Behavioural determinants of malaria risk, prevention, and care-seeking behaviours among forest-goers in Cambodia.

BACKGROUND: Cambodia has made significant progress towards achieving malaria elimination by 2025. Cases continue to decrease and are primarily concentrated in forested areas. Forest-goers are most at risk of malaria due to their proximity to the forest, poor sleeping conditions, frequent mobility, and distance from health services. Consistent use of long-lasting insecticidal nets or hammock nets (LLINs/LLIHNs), early diagnosis and treatment of cases are central to reducing disease burden. The aim of this study was to understand forest-goers' knowledge, attitudes, and practices related to malaria prevention and care-seeking, and to identify key behavioural determinants of LLIN/LLIHN use and prompt care-seeking within 24 h of developing a fever. METHODS: A mixed-methods study design consisting of a cross-sectional survey and qualitative in-depth interviews was implemented in two Cambodian provinces. Survey participants (N = 654) were recruited using respondent driven sampling. Interview participants (N = 28) were selected using purposive sampling. Findings from the survey were analysed using univariate and bivariate analysis and multivariate weighted logistic regression. Interviews were coded and analysed using thematic content analysis. RESULTS: All study participants had heard of malaria and 98% knew that malaria was transmitted by mosquitoes. LLIN/LLIHN ownership was high (94%). Although 99% of participants perceived LLIN/LLIHN use as an important malaria prevention measure, only 76% reported using one during their last visit to the forest. Only 39% of survey participants who reported seeking care did so within the recommended 24 h from fever onset during their last febrile illness. Among all study participants, 43% did not seek any healthcare during their last febrile episode. In controlled regression models, perceived community social norms were significantly associated with LLIN/LLIHN use (OR: 2.7, 96% CI 1.99-2.64) and care-seeking within 24 h of fever onset (OR: 1.7, 95% CI 1.00-2.88). Social support from other forest-goers was also significantly associated with LLIN/LLIHN use (OR: 4.9, 95% CI 1.32-18.12). CONCLUSIONS: Study findings are consistent with other studies on LLIN/LLIHN use and care-seeking behaviours. While rates of LLIN/LLIHN ownership were high among the study population, rates of use were not as high. More concerning were the delayed care-seeking behaviours. Social behaviour change activities should incorporate social norms and social support as mechanisms for behaviour change given the identified positive correlations with LLIN/LLIHN use and prompt care-seeking.

Performance of Ultrasensitive Rapid Diagnostic Tests for Detecting Asymptomatic Plasmodium falciparum.

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.

Hemolytic Dynamics of Weekly Primaquine Antirelapse Therapy Among Cambodians With Acute Plasmodium vivax Malaria With or Without Glucose-6-Phosphate Dehydrogenase Deficiency.

BACKGROUND: Hemoglobin (Hb) data are limited in Southeast Asian glucose-6-phosphate dehydrogenase (G6PD) deficient (G6PD-) patients treated weekly with the World Health Organization-recommended primaquine regimen (ie, 0.75 mg/kg/week for 8 weeks [PQ 0.75]). METHODS: We treated Cambodians who had acute Plasmodium vivax infection with PQ0.75 and a 3-day course of dihydroartemisinin/piperaquine and determined the Hb level, reticulocyte count, G6PD genotype, and Hb type. RESULTS: Seventy-five patients (male sex, 63) aged 5-63 years (median, 24 years) were enrolled. Eighteen were G6PD deficient (including 17 with G6PD Viangchan) and 57 were not G6PD deficient; 26 had HbE (of whom 25 were heterozygous), and 6 had α-/ß-thalassemia. Mean Hb concentrations at baseline (ie, day 0) were similar between G6PD deficient and G6PD normal patients (12.9 g/dL [range, 9‒16.3 g/dL] and 13.26 g/dL [range, 9.6‒16 g/dL], respectively; P = .46). G6PD deficiency (P = <.001), higher Hb concentration at baseline (P = <.001), higher parasitemia level at baseline (P = .02), and thalassemia (P = .027) influenced the initial decrease in Hb level, calculated as the nadir level minus the baseline level (range, -5.8-0 g/dL; mean, -1.88 g/dL). By day 14, the mean difference from the day 7 level (calculated as the day 14 level minus the day 7 level) was 0.03 g/dL (range, -0.25‒0.32 g/dL). Reticulocyte counts decreased from days 1 to 3, peaking on day 7 (in the G6PD normal group) and day 14 (in the G6PD deficient group); reticulocytemia at baseline (P = .001), G6PD deficiency (P = <.001), and female sex (P = .034) correlated with higher counts. One symptomatic, G6PD-deficient, anemic male patient was transfused on day 4. CONCLUSIONS: The first PQ0.75 exposure was associated with the greatest decrease in Hb level and 1 blood transfusion, followed by clinically insignificant decreases in Hb levels. PQ0.75 requires monitoring during the week after treatment. Safer antirelapse regimens are needed in Southeast Asia. CLINICAL TRIALS REGISTRATION: ACTRN12613000003774.

