Efficacy and Safety of AmBisome in Combination with Sodium Stibogluconate or Miltefosine and Miltefosine Monotherapy for African Visceral Leishmaniasis: Phase II Randomized Trial.

BACKGROUND: SSG&PM over 17 days is recommended as first line treatment for visceral leishmaniasis in eastern Africa, but is painful and requires hospitalization. Combination regimens including AmBisome and miltefosine are safe and effective in India, but there are no published data from trials of combination therapies including these drugs from Africa. METHODS: A phase II open-label, non-comparative randomized trial was conducted in Sudan and Kenya to evaluate the efficacy and safety of three treatment regimens: 10 mg/kg single dose AmBisome plus 10 days of SSG (20 mg/kg/day), 10 mg/kg single dose AmBisome plus 10 days of miltefosine (2.5mg/kg/day) and miltefosine alone (2.5 mg/kg/day for 28 days). The primary endpoint was initial parasitological cure at Day 28, and secondary endpoints included definitive cure at Day 210, and pharmacokinetic (miltefosine) and pharmacodynamic assessments. RESULTS: In sequential analyses with 49-51 patients per arm, initial cure was 85% (95% CI: 73-92) in all arms. At D210, definitive cure was 87% (95% CI: 77-97) for AmBisome + SSG, 77% (95% CI 64-90) for AmBisome + miltefosine and 72% (95% CI 60-85) for miltefosine alone, with lower efficacy in younger patients, who weigh less. Miltefosine pharmacokinetic data indicated under-exposure in children compared to adults. CONCLUSION: No major safety concerns were identified, but point estimates of definitive cure were less than 90% for each regimen so none will be evaluated in Phase III trials in their current form. Allometric dosing of miltefosine in children needs to be evaluated. TRIAL REGISTRATION: The study was registered with ClinicalTrials.gov, number NCT01067443

Sodium Stibogluconate (SSG) & Paromomycin Combination Compared to SSG for Visceral Leishmaniasis in East Africa: A Randomised Controlled Trial

Visceral leishmaniasis (VL) is a parasitic disease with about 500,000 new cases each year and is fatal if untreated. The current standard therapy involves long courses, has toxicity and there is evidence of increasing resistance. New and better treatment options are urgently needed. Recently, the antibiotic paromomycin (PM) was tested and registered in India to treat this disease, but the same dose of PM monotherapy evaluated and registered in India was not efficacious in Sudan. This article reports the results of a clinical trial to test the effectiveness of injectable PM either alone (in a higher dose) or in combination with sodium stibogluconate (SSG) against the standard SSG monotherapy treatment in four East African countries—Sudan, Kenya, Ethiopia and Uganda. The study showed that the combination of SSG &PM was as efficacious and safe as the standard SSG treatment, with the advantages of being cheaper and requiring only 17 days rather than 30 days of treatment. In March 2010, a WHO Expert Committee recommended the use of the SSG & PM combination as a first line treatment for VL in East Africa

A clinical algorithm for triaging patients with significant lymphadenopathy in primary health care settings in Sudan

Background: Tuberculosis is a major health problem in developing countries. The distinction between tuberculous lymphadenitis, non-specific lymphadenitis and malignant lymph node enlargement has to be made at primary health care levels using easy, simple and cheap methods. Objective: To develop a reliable clinical algorithm for primary care settings to triage cases ofnon-specific, tuberculous and malignant lymphadenopathies. Methods: Calculation of the odd ratios (OR) of the chosen predictor variables was carried out using logistic regression. The numerical score values of the predictor variables were weighed against their respective OR. The performance of the score was evaluated by the ROC (ReceiverOperator Characteristic) curve. Results: Four predictor variables; Mantoux reading, erythrocytes sedimentation rate (ESR),nocturnal fever and discharging sinuses correlated significantly with TB diagnosis and were included in the reduced model to establish score A. For score B, the reduced model included Mantoux reading, ESR, lymph-node size and lymph-node number as predictor variables for malignant lymph nodes. Score A ranged 0 to 12 and a cut-off point of 6 gave a best sensitivity and specificity of 91% and 90% respectively, whilst score B ranged -3 to 8 and a cut-off point of3 gave a best sensitivity and specificity of 83% and 76% respectively. The calculated area underthe ROC curve was 0.964 (95% CI, 0.949 – 0.980) and -0.856 (95% CI, 0.787 ‑ 0.925) for scores Aand B respectively, indicating good performance. Conclusion: The developed algorithm can efficiently triage cases with tuberculous andmalignant lymphadenopathies for treatment or referral to specialised centres for furtherwork-up