Integrating central nervous system metagenomics and host response for diagnosis of tuberculosis meningitis and its mimics.

The epidemiology of infectious causes of meningitis in sub-Saharan Africa is not well understood, and a common cause of meningitis in this region, Mycobacterium tuberculosis (TB), is notoriously hard to diagnose. Here we show that integrating cerebrospinal fluid (CSF) metagenomic next-generation sequencing (mNGS) with a host gene expression-based machine learning classifier (MLC) enhances diagnostic accuracy for TB meningitis (TBM) and its mimics. 368 HIV-infected Ugandan adults with subacute meningitis were prospectively enrolled. Total RNA and DNA CSF mNGS libraries were sequenced to identify meningitis pathogens. In parallel, a CSF host transcriptomic MLC to distinguish between TBM and other infections was trained and then evaluated in a blinded fashion on an independent dataset. mNGS identifies an array of infectious TBM mimics (and co-infections), including emerging, treatable, and vaccine-preventable pathogens including Wesselsbron virus, Toxoplasma gondii, Streptococcus pneumoniae, Nocardia brasiliensis, measles virus and cytomegalovirus. By leveraging the specificity of mNGS and the sensitivity of an MLC created from CSF host transcriptomes, the combined assay has high sensitivity (88.9%) and specificity (86.7%) for the detection of TBM and its many mimics. Furthermore, we achieve comparable combined assay performance at sequencing depths more amenable to performing diagnostic mNGS in low resource settings.

Poverty and eosinophilia are risk factors for endomyocardial fibrosis (EMF) in Uganda.

OBJECTIVE: To determine the relative risks of socio-demographic, dietary, and environmental factors for endomyocardial fibrosis (EMF) in Uganda. METHOD: Unmatched case control study in Mulago Hospital, Kampala. Cases (n = 61) were sequential patients hospitalized with an echocardiographic diagnosis of EMF from June 1995 to March 1996. Controls (n = 120) were concurrent patients with other forms of heart disease (heart controls, n = 59) and subjects admitted for trauma or elective surgery (hospital controls, n = 61). All consenting subjects answered a structured questionnaire administered by trained interviewers. Complete blood counts, malaria films and stool examination for ova and parasites were performed. Questionnaires elicited information on home address, economic circumstances, variables concerned with environmental exposures and usual diet before becoming ill. RESULTS: After adjustment for age and sex, cases were significantly more likely than controls to have Rwanda/Burundi ethnic origins (P = 0.008). Compared with controls, cases had a lower level of education (P < 0.001 for heart controls and P = 0.07 for hospital controls), were more likely to be peasants (P < 0.001), and to come from Luwero or Mukono Districts (P = 0.003). After further adjustment for peasant occupation, cases were more likely than controls to walk barefoot (P = 0.015), consume cassava as their staple food (P < 0.001) and to lack fish or meat in dietary sauces (P = 0.02). Cases were more likely to exhibit absolute eosinophilia (P = 0.006). The effect of cassava diet was more marked in the younger age group, while the effect of eosinophilia was greater in adults. Socio-economic disadvantage is a risk for EMF. Absolute eosinophilia is a putative cause of EMF, a finding not explained by parasitism. CONCLUSION: Data indicate that relative poverty and environmental factors triggering eosinophilia appear to act in a geographically restricted region of Uganda in the aetiology of EMF.

Echocardiographic diagnosis of heart disease in Uganda.

Five hundred consecutive cardiological patients were reviewed and evaluated by echocardiography in Mulago Hospital as a referral service. All diagnostic problems in cardiology in the hospital and to a certain degree from other institutions were reviewed. The commonest diagnosis was endomyocardial fibrosis (EMF) 19.8%, followed by congenital heart disease (CHD) 15% and rheumatic heart disease (RHD) 11%. The anatomical distribution of fibrotic lesions in EMF (left, right or biventricular) correlated with that found in previous autopsy series from Mulago Hospital thus demonstrating the accuracy of echocardiography. We were able to quantify the contribution of echocardiography to a correct diagnosis which varied between 13% in RHD to 90% in mitral valve prolapse (MVP). Echocardiography was able to confirm the clinical diagnosis of subacute bacterial endocarditis (SBE) in 69% of cases. The obtained data suggests that EMF may be the most common heart disease in Uganda contrary to the pattern of heart disease outlined in earlier works. The favourable cost/benefit ratio of echocardiography (i.e. its easy availability and maintenance), as well as the absence of consumable materials in comparison to other cardiac diagnostic tools such as catheterization, chest X-ray and ECG is emphasized, together with the multipurpose use of the machine.