Research Appraisals
Evidence-based critical appraisals of the latest medical research, systematically evaluated using Oxford CEBM methodology.
Showing 24 appraisals
Emergency medicine journal : EMJ
Are rapid diagnostic tests reliable for the detection of malaria in the emergency department?
A short systematic review assessed the diagnostic accuracy of malaria rapid diagnostic tests in febrile adults from malaria-endemic regions. A database search of MEDLINE, EMBASE, Cochrane and Google Scholar returned 138 papers. Six papers met the inclusion criteria and were included in our analysis.
23 July 2026
Read appraisal →Transactions of the Royal Society of Tropical Medicine and Hygiene
Atomic clarity: how structural biology is shaping blood-stage malaria vaccines
Developing an effective malaria vaccine is challenging because Plasmodium parasites use complex strategies to invade host cells. The blood stage, where parasites replicate inside red blood cells, causes disease symptoms and relies on large multiprotein surface complexes that are difficult to target. Understanding their structure is essential for rational vaccine design. Cryogenic electron microscopy (cryoEM) enables atomic-level analysis of dynamic and membrane-associated complexes without crystallization, revealing key processes such as protein trafficking, nutrient uptake, and host cell remodeling. Recent advances in artificial intelligence and deep learning have improved cryoEM data analysis and structural modeling. Together with genomic data, this integrated approach is accelerating progress toward broadly protective malaria vaccines.
9 July 2026
Read appraisal →Transactions of the Royal Society of Tropical Medicine and Hygiene
Extreme weather effects on health services and communities in low and lower-middle income countries: a thematic systematic review
Most previous research about the dangers of extreme weather events was applicable to populations in high-income countries. Data summarising harms related to extreme weather events in low-income settings are lacking. A systematic review thematically summarising evidence about weather event-linked harms and responses in low- and lower-middle-income countries was conducted. Peer-reviewed and grey literature was systematically searched and selected. Data were extracted about harms, responses and outcomes relevant to six WHO building blocks of healthcare systems. Framework analysis was used to identify predominant themes related to harms, responses and the WHO building blocks. In total, 183 reports were included. Flooding and high winds were the most common types of extreme weather events documented. The main community experience themes identified were the displacement of populations and disruption. The main themes identified for health service delivery were vulnerability, disruption and resilience. Documented examples of resilience or recovery were far fewer for all six WHO healthcare system building blocks than descriptions of vulnerability and disruption. Extreme weather events can be highly disruptive and harmful to healthcare systems and communities in LMIC settings that are often already highly vulnerable.
8 July 2026
Read appraisal →International immunopharmacology
Antimicrobial peptides in malaria and tuberculosis management: a systematic review of emerging evidence
AMPs (Antimicrobial peptides) are small molecules that are crucial components of biological activities, viz wound healing, angiogenesis, antimicrobial activity, immune regulation, and exhibit anticancer properties. This systematic review summarizes the origin, sequence, efficacy, and structure-activity mechanisms of AMPs against tuberculosis and malaria, the world's leading killer infectious diseases, employing the AMP database (APD3) (till June 2025) and PubMed search (January 1965 to June 2025). The comprehension is well addressed by covering the inhibitory activity, SAR (structure-activity relationships), and action mechanisms of AMPs (natural and synthetic) against Mycobacterium tuberculosis and Plasmodium spp., as both pathogens exhibit multidrug resistance. The review also illustrates how these specific motifs, along with their properties such as hydrophobicity, charge, or amphipathicity, influence the AMPs activity against the pathogens. Moreover, challenges in the AMPs use and the way forward, including the recent breakthroughs employing nanocarriers, inhalable formulations for TB, and targeted erythrocyte delivery for malaria, are also highlighted. AMPs have illustrated promising anti-TB and antimalarial efficacy owing to their unique structure and novel mode of action, despite exhibiting varying extents of toxicity. Anti-malarial AMPs are grouped in defensins and cecropins, while the majority of natural anti-TB AMPs are classified as bacteriocins, defensins, and cathelicidins. Synthetic AMPs, in contrast, are designed to enhance activity and selectivity while reducing toxicity and the development of resistance. AMPs have α-helical, β-sheet, or random-coil structures and are cationic, amphipathic, and highly hydrophobic, attributes that contribute to observed anti-TB and anti-malarial potential. A comprehensive understanding of AMP's structure and function, along with the use of artificial intelligence (AI) and machine learning, can provide impetus for AMP therapy as an alternative to tackle tuberculosis and malaria.
