Queen Elizabeth Central Hospital

Abstract Introduction Racemose neurocysticercosis often presents atypically as compared to its parenchymal counterpart. Diagnosis is challenging due to nonspecific clinical features and limited access to confirmatory investigations in resource-limited settings. Case description We report a case of a middle-aged man who presented with a history of headache, vomiting, and seizures followed by slurred speech and dysmetria, which later progressed to hemiparesis and aphasia. Computed tomography revealed multiple large cystic lesions in the left frontal, temporal, and parietal lobes with mass effect. Magnetic resonance imaging was unavailable at the presentation. A neurosurgical stereotactic biopsy confirmed neurocysticercosis. The patient initially improved on albendazole and corticosteroids but relapsed a year later with new neurological deficits, suggesting racemose neurocysticercosis. Discussion Our case highlights the diagnostic and therapeutic challenges of racemose neurocysticercosis and the need for heightened clinical suspicion, timely neuroimaging, histopathological confirmation, and aggressive treatment strategies in low-resource settings.

Pneumococcal meningitis (PM) has persistently poor clinical outcomes, especially in sub-Saharan Africa. To better characterise the inflammatory response and identify factors associated with mortality we compared paired peripheral blood and cerebrospinal fluid (CSF) transcriptomes before the initiation of antibiotics in Malawian adults with proven PM. Blood transcriptional profiles were obtained in 28 patients with PM, with simultaneous paired with CSF profiles available for 13 patients. 15/28 (52 %) patients died. Comparison of the transcriptome between CSF and blood compartments showed upregulation of 2293 differentially expressed genes in CSF and 909 in blood; enriched pathways in CSF included inflammasome activity and neutrophil migration/activation, contrasting with enrichment for pathways including platelet and endothelial activation, cell cycle, cytokine release and oxidative stress in the blood transcriptome. Comparison of CSF profiles between survivors and non-survivors revealed 1829 differentially expressed genes. Non-survivor CSF was enriched for multiple innate inflammatory pathways, including IL-17A and Type 1 interferons and proteolysis. In contrast, minimal transcriptomic differences between outcome groups were detected in blood. Inflammation in PM is characterised by compartmentalised responses in blood and CSF. Poorer outcomes are associated with an dysregulated innate immune host response to S. pneumoniae in the CSF compartment.

Norovirus is one of the most important etiological agents of gastroenteritis (GE) and food-borne diarrhea in all age groups worldwide. Here we report five draft genomes of norovirus isolated from stool samples collected from under-five children presenting with GE in Malawi from 2012 to 2024.

We use machine learning to identify innovative strategies to target azithromycin to the children with watery diarrhea who are most likely to benefit. Using data from a randomized trial of azithromycin for watery diarrhea (NCT03130114), we develop personalized treatment rules given sets of diagnostic, child, and clinical characteristics, employing a robust ensemble machine learning-based procedure. This procedure estimates the child-level expected benefit for a given set of covariates by combining predictions from a library of statistical models. For each rule, we estimate the proportion treated under the rule and the average benefits of treatment. Among 6692 children, treatment under the most comprehensive rule is recommended on average for one third of children. The risk of diarrhea on day 3 is 10.1% lower (95% CI: 5.4, 14.9) with azithromycin compared to placebo among children recommended for treatment (NNT: 10). For day 90 re-hospitalization and death, risk is 2.4% lower (95% CI: 0.6, 4.1; NNT: 42). While pathogen diagnostics are strong determinants of azithromycin effects on diarrhea duration, host characteristics may better predict benefits for re-hospitalization or death. This suggests that targeting antibiotic treatment for severe outcomes among children with watery diarrhea may be possible without access to pathogen diagnostics.

Among the Malawian infants living with HIV and hospitalized with severe pneumonia, bacteria (87%), viruses (85%) and fungi (40%) were detected in the respiratory tract. All infants had polymicrobial codetection, and differences in respiratory microbial codetection groups were significantly associated with age and HIV viral load.

BackgroundMulti-pathogen molecular diagnostics enhance our understanding of the pathogen-specific burden of diarrhea. However, attributing etiology remains challenging in high-burden settings where coinfections are common. The Antibiotics for Children with severe Diarrhea (ABCD) trial provides a unique opportunity to leverage azithromycin treatment response to identify bacterial diarrhea.MethodsWe analyzed data from 6,692 children with watery diarrhea enrolled in ABCD (2017 to 2019) who were randomized to receive azithromycin or placebo. We modelled the heterogeneity in the azithromycin treatment response by the enteric pathogen quantity detected by quantitative PCR using log-binomial regression.ResultsAzithromycin treatment response varied by pathogen quantity, with the strongest effect observed for Shigella. Each log₁₀ increase in Shigella quantity was associated with a 13% reduction (95% CI: 3–23%) in diarrhea risk at day 3 in the azithromycin group compared to placebo. We observed similar, though non-significant, trends for Vibrio cholerae, ST-ETEC, and tEPEC. In contrast, no association was found between pathogen quantity and azithromycin response for Campylobacter, LT-ETEC, or EAEC. These patterns remained consistent when evaluating hospitalization or death risk within 90 days.ConclusionThe observed associations between azithromycin treatment response and pathogen quantity for Shigella, Vibrio cholerae, ST-ETEC, and tEPEC support prior evidence that these pathogens are likely causes of diarrhea when present in high quantities. Conversely, the absence of a similar response pattern for Campylobacter, LT-ETEC, and EAEC is consistent with large-scale studies showing a limited association between their quantities and diarrhea.

