Loiasis is a vector-borne filarial infection endemic to parts of sub-Saharan Africa. It disproportionally affects economically disadvantaged communities in rural, forested regions. To better understand the economic burden of loiasis, we conducted a comprehensive cost-of-illness study in an endemic region of Gabon, with the aim of quantifying the financial costs incurred by individuals infected with the disease from a societal perspective. We conducted a cross-sectional survey in 2023 in rural Gabon. Study participants took part in diagnostic testing for loiasis and were interviewed based on a standardized questionnaire covering a wide range of medical and non-medical costs. Participants reporting eye worm migration or harboring loiasis microfilariae were defined as loiasis positive. Various cost estimates were derived by creating a synthetic control group by means of entropy-balancing and then applying generalized linear models (GLM) for the study region. We show that the average annual costs directly attributable to loiasis amount to 39.94 USD per individual per year. Average cost estimates are primarily driven by indirect costs and direct non-medical costs. We further show that in the rarer cases that individuals seek treatment at formal or informal healthcare providers for loiasis-specific symptoms, costs from the patient's perspective can be excessively high and amount to about 43 percent of the average monthly per capita income in the study region.

BACKGROUND:The emergence of Plasmodium falciparum strains with reduced susceptibility to the artemisinin component of artemisinin combination therapies poses a serious threat to the treatment and control of malaria in sub-Saharan Africa. Regimens consisting of combinations of three or more conventional antimalarials have been proposed as a new treatment paradigm to overcome the impending problem of drug-resistant malaria. It was the aim of the MultiMal study to assess the safety, tolerability, and efficacy of the two novel multidrug antimalarial combination therapies, artesunate-pyronaridine-atovaquone-proguanil (APAP) and artesunate-fosmidomycin-clindamycin (AFC), in comparison with standard artesunate-pyronaridine (AP). METHODS:This open-label, randomised, controlled, clinical, phase 2 trial was done in Lambaréné, Gabon, and Kumasi, Ghana. Patients with uncomplicated malaria who had fever or a history of fever in the preceding 24 h and a parasitaemia in the range of 1000-100 000 per μL of blood were enrolled. Random permuted blocks of variable block sizes stratified by country were computed to generate a treatment allocation sequence. Recruitment was done across three age groups: children aged 6 months to 10 years, adolescents aged 11-17 years, and adults aged 18-65 years. Weight-adjusted oral, once-daily therapy was administered for 3 consecutive days for AP and APAP regimens dosed according to the recommendations of the manufacturer and twice daily for AFC (dose: artesunate 2 mg/kg, fosmidomycin 30 mg/kg, and clindamycin 10 mg/kg). Participants were followed up over a 42-day period. The primary endpoints of the trial, related to pharmacokinetic analyses, are being reported elsewhere; this Article reports the secondary endpoints-safety, tolerability, and efficacy of the treatment regimens (defined as adequate clinical and parasitological response [ACPR]) at days 28 and 42 after treatment initiation. ACPRs were calculated in the intention-to-treat and PCR-corrected per-protocol populations at these timepoints, whereas safety and tolerability outcomes were assessed continuously over the 42-day follow-up period in the safety population. This trial is registered with pactr.samrc.ac.za, PACTR202008909968293 and is complete. FINDINGS:Recruitment and follow-up took place between Jan 5 and Nov 5, 2021. Of 309 screened individuals, 100 patients with uncomplicated malaria were recruited into this clinical trial: 20 semi-immune patients aged 18-65 years, 40 adolescents aged between 11 and 17 years, and finally 40 patients aged 6 months to 10 years. PCR-corrected ACPR in the per-protocol set was 100% (95% CI 80-100) for AP, 100% (90-100) for APAP, and 97% (86-100) for AFC for day 28, and 87·5% (62-98) for AP, 85·3% (69-95) for APAP, and 94·4% (81-99) for AFC on day 42. Uncorrected ACPR in the intention-to-treat set was 85% (95% CI 62-97%) for AP, 87·5% (73-96) for APAP, and 82·5% (67-93) for AFC on day 28, and 70% (46-88) for AP, 75% (59-87) for APAP, and 75% (59-87) for AFC on day 42. There was no evidence for a differential efficacy across AP, APAP, and AFC. The proportion of patients with treatment-emergent adverse events (TEAEs) did not differ across study groups (p=0·37) and all treatment regimens were safe. Three (7%) of 46 TEAEs in the APAP group were severe compared with two (10%) of 20 in the AP control group and zero of 56 in the AFC group; all severe TEAEs were haematological alterations. The other TEAEs were mild or moderate. Moreover, there were two serious adverse events (SAEs) in the APAP group (peptic ulcer disease and chest contusion) and none in the other groups; these SAEs were rated as not related to the study medication. INTERPRETATION:Antimalarial regimens of APAP and AFC have unique characteristics to tackle the development and spread of drug-resistant P falciparum malaria. Given that APAP and AFC were safe, well tolerated, and highly efficacious in this clinical phase 2 study, they constitute promising multidrug combination regimens for further clinical development. FUNDING:German Center for Infection Research.

