Contrasting nephropathic responses to oral administration of extract of cultured Penicillium polonicum in rat and primate.

Liquid- or solid substrate-cultured Penicillium polonicum administered in feed to rats over several days evokes a histopathological response in kidney involving apoptosis and abnormal mitosis in proximal tubules. The amphoteric toxin is yet only partly characterized, but can be isolated from cultured sporulating biomass in a fraction that is soluble in water and ethanol, and exchangeable on either anion- or cation-exchange resins. After several weeks of treatment renal proximal tubule distortion became striking on account of karyocytomegaly, but even treatment for nearly two years remained asymptomatic. Extract from a batch of solid substrate fermentation of P. polonicum on shredded wheat was incorporated into feed for rats during four consecutive days, and also given as an aqueous solution by oral gavage to a vervet monkey daily for 10 days. Treatment was asymptomatic for both types of animal. Rat response was evident as the typical renal apoptosis and karyomegaly. In contrast there was no such response in the primate; and neither creatinine clearance nor any haematological characteristic or serum component concentration deviated from a control or from historical data for this primate. The contrast is discussed concerning other negative findings for P. polonicum in pigs and hamsters. Renal karyomegaly, as a common rat response to persistent exposure to ochratoxin A, is not known in humans suspected as being exposed to more than the usual trace amounts of dietary ochratoxin A. Therefore the present findings question assumptions that human response to ochratoxin A conforms to that in the rat.

Helminthiasis, bystander diseases and vaccines: analysis of interaction.

Helminthiasis has assumed a new medical and veterinary significance following the recognition of its immunomodulatory consequences for the severity of bystander conditions and the efficacy of immunization against non-helminthic diseases of humans and livestock. Recent papers by Jackson et al. and Turner et al. have an important bearing on research in these areas. One of the implications of their work is that the parasitological criterion of egg-positivity versus egg-negativity is too simplistic to use in co-infection and related studies unless accompanied by immunological analysis.

Ascaris, co-infection and allergy: the importance of analysis based on immunological variables rather than egg excretion.

The ratio of Ascaris seropositivity to the presence of eggs in the faeces was 2.44 in children residing near Cape Town, South Africa. Similar and larger ratios have previously been described for children and women living in the city. The new finding strengthens the concept that when helminthic infections occur together with non-helminthic diseases, an analysis of the interaction must include the use of disease-related immunological variables and not be based only on egg excretion status. One of the reasons is that many egg-negative people who live where helminthiasis is highly endemic are immunologically activated as a result of transitory non-patent or intermittent patent infection by Ascaris and/or other worms.

Recall of intestinal helminthiasis by HIV-infected South Africans and avoidance of possible misinterpretation of egg excretion in worm/HIV co-infection analyses.

BACKGROUND: Ascariasis and HIV/AIDS are often co-endemic under conditions of poverty in South Africa; and discordant immune responses to the respective infections could theoretically be affecting the epidemic of HIV/AIDS in various ways. It is well-known that sensitisation to helminthic antigens can aggravate or ameliorate several non-helminthic diseases and impair immunisation against cholera, tetanus and tuberculosis. The human genotype can influence immune responses to Ascaris strongly. With these factors in mind, we have started to document the extent of long-term exposure to Ascaris and other helminths in a community where HIV/AIDS is highly prevalent. In more advanced studies, objectives are to analyse relevant immunological variables (e.g. cytokine activity and immunoglobulin levels). We postulate that when Ascaris is hyperendemic, analysis of possible consequences of co-infection by HIV cannot be based primarily on excretion vs non-excretion of eggs. METHODS: Recall of worms seen in faeces was documented in relation to the age of adult volunteers who were either seropositive (n = 170) or seronegative (n = 65) for HIV. Reasons for HIV testing, deworming treatments used or not used, date and place of birth, and duration of residence in Cape Town, were recorded. Confidence intervals were calculated both for group percentages and the inter-group differences, and were used to make statistical comparisons. RESULTS: In both groups, more than 70% of participants were aware of having passed worms, often both when a child and as an adult. Most of the descriptions fitted Ascaris. Evidence for significantly prolonged exposure to helminthic infection in HIV-positives was supported by more recall of deworming treatment in this group (p < 0.05). Over 90% of the participants had moved to the city from rural areas. CONCLUSION: There was a long-term history of ascariasis (and probably other helminthic infections) in both of the groups that were studied. In women in the same community, and in children living where housing and sanitation are better, Ascaris sero-prevalence exceeded egg-prevalence by two- and three-fold, respectively. For ongoing and future analyses of possible consequences of co-infection by Ascaris (and/or other helminths) and HIV/AIDS (and/or other bystander conditions), comparisons must be based mainly on disease-related immunological variables. Especially in adults, comparisons cannot be based only on the presence or absence of eggs in excreta.

Paradoxical helminthiasis and giardiasis in Cape Town, South Africa: epidemiology and control.

