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Biological sciences, drug discovery and medicine rely heavily on cell phenotype perturbation and microscope observation. However, most cellular phenotypic changes are subtle and thus hidden from us by natural cell variability: two cells in the same condition already look different. In this study, we show that conditional generative models can be used to transform an image of cells from any one condition to another, thus canceling cell variability. We visually and quantitatively validate that the principle of synthetic cell perturbation works on discernible cases. We then illustrate its effectiveness in displaying otherwise invisible cell phenotypes triggered by blood cells under parasite infection, or by the presence of a disease-causing pathological mutation in differentiated neurons derived from iPSCs, or by low concentration drug treatments. The proposed approach, easy to use and robust, opens the door to more accessible discovery of biological and disease biomarkers. Biological research relies on observing cell phenotypes, often obscured by natural variability. Here, the authors use generative modelling to unveil hidden changes triggered by infections, mutations, or drugs, allowing for accessible discovery of biomarkers.

Background The World Health Organization (WHO) recommends that pregnant women in sub-Saharan Africa (SSA) receive a free long-lasting insecticidal net (LLIN) during their first antenatal care (ANC) visit to prevent malaria. This study, conducted in Benin, evaluates the distribution and utilization rates of LLINs provided at the first ANC visit among pregnant women. Methods Data were collected from 14 public and private health centers located in urban and rural areas across Southern, Central, and Northern Benin. Pregnant women were enrolled in the study during their initial ANC visit and were subsequently visited at home twice, where a questionnaire was administered. The study assessed the distribution and use of LLINs during the first ANC visit. After the second home visit, the LLIN found on the pregnant women’s sleeping unit was collected to evaluate its physical integrity and bio-efficacy. Chi-square tests were used to compare each indicator across three variables: region, urban/rural setting, and public/private status of health centers. Results A total of 718 pregnant women were included in the study. LLIN ownership and usage before the first ANC visit were 94% [89-97%] and 93% [85-97%], respectively. During the first ANC visit, 63% [40-80%] of the pregnant women received an LLIN, but only 11% [7-22%] installed it on their sleeping area. During the pregnancy period, 72% [64-78%] of the LLINs in use were found to be either physically damaged or not bio-effective. Conclusion The distribution of LLINs to pregnant women during their first ANC visit was inadequate, with only a small fraction of recipients actively using the net. This shortfall leads to suboptimal protection for this vulnerable population during pregnancy.

Recently, efforts to eliminate malaria have shifted focus from symptomatic cases alone to include asymptomatic carriers, who are now recognized as significant contributors to the disease's transmission and control. This study examines the relationship between asymptomatic malaria infection and hemoglobin levels in Benin. A cohort in Benin was enrolled and categorized into three age groups (under 5 years, 5-15 years, and over 15 years) for follow-up from August to November 2021. Participants were monitored over two months and assessed for malaria infection through microscopy and polymerase chain reaction (PCR) during their three visits. A questionnaire was employed to gather general and clinical characteristics. Multivariate models were utilized to analyze the associations between asymptomatic infection, anemia, and hemoglobin levels. Among 393 participants, 58.2% were diagnosed at enrolment with malaria via PCR, and 30.5% through microscopy. Anemia, defined as hemoglobin levels < 11 g/dL, was observed in 40.5% of the cohort. The risk of anemia declined with increasing age (OR for ages 5-15: 0.64, 95% CI [0.37; 1.09]; OR for over 15 years: 0.34, 95% CI [0.20; 0.59]) compared to children under 5. Individuals with both microscopic and submicroscopic infections exhibited higher odds of anemia (respectively OR = 4.15, 95% CI [2.41; 7.13] and OR = 2.09 [1.22; 3.57]) relative to those uninfected. Hemoglobin levels were consistently lower in participants with microscopic malaria across all age groups (β = -2.73, 95% CI [-3.41; -2.05] for those under 5, β = -1.35, 95% CI [-1.89; -0.82] for ages 5-15, and β = -0.72, 95% CI [-1.34; -0.07]) compared to non-infected individuals. Our findings suggest that asymptomatic malaria infections, including submicroscopic cases, are associated with anemia and decreased hemoglobin levels. This underscores the importance of employing ultrasensitive diagnostic methods for such infections and acknowledging their potential health implications.

