scholarly journals Efficacy and Safety of Paromomycin for Visceral Leishmaniasis: A Systematic Review

2021 ◽  
Vol 2021 ◽  
pp. 1-9
Author(s):  
Pashupati Pokharel ◽  
Rakesh Ghimire ◽  
Pratik Lamichhane
Keyword(s):  
Systematic Review ◽  
Drug Resistance ◽  
Visceral Leishmaniasis ◽  
South America ◽  
South Asia ◽  
Neglected Tropical Diseases ◽  
Tropical Diseases ◽  
Efficacy And Safety ◽  
Kala Azar ◽  
Resource Limited

Visceral leishmaniasis, also known as kala-azar is one of the most commonly neglected tropical diseases affecting a large number of rural and resource-limited people in South Asia, Africa, and South America. Paromomycin, an aminoglycoside drug, is frequently used for the treatment of visceral leishmaniasis. Despite limited therapies for visceral leishmaniasis and emerging drug resistance, a proper review on the action of paromomycin for kala-azar is lacking. This systematic review aims to look for the efficacy and safety aspects of paromomycin for the treatment of visceral leishmaniasis.

scholarly journals Genomic and phenotypic characterization of experimentally selected resistant Leishmania donovani reveals a role for dynamin-1 like protein in the mechanism of resistance to a novel anti-leishmanial compound

2021 ◽  
Author(s):  
Aya Hefnawy ◽  
Gabriel Negreira ◽  
Marlene Jara ◽  
James A. Cotton ◽  
Ilse Maes ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Visceral Leishmaniasis ◽  
Infectious Diseases ◽  
Leishmania Donovani ◽  
Neglected Tropical Diseases ◽  
Arms Race ◽  
Etiological Agent ◽  
Phenotypic Characterization ◽  
Tropical Diseases

AbstractThe implementation of prospective drug resistance (DR) studies in the R&D pipelines is a common practice for many infectious diseases, but not for Neglected Tropical Diseases. Here, we explored and demonstrated the importance of this approach, using as paradigms Leishmania donovani, the etiological agent of Visceral Leishmaniasis (VL), and TCMDC-143345, a promising compound of the GSK ‘Leishbox’ to treat VL. We experimentally selected resistance to TCMDC-143345 in vitro and characterized resistant parasites at genomic and phenotypic levels. We found that it took more time to develop resistance to TCMDC-143345 than to other drugs in clinical use and that there was no cross resistance to these drugs, suggesting a new and unique mechanism. By whole genome sequencing, we found two mutations in the gene encoding the L. donovani dynamin-1-like protein (LdoDLP1) that were fixed at highest drug pressure. Through phylogenetic analysis, we identified LdoDLP1 as a family member of the dynamin-related proteins, a group of proteins that impacts the shapes of biological membranes by mediating fusion and fission events, with a putative role in mitochondrial fission. We found that L. donovani lines genetically engineered to harbor the two identified LdoDLP1 mutations were resistant to TCMDC-143345 and displayed altered mitochondrial properties. By homology modeling, we showed how the two LdoDLP1 mutations may influence protein structure and function. Taken together, our data reveal a clear involvement of LdoDLP1 in the adaptation/resistance of L. donovani to TCMDC-143345.ImportanceHumans and their pathogens are continuously locked in a molecular arms race during which the eventual emergence of pathogen drug resistance (DR) seems inevitable. For neglected tropical diseases (NTDs), DR is generally studied retrospectively, once it has already been established in clinical settings. We previously recommended to keep one step ahead in the host-pathogen arms race and implement prospective DR studies in the R&D pipeline, a common practice for many infectious diseases, but not for NTDs. Here, using Leishmania donovani, the etiological agent of Visceral Leishmaniasis (VL), and TCMDC-143345, a promising compound of the GSK ‘Leishbox’ to treat VL, as paradigms, we experimentally selected resistance to the compound and proceeded to genomic and phenotypic characterization of DR parasites. The results gathered in the present study suggest a new DR mechanism involving the L. donovani dynamin-1 like protein (LdoDLP1) and demonstrate the practical relevance of prospective DR studies.

scholarly journals Socioeconomic Inequalities in Neglected Tropical Diseases: A Systematic Review

