Primary prophylaxis for Pneumocystis carinii pneumonia: a randomized trial comparing cotrimoxazole, aerosolized pentamidine and dapsone plus pyrimethamine.

OBJECTIVE: To compare the efficacy and tolerance of monthly aerosolized pentamidine versus cotrimoxazole versus dapsone plus pyrimethamine to prevent the initial episodes of Pneumocystis carinii pneumonia (PCP) in HIV-infected patients. DESIGN: An open randomized clinical trial. PATIENTS AND METHODS: HIV-infected patients (n = 331) with CD4 cell counts < 200 x 10(6)/l or with AIDS but without a history of PCP or cerebral toxoplasmosis (CT) were randomized to receive pentamidine (300 mg every 4 weeks), cotrimoxazole (160/800 mg 3 days a week) or dapsone plus pyrimethamine (100 and 25 mg weekly). If immunoglobulin G (IgG) antibodies to Toxoplasma were present, patients in the first two groups were randomized further to 25 mg pyrimethamine per week or to no treatment. RESULTS: The mean follow-up was 313 days (range, 30-670 days). The three groups were homogeneous for age, sex, risk group for HIV infection, initial CD4 cell count and mean follow-up. PCP developed in 16 patients, with an estimated cumulative probability of 5.3% at 1 year of follow-up. The PCP rate per year of observation, using an intention-to-treat analysis, was 5.6% [95% confidence interval (CI), 0.9-10.3], 3% (95% CI, 0-6.3) and 8.3% (95% CI, 2.8-13.8) in the groups treated with pentamidine, cotrimoxazole and dapsone plus pyrimethamine, respectively (P > 0.05). Moderate or severe side-effects were observed in one patient on pentamidine, 10 on cotrimoxazole and nine on dapsone plus pyrimethamine (P < 0.05); the study drug had to be discontinued in no, 10 and six patients, respectively (P < 0.05). Neither cotrimoxazole alone nor pyrimethamine combined with dapsone or cotrimoxazole prevented initial episodes of toxoplasmosis among patients with IgG antibodies to Toxoplasma gondii. CONCLUSIONS: Low-dose thrice-weekly cotrimoxazole or weekly dapsone plus pyrimethamine was not significantly worse (differences > 15% would have been detected with 90% certainty) than monthly aerosolized pentamidine in preventing a first episode of PCP in patients at high risk, but aerosolized pentamidine was better tolerated.

Efficacy of octreotide in the management of chronic diarrhoea in AIDS.

Patients with HIV infection were studied to assess the efficacy of octreotide, a somatostatin analogue, in the long-term management of refractory diarrhoea. Dosage of subcutaneous octreotide was increased progressively at 48 h intervals from 150 to 300, 750 and 1500 micrograms/day according to response. Twenty-nine patients, 21 with Cryptosporidium enteritis, one with Isospora belli enteritis and seven with no identifiable pathogen were selected for the study; four of these were excluded from the study because of death during the first month (two cases), abdominal pain and acute pancreatitis (one case each). Twenty-five patients were evaluable for response. Ten patients (four with Cryptosporidium enteritis, five without an identifiable pathogen and one with I. belli enteritis) achieved a complete response (40%) and nine cases (all with cryptosporidial enteritis) had a partial response (36%). Patients with higher weight and Karnofsky performance status and non-cryptosporidial enteritis had a better response to treatment. Mean durations of treatment and response were 4.2 +/- 4.2 and 4.4 +/- 4.5 months, respectively. In the absence of specific agents for cryptosporidial enteritis and HIV enteropathy, octreotide was found to be useful in the management of chronic diarrhoea in AIDS patients.

Schistosomiasis and the Dogon country (Mali)

A previously unknown area of schistosomiasis transmission is reported based on findings from a travelers' clinic in Barcelona. Three species of Schistosoma (S. haematobium, S. mansoni, and S. intercalatum) were diagnosed in a cluster of 43 patients who had been swimming in the Bandiagara and Bankas districts of Mali, where the Dogon people live. Three villages in the Bankas district appear to harbor these three species. The transmission potential of such a focus in this area is outlined. The travelers involved had little or no information on the risks of contracting schistosomiasis in that area. Obtaining a traveler's history, including accurate geographic data, is shown to be a crucial asset for improving epidemiologic research.

Hematospermia: a new etiology of clinical interest.

