Vaccine-induced human monoclonal antibodies to PfRH5 show broadly neutralizing activity against P. falciparum clinical isolates.

Vaccines to the Plasmodium falciparum reticulocyte binding-like protein homologue 5 (PfRH5) target the blood-stage of the parasite life cycle. PfRH5 has the potential to trigger the production of strain-transcendent antibodies and has proven its efficacy both in pre-clinical and early clinical studies. Vaccine-induced monoclonal antibodies (mAbs) to PfRH5 showed promising outcomes against cultured P. falciparum laboratory strains from distinct geographic areas. Here, we assessed the functional impact of vaccine-induced anti-PfRH5 mAbs on more genetically diverse P. falciparum clinical isolates. We used mAbs previously isolated from single B cells of UK adult PfRH5 vaccinees and used ex-vivo growth inhibition activity (GIA) assays to assess their efficacy against P. falciparum clinical isolates. Next-generation sequencing (NGS) was used to assess the breadth of genetic diversity in P. falciparum clinical isolates and to infer the genotype/phenotype relationship involved in antibody susceptibility. We showed a dose-dependent inhibition of clinical isolates with three main GIA groups: high, medium and low. Except for one isolate, our data show no significant differences in the mAb GIA profile between P. falciparum clinical isolates and the 3D7 reference strain, which harbors the vaccine allele. We also observed an additive relationship for mAb combinations, whereby the combination of GIA-low and GIA-medium antibodies resulted in increased GIA, having important implications for the contribution of specific clones within polyclonal IgG responses. While our NGS analysis showed the occurrence of novel mutations in the pfrh5 gene, these mutations were predicted to have little or no functional impact on the antigen structure or recognition by known mAbs. Our present findings complement earlier reports on the strain transcendent potential of anti-PfRH5 mAbs and constitute, to our knowledge, the first report on the susceptibility of P. falciparum clinical isolates from natural infections to vaccine-induced human mAbs to PfRH5.

Persistent carriage of subpatent Plasmodium falciparum parasites associated with clinical malaria in a low transmission area in Senegal.

OBJECTIVES: In low malaria transmission areas, the elimination of the disease has been hampered partly by the existence of a reservoir of subpatent Plasmodium falciparum infections within communities. This reservoir, often undetected, serves as a source of parasites and contributes to ongoing transmission and clinical malaria cases. METHODS: This study, spanning a period of 9 years from June 2014 to December 2022, examined individual variations and long-term subpatent P. falciparum carriage in two matched cohorts of 44 individuals each living in Dielmo village in the Sudanian area of Senegal. Biannual blood samples, collected in June/July and December of each year, underwent P. falciparum diagnosis by quantitative polymerase chain reaction. QGIS and R analytical tools were used to map infections, assess the occurrence and clustering of subpatent and clinical P. falciparum infections, and determine the risk of infection in the vicinity of asymptomatic P. falciparum carriers. RESULTS: The point frequency and long-term P. falciparum carriage were significantly higher among the quantitative polymerase chain reaction (qPCR) positive cohort compared to the negative cohort across the 16 cross-sectional surveys analyzed in this study (19.76% vs 10.99%, P-value <0.001). Asymptomatic carriage events in qPCR-positive group were 18.86 ± 1.72% and significantly greater (P-value = 0.001) than in the qPCR-negative group (11.32 ± 1.32%). The relative risk of P. falciparum infection or clinical malaria calculated with a 95% confidence interval significantly increased in the vicinity of infected individuals and was 1.44 (P-value = 0.53) and 2.64 (P-value = 0.04) when at least one individual in the direct (household) or indirect (block of households) vicinity is infected, respectively. The risk increased to 3.64 (P-value <0.001) if at least 1/5 of individuals in the indirect vicinity were P. falciparum-infected. CONCLUSIONS: The study provides a detailed qualitative and quantitative analysis of the asymptomatic P. falciparum reservoir and its temporal and spatial dynamics within two subgroups of P. falciparum-infected and non-infected individuals in Dielmo village. It identified high-risk populations known as "hotpops" and hotspots that could be targeted by innovative interventions to accelerate the elimination of malaria in Dielmo village.

Two mosquito salivary antigens demonstrate promise as biomarkers of recent exposure to P. falciparum infected mosquito bites.

