Prospects for the development of community-based care in remote rural areas: a stakeholder analysis in Laos.

BACKGROUND: Community-based health programmes have been a cornerstone of primary care in Laos for decades. The study presented here aimed to document prospects for the development of current programmes, considering perceptions about health and health care priorities in the communities, implementation challenges, the policy landscape and opportunities associated with the availability of new technologies. METHODS: The research design primarily involved qualitative in-depth interviews with stakeholders (n = 35) responsible for the planning, management, or implementation of community-based care in Laos at different levels of the health system. These included health managers at central departments or institutes of the Ministry of Health, provincial health departments, district health offices, heads of health centres, village health volunteers, community representatives, and international stakeholders. RESULTS: There was consensus that service delivery is still a challenge in many areas, due to geographic inaccessibility of health facilities, communication barriers, health-seeking behaviour, trust, and gender discrimination, particularly among ethnic minorities. In these settings, community health workers have the potential to extend the reach of the formal health system, acting as cultural brokers across sectors of society, ethnicities, and worldviews. To maximise impact, planners need to carefully consider the implementation model, financing arrangements, health system integration, and changing health priorities in the communities. CONCLUSIONS: This study examined challenges to, and opportunities for, the expansion and health system integration of community-based care in Laos. Further development and horizontal integration of community-based care remains a complex financing and governance challenge, although the renewed emphasis on primary care and the ongoing process of decentralisation provide a favourable policy environment in the country to sustain and potentially expand existing programmes.

Forest malaria and prospects for anti-malarial chemoprophylaxis among forest goers: findings from a qualitative study in Lao PDR.

BACKGROUND: Despite significant decline in malarial incidence and mortality in countries across the Greater Mekong Subregion, the disease remains a public health challenge in the region; transmission continues mainly among people who visit forests in remote areas, often along international borders, where access to primary healthcare is limited. In the absence of effective vector-control measures and limited exposure periods, malaria chemoprophylaxis has been proposed as a strategy to protect forest goers. As a rarely used approach for indigenous populations, questions remain about its feasibility and acceptability. Drawing on in-depth interviews with forest goers and stakeholders, this article examines opportunities and challenges for implementation of anti-malarial chemoprophylaxis for forest goers in Lao PDR. METHODS: In-depth interviews were conducted with 16 forest goers and 15 stakeholders in Savannakhet province, Lao PDR. Interview topics included experience of malaria prevention and health services, and perceptions of prophylaxis as a potential component of malaria elimination strategy. The interviews were transcribed and coded using inductive and deductive approaches for qualitative thematic analysis. RESULTS: In ethnically and geographically diverse villages, awareness of malaria risk prompts forest goers to protect themselves, albeit sub-optimally using available preventive measures. Stakeholders highlighted challenges for targeting at-risk populations and approaches to address forest malaria in southern Lao PDR. Among policymakers, choice and cost of anti-malarials, particularly their efficacy and source of funding, were key considerations for the feasibility of malaria prophylaxis. Acceptability of prophylaxis among forest goers was also influenced by the complexity of the regimen, including the number of tablets and timing of doses. Implementation of prophylaxis may be affected by a lack of transportation and communication barriers in remote communities. CONCLUSION: Adding prophylaxis to existing malaria control activities requires strengthening the capacity of local health workers in Lao PDR. Ideally, this would be part of an integrated approach that includes strategies to address the other febrile illnesses that forest goers describe as priority health concerns. The prophylactic regimen also requires careful consideration in terms of effectiveness and simplicity of dosing.

Evolution of Multidrug Resistance in Plasmodium falciparum: a Longitudinal Study of Genetic Resistance Markers in the Greater Mekong Subregion.

