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The Lancet. Microbe Dec 2023Vaccine development against hookworm is hampered by the absence of the development of protective immunity in populations repeatedly exposed to hookworm, limiting... (Randomized Controlled Trial)
Randomized Controlled Trial
Protective efficacy of short-term infection with Necator americanus hookworm larvae in healthy volunteers in the Netherlands: a single-centre, placebo-controlled, randomised, controlled, phase 1 trial.
BACKGROUND
Vaccine development against hookworm is hampered by the absence of the development of protective immunity in populations repeatedly exposed to hookworm, limiting identification of mechanisms of protective immunity and new vaccine targets. Immunisation with attenuated larvae has proven effective in dogs and partial immunity has been achieved using an irradiated larvae model in healthy volunteers. We aimed to investigate the protective efficacy of immunisation with short-term larval infection against hookworm challenge.
METHODS
We did a single-centre, placebo-controlled, randomised, controlled, phase 1 trial at Leiden University Medical Center (Leiden, Netherlands). Healthy volunteers (aged 18-45 years) were recruited using advertisements on social media and in publicly accessible areas. Volunteers were randomly assigned (2:1) to receive three short-term infections with 50 infectious Necator americanus third-stage filariform larvae (50L3) or placebo. Infection was abrogated with a 3-day course of albendazole 400 mg, 2 weeks after each exposure. Subsequently all volunteers were challenged with two doses of 50L3 at a 2-week interval. The primary endpoint was egg load (geometric mean per g faeces) measured weekly between weeks 12 and 16 after first challenge, assessed in the per-protocol population, which included all randomly assigned volunteers with available data on egg counts at week 12-16 after challenge. This study is registered with ClinicalTrials.gov, NCT03702530.
FINDINGS
Between Nov 8 and Dec 14, 2018, 26 volunteers were screened, of whom 23 enrolled in the trial. The first immunisation was conducted on Dec 18, 2018. 23 volunteers were randomly assigned (15 to the intervention group and eight to the placebo group). Egg load after challenge was lower in the intervention group than the placebo group (geometric mean 571 eggs per g [range 372-992] vs 873 eggs per g [268-1484]); however, this difference was not statistically significant (p=0·10). Five volunteers in the intervention group developed a severe skin rash, which was associated with 40% reduction in egg counts after challenge (geometric mean 742 eggs per g [range 268-1484] vs 441 eggs per g [range 380-520] after challenge; p=0·0025) and associated with higher peak IgG1 titres.
INTERPRETATION
To our knowledge, this is the first study to describe a protective effect of short-term exposure to hookworm larvae and show an association with skin response, eosinophilic response, and IgG1. These findings could inform future hookworm vaccine development.
FUNDING
Dioraphte Foundation.
Topics: Humans; Animals; Dogs; Necator americanus; Healthy Volunteers; Netherlands; Hookworm Infections; Immunoglobulin G; Larva
PubMed: 38042152
DOI: 10.1016/S2666-5247(23)00218-5 -
Parasitology Jan 2024Hookworm infection affects millions globally, leading to chronic conditions like malnutrition and anaemia. Among the hookworm species, stands out as a generalist,...
Hookworm infection affects millions globally, leading to chronic conditions like malnutrition and anaemia. Among the hookworm species, stands out as a generalist, capable of infecting various hosts, including humans, cats, dogs and hamsters. Surprisingly, it cannot establish in mice, despite their close phylogenetic relationship to hamsters. The present study investigated the development of in immunodeficient NSG mice to determine the contribution of the immune system to host restriction. The infections became patent on day 19 post-infection (PI) and exhibited elevated egg production which lasted for at least 160 days PI. Infective larvae reared from eggs released by infected NSG mice were infectious to hamsters and capable of reproduction, indicating that the adults in the NSG mice were producing viable offspring. In contrast, showed limited development in outbred Swiss Webster mice. Furthermore, the closely related canine hookworm was unable to infect and develop in NSG mice, indicating that different mechanisms may determine host specificity even in closely related species. This is the first report of any hookworm species completing its life cycle in a mouse and implicate the immune system in determining host specificity in .
