Anthelmintic and Antibiotic Therapy Resolves Intestinal Inflammatory Infiltration in Experimental Trichuriasis.
Despite significant advances in human health, soil-transmitted helminths (STH) continue to pose a major public health challenge, particularly in impoverished regions. Albendazole has been used to treat STH for over 40 years and remains widely utilized in mass drug administration programs. However, it is estimated that over 1.5 billion people are still infected globally, with Brazil reporting a prevalence of 5.41% for human trichuriasis. The nematode Trichuris muris is widely used in murine models to study trichuriasis due to its impact on the epithelial mucosa, including tissue damage, dysbiosis, bacterial translocation, inflammatory infiltrate, and intestinal layer hypertrophy. These effects contribute to the more severe consequence of high parasite load infections, such as rectal prolapse. Currently, research on the interaction between intestinal helminths and bacteria remains limited, despite its potential contribution to pathological synergy. Drug resistance in conventional STH treatments is a growing concern, highlighting the need for new therapeutic approaches. This study aimed to evaluate the impact of combining the anthelmintic albendazole with the antibiotics piperacillin sodium plus tazobactam on the inflammatory process during chronic experimental trichuriasis. Swiss Webster mice were infected with 150 embryonated T. muris eggs. After 35 days, the mice were divided into four groups: Group 1 (antibiotic treatment), Group 2 (anthelmintic treatment), Group 3 (combined treatment), and Group 4 (control, no treatment). After treatments, the mice were euthanized, and different analyses were conducted. Results showed that untreated mice had a significantly higher number of peritoneal macrophages compared to those that received treatment. Antibiotic-treated mice did not show invading bacteria in the epithelial submucosa, unlike untreated infected mice. The groups that received anthelmintic treatment exhibited a higher number of dead worms compared to the antibiotic-only group. Additionally, the combination of anthelmintic and antibiotic treatments demonstrated more effective control of nematode colonization and bacterial translocation, potentially reducing the secondary impacts of the infection, such as bacterial translocation and the associated inflammatory processes. These findings suggest that our results could pave the way for the development of new treatment protocols for STH, integrating both anthelmintic and antibiotic therapies.
36
- 10.1016/j.actatropica.2019.105226
- Oct 18, 2019
- Acta Tropica
31
- 10.1016/j.tmaid.2015.04.004
- May 1, 2015
- Travel Medicine and Infectious Disease
278
- 10.1111/j.1349-7006.2004.tb03235.x
- Jun 1, 2004
- Cancer Science
202
- 10.1038/s41572-020-0171-3
- May 28, 2020
- Nature Reviews Disease Primers
55
- 10.3347/kjp.2009.47.3.275
- Jan 1, 2009
- The Korean Journal of Parasitology
22
- 10.1111/pim.12032
- Jul 1, 2013
- Parasite Immunology
40
- 10.1016/j.ijpara.2014.09.006
- Dec 5, 2014
- International journal for parasitology
19
- 10.1128/aac.01504-20
- Jan 20, 2021
- Antimicrobial Agents and Chemotherapy
30
- 10.1371/journal.pntd.0005708
- Jun 26, 2017
- PLoS Neglected Tropical Diseases
21
- 10.3390/pathogens10080925
- Jul 22, 2021
- Pathogens
- Dissertation
- 10.14264/uql.2019.581
- Jun 6, 2019
Spatiotemporal impact of an eight-year mass drug administration programme on soil transmitted helminth infections and anaemia in Burundi.
- Research Article
5
- 10.1542/pir.2020-001347
- May 1, 2022
- Pediatrics In Review
Helminth Infections in Children.
