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Clinical Infectious Diseases : An... Jan 2019Periodic mass distribution of benzimidazole anthelminthic drugs is the key strategy to control soil-transmitted helminths (STHs) globally. However, benzimidazoles have... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Periodic mass distribution of benzimidazole anthelminthic drugs is the key strategy to control soil-transmitted helminths (STHs) globally. However, benzimidazoles have low efficacy against Trichuris trichiura, and there are concerns about benzimidazole resistance potentially emerging in humans. Therefore, identifying alternative drug regimens is a pressing priority. We present a systematic review and network meta-analysis comparing the efficacy of 21 different anthelminthic drug regimens, including standard, novel, and combination treatments.
METHODS
We searched PubMed, Medline, Embase, Web of Science, and Cochrane databases and identified studies comparing anthelminthic treatments to each other or placebo. The outcomes calculated were relative risk (RR) of cure and difference in egg reduction rates (dERR). We used an automated generalized pairwise modeling framework to generate mixed treatment effects against a common comparator, the current standard treatment (single-dose albendazole).
RESULTS
Our search identified 4876 studies, of which 114 were included in the meta-analysis. Results identified several drug combinations with higher efficacy than single-dose albendazole for T. trichiura, including albendazole-ivermectin (RR of cure, 3.22 [95% confidence interval {CI}, 1.84-5.63]; dERR, 0.97 [95% CI, .21-1.74]), albendazole-oxantel pamoate (RR, 5.07 [95% CI, 1.65-15.59]; dERR, 0.51 [95% CI, .50-.52]), mebendazole-ivermectin (RR, 3.37 [95% CI, 2.20-5.16]), and tribendimidine-oxantel pamoate (RR, 4.06 [95% CI, 1.30-12.64]).
CONCLUSIONS
There are several promising drug combinations that may enhance the impact of STH control programs on T. trichiura, without compromising efficacy against Ascaris lumbricoides and hookworm. We suggest further, large-scale trials of these drug combinations and consideration of their use in STH control programs where T. trichiura is present.
INTERNATIONAL PROSPECTIVE REGISTER OF SYSTEMATIC REVIEWS REGISTRATION
CRD42016050739.
Topics: Anthelmintics; Ascariasis; Drug Combinations; Humans; Mass Drug Administration; Placebos; Prospective Studies; Treatment Outcome; Trichuriasis
PubMed: 29788074
DOI: 10.1093/cid/ciy423 -
PLoS Neglected Tropical Diseases Apr 2018The soil-transmitted helminths (STH), Ascaris lumbricoides, Trichuris trichiura and hookworms, infect 1.5 billion people worldwide and cause an estimated burden of 3.3... (Meta-Analysis)
Meta-Analysis Review
Efficacy and safety of co-administered ivermectin plus albendazole for treating soil-transmitted helminths: A systematic review, meta-analysis and individual patient data analysis.
BACKGROUND
The soil-transmitted helminths (STH), Ascaris lumbricoides, Trichuris trichiura and hookworms, infect 1.5 billion people worldwide and cause an estimated burden of 3.3 million disability-adjusted life years (DALYs). Current control strategies focus on morbidity reduction through preventive chemotherapy (PC) but the most commonly used recommended drugs (albendazole and mebendazole) are particularly inefficacious against T. trichiura. This, together with the threat of emerging drug resistance, calls for new control strategies, including co-administration with other anthelminthics. Ivermectin plus albendazole is widely used against lymphatic filariasis, but its efficacy and safety against STH infections has not yet been fully understood.
