-
Clinical Microbiology Reviews Oct 2001Hookworms infect perhaps one-fifth of the entire human population, yet little is known about their interaction with our immune system. The two major species are Necator... (Review)
Review
Hookworms infect perhaps one-fifth of the entire human population, yet little is known about their interaction with our immune system. The two major species are Necator americanus, which is adapted to tropical conditions, and Ancylostoma duodenale, which predominates in more temperate zones. While having many common features, they also differ in several key aspects of their biology. Host immune responses are triggered by larval invasion of the skin, larval migration through the circulation and lungs, and worm establishment in the intestine, where adult worms feed on blood and mucosa while injecting various molecules that facilitate feeding and modulate host protective responses. Despite repeated exposure, protective immunity does not seem to develop in humans, so that infections occur in all age groups (depending on exposure patterns) and tend to be prolonged. Responses to both larval and adult worms have a characteristic T-helper type 2 profile, with activated mast cells in the gut mucosa, elevated levels of circulating immunoglobulin E, and eosinophilia in the peripheral blood and local tissues, features also characteristic of type I hypersensitivity reactions. The longevity of adult hookworms is determined probably more by parasite genetics than by host immunity. However, many of the proteins released by the parasites seem to have immunomodulatory activity, presumably for self-protection. Advances in molecular biotechnology enable the identification and characterization of increasing numbers of these parasite molecules and should enhance our detailed understanding of the protective and pathogenetic mechanisms in hookworm infections.
Topics: Ancylostomatoidea; Animals; Antigens, Helminth; Hookworm Infections; Host-Parasite Interactions; Humans; Hypersensitivity; Larva; Protozoan Vaccines
PubMed: 11585781
DOI: 10.1128/CMR.14.4.689-703.2001 -
PLoS Medicine Jan 2012In countries of high endemicity of the soil-transmitted helminth parasites Ascaris lumbricoides, Trichuris trichiura, and hookworm, preventive chemotherapy (i.e.,... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
In countries of high endemicity of the soil-transmitted helminth parasites Ascaris lumbricoides, Trichuris trichiura, and hookworm, preventive chemotherapy (i.e., repeated administration of anthelmintic drugs to at-risk populations) is the main strategy to control morbidity. However, rapid reinfection of humans occurs after successful deworming, and therefore effective preventive measures are required to achieve public health goals with optimal efficiency and sustainability.
METHODS AND FINDINGS
We conducted a systematic review and meta-analysis to assess the effect of sanitation (i.e., access and use of facilities for the safe disposal of human urine and feces) on infection with soil-transmitted helminths. PubMed, Embase, ISI Web of Science, and the World Health Organization Library Database were searched without language restrictions and year of publication (search performed until December 31, 2010). Bibliographies of identified articles were hand-searched. All types of studies reporting data on sanitation availability (i.e., having access at own household or living in close proximity to sanitation facility), or usage, and soil-transmitted helminth infections at the individual level were considered. Reported odds ratios (ORs) of the protective effect of sanitation on soil-transmitted helminth infections were extracted from the papers or calculated from reported numbers. The quality of published studies was assessed with a panel of criteria developed by the authors. Random effects meta-analyses were used to account for observed heterogeneity. Thirty-six publications, consisting of 39 datasets, met our inclusion criteria. Availability of sanitation facilities was associated with significant protection against infection with soil-transmitted helminths (OR = 0.46 to 0.58). Regarding the use of sanitation, ORs of 0.54 (95% confidence interval [CI] 0.28-1.02), 0.63 (95% CI 0.37-1.05), and 0.78 (95% CI 0.60-1.00) were determined for T. trichiura, hookworm, and A. lumbricoides, respectively. The overall ORs, combining sanitation availability and use, were 0.51 (95% CI 0.44-0.61) for the three soil-transmitted helminths combined, 0.54 (95% CI 0.43-0.69) for A. lumbricoides, 0.58 (95% CI 0.45-0.75) for T. trichiura, and 0.60 (95% CI 0.48-0.75) for hookworm.
