Safety and efficacy of paromomycin/miltefosine/liposomal amphotericin B combinations for the treatment of post-kala-azar dermal leishmaniasis in Sudan: A phase II, open label, randomized, parallel arm study.

BACKGROUND: Treatment for post-kala-azar dermal leishmaniasis (PKDL) in Sudan is currently recommended only for patients with persistent or severe disease, mainly because of the limitations of current therapies, namely toxicity and long hospitalization. We assessed the safety and efficacy of miltefosine combined with paromomycin and liposomal amphotericin B (LAmB) for the treatment of PKDL in Sudan. METHODOLOGY/PRINCIPAL FINDINGS: An open-label, phase II, randomized, parallel-arm, non-comparative trial was conducted in patients with persistent (stable or progressive disease for ≥ 6 months) or grade 3 PKDL, aged 6 to ≤ 60 years in Sudan. The median age was 9.0 years (IQR 7.0-10.0y) and 87% of patients were ≤12 years old. Patients were randomly assigned to either daily intra-muscular paromomycin (20mg/kg, 14 days) plus oral miltefosine (allometric dose, 42 days)-PM/MF-or LAmB (total dose of 20mg/kg, administered in four injections in week one) and oral miltefosine (allometric dose, 28 days)-LAmB/MF. The primary endpoint was a definitive cure at 12 months after treatment onset, defined as clinical cure (100% lesion resolution) and no additional PKDL treatment between end of therapy and 12-month follow-up assessment. 104/110 patients completed the trial. Definitive cure at 12 months was achieved in 54/55 (98.2%, 95% CI 90.3-100) and 44/55 (80.0%, 95% CI 70.2-91.9) of patients in the PM/MF and AmB/MF arms, respectively, in the mITT set (all randomized patients receiving at least one dose of treatment; in case of error of treatment allocation, the actual treatment received was used in the analysis). No SAEs or deaths were reported, and most AEs were mild or moderate. At least one adverse drug reaction (ADR) was reported in 13/55 (23.6%) patients in PM/MF arm and 28/55 (50.9%) in LAmB/MF arm, the most frequent being miltefosine-related vomiting and nausea, and LAmB-related hypokalaemia; no ocular or auditory ADRs were reported. CONCLUSIONS/SIGNIFICANCE: The PM/MF regimen requires shorter hospitalization than the currently recommended 60-90-day treatment, and is safe and highly efficacious, even for patients with moderate and severe PKDL. It can be administered at primary health care facilities, with LAmB/MF as a good alternative. For future VL elimination, we need new, safe oral therapies for all patients with PKDL. TRIAL REGISTRATION: ClinicalTrials.gov NCT03399955, https://clinicaltrials.gov/study/NCT03399955 ClinicalTrials.gov ClinicalTrials.gov.

Incidence of delirium in the critical care unit and risk factors in the Central Region, Saudi Arabia.

OBJECTIVES: To determine the incidence and risk factors of delirium in the cardiac care unit (CCU) and intensive care unit (ICU). METHODS: This multicenter prospective observational study was conducted between July 2019 and November 2019 in the central region of Saudi Arabia. All patients admitted to the critical care units were enrolled, and their demographic data and risk factors of delirium were reported. RESULTS: A total of 165 patients were included: 76 (46.1%) admitted to the CCU and 89 (53.9%) admitted to the ICU. The mean age was 55.1±18 years, and 45 (27.3%) were women. We found that 24/165 (14.5%) patients developed delirium during admission. Importantly, variables significantly associated with delirium group were female gender: (24.5% versus 10.8%, p=0.028), malnutrition (29.2% versus 5%, p<0.001), the presence of urinary catheter (75% versus 30.5%, p=0.001), septicemia (50% versus 14.9%, p<0.001), intubation (41.7% versus 10.6%, p=0.001), low hemoglobin (10.79±2.91 versus 12.05±2.77, p=048), and prolonged prothrombin time (PT) (15.87±5.17 versus 13.60±3.28, p=0.011). CONCLUSION: The incidence of delirium was 14.5% among patients admitted to critical care units in the central region of Saudi Arabia. Septicemia, prolonged PT, malnutrition, and urinary catheter are significant predictors of delirium.

Levels of organochlorine pesticides in the blood of people living in areas of intensive pesticide use in Sudan.

Ninety-six human blood samples were collected from six locations that represent areas of intensive pesticide use in Sudan, which included irrigated cotton schemes (Wad Medani, Hasaheesa, Elmanagil, and Elfaw) and sugarcane schemes (Kenana and Gunaid). Blood samples were analyzed for organochlorine pesticide residues by gas liquid chromatography (GLC) equipped with an electron capture detector (ECD). Residues of p,p'-dichlorodiphenyldichloroethylene (DDE), heptachlor epoxide, γ-HCH, and dieldrin were detected in blood from all locations surveyed. Aldrin was not detected in any of the samples analyzed, probably due to its conversion to dieldrin. The levels of total organochlorine burden detected were higher in the blood from people in the irrigated cotton schemes (mean 261 ng ml(-1), range 38-641 ng ml(-1)) than in the blood of people from the irrigated sugarcane schemes (mean 204 ng ml(-1), range 59-365 ng ml(-1)). The highest levels of heptachlor epoxide (170 ng ml(-1)) and γ-HCH (92 ng ml(-1)) were observed in blood samples from Hasaheesa, while the highest levels of DDE (618 ng ml(-1)) and dieldrin (82 ng ml(-1)) were observed in blood samples from Wad Medani and Kenana, respectively. The organochlorine levels in blood samples seemed to decrease with increasing distance from the old irrigated cotton schemes (Wad Medani, Hasaheesa, and Elmanagil) where the heavy application of these pesticides took place historically.

Acute renal failure associated with the Rift Valley fever: a single center study.

Renal impairment is a frequent occurrence among patients with the Rift Valley fever (RVF), and is probably the result of hypovolemia and multiple organ dysfunctions in the majority of cases. This study was conducted to estimate the incidence of renal impairment in patients with RVF as well as to determine the associated mortality. Data of all patients admitted with renal impairment to the Gezira Hospital for Renal Diseases, Sudan, during the epidemic of RVF between September 2007 and January 2008 were analyzed. The total number of patients with RVF was 392 of whom, 194 were admitted to the Medani Teaching Hospital. Renal impairment was detected in 60% of the admitted patients; 90% of them needed dialysis treatment. The mortality rate was 31% in patients with acute renal failure, 25% in those with the hepatorenal syndrome and 31% in patients with primary hepatic involvement and mild renal impairment. The overall mortality was 40%. Our study suggests that RVF remains a major cause of acute renal failure with considerable mortality, although progression to chronic renal failure was not seen. Early renal substitution therapy fosters the best hope for survival.