Increasing resistance in Plasmodium falciparum to artemisinins and their artemisinin combination therapy (ACT) partner drugs jeopardizes effective antimalarial treatment. Resistance is worst in the Greater Mekong subregion. Monitoring genetic markers of resistance can help to guide antimalarial therapy. Markers of resistance to artemisinins (PfKelch mutations), mefloquine (amplification of P. falciparum multidrug resistance-1 [PfMDR1]), and piperaquine (PfPlasmepsin2/3 amplification and specific P. falciparum chloroquine resistance transporter [PfCRT] mutations) were assessed in 6,722 P. falciparum samples from Vietnam, Lao People's Democratic Republic (PDR), Cambodia, Thailand, and Myanmar between 2007 and 2019. Against a high background prevalence of PfKelch mutations, PfMDR1 and PfPlasmepsin2/3 amplification closely followed regional drug pressures over time. PfPlasmepsin2/3 amplification preceded piperaquine resistance-associated PfCRT mutations in Cambodia and reached a peak prevalence of 23/28 (82%) in 2015. This declined to 57/156 (38%) after first-line treatment was changed from dihydroartemisinin-piperaquine to artesunate-mefloquine (ASMQ) between 2014 and 2017. The frequency of PfMDR1 amplification increased from 0/293 (0%) between 2012 and 2017 to 12/156 (8%) in 2019. Amplification of PfMDR1 and PfPlasmepsin2/3 in the same parasites was extremely rare (4/6,722 [0.06%]) and was dispersed over time. The mechanisms conferring mefloquine and piperaquine resistance may be counterbalancing. This supports the development of ASMQ plus piperaquine as a triple artemisinin combination therapy.

Knowledge, attitudes, and practices on climate change and dengue in Lao People's Democratic Republic and Thailand.

BACKGROUND: Dengue is linked with climate change in tropical and sub-tropical countries including the Lao People's Democratic Republic (Laos) and Thailand. Knowledge about these issues and preventive measures can affect the incidence and outbreak risk of dengue. Therefore, the present study was conducted to determine the knowledge, attitudes, and practices (KAP) among urban and rural communities and government officials about climate change and dengue in Laos and Thailand. METHODS: A cross-sectional KAP survey about climate change and dengue were conducted in 360 households in Laos (180 urban and 180 rural), 359 households in Thailand (179 urban and 180 rural), and 20 government officials (10 in each country) using structured questionnaires. Data analysis was undertaken using descriptive methods, principal component analysis (PCA), Chi-square test or Fisher's exact test (as appropriate), and logistic regression. RESULTS: Significant differences among the selected communities in both countries were found in terms of household participant's age, level of education, socioeconomic status, attitude level of climate change and KAP level of dengue (P < 0.05; 95% CI). Overall, participants' KAP about climate change and dengue were low except the attitude level for dengue in both countries. The level of awareness among government officials regarding the climatic relationship with dengue was also low. In Lao households, participants' knowledge about climate change and dengue was significantly associated with the level of education and socioeconomic status (SES) (P < 0.01). Their attitudes towards climate change and dengue were associated with educational level and internet use (P < 0.05). Householders' climate change related practices were associated with SES (P < 0.01) and dengue related practices were associated with educational level, SES, previous dengue experience and internet use (P < 0.01). In Thailand, participants' knowledge about climate change was associated with the level of education and SES (P < 0.01). Their attitudes towards climate change were associated with residence status (urban/rural) and internet use (P < 0.05); climate change related practices were associated with educational level and SES (P < 0.05). Dengue related knowledge of participants was associated with SES and previous dengue experience (P < 0.05); participants' dengue related attitudes and practices were associated with educational level (P < 0.01). CONCLUSION: The findings call for urgently needed integrated awareness programs to increase KAP levels regarding climate change adaptation, mitigation and dengue prevention to improve the health and welfare of people in these two countries, and similar dengue-endemic countries.

Correction to: The use of ultrasensitive quantitative-PCR to assess the impact of primaquine on asymptomatic relapse of Plasmodium vivax infections: a randomized, controlled trial in Lao PDR.

Following publication of the original article [1], it was brought to the authors' attention that one of the names in the author list had been provided with the incorrect spelling.

The use of ultrasensitive quantitative-PCR to assess the impact of primaquine on asymptomatic relapse of Plasmodium vivax infections: a randomized, controlled trial in Lao PDR.

