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Malaria, a lethal protozoan disease transmitted through the bites of female Anopheles mosquitoes infected with Plasmodium parasites, remains a significant global health concern. This study introduces a compartmental mathematical model to explore the impact of insecticide use and malaria treatment based on awareness initiatives. The model incorporates the influence of media-based awareness on the effectiveness of insecticide utilization for malaria control. Key mathematical properties, such as positivity, boundedness of solutions, feasibility, and stability of equilibria, are systematically investigated. Our analysis demonstrates that all solutions to the system are positive and bounded within a specified set of initial conditions, establishing the mathematical soundness and epidemiological relevance of the model. The basic reproduction number R 0 is determined through the next-generation matrix method. Stability analysis reveals that the disease-free equilibrium is globally asymptotically stable when R 0 is less than one, while it becomes unstable if R 0 exceeds one. Global stability of the endemic equilibrium is established using an appropriate quadratic Lyapunov function in cases where R 0 surpasses one. We identify the most sensitive parameters of the model through normalized forward sensitivity indices. In addition, numerical simulations employing the Runge–Kutta method in Python software further validate our findings. Both analytical and numerical results collectively suggest that the integration of awareness-based insecticide usage with malaria treatment holds the potential for malaria elimination. This comprehensive approach not only contributes to the mathematical rigor of the model but also underscores its practical implications for effective malaria control strategies. [ABSTRACT FROM AUTHOR]

In this paper, the dynamical behavior in a delayed Aron–May model for malaria transmission is investigated. The basic reproduction number is defined. The global stability of the malaria-free equilibrium (MFE) is established. By using the Bendixson theorem, a sufficient condition for the global stability of the delay-free equilibrium (DFE) is also established. Furthermore, to deal with the local stability of endemic equilibrium (EE), by means of the stability switches analysis method proposed in [E. Beretta and Y. Kuang, Geometric stability switch criteria in delay differential systems with delay dependent parameters, SIAM J. Math. Anal. 33(5) (2002) 1144–1165.] the related characteristic equation at EE is investigated, and the occurrence of Hopf bifurcation is discussed by using the incubation period in mosquito as a bifurcation parameter. Last, the simulation analysis is also performed to verify the dynamical behavior of the model. [ABSTRACT FROM AUTHOR]

Background: Despite global efforts to reduce and eventually interrupt malaria transmission, the disease remains a pressing public health problem, especially in sub-Saharan Africa. This study presents a detailed spatio-temporal analysis of malaria transmission in Rwanda from 2012 to 2022. The main objective was to gain insights into the evolving patterns of malaria and to inform and tailor effective public health strategies. Methods: The study used yearly aggregated data of malaria cases from the Rwanda health management information system. We employed a multifaceted analytical approach, including descriptive statistics and spatio-temporal analysis across three demographic groups: children under the age of 5 years, and males and females above 5 years. Bayesian spatially explicit models and spatio scan statistics were utilised to examine geographic and temporal patterns of relative risks and to identify clusters of malaria transmission. Results: We observed a significant increase in malaria cases from 2014 to 2018, peaking in 2016 for males and females aged above 5 years with counts of 98,645 and 116,627, respectively and in 2018 for under 5-year-old children with 84,440 cases with notable geographic disparities. Districts like Kamonyi (Southern Province), Ngoma, Kayonza and Bugesera (Eastern Province) exhibited high burdens, possibly influenced by factors such as climate, vector control practices, and cross-border dynamics. Bayesian spatially explicit modeling revealed elevated relative risks in numerous districts, underscoring the heterogeneity of malaria transmission in these districts, and thus contributing to an overall rising trend in malaria cases until 2018, followed by a subsequent decline. Our findings emphasize that the heterogeneity of malaria transmission is potentially driven by ecologic, socioeconomic, and behavioural factors. Conclusions: The study underscores the complexity of malaria transmission in Rwanda and calls for climate adaptive, gender-, age- and district-specific strategies in the national malaria control program. The emergence of both artemisinin and pyrethoids resistance and persistent high transmission in some districts necessitates continuous monitoring and innovative, data-driven approaches for effective and sustainable malaria control. [ABSTRACT FROM AUTHOR]

Malaria still presents a grave threat to the health of pregnancies worldwide with prevention currently stalling as traditional control and prevention strategies are limited by both insecticide and drug resistance. Furthermore, climate change is bringing malaria to locations where it was once eradicated and intensifying malaria in other areas. Even where malaria is not currently common, obstetricians will need to understand the pathogenesis of the disease, how it is transmitted, methods for prevention and treatment in pregnancy, and promising emerging strategies such as vaccines. A renewed global response is needed for this age-old disease in which pregnancy poses specific susceptibility. [ABSTRACT FROM AUTHOR]

Abstract Background Despite global efforts to reduce and eventually interrupt malaria transmission, the disease remains a pressing public health problem, especially in sub-Saharan Africa. This study presents a detailed spatio-temporal analysis of malaria transmission in Rwanda from 2012 to 2022. The main objective was to gain insights into the evolving patterns of malaria and to inform and tailor effective public health strategies. Methods The study used yearly aggregated data of malaria cases from the Rwanda health management information system. We employed a multifaceted analytical approach, including descriptive statistics and spatio-temporal analysis across three demographic groups: children under the age of 5 years, and males and females above 5 years. Bayesian spatially explicit models and spatio scan statistics were utilised to examine geographic and temporal patterns of relative risks and to identify clusters of malaria transmission. Results We observed a significant increase in malaria cases from 2014 to 2018, peaking in 2016 for males and females aged above 5 years with counts of 98,645 and 116,627, respectively and in 2018 for under 5-year-old children with 84,440 cases with notable geographic disparities. Districts like Kamonyi (Southern Province), Ngoma, Kayonza and Bugesera (Eastern Province) exhibited high burdens, possibly influenced by factors such as climate, vector control practices, and cross-border dynamics. Bayesian spatially explicit modeling revealed elevated relative risks in numerous districts, underscoring the heterogeneity of malaria transmission in these districts, and thus contributing to an overall rising trend in malaria cases until 2018, followed by a subsequent decline. Our findings emphasize that the heterogeneity of malaria transmission is potentially driven by ecologic, socioeconomic, and behavioural factors. Conclusions The study underscores the complexity of malaria transmission in Rwanda and calls for climate adaptive, gender-, age- and district-specific strategies in the national malaria control program. The emergence of both artemisinin and pyrethoids resistance and persistent high transmission in some districts necessitates continuous monitoring and innovative, data-driven approaches for effective and sustainable malaria control. Graphical Abstract

Abstract Background Biological control is a promising alternative or complementary approach for controlling vector populations in response to the spread of insecticide resistance in malaria vectors. This study evaluated the efficacy of three selected potential predators on the density and fitness parameters of Anopheles funestus larvae in rural Tanzania. Methods Common predator families Aeshnidae (dragonflies), Coenagrionidae (damselflies), and Notonectidae (backswimmers) and An. funestus group larvae were collected from natural aquatic habitats in rural south-eastern Tanzania. Predators were starved for 12-h while An. funestus larvae were given fish food before starting the experiment. Anopheles funestus larvae were placed into artificial habitats containing predators, exposing them to potential predation. The number of surviving An. funestus larvae were counted every 24-h. An emergence traps were placed at the top of artificial habitats to capture emerging mosquitoes. Emerged mosquitoes were monitored until they died. Female wings were measured and used as a proxy for body size. Generalized linear mixed models (GLMM) with binomial variates at 95% CI and Cox proportional hazard models were used to assess the proportion of dead mosquitoes and the daily survival determined. Results There were significant differences in the number of emerged mosquitoes between the treatment and control groups (P

Abstract Background Livestock keeping is one of the potential factors related to malaria transmission. To date, the impact of livestock keeping on malaria transmission remains inconclusive, as some studies suggest a zooprophylactic effect while others indicate a zoopotentiation effect. This study assessed the impact of livestock management on malaria transmission risks in rural Tanzania. Additionally, the study explored the knowledge and perceptions of residents about the relationships between livestock keeping and malaria transmission risks in a selected village. Methods In a longitudinal entomological study in Minepa village, South Eastern Tanzania, 40 households were randomly selected (20 with livestock, 20 without). Weekly mosquito collection was performed from January to April 2023. Indoor and outdoor collections used CDC-Light traps, Prokopack aspirators, human-baited double-net traps, and resting buckets. A subsample of mosquitoes was analysed using PCR and ELISA for mosquito species identification and blood meal detection. Livestock's impact on mosquito density was assessed using negative binomial GLMMs. Additionally, in-depth interviews explored community knowledge and perceptions of the relationship between livestock keeping and malaria transmission risks. Results A total of 48,677 female Anopheles mosquitoes were collected. Out of these, 89% were Anopheles gambiae sensu lato (s.l.) while other species were Anopheles funestus s.l., Anopheles pharoensis, Anopheles coustani, and Anopheles squamosus. The findings revealed a statistically significant increase in the overall number of An. gambiae s.l. outdoors (RR = 1.181, 95%CI 1.050–1.862, p = 0.043). Also, there was an increase of the mean number of An. funestus s.l. mosquitoes collected in households with livestock indoors (RR = 2.866, 95%CI: 1.471–5.582, p = 0.002) and outdoors (RR = 1.579,95%CI 1.080–2.865, p = 0.023). The human blood index of Anopheles arabiensis mosquitoes from houses with livestock was less than those without livestock (OR = 0.149, 95%CI 0.110–0.178, p

