ABSTRACT
The World Health Organization identifies a strong surveillance system for malaria and its mosquito vector as an essential pillar of the malaria elimination agenda. Anopheles salivary antibodies are emerging biomarkers of exposure to mosquito bites that potentially overcome sensitivity and logistical constraints of traditional entomological surveys. Using samples collected by a village health volunteer network in 104 villages in Southeast Myanmar during routine surveillance, the present study employs a Bayesian geostatistical modeling framework, incorporating climatic and environmental variables together with Anopheles salivary antigen serology, to generate spatially continuous predictive maps of Anopheles biting exposure. Our maps quantify fine-scale spatial and temporal heterogeneity in Anopheles salivary antibody seroprevalence (ranging from 9 to 99%) that serves as a proxy of exposure to Anopheles bites and advances current static maps of only Anopheles occurrence. We also developed an innovative framework to perform surveillance of malaria transmission. By incorporating antibodies against the vector and the transmissible form of malaria (sporozoite) in a joint Bayesian geostatistical model, we predict several foci of ongoing transmission. In our study, we demonstrate that antibodies specific for Anopheles salivary and sporozoite antigens are a logistically feasible metric with which to quantify and characterize heterogeneity in exposure to vector bites and malaria transmission. These approaches could readily be scaled up into existing village health volunteer surveillance networks to identify foci of residual malaria transmission, which could be targeted with supplementary interventions to accelerate progress toward elimination.
Subject(s)
Anopheles , Bayes Theorem , Malaria , Mosquito Vectors , Animals , Anopheles/parasitology , Mosquito Vectors/parasitology , Humans , Malaria/transmission , Malaria/epidemiology , Malaria/immunology , Malaria/parasitology , Seroepidemiologic Studies , Insect Bites and Stings/epidemiology , Insect Bites and Stings/immunology , Insect Bites and Stings/parasitology , Sporozoites/immunologyABSTRACT
BACKGROUND: Despite recent reductions in Vietnam, malaria transmission persists in some areas in forests and farmlands where a high density of Anopheles mosquitoes relative to other environments occurs. To inform effective malaria control measures, it is important to understand vector bionomics and the malaria transmission role of Anopheles spp. in the highland regions of Vietnam. This study was conducted to quantify the abundance, composition and biting behaviour of the Anopheles mosquito population, and the proportion of Plasmodium spp. infected mosquitoes collected from forest and agricultural farm sites in Gia Lai province, Vietnam. METHODS: Forest and agricultural farm sites in Gia Lai province were selected for mosquito collections (total eight sites). Mosquito collection was performed by Human-baited Double Net Trap (HDNT), animal-baited traps (ABT) using cattle, and CDC light traps. Captured mosquitoes were identified morphologically, and salivary glands of Anopheles mosquitoes were examined for sporozoites using microscopy. Plasmodium infection was determined by Polymerase Chain Reaction (PCR), and identification of blood meal type was determined by PCR and diffuse serum agglutination assay. RESULTS: A total of 1815 Anopheles mosquitoes belonging to 19 species were collected by ABT (n = 1169), HDNT (n = 471) and CDC light trap (n = 175). Anopheles abundance and diversity varied by district and environment. Capture by HDNT of Anopheles of vectorial concern was observed between early evening and early morning. Plasmodium vivax infection was determined by PCR in two Anopheles dirus specimens captured by HDNT in forest sites. Blood from a range of hosts could, including human blood, could be detected in species considered primary and secondary vectors An. dirus, and Anopheles aconitus, and Anopheles maculatus, respectively. CONCLUSIONS: A low number of Anopheles spp. considered primary vectors of concern and very low numbers of Plasmodium spp. infected Anopheles mosquitoes were captured at the end of the rainy season in the Central Highlands of Vietnam. However, capture species of vectorial concern by HDNT throughout the early to late evening demonstrates that use of additional personal protective measures could supplement current preventative measures, such as bed nets to prevent exposure to vectors of concern in this region.
