BACKGROUND: Cryptococcal meningitis (CM) is the commonest neurological complication in patients with advanced HIV. Visual disturbance is a frequent presenting symptom. Papilloedema is commonly reported but other ophthalmic findings are not well described. METHODS: We performed an observational study comparing severely immunocompromised HIV-infected patients with and without CM to determine the nature and prevalence of retinal pathology attributable to CM. 70 adult patients were enrolled in Blantyre Malawi, 35 with CM and 35 HIV-infected patients without CM. RESULTS: 79% (19/24) of CM patients examined on day one had evidence of retinal abnormalities compared to 17% (6/35) of HIV-infected controls (p <0.001). In the CM group, retinal whitening was the commonest abnormality (50%), followed by optic disc swelling (29%), haemorrhage (25%) and vascular abnormalities (7%). Retinal whitening was the only abnormality observed in the comparator group (17%). In CM, there was no significant difference between those with and without retinal abnormalities in fungal burden (13,550 cfu/ml vs. 9,150 cfu/ml; p = 0.65), CD4 count (28 cells/µl vs. 76 cells/µl; p = 0.79) or CSF opening pressure (21cm H20 vs. 27cm H20; p = 0.5). There was no association between presence/absence of retinal abnormalities and death (40% 10-week mortality vs. 26%; p = 0.6). CONCLUSIONS: Whether the presence of CM retinopathy could be used as a marker of disease severity warrants further investigation. The observed ophthalmic findings provide a descriptive framework for CM retinopathy to be utilised in future CM studies. TRIAL REGISTRATION: ISRCTN (ISRCTN45035509) 19/06/2012.
BACKGROUND:We investigated the prevalence, diversity, and risk factors for acute leptospirosis in the Febrile Illness Evaluation in a Broad Range of Endemicities (FIEBRE) study. METHODS:Febrile patients aged ≥2 months in Laos, Malawi, Mozambique, and Zimbabwe underwent a standardized clinical and exposure assessment. Acute and convalescent serum were tested by Leptospira microscopic agglutination test (MAT) and acute plasma by lfb1 polymerase chain reaction. A ≥4-fold rise in antibody titer, or a single reciprocal titer ≥800, or Leptospira PCR positive defined confirmed leptospirosis. The identity of possible infecting strains was investigated by MAT and sequencing of PCR products. RESULTS:Of 7851 febrile participants enrolled, 134 (1.7%) had confirmed leptospirosis: 88 (4.6%) in Laos, 17 (1.0%) Malawi, 7 (0.3%) Mozambique, and 22 (1.2%) Zimbabwe, and 23 (0.8%) had supportive evidence of leptospirosis. Participants with leptospirosis had greater odds of headache (adjusted odds ratio [aOR] 2.20, P < .001), rash (aOR 1.45, P < .001), conjunctivitis (aOR 3.33, P < .001), and jaundice (aOR 1.75, P < .001); and had greater odds of being older (aOR 1.02 per year, P < .001), working in rice fields (aOR 6.24, P < .001), drinking river water (aOR 5.11, P = .001). Predominant reactive Leptospira serogroups were Ballum and Icterohemorrhagiae at African sites, and Australis in Laos. Identified species were Leptospira borgpetersenii, L. interrogans, and L. kirschneri. CONCLUSIONS:Leptospirosis was a cause of febrile illness at all sites. Some clinical features helped to identify patients with leptospirosis. Interventions related to rice field work and river exposure may prevent disease. Diverse Leptospira serogroup reactivity was observed and may suggest potential hosts.
Diarrhoea remains a major problem among children in low- and middle-income countries, driven by multiple pathogens including rotavirus, Shigella and enterotoxigenic Escherichia coli (ETEC). Rotavirus vaccines have notably reduced diarrhoea deaths. However, the health consequences associated with Shigella and ETEC, along with rising antimicrobial resistance (AMR), have prompted the WHO to prioritise vaccine development against these two pathogens. Understanding their disease burden is crucial for guiding this effort and informing preparedness for vaccine adoption. We conducted a systematic review and meta-analysis of primary peer-reviewed literature to establish the prevalence, subtypes and AMR patterns of Shigella and ETEC-associated diarrhoea in Ethiopia, Kenya and Malawi, where the authors have established a multidisciplinary research programme addressing gastrointestinal infections. We searched in PubMed, among other databases, for English-language publications from 1 January 2000 to 28 July 2023. The meta-analysis used a random effects model to estimate pooled prevalence. 43 studies were included. Malawi exhibited a higher estimated prevalence of Shigella (24% (95% CI 10% to 39%)) than Ethiopia and Kenya (both with an estimated prevalence of 6%), most likely explained by the application of sensitive, molecular detection methods in Malawi. The overall pooled prevalence of Shigella was 8% (95% CI 6% to 9%). Malawi again displayed higher ETEC prevalence (24% (95% CI 14% to 33%)) compared with Kenya (7% (95% CI 5% to 10%)), with no studies of ETEC identified from Ethiopia. The overall pooled prevalence of ETEC was 11% (95% CI 6% to 15%). Shigella flexneri was the major species of Shigella, and heat-stable ETEC was highly prevalent. Shigella species displayed resistance to several classes of antibiotics, including penicillins, tetracyclines, macrolides and sulphonamides, but susceptibility to fluoroquinolones and cephalosporins. These findings underscore the need for countries to generate updated disease burden estimates for Shigella and ETEC through epidemiologically robust studies that use sensitive diagnostic methods in preparation for vaccine introduction.