BACKGROUND: Trials to assess the efficacy of the radical cure of Plasmodium vivax malaria with 8-aminoquinolines require that most post-treatment relapses are identified, but there is no consensus on the optimal duration of follow-up in either symptomatic or asymptomatic vivax malaria. The efficacy of a 14-day course of primaquine on the cumulative incidence of recurrent asymptomatic P. vivax infections detected by ultrasensitive quantitative PCR (uPCR) as a primary endpoint was assessed. METHODS: A randomized, placebo-controlled, single-blind trial was conducted in four villages of the Lao PDR during 2016-2018 nested in a larger project evaluating mass drug administrations (MDA) with dihydroartemisinin-piperaquine (DP) and a single low-dose primaquine to clear Plasmodium falciparum infections. In the nested sub-study, eligible participants with mono- or mixed P. vivax infections detected by uPCR were randomized to receive either 14 days of primaquine (0.5 mg/kg/day) or placebo during the last round of MDA (round 3) through directly observed therapy. Participants were checked monthly for 12 months for parasitaemia using uPCR. The primary outcome was cumulative incidence of participants with at least one recurrent episode of P. vivax infection. RESULTS: 20 G6PD-normal participants were randomized in each arm. 5 (29%) of 20 participants in the placebo arm experienced asymptomatic, recurrent P. vivax infections, resulting in a cumulative incidence at month 12 of 29%. None of the 20 participants in the intervention arm had recurrent infections (p = 0.047 Fisher's exact test). Participants with recurrent P. vivax infections were found to be parasitaemic for between one and five sequential monthly tests. The median time to recurrence of P. vivax parasitaemia was 178 days (range 62-243 days). CONCLUSIONS: A 14-day course of primaquine in addition to a DP-MDA was safe, well-tolerated, and prevented recurrent asymptomatic P. vivax infections. Long follow-up for up to 12 months is required to capture all recurrences following the treatment of asymptomatic vivax infection. To eliminate all malarias in settings where P. vivax is endemic, a full-course of an 8-aminoquinolines should be added to MDA to eliminate all malarias. Trial registration This study was registered with ClinicalTrials.gov under NCT02802813 on 16th June 2016. https://clinicaltrials.gov/ct2/show/NCT02802813.

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.

Prevalence of G6PD Viangchan variant in malaria endemic areas in Lao PDR: an implication for malaria elimination by 2030.

BACKGROUND: Primaquine is effective against the latent liver stage of Plasmodium vivax. Eliminating the latent liver stage of P. vivax is one of the necessary conditions to achieve the goal of malaria elimination in Lao People's Democratic Republic (PDR) by 2030. However, people with glucose-6-phosphate dehydrogenase (G6PD) deficiency are at risk of haemolysis when ingesting primaquine. The aim of this study was to detect the prevalence of the G6PD Viangchan variant, which is said to be common in Lao PDR and which can result in severe haemolysis in patients exposed to primaquine. METHODS: Blood samples were collected from villagers in three malaria endemic provinces: Champasak and Savannakhet in the south, and Phongsaly in the north. Each blood sample was semi-quantitatively assayed for G6PD enzyme activity using the G6PD Assay Kit-WST Lyophilized (DOJINDO Laboratories, Japan). Blood samples that were found to be G6PD deficient were sequenced to detect G6PD Viangchan mutation. RESULTS: In total, 2043 blood samples were collected from Phongsaly (n = 426, 20.9%), Savannakhet (n = 924, 45.2%), and Champasak (n = 693, 33.9%) provinces in Lao PDR from 2016 to 2017. Of these, 964 (47.2%) were taken from male villagers and 1079 (52.8%) were taken from female villagers. G6PD Viangchan mutation was not detected in Phongsaly province in this study. In Savannakhet province, 48 of the 924 samples (45 males, 3 females) had the G6PD Viangchan mutation (n = 48, 5.2%). In Champasak province, 42 of the 693 samples (18 males, 24 females) had the G6PD Viangchan mutation (n = 42, 6.1%). CONCLUSIONS: G6PD Viangchan variant, which can cause severe haemolysis in the carrier when exposed to primaquine, was detected among 6.1% of the villagers in Champasak and 5.2% in Savannakhet but not in Phongsaly in this study. G6PD Viangchan variant might be common in the south of Laos but not so in the north. In the north, other G6PD deficiency variants might be more prevalent. However, in order not to overlook anyone and ensure a safe primaquine therapy for people living in malaria endemic areas in Lao PDR, G6PD testing is necessary.

