Ifakara Health Institute

Evidence of natural infection with Wolbachia and its negative correlation with Plasmodium falciparum among wild malaria vectors has opened new avenues for utilization of Wolbachia in malaria vector control. However, the interaction between Wolbachia and Plasmodium parasites in mosquitoes tends to be species-specific and may show ecological variations. Among the primary malaria vectors in Tanzania, natural Wolbachia infection has only been observed in Anopheles arabiensis, while there is still limited information on Wolbachia natural infection in Anopheles funestus sensu lato, and its interaction with P.falciparum in the mosquito species. Therefore, this study investigated the prevalence of natural infection and co-infection of Wolbachia and P.falciparum in the An.funestus s.l. in southeastern Tanzania, and characterized the Wolbachia strains detected. The study was conducted in five villages in southeastern Tanzania between March and June 2024. Mosquitoes were collected from 52 households using Centers for Disease Control and Prevention (CDC) light traps and Prokopack aspirators, followed by morphological identification. Detection of An.funestus sibling species and Wolbachia was performed using conventional polymerase chain reaction (PCR) and nested PCR (Wolbachia only). Sanger sequencing was performed as a confirmatory test followed by phylogenetic analysis of the detected Wolbachia strains. P.falciparum sporozoites were detected using enzyme-linked immunosorbent assay (ELISA). Wolbachia was detected in almost half of all wild An.funestus s.l. tested using the primary PCR (prevalence = 46.5%, N = 400); and more than half when nested PCR approach was used (prevalence = 70.8%, N = 400). Only three mosquitoes carried P.falciparum sporozoites (prevalence = 0.8%, N = 400) and only one showed co-infection with Wolbachia (prevalence = 0.3%, n = 400). Sequencing and phylogenetic analysis involving both the 16S rDNA, coxA, and wsp Wolbachia genes showed that the detected strains clustered with Wolbachia supergroup B, specific for Dipterans. Unlike findings from the previous study, this study demonstrates that An.funestus s.l. in southeastern Tanzania are infected with Wolbachia, at a surprisingly high prevalence. This study also provides the first report on Wolbachia-P.falciparum co-infection status in An.funestus s.l. in Tanzania. Further studies with larger sample sizes are needed to confirm the association between native Wolbachia and P.falciparum in wild An.funestus s.l. in southeastern Tanzania.

Background Diagnosis and monitoring of extrapulmonary tuberculosis (EPTB) remains challenging. Ultrasound such as the extended focused assessment for HIV-associated tuberculosis (eFASH) protocol might improve diagnosis and monitoring of treatment responses. This study determined the diagnostic accuracy of eFASH for EPTB and its value in monitoring EPTB treatment response compared with clinical signs and symptoms. Methods We performed a post-hoc analysis of a trial assessing eFASH impact on management of adults with suspected EPTB. Participants who had baseline and follow-up ultrasound examinations were included. We assessed the diagnostic accuracy of eFASH and compared the evolution of eFASH and clinical signs and symptoms in participants with definite EPTB, stratified by favorable treatment outcomes at 6 months. Results In 296 included participants (95 with definite EPTB, 201 with no definite EPTB), the most common eFASH signs were pleural effusion (47%) and pulmonary B-lines with subpleural granular artefacts (34%). Pleural effusion was the only sign that persisted beyond 6 months. eFASH had a sensitivity of 93.7% (95% CI, 86.8-97.6) and a specificity of 37.8% (95% CI, 31.1- 44.9) for definite EPTB. At 2 months, favorable outcomes were similar between participants with full and partial resolution of eFASH signs (83% versus 81%). In contrast, a higher proportion of favorable outcomes was seen in participants with full resolution of clinical signs and symptoms (90% versus 60%). Conclusion eFASH shows high sensitivity but low specificity for definite EPTB. Ultrasound can be used alongside clinical signs and symptoms to monitor treatment response in patients with EPTB.