Background: Measuring malaria transmission intensity using the traditional entomological inoculation rate is difficult. Antibody responses to mosquito salivary proteins such as SG6 have previously been used as biomarkers of exposure to Anopheles mosquito bites. Here, we investigate four mosquito salivary proteins as potential biomarkers of human exposure to mosquitoes infected with P. falciparum: mosGILT, SAMSP1, AgSAP, and AgTRIO. Methods: We tested population-level human immune responses in longitudinal and cross-sectional plasma samples from individuals with known P. falciparum infection from low and moderate transmission areas in Senegal using a multiplexed magnetic bead-based assay. Results: AgSAP and AgTRIO were the best indicators of recent exposure to infected mosquitoes. Antibody responses to AgSAP, in a moderate endemic area, and to AgTRIO in both low and moderate endemic areas, were significantly higher than responses in a healthy non-endemic control cohort (p-values = 0.0245, 0.0064, and <0.0001 respectively). No antibody responses significantly differed between the low and moderate transmission area, or between equivalent groups during and outside the malaria transmission seasons. For AgSAP and AgTRIO, reactivity peaked 2-4 weeks after clinical P. falciparum infection and declined 3 months after infection. Discussion: Reactivity to both AgSAP and AgTRIO peaked after infection and did not differ seasonally nor between areas of low and moderate transmission, suggesting reactivity is likely reflective of exposure to infectious mosquitos or recent biting rather than general mosquito exposure. Kinetics suggest reactivity is relatively short-lived. AgSAP and AgTRIO are promising candidates to incorporate into multiplexed assays for serosurveillance of population-level changes in P. falciparum-infected mosquito exposure.

Snapshot of Anti-SARS-CoV-2 IgG Antibodies in COVID-19 Recovered Patients in Guinea.

Background: Because the regular vaccine campaign started in Guinea one year after the COVID-19 index case, the profile of naturally acquired immunity following primary SARS-CoV-2 infection needs to be deepened. Methods: Blood samples were collected once from 200 patients (90% of African extraction) who were recovered from COVID-19 for at least ~2.4 months (72 days), and their sera were tested for IgG antibodies to SARS-CoV-2 using an in-house ELISA assay against the Receptor Binding Domain (RBD) of the SARS-CoV-2 spike1 protein (RBD/S1-IH kit). Results: Results revealed that 73% of sera (146/200) were positive for IgG to SARS-CoV-2 with an Optical Density (OD) ranging from 0.13 to 1.19 and a median value of 0.56 (IC95: 0.51-0.61). The median OD value at 3 months (1.040) suddenly decreased thereafter and remained stable around OD 0.5 until 15 months post-infection. The OD median value was slightly higher in males compared to females (0.62 vs. 0.49), but the difference was not statistically significant (p-value: 0.073). In contrast, the OD median value was significantly higher among the 60-100 age group (0.87) compared to other groups, with a noteworthy odds ratio compared to the 0-20 age group (OR: 9.69, p-value: 0.044*). Results from the RBD/S1-IH ELISA kit demonstrated superior concordance with the whole spike1 protein ELISA commercial kit compared to a nucleoprotein ELISA commercial kit. Furthermore, anti-spike1 protein ELISAs (whole spike1 and RBD/S1) revealed higher seropositivity rates. Conclusions: These findings underscore the necessity for additional insights into naturally acquired immunity against COVID-19 and emphasize the relevance of specific ELISA kits for accurate seropositivity rates.

Comparative reconstruction of SARS-CoV-2 transmission in three African countries using a mathematical model integrating immunity data.

Objectives: Africa has experienced fewer COVID-19 cases and deaths than other regions, with a contrasting epidemiological situation between countries, raising questions regarding the determinants of disease spread in Africa. Methods: We built a susceptible-exposed-infected-recovered model including COVID-19 mortality data where recovery class is structured by specific immunization and modeled by a partial differential equation considering the opposed effects of immunity decline and immunization. This model was applied to Tunisia, Senegal, and Madagascar. Results: Senegal and Tunisia experienced two epidemic phases. Initially, infections emerged in naive individuals and were limited by social distancing. Variants of concern (VOCs) were also introduced. The second phase was characterized by successive epidemic waves driven by new VOCs that escaped host immunity. Meanwhile, Madagascar demonstrated a different profile, characterized by longer intervals between epidemic waves, increasing the pool of susceptible individuals who had lost their protective immunity. The impact of vaccination on model parameters in Tunisia and Senegal was evaluated. Conclusions: Loss of immunity and vaccination-induced immunity have played crucial role in controlling the African pandemic. SARS-CoV-2 has become endemic now and will continue to circulate in African populations. However, previous infections provide significant protection against severe diseases, thus providing a basis for future vaccination strategies.

