Host preference patterns in domestic and wild settings: Insights into Anopheles feeding behavior.

The adaptation of Anopheles malaria vectors to domestic settings is directly linked to their ability to feed on humans. The strength of this species-habitat association is unequal across the species within the genus, with the major vectors being particularly dependent on humans. However, our understanding of how blood-feeding behavior interacts with and adapts to environmental settings, including the presence of humans, remains limited. Using a field-based approach, we first investigated Anopheles community structure and feeding behavior patterns in domestic and sylvatic settings in La Lopé National Park in Gabon, Central Africa. We characterized the preference indices using a dual-host choice sampling approach across mosquito species, habitats, and seasons. We then quantified the plastic biting behavior of mosquito species in each habitat. We collected individuals from 16 Anopheles species that exhibited significant differences in species composition and abundance between sylvatic and domestic settings. The host-seeking behavior also varied among the seven most abundant species. The general attractiveness to each host, human or animal, remained relatively constant for each species, but with significant variations between habitats across species. These variations, to more generalist and to more anthropophilic behavior, were related to seasonal changes and distance from the village, respectively. Finally, we pointed out that the host choice of major malaria vectors changed in the absence of humans, revealing a plastic feeding behavior of these species. This study highlights the effect of humans on Anopheles distribution and feeding evolution. The characterization of feeding behavior in wild and domestic settings provides opportunities to better understand the interplay between genetic determinants of host preference and ecological factors. Our findings suggest that protected areas may offer alternative thriving conditions to major malaria vectors.

Investigating the Determinants of Malaria Outbreak in Nono Benja Woreda, Jimma Zone, Ethiopia: A Case-Control Study.

Background: Malaria is one of the most widespread infections worldwide, particularly in developing countries. Accordingly, Jimma Zone is one of the widely affected areas by malaria in Ethiopia. In 2020 woreda health offices have reported the possible malaria epidemic that needs further investigation. Accordingly, this study aims to characterize the scope, pinpoint determinants connected to the Nono Benja woreda malaria outbreak, and implement suitable public health management measures. Methods: A descriptive cross-sectional study was followed by an unmatched case-control study with a 1:1 ratio of cases to controls. The sample size of 136 individuals (68 cases and 68 controls) was used. The collected data was imported into Epi-data version 3.1 and analyzed using SPSS version 25.0. By doing multivariate logistic regression association was determined at 95% confidence intervals P value of 5%. Results: A total of 687 instances were identified, giving an overall attack incidence of 1%. The assault rate ranged from 51.6 per 1000 people in Benja rural to 1.1 per 1000 people in Dhokonu Kebele. But there were no recorded deaths. Plasmodium falciparum and Plasmodium vivax were the major types of Plasmodium species reported. From independent variables absence of ITNS [AOR 3.98 (CI = 1.11-24.8)], residing in an unsprayed home [AOR = 3.83 (CI = 1.04-14.08], presence of stagnant water in residential area [AOR = 4.25, CI (1.37-12.24113.10)], and lack of awareness on malaria prevention [AOR = 8.28 (CI 2.31-29.73)] were significantly associated with Malaria outbreak. Conclusion: A number of factors, including lack of ITNS, lack of malaria health education, stagnant water, and IRS (indoor residual spray), were significantly linked with the occurrence of malaria outbreaks. The woreda health office should therefore provide ITNS to the community, use indoor residual spray, and disseminate health information regarding efficient and long-lasting malaria preventive and control techniques.

AlbuMAX supplemented media induces the formation of transmission-competent P. falciparum gametocytes.

Asexual blood stage culture of Plasmodium falciparum is routinely performed but reproducibly inducing commitment to and maturation of viable gametocytes remains difficult. Culture media can be supplemented with human serum substitutes to induce commitment but these generally only allow for long-term culture of asexual parasites and not transmission-competent gametocytes due to their different lipid composition. Recent insights demonstrated the important roles lipids play in sexual commitment; elaborating on this we exposed ring stage parasites (20-24hours hpi) for one day to AlbuMAX supplemented media to trigger induction to gametocytogenesis. We observed a significant increase in gametocytes after AlbuMAX induction compared to serum. We also tested the transmission potential of AlbuMAX inducted gametocytes and found a significant higher oocyst intensity compared to serum. We conclude that AlbuMAX supplemented media induces commitment, allows a more stable and predictable production of transmittable gametocytes than serum alone.

