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Cost of illness of scrub typhus in South India - a population-based, mixed-methods study.
Get PDFBACKGROUND: Scrub typhus is a potentially life-threatening acute febrile illness found in many parts of Asia. This study aimed to estimate the cost of illness among scrub typhus cases in Tamil Nadu, South India and explore treatment-seeking behaviour.
METHODS/PRINCIPAL FINDINGS: Cases were enrolled from a population-based cohort study on scrub typhus in 32,279 individuals living in rural villages. Data on direct and indirect costs were collected using structured questionnaires from 311 scrub typhus cases of which 26 were severe. Thirteen cases with severe infections (or their relatives) underwent in-depth interviews to understand treatment-seeking pathways. The mean age of cases was 41.1 years, and 64% were female. The average monthly household income was USD 236 (standard deviation, SD 155). The average number of workdays missed in severe infection was 18 days per episode (SD 22.2) compared to 4 days (SD 11.6) in non-severe illness. The mean overall cost of illness was USD 189 (SD 495), disaggregating to USD 1,321 (SD 1045) for severe cases and USD 86 (SD 209) for non-severe. In both severe and non-severe cases, hospital admission was common (69/311) and was associated with a cost increase of over USD 400. Costs were almost twice as high in males compared to females. Catastrophic health expenditure exceeding 25% of annual income occurred in 10% of cases. Treatment by traditional healers, untrained practitioners, pharmacies and local clinics was sought even for mild fever of short duration. In-depth interviews revealed that patients preferred to have a one-off treatment enabling them to return to daily routines with little demand for fever diagnostics. There was demand for higher level of care and diagnostic procedures only when symptoms became severe or the case was a child or a pregnant woman.
CONCLUSIONS/SIGNIFICANCE: Hospitalisation, common in both severe and non-severe patients, was the driving factor for high costs. Early case recognition may reduce hospitalisations and health expenditure in highly endemic settings
Feasibility, acceptability and validity of electronic adherence monitoring among adolescents in Zimbabwe: a mixed methods study.
Get PDFBACKGROUND: Electronic monitoring devices (EMDs) may provide an objective method for assessing medication adherence. However, evidence on their validity compared to other adherence measures, their functional feasibility, and their acceptability, especially among adolescents, remains limited. Adolescents face multifaceted adherence challenges, yet there is a lack of evidence to inform the use of digital tools for adherence monitoring and support in this age group, particularly in low-income settings. We assessed feasibility, acceptability, and validity of an EMD among adolescents enrolled in the multi-country clinical trial VITALITY. METHODS: An explanatory sequential mixed methods study was embedded within the Zimbabwean site of the VITALITY trial, a randomised controlled trial evaluating weekly vitamin D supplementation on bone health in adolescents living with HIV. A random sample of 97 participants (aged 11-19 years) was provided an EMD for 24 weeks to monitor adherence to vitamin D or placebo. Validity was assessed by correlating EMD-measured adherence with serum vitamin D levels. Feasibility of the EMD was investigated through records of battery duration, network connectivity, and EMD malfunction. Seventeen participants were purposively selected for qualitative exit interviews to explore acceptability and reasons for discordance between adherence measured through the EMD and pill count. RESULTS: Ninety-seven participants, median age 16.7 (interquartile range13.5, 18.7) years, 50 (51.5%) female were provided with the EMD for a median of 24 (range 22-25) weeks. There was a strong positive correlation between EMD-measured adherence and week-48 vitamin D levels (β = 0.63, 95% CI: 0.42-0.85; R2 = 0.42; p < 0.001), supporting the validity of EMD data as a proxy for medication intake. The EMD functioned reliably despite intermittent network coverage, and no major malfunctions were reported. Adolescents found the EMDs highly acceptable due to their ease of use, discretion, and perceived motivational benefits. CONCLUSIONS: This study demonstrates that EMDs are valid, feasible, and acceptable tools for monitoring adherence among adolescents in low-income settings. These findings support the potential for broader use of EMDs to promote and monitor adherence to long-term treatments in adolescents beyond research settings. TRIAL REGISTRATION: Pan African Clinical Trials Registry (PACTR), PACTR202009897660297
Prevalence of CSF HIV VIRAL Escape and Associations With Neurocognitive Outcomes Among HIV-Associated Meningitis Survivors: A Cohort Study.
