Single nucleotide polymorphisms in the β-tubulin gene family of Ascaris lumbricoides and their potential role in benzimidazole resistance: a systematic review

IntroductionThe most common soil-transmitted helminthic infection is caused by Ascaris lumbricoides (A. lumbricoides). Approximately 4 billion people are at risk of infection globally. The World Health Organisation recommends the administration of benzimidazole- containing deworming drugs (Albendazole and Mebendazole) to all susceptible populations. Due to this high drug pressure, these parasites may develop resistance to current benzimidazole drugs. The β-tubulin gene family is the target gene for benzimidazole deworming drugs. This systematic review aimed to highlight work that explored the genetic mutations in the β-tubulin gene family of A. lumbricoides that are associated with potential benzimidazole resistance.MethodsAn electronic search of several online databases was used to extract eligible articles using specific keywords related to the topic of interest.ResultsThe majority of ascariasis infections occur in the subtropical and tropical regions of sub-Saharan Africa, the Americas and East Asia, although not enough studies were done to extensively cover this geographical range. In the β-tubulin gene family of A. lumbricoides the mutations at codons F200Y (TTC/Phenylalanine to TAC/Tyrosine), E198A (GAG, GAA/Glutamic acid to GCG, GCA/Alanine) and F167Y (TTC, TTT/Phenylalanine to TAC, TAT/Tyrosine) were associated with potential benzimidazole resistance.DiscussionResistant mutations were found in A. lumbricoides samples at codon F167Y from Haiti, Kenya and Panama. The first evidence of the mutation at codon F200Y was observed in Brazil. The codon E198A mutation was the least prevalent and most undetected.ConclusionThere is a serious shortage of studies investigating the prevalence of β-tubulin gene family mutations in A. lumbricoides populations from endemic areas; this is a serious concern as resistance will negatively impact current mass drug administration programmes

Helminthiasis: A Systematic Review of the Immune Interactions Present in Individuals Coinfected with HIV and/or Tuberculosis

Helminth infections are highly endemic in parts of the world where the two killer epidemics caused by Mycobacterium tuberculosis (M.tb) and the human immunodeficiency virus (HIV) intersect. Sub-Saharan Africa is hardest hit by this epidemiological overlap. Consequently, several studies have investigated the immunological outcomes of helminth coinfection with either HIV or M.tb, to elucidate the central hypothesis that chronic infection with helminths exacerbates the course of HIV and tuberculosis disease. However, there is no conclusive evidence to confirm whether helminth-induced immunity modulates HIV- and TB-specific immune responses and their pathogenesis or vice versa. The present chapter summarizes the epidemiology, clinical course, and immune interactions during helminths and HIV/TB coinfections and undertakes a systematic review of the existing literature published from Africa on this subject. The aim was to determine if chronic helminthiasis has a negative impact on HIV and TB infections. A PubMed search was undertaken with no language and time restrictions. Search terms used included a varied combination of “Helminth coinfection and immunity and TB coinfection or TB immunity and HIV coinfection or HIV immunity and Africa.” Names of individual species were also permutated in the search terms. Reviews and bibliographies of selected articles were screened to identify additional relevant articles or studies. Of the total 1021 articles retrieved, 47 were relevant with 31 helminth and HIV coinfection and 16 helminths and TB coinfection articles. While many studies failed to find a negative impact of helminth infection on immune responses to HIV and/or TB, a significant number found evidence of deleterious effects of coinfection with helminths such as immune activation, impaired Th1 responses to TB antigens, higher viral loads, lower CD4+ counts, and increased risks of antiretroviral immunologic failure, mother to child HIV transmission or TB disease. Some of the helminth-induced immune dysregulation was reversed by deworming, while some studies found no benefit of antihelminthic treatment. More studies particularly in Southern Africa are needed to increase the much sought evidence of the impact of deworming among HIV-infected individuals as this seems the most feasible, cost-effective intervention with little or no serious adverse effects. Lastly, with the expansion of ART and increased access to HIV treatment, the effects of helminths on vaccines, TB, and antiretroviral treatments efficacy also need serious consideration, in light of the suggestive evidence of possible immunologic failure due to helminth coinfection