CONCLUSIONS
Despite a number of limitations (e.g., most studies used a cross-sectional design and were of low quality, with potential biases and considerable heterogeneity), our results reveal that sanitation is associated with a reduced risk of transmission of helminthiases to humans. Access to improved sanitation should be prioritized alongside preventive chemotherapy and health education to achieve a durable reduction of the burden of helminthiases.
Topics: Ancylostomatoidea; Animals; Ascariasis; Ascaris lumbricoides; Hookworm Infections; Humans; Nematoda; Nematode Infections; Sanitation; Soil; Trichuriasis; Trichuris
PubMed: 22291577
DOI: 10.1371/journal.pmed.1001162 -
FEMS Immunology and Medical Microbiology Feb 2005Hookworms infect almost one billion people and are a major cause of iron-deficiency anaemia in developing countries of the tropics. Despite their prevalence and the... (Review)
Review
Hookworms infect almost one billion people and are a major cause of iron-deficiency anaemia in developing countries of the tropics. Despite their prevalence and the morbidity they cause, little is known about the immune response to this complex eukaryotic parasite. Recent publications have shed light on the human cellular immune responses to hookworms, as well as mechanisms that hookworms utilize to skew the immune response in its favour. Unlike most other human helminth infections, neither age- nor exposure-related immunity develops in the majority of infected people. A vaccine is therefore a highly desirable goal. To this end, gene sequencing efforts have resulted in the deposition of more than 10,000 hookworm cDNA sequences in the public domain, providing a molecular snapshot of this intriguing parasite and providing novel tools for the development of new control strategies. Significant progress has been made in the development of anti-hookworm recombinant vaccines, and clinical trials are expected to begin in the near future.
Topics: Ancylostoma; Ancylostomiasis; Animals; Cytokines; Humans; Immunity, Cellular; Necator americanus; Necatoriasis; Vaccines
PubMed: 15681140
DOI: 10.1016/j.femsim.2004.11.006 -
Molecules (Basel, Switzerland) Jun 2020Soil-transmitted nematodes (STN) infect 1-2 billion of the poorest people worldwide. Only benzimidazoles are currently used in mass drug administration, with many...
Soil-transmitted nematodes (STN) infect 1-2 billion of the poorest people worldwide. Only benzimidazoles are currently used in mass drug administration, with many instances of reduced activity. Terpenes are a class of compounds with anthelmintic activity. Thymol, a natural monoterpene phenol, was used to help eradicate hookworms in the U.S. South circa 1910. However, the use of terpenes as anthelmintics was discontinued because of adverse side effects associated with high doses and premature stomach absorption. Furthermore, the dose-response activity of specific terpenes against STNs has been understudied. Here we used hollow, porous yeast particles (YPs) to efficiently encapsulate (>95%) high levels of terpenes (52% ) and evaluated their anthelmintic activity on hookworms (, a rodent parasite (), and whipworm (. We identified YP-terpenes that were effective against all three parasites. Further, YP-terpenes overcame albendazole-resistant . These results demonstrate that terpenes are broad-acting anthelmintics. Terpenes are predicted to be extremely difficult for parasites to resist, and YP encapsulation provides water-suspendable terpene materials without surfactants and sustained terpene release that could lead to the development of formulations for oral delivery that overcome fast absorption in the stomach, thus reducing dosage and toxic side effects.
Topics: Albendazole; Ancylostoma; Ancylostomatoidea; Animals; Anthelmintics; Benzimidazoles; Humans; Nematoda; Nematode Infections; Saccharomyces cerevisiae; Terpenes
PubMed: 32605043
DOI: 10.3390/molecules25132958 -
PLoS Neglected Tropical Diseases Aug 2022Periodic administration of anthelmintic drugs is a cost-effective intervention for morbidity control of soil-transmitted helminth (STH) infections. However, with...
BACKGROUND
Periodic administration of anthelmintic drugs is a cost-effective intervention for morbidity control of soil-transmitted helminth (STH) infections. However, with programs expanding, drug pressure potentially selecting for drug-resistant parasites increases. While monitoring anthelmintic drug efficacy is crucial to inform country control program strategies, different factors must be taken into consideration that influence drug efficacy and make it difficult to standardize treatment outcome measures. We aimed to identify suitable approaches to assess and compare the efficacy of different anthelmintic treatments.