Abstract Background Adult mosquito survival is a critical factor in malaria transmission because Anopheles vectors must live at least 11–14 days before they can transmit. However, there is no direct method to assess age. Traditional methods of mosquito age-grading rely on indirect proxies of reproductive history derived from dissection and observation of ovarian features (Detinova and Polovodova methods). Both approaches are labour-intensive, time-consuming, and demand specialized expertise; with little known about the extent to which are used in malaria surveillance programmes, and why they may be deprioritised. This study assessed current practices, capacity, and constraints related to mosquito age-grading for malaria vector surveillance in Africa, including knowledge and use of existing dissection-based methods and emerging alternatives such as infrared spectroscopy. Methods We conducted an online survey of 285 stakeholders from across Africa, including researchers, entomologists, and National Malaria Programme (NMP) personnel, to assess the practices, priorities, and barriers to mosquito age-grading. This was complemented with a series of in-depth interviews and focus group discussions to collect insights and perspectives from stakeholders regarding their familiarity and use of age-grading methods. Findings: More than 70% of survey respondents reported that malaria vector surveillance was routinely conducted by their institutions or countries, with the highest priority given to vector density, species identification, human biting rate, and insecticide resistance. Familiarity (awareness as opposed to knowledge) of age-grading methods was highest for the Detinova (55%) and Polovodova (44%), and lower for newer approaches, including infrared-spectroscopy. Only 50% of respondents indicated that they regularly assessed mosquito age (mostly Detinova method); with > 1/3 considering age-grading to be a high-priority in vector surveillance. Reported barriers to conducting mosquito-age-grading included insufficient technical expertise, perceived impracticality of ovary dissections for large-scale surveillance, inadequate tools, and limited funding. Conclusions Despite its critical role in malaria transmission, mosquito survival and age are rarely assessed in African vector surveillance programs. There is need for greater acknowledgment of these measures and their implications for disease transmission and control, and investment in tools, training, and funding to overcome current operational barriers. Integrating more practical and scalable age-assessment methods could enhance targeting of interventions.

ABSTRACTGlobal efforts to eliminate onchocerciasis are hampered by the lack of a macrofilaricidal drug capable of killing adult parasites. Oxfendazole, a veterinary anthelminthic, exhibits macrofilaricidal activity and holds promise to shorten treatment durations. Phase 1 studies in healthy Caucasian adults demonstrated favorable pharmacokinetics and safety using a veterinary oral liquid formulation. More recently, a Phase 1 bioavailability trial (NCT04920292) evaluated a field‐applicable tablet formulation in healthy African adults. This study presents a secondary analysis to (i) characterize the population pharmacokinetics of oxfendazole and its major metabolites in healthy African adults receiving the tablet formulation and (ii) propose a dosing regimen for Phase 2 evaluation in patients with onchocerciasis. Thirty healthy African adults were enrolled, and plasma concentration–time profiles of oxfendazole, fenbendazole, and oxfendazole sulfone were obtained from 24 participants who received oxfendazole (8 per dose group: 100 mg single dose, 400 mg single dose, 400 mg once daily for 5 days). All cohorts were pooled and analyzed using nonlinear mixed effects modeling. Oxfendazole absorption was best described by first‐order kinetics with first‐pass metabolism. Dose‐limited bioavailability was evident. Disposition was best described by one‐compartment models with linear elimination. Simulations suggested that 400 mg once daily (or 50 mg twice daily) for 5 days is required to achieve putative exposure targets (> 200 ng/mL for 5 days), with low risk of safety concerns. The population pharmacokinetic model adequately described oxfendazole pharmacokinetics in healthy African adults and supports dosing selection for future clinical trials.Trial Registration:ClinicalTrials.gov Identifier: NCT04920292