METHODS AND FINDINGS
We conducted a systematic literature review and meta-analysis on the efficacy and safety of ivermectin-albendazole co-administration in five different databases (i.e. PubMed, ISI Web of Science, ScienceDirect, CENTRAL and clinicaltrials.gov) from 1960 to January 2018. Four studies reporting efficacy of ivermectin-albendazole against STH infections and five studies on its safety met the selection criteria and were included for quantitative analysis. Ivermectin-albendazole was significantly associated with lower risk (risk ratio (RR) = 0.44, 95% confidence interval (CI) = 0.31-0.62) for T. trichiura infection after treatment compared to albendazole alone. The co-administration revealed no or only a marginal benefit on cure and egg reduction rates over albendazole alone for A. lumbricoides and hookworm infections. Adverse events (AEs) occurring after ivermectin-albendazole co-administration were mostly mild and transient. Overall, the number of individuals reporting any AE was not different (RR = 1.09, 95% CI = 0.87-1.36) in co-treated and albendazole-treated patients. However, although not statistically significant, sub-group analysis showed a tendency for slightly more AEs in patients with filariasis treated with ivermectin-albendazole compared to those treated with albendazole alone (RR = 1.29, 95% CI = 0.81-2.05).
CONCLUSIONS
Our findings suggest a good tolerability and higher efficacy of ivermectin-albendazole against T. trichiura compared to the current standard single-dose albendazole treatment, which supports the use of this co-administration in PC programs. Large-scale definitive randomized controlled trials are required to confirm our results.
Topics: Albendazole; Animals; Anthelmintics; Helminthiasis; Helminths; Humans; Ivermectin; Treatment Outcome
PubMed: 29702653
DOI: 10.1371/journal.pntd.0006458 -
Journal of Helminthology May 2019Knowledge of endemic helminths in a resource-limited country such as Nigeria is essential for their diagnosis, treatment and cost-effective control. In the present... (Meta-Analysis)
Meta-Analysis
Knowledge of endemic helminths in a resource-limited country such as Nigeria is essential for their diagnosis, treatment and cost-effective control. In the present study, the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analysis) guideline was employed to determine the prevalence and geographical distribution of zoonotic helminths in food animals slaughtered in Nigerian abattoirs between 1970 and 2016. Pooled prevalence estimate (PPE) was determined by the random-effects model while heterogeneity was evaluated using the Cochran's Q-test. Results from 42 eligible studies reported across 19 Nigerian states revealed 85,466 cases of zoonotic helminths from 3,771,832 slaughtered food animals. Overall PPE was 2.27% (95% confidence interval (CI): 2.25, 2.28). PPEs for sub-groups ranged between 0.51% (95% CI: 0.46, 0.56) and 18.05% (95% CI: 17.12, 19.01) across regions, hosts, study periods and diagnostic methods. Ascaris suum had the highest pooled prevalence of 25.46% (95% CI: 24.04, 26.92). Overall prevalence estimates for cestodes, nematodes and trematodes were 0.60% (95% CI: 0.59, 0.61), 21.51% (95% CI: 20.73, 22.30) and 1.86% (95% CI: 1.84, 1.87), respectively. A high degree of heterogeneity 99.97% (95% CI: 2.25, 2.28, P: 0.000) was observed. Zoonotic helminths were prevalent in slaughtered food animals, with higher prevalence estimates in the north-central region, pigs and during the last decade reviewed. Ascaris suum was the most prevalent helminth, while Fasciola gigantica had the widest geographical distribution. It is envisaged that the present information will help in the formulation of disease-control policies, encourage on-farm good agricultural practices, and adequate hygiene and sanitation in abattoirs and meat-processing plants, with the aim of protecting public health.
Topics: Abattoirs; Animals; Helminthiasis, Animal; Helminths; Nigeria; Prevalence; Topography, Medical; Zoonoses
PubMed: 29502552
DOI: 10.1017/S0022149X18000196 -
Parasites & Vectors Jan 2018The human helminth infections include ascariasis, trichuriasis, hookworm infections, schistosomiasis, lymphatic filariasis (LF) and onchocerciasis. It is estimated that...
BACKGROUND
The human helminth infections include ascariasis, trichuriasis, hookworm infections, schistosomiasis, lymphatic filariasis (LF) and onchocerciasis. It is estimated that almost 2 billion people worldwide are infected with helminths. Whilst the WHO treatment guidelines for helminth infections are mostly aimed at controlling morbidity, there has been a recent shift with some countries moving towards goals of disease elimination through mass drug administration, especially for LF and onchocerciasis. However, as prevalence is driven lower, treating entire populations may no longer be the most efficient or cost-effective strategy. Instead, it may be beneficial to identify individuals or demographic groups who are persistently infected, often termed as being "predisposed" to infection, and target treatment at them.