Ten Spanish male tourists developed hematospermia and ultrasonographic evidence of involvement of the prostate and/or seminal vesicles after recreational exposure in bodies of fresh water in the Dogon country of Mali. Schistosoma eggs were detected in the ejaculate of five men, in the others, eggs were observed in the urine or feces. Three different species were observed: S. intercalatum, S. haematobium, and S. mansoni. Hemospermia and clinical prostatitis may be frequently unrecognized clinical manifestations of the early stages of infection in previously nonexposed persons. Travelers to endemic areas should be advised on the potential dangers of swimming and other exposure in bodies of freshwater.

Design of a one-tube hemi-nested PCR for detection of Toxoplasma gondii and comparison of three DNA purification methods.

The aims of the present study were to design an easy and sensitive DNA amplification method for detection of Toxoplasma gondii with low risk of accidental contamination, and to find a rapid method for purification of clinical samples containing potential inhibitors of the amplification reaction. With a pair of primers amplifying a 619-bp fragment of the B1 gene of this parasite it was possible to detect DNA equivalent to 10 parasites. When a third primer was added to the same tube, sensitivity increased to 0.1 parasite. In a comparison of different DNA purification methods, the High Pure PCR Template Preparation Kit (Boehringer Mannheim, Germany) gave the best results. With this purification method and the one-tube hemi-nested PCR, T. gondii DNA was detected in 14 (87.5%) of 16 clinical specimens (amniotic fluid, broncho-alveolar lavage, bone marrow, blood, liver biopsy) in which the parasite was demonstrated by cell culture.

[Ancylostomiasis and strongyloidiasis: clinico-epidemiologic comparative study of travelers coming from endemic areas]. / Anquilostomiasis y estrongiloidiasis: estudio comparativo clinicoepidemiológico en viajeros procedentes de áreas endémicas.

BACKGROUND: The increase in immigration and adventure travelling by tourists generates a population susceptible to have a type of helminthiasis which we are not familiar with. The clinical-epidemiologic characteristics of different groups of patients with this disease are presented. METHODS: A descriptive retrospective longitudinal study was carried out. The clinical-epidemiologic and imaging laboratory data of 56 patients with ankylostomiasis and strongyloidiasis observed in the Department of Tropical Medicine of the Hospital Clinic i Provincial, in Barcelona, Spain, were collected. RESULTS: Ankylostomiasis and strongyloidiasis represent 2% of the global diseases attended. The risk factor the "use of open footwear" was present in almost all the cases. Among the immigrants this parasitosis may become manifest up to 10 years after the last contact. The digestive form and the accidental finding were the most common forms of presentation among the tourists and immigrants, respectively, with diarrhoea being the most frequent manifestation among the tourists (p = 0.008). Forty-five percent of the patients presented polyparasitism, being more frequently observed among the immigrants (p = 0.025). Anemia was found among 44% of the immigrants while this was not observed in any of the tourists (p = 0.012). No clinical relapse was observed with treatment with mebendazol and thiabendazol. CONCLUSIONS: A clinically different behavior was observed between the two groups of travellers. Although infrequent, the clinical importance ot its diagnosis is based on avoiding severe complications in immunosuppressed individuals and preventing anemia in patients with several diseases.

[Amebic liver abscess: review of 13 cases]. / Absceso hepático amebiano: revisión de 13 casos.

Amebian hepatic abscess (AHA) is the most frequent extraintestinal localization of infection by Entamoeba histolytica. Despite being a disease mainly of tropical zones, it is currently also observed with higher frequency in Spain. Thirteen cases of AHA diagnosed in the authors' hospital over the last 11 years were retrospectively analyzed comparing the data in this series with that of other published series and undertaking a review of this subject. The diagnosis of AHA was established on the basis of the clinical picture together with specific positive serology and compatible echographic imaging. The series was composed of 9 males and 4 females with a mean age of 38.7 years (range 25-55). Five were Spanish, and 8 were immigrants from tropical countries. In 61.5% of the cases echographically guided aspiration puncture was performed with placement of percutaneous drainage being carried out in 38%. Eighty-five percent of patients were treated with more than one amebicide drug (metronidazole or tinidazole together with chloroquine and dehydroemetine). Luminal amebicides were administered lastly. Laparotomy was required in 3 cases due to the presence of complications. No deaths were observed.

