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PLoS Neglected Tropical Diseases Mar 2024Control efforts of soil-transmitted helminthiases rely primarily on large scale administration of anthelminthic drugs. The assessment of drug efficacies and... (Clinical Trial)
Clinical Trial
BACKGROUND
Control efforts of soil-transmitted helminthiases rely primarily on large scale administration of anthelminthic drugs. The assessment of drug efficacies and understanding of drug behavior is pivotal to the evaluation of treatment successes, both in preventive chemo-therapy programs as well as in research of novel treatment options. The current WHO guidelines recommend an interval of 14-21 days between the treatment and follow-up, yet no in-depth analysis of egg excretion patterns of Trichuris trichiura after treatment has been conducted to date.
METHODS
Within the framework of a multi-country trial to assess the efficacy and safety of albendazole-ivermectin combination therapy vs albendazole monotherapy against T. trichiura infections, we conducted a study collecting daily stool samples over the period of 28 days post-treatment in 87 participants in Pak Khan, Lao PDR. Egg counts were derived by duplicate Kato-Katz on-site for T. trichiura, hookworm and Ascaris lumbricoides and stool sample aliquots were subsequently analyzed by qPCR for the detection of T. trichiura infections. Sensitivity and specificity was calculated for each day separately using data derived by Kato-Katz to determine the optimal timepoint at which to assess drug efficacy.
RESULTS
Egg excretion patterns varied across treatment arms. For T. trichiura, only the albendazole-ivermectin treatment led to a considerable reduction in mean egg counts, whereas both treatments reduced hookworm egg counts and A. lumbricoides were cleared in all participants after day 7. For T. trichiura, we found sensitivity to be highest at days 18 and 22 when using egg counts as outcome and days 19 and 24 when using qPCR. Specificity was high (>0.9) from day 14 onwards. For hookworm, the highest sensitivity and specificity were found at days 17 and 25, respectively.
CONCLUSIONS
Based on our study, the ideal time period to assess drug efficacy for soil-transmitted helminth infections would be between day 18 and 24. The current WHO recommendation of 14 to 21 days is likely to yield acceptable outcome measures for soil-transmitted helminth infections.
TRIAL REGISTRATION
NCT03527732.
Topics: Animals; Humans; Albendazole; Ancylostomatoidea; Anthelmintics; Feces; Helminthiasis; Ivermectin; Soil; Trichuriasis; Trichuris
PubMed: 38517907
DOI: 10.1371/journal.pntd.0012073 -
Acta Parasitologica Jun 2024Soil-transmitted nematodes (STNs) are widespread in tropical and subtropical regions, particularly where the communities are socio-economically challenged. We...
PURPOSE
Soil-transmitted nematodes (STNs) are widespread in tropical and subtropical regions, particularly where the communities are socio-economically challenged. We investigated the effect of soil temperature on the prevalence and intensity of STN infection in free-roaming dogs.
METHODS
Fresh faecal samples collected from free-roaming dogs in Digana and Pussellawa town areas in the Kandy District, Sri Lanka, were microscopically analysed for canine STNs. Soil temperature was measured at each sampling site. Highly prevalent canine hookworm Ancylostoma, was further studied using PCR and sequencing, followed by phylogenetic analysis.
RESULTS
The soil temperature ranged between 28 and 31 °C (mean = 29.79 °C) and 18-21 °C (mean = 19.52 °C) in Digana and Pussellawa, respectively, showing a significant difference in the two sites (Students t-test t = 1.68, p < 0.0001). Of the total 44 dogs sampled, 41 (93.2%) were positive for STNs. During microscopic analysis, five nematodes: Ancylostoma spp., Capillaria sp., Strongyloides sp., Toxocara canis, and Trichuris sp., were identified. Ancylostoma species (93.2%) were the most prevalent, followed by Strongyloides sp. (22.7%) and Toxocara canis (15.9%). Infection prevalence of Strongyloides sp. was higher in Digana (40.9%) compared to that in Pussellawa (4.5%; Chi-square test, χ = 8.28, p = 0.004) and also the infection intensity from Digana (EPG = 8.02 ± 20.2) compared to that from Pussellawa (0.45 ± 2.1; Mann Whitney U test, p = 0.006). Amplicons (ITS1-5.8S-ITS2) of the expected size for A. caninum, and A. tubaeforme were produced. An A. caninum sequence reported here (OQ101719) illustrated the highest similarity of 99.2% to one of the local sequences (MZ707153) upon pairwise comparison.