METHODS
The authors searched Embase, MEDLINE, Global Health, and Web of Science for all English language, human-based papers investigating predisposition to helminth infections published up to October 31st, 2017. The varying definitions used to describe predisposition, and the statistical tests used to determine its presence, are summarised. Evidence for predisposition is presented, stratified by helminth species, and risk factors for predisposition to infection are identified and discussed.
RESULTS
In total, 43 papers were identified, summarising results from 34 different studies in 23 countries. Consistent evidence of predisposition to infection with certain species of human helminth was identified. Children were regularly found to experience greater predisposition to Ascaris lumbricoides, Schistosoma mansoni and S. haematobium than adults. Females were found to be more predisposed to A. lumbricoides infection than were males. Household clustering of infection was identified for A. lumbricoides, T. trichiura and S. japonicum. Ascaris lumbricoides and T. trichiura also showed evidence of familial predisposition. Whilst strong evidence for predisposition to hookworm infection was identified, findings with regards to which groups were affected were considerably more varied than for other helminth species.
CONCLUSION
This review has found consistent evidence of predisposition to heavy (and light) infection for certain human helminth species. However, further research is needed to identify reasons for the reported differences between demographic groups. Molecular epidemiological methods associated with whole genome sequencing to determine 'who infects whom' may shed more light on the factors generating predisposition.
Topics: Adult; Age Factors; Ascariasis; Child; Disease Susceptibility; Feces; Female; Helminthiasis; Hookworm Infections; Humans; Intestinal Diseases, Parasitic; Male; Prevalence; Risk Factors; Sex Factors; Soil; Trichuriasis
PubMed: 29382360
DOI: 10.1186/s13071-018-2656-4 -
PLoS Neglected Tropical Diseases Jan 2018Soil-transmitted helminth (STH) infections are among the most prevalent neglected tropical diseases (NTD) worldwide. Since the publication of the WHO road map to combat...
BACKGROUND
Soil-transmitted helminth (STH) infections are among the most prevalent neglected tropical diseases (NTD) worldwide. Since the publication of the WHO road map to combat NTD in 2012, there has been a renewed commitment to control STH. In this study, we analysed the geographical distribution and effect of community type on prevalence of hookworm, Trichuris and Ascaris in south Asia and south east Asia.
METHODOLOGY
We conducted a systematic review of open-access literature published in PubMed Central and the Global Atlas of Helminth Infection. A total of 4182 articles were available and after applying selection criteria, 174 studies from the region were retained for analysis.
PRINCIPAL FINDINGS
Ascaris was the commonest STH identified with an overall prevalence of 18% (95% CI, 14-23%) followed by Trichuris (14%, 9-19%) and hookworm (12%, 9-15%). Hookworm prevalence was highest in Laos, Vietnam and Cambodia. We found a geographical overlap in countries with high prevalence rates for Trichuris and Ascaris (Malaysia, Philippines, Myanmar, Vietnam and Bangladesh). When the effect of community type was examined, prevalence rates of hookworm was comparable in rural (19%, 14-24%) and tribal communities (14%, 10-19%). Tribal communities, however, showed higher prevalence of Trichuris (38%, 18-63%) and Ascaris (32%, 23-43%) than rural communities (13%, 9-20% and 14%, 9-20% respectively). Considerable between and within country heterogeneity in the distribution of STH (I2 >90%) was also noted. When available data from school aged children (SAC) were analysed, prevalence of Ascaris (25% 16-31%) and Trichuris (22%, 14-34%) were higher than among the general population while that of hookworm (10%, 7-16%) was comparable.
CONCLUSIONS/SIGNIFICANCE
Our analysis showed significant variation in prevalence rates between and within countries in the region. Highlighting the importance of community type in prevalence and species mix, we showed that tribal and rural communities had higher hookworm infections than urban communities and for ascariasis and trichuriasis, tribal populations had higher levels of infection than rural populations. We also found a higher prevalence of ascariasis and trichuriasis in SAC compared to the general population but comparable levels of hookworm infections. These key findings need to be taken into account in planning future MDA and other interventions.
