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The New England Journal of Medicine Aug 2004
Review
Topics: Adolescent; Adult; Aged; Ancylostoma; Animals; Anthelmintics; Benzimidazoles; Child; Child, Preschool; Cost of Illness; Emigration and Immigration; Female; Hookworm Infections; Humans; Infant; Larva Migrans; Life Cycle Stages; Male; Middle Aged; Necator; Schools; Travel
PubMed: 15317893
DOI: 10.1056/NEJMra032492 -
Impact of hookworm infection and preventive chemotherapy on haemoglobin in non-pregnant populations.Tropical Medicine & International... Dec 2021To assess the impact of hookworm infection and preventive chemotherapy on haemoglobin levels in non-pregnant populations in endemic areas. (Meta-Analysis)
Meta-Analysis
OBJECTIVE
To assess the impact of hookworm infection and preventive chemotherapy on haemoglobin levels in non-pregnant populations in endemic areas.
METHOD
Systematic review and meta-analysis searching PubMed and Web of Science for articles published since 2010 reporting either hookworm prevalence and Hb concentration (cross-sectional studies) or Hb concentration before and after the implementation of preventive chemotherapy (before-after studies and randomised controlled trials [RCTs]). For papers published before 2010, data were extracted from a previously published systematic review. Random effects meta-analyses were conducted to examine the relationship between Hb concentration and hookworm infection intensity (from cross-sectional studies) and the effect of preventive chemotherapy on Hb concentration (from before-after studies and RCTs). Sensitivity analyses investigated the impact of malaria endemicity and combined interventions for schistosomiasis and nutrition status on Hb concentration.
RESULTS
Among cross-sectional studies, both light- and heavy-intensity hookworm infections were associated with lower Hb in school-aged children. School-aged children with heavy hookworm infection in settings of high malaria endemicity had lower mean Hb than those in settings of low malaria endemicity. In non-pregnant populations, deworming with albendazole was associated with an increase in Hb of 3.02 g/L (95% CI 0.1, 6.0 g/L). No additional benefit was seen with deworming using albendazole co-administered with praziquantel for schistosomiasis infection or iron supplementation for nutrition status.
CONCLUSION
Our findings confirm the benefits of preventive chemotherapy as a public health intervention.
Topics: Anemia; Anthelmintics; Controlled Before-After Studies; Cross-Sectional Studies; Hemoglobins; Hookworm Infections; Humans; Randomized Controlled Trials as Topic
PubMed: 34587315
DOI: 10.1111/tmi.13681 -
PLoS Neglected Tropical Diseases Dec 2021In 1896, a serendipitous laboratory accident led to the understanding that hookworms propagate infection by penetrating skin, a theory that was then confirmed with the... (Review)
Review
In 1896, a serendipitous laboratory accident led to the understanding that hookworms propagate infection by penetrating skin, a theory that was then confirmed with the first experimental human infection, reported in 1901. Experimental human infections undertaken in the 20th century enabled understanding of the natural history of infection and the immune response. More recently, experimental hookworm infection has been performed to investigate the immunomodulatory potential of hookworm infection and for the evaluation of hookworm vaccines and chemotherapeutic interventions. Experimental human hookworm infection has been proven to be safe, with no deaths observed in over 500 participants (although early reports predate systematic adverse event reporting) and no serious adverse events described in over 200 participants enrolled in contemporary clinical trials. While experimental human hookworm infection holds significant promise, as both a challenge model for testing anti-hookworm therapies and for treating various diseases of modernity, there are many challenges that present. These challenges include preparation and storage of larvae, which has not significantly changed since Harada and Mori first described their coproculture method in 1955. In vitro methods of hookworm larval culture, storage, and the development of meaningful potency or release assays are required. Surrogate markers of intestinal infection intensity are required because faecal egg counts or hookworm faecal DNA intensity lack the fidelity required for exploration of hookworm infection as a vaccine/drug testing platform or as a regulated therapy.