Phenotypic changes of γδ T cells in Plasmodium falciparum placental malaria and pregnancy outcomes in women at delivery in Cameroon.

Introduction: Depending on the microenvironment, γδ T cells may assume characteristics similar to those of Th1, Th2, Th17, regulatory T cells or antigen presenting cells. Despite the wide documentation of the effect of Th1/Th2 balance on pregnancy associated malaria and outcomes, there are no reports on the relationship between γδ T cell phenotype change and Placental Malaria (PM) with pregnancy outcomes. This study sought to investigate the involvement of γδ T cells and its subsets in placental Plasmodium falciparum malaria. Methods: In a case-control study conducted in Yaoundé, Cameroon from March 2022 to May 2023, peripheral, placental and cord blood samples were collected from 50 women at delivery (29 PM negative: PM- and 21 PM positive: PM+; as diagnosed by light microscopy). Hemoglobin levels were measured using hemoglobinometer. PBMCs, IVBMCs and CBMCs were isolated using histopaque-1077 and used to characterize total γδ T cell populations and subsets (Vδ1+, Vδ2+, Vδ1-Vδ2-) by flow cytometry. Results: Placental Plasmodium falciparum infection was associated with significant increase in the frequency of total γδ T cells in IVBMC and of the Vδ1+ subset in PBMC and IVBMC, but decreased frequency of the Vδ2+ subset in PBMC and IVBMC. The expression of the activation marker: HLA-DR, and the exhaustion markers (PD1 and TIM3) within total γδ T cells and subsets were significantly up-regulated in PM+ compared to PM- group. The frequency of total γδ T cells in IVBMC, TIM-3 expression within total γδ T cells and subsets in IVBMC, as well as HLA-DR expression within total γδ T cells and Vδ2+ subset in IVBMC were negatively associated with maternal hemoglobin levels. Furthermore, the frequency of total γδ T cells in PBMC and PD1 expression within the Vδ2+ subset in CBMC were negatively associated with birth weight contrary to the frequency of Vδ1-Vδ2- subset in PBMC and HLA-DR expression within the Vδ2+ subset in IVBMC which positively associated with maternal hemoglobin level and birth weight, respectively. Conclusion: The data indicate up-regulation of activated and exhausted γδ T cells in Plasmodium falciparum placental malaria, with effects on pregnancy outcomes including maternal hemoglobin level and birth weight.

Artemisinin herbal combo breakers: navigating malaria treatment's double-edged sword.

Artemisinin-based combination therapies (ACTs) have transformed malaria treatment, boasting high efficacy and tolerability. However, emerging resistance jeopardises their long-term effectiveness. ACTs' ability to target multiple parasite stages mitigates resistance risks, but severe malaria cases may require additional interventions. Research on combining ACTs with adjunctive therapies shows promise, but optimal regimens remain unclear. Vigilant resistance monitoring and innovative approaches are crucial to sustaining ACT efficacy. We highlight the ACTs' benefits, limitations, and potential synergies, emphasising the urgent need for comprehensive strategies to combat malaria's evolving challenges.

75 years' journey of malaria publications in English: what and where?

Malaria has inflicted serious morbidity and mortality across the globe. The major brunt of the disease has been on African, South-East Asian and South American countries. Proportionally, malaria has attracted global research priorities and this is evident from the number of publications related to malaria from across the globe, irrespective of its endemicity. However, formal and exhaustive analyses of these 'malaria publications' are rarely reported. The systematic review and secondary data analyses were done to retrieve information on what has been published on malaria, where is it published, and which countries are major contributors to malaria research.The study presents malaria publications from 1945 to 2020 retrieved using three databases: Web of Science™, Embase® and Scopus®. Exported data were examined to determine the number of publications over time, their subject areas, contributions from various countries/organizations, and top publishing journals.The total number of published records on malaria ranged from 90,282 to 112,698 (due to three different databases). Based on the number of publications, USA, UK, France, and India were identified as the top four countries. Malaria Journal, American Journal of Tropical Medicine & Hygiene, and PLoS One were the most preferred journals, whereas the University of London (Institutions other than LSHTM), the National Institute of Health, the London School of Hygiene and Tropical Medicine, and the University of Oxford appeared to be the top contributing organization.A disproportional contribution to malaria research was observed with non-malaria endemic countries making the largest contribution. Databases differed in their output format and needed standardization to make the outputs comparable across databases.