Forest Goers and Multidrug-Resistant Malaria in Cambodia: An Ethnographic Study.

Multidrug-resistant Plasmodium falciparum malaria on the Cambodia-Thailand border is associated with working in forested areas. Beyond broad recognition of "forest-going" as a risk factor for malaria, little is known about different forest-going populations in this region. In Oddar Meanchey Province in northwestern Cambodia, qualitative ethnographic research was conducted to gain an in-depth understanding of how different populations, mobility and livelihood patterns, and activities within the forest intersect with potentiate malaria risk and impact on the effectiveness of malaria control and elimination strategies. We found that most forest-going in this area is associated with obtaining precious woods, particularly Siamese rosewood. In the past, at-risk populations included large groups of temporary migrants. As timber supplies have declined, so have these large migrant groups. However, groups of local residents continue to go to the forest and are staying for longer. Most forest-goers had experienced multiple episodes of malaria and were well informed about malaria risk. However, economic realities mean that local residents continue to pursue forest-based livelihoods. Severe constraints of available vector control methods mean that forest-goers have limited capacity to prevent vector exposure. As forest-goers access the forest using many different entry and exit points, border screening and treatment interventions will not be feasible. Once in the forest, groups often converge in the same areas; therefore, interventions targeting the mosquito population may have a potential role. Ultimately, a multisectoral approach as well as innovative and flexible malaria control strategies will be required if malaria elimination efforts are to be successful.

Malaria knowledge, preventive actions, and treatment-seeking behavior among ethnic minorities in Ratanakiri Province, Cambodia: a community-based cross-sectional survey.

BACKGROUND: Malaria incidence has been steadily declining in Cambodia, where the government is aiming to eliminate malaria by 2025. Successful malaria elimination requires active engagement and participation of communities to recognize malaria symptoms and the development of prompt treatment-seeking behavior for early diagnosis and appropriate treatment. This study examined malaria knowledge, preventive actions, and treatment-seeking behavior among different groups of ethnic minorities and Khmer in Ratanakiri Province, Cambodia. METHODS: Face-to-face interviews were conducted in December 2015, targeting 388 mothers with children under 2 years old, who belonged to ten ethnic minority groups or the Khmer group living in 62 rural villages in Ratanakiri. In addition to describing mothers' knowledge and actions for malaria prevention, logistic regression analysis was performed to identify determinants of fever during the most recent pregnancy and among children under two. RESULTS: Overall 388 mothers were identified for enrollment into the study of which 377 (97.2%) were included in analyses. The majority of mothers slept under bed nets at home (95.8%) and wore long-sleeved clothes (83.8%) for malaria prevention. However, knowledge of malaria was limited: 44.6% were aware of malaria symptoms, 40.6% knew the malaria transmission route precisely, and 29.2% knew of mosquito breeding places. Staying overnight at a farm hut was significantly associated with having fever during the most recent pregnancy (adjusted odds ratio [AOR] 2.008, 95% confidence interval [CI]: 1.215-3.321) and a child having fever (AOR 3.681, 95% CI 1.943-6.972). Mothers' partaking in a variety of malaria preventive actions was protective against fever in children (AOR 0.292, 95% CI: 0.136-0.650). Among those who had fever during pregnancy, 39.4% did not seek treatment. CONCLUSION: Although the majority of mothers took malaria preventive actions, knowledge of malaria epidemiology and vector ecology and treatment-seeking behavior for fever were limited. Staying overnight at farm huts, regardless of the differences in socio-demographic and socio-cultural characteristics, was strongly associated with fever episodes during pregnancy and childhood. This study indicates the necessity of spreading accurate malaria knowledge, raising awareness of health risks related to agricultural practices, and promoting treatment-seeking behavior among ethnic minorities to strengthen their engagement in malaria elimination.