Topics: Ancylostomatoidea; Animals; Antigens, Helminth; Feces; Female; History, 19th Century; History, 20th Century; History, 21st Century; Hookworm Infections; Human Experimentation; Humans; Research; Vaccines
PubMed: 34882670
DOI: 10.1371/journal.pntd.0009908 -
Acta Tropica Jan 2020Human hookworm, a soil-transmitted helminth (STH) infection caused by either Necator americanus or Anclystoma duodenale, is a major cause of morbidity globally and... (Review)
Review
Human hookworm, a soil-transmitted helminth (STH) infection caused by either Necator americanus or Anclystoma duodenale, is a major cause of morbidity globally and predominantly affects the world's poorest populations. Transmitted primarily by larval invasion of exposed skin, the adults inhabit the host small intestine, where they consume host blood. The resultant chronic iron deficiency anemia can lead to stunted growth and cognitive deficits in children, reduced work capacity in adults, and a variety of pregnancy complications. Historically, successful STH elimination has only been achieved in regions with concomitant significant economic growth. Since 2001, control of the STHs has been attempted via single-dose mass deworming of at-risk school-aged and preschool-aged children within STH-endemic countries, with the goal of morbidity reduction. Research questioning this strategy has grown in recent years, and current studies are evaluating the effectiveness of novel deworming strategies, including multidrug regimens and expansion of deworming to entire communities. While footwear campaigns may be associated with reduced odds of hookworm infection, the evidence supporting the impact of water, sanitation, and hygiene (WASH) interventions upon hookworm is mixed. Progress towards a human hookworm vaccine continues, with promising results from recent Phase 1 trials and several others ongoing. Integrated STH control programs, which combine mass deworming with WASH interventions, are relatively unstudied but may be a promising advancement. Whether interruption of STH transmission can be achieved apart from significant economic growth remains unanswered, but likely the implementation of intensive, integrated control programs will be necessary to achieve that goal.
Topics: Animals; Disease Eradication; Forecasting; Helminthiasis; Hookworm Infections; Humans; Sanitation
PubMed: 31600519
DOI: 10.1016/j.actatropica.2019.105214 -
Vaccine Oct 2022The Necator americanus hemoglobinase, aspartic protease-1 (Na-APR-1), facilitates the ability of adult hookworms to parasitize the intestine of their human hosts. A...
BACKGROUND
The Necator americanus hemoglobinase, aspartic protease-1 (Na-APR-1), facilitates the ability of adult hookworms to parasitize the intestine of their human hosts. A recombinant version of APR-1 protected laboratory animals against hookworm infection by inducing neutralizing antibodies that block the protein's enzymatic activity and thereby impair blood feeding. A catalytically inactive version of the wild-type hemoglobinase (Na-APR-1(M74)) was expressed by infiltrating Nicotiana benthamiana tobacco plants with an Agrobacterium tumefaciens strain engineered to express the vaccine antigen, which was adjuvanted with aluminum hydroxide adjuvant (Alhydrogel).
METHODS
An open-label dose-escalation Phase 1 clinical trial was conducted in 40 healthy, hookworm-naïve adult volunteers in the United States. Participants received 30 or 100 µg of recombinant Na-APR-1(M74) with Alhydrogel or with Alhydrogel co-administered with one of two doses (2.5 or 5.0 µg) of an aqueous formulation of Glucopyranosyl Lipid A (GLA-AF). Intramuscular injections of study vaccine were administered on days 0, 56, and 112.
RESULTS
Na-APR-1(M74)/Alhydrogel was well-tolerated; the most frequent adverse events were mild or moderate injection site tenderness and pain, and mild or moderate nausea and headache. No serious adverse events or adverse events of special interest related to vaccination were observed. Significantly higher levels of antigen-specific IgG antibodies were induced in those who received 100 µg Na-APR-1(M74) than those who received 30 µg of antigen. Adding GLA-AF to Na-APR-1(M74)/Alhydrogel resulted in higher levels of IgG against Na-APR-1(M74) in both the 30 and 100 µg Na-APR-1(M74) groups in comparison to the non-GLA formulations at the same antigen dose.
CONCLUSIONS
Vaccination of hookworm-naïve adults with recombinant Na-APR-1(M74) was well-tolerated, safe, and induced significant IgG responses against the vaccine antigen Na-APR-1(M74). Given these favorable results, clinical trials of this product were initiated in hookworm-endemic areas of Gabon and Brazil.
Topics: Adjuvants, Immunologic; Adult; Aluminum Hydroxide; Ancylostomatoidea; Animals; Antibodies, Neutralizing; Hookworm Infections; Humans; Immunogenicity, Vaccine; Immunoglobulin G; Lipid A; Peptide Hydrolases; Nicotiana; Vaccines
PubMed: 36114129
DOI: 10.1016/j.vaccine.2022.09.017 -
Vaccine Apr 2013Hookworm infection is one of the world's most common neglected tropical diseases and a leading cause of iron deficiency anemia in low- and middle-income countries. A... (Review)
Review
Hookworm infection is one of the world's most common neglected tropical diseases and a leading cause of iron deficiency anemia in low- and middle-income countries. A Human Hookworm Vaccine is currently being developed by the Sabin Vaccine Institute and is in phase 1 clinical testing. The candidate vaccine is comprised of two recombinant antigens known as Na-GST-1 and Na-APR-1, each of which is an important parasite enzyme required for hookworms to successfully utilize host blood as a source of energy. The recombinant proteins are formulated on Alhydrogel(®) and are being tested in combination with a synthetic Toll-like receptor 4 agonist. The aim of the vaccine is to induce anti-enzyme antibodies that will reduce both host blood loss and the number of hookworms attached to the gut. Transfer of the manufacturing technology to the Oswaldo Cruz Foundation (FIOCRUZ)/Bio-Manguinhos (a Brazilian public sector developing country vaccine manufacturer) is planned, with a clinical development plan that could lead to registration of the vaccine in Brazil. The vaccine would also need to be introduced in the poorest regions of Africa and Asia, where hookworm infection is highly endemic. Ultimately, the vaccine could become an essential tool for achieving hookworm control and elimination, a key target in the 2012 London Declaration on Neglected Tropical Diseases.
