Martin J Donnelly

• Liverpool School of Tropical Medicine

Anopheles mosquitoes are major malaria vectors, encompassing several species complexes with diverse life histories, transmission risks and insecticide resistance profiles that challenge malaria control efforts. This study investigated the genetic structure and insecticide resistance profiles of Anopheles gambiae complex mosquitoes in Tanzania. We a...

The invasion of Africa by the Asian urban malaria vector, Anopheles stephensi, endangers 126 million people across a rapidly urbanising continent where malaria is primarily a rural disease. Control of An. stephensi requires greater understanding of its origin, invasion dynamics, and mechanisms of widespread resistance to vector control insecticides...

Introduction Malaria remains a significant public health challenge globally, particularly in sub-Saharan Africa, where progress has stalled in recent years. Long-lasting insecticidal nets (LLINs) are a critical preventive tool against malaria. This study investigated the effectiveness of newer-generation LLINs following a universal coverage campaig...

Long-lasting insecticidal nets (LLINs) are the cornerstone of malaria control, but their effectiveness is threatened by pyrethroid resistance. We embedded a pragmatic, cluster-randomised trial into Uganda’s national LLIN distribution campaign in 2020–2021, comparing pyrethroid-piperonyl butoxide (PBO) LLINs to pyrethroid-pyriproxyfen LLINs. Target...

A dramatic malaria resurgence occurred in areas of Uganda between 2020 and 2022 coincident with the switch to clothianidin-based formulations for indoor residual spraying. During the resurgence, Anopheles funestus numbers increased but when an alternative insecticide, pirimiphos methyl, was reintroduced in 2023, both malaria cases and An. funestus...

The emergence of insecticide resistance is threatening the efforts of malaria control programmes, which rely heavily on a limited arsenal of insecticidal tools, such as insecticide-treated bed nets. Importantly, genomic surveillance of malaria vectors can provide critical, policy-relevant insights into the presence and evolution of insecticide resi...

Background In western Kenya, a cluster-randomized trial is assessing the impact of attractive targeted sugar baits (ATSBs) on malaria in children enrolled in three consecutive cohorts. Here, characteristics of children and households at enrolment, and factors associated with baseline malaria prevalence are described. Methods Children aged 1 to < 1...

Background Anopheles stephensi, a malaria mosquito originally from South Asia and the Middle East, has been expanding across both Asia and Africa in recent decades. The invasion of this species into sub-Saharan Africa is of particular concern given its potential to increase malaria burden, especially in urban environments where An. stephensi thrive...

Background Despite consecutive decades of success in reducing malaria transmission, Ethiopia went off track towards its goal of malaria elimination by 2030, as outlined in the NMCP malaria strategy. Recent malaria outbreaks in Ethiopia are attributed to the emergence and spread of diagnostic and drug-resistant Plasmodium falciparum , increased inse...

Background Ethiopia faces several severe challenges in terms of malaria elimination, including drug resistance and diagnostic evasion in the Plasmodium falciparum parasite, insecticide resistance in the primary Anopheles malaria vector, and, most recently, the invasion of the Asian malaria vector Anopheles stephensi. Novel malaria control methods a...

Introduction: Malaria remains a significant public health challenge globally, particularly in sub-Saharan Africa, where progress has stalled in recent years. Long-lasting insecticidal nets (LLINs) are a critical preventive tool against malaria. This study investigated the effectiveness of newer-generation LLINs following a universal coverage campai...

Malaria control relies on insecticides targeting the mosquito vector, but this is increasingly compromised by insecticide resistance, which can be achieved by elevated expression of detoxifying enzymes that metabolize the insecticide. In diploid organisms, gene expression is regulated both in cis, by regulatory sequences on the same chromosome, and...

Background Endemic African malaria vectors are poorly adapted to typical urban ecologies. However, Anopheles stephensi, an urban malaria vector formerly confined to South Asia and the Persian Gulf, was recently detected in Africa and may change the epidemiology of malaria across the continent. Little is known about the public health implications of...

