Associations of HIV testing and late diagnosis at a Japanese university hospital

OBJECTIVES: This study was conducted to clarify the rate of late diagnosis of HIV infection and to identify relationships between the reasons for HIV testing and a late diagnosis. METHODS: This retrospective cohort study was conducted among HIV-positive patients at the Jikei University Hospital between 2001 and 2014. Patient characteristics from medical records, including age, sex, sexuality, the reason for HIV testing and the number of CD4-positive lymphocytes at HIV diagnosis, were assessed. RESULTS: A total of 459 patients (men, n=437; 95.2%) were included in this study and the median age at HIV diagnosis was 36 years (range, 18-71 years). Late (CD4 cell count <350/mm3) and very late (CD4 cell count <200/mm3) diagnoses were observed in 61.4% (282/459) and 36.6% (168/459) of patients, respectively. The most common reason for HIV diagnosis was voluntary testing (38.6%, 177/459 patients), followed by AIDS-defining illness (18.3%, 84/459 patients). Multivariate analysis revealed a significant association of voluntary HIV testing with non-late and non-very-late diagnoses and there was a high proportion of AIDS-defining illness in the late and very late diagnosis groups compared with other groups. Men who have sex with men was a relative factor for non-late diagnosis, whereas nonspecific abnormal blood test results, such as hypergammaglobulinemia and thrombocytopenia, were risk factors for very late diagnosis. CONCLUSIONS: Voluntary HIV testing should be encouraged and physicians should screen all patients who have symptoms or signs and particularly hypergammaglobulinemia and thrombocytopenia, that may nonspecifically indicate HIV infection.

Características clínicas, diagnósticas y pronosticas de pacientes con neumonía por Pneumocystis jiroveci en individuos infectados por virus de inmunodeficiencia humana e individuos inmunocomprometidos por otra etiología: comparative study of cases in HIV-infected patients and immunocompromised non-HIV-infected patients / Pneumocystis jiroveci pneumonia

Background: Although P. jiroveci pneumonia affects immunocompromised (IC) patients of any etiology, clinical features and prognostic outcomes are different depending if they are patients with HIV infection or other causes of IC. Objectives: To compare clinical and laboratory features as well as outcomes of P. jiroveci pneumonia in HIV versus non-HIV patients. Methods: Retrospective review of clinical records of HIV and non-HIV patients with P. jiroveci pneumonia managed at the Hospital Clínico Universidad Católica in Santiago, Chile, between 2005 and 2007. Results: We included 28 HIV and 45 non-HIV patients with confirmed P. jiroveci pneumonia. The non-HIV population was older (65 vs 36,2 years, p < 0,01), had shorter duration of symptoms (7 [1-21] vs 14 [2-45] days, p < 0,01), required more invasive techniques (60 vs 21%, p < 0,01) and RT-PCR to confirm the diagnosis (93 vs 68%, p < 0,01), were more frequently treated at intensive care units (58 vs. 25%, p < 0,01) requiring artificial ventilation (56 vs 11%, p < 0,01), and had a higher attributable mortality (33% vs 0%, p < 0,01). Conclusions: Our study confirmed that P. jiroveci pneumonia in non-HIV IC patients is more severe, more difficult to diagnose and has higher mortality that in HIV patients. Therefore, it is mandatory to optimize diagnostic and therapeutic strategies for this patients group.

Introducción: Pneumocystis jiroveci puede causar neumonía en pacientes inmunocomprometidos de cualquier etiología, pero las diferencias clínicas y pronósticas entre inmunocomprometidos por VIH y por otras causas han sido poco exploradas. Objetivo: Comparar las características clínicas, de laboratorio y pronóstico de neumonía por P. jiroveci en pacientes inmunocomprometidos por infección VIH versus no infectados por VIH. Métodos: Análisis retrospectivo de casos confirmados de neumonía por P. jiroveci en adultos con infección por VIH y no infectados, entre los años 2005 y 2007. Resultados: Se incluyeron 28 pacientes infectados por VIH y 45 no infectados, con neumonía por P. jiroveci confirmada. La población no infectada por VIH presentaba mayor edad (65 vs 36,2 años, p < 0,01), menor duración de síntomas previos a la consulta (7 [121] vs 14 [2-45] días, p < 0,01), mayor requerimiento de técnica invasora (60 vs 21%, p < 0,01) y estudio molecular (93 vs 68%, p < 0,01) para confirmación diagnóstica, mayor requerimiento de camas críticas (58 vs 25%, p < 0,01), y ventilación mecánica (56 vs 11%, p < 0,01), con mayor mortalidad atribuible (33 vs 0%, p < 0,01). Conclusiones: La neumonía por P. jiroveci en pacientes inmunocomprometidos no infectados por VIH ofrece más dificultades diagnósticas y presenta mayor gravedad y mortalidad que en pacientes con infección por VIH; por esto, es mandatario optimizar los procesos diagnóstico y terapéutico en esta población.

