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BMC Infectious Diseases Apr 2021Malaria and helminths diseases are co-endemic in most parts of sub-Saharan Africa. Immune responses from each of these pathogens interact, and these interactions may...
BACKGROUND
Malaria and helminths diseases are co-endemic in most parts of sub-Saharan Africa. Immune responses from each of these pathogens interact, and these interactions may have implications on vaccines. The GMZ2 malaria vaccine candidate is a fusion protein of Plasmodium falciparum merozoite surface protein 3 (MSP3) and glutamate rich protein (GLURP R0). GMZ2 has recently showed modest efficacy in a phase IIb multicenter trial. Here, we assessed the effect of hookworm (Necator americanus) infection and anthelmintic treatment on naturally acquired antibody responses against GMZ2 and constituent antigens.
METHODS
This longitudinal cross-sectional study was conducted in the Kintampo North Municipality of Ghana. Blood and stool samples were taken from 158 individuals (4-88 years old) infected with either P. falciparum alone (n = 59) or both hookworm and P. falciparum (n = 63) and uninfected endemic controls (n = 36). Stool hookworm infection was detected by the Kato-Katz method and PCR. Malaria parasitaemia was detected by RDT, light microscopy and P. falciparum-specific 18S rRNA gene PCR. Serum samples were obtained prior to hookworm treatment with a single dose of albendazole (400 mg) and 3 weeks (21 days) after treatment. Levels of IgG1, IgG3 and IgM against GMZ2, MSP3 and GLURP R0 were measured by ELISA and compared among the groups, before and after treatment.
RESULTS
Participants with P. falciparum and hookworm co-infection had significantly higher IgG3 levels to GMZ2 than those with only P. falciparum infection and negative control (p < 0.05) at baseline. Treatment with albendazole led to a significant reduction in IgG3 levels against both GMZ2 and GLURP R0. Similarly, IgM and IgG1 levels against MSP3 also decreased following deworming treatment.
CONCLUSION
Individuals with co-infection had higher antibody responses to GMZ2 antigen. Treatment of hookworm/malaria co-infection resulted in a reduction in antibody responses against GMZ2 and constituent antigens after albendazole treatment. Thus, hookworm infection and treatment could have a potential implication on malaria vaccine efficacy.
Topics: Adolescent; Adult; Aged; Aged, 80 and over; Albendazole; Anthelmintics; Antibodies, Protozoan; Antigens, Protozoan; Case-Control Studies; Child; Child, Preschool; Cross-Sectional Studies; Female; Hookworm Infections; Humans; Immunoglobulin G; Longitudinal Studies; Malaria Vaccines; Malaria, Falciparum; Male; Middle Aged; Parasitemia; Protozoan Proteins; Young Adult
PubMed: 33832450
DOI: 10.1186/s12879-021-06027-5 -
BMC Pregnancy and Childbirth Aug 2020Hookworm infection is a major public health problem in developing countries. The main way people become infected with hookworm's larva is through direct skin contact...
Prevalence of hookworm infection and associated factors among pregnant women attending antenatal care at governmental health centers in DEMBECHA district, north West Ethiopia, 2017.
BACKGROUND
Hookworm infection is a major public health problem in developing countries. The main way people become infected with hookworm's larva is through direct skin contact with contaminated soil when walking on barefoot. It is one of a major cause of anemia in pregnant women. The objective was to assess the prevalence and associated factors of hookworm infection among pregnant women who attended antenatal care at governmental health centers in Dembecha district, Ethiopia, 2017.
METHODS
Institutional based cross sectional study was conducted on 306 pregnant women. Study participants were selected by systematic random sampling technique from February 1 to March 30, 2017. Data collectors and supervisors were trained. Semi-structured Amharic version questionnaire was used to collect data using face to face interview technique and stool sample was examined. Collected data were entered by using Epi data version 3.1 and exported to SPSS. The exported data was analyzed and presented by using descriptive summary statistics and tables. After bivariate logistic regression analysis, all variables with a p-value < 0.25 were entered into multivariate logistic regression and p value < 0.05 considered as significantly associated with the outcome variable.
