Chagas disease in the immunosuppressed patient.

This review addresses relevant aspects of Chagas disease in the immunocompromised host. Chagas disease--one of the world's most neglected diseases-has become a global public health concern. Novel transmission modalities, such as organ transplantation, evidence of parasite persistence in chronically infected individuals--with the potential for reactivation under immunosuppression--and the prolonged survival of immunosuppressed patients call for an appraisal of the disease in this particular setting. The management and outcome of solid organ transplantation in the infected recipient with special focus on heart transplantation is addressed. The guidelines for management and the outcome of the recipients of organs from infected donors are discussed, and comments on haematopoietic stem cell transplantation are included. Finally, Chagas disease in other situations of impairment of the immune system, such as HIV/AIDS and autoimmune diseases, are considered. Immunosuppression has become an increasingly frequent condition that might modify the natural history of Trypanosoma cruzi infection. A number of strategies are available for Chagas disease management in the immunosuppressed patient. First, according to recent recommendations from the health authorities in Argentina, most infected patients would benefit from being treated at diagnosis. This has not been validated for patients with different immunosuppressive disorders. A different strategy would involve treating only patients with documented reactivation (either parasitaemia or clinical manifestations). These different approaches are discussed. To reach a diagnosis of parasitaemia, monitoring is essential, either with conventional methods or with molecular techniques that are not yet available in all centres. Collaborative studies are needed to improve the level of evidence, which will allow for better guidelines.

An improved DNA isolation technique for PCR detection of Strongyloides stercoralis in stool samples.

Strongyloides stercoralis is a nematode that causes severe infections in immunocompromised patients. The low parasitic burden of chronically infected patients makes diagnosis difficult to achieve by conventional methods. Here, an in-house (IH) method for the isolation of parasite DNA from stools and a PCR assay for the molecular diagnosis of S. stercoralis were optimized. DNA yield and purity improved with the IH method which included a step of incubation of stool samples with a glycine-SDS buffer and mechanical disruption prior to DNA extraction. For the PCR assay, the addition of bovine serum albumin was required to neutralize inhibitors present in stool. The analytical sensitivity of the PCR using DNA as template, isolated with the IH method, was superior to the commercial one. This study demonstrates that a combined method that adds the step of glycine-SDS buffer incubation plus mechanical disruption prior to DNA isolation with the commercial kit increased PCR sensitivity to levels of the IH method. Finally, our assay was tested on 17 clinical samples. With the IH method for DNA isolation, a S. stercoralis specific band was detected by PCR in the first stool sample in all patients (17/17), while with the commercial kit, our S. stercoralis-specific band was only observed in 7 samples. The superior efficiency of the IH and combined methods over the commercial kit was demonstrated when applied to clinical samples with low parasitic burden. These results show that the DNA extraction procedure is a key to increase sensitivity of the S. stercoralis PCR assay in stool samples. The method developed here could help to improve the molecular diagnosis of S. stercoralis.

Analysis of serious non-AIDS events among HIV-infected adults at Latin American sites.

OBJECTIVE: Acquired immune deficiency appears to be associated with serious non-AIDS (SNA)-defining conditions such as cardiovascular disease, liver and renal insufficiency and non-AIDS-related malignancies. We analysed the incidence of, and factors associated with, several SNA events in the LATINA retrospective cohort. MATERIALS AND METHODS: Cases of SNA events were recorded among cohort patients. Three controls were selected for each case from cohort members at risk. Conditional logistic models were fitted to estimate the effect of traditional risk factors as well as HIV-associated factors on non-AIDS-defining conditions. RESULTS: Among 6007 patients in follow-up, 130 had an SNA event (0.86 events/100 person-years of follow-up) and were defined as cases (40 with cardiovascular events, 54 with serious liver failure, 35 with non-AIDS-defining malignancies and two with renal insufficiency). Risk factors such as diabetes, hepatitis B and C virus coinfections and alcohol abuse showed an association with events, as expected. The last recorded CD4 T-cell count prior to index date (P = 0.0056, with an average difference of more than 100 cells/µL) and area under the CD4 cell curve in the year previous to index date (P = 0.0081) were significantly lower in cases than in controls. CD4 cell count at index date was significantly associated with the outcome after adjusting for risk factors. CONCLUSIONS: The incidence and type of SNA events found in this Latin American cohort are similar to those reported in other regions. We found a significant association between immune deficiency and the risk of SNA events, even in patients under antiretroviral treatment.

[Risk factors associated with multiple-species candidemia]. / Factores de riesgo asociados a candidemias causadas por múltiples especies.

