Female Anopheles Mosquitoes Research Articles

As principais medidas adotadas para controle vetorial e parasitológico da malária: Uma revisão sistemática

Malaria is a parasitic disease caused by protozoa of the genus Plasmodium, which for many years have created serious public health problems worldwide, being one of the main causes of morbidity and mortality in children under 5 years of age and pregnant women. One of the most common forms of transmission is through the bite of an infected female Anopheles mosquito. Due to the lack of an effective vaccine so far, several interventionist measures are carried out to combat it through insecticides against insect vectors. To this end, mosquito nets treated with insecticides based on pyrethroids or deltamethrin have been developed over the years, which facilitated the reduction of malaria transmission in many countries that used them. In addition, there is Causal Chemoprophylaxis (QC), which the World Health Organization (WHO) recommends for use preferably for people classified in the risk group due to the adverse effects that these drugs cause in the victim. This work aims to carry out a survey of the scientific evidence on the main strategies that are adopted for the control of the vector and the malaria parasite, in the period between 2012 and 2020. In this logic, a search was carried out for scientific articles, whose approach was related to the intervention actions used to control the malaria vector and parasite. In this way, a search was made for scientific articles available exclusively in the Scielo journal database, where the articles were filtered, strictly taking advantage of those published in the period from 2012 to 2020. As controlled descriptors, the terms and expressions “control”, “Malaria”, with the Boolean interposition “AND”. 35 articles were obtained, of which 16 were excluded for not addressing the subject of intervention actions for malaria control. Of the 19 selected studies, 12 specifically reported malaria vector or parasite control strategies while 7 dealt only with action plans used for malaria epidemiological surveillance. It is recommended that the next research to be carried out, research more about natural products of plant origin considered promising for a possible replacement of such antibiotics.

The Presence of Malaria Infection among Pregnant Women: Insights from Jinja Regional Referral Hospital

Malaria, transmitted by female Anopheles mosquitoes and caused by plasmodium, manifests in symptoms like fever, chills, vomiting, and anemia, posing heightened risks to pregnant women and young children. This study investigated malaria prevalence and contributing factors among pregnant women attending antenatal clinics at Jinja Regional Referral Hospital from January to June 2019, employing a retrospective cross-sectional approach utilizing existing records. Throughout the study period, the prevalence of malaria infection remained consistently low at 20%. Socioeconomic status emerged as a significant factor affecting malaria treatment, with lower economic standing correlating with higher incidence. While 80% of participants exhibited knowledge about malaria-related complications and preventive measures such as using insecticide-treated mosquito nets and eliminating stagnant water, 20% lacked this crucial awareness. Notably, a disparity was observed in malaria cases between well-educated and less educated attendees at the health unit, with fewer instances among the more educated individuals. Maternal complications primarily centered around anemia, while occurrences of low birth weight and stillbirth were relatively uncommon, attributed to prompt diagnosis and treatment. The study highlighted fluctuating malaria prevalence, indicating the need for extensive awareness campaigns, particularly concerning intermittent preventive treatment during pregnancy (IPT1 and IPT2). Collaborative efforts involving the community, government, hospitals, and even spouses are crucial to disseminate crucial information. Encouraging the consistent use of insecticide-treated mosquito nets during pregnancy should be emphasized, although this aspect wasn't specifically addressed in the study. Keywords: Malaria infection, Maternal mortality, Pregnant women, Antenatal care.

Mechanistic insights into the interaction between the host gut microbiome and malaria.

Malaria is a devastating infectious disease and significant global health burden caused by the bite of a Plasmodium-infected female Anopheles mosquito. Gut microbiota was recently discovered as a risk factor of severe malaria. This review entails the recent advances on the impact of gut microbiota composition on malaria severity and consequence of malaria infection on gut microbiota in mammalian hosts. Additionally, this review provides mechanistic insight into interactions that might occur between gut microbiota and host immunity which in turn can modulate malaria severity. Finally, approaches to modulate gut microbiota composition are discussed. We anticipate this review will facilitate novel hypotheses to move the malaria-gut microbiome field forward.