Subject(s)
Anopheles , Malaria , Plasmodium , Humans , Animals , Cattle , Farms , Vietnam/epidemiology , Mosquito Vectors , Malaria/epidemiology , ForestsABSTRACT
BACKGROUND: Countries of the Greater Mekong Sub-region aim to achieve malaria elimination by 2030. In the region, malaria is concentrated in high-risk areas and populations such as forest-going mobile and migrant populations (MMPs). However, routine protective measures such as long-lasting insecticidal nets do not prevent all infectious bites in these high-risk populations. Evidence for the effectiveness of a personal protection package tailored to forest-going MMPs which is acceptable, feasible, and cost-effective for reducing malaria transmission is required to inform the malaria elimination toolkit in the region. METHODS: A personal protection package consisting of long-lasting insecticidal hammock net, insect repellent and health communication pamphlet was developed in consultation with relevant implementing partners from Cambodia and Lao PDR. An open stepped-wedge cluster-randomised controlled trial will be conducted over a period of 12 months in a minimum of 488 villages (~ 428 in Lao PDR and ~ 60 in Cambodia) to evaluate the effectiveness of the personal protection package. Villages will be randomised into 11 blocks, with blocks transitioned in random order from control to intervention states at monthly intervals, following a 1-month baseline period. The primary outcome of the trial is the prevalence of Plasmodium spp. infection diagnosed by rapid diagnostic test. Difference in prevalence of malaria infection will be estimated across intervention and control periods using generalized linear mixed modelling. Nested within the stepped-wedge cluster-randomised controlled trial is a mixed-methods study to explore the acceptability of the personal protection package, feasibility of implementing a personal protection package as a vector control intervention, and knowledge, attitude and practice of MMPs regarding malaria prevention; and cost-analysis to determine the cost-effectiveness of implementing a personal protection package. DISCUSSION: This study, using a rigorous design and mixed-methods methodology, will evaluate whether a personal protection package can reduce residual malaria transmission among forest-going MMPs in Cambodia and Lao PDR. It will also measure implementation research outcomes such as effectiveness of the intervention package, cost-effectiveness, acceptability, and feasibility, in order to inform potential national and regional policy. Trial registration This trial was prospectively registered on ClinicalTrials.gov (NCT05117567) on 11th November 2021.
Subject(s)
Insect Repellents , Insecticides , Malaria , Transients and Migrants , Cambodia/epidemiology , Forests , Humans , Laos/epidemiology , Malaria/epidemiology , Malaria/prevention & control , Randomized Controlled Trials as TopicABSTRACT
In the Lao People's Democratic Republic (Lao PDR), village health volunteers play an important role in providing health services including those to reduce the burden of malaria. Over the last two decades, the volunteer network has expanded to bring malaria services closer to communities and contributed to the reduction of malaria cases. However, as malaria test positivity rates decreased, many volunteers have lost motivation to continue providing routine malaria services, and other services they provide may not reflect growing healthcare demands for common diseases in the community. This study explored the perspectives, knowledge and inputs of key health stakeholders and community members in southern Lao PDR on community-delivered models in order to refine the volunteer model in the context of Lao PDR's primary health care sector and malaria elimination goals. Semi-structured interviews with multi-level health stakeholders, participatory workshops with community leaders, and focus group discussions with community members and current village health volunteers were conducted. Deductive followed by inductive thematic analysis was used to explore and categorise stakeholders' perspectives on community-delivered models for malaria elimination. Both stakeholders and community members agreed that village health volunteers are essential providers of malaria services in rural communities. Apart from malaria, community members identified dengue, diarrhoea, influenza, skin infections and tuberculosis as priorities (in descending order of importance) and requested community-based primary health care for these diseases. Stakeholders and community members suggested integrating prevention, diagnosis, and treatment services for the five priority diseases into the current malaria volunteer model. A divergence was identified between community members' expectations of health services and the services currently provided by village health volunteers. Stakeholders proposed an integrated model of healthcare to meet the needs of the community and help to maintain volunteers' motivation and the long-term sustainability of the role. An evidence-based, integrated community-delivered model of healthcare should be developed to balance the needs of both community members and stakeholders, with consideration of available resources and current health policies in Lao PDR.
