Helminth Co-infection Research Articles

The extent, nature, and pathogenic consequences of helminth polyparasitism in humans: A meta-analysis.

BackgroundIndividual helminth infections are ubiquitous in the tropics; geographical overlaps in endemicity and epidemiological reports suggest areas endemic for multiple helminthiases are also burdened with high prevalences of intestinal protozoan infections, malaria, tuberculosis (TB), and human immunodeficiency virus (HIV). Despite this, pathogens tend to be studied in isolation, and there remains a need for a better understanding of the community ecology and health consequences of helminth polyparasitism to inform the design of effective parasite control programs.MethodologyWe performed meta-analyses to (i) evaluate the commonality of polyparasitism for helminth-helminth, helminth-intestinal protozoa, helminth-malaria, helminth-TB, and helminth-HIV co-infections, (ii) assess the potential for interspecies interactions among helminth-helminth and helminth-intestinal protozoan infections, and (iii) determine the presence and magnitude of association between specific parasite pairs. Additionally, we conducted a review of reported health consequences of multiply-infected individuals compared to singly- or not multiply-infected individuals.Principal findingsWe found that helminth-helminth and helminth-intestinal protozoan multiple infections were significantly more common than single infections, while individuals with malaria, TB, and HIV were more likely to be singly-infected with these infections than co-infected with at least one helminth. Most observed species density distributions significantly differed from the expected distributions, suggesting the potential presence of interspecies interactions. All significant associations between parasite pairs were positive in direction, irrespective of the combination of pathogens. Polyparasitized individuals largely exhibited lower hemoglobin levels and higher anemia prevalence, while the differences in growth-related variables were mostly statistically insignificant.ConclusionsOur findings confirm that helminth polyparasitism and co-infection with major diseases is common in the tropics. A multitude of factors acting at various hierarchical levels, such as interspecies interactions at the within-host infra-parasite community level and environmental variables at the higher host community level, could explain the observed positive associations between pathogens; there remains a need to develop new frameworks which can consider these multilevel factors to better understand the processes structuring parasite communities to accomplish their control.

Liver fluke (Fasciola hepatica) co-infection with bovine tuberculosis in cattle: A prospective herd-level assessment of herd bTB risk in dairy enterprises.

Co-infection of tuberculosis (TB) and helminths is recognized as a significant problem in regions where such pathogens are endemic and chronic cases exist. Co-infection can modulate the immune system leading to interference with diagnostic tests, increased pathological impacts and pathogen persistence. However, research has found that such interactions between pathogens can be context and species specific. Recent studies have suggested that liver fluke, Fasciola hepatica, infection may impact on immunological responses and diagnostics for bovine tuberculosis (bTB; caused by Mycobacterium bovis) in cattle. Where evidence of such interaction exists, there would be an onus on policy makers to adjust eradication programs to minimize impacts. We assessed the association between herd-level bTB breakdown risk and seasonal variation in liver fluke exposure based on 5,753 bulk tank milk (BTM) samples from 1,494 dairy herds across Northern Ireland. BTM was tested by an IDEXX antibody specific enzyme-linked immunosorbent assay (ELISA) using the 'f2' antigen as a detection agent. The ELISA determined the result based on a sample to (known) positive ratio (S/P%) from which binary status and categories of exposure were derived. Associations were tested using multivariable random effects models. Models predicting bTB risk were not improved with the inclusion of liver fluke exposure levels. Variations in modelling liver fluke exposure (S/P%, binary, categories of exposure) and bTB risk (skin test breakdowns, post-mortem confirmed breakdowns, breakdown size and lag effects) also failed to support associations (neither positive nor negative) between the pathogens at herd-level. These results, along with previously published animal-level data from Northern Ireland, suggest that the nexus between bTB and F.hepatica may have small size effects at the population-level. However, our results also highlight the high prevalence of F.hepatica in cattle in our study population, and therefore we cannot fully discount the potential hypothesis of population-level depression of immune response to M.bovis due to co-infection.

