Hotspots and super-spreaders: Modelling fine-scale malaria parasite transmission using mosquito flight behaviour.

Malaria hotspots have been the focus of public health managers for several years due to the potential elimination gains that can be obtained from targeting them. The identification of hotspots must be accompanied by the description of the overall network of stable and unstable hotspots of malaria, especially in medium and low transmission settings where malaria elimination is targeted. Targeting hotspots with malaria control interventions has, so far, not produced expected benefits. In this work we have employed a mechanistic-stochastic algorithm to identify clusters of super-spreader houses and their related stable hotspots by accounting for mosquito flight capabilities and the spatial configuration of malaria infections at the house level. Our results show that the number of super-spreading houses and hotspots is dependent on the spatial configuration of the villages. In addition, super-spreaders are also associated to house characteristics such as livestock and family composition. We found that most of the transmission is associated with winds between 6pm and 10pm although later hours are also important. Mixed mosquito flight (downwind and upwind both with random components) were the most likely movements causing the spread of malaria in two out of the three study areas. Finally, our algorithm (named MALSWOTS) provided an estimate of the speed of malaria infection progression from house to house which was around 200-400 meters per day, a figure coherent with mark-release-recapture studies of Anopheles dispersion. Cross validation using an out-of-sample procedure showed accurate identification of hotspots. Our findings provide a significant contribution towards the identification and development of optimal tools for efficient and effective spatio-temporal targeted malaria interventions over potential hotspot areas.

Genotyping Plasmodium falciparum gametocytes using amplicon deep sequencing.

BACKGROUND: Understanding the dynamics of gametocyte production in polyclonal Plasmodium falciparum infections requires a genotyping method that detects distinct gametocyte clones and estimates their relative frequencies. Here, a marker was identified and evaluated to genotype P. falciparum mature gametocytes using amplicon deep sequencing. METHODS: A data set of polymorphic regions of the P. falciparum genome was mined to identify a gametocyte genotyping marker. To assess marker resolution, the number of unique haplotypes in the marker region was estimated from 95 Malawian P. falciparum whole genome sequences. Specificity of the marker for detection of mature gametocytes was evaluated using reverse transcription-polymerase chain reaction of RNA extracted from NF54 mature gametocytes and rings from a non-gametocyte-producing strain of P. falciparum. Amplicon deep sequencing was performed on experimental mixtures of mature gametocytes from two distinct parasite clones, as well as gametocyte-positive P. falciparum field isolates to evaluate the quantitative ability and determine the limit of detection of the genotyping approach. RESULTS: A 400 bp region of the pfs230 gene was identified as a gametocyte genotyping marker. A larger number of unique haplotypes was observed at the pfs230 marker (34) compared to the sera-2 (18) and ama-1 (14) markers in field isolates from Malawi. RNA and DNA genotyping accurately estimated gametocyte and total parasite clone frequencies when evaluating agreement between expected and observed haplotype frequencies in gametocyte mixtures, with concordance correlation coefficients of 0.97 [95% CI: 0.92-0.99] and 0.92 [95% CI: 0.83-0.97], respectively. The detection limit of the genotyping method for male gametocytes was 0.41 pfmget transcripts/µl [95% CI: 0.28-0.72] and for female gametocytes was 1.98 ccp4 transcripts/µl [95% CI: 1.35-3.68]. CONCLUSIONS: A region of the pfs230 gene was identified as a marker to genotype P. falciparum gametocytes. Amplicon deep sequencing of this marker can be used to estimate the number and relative frequency of parasite clones among mature gametocytes within P. falciparum infections. This gametocyte genotyping marker will be an important tool for studies aimed at understanding dynamics of gametocyte production in polyclonal P. falciparum infections.

Assessing the implementation fidelity, feasibility, and sustainability of community-based house improvement for malaria control in southern Malawi: a mixed-methods study.