Introduction Malawi is at a unique time point when infectious disease and undernutrition persist while modern diets, and changes in urbanisation, medical treatments and climate change, non-communicable long-term physical and mental health conditions are emerging. Malawi faces high socioeconomic hardships with 75% of families living in poverty with limited access to basic resources. With these demographic changes, very limited research has been undertaken into the determinants of physical and mental health-related trajectories over time, and in particular the role of prenatal and early life exposures in predetermining long-term conditions in later life. The study will establish a unique multigenerational birth cohort across contrasting rural and urban settings in Malawi to examine how pregnancy, early-life and intergenerational factors shape long-term mental and physical health Methods and analysis Generation Malawi is based within the open, health and demographic surveillance sites in rural (southern Karonga District) and urban (high-density sectors of Area 25, Lilongwe) Malawi. The study seeks to enrol up to 5000 pregnant women aged 16 years and above, and their spouses, during early pregnancy. Pregnant women and their spouses are followed up until the delivery date at which time their baby is recruited into the study. Children and their parents are then followed up at 1 week, 6 weeks, 4, 12, 24 and 36 months after delivery. At each point, we conduct detailed interviewer-led questionnaires, physical measurements and collection of bio-samples for immediate analysis and long-term storage. The data from this cohort will help us understand the causes of long-term ill health and, in the future, help develop effective interventions to prevent and promptly treat these conditions. Ethics and dissemination This study protocol was approved by the National Health Science Research Committee in Malawi (number: 21/01/2653) and the Ethics Committee of the College of Medical, Veterinary and Life Sciences at the University of Glasgow, UK (protocol number: 200190183). The formative work for this study was granted ethical clearance by the College of Medicine Research Ethics Committee (protocol number P.11/19/2865). Results will be presented at relevant conferences and published in peer-reviewed journals.
Abstract While a causal link between urogenital schistosomiasis ( Schistosoma haematobium ) and anaemia is well established, quantitative associations between infection intensity and haemoglobin levels across endemic communities, at fine spatial scales, remain insufficiently characterized. As part of the broader Hybridisation in Urogenital Schistosomiasis (HUGS) investigation, we studied the micro-epidemiology of anaemia within two study communities in southern Malawi where S. haematobium remains endemic. Urine samples were examined by microscopy to quantify S. haematobium infection intensity, categorised as low (0–9 eggs/10 mL), moderate (10–49 eggs/10 mL), and heavy (≥50 eggs/10 mL). Individual haemoglobin concentrations were measured using a HemoCue photometer in 1,149 participants from Samama village (Mangochi District) and 977 participants from Mthawira village (Nsanje District). Linear geostatistical models incorporating individual-level characteristics and spatial covariates were used to estimate anaemia prevalence at fine geographical scales. Moderate anaemia (Hb 80–109 g/L) was most prevalent among children aged 6–12 years (45.30% in Samama and 39.54% in Mthawira), while severe anaemia was more frequent among adults aged ≥19 years in both villages. Increasing S. haematobium infection intensity was associated with lower haemoglobin levels, with individuals harbouring heavy infections being at greater risk of moderate-to-severe anaemia. Spatial modelling revealed longer-range spatial correlation in Nsanje (φ = 66.7 km) than in Mangochi (φ = 25.5 km), indicating more spatially persistent risk in Nsanje and more localized heterogeneity in Mangochi. Predicted anaemia prevalence among female children aged 6–12 years with moderate infection intensity ranged from 25–65% in Mangochi and 64–76% in Nsanje. At the micro-epidemiological level, S. haematobium infection intensity was associated with the severity of anaemia, with substantial spatial heterogeneity within and between villages. Identification of high-risk clusters supports targeted interventions, including stepped-up preventive chemotherapy, improved water and sanitation, and iron supplementation.