Get PDFAmong this prospective cohort of 93 Ugandan adults who survived HIV-associated cryptococcal or tuberculous meningitis, baseline secondary cerebrospinal fluid (CSF) HIV viral escape was highly prevalent and was associated with better neurocognitive outcomes at 3 months. Individuals with secondary CSF HIV viral escape were more likely to be antiretroviral therapy-naïve and to exhibit CSF pleocytosis
Interactive Transition Support for Adolescents Living with HIV Comparing Virtual and In-person delivery (InTSHA VIP): a stepped-wedge, cluster-randomised trial in South Africa.
Get PDFBACKGROUND: Adolescents living with HIV(ALHIV) often experience lower retention in care and reduced viral suppression after transitioning to adult care. Differentiated care can enhance the uptake and utilisation of evidence-based transition interventions among populations with the greatest need. We aim to investigate the effectiveness, acceptability, feasibility, implementation, and costs of in-person and mHealth-based adolescent-friendly transition interventions.
METHODS: We are conducting a type 1 hybrid implementation-effectiveness design, with a cluster-randomised, stepped-wedge trial (SWT) to assess the effectiveness of in-person and mHealth-based adolescent-friendly transition interventions on retention in care and viral suppression among adolescents aged 15–19 years with perinatally-acquired HIV and low transition readiness. The SWT will be conducted in 16 clinics in urban (eThekwini) and rural (uMkhanyakude) KwaZulu-Natal over 24 months. Clinics will be randomly allocated to receive the intervention in period 1 (early) or period 2 (delayed). ALHIV, in the standard of care clinics, will be able to access the HIV prevention and treatment services delivered through the primary health clinics. We will use the RE-AIM (Reach, Effectiveness, Adoption, Implementation, and Maintenance) framework to guide our implementation outcomes. The primary outcomes for effectiveness are: (1) retention in care and (2) viral suppression measured in three cross-sectional surveys. We will measure retention in care as 80% of ART pharmacy refills on time, and 80% of scheduled clinic appointments attended, and we define viral suppression as < 200 copies/ml. We will compare the effectiveness and implementation outcomes of the in-person intervention with the mHealth intervention and compare outcomes between urban and rural clinics.
DISCUSSION: The findings of this trial will inform the expansion of differentiated care models for ALHIV to improve the transition process from paediatric to adult HIV care, optimised to support retention in care and viral suppression.
TRIAL REGISTRATION: ClinicalTrials.gov Identifier NCT06035445.
SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12913-026-14070-8
Comparing the national cancer waiting times dataset with other linked electronic health records to measure treatment timeliness: A national cohort study of kidney cancer in England.
Get PDFBACKGROUND: Timely treatment is a vital component of high-quality cancer care. We compared a national purpose-specific dataset of cancer waiting times (CWT) with routinely collected hospital datasets ('comparator datasets') as sources of data on the timeliness of kidney cancer treatment in England. METHODS: 11,937 patients diagnosed with kidney cancer between 1st July 2022 and 31st December 2023 were included, using national linked cancer registry and CWT records. The primary analysis compared CWT records and those in comparator datasets (Hospital Episode Statistics, Systemic Anti-Cancer Therapy, and Radiotherapy datasets) in terms of the number, percentage, and timing of patients receiving treatment. Using CWT records, a secondary analysis assessed the effects of the 'waiting time adjustment policy' to account for patient treatment deferral on distributions of waiting times at patient and provider levels. RESULTS: 6971 patients were identified as having received treatment (within 100 days of decision-to-treat) according to either CWT or comparator datasets. Of these patients, 6434 (92.3%) had treatment according to both CWT and comparator datasets, with 5836 patients (90.7% of 6434) identified as receiving treatment on the same day across both dataset groups, demonstrating strong agreement. Using the waiting time adjustment policy, the mean number of days to treatment decreased from 29.2 to 27.3 days at the patient-level and from 24.3 to 22.6 days at the provider-level. CONCLUSION: This study demonstrates strong agreement in treatment records from a national, purpose-specific, and comparator datasets. Strengths of both data sources can be harnessed in linked data to evaluate treatment timeliness, enabling more detailed assessments of specific treatments and better definition of the start of treatment pathways
Nigeria's post-COVID-19 vaccine manufacturing ambitions: Opportunities and regional implications.