BACKGROUND: Despite significant success in the fight against malaria over the past two decades, malaria control programmes rely on only two insecticidal methods: indoor residual spraying and insecticidal-treated nets. House improvement (HI) can complement these interventions by reducing human-mosquito contact, thereby reinforcing the gains in disease reduction. This study assessed the implementation fidelity, which is the assessment of how closely an intervention aligns with its intended design, feasibility, and sustainability of community-led HI in southern Malawi. METHODS: The study, conducted in 22 villages (2730 households), employed a mixed-methods approach. Implementation fidelity was assessed using a modified framework, with longitudinal surveys collecting data on HI coverage indicators. Quantitative analysis, employing descriptive statistics, evaluated the adherence to HI implementation. Qualitative data came from in-depth interviews, key informant interviews, and focus groups involving project beneficiaries and implementers. Qualitative data were analysed using content analysis guided by the implementation fidelity model to explore facilitators, challenges, and factors affecting intervention feasibility. RESULTS: The results show that HI was implemented as planned. There was good adherence to the intended community-led HI design; however, the adherence could have been higher but gradually declined over time. In terms of intervention implementation, 74% of houses had attempted to have eaves closed in 2016-17 and 2017-18, compared to 70% in 2018-19. In 2016-17, 42% of houses had all four sides of the eaves closed, compared to 33% in 2018-19. Approximately 72% of houses were screened with gauze wire in 2016-17, compared to 57% in 2018-19. High costs, supply shortages, labour demands, volunteers' poor living conditions and adverse weather were reported to hinder the ideal HI implementation. Overall, the community described community-led HI as feasible and could be sustained by addressing these socioeconomic and contextual challenges. CONCLUSION: Our study found that although HI was initially implemented as planned, its fidelity declined over time. Using trained volunteers facilitated the fidelity and feasibility of implementing the intervention. A combination of rigorous community education, consistent training, information, education and communication, and intervention modifications may be necessary to address the challenges and enhance the intervention's fidelity, feasibility, and sustainability.

Impact of cattle on the abundance of indoor and outdoor resting malaria vectors in southern Malawi.

BACKGROUND: Understanding the blood feeding preferences and resting habits of malaria vectors is important for assessing and designing effective malaria vector control tools. The presence of livestock, such as cattle, which are used as blood meal hosts by some malaria vectors, may impact malaria parasite transmission dynamics. The presence of livestock may provide sufficient blood meals for the vectors, thereby reducing the frequency of vectors biting humans. Alternatively, the presence of cattle may enhance the availability of blood meals such that infectious mosquitoes may survive longer, thereby increasing the risk of malaria transmission. This study assessed the effect of household-level cattle presence and distribution on the abundance of indoor and outdoor resting malaria vectors. METHODS: Houses with and without cattle were selected in Chikwawa district, southern Malawi for sampling resting malaria vectors. Prokopack aspirators and clay pots were used for indoor and outdoor sampling, respectively. Each house was sampled over two consecutive days. For houses with cattle nearby, the number of cattle and the distances from the house to where the cattle were corralled the previous night were recorded. All data were analysed using generalized linear models fitted with Poisson distribution. RESULTS: The malaria vectors caught resting indoors were Anopheles gambiae sensu stricto (s.s.), Anopheles arabiensis and Anopheles funestus s.s. Outdoor collections consisted primarily of An. arabiensis. The catch sizes of indoor resting An. gambiae sensu lato (s.l.) were not different in houses with and without cattle (P = 0.34). The presence of cattle near a house was associated with a reduction in the abundance of indoor resting An. funestus s.l. (P = 0.04). This effect was strongest when cattle were kept overnight ≤ 15 m away from the houses (P = 0.03). The blood meal hosts varied across the species. CONCLUSION: These results highlight differences between malaria vector species and their interactions with potential blood meal hosts, which may have implications for malaria risk. Whereas An. arabiensis remained unaffected, the reduction of An. funestus s.s. in houses near cattle suggests a potential protective effect of cattle. However, the low abundance of mosquitoes reduced the power of some analyses and limited the generalizability of the results to other settings. Therefore, further studies incorporating the vectors' host-seeking behaviour/human biting rates are recommended to fully support the primary finding.

Incidence of clinical malaria, acute respiratory illness, and diarrhoea in children in southern Malawi: a prospective cohort study.

BACKGROUND: Malaria, acute respiratory infections (ARIs) and diarrhoea are the leading causes of morbidity and mortality among children under 5 years old. Estimates of the malaria incidence are available from a previous study conducted in southern Malawi in the absence of community-led malaria control strategies; however, the incidence of the other diseases is lacking, owing to understudying and competing disease priorities. Extensive malaria control measures through a community participation strategy were implemented in Chikwawa, southern Malawi from May 2016 to reduce parasite prevalence and incidence. This study assessed the incidence of clinical malaria, ARIs and acute diarrhoea among under-five children in a rural community involved in malaria control through community participation. METHODS: A prospective cohort study was conducted from September 2017 to May 2019 in Chikwawa district, southern Malawi. Children aged 6-48 months were recruited from a series of repeated cross-sectional household surveys. Recruited children were followed up two-monthly for 1 year to record details of any clinic visits to designated health facilities. Incidence of clinical malaria, ARIs and diarrhoea per child-years at risk was estimated, compared between age groups, area of residence and time. RESULTS: A total of 274 out of 281 children recruited children had complete results and contributed 235.7 child-years. Malaria incidence was 0.5 (95% CI (0.4, 0.5)) cases per child-years at risk, (0.04 in 6.0-11.9 month-olds, 0.5 in 12.0-23.9 month-olds, 0.6 in 24.0-59.9 month-olds). Incidences of ARIs and diarrhoea were 0.3 (95% CI (0.2, 0.3)), (0.1 in 6.0-11.9 month-olds, 0.4 in 12.0-23.9 month-olds, 0.3 in 24.0-59.9 month-olds), and 0.2 (95% CI (0.2, 0.3)), (0.1 in 6.0-11.9 month-olds, 0.3 in 12.0-23.9 month-olds, 0.2 in 24.0-59.9 month-olds) cases per child-years at risk, respectively. There were temporal variations of malaria and ARI incidence and an overall decrease over time. CONCLUSION: In comparison to previous studies, there was a lower incidence of clinical malaria in Chikwawa. The incidence of ARIs and diarrhoea were also low and decreased over time. The results are promising because they highlight the importance of community participation and the integration of malaria prevention strategies in contributing to disease burden reduction.

