Maria Eugenia Valls

Pneumocystis jirovecii pneumonia in Spanish HIV-infected patients in the combined antiretroviral therapy era: prevalence of dihydropteroate synthase mutations and prognostic factors of mortality

The incidence of Pneumocystis jirovecii pneumonia (PCP) in HIV-infected patients has decreased thanks to sulfa prophylaxis and combined antiretroviral therapy. The influence of P. jirovecii dihydropteroate synthase (DHPS) gene mutations on survival is controversial and has not been reported in Spain. This prospective multicenter study enrolled 207 HIV-infected patients with PCP from 2000 to 2004. Molecular genotyping was performed on stored specimens. Risk factors for intensive care unit (ICU) admission and mortality were identified using a logistic regression model. Seven patients (3.7%; 95% confidence interval [CI], 1.5-7.5%) had DHPS mutations. Overall mortality was 15% (95% CI, 10-21%), rising to 80% (95% CI, 61-92%) in patients requiring mechanical ventilation. None of the patients with DHPS mutants died, nor did they need ICU admission or mechanical ventilation. PaO(2) <60 mm Hg at admission was a predictor of ICU admission (P = 0.01), and previous antiretroviral therapy predicted non-ICU admission (P = 0.009). PaO(2) <60 mm Hg at admission and ICU admission during the 1st week were predictors of mortality (P = 0.03 and P < 0.001, respectively). The prevalence of DHPS mutants in Spain is low and is not associated with a worse outcome. Severe respiratory failure at admission is the strongest predictor of PCP outcome.

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.

Cyclospora in Patients with Traveller's Diarrhea

Following the description in 1986 of a new enteropathogen called Cyanobacteria-like body (CLB), several outbreaks caused by this microorganism have been described. Since then several research teams have agreed to place CLB in the genus Cyclospora and to establish the epidemiological, pathogenical and clinical features of the illness. This paper describes and assesses those features in 20 travellers diagnosed with CLB and reviews the main literature concerning this enteropathogen. CLB was found in 2.8% of all cases of travellers diarrhea in our series.

Refractory giardiasis in Spanish travellers.

Drug failure is a common cause of symptom persistence after treatment of imported Giardia duodenalis. In this retrospective study we describe a high prevalence of refractory giardiasis in people attended in a travel clinic in Spain, especially those with infections acquired in Asia. Moreover, we discuss various treatment strategies to tackle G. duodenalis that is refractory to nitroimidazoles.

Inflammatory Responses in Blood Samples of Human Immunodeficiency Virus-Infected Patients with Pulmonary Infections

ABSTRACT We analyzed the characteristics of the inflammatory response occurring in blood during pulmonary infections in human immunodeficiency virus (HIV)-infected patients. A prospective study of consecutive hospital admissions of HIV-infected patients with new-onset radiologic pulmonary infiltrates was carried out in a tertiary university hospital from April 1998 to May 2001. Plasma cyclic AMP receptor protein (CRP), interleukin 1β (IL-1β), IL-6, IL-8, IL-10, and tumor necrosis factor alpha (TNF-α) levels were determined at the time of admission and 4, 5, and 6 days later. Patients were included in a protocol addressed to study etiology and outcome of disease. A total of 249 episodes of infection were included, with the main diagnoses being bacterial pneumonia (BP) (118 episodes), Pneumocystis carinii pneumonia (PCP) (41 episodes), and mycobacteriosis (36 episodes). For these three patient groups, at the time of admission the median CRP and cytokine levels were as follows: CRP, 10.2, 3.8 and 5 mg/dl, respectively (P = 0.0001); IL-8, 19, 3, and 2.9 pg/ml (P = 0.045); and TNF-α, 46.4, 44, and 75 pg/ml, respectively (P = 0.029). There were no significant differences in levels of IL-1β, IL-6, or IL-10 among the patient groups. A total of 23 patients died. At the time of admission, HIV-infected patients with BP had higher plasma CRP and IL-8 levels than did PCP and mycobacteriosis patients. TNF-α levels were higher in patients with mycobacteriosis. An elevated IL-8 level (>61 pg/ml) at the time of admission was an independent factor associated with higher mortality (odds ratio, 12; 95% confidence interval, 1.2 to 235.5).

Prevalence of dihydropteroate synthase genotypes before and after the introduction of combined antiretroviral therapy and their influence on the outcome of Pneumocystis pneumonia in HIV-1-infected patients.

