Treatment regimens for post-kala-azar dermal leishmaniasis (PKDL) are usually extrapolated from those for visceral leishmaniasis (VL), but drug pharmacokinetics (PK) can differ due to disease-specific variations in absorption, distribution, and elimination. This study characterized PK differences in paromomycin and miltefosine between 109 PKDL and 264 VL patients from Eastern Africa. VL patients showed 0.
View Article and Find Full Text PDFBackground: With the current treatment options for visceral leishmaniasis (VL), recrudescence of the parasite is seen in a proportion of patients. Understanding parasite dynamics is crucial to improving treatment efficacy and predicting patient relapse in cases of VL. This study aimed to characterize the kinetics of circulating Leishmania parasites in the blood, during and after different antileishmanial therapies, and to find predictors for clinical relapse of disease.
View Article and Find Full Text PDFObjectives: To improve visceral leishmaniasis (VL) treatment in Eastern Africa, 14- and 28-day combination regimens of paromomycin plus allometrically dosed miltefosine were evaluated. As the majority of patients affected by VL are children, adequate paediatric exposure to miltefosine and paromomycin is key to ensuring good treatment response.
Methods: Pharmacokinetic data were collected in a multicentre randomized controlled trial in VL patients from Kenya, Sudan, Ethiopia and Uganda.
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).
Background: To expedite the development of new oral treatment regimens for visceral leishmaniasis (VL), there is a need for early markers to evaluate treatment response and predict long-term outcomes.
Methods: Data from 3 clinical trials were combined in this study, in which Eastern African VL patients received various antileishmanial therapies. Leishmania kinetoplast DNA was quantified in whole blood with real-time quantitative polymerase chain reaction (qPCR) before, during, and up to 6 months after treatment.
Background: Conventional miltefosine dosing (2.5 mg/kg/day) for treatment of visceral leishmaniasis (VL) is less effective in children than in adults. A higher allometric dose (median 3.
View Article and Find Full Text PDFThe development of an accurate protein-based antigen detection assay for diagnosis of active visceral leishmaniasis (VL) would represent a major clinical advance. VL is a serious and fatal disease caused by the parasites Leishmania infantum and Leishmania donovani. The gold standard confirmatory diagnostic test for VL is the demonstration of parasites or their DNA from aspirates from spleen, lymph node, and bone marrow or from blood buffy coats.
View Article and Find Full Text PDFA highly sensitive method was developed to quantitate the antileishmanial agent paromomycin in human plasma, with a lower limit of quantification of 5 ng/mL. Separation was achieved using an isocratic ion-pair ultra-high performance liquid chromatographic (UPLC) method with a minimal concentration of heptafluorobutyric acid, which was coupled through an electrospray ionization interface to a triple quadrupole - linear ion trap mass spectrometer for detection. The method was validated over a linear calibration range of 5 to 1000 ng/mL (r≥0.
View Article and Find Full Text PDFInt J Health Plann Manage
January 2020
Objective: To estimate the direct and indirect costs of diabetes mellitus care at five public health facilities in Kenya.
Methods: We conducted a cross-sectional study in two counties where diabetes patients aged 18 years and above were interviewed. Data on care-seeking costs were obtained from 163 patients seeking diabetes care at five public facilities using the cost-of-illness approach.
Background: There is little information on stroke morbidity in Kenya to inform health care planning. The disability-adjusted life-years (DALYs) are a time-based measure of health status that incorporates both disability and mortality.
Methods: This was a multicenter prospective study in Kenya's public tertiary hospitals conducted in 2015-2017.
Visceral leishmaniasis (VL) is a serious and fatal disease caused by the parasites and The gold standard diagnostic test for VL is the demonstration of parasites or their DNA in spleen, lymph node, or bone marrow aspirates. Serological tests exist but cannot distinguish active VL from either prior exposure to the parasites or previously treated VL disease. Using mass spectroscopy, we have previously identified three protein biomarkers (, , and ) in the urine of VL patients and developed a sensitive and specific urine-based antigen detection assay for the diagnosis of VL that occurs in Brazil (where VL is caused by ).
