Group 2 ILCs: A way of enhancing immune protection against human helminths?

Group 2 innate lymphoid cells (ILC2s) play crucial roles in type 2 immune responses associated with allergic and autoimmune diseases, viral and helminth infections and tissue homoeostasis. Experimental models show that in helminth infections ILC2s provide an early source of type 2 cytokines and therefore are essential for the induction of potentially protective type 2 responses. Much of our knowledge of ILC2s in helminth infections has come from experimental mouse models with very few studies analysing ILC2s in natural human infections. In attempts to harness knowledge from paradigms of the development of protective immunity in human helminth infections for vaccine development, the role of ILC2 cells could be pivotal. So far, potential vaccines against human helminth infections have failed to provide effective protection when evaluated in human studies. In addition to appropriate antigen selection, it is apparent that more detailed knowledge on mechanisms of induction and maintenance of protective immune responses is required. Therefore, there is need to understand how ILC2 cells induce type 2 responses and subsequently support the development of a protective immune response in the context of immunizations. Within this review, we summarize the current knowledge of the biology of ILC2s, discuss the importance of ILC2s in human helminth infections and explore how ILC2 responses could be boosted to efficiently induce protective immunity.

Trichuris suis ova therapy for allergic rhinitis does not affect allergen-specific cytokine responses despite a parasite-specific cytokine response.

BACKGROUND: Parasitic helminths have been shown to reduce inflammation in most experimental models of allergic disease, and this effect is mediated via cytokine responses. However, in humans, the effects of controlled helminth infection on cytokine responses during allergy have not been studied. OBJECTIVE: The aim was to investigate whether infection with the nematode parasite Trichuris suis alters systemic cytokine levels, cellular cytokine responses to parasite antigens and pollen allergens and/or the cytokine profile of allergic individuals. METHODS: In a randomized double-blinded placebo-controlled clinical trial (UMIN trial registry, Registration no. R000001298, Trial ID UMIN000001070, URL: http://www.umin.ac.jp/map/english), adults with grass pollen-induced allergic rhinitis received three weekly doses of 2500 Trichuris suis ova (n = 45) or placebo (n = 44) over 6 months. IFN-γ, TNF-α, IL-4, IL-5, IL-10 and IL-13 were quantified via cytometric bead array in plasma. Cytokines, including active TGF-ß, were also quantified in supernatants from peripheral blood mononuclear cells cultured with parasite antigens or pollen allergens before, during and after the grass pollen season for a sub-cohort of randomized participants (T. suis ova-treated, n = 12, Placebo-treated, n = 10). RESULTS: Helminth infection induced a Th2-polarized cytokine response comprising elevated plasma IL-5 and parasite-specific IL-4, IL-5 and IL-13, and a global shift in the profile of systemic cytokine responses. Infection also elicited high levels of the regulatory cytokine IL-10 in response to T. suis antigens. Despite increased production of T. suis-specific cytokines in T. suis ova-treated participants, allergen-specific cytokine responses during the grass pollen season and the global profile of PBMC cytokine responses were not affected by T. suis ova treatment. CONCLUSIONS AND CLINICAL RELEVANCE: This study suggests that cytokines induced by Trichuris suis ova treatment do not alter allergic reactivity to pollen during the peak of allergic rhinitis symptoms.

Schistosoma haematobium infection levels determine the effect of praziquantel treatment on anti-schistosome and anti-mite antibodies.