15 June 2026
Read appraisal →JMIR public health and surveillance
Digital Health Center App for Community and National Malaria Surveillance in Cambodia: Implementation Case Study
BACKGROUND: By 2015, the emergence and dissemination of multidrug-resistant Plasmodium falciparum in the Greater Mekong Subregion threatened regional and global malaria control efforts. In response, Greater Mekong Subregion countries committed to malaria elimination by 2030, with strengthened surveillance as a strategic pillar. In 2017, Cambodia introduced an elimination-oriented digital Malaria Information System (MIS). Its health center app enables real-time, geo-located, case-based malaria reporting across primary health centers, and is fully integrated with the MIS. OBJECTIVE: This study aimed to evaluate the real-world national implementation of Cambodia's Android-based health center app, considering coverage, fidelity, timeliness, and data use, and their effects on malaria surveillance performance, case management, programmatic response, and public health outcomes. METHODS: System performance and public health use were assessed using system-generated metadata, national surveillance data, and user surveys. Operational indicators included technical performance, data completeness, and reporting timeliness, alongside surveillance outcomes such as case notification, classification, reactive case detection, and foci investigation. Nationwide user experience was measured via a survey of 761 health centers across 21 provinces, with in-depth structured surveys at 9 health centers in 3 provinces. Descriptive analyses evaluated system functionality, contribution to malaria surveillance and response, and usability among frontline health workers. RESULTS: The health center app demonstrated strong technical performance, with rapid loading and resilient data transmission under low-bandwidth conditions, supporting reliable reporting in resource-constrained settings. Integrated real-time dashboards provided analytics for case management, surveillance monitoring, risk stratification, and targeted public health interventions. Data completeness remained high (99%, 89/90 fields in 2024), demonstrating consistent routine use even as case incidence declined. Between January 1, 2025, and July 31, 2025, 69 malaria cases were reported nationally (23 locally acquired, 7 domestically imported, and 39 internationally imported). Of these, 95.7% (66/69) were notified and classified within 1 day. Reactive case detection was completed within 3 days for all 21 eligible cases, and 16 of 19 eligible foci received a response within 7 days, indicating strong operational responsiveness. User surveys showed 96.3% (733/761) of health centers were satisfied or very satisfied, 90.1% (686/761) reported rare or no technical issues, and 91.7% (698/761) found the app easy to navigate. Operational challenges included limited internet connectivity, transport to remote areas, and electricity interruptions. In-depth surveys confirmed high uptake, confidence in reporting, and routine use of surveillance data, although gaps in local analytical capacity were identified. CONCLUSIONS: Developed and managed locally to enhance sustainability, the MIS drove significant reductions in malaria case incidence, with the health center app contributing timely, complete, structured reporting at the point of care. Public health responses were facilitated by real-time analysis, targeted interventions, and decentralized decision-making. User engagement was sustained as malaria cases declined, and further enhancements are planned to ensure seamless transition to postelimination surveillance, reducing the risk of malaria reestablishment in Cambodia.
13 June 2026
Read appraisal →Vaccine
Can a DNA vaccine protect against Chagas disease? A systematic review of preclinical studies.
Chagas disease, caused by Trypanosoma cruzi, remains a major neglected tropical disease with limited treatment options. DNA-based vaccination has been explored as a preventive strategy, but its overall efficacy and translational value remain uncertain. Despite encouraging preclinical findings, the evidence on DNA-based vaccines against T. cruzi remains heterogeneous and has not been systematically integrated across outcomes. A comprehensive review is therefore needed to contextualize the current knowledge and define the translational relevance of this platform. To systematically review preclinical in vivo evidence on the efficacy of DNA-based vaccination against T. cruzi, focusing on parasitological, immunological, histopathological, and cardiac outcomes. PubMed/MEDLINE, Scopus, Embase, and Web of Science were searched without date restrictions. Eligible studies were controlled in vivo experiments evaluating DNA vaccines against T. cruzi in animal models. Two reviewers performed study selection, data extraction, risk-of-bias (SYRCLE) and certainty of evidence (GRADE) assessment independently. Thirty preclinical studies were included. Murine models predominated, especially BALB/c, C57BL/6, and C3H/He mice, although canine studies added translational relevance. Naked plasmid DNA, Salmonella-delivered constructs, and adjuvanted DNA vaccines were the most common platforms. The principal antigens belonged to the trans-sialidase family and amastigote surface proteins. Overall, vaccination was associated with reduced parasitemia, improved survival in several murine models, Th1 immune responses characterized by increased IFN-γ, IgG2a, and CD8+ T-cell activation, as well as attenuation of inflammatory, histopathological, and cardiac damage. In canine models, vaccination also reduced parasite burden and myocardial inflammation, although protection remained incomplete. Confidence in the evidence was limited by substantial heterogeneity in animal background, antigen selection, parasite strain, inoculation route, dosing regimens, and follow-up duration. Frequent unclear risk of bias and incomplete reporting prevented meta-analysis and constrain causal inference. DNA-based vaccination against T. cruzi can induce Th1 immunity and reduce parasitological and tissue injury outcomes, but protection is often partial and rarely sterilizing.
11 June 2026
Read appraisal →International journal of biometeorology
Integrating google trends and hybrid statistical-machine learning models for dengue surveillance in an inland vietnamese province: a 94-month evaluation (2013-2021) with search-signal anomaly screening
Dengue transmission in inland Southeast Asia shows strong seasonality and short-term surges that challenge timely public-health response. We assessed whether province-level Google search activity can support short-horizon dengue monitoring in Dong Nai, Vietnam. Monthly reported dengue cases from July 2013 to April 2021 were aligned with the Google Trends index (GTI) for "Sốt xuất huyết". Models were evaluated using leakage-free rolling-origin expanding-window cross-validation with 3-month validation blocks. We compared a negative binomial (NB) autoregressive baseline, NB models incorporating GTI, tree-based machine-learning models using the same covariates, and a simple NB-random-forest ensemble. Predictive performance was assessed using root mean squared error (RMSE), mean absolute error (MAE), R2, and discrimination for 95th-percentile outbreak exceedance. Cross-correlation peaked at lag 0, indicating that GTI functioned primarily as a contemporaneous nowcasting signal rather than a long-lead predictor. NB models incorporating GTI showed competitive calibration, while boosted tree models achieved the lowest point-estimate errors; XGBoost achieved RMSE ≈ 40.95 and R2 ≈ 0.861 compared with RMSE ≈ 45.23 and R2 ≈ 0.823 for NB with GTI. Adding GTI to the autoregressive NB baseline reduced RMSE by 11.77%, but the 95% confidence interval crossed zero, indicating modest and statistically non-significant incremental gain. Search-signal anomaly screening suggested that GTI spikes largely coincided with epidemic peaks and did not clearly inflate out-of-sample errors. Overall, GTI provides operational value for dengue nowcasting and alert triage in inland provinces, while future systems should integrate climate, vector, mobility, and media-monitoring data.