In-Vivo Anti-Malarial Activity of 80% Methanol Leaf Extract of Croton Dichogamus Pax and Ehretia Cymosa Thonn in Plasmodium Berghei Infected Mice.

Background: Malaria is causing high mortality and morbidity due to Plasmodium's resistance to currently available anti-malarial drugs and mosquito's resistance to insecticides. Thus, there is a critical need to search for novel anti-malarial drugs from natural sources. Therefore, this study investigated in vivo antimalarial activities of two Ethiopian medicinal plants, Croton dichogamus Pax and Ehretia cymosa Thonn, in Plasmodium berghei infected Swiss albino mice. Methods: Soxhlet extraction method using 80% methanol as a solvent was used to prepare crude extracts of the two plants. Acute oral toxicity and 4-day suppressive in vivo antimalarial activity tests were performed on healthy female mice and P. berghei infected male mice, respectively. Antimalarial activity of the crude extracts at doses of 100, 200, and 400 mg/kg and the standard drug, chloroquine were used to assesse in Plasmodium berghei infected Swiss albino mice. Parasitemia level, packed cell volume, body weight, and rectal temperature of the mice were determined before infection (day 0) and after treatment (day 4). Survival time was determined by recording the date on which the mice died, considering the date of infection as day 0. The recorded data were analyzed using ANOVA and SPSS version 24. Results: The result of the acute toxicity study revealed that the crude extracts were non-toxic at doses up to 2 g/kg. The extract of E. cymosa suppressed parasitemia level by 66.28, 63.44 and 63.14% at 400, 200, and 100mg/kg, levels while C. dichogamus extract suppressed parasitemia level by 45.29% at a dose of 400mg/kg. The remaining two dose levels of C.dichogamus extract suppressed parasitemia level by < 30%. Conclusion: C. dichogamus and E. cymosa showed anti-plasmodial activities. E. cymosa exhibited a more pronounced anti-plasmodial effect than C. dichogamus. The activities of both plants observed in this study support their traditional use as antimalarial drugs. Further studies on these plants using solvent fractions are required to identify their active ingredients.

Characterization of Escherichia coli Strains for Novel Production of Plasmodium ovale Lactate Dehydrogenase.

Malaria is one of the most prevalent diseases worldwide with high incidence and mortality. Among the five species that can infect humans, Plasmodium ovale morphologically resembles Plasmodium vivax, resulting in misidentification and confusion in diagnosis, and is responsible for malarial disease relapse due to the formation of hypnozoites. P. ovale receives relatively less attention compared to other major parasites, such as P. falciparum and P. vivax, primarily due to its lower pathogenicity, mortality rates, and prevalence rates. To efficiently produce lactate dehydrogenase (LDH), a major target for diagnosing malaria, this study used three Escherichia coli strains, BL21(DE3), BL21(DE3)pLysS, and Rosetta(DE3), commonly used for recombinant protein production. These strains were characterized to select the optimal strain for P. ovale LDH (PoLDH) production. Gene cloning for recombinant PoLDH production and transformation of the three strains for protein expression were performed. The optimal PoLDH overexpression and washing buffer conditions in nickel-based affinity chromatography were established to ensure high-purity PoLDH. The yields of PoLDH expressed by the three strains were as follows: BL21(DE3), 7.6 mg/L; BL21(DE3)pLysS, 7.4 mg/L; and Rosetta(DE3), 9.5 mg/L. These findings are expected to be highly useful for PoLDH-specific diagnosis and development of antimalarial therapeutics.

Targeting Plasmodium Life Cycle with Novel Parasite Ligands as Vaccine Antigens.