RESULTS
Prevalence of hookworm infection was 32.0%. There was a positive association of hookworm infection with living in single room [AOR =2.8; 95% CI; 1.32-5.81], living with domestic animals [AOR = 3.4; 95% CI; 1.35-8.76], monthly income ≤1500 Ethiopian birr [AOR = 3.7; 95% CI; 1.76-7.64], unavailability of latrine [AOR = 2.2; 95% CI; 1.03-4.55], habit of walking on barefoot [AOR = 4.3; 95% CI; 2.17-8.48] and not habit of hand washing before meal [AOR = 3.4; 95 CI; 1.14-10.12].
CONCLUSION
This study showed high prevalence of hookworm infection among pregnant women in the study area. Living in single room, living with domestic animals, monthly income ≤1500 Ethiopian birr, unavailability of latrine, habit of walking on barefoot and not habit of hand washing before meal had positive association with hookworm infection. Public health measure should focus on availability latrine and separation of humans and domestic animals room to decrease prevalence of hookworm infection among pregnant women.
Topics: Adolescent; Adult; Cross-Sectional Studies; Ethiopia; Female; Health Facilities; Hookworm Infections; Humans; Pregnancy; Pregnancy Complications, Parasitic; Prenatal Care; Prevalence; Public Facilities; Risk Factors; Young Adult
PubMed: 32787866
DOI: 10.1186/s12884-020-03134-0 -
Human Vaccines Nov 2011The human hookworms Necator americanus and Ancylostoma duodenale remain among the most common infections of humans in areas of rural poverty in the developing regions of... (Review)
Review
The human hookworms Necator americanus and Ancylostoma duodenale remain among the most common infections of humans in areas of rural poverty in the developing regions of the world, with an estimated 1 billion people infected with one or more of these parasites. Herein, we review the nearly 100 years of research, development, animal testing, and fieldwork that have led to our current progress in recombinant hookworm vaccines. We begin with the identification of hookworm at the start of the 20th century in Southern US, then discuss the progress in developed countries to eliminate human hookworm infection, and then the industrial development and field use in the 1970s a canine hookworm vaccine(Ancylostoma caninum), and finally our progress to date in the development and clinical testing of an array of recombinant antigens to prevent human hookworm disease from N. americanus infection. Special attention is given to the challenges faced in the development of a vaccine against a blood-feeding nematode, including the epidemiology of infection (high prevalence of infection), pathogenesis (chronic infection that increases with the age of the host), and a robust immune response that fails to confer the protection in the host and a concomitant absence of correlates of protection by a successful vaccine could be developed and tested. Finally, we provide the optimal and acceptable profiles of a human hookworm vaccine, including the proposed indication, target population, and route of administration, as developed by the Human Hookworm Vaccine Initiative, the only group currently working on vaccines targeting this parasite.
Topics: Ancylostoma; Ancylostomatoidea; Ancylostomiasis; Animals; Antigens, Helminth; Dog Diseases; Dogs; Humans; Necator americanus; Necatoriasis; Vaccines, Synthetic
PubMed: 22064562
DOI: 10.4161/hv.7.11.18443 -
PLoS Neglected Tropical Diseases 2015The association of anaemia with intestinal schistosomiasis and hookworm infections are poorly explored in populations that are not limited to children or pregnant women.
BACKGROUND
The association of anaemia with intestinal schistosomiasis and hookworm infections are poorly explored in populations that are not limited to children or pregnant women.
METHODS
We sampled 1,832 individuals aged 5-90 years from 30 communities in Mayuge District, Uganda. Demographic, village, and parasitological data were collected. Infection risk factors were compared in ordinal logistic regressions. Anaemia and infection intensities were analyzed in multilevel models, and population attributable fractions were estimated.