Mansonella streptocerca is a species of neglected skin-dwelling filarial nematode parasite with scarce epidemiologic data from Central Africa. We conducted a cross-sectional survey of 1,007 adults from 51 rural and semiurban communities in Gabon to update prevalence estimates and identify risk factors. Molecular analyses by quantitative PCR detected filarial DNA in 18.3% of skin snips; M. streptocerca predominated (14.2%), and Onchocerca volvulus (3.4%) occurred focally in a single rural area. Blood-dwelling parasite species such as Loa loa, M. perstans, and Mansonella sp. "DEUX" were rarely detected. M. streptocerca infection was 4 times more frequent in rural areas than in semiurban areas and independently associated with male sex, urticaria, and poor housing conditions. Wolbachia DNA occurred in 28% of M. streptocerca-positive samples, suggesting endosymbiosis. Our findings reveal a substantial but overlooked burden of M. streptocerca nematodes in Gabon and emphasize the need for integrated surveillance of skin-dwelling filarial infections in Central Africa.

The recombinant vesicular stomatitis virus-vectored Zaire ebolavirus (rVSVΔG-ZEBOV-GP) vaccine has been recently approved for children. Here, the transcriptomic response to this vaccine was characterised for the first time in children using a targeted gene panel. In a randomised controlled trial in Lambaréné, Gabon, children (n = 114, age 1–12 years old) were immunised with the rVSVΔG-ZEBOV-GP or varicella-zoster vaccine as control. Gene perturbation peaked at D1, and returned to baseline levels between D2 and D14. Genes related to type I/II interferon-signalling, pattern recognition receptors, myeloid cells and cell activation modules were upregulated, while downregulated genes were related to T cell and cytotoxicity modules. Perturbation of type-I IFN genes positively correlated with children’s age. Correlates of D28 ZEBOV-GP antibody titres were identified at D7 post-vaccination. Concluding, these findings provide insights into the vaccine-induced immune regulation at play in children.

The emergence of chloroquine-resistant Plasmodium falciparum in the 1950s posed a global threat to malaria control. Ceasing chloroquine use restored chloroquine-sensitive strains in many African countries. To assess whether chloroquine sensitivity re-emerged in Lambaréné, Gabon, we compiled published and new data on P. falciparum ex vivo chloroquine susceptibility, quantified as half-maximal inhibitory concentration (IC50), from four time points between 2004 and 2024. We then assessed the prevalence of pfcrt and pfmdr1 polymorphisms associated with chloroquine resistance via real-time PCR and Sanger sequencing, respectively, at six different time points between 2009 and 2024. Ex vivo chloroquine susceptibility data revealed a stepwise decrease in the median chloroquine IC50 from 2004 (113.8 nM; IQR: 79.6-163.5 nM, n = 42), 2009 (46.7 nM; IQR: 27.4-76.9 nM, n = 26), and 2017-2018 (15.6 nM; IQR: 6.1-40.9 nM, n = 46) to 2024 (2.1 nM; IQR: 0.8-6.1 nM, n = 39). The chloroquine-sensitive pfcrt haplotype CVMNK increased from 3.6% (1/28) in 2009 to 98.2% (56/57) in 2024, as well as the wild-type pfmdr1 N86 (23.1% (6/16), 2009; 100% (19/19), 2024). Paired molecular and ex vivo analyses revealed an association between IC50 values and CVMNK pfcrt and pfmdr1 N86. Our data provide evidence for the reestablishment of chloroquine-sensitive P. falciparum in Lambaréné, Gabon.

