Plasmodium gametocyte carriage in humans and sporozoite rate in anopheline mosquitoes in Gondar zuria district, Northwest Ethiopia.

Although the overall burden of malaria is decreasing in Ethiopia, a recent report of an unpredictable increased incidence may be related to the presence of community-wide gametocyte-carrier individuals and a high proportion of infected vectors. This study aimed to reveal the current prevalence of gametocyte-carriage and the sporozoite infectivity rate of Anopheles vectors for Plasmodium parasites. A community-based cross-sectional study was conducted from May 01 to June 30/2019. A total of 53 households were selected using systematic random sampling and a 242 study participants were recruited. Additionally,515 adult female Anopheles mosquitoes were collected using Center for Diseases Control and Prevention (CDC) light traps and mouth aspirators. Parasite gametocytemia was determined using giemsa stain microscopy, while sporozoite infection was determined by giemsa staining microscopy and enzyme linked immunosorbent assay (ELISA). Among the total 242 study participants, 5.4% (95%, CI = 2.9-8.3) of them were positive for any of the Plasmodium species gametocyte. Furthermore, being female [AOR = 15.5(95%, CI = 1.71-140.39)], age group between 15-29 years old [AOR = 16.914 (95%, CI = 1.781-160.63)], no ITNs utilization [AOR = 16.7(95%, CI = 1.902 -146.727)], and high asexual parasite density [(95%, CI = 0.057-0.176, P = 0.001, F = 18.402)] were identified as statistically significant factors for gametocyte carriage. Whereas sporozoite infection rate was 11.6% (95%, CI = 8.2-15.5) and 12.7% (95%, CI = 9.6-16.3) by microscopy and ELISA, respectively. Overall, this study indicated that malaria remains to be an important public health problem in Gondar Zuria district where high gametocyte carriage rate and sporozoite infection rate could sustain its transmission and burden. Therefore, in Ethiopia, where malaria elimination program is underway, frequent, and active community-based surveillance of gametocytemia and sporozoite infection rate is important.

[Biological threats to global malaria elimination â ¢ Vector insecticide resistance].

The insecticide resistance is becoming increasingly severe in malaria vectors and has become one of the most important threats to global malaria elimination. Currently, malaria vectors not only have developed high resistance to conventional insecticides, including organochlorine, organophosphates, carbamates, and pyrethroids, but also have been resistant to recently used neonicotinoids and pyrrole insecticides. This article describes the current status of global insecticide resistance in malaria vectors and global insecticide resistance management strategies, analyzes the possible major challenges in the insecticide resistance management, and proposes the response actions, so as to provide insights into global insecticide resistance management and contributions to global malaria elimination.

Combination of computational techniques and RNAi reveal targets in Anopheles gambiae for malaria vector control.

Increasing reports of insecticide resistance continue to hamper the gains of vector control strategies in curbing malaria transmission. This makes identifying new insecticide targets or alternative vector control strategies necessary. CLassifier of Essentiality AcRoss EukaRyote (CLEARER), a leave-one-organism-out cross-validation machine learning classifier for essential genes, was used to predict essential genes in Anopheles gambiae and selected predicted genes experimentally validated. The CLEARER algorithm was trained on six model organisms: Caenorhabditis elegans, Drosophila melanogaster, Homo sapiens, Mus musculus, Saccharomyces cerevisiae and Schizosaccharomyces pombe, and employed to identify essential genes in An. gambiae. Of the 10,426 genes in An. gambiae, 1,946 genes (18.7%) were predicted to be Cellular Essential Genes (CEGs), 1716 (16.5%) to be Organism Essential Genes (OEGs), and 852 genes (8.2%) to be essential as both OEGs and CEGs. RNA interference (RNAi) was used to validate the top three highly expressed non-ribosomal predictions as probable vector control targets, by determining the effect of these genes on the survival of An. gambiae G3 mosquitoes. In addition, the effect of knockdown of arginase (AGAP008783) on Plasmodium berghei infection in mosquitoes was evaluated, an enzyme we computationally inferred earlier to be essential based on chokepoint analysis. Arginase and the top three genes, AGAP007406 (Elongation factor 1-alpha, Elf1), AGAP002076 (Heat shock 70kDa protein 1/8, HSP), AGAP009441 (Elongation factor 2, Elf2), had knockdown efficiencies of 91%, 75%, 63%, and 61%, respectively. While knockdown of HSP or Elf2 significantly reduced longevity of the mosquitoes (p<0.0001) compared to control groups, Elf1 or arginase knockdown had no effect on survival. However, arginase knockdown significantly reduced P. berghei oocytes counts in the midgut of mosquitoes when compared to LacZ-injected controls. The study reveals HSP and Elf2 as important contributors to mosquito survival and arginase as important for parasite development, hence placing them as possible targets for vector control.