Field studies show an association between schistosome infection and atopy, but the effects of anti-helminthic treatment on this association have not yet been investigated in human populations with different schistosome endemicity levels. This study aimed to compare the effects of anti-helminthic treatment on responses directed against the house dust mite Dermatophagoides pteronyssinus (Derp1) and Schistosoma haematobium in Zimbabwean populations living in high and low schistosome infection areas. Derp1- and schistosome-specific IgE and IgG4 antibodies were quantified by ELISA before and 6 weeks after anti-helminthic treatment. Following treatment, there were changes in the immune responses, which varied with place of residence. After allowing for the effects of sex, age and baseline infection intensity, there was no significant treatment effect on the change in anti-schistosome IgE and IgG4 in the high infection area. However, the anti-schistosome IgE/IgG4 ratio increased significantly, while anti-Derp1 IgE responses decreased as a result of treatment. In the low infection area, treatment resulted in a significant increase in anti-worm IgE levels, but there was no significant treatment effect on anti-schistosome or anti-Derp1 IgE/IgG4 ratios. Thus, the study shows that the level of schistosome endemicity affects the host responses to schistosome and mite antigens following anti-helminthic treatment.

Differential recognition patterns of Schistosoma haematobium adult worm antigens by the human antibodies IgA, IgE, IgG1 and IgG4.

Schistosoma haematobium antigen recognition profiles of the human isotypes IgA, IgE, IgG1 and IgG4 were compared by image analysis of western blots. Adult worm antigens separated by two-dimensional gel electrophoresis were probed with pooled sera from Zimbabweans resident in a S. haematobium endemic area, followed by the identification of individual antigenic parasite proteins using mass spectrometry. Overall, IgG1 reacted with the largest number of antigens, followed by IgE and IgA which detected the same number, while IgG4 detected the fewest antigens. IgE recognized all antigens reactive with IgG4 as well as an additional four antigens, an isoform of 28-kDa GST, phosphoglycerate kinase, actin 1 and calreticulin. IgG1 additionally recognized fatty acid-binding protein, triose-phosphate isomerase and heat shock protein 70, which were not recognized by IgA. Recognition patterns varied between some isoforms, e.g. the two fructose 1-6-bis-phosphate aldolase isoforms were differentially recognized by IgA and IgG1. Although the majority of S. haematobium adult worm antigens are recognized by all of the four isotypes, there are clear restrictions in antibody recognition for some antigens. This may partly explain differences observed in isotype dynamics at a population level. Differential recognition patterns for some isoforms indicated in the study have potential importance for vaccine development.

Acquired immune heterogeneity and its sources in human helminth infection.

Similarities in the immunobiology of different parasitic worm infections indicate that co-evolution of humans and helminths has shaped a common anti-helminth immune response. However, recent in vitro and immuno-epidemiological studies highlight fundamental differences and plasticity within host-helminth interactions. The 'trade-off' between immunity and immunopathology inherent in host immune responses occurs on a background of genetic polymorphism, variable exposure patterns and infection history. For the parasite, variation in life-cycle and antigen expression can influence the effector responses directed against them. This is particularly apparent when comparing gastrointestinal and tissue-dwelling helminths. Furthermore, insights into the impact of anti-helminthic treatment and co-infection on acquired immunity suggest that immune heterogeneity arises not from hosts and parasites in isolation, but also from the environment in which immune responses develop. Large-scale differences observed in the epidemiology of human helminthiases are a product of complex host-parasite-environment interactions which, given potential for exposure to parasite antigens in utero, can arise even before a parasite interacts with its human host. This review summarizes key differences identified in human acquired immune responses to nematode and trematode infections of public health importance and explores the factors contributing to these variations.

Circulating cytokine levels and antibody responses to human Schistosoma haematobium: IL-5 and IL-10 levels depend upon age and infection status.