Smartphones for community health in rural Cambodia: A feasibility study.

Background: Village Malaria Workers (VMWs) are lay people trained to provide a valuable role in frontline testing and treatment of malaria in rural villages in Cambodia. Emergence of artemisinin-resistant malaria highlights the essential role of such VMWs in surveillance and early treatment of malaria. Smartphone technology offers huge potential to support VMWs in isolated and resource-poor settings.  Methods: We investigated the feasibility of issuing established VMWs with a smartphone, bespoke Android application and solar charger to support their role. 27 VMWs in Kampong Cham and Kratie provinces participated.  Results: 26/27 of the smartphones deployed were working well at study completion twelve months later. Interviews with VMWs using quantitative and qualitative methods revealed pride, ease of use and reports of faster communication with the smartphone. VMWs also expressed a strong wish to help people presenting with non-malarial fever, for which further potential supportive smartphone applications are increasingly available.  Conclusions: As a result of this pilot study, two smartphone based reporting systems for malaria have been developed at the Cambodian National Malaria Center, and the programme is now being extended nationwide. The full code for the smartphone application is made available to other researchers and healthcare providers with this article. Smartphones represent a feasible platform for developing the VMW role to include other health conditions, thus maintaining the relevance of these important community health workers.

Barriers for pregnant women living in rural, agricultural villages to accessing antenatal care in Cambodia: A community-based cross-sectional study combined with a geographic information system.

BACKGROUND: Maternal morbidity and mortality is still a major public health issue in low- and middle-income countries such as Cambodia. Improving access to antenatal care (ANC) services for pregnant women has been widely recognized as one of the most effective means of reducing maternal mortality and morbidity. As such, this study examined the barriers for pregnant women living in rural, agricultural villages to accessing ANC based on data collected in the Ratanakiri province, one of the least developed provinces in Cambodia, using a combination of a community-based cross-sectional survey and a geographic information system (GIS). METHODS: A community-based cross-sectional survey was conducted among 377 mothers with children under the age of two living in 62 villages in the Ratanakiri province, Cambodia, in December 2015. Face-to-face interviews were conducted to ask mothers about their ANC service use, knowledge of ANC, barriers to accessing health facilities, and complications they experienced during the most recent pregnancy. At the same time, GIS data were also collected using a Global Positioning System (GPS) to accurately measure actual travel distance of pregnant women to access health facilities and to examine geographical and environmental barriers in greater detail. RESULTS: Only a third of the mothers met the recommendations made by the World Health Organization (WHO) of receiving ANC four times or more (achieved ANC4+), and a quarter of the mothers had never received ANC during their most recent pregnancy. Factors positively associated with achieving ANC4+ were mother's secondary or higher education (adjusted odds ratio [AOR] = 5.50, 95% confidence interval [CI]: 1.74, 17.37), being aware that receiving ANC is recommended (AOR = 2.74, 95% CI: 1.25, 6.00), and knowledge about the recommended frequency for ANC (AOR = 2.26, 95% CI: 7.22). Actual travel distance was negatively associated with achieving ANC4+. Mothers who had to travel 10.0-14.9 km were 68% less likely (AOR = 0.32, 95% CI: 0.10, 0.99), and those who had to travel 15.0 km or longer were 79% less likely (AOR = 0.21, 95% CI: 0.07, 0.62) to have achieved ANC 4+, both compared to those who travelled 5.0 km or less. While most previous studies have used a straight-line to measure distance traveled, this study much more accurately measured the actual distance traveled by using a GIS. As a result, there was a statistically significant discrepancy between actual travel distance and straight-line distance. CONCLUSIONS: This study revealed promoting factors and barriers for ANC use among pregnant women living in remote, agricultural villages in Cambodia. Furthermore, this study highlights the importance of measuring travel distances accurately to ensure that targeted interventions for ANC are not misguided by straight-line distances. The methodology used in this study can be applied widely to other developing countries, especially in remote areas with limited road networks where there may be a large discrepancy between actual and straight-line distances.

The use of respondent-driven sampling to assess malaria knowledge, treatment-seeking behaviours and preventive practices among mobile and migrant populations in a setting of artemisinin resistance in Western Cambodia.