2016 ◽  
Vol 10 (5) ◽  
pp. e0004546 ◽  
Author(s):  
Tanja A. J. Houweling ◽  
Henrike E. Karim-Kos ◽  
Margarete C. Kulik ◽  
Wilma A. Stolk ◽  
Juanita A. Haagsma ◽  
...  
Keyword(s):  
Systematic Review ◽  
Neglected Tropical Diseases ◽  
Socioeconomic Inequalities ◽  
Tropical Diseases

scholarly journals Efficacy and Safety of Miltefosine in Treatment of Post-Kala-Azar Dermal Leishmaniasis

2015 ◽  
Vol 2015 ◽  
pp. 1-6 ◽  
Author(s):  
Shyam Sundar ◽  
Anup Singh ◽  
Jaya Chakravarty ◽  
Madhukar Rai
Keyword(s):  
Adverse Effect ◽  
Visceral Leishmaniasis ◽  
Exploratory Study ◽  
Protocol Analysis ◽  
Complete Disappearance ◽  
Efficacy And Safety ◽  
Kala Azar ◽  
One Year

Background. Long regimens for the treatment of post-kala-azar dermal leishmaniasis (PKDL) result in noncompliance. A safe, effective, and acceptable regimen for the treatment of PKDL is still to be developed. Miltefosine has been found to be effective in the treatment of Visceral Leishmaniasis (VL). Hence, its efficacy was tested in patients of PKDL.Methods. In this exploratory study, 33 patients with PKDL aged 10 years and above were administered miltefosine (50 mg for those weighing <25 kg or 100 mg in divided doses for those ≥25 kg and 2.5 mg per kg for children) for 12 weeks and followed up for one year to find out the efficacy.Results. Out of 33 patients, 3 patients withdrew consent. Treatment was stopped due to adverse effect in 1 patient. 28 (96.6%) got cured with complete disappearance of lesion while 1 patient (3.4%) failed treatment by protocol analysis.Conclusion. Miltefosine was found to be effective and safe in the treatment of PKDL.

scholarly journals Aetiology Of Pyrexia With Hepatosplenomegaly: Study Of 50 Cases In MMCH (Bangladesh)

1970 ◽  
Vol 5 (1) ◽  
pp. 7-10
Author(s):  
F Ahammad ◽  
MY Ali ◽  
SH Rahman ◽  
SA Fattah ◽  
MT Alam ◽  
...  
Keyword(s):  
Visceral Leishmaniasis ◽  
Acute Leukemia ◽  
Medical Practice ◽  
Enteric Fever ◽  
Hematological Malignancies ◽  
Clinical Syndrome ◽  
Tropical Diseases ◽  
Haematological Malignancies ◽  
Kala Azar ◽  
Common Causes

Pyrexia with hepatosplenomegaly is a common problem in medical practice globally, specially in tropical countries. In Bangladesh several tropical diseases as well as hematological malignancies are responsible for such clinical syndrome. Again different tropical diseases vary in endemicity in different regions in Bangladesh. In Present study 50 hospitalized cases of pyrexia with hepatosplenomegaly of 15-50 years of age are included from 01.01.2002 to 30.06.2002 in MMCH to find out their aetiologies. Fever with only hepatomegaly, or with only splenomegaly or hepatosplenomegaly without fever was not included in this study. Duration of fever was two weeks to three months. 35(70%) cases were male and 15(30%) were female. 27(54%) cases were visceral leishmaniasis (kala-azar), 8 (16%) malaria, 6 (12%) Acute leukemia (ALL, AML), 3 (6%) Lymphoma, 3(6%) Enteric fever, 2(4%) CML, 1(2%) Disseminated TB. Although kala-azar and malaria are tow common causes of fever with hepatosplenomegaly, haematological malignancies and tuberculosis should be in mind DOI: 10.3329/fmcj.v5i1.6805Faridpur Med. Coll. J. 2010;5(1):7-10

scholarly journals The Neglected Tropical Diseases of India and South Asia: Review of Their Prevalence, Distribution, and Control or Elimination

2011 ◽  
Vol 5 (10) ◽  
pp. e1222 ◽  
Author(s):  
Derek A. Lobo ◽  
Raman Velayudhan ◽  
Priya Chatterjee ◽  
Harajeshwar Kohli ◽  
Peter J. Hotez
Keyword(s):  
South Asia ◽  
Neglected Tropical Diseases ◽  
Tropical Diseases ◽  
And Control

scholarly journals Social marketing interventions for neglected tropical diseases (NTDs): A systematic review protocol

