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Dermatophyte Treatment Failure: A Rapid Global Response to an Emerging Global Health Issue.
Get PDFDermatomycoses, or fungal infections of the skin, hair, and nails, affect nearly a billion people worldwide, especially in countries with a low sociodemographic index (SDI) and amongst vulnerable populations such as young children. Rising global rates of dermatophytosis impose a considerable burden on dermatology and primary care facilities worldwide, particularly on the Indian subcontinent. These infections, often perceived as minor, can severely impact quality of life, causing discomfort, social embarrassment, and contributing to poor sleep.</p
The catalytic tetrad of Aedes aegypti Argonaute 2 is critical for the antiviral activity of the exogenous siRNA pathway
Get PDFViruses transmitted by biting arthropods, arboviruses, pose a significant global health and economic threat. Climate change is exacerbating this issue by expanding the range of disease-carrying vectors. Effective control of arbovirus transmission often relies on targeting the vectors, making it crucial to understand the interactions between the virus and its vector. The exogenous siRNA (exo-siRNA) pathway is a key antiviral defence mechanism in mosquitoes such as Aedes aegypti. Argonaute 2 (Ago2) is a central protein in this pathway, responsible for antiviral activity. While the PIWI domain of Ago proteins is known to mediate slicing activity, not all Ago proteins possess this slicing function. To understand the antiviral mechanism of Ago2 in Ae. aegypti, we aimed to confirm the presence of the catalytic tetrad, a group of amino acids known to be crucial for slicing activity. Here, we confirmed the tetrad (D740, E780, D812, and H950) in Ae. aegypti Ago2 and demonstrated its essential role in antiviral and siRNA pathway activity. Our findings show that the catalytic tetrad is necessary for the degradation of siRNA passenger strands. When the tetrad is absent, siRNA duplexes accumulate, leading to a loss of siRNA pathway function. This underscores the critical role of the tetrad in the antiviral defence mechanism of Ae. aegypti.</p
Prospective longitudinal assessment of Albumin-to-Creatinine ratio (ACR) in a clinical cohort of people living with HIV in Gaborone, Botswana
Get PDFBackgroundPeople living with HIV (PLWH) in sub-Saharan Africa are vulnerable to end organ dysfunction such as albuminuria, which is associated with an increased risk of cardiovascular and renal events. However, the prevalence of persistent albuminuria among PLWH in Africa is unclear. This observational prospective study assessed for persistence of albuminuria in a cohort of PLWH on longterm antiretroviral therapy (ART) across various HIV service platforms in Gaborone, Botswana.MethodsA subgroup of ART treated PLWH (n = 867) from a larger cross-sectional study (n = 1537) assessing prevalence of albuminuria among PLWH at a referral hospital HIV clinic and satellite HIV clinics in Gaborone, were invited to participate in a 12-month long albuminuria prospective cohort study between January 2020 and March 2022. During three planned study visits, albumin-creatinine (ACR) was computed using urine albumin measured using immunoturbidimetric assay and urine creatinine using colorimetric assay (Jaffe method), at the Botswana Harvard HIV Reference Laboratory. ACR trajectory groups were identified using growth mixture models, and factors associated with ACR trajectory were analyzed using modified Poisson regression.ResultsAmong the 623 adults with complete data for all 3 study visits, their baseline median age was 50 (42–57) years with a median HIV disease duration of 13.1 (8.7–16.7) years, and 266 (42.7%) of them were female. Study participants were categorized into two ACR trajectory groups: low increasing ACR, N = 290 (46.5%) and moderate increasing ACR, N = 333 (53.5%) groups. ACR increased by 4.7 mg/g in the slow increasing ACR groups versus 11.5 mg/g in the moderate increasing ACR trajectory group by end of follow-up. Active use of Tenofovir, aRR 1.27 [95% CI 1.02–1.60], p = 0.036, or ACEi/ARB, aRR 1.31 [95% CI 1.07–1.61], p = 0.008, and an elevated baseline ACR, aRR 1.34 [95% CI 1.28–1.41], p < 0.001, were all associated with being in the moderate increasing ACR trajectory group.ConclusionChronic, treated HIV infection was associated with more than 5 fold increase in ACR over 12 months. Future studies should explore the extent to which modifiable risk factors and HIV specific factors for progressive increase in albuminuria could be aggressively controlled among PLWH.</p
Health seeking by people living with non-communicable diseases in a pluralistic health system: the role of informal healthcare providers