FINDINGS
Household and village-level predictors of Schistosoma mansoni and hookworm were opposite in direction or significant for single infections. S. mansoni was found primarily in children, whereas hookworm was prevalent amongst the elderly. Anaemia was more prevalent in individuals with S. mansoni and increased by 2.86 fold (p-value<0.001) with heavy S. mansoni infection intensity. Individuals with heavy hookworm were 1.65 times (p-value = 0.008) more likely to have anaemia than uninfected participants. Amongst individuals with heavy S. mansoni infection intensity, 32.0% (p-value<0.001) of anaemia could be attributed to S. mansoni. For people with heavy hookworm infections, 23.7% (p-value = 0.002) of anaemia could be attributed to hookworm. A greater fraction of anaemia (24.9%, p-value = 0.002) was attributable to heavy hookworm infections in adults (excluding pregnant women) as opposed to heavy hookworm infections in school-aged children and pregnant women (20.2%, p-value = 0.001).
CONCLUSION
Community-based surveys captured anaemia in children and adults affected by S. mansoni and hookworm infections. For areas endemic with schistosomiasis or hookworm infections, WHO guidelines should include adults for treatment in helminth control programmes.
Topics: Adolescent; Adult; Aged; Aged, 80 and over; Anemia; Animals; Child; Child, Preschool; Female; Hookworm Infections; Humans; Male; Middle Aged; Pregnancy; Risk Factors; Rural Population; Schistosomiasis mansoni; Uganda; Young Adult
PubMed: 26513151
DOI: 10.1371/journal.pntd.0004193 -
Tropical Medicine & International... Jul 2010To summarise age- and intensity-stratified associations between human hookworm infection and anaemia and to quantify the impact of treatment with the benzimidazoles,... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVES
To summarise age- and intensity-stratified associations between human hookworm infection and anaemia and to quantify the impact of treatment with the benzimidazoles, albendazole and mebendazole, on haemoglobin and anaemia in non-pregnant populations.
METHODS
Electronic databases (MEDLINE, EMBASE, PubMed) were searched for relevant studies published between 1980 and 2009, regardless of language, and researchers contacted about potential data. Haemoglobin concentration (Hb) was compared between uninfected individuals and individuals harbouring hookworm infections of different intensities, expressed as standardised mean differences (SMD) and 95% confidence intervals (CI). Meta-analysis of randomised control trials (RCTs) investigated the impact of treatment on Hb and anaemia.
RESULTS
Twenty-three cross-sectional studies, six pre- and post-intervention studies and 14 trials were included. Among cross-sectional studies, moderate- and heavy-intensity hookworm infections were associated with lower Hb in school-aged children, while all levels of infection intensity were associated with lower Hb in adults. Among RCTs using albendazole, impact of treatment corresponded to a 1.89 g/l increase (95%CI: 0.13-3.63) in mean Hb while mebendazole had no impact. There was a positive impact of 2.37 g/l (95%CI: 1.33-3.50) on mean Hb when albendazole was co-administered with praziquantel, but no apparent additional benefit of treatment with benzimidazoles combined with iron supplementation. The mean impact of treatment with benzimidazoles alone on moderate anaemia was small (relative risk (RR) 0.87) with a larger effect when combined with praziquantel (RR 0.61).
CONCLUSIONS
Anaemia is most strongly associated with moderate and heavy hookworm infection. The impact of anthelmintic treatment is greatest when albendazole is co-administered with praziquantel.
Topics: Adolescent; Adult; Aged; Albendazole; Anemia; Anthelmintics; Child; Child, Preschool; Female; Hemoglobins; Hookworm Infections; Humans; Infant; Mebendazole; Middle Aged; Praziquantel; Pregnancy; Research Design
PubMed: 20500563
DOI: 10.1111/j.1365-3156.2010.02542.x -
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 -
Nature Communications Jul 2023The reduced prevalence of insulin resistance and type 2 diabetes in countries with endemic parasitic worm infections suggests a protective role for worms against... (Randomized Controlled Trial)
Randomized Controlled Trial
The reduced prevalence of insulin resistance and type 2 diabetes in countries with endemic parasitic worm infections suggests a protective role for worms against metabolic disorders, however clinical evidence has been non-existent. This 2-year randomised, double-blinded clinical trial in Australia of hookworm infection in 40 male and female adults at risk of type 2 diabetes assessed the safety and potential metabolic benefits of treatment with either 20 (n = 14) or 40 (n = 13) Necator americanus larvae (L3) or Placebo (n = 13) (Registration ACTRN12617000818336). Primary outcome was safety defined by adverse events and completion rate. Homoeostatic model assessment of insulin resistance, fasting blood glucose and body mass were key secondary outcomes. Adverse events were more frequent in hookworm-treated participants, where 44% experienced expected gastrointestinal symptoms, but completion rates were comparable to Placebo. Fasting glucose and insulin resistance were lowered in both hookworm-treated groups at 1 year, and body mass was reduced after L3-20 treatment at 2 years. This study suggests hookworm infection is safe in people at risk of type 2 diabetes and associated with improved insulin resistance, warranting further exploration of the benefits of hookworms on metabolic health.