9 June 2026
Read appraisal →Scientific reports
Prevalence and Risk Factors for Cytomegalovirus Retinitis Among People Living with HIV in Sub-Saharan Africa in the Antiretroviral Therapy Era: A Systematic Review and Meta-Analysis
Cytomegalovirus retinitis has remained an alarming and potentially vision-threatening opportunistic disease in the population living with HIV, especially in cases of extreme immunosuppression. Although the introduction of antiretroviral therapy has led to a drastic decline in the number of cytomegalovirus retinitis cases reported in most parts of the world, the current epidemiology of cytomegalovirus retinitis in sub-Saharan Africa has seemed unusual in early reports, unexpectedly portraying low disease prevalence rates despite the high number of HIV cases in the concerned region. This systematic review and meta-analysis aimed to estimate the pooled prevalence of cytomegalovirus retinitis among people living with HIV in sub-Saharan Africa in the antiretroviral therapy era, and to identify associated risk factors. The search of databases included Medline using the search engine PubMed, Google Scholar, and the African Journals Online database named AJOL. For inclusion, studies must have included an eye examination to verify the presence of cytomegalovirus retinitis. The data was combined using the logit transformation model. Heterogeneity was tested using the I-squared test and the Cochran Q test. A total of ten studies involving 1,931 participants from nine sub-Saharan Africa countries were found eligible. The proportion of cytomegalovirus retinitis varied from 0.34% to 15.8%. Pooled prevalence was found to be 3% (95% CI: 1.6-5.4%) with low to moderate inter-study variation (I² = 17.8%). Substantial variation in the proportion was found in different sub-Saharan Africa regions; it was found to be less than 1% in West Africa, 3-4% in Southern Africa, 7% in East Africa and 6% in Central Africa. Across all studies, the strongest and most consistent risk factors for cytomegalovirus retinitis were profound immunosuppression, particularly CD4 < 50 cells/µL. Antiretroviral therapy-naïve status, poor adherence, and presence of advanced AIDS-defining illnesses were additional contextual risk markers. Cytomegalovirus retinitis is an under-recognized but important source of preventable blindness among people living with HIV. Prevalence in sub-Saharan Africa differed from that in Asian early antiretroviral therapy era cohorts but is relevant in settings where late HIV presentation occurs. Systematic retinal screening in people living with HIV with low CD4 counts < 50 cells/µL and expanded HIV care and treatment services are important to prevent blindness due to cytomegalovirus retinitis.
31 May 2026
Read appraisal →PLoS neglected tropical diseases
Feasibility study of an AI-powered mobile app to support cutaneous leishmaniasis diagnosis in the Brazilian Amazon
BACKGROUND: Cutaneous leishmaniasis (CL) remains a major public health challenge, especially in Brazil's Amazon, where environmental and economic pressures sustain transmission. Delayed diagnosis drives morbidity, stigma, and costs. Community health workers are pivotal yet under-equipped for early triage. Artificial intelligence, effective in dermatologic imaging, is underused for CL; feasible, offline clinical tools could accelerate referral and timely care. This study aimed to evaluate the feasibility of an AI-assisted tool for early CL triage in the Brazilian Amazon by: (i) developing an AI model for CL identification from clinical skin lesion images; (ii) integrating the model into an offline-optimized mobile application for resource-limited settings; and (iii) conducting initial, real-world clinical validation. METHODS: Exploratory, IRB-approved feasibility study. Retrospective images from Brazilian Amazon sites informed a two-stage AI pipeline (lesion segmentation+classification) integrated into an offline mobile app. Multicenter validation in ideal- and real-world scenarios. Primary metric AUC-ROC; secondary sensitivity/specificity. One-sided tests: AUC-ROC [Formula: see text]0.70; ideal-world sensitivity [Formula: see text]0.75. RESULTS: For the Classification Model, 64 images were assigned to the test set while 1,160 were used for training and validation (80:20 split), with DenseNet121 yielding the highest accuracy of 0.88. The full AI pipeline (Segmentation and Classification models) achieved an accuracy of 0.81, an F1-score of 0.80, an AUC-ROC of 0.90, and a sensitivity of 0.76. In the ideal-world analysis, sensitivity reached 0.92, the F1-score was 0.84, and specificity was 0.42. CONCLUSIONS: We demonstrate the feasibility of an offline, AI-assisted mobile tool to support triage and referral for cutaneous leishmaniasis in the Brazilian Amazon. Performance reflects preliminary, descriptive point estimates from an initial diagnostic accuracy assessment and should be interpreted with caution; the tool is not intended for standalone diagnosis. Next steps include prospectively powered clinical validation, usability refinements, and regulatory evaluation, including alignment with ANVISA requirements in Brazil. Overall, this work represents an initial step toward closing the gap in clinically supported diagnostic tools for neglected tropical diseases in resource-constrained settings.
30 May 2026
Read appraisal →Renal failure
Prognostic factors in malaria patients with acute kidney injury: a systematic review and meta analysis
This systematic review and meta-analysis aims to evaluate the predictors of mortality in malaria patients with AKI. Studies were searched in PubMed, Scopus, Ebsco, and ScienceDirect. We included observational studies that showed the association between clinical or laboratory abnormalities and mortality, reported in odds ratio. The quality of each study was assessed using the Newcastle-Ottawa Scale. Meta-analysis was performed using R. Sixteen studies with 1,104 patients were analyzed. Factors significantly associated with mortality were respiratory distress syndrome (OR: 18.50, p < 0.001), neurological involvement (OR: 12.83, p < 0.001), disseminated intravascular coagulation (OR: 12.00, p < 0.001), hypotension (OR: 18.23, p < 0.001), oliguria (OR: 3.41, p = 0.002), ventilator requirement (OR: 30.35, p < 0.001), leukocytosis (OR: 4.87, p = 0.003), hyponatremia (OR: 3.67, p = 0.048), acidosis (OR: 4.88, p < 0.001), hyperkalemia (OR: 3.99, p < 0.001), and jaundice (OR: 5.03, p = 0.001). ARDS, neurological involvement, DIC, hypotension, oliguria, ventilator requirement, leukocytosis, hyponatremia, acidosis, hyperkalemia, and jaundice were associated with mortality in malaria patients with AKI. The findings underscored the importance of heightened awareness and vigilance in managing patients with these conditions.