Determination of sporozoite infection rate of indoor resting female Anopheles mosquitoes in Gombe South, Gombe State, Nigeria

Infected female Anopheles mosquitoes are the culprits of malaria. The abundance and distribution of malaria vectors in communities contribute significantly in malaria transmission. Understanding the magnitude and intensity of sporozoite infection rates is very sensitive and powerful indices for describing the epidemiology of malaria which will aid in strategizing malaria control programme. The present study determines the sporozoite infection rates of female Anopheles mosquitoes in the four Local Government Areas (LGA) of Gombe South, Gombe State, Northeastern Nigeria. Mosquitoes were collected using Pyrethrum Spray Catch (PSC) and were dissected to check the presence of sporozoites. Out of the 1,860 female Anopheles mosquitoes dissected, 665(35.8%) were infected with sporozoites. The highest infection rate was observed from Kaltungo LGA 145(41.7%), followed by Billiri LGA 182(36.3%), and 205(35.4%) was recorded from Balanaga. The lowest infectivity rate was observed from Shongom LGA 133(30.9%), p<0.005 which is highly significant statistically. With regards to monthly distribution of sporozoites, the highest infection rate was recorded in December (64.7%), January 60.0%, (64.5%), and August (60.7%) from Balanga, Billiri, Kaltungo and Shongom LGA respectively. Meanwhile the least was observed in July (2.8%), December (7.7%), April (20.0%), and March (11.6%) from Balanga, Billiri, Kaltungo and Shongom LGA respectively, p<0.005 which is highly significant statistically. However, (0.0%) sporozoite infection was obtained in September and March from Billiri, Kaltungo and Shongom LGA respectively. The present study therefore recommends malaria vector control through community based efforts by destruction of mosquitoes breeding sites, use of insect’s repellents, environmental sanitation and application of oil in stagnant water in order to reduce vectors population.

The Effect of the Indoor Residual Spraying (IRS) Program on Reducing Parasite Incidence in the Working Area of the Sea Silau Health Center, Asahan District

Malaria is a severe, life-threatening infectious disease transmitted through the bite of infected female Anopheles mosquitoes. In Asahan Regency, four areas are endemic for malaria, with Silau Laut District having an API rate of 4.8‰ (Annual Parasite Incidence per 1000 at-risk individuals annually). Indoor residual spraying (IRS) with Lambda Cyhalothrin (Icon 100 CS) is used to eradicate mosquito vectors by applying insecticide to walls and ceilings, interrupting transmission. Research aimed to assess IRS effectiveness in reducing malaria incidence in Silau Laut District found a strong positive correlation (0.826 and 0.912) between RDT and microscopic examination results before and after IRS. However, correlations between education and malaria control using IRS and changes in knowledge and attitudes were weak (0.490 and 0.438). Paired T-tests revealed differences in RDT examination results (p = 0.044) and knowledge and attitude levels (p = 0.000) before and after IRS education. No significant difference was observed in microscopic examination results (p = 0.159). Recommendations include intensified efforts in malaria prevention and control, including active case finding, mosquito nest elimination, continued IRS, mesh installation, insecticide-treated bed net use, health education, and regular bioassay testing every 1-2 months for 3-6 months in Silau Laut District.

Reflections on the surge in malaria cases after unprecedented flooding in Pakistan-A commentary.

Malaria is a parasitic infection primarily caused by four main species of the genus Plasmodium, that is, Plasmodium falciparum, Plasmodium ovale, Plasmodium vivax, and Plasmodium malariae. It is transmitted through the bite of the female Anopheles mosquito. It holds the status of one of the leading causes of death in the developing world. Malaria is endemic to Pakistan, and the country experienced the worst floods in its history from April to October 2022. The stagnant flood water served as a breeding ground for mosquitoes, culminating in an alarming spike in malaria cases. According to the World Health Organization (WHO), the number of cases reported till August 2022 was more than in the whole year of 2021. There was more than a twofold rise in cumulative cases in 62 high-burden Pakistani Districts in August 2022 as compared to August 2021. This commentary aims to bring this emerging issue to notice and highlight the most effective probable measures to help eliminate and prevent the hazards the current outbreak poses. Rapid planning and execution are needed to ensure the most efficient and rapid elimination of malaria. To educate the general public, the national government must start public awareness efforts in electronic, print, and social media and deploy solar-powered mobile healthcare units to far-flung areas. Prophylactic and postexposure treatments should be planned because larvicidal preventive measures are less practical in flood-affected vicinities. The most effective preventive strategy is drug prophylaxis, followed by insecticide-treated nets, indoor residual spraying, and untreated nets. Scientists should intensify their investigations for effective medications to alleviate the malaria burden in Pakistan.

