Peter M. Wiest

Intestinal parasites in patients with diarrhea and human immunodeficiency virus infection in Zimbabwe

OBJECTIVES To determine the prevalence of intestinal parasites and risk factors for infection associated with diarrhea in HIV-infected patients in Harare, Zimbabwe. DESIGN Prospective observational study. METHODS Single stool samples were collected from 88 HIV-infected individuals presenting with diarrhea of greater than 1 week duration. Stools were examined for intestinal parasites using modified acid fast stain, fluorescence- labeled monoclonal antibody for Cryptosporidium parvum, as well as a modified trichrome stain and a PCR-based protocol for Enterocytozoon bieneusi. RESULTS C. parvum was detected in 9% (seven out of 82) of samples evaluated, but no Cyclospora was detected. E. bieneusi was detected in 18% (10 out of 55) of stool by trichrome staining and in 51% (28 out of 55) of stool examined by PCR. Risk factors for E. bieneusi infection were: living in rural areas, consumption of nonpiped water, contact with cow dung and household contact with an individual with diarrhea. CONCLUSION E. bieneusi infection was common in HIV-infected patients with diarrhea in Zimbabwe and may be acquired through person-to-person and fecal-oral transmission.

Identification of the Schistosoma japonicum 22.6–kDa Antigen as a Major Target of the Human IgE Response: Similarity of IgE–Binding Epitopes to Allergen Peptides

Human resistance to reinfection with Schistosoma mansoni and Schistosoma haematobium correlates with elevated IgE titers against worm antigens (soluble worm antigen preparation, SWAP). In S. mansoni infection, low levels of reinfection following chemotherapy are associated with the recognition of a cloned tegumental protein Sm22.6. Because of potential species–specific differences in resistance to schistosomes, we attempted to identify Schistosoma japonicum antigens recognized by human IgE. Following a survey of 176 infected individuals in Leyte, Philippines, we show that IgE antibodies from the majority of older, high–IgE/SWAP responders recognize antigens in the 22 (Sj22)–, 45–, 78– and 97–kDa range in SWAP. Limited IgE cross–reactivity between Sj22 and Sm22 was observed following a comparison of Filipino IgE responses to these antigens. The antigen was cloned from an adult S. japonicum λ–ZAP cDNA library (Mindoro strain) by immunoscreening with pooled high–titer IgE antisera and a rabbit anti–Sj22 polyclonal antibody. The deduced amino acid sequence of the identified cDNA clone, MJ–1, showed significant homology to Sm22.6 (74%) and Sj22.6 (99%). Although the molecular sequence of Sj22.6 has already been reported, this is the first demonstration of its recognition by human IgE, thereby strengthening its potential as a vaccine candidate. Using an overlapping peptide approach, four IgE–binding epitopes were identified in Sj22.6, two of which exhibited similarities to known IgE–binding epitopes from codfish (Gad c 1) and β–lactoglobulin–related allergens. These findings suggest that allergy and protective immunity to helminth infection may be linked by the structural similarities of epitopes recognized by human IgE.

Paramyosin: a candidate vaccine antigen against Schistosoma japonicum.

Paramyosin, a 97 kDa myofibrillar protein, is a candidate vaccine antigen for prevention of infection with the human parasite Schistosoma mansoni. To determine if paramyosin would also induce protection against Schistosoma japonicum, paramyosin was biochemically purified from S. japonicum adult worms. SDS‐PAGE demonstrated a single protein with a molecular weight of 97 kDa. In four separate experiments, vaccination of mice with S. japonicum paramyosin without adjuvant induced significant resistance (62%–86%, P < 0.001) against cercarial challenge as compared to controls. These data suggest that S. japonicum paramyosin may represent a candidate vaccine for immunization against schistosomiasis japonica.

Morbidity due to schistosomiasis japonica in the People's Republic of China

Transmission and morbidity induced by Schistosoma japonicum were evaluated in 825 individuals undergoing periodic treatment with praziquantel on Jishan island, Jiangxi Providence, in the Peoples Republic of China. Eggs of S. japonicum were found in the stools of 39.4% of the population; 70% of those infected were less than 20 years of age. Hepatomegaly greater than 3 cm in the midsternal line was detected by physical examination and ultrasonography in 75% and 90% of individuals, respectively, regardless of infection status. Symmers clay pipe-stem fibrosis of the liver was detected by ultrasonography in 20% of all individuals. Hepatitis B surface antigen and antibody to hepatitis C were found in 11% and less than 1% of the population, respectively. Our study suggests that, despite intermittent chemotherapy, morbidity due to S. japonicum is still a significant problem in China.

The epidemiology of morbidity of schistosomiasis

The epidemiology of schistosomiasis is changing because treatment of chronically infected individuals is often followed by reinfection. As a major goal of schistosomiasis control is the reduction of morbidity, direct assessment of disease is essential because infection status is a relatively poor indication of morbidity. Introduction of ultrasonography to the study of schistosomiasis and the increased appreciation of the effects of schistosomiasis on growth and development in children have greatly enhanced our understanding of schistosome-induced morbidity in endemic communities. Peter Wiest here reviews the changes in the assessment of schistosomiasis-induced morbidity.

HLA class II antigens positively and negatively associated with hepatosplenic schistosomiasis in a Chinese population.