One hundred malaria attacks since birth. A longitudinal study of African children and young adults exposed to high malaria transmission.

Background: Despite significant progress in malaria control over the past twenty years, malaria remains a leading cause of child morbidity and mortality in Tropical Africa. As most patients do not consult any health facility much uncertainty persists about the true burden of the disease and the range of individual differences in susceptibility to malaria. Methods: Over a 25-years period, from 1990 to 2015, the inhabitants of Dielmo village, Senegal, an area of intense malaria transmission, have been monitored daily for their presence in the village and the occurrence of diseases. In case of fever thick blood films were systematically examined through microscopy for malaria parasites and patients received prompt diagnosis and treatment. Findings: We analysed data collected in 111 children and young adults monitored for at least 10 years (mean 17.3 years, maximum 25 years) enrolled either at birth (95 persons) or during the two first years of life. A total of 11,599 episodes of fever were documented, including 5268 malaria attacks. The maximum number of malaria attacks in a single person was 112. Three other persons suffered one hundred or more malaria attacks during follow-up. The minimum number of malaria attacks in a single person was 11. The mean numbers of malaria attacks in children reaching their 4th, 7th, and 10th birthdays were 23.0, 37.7, and 43.6 attacks since birth, respectively. Sixteen children (14.4%) suffered ten or more malaria attacks each year at ages 1-3 years, and six children (5.4%) each year at age 4-6 years. Interpretation: Long-term close monitoring shows that in highly endemic areas the malaria burden is higher than expected. Susceptibility to the disease may vary up to 10-fold, and for most children childhood is an endless history of malaria fever episodes. No other parasitic, bacterial or viral infection in human populations has such an impact on health. Funding: The Pasteur Institutes of Dakar and Paris, the Institut de Recherche pour le Développement, and the French Ministry of Cooperation provided funding.

Unveiling P. vivax invasion pathways in Duffy-negative individuals.

Vivax malaria has long been thought to be absent from sub-Saharan Africa owing to the high proportion of individuals lacking the Duffy antigen receptor for chemokines (DARC) in their erythrocytes. The interaction between P. vivax Duffy-binding protein (PvDBP) and DARC is assumed to be the main pathway used by merozoites to invade reticulocytes. However, the increasing number of reports of vivax malaria cases in genotypically Duffy-negative (DN) individuals has raised questions regarding the P. vivax invasion pathway(s). Here, we show that a subset of DN erythroblasts transiently express DARC during terminal erythroid differentiation and that P. vivax merozoites, irrespective of their origin, can invade DARC+ DN erythroblasts. These findings reveal that a large number of DN individuals may represent a silent reservoir of deep P. vivax infections at the sites of active erythropoiesis with low or no parasitemia, and it may represent an underestimated biological problem with potential clinical consequences in sub-Saharan Africa.

Development and comparative evaluation of SARS-CoV-2 S-RBD and N based ELISA tests in various African endemic settings.

Management of the COVID-19 pandemic relies on molecular diagnostic methods supported by serological tools. Herein, we developed S-RBD- and N- based ELISA assays useful for infection rate surveillance as well as the follow-up of acquired protective immunity against SARS-CoV-2. ELISA assays were optimized using COVID-19 Tunisian patients' sera and prepandemic controls. Assays were further validated in 3 African countries with variable endemic settings. The receiver operating curve was used to evaluate the assay performances. The N- and S-RBD-based ELISA assays performances, in Tunisia, were very high (AUC: 0.966 and 0.98, respectively, p < 0.0001). Cross-validation analysis showed similar performances in different settings. Cross-reactivity, with malaria infection, against viral antigens, was noticed. In head-to-head comparisons with different commercial assays, the developed assays showed high agreement. This study demonstrates, the added value of the developed serological assays in low-income countries, particularly in ethnically diverse populations with variable exposure to local endemic infectious diseases.

Linear epitope mapping of the humoral response against SARS-CoV-2 in two independent African cohorts.