Cost of community-led larval source management and house improvement for malaria control: a cost analysis within a cluster-randomized trial in a rural district in Malawi.

BACKGROUND: House improvement (HI) to prevent mosquito house entry, and larval source management (LSM) targeting aquatic mosquito stages to prevent development into adult forms, are promising complementary interventions to current malaria vector control strategies. Lack of evidence on costs and cost-effectiveness of community-led implementation of HI and LSM has hindered wide-scale adoption. This study presents an incremental cost analysis of community-led implementation of HI and LSM, in a cluster-randomized, factorial design trial, in addition to standard national malaria control interventions in a rural area (25,000 people), in southern Malawi. METHODS: In the trial, LSM comprised draining, filling, and Bacillus thuringiensis israelensis-based larviciding, while house improvement (henceforth HI) involved closing of eaves and gaps on walls, screening windows/ventilation spaces with wire mesh, and doorway modifications. Communities implemented all interventions. Costs were estimated retrospectively using the 'ingredients approach', combining 'bottom-up' and 'top-down approaches', from the societal perspective. To estimate the cost of independently implementing each intervention arm, resources shared between trial arms (e.g. overheads) were allocated to each consuming arm using proxies developed based on share of resource input quantities consumed. Incremental implementation costs (in 2017 US$) are presented for HI-only, LSM-only and HI + LSM arms. In sensitivity analyses, the effect of varying costs of important inputs on estimated costs was explored. RESULTS: The total economic programme costs of community-led HI and LSM implementation was $626,152. Incremental economic implementation costs of HI, LSM and HI + LSM were estimated as $27.04, $25.06 and $33.44, per person per year, respectively. Project staff, transport and labour costs, but not larvicide or screening material, were the major cost drivers across all interventions. Costs were sensitive to changes in staff costs and population covered. CONCLUSIONS: In the trial, the incremental economic costs of community-led HI and LSM implementation were high compared to previous house improvement and LSM studies. Several factors, including intervention design, year-round LSM implementation and low human population density could explain the high costs. The factorial trial design necessitated use of proxies to allocate costs shared between trial arms, which limits generalizability where different designs are used. Nevertheless, costs may inform planners of similar intervention packages where cost-effectiveness is known. Trial registration Not applicable. The original trial was registered with The Pan African Clinical Trials Registry on 3 March 2016, trial number PACTR201604001501493.

The effect of community-driven larval source management and house improvement on malaria transmission when added to the standard malaria control strategies in Malawi: a cluster-randomized controlled trial.

BACKGROUND: Current standard interventions are not universally sufficient for malaria elimination. The effects of community-based house improvement (HI) and larval source management (LSM) as supplementary interventions to the Malawi National Malaria Control Programme (NMCP) interventions were assessed in the context of an intensive community engagement programme. METHODS: The study was a two-by-two factorial, cluster-randomized controlled trial in Malawi. Village clusters were randomly assigned to four arms: a control arm; HI; LSM; and HI + LSM. Malawi NMCP interventions and community engagement were used in all arms. Household-level, cross-sectional surveys were conducted on a rolling, 2-monthly basis to measure parasitological and entomological outcomes over 3 years, beginning with one baseline year. The primary outcome was the entomological inoculation rate (EIR). Secondary outcomes included mosquito density, Plasmodium falciparum prevalence, and haemoglobin levels. All outcomes were assessed based on intention to treat, and comparisons between trial arms were conducted at both cluster and household level. RESULTS: Eighteen clusters derived from 53 villages with 4558 households and 20,013 people were randomly assigned to the four trial arms. The mean nightly EIR fell from 0.010 infectious bites per person (95% CI 0.006-0.015) in the baseline year to 0.001 (0.000, 0.003) in the last year of the trial. Over the full trial period, the EIR did not differ between the four trial arms (p = 0.33). Similar results were observed for the other outcomes: mosquito density and P. falciparum prevalence decreased over 3 years of sampling, while haemoglobin levels increased; and there were minimal differences between the trial arms during the trial period. CONCLUSIONS: In the context of high insecticide-treated bed net use, neither community-based HI, LSM, nor HI + LSM contributed to further reductions in malaria transmission or prevalence beyond the reductions observed over two years across all four trial arms. This was the first trial, as far as the authors are aware, to test the potential complementary impact of LSM and/or HI beyond levels achieved by standard interventions. The unexpectedly low EIR values following intervention implementation indicated a promising reduction in malaria transmission for the area, but also limited the usefulness of this outcome for measuring differences in malaria transmission among the trial arms. Trial registration PACTR, PACTR201604001501493, Registered 3 March 2016, https://pactr.samrc.ac.za/ .

