-
Frontiers in Immunology 2022Malaria and helminthic parasites are endemic in tropical countries, and co-infections might influence host-parasite interactions. In this community-based cross-sectional...
BACKGROUND
Malaria and helminthic parasites are endemic in tropical countries, and co-infections might influence host-parasite interactions. In this community-based cross-sectional study, the effect that the presence of soil-transmitted helminths (STH) (Hookworm, and could have on the immunoglobulin (Ig) candidate protein of the malaria vaccine GMZ2 levels was evaluated.
METHODS
Blood, stool, and urine samples were collected from 5-15-year-old children to diagnose (Pf), STH, and , respectively. Identification and quantification of the parasite load of STH and were achieved by light microscopy. A polymerase chain reaction was carried out to detect submicroscopic infections of . Plasma levels of GMZ2 specific IgG and its subclasses were quantified by ELISA.
RESULTS
The median level of total IgG in individuals with co-infection with Pf/. was significantly lower in the mono-infected group with Pf (p = 0.0121) or study participants without infection (=0.0217). Similarly, the median level of IgG1 was statistically lower in Pf/ group compared to Pf-group (=0.0137). Equally, the Pf/ infected individuals posted a lower level of IgG1 compared to Pf-group (p=0.0137) and IgG4 compared to the Pf-group (=0.0144). Spearman rank correlation analyses indicated positive relationships between the densities of (ρ=0.25, =0.015) and (ρ=0.36, 0.0001).
CONCLUSIONS
Hookworm and infections are associated with reduced GMZ2 specific IgG levels. This study shows the possible manipulation of immune responses by helminths for their survival and transmission, which may have serious implications for vaccine development and deployment in helminth-endemic regions.
Topics: Adolescent; Ancylostomatoidea; Animals; Child; Child, Preschool; Coinfection; Cross-Sectional Studies; Helminths; Hookworm Infections; Humans; Immunity; Immunoglobulin G; Malaria; Malaria Vaccines; Malaria, Falciparum; Nigeria; Parasites; Plasmodium falciparum; Soil
PubMed: 36159869
DOI: 10.3389/fimmu.2022.979727 -
PloS One 2022Metabolomics provides a powerful tool to study physiological changes in response to various perturbations such as vaccination. We explored whether metabolomic changes...
Metabolomics provides a powerful tool to study physiological changes in response to various perturbations such as vaccination. We explored whether metabolomic changes could be seen after vaccination in a phase I trial where Gabonese adults living either in rural or semi-urban areas received the subunit hookworm vaccine candidates (Na-GST-1 and Na-APR-1 (M74) adjuvanted with Alhydrogel plus GLA-AF (n = 24) or the hepatitis B vaccine (n = 8) as control. Urine samples were collected and assayed using targeted 1H NMR spectroscopy. At baseline, a set of metabolites significantly distinguished rural from semi-urban individuals. The pre- and post-vaccination comparisons indicated significant changes in few metabolites but only one day after the first vaccination. There was no relationship with immunogenicity. In conclusion, in a small phase 1 trial, urinary metabolomics could distinguish volunteers with different environmental exposures and reflected the safety of the vaccines but did not show a relationship to immunogenicity.
Topics: Adjuvants, Immunologic; Adult; Aluminum Hydroxide; Ancylostomatoidea; Animals; Gabon; Hepatitis B Vaccines; Hookworm Infections; Humans; Immunogenicity, Vaccine
PubMed: 36155987
DOI: 10.1371/journal.pone.0275013 -
Environment International Nov 2022The endangered Australian sea lion, Neophoca cinerea, faces ongoing population decline. Identification of key threats to N. cinerea population recovery, including...
The endangered Australian sea lion, Neophoca cinerea, faces ongoing population decline. Identification of key threats to N. cinerea population recovery, including disease and pollutants, is an objective of the species' recovery plan. Previous studies have identified Uncinaria sanguinis, an intestinal nematode, as a significant cause of disease and mortality in N. cinerea pups. Given the impact of heavy metals on the immune response, investigation of these pollutants is critical. To this end, the concentrations of arsenic (As), total mercury (Hg), cadmium (Cd), chromium (Cr), lead (Pb) and selenium (Se) were determined in blood collected from N. cinerea pups sampled during the 2017/18, 2019 and 2020/21 breeding seasons at Seal Bay Conservation Park, South Australia. Significant differences (p < 0.05) in Hg, As, Cr, and Se concentrations and molar ratio of Se:Hg were seen between breeding seasons. Pup age, maternal parity and inter-individual foraging behaviour were considered factors driving these differences. The concentrations of Hg (357, 198 and 241 µg/L) and As (225, 834 and 608 µg/L) were high in 2017/18, 2019 and 2020/21 respectively with Hg concentrations in the blood of N. cinerea pups above toxicological thresholds reported for marine mammals. The concentration of Se (1332, 647, 763 µg/L) and molar ratio of Se:Hg (9.47, 7.98 and 6.82) were low compared to other pinniped pups, indicating potential vulnerability of pups to the toxic effects of Hg. Significant (p < 0.05) negative associations for Pb and Cd with several red blood cell parameters suggest they could be exacerbating the anaemia caused by hookworm disease. Temporal (age-related) changes in element concentrations were also seen, such that pup age needs to be considered when interpreting bioaccumulation patterns. Further investigation of the role of elevated heavy metal concentrations on N. cinerea pup health, disease and development is recommended, particularly with respect to immunological impacts.