26 May 2026
Read appraisal →PloS one
A qualitative study to inform the design and implementation of AI-driven diagnosis: Challenges, barriers, and clinical insights of physicians
INTRODUCTION: Acute febrile illnesses are significant clinical challenge in tropical regions due to overlapping symptomatology among infections such as dengue, scrub typhus, and leptospirosis. This diagnostic dilemma leads to delays in appropriate treatment and negatively impacted patient outcome due to limited diagnostic tool availability. Recent advancement in artificial intelligence (AI) application in healthcare help in developing diagnostic aiding tool in such clinical dilemma. AIMS: Study aimed to explore physicians' perspectives on diagnostic challenges of tropical Acute-febrile-illnesses and assess perceived utility of AI as a supportive tool in clinical decision-making. METHODS: A qualitative interview was conducted using validated semi-structured interview guide using literature and expert opinion and validated by IPR method. To understand the physicians perspective on management infectious diseases in critical care, interview guide administered among ten physicians with 10-30 years of experience across different centres of India. Interviews were audio-recorded, transcribed verbatim, and thematically analyzed using ATLAS.ti software. RESULTS: Four major themes emerged: clinical experience and practice, diagnostic-challenges, diagnostic-parameters and decision-making, and AI integration in clinical-practice. However, no statistical test can be performed since study mainly focused to understand perception of physicians with respect to managing illness and hence prevalence cannot be determined. Diseases such as dengue, scrub typhus, and leptospirosis were reported as most prevalent, particularly during monsoon seasons. Key diagnostic challenges included overlapping symptoms, diagnostic delays, limited sensitivity/specificity of available tests, and cost constraints. Physicians primarily relied on clinical judgment and laboratory findings, despite the limitations. Most of the participants expressed positive attitudes toward the potential of AI as supportive tool, citing its ability to enhance diagnostic accuracy and streamline clinical workflow with proper validation. CONCLUSIONS: Growing in clinical dilemma AI has significant role in diagnosis of tropical fever with integration of the clinical data & physician perspective can successfully able to incorporate in clinical application.
23 May 2026
Read appraisal →Clinical infectious diseases : an official publication of the Infectious Diseases Society of America
Dolutegravir Reduces Human T-Cell Lymphotropic Virus Type 1 Proviral Load and Improves Neurological Outcomes in a Phase 2 Controlled Trial
BACKGROUND: No specific therapy is approved for human T-cell lymphotropic virus type 1 (HTLV-1) infection. We tested the effect of dolutegravir (DTG) on clinical outcomes and on HTLV-1 proviral load (PVL) in adults with HTLV-1 infection. METHODS: We conducted an open-label, randomized controlled phase 2 trial in Salvador, Brazil. Symptomatic adults with HTLV-1 infection were randomized 1:1 to DTG 50 mg once daily or vitamin C (VTC) 500 mg once daily for 48 weeks. We evaluated changes in gait performance (timed 10-meter walk test [T10MWT]). Key secondary endpoints included change in PVL and prespecified neurofunctional and urinary outcomes. Primary analyses emphasized intragroup and between-group comparisons; exploratory per-protocol analyses were performed for neurofunctional measures. Asymptomatic participants were included for PVL and immunological evaluations. RESULTS: Eighty-three participants (53 symptomatic) were randomized (DTG, n = 43; VTC, n = 40). At week 48, there was no between-group difference in T10MWT. However, DTG use significantly reduced PVL over 48 weeks compared with VTC (P < .001). Exploratory per-protocol analyses found significant improvements associated with DTG use in lower limb spasticity (P < .001), sensory function (light touch, P = .035; pinprick, P = .001), and median nocturia frequency (P = .012). Network analysis of cytokine expression showed a change in the DTG group from baseline to week 48, with loss of negative correlations and a more balanced pattern. DTG was well tolerated, with no unexpected safety signals. CONCLUSIONS: In this pilot randomized trial, DTG use was associated with significantly reduced PVL and improvement in neurofunctional and immunological characteristics of participants in exploratory analyses. These findings provide evidence supporting the use of integrase inhibitors for HTLV-1 infection. Clinical Trials Registration. Brazilian Clinical Trial Register (ReBEC), code RBR-5x7ccxp.