Effect of co-infection with a small intestine-restricted helminth pathogen on oral prion disease pathogenesis in mice

The early replication of some orally-acquired prion strains upon stromal-derived follicular dendritic cells (FDC) within the small intestinal Peyer’s patches is essential to establish host infection, and for the disease to efficiently spread to the brain. Factors that influence the early accumulation of prions in Peyer’s patches can directly influence disease pathogenesis. The host’s immune response to a gastrointestinal helminth infection can alter susceptibility to co-infection with certain pathogenic bacteria and viruses. Here we used the natural mouse small intestine-restricted helminth pathogen Heligmosomoides polygyrus to test the hypothesis that pathology specifically within the small intestine caused by a helminth co-infection would influence oral prion disease pathogenesis. When mice were co-infected with prions on d 8 after H. polygyrus infection the early accumulation of prions within Peyer’s patches was reduced and survival times significantly extended. Natural prion susceptible hosts such as sheep, deer and cattle are regularly exposed to gastrointestinal helminth parasites. Our data suggest that co-infections with small intestine-restricted helminth pathogens may be important factors that influence oral prion disease pathogenesis.

PO 8571 CYTOKINE PROFILE IN ASYMPTOMATIC SCHOOL CHILDREN CO-INFECTED WITH HELMINTHS ANDPLASMODIUM FALCIPARUMIN IBADAN, SOUTH-WEST NIGERIA

BackgroundIntestinal helminths and malaria are among the most prevalent infectious diseases in the tropics. The effect of co-infections on immune response is not clearly understood. We therefore investigated the immune response profile in children with and without symptoms.MethodsA total of 78 afebrile school children (20 helminth/malaria-co-infected, 17 helminth-infected, 19 malaria-infected and 22 uninfected) and 75 febrile children (14 helminth/malaria-co-infected, 16 helminth-infected, 20 malaria-infected and 25 uninfected) were recruited into the study. Helminths were screened using Kato Katz method while malaria parasite screening was done using Giemsa-stained thick blood films. Circulating TNF-α, IFN-γ, IL-1, IL-10 and IL-6 concentrations were assessed by ELISA from serum samples. Data were analysed using analysis of variance.ResultsAmong the afebrile school children, IL-10 was significantly increased in helminth-infected children compared with helminth/malaria-co-infected, malaria-infected and uninfected groups (p<0.05). IFN-γ was significantly elevated in malaria and malaria/helminth-co-infection relative to helminth alone (p<0.05). IL-1 level was significantly higher in single infection of helminth and malaria relative to co-infection and the uninfected groups (p<0.05). An insignificant difference was observed for IL-6 and TNF-α concentrations across all the four groups while among febrile children. IL-6 was significantly increased among helminth alone and helminth/malaria-co-infection relative to malaria-infected group (p<0.05). IL-10 was significantly elevated in co-infected group compared with helminth- or malaria-infected group while TNF-α was significantly increased in helminth and helminth-malaria co-infection compared with uninfected or malaria-infected group (p<0.05). IFN-γ level was insignificant in the infection groups relative to uninfected group (p<0.05); IL-1 level similar across the groups.ConclusionHelminth infection seems to upregulate the Th2 immune response among children with symptomatic uncomplicated malaria while there were no significant changes in Th immune response among afebrile children.

Uncomplicated Malaria and Intestinal Helminth Co-Infections among Schoolchildren in Abobo District, Abidjan (Côte d'Ivoire)

Malaria and soil-transmitted helminth infections are morbidity causes in most tropical areas in the world. In Côte d'Ivoire, their association greats a major public health problem and their coexistence is the subject of very few studies. The current study investigated uncomplicated malaria and intestinal helminths co-infection among schoolchildren in Abobo District, Abidjan. This cross-sectional study was conducted with 256 children aged 2 to 15 recruited at the Anonkoua - Kouté Urban and Community Health Centre and at the El-Rapha health centre in the Commune of Abobo in Abidjan. Blood and stool samples were collected from each child. A thick drop examination was carried out on the blood samples whereas the parasitic examination test consisted of a direct microscopic examination, the simplified Ritchie and the Kato techniques.