Topics: Ancylostomatoidea; Animals; Arsenic; Australia; Cadmium; Chromium; Environmental Pollutants; Female; Hookworm Infections; Lead; Mercury; Mercury Poisoning; Metals, Heavy; Pregnancy; Sea Lions; Selenium
PubMed: 36148712
DOI: 10.1016/j.envint.2022.107521 -
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 2022Hookworms infect more that 400 million people and cause significant socio-economic burden on endemic countries. The lack of efficient vaccines and the emergence of...
Hookworms infect more that 400 million people and cause significant socio-economic burden on endemic countries. The lack of efficient vaccines and the emergence of anthelminthic drug resistance are of major concern. Free-living hookworm larvae infect their hosts the skin and live as adult worms in the small intestine where they feed on host tissue and blood. Excretory/secretory (E/S) products, released by helminths as they migrate through their host, are thought to play a key role in facilitating infection and successful establishment of parasitism. However, E/S products can also elicit protective immune responses that might be harnessed for vaccine development. By performing Western blots with serum of (Nb) infected mice as a model for human hookworm infection, we identified a largely overlapping set of IgG1- and IgE-reactive antigens in E/S from infective L3 stage larvae. Mass spectrometry analysis led to the identification of a new protein family with 6 paralogues in the Nb genome which we termed Nb-LSA1 for " larval secreted protein 1". The recombinantly expressed 17 kDa family member Nb-LSA1a was recognized by antibodies in the serum of Nb immune mice. Immunization of mice with Nb-LSA1a in alum elicited a strong IgG1 response but no detectable antigen-specific IgE. Most importantly, immunized mice were largely protected against a challenge Nb infection. This effect was dependent on the presence of basophils and occurred before the parasites reached the intestine. Therefore, basophils appear to play a critical role for rapid control of infection with L3 stage larvae in mice immunized with a single secreted larval protein. A better understanding of basophil-mediated protective immunity and identification of potent larval antigens of human hookworms could help to develop promising vaccination strategies.
Topics: Ancylostomatoidea; Animals; Antigens, Helminth; Basophils; Humans; Immunoglobulin E; Immunoglobulin G; Larva; Mice; Nippostrongylus
PubMed: 36091065
DOI: 10.3389/fimmu.2022.979491 -
Veterinary Parasitology, Regional... Sep 2022Dogs can harbor various intestinal parasites that have serious clinical, economic, and zoonotic impact. In Morocco, the epidemiological status of those parasites is...
Dogs can harbor various intestinal parasites that have serious clinical, economic, and zoonotic impact. In Morocco, the epidemiological status of those parasites is largely unknown. This study aimed to obtain data on the prevalence of intestinal parasites in various Moroccan dog populations, to identify associated risk factors, to evaluate people's knowledge regarding zoonotic parasites and to estimate the risk of human infection. A total of 291 fecal samples were analyzed using a 33% Zinc Sulphate (ZnSO4) centrifugal flotation and a sheather's sugar simple flotation techniques. In addition, 100 dog owners were asked to fill out a questionnaire about their knowledge regarding canine zoonotic intestinal parasites. Overall, 58% of sampled dogs were positive for at least one parasite species. Ancylostoma/Uncinaria spp. (31.9%), Toxascaris leonina (27.4%), Toxocara canis (27.1%), Cystoisospora spp. (13.4%) and Giardia spp. (7.2%) were the most frequently isolated parasites. The overall prevalence was associated with the dogs' activity, and feces consistency. More specifically, the prevalence of Ancylostoma/Uncinaria spp., Toxascaris leonina and Cystoisospora spp. was associated with dogs' activity and feces consistency and, additionally with age for Cystoisosporaspp.Toxocara canis prevalence was associated with age and feces consistency, while Giardia spp. prevalence was associated with dogs' activity. A weak awareness among dog owners regarding the zoonotic potential of canine intestinal parasites was noticed (33%) especially when their knowledge was compared to another endemic zoonotic disease, i.e. rabies (85%). Furthermore, the rate of respecting the vaccination protocol (82%) was significantly higher than the rate of respecting the deworming protocol (47%). We conclude that intestinal parasites, including the zoonotic ones, were highly prevalent in the dogs sampled in this study whereas people's knowledge about those parasites was very limited. These findings suggest that the risk of human infection is very likely, which highlights the need for effective control programs and health education.
