scholarly journals A qPCR to quantify Wolbachia from few Onchocerca volvulus microfilariae as a surrogate for adult worm histology in clinical trials of antiwolbachial drugs

2022 ◽  
Author(s):  
Stefan Schlabe ◽  
Patricia Korir ◽  
Christine Lämmer ◽  
Frederic Landmann ◽  
Bettina Dubben ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Single Copy ◽  
Post Treatment ◽  
Sub Saharan Africa ◽  
Onchocerca Volvulus ◽  
River Blindness ◽  
Litomosoides Sigmodontis ◽  
Sensitive Tool ◽  
Skin Biopsies ◽  
Sub Saharan

Abstract The filarial nematode Onchocerca volvulus causes onchocerciasis (river blindness), a neglected tropical disease affecting 21 million people, mostly in Sub-Saharan Africa. Targeting the endosymbiont Wolbachia with antibiotics leads to permanent sterilization and killing of adult worms. The gold standard to assess Wolbachia depletion is the histological examination of adult worms in nodules beginning at 6 months post-treatment. However, nodules can only be used once, limiting the time points to monitor Wolbachia depletion. A diagnostic to longitudinally monitor Wolbachia depletion from microfilariae (MF) at more frequent intervals < 6 months post-treatment would accelerate clinical trials of antiwolbachials. We developed a TaqMan qPCR amplifying the single-copy gene wOvftsZ to quantify Wolbachia from as few as one MF that had migrated from skin biopsies and compared quantification using circular and linearized plasmids or synthetic dsDNA (gBlock®). qPCR for MF from the rodent nematode Litomosoides sigmodontis was used to support the reproducibility and validate the principle. The qPCR using as few as 2 MF from O. volvulus and L. sigmodontis reproducibly quantified Wolbachia. Use of a linearized plasmid standard or synthesized dsDNA resulted in numbers of Wolbachia/MF congruent with biologically plausible estimates in O. volvulus and L. sigmodontis MF. The qPCR assay yielded a median of 48.8 (range 1.5–280.5) Wolbachia/O. volvulus MF. The qPCR is a sensitive tool for quantifying Wolbachia in a few MF from skin biopsies and allows for establishing the qPCR as a surrogate parameter for monitoring Wolbachia depletion in adult worms of new antiwolbachial candidates.

scholarly journals Emodepside targets SLO-1 channels of Onchocerca ochengi and induces broad anthelmintic effects in a bovine model of onchocerciasis

2021 ◽  
Vol 17 (6) ◽  
pp. e1009601
Author(s):  
Germanus S. Bah ◽  
Sebastian Schneckener ◽  
Steffen R. Hahnel ◽  
Nicolas H. Bayang ◽  
Helena Fieseler ◽  
...  
Keyword(s):  
Female Worm ◽  
Companion Animals ◽  
Current Control ◽  
Sub Saharan Africa ◽  
Onchocerca Volvulus ◽  
High Dose ◽  
River Blindness ◽  
Onchocerca Ochengi ◽  
Sub Saharan ◽  
Years Lived With Disability

Onchocerciasis (river blindness), caused by the filarial worm Onchocerca volvulus, is a neglected tropical disease mostly affecting sub-Saharan Africa and is responsible for >1.3 million years lived with disability. Current control relies almost entirely on ivermectin, which suppresses symptoms caused by the first-stage larvae (microfilariae) but does not kill the long-lived adults. Here, we evaluated emodepside, a semi-synthetic cyclooctadepsipeptide registered for deworming applications in companion animals, for activity against adult filariae (i.e., as a macrofilaricide). We demonstrate the equivalence of emodepside activity on SLO-1 potassium channels in Onchocerca volvulus and Onchocerca ochengi, its sister species from cattle. Evaluation of emodepside in cattle as single or 7-day treatments at two doses (0.15 and 0.75 mg/kg) revealed rapid activity against microfilariae, prolonged suppression of female worm fecundity, and macrofilaricidal effects by 18 months post treatment. The drug was well tolerated, causing only transiently increased blood glucose. Female adult worms were mostly paralyzed; however, some retained metabolic activity even in the multiple high-dose group. These data support ongoing clinical development of emodepside to treat river blindness.

scholarly journals Conducting clinical trials in sub-Saharan Africa: challenges and lessons learned from the Malawi Cryptosporidium study

Trials ◽  
2020 ◽  
Vol 21 (1) ◽  
Author(s):  
Neema Toto ◽  
Elaine Douglas ◽  
Markus Gmeiner ◽  
Lynn K. Barrett ◽  
Robert Lindblad ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Lessons Learned ◽  
Sub Saharan Africa ◽  
Sub Saharan

scholarly journals Considerations for stakeholder engagement and COVID ‐19 related clinical trials’ conduct in sub‐Saharan Africa

2020 ◽  
Author(s):  
Morenike Oluwatoyin Folayan ◽  
Brandon Brown ◽  
Bridget Haire ◽  
Chinedum Peace Babalola ◽  
Nicaise Ndembi
Keyword(s):  
Clinical Trials ◽  
Stakeholder Engagement ◽  
Sub Saharan Africa ◽  
Sub Saharan

Clinical Trials in Sub-Saharan Africa and Established Standards of Care

JAMA ◽  
2004 ◽  
Vol 292 (2) ◽  
pp. 237 ◽  
Author(s):  
David M. Kent ◽  
D. Mkaya Mwamburi ◽  
Michael L. Bennish ◽  
Bruce Kupelnick ◽  
John P. A. Ioannidis
Keyword(s):  
Clinical Trials ◽  
Sub Saharan Africa ◽  
Standards Of Care ◽  
Sub Saharan

scholarly journals "You can save time if…"—A qualitative study on internal factors slowing down clinical trials in Sub-Saharan Africa

