Evaluation of a chest radiograph reading and recording system for tuberculosis in a HIV-positive cohort.

Aim To assess the impact of introducing a chest radiograph reading and recording system (CRRS) with a short training session, on the accuracy and inter-reader variability of tuberculosis (TB) interpretation of chest radiographs (CXRs) by a group of non-expert readers in a human immunodeficiency virus (HIV)-positive cohort. Materials and methods A set of 139 CXRs was reviewed by a group of eight physicians pre- and post-intervention at two clinics in Shan State, Myanmar, providing HIV/TB diagnosis and treatment services. The results were compared against the consensus of expert radiologists for accuracy. Results Overall accuracy was similar pre- and post-intervention for most physicians with an average area under the receiver operating characteristic curve difference of 0.02 (95% confidence interval: –0.03, 0.07). The overall agreement among physicians was poor pre- and post-intervention (Fleiss κ=0.35 and κ=0.29 respectively). The assessment of agreement for specific disease patterns associated with active TB in HIV-infected patients showed that for intrinsically subtle findings, the agreement was generally poor but better for the more intrinsically obvious disease patterns: pleural effusion (Cohen’s kappa range = 0.37–0.67) and milliary nodular pattern (Cohen’s kappa range = 0.25–0.52). Conclusion This study demonstrated limited impact of the introduction of a CRRS on CXR accuracy and agreement amongst non-expert readers. The role in which CXRs are used for TB diagnosis in a HIV-positive cohort in similar clinical contexts should be reviewed

One hundred years of neglect in paediatric schistosomiasis.

Early in the history of schistosomiasis research, children under 5 years of age were known to be infected. Although this problem was recognized over 100 years ago, insufficient action has been taken to address this issue. Under current policy, such infected children only receive their first antiparasitic treatment (praziquantel - PZQ) upon entry into primary school as current mass drug administration programmes typically target school-aged children. For many infected children, they will wait up to 6 years before receiving their first medication and significant schistosomiasis-related morbidity may have already established. This inequity would not be accepted for other diseases. To unveil some of the reasons behind this neglect, it is paramount to understand the intricate historical relationship between schistosomiasis and British Imperial medicine, to underline its lasting influence on today's public health priorities. This review presents a perspective on the historical neglect of paediatric schistosomiasis, focusing on important gaps that persist from the early days after discovery of this parasite. Looking to end this inequity, we address several issues that need to be overcome to move forward towards the lasting success of schistosomiasis control and elimination efforts

Ischemic stroke as a complication of cryptococcal meningitis and immune reconstitution inflammatory syndrome: a case report.

BACKGROUND: Cryptococcal meningitis remains the leading cause of adult meningitis in Sub-Saharan Africa. Immune Reconstitution Inflammatory Syndrome (IRIS) following anti-retroviral therapy (ART) initiation is an important complication. Here we report the first documented case of a IRIS reaction presenting as an ischemic stroke. CASE PRESENTATION: A 38 year old newly diagnosed HIV-infected, ART naive Malawian male presented to a tertiary referral hospital in Blantyre, Malawi with a 2 week history of headache. A diagnosis of cryptococcal meningitis was made and the patient was started on 1200 mg fluconazole once daily and flucytosine 25 mg/kg four times daily as part of the Advancing Cryptococcal Treatment for Africa (ACTA) clinical trial. There was an initial clinical and microbiological response to anti-fungal treatment and anti-retroviral therapy was started at week 4. The patient re-presented 16 days later with recurrence of headache, fever, and a sudden onset of left sided weakness in the context of rapid immune reconstitution; peripheral CD4 count had increased from a baseline of 29 cells/μl to 198 cells/μl. Recurrence of cryptococcal meningitis was excluded through CSF examination and fungal culture. Magnetic Resonance Imaging (MRI) of the brain demonstrated multi-focal DWI (diffusion weighted imaging) positive lesions consistent with an ischemic stroke. Given the temporal relationship to ART initiation, these MRI findings in the context of sterile CSF with raised CSF protein and a rapid immune reconstitution, following an earlier favorable response to treatment is most consistent with a paradoxical Immune Reconstitution Inflammatory Syndrome. CONCLUSIONS: Stroke is an increasing cause of morbidity and mortality amongst HIV infected persons. Ischemic stroke is a recognized complication of cryptococcal meningitis in the acute phase and is thought to be mediated by an infectious vasculitis. This is the first time an ischemic stroke has been described as part of a paradoxical IRIS reaction. This report adds to the spectrum of clinical IRIS presentations recognized and highlights to clinicians the potential complications encountered at ART initiation in severely immunocompromised patients

A cross-sectional study of periportal fibrosis and Schistosoma mansoni infection among school-aged children in a hard-to-reach area of Madagascar.

