Late reactivation of hepatitis B virus after rituximab-containing chemotherapy for mantle cell lymphoma: a case report.

BACKGROUND: Hepatitis B virus (HBV) reactivation is commonly observed in HBsAg-positive hematologic patients undergoing immunosuppressive chemotherapy. Recent guidelines recommend antiviral prophylaxis to be continued for up to 12 months after the discontinuation of the anticancer regimen. CASE PRESENTATION: We report a case of a patient who underwent antiviral prophylaxis for 26 months after the discontinuation of a rituximab-containing chemotherapy regimen for a lymphoma and was admitted in the infectious diseases department with a 3-day history of jaundice, itching, and dark urine. After excluding other possible causes of acute liver damage, HBV reactivation was suspected. HBV-DNA was 4497000 IU/mL. Following reintroduction of entecavir, we observed a steady decline of ALT, AST, bilirubin and HBV-DNA serum levels, with a rapid resolution of acute hepatitis and an improvement in clinical conditions; one year after the event of HBV reactivation and beginning of antiviral therapy, the patient was virologically suppressed. DISCUSSION: Our study demonstrates that the risk of HBV reactivation in HBsAg-positive patients with undetectable HBV-DNA can occur even after three years from the last administration of rituximab and several months after the withdrawal of prophylactic antiviral therapy in patients with hematological malignancies. This implies that a close monitoring of HBV-related markers including HBV-DNA must continue after the withdrawal of prophylactic NA therapy.

Relevance of intracranial hypertension control in the management of Cryptococcus neoformans meningitis related to AIDS.

PURPOSE: To evaluate the relationship between intracranial hyperpressure (HICP) and mortality in patients with cryptococcal meningitis related to AIDS (CMRA). METHODS: This was an observational retrospective study. Patients were treated according to the Infectious Diseases Society of America recommendations during the evaluation period (days 0, 3, 5 and after hospitalization). High intracranial pressure (HICP) was defined as ICP values of C250 mm H20. The correlation between HICP and mortality at each of the three time points considered was investigated. Statistical analysis on the descriptive parameters and on the probability of a "death" event (odds ratio, OR) at each of those three time points was performed using the statistical software program Epidata. RESULTS: Eighty patients were included in this study, of whom 53 (66.25 %) were male. The average age of the patients was 37.5 ± 8.1 (range 22­55) years. The median CD4?lymphocyte cell count was 35 (range 0­367) cells/ml. Among the entire patient cohort, 53 patients had a favorable outcome, and the mortality rate was 33.75 %. At baseline (day 0), 57 subjects (71.5 %) presented HICP, and these patients had a higher mortality rate than those with a normal ICP, but the difference did not reach statistical significance[OR 1.65, 95 % confidence interval (CI) 0.56­4.84]. On day 3, 41 of the patients presented HICP, and HICP at this timepoint was significantly associated with an increased risk of mortality (OR 4.35, 95 % CI 1.56­12.09). On day 5, 35(43.5 %) patients presented HICP, and HCIP at this time point was also significantly associated with higher mortality (OR 7.23, 95 % CI 2.53­20.14). CONCLUSION: The results of this study confirm an association between HICP and mortality in patients with CMRA and indicate that the control of ICP during the first 5 days of hospitalization is more important than managing HICP only at baseline.

[Histoplasmosis outbreak in Morón, Buenos Aires Province, Argentina]. / Brote de histoplasmosis en la Escuela de Cadetes de la Base Aérea de Morón, Provincia de Buenos Aires, República Argentina.

A histoplasmosis outbreak affecting 6 previously healthy Air Force cadets is herein presented. The patients suffered from fever and respiratory symptoms after having cleaned an abandoned hangar soiled with pigeons and bat droppings. They all presented fever, myalgia, tachypnea, and nonproductive cough. Chest X-ray and CT scan studies showed disseminated reticulonodular images affecting both lungs. Hiliar adenomegalies were also observed. All patients achieved a favourable outcome without antifungal treatment. Both serologic tests searching for specificic antibodies (immunodiffusion and counterimmunoelectrophoresis) and histoplasmin skin tests were positive in all cases. Five soil samples mixed with pigeons and bat droppings were collected from the hangar. Suspensions of these samples were inoculated into 20 hamsters by intraperitoneal injection; mycelial phase of H. capsulatum was isolated from liver and spleen cultures. The genetic profile of this strain was compared with 12 isolates obtained from Argentinean patients, and a great degree of homogeneity was observed (> 96% similarity). Although histoplasmosis is endemic in the wet Pampas, this is the first epidemic outbreak reported south of the 34th parallel.