Tororo District, Uganda experienced a dramatic decrease in malaria burden from 2015–19 during 5 years of indoor residual spraying (IRS) with carbamate (Bendiocarb) and then organophosphate (Actellic) insecticides. However, a marked resurgence occurred in 2020, which coincided with a change to a clothianidin-based IRS formulations (Fludora Fusion/Su...

The primary control methods for the African malaria mosquito, Anopheles gambiae, are based on insecticidal interventions. Emerging resistance to these compounds is therefore of major concern to malaria control programs. The organophosphate (OP), pirimiphos-methyl, is a relatively new chemical in the vector control armory but is now widely used in i...

Pyrethroid bednets treated with the synergist piperonyl butoxide (PBO) offer the possibility of improved vector control in mosquito populations with metabolic resistance. In 2017–2019, we conducted a large-scale, cluster-randomised trial (LLINEUP) to evaluate long-lasting insecticidal nets (LLINs) treated with a pyrethroid insecticide plus PBO (PBO...

Background Disruptions in malaria control due to COVID-19 mitigation measures were predicted to increase malaria morbidity and mortality in Africa substantially. In Uganda, long-lasting insecticidal nets (LLINs) are distributed nationwide every 3–4 years, but the 2020–2021 campaign was altered because of COVID-19 restrictions so that the timing of...

The major malaria mosquitoes, Anopheles gambiae s.l and Anopheles funestus , are some of the most studied organisms in medical research and also some of the most genetically diverse. When designing polymerase chain reaction (PCR) or hybridisation-based molecular assays, reliable primer and probe design is crucial. However, single nucleotide polymor...

Background The effectiveness of long-lasting insecticidal nets (LLINs) are being threatened by growing resistance to pyrethroids. To restore their efficacy, a synergist, piperonyl butoxide (PBO) which inhibits cytochrome P450s has been incorporated into pyrethroid treated nets. A trial of PBO-LLINs was conducted in Uganda from 2017 and we attempted...

Background Vector surveillance is among the World Health Organization global vector control response (2017–2030) pillars. Human landing catches are a gold standard but difficult to implement and potentially expose collectors to malaria infection. Other methods like light traps, pyrethrum spray catches and aspiration are less expensive and less risk...

Background: Tororo District, Uganda experienced a dramatic decrease in malaria burden from 2015-19 following 5 years of indoor residual spraying (IRS) with carbamate (Bendiocarb) and then organophosphate (Actellic) insecticides. However, a marked resurgence occurred in 2020, which coincided with a change to a clothianidin-based IRS formulations (Fl...

To keep ahead of the evolution of resistance to insecticides in mosquitoes, national malaria control programmes must make use of a range of insecticides, both old and new, while monitoring resistance mechanisms. Knowledge of the mechanisms of resistance remains limited in Anopheles arabiensis , which in many parts of Africa is of increasing importa...

The primary control methods for the African malaria mosquito, Anopheles gambiae , are based on insecticidal interventions. Emerging resistance to these compounds is therefore of major concern to malaria control programmes. The organophosphate, pirimiphos-methyl, is a relatively new chemical in the vector control armoury but is now widely used in in...

Introduction Accurate assessments of vector occurrence and abundance, particularly in widespread vector-borne diseases such as malaria, are crucial for the efficient deployment of disease surveillance and control interventions. Although previous studies have explored the benefits of adaptive sampling for identifying disease hotspots (mostly through...

Background: The effectiveness of long-lasting insecticidal nets (LLINs) are being threatened by growing resistance to pyrethroids. To restore their efficacy, a synergist, piperonyl butoxide (PBO) which inhibits cytochrome P450s has been incorporated into pyrethroid treated nets. A trial of PBO-LLINs was conducted in Uganda from 2017 and we attempte...

