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Parasite Immunology Feb 2021Hookworm infection is considered the most prevalent human soil-transmitted helminth infection affecting approximately 500 million people and accounting for 3.2 million... (Review)
Review
Hookworm infection is considered the most prevalent human soil-transmitted helminth infection affecting approximately 500 million people and accounting for 3.2 million disability-adjusted life years lost annually. As with many other neglected tropical diseases, no international surveillance mechanisms that show accurate data on the prevalence of hookworm infection are in place, thus hindering strategies to control parasite transmission. In this review, we unravel the current knowledge in immunopathology and immunoregulation of hookworm infection and present discoveries in drug therapies based on the capability of hookworms to regulate inflammation to treat allergic, inflammatory and metabolic diseases. Additionally, we highlight potential vaccine development and treatments and propose avenues for further inquiry.
Topics: Ancylostomatoidea; Animals; Antibodies, Helminth; Hookworm Infections; Host-Parasite Interactions; Humans; Immunity, Cellular; Immunomodulation; Male; Prevalence; Soil; Vaccines
PubMed: 33012113
DOI: 10.1111/pim.12798 -
BMJ (Clinical Research Ed.) Oct 2017
Topics: Alabama; Ancylostomatoidea; Animals; Disease Outbreaks; Dogs; Hookworm Infections; Humans; Neglected Diseases
PubMed: 29066626
DOI: 10.1136/bmj.j4813 -
Pediatrics in Review Aug 2015• On the basis of research evidence, worm infections are important global child health conditions causing chronic disability that lasts from childhood into adulthood... (Review)
Review
• On the basis of research evidence, worm infections are important global child health conditions causing chronic disability that lasts from childhood into adulthood (Table 1). (2)(3) Evidence Quality: B • On the basis of research evidence, the major worm infections found in developing countries include ascariasis, trichuriasis, hookworm infection, and schistosomiasis; toxocariasis, enterobiasis, and cysticercosis are also found in poor regions of North America and Europe. (4)(9)(13) Evidence Quality: B • On the basis of expert consensus, children and adolescents are often vulnerable to acquiring large numbers of worms, ie, high-intensity infections (Fig 1)(21)(22)(23) Evidence Quality: D • On the basis of expert consensus and research evidence, moderate and heavy worm burdens cause increased morbidity because of growth and intellectual stunting in children and adolescents. Many of these effects may result from helminth-induced malnutrition. (21)(22)(23) Evidence Quality: C • On the basis of expert consensus and research evidence, worm infections are also commonly associated with eosinophilia. (48) (49) Evidence Quality: B • On the basis of research evidence as well as consensus, helminthes can cause inflammation in the lung (asthma), gastrointestinal tract (enteritis and colitis), liver (hepatitis and fibrosis), and urogenital tract. (7)(21)(22)(23)(27)(28)(40)(41)(43) Evidence Quality: B • On the basis of research evidence, microscopy techniques for diagnosis of worm infections in children often exhibit suboptimal sensitivities and specificities, necessitating new or improved diagnostic modalities such as polymerase chain reaction. (54)(55) Evidence Quality: A • On the basis of research evidence and expert consensus, mass drug administration (“preventive chemotherapy”) has becomea standard practice for ministries of health in low- and middle-income countries to control intestinal helminth infections and schistosomiasis. (67)(68) Evidence Quality: B.
Topics: Ascariasis; Child; Cost of Illness; Developing Countries; Endemic Diseases; Enterobiasis; Hookworm Infections; Humans; Trichuriasis; United States
PubMed: 26232464
DOI: 10.1542/pir.36-8-341 -
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 -
The American Journal of Tropical... May 2018
Topics: Albendazole; Ancylostomatoidea; Animals; Double-Blind Method; Farmers; Female; Hookworm Infections; Humans; Power, Psychological
PubMed: 29611502
DOI: 10.4269/ajtmh.17-0934 -
QJM : Monthly Journal of the... Aug 2020
Topics: Abdominal Pain; Adult; Animals; Duodenum; Endoscopy, Digestive System; Female; Hookworm Infections; Humans
PubMed: 31665521
DOI: 10.1093/qjmed/hcz276 -
Expert Review of Vaccines Nov 2021
Topics: Ancylostomatoidea; Animals; Hookworm Infections; Humans; Schistosomiasis; Vaccines
PubMed: 34225549
DOI: 10.1080/14760584.2021.1951244 -
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 -
Frontiers in Immunology 2022Helminth infection-driven changes to immunity in the female reproductive tract (FRT) is an immune axis that is currently understudied but can have major implications for...
Helminth infection-driven changes to immunity in the female reproductive tract (FRT) is an immune axis that is currently understudied but can have major implications for the control of FRT infections. Here we address how human hookworm infection associates with vaginal immune profile and risk of Human papillomavirus (HPV) infection. Stool, blood, cervical swabs and vaginal flushes were collected from women from the Central region of Togo to screen for hookworms ( and high carcinogenic risk HPV types, Kato Katz and PCR, respectively. Cytokine, chemokine and immunoglobulin levels were analysed in cervicovaginal lavages and plasma samples. A pronounced mixed Type 1/Type 2 immune response was detected in the vaginal fluids of women with hookworm infection and this immune signature was a notable feature in hookworm-HPV co-infected women. Moreover, hookworm infection is positively associated with increased risk and load of HPV infection. These findings highlight helminth infection as a significant risk factor for acquiring a sexually transmitted viral infection and potentially raising the risk of subsequent pathology.
Topics: Animals; Female; Humans; Papillomavirus Infections; Hookworm Infections; Vagina; Ancylostomatoidea; Reproductive Tract Infections; Helminthiasis
PubMed: 36330509
DOI: 10.3389/fimmu.2022.1009968