Infectivity of Plasmodium parasites to Aedes aegypti and Anopheles stephensi mosquitoes maintained on blood-free meals of SkitoSnack.

BACKGROUND: Aedes and Anopheles mosquitoes are responsible for tremendous global health burdens from their transmission of pathogens causing malaria, lymphatic filariasis, dengue, and yellow fever. Innovative vector control strategies will help to reduce the prevalence of these diseases. Mass rearing of mosquitoes for research and support of these strategies presently depends on meals of vertebrate blood, which is subject to acquisition, handling, and storage issues. Various blood-free replacements have been formulated for these mosquitoes, but none of these replacements are in wide use, and little is known about their potential impact on competence of the mosquitoes for Plasmodium infection. METHODS: Colonies of Aedes aegypti and Anopheles stephensi were continuously maintained on a blood-free replacement (SkitoSnack; SS) or bovine blood (BB) and monitored for engorgement and hatch rates. Infections of Ae. aegypti and An. stephensi were assessed with Plasmodium gallinaceum and P. falciparum, respectively. RESULTS: Replicate colonies of mosquitoes were maintained on BB or SS for 10 generations of Ae. aegypti and more than 63 generations of An. stephensi. The odds of engorgement by SS- relative to BB-maintained mosquitoes were higher for both Ae. aegypti (OR = 2.6, 95% CI 1.3-5.2) and An. stephensi (OR 2.7, 95% CI 1.4-5.5), while lower odds of hatching were found for eggs from the SS-maintained mosquitoes of both species (Ae. aegypti OR = 0.40, 95% CI 0.26-0.62; An. stephensi OR = 0.59, 95% CI 0.36-0.96). Oocyst counts were similar for P. gallinaceum infections of Ae. aegypti mosquitoes maintained on SS or BB (mean ratio = [mean on SS]/[mean on BB] = 1.11, 95% CI 0.85-1.49). Similar oocyst counts were also observed from the P. falciparum infections of SS- or BB-maintained An. stephensi (mean ratio = 0.76, 95% CI 0.44-1.37). The average counts of sporozoites/mosquito showed no evidence of reductions in the SS-maintained relative to BB-maintained mosquitoes of both species. CONCLUSIONS: Aedes aegypti and An. stephensi can be reliably maintained on SS over multiple generations and are as competent for Plasmodium infection as mosquitoes maintained on BB. Use of SS alleviates the need to acquire and preserve blood for mosquito husbandry and may support new initiatives in fundamental and applied research, including novel manipulations of midgut microbiota and factors important to the mosquito life cycle and pathogen susceptibility.

[While the priest climbs a post, the devil climbs ten: major biological threats from parasite and vector to malaria control and elimination].

Malaria is one of the most serious mosquito-borne infectious diseases in the world. The global malaria control progress has stalled in recent years, which is largely due to the biological threats from the malaria pathogen Plasmodium and the vector Anopheles mosquitoes. This article provides an overview of biological threats to global malaria elimination, including antimalarial drug resistance, deletions in the malaria rapid diagnostic test target P. falciparum histidine-rich protein 2/3 (Pfhrp2/3) genes, vector insecticide resistance and emergence of invasive vector species, so as to provide insights into malaria and vector research and the formulation and adjustment of the malaria control and elimination strategy.