Subject(s)
Malaria , Humans , Laos/epidemiology , Malaria/epidemiology , Malaria/prevention & control , Qualitative Research , Rural Population , VolunteersABSTRACT
INTRODUCTION: In the Greater Mekong Subregion, community health workers, known as malaria volunteers, have played a key role in reducing malaria in the control phase, providing essential malaria services in areas with limited formal healthcare. However, the motivation and social role of malaria volunteers, and testing rates, have declined with decreasing malaria burden and reorientation of malaria programmes from control to elimination. Provision of additional interventions for common health concerns could help sustain the effectiveness of volunteers and maintain malaria testing rates required for malaria elimination accreditation by the WHO. METHODS AND ANALYSIS: The Community-delivered Integrated Malaria Elimination (CIME) volunteer model, integrating interventions for malaria, dengue, tuberculosis, childhood diarrhoea and malaria Rapid Diagnostic Test (RDT)-negative fever, was developed based on global evidence and extensive stakeholder consultations. An open stepped-wedge cluster-randomised controlled trial, randomised at the volunteer level, will be conducted over 6 months to evaluate the effectiveness of the CIME model in Myanmar. One hundred and forty Integrated Community Malaria Volunteers (ICMVs, current model of care) providing malaria services in 140 villages will be retrained as CIME volunteers (intervention). These 140 ICMVs/villages will be grouped into 10 blocks of 14 villages, with blocks transitioned from control (ICMV) to intervention states (CIME), fortnightly, in random order, following a 1-week training and transition period. The primary outcome of the trial is blood examination rate determined by the number of malaria RDTs performed weekly. Difference in rates will be estimated across village intervention and control states using a generalised linear mixed modelling analytical approach with maximum likelihood estimation. ETHICS AND DISSEMINATION: The study was approved by Institutional Review Board, Myanmar Department of Medical Research (Ethics/DMR/2020/111) and Alfred Hospital Ethics Review Committee, Australia (241/20). Findings will be disseminated in peer-review journals, conferences and regional, national and local stakeholder meetings. TRIAL REGISTRATION NUMBER: NCT04695886.
Subject(s)
Malaria , Child , Community Health Workers , Cost-Benefit Analysis , Humans , Malaria/prevention & control , Myanmar , Randomized Controlled Trials as Topic , VolunteersABSTRACT
BACKGROUND: In the Greater Mekong Subregion (GMS), current malaria surveillance strategies rely on a network of village health volunteers (VHVs) reporting the results of rapid diagnostic tests (RDTs), known to miss many asymptomatic infections. Integration of more sensitive diagnostic molecular and serological measures into the VHV network may improve surveillance of residual malaria transmission in hard-to-reach areas in the region and inform targeted interventions and elimination responses. However, data on residual malaria transmission that would be captured by these measures in the VHV-led testing and treatment surveillance network in the GMS is unknown. METHODS: A total of 114 VHVs were trained to collect dried blood spots from villagers undergoing routine RDTs as part of VHV-led active and passive case detection from April 2015 to June 2016. Samples were subjected to molecular testing (quantitative polymerase chain reaction [qPCR]) to determine Plasmodium falciparum and P. vivax infection and serological testing (against P. falciparum and P. vivax antigens) to determine exposure to P. falciparum and P. vivax. RESULTS: Over 15 months, 114 VHVs performed 32,194 RDTs and collected samples for molecular (n = 13,157) and serological (n = 14,128) testing. The prevalence of molecular-detectable P. falciparum and P. vivax infection was 3.2% compared to the 0.16% prevalence of Plasmodium spp. by RDT, highlighting the large burden of infections undetected by standard surveillance. Peaks in anti-P. falciparum, but not P. vivax, merozoite IgG seroprevalence coincided with seasonal P. falciparum transmission peaks, even in those with no molecularly detectable parasites. At the individual level, antibody seropositivity was associated with reduced odds of contemporaneous P. falciparum (OR for PfCSP 0.51 [95%CI 0.35, 0.76], p = 0.001, PfAMA1 0.70 [95%CI 0.52, 0.93], p = 0.01, and PfMSP2 0.81 [95%CI 0.61, 1.08], p = 0.15), but not P. vivax infection (OR PvAMA1 1.02 [95%CI 0.73, 1.43], p = 0.89) indicating a potential role of immunity in protection against molecular-detectable P. falciparum parasitaemia. CONCLUSIONS: We demonstrated that integration and implementation of sample collection for molecular and serological surveillance into networks of VHV servicing hard-to-reach populations in the GMS is feasible, can capture significant levels of ongoing undetected seasonal malaria transmission and has the potential to supplement current routine RDT testing. Improving malaria surveillance by advancing the integration of molecular and serological techniques, through centralised testing approaches or novel point-of-contact tests, will advance progress, and tracking, towards malaria elimination goals in the GMS.