The probability of a sequential Plasmodium vivax infection following asymptomatic Plasmodium falciparum and P. vivax infections in Myanmar, Vietnam, Cambodia, and Laos.

BACKGROUND: Adding 8-aminoquinoline to the treatment of falciparum, in addition to vivax malaria, in locations where infections with both species are prevalent could prevent vivax reactivation. The potential risk of haemolysis under a universal radical cure policy using 8-aminoquinoline needs to be weighed against the benefit of preventing repeated vivax episodes. Estimating the frequency of sequential Plasmodium vivax infections following either falciparum or vivax malaria episodes is needed for such an assessment. METHODS: Quarterly surveillance data collected during a mass drug administration trial in the Greater Mekong Subregion in 2013-17 was used to estimate the probability of asymptomatic sequential infections by the same and different Plasmodium species. Asymptomatic Plasmodium infections were detected by high-volume ultrasensitive qPCR. Quarterly surveys of asymptomatic Plasmodium prevalence were used to estimate the probability of a P. vivax infection following Plasmodium falciparum and P. vivax infections. RESULTS: 16,959 valid sequential paired test results were available for analysis. Of these, 534 (3%) had an initial P. falciparum monoinfection, 1169 (7%) a P. vivax monoinfection, 217 (1%) had mixed (P. falciparum + P. vivax) infections, and 15,039 (89%) had no Plasmodium detected in the initial survey. Participants who had no evidence of a Plasmodium infection had a 4% probability to be found infected with P. vivax during the subsequent survey. Following an asymptomatic P. falciparum monoinfection participants had a 9% probability of having a subsequent P. vivax infection (RR 2.4; 95% CI 1.8 to 3.2). Following an asymptomatic P. vivax monoinfection, the participants had a 45% probability of having a subsequent P. vivax infection. The radical cure of 12 asymptomatic P. falciparum monoinfections would have prevented one subsequent P. vivax infection, whereas treatment of 2 P. vivax monoinfections may suffice to prevent one P. vivax relapse. CONCLUSION: Universal radical cure could play a role in the elimination of vivax malaria. The decision whether to implement universal radical cure for P. falciparum as well as for P. vivax depends on the prevalence of P. falciparum and P. vivax infections, the prevalence and severity of G6PD deficiency in the population and the feasibility to administer 8-aminoquinoline regimens safely. Trial registration ClinicalTrials.gov Identifier: NCT01872702, first posted June 7th 2013, https://clinicaltrials.gov/ct2/show/NCT01872702. This study was registered with ClinicalTrials.gov under NCT02802813 on 16th June 2016. https://clinicaltrials.gov/ct2/show/NCT02802813.

Is the place of birth related to the mother's satisfaction with childbirth? A cross-sectional study in a rural district of the Lao People's Democratic Republic (Lao PDR).

BACKGROUND: The place of birth has been rapidly changing from home to health facility in Lao People's Democratic Republic (Lao PDR) following the strategy to improve the maternal and neonatal mortality. This change in the place of birth might affect the mother's satisfaction with childbirth. The objective of this study was to assess whether the place of birth is related to the mother's satisfaction with childbirth in a rural district of the Lao PDR. METHODS: A community-based survey was implemented in 21 randomly selected hamlets in Xepon district, Savannakhet province, between February and March, 2016. Questionnaire-based interviews were conducted with mothers who experienced a normal vaginal birth in the past 2 years. Satisfaction with childbirth was measured by the Satisfaction with Childbirth Experience Questionnaire. Using the median, the outcome variable was dichotomized into "high satisfaction group" and "low satisfaction group". Logistic regression was performed to assess the association between place of birth and satisfaction with childbirth. Three models were examined: In Model 1, only the predictor of interest (i.e., place of birth) was included. In Model 2, the predictor of interest and the obstetrical predictors were included. In Model 3, in addition to these predictors, socio-demographic and economic predictors were included. A mixed-effects model was used to account for the hierarchical structure. RESULTS: Among the 226 mothers who were included in data analysis, 60.2% gave birth at the health facility and the remaining 39.8% gave birth at home. Logistic regression analysis showed that the mothers who gave birth at the health facility were significantly more likely to have a higher level of satisfaction compared to the mothers who gave birth at home (crude odds ratio: 5.44, 95% confidence interval: 3.03 to 9.75). This association remained even after adjusting for other predictors (adjusted odds ratio: 6.05, 95% confidence interval: 2.81 to 13.03). CONCLUSION: Facility-based birth was significantly associated with a higher level of satisfaction with childbirth among the mothers in the study district where maternal and neonatal mortalities are relatively high. The findings of the present study support the promotion of facility-based birth in a rural district of the Lao PDR.