Community factors affecting participation in larval source management for malaria control in Chikwawa District, Southern Malawi.

BACKGROUND: To further reduce malaria, larval source management (LSM) is proposed as a complementary strategy to the existing strategies. LSM has potential to control insecticide resistant, outdoor biting and outdoor resting vectors. Concerns about costs and operational feasibility of implementation of LSM at large scale are among the reasons the strategy is not utilized in many African countries. Involving communities in LSM could increase intervention coverage, reduce costs of implementation and improve sustainability of operations. Community acceptance and participation in community-led LSM depends on a number of factors. These factors were explored under the Majete Malaria Project in Chikwawa district, southern Malawi. METHODS: Separate focus group discussions (FGDs) were conducted with members from the general community (n = 3); health animators (HAs) (n = 3); and LSM committee members (n = 3). In-depth interviews (IDIs) were conducted with community members. Framework analysis was employed to determine the factors contributing to community acceptance and participation in the locally-driven intervention. RESULTS: Nine FGDs and 24 IDIs were held, involving 87 members of the community. Widespread knowledge of malaria as a health problem, its mode of transmission, mosquito larval habitats and mosquito control was recorded. High awareness of an association between creation of larval habitats and malaria transmission was reported. Perception of LSM as a tool for malaria control was high. The use of a microbial larvicide as a form of LSM was perceived as both safe and effective. However, actual participation in LSM by the different interviewee groups varied. Labour-intensiveness and time requirements of the LSM activities, lack of financial incentives, and concern about health risks when wading in water bodies contributed to lower participation. CONCLUSION: Community involvement in LSM increased local awareness of malaria as a health problem, its risk factors and control strategies. However, community participation varied among the respondent groups, with labour and time demands of the activities, and lack of incentives, contributing to reduced participation. Innovative tools that can reduce the labour and time demands could improve community participation in the activities. Further studies are required to investigate the forms and modes of delivery of incentives in operational community-driven LSM interventions.

Assessment of the Suna trap for sampling mosquitoes indoors and outdoors.

BACKGROUND: Entomological monitoring is important for public health because it provides data on the distribution, abundance and host-seeking behaviour of disease vectors. Various methods for sampling mosquitoes exist, most of which are biased towards, or specifically target, certain portions of a mosquito population. This study assessed the Suna trap, an odour-baited trap for sampling host-seeking mosquitoes both indoors and outdoors. METHODS: Two separate field experiments were conducted in villages in southern Malawi. The efficiency of the Suna trap in sampling mosquitoes was compared to that of the human landing catch (HLC) indoors and outdoors and the Centers for Disease, Control and Prevention Light Trap (CDC-LT) indoors. Potential competition between two Suna traps during simultaneous use of the traps indoors and outdoors was assessed by comparing mosquito catch sizes across three treatments: one trap indoors only; one trap outdoors only; and one trap indoors and one trap outdoors used simultaneously at the same house. RESULTS: The efficiency of the Suna trap in sampling female anophelines was similar to that of HLC indoors (P = 0.271) and HLC outdoors (P = 0.125), but lower than that of CDC-LT indoors (P = 0.001). Anopheline catch sizes in the Suna trap used alone indoors were similar to indoor Suna trap catch sizes when another Suna trap was simultaneously present outdoors (P = 0.891). Similarly, catch sizes of female anophelines with the Suna trap outdoors were similar to those that were caught outdoors when another Suna trap was simultaneously present indoors (P = 0.731). CONCLUSIONS: The efficiency of the Suna trap in sampling mosquitoes was equivalent to that of the HLC. Whereas the CDC-LT was more efficient in collecting female anophelines indoors, the use of this trap outdoors is limited given the requirement of setting it next to an occupied bed net. As demonstrated in this research, outdoor collections are also essential because they provide data on the relative contribution of outdoor biting to malaria transmission. Therefore, the Suna trap could serve as an alternative to the HLC and the CDC-LT, because it does not require the use of humans as natural baits, allows standardised sampling conditions across sampling points, and can be used outdoors. Furthermore, using two Suna traps simultaneously indoors and outdoors does not interfere with the sampling efficiency of either trap, which would save a considerable amount of time, energy, and resources compared to setting the traps indoors and then outdoors in two consecutive nights.

