Dataset Information

Lack of Clinical Pharmacokinetic Studies to Optimize the Treatment of Neglected Tropical Diseases: A Systematic Review.

ABSTRACT:

Introduction

Neglected tropical diseases (NTDs) affect more than one billion people, mainly living in developing countries. For most of these NTDs, treatment is suboptimal. To optimize treatment regimens, clinical pharmacokinetic studies are required where they have not been previously conducted to enable the use of pharmacometric modeling and simulation techniques in their application, which can provide substantial advantages.

Objectives

Our aim was to provide a systematic overview and summary of all clinical pharmacokinetic studies in NTDs and to assess the use of pharmacometrics in these studies, as well as to identify which of the NTDs or which treatments have not been sufficiently studied.

Methods

PubMed was systematically searched for all clinical trials and case reports until the end of 2015 that described the pharmacokinetics of a drug in the context of treating any of the NTDs in patients or healthy volunteers.

Results

Eighty-two pharmacokinetic studies were identified. Most studies included small patient numbers (only five studies included >50 subjects) and only nine (11 %) studies included pediatric patients. A large part of the studies was not very recent; 56 % of studies were published before 2000. Most studies applied non-compartmental analysis methods for pharmacokinetic analysis (62 %). Twelve studies used population-based compartmental analysis (15 %) and eight (10 %) additionally performed simulations or extrapolation. For ten out of the 17 NTDs, none or only very few pharmacokinetic studies could be identified.

Conclusions

For most NTDs, adequate pharmacokinetic studies are lacking and population-based modeling and simulation techniques have not generally been applied. Pharmacokinetic clinical trials that enable population pharmacokinetic modeling are needed to make better use of the available data. Simulation-based studies should be employed to enable the design of improved dosing regimens and more optimally use the limited resources to effectively provide therapy in this neglected area.

SUBMITTER: Verrest L

PROVIDER: S-EPMC5425494 | biostudies-literature | 2017 Jun

REPOSITORIES: biostudies-literature

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Publications

Lack of Clinical Pharmacokinetic Studies to Optimize the Treatment of Neglected Tropical Diseases: A Systematic Review.

Verrest Luka L Dorlo Thomas P C TPC

Clinical pharmacokinetics 20170601 6

<h4>Introduction</h4>Neglected tropical diseases (NTDs) affect more than one billion people, mainly living in developing countries. For most of these NTDs, treatment is suboptimal. To optimize treatment regimens, clinical pharmacokinetic studies are required where they have not been previously conducted to enable the use of pharmacometric modeling and simulation techniques in their application, which can provide substantial advantages.<h4>Objectives</h4>Our aim was to provide a systematic overvi ...[more]

PMID: 27744580

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Project description:BackgroundNeglected tropical diseases (NTDs) are generally assumed to be concentrated in poor populations, but evidence on this remains scattered. We describe within-country socioeconomic inequalities in nine NTDs listed in the London Declaration for intensified control and/or elimination: lymphatic filariasis (LF), onchocerciasis, schistosomiasis, soil-transmitted helminthiasis (STH), trachoma, Chagas' disease, human African trypanosomiasis (HAT), leprosy, and visceral leishmaniasis (VL).MethodologyWe conducted a systematic literature review, including publications between 2004-2013 found in Embase, Medline (OvidSP), Cochrane Central, Web of Science, Popline, Lilacs, and Scielo. We included publications in international peer-reviewed journals on studies concerning the top 20 countries in terms of the burden of the NTD under study.Principal findingsWe identified 5,516 publications, of which 93 met the inclusion criteria. Of these, 59 papers reported substantial and statistically significant socioeconomic inequalities in NTD distribution, with higher odds of infection or disease among poor and less-educated people compared with better-off groups. The findings were mixed in 23 studies, and 11 studies showed no substantial or statistically significant inequality. Most information was available for STH, VL, schistosomiasis, and, to a lesser extent, for trachoma. For the other NTDs, evidence on their socioeconomic distribution was scarce. The magnitude of inequality varied, but often, the odds of infection or disease were twice as high among socioeconomically disadvantaged groups compared with better-off strata. Inequalities often took the form of a gradient, with higher odds of infection or disease each step down the socioeconomic hierarchy. Notwithstanding these inequalities, the prevalence of some NTDs was sometimes also high among better-off groups in some highly endemic areas.ConclusionsWhile recent evidence on socioeconomic inequalities is scarce for most individual NTDs, for some, there is considerable evidence of substantially higher odds of infection or disease among socioeconomically disadvantaged groups. NTD control activities as proposed in the London Declaration, when set up in a way that they reach the most in need, will benefit the poorest populations in poor countries.