Exposure and susceptibility drive reinfection with gastrointestinal parasites in a social primate

Abstract Increased risk of infectious disease transmission has been proposed as one major cost of group living. While factors corresponding to transmission via exposure to infectious stages and susceptibility to contracting infections upon contact are relatively well understood, both aspects are rarely investigated simultaneously. Here, we assessed the influence of exposure and susceptibility measures on strongyle nematode reinfection after experimental deworming of Barbary macaques (Macaca sylvanus) (n = 57). We investigated impacts of behaviour (social bonds, grooming and ground use) and physiology (faecal glucocorticoids, urinary C‐Peptides, urinary neopterin, gastrointestinal [GI] helminth coinfection) on the likelihood of reinfection, using patch occupancy modelling and information theoretic model selection to determine the best models predicting reinfection patterns. Coinfection was the most consistent risk factor, spending time on presumably contaminated soil, interacting with many partners and forming strong same‐sex bonds also tended to increase infection risk. In contrast, strong social bonds with opposite‐sex partners had a consistently protective effect. Our results indicate that coinfections could serve as an integrative measure of individual disease susceptibility. Furthermore, we show that social contact contributes to both exposure and susceptibility to environmentally transmitted parasites, with the outcome depending on specific interaction patterns. A plain language summary is available for this article.

Intestinal helminth infections in HIV-infected patients in Savannakhet after establishment of an HIV registration network in Lao People\u2019s Democratic Republic

BackgroundIn Lao People’s Democratic Republic (PDR), which borders China, Vietnam, Cambodia, Thailand, and Myanmar, the number of HIV-infected patients has increased in recent years. HIV-infected patients diagnosed in Lao PDR are enrolled in a registration network and receive antiretroviral therapy (ART) covered by governmental financial support. Based on the registration network, we investigated intestinal helminth infections and coinfection with HTLV-1 in HIV-infected patients treated with an early intervention using ART in Lao PDR.MethodsThis cross-sectional study of all 252 HIV-infected patients at Savannakhet Provincial Hospital, located in the southern part of Lao PDR, was conducted between February and March 2018. Socioepidemiological information and clinical information were collected from a registration network database and by questionnaire administered to participants. Microscopic examination of intestinal helminth infections in stool samples and particle agglutination for anti-HTLV-1 antibody in plasma were performed.ResultsThe median age of all 252 participants was 39 years old (range, 18–59). Based on the registration network database, there were 156 (61.9%) HIV-infected patients with a CD4-positive cell count ≥ 200 cells/μL and 146 (57.9%) with an HIV viral load < 250 copies/mL. Among 212 stool samples, 75 (35.4%) were found to contain one or more intestinal helminth species, including Opisthorchis viverrini (16.5%), Strongyloides stercoralis (10.8%), hookworm (10.4%), and Taenia saginata (3.3%). This rate of intestinal helminth infections was lower than that of a previous report conducted before the establishment of the registration network for HIV-infected patients in Lao PDR. There was no significant association between intestinal helminth infections and a lower CD4-positive T cell count or higher HIV viral load. HIV-infected patients with anti-HTLV-1 antibody positivity were not found in this cohort.ConclusionThe registration network and an early intervention using ART may provide good medical care and improve the clinical course of HIV-infected patients in Lao PDR. However, the incidence of intestinal helminth infections remains high at 35.4%. The development of a specific medical care system for helminth infection for HIV-infected patients is necessary.

Antagonistic effects of Plasmodium-helminth co-infections on malaria pathology in different population groups in Côte d'Ivoire.