BACKGROUND:The RTS,S/AS01E malaria vaccine provides partial protection against Plasmodium falciparum, largely mediated by antibodies targeting the circumsporozoite protein. Correlates of protection remain incompletely defined and have focused mainly on peak IgG responses to the immunodominant NANP-repeats, with less known about antibody durability or responses to the C-terminus of circumsporozoite protein. METHODS:In this observational study, we evaluated IgG responses to NANP-repeat, C-terminus, and full-length circumsporozoite protein constructs at five timepoints before and after primary and booster vaccination, in children aged 5-17 months from six African countries enrolled in the RTS,S/AS01E phase 3 trial (NCT00866619, 2009-11). Antibody kinetics were analysed with linear regressions, and associations with clinical malaria risk over 1 year with Cox models. FINDINGS:Between May 25, 2009, to March 5, 2010, 1292 children were recruited and included for analysis in this study. IgG levels declined more slowly for C-terminus than for NANP-repeat over 17 months after primary vaccination (geometric mean fold change 0·099 [95% CI 0·089-0·110] vs 0·055 [0·048-0·062]; p<0·0001). The booster significantly enhanced C-terminal IgG, exceeding post-primary peak levels (geometric mean fold change 1·98 [95% CI 1·77-2·21]), whereas NANP-repeat responses were restored but remained below post-primary levels (geometric mean fold changes 0·57 [95% CI 0·51-0·63]). Higher circumsporozoite protein IgG levels correlated with reduced malaria risk, particularly during maintenance phases, with stronger associations for C-terminus, which remained independently protective after adjustment for NANP-repeat antibodies (hazard ratio 0·60, 95% CI 0·43-0·83; p=0·0021). After boosting, maintenance but not peak IgG levels correlated with reduced malaria risk. INTERPRETATION:IgG to circumsporozoite protein C-terminus are more durable than those to the NANP-repeats. Antibody maintenance emerges as a stronger predictor of RTS,S/AS01E vaccine efficacy than peak responses. FUNDING:USA National Institute of Allergy and Infectious Diseases, National Institutes of Health; PATH and Malaria Vaccine Initiative; Spanish Ministerio de Economía y Competitividad; Instituto de Salud Carlos III; CERCA programme; and Secretaria d'Universitats i Recerca del Departament d'Empresa i Coneixement, Generalitat de Catalunya.

BACKGROUND:Highly effective malaria vaccines are crucial to further reduce the burden of malaria. The radiation-attenuated Plasmodium falciparum sporozoite (PfSPZ) Vaccine protects adults; however, there are insufficient efficacy data in child populations. We aimed to assess the safety and efficacy of the PfSPZ Vaccine in children aged 1-12 years in Gabon. METHODS:This randomised, double-blind, placebo-controlled, phase 2 trial was conducted at the Centre de Recherches Médicales de Lambaréné, Lambaréné, Gabon. Healthy children were stratified by age (1-2, 3-6, and 7-12 years) and allocated 2:1 by block randomisation to receive 9·0 × 105 PfSPZ Vaccine or placebo (normal saline), administered by direct venous inoculation on days 1, 8, and 29. Artemether-lumefantrine was given before the third vaccination to clear latent parasitaemia. The co-primary endpoints were safety, evaluated in the intention-to-treat population by severe adverse events within 7 days (solicited) and 28 days (unsolicited) of vaccination and by serious adverse events; and vaccine efficacy, measured as time to first P falciparum-positive thick blood smear (TBS), 2-26 weeks after immunisation in those who received three vaccinations (ie, the modified intention-to-treat population). The trial was registered at ClinicalTrials.gov, NCT03521973, and is complete. FINDINGS:Between June 21, 2018, and April 30, 2019, 345 children were assessed for eligibility, of whom 200 were enrolled to the study: 134 were allocated to receive PfSPZ Vaccine and 66 to receive placebo. 192 participants received three vaccinations and comprised the modified intention-to-treat population. Systemic adverse events were reported by 33 (25%) of 134 participants in the vaccine group (47 events) and 15 (23%) of 66 participants in the placebo group (25 events); subjective fever was the most reported event in both groups. Three grade 3 systemic adverse events were reported (two cases of elevated body temperature and one case of subjective fever), all in the placebo group. 32 serious adverse events were reported across 22 study participants, 13 (10%) of 134 in the vaccine group and nine (14%) of 66 in the placebo group, all of which were considered unrelated to the intervention. There were no treatment-related deaths. 25 (19%) of 129 vaccine recipients and 14 (23%) of 63 placebo recipients became TBS-positive for P falciparum at 2-26 weeks after vaccination. The age-stratum-adjusted vaccine efficacy (1 - hazard ratio) was 9% (95% CI -75 to 53; p=0·78). INTERPRETATION:PfSPZ Vaccine is well tolerated and safe, but it did not prevent P falciparum infection in children in Gabon. Whether presumptive treatment during immunisation or more potent PfSPZ vaccines can establish vaccine efficacy is currently under investigation. FUNDING:German Center for Infection Research, European and Developing Countries Clinical Trials Partnership, National Institute of Allergy and Infectious Diseases, National Institutes of Health, and Sanaria.