Get PDFBackgroundThere is a growing global burden of non-communicable diseases (NCDs), including diabetes, hypertension and cardiovascular diseases. NCDs constitute a growing public health concern in the Low and Middle Income Countries (LMICs), amplified by rapid urbanisation and urban inequality. Urbanisation and associated inequalities, have profound impacts on healthcare provision and health seeking decision making by marginalised populations living in urban informal settlements. The thriving nature of informality, shown through the spread of urbanisation, health pluralism and informal healthcare provision is seen as a mechanism for coping with urban inequalities. Limited understanding of the drivers of health seeking both within policy and practice remain a huge gap in designing a people centred healthcare delivery that meets the needs of people affected by NCD health problems in marginalised urban settings.MethodsWe employed qualitative methods including 18 key informant interviews (KIIs), 3 focus group discussions (FGDs) and 15 narrative interviews, with purposively sampled people living with NCDs, as well as formal and informal healthcare providers, and community chiefs. We analysed our data using the qualitative framework approach, applying the adapted health belief model to understand how health seeking decisions are made by people impacted by NCD lived experiences in informal settlements.FindingsSyncretic beliefs were evident among people living with NCDs in urban informal settlements, showing that people interact with diverse healthcare providers at different times, based on the type and severity of ill health. Health seeking was also influenced by healthcare access barriers, and participants’ biomedical, cultural and religious beliefs about disease causation. Despite the ongoing medical pluralism and syncretic belief systems, the Sierra Leonean health system is yet to understand and adapt to these contextual factors in its response to the NCD epidemic. Moreover, the rigid operational boundaries between formal and informal healthcare service providers continue to impact on the unmet healthcare needs of people living with NCD conditions in marginalised urban settlements in Freetown, Sierra Leone.ConclusionInformal healthcare providers play a critical role in the provision of healthcare services for people living in low resource settings, building a trusted relationship between formal and informal health providers can help to optimise healthcare service delivery that meets the needs of people affected by NCD conditions in marginalised urban settlements.</p
Pilot implementation of short message service for randomisation in a multisite pragmatic factorial clinical trial in Kenya
Get PDFBackgroundThe traditional use of sealed envelopes for randomisation is susceptible to manipulation and the risk of damage to envelopes during shipping and storage. Additionally, the filling and sealing of envelopes are tedious, time-consuming, and error-prone. Other randomisation alternatives such as web-based methods are preferred. However, they are expensive and unsuitable in settings with poor internet infrastructure. Mobile phone-based randomisation using short message service (SMS) potentially offers a low-cost and reliable alternative.MethodsWe developed an SMS-based method for random allocation of treatments. Plain text messaging or an Android app was used to formulate text messages using a fixed syntax consisting of the participant’s unique identifier, trial site, stratum, and the trial name as input parameters. The system verified the input parameters and obtained an allocation from the database before returning a response to the sender. The text response contained the details of the treatment allocation. This was a Study Within A Trial (SWAT) conducted in two sites of a multi-site 3 × 2 factorial clinical trial in Kenya involving two interventions with up to nine possible allocations. SMS randomisation feasibility was assessed by comparing treatment allocations against the master randomisation list for each processed SMS, measuring SMS latency (in seconds), and gathering user feedback via a post-implementation survey.ResultsA total of 218 participants were randomised between the 7th of February 2022 and the 11th of April 2022, out of which 179 were randomised to only one arm while 39 were randomised to both treatment arms. Allocation accuracy was 100%. Median latency was 22 s with the fastest message processed in 10 s and the slowest (non-network delayed) message processed in 2129 s. Four users completed a post-implementation survey.ConclusionsThe pilot study demonstrated that SMS randomisation is easy, user-friendly, fast, accurate, and a feasible alternative randomisation technique.</p
Rebuilding trust and equity in Syria's health system: a governance-driven transition.
