Changes in malaria vector bionomics and transmission patterns in the equatorial forest region of Cameroon between 2000 and 2017.

BACKGROUND Increased use of long-lasting insecticidal nets (LLINs) over the last decade has considerably improved the control of malaria in sub-Saharan Africa. However, there is still a paucity of data on the influence of LLIN use and other factors on mosquito bionomics in different epidemiological foci. The objective of this study was to provide updated data on the evolution of vector bionomics and malaria transmission patterns in the equatorial forest region of Cameroon over the period 2000-2017, during which LLIN coverage has increased substantially. METHODS The study was conducted in Olama and Nyabessan, two villages situated in the equatorial forest region. Mosquito collections from 2016-2017 were compared to those of 2000-2001. Mosquitoes were sampled using both human landing catches and indoor sprays, and were identified using morphological taxonomic keys. Specimens belonging to the An. gambiae complex were further identified using molecular tools. Insecticide resistance bioassays were undertaken on An. gambiae to assess the susceptibility levels to both permethrin and deltamethrin. Mosquitoes were screened for Plasmodium falciparum infection and blood-feeding preference using the ELISA technique. Parasitological surveys in the population were conducted to determine the prevalence of Plasmodium infection using rapid diagnostic tests. RESULTS A change in the species composition of sampled mosquitoes was recorded between the 2000-2001 collections and those of 2016-2017. A drop in the density of the local primary vectors An. nili and An. moucheti in the forest region was recorded, whereas there was an increase in the density of An. gambiae (s.l.), An. marshallii, An. ziemannii and An. paludis. A change in the biting behaviour from indoor to outdoor was recorded in Olama. Very few indoor resting mosquitoes were collected. A change in the night biting cycle was recorded with mosquitoes displaying a shift from night biting to late evening/early in the night. Several mosquitoes were found positive for Plasmodium infection, thus sustaining continuous transmission of malaria in both sites. Reduction of malaria transmission in Nyabessan was lower than that seen in Olama and associated with deforestation and the construction of a dam that may have enabled a more efficient vector, An. gambiae (s.l.), to invade the area. A high level of resistance to pyrethroids (permethrin and deltamethrin) was detected for An. gambiae in both sites. High parasite prevalence was recorded in both sites, with children of 0-16 years being the most affected. In both Olama and Nyabessan, bed net usage appeared to correlate to protection against malaria infection. CONCLUSIONS The study shows important changes in the bionomics of vector populations and malaria transmission patterns in the equatorial forest region. The changes call for more concerted efforts to address challenges such as insecticide resistance, environmental modifications or behavioural changes affecting the performance of current control measures

Extracellular vesicles could be a putative posttranscriptional regulatory mechanism that shapes intracellular RNA levels in Plasmodium falciparum

© 2023 The Author(s). This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY), https://creativecommons.org/licenses/by/4.0/Plasmodium falciparum secretes extracellular vesicles (PfEVs) that contain parasite-derived RNA. However, the significance of the secreted RNA remains unexplored. Here, we compare secreted and intracellular RNA from asexual cultures of six P. falciparum lines. We find that secretion of RNA via extracellular vesicles is not only periodic throughout the asexual intraerythrocytic developmental cycle but is also highly conserved across P. falciparum isolates. We further demonstrate that the phases of RNA secreted via extracellular vesicles are discernibly shifted compared to those of the intracellular RNA within the secreting whole parasite. Finally, transcripts of genes with no known function during the asexual intraerythrocytic developmental cycle are enriched in PfEVs compared to the whole parasite. We conclude that the secretion of extracellular vesicles could be a putative posttranscriptional RNA regulation mechanism that is part of or synergise the classic RNA decay processes to maintain intracellular RNA levels in P. falciparum.Peer reviewe

Variation in the effectiveness of insecticide treated nets against malaria and outdoor biting by vectors in Kilifi, Kenya