Excretory-secretory products from adult helminth <i>Nippostrongylus brasiliensis</i> have <i>in vitro</i> bactericidal activity

Introduction. Intestinal helminths and microbiota share the same anatomical niche during infection and are likely to interact either directly or indirectly. Whether intestinal helminths employ bactericidal strategies that influence their microbial environment is not completely understood.Hypothesis. In the present study, the hypothesis that the adult hookworm Nippostrongylus brasiliensis produces molecules that impair bacterial growth in vitro, is tested.Aim. To investigate the in vitro bactericidal activity of Nippostrongylus brasiliensis against commensal and pathogenic bacteria.Methodology. The bactericidal effect of somatic extract and excretory-secretory products of adult Nippostrongylus brasiliensis on Gram-positive (Staphylococcus aureus) and Gram-negative (Escherichia coli, Salmonella enterica serovar Typhimurium, and Klebsiella pneumoniae) bacteria was assessed using growth assays. Minimum inhibitory concentration and minimum bactericidal concentration assays were performed using excretory-secretory products released from the pathogen.Results. Broad-spectrum in vitro bactericidal activity in excretory-secretory products, but not somatic extract of adult Nippostrongylus brasiliensis was detected. The bactericidal activity of excretory-secretory products was concentration-dependent, maintained after heat treatment, and preserved after repeated freezing and thawing.Conclusion. The results of this study demonstrate that helminths such as Nippostrongylus brasiliensis release molecules via their excretory-secretory pathway that have broad-spectrum bactericidal activity. The mechanisms responsible for this bactericidal activity remain to be determined and further studies aimed at isolating and identifying active bactericidal molecules are needed

The influence of different helminth infection phenotypes on immune responses against HIV in co-infected adults in South Africa

<p>Abstract</p> <p>Background</p> <p>The convergent distribution of the Human Immunodeficiency Virus (HIV) and helminth infections has led to the suggestion that infection with helminths exacerbates the HIV epidemic in developing countries. In South Africa, it is estimated that 57% of the population lives in poverty and carries the highest burden of both HIV and helmith infections, however, the disease interactions are under-researched.</p> <p>Methods</p> <p>We employed both coproscopy and <it>Ascaris lumbricoides</it>-specific serum IgE to increase diagnostic sensitivity and to distinguish between different helminth infection phenotypes and their effects on immune responses in HIV co-infected individuals. Coproscopy was done by formol ether and Kato Katz methods. HIV positive and negative adults were stratified according to the presence or absence of <it>A. lumbricoides </it>and/or <it>Trichuris trichuria </it>eggs with or without elevated <it>Ascaris </it>IgE. Lymphocyte subsets were phenotyped by flow cytometry. Viral loads, serum total IgE and eosinophils were also analysed. Lymphocyte activation markers (CCR5, HLA-DR, CD25, CD38 and CD71) were determined. Non parametric statistics were used to describe differences in the variables between the subgroups.</p> <p>Results</p> <p>Helminth prevalence ranged between 40%-60%. Four distinct subgroups of were identified, and this included egg positive/high <it>Ascaris</it>-specific IgE (egg⁺IgE^hi), egg positive/low IgE (egg⁺IgE^lo), egg negative/high IgE (egg^-IgE^hi) and egg negative/low IgE (egg^-IgE^lo) individuals. The egg⁺IgE^hisubgroup displayed lymphocytopenia, eosinophilia, (low CD4⁺counts in HIV^-group), high viral load (in HIV⁺group), and an activated lymphocyte profile. High <it>Ascaris </it>IgE subgroups (egg⁺IgE^hiand egg^-IgE^hi) had eosinophilia, highest viral loads, and lower CD4⁺counts in the HIV^-group). Egg excretion and low IgE (egg⁺IgE^lo) status demonstrated a modified Th₂immune profile with a relatively competent response to HIV.</p> <p>Conclusions</p> <p>People with both helminth egg excretion and high <it>Ascaris</it>-IgE levels had dysregulated immune cells, high viral loads with more immune activation. A modified Th₂helminth response in individuals with egg positive stools and low <it>Ascaris </it>IgE showed a better HIV related immune profile. Future research on helminth-HIV co-infection should include parasite-specific IgE measurements in addition to coproscopy to delineate the different response phenotypes. Helminth infection affects the immune response to HIV in some individuals with high IgE and egg excretion in stool.</p