Abstract Rationale: We explored the impact of a multicenter, randomized controlled trial (RCT) on clinical care in five hospitals in Sub-Saharan Africa from the perspective of study staff and hospital clinicians. Describing these impacts will facilitate improved research design and increased equity in clinical research. Methods: We conducted a qualitative analysis of the Building Respiratory Support in East Africa Through High-Flow versus Standard Flow Oxygen Evaluation (BREATHE) trial, an RCT comparing high-flow oxygen with usual care across four public and one faith-based hospital in Kenya, Malawi, and Rwanda (ClinicalTrials.gov, NCT05754034). Guided by the Consolidated Framework for Implementation Research (CFIR), we performed a rapid inductive analysis of 50 staff meetings and 9 clinician interviews to identify trial-related facilitators of and barriers to quality care. Results: We identified several facilitators of improved clinical practice from the perspective of trial staff and clinicians. Patients in both arms received increased monitoring, diagnostics (lung ultrasound), and emotional support from study staff, a significant benefit in settings with low clinician-to-patient ratios. Trial-related monitoring helped identify existing clinical gaps. Leadership at some sites were eager to incorporate aspects of trial protocols, such as oxygen titration guidelines, into hospital-wide practice. Trial staff conducted educational sessions for clinical staff, which were well-attended and appreciated. Many felt the trial fostered a culture of academic inquiry and cross-site networking for future clinical trials, for which planning is already underway. One clinician suggested further locally-driven research “would be very good because we can use the effective data which is local..the real population and the real conditions.” Negative impacts (barriers) were also identified. Early in enrollment, adapting to trial activities was burdensome for busy clinicians. Patients were worried about randomization and parallel care pathways. Later, clinicians expressed concern about a vacuum of knowledge and resources that may occur when the trial concludes-"If they left them [HFO devices] without training they cannot benefit us.” These are preliminary results pending further interviews with clinical staff, patients, and caregivers. Conclusion: CFIR-guided analysis of a multicenter RCT in sub-Saharan Africa uncovered impacts of RCT implementation at participating hospitals including increased monitoring and support for patients, identification of care gaps, education for clinical staff, and fostering a culture of inquiry, but also extra clinician burden, patient concerns around randomization, and worries about reduced resources after trial completion. Future researchers should consider these factors during study design and implementation to account for the impact of research on clinical practice.

Abstract Rationale: Although most critical care and pulmonary research is conducted in high-income countries, the barriers and facilitators of randomized controlled trials (RCTs) in resource-constrained settings are poorly characterized. Understanding RCT implementation in these settings can facilitate future studies and ultimately improve equity and generalizability of research. Methods: We analyzed qualitative data from Building Respiratory support in East Africa Through High flow versus standard flow oxygen Evaluation (BREATHE), an RCT comparing clinical outcomes of high-flow oxygen therapy to standard care at resource-constrained, predominantly RCT-inexperienced hospitals in Rwanda, Malawi, and Kenya (ClinicalTrials.govNCT05754034). Employing the Consolidated Framework for Implementation Research (CFIR) and Proctor's Implementation Outcomes Framework, we conducted rapid CFIR-based inductive analysis on 34 weekly staff meetings and 8 clinician interviews to identify barriers, facilitators, and other features of trial implementation. Results: Trial acceptance was facilitated by preexisting trust in local leaders, attentiveness of research assistants, appreciation of increased patient monitoring, education sessions for clinical and study staff, and perception of intervention benefit. Clinicians appreciated receiving the results of diagnostic testing performed by the study, and hospital leadership at one site requested study protocols to adapt for clinical care. Concerns about harm for the intervention were rare. Consent processes were adapted to cultural preferences for extensive family participation, particularly at two sites. Consent was facilitated by language and/or tribe concordance between patient and study staff at three sites. Suspicion of the study intervention occasionally arose surrounding the formal consent process and the switch from hospital device to study device. A government-employed doctors’ strike halted enrollment at one (government) site when few patients were presenting for care, while another (non-government) site was overwhelmed by an influx of critically ill patients, making study enrollment difficult. A public health emergency halted enrollment at two sites when study devices were needed for patients with Marburg virus. Infrastructure challenges included delays in replacing and repairing equipment, as well as adaptations around variable internet connectivity. Both oxygen and electricity interruptions occurred at some sites. Regulatory, data-sharing, and patient protection requirements were substantial, varied by country and over time, and required significant resources to anticipate and manage. These findings are preliminary, pending analysis of additional meetings and interviews. Conclusions: CFIR-guided analysis of BREATHE revealed unique barriers and facilitators to implementation relating to acceptability, environment, consent, communication, critical incidents, infrastructure, and regulatory oversight. These insights could streamline future RCTs in East Africa and other resource-constrained contexts.