Background: Insecticide treated nets (ITNs) protect humans against bites from the Anopheles mosquito vectors that transmit malaria, thereby reducing malaria morbidity and mortality. It has been noted that ITN use leads to a switch from indoor to outdoor feeding among these vectors. It might be expected that outdoor feeding would undermine the effectiveness of ITNs that target indoors vectors, but data are limited. Methods: We linked homestead level geospatial data to clinical surveillance data at a primary healthcare facility in Kilifi County in order to map geographical heterogeneity in ITN effectiveness and observed vector feeding behaviour using landing catches and CDC light traps in six selected areas of varying ITN effectiveness. We quantified the interaction between mosquitoes and humans to evaluate whether outdoor vector biting is a potential explanation for the variation in ITN effectiveness. Results: We observed 37% and 46% visits associated with positive malaria slides among ITN users and non-ITN-users, respectively; ITN use was associated with 32% protection from malaria (crude OR = 0.68, 95% CI: 0.64, 0.73). We obtained modification of ITN effectiveness by geographical area (p=0.016), and identified 6 hotspots using the spatial scan statistic. Majority of mosquitoes were caught outdoor (60%) and were of the An. funestus group (75%). The overall propensity to feed at times when most people were asleep was high; the vast majority of the Anopheles mosquitoes were caught at times when most people are indoors asleep. Estimates for the proportion of human-mosquito contact between the first and last hour when most humans were asleep was consistently high across all locations, ranging from 0.83 to 1.00. Conclusion: Our data do not provide evidence of an epidemiological association between microgeographical variations in ITN effectiveness and variations in the microgeographical distribution of outdoor biting.</ns4:p

Entomological and Anthropological Factors Contributing to Persistent Malaria Transmission in Kenya, Ethiopia, and Cameroon

Introduction In order to improve our understanding of the fundamental limits of core interventions and guide efforts based on prioritization and identification of effective/novel interventions with great potentials to interrupt persistent malaria transmission in the context of high vector control coverage, the drivers of persistent disease transmission were investigated in three eco-epidemiological settings; forested areas in Cameroon, coastal area in Kenya and highland areas in Ethiopia. Methods Mosquitoes were sampled in three eco-epidemiological settings using different entomological sampling techniques and analysed for Plasmodium infection status and blood meal origin in blood-fed specimens. Human behavioural surveys were conducted to assess the knowledge and attitude of the population on malaria and preventive measures, their night activities, and sleeping pattern. The parasitological analysis was conducted to determine the prevalence of Plasmodium infection in the population using rapid diagnostic tests. Results Despite the diversity in the mosquito fauna, their biting behaviour was found to be closely associated to human behaviour in the three settings. People in Kenya and Ethiopia were found to be more exposed to mosquito bites during the early hours of the evening (18-21h) while it was in the early morning (4-6 am) in Cameroon. Malaria transmission was high in Cameroon compared to Kenya and Ethiopia with over 50% of the infected bites recorded outdoors. The non-users of LLINs were 2.5 to 3 times more likely to be exposed to the risk of acquiring malaria compared to LLINs users. Malaria prevalence was high (42%) in Cameroon, and more than half of the households visited had at least one individual infected with Plasmodium parasites. Conclusions The study suggests high outdoor malaria transmission occurring in the three sites with however different determinants driving residual malaria transmission in these areas

IPBES Invasive Alien Species Assessment: Chapter 1. Introducing biological invasions and the IPBES thematic assessment of invasive alien species and their control

Chapter 1: Introducing biological invasions and the IPBES thematic assessment of invasive alien species and their control of the Thematic Assessment Report on Invasive Alien Species and their Control of the Intergovernmental Science-Policy Platform on Biodiversity and Ecosystem Services

CD26/dipeptidyl peptidase IV (CD26/DPPIV) is highly expressed in peripheral blood of HIV-1 exposed uninfected Female sex workers