22 May 2026
Read appraisal →The Journal of infectious diseases
Safety, Tolerability, and Pharmacokinetics of 6-Diazo-5-Oxo-L-Norleucine in Malawian Adults With and Without Malaria: A Phase 1 Dose-Escalation Clinical Trial
BACKGROUND: Cerebral malaria (CM) is a common cause of febrile coma among African children. Despite treatment with highly efficacious intravenous artesunate, CM remains associated with high mortality and neurologic sequelae. In a mouse CM model, the glutamine antagonist 6-diazo-5-oxo-L-norleucine (DON) demonstrated robust efficacy as a potential adjuvant therapy. Before testing DON in children with CM, we investigated tolerability in African adults, including individuals with malaria. METHODS: We conducted an open-label, prospective, dose-escalation, phase 1 clinical trial of single-dose intravenous DON in Blantyre, Malawi. Participants included healthy adults and adults with uncomplicated malaria, enrolled in dose-cohorts of 10 and administered DON at 0.1, 1.0, 5.0, or 10 mg/kg. We assessed adverse events (AEs) and plasma pharmacokinetics. RESULTS: Forty healthy adults and 38 adults with uncomplicated malaria received DON. Transient, asymptomatic creatinine elevation occurred 12 hours postinfusion in 18% of all participants. Nausea and vomiting were uncommon at 0.1 and 1.0 mg/kg but occurred more frequently at 5.0 and 10 mg/kg DON. All DON-related AEs resolved rapidly, without sequelae, and did not significantly differ between healthy and uncomplicated malaria participants. In healthy adults, maximum plasma concentrations increased proportional to dose, but adults with malaria had greater than dose-proportional increases. Terminal half-life ranged from 1.7 to 4.1 hours. CONCLUSIONS: DON was well tolerated in healthy adults and adults with uncomplicated malaria. Higher doses were associated with transient gastrointestinal AEs. Pharmacokinetics were minimally influenced by malaria disease. These results provide critical data to guide dosing strategies for adjunctive DON in children with CM. Clinical Trials Registration. NCT05478720.
18 May 2026
Read appraisal →Philosophical transactions of the Royal Society of London. Series B, Biological sciences
A meta-analysis of gut microbiome research in malnourished African populations: a natural language processing approach
Malnutrition still affects millions of children in Africa. Changes in the gut microbiome have been implicated in malnutrition, but there has been inconsistent nomenclature of microbes. This meta-analysis reviews the microbiome literature using natural language processing (NLP) methods. We searched PubMed for gut microbiome studies of undernourished children living in low- and middle-income countries (LMICs). The primary analysis focused on continental coverage and study characteristics of microbiome research in sub-Saharan Africa (ss-Africa). We also used an NLP tool for normalizing primary data from full-text publications in ss-Africa compared with other LMICs, and between diseased and healthy children. We identified 16 studies. Most studies were conducted in Malawi and characterized the faecal microbiome using 16S rRNA sequencing. For comparison, 18 studies conducted in Bangladesh, India, Pakistan and Peru were included. With this, we identified frequently reported microbes that were distinctly identified in ss-Africa and highlighted possible signatures of an undernourished faecal microbiome across the globe. The consistent associations between elevated Pseudomonadota levels and severe acute malnutrition provide new insights into host-microbiome interactions in African contexts. However, the overlap between taxa associated with healthy and stunting underscores the need for further research to better inform potential targeted interventions in Africa. This article is part of the theme issue 'Biological, biomedical and environmental drivers of stunting'.
15 May 2026
Read appraisal →BMJ global health
Integrated mass drug administration for yaws eradication: evidence from a comparative observational study in Papua New Guinea and a systematic review with network meta-analysis
BACKGROUND: Yaws is a chronic infectious disease that disproportionately affects under-reached communities. In 2023, Papua New Guinea (PNG) reported 100 165 suspected yaws cases, accounting for 45% of cases reported worldwide. The WHO targets yaws eradication by 2030, primarily through mass drug administration (MDA) of azithromycin. This study evaluates the impact of an integrated MDA programme in PNG and reviews global evidence on optimal MDA strategies through a network meta-analysis (NMA). METHODS: A comparative observational study was undertaken analysing outpatient department (OPD) attendances between West New Britain province (WNB; intervention) and New Ireland province (NIP; comparator) from November 2023 to August 2024. The intervention in WNB involved a single-round, integrated four-drug MDA provided in December 2023, comprising azithromycin, ivermectin, diethylcarbamazine and albendazole. Temporal trends in OPD attendances were analysed using negative binomial regression. A Bayesian NMA of six studies identified through a systematic review compared the effectiveness of azithromycin-based regimens for yaws eradication. RESULTS: Between Q3 2023 and Q1 2024, yaws-related OPD attendances in WNB declined significantly, with a 41% (p<0.0001) reduction relative to the comparator province (NIP). This reduction was sustained for at least 6 months following MDA. Over the same period, a 33% decline in total skin-related outpatient attendances was observed. In the NMA, three rounds of azithromycin MDA were associated with lower odds of active yaws at follow-up than observation (OR 0.04, 95% CrI 0.005 to 0.24) and had the highest probability of being ranked most effective. Single-round azithromycin MDA was also associated with reduced odds of active yaws at follow-up (OR 0.15, 95% CrI 0.05 to 0.45). CONCLUSION: In a high-burden setting, a single round of integrated MDA was associated with substantial early reductions in yaws burden. Multi-round azithromycin strategies, particularly three-round regimens, were associated with larger and more sustained reductions in community prevalence. These findings inform considerations for yaws control efforts in settings with persistent transmission.