[Biological threats to global malaria elimination â £ Emergence of invasive vector species].

Driven by international exchanges and climate changes, the invasion and spread of vector Anopheles mosquitoes posed a new challenge to achieving global malaria elimination. Taking the invasion of An. stephensi to exacerbate the malaria epidemic in Africa as an example, this article summarizes the current situation of global Anopheles invasion, and estimates the potential risk of vector Anopheles mosquitoes to unravel the difficulties and challenges in the global malaria elimination program, so as to provide insights into improved early earning and precision control of vector Anopheles mosquito invasion across the world.

Rapid entomological assessment in eight high malaria endemic regencies in Papua Province revealed the presence of indoor and outdoor malaria transmissions.

Malaria in eastern Indonesia remains high despite significant reduction and elimination in other parts of the country. A rapid entomological assessment was conducted in eight high malaria endemic regencies of Papua Province, Indonesia, to expedite malaria elimination efforts in this region. This study aims to characterize specific, actionable endpoints toward understanding where and when malaria transmission is happening, where interventions may function best, and identify gaps in protection that result in continued transmission. The entomological assessment included identifying potential vectors through human landing catch (HLC), indoor morning and night resting collections, identification of larval sites through surveillance of water bodies, and vector incrimination toward understanding exposure to malaria transmission. Human landing catches (HLCs) and larval collections identified 10 Anopheles species, namely Anopheles koliensis, Anopheles punctulatus, Anopheles farauti, Anopheles hinesorum, Anopheles longirostris, Anopheles peditaeniatus, Anopheles tesselatus, Anopheles vagus, Anopheles subpictus and Anopheles kochi. The most common and abundant species found overall were An. koliensis and An. punctulatus, while An. farauti was found in large numbers in the coastal areas of Mimika and Sarmi Regencies. Vector incrimination on Anopheles collected from HLCs and night indoor resting demonstrated that An. koliensis and An. punctulatus carried Plasmodium in Keerom, Jayapura, and Sarmi Regencies. Analysis of HLCs for the most common species revealed that the An. koliensis and An. punctulatus, bite indoors and outdoors at equal rates, while An. farauti predominantly bite outdoors. Larval surveillance demonstrated that most water bodies in and surrounding residential areas contained Anopheles larvae. This study demonstrated indoor and outdoor exposure to mosquito bites and gaps in protection, enabling exposure to infectious bites in all regencies. This explains why current malaria control efforts focusing on indoor protection have failed to substantially reduce malaria incidence in the region. Optimization of insecticide-treated bed nets (ITNs), as well as installment of mosquito screens in houses, may further reduce indoor transmission. For outdoor transmission, the use of community-centric approaches to reduce or eliminate larval sources within and surrounding the village through the guidance of locally stationed entomologists, along with Social and Behavior Change mediated health education towards the local adoption of mosquito protection tools during outdoor activities, may reduce malaria transmission.

Time to implement tailored interventions in Chhattisgarh, east-central India to reach malaria elimination.

BACKGROUND OBJECTIVES: Despite significant progress in malaria control throughout India, Chhattisgarh state continues to be a significant contributor to both malaria morbidity and mortality. This study aims to identify key factors associated with malaria endemicity, with a goal of focusing on these factors for malaria elimination by 2030. METHODS: We employed an analysis and narrative review methodology to summarize the existing evidence on malaria epidemiology in Chhattisgarh. Data encompassing environmental conditions, dominant malaria vectors and their distribution, and the impact of previous interventions on malaria control, were extracted from published literature using PubMed and Google Scholar. This information was subsequently correlated with malaria incidence data using appropriate statistical and geographical methods. RESULTS: Much of the malaria burden in Chhattisgarh state is concentrated in a few specific districts. The primary malaria vectors in these regions are Anopheles culicifacies and An. fluviatilis. High transmission areas are found in tribal belts which are challenging to access and are characterized by densely forested areas that provide a conducive habitat for malaria vectors. INTERPRETATION CONCLUSION: Conducive environmental conditions characterized by high forest cover, community behavior, and insurgency, contribute to high malaria endemicity in the area. Challenges include insecticide resistance in malaria vectors and asymptomatic malaria. Allocating additional resources to high-endemic districts is crucial. Innovative and focused malaria control programs of the country, such as DAMAN and Malaria Mukt Abhiyan, hold immense importance.

