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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 -
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 -
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 -
Parasites & Vectors Jun 2016The epidemiology of soil-transmitted helminth (STH) and Plasmodium co-infections need better understanding. The findings of the individual studies are inconclusive. A... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
The epidemiology of soil-transmitted helminth (STH) and Plasmodium co-infections need better understanding. The findings of the individual studies are inconclusive. A systematic review was conducted to synthesize evidence on the association of STH infection with the prevalence and density of Plasmodium falciparum infection, and its effect on anaemia among children in sub-Saharan Africa (SSA).
METHODS
Relevant studies published before March 6, 2015 were identified by searching Medline (via Pubmed), Embase, Cochrane Library and CINAHL without any language restriction. Studies on P. falciparum and STH co-infection among children in SSA except for case studies were included in this study. Studies were screened for eligibility and data extracted independently by two authors. The primary outcome assessed was the prevalence of P. falciparum infection and the secondary outcomes included P. falciparum density and prevalence of anaemia. Heterogeneity was assessed using Cochrane Q and Moran's I (2) and publication bias was evaluated using Egger test. A random-effects model was used to estimate the summary odds ratio (OR) and the corresponding 95 % confidence intervals (CI).
RESULTS
Out of 2985 articles screened, 11 articles were included in the systematic review; of these seven were considered in the meta-analysis. Of the 11 studies with 7458 study participants, seven were cross-sectional, one prospective cohort and three were randomized controlled trials. Four studies examined the outcome for hookworms, one for Ascaris lumbricoides and six for pooled (at least one) STH species. Eight studies measured prevalence/incidence of uncomplicated P. falciparum infection, two calculated prevalence of asymptomatic P. falciparum infection, three evaluated P. falciparum density and four considered prevalence of P. falciparum infection related anaemia/mean haemoglobin reduction. The odds of asymptomatic/uncomplicated P. falciparum infection were higher among children infected with STH than those uninfected with intestinal helminths (summary Odds Ratio [OR]: 1.4; 95 % Confidence Interval [CI]: 1.05-1.87; I (2) = 36.8 %). Plasmodium falciparum density tended to be higher among children infected with STH than those uninfected with intestinal helminths. However, STH infection was associated with lower odds of P. falciparum infection related anaemia (summary OR: 0.5; 95 % CI: 0.21-0.78; I (2) = 43.3 %).
CONCLUSIONS
The findings suggest that STH infection may increase susceptibility to asymptomatic/uncomplicated P. falciparum infection but may protect malaria-related anaemia in children. Future studies should investigate the effect of STH infection upon the incidence of severe P. falciparum infection among children in SSA.
Topics: Africa South of the Sahara; Child; Coinfection; Helminthiasis; Humans; Malaria, Falciparum; Plasmodium falciparum; Soil
PubMed: 27306987
DOI: 10.1186/s13071-016-1594-2 -
PLoS Neglected Tropical Diseases May 2016Soil-transmitted helminths (STH) have acute and chronic manifestations, and can result in lifetime morbidity. Disease burden is difficult to quantify, yet quantitative... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Soil-transmitted helminths (STH) have acute and chronic manifestations, and can result in lifetime morbidity. Disease burden is difficult to quantify, yet quantitative evidence is required to justify large-scale deworming programmes. A recent Cochrane systematic review, which influences Global Burden of Disease (GBD) estimates for STH, has again called into question the evidence for deworming benefit on morbidity due to STH. In this narrative review, we investigate in detail what the shortfalls in evidence are.
METHODOLOGY/PRINCIPAL FINDINGS
We systematically reviewed recent literature that used direct measures to investigate morbidity from STH and we critically appraised systematic reviews, particularly the most recent Cochrane systematic review investigating deworming impact on morbidity. We included six systematic reviews and meta-analyses, 36 literature reviews, 44 experimental or observational studies, and five case series. We highlight where evidence is insufficient and where research needs to be directed to strengthen morbidity evidence, ideally to prove benefits of deworming.
CONCLUSIONS/SIGNIFICANCE
Overall, the Cochrane systematic review and recent studies indicate major shortfalls in evidence for direct morbidity. However, it is questionable whether the systematic review methodology should be applied to STH due to heterogeneity of the prevalence of different species in each setting. Urgent investment in studies powered to detect direct morbidity effects due to STH is required.