15 May 2026
Read appraisal →Lancet (London, England)
Impact of introducing RTS,S/AS01E malaria vaccine on mortality in young children in Ghana, Kenya, and Malawi: an observational evaluation of a cluster-randomised implementation programme
BACKGROUND: Malaria vaccines have been added to immunisation schedules in 25 sub-Saharan African countries, with the expectation that deaths in young children would be prevented. The introduction of the RTS,S/AS01E malaria vaccine (RTS,S) in Ghana, Kenya, and Malawi in 2019 was evaluated over 4 years to show the impact on mortality in young children and to monitor severe malaria admissions, vaccine uptake, and safety. Favourable evidence on safety and impact on severe malaria admissions during the first 2 years contributed to WHO's recommendations on malaria vaccines. Here, we report the primary analysis of the impact on mortality at 46 months. METHODS: Clusters of administrative units (districts in Ghana, subcounties in Kenya, and groups of immunisation clinics in Malawi), each with an estimated annual birth cohort of about 4000 children, were randomly assigned 1:1 to introduce the RTS,S malaria vaccine in 2019 (implementation areas), or to implement later (comparison areas). RTS,S was delivered in a four-dose schedule, at age 6, 7, 9, and 24 months in Ghana and Kenya, and at age 5, 6, 7, and 22 months in Malawi. Surveillance for post-neonatal mortality in children younger than 5 years was established throughout by a network of 26 000 local reporters who notified deaths in their community. The families were then visited at home by study staff to confirm details and complete a verbal autopsy. Surveillance for severe malaria and other conditions was strengthened in 18 sentinel hospitals serving part of the study area and maintained for 46 months. Uptake of RTS,S and other vaccines was monitored by the Expanded Programme on Immunisation in each country and independently through three household coverage surveys, at baseline, and at about 18 months and 30 months after introduction of RTS,S. The primary outcome of this impact evaluation was mortality due to any cause, except injury, in children eligible to receive three doses of RTS,S. Mortality rate ratios were estimated by comparing the ratio of deaths among vaccine-eligible age groups to deaths in non-eligible age groups between implementation and comparison areas. This evaluation is registered on ClinicalTrials.gov (NCT03806465) and is complete. FINDINGS: 158 clusters (66 in Ghana, 46 in Kenya, and 46 in Malawi) were selected and randomly assigned; 79 areas served as implementation areas and 79 as comparison areas. By the end of the 46-month evaluation period, 1 289 504 children had received the first dose of RTS,S, 1 158 850 had received the second dose, 1 068 039 had received a third dose, and 436 527 had received a fourth dose. Coverage assessed in 2022 was 82·8% (95% CI 80·7-84·9) for the first dose, 71·1% (68·8-73·5) for the third dose, and 39·9% (36·9-42·9) for the fourth dose. Excluding deaths due to injury, there were 5576 deaths in implementation areas versus 6152 in comparison areas in children eligible to have received the third dose of RTS,S, and 7534 versus 7044 deaths among non-eligible children. The mortality rate ratio was 0·87 (95% CI 0·77-0·97; p=0·016). INTERPRETATION: Introduction of the RTS,S malaria vaccine in routine immunisation programmes was associated with a significant reduction in mortality in young children, averting about one in eight deaths, in areas with moderate coverage of three doses of the vaccine and low uptake of the fourth dose. These results highlight the urgency to accelerate the deployment of malaria vaccines in areas of Africa where malaria continues to be a leading cause of child mortality. FUNDING: WHO; Gavi, the Vaccine Alliance; the Global Fund to Fight AIDS, Tuberculosis and Malaria; and Unitaid. TRANSLATIONS: For the French translation of the abstract see Supplementary Materials section.
13 May 2026
Read appraisal →Vaccine
Effects of candidate vaccines against Zika virus infection: A systematic review of the clinical trials
INTRODUCTION: The 2015-2016 Zika virus (ZIKV) pandemic revealed a pathogenic potential, including Guillain-Barré syndrome and Congenital Zika Syndrome (CZS). Despite the decline in incidence, the potential for future circulation and the absence of specific antivirals underscore continued scientific interest in prophylactic vaccine development. OBJECTIVE: To synthesize evidence from clinical trials regarding the safety and preliminary immunogenicity of current ZIKV vaccine candidates. METHODS: This systematic review followed PRISMA guidelines (CRD420251056463). Searches were performed in MEDLINE, Embase, Web of Science, SciELO, and LILACS for clinical trials published between 2015 and 2025. Risk of bias was assessed using the Cochrane RoB 2 tool. RESULTS: Ten Phase 1 clinical trials were included, evaluating four platforms: inactivated virus (ZPIV, TAK-426, VLA1601), DNA (GLS-5700, VRC5283), mRNA (mRNA-1325, mRNA-1893), and viral vector (Ad26.ZIKV.001). All candidates demonstrated acceptable safety profiles, with predominantly mild-to-moderate and transient adverse events (e.g., injection site pain, fatigue, and headache); no vaccine-related serious adverse events were reported. Most platforms induced robust neutralizing antibody responses. Specifically, TAK-426 showed immune persistence for up to two years, while mRNA-1893 maintained responses for 13 months. The viral vector vaccine (Ad26.ZIKV.001) achieved 100% seroconversion with a single dose. Previous orthoflavivirus exposure did not significantly hinder vaccine-induced immunogenicity. Most studies presented a low risk of bias. CONCLUSIONS: ZIKV vaccine candidates across diverse technological platforms are safe and highly immunogenic. The evidence of long-term durability and the success of single-dose or mRNA regimens support the progression of the most promising candidates to Phase 2/3 trials.
12 May 2026
Read appraisal →International health
Neglected tropical diseases in conflict-related humanitarian emergency settings: a systematic review of the literature
Neglected tropical diseases (NTDs) are a group of 21 conditions affecting an estimated 1 billion people worldwide, causing significant mortality and morbidity. WHO has targeted their control, elimination or eradication by 2030, while highlighting that conflict and humanitarian emergencies are risks to achieving this. A systematic review of peer-reviewed literature was undertaken, using terms related to conflict-related humanitarian emergencies (CRHE), based on the Armed Conflict Location & Event Data Project codebook terms for defining emergencies and terms including all WHO-defined NTDs. After a two-stage screening process, 26 papers were included. Common challenges for NTD programmes in CRHE were healthcare access, infrastructure, population movement and data quality. Multisectoral collaboration between actors in conflict-settings was offered as a learning for NTD programmes, along with community participation and decentralisation. Evidence gaps were identified in the knowledge base for certain NTDs and in high-quality evidence for interventions in CRHE. Collaboration is a key area for focused improvement for NTD programmes in CRHE. This should be across sectors and extend to research and analysis approaches, to ensure the most effective interventions are identified and implemented and that NTD road map targets can be achieved.
