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.

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.

Methanolic extract of Agerantum conyzoides exhibited toxicity and growth disruption activities against Anopheles gambiae sensu stricto and Anopheles arabiensis larvae.

BACKGROUND: Vector control remains the mainstay to effective malaria management. The negative implications following persistent application of synthetic insecticides geared towards regulation of mosquito populations have necessitated prospection for ecofriendly effective chemistries. Plant-derived compounds have the potential to control malaria-transmitting mosquito populations. Previously, Agerantum conyzoides extracts have demonstrated toxicity effects on disease-transmitting mosquitoes. However, their efficacy in controlling Afrotropical malaria vectors remains unclear. Herein, the toxicity and growth disruption activities of crude methanolic leaf extract of A. conyzoides on Anopheles gambiae sensu stricto and An. arabiensis larvae were assessed. METHODS: Late third (L3) instars of An. gambiae s.s and An. arabiensis larvae were challenged with increasing doses of crude methanolic extract of A. conyzoides. The larval mortality rates were recorded every 24 h and the LC50 values determined at their associated 95% confidence levels. ANOVA followed by Post-hoc Student-Newman-Keuls (SNK) test was used to compare results between treatment and control groups. Phytochemical profiling of the extract was performed using standard chemical procedures. RESULTS: Treatment of larvae with the methanolic extract depicted dose-dependent effects with highest mortality percentages of ≥ 69% observed when exposed with 250 ppm and 500 ppm for 48 h while growth disruption effects were induced by sublethal doses of between 50-100 ppm for both species. Relative to experimental controls, the extract significantly reduced larval survival in both mosquito species (ANOVA, F(8,126) = 43.16776, P < 0.001). The LC50 values of the extract against An. gambiae s.s ranged between 84.71-232.70 ppm (95% CI 81.17-239.20), while against An. arabiensis the values ranged between 133.46-406.35 ppm (95% CI 131.51-411.25). The development of the juvenile stages was arrested at pupal-larval intermediates and adult emergence. The presence of alkaloids, aglycone flavonoids, triterpenoids, tannins and coumarins can partly be associated with the observed effects. CONCLUSION: The extract displayed considerable larvicidal activity and inhibited emergence of adult mosquitoes relative to experimental controls, a phenomenon probably associated with induced developmental hormone imbalance. Optimization of the bioactive compounds could open pathways into vector control programmes for improved mosquito control and reduced malaria transmission rates.

Mosquitoes Larvicidal Activity of Ocimum kilimandscharicum Oil Formulation under Laboratory and Field-Simulated Conditions.

Mosquitoes are vectors of many severe diseases, including malaria, yellow as well as dengue fever, and lymphatic filariasis. The use of synthetic chemical insecticides for mosquito control has been associated with resistance development and detrimental human, and ecological effects. For a safer alternative, the emulsified Ocimum kilimandscharicum oil formulation was evaluated for its larvicidal activity. The oil was analyzed by GC and GC/MS. The formulations were evaluated against third instar mosquito larvae in the laboratory and later compared with Bacillus thuringiensis subsp. israelensis against An. gambiae under field-simulated conditions. Thirty-nine compounds were identified in the oil, the main ones being D-camphor (36.6%) and limonene (18.6%). The formulation showed significant larval mortalities against An. gambiae and An. arabiensis larvae with LC50 of 0.07 and 0.31 ppm, respectively, at 24 h. Under the field-simulated trial, within 24 h, the formulation showed 98% mortality while Bti had achieved 54%. On day three, it caused 100% mortality while Bti achieved 76.5%. The high bioactivity and sublethal toxic effects to offspring of treated mosquito larvae, in terms of disruption of larval morphological aspects, suggest the high potential of the formulation as a botanical larvicide. The formulation, thus, may provide a valuable alternative for the effective and eco-friendly control of disease vectors.

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.