IntroductionPlasmodium spp. and helminths are co-endemic in many parts of the tropics; hence, co-infection is a common phenomenon. Interactions between Plasmodium and helminth infections may alter the host’s immune response and susceptibility and thus impact on morbidity. There is little information on the direction and magnitude of such interactions and results are conflicting. This study aimed at shedding new light on the potential interactions of Plasmodium and helminth co-infections on anemia and splenomegaly in different population groups in Côte d’Ivoire.MethodologyParasitologic and clinical data were obtained from four cross-sectional community-based studies and a national school-based survey conducted between 2011 and 2013 in Côte d’Ivoire. Six scenarios of co-infection pairs defined as Plasmodium infection or high parasitemia, combined with one of three common helminth infections (i.e., Schistosoma mansoni, S. haematobium, and hookworm) served for analysis. Adjusted logistic regression models were built for each scenario and interaction measures on additive scale calculated according to Rothman et al., while an interaction term in the model served as multiplicative scale measure.Principal findingsAll identified significant interactions were of antagonistic nature but varied in magnitude and species combination. In study participants aged 5–18 years from community-based studies, Plasmodium-hookworm co-infection showed an antagonistic interaction on additive scale on splenomegaly, while Plasmodium-Schistosoma co-infection scenarios showed protective effects on multiplicative scale for anemia and splenomegaly in participants aged 5–16 years from a school-based study.Conclusions/SignificanceNo exacerbation from co-infection with Plasmodium and helminths was observed, neither in participants aged 5–18 years nor in adults from the community-based studies. Future studies should unravel underlying mechanisms of the observed interactions, as this knowledge might help shaping control efforts against these diseases of poverty.

Status of intestinal parasitic infections among rural and urban populations, southwestern Iran

Objective: To evaluate the prevalence and risk factors of intestinal parasitic infections in the urban and rural areas of Shushtar County, southwest Iran. Methods: A total of 1 008 fecal samples were analyzed by direct smear examination, formalin-ether concentration, and Ziehl-Neelsen and trichrome staining; furthermore, PCR was used to distinguish Trichostrongylus and hookworm species based on 28S rRNA gene. Results: Totally, 16.0% cases tested positive, either with a pathogenic or a non-pathogenic parasite. Protozoa were detected in 14.0%, helminths in 1.0%, protozoa and helminth co-infections were detected in 0.3%, and co-infections of two protozoa were detected in 0.7% of cases. The most common protozoa and helminths were Giardia duodenalis (7.7%) and Trichostrongylus spp. (0.5%), respectively. Among five microscopy Trichostrongylus positive cases, Trichostrongylus culbriformis was successfully identified in three isolates by sequencing. In the rural areas, the prevalence of parasitic infection was higher (9.8%) than that in the urban areas (6.2%). A significant association was found between educational level, type of drinking water, animals contact, hand-washing, and clinical symptoms. Conclusions: This study indicates that intestinal parasitic infections remain as a public health priority in Shushtar County. It seems that drinking water and environmental sanitation are the main risk factors of parasitic infections in rural areas.

Anemia among Schoolchildren with Malaria and Soil-Transmitted Helminth Coinfections after Repeated Rounds of Mass Drug Administration in Muheza District, Tanzania.

Coinfections with malaria and soil-transmitted helminths (STHs) has been common among school-aged children in Tanzania. However, after a countrywide scaling up of interventions for malaria and STHs, there are limited data on the prevalence of malaria-STH coinfections and its effect on anemia in schoolchildren in Tanzania. We assessed the distribution and risk factors for malaria, STHs, and malaria-STH coinfections, and its relation to anemia among 445 primary schoolchildren in Muheza district. A semi-structured questionnaire was used to collect demographic characteristics of the children. Malaria rapid diagnostic test (mRDT) was used to diagnose malaria infection. Soil-transmitted helminths were diagnosed using the Kato-Katz technique. Primary outcome was anemia, defined as hemoglobin concentration < 11 g/dL. Chi-square (χ2) or Fisher's exact tests, Kruskal-Wallis or t-test, and logistic models were used as appropriate. Overall, the prevalence of malaria, STHs, malaria-STH coinfection, and anemia were 18.4%, 6.1%, 1.6%, and 19.8%, respectively. Anemic children were more likely to have malaria (adjusted odds ratio [aOR] = 4.538, 95% CI: 2.189-9.409), whereas frequent use of bed nets was associated with reduced risk of malaria (aOR = 0.234, 95% CI: 0.130-0.42). On the other hand, not always using latrines and eating raw uncooked food increased the risk of STH infection. The prevalence of anemia was high and was associated with both malaria and malaria-STH infections, therefore calling for more integrated malaria-STH control approaches to target school-aged children.

