House Screening Reduces Exposure to Indoor Host-Seeking and Biting Malaria Vectors: Evidence from Rural South-East Zambia.

This study evaluated the impact of combining house screens with long-lasting insecticidal nets (LLINs) on mosquito host-seeking, resting, and biting behavior. Intervention houses received house screens and LLINs, while control houses received only LLINs. Centre for Disease Control light traps, pyrethrum spray collections and human landing catches were used to assess the densities of indoor and outdoor host-seeking, indoor resting, and biting behavior of malaria vectors in 15 sentinel houses per study arm per sampling method. The protective efficacy of screens and LLINs was estimated through entomological inoculation rates (EIRs). There were 68% fewer indoor host-seeking Anopheles funestus (RR = 0.32, 95% CI 0.20-0.51, p < 0.05) and 63% fewer An. arabiensis (RR = 0.37, 95% CI 0.22-0.61, p < 0.05) in screened houses than unscreened houses. There was a significantly higher indoor biting rate for unscreened houses (6.75 bites/person/h [b/p/h]) than for screened houses (0 b/p/h) (χ2 = 6.67, df = 1, p < 0.05). The estimated indoor EIR in unscreened houses was 2.91 infectious bites/person/six months, higher than that in screened houses (1.88 infectious bites/person/six months). Closing eaves and screening doors and windows has the potential to reduce indoor densities of malaria vectors and malaria transmission.

Anopheles rufipes implicated in malaria transmission both indoors and outdoors alongside Anopheles funestus and Anopheles arabiensis in rural south-east Zambia.

BACKGROUND: The primary malaria vector-control interventions, indoor residual spraying and long-lasting insecticidal nets, are effective against indoor biting and resting mosquito species. Consequently, outdoor biting and resting malaria vectors might elude the primary interventions and sustain malaria transmission. Varied vector biting and resting behaviour calls for robust entomological surveillance. This study investigated the bionomics of malaria vectors in rural south-east Zambia, focusing on species composition, their resting and host-seeking behaviour and sporozoite infection rates. METHODS: The study was conducted in Nyimba District, Zambia. Randomly selected households served as sentinel houses for monthly collection of mosquitoes indoors using CDC-light traps (CDC-LTs) and pyrethrum spray catches (PSC), and outdoors using only CDC-LTs for 12 months. Mosquitoes were identified using morphological taxonomic keys. Specimens belonging to the Anopheles gambiae complex and Anopheles funestus group were further identified using molecular techniques. Plasmodium falciparum sporozoite infection was determined using sandwich enzyme-linked immunosorbent assays. RESULTS: From 304 indoor and 257 outdoor light trap-nights and 420 resting collection, 1409 female Anopheles species mosquitoes were collected and identified morphologically; An. funestus (n = 613; 43.5%), An. gambiae sensu lato (s.l.)(n = 293; 20.8%), Anopheles pretoriensis (n = 282; 20.0%), Anopheles maculipalpis (n = 130; 9.2%), Anopheles rufipes (n = 55; 3.9%), Anopheles coustani s.l. (n = 33; 2.3%), and Anopheles squamosus (n = 3, 0.2%). Anopheles funestus sensu stricto (s.s.) (n = 144; 91.1%) and Anopheles arabiensis (n = 77; 77.0%) were the dominant species within the An. funestus group and An. gambiae complex, respectively. Overall, outdoor CDC-LTs captured more Anopheles mosquitoes (mean = 2.25, 95% CI 1.22-3,28) than indoor CDC-LTs (mean = 2.13, 95% CI 1.54-2.73). Fewer resting mosquitoes were collected with PSC (mean = 0.44, 95% CI 0.24-0.63). Sporozoite infectivity rates for An. funestus, An. arabiensis and An. rufipes were 2.5%, 0.57% and 9.1%, respectively. Indoor entomological inoculation rates (EIRs) for An. funestus s.s, An. arabiensis and An. rufipes were estimated at 4.44, 1.15 and 1.20 infectious bites/person/year respectively. Outdoor EIRs for An. funestus s.s. and An. rufipes at 7.19 and 4.31 infectious bites/person/year, respectively. CONCLUSION: The findings of this study suggest that An. rufipes may play an important role in malaria transmission alongside An. funestus s.s. and An. arabiensis in the study location.

Small-scale field evaluation of transfluthrin-treated eave ribbons and sandals for the control of malaria vectors in rural Tanzania.