BACKGROUND: South Africa has endorsed a World Health Assembly (WHA) resolution calling for control of soil-transmitted helminths (STHs). In Cape Town, services and housing that exist in old-established suburbs should minimise the prevalence of intestinal parasitic infections, even when residents are poor. Where families live in shacks in densely-populated areas without effective sanitation, more than 90% of children can be infected by STHs. The humoral immune response to worms theoretically favours infection by Mycobacterium tuberculosis and HIV. OBJECTIVES: Obtain estimates of gender-, age-, school-related and overall prevalence of helminthiasis and giardiasis in a low-income but well-serviced community. Assess possible sources of infection. Alert health services to the need for control measures and the threat from protozoal pathogens. Warn that the immune response to intestinal parasites may favour tuberculosis (TB) and HIV/AIDS. METHODS: A cross-sectional study of the prevalence of helminthiasis and giardiasis was carried out in a large, non-selective sample of children attending nine schools. Gender, school and age effects were related to non-medical preventive services, sewage disposal practices and possible sources of infection. RESULTS: The overall STH infestation rate was 55.8%. Prevalence was inluenced by school and age but not by gender. Eggs and cysts were seen at the following prevalence: Ascaris 24.8%; Trichuris 50.6%; Hymenolepis nana 2.2%; Enterobius 0.6%; Giardia 17.3%; hookworm 0.08%; and Trichostrongylus 0.1%. Approximately 60% of sewage sludge is used in a form that will contain viable eggs and cysts. CONCLUSION: Prevalence trends in this old community in Cape Town could indicate infection by swallowing eggs or cysts on food or in water, more than by exposure to polluted soil. Sewage sludge and effluent might be sources of infection. In adjacent, under serviced, newer communities, promiscuous defecation occurs. Probable vectors are discussed. The immune response to intestinal parasites might be a risk factor for HIV/AIDS and TB.

Paradoxical helminthiasis and giardiasis in Cape Town, South Africa: epidemiology and control.

BACKGROUND: South Africa has endorsed a World Health Assembly (WHA) resolution calling for control of soil-transmitted helminths (STHs). In Cape Town, services and housing that exist in old-established suburbs should minimise the prevalence of intestinal parasitic infections, even when residents are poor. Where families live in shacks in densely-populated areas without effective sanitation, more than 90% of children can be infected by STHs. The humoral immune response to worms theoretically favours infection by Mycobacterium tuberculosis and HIV. OBJECTIVES: Obtain estimates of gender-, age-, school-related and overall prevalence of helminthiasis and giardiasis in a low-income but well-serviced community. Assess possible sources of infection. Alert health services to the need for control measures and the threat from protozoal pathogens. Warn that the immune response to intestinal parasites may favour tuberculosis (TB) and HIV/AIDS. METHODS: A cross-sectional study of the prevalence of helminthiasis and giardiasis was carried out in a large, non-selective sample of children attending nine schools. Gender, school and age effects were related to non-medical preventive services, sewage disposal practices and possible sources of infection. RESULTS: The overall STH infestation rate was 55.8%. Prevalence was influenced by school and age but not by gender. Eggs and cysts were seen at the following prevalences: Ascaris 24.8%; Trichuris 50.6%; Hymenolepis nana 2.2%; Enterobius 0.6%; Giardia 17.3%; hookworm 0.08%; and Trichostrongylus 0.1%. Approximately 60% of sewage sludge is used in a form that will contain viable eggs and cysts. CONCLUSIONS: Prevalence trends in this old community in Cape Town could indicate infection by swallowing eggs or cysts on food or in water, more than by exposure to polluted soil. Sewage sludge and effluent might be sources of infection. In adjacent, under-serviced, newer communities, promiscuous defaecation occurs. Probable vectors are discussed. The immune response to intestinal parasites might be a risk factor for HIV/AIDS and TB.

Could control of soil-transmitted helminthic infection influence the HIV/AIDS pandemic.

In May 2001, the World Health Assembly (WHA) estimated that two billion people were infected by soil-transmitted helminths (S-THs) and schistosomiasis, worldwide. The WHA urged member states to recognise that there can be synergy between public health control programmes for S-THs, schistosomiasis and other diseases. This is particularly relevant to the new dimension created by the HIV/AIDS epidemics in the same impoverished communities and countries where helminthiasis is hyperendemic. Immunological adaptation between humans and parasitic helminths has developed during evolution. Review of 109 research papers, 76% (83/109) of which, were published between 1995 and February 2002, revealed increasing evidence that this relationship may have created an opportunity for more rapid infection by the human immunodeficiency virus (HIV), as well as quicker progression to AIDS. Moreover, the efficacy of some vaccines against HIV is likely to be impaired by chronic helminthiasis. For this, there is strong, indirect evidence. There is an urgent need for parasitologists, epidemiologists, immunologists and virologists to undertake comprehensive, transdisciplinary research. On the other hand, there is no current evidence that immunosuppression by HIV facilitates helminthic infection. The situation in regard to strongyloidiasis, however, is not yet clear.