Abstract Background Malaria transmission is known to be perennial and heterogeneous in Benin. Studies assessing local malaria prevalence, transmission levels and vector characteristics are critical for designing, monitoring and evaluating new vector control interventions in community trials. We conducted a study in the Zakpota sub-district of central Benin to collect baseline data on household characteristics, malaria prevalence, vector characteristics and transmission dynamics in preparation for a randomised controlled trial to evaluate the community impact of VECTRON™ T500, a new broflanilide indoor residual spraying (IRS) product. Methods A total of 480 children under 5 years of age from the 15 villages of the sub-district were tested for malaria by rapid diagnostic tests (RDTs). Mosquitoes were collected by human landing catches (HLCs), pyrethrum spray catches (PSCs) and Centers for Disease Control and Prevention miniature light traps (CDC-LTs) in selected houses in each village to assess vector density, composition, vector infectivity and prevalence of insecticide resistance markers. Bioassays were performed to detect vector susceptibility to pyrethroids, broflanilide (6 µg/bottle) and clothianidin (90 µg/bottle). Results A total of 9080 households were enumerated in the 15 study villages. Insecticide-treated net (ITN) usage was > 90%, with 1–2 ITNs owned per household. Houses were constructed mainly with cement (44%) and mud (38%) substrates or a mixture of cement and mud (18%), and 60% of them had open eaves. The overall prevalence of P. falciparum infection was 19% among surveyed children: 20% among females and 18% among males. The haemoglobin rate showed an anaemia (

Abstract 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. Graphical Abstract

Background Asymptomatic carriage of malaria parasites persists even as malaria transmission declines. Low-density infections are often submicroscopic, not detected with rapid diagnostic tests (RDTs) or microscopy but detectable by polymerase chain reaction (PCR). Methods To characterize submicroscopic Plasmodium falciparum carriage in an area of declining malaria transmission, asymptomatic persons >5 years of age in rural Bagamoyo District, Tanzania, were screened using RDT, microscopy, and PCR. We investigated the size of the submicroscopic reservoir of infection across villages, determined factors associated with submicroscopic carriage, and assessed the natural history of submicroscopic malaria over 4 weeks. Results Among 6076 participants, P. falciparum prevalences by RDT, microscopy, and PCR were 9%, 9%, and 28%, respectively, with roughly two-thirds of PCR-positive individuals harboring submicroscopic infection. Adult status, female sex, dry season months, screened windows, and bed net use were associated with submicroscopic carriage. Among 15 villages encompassing 80% of participants, the proportion of submicroscopic carriers increased with decreasing village-level malaria prevalence. Over 4 weeks, 23% of submicroscopic carriers (61 of 266) became RDT positive, with half exhibiting symptoms, while half (133 of 266) were no longer parasitemic at the end of 4 weeks. Progression to RDT-positive patent malaria occurred more frequently in villages with higher malaria prevalence. Conclusions Microheterogeneity in transmission observed at the village level appears to affect both the size of the submicroscopic reservoir and the likelihood of submicroscopic carriers developing patent malaria in coastal Tanzania. [ABSTRACT FROM AUTHOR]

Despite a more than 100‐year effort to combat malaria, it remains one of the most malignant infectious diseases globally, especially in Africa. Malaria is transmitted by several Anopheles mosquitoes. However, until now few studies have investigated future range dynamics of major An. mosquitoes in Africa through a unified scheme. Through a unified scheme, we developed 21 species distribution models to predict the range dynamics of 21 major An. species in Africa under future scenarios and also examined their overall range dynamic patterns mainly through suitability overlap index and range overlap index. Although future range dynamics varied substantially among the 21 An. species, we predicted large future range expansions for all 21 An. species, and increases in suitability overlap index were detected in more than 90% of the African continent for all future scenarios. Additionally, we predicted high range overlap index in West Africa, East Africa, South Sudan, Angola, and the Democratic Republic of the Congo under future scenarios. Although the relative impacts of land use, topography and climate variables on the range dynamics depended on species and spatial scale, climate played the strongest roles in the range dynamics of most species. Africa might face an increasing risk of malaria transmissions in the future, and better strategies are required to address this problem. Mitigating climate change and human disturbance of natural ecosystems might be essential to reduce the proliferation of An. species and the risk of malaria transmissions in Africa in the future. Our strategies against their impacts should be species‐specific. [ABSTRACT FROM AUTHOR]

Background: Biological control is a promising alternative or complementary approach for controlling vector populations in response to the spread of insecticide resistance in malaria vectors. This study evaluated the efficacy of three selected potential predators on the density and fitness parameters of Anopheles funestus larvae in rural Tanzania. Methods: Common predator families Aeshnidae (dragonflies), Coenagrionidae (damselflies), and Notonectidae (backswimmers) and An. funestus group larvae were collected from natural aquatic habitats in rural south-eastern Tanzania. Predators were starved for 12-h while An. funestus larvae were given fish food before starting the experiment. Anopheles funestus larvae were placed into artificial habitats containing predators, exposing them to potential predation. The number of surviving An. funestus larvae were counted every 24-h. An emergence traps were placed at the top of artificial habitats to capture emerging mosquitoes. Emerged mosquitoes were monitored until they died. Female wings were measured and used as a proxy for body size. Generalized linear mixed models (GLMM) with binomial variates at 95% CI and Cox proportional hazard models were used to assess the proportion of dead mosquitoes and the daily survival determined. Results: There were significant differences in the number of emerged mosquitoes between the treatment and control groups (P < 0.001). Thus, all predator species played a significant role in reducing the density of An. funestus mosquitoes (P < 0.001). Furthermore, these predators had notable effects on the fitness parameters and survival of emerged mosquitoes (P < 0.001). Among the three predators studied, Coenagrionidae (damselflies) were most efficient followed by Notonectidae (backswimmers), with Aeshnidae (dragonflies) being the least efficient. Conclusion: Selected aquatic predators have the potential to reduce the survival and density of An. funestus larvae. They might eventually be included within an integrated malaria vector control strategy, ultimately leading to a reduction in malaria transmission. [ABSTRACT FROM AUTHOR]

Malaria remains a global threat and the conventional methods used for combating the disease leave out mosquitoes that feed outdoors. This study addresses the challenge posed by such mosquitoes based on a tool called ivermectin drug which is lethal to mosquitoes that ingest bloodmeal containing a concentration of it. We formulated a mathematical model with three control tools (insecticide treated nets, treatment of infective individuals and ivermectin drug on livestock and humans) for the transmission and control of malaria under optimal condition. The model’s basic reproduction number, R0 was estimated and the local and global stability analyses of the disease-free and endemic equilibrium points of the model were carried out. Sensitivity analysis carried out showed that R0 is most sensitive to the mosquito biting rate and to the proportion of blood meal on human with cattle availability in such a way that any percent increase in the value of any of these parameters will lead to an equal percent increase in the value of R0. The result of an optimal control analysis based on three time dependent controls suggests that the combination of all three controls gives the best result followed by the strategy that combines the use of ivermectin drug and the treatment of infective human. Depending on available resources, any of these is recommended to be adopted in malaria intervention programmes because of their effectiveness on both the infective human and mosquito populations with the potential of contributing significantly to the disease elimination within a minimal time frame. [ABSTRACT FROM AUTHOR]