BACKGROUND:The gap between early diagnostic assumptions and final diagnoses in disease outbreaks represents a persistent challenge in global health despite advancements in diagnostic and response capabilities. OBJECTIVES:To analyse the unfolding 2025 outbreak in the Democratic Republic of Congo (DRC) through the lens of historical cases where initial misattributions contributed to delayed recognition of novel or unexpected threats with varying public health consequences; identifying patterns from past outbreaks that can inform current diagnostic approaches and response strategies. SOURCES:We selected illustrative examples from peer-reviewed publications, focusing on cases with initial diagnostic uncertainties that highlight specific diagnostic patterns relevant to the current DRC outbreak. For the ongoing DRC outbreak, we analysed official World Health Organization Africa bulletins and communications from the DRC Ministry of Health through February and early March 2025. CONTENT:As of beginning of April 2025, health authorities continue investigating clusters of unexplained acute febrile illness in Équateur Province with clinical features that were initially being suggestive of a viral haemorrhagic fever. Primary viral haemorrhagic fever pathogens have now been excluded. From selected historical and recent outbreaks, it can be deduced that diagnostic challenges extend beyond individual cognition to include structural biases in global health systems, methodological limitations and sociocultural factors. IMPLICATIONS:We identified five evidence-informed interventions to mitigate diagnostic delays: systematic consideration of multiple working hypotheses, development of sustainable local diagnostic capacity, enhancement of clinician-to-public-health communication networks, implementation of cognitive debiasing strategies, and strengthening of One Health surveillance platforms. Historical misdiagnoses offer crucial lessons for transforming outbreak response from reactive to anticipatory, potentially averting future epidemics through earlier, more accurate recognition of emerging pathogens within their complex ecological and social contexts.

BACKGROUND:Loiasis, caused by the filarial nematode Loa loa, imposes a significant disease burden in endemic regions in West and Central Africa. Manifestations include adult worms in soft tissue (e.g., the conjunctiva of the eye) and microfilaria in peripheral blood, with clinical presentations ranging from asymptomatic infections to life-threatening organ involvement. Diagnosis remains challenging due to variable microfilaria counts, frequent amicrofilaremic occult infections, and unreliable serological tests. The untargeted plasma proteome reflects broad (patho-)physiological responses, providing valuable insights into the host and disease. METHODS:Applying high-throughput plasma proteomics, we investigated the host responses of 274 patients with different L. loa disease states, including occult loiasis (n = 148), microfilaremia (n = 42), or both (n = 84), compared to 136 L. loa-negative controls. Differentially abundant proteins between L. loa-infected individuals and negative controls were validated using targeted proteomics. RESULTS:Five proteins (IGHG3, IGHG4, ACTBL2, LCP1, and IGLV9-49) were elevated in infected individuals compared to healthy controls. IGHG3, IGHG4, ACTB, and LCP1 increased from L. loa negative over individuals with history of eye worm migration to microfilaremic patients, indicating a comparatively pronounced proteomic host response to microfilaria in the blood. Sixty-three proteins differed depending on self-reported symptoms. The proteomic signatures enabled accurate classification of individuals with occult loiasis (area under the receiver operating characteristic curve [AUROC] = 0.73) and microfilaremia (AUROC = 0.84) by a random forest machine learning model. CONCLUSIONS:Overall, infection with Loa loa alters the host plasma proteome, exhibiting distinct host responses in different infection states and allowing for molecular disease classification of this highly neglected parasitic disease.