Topics: Humans; Cricetinae; Adult; Animals; Dogs; Mice; Ancylostoma; Ancylostomatoidea; Phylogeny; Hookworm Infections; Host Specificity
PubMed: 38018393
DOI: 10.1017/S0031182023001208 -
Acta Parasitologica Mar 2024Hookworms are blood-feeding nematodes that infect millions of people and animals worldwide. The most common species infecting dogs in Europe are representatives of the...
BACKGROUND
Hookworms are blood-feeding nematodes that infect millions of people and animals worldwide. The most common species infecting dogs in Europe are representatives of the family Ancylostomatidae, which differ in invasiology, biology and morphological features. However, the differentiation of invasions of species such as Uncinaria stenocephala and Ancylostoma caninum based on a coproscopic examination is problematic. For this reason, it is recommended to use molecular diagnostics for this purpose. The authors of the article investigated the prevalence of U. stenocephala in dogs kept in various living conditions in Slovakia and developed a two-step morphology-molecular analysis-based strategy to identify the genus and the species of eggs and larvae of the Ancylostomatidae family in dogs.
CONCLUSIONS
In our opinion, this work is very much needed as it shows how to effectively diagnose hookworm infestations. However, we do not agree with the information in the title of the article because such studies have already been carried out in Central Europe by other authors.
Topics: Animals; Dogs; Dog Diseases; Hookworm Infections; Ancylostomatoidea; Slovakia; Prevalence; Larva; DNA, Helminth; Feces
PubMed: 37991680
DOI: 10.1007/s11686-023-00737-3 -
PLoS Neglected Tropical Diseases Nov 2023In Bangladesh, preventive chemotherapy targeting soil-transmitted helminth (STH) infections in school-age children has been implemented since 2008. To evaluate the...
BACKGROUND
In Bangladesh, preventive chemotherapy targeting soil-transmitted helminth (STH) infections in school-age children has been implemented since 2008. To evaluate the success of this strategy, surveys were conducted between 2017 and 2020 in 10 out of 64 districts. We estimate the geographic distribution of STH infections by species at high spatial resolution, identify risk factors, and estimate treatment needs at different population subgroups.
METHODOLOGY
Bayesian geostatistical models were fitted to prevalence data of each STH species. Climatic, environmental, and socioeconomic predictors were extracted from satellite images, open-access, model-based databases, and demographic household surveys, and used to predict the prevalence of infection over a gridded surface at 1 x 1 km spatial resolution across the country, via Bayesian kriging. These estimates were combined with gridded population data to estimate the number of required treatments for different risk groups.
PRINCIPAL FINDINGS
The population-adjusted prevalence of Ascaris lumbricoides, Trichuris trichiura, and hookworm across all ages is estimated at 9.9% (95% Bayesian credible interval: 8.0-13.0%), 4.3% (3.0-7.3%), and 0.6% (0.4-0.9%), respectively. There were 24 out of 64 districts with an estimated population-adjusted STH infection prevalence above 20%. The proportion of households with improved sanitation showed a statistically important, protective association for both, A. lumbricoides and T. trichiura prevalence. Precipitation in the driest month of the year was negatively associated with A. lumbricoides prevalence. High organic carbon concentration in the soil's fine earth fraction was related to a high hookworm prevalence. Furthermore, we estimated that 30.5 (27.2; 36.0) million dosages of anthelmintic treatments for school-age children were required per year in Bangladesh.
CONCLUSIONS/SIGNIFICANCE
For each of the STH species, the prevalence was reduced by at least 80% since treatment was scaled up more than a decade ago. The current number of deworming dosages could be reduced by up to 61% if the treatment strategy was adapted to the local prevalence.
Topics: Child; Animals; Humans; Soil; Bayes Theorem; Bangladesh; Helminthiasis; Hookworm Infections; Helminths; Ancylostomatoidea; Ascaris lumbricoides; Prevalence; Feces
PubMed: 37930980
DOI: 10.1371/journal.pntd.0011656 -
Anais Da Academia Brasileira de Ciencias 2023Enteroparasites are an important public health problem and the treatment seeks to cure and reduce transmission. The aim of this study was to evaluate the therapeutic...