METHODOLOGY
We built an individual participant-level database from 11 randomized controlled trials and two observational studies in which subjects received single-agent or combination therapy, or placebo. Eggs per gram of stool were calculated from egg counts at baseline and post-treatment. Egg reduction rates (ERR; based on mean group egg counts) and individual-patient ERR (iERR) were utilized to express drug efficacy and analyzed after log-transformation with a linear mixed effect model. The analyses were separated by follow-up duration (14-21 and 22-45 days) after drug administration.
PRINCIPAL FINDINGS
The 13 studies enrolled 5,759 STH stool-positive individuals; 5,688 received active medication or placebo contributing a total of 11,103 STH infections (65% had two or three concurrent infections), of whom 3,904 (8,503 infections) and 1,784 (2,550 infections) had efficacy assessed at 14-21 days and 22-45 days post-treatment, respectively. Neither the number of helminth co-infections nor duration of follow-up affected ERR for any helminth species. The number of participants treated with single-dose albendazole was 689 (18%), with single-dose mebendazole 658 (17%), and with albendazole-based co-administrations 775 (23%). The overall mean ERR assessed by day 14-21 for albendazole and mebendazole was 94.5% and 87.4%, respectively on Ascaris lumbricoides, 86.8% and 40.8% on hookworm, and 44.9% and 23.8% on Trichuris trichiura. The World Health Organization (WHO) recommended criteria for efficacy were met in 50%, 62%, and 33% studies of albendazole for A. lumbricoides, T. trichiura, and hookworm, respectively and 25% of mebendazole studies. iERR analyses showed similar results, with cure achieved in 92% of A. lumbricoides-infected subjects treated with albendazole and 93% with mebendazole; corresponding figures for hookworm were 70% and 17%, and for T. trichiura 22% and 20%.
CONCLUSIONS/SIGNIFICANCE
Combining the traditional efficacy assessment using group averages with individual responses provides a more complete picture of how anthelmintic treatments perform. Most treatments analyzed fail to meet the WHO minimal criteria for efficacy based on group means. Drug combinations (i.e., albendazole-ivermectin and albendazole-oxantel pamoate) are promising treatments for STH infections.
Topics: Albendazole; Ancylostomatoidea; Animals; Anthelmintics; Helminthiasis; Helminths; Hookworm Infections; Humans; Mebendazole; Soil; Trichuriasis; Trichuris
PubMed: 35917364
DOI: 10.1371/journal.pntd.0010593 -
Advances in Parasitology 2004The scientific study of human hookworm infection began at the dawn of the twentieth century. In recent years, there have been dramatic improvements in our understanding... (Review)
Review
The scientific study of human hookworm infection began at the dawn of the twentieth century. In recent years, there have been dramatic improvements in our understanding of many aspects of this globally widespread parasite. This chapter reviews recent advances in our understanding in the biology, immunology, epidemiology, public health significance and control of hookworm, and to look forward to the study of this important parasite in the 21st century. Advances in molecular biology has lead to the identification of a variety of new molecules from hookworms, which have importance either in the molecular pathogenesis of hookworm infection or in the host-parasite relationship; some are also promising vaccine targets. At present, relatively little is known about the immune responses to hookworm infection, although it has recently been speculated that hookworm and other helminths may modulate specific immune responses to other pathogens and vaccines. Our epidemiological understanding of hookworm has improved through the development of mathematical models of transmission dynamics, which coupled with decades of field research across multiple epidemiological settings, have shown that certain population characteristics can now be recognised as common to the epidemiology, population biology and control of hookworm and other helminth species. Recent recognition of the subtle, but significant, impact of hookworm on health and education, together with the simplicity, safety, low cost and efficacy of chemotherapy has spurred international efforts to control the morbidity due to infection. Large-scale treatment programmes are currently underway, ideally supported by health education and integrated with the provision of improved water and sanitation. There are also on-going efforts to develop novel anthelmintic drugs and anti-hookworm vaccines.