The incidence of fungemia has increased over the past decade. Multiple-species candidemia (MSC) has been infrequently reported. From 1998 to 2004, of 155 patients with diagnosis of candidemia at the Hospital de Clinicas (University of Buenos Aires), seven cases of MSC were identified (6 adults and 1 newborn) and compared with 21 cases of similar age and sex with monomicrobial candidemia. There were no differences in clinical data and outcome, except for the mediana duration of hospital stay (39 days for patients with MSC vs. 18 days for patients with monomicrobial candidemia, the mean time of central venous catheter permanence previous to candidemia (32 days for patients with MSC vs. 12 days for patients with monomicrobial candidemia and the duration of candidemia (5 days for MSC and 1 day for monomicrobial candidemia. In conclusion, although MSC episodes are less common than those caused by monomicrobial candidemia, modifiable risk factors such as duration of hospitalization and central venous catheter permanence account for the development of MSC.

Factores de riesgo asociados a candidemias causadas por múltiples especies / Risk factors associated with multiple-species candidemia

Los episodios de candidemia han aumentado en la última década. Sin embargo, la publicación de casos de candidemias causadas por múltiples especies (CME) es infrecuente. De un total de 155 candidemias diagnosticadas entre 1998 y 2004 en el Hospital de Clínicas de la Universidad de Buenos Aires, se identificaron 7 casos de CME (6 adultos y 1 neonato), cuyos datos clínicos y evolutivos se compararon con 21 casos de candidemias producidas por una única especie de Candida (CUE) en pacientes de similar edad e igual sexo. No se hallaron mayores diferencias clínicas o evolutivas entre los pacientes con CME y CUE; sin embargo, la mediana del tiempo de internación y del tiempo promedio de permanencia de los catéteres venosos centrales con anterioridad a la candidemia (39 y 32 días para los pacientes con CME vs. 18 y 12 días para aquellos con CUE, respectivamente) resultaron ser factores predisponentes relevantes. La duración de la candidemia fue más prolongada en los pacientes con CME que en los afectados por CUE (5 días vs. 1 día). En conclusión, aunque los episodios de CME son menos frecuentes que los causados por una única especie de Candida, factores de riesgo potencialmente controlables como el tiempo de internación y el tiempo de utilización de catéteres venosos centrales tienen mayor importancia en el desarrollo de CME.

The incidence of fungemia has increased over the past decade. Multiple-species candidemia (MSC) has been infrequently reported. From 1998 to 2004, of 155 patients with diagnosis of candidemia at the Hospital de Clínicas (University of Buenos Aires), seven cases of MSC were identified (6 adults and 1 newborn) and compared with 21 cases of similar age and sex with monomicrobial candidemia. There were no differences in clinical data and outcome, except for the mediana duration of hospital stay (39 days for patients with MSC vs. 18 days for patients with monomicrobial candidemia, the mean time of central venous catheter permanence previous to candidemia (32 days for patients with MSC vs. 12 days for patients with monomicrobial candidemia and the duration of candidemia (5 days for MSC and 1 day for monomicrobial candidemia. In conclusion, although MSC episodes are less common than those caused by monomicrobial candidemia, modifiable risk factors such as duration of hospitalization and central venous catheter permanence account for the development of MSC.

[Hantavirus pulmonary syndrome in southern Argentina]. / Síndrome pulmonar por Hantavirus en el sur andino argentino.

Andes virus was identified in 1995 as the etiologic agent of Hantavirus Pulmonary Syndrome (HPS) in Southern Argentina. We describe herein the main clinical characteristics of 25 HPS confirmed cases acquired in this area between 1993 and September 1999. The mean age was 34 years (range 11-70), with 72% males. Clinical characteristics were similar to those previously reported for Sin Nombre virus (SNV) cases. However, in this group of patients we also observed conjuntival injection in 10/25 (42%), facial flushing in 8/25 (33%), pharyngeal congestion in 7/25 (29%) and petechiae in 3/25 (12%). On the other hand, BUN was increased in 83% of cases (mean 0.77 g/l range 0.31-2.01). Mean serum creatinine concentration was 26.8 mg/l (range: 8.1-110 mg/l) with serum creatinine being higher than 20 mg/l in 8/15 patients (53%). Urinalysis was abnormal in 12/12 cases and was characterized by presence of proteins, red blood cells and granular casts. Aminotransferases were increased in 90% of cases with levels 5-10 times over normal values in 50% of cases. Serum creatine kinase concentration was elevated in 11/14 cases. Two patients required hemodialysis. Case fatality rate was 44% (11/25) and 10 of these cases died among the first 10 days of illness. Mononuclear myocarditis was observed in two cases, a finding that has not been reported for SNV cases. During the 1996 HPS outbreak in Southern Argentina due to Andes virus, there were epidemiological and molecular evidences of person-to-person transmission, a feature not previously shown for other members of the hantavirus genus. These data would also be indicative of some distinctive clinical characteristics of HPS caused by Andes virus, with more frequent renal involvement than in SNV cases.