BACKGROUND: Multi-drug-resistant Plasmodium falciparum threatens malaria elimination efforts in Cambodia and the Greater Mekong Subregion (GMS). Malaria burden in the GMS is higher among certain high-risk demographic groups in Cambodia, especially among migrant and mobile populations (MMPs). This respondent driven sampling (RDS) study was conducted in order to determine malaria knowledge, treatment-seeking behaviours and preventive practices among two MMP groups in Western Cambodia. METHODS: An RDS survey of MMPs was implemented in four purposively-selected communes along the Thai-Cambodia border; two in Veal Veang District and two in Pailin Province, chosen due to their sizeable MMP groups, their convenience of access, and their proximity to Thailand, which allowed for comparison with RDS studies in Thailand. RESULTS: There were 764 participants in Pailin Province and 737 in Veal Veang District. Health messages received in Veal Veang were most likely to come from billboards (76.5%) and family and friends (57.7%), while in Pailin they were most likely to come from sources like radio (57.1%) and television (31.3%). Knowledge of malaria transmission by mosquito and prevention by bed net was above 94% in both locations, but some misinformation regarding means of transmission and prevention methods existed, predominantly in Veal Veang. Ownership of treated bed nets was lower in Pailin than in Veal Veang (25.3% vs 53.2%), while reported use the night before the survey was higher in Pailin than in Veal Veang (57.1% vs 31.6%). Use of private sector health and pharmaceutical services was common, but 81.1% of patients treated for malaria in Pailin and 86.6% in Veal Veang had received a diagnostic test. Only 29.6% of patients treated in Pailin and 19.6% of those treated in Veal Veng reported receiving the indicated first-line treatment. DISCUSSION: Barriers in access to malaria prevention and case management were common among MMPs, with marked variation by site. Resolving both nation-wide and MMP-specific challenges will require targeted interventions that take into account this heterogeneity.

World Malaria Day 2016 in the Kingdom of Cambodia: high-level governmental support embodies the WHO call for "political will to end malaria".

On World Malaria Day 2016, The Kingdom of Cambodia's National celebrations served as a prime of example of how political will is currently being exercised in Cambodia through high-level governmental support for malaria elimination. The main country event was well-planned and coordinated by the National Programme for Parasitology, Entomology and Malaria Control (CNM), and included key contributions from high-ranking political figures, such as His Excellency (H.E) Mam Bun Heng (Minister of Health), and H.E. Keut Sothea (Governor of Pailin Province). There were more than 1000 attendees, ranging from Village Malaria Workers and high school students to CNM's director and other officials in Pailin Province, Western Cambodia. A strong inter-sectoral participation included attendances from the Ministry of Education and high-level representatives of the Cambodian Armed Forces, as well as Malaria Partners like the World Health Organization.

Village malaria worker performance key to the elimination of artemisinin-resistant malaria: a Western Cambodia health system assessment.

BACKGROUND: Village malaria workers (VMWs) and mobile malaria workers (MMWs) are a critical component of Cambodia's national strategy to eliminate Plasmodium falciparum malaria by 2025. Since 2004, VMWs have been providing malaria diagnosis through the use of rapid diagnostic tests and free-of-charge artemisinin-based combination therapy in villages more than 5 km away from the closest health facility. They have also played a key role in the delivery of behaviour change communication interventions to this target population. This study aimed to assess the job performance of VMWs/MMWs, and identify challenges they face, which may impede elimination efforts. METHODS: A mixed-methods assessment was conducted in five provinces of western Cambodia. One hundred and eighty five VMW/MMW participants were surveyed using a structured questionnaire. Qualitative data was gathered through a total of 60 focus group discussions and 65 in-depth interviews. Data triangulation of the qualitative and quantitative data was used during analysis. RESULTS: Overall, VMWs/MMWs met or exceeded the expected performance levels (80 %). Nevertheless, some performance gaps were identified. Misconceptions regarding malaria transmission and prevention were found among workers. The recommended approach for malaria treatment, directly-observed treatment (DOT), had low implementation rates. Stock-outs, difficulties in reaching out to migrant and mobile populations, insufficient means of transportation and dwindling worker satisfaction also affected job performance. DISCUSSION: VMW/MMW job performance must be increased from 80 to 100 % in order to achieve elimination. In order to do this, it is recommended for the national malaria programme to eliminate worker malaria knowledge gaps. Barriers to DOT implementation and health system failures also need to be addressed. The VMW programme should be expanded on several fronts in order to tackle remaining performance gaps. Findings from this evaluation are useful to inform the planning of future activities of the programme and to improve the effectiveness of interventions in a context where artemisinin drug resistance is a significant public health issue.