Profiling of the antibody responses to severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) proteins in African populations is scarce. Here, we performed a detailed IgM and IgG epitope mapping study against 487 peptides covering SARS-CoV-2 wild-type structural proteins. A panel of 41 pre-pandemic and 82 COVID-19 RT-PCR confirmed sera from Madagascar and Senegal were used. We found that the main 36 immunodominant linear epitopes identified were (i) similar in both countries, (ii) distributed mainly in the Spike and the Nucleocapsid proteins, (iii) located outside the RBD and NTD regions where most of the reported SARS-CoV-2 variant mutations occur, and (iv) identical to those reported in European, North American, and Asian studies. Within the severe group, antibody levels were inversely correlated with the viral load. This first antibody epitope mapping study performed in patients from two African countries may be helpful to guide rational peptide-based diagnostic assays or vaccine development.

Plasmodium infection is associated with cross-reactive antibodies to carbohydrate epitopes on the SARS-CoV-2 Spike protein.

Sero-surveillance can monitor and project disease burden and risk. However, SARS-CoV-2 antibody test results can produce false positive results, limiting their efficacy as a sero-surveillance tool. False positive SARS-CoV-2 antibody results are associated with malaria exposure, and understanding this association is essential to interpret sero-surveillance results from malaria-endemic countries. Here, pre-pandemic samples from eight malaria endemic and non-endemic countries and four continents were tested by ELISA to measure SARS-CoV-2 Spike S1 subunit reactivity. Individuals with acute malaria infection generated substantial SARS-CoV-2 reactivity. Cross-reactivity was not associated with reactivity to other human coronaviruses or other SARS-CoV-2 proteins, as measured by peptide and protein arrays. ELISAs with deglycosylated and desialated Spike S1 subunits revealed that cross-reactive antibodies target sialic acid on N-linked glycans of the Spike protein. The functional activity of cross-reactive antibodies measured by neutralization assays showed that cross-reactive antibodies did not neutralize SARS-CoV-2 in vitro. Since routine use of glycosylated or sialated assays could result in false positive SARS-CoV-2 antibody results in malaria endemic regions, which could overestimate exposure and population-level immunity, we explored methods to increase specificity by reducing cross-reactivity. Overestimating population-level exposure to SARS-CoV-2 could lead to underestimates of risk of continued COVID-19 transmission in sub-Saharan Africa.

Putative Biomarkers of Environmental Enteric Disease Fail to Correlate in a Cross-Sectional Study in Two Study Sites in Sub-Saharan Africa.

Environmental enteric dysfunction (EED) is an elusive, inflammatory syndrome of the small intestine thought to be associated with enterocyte loss and gut leakiness and lead to stunted child growth. To date, the gold standard for diagnosis is small intestine biopsy followed by histology. Several putative biomarkers for EED have been proposed and are widely used in the field. Here, we assessed in a cross-sectional study of children aged 2-5 years for a large set of biomarkers including markers of protein exudation (duodenal and fecal alpha-1-antitrypsin (AAT)), inflammation (duodenal and fecal calprotectin, duodenal, fecal and blood immunoglobulins, blood cytokines, C-reactive protein (CRP)), gut permeability (endocab, lactulose-mannitol ratio), enterocyte mass (citrulline) and general nutritional status (branched-chain amino acids (BCAA), insulin-like growth factor) in a group of 804 children in two Sub-Saharan countries. We correlated these markers with each other and with anemia in stunted and non-stunted children. AAT and calprotectin, CRP and citrulline and citrulline and BCAA correlated with each other. Furthermore, BCAA, citrulline, ferritin, fecal calprotectin and CRP levels were correlated with hemoglobin levels. Our results show that while several of the biomarkers are associated with anemia, there is little correlation between the different biomarkers. Better biomarkers and a better definition of EED are thus urgently needed.

Identification of factors associated with residual malaria transmission using school-based serological surveys in settings pursuing elimination.