Síndrome pulmonar por Hantavirus en el sur andino argentino. / [Hantavirus pulmonary syndrome in southern Argentina]

Andes virus was identified in 1995 as the etiologic agent of Hantavirus Pulmonary Syndrome (HPS) in Southern Argentina. We describe herein the main clinical characteristics of 25 HPS confirmed cases acquired in this area between 1993 and September 1999. The mean age was 34 years (range 11-70), with 72

males. Clinical characteristics were similar to those previously reported for Sin Nombre virus (SNV) cases. However, in this group of patients we also observed conjuntival injection in 10/25 (42

), facial flushing in 8/25 (33

), pharyngeal congestion in 7/25 (29

) and petechiae in 3/25 (12

). On the other hand, BUN was increased in 83

of cases (mean 0.77 g/l range 0.31-2.01). Mean serum creatinine concentration was 26.8 mg/l (range: 8.1-110 mg/l) with serum creatinine being higher than 20 mg/l in 8/15 patients (53

). Urinalysis was abnormal in 12/12 cases and was characterized by presence of proteins, red blood cells and granular casts. Aminotransferases were increased in 90

of cases with levels 5-10 times over normal values in 50

of cases. Serum creatine kinase concentration was elevated in 11/14 cases. Two patients required hemodialysis. Case fatality rate was 44

(11/25) and 10 of these cases died among the first 10 days of illness. Mononuclear myocarditis was observed in two cases, a finding that has not been reported for SNV cases. During the 1996 HPS outbreak in Southern Argentina due to Andes virus, there were epidemiological and molecular evidences of person-to-person transmission, a feature not previously shown for other members of the hantavirus genus. These data would also be indicative of some distinctive clinical characteristics of HPS caused by Andes virus, with more frequent renal involvement than in SNV cases.

Influence of ambroxol on amoxicillin levels in bronchoalveolar lavage fluid.

Amoxicillin levels were measured in bronchoalveolar lavage (BAL) fluid samples obtained from patients who after randomization were treated in double-blind fashion either with amoxicillin 1000 mg p.o.t.i.d. or with amoxicillin 1000 mg + ambroxol 60 mg p.o.t.i.d. Antibiotic levels were higher in the group receiving ambroxol (0.32 +/- 0.02 micrograms/ml; n = 8) than in the other one (0.19 +/- 0.02 micrograms/ml; n = 6). This difference was statistically significant (p less than 0.001). Comparisons of protein concentrations in BAL fluid samples and of amoxicillin plasma levels did not show significant differences in the two groups. These results seem to prove that ambroxol is able to increase the antibiotics concentration in the lungs, although the mechanism of action is still unclear. In addition it could be shown that the BAL technique is suitable for exploring the lung concentration of antibiotics.

Shock no asociado a deplecion hidrosalina en un caso de insuficiencia suprarrenal de etiologia metastasica. / Shock non associated with hydrosaline depletion in a case of adrenal gland insufficiency of metastasic etiology

Se presenta el caso de una paciente de 46 anos portadora de un carcinoma pulmonar con metastasis suprarrenales bilaterales que reemplazan casi totalmente las glandulas. El diagnostico se confirmo por la tomografia computada y los hallazgos necropsicos. Se trata de un caso poco comun de insuficiencia suprarrenal que reune un estado de colapso circulatorio junto a edemas. Se jerarquiza el rol de la falta de cortisol en la genesis de los fenomenos descriptos debido a que no pudo corregirse el shock con la administracion de cloruro de sodio en solucion al 0,9% o con la infusion de dopamina, pero si ocurrio luego de la administracion de hidrocortisona intravenosa

Shock no asociado a deplecion hidrosalina en un caso de insuficiencia suprarrenal de etiologia metastasica. / Shock non associated with hydrosaline depletion in a case of adrenal gland insufficiency of metastasic etiology

Se presenta el caso de una paciente de 46 anos portadora de un carcinoma pulmonar con metastasis suprarrenales bilaterales que reemplazan casi totalmente las glandulas. El diagnostico se confirmo por la tomografia computada y los hallazgos necropsicos. Se trata de un caso poco comun de insuficiencia suprarrenal que reune un estado de colapso circulatorio junto a edemas. Se jerarquiza el rol de la falta de cortisol en la genesis de los fenomenos descriptos debido a que no pudo corregirse el shock con la administracion de cloruro de sodio en solucion al 0,9% o con la infusion de dopamina, pero si ocurrio luego de la administracion de hidrocortisona intravenosa