Genome-wide in silico analysis for novel regulators of gametocyte development critical for transmission of Plasmodium falciparum.

Malaria, caused by the unicellular Apicomplexan protozoa of the genus Plasmodium, is an infectious disease transmitted via female Anopheles mosquitoes. The sexual stage (gametocytes) of malaria parasites is the key to the transmission of parasites from vertebrate hosts to mosquitoes, representing critical bottleneck of the parasite life cycle. This study has established a systematic computational pipeline to achieve the genome-wide in silico analysis and find 708 novels potentially indispensable genes for gametocyte development, consisting of 644 protein coding genes, 56 ncRNA genes and 8 pseudogenes, with a total of 191 genes in the transmembrane, 29 protein coding genes to be exported proteins, and 58 genes in apicoplast regions. Furthermore, Gene Ontology analysis showed that the largest cluster was cellular processes with nucleus and cytosol highest, followed by molecular function with binding and oxidoreductase activities abundant. Meanwhile, when a text searched, using PlasmoDB, there were 300 genes with annotations of "putative", and 196 genes with annotations of "unknown function". These data would be helpful to provide potential targets for effective malaria transmission-blocking strategies.

SYNTHESIS, DOCKING AND EVALUATION OF PYRIMIDINE DERIVATIVES AS ANTI-MALARIAL AGENTS

Malaria is endmic disease of tropical and subtropical contries like India, Pakistan, Srilanka, Bangladesh, South Africa etc. There are lot of fatalities and causalities due to malaria every year. There are lot of drugs have been synthesized for controlling this intermittent fever like chloroquine, hydroxychloroquine, pamaquine, primaquine, artimisininine, sulphadoxine, pyrimethamine, dapsone. The pyrimidine derivative synthetic drugs like sulphadoxine and pyramethamine have potential role to treat malaria with fever side effects. The lead molecule is pyrimdine and various groups are attached to this nucleus for optimizing the activity of lead nucleus and its derivative to treat this dangerous disease.
 The main causative organisms are plasmodium falciparm, plasmodium vivex, plasmodium malariae and ovale that cause malaria in patient and transmitted in blood after bitting of female anopheles mosquito that act as vector for plasmodium species.
 The docking studies are also performed by software and proper lead compound is identified with docking studies. The synthesis of compounds were carried out in laboratories with microwave synthesis and newer techniques that are fast and less time consuming of better yield of products. Structure activities relationships are studied and optimum activities are obtained by replacing different functional groups and other groups.

Attitudes and Practices of Insecticide Treated Bed Nets Usage among Rural Dwellers in Oyo State, Nigeria

Aim: Malaria, a life-threatening disease transmitted to humans by the bites of infected female Anopheles mosquitoes, continues to be a significant public health issue, particularly in sub-Saharan Africa. This study was aimed at understanding the attitudes and practices regarding the use of insecticide-treated bed nets (ITNs) among rural dwellers in Oyo state, Nigeria.
 Methodology: The study adopted a cross-sectional design. The questionnaire was developed based on the objectives of the study. Sample size was calculated using the Fisher’s formula. The minimum sample size was 278 and was adjusted to 306 to account for non-response rate of 10%. A multi-stage cluster sampling technique was employed to select the participants.
 Results: The primary understanding of the purpose of ITNs was prevention of mosquito bites (59.67%), and prevention of malaria (40.33%). However, only 74% believed that ITNs could effectively prevent malaria and just 66% considered ITNs safe for use. The practice of ITN usage was quite high, with 93% of respondents possessing ITNs in their households. ITNs were obtained predominantly through free distribution (49%) or purchase (29.67%). Use of ITNs varied among participants, with 28.67% always using it, 41% often using it, and 7% never using it. The reasons for not always using ITNs included discomfort sleeping under it (49%) and perceptions of heat (30%). An analysis of the factors affecting the usage of ITNs indicated a significant association with the age, marital status, level of education, knowledge of ITNs, and beliefs about ITN's effectiveness and safety. The usage of ITNs was particularly low among younger respondents, those who were single or widowed/divorced/separated, those with no formal education or primary education, and those who were unaware of ITNs or did not believe in their effectiveness or safety.
 Conclusion: This study reveals a gap between knowledge and practice in ITN use, with significant barriers being discomfort and a lack of belief in the effectiveness of ITNs. While ownership rates are high, usage rates, especially consistent usage, is low. This was due to misconceptions, especially around the efficacy and safety of ITNs. Moreover, maintenance practices are suboptimal.