Síndrome de reconstitución inmune en HIV y neumonía por Pneumocystis jirovecii / Immune reconstitution syndrome in an HIV-infected patient and Pneumocystis jirovecii pneumonia

El síndrome de reconstitución inmune es un conjunto de fenómenos inflamatorios agudos, que se producen como consecuencia de la recuperación de la inmunidad, generando un empeoramiento paradójico de una infección o de un proceso inflamatorio previo. En los pacientes infectados con el virus de inmunodeficiencia humana este síndrome se produce luego de iniciado el tratamiento antirretroviral. Las infecciones más frecuentes asociadas a esta entidad son las producidas por micobacterias, herpes, criptococosis, hepatitis B, citomegalovirus, Pneumocystis jirovecii y el empeoramiento de la leucoencenfalopatía multifocal progresiva por el virus JC. Presentamos un paciente con virus de inmunodeficiencia humana que desarrolló el síndrome de reconstitución inmune por Pneumocystis jirovecii.

Immune reconstitution syndrome is a set of acute inflammatory phenomena that occur as a result of restored immunity generating a paradoxical worsening of a prior infection or an inflammatory process. This syndrome occurs in human immunodeficiency virus infected patients after starting antiretroviral treatment. The most frequent associated infections are those produced by mycobacteria, herpes, cryptococcosis, hepatitis B, cytomegalovirus, Pneumocystis jirovecii and worsening of progressive multifocal leukoencephalopathy secondary to JC virus. We present the case of a patient with human immunodeficiency virus who developed the immune reconstitution syndrome secondary to Pneumocystis jirovecii.

Infección diseminada por Penicillium marneffei en un paciente HIV-positivo: Primera observación en la República Argentina / Disseminated infection due to Penicillium marneffei related to HIV infection: First observation in Argentina

Se presenta el primer caso humano de peniciliosis por Penicillium marneffei observado en la República Argentina. El paciente era un joven de 16 años, HIV-positivo, procedente de un área rural del sur de China. El paciente fue internado en el Hospital "F. J. Muñiz" por padecer una neumonía grave con insufciencia respiratoria aguda. El agente causal fue aislado de un lavado broncoalveolar y se lo observó en un citodiagnóstico de piel. La identifcación de P. marneffei fue confrmada por las características fenotípicas del aislamiento y la amplifcación del ADNr. El enfermo padecía una infección muy avanzada por HIV que condujo a la aparición simultánea de infecciones por citomegalovirus, Pneumocystis jirovecii y procesos bacterianos nosocomiales. Este complejo cuadro derivó en una evolución fatal.

The frst case observed in Argentina of AIDS-related human penicillosis is herein presented. The patient was a six- teen year-old young man coming from a rural area of southern China. He was admitted at the F. J. Muñiz Hospital of Buenos Aires city with severe pneumonia and adult respiratory distress. Penicillium marneffei was isolated from bronchoalveolar lavage fuid and was microscopically observed in a skin cytodiagnosis. P. marneffei identifcation was confrmed by rRNA amplifcation and its phenotypic characteristics. The patient suffered an advanced HIV infection and also presented several AIDS-related diseases due to CMV, nosocomial bacterial infections and Pneumocystis jirovecii which led to a fatal outcome.

