Patients in sub-Saharan Africa generally have poor anticoagulation control. We review the potential reasons for this poor control, as well as the potential solutions. Challenges include the affordability and centralisation of anticoagulation care, problems with access to medicines and INR monitoring, the lack of locally-validated standardized dosing protocols, and low levels of anticoagulation knowledge among health care workers and patients. Increasing numbers of patients will need anticoagulation in the future because of the epidemiological transition in the region. We propose that locally-developed "warfarin care bundles" which address multiple anticoagulation challenges in combination may be the most appropriate solution in this setting currently.

Background There is need for simple, cost effective and widely available point of care tests for low level health facilities in developing countries to screen for drug resistant tuberculosis (TB) after bacteriological confirmation of TB by smear microscopy. We evaluated the sensitivity and specificity of the mean corpuscular volume (MCV) and CD4/CD8 ratio in discriminating between rifampicin resistant (RR-TB) and rifampicin sensitive (RS-TB) tuberculosis. Methods We performed a secondary analysis of data from a cross sectional study that enrolled adult participants with bacteriologically confirmed pulmonary TB at a national tuberculosis treatment center in Uganda. Blood samples were tested for CD4 and CD8 cell counts, HIV serology and a full hemogram. Rifampicin sensitivity and the bacillary load grade were determined by Xpert MTB/RIF®. Fifty-five participants that had RR-TB (cases) were matched with 110 participants that had RS-TB (controls) for age, sex and HIV status in a ratio of 1:2 respectively. Sensitivity (Se), specificity (Sp), area under curve (AUC) analysis and determination of optimal cut-offs were performed using receiver operating characteristic curves. Results Cases differed from controls with respect to residence (p = 0.031), bacillary load grade (p < 0.010) and MCV (p = 0.021). The Se, Sp and AUC of the MCV (cut-off of > 74.6 femtolitres (fl)) were 88.9%, 34% and 0.607 (p = 0.021) respectively for RR-TB. Among HIV positive participants, the respective Se, Sp and AUC of the MCV for RR-TB (cut-off of > 72.5 fl) were 97.2%, 22.2% and 0.608 (p = 0.061). The respective Se, Sp and AUC of the CD4/CD8 ratio (cut-off of > 0.40) were 67.3%, 50.0% and 0.559 (p = 0.199) on the overall and 54.1%, 71.6% and 0.628 (p = 0.024) among the HIV positive participants for RR-TB. Conclusion The MCV had a high sensitivity but very low specificity for RR-TB. The CD4/CD8 ratio had a low sensitivity and specificity for RR-TB among HIV positive individuals. The utility of either test is low due to low diagnostic accuracy.

Background Heavy consumption of alcohol increases the risk of developing active tuberculosis (TB), contributes to delayed diagnosis and affects adherence to treatment. Within a large urban case-finding project, we sought to determine the prevalence of and factors associated with AUD and to understand the lived experiences of patients with alcohol use disorder (AUD).Methods We carried out a mixed methods study in two large urban districts in Uganda. We collected quantitative data on the prevalence of alcohol use disorder using the Cut, Annoyed, Guilty, Eye opener (CAGE) tool. We conducted focus group discussions (FGDs) to understand lived experiences of patients with AUD particularly challenges with adhering to TB treatment. Factors associated with AUD were examined using a multilevel logistic regression model. Focus group discussions were transcribed, data was analysed inductively and coded into themes.Results Out of 325 TB patients interviewed, 62 (18.7% 95% confidence interval [CI] 18–31%) had AUD. Majority 82.3% (51/62) were men. Being male aOR 3.26 (95% CI 1.45, 7.33) and living in an urban area aOR 1.89 (95% CI: 1.01, 3.53) were significantly associated with AUD. Among patients with AUD, there was a trend towards suboptimal TB treatment outcomes, although this did not reach significance aOR 2.15 (95% CI: 0.95, 4.90). Fourteen patients (eight men and six women) with AUD attended two FGDs. Patients with AUD often did not disclose alcohol use and missed clinic refill appointments due to lack of money to pay the transport fare to the clinic. In addition, lack of food coupled with the long treatment duration were challenges to TB treatment completion.Conclusion A large proportion of TB patients have undisclosed AUD and experience several challenges while on TB treatment. TB care programs need to design interventions in order to address AUD.

Aim Patients on anti-tuberculosis (anti-TB) therapy are at risk of drug-induced liver injury (DILI). and cytokeratin-18 (K18) are exploratory DILI biomarkers. To explore their utility in this global context, circulating miR-122 and K18 concentrations were measured in UK and Ugandan populations on anti-TB therapy for mycobacterial infection. Methods European patients receiving anti-TB therapy were recruited at the Royal Infirmary of Edinburgh, UK (ALISTER-ClinicalTrials.gov Identifier: NCT03211208). African patients with HIV-TB coinfection, receiving anti-TB and anti-retroviral therapy (ART), were recruited at the Infectious Diseases Institute, Kampala, Uganda (SAEFRIF-NCT03982277). Serial blood samples, demographic and clinical data were collected. MiR-122 was quantified using PCR. K18 was quantified using the M65 ELISA. Results The study had 235 participants (healthy volunteers (n=28); ALISTER: active TB (n=30), latent TB (n=88), non-tuberculous mycobacterial infection (n=25); SAEFRIF: HIV-TB coinfection (n=64)). In the absence of DILI, there was no difference in miR-122 and K18 across the groups. Both miR-122 and K18 correlated with alanine transaminase activity (ALT) (miR-122: r=0.52, 95%CI=0.42-0.61, P<0.0001. K18: r=0.42, 95%CI=0.34-0.49, P<0.0001). There were two DILI cases: baseline ALT was 18 and 28 IU/L, peak ALT 431 and 194 IU/L; baseline K18 58 and 219 U/L, peak K18 1247 and 3490 U/L; baseline miR-122 4 and 17 fM, peak miR-122 60 and 336 fM, respectively. Conclusion In European and African patients treated with anti-TB therapy miR-122 and K18 correlated with ALT and increased with DILI. Further work should determine the diagnostic and prognostic utility of miR-122 and K18 in this global context-of-use.What is already known about this subject:• Drug induced liver injury (DILI) is a major concern in the treatment of tuberculosis (TB).• There are new biomarkers for DILI which have the potential to add value because of enhanced specificity/sensitivity compared to current tests. • These mechanistically informative DILI biomarkers have qualifying data from large USA and European studies. However, these markers have not been tested in Africa. Given the global burden of TB our aim was to explore biomarker utility in this global context of use.