The efficacy of mother-to-child placental transfer of antibodies specific to malaria blood stage antigens was investigated in the context of placental malaria infection, taking into account IgG specificity and maternal hypergammaglobulinemia. The impact of the resulting maternal antibody transfer on infections in infants up to the age of 6 months was also explored. This study showed that i) placental malaria was associated with a reduced placental transfer of total and specific IgG, ii) antibody placental transfer varied according to IgG specificity and iii) cord blood malaria IgG levels were similar in infants born to mothers with or without placental malaria. The number of malaria infections was negatively associated with maternal age, whereas it was not associated with the transfer of any malaria-specific IgG from the mother to the fetus. These results suggest that i) malaria-specific IgG may serve as a marker of maternal exposure but not as a useful marker of infant protection from malaria and ii) increasing maternal age contributes to diminishing febrile infections diagnosed in infants, perhaps by means of the transmission of an effective antibody response.

Asymptomatic malaria infection is now recognized as a potential threat to malaria control. However, its prevalence and its dynamics are poorly documented especially in a perennial context of high seasonal transmission. A longitudinal study was conducted in southern Benin to investigate the dynamics of asymptomatic malaria infection and to identify factors influencing it. A cohort of 377 participants was recruited, stratified into three age groups (under 5 years, between 5 and 15 years, over 15 years). After inclusion, two visits were made one-month apart between August and November 2021. Malaria infection was diagnosed by microscopy and PCR and questionnaires were administered to the participants. The dynamics of malaria infection, both submicroscopic (positive PCR / negative blood smear) and microscopic (positive blood smear), and related factors were determined using a mixed ordinal polytomous regression model and a multistate Markov model. The human infectious reservoir consisted primarily of asymptomatic submicroscopic infections (289/512 (56.4%)), followed by asymptomatic microscopic infections (182/512 (35.5%)) and symptomatic infections (41/512 (8%)). The prevalence of asymptomatic infection was highly related to age-group (5-15 years: OR: 4 .12 [2.55-6.67] and > 15 years OR: 2.80 [1.73-4.54] compared to the under 5 years old group). The children under 15 years with asymptomatic infection had the highest risk of becoming symptomatic. The mean duration of asymptomatic infections in 5-15-year-olds was the longest (76.7 days (53.8-109.1)). This study revealed a persistent asymptomatic malaria reservoir over the follow-up period, with substantial variations between age-groups. These findings are important elements to consider for an optimal deployment of malaria control interventions.

Background Pregnant women are a vulnerable population to COVID-19 given an increased susceptibility to severe SARS-CoV-2 infection and pregnancy complications. However, few SARS-CoV-2 serological surveys have been performed among this population to assess the extent of the infection in sub-Saharan countries. The objectives of this study were to determine SARS-CoV-2 seroprevalence among Beninese pregnant women, to identify spatial seropositivity clusters and to analyse factors associated with the infection. Methods A cross-sectional study including women in their third trimester of pregnancy attending the antenatal care (ANC) clinics at Allada (south Benin) and Natitingou (north Benin) was conducted. Rapid diagnostic tests (RDT) for detection of IgG/IgM against the SARS-CoV-2 spike protein were performed using capillary blood. Seroprevalence of SARS-CoV-2 antibodies and associations between SARS-CoV-2 serostatus and maternal characteristics were analyzed by multivariate logistic regression. Spatial analyses were performed using the spatial scan statistics to identify spatial clusters of SARS-CoV-2 infection. Results A total of 861 pregnant women were enrolled between May 4 and June 29, 2022. 58/861 (6.7%) participants reported having received COVID-19 vaccine. None of the participants had been diagnosed with COVID-19 during their pregnancy. SARS-CoV-2 antibodies were detected in 607/802 (75.7%; 95% CI 72.56%–78.62%) of unvaccinated participants. Several urban and rural spatial clusters of SARS-CoV-2 cases were identified in Allada and one urban spatial cluster was identified in Natitingou. Unvaccinated participants from Allada with at least one previous morbidity were at a three-times higher risk of presenting SARS-CoV-2 antibodies (OR = 2.89; 95%CI 1.19%-7.00%). Conclusion Three out of four pregnant women had SARS-CoV-2 antibodies, suggesting a high virus circulation among pregnant women in Benin, while COVID-19 vaccination coverage was low. Pregnant women with comorbidities may be at increased risk of SARS-CoV-2 infection. This population should be prioritized for COVID-19 diagnosis and vaccination in order to prevent its deleterious effects. Trial registration NCT06170320 (retrospectively registered on December 21, 2023).