The WHO reported an estimated 249 million malaria cases and 608,000 malaria deaths in 85 countries in 2022. A total of 94% of malaria deaths occurred in Africa, 80% of which were children under 5. In other words, one child dies every minute from malaria. The RTS,S/AS01 malaria vaccine, which uses the Plasmodium falciparum circumsporozoite protein (CSP) to target sporozoite infection of the liver, achieved modest efficacy. The Malaria Vaccine Implementation Program (MVIP), coordinated by the WHO and completed at the end of 2023, found that immunization reduced mortality by only 13%. To further reduce malaria death, the development of a more effective malaria vaccine is a high priority. Three malaria vaccine targets being considered are the sporozoite liver infection (pre-erythrocytic stage), the merozoite red blood cell infection (asexual erythrocytic stage), and the gamete/zygote mosquito infection (sexual/transmission stage). These targets involve specific ligand-receptor interactions. However, most current malaria vaccine candidates that target two major parasite population bottlenecks, liver infection, and mosquito midgut infection, do not focus on such parasite ligands. Here, we evaluate the potential of newly identified parasite ligands with a phage peptide-display technique as novel malaria vaccine antigens.

A Self-Assembling Pfs230D1-Ferritin Nanoparticle Vaccine Has Potent and Durable Malaria Transmission-Reducing Activity.

Malaria is caused by eukaryotic protozoan parasites of the genus Plasmodium. There are 249 million new cases and 608,000 deaths annually, and new interventions are desperately needed. Malaria vaccines can be divided into three categories: liver stage, blood stage, or transmission-blocking vaccines. Transmission-blocking vaccines prevent the transmission of disease by the mosquito vector from one human to another. Pfs230 is one of the leading transmission-blocking vaccine antigens for malaria. Here, we describe the development of a 24-copy self-assembling nanoparticle vaccine comprising domain 1 of Pfs230 genetically fused to H. pylori ferritin. The single-component Pfs230D1-ferritin construct forms a stable and homogenous 24-copy nanoparticle with good production yields. The nanoparticle is highly immunogenic, as two low-dose vaccinations of New Zealand White rabbits elicited a potent and durable antibody response with high transmission-reducing activity when formulated in two distinct adjuvants suitable for translation to human use. This single-component 24-copy Pfs230D1-ferritin nanoparticle vaccine has the potential to improve production pipelines and the cost of manufacturing a potent and durable transmission-blocking vaccine for malaria control.

On-Chip Impedance Spectroscopy of Malaria-Infected Red Blood Cells.

Malaria is a disease that affects millions of people worldwide, particularly in developing countries. The development of accurate and efficient methods for the detection of malaria-infected cells is crucial for effective disease management and control. This paper presents the electrical impedance spectroscopy (EIS) of normal and malaria-infected red blood cells. An EIS microfluidic device, comprising a microchannel and a pair of coplanar electrodes, was fabricated for single-cell measurements in a continuous manner. Based on the EIS results, the aim of this work is to discriminate Plasmodium falciparum-infected red blood cells from the normal ones. Different from typical impedance spectroscopy, our measurement was performed for the cells in a low-conductivity medium in a frequency range between 50 kHz and 800 kHz. Numerical simulation was utilized to study the suitability parameters of the microchannel and electrodes for the EIS experiment over the measurement frequencies. The measurement results have shown that by using the low-conductivity medium, we could focus on the change in the conductance caused by the presence of a cell in the sensing electrode gap. The results indicated a distinct frequency spectrum of the conductance between the normal and infected red blood cells, which can be further used for the detection of the disease.

In vitro interaction of naphthoquine with ivermectin, atovaquone, curcumin, and ketotifen in the asexual blood stage of Plasmodium falciparum 3D7.