Background: Livestock keeping is one of the potential factors related to malaria transmission. To date, the impact of livestock keeping on malaria transmission remains inconclusive, as some studies suggest a zooprophylactic effect while others indicate a zoopotentiation effect. This study assessed the impact of livestock management on malaria transmission risks in rural Tanzania. Additionally, the study explored the knowledge and perceptions of residents about the relationships between livestock keeping and malaria transmission risks in a selected village. Methods: In a longitudinal entomological study in Minepa village, South Eastern Tanzania, 40 households were randomly selected (20 with livestock, 20 without). Weekly mosquito collection was performed from January to April 2023. Indoor and outdoor collections used CDC-Light traps, Prokopack aspirators, human-baited double-net traps, and resting buckets. A subsample of mosquitoes was analysed using PCR and ELISA for mosquito species identification and blood meal detection. Livestock's impact on mosquito density was assessed using negative binomial GLMMs. Additionally, in-depth interviews explored community knowledge and perceptions of the relationship between livestock keeping and malaria transmission risks. Results: A total of 48,677 female Anopheles mosquitoes were collected. Out of these, 89% were Anopheles gambiae sensu lato (s.l.) while other species were Anopheles funestus s.l., Anopheles pharoensis, Anopheles coustani, and Anopheles squamosus. The findings revealed a statistically significant increase in the overall number of An. gambiae s.l. outdoors (RR = 1.181, 95%CI 1.050-1.862, p = 0.043). Also, there was an increase of the mean number of An. funestus s.l. mosquitoes collected in households with livestock indoors (RR = 2.866, 95%CI: 1.471-5.582, p = 0.002) and outdoors (RR = 1.579,95%CI 1.080-2.865, p = 0.023). The human blood index of Anopheles arabiensis mosquitoes from houses with livestock was less than those without livestock (OR = 0.149, 95%CI 0.110-0.178, p < 0.001). The majority of participants in the in-depth interviews reported a perceived high density of mosquitoes in houses with livestock compared to houses without livestock. Conclusion: Despite the potential for zooprophylaxis, this study indicates a higher malaria transmission risk in livestock-keeping communities. It is crucial to prioritize and implement targeted interventions to control vector populations within these communities. Furthermore, it is important to enhance community education and awareness regarding covariates such as livestock that influence malaria transmission. [ABSTRACT FROM AUTHOR]

Background: Malaria transmission is known to be perennial and heterogeneous in Benin. Studies assessing local malaria prevalence, transmission levels and vector characteristics are critical for designing, monitoring and evaluating new vector control interventions in community trials. We conducted a study in the Zakpota sub-district of central Benin to collect baseline data on household characteristics, malaria prevalence, vector characteristics and transmission dynamics in preparation for a randomised controlled trial to evaluate the community impact of VECTRON™ T500, a new broflanilide indoor residual spraying (IRS) product. Methods: A total of 480 children under 5 years of age from the 15 villages of the sub-district were tested for malaria by rapid diagnostic tests (RDTs). Mosquitoes were collected by human landing catches (HLCs), pyrethrum spray catches (PSCs) and Centers for Disease Control and Prevention miniature light traps (CDC-LTs) in selected houses in each village to assess vector density, composition, vector infectivity and prevalence of insecticide resistance markers. Bioassays were performed to detect vector susceptibility to pyrethroids, broflanilide (6 µg/bottle) and clothianidin (90 µg/bottle). Results: A total of 9080 households were enumerated in the 15 study villages. Insecticide-treated net (ITN) usage was > 90%, with 1–2 ITNs owned per household. Houses were constructed mainly with cement (44%) and mud (38%) substrates or a mixture of cement and mud (18%), and 60% of them had open eaves. The overall prevalence of P. falciparum infection was 19% among surveyed children: 20% among females and 18% among males. The haemoglobin rate showed an anaemia (< 11 g/dl) prevalence of 66%. Anopheles coluzzii and An. gambiae sensu stricto (s.s.) were the two vector species present at an overall proportion of 46% versus 54%, respectively. The human biting rate was 2.3 bites per person per night (b/p/n) and biting occurred mostly indoors compared with outdoors (IRR = 0.776; P = 0.001). The overall proportion of outdoor biting was 44% and exceeded indoor biting in three villages. The sporozoite rate was 2% with a combined yearly entomological inoculation rate (EIR) of 16.1 infected bites per person per year (ib/p/y). There was great variability in malaria transmission risk across the villages, with EIR ranging from 0 to 29.3 ib/p/y. The vector population showed a high intensity of resistance to pyrethroids across the study villages but was largely susceptible to broflanilide and clothianidin. Conclusions: This study found high levels of malaria prevalence, vector density and transmission in the Zakpota sub-district despite the wide use of insecticide-treated nets. The vector population was mostly indoor resting and showed a high intensity of pyrethroid resistance but was generally fully susceptible to broflanilide. These findings demonstrated the suitability of the study area for the assessment of VECTRON™ T500 in a community randomised trial. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Malaria, a mosquito-borne infectious disease caused by the parasite Plasmodium, has been predominantly associated with humans. However, recent studies have uncovered a potential reservoir for Plasmodium spp., within livestock populations. Malaria, caused by the parasitic protozoan Plasmodium spp., is a deadly disease that affects millions of people worldwide. Although human is the primary host for the malaria parasite, it has been discovered that certain animals can also serve as reservoirs. One such potential reservoir is livestock populations, as they have been found to carry Plasmodium spp. parasites. This article will discuss the implications of livestock being potential reservoirs for malaria and the importance of understanding this relationship for effective disease control. Livestock populations have long been overlooked as potential reservoirs for malaria transmission, but recent advancements in diagnostic techniques and surveillance studies have sparked interest in exploring this field. By prioritizing thorough assessments of zoonotic transmission risks, we can gain valuable insights into the role of livestock in malaria transmission and develop effective strategies to reduce the burden of this devastating disease. [ABSTRACT FROM AUTHOR]

With the goal of eradication by 2030, Malaria poses a significant health threat, profoundly influenced by meteorological and hydrological conditions. In support of malaria vector control efforts, we present a high‐resolution, coupled physically‐based modeling approach integrating WRF‐Hydro and VECTRI. This model approach accurately captures topographic details at the scale of larvae habitats in the Nouna Health and Demographic Surveillance Systems in Sub‐Saharan Africa. Our study demonstrates the proficiency of the high‐resolution hydrometeorological model, WRF‐Hydro, in replicating observed climate characteristics. Comparisons with in‐situ local weather data reveal root mean square errors between 0.6 and 0.87 mm/day for rainfall and correlations ranging from 0.79 to 0.87 for temperatures. Additionally, WRF‐Hydro's surface hydrology reproduces the seasonal and intraseasonal variability of the ponded water fraction with 96% accuracy, validated against Sentinel‐1 data at a 100‐m resolution. The VECTRI model demonstrates sensitivity to surface hydrology representation, particularly when comparing conceptual and detailed physical process models, for variables such as larvae density, mosquito abundance, and EIR. The model's ability to replicate the seasonality of malaria transmission aligns well with available cohort malaria data suggesting its potential for predicting the impacts of climate change on mosquito abundance and transmission intensity in endemic tropical and subtropical zones. This integrated approach opens avenues for enhanced understanding and proactive management of malaria. Key Points: A coupled atmosphere‐hydrology‐malaria transmission model system consisting of WRF‐Hydro and VECTRI is developedCoupled WRF‐Hydro‐VECTRI scheme reproduces the peak of malaria as well as the seasonal variabilityVECTRI is sensitive to the representation of mosquito breeding habitat avail‐ability [ABSTRACT FROM AUTHOR]

Abstract Background In malaria endemic regions of the Peruvian Amazon, rainfall together with river level and breeding site availability drive fluctuating vector mosquito abundance and human malaria cases, leading to temporal heterogeneity. The main variables influencing spatial transmission include location of communities, mosquito behaviour, land use/land cover, and human ecology/behaviour. The main objective was to evaluate seasonal and microgeographic biting behaviour of the malaria vector Nyssorhynchus (or Anopheles) darlingi in Amazonian Peru and to investigate effects of seasonality on malaria transmission. Methods We captured mosquitoes from 18:00 to 06:00 h using Human Landing Catch in two riverine (Lupuna, Santa Emilia) and two highway (El Triunfo, Nuevo Horizonte) communities indoors and outdoors from 8 houses per community, during the dry and rainy seasons from February 2016 to January 2017. We then estimated parity rate, daily survival and age of a portion of each collection of Ny. darlingi. All collected specimens of Ny. darlingi were tested for the presence of Plasmodium vivax or Plasmodium falciparum sporozoites using real-time PCR targeting the small subunit of the 18S rRNA. Results Abundance of Ny. darlingi varied across village, season, and biting behaviour (indoor vs outdoor), and was highly significant between rainy and dry seasons (p

Abstract Background Understanding the dynamics of gametocyte production in polyclonal Plasmodium falciparum infections requires a genotyping method that detects distinct gametocyte clones and estimates their relative frequencies. Here, a marker was identified and evaluated to genotype P. falciparum mature gametocytes using amplicon deep sequencing. Methods A data set of polymorphic regions of the P. falciparum genome was mined to identify a gametocyte genotyping marker. To assess marker resolution, the number of unique haplotypes in the marker region was estimated from 95 Malawian P. falciparum whole genome sequences. Specificity of the marker for detection of mature gametocytes was evaluated using reverse transcription-polymerase chain reaction of RNA extracted from NF54 mature gametocytes and rings from a non-gametocyte-producing strain of P. falciparum. Amplicon deep sequencing was performed on experimental mixtures of mature gametocytes from two distinct parasite clones, as well as gametocyte-positive P. falciparum field isolates to evaluate the quantitative ability and determine the limit of detection of the genotyping approach. Results A 400 bp region of the pfs230 gene was identified as a gametocyte genotyping marker. A larger number of unique haplotypes was observed at the pfs230 marker (34) compared to the sera-2 (18) and ama-1 (14) markers in field isolates from Malawi. RNA and DNA genotyping accurately estimated gametocyte and total parasite clone frequencies when evaluating agreement between expected and observed haplotype frequencies in gametocyte mixtures, with concordance correlation coefficients of 0.97 [95% CI: 0.92–0.99] and 0.92 [95% CI: 0.83–0.97], respectively. The detection limit of the genotyping method for male gametocytes was 0.41 pfmget transcripts/µl [95% CI: 0.28–0.72] and for female gametocytes was 1.98 ccp4 transcripts/µl [95% CI: 1.35–3.68]. Conclusions A region of the pfs230 gene was identified as a marker to genotype P. falciparum gametocytes. Amplicon deep sequencing of this marker can be used to estimate the number and relative frequency of parasite clones among mature gametocytes within P. falciparum infections. This gametocyte genotyping marker will be an important tool for studies aimed at understanding dynamics of gametocyte production in polyclonal P. falciparum infections.