Topics: Ancylostoma; Animals; Dog Diseases; Dogs; Humans; Intestinal Diseases, Parasitic; Morocco; Parasites; Prevalence; Risk Factors; Toxocara canis
PubMed: 36041810
DOI: 10.1016/j.vprsr.2022.100775 -
Emerging Infectious Diseases Sep 2022Ancylostoma ceylanicum hookworms are zoonotic parasites that can infect humans. To detect autochthonous transmission, we analyzed human fecal samples collected in 2000....
Ancylostoma ceylanicum hookworms are zoonotic parasites that can infect humans. To detect autochthonous transmission, we analyzed human fecal samples collected in 2000. Multiparallel quantitative PCR detected infection in persons who had never traveled outside Ecuador. These data indicate human transmission of A. ceylanicum in the Americas, although endemicity remains unknown.
Topics: Ancylostoma; Ancylostomatoidea; Ancylostomiasis; Animals; Ecuador; Hookworm Infections; Humans; Zoonoses
PubMed: 35997627
DOI: 10.3201/eid2809.220248 -
Emerging Infectious Diseases Sep 2022Ancylostoma ceylanicum hookworms are recognized agents of human infection in the Asia-Pacific region. We investigated prevalence of zoonotic hookworm infections in dogs...
Ancylostoma ceylanicum hookworms are recognized agents of human infection in the Asia-Pacific region. We investigated prevalence of zoonotic hookworm infections in dogs in Grenada in 2021; 40.8% were infected by hookworms, including Ancylostoma ceylanicum. Surveillance of this parasite in dogs and humans is needed in tropical/subtropical countries in the Americas.
Topics: Ancylostoma; Ancylostomatoidea; Ancylostomiasis; Animals; Dogs; Feces; Grenada; Humans; Zoonoses
PubMed: 35997602
DOI: 10.3201/eid2809.220634 -
Scientific Reports Aug 2022Preventive chemotherapy (PC) that remains the main control strategy recommended by the World Health Organization to achieve the elimination of soil-transmitted helminth...
Preventive chemotherapy (PC) that remains the main control strategy recommended by the World Health Organization to achieve the elimination of soil-transmitted helminth (STH) infections as a public health problem must be strengthened by identifying the remaining transmission hot-spots for the deployment of appropriate control measures. This study was designed to assess the prevalence and infections intensities of soil-transmitted helminths and perform micro scale mapping in order to identify transmission hot-spots for targeted control operations. Stool samples were collected from 1775 children in ten primary schools of eight sub-districts of Makenene in Cameroon. Kato Katz technique was used to process and examine stool samples to detect the eggs of soil-transmitted nematodes. The prevalence of soil-transmitted helminth species as well as the infection intensities was compared. Data visualizations in forms of maps were made using Quantum geographic information system (QGIS) software. The overall prevalence of soil-transmitted helminth infections was 4.8% with a 95% confidence interval (CI) of 3.8-5.9%: 3.0% (95% CI 2.2-3.9) for Ascaris lumbricoides, 1.4% (95% CI 0.9-2.0) for Trichuris trichiura and 0.8% (95% CI 0.5-1.4) for hookworms. The prevalence of soil-transmitted helminth species differ significantly between schools and sub-districts. The intensity of infections was light (2.4%, 1.1% and 0.8%), moderate (0.4%, 0.1% and 0.1%) and heavy (0.2%, 0.2% and 0%) for A. lumbricoides, T. trichiura and hookworm respectively. The mean intensity of infections was 7255 EPG for A. lumbricoides, 2900 EPG for T. trichiura and 298 EPG for hookworm. Between schools, significant difference was recorded in the means of infection intensities of T. Trichiura and hookworms but not for A. lumbricoides. This difference was also significant for T. Trichiura when comparison were between sex. No significant difference were recorded when the comparison were between age. Fine mapping revealed that children harbouring heavy infections were clustered in the same sub-districts; highlighting the presence of high endemicity sub-districts and hot-spots for the transmission of different soil-transmitted helminth species. This study showed a diversity in the prevalence and transmission of different soil-transmitted helminth species. It also hightlighted the need for micro scale mapping to enable the localisation of high endemicity sub-districts and transmission hot-spot sites where targeted control operations must be deployed to achieve STH elimination.
Topics: Ancylostomatoidea; Animals; Ascaris lumbricoides; Child; Feces; Helminthiasis; Helminths; Hookworm Infections; Humans; Prevalence; Soil; Trichuris
PubMed: 35978014
DOI: 10.1038/s41598-022-18285-7 -
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