Evaluation of intensified behaviour change communication strategies in an artemisinin resistance setting.

BACKGROUND: In Cambodia, behaviour change communication (BCC) represents an integral component of malaria efforts aimed at fighting artemisinin resistant parasites and achieving elimination. The multi-pronged BCC interventions include interpersonal communication through village health volunteers (VHVs) and village malaria workers (VMWs), broadcasting malaria prevention, diagnosis and treatment messages via TV, radio and mobile broadcasting units (MBUs), distributing information education and communication (IEC) materials and introducing mobile malaria workers (MMWs) in endemic villages. METHODS: This was a cross sectional household survey using a stratified multi-stage cluster sampling approach, conducted in December 2012. A stratified multi-stage cluster sampling approach was used; 30 villages were selected (15 in each stratum) and a total of 774 households were interviewed. This survey aimed to assess the potential added effect of 'intense' BCC interventions in three Western provinces. Conducted 2 years after start of these efforts, 'non-intense' BCC (niBBC) interventions (e.g., radio or TV) were compared to "intense" BCC (iBBC) implemented through a set of interpersonal communication strategies such as VMWs, VHVs, mobile broadcasting units and listener viewer clubs. RESULTS: In both groups, the knowledge of the mode of malaria transmission was high (96.9 vs 97.2 %; p = 0.83), as well as of fever as a symptom (91.5 vs 93.5 %; p = 0.38). Knowledge of local risk factors, such as staying in the forest (39.7 vs 30.7 %; p = 0.17) or the farm (7.1 vs 5.1 %; p = 0.40) was low in both groups. Few respondents in either group knew that they must get tested if they suspected malaria (0.3 vs 0.1; p = 0.69). However, iBBC increased the discussions about malaria in the family (51.7 vs 35.8 %; p = 0.002) and reported prompt access to treatment in case of fever (77.1 vs 59.4 %; p < 0.01). CONCLUSION: The use of iBCC supported positive improvements in both attitudes and behaviours among the population with regard to malaria compared to mass media (niBCC) only. The significantly increase in people seeking treatment for fever in iBCC villages supports Objective Five of the Strategic Plan in the Cambodia Malaria Elimination Action Framework (2016-2020). Therefore, this study provides evidence for the planning and implementation of future BCC interventions to achieve the elimination of artemisinin resistant Plasmodium falciparum malaria.

Reactive case-detection of malaria in Pailin Province, Western Cambodia: lessons from a year-long evaluation in a pre-elimination setting.

BACKGROUND: As momentum towards malaria elimination grows, strategies are being developed for scale-up in elimination settings. One prominent strategy, reactive case detection (RACD), involves screening and treating individuals living in close proximity to passively detected, or "index" cases. This study aims to use RACD to quantify Plasmodium parasitaemia in households of index cases, and identify risk factors for infection; these data could inform reactive screening approaches and identify target risk groups. METHODS: This study was conducted in the Western Cambodian province of Pailin between May 2013 and March 2014 among 440 households. Index participants/index cases (n = 270) and surrounding households (n = 110) were screened for Plasmodium infection with rapid diagnostic tests (RDT), microscopy and real-time polymerase chain reaction (PCR). Participants were interviewed to identify risk factors. A comparison group of 60 randomly-selected households was also screened, to compare infection levels of RACD and non-RACD households. In order to identify potential risk factors that would inform screening approaches and identify risk groups, multivariate logistic regression models were applied. RESULTS: Nine infections were identified in households of index cases (RACD approach) through RDT screening of 1898 individuals (seven Plasmodium vivax, two Plasmodium falciparum); seven were afebrile. Seventeen infections were identified through PCR screening of 1596 individuals (15 P. vivax, and 22 % P. falciparum/P. vivax mixed infections). In the control group, 25 P. falciparum infections were identified through PCR screening of 237 individuals, and no P. vivax was found. Plasmodium falciparum infection was associated with fever (p = 0.013), being a member of a control household (p ≤ 0.001), having a history of malaria infection (p = 0.041), and sleeping without a mosquito net (p = 0.011). Significant predictors of P. vivax infection, as diagnosed by PCR, were fever (p = 0.058, borderline significant) and history of malaria infection (p ≤ 0.001). CONCLUSION: This study found that RACD identified very few secondary infections when targeting index and neighbouring households for screening. The results suggest RACD is not appropriate, where exposure to malaria occurs away from the community, and there is a high level of treatment-seeking from the private sector. Piloting RACD in a range of transmission settings would help to identify the ideal environment for feasible and effective reactive screening methods.