Experimental schistosome infections induce strong parasite-specific Th2 responses. This study aims to relate human systemic cytokine and antibody levels to schistosome infection levels and history. Levels of anti-Schistosoma haematobium antibodies (directed against crude cercariae, egg and adult worm antigens) and plasma cytokines (IFN-γ, IL-2, IL-4, IL-5, IL-10, IL-13, IL-17, IL-21, and IL-23) were measured by ELISA in 227 Zimbabweans (6-60 years old) in a schistosome-endemic area and related to age and infection status. Egg-positive people had significantly higher levels of specific antibodies, IL-2, IFN-γ and IL-23. In contrast, egg-negative individuals had significantly higher circulating IL-10, IL-4, IL-13 and IL-21 that were detected with high frequency in all participants. Subjects with detectable plasma IL-17 produced few or no eggs. When analyzed by age, IL-4 and IL-10 increased significantly, as did schistosome-specific antibodies. However, when age was combined with infection status, IL-5 declined over time in egg-positive people, while increased with age in the egg-negative group. Older, lifelong residents had significantly higher IL-4 and IL-5 levels than younger egg-negative people. Thus, a mixed Th1/Th2 systemic environment occurs in people with patent schistosome infection, while a stronger Th2-dominated suite of cytokines is evident in egg-negative individuals.

The predicted impact of immunosuppression upon population age-intensity profiles for schistosomiasis.

The slow development of acquired immunity is thought to be responsible for the characteristic convex age-intensity curve seen in human schistosome infection, which peaks earlier in more heavily infected populations (this is described as a peak shift). Schistosomes are able to suppress protective host responses, and it is hypothesized that this suppression is responsible for the delayed development of protective responses. A deterministic mathematical model is used to describe levels of infection and immunity in an endemic population, incorporating protective immune responses which either reduce adult worm burden or reduce superinfection. Suppression, related to current worm burden, is also included and acts against one or both protective responses. If suppression acts against the entire protective response, it is able to delay the development of protective immunity, and the peak shift is predicted to be reversed at higher infection intensities, with removal of the peaks altogether at the highest levels of infection and/or suppression. If only the anti-adult worm protective immune response is vulnerable to suppression, while the anti-reinfection response remains intact, then suppression does not remove the peak in the age-intensity curve. These findings are discussed in the light of existing field and experimental data.

Efficacy and side effects of praziquantel treatment against Schistosoma haematobium infection among primary school children in Zimbabwe.

We examined the efficacy of praziquantel against Schistosoma haematobium among primary school children during a school-based deworming programme in the Burma Valley commercial farming area and the Nyamaropa rural areas in Zimbabwe, where the disease is highly endemic. Among 767 individuals infected with S. haematobium, 675 (88.0%) received treatment. Two single oral doses of 40mg/kg praziquantel were given 6 weeks apart. Of the 675 participants, heavy infection intensity was more common in males than females (chi(2)=6.61, P=0.010). Six weeks later, 624 participants (92.4%) were successfully followed up. The overall cure rate was 88.5% and the egg reduction rate was 98.2%. The highest cure rate was among those individuals with light infection. Seventy-two individuals remained infected at 6 weeks post treatment, among which 3 and 69 individuals had heavy and light infection, respectively. Forty-six of these children resolved following a second round of treatment at 6 weeks follow-up. Of the remaining children successfully followed-up, 22 resolved after a third round of treatment 6 months later. A wide range of observed mild and transient side effects were not associated with egg intensity. The parasitological cure rate was not associated with gender or age. Our study demonstrates that praziquantel is efficacious against S. haematobium in Zimbabwe, although low levels of persistent infection warrant further investigation.

Effect of treating Schistosoma haematobium infection on Plasmodium falciparum-specific antibody responses.