BACKGROUND: Targeted research on residual malaria transmission is important to improve strategies in settings pursuing elimination, where transmission reductions prove challenging. This study aimed to detect and characterize spatial heterogeneity and factors associated with Plasmodium falciparum infections and exposure, P. falciparum apical membrane antigen 1 (PfAMA1) antibody (Ab) response, in the Central Highlands of Madagascar (CHL). METHODS: From May to July 2014, a cross-sectional school-based survey was carried out in 182 fokontany (villages) within 7 health districts of the CHL. Rapid diagnostic tests (RDTs) and a bead-based immunoassay including PfAMA1 antigen biomarker were used to estimate malaria prevalence and seroprevalence, respectively. Local Moran's I index was used to detect spatial "hotspots". Remotely sensed environmental data-temperature, vegetation indices, land covers, and elevation-were used in multivariable mixed-effects logistic regression models to characterize factors associated with malaria infection and cumulative exposure. RESULTS: Among 6,293 school-children ages 2-14 years surveyed, RDT prevalence was low at 0.8% (95% CI 0.6-1.1%), while PfAMA1 Ab seroprevalence was 7.0% (95% CI 6.4-7.7%). Hotspots of PfAMA1 Ab seroprevalence were observed in two districts (Ankazobe and Mandoto). Seroprevalence increased for children living > 5 km from a health centre (adjusted odds ratio (OR) = 1.6, 95% CI 1.2-2.2), and for those experiencing a fever episode in the previous 2 weeks (OR 1.7, 95% CI 1.2-2.4), but decreased at higher elevation (for each 100-m increase, OR = 0.7, 95% CI 0.6-0.8). A clear age pattern was observed whereby children 9-10 years old had an OR of 1.8 (95% CI 1.2-2.4), children 11-12 years an OR of 3.7 (95% CI 2.8-5.0), and children 13-14 years an OR of 5.7 (95% CI 4.0-8.0) for seropositivity, compared with younger children (2-8 years). CONCLUSION: The use of serology in this study provided a better understanding of malaria hotspots and associated factors, revealing a pattern of higher transmission linked to geographical barriers in health care access. The integration of antibody-assays into existing surveillance activities could improve exposure assessment, and may help to monitor the effectiveness of malaria control efforts and adapt elimination interventions.

Seroprevalence of anti-SARS-CoV-2 antibodies in Senegal: a national population-based cross-sectional survey, between October and November 2020.

Objectives: A nationwide cross-sectional epidemiological survey was conducted to capture the true extent of coronavirus disease 2019 (COVID-19) exposure in Senegal. Methods: Multi-stage random cluster sampling of households was performed between October and November 2020, at the end of the first wave of COVID-19 transmission. Anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibodies were screened using three distinct ELISA assays. Adjusted prevalence rates for the survey design were calculated for each test separately, and thereafter combined. Crude and adjusted prevalence rates based on test performance were estimated to assess the seroprevalence. As some samples were collected in high malaria endemic areas, the relationship between SARS-CoV-2 seroreactivity and antimalarial humoral immunity was also investigated. Results: Of the 1463 participants included in this study, 58.8% were female and 41.2% were male; their mean age was 29.2 years (range 0.20-84.8.0 years). The national seroprevalence was estimated at 28.4% (95% confidence interval 26.1-30.8%). There was substantial regional variability. All age groups were impacted, and the prevalence of SARS-CoV-2 was comparable in the symptomatic and asymptomatic groups. An estimated 4 744 392 (95% confidence interval 4 360 164-5 145 327) were potentially infected with SARS-CoV-2 in Senegal, while 16 089 COVID-19 RT-PCR laboratory-confirmed cases were reported by the national surveillance. No correlation was found between SARS-CoV-2 and Plasmodium seroreactivity. Conclusions: These results provide a better estimate of SARS-CoV-2 dissemination in the Senegalese population. Preventive and control measures need to be reinforced in the country and especially in the south border regions.

Changes in Systemic Regulatory T Cells, Effector T Cells, and Monocyte Populations Associated With Early-Life Stunting.

Stunting and environmental enteric dysfunction (EED) may be responsible for altered gut and systemic immune responses. However, their impact on circulating immune cell populations remains poorly characterized during early life. A detailed flow cytometry analysis of major systemic immune cell populations in 53 stunted and 52 non-stunted (2 to 5 years old) children living in Antananarivo (Madagascar) was performed. Compared to age-matched non-stunted controls, stunted children aged 2-3 years old had a significantly lower relative proportion of classical monocytes. No significant associations were found between stunting and the percentages of effector T helper cell populations (Th1, Th2, Th17, Th1Th17, and cTfh). However, we found that HLA-DR expression (MFI) on all memory CD4+ or CD8+ T cell subsets was significantly lower in stunted children compared to non-stunted controls. Interestingly, in stunted children compared to the same age-matched non-stunted controls, we observed statistically significant age-specific differences in regulatory T cells (Treg) subsets. Indeed, in 2- to 3-year-old stunted children, a significantly higher percentage of memory Treg, whilst a significantly lower percentage of naive Treg, was found. Our results revealed that both innate and adaptive systemic cell percentages, as well as activation status, were impacted in an age-related manner during stunting. Our study provides valuable insights into the understanding of systemic immune system changes in stunted children.