Linfoma de células B primario de mama en una paciente con sida. Presentación de un caso y revisión de la literatura / Primary B-cell lymphoma of the breast in an AIDS patient. Case report and literature review

Los LNH constituyen la segunda neoplasia más frecuente en pacientes con VIH. Estas neoplasias están ligadas a la inmunodeficiencia, suelen ser de período de latencia prolongado y más frecuentes en hombres. Más del 95% de estas neoplasias son de fenotipo B, de alto grado de malignidad, extranodales y representan la causa de muerte en un 12% al 16% de los casos. El linfoma no Hodgkin primitivo de mama (LPM) es una entidad infrecuente, que representa el 2,2% de todos los linfomas extranodales y el 0,5% de todas las neoplasias malignas de la mama. Se presenta una mujer con sida y linfoma primario de mama. (AU)

NHL is the second most common neoplasm in patients with HIV. It is linked to immunodeficiency, tends to have a long latency period and is more common in men. More than 95% of these neoplasms are of phenotype B, high-grade, extranodal and are the cause of death in 12% to 16% of cases. Primitive non-Hodgkin lymphoma of the breast is a rare entity, accounting for 2.2% of all extranodal lymphomas and 0.5% of all breast malignancies. A woman with AIDS and primary breast lymphoma is presented. (AU)

Combined cardiohepatic transplantation due to severe heterozygous familiar hypercholesteremia type II: first case in Argentina--a case report.

Heterozygous familial hypercholesteremia type II is a recessive autonomic disease with a population incidence

Respuesta paradojal al tratamiento antituberculoso en una paciente con SIDA / PARODOXICAL RESPONSE TO ANTITUBERCULOSE TREATMENT IN A PATIENT WITH AIDS

La tuberculosis (TB) es una enfermedad infectocontagiosa de gran importancia en la salud pública y representa una de las 10 principales causas de muerte a nivel mundial. Una de las complicaciones del tratamiento antituberculoso es la respuesta paradojal, que se define como un empeoramiento clínico o la aparición de nuevas lesiones en un paciente que comienza un tratamiento antifímico. Esta reacción está mediada por una respuesta de hipersensibilidad a los antígenos de Mycobacterium tuberculosis. Suele aparecer entre 2 y 4 meses luego de iniciado el tratamiento antituberculoso, generalmente precedida por una mejoría inicial del cuadro. Se presenta una mujer con sida y tuberculosis ganglionar con respuesta paradojal a la terapéutica antimicobacteriana y se realiza una revisión bibliográfica del tema.

Tuberculosis (TB) is an infectious disease of great importance in public health and represent one of the 10 leading causes of death worldwide. One of the complication of the antituberculous treatment is the paradoxical reaction, which is defined as a worsening or the appearance of new lesions in a patient receiving antimicobacterial treatment. This paradoxical response is mediated by a hypersensitivity reaction to mycobacterial antigens. It usually appears between 2 and 4 months after initiation of tuberculosis treatment and is preceded by an initial improvement of the clinical condition. Here, we describe a woman with AIDS and lymph node tuberculosis with a paradoxical reaction to antimycobacterial therapy and the subject is reviewed.