Plants used in traditional medicine represent an important source of new compounds. Hallea ledermannii (H. ledermannii) (Krause) Verdc. (Rubiaceae), Gossypium barbadense (G. barbadense) (Malvaceae), Pycnanthus angolensis (P. angolensis) (Myristicaceae), Drypetes gossweileri (D. gossweileri) S. Moore (Euphorbiaceae) and Scyphocephalium ochocoa (S. ochocoa) Warb (Myristicaceae) are five plants widely used in traditional Gabonese medicine as antimicrobials. However, little is known about the active compounds associated with their biological activities. Based on botanical studies and the claims of traditional healers regarding the antimicrobial effects of these plants, a study to evaluate the antimicrobial activity and phyto-chemical profile of aqueous extracts of three plants (bark of H. ledermannii, G. barbadense root bark and P. angolensis bark) and methanolic extracts of two plants (S. ochocoa stem bark and D. gossweileri root bark). Under the guidance of LC-MS detection, identified twenty seven (27) potentially active compounds. Eight (8) of these belong to the quinovic acid-type triterpenoid sap-onins identified in the aqueous extract of H. ledermannii, eleven (11) are dibenzofurans, chroman and stigmasterol detected in the methanolic extract of S. ochocoa and eight (8) compounds in the methanolic extract of D. gossweileri are friedelin, drypemolundein B and gossweilone, to name but a few. In parallel, the five extracts were tested on reference bacterial strains: Staphylococcus aureus ATCC 25923, Pseudomonas aeruginosa ATCC 278533, Salmonella thyphi ATCC 13311, Klebsiella pneumoniae ATCC 700603, Shigella flexneri ATCC 24570. Three of these extracts (aqueous extract of H. ledermannii and two methanolic extracts of S. ochocoa stem bark and D. gossweileri root bark) showed moderate activity against Staphylococcus aureus ATCC 25923, with inhibition zones of 12.3 ± 0.5 mm, 10.1 ± 0.5 mm and 7,6 ± 0 mm respectively. In addition, we assessed the toxicity of the three extracts that showed antimicrobial activity using an invertebrate model, Galleria mellonella (GM). We found that the LD varied according to the concentration of the plant material. The aqueous extract of H. ledermannii and the methanolic extracts of S. ochocoa and D. gossweileri were not toxic to G. mellonella. The LD50s (mg/mL) obtained were 93.2 mg/mL [717.2 g/kg body weight (bw)] and 100 mg/mL (762.3 g/kg bw), 95.4 mg/mL [721.1 g/kg body weight (bw)].

Mother's milk is the complete food of choice and the best nutritional source for its bio-immunological richness and its microbiota composed of lactic acid bacteria. The aim of this study was to assess the probiotic potential of the lactic acid bacteria present in breast milk. 34 samples (colostrum, transition milk, mature milk) were taken from breastfeeding women. They were enriched and inoculated onto MRS and MRS+cysteine agar. The sensitivity profile of the bacterial strains was assessed using the diffusion method. PCR was used to search for resistance genes specific to the target bacteria after extraction of the genomic DNA from the isolated strains. Their probiotic capacity was explored by assessing their ability to develop under different conditions. Forty-nine bacterial strains were isolated and Lactobacillus acidophilus was the most representative species in the three types of milk. These strains were able to develop both in hostile conditions and over a wide range of temperatures. They also showed antibacterial activity against pathogenic strains of Salmonella typhimurium, multi-resistant Staphylococcus aureus and Escherichia coli (ATCC25299). These results show that breast milk has potential probiotic activity that can be explored further to make the most of it, particularly in terms of antibiotic therapy.