Knowledge on Malaria and Health Seeking Behavior among the People of Belauri Municipality of Nepal: A Cross-Sectional Study

Background: Malaria infection is transmitted to humans through the bite of infected female Anopheles mosquitoes and 247 million cases of malaria in 2021, an increase from 245 million cases in 2020. The objective of the study was to assess the level of knowledge and health seeking behavior on malaria among the people of Belauri Municipality of Nepal. Method: A Cross-sectional descriptive study was done among randomly selected 387 households. Head of the households were the respondents for face to face interview. Pretested and validated tool was used for data collection. Statistical Package for Social Sciences version 20 used for data analysis. Percentages, frequency, bivariate and multivariate analysis has been to measure the distribution and level of association. Results: Overall knowledge about symptoms of malaria was good among 57.9% and who possessed a good understanding of malaria symptoms tended to seek treatment from modern health facilities during a malaria fever. Of these individuals, 43.8% sought treatment from public health facilities, while 32.7% sought treatment from private health facilities, resulting in a total of 76.5% seeking treatment from modern health facilities. However, the analysis found that the level of knowledge regarding malaria symptoms was not statistically significant (p=0.13) in relation to health-seeking behavior. Conclusions: For success of malaria prevention, programs should be designed to increase level of knowledge and also the translation of knowledge domain into appropriate health care seeking behavior in malaria fever.

ANALISIS DAN SIMULASI MODEL SUSCEPTIBLE INFECTIVE TREATMENT RECOVERY PADA PENYEBARAN PENYAKIT MALARIA DI KOTA MEDAN

Malaria is an infectious disease caused by plasmodium, which is a single-celled living creature belonging to the group of protozoan parasites, malaria is transmitted through the bite of a female Anopheles mosquito containing plasmodium in it. Plasmodium carried through mosquito bites will live and reproduce in human red blood cells. This disease attacks all age groups, both men and women. People who are exposed to malaria will have symptoms of fever, chills, sweats, headaches, nausea or vomiting. Patients who show clinical symptoms must undergo laboratory tests to confirm their positive malaria status. The purpose of this study was to determine the model of the spread of Malaria and to analyze the stability of the model of Malaria. This study uses the SITR mathematical model which involves 4 population compartments, namely Susceptible (S), Invective (I), Treatment (T), Recovery (R). The data used is secondary data obtained from the Medan City Health Office through the Medan City Health Office. From this study, the SITR mathematical model was obtained, two equilibrium points, namely the point of disease and endemic from the SITR model with a basic Reproductive value of = 0, 2693449588 or < 1. The greater the basic reproduction number, the more likely it is that malaria will spread, but the more the smaller the basic reproduction number, the smaller the chance for malaria to spread and will gradually disappear

Investigating the breeding habitats and kdr allele frequency of malaria vectors in Anambra Central Senatorial Zone, Southeast Nigeria

Malaria, transmitted by infected female Anopheles mosquitoes, is a parasitic disease of major public health importance in Nigeria. Various classes of insecticides have played significant role in the control and elimination of malaria by attacking the vectors. Unfortunately, the success of the use of insecticides in the control of malaria vectors is threatened by the emergence of insecticidal resistance. This study was therefore aimed at determining the resistance status of Anopheles gambiae s. l. in communities in Anambra State, southeast Nigeria. Larval samples were collected from diverse habitats and reared to adult for susceptibility test. Target site resistance assays were carried out and genotypic differentiation test was performed to assess variability of the allelic frequencies of the kdr (L1014F) mutation. The results showed that Anopheles gambiae was the predominant vector (54.2%), followed by Anopheles coluzzii (45.8%). The distribution of the frequency of resistant allele of the kdr gene F (L1014F) showed that the number of homozygous resistant genotype (RR) in Awka North LGA for An. gambiae and An. coluzzii species was highest (31), followed by Awka South (20), and Njikoka (5) LGAs. Also, the number of Heterozygous resistant genotype (Rr) was highest in Awka South (7), followed by Awka North (2), and none was recorded in Njikoka LGA. Homozygous resistant genotype (RR) was frequently observed in the three study areas of Anambra State and is a threat to the use of pyrethroids for insecticidal control of malaria vectors. There is an urgent need for implementation of insecticide resistance management and monitoring in Anambra State to assess the spread of resistance which may expand malaria vector resistance to the remaining classes of insecticides (organophosphates and carbamates) on the long run.

