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

Clinical factors for severity of Plasmodium falciparum malaria in hospitalized adults in Thailand.

Plasmodium falciparum is a major cause of severe malaria in Southeast Asia, however, there is limited information regarding clinical factors associated with the severity of falciparum malaria from this region. We performed a retrospective case-control study to compare clinical factors and outcomes between patients with severe and non-severe malaria, and to identify clinical factors associated with the requirement for intensive care unit (ICU) admission of patients with severe falciparum malaria among hospitalized adults in Southeast Asia. A total of 255 patients with falciparum malaria in the Hospital for Tropical Diseases in Bangkok, Thailand between 2006 and 2012 were included. We identified 104 patients with severe malaria (cases) and 151 patients with non-severe malaria (controls). Patients with falciparum malaria with following clinical and laboratory characteristics on admission (1) referrals, (2) no prior history of malaria, (3) body temperature of >38.5°C, (4) white blood cell counts >10×10(9)/µL, (5) presence of schizonts in peripheral blood smears, and (6) albumin concentrations of <3.5 g/dL, were more likely to develop severe malaria (P<0.05). Among patients with severe malaria, patients who met ≥3 of the 2010 WHO criteria had sensitivity of 79.2% and specificity of 81.8% for requiring ICU admission. Multivariate analysis identified the following as independent associated factors for severe malaria requiring ICU admission; (1) ethnicity of Thai [odds ratio (OR) = 3.601, 95% confidence interval (CI) = 1.011-12.822] or Myanmar [OR = 3.610, 95% CI = 1.138-11.445]; (2) referrals [OR = 3.571, 95% CI = 1.306-9.762]; (3) no prior history of malaria [OR = 5.887, 95% CI = 1.354-25.594]; and (4) albumin concentrations of <3.5 g/dL [OR = 7.200, 95% CI = 1.802-28.759]. Our findings are important for the clinical management of patients with malaria because it can help early identification of patients that could develop severe malaria and require ICU admission. Early identification and the timely initiation of appropriate treatments may well improve the outcomes and reduce the mortality of these patients

Baseline characteristics, clinical parameters, management and outcomes of hospitalized patients with falciparum malaria (severe or non-severe malaria).

<p><b>Note:</b> IQR = interquartile range; WBC = white blood cell counts; FCT = fever clearance time; PCT = parasite clearance time.</p

Baseline characteristics, clinical and laboratory parameters, management and outcomes of hospitalized patients with severe falciparum malaria (ICU or without ICU admission).

<p><b>Note:</b> ICU = intensive care unit; IQR = interquartile range; WBC = white blood cell counts; FCT = fever clearance time; PCT = parasite clearance time.</p

Patient recruitment flow chart.

<p>Patient recruitment flow chart.</p

Baseline characteristics, clinical parameters, management and outcomes of patients with severe falciparum malaria requiring ICU (with shock or without shock).

<p><b>Note:</b> ICU = intensive care unit; IQR = interquartile range; WBC = white blood cell counts; FCT = fever clearance time; PCT = parasite clearance time.</p

Sensitivity and specificity of the 2010 WHO criteria for requiring intensive care unit in hospitalized patients with severe falciparum malaria.

<p><b>Note:</b> WHO = World Health Organization; ICU = intensive care unit.</p

Univariate and multivariate logistic regression analysis of baseline characteristic, as well as clinical and laboratory parameters for requirement of ICU in hospitalized patients with severe falciparum malaria.

<p><b>Note:</b> ICU = intensive care unit; OR = odds ratio; CI = confidence interval.</p

All Serious Adverse Events (non-related events and related adverse drug reactions) by System Organ Class (bold) and Preferred Term according to MedDRA.

<p>MedDRA, Medical Dictionary of Regulatory Activities; SSG, sodium stibogluconate (20 mg/kg/day for 30 days); PM paromomycin sulphate (20 mg/kg/day for 21 days); SSG & PM (SSG 20 mg/kg/day & PM at 15 mg/kg/day for 17 days); NR, non-related Serious Adverse Events; SADR, Serious Adverse Drug Reaction.</p>a<p>Death due to an unknown cause.</p>b<p>Raised bilirubin/jaundice.</p>c<p>Abdominal sepsis and malaria were considered as unlikely related to the drug by the investigators.</p>d<p>2 PM patients withdrew consent after 4 and 6 days on treatment and 1 SSG & PM patient after 6 days on treatment, no SAE reported prior to withdrawal.</p