Much of our understanding of malaria transmission comes from mosquito feeding assays using Anopheles mosquitoes from colonies that are well adapted to membrane feeding. This raises the question whether results from colony mosquitoes lead to overestimates of outcomes in wild Anopheles mosquitoes. We successfully established an Anopheles colony using...

Background Endemic African malaria vectors are poorly adapted to typical urban ecologies. However, Anopheles stephensi, an urban malaria vector formerly confined to South Asia and the Persian Gulf, was recently detected in Africa and may change the epidemiology of malaria across the continent. Little is known about the public health implications of...

Background Children in Kenya spend a substantial amount of time at school, including at dawn and dusk when mosquitoes are active. With changing vector behaviour towards early morning biting, it is important to determine whether there is an additional risk of transmission in schools. This study sought to understand whether late morning biting by Ano...

Malaria control relies on insecticides targeting the mosquito vector, but this is increasingly compromised by insecticide resistance, which can be achieved by elevated expression of detoxifying enzymes that metabolize the insecticide. In diploid organisms, gene expression is regulated both in cis, by regulatory sequences on the same chromosome, and...

Vector control interventions often lack comprehensive information on vector population distribution and dynamics. This knowledge gap poses challenges in targeting interventions effectively, especially in areas with heterogeneous transmission and where complementary vector control tools may be required to achieve sustained impact on disease transmis...

Background: Children in Kenya spend a substantial amount of time at school, including at dawn and dusk when mosquitoes are active. If schools do not have adequate malaria transmission prevention, they can become hotspots for infection. With changing vector behaviour towards early morning biting, it is important to determine whether there is an addi...

Background Enhanced vector surveillance, is one of the 4 pillars of the WHO’s global vector control response (2017–2030). Human landing catches are the gold standard for entomological surveys but are difficult to implement and expose collectors to mosquito bites and potentially to malaria infection. Other surveillance tools such as light traps, pyr...

Resistance to insecticides in Anopheles mosquitoes threatens the effectiveness of malaria control, but the genetics of resistance are only partially understood. We performed a large scale multi-country genome-wide association study of resistance to two widely used insecticides: deltamethrin and pirimiphos-methyl, using sequencing data from An. gamb...

Background Entomological surveillance is traditionally conducted by supervised teams of trained technicians. However, it is expensive and limiting in the number of sites visited. Surveillance through community-based collectors (CBC) may be more cost-effective and sustainable for longitudinal entomological monitoring. This study evaluated the effici...

Natural history collections represent a vast biological and genetic resource, which has remained largely untapped. We revisit mosquito collections of varying ages; some made by early tropical medicine pioneers over 100 years ago. By applying species-specific primers, a panel of forensic short tandem repeat (STR) markers, and Plasmodium diagnostics,...

Understanding the contribution of asymptomatic Plasmodium carriers in malaria transmission might be helpful to design and implement new control measures. The present study explored the prevalence of asymptomatic and symptomatic Plasmodium infections (asexual and sexual stages) and the contribution of asymptomatic P. falciparum carriers to Anopheles...

Developing robust and standardised approaches for testing mosquito populations against insecticides is vital for understanding the effectiveness of new active ingredients or formulations. Methods for testing mosquito susceptibility against contact insecticides or products, such as those delivered through public health programmes, are well-establish...

Understanding the behavior and ecology of local malaria vectors is essential for the effectiveness of the commonly used vector-targeted malaria control tools in areas of low malaria transmission. This study was conducted to determine species composition, biting behavior and infectivity of the major Anopheles vectors of Plasmodium falciparum in low...

Resistance to pyrethroid and organophosphate insecticides in the malaria vector Anopheles gambiae (s.l.) is conferred by a variety of genetic mutations, including single nucleotide polymorphisms (SNPs) and copy number variants (CNVs). Knowledge of the distribution of these mutations in mosquito populations is a prerequisite for establishing better...

