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Biology subjects

Hamainza, B.

Publications and source records attributed to Hamainza, B..

3 recordsLinked to original sources

Potential impacts of supplementing next generation long-lasting insecticidal nets with household-scale micro-mosaic deployment of indoor residual spraying with insecticides upon rates of incipient resistance trait emergence and selection

Prolonged use of the few insecticide classes available for long-lasting insecticidal nets (LLINs) and indoor residual spraying (IRS) has driven widespread physiological resistance of malaria vector mosquitoes to this limited arsenal of active ingredients. However, recent innovations like next-generation LLINs (NG-LLINs) containing two complementary insecticides and new insecticide classes for IRS offer new opportunities for pre-emptive resistance management by deploying more diversified actives as mixtures, combinations, rotations or mosaics. Here a deterministic model of mosquito foraging behaviour was formulated to predict the probabilities of deterrence, mortality or successful feeding across repeated feeding attempts in scenarios with different combinations of NG-LLINs and/or IRS micro-mosaics with varying levels of insecticide diversification between neighbouring houses. Final fates were classified based on whether or not the mosquito eventually died or successfully fed, and whether the latter occurred indoors or outdoors after exposure to zero, one or several IRS insecticides. The primary outcome was the probability that a single F mosquito carrying a novel resistance trait to a new IRS insecticide successfully feeds, survives and reproduces, thereby establishing those traits within the population. The secondary outcome was the selection coefficient governing the spread of such novel resistance traits from the F generation onwards. For highly anthropophagic and endophagic vectors like Anopheles funestus, combining NG-LLINs with IRS micro-mosaics using two insecticides may reduce emergence rates for novel resistance traits against IRS insecticides by approximately 2 to 2.5-fold, mainly through direct killing by NG-LLINs, although exposure to both IRS actives when forced to visit multiple houses also contributes to a lesser extent. However, such resistance management benefits are fundamentally constrained by outdoor feeding behaviours that limit or completely prevent indoor insecticide exposure. Increasing IRS micro-mosaic insecticide diversity beyond two actives is unlikely to further dampen resistance emergence rates because few mosquitoes survive long enough without feeding to encounter several IRS treatments. Once a resistance trait becomes established in the vector population, selection coefficients remain consistently high enough to force the spread of those traits, regardless of intervention combination. For more exophagic, zoophagic vectors like An. arabiensis, NG-LLINs plus IRS micro-mosaics are not expected to provide any meaningful resistance management benefit because frequent outdoor feeding, often on animals, allows them to largely avoid insecticide exposure altogether. Exclusively indoor-focused vector control strategies may not satisfactorily slow insecticide resistance emergence and spread, so new outdoor protection measures that close these coverage gaps with complementary insecticides will be needed.

genetics↗

Flexible and cost-effective genomic surveillance of P. falciparum malaria with targeted nanopore sequencing

Genomic surveillance of Plasmodium falciparum malaria can provide policy-relevant information about antimalarial drug resistance, rapid diagnostic test failure, and the evolution of vaccine targets. Yet the large and low complexity genome of P. falciparum limits the scope of genomic surveillance, as whole-genome sequencing approaches are costly and targeted approaches are challenging to develop. Moreover, the majority of the morbidity and mortality caused by P. falciparum occurs in sub-Saharan Africa, where resource constraints can make implementing genomic surveillance difficult. Here, we demonstrate a flexible and cost-effective approach for targeted nanopore sequencing of P. falciparum to enable genomic surveillance of malaria in low-resource settings. We release open-source software that facilitates rapid and flexible design of amplicon sequencing panels for P. falciparum, coupled with a simple and cost-effective protocol that uses dried blood spots as input. We use this software to design two amplicon panels. The first, called NOMADS8, targets seven major antimalarial drug-resistance associated genes as well as the highly polymorphic gene msp2. The second, NOMAD16, incorporates an additional eight genes including the vaccine target csp and genes coding for the antigens detected in rapid diagnostic tests, hrp2 and hrp3. The panels generate reads between 3 to 4kbp that span the entire coding sequence of most target genes. We validate the panels and protocol on mock and field samples, demonstrating robust sequencing coverage across targets, high single-nucleotide polymorphism calling accuracy within coding sequences, and the ability to explore the within-sample diversity of mixed P. falciparum infections.

genomics↗

Effective strategies for preventing reestablishment of malaria in areas with recent elimination and high transmission potential

Maintaining zero transmission after malaria elimination will be a challenging task for many countries where malaria is still endemic. When local transmission potential is high, and importation of malaria infections continues from neighboring areas with ongoing transmission, malaria programs must develop robust surveillance and outbreak response systems. However, the requirements for such systems remain unclear. Using an agent-based, spatial microsimulation model of two areas in southern Zambia, where elimination efforts are currently underway, we compare the ability of various routine and reactive intervention packages to maintain near-zero prevalence in the face of continued importation. We find that in formerly moderate-transmission areas, high treatment rate of symptomatic malaria is sufficient to prevent reestablishment of malaria. Routine redistributions of insecticide-treated nets and reactive case detection with antimalarial drugs cannot completely compensate for inadequate case management. In formerly high-transmission areas, excellent case management and maintenance of good bednet coverage are both required to prevent resurgence, and outbreak response with antimalarial drugs or additional vector control is also necessary. These results begin to describe the essential criteria for operations that successfully prevent reestablishment of malaria post-elimination and highlight the need for both long-term, sustainable excellence in primary care and comprehensive surveillance that feeds into rapid and flexible outbreak response.\n\nAuthor SummaryThe global community is working toward malaria elimination, but some areas will eliminate before others. Eliminated areas will need to develop intervention programs capable of preventing imported infections from leading to reestablishment, a particular challenge when transmission was previously very high. Past experience has shown that stopping elimination interventions leads to massive resurgence, but it is unclear which interventions must be continued, which can be stopped to conserve resources, and what new interventions should be deployed. Using a simulation model built to capture malaria transmission and intervention history of two areas that recently made enormous progress toward elimination, we tested how well different intervention programs were able to prevent reestablishment of malaria. We found that treating as many symptomatic cases as possible was the single most important intervention to implement. In some contexts, this intervention alone was sufficient to prevent reestablishment. Other areas with historically higher transmission required maintaining vector control to contain mosquito populations. Localized outbreak response with antimalarial drugs or additional vector control was also necessary and predicted to be a highly efficient use of resources. These findings provide quantitative guidance for policy-makers considering how to stratify eliminated areas and plan new operational modes for the post-elimination era.

ecology↗