Topics: Ancylostomatoidea; Animals; Cost of Illness; History, 21st Century; Hookworm Infections; Humans; Intestinal Diseases, Parasitic
PubMed: 15603764
DOI: 10.1016/S0065-308X(04)58004-1 -
PLoS Neglected Tropical Diseases Sep 2008Hookworm infection is among the major causes of anaemia in poor communities, but its importance in causing maternal anaemia is poorly understood, and this has hampered... (Review)
Review
BACKGROUND AND OBJECTIVES
Hookworm infection is among the major causes of anaemia in poor communities, but its importance in causing maternal anaemia is poorly understood, and this has hampered effective lobbying for the inclusion of anthelmintic treatment in maternal health packages. We sought to review existing evidence on the role of hookworm as a risk factor for anaemia among pregnant women. We also estimate the number of hookworm infections in pregnant women in sub-Saharan Africa (SSA).
METHODS
Structured searches using MEDLINE and EMBASE as well as manual searches of reference lists were conducted, and unpublished data were obtained by contacting authors. Papers were independently reviewed by two authors, and relevant data were extracted. We compared haemoglobin concentration (Hb) according to intensity of hookworm infection and calculated standardised mean differences and 95% confidence intervals. To estimate the number of pregnant women, we used population surfaces and a spatial model of hookworm prevalence.
FINDINGS
One hundred and five reports were screened and 19 were eligible for inclusion: 13 cross-sectional studies, 2 randomised controlled trials, 2 non-randomised treatment trials and 2 observational studies. Comparing uninfected women and women lightly (1-1,999 eggs/gram [epg]) infected with hookworm, the standardised mean difference (SMD) was -0.24 (95% CI: -0.36 to -0.13). The SMD between women heavily (4000+ epg) infected and those lightly infected was -0.57 (95% CI: -0.87 to -0.26). All identified intervention studies showed a benefit of deworming for maternal or child health, but since a variety of outcomes measures were employed, quantitative evaluation was not possible. We estimate that 37.7 million women of reproductive age in SSA are infected with hookworm in 2005 and that approximately 6.9 million pregnant women are infected.
CONCLUSIONS
Evidence indicates that increasing hookworm infection intensity is associated with lower haemoglobin levels in pregnant women in poor countries. There are insufficient data to quantify the benefits of deworming, and further studies are warranted. Given that between a quarter and a third of pregnant women in SSA are infected with hookworm and at risk of preventable hookworm-related anaemia, efforts should be made to increase the coverage of anthelmintic treatment among pregnant women.
Topics: Africa South of the Sahara; Ancylostomatoidea; Anemia; Animals; Ecosystem; Female; Geography; Hookworm Infections; Humans; Pregnancy; Pregnancy Complications; Risk Factors
PubMed: 18820740
DOI: 10.1371/journal.pntd.0000291 -
Parasite Immunology 2004Advances in hookworm immunoepidemiology are reviewed. Recent studies demonstrate a mixed Th1/Th2 response in human hookworm infection, with immunosuppression of specific... (Review)
Review
Advances in hookworm immunoepidemiology are reviewed. Recent studies demonstrate a mixed Th1/Th2 response in human hookworm infection, with immunosuppression of specific and nonspecific IFN-gamma responses. There is increasing evidence for protective immunity in human hookworm infection, including anti-larval IL-5- and IgE-dependent mechanisms, and for immunological interactions between hookworm infection and other diseases.
Topics: Ancylostoma; Ancylostomiasis; Animals; Hookworm Infections; Humans; Necator americanus; Necatoriasis
PubMed: 15771680
DOI: 10.1111/j.0141-9838.2004.00727.x -
Parasites & Vectors Nov 2022The Geshiyaro project is a 5-year intervention to assess the impact of community- and school-based water, sanitation, and hygiene (WaSH) interventions on reducing...
BACKGROUND
The Geshiyaro project is a 5-year intervention to assess the impact of community- and school-based water, sanitation, and hygiene (WaSH) interventions on reducing infection with soil-transmitted helminths (STH) and schistosome parasites in combination with deworming in Wolayita zone, Ethiopia.
