The impact of targeted malaria elimination with mass drug administrations on falciparum malaria in Southeast Asia: A cluster randomised trial.

BACKGROUND: The emergence and spread of multidrug-resistant Plasmodium falciparum in the Greater Mekong Subregion (GMS) threatens global malaria elimination efforts. Mass drug administration (MDA), the presumptive antimalarial treatment of an entire population to clear the subclinical parasite reservoir, is a strategy to accelerate malaria elimination. We report a cluster randomised trial to assess the effectiveness of dihydroartemisinin-piperaquine (DP) MDA in reducing falciparum malaria incidence and prevalence in 16 remote village populations in Myanmar, Vietnam, Cambodia, and the Lao People's Democratic Republic, where artemisinin resistance is prevalent. METHODS AND FINDINGS: After establishing vector control and community-based case management and following intensive community engagement, we used restricted randomisation within village pairs to select 8 villages to receive early DP MDA and 8 villages as controls for 12 months, after which the control villages received deferred DP MDA. The MDA comprised 3 monthly rounds of 3 daily doses of DP and, except in Cambodia, a single low dose of primaquine. We conducted exhaustive cross-sectional surveys of the entire population of each village at quarterly intervals using ultrasensitive quantitative PCR to detect Plasmodium infections. The study was conducted between May 2013 and July 2017. The investigators randomised 16 villages that had a total of 8,445 residents at the start of the study. Of these 8,445 residents, 4,135 (49%) residents living in 8 villages, plus an additional 288 newcomers to the villages, were randomised to receive early MDA; 3,790 out of the 4,423 (86%) participated in at least 1 MDA round, and 2,520 out of the 4,423 (57%) participated in all 3 rounds. The primary outcome, P. falciparum prevalence by month 3 (M3), fell by 92% (from 5.1% [171/3,340] to 0.4% [12/2,828]) in early MDA villages and by 29% (from 7.2% [246/3,405] to 5.1% [155/3,057]) in control villages. Over the following 9 months, the P. falciparum prevalence increased to 3.3% (96/2,881) in early MDA villages and to 6.1% (128/2,101) in control villages (adjusted incidence rate ratio 0.41 [95% CI 0.20 to 0.84]; p = 0.015). Individual protection was proportional to the number of completed MDA rounds. Of 221 participants with subclinical P. falciparum infections who participated in MDA and could be followed up, 207 (94%) cleared their infections, including 9 of 10 with artemisinin- and piperaquine-resistant infections. The DP MDAs were well tolerated; 6 severe adverse events were detected during the follow-up period, but none was attributable to the intervention. CONCLUSIONS: Added to community-based basic malaria control measures, 3 monthly rounds of DP MDA reduced the incidence and prevalence of falciparum malaria over a 1-year period in areas affected by artemisinin resistance. P. falciparum infections returned during the follow-up period as the remaining infections spread and malaria was reintroduced from surrounding areas. Limitations of this study include a relatively small sample of villages, heterogeneity between villages, and mobility of villagers that may have limited the impact of the intervention. These results suggest that, if used as part of a comprehensive, well-organised, and well-resourced elimination programme, DP MDA can be a useful additional tool to accelerate malaria elimination. TRIAL REGISTRATION: ClinicalTrials.gov NCT01872702.

Human infection with Plasmodium knowlesi on the Laos-Vietnam border.

BACKGROUND: Border malaria in the Greater Mekong region of Southeast Asia poses a serious threat to the health of the ethnic minority populations of the region. Traditionally thought to be caused primarily by the malaria parasites Plasmodium falciparum and Plasmodium vivax, recently a zoonotic parasite, Plasmodium knowlesi, has been identified in some countries of the region. The presence of this parasite poses a challenge to malaria control programmes, as it is maintained in a zoonotic reservoir of forest-dwelling macaque monkeys. METHODS: A cross-sectional malaria parasite species prevalence survey was conducted along the Laos-Vietnam border in the central part of the two countries. Human blood samples were collected from Savannakhet in Laos and Quang Tri in Vietnam between August and October 2010 and assayed for the presence of human malaria parasite species and P. knowlesi. A PCR targeting the 18S small subunit ribosomal RNA gene and circumsporozoite protein gene was used for Plasmodium species identification. RESULTS: Nine cases of P. knowlesi were detected by PCR in blood samples from the Laos side and three from the Vietnam side. All P. knowlesi infections were found in co-infection with P. vivax, with some triple infections of P. knowlesi, P. vivax and P. falciparum detected in Laos. Phylogenetic analysis of these parasites suggests that P. knowlesi is circulating in the Laos-Vietnam border region. CONCLUSION: This report shows that P. knowlesi is transmited on both sides of the Vietnam-Laos border. Continued monitoring of the range and prevalence of P. knowlesi on both the sides of Laos-Vietnam border is of importance to the National Malaria Control Programmes of both countries.