Sifilides elegantes de BROCQ en una paciente con SIDA y sífilis secundaria. Presentación de un caso y revisión de la literatura / 5 BROCQ ELEGANTS SYPHILIDES IN A PATIENT WITH AIDS AND SECONDARY SYPHILLIS

La coinfección entre el Treponema pallidum y el virus de la inmunodeiciencia humana (VIH) altera el curso clínico clásico de la sífilis aumentando la probabilidad de aparición de formas atípicas del secundarismo sifilítico. Entre estas formas se ha descripto a la sífilis elegante, entidad caracterizada por un exantema maculopapuloso descamativo, de aspecto anular, por lo general, con indemnidad de las regiones palmo plantar y de las mucosas. Se presenta un caso de sífilis secundaria, con lesiones típicas por su aspecto y localización, de sifílides elegantes en una paciente con diagnóstico de sida

Co-infection between Treponema pallidum and HIV alters the classic clinical course of syphilis, increasing the likelihood of atypical forms of syphilitic secondaryism. Among these forms, elegant syphilis has been described, an entity characterized by a desquamating maculopapular rash of annular appearance, with indemnity of the palmoplantar surface and mucous regions. Here, we present a case of secondary syphilis with typical lesions of elegant syphillides, in a patient diagnosed with AIDS

[Antiviral sensitivity of herpes simplex virus in immunocompromised patients]. / Estudio de sensibilidad antiviral de virus herpes simplex en pacientes trasplantados.

The Herpes simplex Virus (HSV) resistance to acyclovir (ACV) occurs in a 5% of the inmunocompromised patients, approximately. The treatment with analogs of nucleosides, causes the appearance of resistent HSV-ACV stocks (ACVr) which can be produced by alteration in genes coding for the TK or the DNA-polymerase. A previous large-scale clinical study on ACVr HSV strains isolated from patients infected with human immunodeficiency virus indicated that 96% of ACVr HSV mutants were low producers of, or deficient in, TK activity (TK-), with 4% being TK mutants with an altered substrate specificity. No DNA Pol mutants were isolated. The pirophosphate analogs generate resistance in the gene of DNA-polymerase by mutation. In this paper we show the methodology used for the determination of sensibilite profiles to ACV and Phoscarnet (PFA) in a population of inmunocompromised patients. We analized 46 HSV strain from vesicular injuries of transplanted patients. All samples, were inoculated in human fibroblasts and the HSV isolates were identified by inmunofluorescence whith monoclonal antibodies. These strains were amplified and the profile of susceptibility determinated in Vero cells, using 100 tissue culture inhibition dosis 50 (TCID50) of each Viral stock and the specific antiviral drugs in different concentrations. The cytopathic effect (CPE) was evaluated after 72hs. post infection. The 50% inhibitory concentration (CI50) was calculated from the percentage of inhibition of the ECP based on the concentration of the drug. From 46 isolations, 26 were HSV-1 and 20 were HSV-2. Two of them, one HSV-1 and one HSV-2, were resistant to ACV and none of the isolates were resistant to PFA.

Brote de histoplasmosis en la Escuela de Cadetes de la Base Aérea de Morón, Provincia de Buenos Aires, República Argentina / Histoplasmosis outbreak in Morón, Buenos Aires Province, Argentina

Se describe un brote de histoplasmosis que afectó a 6 cadetes de la Fuerza Aérea Argentina, sin antecedentes patológicos previos. Todos consultaron por problemas respiratorios después de haber limpiado un hangar. En ese recinto se encontraron abundantes deyecciones de animales, presuntamente de palomas y murciélagos. Los pacientes sufrieron fiebre, mialgias, taquipnea y tos no productiva. Las radiografías y tomografías de tórax mostraron imágenes pulmonares micronodulares, engrosamiento de los tabiques interalveolares y adenopatías hiliares. Todos tuvieron una evolución favorable y no requirieron tratamiento antifúngico. Las pruebas de inmunodifusión y contrainmunoelectroforesis con antígenos de Histoplasma capsulatum fueron positivas, al igual que las intradermorreacciones con histoplasmina. Se recogieron 5 muestras de tierra del lugar, las que fueron inoculadas por vía intraperitoneal a 20 hámsteres. De los cultivos de hígado y bazo de dichos animales se consiguió aislar la fase micelial de H. capsulatum. La cepa aislada se comparó con las obtenidas de 12 pacientes argentinos utilizando perfiles genéticos y se observó un clado único con más de 96% de similitud, lo que confirma la homogeneidad de las cepas argentinas. Si bien la histoplasmosis es endémica en la Pampa húmeda, este es el primer brote totalmente documentado al sur del paralelo 34°.

