Oesophageal varices, schistosomiasis, and mortality among patients admitted with haematemesis in Mwanza, Tanzania: a prospective cohort study.

BACKGROUND: Upper gastrointestinal bleeding (UGIB) is a common cause of hospital admissions worldwide. Aetiologies vary by sociodemographics and geography. Retrospective studies of endoscopies in much of Africa have documented oesophageal varices as a leading cause of UGIB. Prospective studies describing outcomes and associations with clinical factors are lacking. METHODS: We conducted a prospective cohort study at a referral hospital in Mwanza, Tanzania where schistosomiasis is endemic. Adults admitted with haematemesis underwent laboratory workup, schistosomiasis antigen testing and elective endoscopy, and were followed for two months for death or re-bleeding. We assessed predictors of endoscopic findings using logistic regression models, and determined prediction rules that maximised sensitivity and positive predictive value (PPV). RESULTS: Of 124 enrolled patients, 13 died within two months (10%); active schistosomiasis prevalence was 48%. 64/91(70%) patients had oesophageal varices. We found strong associations between varices and numerous demographic or clinical findings, permitting construction of simple, high-fidelity prediction rules for oesophageal varices applicable even in rural settings. Portal vein diameter ≥ 13 mm or water sourced from the lake yielded sensitivity, specificity, PPV and NPV >90% for oesophageal varices; presence of splenomegaly or water sourced from the lake maintained sensitivity and PPV >90%. CONCLUSIONS: Our results guide identification of patients, via ultrasound and clinical examination, likely to have varices for whom referral for endoscopy may be life-saving. Furthermore, they support empiric anti-schistosome treatment for patients with UGIB in schistosome-endemic regions. These interventions have potential to reduce UGIB-related morbidity and mortality in Africa

AMBITION-cm : intermittent high dose AmBisome on a high dose fluconazole backbone for cryptococcal meningitis induction therapy in sub-Saharan Africa : study protocol for a randomized controlled trial

Cryptococcal meningitis (CM) is a leading cause of mortality among HIV-infected individuals in Africa. Poor outcomes from conventional antifungal therapies, unavailability of flucytosine, and difficulties administering 14 days of amphotericin B are key drivers of this mortality. Novel treatment regimes are needed. This study examines whether short-course high-dose liposomal amphotericin B (AmBisome), given with high dose fluconazole, is non-inferior (in terms of microbiological and clinical endpoints) to standard-dose 14-day courses of AmBisome plus high dose fluconazole for treatment of HIV-associated CM.; This is an adaptive open-label phase II/III randomised non-inferiority trial comparing alternative short course AmBisome regimens. Step 1 (phase II) will compare four treatment arms in 160 adult patients (≥18 years old) with a first episode of HIV-associated CM, using early fungicidal activity (EFA) as the primary outcome: 1) AmBisome 10 mg/kg day one (single dose); 2) AmBisome 10 mg/kg day one and AmBisome 5 mg/kg day three (two doses); 3) AmBisome 10 mg/kg day one, and AmBisome 5 mg/kg days three and seven (three doses); and 4) AmBisome 3 mg/kg/d for 14 days (control); all given with fluconazole 1200 mg daily for 14 days. STEP 2 (phase III) will enrol 300 participants and compare two treatment arms using all-cause mortality within 70 days as the primary outcome: 1) the shortest course AmBisome regimen found to be non-inferior in terms of EFA to the 14-day control arm in STEP 1, and 2) AmBisome 3 mg/kg/d for 14 days (control), both given with fluconazole 1200 mg daily for 14 days. STEP 2 analysis will include all patients from STEP 1 and STEP 2 taking the STEP 2 regimens. All patients will be followed for ten weeks, and mortality and safety data recorded. All patients will receive consolidation therapy with fluconazole 400-800 mg daily and ART in accordance with local guidelines. The primary analysis (for both STEP 1 and STEP 2) will be intention-to-treat