Abstract Background Mosquitoes belonging to the Anopheles gambiae sensu lato complex play a major role in malaria transmission across Africa. This study assessed the relative importance of members of An. gambiae s.l. in malaria transmission in two rural villages in the Republic of the Congo. Methods Adult mosquitoes were collected using electric aspirators from June to September 2022 in Djoumouna and Ntoula villages and were sorted by taxa based on their morphological features. Anopheles gambiae s.l. females were also molecularly identified. A TaqMan-based assay and a nested polymerase chain reaction (PCR) were performed to determine Plasmodium spp. in the mosquitoes. Entomological indexes were estimated, including man-biting rate, entomological inoculation rate (EIR), and diversity index. Results Among 176 mosquitoes collected, An. gambiae s.l. was predominant (85.8%), followed by Culex spp. (13.6%) and Aedes spp. (0.6%). Three members of the An. gambiae s.l. complex were collected in both villages, namely An. gambiae sensu stricto (74.3%), Anopheles coluzzii (22.9%) and Anopheles arabiensis (2.8%). Three Plasmodium species were detected in An. gambiae s.s. and An. coluzzii (Plasmodium falciparum, P. malariae and P. ovale), while only P. falciparum and P. malariae were found in An. arabiensis. In general, the Plasmodium infection rate was 35.1% (53/151) using the TaqMan-based assay, and nested PCR confirmed 77.4% (41/53) of those infections. The nightly EIR of An. gambiae s.l. was 0.125 infectious bites per person per night (ib/p/n) in Djoumouna and 0.08 ib/p/n in Ntoula. The EIR of An. gambiae s.s. in Djoumouna (0.11 ib/p/n) and Ntoula (0.04 ib/p/n) was higher than that of An. coluzzii (0.01 and 0.03 ib/p/n) and An. arabiensis (0.005 and 0.0 ib/p/n). Conclusions This study provides baseline information on the dominant vectors and dynamics of malaria transmission in the rural areas of the Republic of the Congo during the dry season. In the two sampled villages, An. gambiae s.s. appears to play a predominant role in Plasmodium spp. transmission. Graphical Abstract

Irrigation not only helps to improve food security but also creates numerous water bodies for mosquito production. This study assessed the effect of irrigation on malaria vector bionomics and transmission in a semi-arid site with ongoing malaria vector control program. The effectiveness of CDC light traps in the surveillance of malaria vectors was also evaluated relative to the human landing catches (HLCs) method. Adult mosquitoes were sampled in two study sites representing irrigated and non-irrigated agroecosystems in western Kenya using a variety of trapping methods. The mosquito samples were identified to species and assayed for host blood meal source and Plasmodium spp. sporozoite infection using polymerase chain reaction. Anopheles arabiensis was the dominant malaria vector in the two study sites and occurred in significantly higher densities in irrigated study site compared to the non-irrigated study site. The difference in indoor resting density of An. arabiensis during the dry and wet seasons was not significant. Other species, including An. funestus, An. coustani, and An. pharoensis, were collected. The An. funestus indoor resting density was 0.23 in irrigated study site while almost none of this species was collected in the non-irrigated study site. The human blood index (HBI) for An. arabiensis in the irrigated study site was 3.44% and significantly higher than 0.00% for the non-irrigated study site. In the irrigated study site, the HBI of An. arabiensis was 3.90% and 5.20% indoor and outdoor, respectively. The HBI of An. funestus was 49.43% and significantly higher compared to 3.44% for An. arabiensis in the irrigated study site. The annual entomologic inoculation rate for An. arabiensis in the irrigated study site was 0.41 and 0.30 infective bites/person/year indoor and outdoor, respectively, whereas no transmission was observed in the non-irrigated study site. The CDC light trap performed consistently with HLC in terms of vector density. These findings demonstrate that irrigated agriculture may increase the risk of malaria transmission in irrigated areas compared to the non-irrigated areas and highlight the need to complement the existing malaria vector interventions with novel tools targeting the larvae and both indoor and outdoor biting vector populations.

Background Subclinical inflammation and cognitive deficits have been separately associated with asymptomatic Plasmodium falciparum infections in schoolchildren. However, whether parasite-induced inflammation is associated with worse cognition has not been addressed. We conducted a cross-sectional pilot study to better assess the effect of asymptomatic P. falciparum parasitemia and inflammation on cognition in Kenyan schoolchildren. Methods We enrolled 240 children aged 7–14 years residing in high malaria transmission in Western Kenya. Children performed five fluid cognition tests from a culturally adapted NIH toolbox and provided blood samples for blood smears and laboratory testing. Parasite densities and plasma concentrations of 14 cytokines were determined by quantitative PCR and multiplex immunoassay, respectively. Linear regression models were used to determine the effects of parasitemia and plasma cytokine concentrations on each of the cognitive scores as well as a composite cognitive score while controlling for age, gender, maternal education, and an interaction between age and P. falciparum infection status. Results Plasma concentrations of TNF, IL-6, IL-8, and IL-10 negatively correlated with the composite score and at least one of the individual cognitive tests. Parasite density in parasitemic children negatively correlated with the composite score and measures of cognitive flexibility and attention. In the adjusted model, parasite density and TNF, but not P. falciparum infection status, independently predicted lower cognitive composite scores. By mediation analysis, TNF significantly mediated ~29% of the negative effect of parasitemia on cognition. Conclusions Among schoolchildren with PCR-confirmed asymptomatic P. falciparum infections, the negative effect of parasitemia on cognition could be mediated, in part, by subclinical inflammation. Additional studies are needed to validate our findings in settings of lower malaria transmission and address potential confounders that could affect both inflammation and cognitive performance. [ABSTRACT FROM AUTHOR]

A linear multistep method is transformed into an iterative method based on the Patade and Bhalekar technique for the numerical solution of an optimal control problem modeled for mosquito and insecticide management using forward-backward sweep methods via Pontryagin's principle. Stability and convergence analysis of the iterative method are carried out and it is found to be stable, convergent, and of order four. Results obtained by the method clearly show that the population of mosquitoes can be minimized to a large extent using the new iterative method while reducing the harmful effects of the insecticide, which subsequently reduces the spread of malaria. [ABSTRACT FROM AUTHOR]

Background: In malaria endemic regions of the Peruvian Amazon, rainfall together with river level and breeding site availability drive fluctuating vector mosquito abundance and human malaria cases, leading to temporal heterogeneity. The main variables influencing spatial transmission include location of communities, mosquito behaviour, land use/land cover, and human ecology/behaviour. The main objective was to evaluate seasonal and microgeographic biting behaviour of the malaria vector Nyssorhynchus (or Anopheles) darlingi in Amazonian Peru and to investigate effects of seasonality on malaria transmission. Methods: We captured mosquitoes from 18:00 to 06:00 h using Human Landing Catch in two riverine (Lupuna, Santa Emilia) and two highway (El Triunfo, Nuevo Horizonte) communities indoors and outdoors from 8 houses per community, during the dry and rainy seasons from February 2016 to January 2017. We then estimated parity rate, daily survival and age of a portion of each collection of Ny. darlingi. All collected specimens of Ny. darlingi were tested for the presence of Plasmodium vivax or Plasmodium falciparum sporozoites using real-time PCR targeting the small subunit of the 18S rRNA. Results: Abundance of Ny. darlingi varied across village, season, and biting behaviour (indoor vs outdoor), and was highly significant between rainy and dry seasons (p < 0.0001). Biting patterns differed, although not significantly, and persisted regardless of season, with peaks in highway communities at ~ 20:00 h in contrast to biting throughout the night (i.e., 18:00–06:00) in riverine communities. Of 3721 Ny. darlingi tested for Plasmodium, 23 (0.62%) were infected. We detected Plasmodium-infected Ny. darlingi in both community types and most (20/23) were captured outdoors during the rainy season; 17/23 before midnight. Seventeen Ny. darlingi were infected with P. vivax, and 6 with P. falciparum. No infected Ny. darlingi were captured during the dry season. Significantly higher rates of parity were detected in Ny. darlingi during the rainy season (average 64.69%) versus the dry season (average 36.91%) and by community, Lupuna, a riverine village, had the highest proportion of parous to nulliparous females during the rainy season. Conclusions: These data add a seasonal dimension to malaria transmission in peri-Iquitos, providing more evidence that, at least locally, the greatest risk of malaria transmission is outdoors during the rainy season mainly before midnight, irrespective of whether the community was located adjacent to the highway or along the river. [ABSTRACT FROM AUTHOR]