We provide a reproducible and scalable Snakemake workflow, called RNA‐Seq‐Pop, which provides end‐to‐end analysis of RNA‐Seq data sets. The workflow allows the user to perform quality control, differential expression analyses, and call genomic variants. Additional options include the calculation of allele frequencies of variants of interest, summar...

Introduction. Entomological surveillance is traditionally conducted by supervised teams of trained technicians. However, it is expensive and limiting in the number of sites visited. Surveillance through community-based collectors (CBC) may be more cost-effective and sustainable for longitudinal entomological monitoring. This study evaluated the eff...

Abstract Background Insecticides play a key role in rural farming; however, their over- or misuse has been linked with a negative impact on malaria vector control policies. This study was conducted amongst agricultural communities in Southern Côte d’Ivoire to identify which insecticides are used by local farmers and how it relates to the perception...

Insecticide resistance threatens recent progress on malaria control in Africa. To characterize pyrethroid resistance in Uganda, Anopheles gambiae (s.s.) and Anopheles arabiensis were analyzed from 11 sites with varied vector control strategies. Mosquito larvae were collected between May 2018 and December 2020. Sites were categorized as receiving no...

The glutathione S-transferases (GST) genes are a multigene family of enzymes involved in the metabolism of endogenous and xenobiotic compounds by catalysing the conjugation of the reduced form of glutathione to the substrate. The epsilon class of GST (GSTe), unique to arthropods, is known to be involved in the detoxification process of several clas...

The Program for Resistance, Immunology, Surveillance, and Modeling of Malaria (PRISM) has been conducting malaria research in Uganda since 2010 to improve the understanding of the disease and measure the impact of population-level control interventions in the country. Here, we will summarize key research findings from a series of studies addressing...

Five years of sustained indoor residual spraying (IRS) of insecticide from 2014 to 2019, first using a carbamate followed by an organophosphate, was associated with a marked reduction in the incidence of malaria in five districts of Uganda. We assessed changes in malaria incidence over an additional 21 months, corresponding to a change in IRS formu...

Background Long-lasting insecticidal nets (LLINs) are the foundation of malaria control but resistance of mosquito vectors to pyrethroids threatens their effectiveness. We embedded a cluster-randomised trial into Uganda's 2017–18 campaign to distribute LLINs. LLINs with piperonyl butoxide (PBO) reduced parasite prevalence more effectively than conv...

The cause of malaria transmission has been known for over a century but it is still unclear whether entomological measures are sufficiently reliable to inform policy decisions in human health. Decision-making on the effectiveness of new insecticide-treated nets (ITNs) and the indoor residual spraying of insecticide (IRS) have been based on epidemio...

Studies of insecticide resistance provide insights into the capacity of populations to show rapid evolutionary responses to contemporary selection. Malaria control remains heavily dependent on pyrethroid insecticides, primarily in long lasting insecticidal nets (LLINs). Resistance in the major malaria vectors has increased in concert with the expan...

Long-lasting insecticidal nets (LLINs) supplemented with the synergist piperonyl butoxide have been developed in response to growing pyrethroid resistance; however, their durability in the field remains poorly described. A pragmatic cluster-randomised trial was embedded into Ugandaʼs 2017–2018 LLIN distribution to compare the durability of LLINs wi...

Five years of sustained indoor residual spraying (IRS) of insecticide from 2014 to 2019, first using a carbamate followed by an organophosphate, was associated with a marked reduction in the burden of malaria in five districts of Uganda. We assessed malaria burden over an additional 21 months, corresponding to a change in IRS formulations using clo...

Long Lasting Insecticidal Nets (LLINs) supplemented with the synergist piperonyl butoxide have been developed in response to growing pyrethroid resistance however their durability in the field remains poorly described. A pragmatic cluster-randomised trial was embedded into Uganda’s 2017-2018 distribution to compare the durability of LLINs with and...