Treatment-seeking behaviour for febrile illnesses and its implications for malaria control and elimination in Savannakhet Province, Lao PDR (Laos): a mixed method study.

BACKGROUND: How people respond to febrile illness is critical to malaria prevention, control, and ultimately elimination. This article explores factors affecting treatment-seeking behaviour for febrile illnesses in a remote area of Lao PDR. METHODS: Household heads or their representatives (n = 281) were interviewed using a structured questionnaire. A total of twelve focus group discussions (FGDs) each with eight to ten participants were conducted in four villages. In addition, observations were recorded as field notes (n = 130) and were used to collect information on the local context, including the treatment seeking behaviour and the health services. RESULTS: Almost three-quarters (201/281) of respondents reported fever in past two months. Most (92%, 185/201) sought treatment of which 80% (149/185) sought treatment at a health centre. Geographic proximity to a health centre (AOR = 6.5; CI = 1.74-24.25; for those < 3.5 km versus those > 3.6 km) and previous experience of attending a health centre (AOR = 4.7; CI = 1.2-19.1) were strong predictors of visiting a health centre for febrile symptoms. During FGDs, respondents described seeking treatment from traditional healers and at health centre for mild to moderate illnesses. Respondents also explained how if symptoms, including fever, were severe or persisted after receiving treatment elsewhere, they sought assistance at health centres. Access to local health centres/hospitals was often constrained by a lack of transportation and an ability to meet the direct and indirect costs of a visit. CONCLUSION: In Nong District, a rural area bordering Vietnam, people seek care from health centres offering allopathic medicine and from spiritual healers. Decisions about where and when to attend health care depended on their economic status, mobility (distance to the health centre, road conditions, availability of transport), symptoms severity and illness recognition. Current and future malaria control/elimination programmes could benefit from greater collaboration with the locally accessible sources of treatments, such as health volunteers and traditional healers.

The dynamic of asymptomatic Plasmodium falciparum infections following mass drug administrations with dihydroarteminisin-piperaquine plus a single low dose of primaquine in Savannakhet Province, Laos.