Vectors, knowledge, attitudes, and practices in relation to malaria transmission in Bauchi State, Nigeria.

BACKGROUND OBJECTIVES: Malaria remains a major public health concern in Nigeria and the vector (Anopheles species) can only be controlled effectively by having good knowledge of its composition and potential for disease transmission. This work aimed at surveying indoor malaria vectors and, Knowledge, Attitudes, and Practices (KAP) in relation to disease transmission in Toro LGA, Bauchi State, Nigeria. METHODS: Mosquitoes were collected by Pyrethrum Spray Catch (PSC) between October and December 2019 and were morphologically identified using standard keys. Blood samples were collected from individuals who slept in the rooms where PSC was conducted. Thick and thin blood smears were made for malaria parasite examination. Questionnaires were administered to 120 participants for the KAP studies. RESULTS: Ninety-seven Anopheles mosquitoes were collected and identified as Anopheles gambiae 76 (78.35%), An. funestus 20 (20.62%) and An. coustani 1(1.03%). The overall malaria prevalence was 15.8%. KAP studies revealed that measures and treatment-seeking behaviours against malaria varied significantly (P<0.05) among the respondents. Sleeping under a net 55 (45.8%) and use of insecticides 24 (20.0%) were some of the preventive measures highlighted while the treatment-seeking behaviours included visit to a pharmacy 74 (61.7%) and use of local herbs 11 (9.2%). INTERPRETATION CONCLUSION: This work revealed that An. gambiae and An. funestus are predominant malaria vectors in the area. The KAP information demonstrated fair knowledge about the disease by the respondents. Therefore, public enlightenment about malaria prevention, control and treatment is recommended to address the few but highly negative impact knowledge gaps about malaria.

À la carte: how mosquitoes choose their blood meals.

Mosquitoes are important vectors for human diseases, transmitting pathogens that cause a range of parasitic and viral infections. Mosquito blood-feeding is heterogeneous, meaning that some human hosts are at higher risk of receiving bites than others, and this heterogeneity is multifactorial. Mosquitoes integrate specific cues to locate their hosts, and mosquito attraction differs considerably between individual human hosts. Heterogeneous mosquito biting results from variations in both host attractiveness and availability and can impact transmission of vector-borne diseases. However, the extent and drivers of this heterogeneity and its importance for pathogen transmission remain incompletely understood. Here, we review methods and recent data describing human characteristics that affect host-seeking behavior and host preferences of mosquito disease vectors, and the implications for vector-borne disease transmission.

LLIN Evaluation in Uganda Project (LLINEUP)-effects of a vector control trial on Plasmodium infection prevalence and genotypic markers of insecticide resistance in Anopheles vectors from 48 districts of Uganda.

