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.

Systemic strongyloidiasis in patients infected with the human immunodeficiency virus. A report of 3 cases and review of the literature.

We report 3 cases of systemic strongyloidiasis in HIV-infected individuals and review 11 additional cases reported in the English-language literature. Systemic strongloidiasis is a rare and potentially fatal complication of late-stage HIV disease. A combination of gastrointestinal and respiratory symptoms in an HIV-infected patient who has been to an endemic area should prompt the clinician to search for S. stercoralis in stool and sputum specimens. Treatment failures occur commonly, and careful follow-up is warranted. New antihelminthic drugs (such as ivermectin) seem promising and need to be evaluated in controlled studies.

Cardiomyopathy associated with the acquired immune deficiency syndrome.

Three cases of congestive cardiomyopathy complicating the acquired immune deficiency syndrome (AIDS) are reported. In one case, acute cardiac decompensation resulted in prolonged but ultimately reversible cardiogenic shock. In the second case, clinical signs of cardiac disease were precipitated by acute renal failure and fluid overload. In the third, congestive heart failure developed spontaneously and responded promptly to administration of diuretics but the patient died suddenly, apparently due to an arrhythmia. The etiology of cardiomyopathy in AIDS is unclear and the manifestations of cardiomyopathy in this setting range from subclinical to life threatening.

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.

Screening of murine monoclonal antibodies against living schistosomula of Schistosoma mansoni by radioimmunoassay.

A radioimmunoassay was developed to screen supernatants of murine monoclonal antibodies against surface antigens of living schistosomula of Schistosoma mansoni. Of 196 clones screened, 10% bound schistosomula. Of these, 74% bound only schistosomula. The remaining molecules also reacted with soluble adult worm antigens and soluble egg antigens as determined by enzyme-linked immunosorbent assay. Immunoblot analysis demonstrated that monoclonal antibody 204-3E4 reacted with a 68 kDa protein, a glycoprotein that induces substantial resistance against S. mansoni infection. Recognition of an 18 kDa antigen by 204-3F1 antibody was stage-specific with the antigen being expressed in cercariae, 3- and 24-h-old parasites but not 4-day, lung stage or adult worms. Monoclonal antibody 204-4E3 reacted with purified S. mansoni paramyosin. These data indicate that radioimmunoassay using living schistosomula is a rapid alternative method to identify murine hybridomas that secrete antibodies which react with surface antigens of S. mansoni.

Serious infectious complications of corticosteroid therapy for COPD.

We report seven elderly patients with COPD who developed serious infectious complications during prolonged treatment with high doses of corticosteroids. Infections included invasive pulmonary aspergillosis, Herpes simplex stomatitis and esophagitis, cytomegalovirus pneumonia, bacterial sepsis, fungemia and meningitis due to Cryptococcus neoformans. Each of the three patients who developed invasive aspergillus pneumonia died. The efficacy of prolonged therapy with high doses of corticosteroids in patients with COPD is not proven. These cases illustrate the potential for serious infections in patients with COPD treated with corticosteroids.

Determinants of surface membrane maturation during the cercarial-schistosomula transformation of Schistosoma mansoni.

The transformation of free-living cercariae to parasitic schistosomula of Schistosoma mansoni is accompanied by the formation of a multilaminate surface membrane which binds concanavalin A (Con A). This transition normally occurs with penetration of intact skin of the mammalian host, but can be accomplished by vortexing and incubating organisms at 37 degrees C in complex tissue culture medium (e.g., Earle's lactalbumin). We determined the minimal conditions that initiate surface maturation by monitoring surface changes by transmission electron microscopy and surface fluorescein-conjugated Con A labeling. Cercariae incubated in water for 2 hr at 37 degrees C retained their trilaminate surface and were non-fluorescent. After incubation in 116 mM NaCl for 3 hr at 23 degrees C, no organisms were covered by intense surface fluorescence; increasing the temperature to 37 degrees C resulted in 50% of the parasites becoming fluorescent. The addition of 26 mM NaHCO3 (pH 7.4) to parasites incubated in NaCl at 37 degrees C resulted in 98% of the organisms binding Con A. No significant difference in surface Con A binding was found between organisms incubated with the chelators EGTA or EDTA and controls. Mechanical stimulus by itself was not effective in stimulating surface maturation. The conditions that initiated surface maturation were elevation of temperature to 37 degrees C and NaHCO3-containing medium.

Developmental expression of protein kinase C activity in Schistosoma mansoni.