BACKGROUND:Iron deficiency, anemia, and infectious diseases contribute largely to the disease burden among children in Sub-Saharan Africa. Accurate assessment of iron status and its relationship with infections is essential for refining iron supplementation strategies. METHODS:We report retrospectively analyzed data from a cross-sectional study of children aged 2-17 years with acute febrile illness (fever ≤7 days) in Lambaréné, Gabon (NCT03047642). Symptom-based microbiological testing identified infection etiology. Blood count, C-reactive protein, iron parameters, and cytokines levels assessed iron deficiency, anemia, and immune activation. RESULTS:Among 415 screened children with acute febrile illness, hemoglobin and iron parameters are available in 197. Of those, 145 (73.6%) are anemic: 53 (36.6%) show anemia of inflammation (AI), 11 (7.6%) iron-deficiency anemia (IDA), and 29 (20.0%) combined AI/IDA. Others are categorized as multifactorial, with mostly microcytic anemia, transferrin saturation (TSAT) ≥ 20% and varying ferritin levels. TSAT is negatively associated with IL-10, IL-6, and IL-2 in the malaria-positive group, with IL-10 also showing a positive correlation with parasitemia counts. In malaria-negative children with undetermined pathogens, IFN-γ and IL-4 levels are positively associated with TSAT and ferritin. CONCLUSIONS:These findings highlight iron dyshomeostasis in infectious diseases and confirm associations between iron availability and immune activation to causative pathogens.

Access to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) testing is limited in rural sub-Saharan Africa. We evaluated the performance of the Siemens CLINITEST ® rapid coronavirus disease 2019 antigen test under real-life conditions during the pandemic in rural Gabon. From August 2021 to February 2022, 277 participants were tested in Sindara and Lambaréné, Gabon, via outpatient mobile services. Of these participants, 54.6% were female, with a median age of 29 years (interquartile range: 12–55). The test performance was analyzed for the main population and for SARS-CoV-2 infected sub-populations at both study sites (Lambaréné and Sindara). We further evaluated subpopulations with higher viral loads using a cycle threshold (Ct) value restricted to <35, 30, 25, and 20. Overall test sensitivity in the main population was 33.3% (95% CI: 23.6–44.3%), improving to 83.3% (95% CI: 35.9–99.6%) with a Ct value of <20. Specificity across all populations was 100% (190/190; 95% CI: 98.1–100%). The prevalence of polymerase chain reaction-defined SARS-CoV-2 was 31.4%. The positive predictive value was 100% (95% CI: 88.1–100%), and negative predictive value was 76.6% (95% CI: 70.8–81.7%). Sensitivity in Sindara was 71.4% (95% CI: 29–96.3%) and 30% (95% CI: 20.3–41.3%) in Lambaréné. The Siemens CLINITEST ® demonstrated high specificity but low sensitivity overall. However, it exceeded the WHO-defined quality criteria of 80% in participants with high viral loads, making it a useful tool in resource-limited settings.

Background The RTS,S/AS01E malaria vaccine showed lower antibody response and protective efficacy in infants aged 6-12 weeks compared with children aged 5-17 months (for whom this vaccine is recommended). We aimed to study the effect of previous Plasmodium falciparum exposure on the antibody responses to RTS,S/AS01E vaccination in infants and children, and the mediating effect of baseline (including maternal) anti-circumsporozoite protein (CSP) antibodies. Methods In this observational study, we included children and infants from six African countries (Burkina Faso, Gabon, Ghana, Kenya, Mozambique, and Tanzania) enrolled in the MAL067 immunology ancillary study of the RTS,S/ AS01E phase 3 clinical trial from March 27, 2009, to Jan 21, 2011. We used comparator-vaccinated infants and children to identify antibody-based signatures of previous P falciparum exposure, which were later applied to RTS,S/AS01E- vaccinated infants and children. In these participants, we explored the relationship between vaccine antibody immunoglobulin G (IgG) responses measured by ELISA and pre-vaccination serological markers of malaria exposure by assessing the IgG levels against 1000 P falciparum antigens using partial proteome microarrays. Findings We included 718 comparator-vaccinated infants (348 [48%]) and children (370 [52%]) and 606 RTS,S/AS01E- vaccinated infants (329 [54%]) and children (277 [46%]). Anti-CSP IgG responses to primary vaccination did not correlate with a baseline signature of previous exposure in children, suggesting that prior P falciparum exposure does not significantly affect antibody immunogenicity in children (Pearson's r=-002 [95% CI -013 to 010]). By contrast, high P falciparum exposure signature levels at the time of vaccination in infants, presumably driven by maternally transferred antibodies and declining within the initial 6-12 months of life, correlated with reduced RTS,S/AS01E responses (r=-017 [-027 to -006]). This negative correlation was stronger for anti-CSP IgG than for the exposure signature or any other more immunogenic blood stage P falciparum antigens (r=-042 [-050 to -033]), persisted after adjustment by baseline levels of the exposure signature (semi-partial correlation r=-044 [-055 to -033]), and involved antibodies to the central NANP region (r=-039 [-049 to -028]) but not the C-terminal region (r=002 [-010 to 015]) of CSP. The negative effect of maternal anti-CSP IgG in infants did not appear to be confounded by other malaria transmission-dependent variables.