[Myositis caused by Pleistophora in a patient with AIDS]. / Miositis por Pleistophora en un paciente con sida.

The third case in the literature is reported of an infection produced by Pleistophora. The clinical detail of the three cases are discussed. Two of the patients-including the reported one-were infected by HIV. All patients suffered from myositis with fever, resting and at palpation myalgia, and progressive weakness. Blood tests showed anaemia and high levels of muscle enzymes. Necrotic muscle fibrosis induced disabling contractures. Diagnosis was obtained by detecting the protozoon in a muscle biopsy. The spores may be detectable by means of different staining methods at light microscopy although electron microscopy remains the most reliable technique. Since this is such a rare condition there is no known treatment. Whether the albendazole could be as useful as occurs in patients infected by other genera of microsporidia in still uncertain.

[Seroprevalence of toxoplasmosis in women of childbearing age, 1992-1999].

UNLABELLED: To determine the need of prenatal screening for toxoplasmosis in our hospital from a seroepidemiological point of view. PATIENTS AND METHODS: The prevalence of IgG anti-T. gondii was retrospectively analyzed in 7.090 women of childbearing age attended in the Hospital Clínic of Barcelona from February 1992 to April 1999. The association among the seroprevalence and the variables year, age, birthplace (province of Barcelona/other provinces) and place of residence (urban/rural) was analyzed. A decreasing trend was observed in the prevalence (p < 0.001), currently being < 40% in the average women between 15 and 45 years. Infection was also directly related to age of women (p < 0.001) and birthplace out of the province of Barcelona (p = 0.001). Habitat (rural or urban) was not associated with seroprevalence. Prenatal screening for toxoplasmosis is necessary due to the high rate of seronegative women exposed to infection and the evidence of a high number of primoinfections in the childbearing period.

[Intestinal microsporidiosis in patients with AIDS: study of 3 cases]. / Microsporidiosis intestinal en enfermos con sida: estudio de tres casos.

Enterocytozoon bieneusi is a protozoa belonging to the Microsporidia family which prevalence has increased in AIDS patients. Although diagnosis is performed by the demonstration of the parasite in the epithelium of the small intestine by light and electron microscopy, techniques allowing diagnosis from stools or duodenal or biliary aspirates have recently been described. Three cases of intestinal microsporidiosis diagnosed by the mentioned method are reported. The patients were 3 males with chronic diarrhea of several months of evolution with an important ponderal loss. All were in advanced stages of HIV infection with CD4-lymphocyte counts lower than 0.1 x 10(9)/l. In all the patients in whom intestinal absorption tests were performed these were found to be altered. One of the patients presented concommitant cholestasis with parasitation by E. bieneusi being demonstrated as by the biliary route in this patient. Confirmation of infection by E. bieneusi was performed in the 3 cases by electron microscopy study of stools. A review of intestinal microsporidiosis in AIDS patients is carried out and the therapeutic possibilities available for this infection are discussed.

[Schistosomiasis imported by Spanish travelers: clinico-epidemiologic study of 80 cases]. / Esquistosomiasis importada por viajeros españoles: estudio clínico epidemiológico de 80 casos.

BACKGROUND: Swimming in rivers or lakes is a risk activity, in areas where the life cycle of schistosomiasis occurs. This report presents and analyzes the clinical presentation and epidemiological data of 80 Spanish travellers. PATIENTS AND METHODS: Descriptive longitudinal and retrospective study that includes clinicoepidemiological and the laboratory data and imaging diagnosis. Patients were seen at the Section of Tropical Medicine, Hospital Clínic i Provincial, Barcelona. RESULTS: Most patients acquired the infection in the Dogon country of Mall. 25% of them presented with symptoms related to the genital tract. In some groups, 45% of travellers that swam, contracted the infection. The most prevalent species diagnosed was S. haematobium and 10 travellers presented with mixed infections. CONCLUSIONS: The trip to the Dogon country should be considered as "a risk activity". Travellers Advice Clinics should include the subject of swimming in infected waters in their routine counselling. Genital tract localizations were registered for three species of schistosome. The classical clinical presentation of schistosomiasis in the endemic areas differs considerably from that seen in travellers.

[Analysis of a case of severe congenital toxoplasmosis]. / Análisis de un caso de toxoplasmosis congénita grave.