Enteroparasites are an important public health problem and the treatment seeks to cure and reduce transmission. The aim of this study was to evaluate the therapeutic efficacy of anthelmintic treatment in individuals living in a rural community area in Camamu, Bahia, Brazil. The parasitological diagnosis was performed by spontaneous sedimentation, Baermann-Moraes and Agar Plate Culture methods. A total of 212 individuals were evaluated. The most frequent helminth was Trichuris trichiura, 24.5% (52/212), followed by Ascaris lumbricoides, 21.2% (45/212), hookworms, 16.5% (35/212), and S. stercoralis, 4.7% (10/212). In the anthelmintic treatment follow up, T. trichiura infection presented the lowest parasitological cure rate, only 60.6% (20/33). Hookworm, Ascaris lumbricoides and Strongyloides stercoralis infections demonstrated cure rates of 70.5 (12/17), 78.1 (25/32) and 100% (5/5), respectively. Individuals who remained infected underwent a new drug therapy. The second parasitological cure rate for T. trichiura was 38.5% (5/13), and 66.7% (2/3) and 75% (3/4) for hookworms and Ascaris lumbricoides, respectively. Trichuris trichiura infection presented the lowest parasitological cure rate at this second evaluation. This reinforces the need to perform a follow-up of all treated individuals. The possibility of drug resistance denotes the necessity for studies to clarify the mechanisms and to evaluate new therapeutic approaches.
Topics: Animals; Humans; Follow-Up Studies; Brazil; Rural Population; Anthelmintics; Hookworm Infections; Ancylostomatoidea; Ascaris lumbricoides; Feces; Prevalence
PubMed: 37909545
DOI: 10.1590/0001-3765202320230323 -
BMC Veterinary Research Oct 2023The zoonotic hookworms Ancylostoma caninum and Uncinaria stenocephala are widespread soil-transmitted helminths in dogs in Europe. Given the veterinary and public health...
BACKGROUND
The zoonotic hookworms Ancylostoma caninum and Uncinaria stenocephala are widespread soil-transmitted helminths in dogs in Europe. Given the veterinary and public health importance of hookworms in dogs and the recent changes in the molecular epidemiology of some species, there is a need to continuously monitor the epidemiological and molecular prevalence of these parasites also at the "local" level. The present study aimed to update the epidemiological scenario of hookworm infections in both owned and stray dogs in southern Italy and to discriminate between different hookworm species (A. caninum and U. stenocephala) through molecular analyses. For this purpose, a retrospective analysis was performed over 10 years (2011-2021), including a total of 7008 owned dogs and 5642 stray dogs referred to our laboratory for copromicroscopic examinations. Moreover, 72 faecal samples, from dogs naturally infected by hookworms, were used to discriminate between A. caninum and U. stenocephala using two PCR protocols. Prior to molecular analyses, a subsample of 40/72 positive faecal samples was used for morphometric investigations on hookworm eggs.
RESULTS
The results of the ten-year retrospective analysis (2011-2021) showed an overall prevalence of hookworm infection of 9.16%, specifically 5.1% in owned dogs and 14.2% in stray dogs. Logistic regression showed a significant association between positivity to hookworms and the variable "puppies" both in stray (13.84%; OR = 2.4) and owned (7.07%; OR = 2.2) dogs. The results of molecular analyses showed that positivity was confirmed only in 21/72 samples, specifically, 6 samples using protocol A and 19 with protocol B. Sequencing revealed 15 samples positive to U. stenocephala and 6 to A. caninum.
CONCLUSIONS
The findings of this study showed a high prevalence of hookworm infections in dogs in southern Italy, updating the epidemiological scenario of the last decade. Moreover, the results of the study revealed the first identification of hookworm species in dogs in Italy by molecular studies, highlighting that U. stenocephala is more prevalent than A. caninum.