An histoplasmosis outbreak affecting 6 previously healthy Air Force cadets is herein presented. The patients suffered from fever and respiratory symptoms after having cleaned an abandoned hangar soiled with pigeons and bat droppings. They all presented fever, myalgia, tachypnea, and nonproductive cough. Chest X-ray and CT scan studies showed disseminated reticulonodular images affecting both lungs. Hiliar adenomegalies were also observed. All patients achieved a favourable outcome without antifungal treatment. Both serologic tests searching for specificic antibodies (immunodiffusion and counterimmunoelectrophoresis) and histoplasmin skin tests were positive in all cases. Five soil samples mixed with pigeons and bat droppings were collected from the hangar. Suspensions of these samples were inoculated into 20 hamsters by intraperitoneal injection; mycelial phase of H. capsulatum was isolated from liver and spleen cultures. The genetic profile of this strain was compared with 12 isolates obtained from Argentinean patients, and a great degree of homogeneity was observed (> 96% similarity). Although histoplasmosis is endemic in the wet Pampas, this is the first epidemic outbreak reported south of the 34th parallel.

Mycoses in the transplanted patient.

The incidence of invasive fungal infection (IFI) has increased considerably over the past 20 years, and transplant recipients are at especially high risk for fungal infections owing to their overall immunosuppressed condition. Organ transplantation procedures were incorporated as a therapeutic option for many patients who lacked the normal functions of organs such as the heart, liver, kidney, lung, pancreas and small bowel. The prevalence of IFI in solid organ transplant (SOTR) patients ranges from 5 to 50% in kidney and liver transplants, respectively. In bone marrow transplant (BMT) patients, IFI are major causes of morbidity and mortality due to the protracted neutropenic period and graft-versus-host disease. Candida spp. and Aspergillus spp. account for >80% of fungal episodes in both SOTR and BMT. The development of new immunosuppressive agents, new prophylaxis strategies (as pre-emptive therapy) and the improvement in surgical techniques led to increase survival of transplant recipients. In this session, a clear and concise update of the recent advances in the laboratory diagnosis of candidiasis and aspergillosis in this kind of patients was presented. However, we still need to establish more rapid, sensitive and specific methods for IFI diagnosis. Representatives of the 'Subcomision de Infecciones en el Paciente Neutropenico y Transplantado (SIPNYT)' de la Sociedad Argentina de Infectologia (SADI), presented the results of an unusual multicenter study both retrospective and descriptive studies of IFI in SOTR and BMT patients in Argentina. In addition, a study of IFI in 1,861 SOTR patients from four centers and the analysis of IFI in 2,066 BMT patients from all 12 BMT centers from Argentina was presented. From these studies it can be concluded that 'all transplant recipients are not the same' and that they should be stratified according to their different risk degrees in order to determine the best prophylaxis and treatment strategies.

Chagas' disease in patients with kidney transplants: 7 years of experience 1989-1996.

Chagas' disease was present in 17.22% of persons undergoing kidney transplantation in an Argentine Hospital. The criterion for attributing reactivation of chronic Chagas' disease and transmission of Trypanosoma cruzi to grafts was detection of parasites in blood (patent parasitemia) or tissues. Reactivation was diagnosed in 5 (21.7%) of 23 recipients. Ten (43.4%) of 23 chagasic recipients without reactivation of chronic Chagas' disease had abrogation of serological reactivity. T. cruzi infection was transmitted to 3 (18.7%) of 16 non-chagasic recipients. Reactivation and infection were diagnosed by patent parasitemia or cutaneous panniculitis. For diagnosis, detection of parasites in blood and tissues had more relevance than serology. Sequential monitoring detected early reactivation and infection, permitting application of preemptive or therapeutic therapy with benznidazole, thus inhibiting, in all patients, severe clinical disease produced by a progressive and systemic replication of the parasite.