Get PDFBACKGROUND: Global health emergencies consistently expose and exacerbate vaccine inequities, with high-income countries prioritising their populations and leaving low- and middle-income countries (LMICs) facing delays and shortages. Diseases primarily affecting LMICs receive limited attention from global vaccine developers because of perceived low market value and limited financial return, further entrenching these disparities. Africa's limited investment in vaccine manufacturing has heightened its vulnerability during outbreaks, including yellow fever, Ebola, meningococcal meningitis, mpox, and most recently, coronavirus disease 2019 (COVID-19). AIM: This study examines the barriers to vaccine equity in Africa and critically analyses Nigeria's post-COVID-19 efforts to establish a viable, local vaccine manufacturing ecosystem. SETTING: The research focuses on Nigeria within the broader African vaccine manufacturing landscape, using it as a case study to explore both national and continental dynamics. METHODS: The study draws on document analysis of strategic plans, regulatory reports, and partnership announcements, complemented by qualitative insights from key informant interviews with stakeholders involved in vaccine policy, regulation, and production in Nigeria and across West Africa. RESULTS: Post-pandemic momentum has catalysed significant shifts: Nigeria has developed a national vaccine manufacturing strategy and secured international partnerships and financing commitments. The regulatory authority, National Agency for Food and Drug Administration and Control (NAFDAC), achieved the World Health Organization (WHO) Maturity Level 3 status, marking critical progress. Nonetheless, persistent gaps remain in research and development capacity, workforce development, regulatory agility, and infrastructure readiness. CONCLUSION: While Nigeria has made notable progress since the COVID-19 pandemic, sustainable vaccine manufacturing requires long-term investment in research and development, policy reform, skills development, and regional cooperation. Failure to address these challenges systematically risks undermining current gains. CONTRIBUTION: This article provides insights to support ongoing and future investments in Nigeria's vaccine manufacturing sector, guiding government policy, international partnerships, and potential investors
Pathways, outputs and impact of NIH-supported bioinformatics and genomics graduate trainees in Africa.
Get PDFGlobal biomedical and health research is increasingly relying on genomic and computational approaches, largely driven by the increasing volumes of nucleic acid sequencing. Concurrently, epidemiological studies and clinical records are generating enormous amounts of data amenable to disease modeling, machine learning, and artificial intelligence techniques. Bioinformatics and data science expertise is therefore essential for improved population health. Accordingly, in 2012, the US National Institutes of Health (NIH) in partnership with the Wellcome Trust, and with support from the African Society for Human Genetics, initiated the H3Africa (Human Heredity and Health in Africa) consortium. One of its key goals was to build capacity among African scientists to lead research on genetic and environmental contributors to health and disease across the continent. In 2017, the NIH provided funding to support the establishment of four graduate bioinformatics training programs across five African universities. Over seven years, these programs enrolled multiple trainees (n > 270), with >110 earning Master's degrees and >20 completing PhDs in Bioinformatics. It is thus timely to evaluate the outcomes and impact of these programs, particularly regarding graduation rates, career trajectories, and the institutions and research domains their alumni are serving. We also assess employment outcomes and the nature of the research they are enabling (n > 110 peer-reviewed articles). We additionally include the progress and outputs of the programs' instructors, which were partially enabled by program resources, networks, and trainees. Overall, this review paints valuable insights into the pioneering role of NIH extramural support in shaping Africa's biomedical research landscape
Imprecision in tuberculosis infection outcomes: implications for non-inferiority vaccine trials.
Get PDFBACKGROUND: Randomized trials comparing new vaccines against tuberculosis for use in neonates and infants, for whom Bacille Calmette-Guérin vaccination is established practice, are using tuberculosis infection as the primary endpoint in a non-inferiority design. Markers of tuberculosis infection have imperfect sensitivity and specificity. Flaws in the non-inferiority trial design typically bias towards non-inferiority, which may result in falsely declaring non-inferiority. METHODS: We conducted a statistical simulation study to assess the impact of imperfect markers of tuberculosis infection on the interpretation of tuberculosis vaccine trials testing a non-inferiority hypothesis of an infection primary outcome in a two-arm randomized comparison. Data were generated in three 2-year cumulative risk of tuberculosis infection scenarios (2%, 5%, and 8%). The specificity of tests of tuberculosis infection was assumed to range from 100% to 85%, while the sensitivity was assumed to range from 100% to 64%. Log-binomial regression was used to estimate the relative risk of tuberculosis infection. RESULTS: With 100% sensitivity and specificity, type I error and power were both approximately equal to the expected values (2.5% and 80%, respectively) in all three cumulative tuberculosis risk scenarios. With modest deviations from perfect sensitivity and specificity (95% for both), the risk of falsely declaring non-inferiority was 96.8%, 53.2%, and 27.8% in the 2%, 5%, and 8% cumulative tuberculosis risk infection scenarios, respectively. DISCUSSION: Tuberculosis vaccine non-inferiority trials using an infection primary outcome must be designed and interpreted accounting for the specificity of the tools used to measure infection, otherwise they risk declaring non-inferiority by default
The L1014F Kdr mutation is associated with a higher prevalence and load of the Plasmodium-blocking symbiont Microsporidia MB In Anopheles Gambiae s.l. In Benin
Get PDFIntroduction: The Plasmodium transmission-blocking endosymbiont Microsporidia MB was previously identified in Anopheles gambiae s.l., but its association with the carriage of the genotypes of the L1014F kdr mutation, as well as the ecological factors driving its geographical distribution remain understudied.