BACKGROUND: The increase in multidrug resistant Plasmodium falciparum infections threatens the malaria elimination goals in countries within the Greater Mekong Sub-region. A multi-pronged approach assuring access to basic malaria control measures, including insecticide-treated bed nets and early diagnosis and treatment was followed by mass drug administrations (MDA) in southern Savannakhet Province, Laos. The main objective of this study was to evaluate the effectiveness and safety of mass drug administrations as well as their effects on the dynamic of asymptomatic P. falciparum infections in 4 malaria endemic villages. METHODS: Two villages were randomized to early MDA consisting of 3 rounds of a 3-day course of dihydroartemisinin-piperaquine with a single low dose of primaquine. In the other 2 villages MDA was deferred by 1 year. A total of 1036 residents were enrolled in early MDA villages and 883 in control villages (deferred-MDA). Tri-monthly parasitaemia surveys using uPCR were conducted for a year in the 4 villages. RESULTS: Eighty-four percent (872/1036) of the residents participated in the MDAs, of whom 90% (781/872) completed 3 rounds of MDA (9 doses). In intervention villages, the prevalence of asymptomatic P. falciparum infections decreased by 85% after MDA from 4.8% (95% CI 3.4-6.4) at baseline (month 0 or M0) to 0.7% (95% CI 0.3-1.6) at month 12. In control villages there was a decrease of 33% in P. falciparum prevalence between M0: 17.5% (95% CI 15.9-20.3) and M12: 11.6% (95% CI 9.3-14.2). In bivariate and multivariate analyses P. falciparum infections were significantly reduced with early MDA (adjusted incidence rate ratios (AIRR): 0.08, CI 0.01-0.091) and completion of 3 MDA rounds (AIRR: 0.06; CI 0.01-0.66). A quarter of participants (226/872) reported adverse events of which 99% were mild. CONCLUSION: The study found a significant reduction in P. falciparum prevalence and incidence following MDA. MDA was safe, well tolerated, feasible, and achieved high population coverage and adherence. MDAs must be integrated in multi-pronged approaches such as vector control and preventive measures with a focus on specific risk groups such as mobile, migrant population and forest goers for a sustained period to eliminate the remaining parasite reservoirs. Trial registration ClinicalTrials.gov Identifier: NCT01872702.

Why do people participate in mass anti-malarial administration? Findings from a qualitative study in Nong District, Savannakhet Province, Lao PDR (Laos).

BACKGROUND: As a part of targeted malaria elimination (TME) in the Greater Mekong Sub-region (GMS), mass drug administration (MDA) with anti-malarials was conducted in four villages in Nong District, Savannakhet Province, Lao PDR (Laos). A high proportion of the target population participated in the MDA, with over 87% agreeing to take the anti-malarial. Drawing on qualitative data collected alongside the MDA, this article explores the factors that led to this high population coverage. METHODS: Qualitative data collection methods included observations, which were recorded in field notes, focus group discussions (FGDs), and semi-structured interviews (SSIs). Data were collected on local context, MDA-related knowledge, attitudes and perceptions. FGDs and SSIs were audio-recorded, transcribed and translated to English. All transcriptions and field notes underwent qualitative content analysis using QSR NVivo. RESULTS: Respondents recognized malaria as a health concern and described the need for a malaria control program. The risk of malaria including asymptomatic infection was explained in terms of participants' work in forest and fields, and poor hygiene. During the MDA rounds, there was an improvement in knowledge on the concept of asymptomatic malaria, the rationale of MDA and the blood test. In all four villages, poverty affected access to healthcare and the provision of free care by TME was highly appreciated. TME was jointly undertaken by research staff and local volunteers. Authorities were involved in all TME activities. Lao Theung communities were cohesive and community members tended to follow each other's behaviour closely including participation in MDA. Factors such as understanding the concept and rationale of the study, free health care, collaboration with the village volunteers, support from authorities and cohesive communities contributed in building trust and high population coverage in MDA. CONCLUSION: Future malaria control programmes can become successful in achieving the high coverage in MDAs drawing from the success of TME in Laos. A high population coverage in TME was a combination of various factors that included the community engagement to promote the concept and rationale of MDA for asymptomatic malaria in addition to their baseline understanding of malaria as a health concern, provision of free primary health care, partnering of the research with local volunteers and authorities, building social relationship with community members and the cohesive nature of the communities boosted the trust and participation in MDA.

Comparison of glucose-6 phosphate dehydrogenase status by fluorescent spot test and rapid diagnostic test in Lao PDR and Cambodia.