Globalization effects on the reports of non-endemic parasitosis in Italy

Protozoa and helminths are responsible for several intestinal parasite infections (IPIs). Generally, helminth infections are very unsafe but scarcely reported in high-income countries, while protozoa and helminth co-infections are usually reported in children living in inadequate hygienic-sanitary conditions and in rural areas. However, the impact of growing globalization, intense travelling, international adoptions and high levels of immigrants and refugees has significantly incremented the incidence of orofecal parasitosis in non-endemic areas. Although most IPs clear without treatment when population, even children, emigrate from endemic to different geographical areas, some IPIs such as strongyloidiasis may persist for decades as subclinical infections or as low-grade disease with nonspecific clinical manifestations, unless to reappear under impairment conditions. Herein we report an unusual case of Giardia lamblia and Trichuris spp. chronic asymptomatic co-infection in a healthy adopted Romanian child, living in a Central Italy rural area, and a hidden case of Strongyloides stercoralis in an adopted Burundian child, resident in South Italy, long misdiagnosed as a recurrent undefined dermatitis. Our report suggests the need to review primary care practitioner guidelines and children’s hospital procedures for appropriate IPIs screening and follow-up, hence providing new screening and prevention strategies, in agreement with international guidelines.

Helminth Infections Induce Tissue Tolerance Mitigating Immunopathology but Enhancing Microbial Pathogen Susceptibility.

Helminths are ubiquitous and have chronically infected vertebrates throughout their evolution. As such helminths have likely exerted considerable selection pressure on our immune systems. The large size of multicellular helminths and their limited replicative capacity in the host necessarily elicits different host protective mechanisms than the immune response evoked by microbial pathogens such as bacteria, viruses and intracellular parasites. The cellular damage resulting from helminth migration through tissues is a major trigger of the type 2 and regulatory immune responses, which activates wound repair mechanisms that increases tissue tolerance to injury and resistance mechanisms that enhance resistance to further colonization with larval stages. While these wound healing and anti-inflammatory responses may be beneficial to the helminth infected host, they may also compromise the host's ability to mount protective immune responses to microbial pathogens. In this review we will first describe helminth-induced tolerance mechanisms that develop in specific organs including the lung and the intestine, and how adaptive immunity may contribute to these responses through differential activation of T cells in the secondary lymphoid organs. We will then integrate studies that have examined how the immune response is modulated in these specific tissues during coinfection of helminths with viruses, protozoa, and bacteria.

Complex interactions in soil-transmitted helminth co-infections from a cross-sectional study in Sri Lanka.

BackgroundCo-infection with multiple soil-transmitted helminth (STH) species is common in communities with a high STH prevalence. The life histories of STH species share important characteristics, particularly in the gut, and there is the potential for interaction, but evidence on whether interactions may be facilitating or antagonistic are limited.MethodsData from a pretreatment cross-sectional survey of STH egg deposition in a tea plantation community in Sri Lanka were analysed to evaluate patterns of co-infection and changes in egg deposition.ResultsThere were positive associations between Trichuris trichiura (whipworm) and both Necator americanus (hookworm) and Ascaris lumbricoides (roundworm), but N. americanus and Ascaris were not associated. N. americanus and Ascaris infections had lower egg depositions when they were in single infections than when they were co-infecting. There was no clear evidence of a similar effect of co-infection in Trichuris egg deposition.ConclusionsAssociations in prevalence and egg deposition in STH species may vary, possibly indicating that effects of co-infection are species dependent. We suggest that between-species interactions that differ by species could explain these results, but further research in different populations is needed to support this theory.

GUT PARASITE LEVELS ARE ASSOCIATED WITH SEVERITY OF RESPONSE TO IMMUNE CHALLENGE IN A WILD SONGBIRD.