12 May 2026
Read appraisal →Transactions of the Royal Society of Tropical Medicine and Hygiene
Quality of life in Indian people affected by leprosy? A systematic review from the country with the highest burden of leprosy cases.
Quality of life (QoL) is important for people with leprosy since the disease can cause physical and psychological problems. These problems may result in stigma and social discrimination. India reported 107 851 new leprosy cases for the year 2023-24, accounting for 61.6% of new cases detected globally. This systematic review was conducted to assess the QoL among people affected by leprosy in India using existing literature. The Scopus, PubMed and Infolep databases were searched for articles for this systematic review and included only studies conducted in India. The critical appraisal tool of cross-sectional studies (AXIS) was used to assess the study quality and risk of bias. The search identified 253 articles. After screening titles and abstracts, 23 full-text articles were assessed for eligibility and 12 studies were included in the systematic review. The World Health Organization Quality of Life-Bref instrument was used to measure QoL. Of the 12 studies, the factors of disability (9 studies) and old age (8 studies) were highly associated with low levels of QoL. Five studies identified that low levels of QoL are associated with being female with the leprosy. Early identification and prevention of disabilities are important steps in improving the QoL. Increased investment is needed in leprosy programmatic activities and research to achieve the target of zero leprosy.
10 May 2026
Read appraisal →ChemMedChem
A Novel Triose Phosphate Isomerase Inhibitor With Dual Trypanosomicidal Activity was Identified Using Artificial Intelligence-Based Virtual Screening
Chagas disease and leishmaniasis are neglected protozoan diseases recognized by the World Health Organization as major public health problems. These diseases affect millions of people worldwide, yet effective treatments remain unavailable. Triosephosphate isomerase (TIM), a glycolytic enzyme that exhibits high catalytic efficiency for the isomerization of glyceraldehyde-3-phosphate and dihydroxyacetone-phosphate exclusively in its dimeric form, was subjected to virtual screening. Using a deep neural network for structure-based drug design that predicts binding affinity between small molecules and proteins of known structure, 12.5 million commercially available compounds were screened. From this, 82 compounds were selected for in vitro evaluation. Six compounds inhibited TIM from Trypanosoma cruzi, three of which exhibited anti-T. cruzi activity. Eight compounds demonstrated activity against the parasites T. cruzi and Leishmania infantum. Two compounds showed similar potency against both parasites: 3-(1-acetyl-5-(4-bromophenyl)-4,5-dihydro-1H-pyrazol-3-yl)-4-hydroxy-6-methyl-2H-pyran-2-one (IC50 = 16 ± 3 μM) and 3-[(4-bromophenyl)sulfanyl]-1-(3-nitrophenyl)propan-1-one (IC50 = 12 ± 1 μM). These compounds exhibit favorable selectivity and toxicological profiles, as well as in vivo activity, indicating their potential for future drug development.
2 May 2026
Read appraisal →Lancet (London, England)
Safety and efficacy of the monoclonal antibody L9LS for malaria prevention in children exposed to perennial malaria transmission in Kenya: a randomised, double-blind, placebo-controlled, phase 2 trial
BACKGROUND: Malaria remains a major cause of mortality globally, especially among young children in sub-Saharan Africa. The long-acting monoclonal antibody L9LS has shown high efficacy in preventing malaria in children aged 6-10 years exposed to seasonal transmission but remains untested in perennial transmission settings and younger children. We assessed the safety, tolerability, and efficacy of L9LS in infants and children in a high perennial malaria transmission setting. METHODS: This double-blind, two-part, randomised, placebo-controlled, phase 2 trial was done in Siaya county in western Kenya. In parts 1a and 1b, we tested the safety and tolerability of L9LS using an age de-escalation and dose escalation approach and randomly assigned (3:1) cohorts of healthy children (three cohorts aged 5-10 years, three cohorts aged 5-59 months, and two cohorts aged 5-71 months) to L9LS at doses of 5, 10, 20, 30, or 40 mg/kg subcutaneously or to placebo (normal saline). In part 2, healthy children aged 5-59 months were randomly assigned (1:1:1) by use of centralised computer-generated lists to receive two doses of L9LS at 10-20 mg/kg at baseline and month 6, one dose of L9LS at baseline and placebo at month 6, or placebo at both timepoints. Children were followed up for 12 months with monthly clinic visits and blood smear collections. Primary safety outcomes were incidence and severity of local and systemic solicited adverse events within 7 days of dosing and serious adverse events throughout follow-up. The primary efficacy endpoint was Plasmodium falciparum infection detected by blood smear over 12 months. Primary analyses were done in the modified intention-to-treat population, consisting of all randomly assigned participants who received the study intervention. This trial is registered with ClinicalTrials.gov (NCT05400655) and is complete. FINDINGS: In parts 1a and 1b, 96 children were enrolled and randomly assigned between Oct 1, 2022, and Jan 16, 2024; 72 participants were assigned to L9LS and 24 were assigned to placebo. In part 2, 324 children aged 5-59 months were enrolled and randomly assigned between Jan 26 and June 2, 2023; 108 children were assigned to one-dose L9LS, 106 to two-dose L9LS, and 110 to placebo. Across all study parts, grade 3 or worse treatment-related adverse events occurred after four (1%) of 384 L9LS injections and two (1%) of 338 placebo injections; these events all resolved by study end. The proportion of solicited and unsolicited adverse events was similar across all L9LS dose groups. There were no serious adverse events related to the trial. In part 2, 70 (66%) of 106 children in the two-dose L9LS group had at least one P falciparum infection during the 12-month follow-up versus 91 (83%) of 110 children in the placebo group (protective efficacy 42·7%, 95% CI 22·5-57·7; p=0·0003). INTERPRETATION: L9LS was protective against malaria in young children in western Kenya without evident safety concerns over 6-12 months. A higher dose of L9LS might be needed to achieve high-level efficacy against malaria in young children exposed to intense perennial P falciparum transmission. FUNDING: Gates Foundation.