Naphthoquine is a promising candidate for antimalarial combination therapy. Its combination with artemisinin has demonstrated excellent efficacy in clinical trials conducted across various malaria-endemic areas. A co-formulated combination of naphthoquine and azithromycin has also shown high clinical efficacy for malaria prophylaxis in Southeast Asia. Developing new combination therapies using naphthoquine will provide additional arsenal responses to the growing threat of artemisinin resistance. Furthermore, due to its long half-life, the possible interaction of naphthoquine with other drugs also needs attention. However, studies on its pharmacodynamic interactions with other drugs are still limited. In this study, the in vitro interactions of naphthoquine with ivermectin, atovaquone, curcumin, and ketotifen were evaluated in the asexual stage of Plasmodium falciparum 3D7. By using the combination index analysis and the SYBR Green I-based fluorescence assay, different interaction patterns of selected drugs with naphthoquine were revealed. Curcumin showed a slight but significant synergistic interaction with naphthoquine at lower effect levels, and no antagonism was observed across the full range of effect levels for all tested ratios. Atovaquone showed a potency decline when combined with naphthoquine. For ivermectin, a significant antagonism with naphthoquine was observed at a broad range of effect levels below 75% inhibition, although no significant interaction was observed at higher effect levels. Ketotifen interacted with naphthoquine similar to ivermectin, but significant antagonism was observed for only one tested ratio. These findings should be helpful to the development of new naphthoquine-based combination therapy and the clinically reasonable application of naphthoquine-containing therapies. IMPORTANCE: Pharmacodynamic interaction between antimalarials is not only crucial for the development of new antimalarial combination therapies but also important for the appropriate clinical use of antimalarials. The significant synergism between curcumin and naphthoquine observed in this study suggests the potential value for further development of new antimalarial combination therapy. The finding of a decline in atovaquone potency in the presence of naphthoquine alerts to a possible risk of treatment or prophylaxis failure for atovaquone-proguanil following naphthoquine-containing therapies. The observation of antagonism between naphthoquine and ivermectin raised a need for concern about the applicability of naphthoquine-containing therapy in malaria-endemic areas with ivermectin mass drug administration deployed. Considering the role of atovaquone-proguanil as a major alternative when first-line artemisinin-based combination therapy is ineffective and the wide implementation of ivermectin mass drug administration in malaria-endemic countries, the above findings will be important for the appropriate clinical application of antimalarials involving naphthoquine-containing therapies.

Can neonicotinoid and pyrrole insecticides manage malaria vector resistance in high pyrethroid resistance areas in Côte d'Ivoire?

BACKGROUND: Anopheles mosquito resistance to insecticide remains a serious threat to malaria vector control affecting several sub-Sahara African countries, including Côte d'Ivoire, where high pyrethroid, carbamate and organophosphate resistance have been reported. Since 2017, new insecticides, namely neonicotinoids (e.g.; clothianidin) and pyrroles (e.g.; chlorfenapyr) have been pre-qualified by the World Health Organization (WHO) for use in public health to manage insecticide resistance for disease vector control. METHODS: Clothianidin and chlorfenapyr were tested against the field-collected Anopheles gambiae populations from Gagnoa, Daloa and Abengourou using the WHO standard insecticide susceptibility biossays. Anopheles gambiae larvae were collected from several larval habitats, pooled and reared to adulthood in each site in July 2020. Non-blood-fed adult female mosquitoes aged 2 to 5 days were exposed to diagnostic concentration deltamethrin, permethrin, alpha-cypermethrin, bendiocarb, and pirimiphos-methyl. Clothianidin 2% treated papers were locally made and tested using WHO tube bioassay while chlorfenapyr (100 µg/bottle) was evaluated using WHO bottle assays. Furthermore, subsamples of exposed mosquitoes were identified to species and genotyped for insecticide resistance markers including the knock-down resistance (kdr) west and east, and acetylcholinesterase (Ace-1) using molecular techniques. RESULTS: High pyrethroid resistance was recorded with diagnostic dose in Abengourou (1.1 to 3.4% mortality), in Daloa (15.5 to 33.8%) and in Gagnoa (10.3 to 41.6%). With bendiocarb, mortality rates ranged from 49.5 to 62.3%. Complete mortality (100% mortality) was recorded with clothianidin in Gagnoa, 94.9% in Daloa and 96.6% in Abengourou, while susceptibility (mortality > 98%) to chlorfenapyr 100 µg/bottle was recorded at all sites and to pirimiphos-methyl in Gagnoa and Abengourou. Kdr-west mutation was present at high frequency (0.58 to 0.73) in the three sites and Kdr-east mutation frequency was recorded at a very low frequency of 0.02 in both Abengourou and Daloa samples and absent in Gagnoa. The Ace-1 mutation was present at frequencies between 0.19 and 0.29 in these areas. Anopheles coluzzii represented 100% of mosquitoes collected in Daloa and Gagnoa, and 72% in Abengourou. CONCLUSIONS: This study showed that clothianidin and chlorfenapyr insecticides induce high mortality in the natural and pyrethroid-resistant An. gambiae populations in Côte d'Ivoire. These results could support a resistance management plan by proposing an insecticide rotation strategy for vector control interventions.

