Can eradication of helminthic infections change the face of AIDS and tuberculosis?

doi:10.1016/S0167-5699(99)01499-1

Immunology Today

Volume 20, Issue 11, 1 November 1999, Pages 485-487

Immunology Today

https://doi.org/10.1016/S0167-5699(99)01499-1 Get rights and content

Abstract

Helminth infections impair the host’s immune response to HIV and tuberculosis (TB) and might contribute to the spread of these diseases. Thus, eradication of helminth infections may have a major impact on both HIV and TB in the developing world.

Section snippets

Helminthic infection and HIV

The immigration of Ethiopian Jews to Israel, some of them infected with HIV, provided us with a unique opportunity to test and support our hypothesis by the following findings.

1.
The vast majority of the Ethiopian immigrants were infested with helminths and had immune dysregulation with a dominant T helper 2 (Th2)-type immune profile that returned to normal with eradication of helminths3, 4.
2.
Peripheral blood mononuclear cells obtained from Ethiopian immigrants were highly susceptible to infection

TB and the immune response

TB and HIV/AIDS share a number of common features, have a similar geographic distribution and each exacerbates the other¹⁴. In both diseases the onset is slow, the pathogens, localized within immune cells, evade and suppress the host immune response, and the host controls both infections by multiple mechanisms. The most important mechanism for the control of both pathogens is a Th1 immune response.

After infection with M. tuberculosis, more than 90% of individuals do not develop overt TB (Ref. 14

Protective immunity and helminthic infections

Several studies have shown that helminthic infections can affect the immune response to inciting antigens and pathogens, jeopardizing the host’s ability to generate protective immunity to both HIV and mycobacteria (reviewed in Ref. 21).

1.
Schistosome-infected mice with a dominant Th2 immune profile have a Th2 ‘skewed’ immune response to sperm whale myoglobin and to HIV envelope antigens, which is accompanied by downregulation of Th1 cytokines and an impaired cytotoxic T lymphocyte (Th1) response.
2.

Practical implications and unresolved issues

Eradication of helminthic infection on a large scale is feasible, relatively inexpensive and simple, and should become a priority for public health in developing countries.Indeed, the South African government has recently embarked on a large-scale helminth eradication programme involving over a million school children, with the purpose of correcting growth and cognitive impairments observed in helminth-infested populations². We suggest here that deworming will also have a huge impact on the

Acknowledgements

We thank our co-workers and students for their diligence, and gratefully acknowledge support by the Institute of Advanced Therapy (IAT) for Center of Excellence in AIDS Research and the Horowitz Foundation to Z.B.; the KAMEA fellowship to A.K.; and the Glaxo Wellcome Action TB Programme and a Wellcome Trust Senior Research Fellowship to A.D.B.