To identify possible associations between host genetic factors and the onset of liver fibrosis following Schistosoma japonicum infection, the major histocompatibility class II alleles of 84 individuals living on an island (Jishan) endemic for schistosomiasis japonica in the Poyang Lake Region of Southern China were determined. Forty patients exhibiting advanced schistosomiasis, characterised by extensive liver fibrosis, and 44 age and sex-matched control subjects were assessed for the class II haplotypes HLA-DRB1 and HLA-DQB1. Two HLA-DRB1 alleles, HLA-DRB1*0901 (P=0.012) and *1302 (P=0.039), and two HLA-DQB1 alleles, HLA-DQB1*0303 (P=0.012) and *0609 (P=0.037), were found to be significantly associated with susceptibility to fibrosis. These associated DRB1 and DQB1 alleles are in very strong linkage disequilibrium, with DRB1*0901-DQB1*0303 and DRB1*1302-DQB1*0609 found as common haplotypes in this population. In contrast, the alleles HLA-DRB1*1501 (P=0.025) and HLA-DQB1*0601 (P=0.022) were found to be associated with resistance to hepatosplenic disease. Moreover, the alleles DQB1*0303 and DRB1*0901 did not increase susceptibility in the presence of DQB1*0601, indicating that DQB1*0601 is dominant over DQB1*0303 and DRB1*0901. The study has thus identified both positive and negative associations between HLA class II alleles and the risk of individuals developing moderate to severe liver fibrosis following schistosome infection.

Schistosomiasis japonica on Jishan Island, Jiangxi Province, People's Republic of China: persistence of hepatic fibrosis after reduction of the prevalence of infection with age

Hepatic fibrosis due to schistosomiasis japonica was examined by ultrasonography in a cross-sectional community study of 825 individuals on Jishan Island, Jiangxi Province, China. The prevalence of active infection was 39.4% with peak infection in the 10-19.9 years age group followed by a significant decline. A similar pattern was observed for intensity of infection. The prevalence of hepatomegaly in the midsternal line > or = 6 cm peaked at 60% in the fourth decade and remained elevated. A progressive increase in the severity of hepatic periportal fibrosis was observed with age, with advanced fibrosis peaking in the fifth decade. The proportion of individuals with advanced fibrosis was significantly greater in males than in females despite equivalent prevalence and intensity of schistosome infection. In addition, a positive association (P < 0.01) was found between periportal fibrosis and both hepatomegaly > or = 6 cm and splenomegaly. This study suggests that the natural history of schistosomiasis japonica in this hyperendemic community in China is marked by persistence of hepatomegaly and schistosome-induced periportal fibrosis in adults despite a decrease in the prevalence of infection.

Malaria in travelers in Rhode Island : a review of 26 cases

PURPOSE We reviewed our experience with malaria in two community hospitals in Rhode Island from 1986 to 1990. RESULTS Twenty-six patients with malaria were identified. Fifteen patients were immigrants who had acquired malaria while visiting their country of origin, particularly West Africa. Fever was present in 67% of cases and gastrointestinal complaints were prominent in 26%. Individuals with a past history of malaria could accurately distinguish current malarial infections from other febrile illnesses. Two patients developed cerebral malaria. Plasmodium falciparum was identified in 77% of the cases. CONCLUSIONS Malaria is an important diagnosis that United States physicians must consider in the medical evaluation of returning travelers. A significant increase in the number of cases of P. falciparum acquired in East Africa has been reported in recent years. P. falciparum infection must be rapidly diagnosed and treated since delays may result in complications of malaria that may lead to death. Mefloquine is currently recommended by the Centers for Disease Control for prevention of malaria in travelers visiting countries endemic for chloroquine-resistant malaria. This change may alter the epidemiology of malaria in the United States in the future.

Enterocytozoon bieneusi infection in patients without evidence of immunosuppression: two cases from Zimbabwe found to have positive stools by PCR.

Patients infected with human immunodeficiency virus (HIV) often also have intestinal infections with Enterocytozoon bieneusi. Recently, infection with this microsporidian has been described in immunocompetent subjects, mainly from Europe. When the stools of six HIV-negative patients who presented with diarrhoea in Zimbabwe were investigated, using a recently described protocol based on PCR, two patients were found to have E. bieneusi infections. These two individuals presented with a self limited diarrhoea, abdominal cramping and nausea. These data indicate that E. bieneusi may be a more common cause of diarrhoea in Zimbabwe than previously thought. Larger, prospective studies are needed.

Inhibition of phosphoinositide turnover by praziquantel in Schistosoma mansoni.

The effect of praziquantel on phosphoinositide turnover was examined in Schistosoma mansoni to determine if this anthelminthic modulates signal transduction pathways in parasites. Adult worms were radiolabeled with [3H]myoinositol for 24 hr and total inositol phosphate levels determined in the presence of praziquantel. Praziquantel inhibited inositol phosphate turnover when activated with NaF plus AlCl3 or with the nonhydrolyzable guanine nucleotide-binding protein analogue GTP gamma S. Furthermore, praziquantel decreased basal turnover of inositol phosphates. Inhibition was seen in both male and female worms as well as in schistosomula. These data indicate that inhibition of phosphoinositide turnover may contribute to the effect of praziquantel on parasite survival within the definitive host.