Henk D. F. H. Schalling

In malaria-endemic regions, women remain vulnerable to Plasmodium falciparum infection at the time of delivery. However, the immunological mechanisms underlying infection-associated inflammation in primigravid women remain poorly characterized. This exploratory study investigated cytokine-based immune profiles reflecting malaria infection status at delivery. We assessed 33 primigravid women from Nanoro, Burkina Faso (mean age 19 years; range 18–20.5) at childbirth. Antibody responses to P. falciparum antigens (PfCSP, PfAMA-1, and EBA-175) and plasma levels of cytokines (IL-4, IL-10, IL-6, TNF-α, and IFN-γ) were quantified using enzyme immunoassays. Multivariate analyses, including principal component analysis (PCA) and hierarchical clustering, identified three distinct immune profiles: (1) a low-inflammatory cluster with reduced IL-6 and TNF-α, (2) a TNF-α–dominant cluster, and (3) a highly pro-inflammatory cluster with elevated IL-6 and TNF-α. Cluster stability was supported by bootstrap analysis (AU ≥ 92%). All women in the most inflammatory cluster were P. falciparum–positive at delivery (Fisher’s exact test, p = 0.04; exploratory association). These cytokine-driven profiles reflect biologically distinct inflammatory states associated with concurrent infection at delivery rather than predictive immune predispositions. The findings underscore the potential of cytokine profiling as a hypothesis-generating tool to guide future longitudinal studies on immune regulation and the postpartum period.

Reducing the burden of malaria in pregnant women remains a major challenge for control programmes. Decreasing immunity may increase the vulnerability of pr

Introduction: In malaria-endemic regions, women remain vulnerable to malaria infection even at the time of delivery and shortly thereafter. However, the immunological mechanisms underlying this susceptibility remain poorly characterized. This exploratory study investigated whether cytokine-based immune profiles could help identify primigravid women at increased risk of malaria infection at delivery, potentially informing postpartum risk prediction. Methods: We assessed a cohort of 33 primigravid women from Nanoro, Burkina Faso (mean age 19 years; range 18–20.5), at the time of delivery. Immune profiles were developed by measuring antibody responses to Plasmodium falciparum antigens (PfCSP, PfAMA-1, and EBA-175) and levels of key cytokines (IL-4, IL-10, IL-6, TNF-α, and IFN-γ) using enzyme immunoassays. Multivariate analyses, including principal component analysis (PCA) and hierarchical clustering, were used to detect immune profile patterns. Results: Three distinct immune profiles were identified: (1) a low-inflammatory cluster with reduced IL-6 and TNF-α; (2) a TNF-α–dominant cluster; and (3) a highly pro-inflammatory cluster with elevated IL-6 and TNF-α. Bootstrapping confirmed the stability of these clusters (AU ≥ 92%). All women in the most inflammatory cluster were infected with Plasmodium falciparum at delivery (Fisher’s exact test, p = 0.04). Conclusions: Cytokine-driven immune profiles at delivery reflect biologically distinct inflammatory states among primigravidae. Elevated IL-6 and TNF-α levels were strongly associated with active malaria infection at delivery. These findings highlight the potential of cytokine-based profiling as a hypothesis-generating tool for identifying women at increased risk of malaria around childbirth.

Background: According to the World Health Organization’s recent report, malaria remains a major health challenge during pregnancy and for postpartum women in endemic regions. While immune alterations during pregnancy are well characterized, postpartum cytokine dynamics and their impact on malaria susceptibility remain poorly defined. This study uniquely investigates how cytokine balance shifts, contribute to malaria susceptibility in primigravid women during the postpartum period. Methods: A total of 33 Burkinabe women were enrolled at delivery and followed up at 1 and 3 months postpartum. Serum cytokine concentrations (IL-4, IL-6, IL-10, TNF-α, IFN-γ) were quantified by ELISA. Malaria infection was detected by PCR and microscopy. Statistical analyses included effect size calculations and cluster analyses to assess immune profiles. Results: At delivery, 48.5% of women tested positive for malaria by PCR. Malaria-infected women had significantly elevated IL-10 levels and a decreased IL-6:IL-10 ratio compared with non-infected women (p = 0.005). This anti-inflammatory shift persisted into the during early postpartum period. Strong correlations were observed between IL-10 levels and malaria infection (σ = 0.9, p < 0.001). Of note, IL-4 also showed a significant effect, highlighting a complex immunoregulatory environment. Conclusion: Our findings reveal, for the first time in a Sub-Saharan primigravid cohort, that an IL-10-dominant cytokine profile at delivery is strongly associated with postpartum malaria susceptibility. Modulating cytokine responses could represent a novel therapeutic approach to improving maternal health in malaria-endemic regions.