BACKGROUND: Glucose-6-phosphate dehydrogenase (G6PD) deficiency is the most common enzymopathy worldwide. Primaquine is the only licensed drug that effectively removes Plasmodium vivax hypnozoites from the human host and prevents relapse. While well tolerated by most recipients, primaquine can cause haemolysis in G6PD deficient individuals and is, therefore, underused. Rapid diagnostic tests (RDTs) could permit ascertainment of G6PD status outside of laboratory settings and hence safe treatment in remote areas. The performance of the fluorescent spot test (Trinity, Ireland; FST) and a G6PD RDT (Carestart, USA) against spectrophotometry were assessed. METHODS: Participants were enrolled during cross-sectional surveys in Laos and by purposive sampling in Cambodia. FST and RDT were performed during village surveys and 3 mL of venous blood was collected for subsequent G6PD measurement by spectrophotometry. RESULTS: A total of 757 participants were enrolled in Laos and 505 in Cambodia. FST and RDT performed best at 30% cut-off activity and performed significantly better in Laos than in Cambodia. When defining intermediate results as G6PD deficient, the FST had a sensitivity of 100% (95%CI 90-100) and specificity of 90% (95%CI 87.7-92.2) in Laos and sensitivity of 98% (94.1-99.6) and specificity of 71% (95%CI 66-76) in Cambodia (p < 0.001). The RDT had sensitivity and specificity of 100% (95%CI 90-100) and 99% (95%CI 97-99) in Laos and sensitivity and specificity of 91% (86-96) and 93% (90-95) in Cambodia (p < 0.001). The RDT performed significantly better (all p < 0.05) than the FST when intermediate FST results were defined as G6PD deficient. CONCLUSION: The interpretation of RDT results requires some training but is a good alternative to the FST. Trial registration clinicaltrials.gov; NCT01872702; 06/27/2013; https://clinicaltrials.gov/ct2/show/NCT01872702.

Factors associated with population coverage of targeted malaria elimination (TME) in southern Savannakhet Province, Lao PDR.

BACKGROUND: Targeted malaria elimination (TME) in Lao PDR (Laos) included three rounds of mass drug administrations (MDA) against malaria followed by quarterly blood surveys in two villages in Nong District at Savannakhet Province. The success of MDA largely depends upon the efficacy of the anti-malarial drug regimen, local malaria epidemiology and the population coverage. In order to explore the reasons for participation in TME, a quantitative survey was conducted after the completion of the three rounds of MDA. METHODS: The survey was conducted in two villages with a total of 158 households in July and August 2016. Among the 973 villagers eligible for participation in the MDA, 158 (16.2%) adults (> 18 years) were selected, one each from every household for the interviews using a quantitative questionnaire. RESULTS: 150/158 (94.9%) respondents participated at least in one activity (taking medicine or testing their blood) of TME. 141/150 (94.0%) respondents took part in the MDA and tested their blood in all three rounds. 17/158 (10.7%) were partial or non-participants in three rounds of MDA. Characteristics of respondents which were independently associated with completion of three rounds of MDA included: attending TME meetings [AOR = 12.0 (95% CI 1.1-20.5) (p = 0.03)], knowing that malaria can be diagnosed through blood tests [AOR = 5.6 (95% CI 1.0-32.3) (p = 0.05)], all members from household participated [AOR = 4.2 (95% CI 1.3-14.0) (p = 0.02)], liking all aspects of TME [AOR = 17.2 (95% CI 1.6-177.9) (p = 0.02)] and the perception that TME was important [AOR = 14.9 (95% CI 1.3-171.2) (p = 0.03)]. CONCLUSION: Complete participation in TME was significantly associated with participation in community engagement activities, knowledge that the blood tests were for malaria diagnosis, family members' participation at TME and perceptions that TME was worthwhile. A responsive approach to community engagement that includes formative research and the involvement of community members may increase the uptake of the intervention.

Towards malaria elimination in Savannakhet, Lao PDR: mathematical modelling driven strategy design.