METHODS
A population-based, cross-sectional census and parasitological mapping activity was conducted between 2018 and 2019. Individuals in the census were identified using either a registered study ID card or biometric fingerprint to enable linkage of their household WaSH data with baseline STH and schistosome prevalence for risk analysis.
RESULTS
Prevalence of STH was 15.5% for any STH species, 9.47% for Ascaris lumbricoides, 1.78% for Trichuris trichiura, and 7.24% for hookworm. Intestinal schistosomiasis (Schistosoma mansoni) infection prevalence was 0.85% by Kato Katz, 21.6% by POC-CCA trace positive (Tr +), and 13.3% trace negative (Tr-). Microhaematuria was 2.77%, with 0.13% of people examined with S. haematobium eggs detected by urine filtration. At the household level, increased (> 30 min) time taken to collect drinking water, sharing a latrine, and lack of handwashing facilities were all associated with a greater risk of A. lumbricoides, hookworm, and S. mansoni infection. Not disposing of infant stool at the household and clothes washing/recreational freshwater contact were significantly associated with higher risk of schistosomiasis infection. Aggregating WaSH data at the community level showed odds of A. lumbricoides, hookworm, and T. trichiura infection were significantly lower as both community sanitation coverage and access to improved drinking water improved.
CONCLUSIONS
The principal finding of this study is that lack of access to WaSH, such as improved drinking water and shared toilet and hand-washing facilities, were linked to an increased risk of infection with STH and schistosome parasites. These associations are difficult to establish at an individual household level because of wide variability in access between houses but are detectable when coverage is aggregated at the community level. Maintenance of WaSH facilities as well as increased access within the whole community is important in influencing the community-wide prevalence of infection with STH and schistosome parasites.
Topics: Infant; Animals; Humans; Sanitation; Soil; Prevalence; Cross-Sectional Studies; Drinking Water; Ethiopia; Hygiene; Helminths; Hookworm Infections; Ancylostomatoidea; Schistosoma mansoni; Feces; Schistosomatidae; Helminthiasis
PubMed: 36333779
DOI: 10.1186/s13071-022-05465-7 -
Microbes and Infection Dec 2012Hookworm disease from Necator americanus and Ancylostoma duodenale affects approximately 700 million people, with N. americanus being the predominant species. Unlike... (Review)
Review
Hookworm disease from Necator americanus and Ancylostoma duodenale affects approximately 700 million people, with N. americanus being the predominant species. Unlike other pathogens (e.g., bacterial infections), where "virulence" is described in regards to acute pathogenesis and case-fatality, hookworms are well-evolved, multicellular parasites that establish long-term infections in their human hosts with a subtle and chronic, but insidious, pathogenesis, usually in the form of iron deficiency anemia from parasite blood feeding that, over time, has devastating effects on the human host especially when it involves children or women of child bearing years. As such, many of the typical terms for "virulence factors" used in other reviews in this special edition cannot be applied to hookworm (e.g., "colonization", "invasion", "or "toxicity"); rather the virulence of hookworm infection comes in terms of their ability to maintain a chronic blood-feeding infection in the lumen of relatively healthy human hosts, an infection that is usually measured in years but can sometimes be measured in decades. In the current manuscript, we describe the routes of invasion hookworms take into their human hosts and the means by which they modulate the human immune system to maintain this long-term parasitism. Little data on hookworm infection comes from actual human infections; instead, much of the data is derived from observations of laboratory animal models, in which hookworms fail to establish this distinctive "chronic infection," either due to physiological or immunological responses of these animal models. Hence, the mode and effects of chronic immunity must be extrapolated from this very different sort of infection to humans. Herein, we aim to synthesize immunological information from both types of models in the context of immune regulation and protection in order to identify future research focuses for the development of new treatment alternatives (i.e. drugs and vaccines).
Topics: Ancylostomatoidea; Animals; Hookworm Infections; Host-Parasite Interactions; Humans; Virulence Factors
PubMed: 23006854
DOI: 10.1016/j.micinf.2012.09.002