Novel Cross-Border Approaches to Optimise Identification of Asymptomatic and Artemisinin-Resistant Plasmodium Infection in Mobile Populations Crossing Cambodian Borders.

BACKGROUND: Human population movement across country borders presents a real challenge for malaria control and elimination efforts in Cambodia and its neighbouring countries. To quantify Plasmodium infection among the border-crossing population, including asymptomatic and artemisinin resistant (AR) parasites, three official border crossing points, one from each of Cambodia's borders with Thailand, Laos and Vietnam, were selected for sampling. METHODS AND FINDINGS: A total of 3206 participants (of 4110 approached) were recruited as they crossed the border, tested for malaria and interviewed. By real-time polymerase chain reaction (RT-PCR), 5.4% of all screened individuals were found to harbour Plasmodium parasites. The proportion was highest at the Laos border (11.5%). Overall there were 97 P. vivax (55.7%), 55 P. falciparum (31.6%), two P. malariae (1.1%) and 20 mixed infections (11.5%). Of identified infections, only 20% were febrile at the time of screening. Of the 24 P. falciparum samples where a further PCR was possible to assess AR, 15 (62.5%) had mutations in the K13 propeller domain gene, all from participants at the Laos border point. Malaria rapid diagnostic test (RDT) pLDH/HRP-2 identified a positivity rate of 3.2% overall and sensitivity compared to RT-PCR was very low (43.1%). Main individual risk factors for infection included sex, fever, being a forest-goer, poor knowledge of malaria prevention methods and previous malaria infection. Occupation, day of the week and time of crossing (morning vs. afternoon) also appeared to play an important role in predicting positive cases. CONCLUSIONS: This study offers a novel approach to identify asymptomatic infections and monitor AR parasite flow among mobile and migrant populations crossing the borders. Similar screening activities are recommended to identify other hot borders and characterise potential hot spots of AR. Targeted "customised" interventions and surveillance activities should be implemented in these sites to accelerate elimination efforts in the region.

Tolerability and safety of weekly primaquine against relapse of Plasmodium vivax in Cambodians with glucose-6-phosphate dehydrogenase deficiency.

BACKGROUND: Primaquine is used to prevent Plasmodium vivax relapse; however, it is not implemented in many malaria-endemic countries, including Cambodia, for fear of precipitating primaquine-induced acute haemolytic anaemia in patients with glucose-6-phosphate dehydrogenase deficiency (G6PDd). Reluctance to use primaquine is reinforced by a lack of quality safety data. This study was conducted to assess the tolerability of a primaquine regimen in Cambodian severely deficient G6PD variants to ascertain whether a weekly primaquine could be given without testing for G6PDd. METHODS: From January 2013 to January 2014, Cambodians with acute vivax malaria were treated with dihydroartemisinin/piperaquine on days (D) 0, 1 and 2 with weekly doses of primaquine 0.75 mg/kg for 8 weeks (starting on D0, last dose on D49), and followed until D56. Participants' G6PD status was confirmed by G6PD genotype and measured G6PD activity. The primary outcome was treatment completion without primaquine toxicity defined as any one of: (1) severe anaemia (haemoglobin [Hb] <7 g/dL), (2) a >25 % fractional fall in Hb from D0, (3) the need for a blood transfusion, (4) haemoglobinuria, (5) acute kidney injury (an increase in baseline serum creatinine >50 %) or (6) methaemoglobinaemia >20 %. RESULTS: We enrolled 75 patients with a median age of 24 years (range 5-63); 63 patients (84 %) were male. Eighteen patients were G6PDd (17/18 had the Viangchan variant) and had D0 G6PD activity ranging from 0.1 to 1.5 U/g Hb (median 0.85 U/g Hb). In the 57 patients with normal G6PD (G6PDn), D0 G6PD activity ranged from 6.9 to 18.5 U/g Hb (median 12 U/g Hb). Median D0 Hb concentrations were similar (P = 0.46) between G6PDd (13 g/dL, range 9.6-16) and G6PDn (13.5 g/dL, range 9-16.3) and reached a nadir on D2 in both groups: 10.8 g/dL (8.2-15.3) versus 12.4 g/dL (8.8-15.2) (P = 0.006), respectively. By D7, five G6PDd patients (27.7 %) had a >25 % fall in Hb, compared to 0 G6PDn patients (P = 0.00049). One of these G6PDd patients required a blood transfusion (D0-D5 Hb, 10.0-7.2 g/dL). No patients developed severe anaemia, haemoglobinuria, a methaemoglobin concentration >4.9 %, or acute kidney injury. CONCLUSIONS: Vivax-infected G6PDd Cambodian patients demonstrated significant, mostly transient, falls in Hb and one received a blood transfusion. Weekly primaquine in G6PDd patients mandates medical supervision and pre-treatment screening for G6PD status. The feasibility of implementing a package of G6PDd testing and supervised primaquine should be explored. TRIAL REGISTRATION: The trial was registered on 3/1/2013 and the registration number is ACTRN12613000003774.