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 LLINs), as compared to conventional, pyrethroid-only LLINs across 104 health sub-districts (HSDs) in Uganda. In LLINEUP, and similar trials in Tanzania, PBO LLINs were found to provide greater protection against malaria than conventional LLINs, reducing parasitaemia and vector density. In the LLINEUP trial, we conducted cross-sectional household entomological surveys at baseline and then every 6 months for two years, which we use here to investigate longitudinal changes in mosquito infection rate and genetic markers of resistance. Overall, 5395 female Anopheles mosquitoes were collected from 5046 households. The proportion of mosquitoes infected (PCR-positive) with Plasmodium falciparum did not change significantly over time, while infection with non-falciparum malaria decreased in An. gambiae s.s., but not An. funestus. The frequency of genetic markers associated with pyrethroid resistance increased significantly over time, but the rate of change was not different between the two LLIN types. The knock-down resistance (kdr) mutation Vgsc-995S declined over time as Vgsc-995F, the alternative resistance mutation at this codon, increased. Vgsc-995F appears to be spreading into Uganda. Distribution of LLINs in Uganda was previously found to be associated with reductions in parasite prevalence and vector density, but here we show that the proportion of infective mosquitoes remained stable across both PBO and non-PBO LLINs, suggesting that the potential for transmission persisted. The increased frequency of markers of pyrethroid resistance indicates that LLIN distribution favoured the evolution of resistance within local vectors and highlights the potential benefits of resistance management strategies.Trial registration: This study is registered with ISRCTN, ISRCTN17516395. Registered 14 February 2017, http://www.isrctn.com/ISRCTN17516395 .

Eliminating malaria vectors with precision-guided sterile males.

Controlling the principal African malaria vector, the mosquito Anopheles gambiae, is considered essential to curtail malaria transmission. However, existing vector control technologies rely on insecticides, which are becoming increasingly ineffective. Sterile insect technique (SIT) is a powerful suppression approach that has successfully eradicated a number of insect pests, yet the A. gambiae toolkit lacks the requisite technologies for its implementation. SIT relies on iterative mass releases of nonbiting, nondriving, sterile males which seek out and mate with monandrous wild females. Once mated, females are permanently sterilized due to mating-induced refractoriness, which results in population suppression of the subsequent generation. However, sterilization by traditional methods renders males unfit, making the creation of precise genetic sterilization methods imperative. Here, we introduce a vector control technology termed precision-guided sterile insect technique (pgSIT), in A. gambiae for inducible, programmed male sterilization and female elimination for wide-scale use in SIT campaigns. Using a binary CRISPR strategy, we cross separate engineered Cas9 and gRNA strains to disrupt male-fertility and female-essential genes, yielding >99.5% male sterility and >99.9% female lethality in hybrid progeny. We demonstrate that these genetically sterilized males have good longevity, are able to induce sustained population suppression in cage trials, and are predicted to eliminate wild A. gambiae populations using mathematical models, making them ideal candidates for release. This work provides a valuable addition to the malaria genetic biocontrol toolkit, enabling scalable SIT-like confinable, species-specific, and safe suppression in the species.

Vectorial drivers of malaria transmission in Jabi Tehnan district, Amhara Regional State, Ethiopia.

Among the factors affecting the effectiveness of malaria control is poor knowledge of the entomologic drivers of the disease. We investigated anopheline populations as part of a baseline study to implement house screening of windows and doors as a supplementary malaria control tool towards elimination in Jabi Tehnan district, Amhara Regional State of Ethiopia. The samples were surveyed monthly using CDC light traps between June 2020 and May 2021. Mosquito trap density (< 3 mosquitoes/trap) was low, however, with a high overall Plasmodium sporozoite rate (9%; indoor = 4.3%, outdoor = 13.1%) comprising P. falciparum (88.9%) and P. vivax (11.1%). Anopheles gambiae s.l., mostly An. arabiensis, comprised > 80% of total anopheline captures and contributed ~ 42% of Plasmodium-infected mosquitoes. On the other hand, morphologically scored Anopheles funestus s.l., constituting about 6% of anopheline collections, accounted for 50% of sporozoite-infected mosquitoes. Most of the infected An. funestus s.l. specimens (86.7%) were grouped with previously unknown or undescribed Anopheles species previously implicated as a cryptic malaria vector in the western Kenyan highlands, confirming its wider geographic distribution in eastern Africa. Other species with Plasmodium infection included An. longipalpis C, An. theileri, An. demillioni, and An. nili. Cumulatively, 77.8% of the infected mosquitoes occurred outdoors. These results suggest efficient malaria parasite transmission despite the low vector densities, which has implications for effective endpoint indicators to monitor malaria control progress. Additionally, the largely outdoor infection and discovery of previously unknown and cryptic vectors suggest an increased risk of residual malaria transmission and, thus, a constraint on effective malaria prevention and control.