Topics: Ascariasis; Asia, Southeastern; Humans; Prevalence; Rural Population; Topography, Medical; Trichuriasis; Urban Population
PubMed: 29346440
DOI: 10.1371/journal.pntd.0006153 -
Pathogens and Global Health Feb 2018Contamination of edible fruits and vegetables is now a global public health issue despite their health benefits as non-pharmacological prophylaxis against chronic... (Meta-Analysis)
Meta-Analysis Review
Contamination of edible fruits and vegetables is now a global public health issue despite their health benefits as non-pharmacological prophylaxis against chronic diseases. Studies that will harness the extent of parasitic contaminations will ensure public health protection. Here, the prevalence and distribution of parasites of importance for human health on fruits and vegetables in Nigeria were determined through a systematic review and meta-analysis of published data. The random-effects model was used to determine pooled prevalence estimate (PPE). Heterogeneity was evaluated by the Cochran's Q-test. Parasites overall PPE of 32.4% (95% CI: 0.73, 0.91) was observed from 19 eligible studies reported across 13 Nigerian states. Sub-groups PPEs ranged between 3.5% (95% CI: 0.45, 1.86) and 58.5% (95% CI: 1.40, 4.09). A high degree of heterogeneity 97.53% (95% CI: 0.30, 0.46, P: 0.000) was observed within studies and sub-groups. Cryptosporidium species were the most prevalent, while Ancylostoma duodenale and Ascaris lumbricoides had the widest geographical distribution. Pineapple (Prev: 41.3%, 95% CI: 0.40, 0.75) and lettuce (Prev: 51.5%, 95% CI: 0.37, 0.68) recorded the highest level of parasitic contamination. Parasites of importance for human health are prevalent on edible fruits and vegetables in Nigeria. Prevalence estimates were highest in the South-eastern region and during the most recent decade. Adequate washing of fruits and vegetables, on-farm irrigation of vegetables using good sources of water and adequate hygiene by food handlers will help the general public to maximize the health benefits associated with the intake of fruits and vegetables while minimizing the risk of acquiring parasitic infections.
Topics: Animals; Food Contamination; Fruit; Nigeria; Parasites; Prevalence; Vegetables
PubMed: 29336229
DOI: 10.1080/20477724.2018.1425604 -
PLoS Neglected Tropical Diseases Nov 2017Human excreta is a low cost source of nutrients vital to plant growth, but also a source of pathogens transmissible to people and animals. We investigated the... (Meta-Analysis)
Meta-Analysis Review
Human excreta is a low cost source of nutrients vital to plant growth, but also a source of pathogens transmissible to people and animals. We investigated the cost-savings and infection risk of soil transmitted helminths (STHs) in four scenarios where farmers used either inorganic fertilizer or fresh/composted human excreta supplemented by inorganic fertilizer to meet the nutrient requirements of rice paddies in the Red River Delta, Vietnam. Our study included two main components: 1) a risk estimate of STH infection for farmers who handle fresh excreta, determined by systematic review and meta-analysis; and 2) a cost estimate of fertilizing rice paddies, determined by nutrient assessment of excreta, a retailer survey of inorganic fertilizer costs, and a literature review to identify region-specific inputs. Our findings suggest that farmers who reuse fresh excreta are 1.24 (95% CI: 1.13-1.37, p-value<0.001) times more likely to be infected with any STH than those who do not handle excreta or who compost appropriately, and that risk varies by STH type (Ascaris lumbricoides RR = 1.17, 95% CI = 0.87-1.58, p-value = 0.29; Hookworm RR = 1.02, 95% CI = 0.50-2.06, p-value = 0.96; Trichuris trichiura RR = 1.38, 95% CI = 0.79-2.42, p-value = 0.26). Average cost-savings were highest for farmers using fresh excreta (847,000 VND) followed by those who composted for 6 months as recommended by the WHO (312,000 VND) and those who composted for a shorter time (5 months) with lime supplementation (37,000 VND/yr); however, this study did not assess healthcare costs of treating acute or chronic STH infections in the target group. Our study provides evidence that farmers in the Red River Delta are able to use a renewable and locally available resource to their economic advantage, while minimizing the risk of STH infection.