Background Resistance in malaria vectors to pyrethroids, the most widely used class of insecticides for malaria vector control, threatens the continued efficacy of vector control tools. Target-site resistance is an important genetic resistance mechanism caused by mutations in the voltage-gated sodium channel ( Vgsc ) gene that encodes the pyrethroi...

Insecticide resistance provides both a pressing threat to the control of vector-borne diseases and insights into the remarkable capacity of natural populations to show rapid evolutionary responses. Malaria control remains heavily dependent on deployment of insecticides, primarily in long lasting insecticide treated nets (LLINs), but resistance in t...

Background Concern that insecticide resistant mosquitoes are threatening malaria control has driven the development of new types of insecticide treated nets (ITNs) and indoor residual spraying (IRS) of insecticide. Malaria control programmes have a choice of vector control interventions although it is unclear which controls should be used to combat...

Many vector-borne diseases are controlled by methods that kill the insect vectors responsible for disease transmission. Recording the age structure of vector populations provides information on mortality rates and vectorial capacity, and should form part of the detailed monitoring that occurs in the wake of control programmes, yet tools for obtaini...

Introduction: Longitudinal monitoring of outdoor-biting malaria vector populations is becoming increasingly important in understanding the dynamics of residual malaria transmission. However, the human landing catch (HLC), the gold standard for measuring human biting rates indoors and outdoors, is costly and raises ethical concerns related to incre...

Many vector-borne diseases are controlled by methods that kill the insect vectors responsible for disease transmission. Recording the age structure of vector populations provides information on mortality rates and vectorial capacity, and should form part of the detailed monitoring that occurs in the wake of control programmes, yet tools for obtaini...

Abstract Background Long-lasting insecticidal nets (LLINs) and indoor residual spraying (IRS) are the malaria control interventions primarily responsible for reductions in transmission intensity across sub-Saharan Africa. These interventions, however, may have differential impact on Anopheles species composition and density. This study examined the...

Identification of partial sweeps, which include both hard and soft sweeps that have not currently reached fixation, provides crucial information about ongoing evolutionary responses. To this end, we introduce partialS/HIC, a deep learning method to discover selective sweeps from population genomic data. partialS/HIC uses a convolutional neural netw...

Transmission-blocking vaccines and drugs are likely to be key interventions in efforts to achieve malaria elimination. However, transmission-blocking studies are reliant upon a limited number of culture-adapted strains of Plasmodium falciparum with limited genetic variability, or on field isolates which are only maintained transiently in the labora...

Resistance to pyrethroid insecticides is a major concern for malaria vector control. Pyrethroids target the voltage‐gated sodium channel (VGSC), an essential compo nent of the mosquito nervous system. Substitutions in the amino acid sequence can inducing a resistance phenotype. We use whole‐genome sequence data from phase 2 of the Anopheles gambiae...

Introduction. Longitudinal monitoring of outdoor-biting malaria vector populations is becoming increasingly important in understanding the dynamics of residual malaria transmission. However, the human landing catch (HLC), the gold standard for measuring human biting rates indoors and outdoors, is costly and raises ethical concerns related to increa...

Vector population control using insecticides is a key element of current strategies to prevent malaria transmission in Africa. The introduction of effective insecticides, such as the organophosphate pirimiphos-methyl, is essential to overcome the recurrent emergence of resistance driven by the highly diverse Anopheles genomes. Here, we use a popula...

Objective: This study assessed the susceptibility status of the malaria vector Anopheles culicifacies within the Keshkal sub-district, Chhattisgarh, India. Anopheles culicifacies were collected in 23 sub-centres (~2000-3000 inhabitants/ sub-centre) of Keshkal sub-district in 2013- 2014. Adult female An. culicifacies were exposed to the World Health...