CONCLUSION
Digana, with a higher soil temperature than Pussellawa, had a significantly higher prevalence and infection intensity, particularly Strongyloides sp. This study also signifies the first molecular identification of hookworm species A. tubaeforme in Sri Lanka.
Topics: Animals; Dogs; Soil; Sri Lanka; Dog Diseases; Feces; Temperature; Ancylostoma; Phylogeny; Prevalence; Ancylostomiasis; Nematoda
PubMed: 38514604
DOI: 10.1007/s11686-024-00829-8 -
The Lancet. Infectious Diseases Jul 2024
Topics: Humans; Hookworm Infections; Animals; Vaccines; Ancylostomatoidea
PubMed: 38513685
DOI: 10.1016/S1473-3099(24)00145-2 -
The Lancet. Infectious Diseases Jul 2024A human hookworm vaccine is being developed to protect children against iron deficiency and anaemia associated with chronic infection with hookworms. Necator americanus... (Randomized Controlled Trial)
Randomized Controlled Trial
Safety and immunogenicity of the co-administered Na-APR-1 and Na-GST-1 hookworm vaccines in school-aged children in Gabon: a randomised, controlled, observer-blind, phase 1, dose-escalation trial.
BACKGROUND
A human hookworm vaccine is being developed to protect children against iron deficiency and anaemia associated with chronic infection with hookworms. Necator americanus aspartic protease-1 (Na-APR-1) and N americanus glutathione S-transferase-1 (Na-GST-1) are components of the blood digestion pathway critical to hookworm survival in the host. Recombinant Na-GST-1 and catalytically inactive Na-APR-1 (Na-APR-1[M74]) adsorbed to Alhydrogel were safe and immunogenic when delivered separately or co-administered to adults in phase 1 trials in non-endemic and endemic areas. We aimed to investigate the safety and immunogenicity of these antigens in healthy children in a hookworm-endemic area.
METHODS
This was a randomised, controlled, observer-blind, phase 1, dose-escalation trial, conducted in a clinical research centre, in 60 children aged six to ten years in Lambaréné, a hookworm-endemic region of Gabon. Healthy children (determined by clinical examination and safety laboratory testing) were randomised 4:1 to receive co-administered Na-GST-1 on Alhydrogel plus Na-APR-1(M74) on Alhydrogel and glucopyranosyl lipid A in aqueous formulation (GLA-AF), or co-administered ENGERIX-B hepatitis B vaccine (HBV) and saline placebo, injected into the deltoid of each arm. Allocation to vaccine groups was observer-masked. In each vaccine group, children were randomised 1:1 to receive intramuscular injections into each deltoid on two vaccine schedules, one at months 0, 2, and 4 or at months 0, 2, and 6. 10 μg, 30 μg, and 100 μg of each antigen were administered in the first, second, and third cohorts, respectively. The intention-to-treat population was used for safety analyses; while for immunogenicity analyses, the per-protocol population was used (children who received all scheduled vaccinations). The primary outcome was to evaluate the vaccines' safety and reactogenicity in healthy children aged between six and ten years. The secondary outcome was to measure antigen-specific serum IgG antibody levels at pre-vaccination and post-vaccination timepoints by qualified ELISAs. The trial is registered with ClinicalTrials.gov, NCT02839161, and is completed.
FINDINGS
Between Jan 23 and Oct 3, 2017, 137 children were screened, of whom 76 were eligible for this trial. 60 children were recruited, and allocated to either 10 μg of the co-administered antigens (n=8 for each injection schedule), 30 μg (n=8 for each schedule), 100 μg (n=8 for each schedule), or HBV and placebo (n=6 for each schedule) in three sequential cohorts. Co-administration of the vaccines was well tolerated; the most frequent solicited adverse events were mild-to-moderate injection-site pain, observed in up to 12 (75%) of 16 participants per vaccine group, and mild headache (12 [25%] of 48) and fever (11 [23%] of 48). No vaccine-related serious adverse events were observed. Significant anti-Na-APR-1(M74) and anti-Na-GST-1 IgG levels were induced in a dose-dependent manner, with peaks seen 14 days after the third vaccinations, regardless of dose (for Na-APR-1[M74], geometric mean levels [GML]=2295·97 arbitrary units [AU] and 726·89 AU, while for Na-GST-1, GMLs=331·2 AU and 21·4 AU for the month 0, 2, and 6 and month 0, 2, and 4 schedules, respectively). The month 0, 2, and 6 schedule induced significantly higher IgG responses to both antigens (p=0·01 and p=0·04 for Na-APR-1[M74] and Na-GST-1, respectively).