Epidemiological characteristics of pulmonary pneumocystosis and concurrent infections in pigs in Jeju Island, Korea

Epidemiological characteristics of swine pulmonary Pneumocystis (P.) carinii and concurrent infections were surveyed on Jeju Island, Korea, within a designated period in 172 pigs submitted from 54 farms to the Department of Veterinary Medicine, Jeju National University. The submitted cases were evaluated by histopathology, immunohistochemistry, PCR/RT-PCR, and bacteriology. P. carinii infection was confirmed in 39 (22.7%) of the 172 pigs. Histopathologically, the lungs had moderate to severe lymphohistioctyic interstitial pneumonia with variable numbers of fungal organisms within lesions. Furthermore, porcine reproductive and respiratory syndrome virus (PRRSV) and porcine circovirus type 2 (PCV-2) co-infection was a common phenomenon (12.8%, 20.5%, and 48.7% were positive for PRRS, PCV-2, or both, respectively, as determined by PCR/RT-PCR). Infection was much more concentrated during winter (December to March) and 53.8% of the infected pigs were 7- to 8-weeks old. In addition, three pigs showed co-infection with bacteria such as Pasteurella multocida and Streptococcus suis. The results of the present study suggest that the secondary P. carinii infection is common following primary viral infection in swine in Korea. They further suggest that co-infection of P. carinii might be enhanced by the virulence of primary pathogens or might have synergistic effects in the pigs with chronic wasting diseases.

Neumotórax en pacientes con SIDA: Actualización sobre el tema / Pneumothorax in patients with AIDS: Update on the theme

La aparición de neumotórax como complicación de la neumonía por Pneumocistis carinii (PCP) en pacientes con SIDA, es muy frecuente desde los inicios de la pandemia en 1982, y comporta gran mortalidad. En este trabajo se reporta una serie de 25 pacientes con neumotórax como complicación de la Pneumocistis carinii en pacientes con SIDA, tratado por los autores durante cinco a ños de trabajo discontinuos en el cono sur africano: tres en Sudáfrica y dos en Zimbabwe. Se reportan los datos demográficos y el estado de los mismos al llegar a la sala de cirugía y su evolución después de tratados quirúrgicamente. La toracotomía fue necesaria en ocho pacientes (32 por ciento), diez pacientes necesitaron cuidados de terapia intensiva (40 por ciento), y la mortalidad global fue del 32 por ciento. Se revisa la información actualizada sobre el tema, destacando las pautas terapéuticas más aceptadas internacionalmente. Conflictos de interés: Los autores no declaran conflicto de interés con editores, patrocinadores ni otros autores.

Pneumothorax as a Pneumocistis carinii pneumonia complication in patients with AIDS is very frequent since the pandemic beginnings in 1982, and it is accompanied by a high mortality. In this work we report a series of 25 patients with Pneumothorax as a Pneumocistis carinii pneumonia complication in patients with AIDS, treated by the authors during five years of discontinuous work in the Southern Africa cone: three years in South Africa and two years in Zimbabwe. We report demographic data, the status of the patients when they arrived to the Surgery Service and their evolution after surgery. Thoracotomy was needed in eight patients (32 percent), ten patients needed intensive care (40 percent), and the global mortality was 32 percent. We review the updated information on the theme, emphasizing the most accepted therapeutic guidelines at the international level.

Concurrent infection of pneumocystis pneumonia and pulmonary tuberculosis in an HIV-seronegative patient.

Co-infection with Pneumocystis jirovecii and Mycobacterium tuberculosis is rarely reported in patients without human immunodeficiency virus (HIV) infection. We describe the case of a 33-year-old HIV-negative female patient who was on long-term oral corticosteroids for rheumatoid arthritis and admitted with for respiratory distress and diffuse infiltrative pneumopathy in whom concurrent infection with Mycobacterium tuberculosis and Pneumocystis jiroveci was confirmed by bronchoalveolar lavage (BAL) fluid examination.