- Research Article
20
- 10.1186/s13071-017-2505-x
- Nov 23, 2017
- Parasites & Vectors
BackgroundInvestigating the effect of successive annual deworming rounds on the spatiotemporal distribution of infection prevalence and numbers at risk for soil-transmitted helminths (STHs) can help identify communities nearing elimination and those needing further interventions. In this study, we aim to quantify the impact of an 8-year mass drug administration (MDA) programme (from 2007 to 2014) on the spatiotemporal distribution of prevalence of STH infections and to estimate the number of school-aged children infected with STHs in Burundi.MethodsDuring annual longitudinal school-based surveys in Burundi between 2007 and 2011, STH infection and anthropometric data for a total of 40,656 children were collected; these data were supplemented with data from a national survey conducted in 2014. Bayesian model based geostatistics (MBG) were used to generate predictive prevalence maps for each STH species and year. The numbers of children at-risk of infection per district between 2008 and 2014 were estimated as the product of the predictive prevalence maps and population density maps.ResultsOverall, the degree of spatial clustering of STH infections decreased between 2008 and 2011; in 2014 the geographical clusters of all STH infections reappeared. The reduction in prevalence was small for Ascaris lumbricoides and Trichuris trichiura in the centre and central north of the country. Our predictive prevalence maps for hookworm indicate a reduction in prevalence along the periphery of the country. The predicted number of children infected with any STH species decreased substantially between 2007 and 2011, but in 2014 there was an increase in the predicted number of children infected with A. lumbricoides and T. trichiura. In 2014, the districts with the highest predicted number of children infected with A. lumbricoides, T. trichiura and hookworms were Kibuye district (n = 128,903), Mabayi district (n = 35,302) and Kiremba (n = 87,511), respectively.ConclusionsWhile the MDA programme in Burundi resulted in a reduction in STH prevalence, this reduction was spatiotemporally heterogeneous, with some pockets of high prevalence remaining, suggesting that treatment coverage and complementary interventions should be evaluated to improve impact.
- Research Article
14
- 10.1186/s13071-017-2177-6
- May 23, 2017
- Parasites & vectors
BackgroundCurrent WHO guidelines for soil-transmitted helminth (STH) control focus on mass drug administration (MDA) targeting preschool-aged (pre-SAC) and school-aged children (SAC), with the goal of eliminating STH as a public health problem amongst children. Recently, attention and funding has turned towards the question whether MDA alone can result in the interruption of transmission for STH. The lymphatic filariasis (LF) elimination programme, have been successful in reaching whole communities. There is the possibility of building upon the infrastructure created for these LF-programmes to enhance the control of STH. Using hookworm as an example, we explore what further MDA coverage might be required to induce interruption of transmission for hookworm in the wake of a successful LF programme.ResultsAnalyses based on the model of STH transmission and MDA impact predict the effects of previous LF control by MDA over five years, on a defined baseline prevalence of STH in an area with a defined transmission intensity (the basic reproductive number R0). If the LF MDA programme achieved a high coverage (70, 70 and 60% for pre-SAC, SAC and adults, respectively) we expect that in communities with a hookworm prevalence of 15%, after 5 years of LF control, the intrinsic R0 value in that setting is 2.47. By contrast, if lower LF coverages were achieved (40, 40 and 30% for pre-SAC, SAC and adults, respectively), with the same prevalence of 15% at baseline (after 5 years of LF MDA), the intrinsic hookworm R0 value is predicted to be 1.67. The intrinsic R0 value has a large effect on the expected successes of follow-up STH programmes post LF MDA. Consequently, the outcomes of identical programmes may differ between these communities.ConclusionTo design the optimal MDA intervention to eliminate STH infections, it is vital to have information on historical MDA programmes and baseline prevalence to estimate the intrinsic transmission intensity for the defined setting (R0). The baseline prevalence alone is not sufficient to inform policy for the control of STH, post cessation of LF MDA, since this will be highly dependent on the intensity and effectiveness of past programmes and the intrinsic transmission intensity of the dominant STH species in any given setting.