UJI EFEKTIVITAS KOMBINASI EKSTRAK DAUN SIRIH HIJAU “PIPER BETLE L” DAN MADU SEBAGAI ANTIMALARIA PADA MENCIT YANG DIINFEKSI PLASMODIUM BERGHEI

Malaria is an infectious disease caused by the parasite Plasmodium sp. transmitted by the female Anopheles mosquito vector through its bite. Patients infected with malaria worldwide in the last two decades have increased, mainly due to the emergence of strains of Plasmodium falciparum that have become resistant to antimalarial drugs. This has resulted in the emergence of efforts to find alternative medicinal plants that can overcome this problem. One of the plants that have the potential to be developed is Piper betle L, or commonly known as green betel plant. This study aims to determine the effect of green betel leaf extract (Piper betle L) and honey at doses of 50, 100, and 200 mg/kgBW as antimalarials in Balb/c mice infected with Plasmodium berghei. This study is an in vivo experimental study using the Randomized Post-test Only Controlled Group method design using 24 samples of mice which were divided into four groups, one negative control group and three treatment groups. The average degree of parasitemia in the control group was 45.51%, the treatment group at a dose of 50 mg/kgBW was 35.71%, a dose of 100 mg/kgBW was 30.96% and a dose of 200 mg/kgBW was 31.67%. Based on the results of the analysis using One Way ANOVA, it was found that the mean difference between the control and treatment groups with p value <0.001 was found. The results showed that green betel leaf extract (Piper betle L) could inhibit the growth of Plasmodium berghei by looking at the mean difference between the control group and the treatment group and obtained that the average treatment group of 100 mg/kgBW and 200 mg/kgBW were equally effective at inhibiting parasitemia levels.
 Keywords : Antimalarial, Piper betle L, Degree of Parasitemia

Clinical Trends of Malaria in Abbasia Fever Hospital over a Period of Two Years

Background Malaria is an acute systemic illness caused by infection with Plasmodium parasites that lives part of its life in humans and part in female Anopheles mosquitoes. It remains one of the major killers of humans, population worldwide. Objective To study clinical trends and prevalance of malaria in Abbasia Fever hospital over a period of two years. Patients and Methods This study was conducted in co-operation between Tropical Medicine Department, Faculty of Medicine, Ain Shams University and Abbasia Fever hospital. The current study was conducted on 200 Malarial patients admitted to Abbasia fever Hospital in Cairo (time) to be treated according to the protocol of treatment of malaria which was approved by Ministry of Health in Egypt. Results According to the treatment of malaria, the present study revealed that the best response in studied cases was to the mono-therapy. Concerning the clinical outcome of the studied cases, most of the studied cases (189 patients) were cured in the sense of clinical and parasitological improvement. Regarding comparative results among the studied cases, complicated malaria was more frequent in male and non-Egyptian and pregnant women. Conclusion Malaria should be considered as a cause of fever in relevant target patients. Malaria disease is commoner in the younger ago group. In Egypt, no endogenous malaria cases have been reported since1998 until 2014 a malaria outbreak was discovered in Aswan. Malaria cases in Egypt are usually coming from endemic area in Africa. Mortality due to malaria disease is unusual, and may result from improper chemoprophylaxis and missed diagnosis or late treatment. Monotherapy is preferable than Combined therapy (polytherapy) as it is more effective among the studied malarial cases. Tools of prophylaxis are insect repellents, protective clothes, bed nets and chemoprophylaxis.

Surveillance of Malaria Cases among Residents of Villages of Tarwa Block, Azamgarh

Malaria is a protozoal disease caused by infection with parasites of genus plasmodium and transmitted to man by certain species of infected female anopheles mosquito. This mosquito is mainly found in tropical countries. Study was conducted in villages of Tarwa block, Azamgarh Uttar Pradesh, India. It was a cross sectional study where total 50 cases were studied. It was found that maximum affected population were from 10-45 year age group. Also found that all cases were suffering from fever followed by myalgia (82%), headache (78%) and retro-orbital pain in 73% of cases. During this surveillance study it was found that main source of mosquito breeding were standing water, containers, drains and gutters, water storage tanks, bird baths, flower pot saucers, ponds and lakes, pools, septic tank and sewage and marshes and wetlands.