Presentación inhabitual de un caso de neumonía bulosa aguda bilateral por Pneumocystis jiroveci complicada con neumotórax / Unusual presentation of bilateral bullous Pneumocystis jiroveci pneumonia complicated with pneumothorax

En los pacientes con infección por el virus de la inmunodeficiencia humana (VIH), el neumotórax se observa generalmente en etapas avanzadas de la enfermedad, asociado a patógenos como Mycobacterium tuberculosis o Pneumocystis jiroveci, en individuos tabáquicos y drogadictos endovenosos. Presentamos un caso de presentación inhabitual: varón homosexual, 30 años de edad, con tos durante un mes, dificultad respiratoria progresiva y baja de peso, agregándose posteriormente diarrea. Fue hospitalizado con los diagnósticos de insuficiencia respiratoria, neumopatía atípica y observación de infección por VIH. Evolucionó mal, complicándose a los 15 días con neumotórax y bulas pulmonares. El LDH elevado y después la inmunofluorescencia directa (+) confirmaron la etiología: P. jiroveci. El test de ELISA confirmó la pre-existencia de una infección por VIH. A pesar de una terapia enérgica con cotrimoxazol, corticoesteroides y oxígeno, el paciente falleció a los 21 días de su ingreso. Se describen las estrategias recomendadas para el manejo del neumotórax que acontece durante la neumonía por P. jiroveci en los pacientes portadores de infección por VIH.

In patients with human immunodeficiency virus infection, pneumothorax overcomes in advanced stages of the illness, associated with infections by Mycobacterium tuberculosis or Pneumocystis jiroveci, in smokers and intravenous drug users. We present a case with this unusual complication: homosexual man, 30 years of age, with a history of one month of cough, progressive dyspnea, weight loss and diarrhea. He was hospitalized with the diagnosis of atypical pneumonia, respiratory failure and a presumptive HIV infection. His clinical course was complicated by the presence of bullae and pneumothorax by day 15 of hospitalization. The existence of Pneumocystis jiroveci in sputum was confirmed by a direct immunofluorescence test. The patient was treated with sulpha-trimethoprim, steroids, oxygen, but he died 21 days after admittance. The strategies recommended for treatment of pneumothorax appeared during P. jiroveci pneumonia in HIV positive patients are summarized.

Postmortem pathology of opportunistic infection in a HIV positive patient--a case report.

An autopsy case of HIV positive patient with multiple opportunistic infections is described. We received heart, lungs, spleen and both the kidneys along with pieces of cerebrum for anatomy and histopathological examination. Histology of organs revealed disseminated non-granulomatous necrotizing type of tissue reaction with superadded infection with Cryptococcus neoformans (C. neoformans) in liver and brain. Pneumocysts carini (P. carini) induced pneumonia in lungs, disseminated mycobacterial infection in spleen, lungs, liver and kidneys and acute fibrinous meningitis with superadded infection with C. neoformans in brain. Special stains were carried out to demonstrate different organisms.

Neumonía por Pneumocystis carinii en niños infectados por el virus de inmunodeficiencia humana (VIH) / Pneumonia Due to Pneumocystis carinii in HIV-Infected Children

La introducción de nuevos agentes antirretrovirales y el desarrollo de nuevos esquemas de profilaxis antimicrobiana contra agentes oportunistas, ha conducido a una mejor calidad de vida en los pacientes infectados por el virus de la inmunodeficiencia humana (VIH). Estos nuevos esquemas de tratamiento han cambiado la epidemiología de las infecciones oportunistas que, previo al uso de terapia antirretroviral (AR V) altamente activa, se presentaban con una elevada frecuencia en los niños infectados por el VIH. Específicamente, la neumonía por Pneumocystis carinii (PCP) ocurría en 12 al 40% de estos pacientes y estaba asociada con una elevada mortalidad. Actualmente, el uso de la terapia antirretroviral combinada y la administración de esquemas de profilaxis han resultado en una disminución importante en los casos de PCP. Sin embargo, en países en vías de desarrollo como el nuestro, la terapia altamente activa y la administración de estas profilaxis no están al alcance de todos los pacientes, por lo se encuentran en alto riesgo de presentar infecciones oportunistas, sobre todo producidas por Pneumocystis carinii, las cuales pueden acortar y afectar notablemente su supervivencia. El propósito de este articulo es hacer una revisión de la neumonía debida al Pneumocystis carinii, con especial énfasis, en las características epidemiológicas, clínicas y terapéuticas de la enfermedad en niños con VIH/SIDA.