- Research Article
23
- 10.1371/journal.pntd.0008037
- Apr 13, 2020
- PLOS Neglected Tropical Diseases
BackgroundThe scientific community has recently summarized the desired characteristics for diagnostic tools across the different phases of a soil-transmitted helminth (STH) mass drug administration (MDA) program. Although serology meets some of the desired criteria, there is a scarcity of data on baseline serological profiles in human populations, both prior to and during MDA programs.MethodsIn this study, we compared the copromicroscopic and the serological infection profiles in 600 school-aged children (SAC) and 600 adults at the advent of the MDA program in Jimma Town, Ethiopia. The serological profiles were examined by two ELISAs that measure IgG4 responses to the Ascaris suum haemoglobin antigen (AsHb) and a somatic extract of lung stage larvae (AsLungL3). Three years into the MDA program, we sampled another group of 600 SAC from the same schools to assess the reduction in prevalence and intensity of Ascaris infections measured by copromicroscopy and serology.Principal findingsPrior to the start of MDA, copromicroscopy revealed an Ascaris prevalence of 31.0% and a mean fecal egg count of 2,919 eggs per gram (EPG) in SAC. Following three years of biannual treatment, the prevalence reduced to 13.2% (57.8% reduction) and the mean fecal egg count to 1,513 EPG (48.1% reduction). This reduction was also reflected in the serological results. The seroprevalence reduced with 40.9% and 27.4% and the mean optical density ratio reduced with 44.2% and 38.2% as measured by the AsHb or AsLungL3 ELISA respectively. We also showed that, despite a decreasing coproprevalence, seroprevalence to Ascaris increased with age.ConclusionsThis study is the first to provide IgG4 response profiles of an endemic population to two different A. suum antigens. The results suggest that exposure to the infectious stages of Ascaris reaches beyond SAC alone. Furthermore, it highlights the possible use of serological assays to monitor changes in STH exposure during MDA programs.
- Dissertation
- 10.5451/unibas-005664561
- Jan 1, 2011
Diagnosis, epidemiology and control of soil-transmitted helminth infection in Zanzibar, Tanzania
- Research Article
7
- 10.1016/j.actatropica.2017.03.037
- Apr 1, 2017
- Acta Tropica
Estimating occurrence of Strongyloides stercoralis in the Caribbean island countries: Implications for monitoring and control
- Research Article
8
- 10.1111/cea.12129
- May 28, 2013
- Clinical & Experimental Allergy
Soil-transmitted helminth (STH) infections have been suggested to protect from allergic sensitization and atopic diseases. Consequently, anthelminthic treatment would increase the prevalence of atopic disease in STH endemic populations. To investigate the effect of deworming on allergic sensitization and atopic diseases in Cuban schoolchildren. We followed up 108 STH positive schoolchildren aged 5-13 in six-monthly intervals for 24months. Four consecutive groups of, respectively, 104, 56, 68, and 53 STH positive children were used as 'untreated' reference groups to assess general time trends. STH infections were diagnosed by stool examination. Asthma, allergic rhinoconjunctivitis, and atopic dermatitis were diagnosed by International Study of Asthma and Allergies in Childhood (ISAAC) questionnaire and allergic sensitization by skin prick testing (SPT). At each time point, STH positive children were treated with one single dose of 500mg mebendazole. After deworming, the frequency of asthma significantly decreased (P<0.001) while the frequency of allergic rhinoconjunctivitis and atopic dermatitis was not affected (P=0.129 and P=0.751, respectively). The percentage of SPT positives temporarily increased (P<0.001) and subsequently returned to nearly baseline values (P=0.093). In the references groups, no change over time was observed in the proportion of children with allergic sensitization and atopic diseases (P>0.05). Our results indicate that atopic diseases do not increase after anthelminthic treatment. Allergic sensitization on the other hand increases after deworming. As this increase appears only temporarily, deworming of schoolchildren does not seem to be a risk factor for the development of allergic sensitization, nor for atopic diseases.
