Can repellents prevent malaria in Tanzania?

Background: Current malaria control tools, long lasting insecticidal nets and indoor residual spraying have had a significant impact on malaria transmission in sub-Saharan Africa. However these tools will not be able to eradicate malaria and there is need for complementary tools if this goal is to be attained. This work focused on evaluating and recommending tools that can be used to complement current control tools with emphasis on outdoor and early evening transmission. The main tool evaluated in this thesis was a topical repellent to be used in the early evening. Other tools recommended were spatial repellents and permethrin- impregnated clothing. Methods: A repellent efficacy trial was conducted in the semi-field and field setting to evaluate the protection from early evening biting given by a topical repellent lotion containing 15% N.N-diethyl-m-toluamide (DEET). A cluster randomized, placebo controlled clinical trial, designed to assess the effect of 15% DEET against malaria transmitted in the early evening was then conducted in a village in rural Tanzania. A total of 940 households were recruited and randomized, with 462 households randomized to the intervention arm and 462 households randomized to the control arm. The feasibility of lotion repellent use was assessed using entry and exit questionnaires. Focus group discussions were conducted 3 years after a clinical trial to assess the community knowledge, attitude and practice towards a different set of repellents to those used during the clinical trial. A systematic review was then conducted to put the results of this trial in context with other repellent trials. An attempt was made to design a clinical trial taking into account the shortcomings of the current and other repellent trials reviewed. Findings: Topical repellents containing 15% DEET provided >80% protection against early evening biting over four hours. According to protocol analysis of the cluster randomized trial found no difference between the intervention and control arms after accounting for socio-economic status, education of household head and household construction materials (Wilcoxon rank sum z = 0.529, p = 0.596). The most important predictor of malaria in this study was age, with younger age categories significantly associated with greater malaria risk. Socio-economic status was not associated with malaria. Compliance to repellent use was reported to be 80% during the study. From the FGDs, it emerged that community knowledge was the major barrier to repellent use, followed closely with availability. The community preferred using long lasting insecticidal nets (LLINs) because of their cost effectiveness. However, the community preferred using repellents in the early evening before employing LLINs. Interpretation: This study demonstrates that topical repellents have no effect against early evening malaria transmission in this community. However, shortcomings in the design and implementation might have masked the treatment effect and better-designed studies are required to establish repellents effect in this setting. Topical repellents provided protection against early evening biting and were readily accepted and used in this community, indicating the potential of using repellents complimentary to LLINs in this setting. The short-term duration of effect of this repellent, required frequent reapplication and therefore impacted compliance, emphasizing that future studies should consider using longer lasting tools such as spatial repellents

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

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. Sandals affixed with hessian bands measuring 48 cm 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 cm 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. In semi-field tests, sandals fitted with hessian bands measuring 48 cm 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 cm 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 cm 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. 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

Ion transport and structural dynamics in homologous ammonium and phosphoniumbased room temperature ionic liquids

Charge transport and structural dynamics in a homologous pair of ammonium and phosphonium based room temperature ionic liquids (ILs) have been characterized over a wide temperature range using broadband dielectric spectroscopy and quasi-elastic light scattering spectroscopy. We have found that the ionic conductivity of the phosphonium based IL is significantly enhanced relative to the ammonium homolog, and this increase is primarily a result of a lower glass transition temperature and higher ion mobility. Additionally, these ILs exhibit pronounced secondary relaxations which are strongly influenced by the atomic identity of the cation charge center. While the secondary relaxation in the phosphonium IL has the expected Arrhenius temperature dependence characteristic of local beta relaxations, the corresponding relaxation process in the ammonium IL was found to exhibit a mildly non-Arrhenius temperature dependence in the measured temperature range—indicative of molecular cooperativity. These differences in both local and long-range molecular dynamics are a direct reflection of the subtly different inter-ionic interactions and mesoscale structures found in these homologous ILs

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

AVAILABILITY OF DATA AND MATERIALS : Information was searched and obtained from published data in the PubMed search engine. The datasets used and/or analysed during this study can be obtained from the corresponding author on reasonable request.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.The AFRO-II Project under the auspices of the Global Environment Facility/United Nations Environment Programme (GEF/UNEP) through the World Health Organization Regional Office for Africa (WHO-AFRO); icipe’s core donors, the Foreign, Commonwealth & Development Office (FCDO) of the UK Government; Swedish International Development Cooperation Agency (Sida); the Swiss Agency for Development and Cooperation (SDC); Federal Democratic Republic of Ethiopia; and the Kenyan Government.https://malariajournal.biomedcentral.comhj2023School of Health Systems and Public Health (SHSPH

The combined impact of LLINs, house screening, and pull‑push technology for improved malaria control and livelihoods in rural Ethiopia : study protocol for household randomised controlled trial