Complete series method (CSM): a convenient method to reduce daily heterogeneity when evaluating the regeneration time (RT) of insecticide-treated nets (ITNs).

BACKGROUND: "Regeneration time" (RT) denotes the time required to obtain a stable mortality rate for mosquitoes exposed to insecticide-treated nets (ITNs) after three consecutive washes of a net in a day. The RT informs the wash interval used to artificially age ITNs to simulate their lifetime performance under user conditions (20 washes). RT was estimated following World Health Organization (WHO) longitudinal method (LM) procedures. Longitudinal evaluation may introduce heterogeneity due to mosquito batch variability, complicating RT determination. To overcome this, nets at each stage of regeneration (i.e., 1, 2, 3, 5 and 7 days post wash) were prepared in advance and refrigerated; then, a complete regeneration series was tested with a single mosquito batch on 1 testing day, completing four series over 4 days. This study compared the complete series method (CSM) against the LM. METHODS: The overall heterogeneity in the methods for estimating RT of one incorporated alpha-cypermethrin and piperonyl butoxide (PBO) and one incorporated permethrin with PBO ITNs was determined using laboratory-reared resistant Anopheles arabiensis under standard laboratory conditions. LM methods and CSM were compared in two experiments with refrigerated nets acclimated for (i) 2 h (test 1) and (ii) 3 h (test 2). Four regeneration replicates per day were tested per ITN product with 50 mosquitoes exposed per replicate (equivalent sample size to LM). The heterogeneity from these methods was compared descriptively. RESULTS: The intra-method variability for unwashed pieces was minimal, with variance of 1.26 for CSM and 1.18 for LM. For unwashed nets, LM had substantially greater variance and ratio of LM:CSM was 2.66 in test 1 and 2.49 in test 2. The magnitude of mortality measured in bioassays depended on sample acclimation after refrigeration. CONCLUSIONS: The CSM is a convenient method for determining the regeneration times. ITNs are prepared in advance, reducing pressure to prepare all samples to start on a single day. A complete regeneration series of samples is removed from the refrigerator, defrosted and evaluated on a single day with one mosquito batch reducing the influence of mosquito batch heterogeneity on results. Replicates can be conducted over several days but do not have to be conducted on consecutive days, allowing easy facility scheduling.

Trends of malaria cases (plasmodium species) in Gute Health Center, Wayu Tuka District, East Wollega Zone, (2013-2022): A cross-sectional study.

Background: Malaria is one of the biggest public health challenges in Ethiopia that has hampered the country's economic growth and development, and the government is on track to reduce malaria prevalence by 80% by 2025. Objective: As a result, the purpose of this study was to examine the trends in malaria prevalence in Wayu Tuqa District, Gute Health Center, over the last 10 years (2013-2022). Material and Methods: A retrospective analysis was undertaken to identify the patterns of malaria cases in Wayu Tuqa District, Gute Health Center, from 2013 to 2022 by evaluating the malaria registration laboratory logbook. All socio-demographic data, as well as the year, month, and malaria prevalence, were obtained using a predesigned data collection form from previous years. Results: In this study, 3402 (22.50%) of the total 15,040 probable patients had malaria. P. falciparum was the most common species, accounting for 82.84% (2818) of the total, followed by P. vivax (16.00%) (547). Males and people over the age of 15 were the most affected demographics. Conclusion: In this study, the highest number of malaria cases were observed in 2021 and 2022, respectively. Furthermore, the autumn season had the highest incidence of malaria cases, 40% (1339), while the spring season had the lowest prevalence, 16% (546). The general trend of plasmodium species at Gute Health Center over the previous 10 years (2013-2022) has not shown inconsistent trends. As a result, proper malaria prevention and control planning, implementation, and monitoring should be strengthened at all levels.

