Concurrent Nematode Infection Research Articles

The devil is in the details-Host disease and co-infections are associated with zoonotic pathogen carriage in Norway rats (Rattus norvegicus).

Traditionally, zoonotic pathogen ecology studies in wildlife have focused on the interplay among hosts, their demographic characteristics and their pathogens. But pathogen ecology is also influenced by factors that traverse the hierarchical scale of biological organization, ranging from within-host factors at the molecular, cellular and organ levels, all the way to the host population within a larger environment. The influence of host disease and co-infections on zoonotic pathogen carriage in hosts is important because these factors may be key to a more holistic understanding of pathogen ecology in wildlife hosts, which are a major source of emerging infectious diseases in humans. Using wild Norway rats (Rattus norvegicus) as a model species, the purpose of this study was to investigate how host disease and co-infections impact the carriage of zoonotic pathogens. Following a systematic trap and removal study, we tested the rats for the presence of two potentially zoonotic bacterial pathogens (Bartonella tribocorum and Leptospira interrogans) and assessed them for host disease not attributable to these bacteria (i.e., nematode parasites, and macroscopic and microscopic lesions). We fitted multilevel multivariable logistic regression models with pathogen status as the outcome, lesions and parasites as predictor variables and city block as a random effect. Rats had significantly increased odds of being infected with B.tribocorum if they had a concurrent nematode infection in one or more organ systems. Rats with bite wounds, any macroscopic lesion, cardiomyopathy or tracheitis had significantly increased odds of being infected with L.interrogans. These results suggest that host disease may have an important role in the ecology and epidemiology of rat-associated zoonotic pathogens. Our multiscale approach to assessing complex intrahost factors in relation to zoonotic pathogen carriage may be applicable to future studies in rats and other wildlife hosts.

Susceptibility to Ticks and Lyme Disease Spirochetes Is Not Affected in Mice Coinfected with Nematodes.

Small rodents serve as reservoir hosts for tick-borne pathogens, such as the spirochetes causing Lyme disease. Whether natural coinfections with other macroparasites alter the success of tick feeding, antitick immunity, and the host's reservoir competence for tick-borne pathogens remains to be determined. In a parasitological survey of wild mice in Berlin, Germany, approximately 40% of Ixodes ricinus-infested animals simultaneously harbored a nematode of the genus Heligmosomoides. We therefore aimed to analyze the immunological impact of the nematode/tick coinfection as well as its effect on the tick-borne pathogen Borrelia afzelii. Hosts experimentally coinfected with Heligmosomoides polygyrus and larval/nymphal I. ricinus ticks developed substantially stronger systemic type 2 T helper cell (Th2) responses, on the basis of the levels of GATA-3 and interleukin-13 expression, than mice infected with a single pathogen. During repeated larval infestations, however, anti-tick Th2 reactivity and an observed partial immunity to tick feeding were unaffected by concurrent nematode infections. Importantly, the strong systemic Th2 immune response in coinfected mice did not affect susceptibility to tick-borne B. afzelii. An observed trend for decreased local and systemic Th1 reactivity against B. afzelii in coinfected mice did not result in a higher spirochete burden, nor did it facilitate bacterial dissemination or induce signs of immunopathology. Hence, this study indicates that strong systemic Th2 responses in nematode/tick-coinfected house mice do not affect the success of tick feeding and the control of the causative agent of Lyme disease.

Complex interaction between proliferative kidney disease, water temperature and concurrent nematode infection in brown trout

Proliferative kidney disease (PKD) is a temperature-dependent disease caused by the myxozoan Tetracapsuloides bryosalmonae. It is an emerging threat to wild brown trout Salmo trutta fario populations in Switzerland. Here we examined (1) how PKD prevalence and pathology in young-of-the-year (YOY) brown trout relate to water temperature, (2) whether wild brown trout can completely recover from T. bryosalmonae-induced renal lesions and eliminate T. bryosalmonae over the winter months, and (3) whether this rate and/or extent of the recovery is influenced by concurrent infection. A longitudinal field study on a wild brown trout cohort was conducted over 16 mo. YOY and age 1+ fish were sampled from 7 different field sites with various temperature regimes, and monitored for infection with T. bryosalmonae and the nematode Raphidascaris acus. T. bryosamonae was detectable in brown trout YOY from all sampling sites, with similar renal pathology, independent of water temperature. During winter months, recovery was mainly influenced by the presence or absence of concurrent infection with R. acus larvae. While brown trout without R. acus regenerated completely, concurrently infected brown trout showed incomplete recovery, with chronic renal lesions and incomplete translocation of T. bryosalmonae from the renal interstitium into the tubular lumen. Water temperature seemed to influence complete excretion of T. bryosalmonae, with spores remaining in trout from summer-warm rivers, but absent in trout from summer-cool rivers. In the following summer months, we found PKD infections in 1+ brown trout from all investigated river sites. The pathological lesions indicated a re-infection rather than a proliferation of remaining T. bryosalmonae. However, disease prevalence in 1+ trout was lower than in YOY.