Background: Understanding the dynamics of gametocyte production in polyclonal Plasmodium falciparum infections requires a genotyping method that detects distinct gametocyte clones and estimates their relative frequencies. Here, a marker was identified and evaluated to genotype P. falciparum mature gametocytes using amplicon deep sequencing. Methods: A data set of polymorphic regions of the P. falciparum genome was mined to identify a gametocyte genotyping marker. To assess marker resolution, the number of unique haplotypes in the marker region was estimated from 95 Malawian P. falciparum whole genome sequences. Specificity of the marker for detection of mature gametocytes was evaluated using reverse transcription-polymerase chain reaction of RNA extracted from NF54 mature gametocytes and rings from a non-gametocyte-producing strain of P. falciparum. Amplicon deep sequencing was performed on experimental mixtures of mature gametocytes from two distinct parasite clones, as well as gametocyte-positive P. falciparum field isolates to evaluate the quantitative ability and determine the limit of detection of the genotyping approach. Results: A 400 bp region of the pfs230 gene was identified as a gametocyte genotyping marker. A larger number of unique haplotypes was observed at the pfs230 marker (34) compared to the sera-2 (18) and ama-1 (14) markers in field isolates from Malawi. RNA and DNA genotyping accurately estimated gametocyte and total parasite clone frequencies when evaluating agreement between expected and observed haplotype frequencies in gametocyte mixtures, with concordance correlation coefficients of 0.97 [95% CI: 0.92–0.99] and 0.92 [95% CI: 0.83–0.97], respectively. The detection limit of the genotyping method for male gametocytes was 0.41 pfmget transcripts/µl [95% CI: 0.28–0.72] and for female gametocytes was 1.98 ccp4 transcripts/µl [95% CI: 1.35–3.68]. Conclusions: A region of the pfs230 gene was identified as a marker to genotype P. falciparum gametocytes. Amplicon deep sequencing of this marker can be used to estimate the number and relative frequency of parasite clones among mature gametocytes within P. falciparum infections. This gametocyte genotyping marker will be an important tool for studies aimed at understanding dynamics of gametocyte production in polyclonal P. falciparum infections. [ABSTRACT FROM AUTHOR]

The study presents a novel mathematical framework for addressing Ebola and malaria concerns in Sub-Saharan Africa that combines Laplace transformation with Caputo fractional order derivative. It takes into account socioeconomic aspects that influence disease dynamics and uses the basic reproduction number to quantify transmission dynamics. Extensive numerical simulations using Maple 18 software are used to investigate the effect of fractional order derivatives on disease dynamics. It shows how the Laplace-Adomian decomposition approach simplifies nonlinear equations and generates control solutions. It emphasizes the necessity of turning discoveries into concrete plans and encourages stakeholders to be proactive in implementing them. Overall, the study emphasizes the importance of proactive disease management measures and the promise of novel approaches to treating infectious diseases. Stakeholders may create a more resilient response to these health emergencies by working together to adopt these measures. [ABSTRACT FROM AUTHOR]

A primary use of malaria parasite genomics is identifying highly related infections to quantify epidemiological, spatial, or temporal factors associated with patterns of transmission. For example, spatial clustering of highly related parasites can indicate foci of transmission and temporal differences in relatedness can serve as evidence for changes in transmission over time. However, for infections in settings of moderate to high endemicity, understanding patterns of relatedness is compromised by complex infections, overall high forces of infection, and a highly diverse parasite population. It is not clear how much these factors limit the utility of using genomic data to better understand transmission in these settings. In particular, further investigation is required to determine which patterns of relatedness we expect to see with high quality, densely sampled genomic data in a high transmission setting and how these observations change under different study designs, missingness, and biases in sample collection. Here we investigate two identity-by-state measures of relatedness and apply them to amplicon deep sequencing data collected as part of a longitudinal cohort in Western Kenya that has previously been analysed to identify individual-factors associated with sharing parasites with infected mosquitoes. With these data we use permutation tests, to evaluate several hypotheses about spatiotemporal patterns of relatedness compared to a null distribution. We observe evidence of temporal structure, but not of finescale spatial structure in the cohort data. To explore factors associated with the lack of spatial structure in these data, we construct a series of simplified simulation scenarios using an agent based model calibrated to entomological, epidemiological and genomic data from this cohort study to investigate whether the lack of spatial structure observed in the cohort could be due to inherent power limitations of this analytical method. We further investigate how our hypothesis testing behaves under different sampling schemes, levels of completely random and systematic missingness, and different transmission intensities. [ABSTRACT FROM AUTHOR]

Background: Mosquitoes belonging to the Anopheles gambiae sensu lato complex play a major role in malaria transmission across Africa. This study assessed the relative importance of members of An. gambiae s.l. in malaria transmission in two rural villages in the Republic of the Congo. Methods: Adult mosquitoes were collected using electric aspirators from June to September 2022 in Djoumouna and Ntoula villages and were sorted by taxa based on their morphological features. Anopheles gambiae s.l. females were also molecularly identified. A TaqMan-based assay and a nested polymerase chain reaction (PCR) were performed to determine Plasmodium spp. in the mosquitoes. Entomological indexes were estimated, including man-biting rate, entomological inoculation rate (EIR), and diversity index. Results: Among 176 mosquitoes collected, An. gambiae s.l. was predominant (85.8%), followed by Culex spp. (13.6%) and Aedes spp. (0.6%). Three members of the An. gambiae s.l. complex were collected in both villages, namely An. gambiae sensu stricto (74.3%), Anopheles coluzzii (22.9%) and Anopheles arabiensis (2.8%). Three Plasmodium species were detected in An. gambiae s.s. and An. coluzzii (Plasmodium falciparum, P. malariae and P. ovale), while only P. falciparum and P. malariae were found in An. arabiensis. In general, the Plasmodium infection rate was 35.1% (53/151) using the TaqMan-based assay, and nested PCR confirmed 77.4% (41/53) of those infections. The nightly EIR of An. gambiae s.l. was 0.125 infectious bites per person per night (ib/p/n) in Djoumouna and 0.08 ib/p/n in Ntoula. The EIR of An. gambiae s.s. in Djoumouna (0.11 ib/p/n) and Ntoula (0.04 ib/p/n) was higher than that of An. coluzzii (0.01 and 0.03 ib/p/n) and An. arabiensis (0.005 and 0.0 ib/p/n). Conclusions: This study provides baseline information on the dominant vectors and dynamics of malaria transmission in the rural areas of the Republic of the Congo during the dry season. In the two sampled villages, An. gambiae s.s. appears to play a predominant role in Plasmodium spp. transmission. [ABSTRACT FROM AUTHOR]

Malaria, a devastating disease caused by the Plasmodium parasite and transmitted through the bites of female Anopheles mosquitoes, remains a significant public health concern, claiming over 600,000 lives annually, predominantly among children. Novel tools, including the application of Wolbachia, are being developed to combat malariatransmitting mosquitoes. This study presents a modified susceptible-exposed-infectious-recovered-susceptible (SEIRS) compartmental mathematical model to evaluate the impact of awareness-based control measures on malaria transmission dynamics, incorporating mosquito interactions and seasonality. Employing the next-generation matrix approach, we calculated a basic reproduction number (R0) of 2.4537, indicating that without robust control measures, the disease will persist in the human population. The model equations were solved numerically using fourth and fifth-order Runge-Kutta methods. The model was fitted to malaria incidence data from Kenya spanning 2000 to 2021 using least squares curve fitting. The fitting algorithm yielded a mean absolute error (MAE) of 2.6463 when comparing the actual data points to the simulated values of infectious human population (Ih). This finding indicates that the proposed mathematical model closely aligns with the recorded malaria incidence data. The optimal values of the model parameters were estimated from the fitting algorithm, and future malaria dynamics were projected for the next decade. The research findings suggest that social media-based awareness campaigns, coupled with specific optimization control measures and effective management methods, offer the most cost-effective approach to managing malaria. [ABSTRACT FROM AUTHOR]

Locally acquired malaria is rare in the US; however, in 2023, cases were reported in Florida, Texas, Maryland, and Arkansas. Prompt diagnosis and treatment of malaria are essential to prevent severe malaria disease. This article details malaria and offers treatment guidelines. [ABSTRACT FROM AUTHOR]

Abstract Despite a more than 100‐year effort to combat malaria, it remains one of the most malignant infectious diseases globally, especially in Africa. Malaria is transmitted by several Anopheles mosquitoes. However, until now few studies have investigated future range dynamics of major An. mosquitoes in Africa through a unified scheme. Through a unified scheme, we developed 21 species distribution models to predict the range dynamics of 21 major An. species in Africa under future scenarios and also examined their overall range dynamic patterns mainly through suitability overlap index and range overlap index. Although future range dynamics varied substantially among the 21 An. species, we predicted large future range expansions for all 21 An. species, and increases in suitability overlap index were detected in more than 90% of the African continent for all future scenarios. Additionally, we predicted high range overlap index in West Africa, East Africa, South Sudan, Angola, and the Democratic Republic of the Congo under future scenarios. Although the relative impacts of land use, topography and climate variables on the range dynamics depended on species and spatial scale, climate played the strongest roles in the range dynamics of most species. Africa might face an increasing risk of malaria transmissions in the future, and better strategies are required to address this problem. Mitigating climate change and human disturbance of natural ecosystems might be essential to reduce the proliferation of An. species and the risk of malaria transmissions in Africa in the future. Our strategies against their impacts should be species‐specific.

