To assess and compare the prevalence, severity and prognosis of anti-TB drug induced hepatotoxicity (DIH) in HIV positive and HIV negative tuberculosis (TB) patients in Ethiopia. In this study, 103 HIV positive and 94 HIV negative TB patients were enrolled. All patients were evaluated for different risk factors and monitored biochemically and clinically for development of DIH. Sub-clinical hepatotoxicity was observed in 17.3% of the patients and 8 out of the 197 (4.1%) developed clinical hepatotoxicity. Seven of the 8 were HIV positive and 2 were positive for HBsAg. Sub-clinical hepatotoxicity was significantly associated with HIV co-infection (p = 0.002), concomitant drug intake (p = 0.008), and decrease in CD4 count (p = 0.001). Stepwise restarting of anti TB treatment was also successful in almost all the patients who developed clinical DIH. We therefore conclude that anti-TB DIH is a major problem in HIV-associated TB with a decline in immune status and that there is a need for a regular biochemical and clinical follow up for those patients who are at risk.

A typical trait of chronic tuberculosis (TB) is substantial weight loss that concurs with a drop in blood hemoglobin (Hb) levels, causing anemia. In this observational study, we explored Hb levels in 345 pulmonary TB patients. They were divided into anemic or non-anemic groups which related to clinical symptoms, anthropometric measurements, and immune status. Data was obtained in a randomized controlled trial that we previously conducted using nutritional supplementation of TB patients in Ethiopia. A post hoc analysis demonstrated that anemic patients have a higher composite clinical TB score at baseline than non-anemic patients. Consequently, Hb values were significantly lower in underweight patients with moderate to severe disease and/or cavitary TB compared to normal weight patients with mild disease or non-cavitary TB. Anemia was associated with a low body mass index (BMI), low mid-upper arm circumference (MUAC), lower peripheral CD4 and CD8 T cells counts and IFN-γ levels, and a higher erythrocyte sedimentation rate (ESR). Chronic inflammation and TB disease progression appeared to be driven by elevated systemic levels of pro-inflammatory IL-6 in anemic patients. Multivariable modeling confirmed that a low Hb and a low BMI were key variables related to an unfavorable TB disease status. Although Hb levels increased with successful chemotherapy, anemic TB patients maintained a slower clinical recovery compared to non-anemic patients during the intensive phase treatment (two months). In conclusion, anemia is a strong predictor of wasting, disease severity, inflammation, and slower recovery in patients with pulmonary TB.

Pneumocystis pneumonia (PCP) has been considered a rare disease in sub-Saharan Africa. However, a rising prevalence has been noted recently. The objective of this study was to determine the relative prevalence of PCP and other pulmonary opportunistic diseases in patients infected with HIV in Ethiopia. 131 consecutive patients with respiratory symptoms and atypical chest X-ray, who were sputum smear-negative for AFB and seroreactive for HIV, underwent clinical evaluation and investigation for Pneumocystis jiroveci and Mycobacterium tuberculosis from sputum and bronchoalveolar lavage (BAL), and fungal and bacterial pathogens from BAL alone. Bacterial infections, Pneumocystis pneumonia (PCP) and pulmonary tuberculosis (PTB) occurred in 44 (33.6%), 39 (29.7%) and 31 (23.7%) patients, respectively. Pulmonary Kaposi sarcoma and non-specific interstitial pneumonitis occurred in 4 patients each. In a multivariate regression model, predictors of PCP were typical chest X-ray and low CD4 count while purulent sputum predicted bacterial infection. The sensitivity of physicians and chest X-ray diagnosis was particularly low for PTB and bacterial infections. We conclude that chronic bacterial infection and Pneumocystis pneumonia are important differential diagnoses in HIV-infected, smear-negative PTB patients presenting with atypical chest X-ray. We therefore need to escalate the use of preventive and highly active antiretroviral (HAART) treatment in order to prevent a PCP epidemic.

Dysbiosis and a dysregulated gut immune barrier function contributes to chronic immune activation in HIV-1 infection. We investigated if nutritional supplementation with vitamin D and phenylbutyrate could improve gut-derived inflammation, selected microbial metabolites, and composition of the gut microbiota. Treatment-naïve HIV-1-infected individuals (n = 167) were included from a double-blind, randomized, and placebo-controlled trial of daily 5000 IU vitamin D and 500 mg phenylbutyrate for 16 weeks (Clinicaltrials.gov NCT01702974). Baseline and per-protocol plasma samples at week 16 were analysed for soluble CD14, the antimicrobial peptide LL-37, kynurenine/tryptophan-ratio, TMAO, choline, and betaine. Assessment of the gut microbiota involved 16S rRNA gene sequencing of colonic biopsies. Vitamin D + phenylbutyrate treatment significantly increased 25-hydroxyvitamin D levels (p < 0.001) but had no effects on sCD14, the kynurenine/tryptophan-ratio, TMAO, or choline levels. Subgroup-analyses of vitamin D insufficient subjects demonstrated a significant increase of LL-37 in the treatment group (p = 0.02), whereas treatment failed to significantly impact LL-37-levels in multiple regression analysis. Further, no effects on the microbiota was found in number of operational taxonomic units (p = 0.71), Shannon microbial diversity index (p = 0.82), or in principal component analyses (p = 0.83). Nutritional supplementation with vitamin D + phenylbutyrate did not modulate gut-derived inflammatory markers or microbial composition in treatment-naïve HIV-1 individuals with active viral replication.

Low vitamin D (vitD₃) is one of the most common nutritional deficiencies in the world known to be associated with numerous medical conditions including infections such as tuberculosis (TB). In this study, vitD₃ status and its association with the antimicrobial peptide, human cathelicidin (LL-37), was investigated in Ethiopian patients with different clinical forms of TB. Patients with active TB (n = 77) and non-TB controls (n = 78) were enrolled in Ethiopia, while another group of non-TB controls (n = 62) was from Sweden. Active TB included pulmonary TB (n = 32), pleural TB (n = 20), and lymph node TB (n = 25). Concentrations of 25-hydroxyvitamin D₃ (25(OH)D₃) were assessed in plasma, while LL-37 mRNA was measured in peripheral blood and in samples obtained from the site of infection. Median 25(OH)D₃ plasma levels in active TB patients were similar to Ethiopian non-TB controls (38.5 versus 35.0 nmol/L) and vitD₃ deficiency (<50 nmol/L) was common in both groups (73%). Ethiopians (low latitude) had significantly lower 25(OH)D₃ levels compared with Swedish non-TB controls (51.0 nmol/L, high latitude), but vitD₃ status was not affected by tuberculin-positivity or HIV infection. Patients with local lymph node TB had significantly higher 25(OH)D₃ levels compared with pulmonary TB patients (48.0 versus 29.0 nmol/L). Moreover, plasma 25(OH)D₃ levels correlated with local LL-37 expression in granulomatous lesions in TB infected lymph nodes. Instead, systemic LL-37 mRNA expression in blood cells was elevated compared with the site of infection in pulmonary and pleural TB. Low vitD₃ status may be associated with an enhanced peripheral expression of LL-37 in patients with intrathoracic TB that could result from chronic inflammation.