BACKGROUND: The overlapping geographical and socio-economic distribution of malaria and helminth infection has led to several studies investigating the immunological and pathological interactions of these parasites. This study focuses on the effect of treating schistosome infections on natural human immune responses directed against plasmodia merozoite surface proteins MSP-1 (DPKMWR, MSP1(19)), and MSP-2 (CH150 and Dd2) which are potential vaccine candidates as well as crude malaria (schizont) and schistosome (whole worm homogenate) proteins. METHODS: IgG1 and IgG3 antibody responses directed against Schistosoma haematobium crude adult worm antigen (WWH) and Plasmodium falciparum antigens (merozoite surface proteins 1/2 and schizont extract), were measured by enzyme linked immunosorbent assay (ELISA) in 117 Zimbabweans (6-18 years old) exposed to S. haematobium and P. falciparum infection. These responses were measured before and after anti-helminth treatment with praziquantel to determine the effects of treatment on anti-plasmodial/schistosome responses. RESULTS: There were no significant associations between antibody responses (IgG1/IgG3) directed against P. falciparum and schistosomes before treatment. Six weeks after schistosome treatment there were significant changes in levels of IgG1 directed against schistosome crude antigens, plasmodia crude antigens, MSP-1(19), MSP-2 (Dd2), and in IgG3 directed against MSP-1(19). However, only changes in anti-schistosome IgG1 were attributable to the anti-helminth treatment. CONCLUSION: There was no association between anti-P. falciparum and S. haematobium antibody responses in this population and anti-helminth treatment affected only anti-schistosome responses and not responses against plasmodia crude antigens or MSP-1 and -2 vaccine candidates.

Changes in the humoral immune responses after chemotherapy in single and co-infected individuals with Schisosoma haematobium and Plasmodium falciparum.

OBJECTIVE: To determine the effects of chemotherapy on the humoral immune responses in single and coinfected individuals with Schistosoma haematobium and Plasmodium falciparum. DESIGN: Prospective assessment of the humoral immune responses after treatment with praziquantel for schistosomiasis and chloroquine for malaria. SETTING: The study was carried out in four rural schools in Goromonzi and Mtoko districts 50km and 143km away from Harare respectively where both schistosomiasis and malaria are endemic. SUBJECTS: 555 school children aged 8 to 19 years; 298 from Goromonzi and 257 from Mtoko. MAIN OUTCOME MEASURES: Standard ELISA assays were carried out on the sera for immmunoglobin A (IgA), immmunoglobin E (IgE), immmunoglobin M (IgM) and immmunoglobin G (IgG) against the Schistosoma haematobium soluble worm antigen (SWA), soluble egg antigen (SEA), cercaria antigen (CERCA) and the Plasmodium falciparum malaria antigen (MALA). Eosinophil count was also done on Giemsa stained smears. RESULTS: Treatment resulted in a decrease of sera IgA levels against SEA in those individuals that had schistosomiasis only and there was a significant increase of sera IgE against the cercaria antigen (p < 0.05). Those that had malaria whether singly or coinfected sera IgE against MALA decreased but sera IgE against SEA increased. Sera IgE against SEA increased significantly (p < 0.05) in those that had neither infections who had been given praziquantel treatment. Eosinophilia was evident in parasitic infections. CONCLUSION: Schistosomiasis is a problem in rural settings as in all the four schools > 50% of the pupils were infected, whilst those that were < 15 years of age had high egg intensities. There was a rise in sera IgE antibodies against SEA and CERCA in all the cases that were treated with praziquantel, an indication that treatment does alter the immune response favouring resistance to infection by Schistosoma haematobium. Those that had malaria singly or coinfected produced high levels of sera IgE against SEA an indication that malaria infection influences the cytokine environment to favour production of IgE isotypes against the schistosome egg antigen.

Heterogeneities in anti-schistosome humoral responses following chemotherapy.

Schistosomiasis is a major public health problem in Africa, the Middle East, Asia and South America. The main control strategy is to treat infected people with anthelmintic drugs, principally the safe and relatively cheap drug praziquantel. Several treatment re-infection studies in humans have shown that praziquantel can have long-term effects beyond a transient reduction of infection intensity. These long-term effects include the altering of schistosome-specific immune responses in humans, which is associated with resistance to re-infection. Differences have been observed in treatment-induced immunological changes between individuals and between populations. This article discusses the contributions of host- and parasite-related heterogeneities to post-treatment humoral responses in humans infected with Schistosoma mansoni and Schistosoma haematobium and considers the practical implications of such heterogeneity for schistosome immuno-epidemiology studies.