Summary: Background: Plasmodium blood-stage parasites balance asexual multiplication with gametocyte development. Few studies link these dynamics with parasite genetic markers in vivo; even fewer in longitudinally monitored infections. Environmental influences on gametocyte formation, such as mosquito exposure, may influence the parasite's investment in gametocyte production. Methods: We investigated gametocyte production and asexual multiplication in two Plasmodium falciparum infected populations; a controlled human malaria infection (CHMI) study and a 28-day observational study in naturally infected individuals in Burkina Faso with controlled mosquito exposure. We measured gene transcript levels previously related to gametocyte formation (ap2-g, surfin1.2, surfin13.1, gexp-2) or inhibition of asexual multiplication (sir2a) and compared transcript levels to ring-stage parasite and mature gametocyte densities. Findings: Three of the five markers (ap2-g, surfin1.2, surfin13.1) predicted peak gametocytaemia in the CHMI study. An increase in all five markers in natural infections was associated with an increase in mature gametocytes 14 days later; the effect of sir2a on future gametocytes was strongest (fold change = 1.65, IQR = 1.22–2.24, P = 0.004). Mosquito exposure was not associated with markers of gametocyte formation (ap2-g P = 0.277; sir2a P = 0.499) or carriage of mature gametocytes (P = 0.379). Interpretation: All five parasite genetic markers predicted gametocyte formation over a single cycle of gametocyte formation and maturation in vivo; sir2a and ap2-g were most closely associated with gametocyte growth dynamics. We observed no evidence to support the hypothesis that exposure to Anopheles mosquito bites stimulates gametocyte formation. Funding: This work was funded by the Bill & Melinda Gates Foundation (INDIE OPP1173572), the European Research Council fellowship (ERC-CoG 864180) and UKRI Medical Research Council (MR/T016272/1) and Wellcome Center (218676/Z/19/Z).

BackgroundEvolutionary pressures lead to the selection of efficient malaria vectors either resistant or susceptible to Plasmodium parasites. These forces may favour the introduction of species genotypes that adapt to new breeding habitats, potentially having an impact on malaria transmission. Thioester-containing protein 1 (TEP1) of Anopheles gambiae complex plays an important role in innate immune defenses against parasites. This study aims to characterize the distribution pattern of TEP1 polymorphisms among populations of An. gambiae sensu lato (s.l.) in western Kenya.MethodsAnopheles gambiae adult and larvae were collected using pyrethrum spray catches (PSC) and plastic dippers respectively from Homa Bay, Kakamega, Bungoma, and Kisumu counties between 2017 and 2020. Collected adults and larvae reared to the adult stage were morphologically identified and then identified to sibling species by PCR. TEP1 alleles were determined in 627 anopheles mosquitoes using restriction fragment length polymorphisms-polymerase chain reaction (RFLP-PCR) and to validate the TEP1 genotyping results, a representative sample of the alleles was sequenced.ResultsTwo TEP1 alleles (TEP1*S1 and TEP1*R2) and three corresponding genotypes (*S1/S1, *R2/S1, and *R2/R2) were identified. TEP1*S1 and TEP1*R2 with their corresponding genotypes, homozygous *S1/S1 and heterozygous *R2/S1 were widely distributed across all sites with allele frequencies of approximately 80% and 20%, respectively both in Anopheles gambiae and Anopheles arabiensis. There was no significant difference detected among the populations and between the two mosquito species in TEP1 allele frequency and genotype frequency. The overall low levels in population structure (FST = 0.019) across all sites corresponded to an effective migration index (Nm = 12.571) and low Nei's genetic distance values (

The effect of environmental immunity on the mathematical modeling of malaria transmission between vector and host population is investigated in this study using appropriate standard procedures. We develop a mathematical SIR-SI model incorporating environmental immunity parameters to describe the dynamics transmission rates of both humans and vectors with the assumption that an individual develops environmental immunity on the infected and recovered classes. The model is analyzed by the reproduction number derived using the next-generation matrix method and its stability is checked by Jacobian matrix. We demonstrate that the disease-free equilibrium is locally asymptotically stable if Ro < 1 (Ro -- reproduction number) and is unstable if Ro > 1. Numerical simulation indicates that, with acquired environmental immunity due to nutrition and medicinal herbs, the spread of malaria can be significantly impacted by increasing the recovered class and lowering the infected class. [ABSTRACT FROM AUTHOR]

An effort is made to understand the role of El Nino-Southern Oscillation (ENSO) and Indian Ocean Dipole (IOD) events on the malaria transmission intensity over India during the period 1951–2020 (70 years) with the help of a realistically simulated dynamical malaria model. The results suggest that the La Nina years pose a greater threat of malaria disease, especially in the densely populated Indian states. During El Nino years, the malaria transmission intensity and distribution over India greatly reduce, except in the regions such as Orissa, Chhattisgarh, Jharkhand, Western Ghats, parts of Madhya Pradesh, and Andhra Pradesh. It is found that in the positive IOD years, the malaria transmission intensity increases (decreases) over the entire central Indian region and along coastal regions of Tamil Nadu and Kerala (southern peninsular states of India and northeast India). An almost opposite behavior is seen during the negative IOD years. The malaria transmission variability over India is becoming increasingly heterogeneous in recent decades during the El Nino and La Nina years as a result of global warming. The period of 1986–2020 witnessed a substantial decrease (increase) in the malaria transmission intensity during the positive (negative) IOD years, except for a few regions of India. The implications of the results presented in the paper linking the ENSO and IOD signals with the intensity and distribution of malaria over India in a warming world are enormous, especially for the densely populated Indian states. [ABSTRACT FROM AUTHOR]

Malaria is a significant public health concern, especially in tropical regions. It remains endemic in many areas where malaria mosquitoes are prevalent. This study investigates the viability of insecticide zooprophylaxis (IZ) in conjunction with Long Lasting Insecticidal Nets (LLINs) as a strategic approach to combat malaria transmission, particularly in regions dominated by zoophagic vectors. Through the presentation and analysis of a mathematical model that integrates IZ and LLINs for the control of Anopheles arabiensis (An. arabiensis), the research underscores IZ's role in reducing zoophagic vector populations and enhancing malaria control efforts. Notably, the study reveals that achieving comprehensive coverage of LLINs and IZ distribution systems can reduce the basic reproduction number (R0) below 1. Furthermore, the research highlights the potential for substantial reductions in human biting rates, vectorial capacity and Entomological Inoculation Rate (EIR) when high intervention coverage encompasses all zoophagy blood sources for malaria vectors. [ABSTRACT FROM AUTHOR]

ABSTRACTNeddylation is a type of posttranslational modification known to regulate a wide range of cellular processes by covalently conjugating the ubiquitin-like protein Nedd8 to target proteins at lysine residues. However, the role of neddylation in malaria parasites has not been determined. Here, for the first time, we showed that neddylation plays an essential role in malaria transmission in Plasmodium berghei. We found that disruption of Nedd8 did not affect blood-stage propagation, gametocyte development, gamete formation, or zygote formation while abolishing the formation of ookinetes and further transmission of the parasites in mosquitoes. These phenotypic defects in Nedd8 knockout parasites were complemented by reintroducing the gene that restored mosquito transmission to wild-type levels. Our data establish the role of P. berghei Nedd8 in malaria parasite transmission.IMPORTANCENeddylation is a process by which Nedd8 is covalently attached to target proteins through three-step enzymatic cascades. The attachment of Nedd8 residues results in a range of diverse functions, such as cell cycle regulation, metabolism, immunity, and tumorigenesis. The potential neddylation substrates are cullin (CUL) family members, which are implicated in controlling the cell cycle. Cullin neddylation leads to the activation of cullin-RING ubiquitin ligases, which regulate a myriad of biological processes through target-specific ubiquitylation. Neddylation possibly regulates meiosis in zygotes, which subsequently develop into ookinetes. Our findings point to an essential function of this neddylation pathway and highlight its possible importance in designing novel intervention strategies.