ADDITIONAL FILE 1. Ethics Review approval letter.ADDITIONAL FILE 2. Ethics information sheet and consent form.BACKGROUND : The combined application of long-lasting insecticidal nets (LLINs) and indoor residual spraying (IRS) are commonly used malaria interventions that target indoor Anopheles vectors. Recent studies on the effects of house screening (HS) and LLINs have demonstrated a reduction in indoor vector densities and malaria when the interventions are combined. In addition, complementary interventions are needed to curb co-occurring pest populations which pose menace to agricultural crop productivity and food security. However, interventions that impact malaria mainly centre on public health strategies, overlooking subtle but important component of agricultural measures. Addressing the coexisting risks of malaria and crop pests could contribute to improved livelihood of communities. METHODS : A four-armed household, cluster-randomized, controlled study will be conducted to assess the combined impact of HS, LLINs and push-pull agricultural technology (PPT) against clinical malaria in children in Ethiopia. The unit of randomization will be the household, which includes a house and its occupants. A total of 838 households will be enrolled in this study. In this trial 246 households will receive LLINs and HS, 250 will receive LLINs, HS and PPT, 175 households will receive LLINs and PPT. The remaining 167 houses which receive LLINs only will be used as control. One child aged ≤14 years will be enrolled per household in each treatment and followed for clinical malaria using active case detection to estimate malaria incidence for two malaria transmission seasons. DISCUSSION : Episodes of clinical malaria, density of indoor biting malaria vectors, sporozoite infection rate, improved crop infestation rate, crop yield gain, livestock productivity and cost effectiveness analysis will be the end points of this study. Socio-economic, social demographic, cost-effectiveness analysis will be conducted using qualitative and participatory methods to explore the acceptability of HS and PPT. Documenting the combined impact of LLINs, HS and PPT on the prevalence of clinical malaria and crop pest damage will be the first of its kind. TRIAL REGISTRATION : Pan African Clinical Trials Registry, PACTR202006878245287. 24/06/2020.Norwegian Agency for Development Cooperation (NORAD) through the project Combating Arthropod Pests for Better Health, Food and Resilience to Climate Change (CAP-Africa).http://www.biomedcentral.com/bmcpublichealtham2023School of Health Systems and Public Health (SHSPH)UP Centre for Sustainable Malaria Control (UP CSMC

Observing the distribution of mosquito bites on humans to inform personal protection measures against malaria and dengue vectors

Background Understanding mosquito biting behaviours is important for designing and evaluating protection methods against nuisance biting and mosquito-borne diseases (e.g. dengue, malaria and zika). We investigated the preferred biting sites by Aedes aegypti and Anopheles arabiensis on adult volunteers in standing or sleeping positions; and estimated the theoretical protection limits affordable from protective clothing or repellent-treated footwear. Methods Adult volunteers dressed in shorts and t-shirts were exposed to infection-free laboratory-reared mosquitoes inside screened chambers from 6am to noon (for day-biting Ae. aegypti) or 6pm to midnight (night-biting An. arabiensis). Attempted bites on different body parts were recorded. Comparative observations were made on same volunteers while wearing sandals treated with transfluthrin, a vapour-phase pyrethroid that kills and repels mosquitoes. Results An. arabiensis bites were mainly on the lower limbs of standing volunteers (95.9% of bites below the knees) but evenly-distributed over all exposed body surfaces when the volunteers were on sleeping positions (only 28.8% bites below knees). Ae. aegypti bites were slightly concentrated on lower limbs of standing volunteers (47.7% below knees), but evenly-distributed on sleeping volunteers (23.3% below knees). Wearing protective clothing that leave only hands and head uncovered (e.g. socks + trousers + long-sleeved shirts) could theoretically prevent 78–83% of bites during sleeping, and at least 90% of bites during non-sleeping hours. If the feet are also exposed, protection declines to as low as 36.3% against Anopheles. The experiments showed that transfluthrin-treated sandals reduced An. arabiensis by 54–86% and Ae. aegypti by 32–39%, but did not change overall distributions of bites. Conclusion Biting by An. arabiensis and Ae. aegypti occur mainly on the lower limbs, though this proclivity is less pronounced in the Aedes species. However, when hosts are on sleeping positions, biting by both species is more evenly-distributed over the exposed body surfaces. High personal protection might be achieved by simply wearing long-sleeved clothing, though protection against Anopheles particularly requires covering of feet and lower legs. The transfluthrin-treated footwear can reduce biting risk, especially by An. arabiensis. These findings could inform the design and use of personal protection tools (both insecticidal and non-insecticidal) against mosquitoes and mosquito-borne diseases

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.The AFRO-II Project under the auspices of the Global Environment Facility/United Nations Environment Programme (GEF/UNEP) through the World Health Organization Regional Office for Africa (WHO-AFRO); icipe’s core donors, Foreign, Commonwealth & Development Office (FCDO) of the UK Government; Swedish International Development Cooperation Agency (Sida); the Swiss Agency for Development and Cooperation (SDC); Federal Democratic Republic of Ethiopia; and the Kenyan Government.https://malariajournal.biomedcentral.comam2022School of Health Systems and Public Health (SHSPH)UP Centre for Sustainable Malaria Control (UP CSMC

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

AVAILABILITY OF DATA AND MATERIALS : The datasets used and/or analysed during the current study are available from the corresponding author on reasonable request.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 enzymelinked 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.Global Environmental Fund (GEF) through United Nations Environmental Programme (UNEP) and the WHO-Africa Regional Office (WHO-AFRO); the Swedish International Development Cooperation Agency (Sida); the Swiss Agency for Development and Cooperation (SDC); the Australian Centre for International Agricultural Research (ACIAR); the Federal Democratic Republic of Ethiopia; and the Government of the Republic of Kenya.https://malariajournal.biomedcentral.com/am2024School of Health Systems and Public Health (SHSPH)SDG-03:Good heatlh and well-bein

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

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 subSaharan 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. Crosssectional 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.The multi-country trial is funded as part of the AFRO-II project by the Global Environment Facility (GEF Project ID 4668) through the United Nations Environment Programme (UNEP) and the World Health Organization Regional Office for Africa (WHO-AFRO). Co-financing support is provided by the respective project countries for in-country activities and for technical support by icipe’s core funders including the UK’s Foreign, Commonwealth & Development Office (FCDO); the Swedish International Development Cooperation Agency (Sida); the Swiss Agency for Development and Cooperation (SDC); the Federal Democratic Republic of Ethiopia; and the Government of the Republic of Kenya. The views expressed herein do not necessarily reflect the official opinion of the donors.http://www.trialsjournal.comdm2022School of Health Systems and Public Health (SHSPH