No full textIn December, 2024, after more than 50 years in power in Syria, the regime of the Assad family was swept away. This dramatic political shift illuminated the state of health in Syria, exposing widespread fractures in a health system that has been politicised and fragmented, including widespread erosion of public trust in medical care.1 Health has been decimated during Syria's almost 14-year conflict by attacks on infrastructure, the forced exodus of health-care workers, and severe under-resourcing. The emergence of subnational health systems since early in the conflict has fragmented health-care delivery, leading to parallel governance structures.1 Syria's new transitional government, led by transitional President Ahmed al-Sharaa, therefore faces a profound challenge: how to re-establish trust in services and rebuild a cohesive, development-focused, resilient health-care system from these fragmented pieces.</p
Factors influencing uptake of COVID-19 diagnostics in Sub-Saharan Africa: a rapid scoping review
Get PDFBackgroundDiagnostics are critical for preventing COVID-19 transmission, enabling disease management and engagement with care. However, COVID-19 testing uptake remained low in low- and middle- income countries in Sub-Saharan Africa (SSA) during the recent pandemic, due to issues of supply, access and acceptability. Early studies conducted outside of the region provide insight into uptake of COVID-19 testing, however there has been no systematic research within the region. The aim of this scoping review is to investigate factors influencing uptake of COVID-19 testing in different settings across SSA.Materials and methodsInclusion criteria was any study employing qualitative or mixed methodologies, addressing uptake of COVID-19 testing conducted in SSA. MEDLINE, PubMed, Google Scholar, Web of Science, and Africa-Wide Information were searched. Thematic content analysis was conducted across all included articles until saturation was attained.ResultsIn total 2994 articles were identified and fourteen reviewed. Structural, social, epidemiological, informational, and political elements affected how the public interacted with COVID-19 testing. Coverage was limited by insufficient diagnostic capabilities caused by a shortage of laboratory resources and trained personnel. False information spread through social media led to testing misperceptions and apprehension. Testing hesitancy was ascribed to fear of restrictive measures and the possibility of social harms if positive. Facility-based testing was physically inaccessible and perceived as lacking privacy, whereas self-testing distributed by the community removed lengthy distances and prevented stigma. Perceptions that COVID-19 was not severe and low numbers of confirmed cases in comparison to other settings undermined public urgency for testing. Low testing frequency led to low-rate assumptions, which in turn generated denial and othering narratives. Politicians’ acceptance or denial of COVID-19 affected the mobilization of the health system, and their model actions—such as testing openly—promoted public confidence and involvement in interventions.ConclusionsThis review emphasizes the necessity of strong political commitments to enhancing health systems for future pandemic preparedness. Response plans should consider contextual elements that affect how people react to interventions and perceive health emergencies. Community-driven self-testing distribution could enhance the uptake of diagnostics through addressing socio-economic constraints impacting facility-delivered testing.</p
A multifaceted intervention to improve diagnosis and early management of hospitalised patients with suspected acute brain infections in Brazil, India, and Malawi: an international multicentre intervention study
Get PDFBackgroundBrain infections pose substantial challenges in diagnosis and management and carry high mortality and morbidity, especially in low-income and middle-income countries. We aimed to improve the diagnosis and early management of patients admitted to hospital (adults aged 16 years and older and children aged >28 days) with suspected acute brain infections at 13 hospitals in Brazil, India, and Malawi.MethodsWith hospital stakeholders, policy makers, and patient and public representatives, we co-designed a multifaceted clinical and laboratory intervention, informed by an evaluation of routine practice. The intervention, tailored for each setting, included a diagnostic and management algorithm, a lumbar puncture pack, a testing panel, and staff training. We used multivariable logistic regression and interrupted time series analysis to compare the coprimary outcomes—the percentage of patients achieving a syndromic diagnosis and the percentage achieving a microbiological diagnosis before and after the intervention. The study was registered at ClinicalTrials.gov (NCT04190303) and is complete.FindingsBetween Jan 5, 2021, and Nov 30, 2022, we screened 10 462 patients and enrolled a total of 2233 patients at 13 hospital sites connected to the four study centres in Brazil, India, and Malawi. 1376 (62%) were recruited before the intervention and 857 (38%) were recruited after the intervention. 2154 patients (96%) had assessment of the primary outcome (1330 [62%] patients recruited pre-intervention and 824 [38%] recruited post-intervention). The median age across centres was 23 years (IQR 6–44), with 1276 (59%) being adults aged 16 years or older and 888 (41%) children aged between 29 days and 15 years; 1264 (59%) patients were male and 890 (41%) were female. Data on race and ethnicity were not recorded. 