Life history trade-offs have been posited to shape wild animals' immune responses against microparasites (e.g., bacteria, viruses). However, coinfection with gut helminths may bias immune phenotypes away from inflammatory responses and could be another mechanism underlying variation in immune responses. We examined how the magnitude of a common and costly response to microparasites, the acute phase response (APR), varied with helminth coinfection at both the individual and the population levels in Song Sparrows ( Melospiza melodia). The APR includes fever and sickness behaviors, like lethargy and anorexia, and provides a whole-organism metric of immune activation. We combined data on fever and lethargy in response to an immune challenge (lipopolysaccharide) with postmortem data assessing helminth burdens and data on malarial parasite infection from blood samples in sparrows from two populations: southern California and western Washington, US. We predicted that birds with higher helminth burdens would express less severe APRs, at both the individual and population levels. Furthermore, we predicted that these reduced immune responses would diminish resistance against malarial parasites and would thus be associated with higher prevalences of such parasites. Previously, Song Sparrows from Washington have been shown to mount less severe APRs than those from California. In our study, Washington birds also exhibited higher helminth burdens and a higher prevalence of one type of avian malarial parasite. Because of low variation in helminth burdens in California (median=0, range=0-3), we tested within-population relationships only in birds from Washington, where the severity of fever and lethargy correlated negatively with helminth burden. These results suggested that helminth coinfection could help mediate immune responsiveness in wild songbirds.

Schistosomiasis Induces Persistent DNA Methylation and Tuberculosis-Specific Immune Changes.

Epigenetic mechanisms, such as DNA methylation, determine immune cell phenotype. To understand the epigenetic alterations induced by helminth coinfections, we evaluated the longitudinal effect of ascariasis and schistosomiasis infection on CD4+ T cell DNA methylation and the downstream tuberculosis (TB)-specific and bacillus Calmette-Guérin-induced immune phenotype. All experiments were performed on human primary immune cells from a longitudinal cohort of recently TB-exposed children. Compared with age-matched uninfected controls, children with active Schistosoma haematobium and Ascaris lumbricoides infection had 751 differentially DNA-methylated genes, with 72% hypermethylated. Gene ontology pathway analysis identified inhibition of IFN-γ signaling, cellular proliferation, and the Th1 pathway. Targeted real-time quantitative PCR after methyl-specific endonuclease digestion confirmed DNA hypermethylation of the transcription factors BATF3, ID2, STAT5A, IRF5, PPARg, RUNX2, IRF4, and NFATC1 and cytokines or cytokine receptors IFNGR1, TNFS11, RELT (TNF receptor), IL12RB2, and IL12B (p < 0.001; Sidak-Bonferroni). Functional blockage of the IFN-γ signaling pathway was confirmed, with helminth-infected individuals having decreased upregulation of IFN-γ-inducible genes (Mann-Whitney p < 0.05). Hypomethylation of the IL-4 pathway and DNA hypermethylation of the Th1 pathway was confirmed by Ag-specific multidimensional flow cytometry demonstrating decreased TB-specific IFN-γ and TNF and increased IL-4 production by CD4+ T cells (Wilcoxon signed-rank p < 0.05). In S. haematobium-infected individuals, these DNA methylation and immune phenotypic changes persisted at least 6 mo after successful deworming. This work demonstrates that helminth infection induces DNA methylation and immune perturbations that inhibit TB-specific immune control and that the duration of these changes are helminth specific.

Distinct clinical characteristics and helminth co-infections in adult tuberculosis patients from urban compared to rural Tanzania

BackgroundDifferences in rural and urban settings could account for distinct characteristics in the epidemiology of tuberculosis (TB). We comparatively studied epidemiological features of TB and helminth co-infections in adult patients from rural and urban settings of Tanzania.MethodsAdult patients (≥ 18 years) with microbiologically confirmed pulmonary TB were consecutively enrolled into two cohorts in Dar es Salaam, with ~ 4.4 million inhabitants (urban), and Ifakara in the sparsely populated Kilombero District with ~ 400 000 inhabitants (rural). Clinical data were obtained at recruitment. Stool and urine samples were subjected to diagnose helminthiases using Kato-Katz, Baermann, urine filtration, and circulating cathodic antigen tests. Differences between groups were assessed by χ2, Fisher’s exact, and Wilcoxon rank sum tests. Logistic regression models were used to determine associations.ResultsBetween August 2015 and February 2017, 668 patients were enrolled, 460 (68.9%) at the urban and 208 (31.1%) at the rural site. Median patient age was 35 years (interquartile range [IQR]: 27–41.5 years), and 454 (68%) were males. Patients from the rural setting were older (median age 37 years vs. 34 years, P = 0.003), had a lower median body mass index (17.5 kg/m2 vs. 18.5 kg/m2, P < 0.001), a higher proportion of recurrent TB cases (9% vs. 1%, P < 0.001), and in HIV/TB co-infected patients a lower median CD4 cell counts (147 cells/μl vs. 249 cells/μl, P = 0.02) compared to those from urban Tanzania. There was no significant difference in frequencies of HIV infection, diabetes mellitus, and haemoglobin concentration levels between the two settings. The overall prevalence of helminth co-infections was 22.9% (95% confidence interval [CI]: 20.4–27.0%). The significantly higher prevalence of helminth infections at the urban site (25.7% vs. 17.3%, P = 0.018) was predominantly driven by Strongyloides stercoralis (17.0% vs. 4.8%, P < 0.001) and Schistosoma mansoni infection (4.1% vs. 16.4%, P < 0.001). Recurrent TB was associated with living in a rural setting (adjusted odds ratio [aOR]: 3.97, 95% CI: 1.16–13.67) and increasing age (aOR: 1.06, 95% CI: 1.02–1.10).ConclusionsClinical characteristics and helminth co-infections pattern differ in TB patients in urban and rural Tanzania. The differences underline the need for setting-specific, tailored public health interventions to improve clinical management of TB and comorbidities.