The role of health animators in malaria control: a qualitative study of the health animator (HA) approach within the Majete malaria project (MMP) in Chikwawa District, Malawi.

BACKGROUND: Malaria continues to place a high burden on communities due to challenges reaching intervention target levels in Chikwawa District, Malawi. The Hunger Project Malawi is using a health animator approach (HA) to address gaps in malaria control coverage. We explored the influence of community-based volunteers known as health animators (HAs) in malaria control. We assessed the impact of HAs on knowledge, attitudes, and practices towards malaria interventions. METHODS: This paper draws on the qualitative data collected to explore the roles of communities, HAs and formal health workers attending and not attending malaria workshops for malaria control. Purposive sampling was used to select 78 respondents. We conducted 10 separate focus group discussions (FGDs)-(n = 6) with community members and (n = 4) key informants. Nine in-depth interviews (IDIs) were held with HAs and Health Surveillance Assistants (HSAs) in three focal areas near Majete Wildlife Reserve. Nvivo 11 was used for coding and analysis. We employed the framework analysis and social capital theory to determine how the intervention influenced health and social outcomes. RESULTS: Using education, feedback sessions and advocacy in malaria workshop had mixed outcomes. There was a high awareness of community participation and comprehensive knowledge of the HA approach as key to malaria control. HAs were identified as playing a complementary role in malaria intervention. Community members' attitudes towards advocacy for better health services were poor. Attendance in malaria workshops was sporadic towards the final year of the intervention. Respondents mentioned positive attitudes and practices on net usage for prevention and prompt health-seeking behaviours. CONCLUSION: The HA approach is a useful strategy for complementing malaria prevention strategies in rural communities and improving practices for health-seeking behaviour. Various factors influence HAs' motivation, retention, community engagement, and programme sustainability. However, little is known about how these factors interact to influence volunteers' motivation, community participation and sustainability over time. More research is needed to explore the acceptability of an HA approach and the impact on malaria control in other rural communities in Malawi.

Community-based malaria control in southern Malawi: a description of experimental interventions of community workshops, house improvement and larval source management.

BACKGROUND: Increased engagement of communities has been emphasized in global plans for malaria control and elimination. Three interventions to reinforce and complement national malaria control recommendations were developed and applied within the context of a broad-based development initiative, targeting a rural population surrounding a wildlife reserve. The interventions, which were part of a 2-year research trial, and assigned to the village level, were implemented through trained local volunteers, or 'health animators', who educated the community and facilitated collective action. RESULTS: Community workshops on malaria were designed to increase uptake of national recommendations; a manual was developed, and training of health animators conducted, with educational content and analytical tools for a series of fortnightly community workshops in annual cycles at village level. The roll-back malaria principle of diagnosis, treatment and use of long-lasting insecticidal nets was a central component of the workshops. Structural house improvement to reduce entry of malaria vectors consisted of targeted activities in selected villages to mobilize the community into voluntarily closing the eaves and screening the windows of their houses; the project provided wire mesh for screening. Corrective measures were introduced to respond to field challenges. Committees were established at village level to coordinate the house improvement activities. Larval source management (LSM) in selected villages consisted of two parts: one on removal of standing water bodies by the community at large; and one on larviciding with bacterial insecticide Bacillus thuringiensis israelensis by trained village committees. Community workshops on malaria were implemented as 'core intervention' in all villages. House improvement and LSM were implemented in addition to community workshops on malaria in selected villages. CONCLUSIONS: Three novel interventions for community mobilization on malaria prevention and control were described. The interventions comprised local organizational structure, education and collective action, and incorporated elements of problem identification, planning and evaluation. These methods could be applicable to other countries and settings.

Explaining variation in adult Anopheles indoor resting abundance: the relative effects of larval habitat proximity and insecticide-treated bed net use.

