Paromomycin and Miltefosine Combination as an Alternative to Treat Patients With Visceral Leishmaniasis in Eastern Africa: A Randomized, Controlled, Multicountry Trial.

BACKGROUND: This study aimed to determine whether paromomycin plus miltefosine (PM/MF) is noninferior to sodium stibogluconate plus paromomycin (SSG/PM) for treatment of primary visceral leishmaniasis in eastern Africa. METHODS: An open-label, phase 3, randomized, controlled trial was conducted in adult and pediatric patients at 7 sites in eastern Africa. Patients were randomly assigned to either 20 mg/kg paromomycin plus allometric dose of miltefosine (14 days), or 20 mg/kg sodium stibogluconate plus 15 mg/kg paromomycin (17 days). The primary endpoint was definitive cure after 6 months. RESULTS: Of 439 randomized patients, 424 completed the trial. Definitive cure at 6 months was 91.2% (155 of 170) and 91.8% (156 of 170) in the PM/MF and SSG/PM arms in primary efficacy modified intention-to-treat analysis (difference, 0.6%; 97.5% confidence interval [CI], -6.2 to 7.4), narrowly missing the noninferiority margin of 7%. In the per-protocol analysis, efficacy was 92% (149 of 162) and 91.7% (155 of 169) in the PM/MF and SSG/PM arms (difference, -0.3%; 97.5% CI, -7.0 to 6.5), demonstrating noninferiority. Treatments were well tolerated. Four of 18 serious adverse events were study drug-related, and 1 death was SSG-related. Allometric dosing ensured similar MF exposure in children (<12 years) and adults. CONCLUSIONS: PM/MF and SSG/PM efficacies were similar, and adverse drug reactions were as expected given the drugs safety profiles. With 1 less injection each day, reduced treatment duration, and no risk of SSG-associated life-threatening cardiotoxicity, PM/MF is a more patient-friendly alternative for children and adults with primary visceral leishmaniasis in eastern Africa. CLINICAL TRIALS REGISTRATION: NCT03129646.

Performance of loop-mediated isothermal amplification assay in the diagnosis of pulmonary tuberculosis in a high prevalence TB/HIV rural setting in Uganda.

BACKGROUND: Smear microscopy lacks sensitivity especially in HIV co-infection, resulting in undiagnosed tuberculosis (TB) and high mortality. The loop-mediated isothermal amplification (TB-LAMP) assay can be staged with minimal infrastructure, is rapid, low cost and detection can be with the naked eye. We assessed feasibility and performance of Eiken TB-LAMP test at point-of-need in TB diagnosis in a high prevalence TB/HIV rural setting in Uganda. METHODS: From October 2013-February 2014, TB-LAMP testing was performed on sputum specimens from outpatient presumptive TB adults at a district hospital and two low-level health centers in Kiboga District where smear microscopy is the available routine diagnostic option. TB-LAMP was performed by a technician after a week of training in the district hospital. The technician had no prior experience in the technology. Samples from the low-level health centers were transported to the district hospital for TB-LAMP. RESULTS: Of the 233 presumptive TB (126 at hospital); 113 (48.5%) were HIV-infected; 129 (55%) male; median age 40 (IQR 30-53). Compared to MTB culture, overall sensitivity and specificity of TB-LAMP were 55.4% (95 CI 44.1-66.3) and 98.0% (95 CI 94.3-99.6) respectively. Among HIV-infected participants, TB-LAMP sensitivity and specificity were 52.3% (95 CI 36.7-67.5%) and 97.1% (95 CI 89.9-99.6) respectively; and 24.4% (95% CI 12.9-39.5) and 98.6% (95% CI 95.1-99.8) respectively among smear-negatives. TB-LAMP sensitivity and specificity were 62.2% (95% CI 44.8-77.5) and 97.8% (95% CI 92.1-99.7) in the hospital setting where central testing occurred compared to 50.0% (95% CI 34.9-65.1) and 98.4% (95% CI 91.2-100) respectively in low-level health centers where specimens were transported centrally. CONCLUSIONS: In this high prevalence TB/HIV rural setting, TB-LAMP performs better than conventional smear microscopy in diagnosis of MTB among presumptive TB patients although the sensitivity is lower than that reported by the World Health Organization. TB-LAMP can easily be performed following a short training period and in absence of sophisticated infrastructure and expertise.