Proliferative capacity and cytokine production by cells of HIV-infected and uninfected adults with different helminth infection phenotypes in South Africa

CITATION: Mkhize-Kwitshana, Z. L., Mabaso, M. L. & Walzl, G. 2014. Proliferative capacity and cytokine production by cells of HIV-infected and uninfected adults with different helminth infection phenotypes in South Africa. BMC Infectious Diseases, 14:499, doi:10.1186/1471-2334-14-499.The original publication is available at http://bmcinfectdis.biomedcentral.comBackground: It has been suggested that the proliferative capacity of cells from individuals with HIV or both HIV and helminth infections is attenuated and cytokine production is dysregulated. This study describes peripheral blood mononuclear cell proliferation capacity and cytokine profile from individuals with HIV or both HIV and helminth infections in South Africa. Methods: Forty HIV-infected and 22 HIV-uninfected participants were randomly selected and stratified into different helminth infection phenotypes by egg excretion and Ascaris lumbricoides specific –immunoglobulin-E (IgE) levels. Five day cell cultures of participants, unstimulated or stimulated with Phytohaemaglutinnin, Streptokinase, HIV-1 p24 and Ascaris lumbricoides worm antigens were stained with monoclonal antibody-fluorochrome conjugates (Ki67-FITC and CTLA-APC-4). Percentage expression of Ki67 and CTLA-4 was measured to determine cell proliferation and regulation, respectively. Culture supernatants were analysed for the expression of 13 cytokines using the Bioplex (BioRad) system. Kruskal Wallis was used to test for differences in variables between helminth infected subgroups who were either having eggs in stool and high IgE (egg+IgEhi); or eggs in stool and low IgE (egg+IgElo); or no eggs in stool and high IgE (egg−IgEhi) and those without helminth infection (egg−IgElo). Results: Individuals excreting eggs in stool with high serum IgE (egg+IgEhi phenotype) had potent mitogen responses but consistently produced low, but statistically non-significant antigen–specific (HIV−1 p24 (p = 0.41) and Ascaris (p = 0.19) and recall antigen (Streptokinase; p = 0.31) Ki67 responses. The group also had reduced type 1 cytokines. Individuals excreting eggs in stool with low serum IgE( egg+IgElo phenotype) had a more favourable antiviral profile, characterized by higher IFNγ, IL-2, lower IL-4 and higher IL-10 production. Conclusion: The findings suggest that dual HIV/helminth infection with egg excretion and/or high Ascaris IgE phenotye may be linked with poor proliferative capacity and deleterious cytokine profile with regards to HIV control.http://bmcinfectdis.biomedcentral.com/articles/10.1186/1471-2334-14-499Publisher's versio

Overview of Maternal, Neonatal and Child Deaths in South Africa: Challenges, Opportunities, Progress and Future Prospects

Background: The fact that most sub-Saharan Africa countries including South Africa (SA) are not on track to meet the 2015 target of improving maternal, neonate and child health (MNCH) is a major public health concern. The aim of this paper to give an overview of the current state of MNC deaths in SA, their relative causes, highlight challenges, existing opportunities, progress made and future prospects. Methods: The overview involved a synthesis and review of recent data and information from key national representative peer reviewed articles and grey literature from the National Department of Health and related stakeholder reports. Results: Since 1990 the situation in SA aroused a lot of research interest in tracing the historical context of the problem, evaluating progress made and actions for improving MNCH. In 2009 the SA government established three national committees for confidential enquiry on MNC deaths. Multifactorial systems’ related challenges were identified. Subsequently, the new National Strategic Plan for MNC and Women’s Health and Nutrition has, in addition to provision of comprehensive interventions, been linked and aligned with efforts to strengthen the health systems particularly through the re-engineering of the Primary Health Care (PHC) services and district health systems. Conclusion and Global Health Implications: The overview gives an insight of the process that has influenced MNCH policy and programs in the country. The SA experience and current MNCH situation may be different compared to other African countries, however, the political commitment and government stewardship coupled with critical and yet complimentary research is exemplary, especially, given several global and regional plans and commitments to improve MNCH in the continent. Keywords: South Africa • Maternal, neonatal, child deaths • Health • Interventions • Millennium Development Goals Copyright 2014 © Mabaso et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited

Immunological Interactions between Intestinal Helminth Infections and Tuberculosis

Helminth infections are among the neglected tropical diseases affecting billions of people globally, predominantly in developing countries. Helminths&rsquo; effects are augmented by coincident tuberculosis disease, which infects a third of the world&rsquo;s population. The role of helminth infections on the pathogenesis and pathology of active tuberculosis (T.B.) remains controversial. Parasite-induced suppression of the efficacy of Bacille Calmette-Guerin (BCG) has been widely reported in helminth-endemic areas worldwide. T.B. immune response is predominantly proinflammatory T-helper type 1 (Th1)-dependent. On the other hand, helminth infections induce an opposing anti-inflammatory Th2 and Th3 immune-regulatory response. This review summarizes the literature focusing on host immune response profiles during single-helminth, T.B. and dual infections. It also aims to necessitate investigations into the complexity of immunity in helminth/T.B. coinfected patients since the research data are limited and contradictory. Helminths overlap geographically with T.B., particularly in Sub-Saharan Africa. Each disease elicits a response which may skew the immune responses. However, these effects are helminth species-dependent, where some parasites have no impact on the immune responses to concurrent T.B. The implications for the complex immunological interactions that occur during coinfection are highlighted to inform government treatment policies and encourage the development of high-efficacy T.B. vaccines in areas where helminths are prevalent

Rodent-borne zoonoses in Qatar: A possible One-Health framework for the intervention of future epidemic

The increasing frequency of spillover of zoonotic pathogens from animals to humans in recent years highlights a need to develop a more comprehensive framework to investigate and prevent pathogens of animal origin, including rodents. Despite the presence of several species of rodents, there is a certain knowledge gap regarding rodent-borne zoonoses in Qatar. The current review provides an update on rodent-borne zoonoses in Qatar, its possible drivers and transmission dynamics, and proposed a One Health framework for intervention. Following an extensive literature review, we conducted a field investigation. Then the qualitative information and knowledge gaps were addressed with a virtual discussion with national, regional, and international experts in the relevant field. Overall, Rattus norvegicus population was found to be more prevalent, followed by Rattus rattus, and M. musculus, which are mainly found in animal farms, followed by agricultural farms, residential areas, and other facilities. Over 50% of rodents carry at least one pathogen of public health importance. Several pathogens were identified at the human, animal, and ecosystem interface, which can be mediated in transmission by rodents. E. coli, Salmonella spp., and Campylobacter spp. are the frequently reported bacteria. Hymenolepis spp., Cryptosporidium spp., Giardia spp., Entamoeba spp., and Toxoplasma spp. are the major parasites. In addition, many vectors, including Ornithonyssus bacoti and Xenopsylla astia were reported in this country. Based on the changes over the past 70 years in Qatar, seven drivers have been identified, which could be important in rodent-borne disease emergences, such as the Oil and gas revolution, fast population growth, rapid urbanization, importation of food and agricultural products, agricultural and livestock development, farm biosecurity, and stray animals. The experts emphasized that mixed-species animal farming with poor biosecurity and management can be associated to increase the risk of zoonoses. Moreover, rapid urbanization and global climate change together can alter the ecosystem of the country and impact on vectors and vector-borne diseases. Finally, the One Health framework has been proposed for the surveillance, and mitigation of any future spillover or epidemic of rodent-borne zoonoses