Background Despite several years of school-based MDA implementation, STH infections remain an important public health problem in Benin, with a country-wide prevalence of 20% in 2015. The DeWorm3 study is designed to assess the feasibility of using community-based MDA with albendazole to interrupt the transmission of STH, through a series of cluster-randomized trials in Benin, India and Malawi. We used the pre-treatment baseline survey data to describe and analyze the factors associated with STH infection in Comé, the study site of the DeWorm3 project in Benin. These data will improve understanding of the challenges that need to be addressed in order to eliminate STH as a public health problem in Benin. Methods Between March and April 2018, the prevalence of STH (hookworm spp., Ascaris and Trichuris trichiura) was assessed by Kato-Katz in stool samples collected from 6,153 residents in the community of Comé, Benin using a stratified random sampling procedure. A standardized survey questionnaire was used to collect information from individual households concerning factors potentially associated with the presence and intensity of STH infections in pre-school (PSAC, aged 1-4), school-aged children (SAC, aged 5-14) and adults (aged 15 and above). Multilevel mixed-effects models were used to assess associations between these factors and STH infection. Results The overall prevalence of STH infection was 5.3%; 3.2% hookworm spp., 2.1% Ascaris lumbricoides and 0.1% Trichuris. Hookworm spp. were more prevalent in adults than in SAC (4.4% versus 2.0%, respectively; p = 0.0001) and PSAC (4.4% versus 1.0%, respectively; p<0.0001), whilst Ascaris lumbricoides was more prevalent in SAC than in adults (3.0% versus 1.7%, respectively; p = 0.004). Being PSAC (adjusted Odds Ratio (aOR) = 0.2, p< 0.001; adjusted Infection Intensity Ratio (aIIR) = 0.1, p<0.001) or SAC (aOR = 0.5, p = 0.008; aIIR = 0.3, p = 0.01), being a female (aOR = 0.6, p = 0.004; aIIR = 0.3, p = 0.001), and having received deworming treatment the previous year (aOR = 0.4, p< 0.002; aIIR = 0.2, p<0.001) were associated with a lower prevalence and intensity of hookworm infection. Lower income (lowest quintile: aOR = 5.0, p<0.001, 2.sup.nd quintile aOR = 3.6, p = 0.001 and 3.sup.rd quintile aOR = 2.5, p = 0.02), being a farmer (aOR = 1.8, p = 0.02), medium population density (aOR = 2.6, p = 0.01), and open defecation (aOR = 0.5, p = 0.04) were associated with a higher prevalence of hookworm infection. Lower education-no education, primary or secondary school- (aIIR = 40.1, p = 0.01; aIIR = 30.9, p = 0.02; aIIR = 19.3, p = 0.04, respectively), farming (aIIR = 3.9, p = 0.002), natural flooring (aIIR = 0.2, p = 0.06), peri-urban settings (aIIR = 6.2, 95%CI 1.82-20.90, p = 0.003), and unimproved water source more than 30 minutes from the household (aIIR = 13.5, p = 0.02) were associated with a higher intensity of hookworm infection. Improved and unshared toilet was associated with lower intensity of hookworm infections (aIIR = 0.2, p = 0.01). SAC had a higher odds of Ascaris lumbricoides infection than adults (aOR = 2.0, p = 0.01) and females had a lower odds of infection (aOR = 0.5, p = 0.02). Conclusion Hookworm spp. are the most prevalent STH in Comé, with a persistent reservoir in adults that is not addressed by current control measures based on school MDA. Expanding MDA to target adults and PSAC is necessary to substantially impact population prevalence, particularly for hookworm. Trial registration ClinicalTrials.gov NCT03014167.