BACKGROUND: To describe a case of severe congenital toxoplasmosis because of inadequate surveillance of a seronegative pregnant woman and to evaluate the usefulness of different microbiological diagnostic methods after birth. METHODS: We applied serology, DNA amplification by one-tube semi-nested PCR, cell culture and mice inoculation analysis. RESULTS: Anti. T. gondii serology was useful for the diagnosis of congenital toxoplasmosis. PCR analysis of neonate cerebrospinal fluid and peripheral blood were positive, and yielded negative results after a few days of specific treatment. Cellular culture and mice inoculation yielded negative results. CONCLUSIONS: Our results suggest that serology and PCR are useful methods for the diagnosis of toxoplasmosis in newborns. Prenatal toxoplasmosis screening and suitable follow up of the seronegative pregnant women are necessary to prevent cases of severe infection in our area.

[Enteritis caused by Isospora belli in patients with the acquired immunodeficiency syndrome. Description of 9 cases]. / Enteritis por Isospora belli en pacientes con síndrome de inmunodeficiencia adquirida. Descripción de nueve casos.

The features of the nine first cases of Isospora belli enteritis in patients with acquired immunodeficiency syndrome (AIDS) diagnosed in the Hospital Cliníc i Provincial of Barcelona from September 1984 to May 1989 are reported. All patients were male, five were homosexual and four were parenteral drug abusers. The clinical presentation was watery diarrhea without pathological products lasting for more than one month. Five patients had features of dehydration, five had malabsorption, two had fever and one had metabolic acidosis. Enteritis by I. belli was the first opportunistic infection in eight of the nine cases. The number of T4 lymphocytes was lower than 0.4 x 10(9)/l in four of the seven patients in whom it was measured, and the p24 antigen was detected in serum in three out of five. The response to co-trimoxazole, both in the acute phase and as maintenance therapy, was satisfactory; however, two patients had recurrences despite maintenance therapy with co-trimoxazole. In one of them I. belli was clinically resistant to co-trimoxazole therapy and to other drugs, the diarrhea only responding to the administration of a somatostatin analogue (SMS 201-995).

[Incidence of enteropathogens in patients with human immunodeficiency virus infection]. / Incidencia de enteropatógenos en pacientes con infección por el virus de la immunodeficiencia humana.

BACKGROUND: To establish the incidence of diarrhea and its evolution over time, the causal microorganisms, recurrence and associated mortality in patients with AIDS or severe immunologic alterations (CD4 lymphocytes lower than 0.5 x 10(9)/l). METHODS: A prospective longitudinal study was carried out from 1984 to 1992. The following patients were included in the study: 1) all those patients with diarrhea in whom a pathogenic microorganism was identified in the stools, and 2) patients with fever and positive blood cultures for enteropathogenic bacteria. The patients belonged to a series of 1,456 patients with infection by HIV. RESULTS: Of the 1,456 controlled patients, 253 (17%) had infection by enteropathogenic microorganisms. The incidence was greater in homosexual patients (26%) than in drug addicts (12%). The most frequent germs were Cryptosporidium, in 104 episodes and Salmonella sp. in 78 episodes (31 as isolated bacteria). The mortality in the 15 days following isolation was 2%, the referred microorganisms being the most frequent responsible for the deaths. The mean of CD4 lymphocytes in the patients with enteropathogens was 0.17 x 10(9)/l). SD 0.14 x 10(9)/l). In patients with infection by Cryptosporidium the CD4 lymphocyte count was lower than that observed in the cases of infection by Isospora belli. Prior to 1988, 21% of the patients had infection by enteropathogenic bacteria and 23% by parasites, those percentages being 3% and 6%, respectively in 1991. CONCLUSIONS: Infections by enteropathogenic microorganisms in patients with infection by the human immunodeficiency virus in an advanced stage are frequent, particularly, in homosexuals. The patients with enteritis by Cryptosporidium have a greater grade of immunosuppression (CD4 lymphocytes lower than 0.1 x 10(9)/l) than patients with infection by other enteropathogenic microorganisms. In the last few years, the incidence of enteropathogenic bacteria, especially Salmonella sp. and protozoa has decreased [corrected].

[Chronic enteropathy of unknown etiology in patients with AIDS. An analysis of 40 cases]. / Enteropatía crónica de etiología desconocida en pacientes con SIDA. Análisis de 40 casos.