The multicellular parasite Schistosoma mansoni undergoes complex physiologic changes during development from infective cercariae to adult worms in the mammalian host. The present study examined changes in protein kinase C (PKC) activity in S. mansoni during parasite maturation. Activation of PKC required Ca+2, phosphatidylserine, and either diacylglycerol or phorbol ester similar to mammalian PKC enzyme. A nine-fold increase in total PKC activity was found in adult worms as compared with larval parasites. Transformation of infective cercariae to parasitic schistosomula was associated with translocation of PKC activity from the cytosolic to membrane fraction. Tegumental extracts demonstrated significant PKC activity, suggesting a signal transduction system in the surface of the parasite. These data indicate that PKC activity is differentially expressed during parasite development and may have critical roles in regulation of cellular events in S. mansoni.

Impact of annual screening and chemotherapy with praziquantel on schistosomiasis japonica on Jishan Island, People's Republic of China.

The impact of annual screening and treatment with praziquantel on schistosomiasis japonica was examined on Jishan Island in Po Yang Lake, Jiangxi Province. China. Prevalence of infection in the community decreased from 39% in year 1 to 33% in year 3 with a corresponding decrease in the geometric mean egg count from 51 eggs per gram of stool (epg) to 31 epg. The most dramatic changes in infection status and intensity of infection were observed in younger individuals (0-19 years of age). The prevalence of hepatosplenomegaly also significantly decreased, again primarily in younger individuals. No change in the community prevalence of schistosome-induced hepatic fibrosis was observed as determined by ultrasonography. Longitudinal cohort analysis, however, demonstrated significant improvement in treated individuals with advanced hepatic fibrosis. These data indicate that annual screening and treatment had a significant impact on infection status and morbidity and suggest that community therapy may be an effective approach to control schistosomiasis japonica in lake regions and marshlands in China. Further studies are necessary to determine the optimal and most cost-effective approach for drug delivery.

Child growth, nutritional status, and schistosomiasis japonica in Jiangxi, People's Republic of China.

The association between schistosomiasis japonica and nutritional status and child growth was studied cross-sectionally in 239 males and females (age range 4-19.9 years) residing in Jishan Island in Po Yang Lake in an endemic region of Jiangxi, China. The presence of Schistosoma japonicum eggs in Kato stool smears and the intensity of schistosomiasis as assessed by quantitative egg count were determined, as were the presence of hookworm, Ascaris, and Trichuris eggs. Anthropometric measures included stature, weight, weight-for-height, upper arm muscle area, and the sum of triceps and subscapular skinfold thickness. The association between schistosomiasis and nutritional status and growth was analyzed with multivariable models adjusted for the influence of age, age2, and polyparasitism. The prevalence of schistosomiasis was approximately 70% in both males and females. Current schistosomiasis and its intensity were significantly related to reduced stature, weight, weight-for-height, and the sum of skinfolds (all P < 0.01) in females across the entire age-span. The greatest age-specific differences were during adolescence in females: 4 cm in height and 5 kg in weight. In males, intensity of schistosomiasis was related (P < 0.03) only to the sum of skinfolds. The cross-sectional associations between anthropometric reductions and schistosomiasis japonica in childhood and adolescence indicate a strong independent effect of infection on malnutrition and growth in this population from a highly endemic region of China.

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.

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 People's 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. Symmer's 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.

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.

[Clinico-epidemiological investigation of schistosome-induced hepatosplenomegaly: a community-based study in Jishan, Xinjian County, Jiangxi].

Since the primary objective of mass chemotherapy in schistosomiasis control is reduction of schistosome-induced morbidity, it would be reasonable to assess the impact of a control program on the morbidity in a given population by investigating hepato-splenomegaly associated with schistosomiasis in a schistosomiasis endemic area. In this paper, the authors described the relationship between the prevalence, intensity and morbidity of Schistosoma japonicum infection in terms of stool egg count and ultrasonographically detectable hepatosplenomegaly in a community-based study. It was found that the epidemiological pattern of the infection in this study community was quite different from our usual understanding, that is, the prevalence remained relatively high (39.4%) when the intensity became lower. This unusual pattern might be resulted from intermittent and sporadic chemotherapy associated with frequent exposure of people to the infection in an area of high transmission. It was surprised to note that despite the praziquantel treatment carried out over the past years, the prevalence of hepatosplenomegaly induced by schistosomiasis in this community was still very high, suggesting that intermittent and sporadic chemotherapy might render little impact on schistosomiasis-induced morbidity. The investigation also showed that ultrasonography was a sensitive tool for assessing morbidity associated with schistosome infection.

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.

Microtubule inhibitors block Cryptosporidium parvum infection of a human enterocyte cell line.

No effective therapy exists for Cryptosporidium parvum, a coccidial protozoan parasite that causes severe diarrhea in patients with AIDS. The role of microtubules in parasite invasion of host cells was investigated by incubating 10(7) oocysts with a HT 29.74 cell line for 24 h in the presence of microtubule-disrupting drugs. The number of parasites per 1,000 cells was reduced by 77% (P < 0.001, n = 4) from 182 +/- 3 in untreated cells to 42 +/- 4 in cells treated with 10(-4) M colchicine. Inhibition of C. parvum infection was concentration dependent. Similar results were seen with a second microtubular depolymerization agent, vinblastine. These data suggest that microtubules are important in host cell invasion by C. parvum and may represent targets for development of new therapeutic drugs for treatment of cryptosporidiosis.