BACKGROUND: Early-evening and outdoor-biting mosquitoes may compromise the effectiveness of frontline malaria interventions, notably insecticide-treated nets (ITNs). This study aimed to evaluate the efficacy of low-cost insecticide-treated eave ribbons and sandals as supplementary interventions against indoor-biting and outdoor-biting mosquitoes in south-eastern Tanzania, where ITNs are already widely used. METHODS: This study was conducted in three villages, with 72 households participating (24 households per village). The households were divided into four study arms and assigned: transfluthrin-treated sandals (TS), transfluthrin-treated eave ribbons (TER), a combination of TER and TS, or experimental controls. Each arm had 18 households, and all households received new ITNs. Mosquitoes were collected using double net traps (to assess outdoor biting), CDC light traps (to assess indoor biting), and Prokopack aspirators (to assess indoor resting). Protection provided by the interventions was evaluated by comparing mosquito densities between the treatment and control arms. Additional tests were done in experimental huts to assess the mortality of wild mosquitoes exposed to the treatments or controls. RESULTS: TERs reduced indoor-biting, indoor-resting and outdoor-biting Anopheles arabiensis by 60%, 73% and 41%, respectively, while TS reduced the densities by 18%, 40% and 42%, respectively. When used together, TER & TS reduced indoor-biting, indoor-resting and outdoor-biting An. arabiensis by 53%, 67% and 57%, respectively. Protection against Anopheles funestus ranged from 42 to 69% with TER and from 57 to 74% with TER & TS combined. Mortality of field-collected mosquitoes exposed to TER, TS or both interventions was 56-78% for An. arabiensis and 47-74% for An. funestus. CONCLUSION: Transfluthrin-treated eave ribbons and sandals or their combination can offer significant household-level protection against malaria vectors. Their efficacy is magnified by the transfluthrin-induced mortality, which was observed despite the prevailing pyrethroid resistance in the study area. These results suggest that TER and TS could be useful supplementary tools against residual malaria transmission in areas where ITN coverage is high but additional protection is needed against early-evening and outdoor-biting mosquitoes. Further research is needed to validate the performance of these tools in different settings, and assess their long-term effectiveness and feasibility for malaria control.

The economic impacts of house screening against malaria transmission: Experimental evidence from eastern Zambia.

Malaria imposes an economic burden for human populations in many African countries, and this burden may be reduced through house screening initiatives. We use a randomized controlled trial to measure the economic impacts of house screening against malaria infection. We use a sample of 800 households from 89 villages in rural and peri-urban Zambia to collect baseline data in August 2019 and endline data in August 2020. The main outcome variables are (self-reported) malaria prevalence rates, labor supply, and income, and consider individual and household-level outcomes. House screening reduces malaria prevalence, the number of sick days due to malaria, and the number of malaria episodes. Impacts on adults are more pronounced than on children. In terms of economic impacts, house screening increases labor supply and (household) income. We find particularly large effects on labor supply for women household members. A cost-benefit analysis, based on estimated benefits and measured costs, suggests that the private benefits of house screening exceed the costs. While not all houses are suitable for house screening, we conclude that screening is a promising and cost-effective approach to reduce malaria infections.

Six decades of malaria vector control in southern Africa: a review of the entomological evidence-base.

BACKGROUND: Countries in the southern Africa region have set targets for malaria elimination between 2020 and 2030. Malaria vector control is among the key strategies being implemented to achieve this goal. This paper critically reviews published entomological research over the past six decades in three frontline malaria elimination countries namely, Botswana Eswatini and Namibia, and three second-line malaria elimination countries including Mozambique, Zambia, and Zimbabwe. The objective of the review is to assess the current knowledge and highlight gaps that need further research attention to strengthen evidence-based decision-making toward malaria elimination. METHODS: Publications were searched on the PubMed engine using search terms: "(malaria vector control OR vector control OR malaria vector*) AND (Botswana OR Swaziland OR Eswatini OR Zambia OR Zimbabwe OR Mozambique)". Opinions, perspectives, reports, commentaries, retrospective analysis on secondary data protocols, policy briefs, and reviews were excluded. RESULTS: The search resulted in 718 publications with 145 eligible and included in this review for the six countries generated over six decades. The majority (139) were from three countries, namely Zambia (59) and Mozambique (48), and Zimbabwe (32) whilst scientific publications were relatively scanty from front-line malaria elimination countries, such as Namibia (2), Botswana (10) and Eswatini (4). Most of the research reported in the publications focused on vector bionomics generated mostly from Mozambique and Zambia, while information on insecticide resistance was mostly available from Mozambique. Extreme gaps were identified in reporting the impact of vector control interventions, both on vectors and disease outcomes. The literature is particularly scanty on important issues such as change of vector ecology over time and space, intervention costs, and uptake of control interventions as well as insecticide resistance. CONCLUSIONS: The review reveals a dearth of information about malaria vectors and their control, most noticeable among the frontline elimination countries: Namibia, Eswatini and Botswana. It is of paramount importance that malaria vector research capacity and routine entomological monitoring and evaluation are strengthened to enhance decision-making, considering changing vector bionomics and insecticide resistance, among other determinants of malaria vector control.