A heparin-binding protein of Plasmodium berghei is associated with merozoite invasion of erythrocytes

BackgroundMalaria caused by Plasmodium species is a prominent public health concern worldwide, and the infection of a malarial parasite is transmitted to humans through the saliva of female Anopheles mosquitoes. Plasmodium invasion is a rapid and complex process. A critical step in the blood-stage infection of malarial parasites is the adhesion of merozoites to red blood cells (RBCs), which involves interactions between parasite ligands and receptors. The present study aimed to investigate a previously uncharacterized protein, PbMAP1 (encoded by PBANKA_1425900), which facilitates Plasmodium berghei ANKA (PbANKA) merozoite attachment and invasion via the heparan sulfate receptor.MethodsPbMAP1 protein expression was investigated at the asexual blood stage, and its specific binding activity to both heparan sulfate and RBCs was analyzed using western blotting, immunofluorescence, and flow cytometry. Furthermore, a PbMAP1-knockout parasitic strain was established using the double-crossover method to investigate its pathogenicity in mice.ResultsThe PbMAP1 protein, primarily localized to the P. berghei membrane at the merozoite stage, is involved in binding to heparan sulfate-like receptor on RBC surface of during merozoite invasion. Furthermore, mice immunized with the PbMAP1 protein or passively immunized with sera from PbMAP1-immunized mice exhibited increased immunity against lethal challenge. The PbMAP1-knockout parasite exhibited reduced pathogenicity.ConclusionsPbMAP1 is involved in the binding of P. berghei to heparan sulfate-like receptors on RBC surface during merozoite invasion.

Plasmodium microtubule-binding protein EB1 is critical for partitioning of nuclei in male gametogenesis.

Sexual reproduction of the malaria parasites is critical for their transmission to a mosquito vector. Several signaling molecules, such as kinases and phosphatases, are known to regulate this process. We previously demonstrated that Plasmodium falciparum (Pf) Ca2+-dependent protein kinase 4 (CDPK4) and serine/arginine-rich protein kinase 1 (SRPK1) are critical for axoneme formation during male gametogenesis, with genetic deletion of either gene causing a complete block in parasite transmission to the mosquito. A comparative phospho-proteome analysis of Pfcdpk4- and RNA-seq analysis of Pfsrpk1- gametocytes showed that these kinases regulate similar biological processes linked to both microtubule (MT) dynamics and cell motility. One of these proteins was a nuclear MT-associated End Binding protein 1 (EB1), which was hypophosphorylated in Pfcdpk4- gametocytes. To study the functional relevance of EB1, we created gene deletion parasites for EB1. We further demonstrate that Pfeb1- parasites like WT NF54 parasites proliferate normally as asexuals and undergo gametocytogenesis and gametogenesis. Strikingly, these parasites suffer a severe defect in nuclear segregation and partitioning of nuclei into emerging microgametes. Further genetic crosses utilizing male- and female-sterile parasites revealed that Pfeb1- parasites only suffer a male fertility defect. Overall, our study reveals an essential function for PfEB1 in male gamete nuclear segregation and suggests a potential therapeutic avenue in the design of transmission-blocking drugs to prevent malaria transmission from humans to mosquito. IMPORTANCE Gametogenesis and subsequent gamete fusion are central to successful transmission of the malaria parasites to a female Anopheles mosquito vector and completion of the sexual phase of the parasite life cycle. Male gametogenesis involves the formation of axonemes inside male gametes from male gametocytes via active cytoskeleton remodeling. The tubulin and tubulin-binding proteins are, thus, attractive anti-malarial drug targets. In the present study, we demonstrate that a microtubule-binding protein PfEB1 is essential for male gamete fertility, specifically for the inheritance of nuclei from activated male gametocytes. Targeting PfEB1 function may provide new avenues into designing interventions to prevent malaria transmission and disease spread.