- Research Article
56
- 10.1097/qco.0b013e328358993a
- Dec 1, 2012
- Current Opinion in Infectious Diseases
With the London Declaration on neglected tropical disease (NTD), we are entering a new era of combating NTDs. However, the worldwide prospects of increased mass drug administration (MDA) treatments warrant caution on the development of anthelmintic resistance. In this review, we discuss the practical implications of MDA programs on the development of anthelmintic resistance in human soil-transmitted helminths (STH). There is poor evidence of anthelmintic resistance in human STH. Moreover, there is presumptive evidence that the refugia in MDA programs to control human STH is currently large, suggesting that the development of anthelmintic resistance in STH will be slow or may not occur. It remains unclear whether the current MDA strategy to control STH will sufficiently delay or prevent the development of anthelmintic resistance. First, differences in efficacy across and within STH species, and seasonal transmission of STH have not yet been considered. Second, any surveillance system to monitor drug efficacy is lacking. Finally, there is still no agreed strategy on how to deal with anthelmintic resistance once it emerges. Although anthelmintic resistance in human STH is currently of limited concern, various actions should be put in place for its delay and monitoring, and strategies should be developed in case anthelmintic resistance occurs.
- Research Article
6
- 10.3390/ph16020139
- Jan 17, 2023
- Pharmaceuticals
Mass drug administration (MDA) of single-dose albendazole to all at-risk populations as preventive chemotherapy (deworming) is recommended by WHO to halt transmission of soil-transmitted helminth (STH) in endemic countries. We assessed the effectiveness of single-dose albendazole against STH infection in the western province of Rwanda, where STH prevalence remains high despite the implementation of preventive chemotherapy for over a decade. Two weeks before the scheduled MDA, 4998 school children (5-15 years old) were screened for STH infections (Ascaris lumbricoides, Trichuris trichiura, and hookworm), and 1526 children who tested positive for at least one type of STH parasite were enrolled and received single-dose albendazole (400 mg) through MDA. A follow-up stool exam was performed at three weeks post-treatment using Kato-Katz. Efficacy was assessed by cure rate (CR), defined as the proportion of children who became egg-free, and egg reduction rates (ERRs) at three weeks post-treatment. The CR and ERR for hookworms (CR = 96.7%, ERR = 97.4%) was above, and for Ascaris lumbricoides (CR = 95.1%, ERR = 94.6%) was borderline compared with the WHO efficacy threshold (CR and ERR ≥ 95%). However, the CR and ERR for T. trichiura (CR = 17.6% ERR = 40.3%) were below the WHO threshold for efficacy (CR and ERR ≥ 50%). Having moderate-to-heavy infection intensity and coinfection with another type of STH parasites were independent risk factors for lower CR and ERR against Trichirus trichiura (p < 0.001). Single-dose albendazole used in the MDA program is efficacious for the treatment and control for hookworms and Ascaris lumbricoides infections but not effective for Trichirus trichiura. An alternative treatment regimen is urgently needed to prevent, control, and eliminate STH as a public health problem.
- Front Matter
1
- 10.1016/s2666-5247(22)00008-8
- Feb 1, 2022
- The Lancet Microbe
Including women in deworming the world
- Research Article
5
- 10.5530/ijmedph.2.2011.14
- Apr 28, 2011
- International Journal of Medicine and Public Health
International Journal of Medicine and Public Health,2011,1,2,57-59.DOI:10.5530/ijmedph.2.2011.14Published:Apr/2011Type:Short CommunicationPrevalence and Distribution of Soil Transmitted Helminths (STH) among Asymptomatic School Going Children in South Chennai, Tamil Nadu, IndiaN Anbumani, and M Mallika Anbumani. N., Mallika M. Associate Professor, Department of Microbiology, Sri Ramachandra University, Porur, Chennai-600116. Department of Microbiology, Sri Ramachandra University, Porur, Chennai-600116, Tamil nadu, INDIA. Abstract:Soil transmitted helminth (STH ) infections represent a major health problem in poor and developing countries. We conducted a pilot study to determine the prevalence of STH among school going children of Kancheepuram district. Three hundred and fifty eight children in the age group of 5-10 years were examined for STH. One hundred and fourteen of the 358 (40%) were tested positive for various intestinal helminths. The various intestinal helminths are Ascaris lumbricoides, Trichuris trichiura and Taenia species. At least one intestinal helminth was detected in 25.13% (90/358) children and multiple helminth infestation was recorded in 15.08% (54/358). The most common parasitic helminth was A. lumbricoides 60% (84/144) followed by T. trichiura 4.17% (6/144). A. lumbricoides was found as single type infection as well as in association with other helminths in mixed type infection. This study emphasizes the need for improved sanitation and better living conditions for the school-age children in rural areas. Keywords:NillView:PDF (194.46 KB)