Breadth of Fc-mediated effector function correlates with clinical immunity following human malaria challenge.

Malaria is a life-threatening disease of global health importance, particularly in sub-Saharan Africa. The growth inhibition assay (GIA) is routinely used to evaluate, prioritize, and quantify the efficacy of malaria blood-stage vaccine candidates but does not reliably predict either naturally acquired or vaccine-induced protection. Controlled human malaria challenge studies in semi-immune volunteers provide an unparalleled opportunity to robustly identify mechanistic correlates of protection. We leveraged this platform to undertake a head-to-head comparison of seven functional antibody assays that are relevant to immunity against the erythrocytic merozoite stage of Plasmodium falciparum. Fc-mediated effector functions were strongly associated with protection from clinical symptoms of malaria and exponential parasite multiplication, while the gold standard GIA was not. The breadth of Fc-mediated effector function discriminated clinical immunity following the challenge. These findings present a shift in the understanding of the mechanisms that underpin immunity to malaria and have important implications for vaccine development.

Murine model captures evolution of edema in experimental cerebral malaria.

A complex series of studies by Oelschlegel et al. in a murine model of cerebral malaria establishes a temporal sequence of events linking decreased venous efflux to impaired perfusion, edema, and neuroinflammation. The relevance to human cerebral malaria is discussed, including the heterogeneity recognized in recent investigations of cerebrovascular hemodynamics.

Towards malaria elimination: a reflection about digital notification modules to improve malaria cases notification speed and follow-up in the Brazilian Amazon region.

BACKGROUND: Health information systems (HIS) are a pivotal element in epidemiological surveillance. In Brazil, malaria persists as a public health challenge, with 99% of its occurrences concentrated in the Amazon region, where cases are reported through the HIS Sivep-Malaria. Recent technological advancements indicate that case notifications can be expedited through more efficient systems with broader coverage. The objective of this study is to analyse opportunities for notification within Sivep-Malaria and explore the implementation of mobile electronic devices and applications to enhance the performance of malaria case notifications and use. METHODS: This descriptive study analyses data on malaria-positive cases in the Brazilian Amazon from 2004 to 2022. Malaria Epidemiological Surveillance System (Sivep-Malaria) data were used. The Brazilian Amazon region area is approximately 5 million km2 across nine different states in Brazil. Data entry opportunities were assessed by considering the time difference between the 'date of data entry' and the 'date of notification.' Descriptive statistics, including analyses of means and medians, were conducted across the entire Amazon region, and for indigenous population villages and gold mining areas. RESULTS: Between 2004 and 2022, 6,176,878 new malaria cases were recorded in Brazil. The average data entry opportunity throughout the period was 17.9 days, with a median of 8 days. The most frequently occurring value was 1 day, and 99% of all notifications were entered within 138 days, with 75.0% entered within 20 days after notification. The states with the poorest data entry opportunities were Roraima and Tocantins, with averages of 31.3 and 31.0 days, respectively. For indigenous population villages and gold mining areas, the median data entry opportunities were 23 and 15 days, respectively. CONCLUSIONS: In malaria elimination, where surveillance is a primary strategy for evaluating each reported case, reducing notification time, enhancing data quality and being able to follow-up cases through computerized reports offer significant benefits for cases investigation. Technological improvements in Sivep-Malaria could yield substantial benefits for malaria control in Brazil, aiding the country in achieving disease elimination and fulfilling the Sustainable Development Goals.

The behaviour of adult Anopheles gambiae, sub-Saharan Africa's principal malaria vector, and its relevance to malaria control: a review.