Effects of next-generation, dual-active-ingredient, long-lasting insecticidal net deployment on insecticide resistance in malaria vectors in Tanzania: an analysis of a 3-year, cluster-randomised controlled trial

Insecticide resistance among malaria-vector species is a pervasive problem that might jeopardise global disease-control efforts. Novel vector-control tools with different modes of action, including long-lasting insecticidal nets (LLINs) incorporating new active ingredients, are urgently needed to delay the evolution and spread of insecticide resistance. We aimed to measure phenotypic and genotypic insecticide-resistance profiles among wild Anopheles collected over 3 years to assess the longitudinal effects of dual-active-ingredient LLINs on insecticide resistance. For this analysis, data nested in a 3-year, four parallel-arm, superiority cluster-randomised controlled trial (cRCT) in Tanzania, collected from 84 clusters (39 307 households) formed of 72 villages in the Misungwi district, were used to measure insecticide-resistance profiles among female Anopheles mosquitoes via insecticide-resistance bioassays and quantitative RT-PCR of metabolic-resistance genes. Wild, blood-fed, indoor-resting mosquitoes were collected annually during the rainy seasons from house walls in clusters from all four trial groups. Mosquitoes were morphologically identified as An gambiae sensu lato (SL) or An funestus SL before separate bioassay testing. The primary outcomes were lethal-dose values for α-cypermethrin, permethrin, and piperonyl butoxide pre-exposure plus permethrin-resistance intensity bioassays, mortality 72 h after insecticidal exposure for chlorfenapyr bioassays, fertility reduction 72 h after insecticidal exposure for pyriproxyfen bioassays, and fold change in metabolic-enzyme expression relative to an insecticide-susceptible laboratory strain. All primary outcomes were measured in An funestus SL 1 year, 2 years, and 3 years after LLIN distribution. Primary outcomes were also assessed in An gambiae SL if enough mosquitoes were collected. The cRCT is registered with ClinicalTrials.gov (NCT03554616). Between May 24, 2019, and Oct 25, 2021, 47 224 female Anopheles were collected for resistance monitoring. In the pyrethroid (PY)-LLIN group, there were significant increases in α-cypermethrin-resistance intensity (year 1 LD50=9·52 vs year 2 76·20, p<0·0001) and permethrin-resistance intensity (year 1 13·27 vs year 2 35·83, p=0·0019) in An funestus SL. In the pyriproxyfen PY-LLIN group, there was similar increase in α-cypermethrin-resistance intensity (year 1 0·71 vs year 2 81·56, p<0·0001) and permethrin-resistance intensity (year 1 5·68 vs year 2 50·14, p<0·0001). In the piperonyl butoxide PY-LLIN group, α-cypermethrin-resistance intensity (year 1 33·26 vs year 3 70·22, p=0·0071) and permethrin-resistance intensity (year 1 47·09 vs year 3 2635·29, p<0·0001) also increased over time. In the chlorfenapyr PY-LLIN group, there were no effects on α-cypermethrin-resistance intensity (year 1 0·42 vs year 3 0·99, p=0·54) or permethrin-resistance intensity (data were not estimable due to nearly 100% mortality). There were also minimal reductions in chlorfenapyr susceptibility. However, in the chlorfenapyr PY-LLIN group, a significant decline in piperonyl-butoxide synergy was seen by year 3 (year 1 0·02 vs year 3 0·26, p=0·020). Highly over-expressed detoxification enzymes showed dynamic patterns of selection throughout the trial. Our phenotypic data supports trial epidemiological findings; chlorfenapyr PY-LLINs provided superior protection from malaria across multiple transmission seasons, with few effects on insecticide-resistance selection. Rapid pyrethroid-resistance intensification in the piperonyl butoxide PY-LLIN group and pre-existing tolerance of pyriproxyfen in vector populations might explain the poorer performance of these two interventions regarding malaria outcomes. Further work is required to elucidate the potential mechanisms driving cross-resistance between pyrethroids and novel active ingredients to better inform the design of pre-emptive resistance-management strategies. UK Department for International Development; UK Medical Research Council; Wellcome Trust; UK Department of Health and Social Care; UK Foreign, Commonwealth and Development Office; and The Bill and Melinda Gates Foundation via the Innovative Vector Control Consortium.