Topics: Agriculture; Ancylostomatoidea; Animals; Ascariasis; Ascaris lumbricoides; Body Fluids; Cost-Benefit Analysis; Feces; Hookworm Infections; Humans; Linear Models; Soil; Trichuriasis; Trichuris; Vietnam
PubMed: 29176840
DOI: 10.1371/journal.pntd.0006088 -
PLoS Neglected Tropical Diseases Oct 2017Preventive chemotherapy and transmission control (PCT) by mass drug administration is the cornerstone of the World Health Organization (WHO)'s policy to control... (Review)
Review
BACKGROUND
Preventive chemotherapy and transmission control (PCT) by mass drug administration is the cornerstone of the World Health Organization (WHO)'s policy to control soil-transmitted helminthiases (STHs) caused by Ascaris lumbricoides (roundworm), Trichuris trichiura (whipworm) and hookworm species (Necator americanus and Ancylostama duodenale) which affect over 1 billion people globally. Despite consensus that drug efficacies should be monitored for signs of decline that could jeopardise the effectiveness of PCT, systematic monitoring and evaluation is seldom implemented. Drug trials mostly report aggregate efficacies in groups of participants, but heterogeneities in design complicate classical meta-analyses of these data. Individual participant data (IPD) permit more detailed analysis of drug efficacies, offering increased sensitivity to identify atypical responses potentially caused by emerging drug resistance.
METHODOLOGY
We performed a systematic literature review to identify studies concluding after 2000 that collected IPD suitable for estimating drug efficacy against STH. We included studies that administered a variety of anthelmintics with follow ups less than 60 days after treatment. We estimated the number of IPD and extracted cohort- and study-level meta-data.
PRINCIPAL FINDINGS
We estimate that there exist individual data on approximately 35,000 participants from 129 studies conducted in 39 countries, including 34 out of 103 countries where PCT is recommended. We find significant heterogeneity in diagnostic methods, times of outcome assessment, and the reported measure of efficacy. We also quantify cohorts comprising pre-school age children, pregnant women, and co-infected participants, including with HIV.
CONCLUSIONS
We argue that establishing a global IPD repository would improve the capacity to monitor and evaluate the efficacy of anthelmintic drugs, respond to changes and safeguard the ongoing effectiveness of PCT. Establishing a fair, transparent data governance policy will be key for the engagement of the global STH community.
Topics: Anthelmintics; Clinical Trials as Topic; Helminthiasis; Humans; Meta-Analysis as Topic; Soil
PubMed: 29088274
DOI: 10.1371/journal.pntd.0006053 -
BMJ (Clinical Research Ed.) Sep 2017To evaluate efficacies of anthelmintic drugs against soil transmitted helminths in terms of cure rates and egg reduction rates. Systematic review and network... (Meta-Analysis)
Meta-Analysis Review
To evaluate efficacies of anthelmintic drugs against soil transmitted helminths in terms of cure rates and egg reduction rates. Systematic review and network meta-analysis. PubMed, ISI Web of Science, Embase, ScienceDirect, the Cochrane Central Register of Clinical Trials, and the World Health Organization library database from 1960 until 31 December 2016. Randomised controlled trials evaluating the efficacy of a single dose regimen of albendazole, mebendazole, levamisole, and pyrantel pamoate against , hookworm ( and ) and The primary outcomes included cure rates analysed by network meta-analysis with mixed logistic regression models and egg reduction rates with mixed linear models. 55 and 46 randomised controlled trials were included in the analysis of cure rates and egg reduction rates, respectively. All drugs were highly efficacious against Albendazole showed the highest efficacy against hookworm infections with a cure rate of 79.5% (95% confidence interval 71.5% to 85.6%) and an egg reduction rate of 89.6% (81.9% to 97.3%). All drugs had low efficacy against , with mebendazole showing the highest cure rate of 42.1% (25.9% to 60.2%) and egg reduction rate of 66.0% (54.6% to 77.3%). Estimates for the years 1995 and 2015 showed significant reductions in efficacy of albendazole against : by 2015 the egg reduction rates fell from 72.6% (53.7% to 91.5%) to 43.4% (23.5% to 63.3%; P=0.049) and the cure rates fell from 38.6% (26.2% to 52.7%) to 16.4 (7.7% to 31.3%; P=0.027). All four currently recommended drugs show limitations in their efficacy profile. While only albendazole showed good efficacy against hookworm infection, all drugs had low efficacy against The decrease in efficacy of albendazole against over the past two decades is of concern. The findings indicate the need for strengthening efforts to develop new drug treatments, with a particular focus on drugs against .