Background More than 20 million people are infected with L. loa, and around 40 million live in high or intermediate-risk areas in West- and Central Africa. Although loiasis is associated with significant morbidity and excess mortality, little is known about the perception of loiasis by affected communities. This study assessed the knowledge, attitudes, and practices in the rural population of Sindara, Gabon, a region characterized by high loiasis prevalence. Methods A community-based cross-sectional survey was conducted in Gabon between January and June 2022. During systematic door-to-door visits, randomly selected inhabitants were invited to participate in this questionnaire based survey. Venous blood was collected at midday from all participants for microscopic detection of filarial infection and clinical signs of loiasis were assessed. Results A total of 150 participants were recruited, of which 66% were infected by L. loa. While almost everyone had some knowledge about L. loa, 72% of the participants understood that L. loa is a parasitic worm. The transmission of L. loa via the deer fly was known to only 21% of participants. The most frequently mentioned clinical symptoms attributed to loiasis were itching (84%), eye worm migration (59%), and conjunctivitis-like symptoms (53%). Participants who experienced migratory loiasis had better knowledge of loiasis and considered it as more serious. Traditional and herbal medicine was reported most often as an available treatment option (72%). While the formal healthcare sector was mentioned as the preferred treatment provider, 60% of the reported infections were treated by traditional medical practitioners. Conclusion Loiasis is in general well known by this community residing in a region of high L. loa transmission. Important gaps in knowledge were discovered foremost regarding the mode of transmission. The available healthcare system does not seem to provide adequate management for loiasis.

Background The parasitic disease loiasis is associated with significant morbidity and mortality. Individuals with hyper-microfilaremia (greater than 20,000 microfilariae per mL of blood) may suffer from serious treatment-related or spontaneous adverse events. Diagnosing loiasis remains complex and primarily relies on direct parasite detection. In this study, we analyzed the performance of various diagnostic tests and the influence of parasitological and clinical factors on test outcomes in samples from individuals living in an endemic region. Methods Data and samples were collected from rural Gabon. Loiasis was defined as either detectable microfilaremia, or a positive history of eyeworm as assessed by the RAPLOA questionnaire. Diagnostic testing included a quantitative PCR (qPCR) for detection of Loa loa DNA in blood samples, an in-house crude L. loa antigen IgG ELISA, and a rapid test for antibodies against the Ll-SXP-1 antigen (RDT). Sensitivity and specificity were determined for each test and factors potentially influencing outcomes were evaluated in an exploratory analysis. Results ELISA, RDT and qPCR results were available for 99.8%, 78.5%, and 100% of the 1,232 participants, respectively. The ELISA and RDT had only modest diagnostic accuracy. qPCR was specific for L. loa microfilaremia and Cycle threshold values correlated with microfilarial density. Anti-L. loa IgG levels were highest in occult loiasis, and antibody levels correlated inversely with L. loa microfilarial density as did RDT line intensities. Only 84.6% and 16.7% of hyper-microfilaremic individuals tested positive by ELISA (11/13) and RDT (2/12), respectively. Conclusion None of the tests demonstrated high sensitivity and specificity for loiasis. Indirect diagnostic assays were characterized by low specificity. Additionally, hyper-microfilaremic individuals often tested negative by RDT and ELISA, indicating that these tests are not suitable for individual case management in endemic populations.