BACKGROUND: The number of Plasmodium falciparum malaria cases around the world has decreased substantially over the last 15 years, but with the spread of resistance against anti-malarial drugs and insecticides, this decline may not continue. There is an urgent need to consider alternative, accelerated strategies to eliminate malaria in countries like Lao PDR, where there are a few remaining endemic areas. A deterministic compartmental modelling tool was used to develop an integrated strategy for P. falciparum elimination in the Savannakhet province of Lao PDR. The model was designed to include key aspects of malaria transmission and integrated control measures, along with a user-friendly interface. RESULTS: Universal coverage was the foundation of the integrated strategy, which took the form of the deployment of community health workers who provided universal access to early diagnosis, treatment and long-lasting insecticidal nets. Acceleration was included as the deployment of three monthly rounds of mass drug administration targeted towards high prevalence villages, with the addition of three monthly doses of the RTS,S vaccine delivered en masse to the same high prevalence sub-population. A booster dose of vaccine was added 1 year later. The surveillance-as-intervention component of the package involved the screening and treatment of individuals entering the simulated population. CONCLUSIONS: In this modelling approach, the sequential introduction of a series of five available interventions in an integrated strategy was predicted to be sufficient to stop malaria transmission within a 3-year period. These interventions comprised universal access to early diagnosis and adequate treatment, improved access to long-lasting insecticidal nets, three monthly rounds of mass drug administration together with RTS,S vaccination followed by a booster dose of vaccine, and screening and treatment of imported cases.

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 malaria, growth status, and anaemia among children in Lao People's Democratic Republic: a cross-sectional study.

BACKGROUND: Asymptomatic malaria can be observed in both stable endemic areas and unstable transmission areas. However, although much attention has been given to acute malaria infections, relatively little attention has been paid to asymptomatic malaria. Nonetheless, because the asymptomatic host serves as a reservoir for the malaria parasite, asymptomatic malaria is now recognized as an important obstacle to malaria elimination. Asymptomatic malaria is also associated with anaemia, a global public health problem with serious consequences on human health as well as social and economic development. In Lao People's Democratic Republic (Lao PDR), malaria, anaemia, and malnutrition are serious public health concerns. However, few studies have focused on the relationship between these variables. Therefore, this study investigated the relationship between asymptomatic malaria, growth status, and the prevalence of anaemia among children aged 120 months old or younger in rural villages in Lao PDR. METHODS: In December 2010 and March 2011, data were collected from five villages in Savannakhet province. Anthropometric measurements, blood samples, and malaria rapid diagnostic tests were conducted. The presence of malaria was confirmed with polymerase chain reaction assays for Plasmodium falciparum. Underweight status, stunting, and anaemia were defined according to World Health Organization standards. RESULTS: The mean age of participants (n = 319) was 88.3 months old (Standard Deviation: 20.6, ranged from 30-119 months old), and 20 participants (6.3 %) had an asymptomatic malaria infection, 92 (28.8 %) were anaemic, 123 (38.6 %) were underweight, and 137 (42.9 %) were stunted. Stunted children were more likely to be infected with asymptomatic malaria [odds ratio (OR) 3.34, 95 % confidence interval (CI) 1.25-8.93], and asymptomatic malaria was associated with anaemia [OR 5.17, 95 % CI 1.99-13.43]. CONCLUSIONS: These results suggest a significant association between asymptomatic malaria and anaemia in children. Furthermore, stunted children were more likely to have lower Hb levels and to be infected with asymptomatic malaria than children without stunting. However, further studies examining the impact of asymptomatic malaria infection on children's nutritional and development status are necessary.

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.

First Record of Paramphistomes Fischoederius cobboldi and Paramphistomum epiclitum Detected in Bovine Rumen from a Local Market of Savannakhet Province, Lao PDR.

In the present study, we report on the occurrence of paramphistomes, Fischoederius cobboldi and Paramphistomum epiclitum, in Lao PDR with the basis of molecular data. Parasite materials were collected from bovines bred in Ban Lahanam area, Savannakhet Province, Lao PDR at Lahanam public market. Morphological observations indicated 2 different species of paramphistomes. The mitochondrial gene cox1 of the specimens was successfully amplified by PCR and DNA sequencing was carried out for diagnosis of 11 specimens. Pairwise alignment of cox1 sequences were performed and confirmed F. cobboldi and P. epiclitum infecting bovines in Laos. Although there were many limiting points, as the small number of worm samples, and the restricted access of the animal host materials, we confirmed for the first time that 2 species of paramphistomes, F. cobboldi and P. epiclitum, are distributed in Lao PDR. More studies are needed to confirm the paramphistome species present in Savannakhet and its hosts to clear the natural history of these parasites of ruminants in the region and measure the impact of this parasite infection in the life and health of the local people.