Household clustering of asymptomatic malaria infections in Xepon district, Savannakhet province, Lao PDR.

BACKGROUND: In the Lao PDR, malaria morbidity and mortality have remarkably decreased over the past decade. However, asymptomatic infections in rural villages contribute to the on-going local transmission. The primary objective of this study was to explore the characteristics of infections in a malaria-endemic district of the Lao PDR. The specific objectives were to investigate the prevalence and species of malaria parasites using molecular methods and to assess individual and household parasite levels and the characteristics associated with malaria infection. METHODS: The study population included 870 participants from 236 households in 10 villages of the Xepon district. Interviews, blood examinations and body temperature measurements were conducted between August and September 2013. A multilevel logistic regression model, with adjustment for clustering effects, was used to assess the association between predictor variables and an outcome variable (malaria infection status as principally determined by PCR). The predictive factors included individual-level factors (age, gender, past fever episode, and forest activity during night time) and household-level factors (household member size, household bed net usage/density and a household with one other malaria-infected member). RESULTS: Fifty-two participants (including 26 children) tested positive (positive rate: 6.0 %): Plasmodium falciparum mono-infection was the most common infection (n = 41, 78.8 %), followed by P. falciparum and Plasmodium vivax mixed infections (n = 9, 17.3 %). The majority of infected participants (n = 42, 80.8 %) had no fever episodes in the two previous weeks or a measurable fever (>37 °C) at the time of survey. Living in a household with one other malaria-infected member significantly increased the odds of infection (odds ratio 24.33, 95 % confidence interval 10.15-58.32). Among the 40 households that had at least one infected member, nine households were responsible for 40.4 % of the total infections. CONCLUSIONS: Plasmodium vivax was detected more frequently than it was reported from the district hospital. Most infections were asymptomatic and sub-microscopic and were highly clustered within households. To further eliminate malaria in Xepon and other similar settings in the country, the National Malaria Control Programme should consider household-based strategies, including reactive case detection targeting the household members of index cases.

Asymptomatic Plasmodium infections in 18 villages of southern Savannakhet Province, Lao PDR (Laos).

BACKGROUND: A large fraction of Plasmodium infections do not cause clinical signs and symptoms of disease and persist at densities in blood that are not detectable by microscopy or rapid diagnostic tests. These infections may be critical as a transmission reservoir in areas of low malaria endemicity. Understanding the epidemiology of these infections would be helpful for malaria elimination. METHODS: A cross-sectional survey was conducted in Thapangthong and Nong Districts of Savannakhet Province, Lao PDR, to determine the prevalence of parasitaemia. A total of 888 blood samples were collected from afebrile volunteers aged ≥15 years in 18 villages during March and July 2015. Plasmodium infections were diagnosed by rapid diagnostic tests (RDT) and high volume, ultra-sensitive quantitative polymerase chain reaction (uPCR). RESULTS: uPCR detected Plasmodium infections in 175 of 888 samples (20 %). The species distribution was Plasmodium falciparum 3.6 % (32/888), Plasmodium vivax 11.1 % (99/888), mixed infections with P. falciparum and P. vivax 1.6 % (14/888) and Plasmodium of undetermined species 3.4 % (30/888). RDT identified only 2 % (18/888) positive cases. Using uPCR as reference, the sensitivity and specificity of RDTs were 28 and 100 %, respectively, in detecting P. falciparum infections, and 3 and 99 % in detecting asymptomatic P. vivax infections. The K13 kelch propeller domain C580Y mutation, associated with reduced susceptibility to artemisinin derivatives, was found in 75 % (12/18) of P. falciparum isolates from Thapangthong and in 7 % (2/28) from Nong (p < 0.001). In a multivariate analysis, males were more likely to have P. vivax infections [adjusted odds ratio (aOR) 4.76 (95 % CI 2.84-8.00)] while older villagers were at lower risk for parasitaemia [aOR for increasing age 0.98 (95 % CI 0.96-0.99)]. CONCLUSION: There is a high prevalence of asymptomatic Plasmodium infections in southern Savannakhet. Artemisinin-resistant P. falciparum strains form an increasing proportion of the parasite population in Thapangthong District and are already present in the more remote Nong District. This worrying trend has wider implications for Laos and could reverse the gains achieved by the successful control of malaria in Laos and the Greater Mekong Sub-region (GMS). Rapid elimination of P. falciparum has to be a top priority in Laos as well as in the wider GMS.

Snakebites in Two Rural Districts in Lao PDR: Community-Based Surveys Disclose High Incidence of an Invisible Public Health Problem.