Cytokine profiles among patients co-infected with Plasmodium falciparum malaria and soil borne helminths attending Kampala International University Teaching Hospital, in Uganda

BackgroundMalaria and helminths share the same geographical distribution in tropical Africa. Studies of the interaction of helminth and malaria co-infection in humans have been few and are mainly epidemiological, with little information on cellular immune responses. This study aimed to determine Cytokine profiles among patients co-infected with Plasmodium falciparum malaria and soil borne helminth attending Kampala International University Teaching Hospital (KIU).MethodsA case control study of 240 patients were recruited at KIU teaching hospital. Patients with Plasmodium falciparum malaria were 55 (22.9%) and those with soil-borne helminths were 63 (26.3%). The controls were 89 (37.1%), while those co-infected with Plasmodium falciparum malaria and soil-borne helminths were 33 (13.8%). Cases were defined as having a positive blood smear for P. falciparum malaria, those with helminths or co-infections of the two. Negative controls were those with a negative blood smear for P. falciparum malaria and those with no stool parasitic infections. Patients presenting with signs and symptoms of malaria or those suspected of having helminths were recruited for the study. A panel of five cytokines (IFN-γ, TNF-α, IL-6, TGF-β and IL-10) were assayed from plasma samples in patients with and without Plasmodium falciparum malaria, patients with and without helminth, and then those co-infected with the two diseases diagnosis was done using thick blood smears stained with 10% Giemsa and stool examination was done following the Kato Katz technique following standard procedures.ResultsThe prevalence of Plasmodium falciparum malaria by sex was 28 (11.7%) and 27 (11.3%) in male and female respectively. The overall prevalence of soil borne helminth was 26.3%, and among those harbouring helminths, 13.8% were co-infected with Plasmodium falciparum. Cytokine levels significantly differed across Plasmodium falciparum malaria, soil borne helminth infected patients and health controls for IFN-γ (P = 0.023), IL-10 (P = 0.008) and TGF-β (P = 0.0001). Cytokine levels significantly differed across Plasmodium falciparum malaria, soil borne helminth infected patients and patients co-infected with Plasmodium falciparum malaria and soil borne helminth for IL-10 (P = 0.004), IL-6 (P = 0.011) and TGF-β (P = 0.003).ConclusionAn up-regulation of IFN-γ during Plasmodium falciparum malaria and an up-regulation of IL-10 and TGF-β in soil borne helminth infections was demonstrated. We demonstrate that co-infections of Plasmodium falciparum and soil borne helminth lead to an up-regulation of IL-10 and IL-6 and a down-regulation of TGF-β.Trial registration No17/10-16

Correction: Cutting Edge: Helminth Coinfection Blocks Effector Differentiation of CD8 T Cells through Alternate Host Th2- and IL-10-Mediated Responses.