Malaria and the mobile and migrant population in Cambodia: a population movement framework to inform strategies for malaria control and elimination.

BACKGROUND: The relationships between human population movement (HPM) and health are a concern at global level. In the case of malaria, those links are crucial in relation to the spread of drug resistant parasites and to the elimination of malaria in the Greater Mekong sub-Region (GMS) and beyond. The mobile and migrant populations (MMP) who are involved in forest related activities are both at high risk of being infected with malaria and at risk of receiving late and sub-standard treatment due to poor access to health services. In Cambodia, in 2012, the National Malaria Control Programme (NMCP) identified, as a key objective, the development of a specific strategy for MMPs in order to address these challenges. A population movement framework (PMF) for malaria was developed and operationalized in order to contribute to this strategy. METHODS: A review of the published and unpublished literature was conducted. Based on a synthesis of the results, information was presented and discussed with experienced researchers and programme managers in the Cambodian NMCP and led to the development and refinement of a PMF for malaria. The framework was "tested" for face and content validity with national experts through a workshop approach. RESULTS: In the literature, HPM has been described using various spatial and temporal dimensions both in the context of the spread of anti-malarial drug resistance, and in the context of malaria elimination and previous classifications have categorized MMPs in Cambodia and the GMS through using a number of different criteria. Building on these previous models, the PMF was developed and then refined and populated with in-depth information relevant to Cambodia collected from social science research and field experiences in Cambodia. The framework comprises of the PMF itself, MMP activity profiles and a Malaria Risk Index which is a summation of three related indices: a vulnerability index, an exposure index and an access index which allow a qualitative ranking of malaria risk in the MMP population. Application of currently available data to the framework illustrates that the highest risk population are those highly mobile populations engaged in forest work. CONCLUSION: This paper describes the process of defining MMPs in Cambodia, identifying the different activities and related risks to appropriately target and tailor interventions to the highest risk groups. The framework has been used to develop more targeted behaviour change and outreach interventions for MMPs in Cambodia and its utility and effectiveness will be evaluated as part of those interventions.

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.

Integrating child health services into malaria control services of village malaria workers in remote Cambodia: service utilization and knowledge of malaria management of caregivers.

BACKGROUND: Malaria and other communicable diseases remain major threats in developing countries. In Cambodia, village malaria workers (VMWs) have been providing malaria control services in remote villages to cope with the disease threats. In 2009, the VMW project integrated child health services into the original malaria control services. However, little has been studied about the utilization of VMWs' child health services. This study aimed to identify determinants of caregivers' VMW service utilization for childhood illness and caregivers' knowledge of malaria management. METHODS: A cross-sectional study was conducted in 36 VMW villages of Kampot and Kampong Thom provinces in July-September 2012. An equal number of VMW villages with malaria control services only (M) and those with malaria control plus child health services (M+C) were selected from each province. Using structured questionnaires, 800 caregivers of children under five and 36 VMWs, one of the two VMWs who was providing VMW services in each study village were interviewed. RESULTS: Among the caregivers, 23% in M villages and 52% in M+C villages utilized VMW services for childhood illnesses. Determinants of caregivers' utilization of VMWs in M villages included their VMWs' length of experience (AOR = 11.80, 95% confidence interval [CI] = 4.46-31.19) and VMWs' service quality (AOR = 2.04, CI = 1.01-4.11). In M+C villages, VMWs' length of experience (AOR = 2.44, CI = 1.52-3.94) and caregivers' wealth index (AOR = 0.35, CI = 0.18-0.68) were associated with VMW service utilization. Meanwhile, better service quality of VMWs (AOR = 3.21, CI = 1.34-7.66) and caregivers' literacy (AOR = 9.91, CI = 4.66-21.05) were positively associated with caregivers' knowledge of malaria management. CONCLUSIONS: VMWs' service quality and length of experience are important determinants of caregivers' utilization of VMWs' child health services and their knowledge of malaria management. Caregivers are seeking VMWs' support for childhood illnesses even if they are providing only malaria control services. This underlines the importance of scaling-up VMWs' capacity by adding child health services of good quality, which will result in improving child health status in remote Cambodia.