Background: Visceral leishmaniasis (VL) is a severe parasitic disease transmitted by phlebotomine sandflies. VL is endemic in West Pokot County, Kenya, where effective strategies to interrupt transmission are impeded by the limited understanding of VL risk factors. Therefore, this case–control study aimed to explore environmental, behavioural and household determinants of VL in West Pokot.Methods: From November 2022 to January 2023, a structured questionnaire was administered to 36 symptomatic primary VL cases attending Kacheliba Sub‐County Hospital in West Pokot and to 50 healthy controls from local villages. The VL status of all participants was confirmed using an rK39 rapid diagnostic test. Associations between questioned determinants and VL were investigated by means of age‐corrected univariate logistic regression analysis.Results: Significant associations were found between VL and housing characteristics, such as window presence and floor type. VL cases more frequently reported the presence of cattle, dogs and sheep in their house yards. VL was also associated with cutting down trees in the house yard and house proximity to several Acacia tree species. Furthermore, outdoor activities, including travelling outside the residence for more than 2 weeks, activities near termite mounds, and forest activities during the rainy season, increased the risk of VL.Conclusions: This work reports a number of previously undescribed risk factors for VL in the understudied West Pokot focus. The results suggest VL transmission occurs both peri‐domestically at night and outdoors during the day, particularly when sandfly resting sites are disturbed. Our findings warrant further research into sandfly ecology and potential zoonotic parasite reservoirs in West Pokot.

Visceral leishmaniasis (VL) is a severe infectious disease caused by protozoan parasites of the Leishmania donovani complex. Blood cytokine concentrations in VL patients can inform us about underlying immunopathogenesis and may serve as a biomarker for treatment effectiveness. However, cytokine levels have not yet been studied in VL patients from Kenya, where case load is high. This study measured the serum cytokine profile, blood parasite load and clinical and haematological features of VL patients from West Pokot County, Kenya, over the course of treatment with sodium stibogluconate and paromomycin (SSG-PM). VL patients recruited at the hospital presented with splenomegaly and weight loss, and frequently had pancytopenia and anaemia. Median Leishmania parasite load in blood, determined with real-time polymerase chain reaction, was 2.6 × 10⁴ parasite equivalents mL⁻¹. Compared to endemic healthy controls, serum interferon gamma (IFN-γ), interleukin 5 (IL-5), IL-6, IL-10, IL-12p70, IL-17A and IL-27 were significantly elevated in untreated VL patients. Severe VL was associated with higher IL-10 and lower IFN-γ levels. After 17 daily injections with SSG-PM, disease symptoms disappeared, leukocyte and thrombocyte counts significantly increased, and blood parasite load decreased to undetectable levels in all VL patients. There was a significant decrease in IL-10 and IL-6, whereas IL-17A levels increased; the remaining cytokines showed no significant concentration change during treatment. In conclusion, the results suggest that SSG-PM treatment of VL patients from West Pokot was effective. Moreover, both inflammatory and regulatory immune responses appeared to decrease during treatment, although the increase in IL-17A could reflect a partial continuation of immune activation.

Malaria, a major global health concern, requires effective diagnostic tools for patient care, disease control, and elimination. The pathway from concept to the adoption of diagnostic products is complex, involving multiple steps and stakeholders. To map this process, our study introduces a malaria-specific diagnostic pathway, synthesising existing frameworks with expert insights. Comprising six major stages and 31 related activities, the pathway retains the core stages from existing frameworks and integrates essential malaria diagnostic activities, such as WHO prequalification processes, global stakeholder involvement, and broader health systems considerations. To understand the scope and availability of evidence guiding the activities along this pathway, we conducted an online survey with 113 participants from various stages of the malaria diagnostic pathway. The survey assessed perceptions on four critical attributes of evidence: clear requirements, alignment with user needs, accuracy and reliability, and public and free availability. It also explored the types of evidence used and the challenges and potential solutions related to evidence generation and use. Respondents reported using a broad range of formal and informal data sources. Findings indicated differing levels of agreement on the attributes across pathway stages, with notable challenges in the Approvals and Manufacturing stage and consistent concerns regarding the public availability of data/evidence. The study offers valuable insights for optimising evidence generation and utilisation across the malaria diagnostic pathway. It highlights the need for enhanced stakeholder collaboration, improved data availability, and increased funding to support effective evidence generation, sharing, and use. We propose actionable solutions, including the use of public data repositories, progressive data sharing policies, open-access publishing, capacity-building initiatives, stakeholder engagement forums, and innovative funding solutions. The developed framework and study insights have broader applications, offering a model adaptable for other diseases, particularly for neglected tropical diseases, which face similar diagnostic challenges.