<p>Abstract</p> <p>Background</p> <p>Design of effective vaccines against the human immunodeficiency virus (HIV-1) continues to present formidable challenges. However, individuals who are exposed HIV-1 but do not get infected may reveal correlates of protection that may inform on effective vaccine design. A preliminary gene expression analysis of HIV resistant female sex workers (HIV-R) suggested a high expression CD26/DPPIV gene. Previous studies have indicated an anti-HIV effect of high CD26/DPPIV expressing cells in vitro. Similarly, high CD26/DPPIV protein levels in vivo have been shown to be a risk factor for type 2 diabetes. We carried out a study to confirm if the high CD26/DPPIV gene expression among the HIV-R were concordant with high blood protein levels and its correlation with clinical type 2 diabetes and other perturbations in the insulin signaling pathway.</p> <p>Results</p> <p>A quantitative CD26/DPPIV plasma analysis from 100 HIV-R, 100 HIV infected (HIV +) and 100 HIV negative controls (HIV Neg) showed a significantly elevated CD26/DPPIV concentration among the HIV-R group (mean 1315 ng/ml) than the HIV Neg (910 ng/ml) and HIV + (870 ng/ml, p < 0.001). Similarly a FACs analysis of cell associated DPPIV (CD26) revealed a higher CD26/DPPIV expression on CD4+ T-cells derived from HIV-R than from the HIV+ (90.30% vs 80.90 p = 0.002) and HIV Neg controls (90.30% vs 82.30 p < 0.001) respectively. A further comparison of the mean fluorescent intensity (MFI) of CD26/DPPIV expression showed a higher DPP4 MFI on HIV-R CD4+ T cells (median 118 vs 91 for HIV-Neg, p = 0.0003). An evaluation for hyperglycemia, did not confirm Type 2 diabetes but an impaired fasting glucose condition (5.775 mmol/L). A follow-up quantitative PCR analysis of the insulin signaling pathway genes showed a down expression of NFκB, a central mediator of the immune response and activator of HIV-1 transcription.</p> <p>Conclusion</p> <p>HIV resistant sex workers have a high expression of CD26/DPPIV in tandem with lowered immune activation markers. This may suggest a novel role for CD26/DPPIV in protection against HIV infection in vivo.</p

The Major Yolk Protein Vitellogenin Interferes with the Anti-Plasmodium Response in the Malaria Mosquito Anopheles gambiae

Functional gene analysis in malaria mosquitoes reveals molecules underpinning the trade-off between efficient reproduction and the antiparasitic response

Toxin-Based Therapeutic Approaches

Protein toxins confer a defense against predation/grazing or a superior pathogenic competence upon the producing organism. Such toxins have been perfected through evolution in poisonous animals/plants and pathogenic bacteria. Over the past five decades, a lot of effort has been invested in studying their mechanism of action, the way they contribute to pathogenicity and in the development of antidotes that neutralize their action. In parallel, many research groups turned to explore the pharmaceutical potential of such toxins when they are used to efficiently impair essential cellular processes and/or damage the integrity of their target cells. The following review summarizes major advances in the field of toxin based therapeutics and offers a comprehensive description of the mode of action of each applied toxin

Analyse protéomique de la réponse d'Anopheles gambiae à l'infection par Plasmodium berghei

L’anophèle, vecteur du paludisme chez l’homme, acquiert le Plasmodium au cours du repas sanguin. Sa réponse immunitaire s’oppose à l’invasion du parasite. TEP1 est un facteur antiparasitaire homologue au facteur C3 du complément. Pour étudier la réponse antiparasitaire TEP1-dépendante, nous avons entrepris une analyse protéomique sur intestins de moustiques transgéniques infectés et présentons les protéines identifiées. Nous avons montré que la Lipophorine et la Vitellogénine, protéines fournissant des nutriments aux ovocytes en développement, influencent la réponse antiparasitaire en réduisant l’efficacité antiparasitaire de TEP1. De plus, les facteurs de transcription Cactus/Rel1-Rel2, contrôlant l’expression de facteurs immunitaires, régulent également l’expression de la vitellogénine. Ces résultats mettent en évidence des liens multiples entre reproduction et immunité, établissant une base moléculaire aux interactions soupçonnées entre ces processus.Malaria is a mosquito-borne infectious disease yearly affecting an estimated 500 million humans, of which 1 to 2 million (mostly children in Sub-Saharan Africa) succumb to the disease. Malaria transmission is initiated when a female mosquito ingests gametocytes during a blood meal, required for ovary development. Thus, feeding on a malaria-infected host will simultaneously activate oogenesis and allow malaria parasites to invade mosquito tissues. However, the parasites undergo massive losses during their development in the vector, due to the powerful immune response that mosquitoes mount against the invading parasites. The basis of this antiparasitic response has been investigated previously using reverse genetic approaches and has identified several antiparasitic molecules including TEP1, a homologue of vertebrate complement factor C3, which mediates parasite killing in a complement-like manner. However, additional mosquito factors involved in this killing mechanism including effector molecules are yet to be identified. To this aim, transgenic mosquitoes with TEP1 gain-of-function (GOF) and loss-of-function (LOF) were established, and transcriptional analysis of their immune response during parasite development performed as a basis for examining the pathway. Because transcript levels do not always correlate with protein abundance, we complemented the microarray analysis with a proteomic analysis of the mosquito response towards a Plasmodium berghei infection in the midgut tissues.[…