Contrasting cellular responses in Schistosoma haematobium infected and exposed individuals from areas of high and low transmission in Zimbabwe.

The study compared cytokine profiles of individuals from two areas with different transmission patterns for Schistosoma haematobium. One area was a high transmission (HT) while the other was a low transmission (LT) area for S. haematobium. Observations on cellular immune responses were made on stimulated peripheral blood mononuclear cells (PBMC), which were collected pre-treatment, then at 12 and 18 months post treatment. Stimulation was with schistosome worm and egg antigens and a mitogen, phaetohaemaglutinin (PHA). Observations were made on PBMC proliferation and the profiles of cytokine produced over a 5-day incubation period. The two distinct areas showed significant differences on both levels of proliferation and cytokine production for all the measured classes (IL-4, IL-5, IL-10 and IFN-gamma). PBMC from individuals from the LT area had high levels of proliferation but low cytokine production to both antigen stimulants while PBMC from individuals from the HT area showed low levels of proliferation but high cytokine production levels. Prior to treatment, individuals not excreting schistosome ova in the HT area had higher levels of proliferation to the stimulants, than the infected individuals. However, after treatment re-infected individuals showed high levels of proliferation. Before treatment, both infected and uninfected groups showed low and similar ratios, respectively, of IL-4:IFN-gamma, IL-5:IFN-gamma and IL-10:IFN-gamma, while IFN-gamma was high in the infected individuals. After treatment the non re-infected had higher levels of IL-4, IL-5 and IL-10, with the infected having high levels of IFN-gamma. Th1-like response dominated during infection with the Th2-like responses dominating post treatment and in uninfected individuals. The results indicated that the cytokine balance determines, in part, susceptibility or resistance to S. haematobium infection.

On the calculation of intestinal schistosome infection intensity.

The effects of using different methods to calculate individual infection intensities on the age-infection distribution of Schistosoma mansoni field data are demonstrated. Methods are tested on a maximum of three stool samples per person collected on three consecutive days; the methods considered for the calculation of individual infection intensities are the geometric mean (GM), arithmetic mean (AM) and pseudo geometric mean (GM of stool samples instead of replicates). In addition, the effects of calculating the infection intensity for each age group using either AMs or GMs are compared. Differences occur in the shape of the age-infection profiles obtained by using either the arithmetic or geometric group mean. When using the AM, peak infection intensity occurs in a younger age group compared to using the GM, and all three methods of calculating individual infection intensity give the first peak of infection in the same age group. However, differences occur in the position of the second peak which occurs earlier with the two GMs than with the AM. Bootstrapping procedures show that the individual AM, gives a different age group for the first peak of infection at least 25% of the time when compared to either of the GMs, and 31% of the time for the second peak, while the two GMs give the same peak age groups around 90-92% of the time for both peaks. When using the GM, to calculate infection intensity for each age group, there are no differences between the three methods used to calculate individual infection intensity. This is confirmed by bootstrapping procedures. The results are discussed in relation to the distribution of parasites and levels of parasite aggregation. The implications of the results for field studies are also discussed.

Consequences of polyparasitism on anaemia among primary school children in Zimbabwe.