View Article and Find Full Text PDFInt J Health Plann Manage
April 2019
Background: Hypertension in low- and middle-income countries, including Kenya, is of economic importance due to its increasing prevalence and its potential to present an economic burden to households. In this study, we examined the patient costs associated with obtaining care for hypertension in public health care facilities in Kenya.
Methods: We conducted a cross-sectional study among adult respondents above 18 years of age, with at least 6 months of treatment in two counties.
Background: Few longitudinal studies have examined associations between risk factors during pregnancy and mental health outcomes during the postpartum period. We used a cohort study design to estimate the prevalence, incidence and correlates of significant postpartum depressive symptoms in Kenyan women.
Methods: We recruited adult women residing in an urban, resource-poor setting and attending maternal and child health clinics in two public hospitals in Nairobi, Kenya.
Background: Convenient, safe, and effective treatments for visceral leishmaniasis in Eastern African children are lacking. Miltefosine, the only oral treatment, failed to achieve adequate efficacy, particularly in children, in whom linear dosing (2.5 mg/kg/day for 28 days) resulted in a 59% cure rate, with lower systemic exposure than in adults.
View Article and Find Full Text PDFCerebrovasc Dis Extra
October 2018
Background: Despite the increasing global burden of stroke, there are limited data on stroke from Kenya to guide in decision-making. Stroke occurrence in sub-Saharan Africa has been associated with poor health outcomes. This study sought to establish the stroke incidence density and mortality in Kenya's leading public tertiary hospitals for purposes of informing clinical practice and policy.
View Article and Find Full Text PDFSeveral methods have been developed for the detection of Leishmania, mostly targeting the minicircle kinetoplast DNA (kDNA). A new RNA real-time quantitative PCR (qPCR) assay was developed targeting the conserved and highly expressed spliced-leader (SL) mini-exon sequence. This study compared the limits of detection of various real-time PCR assays in hamsters infected with Leishmania infantum, in spiked human blood, and in clinical blood samples from visceral leishmaniasis patients.
View Article and Find Full Text PDFBackground: Visceral leishmaniasis (VL) is a systemic parasitic disease that is fatal unless treated. In Kenya, national VL guidelines rely on microscopic examination of spleen aspirate to confirm diagnosis. As this procedure is invasive, it cannot be safely implemented in peripheral health structures, where non-invasive, accurate, easy to use diagnostic tests are needed.
View Article and Find Full Text PDFBackground: Alternative treatments for visceral leishmaniasis (VL) are required in East Africa. Paromomycin sulphate (PM) has been shown to be efficacious for VL treatment in India.
Methods: A multi-centre randomized-controlled trial (RCT) to compare efficacy and safety of PM (20 mg/kg/day for 21 days) and PM plus sodium stibogluconate (SSG) combination (PM, 15 mg/kg/day and SSG, 20 mg/kg/day for 17 days) with SSG (20 mg/kg/day for 30 days) for treatment of VL in East Africa.
Visceral leishmaniasis (VL) seroprevalence in Kenya is unknown because of the lack of a practical and accurate diagnostic test or surveillance system. A novel serological assay was used to estimate the seroprevalence of Leishmania-specific antibodies, and Global Information System and spatial clustering techniques were applied to study the presence of spatial clusters in Parkarin and Loboi villages in Baringo District in 2001. VL seroprevalences were 52.
View Article and Find Full Text PDFSitamaquine (WR6026) is an 8-aminoquinoline in development for the oral treatment of visceral leishmaniasis (VL). This was an open-label, dose-increasing study to determine the dose-response and safety profile for sitamaquine in Kenyan patients with VL caused by Leishmania donovani. Patients (mean age 15.
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