Topics: Animals; Dogs; Ancylostomatoidea; Retrospective Studies; Dog Diseases; Hookworm Infections; Italy; Feces; Ancylostoma
PubMed: 37833701
DOI: 10.1186/s12917-023-03765-3 -
PLoS Neglected Tropical Diseases Sep 2023Soil-transmitted helminth (STH) infections are caused by roundworms (Ascaris lumbricoides), whipworms (Trichuris trichiura), and hookworms (Necator americanus and...
BACKGROUND
Soil-transmitted helminth (STH) infections are caused by roundworms (Ascaris lumbricoides), whipworms (Trichuris trichiura), and hookworms (Necator americanus and Ancylostoma duodenale). In Uganda, baseline surveys conducted during the late 1990s and early 2000s suggested STH infections were common, with prevalence >50% among surveyed schoolchildren. In 2003, a national program was launched with mass preventative chemotherapy (PC) and health education for children 1-14 years old. Little evidence is available to show the impact of national deworming.
METHODS
We conducted population-based, cross-sectional household surveys in five districts (Buikwe, Kassanda, Kiryandongo, Kisoro, and Rubanda) in March and May 2022. Our primary objective was to estimate STH prevalence by species due to infections of any intensity and infections of moderate-to-heavy intensity among preschool-aged children (PSAC, 1-4 years old), school-aged children (SAC, 5-14 years old), and women of reproductive age (WRA, 15-49 years old). Laboratory technicians used duplicate Kato-Katz microscopy to determine fecal egg count.
RESULTS
Overall, 3,352 PSAC; 3,884 SAC; and 1,226 WRA provided stool samples. The prevalence of any infection remained high in Kisoro at or above ~50% within all risk groups. In other districts, the prevalence of any infection ranged from approximately 5 to 16% among PSAC, 6 to 23% among SAC, and 12 to 19% among WRA. Moderate-to-heavy intensity infection prevalence was highest in Kisoro (~15-26%), followed by Rubanda (<5%), and was ≤1% in other districts. A. lumbricoides and T. trichiura infections were largely confined to Kisoro and Rubanda, whereas hookworm was most common in other districts.
CONCLUSIONS
The STH prevalence has decreased markedly in three districts in Uganda. Based on our findings, the national deworming program should consider decreasing PC distribution frequency in these districts per the World Health Organization guidelines. Efforts are needed to understand why the Kisoro and Rubanda districts did not demonstrate similar gains.
Topics: Child; Child, Preschool; Animals; Humans; Female; Adolescent; Young Adult; Adult; Middle Aged; Infant; Uganda; Cross-Sectional Studies; Prevalence; Helminthiasis; Ancylostoma
PubMed: 37751418
DOI: 10.1371/journal.pntd.0011605 -
PLoS Neglected Tropical Diseases Aug 2023Rapid increases in human populations and environmental changes of past decades have led to changes in rates of contact and spatial overlap with wildlife. Together with...
Rapid increases in human populations and environmental changes of past decades have led to changes in rates of contact and spatial overlap with wildlife. Together with other historical, social and environmental processes, this has significantly contributed to pathogen transmission in both directions, especially between humans and non-human primates, whose close phylogenetic relationship facilitates cross-infections. Using high-throughput amplicon sequencing, we studied strongylid communities in sympatric western lowland gorillas, central chimpanzees and humans co-occurring in an unprotected area in the northern periphery of the Dja Faunal Reserve, Cameroon. At the genus level, we classified 65 strongylid ITS-2 amplicon sequencing variants (ASVs) in humans and great apes. Great apes exhibited higher strongylid diversity than humans. Necator and Oesophagostomum were the most prevalent genera, and we commonly observed mixed infections of more than one strongylid species. Human strongylid communities were dominated by the human hookworm N. americanus, while great apes were mainly infected with N. gorillae, O. stephanostomum and trichostrongylids. We were also able to detect rare strongylid taxa (such as Ancylostoma and Ternidens). We detected eight ASVs shared between humans and great apes (four N. americanus variants, two N. gorillae variants, one O. stephanostomum type I and one Trichostrongylus sp. type II variant). Our results show that knowledge of strongylid communities in primates, including humans, is still limited. Sharing the same habitat, especially outside protected areas (where access to the forest is not restricted), can enable mutual parasite exchange and can even override host phylogeny or conserved patterns. Such studies are critical for assessing the threats posed to all hosts by increasing human-wildlife spatial overlap. In this study, the term "contact" refers to physical contact, while "spatial overlap" refers to environmental contact.