Colonization of Anopheles coustani, a neglected malaria vector in Madagascar.

Anopheles coustani has long been recognized as a secondary malaria vector in Africa. It has recently been involved in the transmission of both Plasmodium falciparum and P. vivax in Madagascar. As most secondary malaria vectors, An. coustani mainly bites outdoors, which renders the control of this mosquito species difficult using classical malaria control measures, such as the use of bed nets or indoor residual spraying of insecticides. For a better understanding of the biology and vector competence of a vector species, it is useful to rear the species in the laboratory. The absence of a colony hinders the assessment of the bionomics of a species and the development of adapted control strategies. Here, we report the first successful establishment of an An. coustani colony from mosquitoes collected in Madagascar. We used a forced copulation procedure as this mosquito species will not mate in cages. We describe our mosquito colonization procedure with detailed biological features concerning larval to adult development and survival, recorded over the first six critical generations. The procedure should be easily applicable to An. coustani from different African countries, facilitating local investigation of An. coustani vector competence and insecticide resistance using the colony as a reference.

Title: Colonisation d'Anopheles coustani, vecteur négligé du paludisme à Madagascar. Abstract: Anopheles coustani est reconnu depuis longtemps comme un vecteur secondaire du paludisme en Afrique. Il a récemment été impliqué dans la transmission de Plasmodium falciparum et de P. vivax à Madagascar. Comme la plupart des vecteurs secondaires du paludisme, An. coustani pique principalement à l'extérieur, ce qui rend difficile le contrôle de cette espèce de moustique par les mesures classiques de lutte contre le paludisme telles que l'utilisation de moustiquaires ou la pulvérisation intradomiciliaire d'insecticides à effet rémanent. Pour une meilleure compréhension de la biologie et de la compétence vectorielle d'une espèce vectrice, il est utile d'élever l'espèce en laboratoire. L'absence de colonie gêne l'évaluation de la bionomie d'une espèce et le développement de stratégies de contrôle adaptées. Nous rapportons ici le premier établissement réussi d'une colonie d' An. coustani issue de moustiques collectés à Madagascar. Nous avons utilisé une procédure de copulation forcée car cette espèce de moustique ne s'accouple pas en cage. Nous décrivons notre procédure de colonisation des moustiques avec des caractéristiques biologiques détaillées concernant le développement et la survie des stades larvaires aux adultes, enregistrées au cours des six premières générations critiques. La procédure devrait être facilement applicable aux An. coustani de différents pays africains, facilitant les enquêtes locales sur la compétence vectorielle d'An. coustani et sa résistance aux insecticides, en utilisant une colonie comme référence.

Altered thermal preferences of infected or immune-challenged Aedes aegypti and Aedes japonicus mosquitoes.

Temperature is a critical factor shaping physiology, life cycle, and behaviour of ectothermic vector insects, as well as the development and multiplication of pathogens within them. However, the influence of pathogen infections on thermal preferences (behavioural thermoregulation) is not well-understood. The present study examined the thermal preferences of mosquitoes (Aedes aegypti and Ae. japonicus) infected with either Sindbis virus (SINV) or Dirofilaria immitis over 12 days post exposure (p.e.) or injected with a non-pathogenic Sephadex bead over 24 h in a thermal gradient (15-30 °C). SINV-infected Ae. aegypti preferred 5 °C warmer temperatures than non-infected ones at day 6 p.e., probably the time of highest innate immune response. In contrast, D. immitis-infected Ae. japonicus preferred 4 °C cooler temperatures than non-infected ones at day 9 p.e., presumably a stress response during the migration of third instar larvae from their development site to the proboscis. Sephadex bead injection also induced a cold preference in the mosquitoes but to a level that did not differ from control-injections. The cold preference thus might be a strategy to escape the risk of desiccation caused by the wound created by piercing the thorax. Further research is needed to uncover the genetic and physiological mechanisms underlying these behaviours.