BACKGROUND: Spatial determinants of malaria risk within communities are associated with heterogeneity of exposure to vector mosquitoes. The abundance of adult malaria vectors inside people's houses, where most transmission takes place, should be associated with several factors: proximity of houses to larval habitats, structural characteristics of houses, indoor use of vector control tools containing insecticides, and human behavioural and environmental factors in and near houses. While most previous studies have assessed the association of larval habitat proximity in landscapes with relatively low densities of larval habitats, in this study these relationships were analysed in a region of rural, lowland western Kenya with high larval habitat density. METHODS: 525 houses were sampled for indoor-resting mosquitoes across an 8 by 8 km study area using the pyrethrum spray catch method. A predictive model of larval habitat location in this landscape, previously verified, provided derivations of indices of larval habitat proximity to houses. Using geostatistical regression models, the association of larval habitat proximity, long-lasting insecticidal nets (LLIN) use, house structural characteristics (wall type, roof type), and peridomestic variables (cooking in the house, cattle near the house, number of people sleeping in the house) with mosquito abundance in houses was quantified. RESULTS: Vector abundance was low (mean, 1.1 adult Anopheles per house). Proximity of larval habitats was a strong predictor of Anopheles abundance. Houses without an LLIN had more female Anopheles gambiae s.s., Anopheles arabiensis and Anopheles funestus than houses where some people used an LLIN (rate ratios, 95% CI 0.87, 0.85-0.89; 0.84, 0.82-0.86; 0.38, 0.37-0.40) and houses where everyone used an LLIN (RR, 95% CI 0.49, 0.48-0.50; 0.39, 0.39-0.40; 0.60, 0.58-0.61). Cooking in the house also reduced Anopheles abundance across all species. The number of people sleeping in the house, presence of cattle near the house, and house structure modulated Anopheles abundance, but the effect varied with Anopheles species and sex. CONCLUSIONS: Variation in the abundance of indoor-resting Anopheles in rural houses of western Kenya varies with clearly identifiable factors. Results suggest that LLIN use continues to function in reducing vector abundance, and that larval source management in this region could lead to further reductions in malaria risk by reducing the amount of an obligatory resource for mosquitoes near people's homes.

Assessment of the effect of larval source management and house improvement on malaria transmission when added to standard malaria control strategies in southern Malawi: study protocol for a cluster-randomised controlled trial.

BACKGROUND: Due to outdoor and residual transmission and insecticide resistance, long-lasting insecticidal nets (LLINs) and indoor residual spraying (IRS) will be insufficient as stand-alone malaria vector control interventions in many settings as programmes shift toward malaria elimination. Combining additional vector control interventions as part of an integrated strategy would potentially overcome these challenges. Larval source management (LSM) and structural house improvements (HI) are appealing as additional components of an integrated vector management plan because of their long histories of use, evidence on effectiveness in appropriate settings, and unique modes of action compared to LLINs and IRS. Implementation of LSM and HI through a community-based approach could provide a path for rolling-out these interventions sustainably and on a large scale. METHODS/DESIGN: We will implement community-based LSM and HI, as additional interventions to the current national malaria control strategies, using a randomised block, 2 × 2 factorial, cluster-randomised design in rural, southern Malawi. These interventions will be continued for two years. The trial catchment area covers about 25,000 people living in 65 villages. Community participation is encouraged by training community volunteers as health animators, and supporting the organisation of village-level committees in collaboration with The Hunger Project, a non-governmental organisation. Household-level cross-sectional surveys, including parasitological and entomological sampling, will be conducted on a rolling, 2-monthly schedule to measure outcomes over two years (2016 to 2018). Coverage of LSM and HI will also be assessed throughout the trial area. DISCUSSION: Combining LSM and/or HI together with the interventions currently implemented by the Malawi National Malaria Control Programme is anticipated to reduce malaria transmission below the level reached by current interventions alone. Implementation of LSM and HI through a community-based approach provides an opportunity for optimum adaptation to the local ecological and social setting, and enhances the potential for sustainability. TRIAL REGISTRATION: Registered with The Pan African Clinical Trials Registry on 3 March 2016, trial number PACTR201604001501493.

Malaria control in rural Malawi: implementing peer health education for behaviour change.

BACKGROUND: Interventions to reduce malaria burden are effective if communities use them appropriately and consistently. Several tools have been suggested to promote uptake and use of malaria control interventions. Community workshops on malaria, using the 'Health Animator' approach, are a potential behaviour change strategy for malaria control. The strategy aims to influence a change in mind-set of vulnerable populations to encourage self-reliance, using community volunteers known as Health Animators. The aim of the paper is to describe the process of implementing community workshops on malaria by Health Animators to improve uptake and use of malaria control interventions in rural Malawi. METHODS: This is a descriptive study reporting feasibility, acceptability, appropriateness and fidelity of using Health Animator-led community workshops for malaria control. Quantitative data were collected from self-reporting and researcher evaluation forms. Qualitative assessments were done with Health Animators, using three focus groups (October-December 2015) and seven in-depth interviews (October 2016-February 2017). RESULTS: Seventy seven health Animators were trained from 62 villages. A total of 2704 workshops were conducted, with consistent attendance from January 2015 to June 2017, representing 10-17% of the population. Attendance was affected by social responsibilities and activities, relationship of the village leaders and their community and involvement of Community Health Workers. Active discussion and participation were reported as main strengths of the workshops. Health Animators personally benefited from the mind-set change and were proactive peer influencers in the community. Although the information was comprehended and accepted, availability of adequate health services was a challenge for maintenance of behaviour change. CONCLUSION: Community workshops on malaria are a potential tool for influencing a positive change in behaviour towards malaria, and applicable for other health problems in rural African communities. Social structures of influence and power dynamics affect community response. There is need for systematic monitoring of community workshops to ensure implementation fidelity and strengthening health systems to ensure sustainability of health behaviour change.