Evaluating the efficacy, impact, and feasibility of community-based house screening as a complementary malaria control intervention in southern Africa: a study protocol for a household randomized trial.

BACKGROUND: Concerted effort to control malaria has had a substantial impact on the transmission of the disease in the past two decades. In areas where reduced malaria transmission is being sustained through insecticide-based vector control interventions, primarily long-lasting insecticidal nets (LLINs) and indoor residual spraying (IRS), non-insecticidal complementary tools will likely be needed to push towards malaria elimination. Once interruption in local disease transmission is achieved, insecticide-based measures can be scaled down gradually and eventually phased out, saving on costs of sustaining control programs and mitigating any unintended negative health and environmental impacts posed by insecticides. These non-insecticidal methods could eventually replace insecticidal methods of vector control. House screening, a non-insecticidal method, has a long history in malaria control, but is still not widely adopted in sub-Saharan Africa. This study aims to add to the evidence base for this intervention in low transmission settings by assessing the efficacy, impact, and feasibility of house screening in areas where LLINs are conventionally used for malaria control. METHODS: A two-armed, household randomized clinical trial will be conducted in Mozambique, Zambia, and Zimbabwe to evaluate whether combined the use of house screens and LLINs affords better protection against clinical malaria in children between 6 months and 13 years compared to the sole use of LLINs. Eight hundred households will be enrolled in each study area, where 400 households will be randomly assigned the intervention, house screening, and LLINs while the control households will be provided with LLINs only. Clinical malaria incidence will be estimated by actively following up one child from each household for 6 months over the malaria transmission season. Cross-sectional parasite prevalence will be estimated by testing all participating children for malaria parasites at the beginning and end of each transmission season using rapid diagnostic tests. CDC light traps and pyrethrum spray catches (PSC) will be used to sample adult mosquitoes and evaluate the impact of house screening on indoor mosquito density, species distribution, and sporozoite rates. DISCUSSION: This study will contribute epidemiological data on the impact of house screening on malaria transmission and assess the feasibility of its implementation on a programmatic scale. TRIAL REGISTRATION: ClinicalTrials.gov PACTR202008524310568 . Registered on August 11, 2020.

Malaria in Eswatini, 2012-2019: a case study of the elimination effort.

Eswatini was the first country in sub-Saharan Africa to pass a National Malaria Elimination Policy in 2011, and later set a target for elimination by the year 2020. This case study aimed to review the malaria surveillance data of Eswatini collected over 8 years between 2012 and 2019 to evaluate the country's efforts that targeted malaria elimination by 2020. Coverage of indoor residual spraying (IRS) for vector control and data on malaria cases were provided by the National Malaria Programme (NMP) of Eswatini. The data included all cases treated for malaria in all health facilities. The data was analysed descriptively. Over the 8 years, a total of 5511 patients reported to the health facilities with malaria symptoms. The case investigation rate through the routine surveillance system increased from 50% in 2012 to 84% in 2019. Incidence per 1000 population at risk fluctuated over the years, but in general increased from 0.70 in 2012 to 1.65 in 2019, with the highest incidence of 3.19 reported in 2017. IRS data showed inconsistency in spraying over the 8 years. Most of the cases were diagnosed by rapid diagnostic test (RDT) kits in government (87.6%), mission (89.1%), private (87%) and company/industry-owned facilities (84.3%), either singly or in combination with microscopy. Eswatini has fallen short of achieving malaria elimination by 2020. Malaria cases are still consistently reported, albeit at low rates, with occasional localized outbreaks. To achieve elimination, it is critical to optimize timely and well-targeted IRS and to consider rational expansion of tools for an integrated malaria control approach in Eswatini by including tools such as larval source management, long-lasting insecticidal nets (LLINs), screening of mosquito house entry points, and chemoprophylaxis. The establishment of rigorous routine entomological surveillance should also be prioritized to determine the local malaria vectors' ecology, potential species diversity, the role of secondary vectors and insecticide resistance.