Efficacy of pyrethroid-pyriproxyfen and pyrethroid-chlorfenapyr nets on entomological indicators of malaria transmission: third year of a randomised controlled trial in Benin.

The present cluster-randomised control trial aims to assess the entomological efficacy of pyrethroid-pyriproxyfen and pyrethroid-chlorfenapyr LLINs compared to the standard pyrethroid-only LLINs, in their third year of community usage. Adult mosquito collections were performed every 3 months, in 4 randomly selected houses in each of the 60 trial clusters, using human landing catches. Adult mosquitoes were morphologically identified and Anopheles vectors were molecularly speciated and screened for the presence of the L1014F kdr mutation using PCR. Plasmodium falciparum sporozoite infection was assessed using ELISA. A subset of An. gambiae s.l. was also dissected to examine parity and fertility rates across study arms. There was no evidence of a significant reduction in indoor vector density and entomological inoculation rate by the pyrethroid-pyriproxyfen [DR 0.94 (95% CI 0.46-1.88), p = 0.8527; and RR 1.10 (95% CI 0.44-2.72), p = 0.8380], and pyrethroid-chlorfenapyr [DR 0.74 (95% CI 0.37-1.48), p = 0.3946; and RR 1.00 (95% CI 0.40-2.50), p = 0.9957] LLINs, respectively. The same trend was observed outdoors. Frequencies of the L1014F kdr mutation, as well as parous and fertility rates, were similar between study arms. In the third year after net distribution, entomological indicators show that the two dual active-ingredients nets performed similarly to the standard pyrethroid-only LLIN. To maintain malaria gains, it is crucial that net distribution cycles fit with their operational lifespan.

Utility of plasma anti-gSG6-P1 IgG levels in determining changes in Anopheles gambiae bite rates in a rural area of Cameroon.

The applicability of the specific human IgG antibody response to Anopheles gambiae salivary Gland Protein-6 peptide 1 (gSG6-P1 salivary peptide) as a biomarker able to distinguish the level of exposure to mosquito bites according to seasonal variations has not yet been evaluated in Central African regions. The study aimed to provide the first reliable data on the IgG anti-gSG6-P1 response in rural area in Cameroon according to the dry- and rainy-season. Between May and December 2020, dry blood samples were collected from people living in the Bankeng village in the forest area of the Centre region of Cameroon. Malaria infection was determined by thick-blood smear microscopy and multiplex PCR. The level of IgG anti-gSG6-P1 response, was assessed by enzyme-linked immunosorbent assay. Anopheles density and aggressiveness were assessed using human landing catches. The prevalence of malaria infection remains significantly higher in the rainy season than in the dry season (77.57% vs 61.44%; p = 0.0001). The specific anti-gSG6-P1 IgG response could be detected in individuals exposed to few mosquito bites and showed inter-individual heterogeneity even when living in the same exposure area. In both seasons, the level of anti-gSG6-P1 IgG response was not significantly different between Plasmodium infected and non-infected individuals. Mosquito bites were more aggressive in the rainy season compared to the dry season (human biting rate-HBR of 15.05 b/p/n vs 1.5 b/p/n) where mosquito density was very low. Infected mosquitoes were found only during the rainy season (sporozoite rate = 10.63% and entomological inoculation rate-EIR = 1.42 ib/p/n). The level of IgG anti-gSG6-P1 response was significantly higher in the rainy season and correlated with HBR (p ˂ 0.0001). This study highlights the high heterogeneity of individual's exposure to the Anopheles gambiae s.l vector bites depending on the transmission season in the same area. These findings reinforce the usefulness of the anti-gSG6-P1 IgG response as an accurate immunological biomarker for detecting individual exposure to Anopheles gambiae s.l. bites during the low risk period of malaria transmission in rural areas and for the differentiating the level of exposure to mosquitoes.

Repeat controlled human Plasmodium falciparum infections delay bloodstream patency and reduce symptoms.