BACKGROUND: The Lao PDR (Laos) is one of the least developed countries in Asia with an estimated 25% of the population living in poverty. It is the habitat of some highly venomous snakes and the majority of the population earns their living from agricultural activities. Under these circumstances the incidence of snakebites is expected to be high. METHODS: Two cross-sectional, community-based surveys were performed in Champone and Phin district, Savannakhet province, Lao PDR to estimate snakebite incidence. Multistage random sampling was used. In the first stage approximately 40% of all villages in each district were randomly selected. In the second stage 33% of all households in each village were randomly chosen. Members of the selected households were interviewed about snakebites during the previous 12 months. RESULTS: Thirty-five of 9856 interviewees reported a snakebite in a 12 month period in Champone district and 79 of 7150 interviewees in Phin district. The estimated incidence is 355 snakebites per 100,000 persons per year and 1105 per 100,000 in Champone and Phin district respectively. All snakebite victims received treatment by traditional healers or self-treatment at home and nobody went to a hospital. Incidence of snakebites, calculated on the basis of hospital records of 14 district hospitals and Savannakhet provincial hospital, ranged from 3 to 14 cases per 100,000 persons per year between 2012 and 2014. CONCLUSION: Incidence of snakebites is high in rural communities in Laos with significant regional differences. Poverty most likely contributes significantly to the higher number of snakebites in Phin district. Hospital statistics profoundly underestimates snakebite incidence, because the majority of snakebite victims receive only treatment by traditional healers or self-treatment in their village. There is an urgent need to train medical staff and students in management of snakebite patients and make snake antivenom available to cope effectively with this important public health problem in order to prevent fatalities and disabilities.

Households with Insufficient Bednets in a Village with Sufficient Bednets: Evaluation of Household Bednet Coverage Using Bednet Distribution Index in Xepon District, Lao PDR.

In Lao PDR, the National Malaria Control Program (NMCP) evaluates bednet coverage, often at the village level, using a coverage target of one net per 2.5 (or fewer) persons in a given population. However, in villages that meet the target, not all households necessarily meet the target or utilize all available bednets. This study explored households that fell short of the target and household utilization of bednets in villages that met the target of bednet coverage set by the NMCP. The person per net ratio (PPNR), which is defined as the population divided by the number of available bednets in a household/village, was used to determine whether a household/village met the NMCP target. Using a household survey, we collected and analyzed the data of 635 households in 17 villages in Xepon district in 2012. Households that fell short of the target (households with a PPNR of > 2.5 or no bednet) existed in every village. The proportion of these households differed greatly among the villages, ranging from 3.4-50%, with some households falling far short. Of the 635 households, 275 (43.5%) had at least one bednet that was not being used on the night preceding the survey and 131 (20.6%) had at least two. In conclusion, in villages that met the NMCP target, a considerable number of households fell short of the target, and the available bednets were not fully utilized in many of the surveyed households.

Village health volunteers' social capital related to their performance in Lao People's Democratic Republic: a cross-sectional study.

BACKGROUND: Improving the performance of community health workers (CHWs) is a global issue. The relationship between CHWs and their community may impact their performance. In Lao People's Democratic Republic (Lao PDR), CHW are called village health volunteers (VHV). Lao PDR has a problem with VHV inactivity, especially in rural areas. This study focused on which aspects of social capital are related to VHV performance. METHODS: This research represents a cross-sectional study with a quantitative survey based primarily on interviews using a semi-structured questionnaire. Interviews were conducted with 149 VHVs living and working in the Sepon District. VHV performance evaluation was measured with scores on a 5-point scale, and the cutoff point for designating performance as good or poor was set at the median score. This evaluation of VHV performance was conducted as a self-evaluation by VHVs and by health center staff who were supervisors of the VHVs. Measurement of social capital was accomplished using the short version of the Adapted Social Capital Assessment Tool (SASCAT). For statistical analyses, logistic regression was used to calculate adjusted odds ratios (OR) and 95% confidence intervals (CI). RESULTS: The results of multiple logistic regression adjusted by moderator variables showed that citizenship activities in the structural social capital component of SASCAT were significantly related to performance in self-evaluation by VHVs (adjusted OR: 2.10, 95% CI: 1.19-3.71) and the evaluations by health center staff (adjusted OR: 1.67, 95% CI: 1.01-2.77). Support from groups (adjusted OR: 1.87, 95% CI: 1.27-2.76) and cognitive social capital (adjusted OR: 7.48, 95% CI: 2.14-26.10) were found to be significantly associated but only for VHV self-evaluation. CONCLUSIONS: The results suggest that individuals who interact with important figures in the community and who cooperate with other villagers whenever problems arise, i.e., have social capital, exhibit good performance as VHVs. These findings suggest that increasing citizenship activities could increase the retention rate of CHWs and help improve their performance. Citizenship activities could also be used as a predictive indicator when selecting new CHWs.

Successful mobile phone network-based approach to integration of the health care system in rural Laos: strengthening lay health worker performance.