Nearly 5 million children die each year of preventable causes, with pneumonia being a key contributor. The Integrated Management of Childhood Illnesses guidelines improve health care workers' diagnostic and management capabilities by relying mostly on clinical signs. Though there have been successes, challenges in the consistent application of IMCI and the accurate diagnosis of conditions like hypoxemia remain. Next generation pulse oximeters add functionality to stand alone pulse oximeters, like measurement of respiratory rate, temperature, and hemoglobin. While the TIMCI project sought to address gaps in the introduction of pulse oximetry in India, Kenya, Senegal, and Tanzania, research was also conducted to strengthen the market for multimodal pulse oximetry (PO) devices by filling evidence gaps around ideal product attributes and the validation of available and near to market photoplethysmography-derived clinical measurement tools (medical device and smartphone-based). A mixed-methods evaluation measured usability and diagnostic accuracy using multimodal PO devices among primary care providers in the four countries. Results showed good usability, minimal user errors, and high satisfaction and system usability scores across all devices. Additionally, across all age categories, device performance for hypoxemia, tachycardia, and fever exceeded 80% agreement; respiratory rate measurements exhibited greater variability in percent agreement between devices. A target product profile and an open-source data repository were developed to further advance device development and market alignment. This research provided data on the performance of various multimodal PO devices, considering different form factors and product attributes. Technological progress continues to expand opportunities for the collection of clinical measurements and data. Supporting providers with decision support and automated documentation tools ensures that the information generated is actionable and utilized, while an emphasis on integrated technologies is essential to maximize provider capabilities and improve the diagnosis and management of childhood illnesses in low- and middle-income countries.

Background: Antimicrobial stewardship (AMS) programs have implemented various surveillance interventions, such as profiling bacterial resistance patterns and developing economic cases for effective management. However, there has been comparatively less focus on evaluating the Drug Resistance Index (DRI). The DRI serves as a crucial instrument for evaluating the efficacy of antimicrobial therapies and examining the patterns of bacterial resistance. Evaluating the efficacy of antibiotics and effectively communicating the issue of antimicrobial resistance are crucial components in developing AMS programs within hospital environments. Objective: This study utilised the DRI to analyse the distribution of multidrug-resistant organisms (MDROs) associated with widely prescribed antimicrobials at Benjamin Mkapa Hospital (BMH), focusing on their application in treating both Gram-positive and Gram-negative infections. Methods: A retrospective descriptive study was conducted using combined data on total bacterial isolates, resistance isolates, and antibiotic usage to calculate the DRI over the years 2020, 2021, and 2022. Results: The three-year DRI for the priority pathogens Escherichia coli and Klebsiella pneumoniae isolated from urine samples is 46%. The average three-year DRIs for pathogens isolated from blood samples were as follows: Acinetobacter baumannii (37%), Escherichia coli (65%), Klebsiella pneumoniae (62%), Streptococcus pneumoniae (60%), and Staphylococcus aureus (63%). Additionally, the DRIs for bacteria isolated from pus and wound swabs were: Acinetobacter baumannii (60%), Escherichia coli (57%), Klebsiella pneumoniae (66%), Pseudomonas aeruginosa (34%) and Staphylococcus aureus (75%). Conclusion: All evaluated priority pathogens displayed multidrug resistance, with DRI values surpassing 25%, a clear indicator of escalating antimicrobial resistance (AMR). These findings underscore the necessity for robust antibiotic stewardship programs within healthcare institutions, alongside the regular dissemination of antibiotic consumption data to the BMH. Additionally, the formulation of comprehensive policies and treatment guidelines is essential to regulate antibiotic prescriptions effectively, thereby preserving their long-term efficacy. These initiatives are pivotal in the fight against AMR, facilitating the restoration of antimicrobial susceptibility and mitigating the DRI.

Malaria vaccines provide waning protection from disease that is correlated with the production of antibodies to the repeat region of the liver-stage circumsporozoite protein (CSP). CSP-based vaccines display limited durability in malaria-naïve individuals yet are even less effective in malaria-experienced individuals, suggesting the generation of non-optimal humoral immunity in response to both infection and vaccination. To address this hypothesis, we performed a cross-species, comprehensive analysis of B cell responses to CSP after Plasmodium infection or immunization, focusing our analysis on the repeat and C-terminus domains included in malaria subunit vaccines. Herein we demonstrate that while multiple factors may impinge on strong, lasting protective CSP-specific immunity, two forces predominantly impact proper memory B cell differentiation; a) inhibition of germinal center formation by infection and b) skewed B cell differentiation due to the repetitive nature of the protective region of the CSP protein.