Concurrent nematode infection and pregnancy induce physiological responses that impair linear growth in the murine foetus

This study examined concurrent stresses of nematode infection and pregnancy using pregnant and non-pregnant CD1 mice infected 3 times with 0, 50 or 100 Heligmosomoides bakeri larvae. Physiological, energetic, immunological and skeletal responses were measured in maternal and foetal compartments. Resting metabolic rate (RMR) was elevated by pregnancy, but not by the trickle infection. Energy demands during pregnancy were met through increased food intake and fat utilization whereas mice lowered their body temperature during infection. Both infection and pregnancy increased visceral organ mass and both altered regional bone area and mineralization. During pregnancy, lumbar mineralization was lower but femur area and mineralization were higher. On the other hand, infection lowered maternal femur bone area and this was associated with higher IFN-gamma in maternal serum of heavily infected pregnant mice. Infection also reduced foetal crown-rump length which was associated with higher amniotic fluid IL-1 beta.

Regulatory T cells (Tregs) contribute to suppression of anti-malarial immunity by concurrent nematode infection (51.1)

Abstract Here, we investigated the mechanisms involved in modulation of anti-malarial immunity by concurrent nematode infection. Both WT C57BL/6 (B6) and STAT-6 deficient (KO) mice co-infected with the gastrointestinal nematode Heligmosomoides polygyrus (Hp) 2 wk prior to blood-stage Plasmodium chabaudi AS (Pc) infection had significantly higher parasitemias and significantly lower serum IFN-γ levels compared to their respective controls infected with Pc alone. Hp-infected STAT-6 KO compared to WT mice produced significantly lower levels of Th2 cytokines (IL-4, IL-13) but Tregs (CD4+CD25+Foxp3− and CD4+CD25−Foxp3+) were significantly and similarly increased within 2 wk after Hp infection in both strains. Transfer of CD4+CD25+ Tregs from uninfected and Hp-infected B6 mice significantly increased malaria parasitemia in recipient mice while depletion of CD25+ cells suppressed parasitemia in Pc-infected mice but not in co-infected mice. FACS analysis revealed that anti-CD25 mAb (PC61) treatment reduced both CD4+CD25+ Tregs and CD4+Foxp3+ Tregs in Pc-infected but not in co-infected mice. Co-infection with Hp significantly enhanced Pc-induced TGF-β1 and IL-10 production. In vivo neutralization of TGF-β1 and blocking IL-10R with mAbs significantly reduced parasitemia in both Pc-infected and co-infected B6 mice; anti-IL-10R mAb treatment resulted in severe mortality. These results suggest that Tregs, and possibly immunoregulatory but not Th2 cytokines, contribute to suppression of anti-malarial immunity in nematode and malaria co-infected mice.

Modulation of malaria-induced immunopathology by concurrent nematode infection (46.8)

Abstract Gastrointestinal nematode infections, highly prevalent in malaria endemic areas, are known to modulate host immune responses to unrelated pathogens. However, the complex relationship between worms and malaria and the impact on malarial incidence vs. severity are unclear. Previously, we observed that C57BL/6 (B6) mice infected with the gastrointestinal nematode Heligosomoides polygyrus (Hp) for 2 wks before blood-stage Plasmodium chabaudi AS (Pc) infection developed significantly higher parasitemia compared to mice infected with Pc alone. Despite this, malaria-induced body weight loss, anemia and hepatosplenic damage were not exacerbated in co-infected mice. Indeed, there was less severe hypothermia and hypoglycemia and more robust reticulocytosis in co-infected mice. Co-infection with Hp suppressed type 1 immune responses induced by P. chabaudi infection with significantly reduced plasma levels of IFN-γ, TNF-α and nitric oxide, but increased IL-6 and IL-10 levels. Co-infected STAT-6−/− mice, which have disrupted Th2 responses, experienced only slightly more severe hypothermia, hypoglycemia, and anemia than co-infected WT B6 mice while in vivo administration of anti-IL-10R (1B1.2) mAb resulted in higher mortality in co-infected WT mice. Although concurrent nematode infection resulted in increased parasitemia due to impaired anti-malarial type 1 immunity, our data suggest that malaria-associated pathology is alleviated by a complex immunoregulatory network, possibly involving IL-10, and, to a lesser extent, Th2 cytokines.