Abstract Background The extrinsic incubation period (EIP), defined as the time it takes for malaria parasites in a mosquito to become infectious to a vertebrate host, is one of the most influential parameters for malaria transmission but remains poorly understood. The EIP is usually estimated by quantifying salivary gland sporozoites in subsets of mosquitoes, which requires terminal sampling. However, assays that allow repeated sampling of individual mosquitoes over time could provide better resolution of the EIP. Methods We tested a non-destructive assay to quantify sporozoites of two rodent malaria species, Plasmodium chabaudi and Plasmodium berghei, expelled throughout 24-h windows, from sugar-soaked feeding substrates using quantitative-PCR. Results The assay is able to quantify sporozoites from sugar-soaked feeding substrates, but the prevalence of parasite-positive substrates was low. Various methods were attempted to increase the detection of expelled parasites (e.g. running additional technical replicates; using groups rather than individual mosquitoes), but these did not increase the detection rate, suggesting that expulsion of sporozoites is variable and infrequent. Conclusions We reveal successful detection of expelled sporozoites from sugar-soaked feeding substrates. However, investigations of the biological causes underlying the low detection rate of sporozoites (e.g. mosquito feeding behaviour, frequency of sporozoite expulsion or sporozoite clumping) are needed to maximise the utility of using non-destructive assays to quantify sporozoite dynamics. Increasing detection rates will facilitate the detailed investigation on infection dynamics within mosquitoes, which is necessary to explain the highly variable EIP of Plasmodium and to improve understanding of malaria transmission dynamics. Graphical Abstract

Abstract Background Malaria transmission in Africa is facilitated by multiple species of Anopheles mosquitoes. These vectors have different behaviors and vectorial capacities and are affected differently by vector control interventions, such as insecticide-treated nets and indoor residual spraying. This review aimed to assess changes in the contribution of different vector species to malaria transmission in east and southern Africa over 20 years of widespread insecticide-based vector control. Methods We searched PubMed, Global Health, and Web of Science online databases for articles published between January 2000 and April 2023 that provided species-specific sporozoite rates for different malaria vectors in east and southern Africa. We extracted data on study characteristics, biting rates, sporozoite infection proportions, and entomological inoculation rates (EIR). Using EIR data, the proportional contribution of each species to malaria transmission was estimated. Results Studies conducted between 2000 and 2010 identified the Anopheles gambiae complex as the primary malaria vector, while studies conducted from 2011 to 2021 indicated the dominance of Anopheles funestus. From 2000 to 2010, in 57% of sites, An. gambiae demonstrated higher parasite infection prevalence than other Anopheles species. Anopheles gambiae also accounted for over 50% of EIR in 76% of the study sites. Conversely, from 2011 to 2021, An. funestus dominated with higher infection rates than other Anopheles in 58% of sites and a majority EIR contribution in 63% of sites. This trend coincided with a decline in overall EIR and the proportion of sporozoite-infected An. gambiae. The main vectors in the An. gambiae complex in the region were Anopheles arabiensis and An. gambiae sensu stricto (s.s.), while the important member of the An. funestus group was An. funestus s.s. Conclusion The contribution of different vector species in malaria transmission has changed over the past 20 years. As the role of An. gambiae has declined, An. funestus now appears to be dominant in most settings in east and southern Africa. Other secondary vector species may play minor roles in specific localities. To improve malaria control in the region, vector control should be optimized to match these entomological trends, considering the different ecologies and behaviors of the dominant vector species. Graphical Abstract

Abstract Background The impact of metabolic resistance to insecticides on malaria transmission remains poorly characterised notably through application of entomological parameters. The lack of resistance markers has been one of the limiting factors preventing a robust assessment of such impact. To this end, the present study sought to investigate how the L119F-Gste2 metabolic gene influences entomological parameters underpinning mosquitos’ propensity to transmit Plasmodium spp. Methods Longitudinal studies were carried out in Mibellon and Elende, two different eco-climatic settings in Cameroon and mosquitoes were collected using Human Landing Catch (HLC), Centre for Disease Control Light Trap (CDC-LT) and Pyrethrum Spray Catch (PSC) technics. Plasmodium sporozoite parasites were detected by TaqMan and Nested PCR, and blood meal origin by ELISA. The allele-specific PCR (AS-PCR) method was used to genotype the L119F-GSTe2 marker and association with malaria transmission was established by comparing key transmission parameters such as the Entomological Inoculation Rate (EIR) between individuals with different L119F-GSTe2 genotypes. Results An. funestus s.l was the predominant malaria vector collected during the entomological survey in both sites (86.6% and 96.4% in Elende and Mibellon, respectively) followed by An. gambiae s.l (7.5% and 2.4%, respectively). Sporozoite infection rates were very high in both collection sites (8.7% and 11% in Elende and Mibellon, respectively). An. funestus s.s exhibited a very high entomological inoculation rate (EIR) (66 ib/h/month and 792 ib/h/year) and was responsible for 98.6% of all malaria transmission events occurring in both sites. The Human Blood Index was also high in both locations (HBI = 94%). An. funestus s.s. mosquitoes with both 119 F/F (RR) and L119F (RS) genotypes had a significantly higher transmission intensity than their susceptible L/L119 (SS) counterparts (IRR = 2.2, 95%CI (1.1–5.2), p = 0.03; IRR = 2.5, 95% CI (1.2–5.8), p = 0.01 respectively). Conclusion This study highlights the major role that An. funestus s.s plays in malaria transmission in Cameroon with an aggravation from GSTe2-based metabolic resistance.

Abstract Background Pyrethroid resistance in the key malaria vectors threatens the success of pyrethroid-treated nets. To overcome pyrethroid resistance, Interceptor® G2 (IG2), a ‘first-in-class’ dual insecticidal net that combines alpha-cypermethrin with chlorfenapyr, was developed. Chlorfenapyr is a pro-insecticide, requiring bio-activation by oxidative metabolism within the insect’s mitochondria, constituting a mode of action preventing cross-resistance to pyrethroids. Recent epidemiological trials conducted in Benin and Tanzania confirm IG2’s public health value in areas with pyrethroid-resistant Anopheles mosquitoes. As chlorfenapyr might also interfere with the metabolic mechanism of the Plasmodium parasite, we hypothesised that chlorfenapyr may provide additional transmission-reducing effects even if a mosquito survives a sub-lethal dose. Methods We tested the effect of chlorfenapyr netting to reduce Plasmodium falciparum transmission using a modified WHO tunnel test with a dose yielding sub-lethal effects. Pyrethroid-resistant Anopheles gambiae s.s. with L1014F and L1014S knockdown resistance alleles and expression levels of pyrethroid metabolisers CYP6P3, CYP6M2, CYP4G16 and CYP6P1 confirmed by quantitative reverse transcription polymerase chain reaction (RT-qPCR) prior to conducting experiments were exposed to untreated netting and netting treated with 200 mg/m3 chlorfenapyr for 8 h overnight and then fed on gametocytemic blood meals from naturally infected individuals. Prevalence and intensity of oocysts and sporozoites were determined on day 8 and day 16 after feeding. Results Both prevalence and intensity of P. falciparum infection in the surviving mosquitoes were substantially reduced in the chlorfenapyr-exposed mosquitoes compared to untreated nets. The odds ratios in the prevalence of oocysts and sporozoites were 0.33 (95% confidence interval; 95% CI 0.23–0.46) and 0.43 (95% CI 0.25–0.73), respectively, while only the incidence rate ratio for oocysts was 0.30 (95% CI 0.22–0.41). Conclusion We demonstrated that sub-lethal exposure of pyrethroid-resistant mosquitoes to chlorfenapyr substantially reduces the proportion of infected mosquitoes and the intensity of the P. falciparum infection. This will likely also contribute to the reduction of malaria in communities beyond the direct killing of mosquitoes. Graphical Abstract