Topics: Animals; Humans; Cameroon; Phylogeny; Pan troglodytes; Ancylostoma; Animals, Wild
PubMed: 37624869
DOI: 10.1371/journal.pntd.0011499 -
Parasites & Vectors Aug 2023For decades, zinc sulfate centrifugal fecal flotation microscopy (ZCF) has been the mainstay technique for gastrointestinal (GI) parasite screening at veterinary clinics...
BACKGROUND
For decades, zinc sulfate centrifugal fecal flotation microscopy (ZCF) has been the mainstay technique for gastrointestinal (GI) parasite screening at veterinary clinics and laboratories. Elsewhere, PCR has replaced microscopy because of generally increased sensitivity and detection capabilities; however, until recently it has been unavailable commercially. Therefore, the primary aim of this study was to compare the performance of real-time PCR (qPCR) and ZCF for fecal parasite screening. Secondary aims included further characterization of markers for hookworm treatment resistance and Giardia spp. assemblages with zoonotic potential and qPCR optimization.
METHODS
A convenience sampling of 931 canine/feline fecal samples submitted to a veterinary reference laboratory for routine ZCF from the Northeast US (11/2022) was subsequently evaluated by a broad qPCR panel following retention release. Detection frequency and agreement (kappa statistics) were evaluated between ZCF and qPCR for seven GI parasites [hookworm/(Ancylostoma spp.), roundworm/(Toxocara spp.), whipworm/(Trichuris spp.), Giardia duodenalis, Cystoisospora spp., Toxoplasma gondii, and Tritrichomonas blagburni] and detections per sample. Total detection frequencies were compared using a paired t-test; positive sample and co-infection frequencies were compared using Pearson's chi-squared test (p ≤ 0.05 significant) and qPCR frequency for hookworm benzimidazole (BZ) resistance (F167Y) and zoonotic Giardia spp. assemblage markers calculated. Confirmatory testing, characterization, and qPCR optimization were carried out with Sanger sequencing.
RESULTS
qPCR detected a significantly higher overall parasite frequency (n = 679) compared to ZCF (n = 437) [p = < 0.0001, t = 14.38, degrees-of-freedom (df) = 930] and 2.6 × the co-infections [qPCR (n = 172) vs. ZCF (n = 66)], which was also significant (p = < 0.0001, X = 279.49; df = 1). While overall agreement of parasite detection was substantial [kappa = 0.74; (0.69-0.78], ZCF-undetected parasites reduced agreement for individual and co-infected samples. qPCR detected markers for Ancylostoma caninum BZ resistance (n = 5, 16.1%) and Giardia with zoonotic potential (n = 22, 9.1%) as well as two parasites undetected by ZCF (T. gondii/T. blagburni). Sanger sequencing detected novel roundworm species, and qPCR optimization provided detection beyond ZCF.
CONCLUSIONS
These results demonstrate the statistically significant detection frequency advantage offered by qPCR compared to routine ZCF for both single and co-infections. While overall agreement was excellent, this rapid, commercially available qPCR panel offers benefits beyond ZCF with detection of markers for Giardia assemblages with zoonotic potential and hookworm (A. caninum) BZ resistance.
Topics: Cats; Animals; Dogs; United States; Parasites; Cat Diseases; Coinfection; Dog Diseases; Intestinal Diseases, Parasitic; Giardiasis; Ancylostoma; Giardia; Gastropoda; Real-Time Polymerase Chain Reaction
PubMed: 37587483
DOI: 10.1186/s13071-023-05904-z -
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