INTERPRETATION
Co-administration of recombinant Na-APR-1(M74) and Na-GST-1 to school-aged Gabonese children was well tolerated and induced significant IgG responses. These results justify further evaluation of this antigen combination in proof-of-concept controlled-infection and efficacy studies in hookworm-endemic areas.
FUNDING
European Union Seventh Framework Programme.
Topics: Humans; Male; Child; Female; Gabon; Necator americanus; Animals; Hookworm Infections; Antigens, Helminth; Antibodies, Helminth; Glutathione Transferase; Single-Blind Method; Vaccines; Immunogenicity, Vaccine
PubMed: 38513684
DOI: 10.1016/S1473-3099(24)00104-X -
Molecular Medicine (Cambridge, Mass.) Mar 2024My scientific life in translational medicine runs in two parallel, yet often converging paths. The first, is four-decade-long commitment to develop new vaccines for...
My scientific life in translational medicine runs in two parallel, yet often converging paths. The first, is four-decade-long commitment to develop new vaccines for parasitic and neglected tropical diseases, as well as pandemic threats. This includes a vaccine for human hookworm infection that I began as an MD-PhD student in New York City in the 1980s, and a new low-cost COVID vaccine that reached almost 100 million people in low- and middle-income countries. Alongside this life in scientific research, is one in public engagement for vaccine and neglected disease diplomacy to ensure that people who live in extreme poverty can benefit from access to biomedical innovations. A troubling element has been the daunting task of countering rising antivaccine activism, which threatens to undermine our global vaccine ecosystem. Yet, this activity may turn out to become just as important for saving lives as developing new vaccines.
Topics: Child; Humans; Child Health; COVID-19 Vaccines; Global Health; Hookworm Infections; Vaccines, Synthetic
PubMed: 38491420
DOI: 10.1186/s10020-024-00786-y -
Parasites & Vectors Mar 2024The impact of access to improved water, sanitation and hygiene (WASH) and health education on large-scale deworming programs aimed at controlling soil-transmitted...
Investigating the effect of a school-based WASH intervention on soil-transmitted helminth and schistosome infections and nutritional status of school children in Ethiopia: a quasi-experimental study.
BACKGROUND
The impact of access to improved water, sanitation and hygiene (WASH) and health education on large-scale deworming programs aimed at controlling soil-transmitted helminth (STH) and schistosome (SCH) infections has not been well studied. We assessed the additional impact of improved WASH infrastructure and health education at schools on STH and SCH infections in Ethiopia.
METHODS
The study used a quasi-experimental design under which 30 schools were assigned to either an intervention (15 schools) or control (15 schools) arm. Both arms received a standard deworming treatment and lunch. In the intervention arm, improved WASH and health education were provided. At three consecutive time points (baseline in 2013, 2014 and 2015), the prevalence and intensity of STH and SCH infections and the nutritional status [hemoglobin concentrations and physical growth (height and weight)] were determined. To verify whether interventions were successfully implemented, the WASH status at school and the student knowledge, attitudes and practices related to WASH (WASH-KAP) were recorded. Differences in metrics between arms at baseline (2013) and follow-up (2015) were assessed both within and between the arms.
RESULTS
A significant increase in scores for both the school WASH and student KAP was found in the intervention arm, indicating successful implementation of the intervention. The prevalence of any STH infection was significantly reduced in the intervention arm but not in the control arm (F = 4.486, p = 0.034). There was a significantly greater reduction in the intensity of infection of hookworm and Ascaris lumbricoides compared to baseline in both arms. The intervention did not affect school children's height-for-age z-score (intervention arm * time coef = 0.12, p = 0.400) and body mass index-for-age z-scores (intervention * time coef = - 0.06, p = 0.526). Hemoglobin concentrations increased significantly more in the control than the intervention arm (coef = - 0.16, p = 0.006).