Modeling larval malaria vector habitat locations using landscape features and cumulative precipitation measures.

BACKGROUND: Predictive models of malaria vector larval habitat locations may provide a basis for understanding the spatial determinants of malaria transmission. METHODS: We used four landscape variables (topographic wetness index [TWI], soil type, land use-land cover, and distance to stream) and accumulated precipitation to model larval habitat locations in a region of western Kenya through two methods: logistic regression and random forest. Additionally, we used two separate data sets to account for variation in habitat locations across space and over time. RESULTS: Larval habitats were more likely to be present in locations with a lower slope to contributing area ratio (i.e. TWI), closer to streams, with agricultural land use relative to nonagricultural land use, and in friable clay/sandy clay loam soil and firm, silty clay/clay soil relative to friable clay soil. The probability of larval habitat presence increased with increasing accumulated precipitation. The random forest models were more accurate than the logistic regression models, especially when accumulated precipitation was included to account for seasonal differences in precipitation. The most accurate models for the two data sets had area under the curve (AUC) values of 0.864 and 0.871, respectively. TWI, distance to the nearest stream, and precipitation had the greatest mean decrease in Gini impurity criteria in these models. CONCLUSIONS: This study demonstrates the usefulness of random forest models for larval malaria vector habitat modeling. TWI and distance to the nearest stream were the two most important landscape variables in these models. Including accumulated precipitation in our models improved the accuracy of larval habitat location predictions by accounting for seasonal variation in the precipitation. Finally, the sampling strategy employed here for model parameterization could serve as a framework for creating predictive larval habitat models to assist in larval control efforts.

Variation in spatial population structure in the Anopheles gambiae species complex.

Anopheles gambiae, Anopheles coluzzii , and Anopheles arabiensis are three of the most widespread vectors of malaria parasites, with geographical ranges stretching across wide swaths of Africa. Understanding the population structure of these closely related species, including the extent to which populations are connected by gene flow, is essential for understanding how vector control implemented in one location might indirectly affect vector populations in other locations. Here, we assessed the population structure of each species based on whole-genome sequences from the third phase of the Anopheles gambiae 1000 Genomes Project. The data set included single nucleotide polymorphisms from whole genomes of 2,242 individual mosquitoes sampled from 119 locations across 19 African countries. We found that A. gambiae sampled from several countries in West and Central Africa showed low genetic differentiation from each other according to principal components analysis (PCA) and ADMIXTURE modeling. Using Estimated Effective Migration Surfaces (EEMS), we showed that this low genetic differentiation indicates high effective migration rates for A. gambiae across this region. Outside of this region, we found six groups of sampling locations from Central, East, and Southern Africa for which A. gambiae showed higher genetic differentiation, and lower effective migration rates, between each other and the West/Central Africa group. These results indicate that the barriers to and corridors for migration between populations of A. gambiae differ across the geographical range of this malaria vector species. Using the same methods, we found higher genetic differentiation and lower migration rates between populations of A. coluzzii in West and Central Africa than for A. gambiae in the same region. On the other hand, we found lower genetic differentiation and higher migration rates between populations of A. arabiensis in Tanzania, compared to A. gambiae in the same region. These differences between A. gambiae, A. coluzzii , and A. arabiensis indicate that migration barriers and corridors may vary between species, even for very closely related species. Overall, our results demonstrate that migration rates vary both between and within species of Anopheles mosquitoes, presumably based on species-specific responses to the ecological or environmental conditions that may impede or facilitate migration, and the geographical patterns of these conditions across the landscape. Together with previous findings, this study provides robust evidence that migration rates between populations of malaria vectors depend on the ecological context, which should be considered when planning surveillance of vector populations, monitoring for insecticide resistance, and evaluating interventions.

Community Participation in Habitat Management and Larviciding for the Control of Malaria Vectors in Southern Malawi.