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Equal contributions of feline immunodeficiency virus and coinfections to morbidity in African lions
2021, International Journal for Parasitology: Parasites and Wildlife
Feline immunodeficiency virus (FIV) is a pathogenic lentivirus related to human and simian immunodeficiency viruses that has been associated with AIDS-like pathologies in domestic and wild cats, as well as in hyenas. Despite known pathologies, progressive immunosuppression and ill health effects driven by these lentiviruses in association with other secondary infections remain understudied in free-ranging species. Here, the role of coinfections by gastrointestinal parasites and tick-borne hemoparasites for FIV disease progression was explored in 195 free-ranging African lions (Panthera leo) living in Kruger National Park (KNP), South Africa. Using statistical methodology, we evaluated the effects of FIV on a range of health indicators to explore how direct and indirect effects of FIV and associated coinfections align to determine lion health outcomes. Findings show direct negative effects of FIV on host immunity and nutritional status, and exacerbation of aggressive behaviors, conditions which may increase exposure/susceptibility to other secondary infections. When taken together, the contribution of coinfecting parasites to morbidity in lions is of similar magnitude as direct effects of FIV infection alone, suggesting that the particular coinfection assemblage may play a role in mediating disease progression within natural lion populations.
Predictors of helminth parasite infection in female chacma baboons (Papio ursinus)
2021, International Journal for Parasitology: Parasites and Wildlife
Citation Excerpt :
On the other hand, if infective stages of parasites differ spatially or temporally, then hosts are less likely to experience coinfection (e.g., Kelly-Hope et al., 2006; Warburton et al., 2016). Likewise, if one parasite species competitively excludes another parasite species (e.g., Holmes 1961; Stancampiano et al., 2010) or if infection with one parasite reduces host susceptibility to other parasites (e.g., Bentwich et al., 1999; Jolles et al., 2008), then hosts are expected to have reduced risk of coinfection. Thus, patterns of coinfection are driven by multiple factors including host exposure to and susceptibility to different parasite species.
Helminth parasite infection can impose major consequences on host fitness. Several factors, including individual characteristics of hosts, environmental conditions, and patterns of coinfection, are thought to drive variation in parasite risk. Here, we report on four key drivers of parasite infection—phase of reproduction, steroid hormone profiles, rainfall, and patterns of coinfection—in a population of wild female chacma baboons (Papio ursinus) in South Africa. We collected data on reproductive state and hormone profiles over a 3-year span, and quantified helminth parasite burdens in 2955 fecal samples from 24 female baboons. On a host level, we found that baboons are sensitive to parasite infection during the costliest phases of the reproductive cycle: pregnant females harbored higher intensities of Protospirura eggs than cycling and lactating females; lactating and cycling females had a higher probability of Oesophagostomum infection than pregnant females; and cycling females exhibited lower Trichuris egg counts than pregnant and lactating females. Steroid hormones were associated with both immunoenhancing and immunosuppressive properties: females with high glucocorticoid concentrations exhibited high intensities of Trichuris eggs but were at low risk of Oesophagostomum infection; females with high estrogen and progestagen concentrations exhibited high helminth parasite richness; and females with high progestagen concentrations were at high risk of Oesophagostomum infection but exhibited low Protospirura egg counts. We observed an interaction between host reproductive state and progestagen concentrations in infection intensity of Protospirura: pregnant females exhibited higher intensities and non-pregnant females exhibited lower intensities of Protospirura eggs with increasing progestagen concentrations. At a population level, rainfall patterns were dominant drivers of parasite risk. Lastly, helminth parasites exhibited positive covariance, suggesting that infection probability increases if a host already harbors one or more parasite taxa. Together, our results provide a holistic perspective of factors that shape variation in parasite risk in a wild population of animals.
Urban-rural differences in immune responses to mycobacterial and tetanus vaccine antigens in a tropical setting: A role for helminths?
2020, Parasitology International
Citation Excerpt :
However, pre-immunisation exposure cannot explain observations for vaccines against rare pathogens, such as Ebola [7]. Another long-held hypothesis is that helminth infections, which are highly prevalent in rural tropical settings, modulate vaccine responses by suppressing the Th1 responses necessary for protection against several pathogens targeted by vaccines [17,18]. In animal models, helminths generally impair priming and accelerate waning of vaccine responses, but effects vary with helminth species and vaccine type [19].