Prevalence and factors associated with human Taenia solium taeniosis and cysticercosis in twelve remote villages of Ranomafana rainforest, Madagascar.

BACKGROUND: Infections with the tapeworm Taenia solium (taeniosis and cysticercosis) are Neglected Tropical Diseases (NTD) highly endemic in Madagascar. These infections are however underdiagnosed, underreported and their burden at the community level remains unknown especially in rural remote settings. This study aims at assessing the prevalence of T. solium infections and associated risk factors in twelve remote villages surrounding Ranomafana National Park (RNP), Ifanadiana District, Madagascar. METHODOLOGY: A community based cross-sectional survey was conducted in June 2016. Stool and serum samples were collected from participants. Tapeworm carriers were identified by stool examination. Taenia species and T. solium genotypes were characterised by PCR and sequencing of the mitochondrial cytochrome c oxidase subunit 1 (cox1) gene. Detection of specific anti-cysticercal antibodies (IgG) or circulating cysticercal antigens was performed by ELISA or EITB/Western blot assays. PRINCIPAL FINDINGS: Of the 459 participants with paired stool and blood samples included ten participants from seven distinct villages harbored Taenia spp. eggs in their stools samples DNA sequencing of the cox1 gene revealed a majority of T. solium Asian genotype (9/10) carriage. The overall seroprevalences of anti-cysticercal IgGs detected by ELISA and EITB were quite similar (27.5% and 29.8% respectively). A prevalence rate of 12.4% of circulating cysticercal antigens was observed reflecting cysticercosis with viable cysts. Open defecation (Odds Ratio, OR = 1.5, 95% CI: 1.0-2.3) and promiscuity with households of more than 4 people (OR = 1.9, 95% CI: 1.1-3.1) seem to be the main risk factors associated with anticysticercal antibodies detection. Being over 15 years of age would be a risk factor associated with an active cysticercosis (OR = 1.6, 95% CI: 1.0-2.7). Females (OR = 0.5, 95% CI: 0.3-0.9) and use of river as house water source (OR = 0.3, 95% CI: 0.1-1.5) were less likely to have cysticercosis with viable cysts. CONCLUSIONS/SIGNIFICANCE: This study indicates a high exposure of the investigated population to T. solium infections with a high prevalence of cysticercosis with viable cysts. These data can be useful to strengthen public health interventions in these remote settings.

Hydroxychloroquine and Azithromycin Treatment of Hospitalized Patients Infected with SARS-CoV-2 in Senegal from March to October 2020.

As of today, little data is available on COVID-19 in African countries, where the case management relied mainly on a treatment by association between hydroxychloroquine (HCQ) and azithromycin (AZM). This study aimed to understand the main clinical outcomes of COVID-19 hospitalized patients in Senegal from March to October 20202. We described the clinical characteristics of patients and analysed clinical status (alive and discharged versus hospitalized or died) at 15 days after Isolation and Treatment Centres (ITC) admission among adult patients who received HCQ plus AZM and those who did not receive this combination. A total of 926 patients were included in this analysis. Six hundred seventy-four (674) (72.8%) patients received a combination of HCQ and AZM. Results showed that the proportion of patient discharge at D15 was significantly higher for patients receiving HCQ plus AZM (OR: 1.63, IC 95% (1.09-2.43)). Factors associated with a lower proportion of patients discharged alive were: age ≥ 60 years (OR: 0.55, IC 95% (0.36-0.83)), having of at least one pre-existing disorder (OR: 0.61, IC 95% (0.42-0.90)), and a high clinical risk at admission following NEWS score (OR: 0.49, IC 95% (0.28-0.83)). Few side effects were reported including 2 cases of cardiac rhythmic disorders in the HCQ and AZM group versus 13 in without HCQ + AZM. An improvement of clinical status at 15 days was found for patients exposed to HCQ plus AZM combination.

Plasmodium infection induces cross-reactive antibodies to carbohydrate epitopes on the SARS-CoV-2 Spike protein.

Individuals with acute malaria infection generated high levels of antibodies that cross-react with the SARS-CoV-2 Spike protein. Cross-reactive antibodies specifically recognized the sialic acid moiety on N-linked glycans of the Spike protein and do not neutralize in vitro SARS-CoV-2. Sero-surveillance is critical for monitoring and projecting disease burden and risk during the pandemic; however, routine use of Spike protein-based assays may overestimate SARS-CoV-2 exposure and population-level immunity in malaria-endemic countries.