Anopheles stephensi (Diptera: Culicidae), a primary malaria vector native to south Asia and the Arabian peninsula, has recently spread to Sri Lanka and the Horn of Africa (HOA). Its arrival poses a serious challenge to malaria control initiatives, particularly in the rapidly urbanized African settings because it can transmit both Plasmodium falciparum (Haemosporida: Plasmodidae) and Plasmodium vivax (Haemosporida: Plasmodidae). This threat is compounded by the vector's growing resistance to insecticides, particularly pyrethroids, the backbone of indoor residual spraying (IRS) and insecticide-treated nets (ITNs). The use of dichlorodiphenyltrichloroethane (DDT), which exhibits a comparable mode of action to pyrethroids, significantly increases the likelihood of cross-resistance development. This review presents the first regionally integrated synthesis of An. stephensi susceptibility to pyrethroids and DDT. The analysis encompasses phenotypic resistance and underlying molecular mechanisms across the World Health Organization (WHO) Eastern Mediterranean Region, the Indian subcontinent and the HOA regions where the species is either native or invasive. Twenty-one studies published over the past two decades were identified through searches in five electronic databases. The findings revealed confirmed resistance to multiple pyrethroid compounds such as permethrin, deltamethrin, lambdacyhalothrin, alpha-cypermethrin, and cyfluthrin, as well as DDT, while susceptibility to etofenprox varied by location. Geographic variability was observed in intensity of resistance and allele distribution across Iranian sites. Mechanistically, resistance was linked to both target-site knockdown resistance (kdr) mutations (L1014F and L1014S) and metabolic detoxification pathways involving cytochrome P450s, glutathione S-transferases (GSTs), and esterases. These findings underscore the escalating menace that insecticide resistance poses to malaria vector control, particularly in newly invaded regions characterized by inadequate surveillance infrastructure and pronounced reliance on pyrethroid-based interventions. This review advocates for the establishment of comprehensive global monitoring frameworks and the formulation of evidence-based resistance management strategies tailored to local vector ecologies and resistance mechanisms.

Pain is understudied in Africa, and there are no data on high-impact chronic pain from this region. In this study, we assessed the prevalence of unspecified pain, chronic pain, and high-impact chronic pain, and their determinants in Lesotho, Southern Africa. We conducted a household-based, cross-sectional survey among adults aged 18 years or older in 120 randomly sampled villages across Butha-Buthe and Mokhotlong districts in Lesotho. Among the 6039 adults included, the median age was 39 years (interquartile range: 27-58), and 3153 of 6039 participants (52.2%) were female. Overall, 1194 participants (19.8%) had unspecified pain (95% confidence interval [CI]: 18.8-20.8), 909 (15.1%) had chronic pain (95% CI: 14.2-16.0), and 428 (7.1%) had high-impact chronic pain (95% CI: 6.5-7.8) corresponding to 47.1% among the participants with chronic pain. Higher age groups were associated with increasing odds of unspecified pain, chronic pain, and high-impact chronic pain. Male participants were less likely to have unspecified pain (adjusted odds ratio [aOR], 0.65; 95% CI: 0.55-0.76; P < 0.001) and chronic pain (aOR, 0.79; 95% CI: 0.65-0.96; P = 0.019). There was no association between sex and high-impact chronic pain. Furthermore, high-impact chronic pain was associated with arterial hypertension, diabetes mellitus, moderate-to-high risk of depression, moderate-to-high risk of generalized anxiety disorder, and household wealth. The prevalence of chronic pain and high-impact chronic pain was elevated in our study population. Associations with further noncommunicable chronic conditions, such as arterial hypertension and diabetes mellitus, support the need for health systems to provide integrated chronic care which includes pain management.