Evaluation of personal protection afforded by repellent-treated sandals against mosquito bites in south-eastern Tanzania.

BACKGROUND: Outdoor and early evening mosquito biting needs to be addressed if malaria elimination is to be achieved. While indoor-targeted interventions, such as insecticide-treated nets and indoor residual spraying, remain essential, complementary approaches that tackle persisting outdoor transmission are urgently required to maximize the impact. Major malaria vectors principally bite human hosts around the feet and ankles. Consequently, this study investigated whether sandals treated with efficacious spatial repellents can protect against outdoor biting mosquitoes. METHODOLOGY: Sandals affixed with hessian bands measuring 48 cm2 treated with 0.06 g, 0.10 g and 0.15 g of transfluthrin were tested in large cage semi-field and full field experiments. Sandals affixed with hessian bands measuring 240 cm2 and treated with 0.10 g and 0.15 g of transfluthrin were also tested semi field experiments. Human landing catches (HLC) were used to assess reduction in biting exposure by comparing proportions of mosquitoes landing on volunteers wearing treated and untreated sandals. Sandals were tested against insectary reared Anopheles arabiensis mosquitoes in semi-field experiments and against wild mosquito species in rural Tanzania. RESULTS: In semi-field tests, sandals fitted with hessian bands measuring 48 cm2 and treated with 0.15 g, 0.10 g and 0.06 g transfluthrin reduced mosquito landings by 45.9%, (95% confidence interval (C.I.) 28-59%), 61.1% (48-71%), and 25.9% (9-40%), respectively compared to untreated sandals. Sandals fitted with hessian bands measuring 240 cm2 and treated with 0.15 g and 0.10 g transfluthrin reduced mosquito landings by 59% (43-71%) and 64% (48-74%), respectively. In field experiments, sandals fitted with hessian bands measuring 48 cm2 and treated with 0.15 g transfluthrin reduced mosquito landings by 70% (60-76%) against Anopheles gambiae sensu lato, and 66.0% (59-71%) against all mosquito species combined. CONCLUSION: Transfluthrin-treated sandals conferred significant protection against mosquito bites in semi-field and field settings. Further evaluation is recommended for this tool as a potential complementary intervention against malaria. This intervention could be particularly useful for protecting against outdoor exposure to mosquito bites. Additional studies are necessary to optimize treatment techniques and substrates, establish safety profiles and determine epidemiological impact in different settings.

Feasibility of repellent use in a context of increasing outdoor transmission: a qualitative study in rural Tanzania.

BACKGROUND: Extensive employment of long-lasting insecticidal nets (LLINs) and indoor residual spraying (IRS) has substantially reduced malaria morbidity and mortality in sub-Saharan Africa. These tools target indoor resting and biting vectors, and may select for vectors that bite and rest outdoors. Thus, to significantly impact this residual malaria transmission outdoors, tools targeting outdoor transmission are required. Repellents, used for personal protection, offer one solution. However, the effectiveness of this method hinges upon its community acceptability. This study assessed the feasibility of using repellents as a malaria prevention tool in Mbingu village, Ulanga, Southern Tanzania. METHODOLOGY: Change in knowledge, attitude and practice (KAP) in relation to repellent use was assessed before and after the implementation of a cluster randomized clinical trial on topical repellents in rural Tanzania where repellent and placebo lotion were provided free of charge to 940 households for a period of 14 months between July 2009 and August 2010. Compliance, defined as the number of evenings that participants applied the recommended dose of repellent every month during the study period, was assessed using questionnaires, administered monthly during follow up of participants in the clinical trial. Focus group discussions (FGDs) were conducted in the same community three years later to assess the community's KAP in relation to repellents and preference to different repellent formats. RESULTS: At baseline, only 0.32% (n=2) households in the intervention arm and no households in the control arm had ever used topical repellents. During follow-up surveys, significantly more households, 100% (n=457) in intervention arm relative to the control, 84.03% (n=379), (p=<0.001) perceived the repellent to be effective.Post-study, 99.78% (n=462) and 99.78% (n=463), (p=0.999) in the intervention and control arms respectively, were willing to continue repellent use. Mosquito nuisance motivated repellent use. From the FGDs, it emerged that most respondents preferred bed nets to repellents because of their longevity and cost effectiveness. CONCLUSION: High repellent acceptability indicates their feasibility for malaria control in this community. However, to improve the community's uptake of repellents for use complimentary to LLINs for early evening and outdoor protection from mosquito bites, longer lasting and cheap formats are required.