Reduced Protective Efficacy of a Blood-Stage Malaria Vaccine by Concurrent Nematode Infection

Helminth infections, which are prevalent in areas where malaria is endemic, have been shown to modulate immune responses to unrelated pathogens and have been implicated in poor efficacy of malaria vaccines in humans. We established a murine coinfection model involving blood-stage Plasmodium chabaudi AS malaria and a gastrointestinal nematode, Heligmosomoides polygyrus, to investigate the impact of nematode infection on the protective efficacy of a malaria vaccine. C57BL/6 mice immunized with crude blood-stage P. chabaudi AS antigen in TiterMax adjuvant developed strong protection against malaria challenge. The same immunization protocol failed to induce strong protection in H. polygyrus-infected mice. Immunized nematode-infected mice produced significantly lower levels of malaria-specific antibody than nematode-free mice produced. In response to nematode and malarial antigens, spleen cells from immunized nematode-infected mice produced significantly lower levels of gamma interferon but more interleukin-4 (IL-4), IL-13, and IL-10 in vitro than spleen cells from immunized nematode-free mice produced. Furthermore, H. polygyrus infection also induced a strong transforming growth factor beta1 response in vivo and in vitro. Deworming treatment of H. polygyrus-infected mice before antimalarial immunization, but not deworming treatment after antimalarial immunization, restored the protective immunity to malaria challenge. These results demonstrate that concurrent nematode infection strongly modulates immune responses induced by an experimental malaria vaccine and consequently suppresses the protective efficacy of the vaccine against malaria challenge.

Impairment of Protective Immunity to Blood-Stage Malaria by Concurrent Nematode Infection

Helminthiases, which are highly prevalent in areas where malaria is endemic, have been shown to modulate or suppress the immune response to unrelated antigens or pathogens. In this study, we established a murine model of coinfection with a gastrointestinal nematode parasite, Heligmosomoides polygyrus, and the blood-stage malaria parasite Plasmodium chabaudi AS in order to investigate the modulation of antimalarial immunity by concurrent nematode infection. Chronic infection with the nematode for 2, 3, or 5 weeks before P. chabaudi AS infection severely impaired the ability of C57BL/6 mice to control malaria, as demonstrated by severe mortality and significantly increased malaria peak parasitemia levels. Coinfected mice produced significantly lower levels of gamma interferon (IFN-gamma) during P. chabaudi AS infection than mice infected with malaria alone. Concurrent nematode infection also suppressed production of type 1-associated, malaria-specific immunoglobulin G2a. Mice either infected with the nematode alone or coinfected with the nematode and malaria had high transforming growth factor beta1 (TGF-beta1) levels, and concurrent nematode and malaria infections resulted in high levels of interleukin-10 in vivo. Splenic CD11c(+) dendritic cells (DC) from mice infected with malaria alone and coinfected mice showed similarly increased expression of CD40, CD80, and CD86, but DC from coinfected mice were unable to induce CD4(+) T-cell proliferation and optimal IFN-gamma production in response to the malaria antigen in vitro. Importantly, treatment of nematode-infected mice with an anthelmintic drug prior to malaria infection fully restored protective antimalarial immunity and reduced TGF-beta1 levels. These results demonstrate that concurrent nematode infection strongly modulates multiple aspects of immunity to blood-stage malaria and consequently impairs the development of protective antimalarial immunity.

Enzyme-linked immunosorbent assay (ELISA) for the detection of antibodies to Anoplocephala perfoliata in horse sera

A scolex antigen of the horse tapeworm Anoplocephala perforliata containing at least 14 different proteins was employed in an enzyme-linked immunosorbent assay (ELISA) for detection of antibodies to A. perfoliata in equine sera. The assay was applied to sera from 426 slaughtered horses with different numbers of worms and with varying degrees of intestinal lesions. As measured by the ELISA, there was a very strong effect on the antibody levels both from the number of tapeworms present and from the intestinal lesion score. However, considerable individual variation was observed between horses with similar worn counts. The ELISA values of horses that were either negative for strongyles and tapeworms or positive only for strongyles were similar, whereas both of these groups differed significantly from animals that harboured only A. perfoliata. Thus it seemed that cross-reactivity with concurrent nematode infections did not occur. Furthermore, a significant seasonal pattern in antibody levels was observed which reflected the establishment of newly acquired infections. No observations were made of confounding effects owing to age and previous anthelmintic treatment of the horses. It is concluded that the ELISA presented here has a potential for monitoring A. perfoliata infection on a herd level and can be used as a complementary diagnostic tool in epidemiological studies. The present study indicates that transmission of A. perfoliata in Central Sweden occurred during a short period in spring and more consistently in late autumn.