Larval source management (LSM) could reduce malaria transmission when executed alongside core vector control strategies. Involving communities in LSM could increase intervention coverage, reduce operational costs, and promote sustainability via community buy-in. We assessed the effectiveness of community-led LSM to reduce anopheline larval densities in 26 villages along the perimeter of Majete Wildlife Reserve in southern Malawi. The communities formed LSM committees which coordinated LSM activities in their villages following specialized training. Effectiveness of larviciding by LSM committees was assessed via pre- and post-spray larval sampling. The effect of community-led LSM on anopheline larval densities in intervention villages was assessed via comparisons with densities in non-LSM villages over a period of 14 months. Surveys involving 502 respondents were undertaken in intervention villages to explore community motivation and participation, and factors influencing these outcomes. Larviciding by LSM committees reduced anopheline larval densities in post-spray sampling compared with pre-spray sampling (P < 0.0001). No differences were observed between anopheline larval densities during pre-spray sampling in LSM villages and those in non-LSM villages (P = 0.282). Knowledge about vector biology and control, and someone's role in LSM motivated community participation in the vector control program. Despite reducing anopheline larval densities in LSM villages, the impact of the community-led LSM could not be detected in our study setting because of low mosquito densities after scale-up of core malaria control interventions. Still, the contributions of the intervention in increasing a community's knowledge of malaria, its risk factors, and its control methods highlight potential benefits of the approach.

Community-based house improvement for malaria control in southern Malawi: Stakeholder perceptions, experiences, and acceptability.

House improvement (HI) refers to the full screening or closing of openings such as windows, doors, and eaves, as well as the installation of ceilings, to reduce mosquito-human contact indoors. HI is a viable supplementary intervention that reduces malaria transmission further than the existing strategies alone. In Malawi, HI has not been widely implemented and evaluated for malaria control. Concerns about lack of local evidence, durability in different epidemiological and cultural settings, and the cost of large-scale implementation are among the reasons the strategy is not utilised in many low-income countries. This study assessed community perceptions, experiences, and acceptability of community-led HI in Chikwawa district, southern Malawi. This was a qualitative study where separate focus group discussions were conducted with members from the general community (n = 3); health animators (n = 3); and HI committee members (n = 3). In-depth interviews were conducted with community members (n = 20), and key-informant interviews were conducted with health surveillance assistants and chiefs (n = 23). All interviews were transcribed and coded before performing a thematic content analysis to identify the main themes. Coded data were analysed using Nvivo 12 Plus software. Study participants had a thorough understanding of HI. Participants expressed satisfaction with HI, and they reported enabling factors to HI acceptability, such as the reduction in malaria cases in their villages and the safety and effectiveness of HI use. Participants also reported barriers to effective HI implementation, such as the unavailability and inaccessibility of some HI materials, as well as excessive heat and darkness in HI houses compared to non-HI houses. Participants indicated that they were willing to sustain the intervention but expressed the need for strategies to address barriers to ensure the effectiveness of HI. Our results showed the high knowledge and acceptability of HI by participants in the study area. Intensive and continued health education and community engagement on the significance of HI could help overcome the barriers and improve the acceptability and sustainability of the intervention.

Identifying Plasmodium falciparum transmission patterns through parasite prevalence and entomological inoculation rate.

Background: Monitoring malaria transmission is a critical component of efforts to achieve targets for elimination and eradication. Two commonly monitored metrics of transmission intensity are parasite prevalence (PR) and the entomological inoculation rate (EIR). Comparing the spatial and temporal variations in the PR and EIR of a given geographical region and modelling the relationship between the two metrics may provide a fuller picture of the malaria epidemiology of the region to inform control activities. Methods: Using geostatistical methods, we compare the spatial and temporal patterns of Plasmodium falciparum EIR and PR using data collected over 38 months in a rural area of Malawi. We then quantify the relationship between EIR and PR by using empirical and mechanistic statistical models. Results: Hotspots identified through the EIR and PR partly overlapped during high transmission seasons but not during low transmission seasons. The estimated relationship showed a 1-month delayed effect of EIR on PR such that at lower levels of EIR, increases in EIR are associated with rapid rise in PR, whereas at higher levels of EIR, changes in EIR do not translate into notable changes in PR. Conclusions: Our study emphasises the need for integrated malaria control strategies that combine vector and human host managements monitored by both entomological and parasitaemia indices. Funding: This work was supported by Stichting Dioraphte grant number 13050800.

Maximizing Impact: Can Interventions to Prevent Clinical Malaria Reduce Parasite Transmission?

Malaria interventions may reduce the burden of clinical malaria disease, the transmission of malaria parasites, or both. As malaria interventions are developed and evaluated, including those interventions primarily targeted at reducing disease, they may also impact parasite transmission. Achieving global malaria eradication will require optimizing the transmission-reducing potential of all available interventions. Herein, we discuss the relationship between malaria parasite transmission and disease, including mechanisms by which disease-targeting interventions might also impact parasite transmission. We then focus on three malaria interventions with strong evidence for reducing the burden of clinical malaria disease and examine their potential for also reducing malaria parasite transmission.