A cluster-randomized controlled trial to assess the effectiveness of using 15% DEET topical repellent with long-lasting insecticidal nets (LLINs) compared to a placebo lotion on malaria transmission.

BACKGROUND: Long-lasting insecticidal nets (LLINs) have limited effect on malaria transmitted outside of sleeping hours. Topical repellents have demonstrated reduction in the incidence of malaria transmitted in the early evening. This study assessed whether 15% DEET topical repellent used in combination with LLINs can prevent greater malaria transmission than placebo and LLINs, in rural Tanzania. METHODS: A cluster-randomized, placebo-controlled trial was conducted between July 2009 and August 2010 in a rural Tanzanian village. Sample size calculation determined that 10 clusters of 47 households with five people/household were needed to observe a 24% treatment effect at the two-tailed 5% significance level, with 90% power, assuming a baseline malaria incidence of one case/person/year. Ten clusters each were randomly assigned to repellent and control groups by lottery. A total of 4,426 individuals older than six months were enrolled. All households in the village were provided with an LLIN per sleeping space. Repellent and placebo lotion was replaced monthly. The main outcome was rapid diagnostic test (RDT)-confirmed malaria measured by passive case detection (PCD). Incidence rate ratios were estimated from a Poisson model, with adjustment for potential confounders, determined a priori. According-to-protocol approach was used for all primary analyses. RESULTS: The placebo group comprised 1972.3 person-years with 68.29 (95% C.I 37.05-99.53) malaria cases/1,000 person-years. The repellent group comprised 1,952.8 person-years with 60.45 (95% C.I 48.30-72.60) cases/1,000 person-years, demonstrating a non-significant 11.44% reduction in malaria incidence rate in this group, (Wilcoxon rank sum z=0.529, p=0.596). Principal components analysis (PCA) of the socio-economic status (SES) of the two groups demonstrated that the control group had a higher SES (Pearson's chi square=13.38, p=0.004). CONCLUSIONS: Lack of an intervention effect was likely a result of lack of statistical power, poor capture of malaria events or bias caused by imbalance in the SES of the two groups. Low malaria transmission during the study period could have masked the intervention effect and a larger study size was needed to increase discriminatory power. Alternatively, topical repellents may have no impact on malaria transmission in this scenario. Design and implementation of repellent intervention studies is discussed. TRIAL REGISTRATION: The trial was registered ISRCTN92202008--http://www.controlled-trials.com/ISRCTN92202008.

Use of a semi-field system to evaluate the efficacy of topical repellents under user conditions provides a disease exposure free technique comparable with field data.

BACKGROUND: Before topical repellents can be employed as interventions against arthropod bites, their efficacy must be established. Currently, laboratory or field tests, using human volunteers, are the main methods used for assessing the efficacy of topical repellents. However, laboratory tests are not representative of real life conditions under which repellents are used and field-testing potentially exposes human volunteers to disease. There is, therefore, a need to develop methods to test efficacy of repellents under real life conditions while minimizing volunteer exposure to disease. METHODS: A lotion-based, 15% N, N-Diethyl-3-methylbenzamide (DEET) repellent and 15% DEET in ethanol were compared to a placebo lotion in a 200 sq m (10 m × 20 m) semi-field system (SFS) against laboratory-reared Anopheles arabiensis mosquitoes and in full field settings against wild malaria vectors and nuisance-biting mosquitoes. The average percentage protection against biting mosquitoes over four hours in the SFS and field setting was determined. A Poisson regression model was then used to determine relative risk of being bitten when wearing either of these repellents compared to the placebo. RESULTS: Average percentage protection of the lotion-based 15% DEET repellent after four hours of mosquito collection was 82.13% (95% CI 75.94-88.82) in the semi-field experiments and 85.10% (95% CI 78.97-91.70) in the field experiments. Average percentage protection of 15% DEET in ethanol after four hours was 71.29% (CI 61.77-82.28) in the semi-field system and 88.24% (84.45-92.20) in the field. CONCLUSIONS: Semi-field evaluation results were comparable to full-field evaluations, indicating that such systems could be satisfactorily used in measuring efficacy of topically applied mosquito repellents, thereby avoiding risks of exposure to mosquito-borne pathogens, associated with field testing.