2 May 2026
Read appraisal →PloS one
upsML: A high-accuracy machine learning classifier for predicting Plasmodium falciparum var gene upstream groups
Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1), encoded by the hypervariable var gene family, is central to malaria pathogenesis, influencing both disease severity and immune evasion. Classifying var genes into upstream groups (upsA, upsB, upsC, upsE) is important for understanding parasite biology and clinical outcomes, but remains challenging, especially with partial sequences, such as the DBLα tag or RNA-Seq assemblies. We developed upsML, a machine-learning-based classifier trained on 2,530 curated var genes, to accurately assign upstream groups based on sequence features from different partial gene regions. We compared seven methods, including support vector machines, random forests, XGBoost, and HMMER models. Several models in upsML achieve accuracies of 83% for DBLα-tag sequences and 92% for full-length PfEMP1 sequences, thereby significantly outperforming existing tools. Additionally, we developed a model to distinguish internal from subtelomeric var genes, which we applied to a global collection of P. falciparum genomes, revealing a higher frequency of internal var genes in Asia. upsML is available at https://github.com/sii-scRNA-Seq/upsML, providing a robust and efficient resource for large-scale var gene analysis. It can classify var genes from 20 genomes in under one second.
17 Apr 2026
Read appraisal →Journal of chemical information and modeling
Multiscale-Aware Graph Embedding Approach Uncovers LC-61, a Potent Anti-Leishmania infantum Compound
Visceral leishmaniasis caused by Leishmania infantum remains a lethal disease with few therapeutic options, necessitating innovative computational methods and approaches to accelerate drug discovery. Here, we present a graph neural network (GNN) framework incorporating well-established multiscale mechanisms to improve the identification of novel antileishmanial compounds. Across two classificatory antileishmanial data sets, our GNNs demonstrated significant improvements in predictive performance, with area under the receiver operating characteristic curve (AUC) increases of 2.2-29.2% on the imbalanced data set (activity cutoff: 1 μM) and 3.4-22.5% on the balanced data set (activity cutoff: 10 μM) compared to default GNNs. Subsequently, the framework was applied to screen a library of approximately 1.3 million compounds, pinpointing LC-61 as a potent antileishmanial agent with nanomolar activity against intracellular L. infantum (IC50 = 0.076 μM) and minimal cytotoxicity to macrophages (THP-1 CC50 = 157 μM). A comprehensive in vitro ADME profiling revealed that LC-61 combines high solubility at both acidic and physiological pH (>28 μg/mL), balanced lipophilicity (eLogD = 4.07), and favorable passive permeability (PAMPA = 4.86 × 10-6 cm/s), while exhibiting lower microsomal stability. Overall, our GNN framework effectively accelerated the discovery of LC-61, a novel and biologically validated hit suitable for hit-to-lead optimization.
14 Apr 2026
Read appraisal →Journal of clinical microbiology
Etiologies of community-acquired febrile illness identified by TaqMan Array Card qPCR on blood samples: a systematic review and meta-analysis
UNLABELLED: Community-acquired febrile illness presents a significant diagnostic challenge. The TaqMan Array Card (TAC) enables simultaneous detection of many bacterial, viral, parasitic, and fungal pathogens. This systematic review aimed to characterize the etiologies of community-acquired fever diagnosed by TAC directly on blood specimens. A systematic search of PubMed, Scopus, Embase, and Web of Science (from inception to January 2026 in English) identified studies using TAC to detect pathogens directly in human blood to identify the etiology of community-acquired febrile illness. Eligible studies were appraised using a modified Joanna Briggs Institute (JBI) checklist. Pooled proportions and meta-analyses were conducted using a random-effects model. A total of 16 studies comprising 8,937 participants from 12 African and Asian countries met inclusion criteria. TAC detected at least 1 pathogen in 0.43 (95% CI [0.32; 0.54]), with high between-study heterogeneity (I² = 99%). Parasitic infections were most common (56%), nearly all due to Plasmodium spp., followed by bacterial (26%), viral (22%), and fungal (0.5%) etiologies. Plasmodium spp., Rickettsia spp., dengue virus, Lassa fever virus, Streptococcus pneumoniae, Orientia tsutsugamushi, Mycobacterium tuberculosis complex, and Salmonella spp. were the most frequently identified pathogens. Culture-negative bacteria accounted for 56% of bacterial detections. Positivity with more than 1 organism occurred in 6% of cases. TAC showed strong concordance with blood culture for culturable organisms (positive agreement: 73%, 95%CI [0.53; 0.89]; negative: 98%, 95%CI [0.95; 1.00]). TAC provides culture-independent pathogen detection and reveals overlooked causes of febrile illness, such as culture-negative bacteria. Its application may improve clinical diagnosis and surveillance programs. IMPORTANCE: Accurate identification of the causes of community-acquired febrile illness is essential for guiding clinical decision-making, surveillance programs, and public health response. This systematic review and meta-analysis synthesizes data from more than 8,937 patients across Africa and Asia tested with blood-based TaqMan Array Card (TAC) assays. TAC enabled broad, culture-independent detection of bacterial, viral, parasitic, and fungal pathogens-revealing both expected causes, such as Plasmodium spp. and dengue virus, and neglected culture-negative bacteria including Orientia tsutsugamushi, Coxiella burnetii, and Rickettsia spp. By uncovering these underrecognized etiologies, TAC provides valuable pathogen-level data to strengthen fever surveillance, inform outbreak detection, and refine regional disease prioritization frameworks. These findings highlight the potential of high-throughput molecular diagnostics to enhance infectious disease control, particularly in resource-limited settings.
9 Apr 2026
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