Abstract Background Malaria is endemic in Senegal, with seasonal transmission, and the entire population is at risk. In recent years, high malaria incidence has been reported in urban and peri-urban areas of Senegal. An urban landscape analysis was conducted in three cities to identify the malaria transmission indicators and human behavior that may be driving the increasing malaria incidence occurring in urban environments. Specifically, mosquito vector bionomics and human sleeping behaviors including outdoor sleeping habits were assessed to guide the optimal deployment of targeted vector control interventions. Methods Longitudinal entomological monitoring using human landing catches and pyrethrum spray catches was conducted from May to December 2019 in Diourbel, Kaolack, and Touba, the most populous cities in Senegal after the capital Dakar. Additionally, a household survey was conducted in randomly selected houses and residential Koranic schools in the same cities to assess house structures, sleeping spaces, sleeping behavior, and population knowledge about malaria and vector control measures. Results Of the 8240 Anopheles mosquitoes collected from all the surveyed sites, 99.4% (8,191) were An. gambiae s.l., and predominantly An. arabiensis (99%). A higher number of An. gambiae s.l. were collected in Kaolack (77.7%, n = 6496) than in Diourbel and Touba. The overall mean human biting rate was 14.2 bites per person per night (b/p/n) and was higher outdoors (15.9 b/p/n) than indoors (12.5 b/p/n). The overall mean entomological inoculation rates ranged from 3.7 infectious bites per person per year (ib/p/y) in Diourbel to 40.2 ib/p/y in Kaolack. Low anthropophilic rates were recorded at all sites (average 35.7%). Of the 1202 households surveyed, about 24.3% of household members slept outdoors, except during the short rainy season between July and October, despite understanding how malaria is transmitted and the vector control measures used to prevent it. Conclusion Anopheles arabiensis was the primary malaria vector in the three surveyed cities. The species showed an outdoor biting tendency, which represents a risk for the large proportion of the population sleeping outdoors. As all current vector control measures implemented in the country target endophilic vectors, these data highlight potential gaps in population protection and call for complementary tools and approaches targeting outdoor biting malaria vectors. Graphical Abstract

In this paper, we formulate a mathematical model of malaria transmission dynamics with impulsive and periodic release of Wolbachia-infected male mosquitoes. Our objective is to evaluate the impact of periodic release of Wolbachia-infected male mosquitoes on malaria transmission. Subsequently, to find out how often and in what quantities Wolbachia-infected male mosquitoes need to be released to effectively reduce malaria transmission. By using the comparison principle, Floquet theory and some of the analytical methods, we obtain the basic reproduction number. Then, we demonstrated that the disease-free periodic solution is globally stable if the reproduction number is less than unity, and we prove the uniform persistence of the disease if the reproduction number is greater than unity. Finally, we perform numerical simulations to illustrate our theoretically pertinent results. [ABSTRACT FROM AUTHOR]

Abstract A workshop on implementation strategies for the introduction of the RTS,S/AS01 (RTS,S) malaria vaccine in countries with areas of highly seasonal transmission, was held as a hybrid meeting in Dakar, Senegal, and online, 23–25 January 2023. Delegates from Expanded Programmes on Immunization (EPI) and National Malaria Control Programmes (NMCPs) from 13 African countries, and representatives from key stakeholders participated. RTS,S is the first malaria vaccine to be recommended by the World Health Organization (WHO). The recommendation followed pilot implementation of the vaccine in Ghana, Kenya and Malawi, which showed that introduction of the vaccine was highly effective at scale, and was associated with a 30% reduction in hospital admissions with severe malaria in age groups eligible to have received the vaccine and no evidence of the safety signals that had been observed in the phase 3 trial. Clinical trials in Mali and Burkina Faso, showed that in children receiving Seasonal Malaria Chemoprevention (SMC), providing the vaccine just prior to high transmission seasons, matching the period of highest efficacy to the peak transmission season, resulted in substantial reduction in the incidence of clinical malaria and of severe malaria. While SMC has been successfully scaled-up despite the challenges of delivery, there is no established platform for seasonal vaccine delivery and no real-world experience. The objectives of this workshop were, therefore, to share experiences from countries that have introduced the RTS,S vaccine in routine child vaccination programmes, with SMC-implementing countries as they consider malaria vaccine introduction, and to explore implementation strategies in countries with seasonal transmission and where EPI coverage may be low especially in the second year of life. Practical implementation challenges, lessons learned for vaccine introduction, and research questions, towards facilitating the introduction of the RTS,S (and other malaria vaccines) in countries with seasonal malaria transmission were discussed.

Abstract Background A better understanding of vector distribution and malaria transmission dynamics at a local scale is essential for implementing and evaluating effectiveness of vector control strategies. Through the data gathered in the framework of a cluster randomized controlled trial (CRT) evaluating the In2Care (Wageningen, Netherlands) Eave Tubes strategy, the distribution of the Anopheles vector, their biting behaviour and malaria transmission dynamics were investigated in Gbêkê region, central Côte d’Ivoire. Methods From May 2017 to April 2019, adult mosquitoes were collected monthly using human landing catches (HLC) in twenty villages in Gbêkê region. Mosquito species wereidentified morphologically. Monthly entomological inoculation rates (EIR) were estimated by combining the HLC data with mosquito sporozoite infection rates measured in a subset of Anopheles vectors using PCR. Finally, biting rate and EIR fluctuations were fit to local rainfall data to investigate the seasonal determinants of mosquito abundance and malaria transmission in this region. Results Overall, Anopheles gambiae, Anopheles funestus, and Anopheles nili were the three vector complexes found infected in the Gbêkê region, but there was a variation in Anopheles vector composition between villages. Anopheles gambiae was the predominant malaria vector responsible for 84.8% of Plasmodium parasite transmission in the area. An unprotected individual living in Gbêkê region received an average of 260 [222–298], 43.5 [35.8–51.29] and 3.02 [1.96–4] infected bites per year from An. gambiae, An. funestus and An. nili, respectively. Vector abundance and malaria transmission dynamics varied significantly between seasons and the highest biting rate and EIRs occurred in the months of heavy rainfall. However, mosquitoes infected with malaria parasites remained present in the dry season, despite the low density of mosquito populations. Conclusion These results demonstrate that the intensity of malaria transmission is extremely high in Gbêkê region, especially during the rainy season. The study highlights the risk factors of transmission that could negatively impact current interventions that target indoor control, as well as the urgent need for additional vector control tools to target the population of malaria vectors in Gbêkê region and reduce the burden of the disease.

Abstract Background Asymptomatic malaria infections (Plasmodium falciparum) are common in school-aged children and represent a disease transmission reservoir as they are potentially infectious to mosquitoes. To detect and treat such infections, convenient, rapid and reliable diagnostic tools are needed. In this study, malaria rapid diagnostic tests (mRDT), light microscopy (LM) and quantitative polymerase chain reaction (qPCR) were used to evaluate their performance detecting asymptomatic malaria infections that are infectious to mosquitoes. Methods One hundred seventy asymptomatic school-aged children (6–14 years old) from the Bagamoyo district in Tanzania were screened for Plasmodium spp. infections using mRDT (SD BIOLINE), LM and qPCR. In addition, gametocytes were detected using reverse transcription quantitative polymerase chain reaction (RT-qPCR) for all qPCR-positive children. Venous blood from all P. falciparum positive children was fed to female Anopheles gambiae sensu stricto mosquitoes via direct membrane feeding assays (DMFAs) after serum replacement. Mosquitoes were dissected for oocyst infections on day 8 post-infection. Results The P. falciparum prevalence in study participants was 31.7% by qPCR, 18.2% by mRDT and 9.4% by LM. Approximately one-third (31.2%) of asymptomatic malaria infections were infectious to mosquitoes in DMFAs. In total, 297 infected mosquitoes were recorded after dissections, from which 94.9% (282/297) were derived from infections detected by mRDT and 5.1% (15/297) from subpatent mRDT infections. Conclusion The mRDT can be used reliably to detect children carrying gametocyte densities sufficient to infect high numbers of mosquitoes. Subpatent mRDT infections contributed marginally to the pool of oocyts-infected mosquitoes. Graphical Abstract

Abstract Background Studies have explored the correlates of insecticide-treated nets in Nigeria. The few studies that focused on Northern Nigeria mostly examined individual correlates, but largely ignored the community correlates. Also, the persistence of armed insurgencies in the region calls for more research attention. This study examines the utilization and the associated individual and community factors of insecticide-treated nets in Northern Nigeria. Methods The study adopted a cross-sectional design. Data were extracted from the 2021 Nigeria Malaria Indicator Survey (NMIS). A weighted sample size of 6873 women was analysed. The outcome variable was the utilization of insecticide-treated nets. The explanatory variables selected at the individual/household level were maternal age, maternal education, parity, religion, sex of head of household, household wealth, and household size. The variables selected at the community level were the type of place of residence, geo-political zone of residence, the proportion of children under five who slept under a bed net, the proportion of women aged 15–49 who heard malaria media messages, and the community literacy level. Two variables, namely, the number of mosquito bed nets in the household, and the number of rooms used for sleeping were included for statistical control. Three multilevel mixed-effect regression models were fitted. Results The majority of childbearing women (71.8%) utilized insecticide-treated nets. Parity and household size were the significant individual/household characteristics associated with the utilization of insecticide-treated nets. The proportion of under-five children in the community who slept under mosquito bed nets, and the geopolitical zone of residence were significant community correlates of the use of insecticide-treated nets. In addition, the number of rooms for sleeping, and the number of mosquito bed nets in the households were significantly associated with the utilization of insecticide-treated nets. Conclusion Parity, household size, number of sleeping rooms, number of treated bed nets, geo-political zone of residence, and proportion of under-five children sleeping under bed nets are important associated factors of the utilization of insecticide-treated nets in Northern Nigeria. Existing malaria preventive initiatives should be strengthened to target these characteristics.