Project description:BackgroundNigeria carries the highest burden and diversity of neglected tropical diseases (NTDs) in sub-Saharan Africa and is preparing to scale up its efforts to control/eliminate these diseases. To achieve this it will require a range of internal technical support and expertise for mapping, monitoring and evaluating, operational research and documenting its success. In order to begin to evaluate this potential in Nigeria, this study collated and analysed information for lymphatic filariasis (LF), onchocerciasis, schistosomiasis and soil-transmitted helminths (STH), which are currently being targeted with preventive chemotherapy through mass drug administration (MDA).Methodology/principal findingsInformation from 299 scientific articles published on the selected NTDs in 179 journals between January 2008 and September 2013 was extracted and systematically compiled into a geo-referenced database for analysis and mapping. The highest number of articles was from the southern geo-political zones of the country. The majority of articles focused on one specific disease, and schistosomiasis and STH were found to have the highest and most wide ranging research output. The main type of study was parasitological, and the least was biotechnological. Nigerian authors were mostly affiliated with universities, and there was a wide range of international co-authors from Africa and other regions, especially the USA and UK. The majority of articles were published in journals with no known impact factor.Conclusions/significanceThe extensive database and series of maps on the research capacity within Nigeria produced in this study highlights the current potential that exists, and needs to be fully maximized for the control/elimination of NTDs in the country. This study provides an important model approach that can be applied to other low and middle income countries where NTDs are endemic, and NTD programmes require support from the expertise within their own country, as well as internationally, to help raise their profile and importance.

Project description:BackgroundNeglected tropical diseases (NTDs) affect more than one billion people living in vulnerable conditions. In spite of initiatives recently contributing to fill NTDs gaps on national and local prevalence and distribution, more epidemiological data are still needed for effective control and elimination interventions.Main textMozambique is considered one of the countries with highest NTDs burden although available data is scarce. This study aims to conduct a systematic review on published available data about the burden and distribution of the different NTDs across Mozambique since January 1950 until December 2018. We identified manuscripts from electronic databases (Pubmed, EmBase and Global Health) and paper publications and grey literature from Mozambique Ministry of Health. Manuscripts fulfilling inclusion criteria were: cross-sectional studies, ecological studies, cohorts, reports, systematic reviews, and narrative reviews capturing epidemiological information of endemic NTDs in Mozambique. Case-control studies, letters to editor, case reports and case series of imported cases were excluded. A total of 466 manuscripts were initially identified and 98 were finally included after the revision following PRISMA guidelines. Eleven NTDs were reported in Mozambique during the study span. Northern provinces (Nampula, Cabo Delgado, Niassa, Tete and Zambezia) and Maputo province had the higher number of NTDs detected. Every disease had their own report profile: while schistosomiasis have been continuously reported since 1952 until nowadays, onchocerciasis and cysticercosis last available data is from 2007 and Echinococcosis have never been evaluated in the country. Thus, both space and time gaps on NTDs epidemiology have been identified.ConclusionsThis review assembles NTDs burden and distribution in Mozambique. Thus, contributes to the understanding of NTDs epidemiology in Mozambique and highlights knowledge gaps. Hence, the study provides key elements to progress towards the control and interruption of transmission of these diseases in the country.

Project description:BackgroundSubcutaneous (deep) mycoses are a chronic infectious disease of the skin and underlying structures endemic in tropical countries. The disease has serious medical and socioeconomic consequences for patients, communities and health services in endemic areas. The inclusion of mycetoma and other subcutaneous mycoses in the list of Neglected Tropical Diseases by WHO highlights the need to assess the burden of these diseases and establish control programs where necessary. In Ethiopia no strategies can be devised because of a lack of epidemiologic information. To address this evidence gap, we performed a national rapid assessment of the geographic distribution of subcutaneous mycoses.MethodologyWe conducted a rapid retrospective assessment using hospital records to identify all suspected and confirmed cases of subcutaneous mycoses in 13 referral hospitals across the country between 2015 and 2022. In each hospital the logbooks were reviewed for diagnoses of subcutaneous mycosess, as diagnosed per routine practice. Descriptive analysis was done.ResultFrom 13 hospitals we extracted 143 cases of subcutaneous mycoses, registered from July 2018 to September 2022. 118 (82.5%) patients were diagnosed as mycetoma, 21 (14.7%) as chromoblastomycosis and the remaining 4 (2.8%) as sporotrichosis. The mean age of patients was 35.8 years (SD = 14.5). 101 (70.6%) patients were male and 96 (67.1%) patients were farmers. 64 (44.8%) cases were from the Tigray regional state. 56 (65.9%) patients had information on diagnostic microscopic evaluation: for mycetoma histopathologic evaluation and fine needle aspiration cytology had a higher positivity rate while for chromoblastomycosis potassium hydroxide (KOH) staining had a better yield. The main clinical presentations were nodules, sinuses and infiltrative plaques on the skin. Radiologic findings of bone involvement was present in some.ConclusionsMycetoma and other subcutaneous mycoses are endemic in Ethiopia, with cases reported from almost all regions with the highest cases numbers reported from the northern part of the country. A routine program and systems should be developed to identify and document the burden of subcutaneous fungal infections in the country. Diagnosis and treatment guidelines should be developed.