The objective of this study was to determine whether the prevalence of Pneumocystis jirovecii dihydropteroate synthase (DHPS) gene mutations has changed since the introduction of combined antiretroviral therapy (cART) and whether the mutations are associated with poor outcome in Spanish HIV-1-infected patients with Pneumocystis pneumonia (PcP). We studied 167 PcP episodes in HIV-1-infected patients diagnosed during the pre-cART (1989-1995) and cART (2001-2004) periods. Molecular genotyping of DHPS was successfully performed in 98 patients (43 pre-cART and 55 cART). Seventeen patients (17/98, 17%; 95% confidence interval [CI], 10-25%) had mutations in the DHPS gene: 14 patients (14/43, 33%; 95% CI, 19-49%) from the pre-cART period and 3 patients (3/55, 5.5%; 95% CI, 1.3-16%) from the cART period (P < 0.01). In the multivariate analysis, the pre-cART period, previous PcP prophylaxis with sulfa drugs, and homosexuality as an HIV risk factor were found to be associated with a higher risk of presenting DHPS mutations. Overall, 95% of patients were treated with trimethoprim and sulfamethoxazole (TMP-SMX). In-hospital mortality was similar in patients with (out) mutations (6% versus 11%, P = 0.84). DHPS gene mutations were more common during the pre-cART period and were associated with previous sulfa exposure and homosexuality. However, their presence did not worsen prognosis of PcP. The response to TMP-SMX with therapeutic doses was successful in most cases.

Ciclosporiasis: estudio clinicoepidemiológico en viajeros con Cyclospora cayetanensis importada

Fundamento Conocer las caracteristicas clinicas y epidemiologicas de la enteritis por Cyclospora cayetanenesis Pacientes Y Metodo Protocolo clinico, epidemiologico y microbiologico de estudio en viajeros a paises de renta baja Resultados Se diagnostico ciclosporiasis a 55 pacientes. El 96% consultaron por diarrea del viajero (DV). Las caracteristicas mas llamativas de la DV eran la persistencia de la diarrea (mas de 2 semanas de evolucion), que afectaba a 38 pacientes (69%), y una perdida igual o superior a 3 kg de peso en el 38% de pacientes de la serie. En el 36% de los casos la DV se inicio despues del viaje. Aunque cosmopolita, C. cayetanensis se aislo con mas frecuencia en viajeros a America Latina, el subcontinente indio y el sudeste asiatico. Solo en 5 viajeros se detecto algun factor de riesgo potencialmente especifico: frambuesas en tres casos, leche de bufalo en uno y ceviche en uno. Conclusiones C. cayetanensis es un enteropatogeno emergente, que se aisla en un 2 a un 4% de los pacientes afectados de DV y debe formar parte del diagnostico diferencial en esta enfermedad.

Paludismo importado de Senegal: a propósito de 17 casos en el año 2000

BACKGROUND AND OBJECTIVE: Senegal is increasingly becoming a touristic target for many people. In 2000, there was a greater number of cases of malaria in patients from this country. Our objective was to analyze such increase, to describe the characteristics of these patients and to identify the reasons for it. PATIENTS AND METHOD: From 1999 to 2002 we prospectively collected the clinical and epidemiological data of all consecutive malaria cases seen in the Unit of Tropical Medicine of the Hospital Clinic (Barcelona, Spain). RESULTS: We attended 276 patients, 74 of them during 2000; of them, 17 had travelled to Senegal and Gambia. Their mean age was 36.58 (6.9) years and 12% were women. 59% patients were Spaniards, 35% were native of Senegal and 6% of Gambia. Reason of travel was tourism in 9 cases (53%) and a visit to the family in 7 cases (41%). Mean duration of the visit was 31 (20.6) days and only 17.6% patients did a right prophylaxis. Plasmodium falciparum was the commonest species (88%). The number of patients with malaria who had visited Senegal ranged from 6.6% in 1996 to 20% in 2000 to 6.3% in 2002 (p<0.05). CONCLUSIONS: There was an unexpected increase of malaria imported from Senegal in 2000 in our Unit. Changes in both the dynamics of malaria transmission and tourism offers may account for an unsuspected increase of malaria cases.

Cuánta primaquina es necesaria para erradicar los hipnozoitos de Plasmodium vivax

Introduccion La terapia con primaquina es, hasta el momento actual, la unica disponible para el tratamiento radical de la malaria por Plasmodium vivax . La dosis optima de primaquina para evitar las recaidas de P. vivax es un tema aun en discusion Casos clinicos Se describen 3 casos de malaria por P. vivax de diferentes areas geograficas en los que se constato tolerancia a las dosis convencionales de primaquina y en algun caso incluso a dosis elevadas. Comentario La tolerancia de P. vivax a la primaquina es un problema creciente en la practica diaria por lo que es necesario reevaluar la dosis necesaria para erradicar los hipnozoitos intrahepaticos de P. vivax .