BACKGROUND: A cross-sectional survey was performed to estimate the prevalence of periportal fibrosis in children based on ultrasound examination in the Marolambo district of the Atsinanana region of Madagascar. This is a remote area known to have a high prevalence of intestinal schistosomiasis. METHODS: School-aged children (5-14 y) were selected from six villages for parasitological and sonographic examination. Circulating cathodic antigen (CCA) tests and Kato Katz (KK) stool microscopy were performed. Video-clips of liver views were recorded with a SonoSite iViz and interpreted in the UK by comparison with standardised images (WHO protocol). RESULTS: The prevalence of schistosomiasis according to CCA testing was 97.8% (269/275) and 73.8% (203/275) by KK. Sonographic evidence of periportal fibrosis was observed in 11.3% (31/275). The youngest children with fibrosis were aged 6 y. Fibrosis was more common in older children (p=0.03) but was not associated with either infection intensity category (p=0.07) or gender (p=0.67). CONCLUSIONS: Findings of periportal fibrosis among children in these hard-to-reach villages suggests chronic Schistosoma mansoni infection from a very young age. This may reflect other similarly remote schistosomiasis-endemic areas and reinforces the need to investigate morbidity in neglected communities to understand the true extent of disease burden in endemic countries

Etiology and Risk Factors for Mortality in an Adult Community-acquired Pneumonia Cohort in Malawi

RATIONALE In the context of rapid antiretroviral therapy (ART) rollout and an increasing burden of non-communicable diseases, there are few contemporary data describing the aetiology and outcome of community-acquired pneumonia (CAP) in sub-Saharan Africa. OBJECTIVES To describe the current aetiology of CAP in Malawi and identify risk factors for mortality. METHODS We conducted a prospective observational study of adults hospitalised with CAP to a teaching hospital in Blantyre, Malawi. Aetiology was defined by blood culture, Streptococcus pneumoniae urinary antigen detection, sputum mycobacterial culture and Xpert MTB/RIF, and nasopharyngeal aspirate multiplex PCR. MEASUREMENTS AND MAIN RESULTS In 459 patients (285 [62.1%] males; median age 34.7 [IQR: 29.4-41.9] years), 30-day mortality was 14.6% (64/439) and associated with male sex (adjusted odds ratio 2.60 [95% CI: 1.17-5.78]), symptom duration >7 days (2.78 [1.40-5.54]), tachycardia (2.99 [1.48-6.06]), hypoxaemia (4.40 [2.03-9.51]) and inability to stand (3.59 [1.72-7.50]). HIV was common (355/453; 78.4%), frequently newly diagnosed (124/355; 34.9%), but not associated with mortality. S. pneumoniae (98/458 [21.4%]) and Mycobacterium tuberculosis (75/326 [23.0%]) were the most frequently identified pathogens. Viral infection occurred in 32.6% (148/454) with influenza (40/454 [8.8%]) most common. Bacterial-viral co-infection occurred in 9.1% (28/307). Detection of M. tuberculosis was associated with mortality (aOR 2.44 [1.19-5.01]). CONCLUSIONS In the ART era, CAP in Malawi remains predominantly HIV-associated with a large proportion attributable to potentially vaccine-preventable pathogens. Strategies to increase early detection and treatment of tuberculosis and improve supportive care, in particular the correction of hypoxaemia, should be evaluated in clinical trials to address CAP-associated mortality

One hundred years of neglect in paediatric schistosomiasis

Early in the history of schistosomiasis research, children under 5 years of age were known to be infected. Although this problem was recognized over 100 years ago, insufficient action has been taken to address this issue. Under current policy, such infected children only receive their first antiparasitic treatment (praziquantel – PZQ) upon entry into primary school as current mass drug administration programmes typically target school-aged children. For many infected children, they will wait up to 6 years before receiving their first medication and significant schistosomiasis-related morbidity may have already established. This inequity would not be accepted for other diseases. To unveil some of the reasons behind this neglect, it is paramount to understand the intricate historical relationship between schistosomiasis and British Imperial medicine, to underline its lasting influence on today's public health priorities. This review presents a perspective on the historical neglect of paediatric schistosomiasis, focusing on important gaps that persist from the early days after discovery of this parasite. Looking to end this inequity, we address several issues that need to be overcome to move forward towards the lasting success of schistosomiasis control and elimination efforts

A clinical and molecular epidemiological survey of hepatitis C in Blantyre, Malawi, suggests a historic mechanism of transmission

Hepatitis C virus (HCV) is a leading cause of liver disease worldwide. There are no previous representative community HCV prevalence studies from Southern Africa, and limited genotypic data. Epidemiological data are required to inform an effective public health response. We conducted a household census-based random sampling serological survey, and a prospective hospital-based study of patients with cirrhosis and hepatocellular carcinoma (HCC) in Blantyre, Malawi. We tested participants with an HCV antigen/antibody ELISA (Monolisa, Bio-Rad), confirmed with PCR (GeneXpert, Cepheid) and used line immunoassay (Inno-LIA, Fujiribio) for RNA-negative participants. We did target-enrichment whole-genome HCV sequencing (NextSeq, Illumina). Among 96,386 censused individuals, we randomly selected 1661 people aged ≥16 years. Population-standardized HCV RNA prevalence was 0.2% (95% CI 0.1–0.5). Among 236 patients with cirrhosis and HCC, HCV RNA prevalence was 1.9% and 5.0%, respectively. Mapping showed that HCV RNA+ patients were from peri-urban areas surrounding Blantyre. Community and hospital HCV RNA+ participants were older than comparator HCV RNA-negative populations (median 53 vs 30 years for community, p = 0.01 and 68 vs 40 years for cirrhosis/HCC, p < 0.001). Endemic HCV genotypes (n = 10) were 4v (50%), 4r (30%) and 4w (10%). In this first census-based community serological study in Southern Africa, HCV was uncommon in the general population, was centred on peri-urban regions and was attributable for <5% of liver disease. HCV infection was observed only among older people, suggesting a historic mechanism of transmission. Genotype 4r, which has been associated with treatment failure with ledipasvir and daclatasvir, is endemic