BACKGROUND: Data about the etiology of chronic enteropathy in AIDS patients are scarce and are very dependent upon the geographical area. The aim of this study was to detect microorganisms potentially associated with chronic enteropathy in AIDS patients with diarrhoea for more than one month, and initial negative routine stool bacterial cultures and examinations for ova and parasites. The degrees of associated intestinal malabsorption and immunodeficiency were also analysed. PATIENTS AND METHODS: Forty consecutive patients were recruited from January 1993 to December 1994. The following studies were performed: Intestinal absorption tests (d-xylose and 14C-triolein), CD4/CD8 cell counts, microbiological studies (standard stool cultures for detection of bacteria and examinations for ova and parasites including the detection of Enterocitozoon bieneusi spores by the Weber's stain), upper gastrointestinal endoscopy or colonoscopy with intestinal biopsies and blood cultures for CMV and mycobacteria. RESULTS: The median duration of diarrhoea was 4 months and the mean weight loss was 8.4 kg. Ninety percent of patients had less than 0.1 x 10(9) CD4+ cells/l, with a mean CD4+ cell count of 0.035 x 10(9)/l. Malabsorption was found in 84% of patients. An etiological diagnosis of chronic enteropathy was reached in 60% of the patients. The yield of pathological examination was 37% and the microbiological test using samples of faeces and blood were positive in 45% and 20% of cases respectively. The most frequently identified microorganisms were CMV (10 cases), E. bieneusi (9), enterobacteria (8), Cryptosporidium parvum (5), Leishmania donovani (2). Patients with enteropathy caused by E. bieneusi had lower count of CD4 cells (p = 0.005) and with higher serum levels of alkaline phosphatase (p = 0.02) than patients with CMV enteropathy. CONCLUSIONS: Stool Weber's stain and CMV and mycobacterial blood cultures should be added to the standard work-up diagnosis in patients with chronic diarrhoea and a CD4+cells count below 0.1 x 10(9) l. Upper and/or lower gastrointestinal endoscopies with intestinal biopsies should be performed only in patients with persistent diarrhea without microbiological diagnosis or a lack of response to treatment.

Aetiology of traveller's diarrhoea: evaluation of a multiplex PCR tool to detect different enteropathogens.

Traveller's diarrhoea (TD) is the most common illness reported in international travellers. TD is caused by a wide range of pathogens, including bacteria, viruses and parasites. Multiplex PCR assays can be especially useful for studying the aetiology of TD. The first objective of this study was to evaluate the utility of the commercially available multiplex PCR (xTAG(®) Gastrointestinal Pathogen Panel (GPP)) for the diagnosis of TD. A total of 185 stool specimens obtained from 174 patients were processed using the GPP assay. This test detected 86 pathogens in 67 stool samples (67/185, 36.2%). Sixteen pathogens out of 86 were also detected by routine testing. The remaining pathogens (n = 70) required further confirmation by alternative techniques. Finally, 60 out of 70 pathogens were confirmed. The second objective of this study was to analyse the aetiology of TD based on the results obtained by the GPP test and routine methods. The primary pathogens causing TD were Shigella (24.2%) followed by enterotoxigenic Escherichia coli (ETEC) (23.2%), enteroaggregative E. coli (14.7%) and Giardia (13.7%). Significant regional differences were observed for ETEC with 19.4% of TD cases acquired in Africa, 11.3% in Asia and none in South Central (SC) America (p 0.01), Giardia was found in 1.5% of cases among those who had travelled to Africa, 14.1% of those who had travelled to Asia and 3% of those who had travelled to SC America (p 0.01). In conclusion, the GPP test improved the detection of enteropathogens and allowed better assessment of the aetiology of TD.

A family cluster of giardiasis with variable treatment responses: refractory giardiasis in a family after a trip to India.

Persistence of giardiasis after some of the recommended drugs is occurring with increasing frequency. We describe the follow-up of four members of a family with giardiasis through microscopic observation, immunochromatography and PCRs of tpi and ß-giardin genes. Three patients did not respond to tinidazole but they were cured after quinacrine. However, PCR became negative at 2 months after negativization of stools in two patients and after 1 year in one patient. In all cases Giardia assemblage B was characterized with high homology between all isolates. Further studies are needed to determine the value of PCR in the diagnosis of Giardia infections.