The effect of concomitant infection with schistosomes, Plasmodium falciparum and soil transmitted helminths (STHs) on anaemia was determined in 609 Zimbabwean primary school children. P. falciparum, haemoglobin levels and serum ferritin were determined from venous blood. Kato Katz, formal ether concentration and urine filtration techniques were used to assess prevalence of Schistosoma mansoni, STHs and Schistosoma haematobium infections. The prevalence of S. haematobium, S. mansoni, P. falciparum, hookworm, Trichuris trichiura and Ascaris lumbricoides were 52.3%, 22.7%, 27.9%, 23.7%, 2.3% and 2.1%, respectively. The overall prevalence of anaemia and iron deficiency anaemia (IDA) were 48.4% (277/572) and 38.1% (181/475). Haemoglobin levels among children who had P. falciparum, S. haematobium and hookworm were lower than negative individuals, p<0.001, p<0.001 and p=0.030, respectively. The prevalence of anaemia and IDA in co-infections was almost double that in single infection. Children with P. falciparum/STHs/schistosome and schistosomes/P. falciparum co-infections recorded higher prevalence of anaemia and IDA (80.8% and 57.4%, respectively) than other combinations, p<0.001. Logistic regression revealed that, age group > or = 14 years, P. falciparum, S. haematobium light and heavy infections, and S. mansoni moderate and heavy infection, hookworm light infection were predictors of anaemia. This study suggests that integrated school based de-worming and malaria control have the potential to reduce the burden of anaemia.

The burden of polyparasitism among primary schoolchildren in rural and farming areas in Zimbabwe.

A cross-sectional study was conducted in Zimbabwe among 1303 primary schoolchildren from a rural (53.3%) and a commercial farming area (46.7%) to determine the prevalence of co-infection by helminths and Plasmodium falciparum. Urine was examined on three successive days using the filtration method. Two stool specimens were processed using the Kato-Katz method and a third specimen was processed using the sedimentation method. Plasmodium falciparum was diagnosed from thick blood films. The prevalence of Schistosoma haematobium in the rural and farming areas was 66.8% and 52.3%, respectively, and for S. mansoni the prevalence was 12.4% and 22.7%, respectively. Plasmodium falciparum, hookworms, Ascaris lumbricoides and Trichuris trichiura occurred only in the farming area, with a prevalence of 27.9%, 23.7%, 2.1%, 2.3%, respectively. Co-infection and triple infection with schistosomes, P. falciparum and soil-transmitted helminths occurred in the commercial farming area only. Hookworm and S. mansoni infections were associated with P. falciparum malaria (P<0.001, OR=2.48, 95% CI 1.56-3.93 and P=0.005, OR=1.85, 95% CI 1.20-2.87, respectively). Overlap of helminths with malaria is a concern among primary schoolchildren and incorporating helminth control in programmes aiming to control malaria will improve funding and increase the efficiency of control for neglected tropical diseases in identified co-endemic settings.

Anti-malaria humoral responses in children exposed to Plasmodium falciparum and Schistosoma haematobium.

Antibody responses directed against the Plasmodium falciparum antigens, total extract, anti-merozoite surface protein-3 (MSP3b) and glutamate-rich protein (Glurp-R0) were studied in 42 children exposed to both Schistosoma haematobium and P. falciparum infections. The association between levels of the anti-malaria IgG subclasses and IgM with host age, sex, schistosome infection intensity and schistosome specific antibodies was studied before chemotherapeutic treatment of schistosome infections. This showed a significant negative association between schistosome infection intensity and levels of IgG1, IgG3, and IgG4 directed against malaria total extract antigen, and a positive association between levels of anti-schistosome soluble egg antigen IgG2, IgG3, and IgG4 and levels of the same subclasses directed against malaria total extract antigens. The effect of treating schistosome infections with praziquantel on malaria specific responses was also studied. This treatment resulted in increases in significant IgG4 levels against MSP3b and IgM against Glurp R0. Treatment also resulted in a significant decrease in IgG4 levels against Glurp R0. Host age, sex or pre-treatment infection intensity was not associated with the magnitude of change in the two IgG4 responses while males showed a significantly higher increase in levels of IgM. The results suggest cross reactivity between schistosome and malaria antigens in this population.

Anti-schistosome antibody responses in children coinfected with malaria.

People residing in schistosome endemic areas are often infected with other parasites. The interaction of the parasites in the host has important implications in the development of acquired immunity to schistosomiasis, and schistosome immuno-epidemiology. An analysis of specific anti-schistosome egg responses in children coinfected with schistosomiasis and malaria shows that malaria positive children produce significantly more anti-schistosome IgE and IgG3 than schistosome infected children who are negative for malaria.