Methods: Adult mosquitoes were field-collected using human landing catches (HLCs) across 60 villages in the Covè, Ouinhi, and Zangnanado communes of southern Benin. After morphological identification, a sub-sample of An. gambiae s.l. were molecularly speciated, and genotypied for the L1014F kdr mutation by Polymerase Chain Reaction (PCR). Enzyme-Linked Immunosorbent Assay (ELISA) and qPCR were also used to assess infection with Plasmodium falciparum sporozoites and Microsporidia MB, respectively. The environmental variables that drive the habitat suitability for Microsporidia MB were also assessed using Maximum Entropy (MaxEnt) modelling.
Results: The An. gambiae complex (N = 1040) was composed of 93.7% An. coluzzii, 4.4% An. gambiae s.s., 0.2% An. gambiae s.s./coluzzii hybrids, while the rest failed to amplify. Infection prevalence with Microsporidia MB was 1.6% (95% CI: 0.7–3.3) in An. coluzzii and 2.2% (95% CI: 0.1–13.2) in An. gambiae s.s. The P. falciparum sporozoite rate was 2% (95% CI: 1.2–3.1, N = 974) in An. coluzzii, and null in An. gambiae s.s. (N = 46). None of the mosquitoes infected with Microsporidia MB were infected with P. falciparum. The frequency of the L1014F kdr mutation was 75.1% (95% CI: 73.1–76.9) in An. coluzzii and 91.3% (95% CI: 83.1–95.9) in An. gambiae s.s. Microsporidia MB was absent in kdr-SS mosquitoes but was present in low proportions in both kdr-RS and kdr-RR mosquitoes (1.9%, 95% CI: 0.6–5.1). The mean load of Microsporidia MB DNA was higher in kdr-RR (23.23 ng/µl, 95% CI: 18.77–28.48) compared to kdr-RS (10.13 ng/µl, 95% CI: 7.36–13.91) mosquitoes. The elevation and soil contributed to explain, at 78% and 20% respectively, the habitat suitability for Microsporidia MB.
Conclusion: In this study, we demonstrated that An. gambiae s.l. mosquitoes bearing the L1014F kdr resistant allele was associated with a higher prevalence and load of Microsporidia MB than their susceptible counterparts. Moreover, the geographical distribution of Microsporidia MB was found to be influenced by certain environmental conditions, which warrant further large-scale investigations
Resolving plasmid-encoded carbapenem resistance dynamics and reservoirs in a hospital setting through nanopore sequencing.
Get PDFThe growing resistance of Enterobacterales to last-resort antibiotics such as carbapenems puts a significant burden on healthcare systems, also due to plasmids driving a rapid spread of carbapenem resistance. We here evaluate the use of long-read nanopore sequencing to investigate carbapenem resistance dynamics and the role of plasmid transfers and environmental reservoirs in the hospital setting. Over 13 months, routine clinical diagnostics identified recurring isolates of carbapenem-resistant Citrobacter species carrying Klebsiella pneumoniae carbapenemases (KPCs) and/or OXA-48-like carbapenemases from patient screening and hospital drain samples. While routine diagnostic approaches provided limited insights into the carbapenem resistance dynamics, we show that near-complete de novo assembly of chromosomes and plasmids by long-read nanopore sequencing allowed for high-resolution strain identification, plasmid profiling, and antibiotic resistance gene detection. Notably, genomically nearly indistinguishable Citrobacter freundii of the high-risk sequence type ST91 genomes were recovered from screening samples collected in the same hospital room 1 year apart. We further provide evidence of a KPC-2-encoding IncN plasmid that is likely to have spread across bacterial species and between patient and drain isolates, which emphasizes the role of contaminated drains in the persistence and dissemination of antimicrobial resistance within the hospital environment. Overall, this study demonstrates the value of long-read nanopore sequencing for uncovering the complex dynamics of carbapenem resistance spread and persistence in the hospital setting and its potential implications for infection prevention and control