Project description:BackgroundThe World Health Organization's (WHO) Neglected Tropical Disease (NTD) Road Map for 2021-2030 was recently endorsed by all member states at the World Health Assembly in November 2020. Although only 3 of the 20 NTDs are endemic in Canada (i.e., echinococcosis, rabies, and scabies), the Canadian research community has contributed to advancing the knowledge base of all 20 NTDs. Previous research comprehensively detailed Canadian research on 11 NTDs between 1950 and 2010 using a network analysis approach. The specific objective of the present analysis was to update the publication record over the last decade (2010-2019) to include all 20 NTDs.Materials and methodsA bibliometric analysis was conducted in Scopus and Web of Science databases (for English or French articles published between January 1, 2010 and December 31, 2019) using appropriate search terms for each of the 20 NTDs and where at least 1 of the authors had a Canadian institution address. A 21st search was added to include publications including multiple NTDs or a discussion of NTDs in general. Following assessment of inclusion and exclusion criteria, 2 reviewers independently screened all abstracts, with discordant observations rereviewed to arrive at an agreement. Duplicates were removed.ResultsA total of 1,790 publications were retrieved (1,738 with a disease-specific NTD focus and 52 with a general NTD focus, resulting in 1,659 unique publications), giving an average of over 160 articles per year. Over 80% were classified as full-length research articles. The top 3 journals in terms of frequency were PLOS Neglected Tropical Diseases, PLOS ONE, and the American Journal of Tropical Medicine and Hygiene. Authors' institutions were from all Canadian provinces. While all 20 NTDs were addressed in these publications, the 5 most commonly studied were leishmaniasis, dengue fever and chikungunya, Chagas disease, soil-transmitted helminthiases, and rabies.ConclusionsCanadian researchers across the country have contributed to the evidence base of all 20 NTDs, publishing an average of over 160 publications per year between 2010 and 2019. As WHO NTD Road Map 2021-2030 rolls out globally, the Canadian research community, in collaboration with its partners and in solidarity with people living in vulnerable circumstances in endemic regions worldwide, is well positioned to meet future research challenges so that the goal of eliminating the disease burden attributable to NTDs can be achieved.

Project description:BackgroundThe control of neglected tropical diseases (NTDs) has primarily focused on preventive chemotherapy and case management. Less attention has been placed on the role of ensuring access to adequate water, sanitation, and hygiene and personal preventive measures in reducing exposure to infection. Our aim was to assess whether footwear use was associated with a lower risk of selected NTDs.MethodologyWe conducted a systematic review and meta-analysis to assess the association between footwear use and infection or disease for those NTDs for which the route of transmission or occurrence may be through the feet. We included Buruli ulcer, cutaneous larva migrans (CLM), leptospirosis, mycetoma, myiasis, podoconiosis, snakebite, tungiasis, and soil-transmitted helminth (STH) infections, particularly hookworm infection and strongyloidiasis. We searched Medline, Embase, Cochrane, Web of Science, CINAHL Plus, and Popline databases, contacted experts, and hand-searched reference lists for eligible studies. The search was conducted in English without language, publication status, or date restrictions up to January 2014. Studies were eligible for inclusion if they reported a measure of the association between footwear use and the risk of each NTD. Publication bias was assessed using funnel plots. Descriptive study characteristics and methodological quality of the included studies were summarized. For each study outcome, both outcome and exposure data were abstracted and crude and adjusted effect estimates presented. Individual and summary odds ratio (OR) estimates and corresponding 95% confidence intervals (CIs) were calculated as a measure of intervention effect, using random effects meta-analyses.Principal findingsAmong the 427 studies screened, 53 met our inclusion criteria. Footwear use was significantly associated with a lower odds of infection of Buruli ulcer (OR=0.15; 95% CI: 0.08-0.29), CLM (OR=0.24; 95% CI: 0.06-0.96), tungiasis (OR=0.42; 95% CI: 0.26-0.70), hookworm infection (OR=0.48; 95% CI: 0.37-0.61), any STH infection (OR=0.57; 95% CI: 0.39-0.84), strongyloidiasis (OR=0.56; 95% CI: 0.38-0.83), and leptospirosis (OR=0.59; 95% CI: 0.37-0.94). No significant association between footwear use and podoconiosis (OR=0.63; 95% CI: 0.38-1.05) was found and no data were available for mycetoma, myiasis, and snakebite. The main limitations were evidence of heterogeneity and poor study quality inherent to the observational studies included.Conclusions/significanceOur results show that footwear use was associated with a lower odds of several different NTDs. Access to footwear should be prioritized alongside existing NTD interventions to ensure a lasting reduction of multiple NTDs and to accelerate their control and elimination.Protocol registrationPROSPERO International prospective register of systematic reviews CRD42012003338.

Dataset Information

Lack of Clinical Pharmacokinetic Studies to Optimize the Treatment of Neglected Tropical Diseases: A Systematic Review.

Introduction

Objectives

Methods

Results

Conclusions

Publications

Lack of Clinical Pharmacokinetic Studies to Optimize the Treatment of Neglected Tropical Diseases: A Systematic Review.

Similar Datasets

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