2017 ◽  
Author(s):  
Nathaly Aya Pastrana ◽  
J Jaime Miranda ◽  
Claire Somerville ◽  
David Beran ◽  
L Suzanne Suggs
Keyword(s):  
Systematic Review ◽  
Social Marketing ◽  
Hierarchical Model ◽  
Assessment Tool ◽  
Neglected Tropical Diseases ◽  
Meta Analysis ◽  
World Health ◽  
Tropical Diseases ◽  
Behavioral Determinants ◽  
Language Restriction

Background. Social marketing influences behaviors to improve the health and wellbeing of individuals and society, and this approach could be used in the field of public health for the prevention and control Neglected Tropical Diseases (NTDs). NTDs are diseases of poverty that place a burden in individuals, communities and health systems, and that exacerbate the cycle of poverty. Differences in risk and socio-cultural factors make women and children differently vulnerable. Guided by the Hierarchical Model of Social Marketing, this systematic review will assess the breadth of coverage of social marketing interventions about the 17 World Health Organization’s priority NTDs. Additionally, it will use the WHO Gender Assessment Tool (GAT) to assess the gender responsiveness of the included interventions. Methods. This protocol follows the guidelines of the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols (PRISMA-P). Searches will be conducted in the databases of PubMed, EbscoHost, ProQuest, Web of Science (WOS), Global Index Medicus and Virtual Health Library (VHL) Regional Portal, and there will be no language restriction. Social marketing interventions implemented at the community, health facility and public policy settings will be included if they target an NTD; it applies at least 1 of the 4 core social marketing concepts, and 1 of the 5 social marketing techniques as described in the Hierarchical Model of Social Marketing. Data management of records will be done in Covidence, a Cochrane systematic review platform, and of data extracted in Excel. The QATSDD Critical Appraisal Tool will be used to assess the quality of individual studies in terms of how they report their research processes. Discussion. The results of this review will contribute to understand the social marketing concepts and techniques that have been used to address NTDs, and their behavioral determinants and behavioral outcomes. Furthermore, the results of this review will bring together the strengths from multidisciplinary fields by integrating gender, social marketing and NTDs in a systematic manner. Systematic review registration. PROSPERO CRD42017063858

scholarly journals Emerging Resistance of Neglected Tropical Diseases: A Scoping Review of the Literature

2019 ◽  
Vol 16 (11) ◽  
pp. 1925 ◽  
Author(s):  
Folahanmi T. Akinsolu ◽  
Priscilla O. Nemieboka ◽  
Diana W. Njuguna ◽  
Makafui N. Ahadji ◽  
Dora Dezso ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Assessment Tool ◽  
Neglected Tropical Diseases ◽  
Experimental Studies ◽  
Surveillance Systems ◽  
Tropical Diseases ◽  
Global Public Health ◽  
Preventive Chemotherapy ◽  
Clinical Resistance ◽  
Socio Demographic Factors

Background: Antimicrobial resistance (AMR) is a global public health threat with the potential to cause millions of deaths. There has been a tremendous increase in the use of antimicrobials, stemming from preventive chemotherapy elimination and control programs addressing neglected tropical diseases (NTDs). This study aims to identify the frequency of drug resistance for 11 major NTDs and 20 treatment drugs within a specific period by systematically analyzing the study design, socio-demographic factors, resistance, and countries of relevant studies. Methods: Adhering to PRISMA guidelines, we performed systematic reviews of the major 11 NTDs to identify publications on drug resistance between 2000 and 2016. A quality assessment tool adapted for evaluating observational and experimental studies was applied to assess the quality of eligible studies. Results: One of the major findings is that six NTDs have information on drug resistance, namely human African trypanosomiasis, leishmaniasis, onchocerciasis, schistosomiasis, soil-transmitted helminths, and trachoma. Many studies recorded resistance due to diagnostic tests, and few studies indicated clinical resistance. Although most studies were performed in Africa where there is the occurrence of several NTDs, there was no link between disease burden and locations of study. Conclusions: Based on this study we deduce that monitoring and surveillance systems need to be strengthened to enable the early detection of AMR and the mitigation of its global spread.

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