Concurrent helminth infection potently inhibits T cell immunity; however, whether helminthes prevent T cell priming or skew clonal recruitment and effector differentiation is not known. Using coinfection with two natural mouse pathogens, Heligmosomoides polygyrus and Toxoplasma gondii, to investigate the negative impact of helminthes on the CD8 T cell response, we demonstrate helminth-induced suppression of IL-12–dependent differentiation of killer-like receptor G1 + effector CD8 T cells and IFN-γ production. Nevertheless, reversal of helminth suppression of the innate IL-12 response of CD8α + dendritic cells, which occurred in STAT6-deficient mice, was not sufficient to normalize CD8 T cell differentiation. Instead, a combined deficiency in IL-4 and IL-10 was required to reverse the negative effects of helminth coinfection on the CD8 T cell response. Monoclonal T. gondii –specific CD8 T cells adoptively transferred into coinfected mice recapitulated the spectrum of helminth-induced effects on the polyclonal CD8 T response, indicating the lack of requirement for clonal skewing.

Hookworm infection is associated with decreased CD4+ T cell counts in HIV-infected adult Ugandans.

Most studies evaluating epidemiologic relationships between helminths and HIV have been conducted in the pre-ART era, and evidence of the impact of helminth infections on HIV disease progression remains conflicting. Less is known about helminth infection and clinical outcomes in HIV-infected adults receiving antiretroviral therapy (ART). We sampled HIV-infected adults for eight gastrointestinal parasites and correlated parasitic infection with demographic predictors, and clinical and immunologic outcomes. Contrasting with previous studies, we measured parasitic infection with a quantitative, highly sensitive and specific polymerase chain reaction (PCR) method. This cohort study enrolled HIV-infected Ugandans from August-September 2013 in Mbale, Uganda and collected stool and blood samples at enrollment. Real-time PCR quantified stool: Ascaris lumbricoides, Ancylostoma duodenale, Necator americanus, Strongyloides stercoralis, Trichuris trichiura, Cryptosporidium spp., Entamoeba histolytica, and Giardia intestinalis infection. Generalized linear models assessed relationships between parasitic infection and clinical or demographic data. 35% of participants (71/202) tested positive for ≥1 helminth, mainly N. americanus (55/199, 28%), and 4.5% (9/202) were infected with ≥2 stool parasites. Participants with hookworm infection had lower average CD4+ cell counts (-94 cells/mcL, 95%CI: -141, -48 cells/mcL; p<0.001) after adjustment for sex, CD4+ nadir at clinic entry, and time on ART. The high prevalence of parasitic infection and correlation with decreased CD4+ concentrations highlight the need to re-examine the effects of invasive helminth co-infection in rural, HIV-infected populations in the era of widely available ART. Elucidating the relationship between hookworm infection and immune recovery could provide opportunities for health optimization, e.g. integrated deworming, in these vulnerable populations.

High prevalence of Plasmodium falciparum and soil-transmitted helminth co-infections in a periurban community in Kwara State, Nigeria.

Prevalence of malaria and soil-transmitted helminth infections, and the burden of disease are enormous in sub-Saharan Africa. Co-infections aggravate the clinical outcome, but are common due to an overlap of endemic areas. A cross-sectional survey was conducted to assess prevalence, intensity of infection and association between malaria and soil-transmitted helminth infections in a typical periurban community in Kwara State. Fresh blood and faecal samples were examined using thick blood film and Kato-Katz smear techniques. A total of 383/471 study participants (81.3%) were infected with at least one parasite species, with the following prevalences and mean infection intensities: Plasmodium falciparum 63.7% (2313.6 parasites/μl); Ascaris lumbricoides 63.1% (3152.1 epg); Trichuris trichiura 53.3% (1043.5 epg); and hookworms 30.1% (981.7 epg). Sixty-three percent of the study population were co-infected with two or more parasite species. The prevalence of ascariasis was significantly higher in individuals infected with P. falciparum (adjusted OR: 5.87; 95% CI: 3.30-10.42). Heavy A. lumbricoides and T. trichiura infections were associated with high P. falciparum parasitaemia. Co-endemicity of malaria and soil transmitted helminth infections is an important public health problem in the study area. Multi-target integrated approaches focusing on disease intervention are essential to mitigate morbidity caused by multiple infections.