Activation of protein kinase C by phorbol esters disrupts the tegument of Schistosoma mansoni.

The tegument of the human parasite Schistosoma mansoni is critical for parasite survival within the mammalian host. The role of protein kinase C (PKC), a major effector molecule in the phosphoinositide pathway, in maintaining the structural organization of this syncytial layer was examined in adult worms. Phorbol 12-myristate, 13-acetate (PMA) and phorbol 12,13-dibutyrate (PDB), phorbol esters that activate PKC, induced formation of surface vesicles as determined by light and scanning electron microscopy. Similar results were seen with sn-2-dioctanoyl-glycerol, a synthetic analogue of diacylglycerol. No effect was seen in parasites incubated with 4-alpha-phorbol ester or alpha isomers of PMA or PDB, compounds that do not activate PKC. Vesicle formation was reversible in parasites treated with sn-2-dioctanoyl-glycerol but not with phorbol esters. The tegument of male worms was more sensitive to the effect of phorbol esters than females. Transmission electron microscopy revealed vacuolization of the tegument. These data suggest that signal transduction pathways may have a critical role in the maintenance of the structural integrity of the tegument of parasitic helminths.

Traveler's diarrhea: methods of prevention and treatment.

Traveler's diarrhea can often be avoided by following safe food and water practices while traveling in developing countries. Prophylactic agents are generally not indicated in the prevention of traveler's diarrhea. Should traveler's diarrhea develop, fluid replacement is the principal therapeutic modality. Other useful treatments include bismuth subsalicylate or anti-motility agents such as loperamide or diphenoxylate. Early empiric use of antimicrobial agents including trimethoprim-sulfamethoxazole or quinolone agents offers an excellent means of treating traveler's diarrhea and preventing its potential complications. Travelers who develop dysentery, high fever, or prolonged diarrhea lasting more than 10-14 days should seek medical attention for specific diagnosis and appropriate antimicrobial therapy.

Schistosoma mansoni: protein phosphorylation during transformation of cercariae to schistosomula.

Infectivity of the multicellular pathogen Schistosoma mansoni for the human host is dependent upon the ability of free-living cercariae to transform rapidly into parasitic schistosomula. The biochemical pathways that regulate this transitional period are unknown. The role of protein phosphorylation was investigated by examining the incorporation of [32Pi]phosphate into proteins of S. mansoni. A sevenfold increase in total phosphorylation was found in 3-hr-old schistosomula as compared to cercariae. Analysis of radiolabeled proteins by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and autoradiography demonstrated that a 14-kDa protein served as a marker for transformation, being phosphorylated in schistosomula but not cercariae. The protein was phosphorylated on a serine residue. Phosphorylation was stimulated by a shift of parasites from water to salt-containing medium at 23 degrees C. Incubation of organisms in water at 37 degrees C did not initiate phosphorylation of this protein. The 14-kDa phosphoprotein was extracted from parasite homogenates with 1 M NaCl but was insoluble in 1% Triton X-100. Protein phosphorylation during the cercarial-schistosomula transformation may represent an important biochemical event that regulates infectivity of the parasite for the human host.

Inhibition of surface membrane maturation in schistosomula of Schistosoma mansoni.

The surface membrane of the multicellular parasite Schistosoma mansoni is radically reorganized during the transformation of cercariae into schistosomula. The current study investigates factors involved in maturation of the surface from a trilaminate to a multilaminate membrane. When maturation was induced in the presence of puromycin (900 microM), the acquisition of a multilaminate surface and stainability with fluorescein-conjugated Con A were similar to that of control parasites. Similarly, although organisms treated with monensin (0.1 microM) for 3 hr showed large vacuoles in the perinuclear cytoplasm of the subtegumental cells, the surface membrane became multilaminate. In contrast, microtubule-active drugs interfered with maturation: the surface remained largely trilaminate and the percentage of organisms binding Con A to their surface was significantly reduced. Furthermore, large accumulations of multilaminate bodies were found in the subtegumental cells of colchicine-treated parasites, whereas few were seen in the controls. Colchicine-treated schistosomula failed to mature to adult worms upon injection into mice and, like cercariae, they were water tolerant. We therefore conclude that the components that constitute the schistosomula surface preexist in cercariae and suggest that they are stored in multilaminate bodies before being transported to the surface with the help of microtubules. The acquisition of the multilaminate membrane may be essential for survival of the parasites in vivo and in vitro.