Topics: Anemia; Animals; Anthelmintics; Ascariasis; Ascaris lumbricoides; Chronic Disease; Cost of Illness; Helminthiasis; Humans; Prevalence; Soil
PubMed: 27196100
DOI: 10.1371/journal.pntd.0004566 -
Parasites & Vectors Jan 2016Soil-transmitted helminth (STH) infections of humans fall within the World Health Organization's (WHO) grouping termed the neglected tropical diseases (NTDs). It is... (Review)
Review
Soil-transmitted helminth (STH) infections of humans fall within the World Health Organization's (WHO) grouping termed the neglected tropical diseases (NTDs). It is estimated that they affect approximately 1.4 billion people worldwide. A significant proportion of these infections are in the population of Southeast Asia. This review analyses published data on STH prevalence and intensity in Southeast Asia over the time period of 1900 to the present to describe age related patterns in these epidemiological measures. This is with a focus on the four major parasite species affecting humans; namely Ascaris lumbricoides, Trichuris trichiura and the hookworms; Necator americanus and Ancylostoma duodenale. Data were also collected on the diagnostic methods used in the published surveys and how the studies were designed to facilitate comparative analyses of recorded patterns and changes therein over time. PubMed, Google Scholar, EMBASE, ISI Web of Science, Cochrane Database of Systematic Reviews and the Global Atlas of Helminth Infections search engines were used to identify studies on STH in Southeast Asia with the search based on the major key words, and variants on, "soil-transmitted helminth" "Ascaris" "Trichuris" "hookworm" and the country name. A total of 280 studies satisfied the inclusion criteria from 11 Southeast Asian countries; Brunei, Cambodia, Indonesia, Lao People's Democratic Republic (Lao PDR), Malaysia, Myanmar, Philippines, Singapore, Thailand, Timor-Leste and Vietnam. It was concluded that the epidemiological patterns of STH infection by age and species mix in Southeast Asia are similar to those reported in other parts of the world. In the published studies there were a large number of different diagnostic methods used with differing sensitivities and specificities, which makes comparison of the results both within and between countries difficult. There is a clear requirement to standardise the methods of both STH diagnosis in faecal material and how the intensity of infection is recorded and reported in future STH research and in monitoring and evaluation (M&E) of the impact of continuing and expanding mass drug administration (MDA) programmes.
Topics: Ancylostoma; Ancylostomatoidea; Animals; Ascariasis; Ascaris lumbricoides; Asia, Southeastern; Feces; Helminthiasis; Helminths; Hookworm Infections; Humans; Prevalence; Research; Soil; Surveys and Questionnaires; Trichuriasis; Trichuris
PubMed: 26813007
DOI: 10.1186/s13071-016-1310-2 -
Parasites & Vectors May 2014The relationship between nutrition and soil-transmitted helminthiasis is complex and warrants further investigation. We conducted a systematic review examining the... (Review)
Review
BACKGROUND
The relationship between nutrition and soil-transmitted helminthiasis is complex and warrants further investigation. We conducted a systematic review examining the influence of nutrition on infection and re-infection with soil-transmitted helminths (i.e. Ascaris lumbricoides, hookworm, Trichuris trichiura and Strongyloides stercoralis) in humans. Emphasis was placed on the use of nutritional supplementation, alongside anthelminthic treatment, to prevent re-infection with soil-transmitted helminths.
METHODS
We searched eight electronic databases from inception to 31 July 2013, with no restriction of language or type of publication. For studies that met our inclusion criteria, we extracted information on the soil-transmitted helminth species, nutritional supplementation and anthelminthic treatment. Outcomes were presented in forest plots and a summary of findings (SoF) table. An evidence profile (EP) was generated by rating the evidence quality of the identified studies according to the GRADE system.
RESULTS
Fifteen studies met our inclusion criteria; eight randomised controlled trials and seven prospective cohort studies. Data on A. lumbricoides were available from all studies, whereas seven and six studies additionally contained data on T. trichiura and hookworm, respectively. None of the studies contained data on S. stercoralis. Positive effects of nutritional supplementation or the host's natural nutritional status on (re-)infection with soil-transmitted helminths were reported in 14 studies, while negative effects were documented in six studies. In terms of quality, a high, low and very low quality rating was assigned to the evidence from four, six and five studies, respectively.
CONCLUSIONS
Our findings suggest that the current evidence-base is weak, precluding guidelines on nutrition management as a potential supplementary tool to preventive chemotherapy targeting soil-transmitted helminthiasis. Moreover, several epidemiological, immunological and methodological issues have been identified, and these should be considered when designing future studies.
Topics: Anthelmintics; Child; Child, Preschool; Helminthiasis; Humans; Infant; Nutritional Status
PubMed: 24885622
DOI: 10.1186/1756-3305-7-229