Background: Previous studies in the Bono Region (middle belt) of Ghana have reported persistent Onchocerca volvulus infection and associated morbidities after nearly three decades of ivermectin treatment. This study aimed to assess the usability, acceptability and cost of the Ov16 SD BIOLINE rapid diagnostic test (Ov16 RDT) in onchocerciasis surveillance activities in the middle belt of Ghana. Methodology: A cross-sectional study was conducted in 6 endemic communities in the Tain District and Wenchi Municipality. A total of 254 individuals (54% females; median age (range)=31 (5–83) years), agreed to participate in Ov16 RDT (100%), skin-snip microscopy (37%) and nodule palpation (100%). Post-test interviews were conducted for all 94 participants tested by all three diagnostics. A cost analysis based on testing 400 people was performed. Principal findings: Ov16 seroprevalence was 23.6% (60/254, 95%CI=18.8%–29.2%); microfilarial prevalence 11.7% (11/94, 95%CI = 6.7%–19.8%) and nodule prevalence 5.5% (14/254, 95%CI=3.3%–9.0%). The proportion of Ov16 seropositive females (43/136, 31.6%) was twice that of males (17/117, 14.5%). Among 5–9-year-olds, Ov16 seroprevalence was 11.1% (3/27), microfilarial prevalence 23.1% (3/13) and nodule prevalence 3.7% (1/27). For the 94 participants with all three tests, there was no association between the results of Ov16 RDT, skin-snip microscopy and/or nodule palpation. Most participants and technicians preferred Ov16 RDT because of being less painful and invasive, easier to use and faster. Had 400 participants been tested, the total cost per individual would be US$24 (Ov16 RDT) and US$74 (skin-snip microscopy). Conclusions: Ov16 RDT is more acceptable and affordable (a third of the cost) compared to skin-snipping for surveillance activities in transmission hotspots in Ghana. Author summary: Onchocerciasis (River blindness) is a neglected tropical disease targeted by the World Health Organization for elimination of transmission in 12 endemic countries by 2030. There is a need for field-friendly, acceptable and affordable tools to monitor progress towards elimination. In Ghana, the SD BIOLINE Ov16 rapid diagnostic test (Ov16 RDT) has been used in several epidemiological surveys, but its usability, acceptability and cost have not been assessed. We studied 6 endemic communities with persistent infection after nearly three decades of ivermectin treatment. The prevalence of seropositivity by Ov16 RDT was twice the prevalence of skin-snip microscopy positivity and four times the prevalence of nodule-palpation positivity. For the individuals tested by all three diagnostics, we found no agreement between the results of Ov16 RDT and skin-snip microscopy (and/or nodule palpation), likely owing to the long-term treatment in the study area. The Ov 16 RDT was acceptable to both study participants and technicians because it was less painful and invasive, and yielded results more quickly. The cost of skin-snip microscopy would be thrice that of Ov16 RDT when testing 400 individuals. Ov16 RDT is more acceptable and less costly than skin-snipping for surveillance activities in transmission hotspots in Ghana.

This study aimed to evaluate scientific evidence of the benefit of the use of insecticide-treated nets (ITNs) and Intermittent preventive treatment (IPT) on the birth weight of newborns and the hemoglobin level of the mother when used to prevent malaria during pregnancy. This cross-sectional analytical study was conducted on 467 hospitalized women in the Maternity Ward of Centre Hospitalier de Kingasani II, in the Democratic Republic of the Congo. Data were collected using a structured questionnaire that was pre-tested during a face-to-face interview. Apart from basic statistics, the chi-square test was used to compare proportions. Multivariate analysis (logistic regression) was used to identify variables significantly associated with the 95% confidence interval (CI). The ITN ownership rate was 81% (95% CI: 77–84) and the ITN use rate was 66% (95% CI: 62–70). Sixty-five percent (95% CI: 60–69) reported having received at least three doses of IPT during pregnancy with sulfadoxine-pyramethemine (IPTp-SP). There was a statistically significant difference in hemoglobin levels between hospitalized women who did not use the ITN (9.4 g/dL IIQ: 8.7–9.9) and those who did (11 g/dL IIQ: 9.8–12.2). The non-use of the ITN was associated with low birth weight (aOR = 3.6; 95% CI: 2.1–6.2; p < 0.001) and anemia in pregnant women (cOR = 2.41; 95% CI: 1.16–5.01; p = 0.018). The use of ITN and taking at least three doses of ITP during pregnancy are associated with good birth weight. The number of doses of IPTp received during antenatal care is associated with the maternal hemoglobin level in the third trimester of pregnancy.