Several vaccines elicit lower efficacy or impaired immune responses in rural compared to urban settings, and in tropical low-income countries compared to high-income countries. An unresolved hypothesis is that immunomodulation by parasitic infections such as helminths (prevalent in rural tropical settings) contributes to suppression of vaccine responses. Among 1–17-year-old Ugandan residents of rural Schistosoma mansoni (Sm)-endemic islands and proximate urban communities with lower helminth exposure, we assessed plasma antibody and whole blood assay cytokine responses to tetanus toxoid (TT) and purified protein derivative of Mycobacterium tuberculosis (PPD). These were taken to represent recall responses to tetanus and BCG vaccination in infancy. PPD-specific responses are additionally induced by tuberculous and non-tuberculous mycobacterial exposure. Urban-rural comparisons showed that PPD-specific IFN-γ and IL-13 and TT-specific IL-13 and IgG concentrations were lower in the rural setting, but that PPD-specific IgE concentrations were higher. Among rural participants, Sm infection was inversely associated with PPD-specific IFN-γ, while nematode infection was positively associated with PPD-specific IgG. Among urban participants, Sm infection was positively associated with PPD-specific responses but inversely associated with TT-specific responses, while nematode infection was inversely associated with TT-specific IgG and IgG4, but no associations were observed with PPD-specific responses. Despite these associations, for the urban-rural comparisons there were no notable changes in test statistics after adjusting for current helminth infections, suggesting that helminths were not the sole explanation for the urban-rural differences observed. Helminths likely work in concert with other environmental exposures and operational factors to influence vaccine response.
Unknown age in health disorders: A method to account for its cumulative effect and an application to feline viruses interactions
2015, Epidemics
Parasite interactions have been widely evidenced experimentally but field studies remain rare. Such studies are essential to detect interactions of interest and access (co)infection probabilities but face methodological obstacles. Confounding factors can create statistical associations, i.e. false parasite interactions. Among them, host age is a crucial covariate. It influences host exposition and susceptibility to many infections, and has a mechanical effect, older individuals being more at risk because of a longer exposure time. However, age is difficult to estimate in natural populations. Hence, one should be able to deal at least with its cumulative effect. Using a SI type dynamic model, we showed that the cumulative effect of age can generate false interactions theoretically (deterministic modeling) and with a real dataset of feline viruses (stochastic modeling). The risk to wrongly conclude to an association was maximal when parasites induced long-lasting antibodies and had similar forces of infection. We then proposed a method to correct for this effect (and for other potentially confounding shared risk factors) and made it available in a new R package, Interatrix. We also applied the correction to the feline viruses. It offers a way to account for an often neglected confounding factor and should help identifying parasite interactions in the field, a necessary step towards a better understanding of their mechanisms and consequences.
Effects of albendazole on the clinical outcome and immunological responses in helminth co-infected tuberculosis patients: A double blind randomised clinical trial
2015, International Journal for Parasitology
Citation Excerpt :
One reason could be that helminth infection modulates the immune response by skewing the Th1/Th2 balance and thereby attenuating the effects of the BCG vaccine (Elias et al., 2008). Several experimental studies confirm the immunomodulatory effect of helminths during TB (Bentwich et al., 1999; Borkow et al., 2001; Elias et al., 2005; Potian et al., 2011; Salgame et al., 2013). One of these studies clearly showed that Nippostrongylus brasiliensis infection was associated with impaired killing of Mycobacterium tuberculosis (Mtb), an effect primarily mediated by a switch to alternatively activated macrophages (AAMs) by IL-4 (Potian et al., 2011).
Despite several review papers and experimental studies concerning the impact of chronic helminth infection on tuberculosis in recent years, there is a scarcity of data from clinical field studies in highly endemic areas for these diseases. We believe this is the first randomised clinical trial investigating the impact of albendazole treatment on the clinical and immunological outcomes of helminth co-infected tuberculosis patients. A randomised, double-blind, placebo-controlled trial of albendazole (400 mg per day for 3 days) in helminth-positive tuberculosis patients was conducted in Gondar, Ethiopia. The primary outcome was clinical improvement (ΔTB score) after 2 months. Among secondary outcomes were changes in the levels of eosinophils, CD4+ T cells, regulatory T cells, IFN-γ, IL-5 and IL-10 after 3 months. A total of 140 helminth co-infected tuberculosis patients were included with an HIV co-infection rate of 22.8%. There was no significant effect on the primary outcome (ΔTB score: 5.6 ± 2.9 for albendazole versus 5.9 ± 2.5 for placebo, P = 0.59). The albendazole-treated group showed a decline in eosinophil cells (P = 0.001) and IL-10 (P = 0.017) after 3 months. In an exploratory analysis after 12 weeks, the albendazole treated group showed a trend towards weight gain compared with the placebo group (11.2 ± 8.5 kg versus 8.2 ± 8.7 kg, P = 0.08)). The reductions in eosinophil counts and IL-10 show that asymptomatic helminth infection significantly affects host immunity during tuberculosis and can be effectively reversed by albendazole treatment. The clinical effects of helminth infection on chronic infectious diseases such as tuberculosis merit further characterisation.
The Effect of Intensive Praziquantel Treatment on Vaccine-Specific Responses Among Schoolchildren in Ugandan Schistosomiasis-Endemic Islands: Results of the Popvac a Randomised, Controlled Trial
2023, SSRN

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TrendsCan eradication of helminthic infections change the face of AIDS and tuberculosis?

Abstract

Section snippets

Helminthic infection and HIV

TB and the immune response

Protective immunity and helminthic infections

Practical implications and unresolved issues

Acknowledgements

Immunol. Today

Lancet

Parasitol. Today

Immunol. Today

Lancet

Br. Med. Bull.

Clin. Exp. Immunol.

Immunologist

AIDS

Clin. Exp. Immunol.

J. Acquired Immune Defic. Syndr. Hum. Retrovirol.

Trends
Can eradication of helminthic infections change the face of AIDS and tuberculosis?