Regulatory T cells (Treg) play a prominent role in utero tolerating non-inherited maternal antigens and in regulating immune responses against pathogens at birth. This study investigates Treg immunity in newborns in West Africa, where sepsis remains a major public health problem. Treg phenotypes on neonates subgroups with early-onset sepsis (EOS), presumed sepsis, and healthy newborn with and without prenatal risk factors were evaluated. Treg phenotypes varied according to prenatal conditions, with increase in Treg frequency and Foxp3 expression in healthy newborns with prenatal risk factors compared to those with none risk. Compared to healthy newborns with prenatal risk factors, EOS neonates had a significantly reduced frequency of Treg and Foxp3 expression. In the Treg pool, higher frequency of activated Treg was observed in EOS neonates, suggesting an in-utero activation upstream of the sepsis onset. Their migration to the infection site may explain the reduced frequency of circulating Integrin α4β1 + Treg suggestive of homing to the endothelial tissue. EOS neonates show increases expression of CTLA-4, PD-1 and CD39 on Treg, which negatively regulate the activation of effector T cells (Teff) corroborating by the lower frequency of Teff in EOS neonates. The higher frequency of CD39 + Treg and the lower frequency of integrinα4β1 + Treg in EOS non-survivor suggests that Treg exhaustement and endothelial homing are associated with outcome severity. Neonates developing EOS are born with an altered Treg phenotypic profile. Treg expression of CTLA-4, PD-1, CD39, and integrinα4β1 cell markers can be considered as early warning or diagnostic markers of EOS.

Objective In the framework of EVALMOUS study aiming to assess the use and effectiveness of mosquito nets by pregnant women and other members of their household in a lagoon area in southern Benin, the behaviour of pregnant women relative to the time they go to bed using the net were recorded. Malaria vectors biting rhythm, Plasmodium falciparum infection and insecticide resistance genes in malaria vectors were also determined. Results Overall, 3848 females of Anopheles gambiae s. l were collected and 280 pregnant women responded to the survey. Almost all Anopheles gambiae s. l. tested were Anopheles coluzzi Coetzee and Wilkerson 2013 (Diptera: Culicidae). The CSP index in malaria vector was 1.85% and the allelic frequency of kdr gene was 74.4%. Around 90% of bites and Plasmodium falciparum Welch, 1897 (Haemosporida: Plasmodiidae) transmission occurred between 10 p.m. and 6 a.m., which coincides with the period when more than 80% of pregnant women were under bednet. Despite a slight early evening and early morning biting activity of malaria vectors in the study area, the good use of nets might remain a useful protection tool against mosquito biting and malaria transmission.

Background The objective of this study was to estimate malaria transmission and insecticide resistance status in malaria vectors in Adjrako village from Zè District in Southern Benin. The present study was carried out prior to investigations on infectivity of blood from asymptomatic carriers of Plasmodium falciparum to malaria vector mosquitoes . Methods Human landing collections (HLCs) were performed in Adjrako village during the rainy season (September—November 2021). In this village, host-seeking mosquitoes were collected during three nights per survey from 22:00 to 06:00 in six randomly selected houses. Malaria vectors were dissected in orders to determinate their parity. Plasmodium falciparum infection in malaria vectors was determined by qPCR and the entomological inoculation rate (EIR) was calculated. The World Health Organization (WHO) insecticide susceptibility test-kits were used to evaluate the susceptibility of Anopheles gambiae sensu lato ( s.l. ) to deltamethrin at 0.05% and bendiocarb at 0.1%. Results A total of 3260 females of mosquitoes belonging to 4 genera ( Anopheles , Culex , Aedes and Mansonia ) were collected. Most of the mosquitoes collected were An. gambiae sensu lato ( s.l. ). The entomological inoculation rate (EIR) for the three collection months was 8.7 infective bites per person and the parity rate was 84%. Mortality rates of An. gambiae s.l. exposed to 0.05% deltamethrin and 0.1% bendiocarb were 18% and 96%, respectively, indicating that this vector population was resistant to deltamethrin and possibly resistant to bendiocarb in the study area. Conclusion This study showed that malaria transmission is effective in the study area and that An. gambiae s.l. is the main malaria vector. The entomological parameters indicate this study area is potentially favourable for investigations on P. falciparum asymptomatic carriers.