Topics: Animals; Anthelmintics; Female; Helminthiasis; Helminths; Humans; Male; Network Meta-Analysis; Randomized Controlled Trials as Topic; Soil; Treatment Outcome
PubMed: 28947636
DOI: 10.1136/bmj.j4307 -
Lancet (London, England) Jan 2017Soil-transmitted helminth infections are a major global health issue, causing substantial morbidity in the world's poorest populations. Regular delivery of anthelmintic... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Soil-transmitted helminth infections are a major global health issue, causing substantial morbidity in the world's poorest populations. Regular delivery of anthelmintic drugs is the mainstay for global soil-transmitted helminth control. Deworming campaigns are often targeted to school-aged children, who are at high risk of soil-transmitted-helminth-associated morbidity. However, findings from modelling studies suggest that deworming campaigns should be expanded community-wide for effective control of soil-transmitted helminth transmission. We aimed to do a systematic review and meta-analysis to compare the effect of mass (community-wide) and targeted (children only) anthelmintic delivery strategies on soil-transmitted helminth prevalence in school-aged children.
METHODS
In this systematic review and meta-analysis, we searched MEDLINE, Embase, and Web of Science for articles published on or before Nov 5, 2015, reporting soil-transmitted helminth prevalence before and after distribution of albendazole or mebendazole, either targeted to children or delivered to the whole community. We excluded studies in which drug delivery was restricted to infected individuals or to a subset of the community or school, or if follow-up time was less than 3 months or greater than 18 months after drug delivery. We extracted data on study year, country, drug administration strategy, drug dose, number of deworming rounds, treatment coverage, diagnostic method, follow-up interval, and soil-transmitted helminth prevalence before and after treatment. We used inverse variance weighted generalised linear models, with prevalence reduction as the outcome variable, to examine the effect of mass versus targeted drug administration, as well as baseline prevalence, number of drug doses, and follow-up time. This study is registered with PROSPERO, number CRD42016026929.
FINDINGS
Of 10 538 studies identified, 56 studies were eligible for the systematic review and 38 of these were included in meta-analysis. Results of the regression models showed that mass deworming led to a significantly greater reduction in prevalence in children than targeted deworming, for both hookworm (odds ratio 4·6, 95% CI 1·8-11·6; p=0·0020) and Ascaris lumbricoides (16·4, 2·1-125·8; p=0·0092), with no effect seen for Trichuris trichiura. There was significant heterogeneity across studies; for targeted studies I was 97% for A lumbricoides and hookworm, and 96% for T trichiura, and for mass studies, I was 89% for A lumbricoides, 49% for hookworm, and 66% for T trichiura.
INTERPRETATION
The results of this meta-analysis suggest that expanding deworming programmes community-wide is likely to reduce the prevalence of soil-transmitted helminths in the high-risk group of school-aged children, which could lead to improved morbidity outcomes. These findings are in support of recent calls for re-evaluation of global soil-transmitted helminth control guidelines.
FUNDING
None.
Topics: Adolescent; Ancylostomatoidea; Animals; Anthelmintics; Ascaris lumbricoides; Child; Child, Preschool; Communicable Disease Control; Helminthiasis; Humans; Soil; Trichuris
PubMed: 27979381
DOI: 10.1016/S0140-6736(16)32123-7