A comparison of humoral responses to Schistosoma haematobium in areas with low and high levels of infection.

Antibody responses to Schistosoma haematobium of 280 Zimbabweans were studied in two areas of differing infection levels. 133 of the subjects came from a low infection area with a prevalence of 33.8% and geometric mean infection intensity of 0.8 eggs per 10ml of urine, while 147 of the subjects came from a high infection area with a prevalence of 62.7% and geometric mean intensity of 3.2 eggs per 10 ml of urine. Both the age-prevalence and age-intensity curves exhibited a peak shift. IgA, IgE, IgG, IgG1, IgG2, IgG3, IgG4, and IgM antibody levels against soluble egg antigen (SEA) and whole worm homogenate (WWH) were assayed by ELISA. Females produced significantly more anti-SEA IgG1, IgG4, IgM, anti-WWH IgE and IgG1. People from the high infection area produced significantly more anti-SEA IgE, IgG3 and anti-WWH IgG3 and significantly lower levels of anti-SEA IgA, IgM and anti-WWH IgM when the effects of infection intensity, sex and age had been allowed for. The age profiles of anti-SEA IgA, IgG and anti-WWH IgA and IgM reflected current levels of infection while anti-WWH IgG1, IgG2 and anti-SEA IgG1 evolved more slowly with age, and anti-WWH IgE rose with age in both areas. Some antibody responses, anti-SEA/WWH IgM, anti-SEA IgG1 and possibly anti-SEA/ WWH IgA showed different age profiles in the two areas, with changes in antibody levels occurring at a younger age in the high infection area suggesting that immune responses are evolving more rapidly in residents of this area. This result clearly demonstrates that antibody levels are not a function of age alone.

Changes in specific anti-egg antibody levels following treatment with praziquantel for Schistosoma haematobium infection in children.

Fifty-seven children 6-15 years old resident in a Schistosoma haematobium endemic area in eastern Zimbabwe were treated with praziquantel at 40 mg/kg body weight. Levels of IgA, IgE, IgG1, IgG2, IgG3, IgG4, and IgM antibodies against soluble egg antigen (SEA) were assayed by ELISA before treatment and at 18 and 36 weeks following treatment. Prevalence of infection (as determined by urine egg counts) was 65% before treatment, all children were confirmed egg negative six weeks after treatment, and reinfection prevalence was 4% at 18 weeks and 21% at 36 weeks after treatment. At 18 weeks after treatment, there was a massive increase in IgG1 levels and significant increases in IgE and IgG4 levels and significant decreases in IgA and IgG2 levels. Similar patterns occurred at 36 weeks after treatment. Egg positive children showed a more marked increase in IgG1 and (for older children) a more marked decrease in IgG2 levels. There were no other effects of age or sex. IgA and IgG1 levels fell significantly between 18 and 36 weeks following treatment but not to pretreatment levels. The results show that specific anti-egg antibody responses are highly sensitive to the effects of praziquantel treatment. A possible consequence is that the susceptibility of children to infection with S. haematobium is altered by chemotherapy; this requires further investigation.

Exposure, infection and immune responses to Schistosoma haematobium in young children.

Behavioural, parasitological and immunological data were obtained from 48 children up to 6 years old, resident in a Schistosoma haematobium endemic area in Zimbabwe. The children averaged more than 1 contact with infective water bodies every 3 days and all showed immunological evidence of exposure (an anti-cercarial and/or anti-egg antibody response). IgM was the dominant isotype and appeared in the youngest children, followed by IgA, IgE and IgG3. However, only 38 children showed evidence of infection (an anti-egg response or eggs in urine) and only 14 were excreting eggs. The best estimates from these data are that less than 1 in 100 contacts results in infection and less than 1 in 1000 result in egg output. This suggests that there may be substantial attrition of invading cercaria even in naïve individuals.