doses for paediatric-friendly formulations. Development of similar age-based dosing recommendations for Africa is needed. Electronic supplementary material The online version of this article (doi:10.1186/s12916-016-0701-8) contains supplementary material, which is available to authorized users.