Feohifomicosis y mucormisosis (zigomicosis) en un paciente receptor de un trasplante de riñón cadavérico / Phaeohyphomicosis and mucormycosis in cadeverous kidney transplant recipient

Se presentan los datos clínicos, microbiológicos y terapéuticos de un paciente que presentó una micosis doble en el miembro superior izquierdo. Era un enfermo de 49 años de edad, de sexo masculino, que había recibido un trasplante de riñón cadavérico y fue internado en el Hospital Argerich de Buenos Aires con lesiones inflamatorias seudotumorales ubicadas en el hombro y en la muñeca del brazo izquierdo. Había sufrido una insuficiencia renal crónica compensada con hemodiálisis y en julio de 1993 se le efectuó un trasplante de riñón cadavérico. Se le administró un tratamiento inmunodepresor que incluía metilprednisona, ciclosporina y azatioprina. Presentó dos episodios de rechazo agudo del trasplante que fueron controlados con altas dosis de corticosteriodes por vía intravenosa. En 1993 se le detectó una diabetes que fue tratada con glibenclamida. El paciente vivía en el Gran Buenos Aires en una casa de madera, sin instalaciones sanitarias adecuadas. Trabajaba como jardinero y cultivando vegetales, en ambas tareas manejaba abonos. No había tenido antecedentes de infecciones previas y había abandonado el control médico varios meses antes de su internación. En el momento de su ingreso se comprobaron una lesión abscedada en el hombro izquierdo, una placa con grandes nódulos en la muñeca izquierda y un nódulo aislado en el ángulo del maxilar inferior derecho. Se llevaron a cabo punciones aspirativas, drenajes quirúrgicos y resecciones de los cuales se obtuvieron muestras para los exámenes histopatológicos y microbiológicos. Los estudios microbiológicos acusaron: 1) en el hombro izquierdo hifas hialinas anchas no septadas y desarrollo de un hongo del género Mucor; 2) de la lesión de la muñeca izquierda hifas septadas, estrechas y pardas y desarrollo de un hongo dermatiáceo que no pudo ser clasificado por no presentar fructificación y 3) del nódulo del maxilar se obtuvo el desarrollo de Streptococcus viridans y Porphyromonas sp. Las infecciones micóticas fueron tratadas exitosamente con anfotericina B acompañada de drenaje quirúrgico y resección. La infección bacteriana se controló con amoxicilina/ácido clavulánico. Se efectuó un tratamiento supresivo con itraconazol para evitar la recaída de la feohifomicosis durante 6 meses y se prosiguió el control del paciente durante 1 año, sin haber presentado recaídas

Estudio de sensibilidad antiviral de virus herpes simplex en pacientes trasplantados / [Antiviral sensitivity of herpes simplex virus in immunocompromised patients]

The Herpes simplex Virus (HSV) resistance to acyclovir (ACV) occurs in a 5

of the inmunocompromised patients, approximately. The treatment with analogs of nucleosides, causes the appearance of resistent HSV-ACV stocks (ACVr) which can be produced by alteration in genes coding for the TK or the DNA-polymerase. A previous large-scale clinical study on ACVr HSV strains isolated from patients infected with human immunodeficiency virus indicated that 96

of ACVr HSV mutants were low producers of, or deficient in, TK activity (TK-), with 4

being TK mutants with an altered substrate specificity. No DNA Pol mutants were isolated. The pirophosphate analogs generate resistance in the gene of DNA-polymerase by mutation. In this paper we show the methodology used for the determination of sensibilite profiles to ACV and Phoscarnet (PFA) in a population of inmunocompromised patients. We analized 46 HSV strain from vesicular injuries of transplanted patients. All samples, were inoculated in human fibroblasts and the HSV isolates were identified by inmunofluorescence whith monoclonal antibodies. These strains were amplified and the profile of susceptibility determinated in Vero cells, using 100 tissue culture inhibition dosis 50 (TCID50) of each Viral stock and the specific antiviral drugs in different concentrations. The cytopathic effect (CPE) was evaluated after 72hs. post infection. The 50

inhibitory concentration (CI50) was calculated from the percentage of inhibition of the ECP based on the concentration of the drug. From 46 isolations, 26 were HSV-1 and 20 were HSV-2. Two of them, one HSV-1 and one HSV-2, were resistant to ACV and none of the isolates were resistant to PFA.