Loiasis, a filarial pathogen exclusively endemic in central and western Africa, causes a wide spectrum of symptoms. Understanding the breadth of its clinical manifestations is of importance for adequate patient care and to understand its disease burden. Recurring transient pain in the oral cavity was reported as a self-perceived symptom of loiasis in in-depth interviews of patients in a high transmission region in Gabon. Pain was described as stabbing in character and transient for a few days in its temporal course. A quantitative epidemiological survey indicated that transient tooth pain was experienced by 22% of patients infected with Loa loa. Among those individuals, it was exclusively reported by patients suffering from migratory loiasis (24%). Similar findings have been previously described for other filarial pathogens, indicating that transient swellings of the periodontium and the soft tissue of the oral cavity may explain this symptom reported by patients with migratory loiasis.

The consequent use of malaria rapid diagnostic tests (RDTs) preceding a treatment decision has improved the global management of malaria. A combination RDT, including an inflammation marker to potentially guide antibiotic prescription, could improve the management of acute febrile illness (AFI). We performed a prospective, cross-sectional study in Gabon evaluating the STANDARD Malaria/CRP DUO (S-DUO) RDT. Participants aged 2 to 17 years with fever at presentation and/or a history of fever < 7 days were enrolled. Expert microscopy, SD Bioline Malaria Ag P.f/Pan test for malaria detection, and NycoCard CRP device for CRP were used as comparators. AFI cases were classified on a spectrum encompassing bacterial vs. non-bacterial infection. 415 participants with AFI were enrolled. S-DUO RDT sensitivity and specificity for malaria detection vs. microscopy were 99·1

Background and Objectives:Point-of-care testing using nonsputum samples like serum or plasma proteins can improve tuberculosis (TB) patients access to a definitive diagnosis, especially in resource-constrained and remote areas. Recently, approximately 400 proteins were identified as playing a role in the pathogenesis of TB, offering a translational clinical research repository for TB. In a previous manuscript, we proved the potential use of these proteins for point-of-care testing for active TB diagnosis. The present work aims to confirm the performance of single and combination proteins to select the best candidate biomarkers for further development as a diagnostic testing tool for active TB. Methods:Seventy-four participants were assessed on the diagnostic performance of 17 single proteins and combinations of 2 to 4 proteins to diagnose active TB. The selection criteria included differential expression of the proteins between active TB and community-acquired pneumonia (CAP) and a performance rate ≥70% for active TB. Results:SULT4A1, WASPF3, SPTLC1, FAM107B, SORCS2, and CYTOb561 were differentially expressed in TB compared to CAP patients. Two single proteins, SULT4A1 and WASPF3, performed ≥70% to discriminate active TB from CAP patients. The diagnostic performance of 3 protein-based combinations of active TB was 81% after leave-one-out cross-validation. Conclusion:Single proteins and 3 protein-based combinations are candidate biomarkers for diagnosing active TB disease. A large and prospective study will confirm their performance as complementary diagnostic tools to rapid diagnostic methods for detecting active TB.

Objectives: Despite evidence of praziquantel's (PZQ) safety for treating schistosomiasis in pregnancy, many countries withhold treatment. Only two randomized controlled trials have investigated PZQ in pregnancy, none involving Schistosoma haematobium. Methods: Pregnant women during the second trimester in Lambaréné (Gabon) were screened for S. haematobium infection using urine microscopy and circulating anodic antigen detection. Participants positive for either test were randomized (3:1) to single-dose PZQ 40 mg/kg during pregnancy versus no treatment during pregnancy. Investigators were blinded for allocation. Primary outcomes were reduction of egg (egg reduction rate [ERR]) and antigen production (infection reduction rate [IRR]) while explorative outcomes included assessment of cure rate, adverse events, maternal hemoglobin levels, maternal anemia prevalence at delivery, pregnancy outcomes, and newborn anthropometric parameters. Results: Of 761 women screened 165 were eligible and randomized (intervention n = 124, control n = 41). Of them, 124 completed the study (n = 90 and n = 34, respectively). Treatment led to a significantly higher ERR (95.0% [91-97%] vs 27.0% [−42-63%]) and IRR (95% [91-97%] vs 56% [14-78%]). Common adverse events were dizziness, nausea, and vomiting. Maternal anemia at delivery was significantly lower in the intervention group (odds ratio: 0.40 [0.16;0.96], P = 0.04). No increased risk for adverse pregnancy outcomes was observed. Conclusions: This first randomized controlled trial investigating PZQ in pregnant women with S. haematobium found PZQ to be safe, effective, and reducing maternal anemia. We recommend treating confirmed infections to prevent morbidity in pregnant women.