CONCLUSIONS
Although the intervention did increase school WASH and student WASH-KAP, our study found poor evidence of the additional benefit of improved WASH and health education to deworming and school food programs on parasite re-infection and the health outcomes of children.
Topics: Child; Animals; Humans; Sanitation; Soil; Nutritional Status; Water; Ethiopia; Helminths; Hygiene; Schistosoma; Hemoglobins
PubMed: 38486228
DOI: 10.1186/s13071-024-06155-2 -
PloS One 2024Intestinal parasitic infections (IPIs) are major public health problems in developing countries. This study was conducted to determine the prevalence and associated risk...
Intestinal parasitic infections (IPIs) are major public health problems in developing countries. This study was conducted to determine the prevalence and associated risk factors of IPIs at Debarq Primary Hospital in northwest Ethiopia. A health facility-based cross-sectional study was conducted from March 2022 to June 2022. The study participants were recruited from patients who visited Debarq Primary Hospital during the study period. Stool samples were collected from each participant and examined for intestinal parasites using direct wet-mount and formal-ether concentration techniques. Socio-demographic data were collected using a structured questionnaire. Out of 422 individuals examined, 33.64% were infected with at least one intestinal parasite species. Entamoeba histolytica/dispar, Giardia intestinalis, Ascaris lumbricoides, and hookworm were found in 12.79%, 8.53%, 7.10%, and 1.65% of the participants, respectively. Double and triple parasite infections were found in 2.37% and 0.23% of the participants, respectively. A habit of eating unwashed vegetables (Adjusted odds ratio (AOR) = 9.98, 95% confidence interval (CI) = 2.68-37.14) and low income (AOR = 6.66, 95% CI = 1.87-23.70) were associated with increased odds of IPIs. Participants with a habit of hand washing after using the toilet had 0.05 (95% CI = 0.13-0.22) lower odds of IPIs than those who did not. In conclusion, IPIs are common among Debarq Primary Hospital patients and are associated with factors such as low income, not washing hands after using the toilet, and eating unwashed vegetation, necessitating control and prevention efforts in the study area that include health education and the provision and use of sanitary facilities.
Topics: Humans; Ethiopia; Prevalence; Cross-Sectional Studies; Intestinal Diseases, Parasitic; Risk Factors; Hospitals
PubMed: 38451932
DOI: 10.1371/journal.pone.0298767 -
Indian Journal of Pathology &... Feb 2024Infections caused due to zoonotic hookworms are rare and are often under reported. Here we report a case of diarrheal disease caused by Ancylostoma ceylanicum, an...
Infections caused due to zoonotic hookworms are rare and are often under reported. Here we report a case of diarrheal disease caused by Ancylostoma ceylanicum, an important emerging zoonotic hookworm. There is limited knowledge about the epidemiology and disease burden of A. ceylanicum infections in Kerala. A 50-year-old male patient presented with complaints of loose stools for past five weeks. The laboratory investigations revealed a high total WBC count and eosinophil count. Diagnostic colonoscopy showed numerous worms which were identified as A. ceylanicum. Timely diagnosis aided in successful treatment of the patient. Improvement in diagnostic tools and awareness enable accurate and early detection of this neglected but emerging pathogen.
PubMed: 38427762
DOI: 10.4103/ijpm.ijpm_385_23 -
PloS One 2024The impact of the Global Programme to Eliminate Lymphatic Filariasis (GPELF) (initiated in 2000 in Ghana and ran for 12 years) in mitigating soil-transmitted helminth...
The effectiveness of albendazole against hookworm infections and the impact of bi-annual treatment on anaemia and body mass index of school children in the Kpandai district of northern Ghana.