- Research Article
38
- 10.1067/mob.2003.78
- Jan 1, 2003
- American Journal of Obstetrics and Gynecology
Use of anthelminthic drugs during pregnancy
- Research Article
6
- 10.3389/fpubh.2021.637866
- Mar 24, 2021
- Frontiers in Public Health
Kenya, just like other countries with endemic soil-transmitted helminths (STH), has conducted regular mass drug administration (MDA) program for the last 5 years among school aged children as a way to reduce STH infections burden in the country. However, the point of interruption of transmission of these infections still remains unclear. In this study, we developed and analyzed an age structured mathematical model to predict the elimination period (i.e., time taken to interrupt STH transmission) of these infections in Kenya. The study utilized a deterministic age structured model of the STH population dynamics under a regular treatment program. The model was applied to three main age groups: pre-school age children (2–4 years), school age children (5–14 years), and adult populations (≥15 years) and compared the impact of two interventions on worm burden and elimination period. The model-simulated results were compared with the 5 year field data from the Kenyan deworming program for all the three types of STH (Ascaris lumbricoides, Trichuris trichiura, and hookworm). The model demonstrated that the reduction of worm burden and elimination period depended heavily on four parameter groups; drug efficacy, number of treatment rounds, MDA and water, sanitation and hygiene (WASH) coverage. The analysis showed that for STH infections to be eliminated using MDA alone in a short time period, 3-monthly MDA plan is desired. However, complementation of MDA with WASH at an optimal (95%) coverage level was most effective. These results are important to the Kenyan STH control program as it will guide the recently launched Breaking Transmission Strategy.
- Dissertation
- 10.31390/gradschool_dissertations.4953
- Jan 1, 2019
Soil-transmitted helminth (STH) infections impact billions of people worldwide. The traditional STH control approach is a morbidity control strategy implementing mass drug administration (MDA) programs targeting school-aged children (SAC). In Brazil, this control strategy has decreased STH prevalence to less than 20% in most of the country and providing an opportunity to transition from the morbidity control program and towards a surveillance and response system geared towards STH elimination. Surveillance and response systems geared towards elimination require the implementation higher accuracy diagnostics to detect infection in low-transmission communities, surveillance of entire households, high-resolution modeling at the household-habitat scale, and targeted treatment approaches tailored to specific communities. This study proposed to create a STH elimination surveillance and response system for the city of Feira de Santana, Brazil. Three communities were evaluated using three diagnostic techniques, entire households were sampled, and high resolution (30 m2) and very high-resolution (VHR) (m2) satellite products were utilized to produce STH ecological niche models (ENMs). In a separate study, a zoonotic Ascaris case in the southern United States was examined. The comparison of the mini-FLOTAC, quantitative PCR (qPCR) and the Ministry of Health Kato-Katz thick smear diagnostic tests revealed that the qPCR diagnostic quantified a significantly greater number of hookworm eggs in stool samples than either the Kato-Katz or the NaCl mini-FLOTAC. Sampling revealed the need to test whole families, as the mean age of STH (29.03), hookworm (29.0), Ascaris lumbricoides (22.29), and Trichuris trichiura (19.2) infections demonstrated. The production of ENMs using the VHR satellites GeoEye-1 (GE1) and WorldView-2 (WV2), and the high-resolution satellite Landsat 8, demonstrated that GE1 provided either superior or comparable model performed compared to WV2, and provided the resolution needed to effectively model STH niches at the household and its surrounding habitat. The differing STH prevalence and environmental risk factors between the 3 communities demonstrated the need to evaluate communities individually and craft targeted interventions. Genetic analysis in the case study determined that the cause of infection was zoonotic Ascaris suum. This study outlined steps towards implementing an STH elimination surveillance and response system for Fiera de Santana, Brazil.
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