Promoting community knowledge and action for malaria control in rural Cambodia: potential contributions of Village Malaria Workers.

BACKGROUND: Cambodia has been investing in Village Malaria Workers (VMWs) to improve malaria case management in rural areas. This study assessed the quality of the VMWs' services compared to those by a government-run health center from the perspective of community members. We focused on VMWs' contribution to promote their action to control malaria. A community-based cross-sectional study was conducted in Kampot province in 2009. Interviews were conducted at every accessible household in a village with VMWs (n = 153) and a village with a health center (n = 159), using interviewer administered questionnaire. Preference of the interview was given to female household head. Multiple regression analyses were run to compare knowledge about malaria, preventive measures taken, and time before first malaria treatment between the two villages. FINDINGS: The villagers perceived the VMWs' services equally as good as those provided by the health center. After controlling for confounding factors, the following indicators did not show any statistical significance between two villages: community members' knowledge about malaria transmission (AOR = 0.60, 95% CI = 0.30-1.22) and government-recommended antimalarial (AOR = 0.55, 95% CI = 0.25-1.23), preventive measures taken (Beta = -0.191, p = 0.315), and time before the first treatment (Beta = 0.053, p = 0.721). However, knowledge about malaria symptoms was significantly lower in the village with VMWs than the village with a health center (AOR = 0.40, 95% CI = 0.19-0.83). CONCLUSIONS: VMWs played an equivalent role as the health center in promoting malaria knowledge, action, and effective case management. Although VMWs need to enhance community knowledge about malaria symptoms, the current government policy on VMWs is reasonable and should be expanded to other malaria endemic villages.

Scale-up of community-based malaria control can be achieved without degrading community health workers' service quality: the Village Malaria Worker project in Cambodia.

BACKGROUND: Malaria control has been scaled up in many developing countries in their efforts to achieve the Millennium Development Goals. Cambodia recently scaled up their Village Malaria Worker (VMW) project by substantially increasing the number of VMWs and expanding the project's health services to include treatment of fever, diarrhoea, and Acute Respiratory Infections (ARI) in children under five. This study examined if the scale-up interfered with VMWs' service quality, actions, and knowledge of malaria control, and analysed VMWs' overall achievements and perceptions of the newly added health services. METHODS: Structured interviews were conducted pre scale-up in February-March 2008 with 251 VMWs and post scale-up in July-August 2010 with 252 VMWs. Comparing the pre and post scale-up survey results (n = 195), changes were examined in terms of VMWs' 1) service quality, 2) malaria prevention and vector control actions, and 3) knowledge of malaria epidemiology and vector ecology. In addition, VMWs' newly added health services were descriptively analysed based on the post scale-up survey (n = 252). RESULTS: VMWs' service quality and actions significantly improved overall during the scale-up of the VMW project (mean index score: +0.805, p < 0.001; +2.923, p < 0.001; respectively). Although most of knowledge areas also showed significant improvement (between +0.256 and +0.499, p < 0.001), less than half (10.3%-47.7%) of the VMWs correctly answered a set of questions on malaria epidemiology and vector ecology, even in the post scale-up survey. About 70% of the respondents reported that their health services to control malaria remained the same or that they were more active after the scale-up. Two-thirds (66.3%) had become more enthusiastic about serving as a VMW since the scale-up, and all but one respondent reported being willing to continue the new services. CONCLUSIONS: The Cambodian experience clearly demonstrated that a nationwide scale-up of community-based malaria control can be achieved without degrading community health workers' service quality. The government's strategy to expand VMWs' health services, while providing sufficient training to maintain the quality of their original malaria control services, could have contributed to the improvement of VMW's service quality, actions, and knowledge in spite of the rapid scale-up of the project.