1020 (77%) of 1320 patients received a syndromic diagnosis before the intervention, rising to 701 (86%) of 813 after the intervention (adjusted odds ratio [aOR] 1·81 [95% CI 1·40–2·34]; p<0·0001). A microbiological diagnosis was made in 294 (22%) of 1330 patients pre-intervention, increasing to 250 (30%) of 824 patients post-intervention (aOR 1·46 [95% CI 1·18–1·79]; p=0·00040). Interrupted time series analysis confirmed that these increases exceeded a modest underlying trend of improvement over time. The percentage receiving a lumbar puncture, time to appropriate therapy, and functional outcome also improved.InterpretationDiagnosis and management of patients with suspected acute brain infections improved following introduction of a simple intervention package across a diverse range of hospitals on three continents. The intervention is now being implemented in other settings as part of the WHO Meningitis Roadmap and encephalitis control initiatives.</p
Cameroonian blackflies (Diptera: Simuliidae) harbour a plethora of (RNA) viruses
Get PDFStrong epidemiological evidence suggests that onchocerciasis may be associated with epilepsy – hence the name onchocerciasis-associated epilepsy (OAE). However, the pathogenesis of OAE still needs to be elucidated, as recent studies failed to detect Onchocerca volvulus in the central nervous system of persons with OAE. Therefore, it was suggested that a potentially neurotropic virus transmitted by blackflies could play a role in triggering OAE. To investigate this hypothesis, adult blackflies were collected in an onchocerciasis-endemic area with a high OAE prevalence in the Ntui Health District, Cameroon. A viral particle-based shotgun sequencing approach was used to detect viral sequences in fifty-five pools of ten blackflies. A very high abundance of viral reads was detected across multiple (novel) viral families, including viral families associated with human disease. Although, no genomes closely related to known neurotropic viruses were found in the blackfly virome, the plethora of novel viruses representing novel species, genera and even families, warrant further exploration for their potential to infect vertebrates. These results could serve as a first step for studying the viruses associated with the hematophagous blackfly, which also could be present in their nematode host O. volvulus. Exploring the diversity of viruses in blackflies should be included in the active surveillance of zoonotic diseases.</p
Understanding treatment initiation pathways and associated costs among people with pulmonary tuberculosis in a peri-urban area of Mozambique: a cross-sectional study
Get PDFBackgroundPeople with tuberculosis (TB) may seek care from healthcare providers without designated TB diagnosis and treatment services. This can lead to missed or delayed diagnosis and erroneous treatment for other diseases before being correctly diagnosed with TB. Such delays can contribute to increased out-of-pocket expenditures and lost income. We described TB treatment initiation pathways, including the type and number of pre-treatment healthcare providers visited, the time to TB treatment initiation, and the associated costs, among adults with pulmonary TB in Maputo, Mozambique.MethodsWe conducted a cross-sectional survey from December 2017 to January 2020 among adults (≥ 18 years) with pulmonary TB initiating TB treatment in health facilities with TB services in Maputo city and Maputo province, Mozambique. We used a locally adapted version of the World Health Organization’s TB Patient Cost Survey tools to collect health and socioeconomic data including symptoms, type and number of pre-treatment healthcare providers visited, and out-of-pocket costs and lost income. Logistic regression models were used to evaluate the associations of health and socioeconomic variables with the number of pre-treatment healthcare providers visited.ResultsOf 416 enrolled participants, 268 (64.4%) were male. Median age was 34.0 (IQR: 27.0–42.0) years, and 172/416 (41.4%) were breadwinners. Nearly two-thirds (61.5%, 256/416) visited two or more healthcare providers before TB treatment initiation. The mean times to first healthcare provider visits and initiation of TB treatment were 1.5 weeks (SD = 4.9) and 7.7 weeks (SD = 5.5), respectively. The mean cost of care-seeking was equivalent to 53.7% (95%CI = 38.8–68.5%) of the monthly household income and increased with additional visits to healthcare providers. Longer duration of TB symptoms prior to TB treatment initiation (aOR 6.0 [95%CI = 3.6–9.9], p < 0.001) and being in the least poor quintile of households (aOR 2.6 [95%CI = 1.3–5.5], p = 0.011) were associated with visiting two or more pre-treatment healthcare providers.ConclusionsMost people with TB symptoms sought care within two weeks but TB treatment initiation was delayed to nearly two months after symptoms onset. This suggests that delays in TB treatment initiation may be attributable to health system factors rather than the care-seeking behaviour of people with TB in Maputo, Mozambique. Additionally, there was a substantial financial burden of care-seeking exacerbated by additional healthcare provider visits. Evidence on interventions to address delays in diagnosis and treatment, and their associated health and socioeconomic impacts in Mozambique is urgently needed.</p