Topics: Animals; Male; Female; Diabetes Mellitus, Type 2; Insulin Resistance; Hookworm Infections; Necator americanus; Fasting
PubMed: 37495576
DOI: 10.1038/s41467-023-40263-4 -
Antimicrobial Agents and Chemotherapy Jan 2021Tribendimidine has been successful in treating hookworm infections and may serve as an alternative to albendazole should resistance arise. Our aims were to (i)...
Tribendimidine has been successful in treating hookworm infections and may serve as an alternative to albendazole should resistance arise. Our aims were to (i) characterize the pharmacokinetics (PK) of tribendimidine's primary metabolite, deacetylated amidantel (dADT), and secondary metabolite, acetylated derivative of amidantel (adADT), in school-aged children and adolescents, (ii) link exposure to efficacy against hookworm, and (iii) evaluate whether tribendimidine pharmacotherapy in children could be further improved. First, a population PK model was developed based on dried-blood-spot samples collected from 155 school-aged children and adolescents with hookworm infections, following tribendimidine doses ranging from 100 to 400 mg. Second, an exposure-response analysis was conducted to link the active metabolite dADT to cure rates (CRs) and egg reduction rates (ERRs). Third, simulations were performed to identify a treatment strategy associated with >90% CRs. A two-compartmental model with transit compartments describing observed delay in absorption adequately described PK data of dADT and adADT. Allometric scaling was included to account for growth and development. The absorption rate was 56% lower with 200-mg tablets than with 50-mg tablets, while the extent of absorption remained unaffected. The identified models linking dADT exposure to ERRs and CRs showed shallow curves, as increasing exposure led to marginal efficacy increase. Combination therapy should be considered, as a 12-fold-higher dose would be needed to achieve 95% ERRs and CRs >90% with tribendimidine alone. Further studies are warranted to evaluate safety of higher tribendimidine doses and combination therapies with other anthelmintic agents to improve treatment strategy for children with hookworm infection.
Topics: Adolescent; Albendazole; Ancylostomatoidea; Animals; Anthelmintics; Child; Hookworm Infections; Humans; Phenylenediamines; Treatment Outcome
PubMed: 33139293
DOI: 10.1128/AAC.01778-20 -
The Lancet. Microbe Jan 2022The global distribution and morbidity effects for each specific hookworm species is unknown, which prevents implementation of the optimum intervention for local hookworm... (Review)
Review
The global distribution and morbidity effects for each specific hookworm species is unknown, which prevents implementation of the optimum intervention for local hookworm control. We did two systematic reviews of studies on the proportion of hookworm isolates of each species and genus by region of the world and associations between hookworm species-specific infections and morbidity outcomes, particularly severe anaemia. Necator americanus and Ancylostoma spp were present in all regions of the world, although at different ratios. No clear evidence was found for the differential morbidity effects of different hookworm species. Diagnostic methods that differentiate between hookworm species, including molecular methods, need to be developed for widespread use in control programmes to elucidate key features of hookworm epidemiology and control.
Topics: Ancylostoma; Ancylostomatoidea; Animals; Feces; Hookworm Infections; Humans; Morbidity
PubMed: 35544117
DOI: 10.1016/S2666-5247(21)00181-6 -
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