BACKGROUND: Mosquitoes of the Anopheles gambiae complex are one of the major vectors of malaria in sub-Saharan Africa. Their ability to transmit this disease of major public health importance is dependent on their abundance, biting behaviour, susceptibility and their ability to survive long enough to transmit malaria parasites. A deeper understanding of this behaviour can be exploited for improving vector surveillance and malaria control. FINDINGS: Adult mosquitoes emerge from aquatic habitats at dusk. After a 24 h teneral period, in which the cuticle hardens and the adult matures, they may disperse at random and search upwind for a mate or to feed. Mating generally takes place at dusk in swarms that form over species-specific 'markers'. Well-nourished females may mate before blood-feeding, but the reverse is true for poorly-nourished insects. Females are monogamous and only mate once whilst males, that only feed on nectar, swarm nightly and can potentially mate up to four times. Females are able to locate hosts by following their carbon dioxide and odour gradients. When in close proximity to the host, visual cues, temperature and relative humidity are also used. Most blood-feeding occurs at night, indoors, with mosquitoes entering houses mainly through gaps between the roof and the walls. With the exception of the first feed, females are gonotrophically concordant and a blood meal gives rise to a complete egg batch. Egg development takes two or three days depending on temperature. Gravid females leave their resting sites at dusk. They are attracted by water gradients and volatile chemicals that provide a suitable aquatic habitat in which to lay their eggs. CONCLUSION: Whilst traditional interventions, using insecticides, target mosquitoes indoors, additional protection can be achieved using spatial repellents outdoors, attractant traps or house modifications to prevent mosquito entry. Future research on the variability of species-specific behaviour, movement of mosquitoes across the landscape, the importance of light and vision, reproductive barriers to gene flow, male mosquito behaviour and evolutionary changes in mosquito behaviour could lead to an improvement in malaria surveillance and better methods of control reducing the current over-reliance on the indoor application of insecticides.

The influence of oviposition status on measures of transmission potential in malaria-infected mosquitoes depends on sugar availability.

BACKGROUND: Like other oviparous organisms, the gonotrophic cycle of mosquitoes is not complete until they have selected a suitable habitat to oviposit. In addition to the evolutionary constraints associated with selective oviposition behavior, the physiological demands relative to an organism's oviposition status also influence their nutrient requirement from the environment. Yet, studies that measure transmission potential (vectorial capacity or competence) of mosquito-borne parasites rarely consider whether the rates of parasite replication and development could be influenced by these constraints resulting from whether mosquitoes have completed their gonotrophic cycle. METHODS: Anopheles stephensi mosquitoes were infected with Plasmodium berghei, the rodent analog of human malaria, and maintained on 1% or 10% dextrose and either provided oviposition sites ('oviposited' herein) to complete their gonotrophic cycle or forced to retain eggs ('non-oviposited'). Transmission potential in the four groups was measured up to 27 days post-infection as the rates of (i) sporozoite appearance in the salivary glands ('extrinsic incubation period' or EIP), (ii) vector survival and (iii) sporozoite densities. RESULTS: In the two groups of oviposited mosquitoes, rates of sporozoite appearance and densities in the salivary glands were clearly dependent on sugar availability, with shorter EIP and higher sporozoite densities in mosquitoes fed 10% dextrose. In contrast, rates of appearance and densities in the salivary glands were independent of sugar concentrations in non-oviposited mosquitoes, although both measures were slightly lower than in oviposited mosquitoes fed 10% dextrose. Vector survival was higher in non-oviposited mosquitoes. CONCLUSIONS: Costs to parasite fitness and vector survival were buffered against changes in nutritional availability from the environment in non-oviposited but not oviposited mosquitoes. Taken together, these results suggest vectorial capacity for malaria parasites may be dependent on nutrient availability and oviposition/gonotrophic status and, as such, argue for more careful consideration of this interaction when estimating transmission potential. More broadly, the complex patterns resulting from physiological (nutrition) and evolutionary (egg-retention) trade-offs described here, combined with the ubiquity of selective oviposition behavior, implies the fitness of vector-borne pathogens could be shaped by selection for these traits, with implications for disease transmission and management. For instance, while reducing availability of oviposition sites and environmental sources of nutrition are key components of integrated vector management strategies, their abundance and distribution are under strong selection pressure from the patterns associated with climate change.