High prevalence of intestinal parasite infestations among stunted and control children aged 2 to 5 years old in two neighborhoods of Antananarivo, Madagascar.

BACKGROUND: This study aimed to compare the prevalence of intestinal parasite infestations (IPIs) in stunted children, compared to control children, in Ankasina and Andranomanalina Isotry (two disadvantaged neighborhoods of Antananarivo, Madagascar), to characterize associated risk factors and to compare IPI detection by real-time PCR and standard microscopy techniques. METHODOLOGY/PRINCIPAL FINDINGS: Fecal samples were collected from a total of 410 children (171 stunted and 239 control) aged 2-5 years. A single stool sample per subject was examined by simple merthiolate-iodine-formaldehyde (MIF), Kato-Katz smear and real-time PCR techniques. A total of 96.3% of the children were infested with at least one intestinal parasite. The most prevalent parasites were Giardia intestinalis (79.5%), Ascaris lumbricoides (68.3%) and Trichuris trichiura (68.0%). For all parasites studied, real-time PCR showed higher detection rates compared to microscopy (G. intestinalis [77.6% (n = 318) versus 20.9% (n = 86)], Entamoeba histolytica [15.8% (n = 65) versus 1.9% (n = 8)] and A. lumbricoides [64.1% (n = 263) versus 50.7% (n = 208)]). Among the different variables assessed in the study, age of 4 to 5 years (AOR = 4.61; 95% CI, (1.35-15.77)) and primary and secondary educational level of the mother (AOR = 12.59; 95% CI, (2.76-57.47); AOR = 9.17; 95% CI, (2.12-39.71), respectively) were significantly associated with IPIs. Children drinking untreated water was associated with infestation with G. intestinalis (AOR = 1.85; 95% CI, (1.1-3.09)) and E. histolytica (AOR = 1.9; 95% CI, (1.07-3.38)). E. histolytica was also associated with moderately stunted children (AOR = 0.37; 95% CI, 0.2-0.71). Similarly, children aged between 4 and 5 years (AOR = 3.2; 95% CI (2.04-5.01)) and living on noncemented soil types (AOR = 1.85; 95% CI, (1.18-2.09)) were associated with T. trichiura infestation. CONCLUSIONS/SIGNIFICANCE: The prevalence of IPIs is substantial in the studied areas in both stunted and control children, despite the large-scale drug administration of antiparasitic drugs in the country. This high prevalence of IPIs warrants further investigation. Improved health education, environmental sanitation and quality of water sources should be provided.

Fine-scale Spatiotemporal Mapping of Asymptomatic and Clinical Plasmodium falciparum Infections: Epidemiological Evidence for Targeted Malaria Elimination Interventions.

BACKGROUND: A detailed understanding of the contribution of the asymptomatic Plasmodium reservoir to the occurrence of clinical malaria at individual and community levels is needed to guide effective elimination interventions. This study investigated the relationship between asymptomatic Plasmodium falciparum carriage and subsequent clinical malaria episodes in the Dielmo and Ndiop villages in Senegal. METHODS: The study used a total of 2792 venous and capillary blood samples obtained from asymptomatic individuals and clinical malaria datasets collected from 2013 to 2016. Mapping, spatial clustering of infections, and risk analysis were performed using georeferenced households. RESULTS: High incidences of clinical malaria episodes were observed to occur predominantly in households of asymptomatic P falciparum carriers. A statistically significant association was found between asymptomatic carriage in a household and subsequent episode of clinical malaria occurring in that household for each individual year (P values were 0.0017, 6 × 10-5, 0.005, and 0.008 for the years 2013, 2014, 2015, and 2016 respectively) and the combined years (P = 8.5 × 10-8), which was not found at the individual level. In both villages, no significant patterns of spatial clustering of P falciparum clinical cases were found, but there was a higher risk of clinical episodes <25 m from asymptomatic individuals in Ndiop attributable to clustering within households. CONCLUSION: The findings provide strong epidemiological evidence linking the asymptomatic P falciparum reservoir to clinical malaria episodes at household scale in Dielmo and Ndiop villagers. This argues for a likely success of a mass testing and treatment intervention to move towards the elimination of malaria in the villages of Dielmo and Ndiop.