Topics: Academies and Institutes; Ancylostomatoidea; Animals; Antigens, Helminth; Biomedical Research; Clinical Trials, Phase I as Topic; Global Health; Hookworm Infections; Humans; Public Sector; Public-Private Sector Partnerships; Recombinant Proteins; Technology Transfer; Toll-Like Receptor 4; Vaccines
PubMed: 23598487
DOI: 10.1016/j.vaccine.2012.11.034 -
PLoS Neglected Tropical Diseases Jun 2022Hookworm disease is endemic in China and is widespread globally. The disease burden to humans is great.
BACKGROUND
Hookworm disease is endemic in China and is widespread globally. The disease burden to humans is great.
METHODS
The study described the national surveillance of hookworm implemented in 31 provinces/autonomous regions/municipalities (P/A/Ms) of China in 2019. Each P/A/M determined the number and location of surveillance spots (counties). A unified sampling method was employed, and at least 1000 subjects were investigated in each surveillance spot. The modified Kato-Katz thick smear method was employed for stool examination. Fifty samples positive with hookworm eggs were cultured in each surveillance spot to discriminate species between A. duodenale and N. americanus. Twenty-five soil samples were collected from each surveillance spot and examined for hookworm larva. The 2019 surveillance results were analyzed and compared with that of 2016-2018.
RESULTS
A total of 424766 subjects were investigated in 31 P/A/Ms of China in 2019, and the overall hookworm infection rate was 0.85% (3580/424766). The weighted infection and standard infection rates were 0.66% (4288357/648063870) and 0.67% (4343844/648063870), respectively. Sichuan province had the highest standard infection rate (4.75%) in 2019, followed by Chongqing (2.54%) and Hainan (2.44%). The standard infection rates of other P/A/Ms were all below 1%, with no hookworm detected in 15 P/A/Ms. The standard hookworm infection rate in the males and the females were 0.61% (2021216/330728900) and 0.71% (2267141/317334970), respectively, with a significant difference between different genders ([Formula: see text] = 17.23, P<0.0001). The highest standard hookworm infection rate (1.97%) was among age ≥ 60 years, followed by 45~59 years (0.77%), 15~44 years (0.37%), and 7~14 years (0.20%). The lowest standard infection rate was among the 0~6 years age group (0.12%). A significant difference was observed among different age groups ([Formula: see text] = 2 305.17, P<0.0001). The constitute ratio for N. americanus, A. duodenale, and coinfection was 78.70% (1341/1704), 2.03% (346/1704), and 1.00% (17/1704), respectively. The detection rate of hookworm larva from soil was 3.45% (71/2056).
CONCLUSION
The national surveillance showed that the hookworm infection rate has been decreasing annually from 2016 to 2019, and it is now below 1%. China has made significant progress in controlling hookworm. The national surveillance system is an important way to understand the endemic status and provide important information in this process and thus needs to be continually optimized.
Topics: Ancylostomatoidea; Animals; China; Feces; Female; Hookworm Infections; Humans; Male; Middle Aged; Prevalence; Soil
PubMed: 35679319
DOI: 10.1371/journal.pntd.0010405 -
Parasites & Vectors Mar 2020Hookworm infection is a major public health problem that threatens about 500 million people throughout tropical areas of the world. Adult hookworms survive for many... (Review)
Review
Hookworm infection is a major public health problem that threatens about 500 million people throughout tropical areas of the world. Adult hookworms survive for many years in the host intestine, where they suck blood, causing iron deficiency anemia and malnutrition. Numerous molecules, named excretory/secretory (ES) products, are secreted by hookworm adults and/or larvae to aid in parasite survival and pathobiology. Although the molecular cloning and characterization of hookworm ES products began 25 years ago, the biological role and molecular nature of many of them are still unclear. Hookworm ES products, with distinct structures and functions, have been linked to many essential events in the disease pathogenesis. These events include host invasion and tissue migration, parasite nourishment and reproduction, and immune modulation. Several of these products represent promising vaccine targets for controlling hookworm disease and therapeutic targets for many inflammatory diseases. This review aims to summarize our present knowledge about hookworm ES products, including their role in parasite biology, host-parasite interactions, and as vaccine and pharmaceutical targets and to identify research gaps and future research directions in this field.