Background Long lasting insecticidal nets (LLINs) and indoor residual spraying (IRS) are malaria control interventions primarily responsible for reductions in transmission intensity across sub-Saharan Africa. These interventions, however, may have differential impact on Anopheles species composition and density. Here, we studied the changing patter...

Background Long lasting insecticidal nets (LLINs) and indoor residual spraying (IRS) are malaria control interventions primarily responsible for reductions in transmission intensity across sub-Saharan Africa. These interventions, however, may have differential impact on Anopheles species composition and density. Here, we studied the changing patter...

We investigated genetic variation at 37 newly-developed microsatellite loci in populations of the tsetse fly Glossina fuscipes fuscipes captured from the upper and lower reaches of a single hydrographical network within an endemic Human African Trypanosomiasis focus. Our primary aim was to assess the impact of vector control using insecticide-treat...

The evolution of insecticide resistance mechanisms in natural populations of Anopheles malaria vectors is a major public health concern across Africa. Using genome sequence data, we study the evolution of resistance mutations in the resistance to dieldrin locus (Rdl), a GABA receptor targeted by several insecticides, but most notably by the long-di...

Vector population control using insecticides is a key element of current strategies to prevent malaria transmission in Africa. The introduction of effective insecticides, such as the organophosphate pirimiphos-methyl, is essential to overcome the recurrent emergence of resistance driven by the highly diverse Anopheles genomes. Here, we use a popula...

Background Long-lasting insecticidal nets (LLINs) are the primary malaria prevention tool, but their effectiveness is threatened by pyrethroid resistance. We embedded a pragmatic cluster-randomised trial into Uganda's national LLIN campaign to compare conventional LLINs with those containing piperonyl butoxide (PBO), a synergist that can partially...

Abstract Indoor residual spraying (IRS) of insecticides is a major vector control strategy for malaria prevention. We evaluated the impact of a single round of IRS with the organophosphate, pirimiphos-methyl (Actellic 300CS), on entomological and parasitological parameters of malaria in Migori County, western Kenya in 2017, in an area where primary...

The evolution of insecticide resistance mechanisms in natural populations of Anopheles malaria vectors is a major public health concern across Africa. Using genome sequence data, we study the evolution of resistance mutations in the resistance to dieldrin gene (Rdl), a GABA receptor targeted by several insecticides, but most notably by the long-dis...

Mosquito control remains a central pillar of efforts to reduce malaria burden in sub-Saharan Africa. However, insecticide resistance is entrenched in malaria vector populations, and countries with high malaria burden face a daunting challenge to sustain malaria control with a limited set of surveillance and intervention tools. Here we report on the...

Background: Malaria vector control and research rely heavily on monitoring mosquito populations for the development of resistance to public health insecticides. One standard method for determining resistance in adult mosquito populations is the World Health Organization test (WHO bioassay). The WHO bioassay kit consists of several acrylic pieces t...

Over the past two decades efforts to control malaria have halved the number of cases globally, yet burdens remain high in much of Africa and the elimination of malaria has not been achieved even in areas where extreme reductions have been sustained, such as South Africa 1,2. Studies seeking to understand the paradoxical persistence of malaria in ar...

Over the past two decades efforts to control malaria have halved the number of cases globally, yet burdens remain high in much of Africa and the elimination of malaria has not been achieved even in areas where extreme reductions have been sustained, such as South Africa1,2. Studies seeking to understand the paradoxical persistence of malaria in are...

The spread of resistance to insecticides in disease-carrying mosquitoes poses a threat to the effectiveness of control programmes, which rely largely on insecticide-based interventions. Monitoring mosquito populations is essential, but obtaining phenotypic measurements of resistance is laborious and error-prone. High-throughput genotyping offers th...

Background Malaria vector control and research rely heavily on monitoring mosquito populations for the development of resistance to public health insecticides. One standard method for determining susceptibility in adult mosquito populations is the World Health Organization test (WHO bioassay). The WHO bioassay kit consists of several acrylic pieces...