Resistance of Anopheles stephensi to selected insecticides used for indoor residual spraying and long-lasting insecticidal nets in Ethiopia

BackgroundMalaria, transmitted by the bite of infective female Anopheles mosquitoes, remains a global public health problem. The presence of invasive Anopheles stephensi, capable of transmitting Plasmodium vivax and Plasmodium falciparum, was first reported in Ethiopia in 2016. The ecology of this mosquito species differs from that of Anopheles arabiensis, the primary malaria vector in Ethiopia. This study aimed to evaluate the efficacy of selected insecticides, which are used in indoor residual spraying (IRS) and selected long-lasting insecticidal nets (LLINs) for malaria vector control against adult An. stephensi.MethodsAnopheles stephensi mosquitoes were collected as larvae and pupae from Awash Subah Kilo Town and Haro Adi village, Ethiopia. Adult female An. stephensi, reared from larvae and pupae collected from the field, aged 3–5 days were exposed to impregnated papers of IRS insecticides (propoxur 0.1%, bendiocarb 0.1%, pirimiphos-methyl 0.25%), and insecticides used in LLINs (alpha-cypermethrin 0.05%, deltamethrin 0.05% and permethrin 0.75%), using diagnostic doses and WHO test tubes in a bio-secure insectary at Aklilu Lemma Institute of Pathobiology, Addis Ababa University. For each test and control tube, batches of 25 female An. stephensi were used to test each insecticide used in IRS. Additionally, cone bioassay tests were conducted to expose An. stephensi from the reared population to four brands of LLINs, MAGNet™ (alpha-cypermethrin), PermaNet® 2.0 (deltamethrin), DuraNet© (alpha-cypermethrin) and SafeNet® (alpha-cypermethrin). A batch of ten sugar-fed female mosquitoes aged 2–5 days was exposed to samples taken from five positions/sides of a net. The data from all replicates were pooled and descriptive statistics were used to describe features of the data.ResultsAll An. stephensi collected from Awash Subah Kilo Town and Haro Adi village (around Metehara) were resistant to all tested insecticides used in both IRS and LLINs. Of the tested LLINs, only MAGNet™ (alpha-cypermethrin active ingredient) caused 100% knockdown and mortality to An. stephensi at 60 min and 24 h post exposure, while all other net brands caused mortality below the WHO cut-off points (< 90%). All these nets, except SafeNet®, were collected during LLIN distribution for community members through the National Malaria Programme, in December 2020.ConclusionsAnopheles stephensi is resistant to all tested insecticides used in IRS and in the tested LLIN brands did not cause mosquito mortality as expected, except MAGNet. This suggests that control of this invasive vector using existing adult malaria vector control methods will likely be inadequate and that alternative strategies may be necessary.

Investigating Practices Among Fish Farmers That Predispose Them To Malaria Infection: An Analytical Cross Section Survey In Mongu And Limulunga Districts Of Western Province, Zambia

Malaria is a parasitic disease that is transmitted between humans through the bite of the infected female Anopheles mosquito. Zambia has recently experienced a growing demand for fish, which is largely triggered by the growing population and an emergent urban middle class within Zambia and neighbouring countries. Various fish farming practices are carried out on small-scale, smallholder and commercial levels. Western Province is among the provinces in Zambia where fish farming is done. In 2014, Zambia became the sixth largest producer of farmed fish (mainly breams – a local name for tilapia) in Africa and the largest in the Southern African Development Community (SADC) and between 2012 and 2015, the malaria prevalence started to climb from 12.6 to 15.6 per cent in Western Province of Zambia. This study set out to investigate the practices of fish farmers that predispose them to malaria infection in Mongu (45) and Limulunga (30) districts of the western province of Zambia. The data collection tool was an interviewer-administered questionnaire (demographic characteristics, malaria knowledge, and fish farming practices). The data were analysed using the Statistical Package for Social Sciences (SPSS) version 22. Out of a total of 75 fish farmers, 83% of the participants had good knowledge of malaria while 17% had poor knowledge, and an association was found between the two highest levels of education (Tertiary and Secondary) and knowledge on malaria according to the chi-squared test (p&lt;0.005) and also showed that 73% (n=55) had their ponds near their houses and 3% (n=20) had their ponds far from their houses. Practices such as not draining ponds, working around the ponds at night without protective clothing, and having ponds near households predispose fish farmers to malaria infection in Mongu and Limulunga districts in Western Province, Zambia. Collectively, 21% of fish farmers practice unsafe fish farming, which could potentially increase malaria transmission levels in Western Province, Zambia.