Topics: Ancylostoma; Ancylostomatoidea; Animals; Antioxidants; Body Fluids; Cloning, Molecular; Female; Helminth Proteins; Hookworm Infections; Host-Parasite Interactions; Humans; Immunologic Factors; Male; Peptide Hydrolases; Protease Inhibitors; Vaccines
PubMed: 32171305
DOI: 10.1186/s13071-020-04010-8 -
Transactions of the Royal Society of... Aug 2022A large number of studies have assessed risk factors for infection with soil-transmitted helminths (STH), but few have investigated the interactions between the...
BACKGROUND
A large number of studies have assessed risk factors for infection with soil-transmitted helminths (STH), but few have investigated the interactions between the different parasites or compared these between host species across hosts. Here, we assessed the associations between Ascaris, Trichuris, hookworm, strongyle and Toxocara infections in the Philippines in human and animal hosts.
METHODS
Faecal samples were collected from humans and animals (dogs, cats and pigs) in 252 households from four villages in southern Philippines and intestinal helminth infections were assessed by microscopy. Associations between worm species were assessed using multiple logistic regression.
RESULTS
Ascaris infections showed a similar prevalence in humans (13.9%) and pigs (13.7%). Hookworm was the most prevalent infection in dogs (48%); the most prevalent infection in pigs was strongyles (42%). The prevalences of hookworm and Toxocara in cats were similar (41%). Statistically significant associations were observed between Ascaris and Trichuris and between Ascaris and hookworm infections in humans, and also between Ascaris and Trichuris infections in pigs. Dual and triple infections were observed, which were more common in dogs, cats and pigs than in humans.
CONCLUSIONS
Associations are likely to exist between STH species in humans and animals, possibly due to shared exposures and transmission routes. Individual factors and behaviours will play a key role in the occurrence of co-infections, which will have effects on disease severity. Moreover, the implications of co-infection for the emergence of zoonoses need to be explored further.
Topics: Ancylostomatoidea; Animals; Ascaris; Cats; Coinfection; Dogs; Feces; Helminthiasis; Helminths; Hookworm Infections; Humans; Intestinal Diseases, Parasitic; Philippines; Prevalence; Soil; Swine; Trematode Infections; Trichuris
PubMed: 35169848
DOI: 10.1093/trstmh/trac002 -
American Journal of Human Biology : the... Mar 2020Despite public health concerns about hookworm infection in pregnancy, little is known about immune profiles associated with hookworm (Necator americanus and Ancylostoma...
OBJECTIVES
Despite public health concerns about hookworm infection in pregnancy, little is known about immune profiles associated with hookworm (Necator americanus and Ancylostoma duodenale) infection during pregnancy. Fetal tolerance requirements may constrain maternal immune response to hookworm, thereby increasing susceptibility to new infections or increasing hemoglobin loss. To explore this possibility, we study systemic immune response and hemoglobin levels in a natural fertility population with endemic helminthic infection.
METHODS
We used Bayesian multilevel models to analyze mixed longitudinal data on hemoglobin, hookworm infection, reproductive state, eosinophils, and erythrocyte sedimentation rate (ESR) to examine the effects of pregnancy and hookworm infection on nonspecific inflammation, cellular parasite response, and hemoglobin among 612 Tsimane women aged 15-45 (1016 observations).
RESULTS
Pregnancy is associated with lower eosinophil counts and lower eosinophil response to hookworm, particularly during the second and third trimesters. Both hookworm and pregnancy are associated with higher ESR, with evidence for an interaction between the two causing further increases in the first trimester. Pregnancy is moderately associated with higher odds of hookworm infection (OR: 1.23, 95% CI: 0.83 to 1.83). Pregnancy and hookworm both decrease hemoglobin and may interact to accentuate this effect in the first-trimester of pregnancy (Interaction: β: -0.30 g/dL; CI: -0.870 to 0.24).
CONCLUSIONS
Our findings are consistent with a possible trade-off between hookworm immunity and successful pregnancy, and with the suggestion that hookworm and pregnancy may have synergistic effects, particularly in the first trimester.
Topics: Adolescent; Adult; Ancylostoma; Ancylostomiasis; Animals; Bolivia; Female; Horticulture; Humans; Indians, South American; Middle Aged; Necator americanus; Necatoriasis; Occupational Diseases; Pregnancy; Prevalence; Young Adult
PubMed: 31642576
DOI: 10.1002/ajhb.23337