The impact of the Global Programme to Eliminate Lymphatic Filariasis (GPELF) (initiated in 2000 in Ghana and ran for 12 years) in mitigating soil-transmitted helminth (STH) infections in LF-endemic areas is unknown. During a 1-year hiatus which ensued between 2011 and 2012, a longitudinal study was conducted to determine GPELF effect on hookworm infections in selected communities involved in the programme since its inception, while measuring the effectiveness of biannual ALB treatments on schoolchildren living in such communities. A total of 399 school children aged 3 to 18 years were randomly selected from four communities in the Kpandai district of northern Ghana. Each presented a single stool sample at baseline, 21 days post-treatment, at the 3rd and 6th months, 21 days post-second intervention (i.e. following sample collection and treatment with ALB in the 6th month), and in the ninth month of the study period. Haemoglobin (hb) levels were also measured at all time points using finger prick blood samples and a URIT digital test kit. Each participant submitting a sample, was treated with a single-dose ALB (400mg) at baseline and in the sixth month. Stool samples were processed by preparing duplicate Kato-Katz slides per sample, and examined by microscopy. The Body Mass Index-for-age z-scores (BAZ) of participants were assessed following the determination of BMIs at each time point by measuring their height and weight with a stadiometer and weighing scale. Overall hookworm prevalences were 25.68% (95% CI = 20.51-31.75) at baseline, 11.18% (95% CI = 7.87-15.41) 21 days post-treatment, 11.78% (95% CI = 8.38-16.11) and 6.95% (95% CI = 4.41-10.43) in the 3rd and 6th months, 0.91% (95% CI = 0.19-2.65) 21 days post-second intervention, and 8.46% (95% CI = 5.62-12.23) in the ninth month. Observed overall faecal egg count reduction rates (ERRs) were 94.21% (95% CI = 81.50%- 100.00%) 21 days after baseline treatment, 97.70% (95% CI = 85.08-100.00) and 96.95% (95% CI = 84.18%- 100.00%) in the 3rd and 6th months, 99.98% (95% CI = 86.42%- 100.00%) 21 days post-second intervention, and 17.18% (95% CI = 14.07%- 20.67%) in the 9th month. Respective cure rates (CRs) were 62.35% (95% CI = 46.71-81.56%), 85.88% (95% CI = 67.32-100.00%), 87.06% (95% CI = 68.36%- 100.00%), 98.82% (95% CI = 78.83%- 100.00%), and 36.36% (95% CI = 9.91%- 93.11%). Additionally, increases in the percent frequency of 'normal hb' (p < 0.01) were observed across the study time points, whilst 'normal BAZ' cases remained high (from 94.87% to 98.87%) throughout the study period. These findings primarily indicate satisfactory effectiveness of ALB which may be maintainable in mass drug administration programmes by the modification of treatment strategies from annual to bi-annual regimes. This could minimize the likelihood of emerging poorly-responding hookworm phenotypes in Ghana. Additionally, a positive impact of bi-annual treatment on participant anaemia status is herein indicated with particular regard to the school children in our cohort.
Topics: Child; Humans; Albendazole; Body Mass Index; Ghana; Longitudinal Studies; Hookworm Infections; Anemia; Elephantiasis, Filarial; Feces; Anthelmintics; Soil; Helminthiasis
PubMed: 38427660
DOI: 10.1371/journal.pone.0294977 -
Cytokine May 2024Over the years, there has been progress in understanding the molecular aspects of iron metabolism and erythropoiesis. However, despite research conducted both in...
Over the years, there has been progress in understanding the molecular aspects of iron metabolism and erythropoiesis. However, despite research conducted both in laboratories and living organisms, there are still unanswered questions due to the complex nature of these fields. In this study we investigated the effects of hookworm infection on iron metabolism and how the hosts response to anemia is affected using hamsters infected with Ancylostoma ceylanicum as a model. Our data revealed interesting relationships between infection-induced anemia, erythropoiesis, iron metabolism, and immune modulation, such that the elevated production of erythropoietin (EPO) in renal tissue indicated intensified erythropoiesis in response to anemia. Additionally, the increased expression of the erythroferrone (ERFE) gene in the spleen suggested its involvement in iron regulation and erythropoiesis. Gene expression patterns of genes related to iron metabolism varied in different tissues, indicating tissue-specific adaptations to hypoxia. The modulation of pro-inflammatory and anti-inflammatory cytokines highlighted the delicate balance between immune response and erythropoiesis. Data derived from the investigation of changes induced in iron metabolism and stress erythropoiesis following anemia aid in our understanding of mechanisms related to blood spoliation and anemia, which could potentially be extrapolated or compared to other types or causes of anemia. These findings also contribute to our understanding of the pathophysiology of erythropoiesis in the context of blood loss.
Topics: Humans; Erythropoiesis; Hepcidins; Anemia; Iron; Erythropoietin; Hookworm Infections
PubMed: 38412767
DOI: 10.1016/j.cyto.2024.156559