Resistance to clinical malaria takes years to develop even in hyperendemic regions and sterilizing immunity has rarely been observed. To evaluate the maturation of the host response against controlled repeat exposures to P. falciparum (Pf) NF54 strain-infected mosquitoes, we systematically monitored malaria-naïve participants through an initial exposure to uninfected mosquitoes and 4 subsequent homologous exposures to Pf-infected mosquitoes over 21 months (n = 8 males) (ClinicalTrials.gov# NCT03014258). The primary outcome was to determine whether protective immunity against parasite infection develops following repeat CHMI and the secondary outcomes were to track the clinical signs and symptoms of malaria and anti-Pf antibody development following repeat CHMI. After two exposures, time to blood stage patency increases significantly and the number of reported symptoms decreases indicating the development of clinical tolerance. The time to patency correlates positively with both anti-Pf circumsporozoite protein (CSP) IgG and CD8 + CD69+ effector memory T cell levels consistent with partial pre-erythrocytic immunity. IFNγ levels decrease significantly during the participants' second exposure to high blood stage parasitemia and could contribute to the decrease in symptoms. In contrast, CD4-CD8 + T cells expressing CXCR5 and the inhibitory receptor, PD-1, increase significantly after subsequent Pf exposures, possibly dampening the memory response and interfering with the generation of robust sterilizing immunity.

Immune mechanisms targeting malaria transmission: opportunities for vaccine development.

INTRODUCTION: Malaria continues to remain a major global health problem with nearly a quarter of a billion clinical cases and more than 600,000 deaths in 2022. There has been significant progress toward vaccine development, however, poor efficacy of approved vaccines requiring multiple immunizing doses emphasizes the need for continued efforts toward improved vaccines. Progress to date, nonetheless, has provided impetus for malaria elimination. AREAS COVERED: In this review we will focus on diverse immune mechanisms targeting gametocytes in the human host and gametocyte-mediated malaria transmission via the mosquito vector. EXPERT OPINION: To march toward the goal of malaria elimination it will be critical to target the process of malaria transmission by mosquitoes, mediated exclusively by the sexual stages, i.e. male, and female gametocytes, ingested from infected vertebrate host. Studies over several decades have established antigens in the parasite sexual stages developing in the mosquito midgut as attractive targets for the development of transmission blocking vaccines (TBVs). Immune clearance of gametocytes in the vertebrate host can synergize with TBVs and directly aid in maintaining effective transmission reducing immune potential.

Geospatial joint modeling of vector and parasite serology to microstratify malaria transmission.

The World Health Organization identifies a strong surveillance system for malaria and its mosquito vector as an essential pillar of the malaria elimination agenda. Anopheles salivary antibodies are emerging biomarkers of exposure to mosquito bites that potentially overcome sensitivity and logistical constraints of traditional entomological surveys. Using samples collected by a village health volunteer network in 104 villages in Southeast Myanmar during routine surveillance, the present study employs a Bayesian geostatistical modeling framework, incorporating climatic and environmental variables together with Anopheles salivary antigen serology, to generate spatially continuous predictive maps of Anopheles biting exposure. Our maps quantify fine-scale spatial and temporal heterogeneity in Anopheles salivary antibody seroprevalence (ranging from 9 to 99%) that serves as a proxy of exposure to Anopheles bites and advances current static maps of only Anopheles occurrence. We also developed an innovative framework to perform surveillance of malaria transmission. By incorporating antibodies against the vector and the transmissible form of malaria (sporozoite) in a joint Bayesian geostatistical model, we predict several foci of ongoing transmission. In our study, we demonstrate that antibodies specific for Anopheles salivary and sporozoite antigens are a logistically feasible metric with which to quantify and characterize heterogeneity in exposure to vector bites and malaria transmission. These approaches could readily be scaled up into existing village health volunteer surveillance networks to identify foci of residual malaria transmission, which could be targeted with supplementary interventions to accelerate progress toward elimination.