INTRODUCTION: Little has been reported regarding how the effects of mobile phone-based improvements to healthcare worker communications may improve the activities of lay health workers, who form the crucial bridge between the official healthcare system and rural/remote communities. The objective of this study was to establish and assess the usefulness of a mobile phone-based communication network between village health volunteers (VHVs) and their supervisors in a rural district of Laos. METHODS: This study involved 154 villages out of a total of 158 villages located in Xepone district, Laos. Mobile phones with pre-paid cards were provided to 154 VHVs and 11 VHV supervisors; all were trained in the use of the phones and instructed to use the provided phone ad libitumfor work purposes. The supervisors recorded how or whether VHVs submitted their regular monthly vital event surveillance report and also took note of information pertaining to subject(s) discussed in the phone calls, whenever a call was made to or received from a VHV. RESULTS: In the 6-month period following mobile phone distribution, the group of supervisors received a total of 364 calls from VHVs. The most common purposes for the calls were the delivery of the monthly report; the second-most frequent purpose was the seeking of advice on case management, vitamin A distribution and delivery. The group of supervisors together made a total of 478 calls to VHVs during the 6-month period; the most frequent purpose was to request the monthly report and, second-most frequently, to inform in advance the scheduling of meetings, training, and outreach activities such as immunizations and health check-ups. Compared to the baseline, the number of villages with VHV submissions of monthly vital event surveillance reports significantly increased from 79 (51.3%) to 127 (82.5%) at 6 months after phone distribution. This increase was maintained at the 1-year time point (81.2%). CONCLUSION: The district-wide mobile phone communication network facilitated regular reporting, the seeking of advice, and the delivery of information regarding scheduling of various activities. The improved frequency and quality of communications has strong potential to translate into an improvement in health outcomes of people living in geographically remote and rural communities.

Joint malaria surveys lead towards improved cross-border cooperation between Savannakhet province, Laos and Quang Tri province, Vietnam.

BACKGROUND: In Savannakhet province, Laos and Quang Tri province, Vietnam, malaria is still an important health problem and most cases are found in the mountainous, forested border areas where ethnic minority groups live. The objectives of this study were to obtain a better joint understanding of the malaria situation along the border and, on the basis of that, improve malaria control methods through better cooperation between the two countries. METHODS: Fourteen villages in Savannakhet and 22 villages in Quang Tri were randomly selected within 5 km from the border where a blood survey for microscopic diagnosis (n = 1256 and n = 1803, respectively), household interviews (n = 400, both sides) and vector surveys were conducted between August and October 2010. Satellite images were used to examine the forest density around the study villages. RESULTS: Malaria prevalence was significantly higher in Laos (5.2%) than in Vietnam (1.8%) and many other differences were found over the short distance across the border. Bed net coverage was high (> 90%) in both Laos and Vietnam but, while in Laos more than 60% of the nets were long-lasting insecticide-treated, Vietnam used indoor residual spraying in this area and the nets were untreated. Anopheles mosquitoes were more abundant in Laos than in Vietnam, especially many Anopheles dirus were captured in indoor light traps while none were collected in Vietnam. The forest cover was higher around the Lao than the Vietnamese villages. After this study routine exchange of malaria surveillance data was institutionalized and for the first time indoor residual spraying was applied in some Lao villages. CONCLUSIONS: The abundance of indoor-collected An. dirus on the Laos side raises doubts about the effectiveness of a sole reliance on long-lasting insecticide-treated nets in this area. Next to strengthening the early detection, correct diagnosis and prompt, adequate treatment of malaria infections, it is recommended to test focal indoor residual spraying and the promotion of insect repellent use in the early evening as additional vector interventions. Conducting joint malaria surveys by staff of two countries proved to be effective in stimulating better collaboration and improve cross-border malaria control.

Determinants of monthly reporting by village health volunteers in a poor rural district of Lao PDR.

Village health volunteers (VHV) are community members trained as lay health workers. They are engaged in a variety of health care programs in which they are often required to make regular reports to their supervisors, including community-based surveillance data. The objective of this study was to identify factors influencing monthly reporting activities among VHV in a remote area of Lao PDR. Data were collected through structured interviews with VHV in November 2008. Logistic regression analysis was conducted to assess associations between completion of monthly reporting and socio-demographic and economic factors and VHV-related factors, such as training, experience, type of main job, and satisfaction with incentives. Of the 137 VHVs from 97 villages interviewed, 39.4% stated they submitted their monthly report at least once over the past three months. Most frequently mentioned reasons for not reporting were "no money to visit health center", "no time to visit health center", and the "health center is located too far". Logistic regression analysis showed failure to report was associated with longer distances between the VHV village and the responsible health center, lower levels of education, fewer training sessions attended by the VHV, and the type of main job of the VHV. Although most VHVs owned vehicles and were given financial support for travel, difficulty traveling to the responsible health center remains the leading cause for failure to report.