PLoS ONE ◽  
2017 ◽  
Vol 12 (3) ◽  
pp. e0173796 ◽  
Author(s):  
Nerina Vischer ◽  
Constanze Pfeiffer ◽  
Manuela Limacher ◽  
Christian Burri
Keyword(s):  
Clinical Trials ◽  
Qualitative Study ◽  
Sub Saharan Africa ◽  
Internal Factors ◽  
Slowing Down ◽  
Sub Saharan

Clinical trials to improve childhood cancer care and survival in sub-Saharan Africa

2013 ◽  
Vol 10 (10) ◽  
pp. 599-604 ◽  
Author(s):  
Trijn Israëls ◽  
Joyce Kambugu ◽  
Francine Kouya ◽  
Nader Kim El-Mallawany ◽  
Peter B. Hesseling ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Childhood Cancer ◽  
Cancer Care ◽  
Sub Saharan Africa ◽  
Sub Saharan

scholarly journals Three monthly doses of 60 mg/kg praziquantel for Schistosoma haematobium infection is a safe and effective treatment regimen.

2020 ◽  
Author(s):  
Samuel Nkansah Darko ◽  
Henry Hanson ◽  
Sampson Twumasi Ankrah ◽  
Sandra Baffour ◽  
Priscilla Adjei-Kusi ◽  
...  
Keyword(s):  
Renal Function ◽  
Schistosoma Haematobium ◽  
Post Treatment ◽  
Sub Saharan Africa ◽  
Gamma Glutamyl Transferase ◽  
Disease Epidemiology ◽  
Sub Saharan ◽  
Pre Treatment ◽  
And Gender ◽  
Glutamyl Transferase

Abstract Background Praziquantel (PZQ) is the standard treatment for Schistosomiasis in sub-Saharan Africa. However, there is evidence suggesting praziquantel treatment failure in Schistosome infections with associated potential renal impairment. The objective of this study was to determine the effect of three monthly doses of 60 mg/kg/day PZQ on schistosome egg count, liver and renal function during the treatment of urinary schistosomiasis in Ghana. Methods A nested case-control study was designed from a cohort screened for schistosomiasis; 28 schistosomiasis positive cases by microscopy matched with 53 healthy controls by age and gender. The study population was urban dwellers from the Asokwa sub-metropolitan area, Kumasi in Ghana. Participants were within the age range of 6 to 30 years. We assessed Schistosoma haematobium egg counts in urine and its associated impact on liver and renal function at baseline, treatment and post-treatment phases using serum. Results Of the 28 cases and 53 controls, 78.6% and (81.1% were males respectively. Globulin levels before treatment was higher in cases [36.7 (32.8, 40.1) vrs 30.5 (22.4, 33.8) , p=0.005] at pre-treatment but not at post-treatment [35.8 (31.2, 39.1)vrs 37.4 (29.7, 43.0), p= 0.767]. Estimated cure rate was 42.9%, 46.4% and 96.4% after first, second and third dose respectively. Schistosome egg counts dropped significantly (p= 0.001) from before second dose to post-treatment. Similarly, levels of alanine aminotransferase (p=0.001), aspartate aminotransferase (p=0.028) and gamma glutamyl transferase (p=0.001) significantly declined towards post-treatment. Estimated glomerular filtration rate significantly improved from before second dose to post-treatment using both the Chronic Kidney Disease Epidemiology Program (p=0.001) and 4-variable Modification of Diet in Renal Disease (p=0.002) equations. Conclusion Treatment of urinary Schistosoma hematobium infections with a repeated high monthly dose of 60 mg/kg of praziquantel for 3 months is safe and effective.

scholarly journals Cancer Clinical Trials in Africa—An Untapped Opportunity: Recommendations From AORTIC 2019 Conference Special Interest Group in Clinical Trials

2021 ◽  
pp. 1358-1363
Author(s):  
Abiola Ibraheem ◽  
Colin Pillai ◽  
Ifeoma Okoye ◽  
J. Joshua Smith ◽  
Diane Reidy-Lagunes ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Clinical Trials ◽  
Sub Saharan Africa ◽  
Cancer Clinical Trials ◽  
Future Directions ◽  
Secondary Purpose ◽  
Health Care Burden ◽  
Sub Saharan ◽  
Cancer Disparity ◽  
And Training

Cancer is now a formidable health care burden in sub-Saharan Africa (SSA) due to lifestyle westernization and longer life expectancy. The exponential increase in cancer incidence coupled with high mortality rate is not comparable with that seen in westernized countries. To address global cancer disparity, globalization of cancer clinical trials to involve sub-Saharan Africa can serve as a platform where innovative targeted therapies can be made available to patients in the environ. In the 2019 African Organization for Research and Training in Cancer (AORTIC) conference held at Maputo, Mozambique, a group of clinical trialists spanning across multiple continents highlighted the opportunities in Africa for the conduct of cancer clinical trials. The secondary purpose of the meeting was to address the belief that Africa was incapable of conducting interventional cancer trials but showed the in-continent strengths, such as available capacities, trained local clinical trialists with clinical trial experiences, clinical trial consortia, local capabilities, mapping out logistics, ethical consideration, political will, real-time benefits of clinical trials to clinical practice, and future directions for trials.

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