Introduction of new antiretroviral agents and development of new prophylaxis schedules against opportunistic microorganisms have allowed increase in survival as well as better quality of life in HIV-infected patients. These new treatment schedules have changed the epidemiology of opportunistic infections that previous to use of highly active antiretroviral therapy (HAART), fomerly occurred with high frequency in HIV-infected children. Specifically, pneumonia due to Pneumocystis carinii formerly occurred in 12 to 80% of these patients and was associated with high mortality. Currently, with use of combined antiretroviral therapy (ART) and prophylactic treatments important reduction of PCP has been observed. However, despite these benefits ART is not yet available for many patients from several developing countries who are at risk for opportunistic infections, mainly due to Pneumocystis carinii. which can affect life expectancy. Therefore, the purpose of this paper was a review of epidemiologic, clinical, and therapeutic characteristics of P. carinii pneumonia in HIV-infected children.

Pneumocystis carinii pneumonia and its association with other opportunistic infections in AIDS--an autopsy report of five cases.

Pneumocystis carinii pneumonia (PCP) has been reported as one of the opportunistic pathogens in AIDS. The significance of this pathogen in AIDS is well established so that, the diagnosis of PCP in an adult simultaneously establishes the diagnosis of AIDS. This point is well emphasised in the CDC case definition of AIDS. In western literature, the occurrence of PCP in AIDS is widely reported. However, in Indian literature only sporadic case reports have been documented. This study reports 5 cases of PCP encountered amongst 34 AIDS-autopsies studied. PCP alone was present in 2 cases. It is worth noting that it was simultaneously associated with cryptococcosis, tuberculosis and CMV in 3 remaining cases, highlighting the need for extensive investigations even after establishing the diagnosis of PCP in a known full blown AIDS patient.

Visceral leishmaniosis caused by Leishmania (L.) mexicana in a Mexican patient with human immunodeficiency virus infection

A 36 year old male was admitted in December 1997 to hospital with afternoon fever, malaise and hepatosplenomegaly. He also had a dry cough, dyspnoea and anaemia. Pneumonia caused by Pneumocystis carinii and human immunodeficiency virus (HIV) infection were documented. The HIV infection was confirmed in 1997 with 290,000 virus copies. The patient had been in the Mexican State of Chiapas which is known to be endemic for visceral leishmaniosis (VL) and localized cutaneous leishmaniosis (LCL). The visceral symptoms were diagnosed as VL and the causal agent was identified as Leishmania (L.) mexicana. Identification of Leishmania was carried out by the analysis of amplified DNA with specific primers belonging to the Leishmania subgenus and by dot blot positive hybridisation of these polymerase chain reaction derived products with kDNA from the L. (L.) mexicana MC strain used as probe. This is the first case in Mexico of VL caused by a species of Leishmania that typically produces a cutaneous disease form.

Comparative yield of different respiratory samples for diagnosis of Pneumocystis carinii infections in HIV-seropositive and seronegative individuals in India.

Respiratory specimens were prospectively examined for Pneumocystis carinii from 53 patients. The majority of specimens were comprised of expectorated sputum, induced sputum, broncho-alveolar lavage (BAL), and tracheal aspirates. In only four patients Pneumocystis carinii (P. carinii) was detected. All the samples were produced by broncho-alveolar lavage. Candida spp and Aspergillus spp were also identified in a small number of patients. Acid-fast-bacilli were not detected in any of the cases under study. There were no sex-related differences in distribution. The present prospective study was undertaken in order to determine P. carinii infections in human immunodeficiency virus (HIV) seropositive and seronegative individuals. Expectorated sputum samples were probably the major limiting factor in low positivity for detection of P. carinii and study of BAL specimens would be more useful for better results.

Apnea severa: signo precoz de neumonía por pneumocystis carinnii en un lactante VIH negativo / Apnea as an early sign of pneumocystis carinii pneumonia in an HIV negative infant

A few reports in the medical literature suggest an association between Pneumocystis caring and apnea in small infants. This patient, a 1 month 20 days old, HIV negative, infant girl weighing 2,000 grams was admitted to hospital after presenting a severe episode of apnea with cyanosis and bradicardia. She progressively developed bronchopneumonia by P. carinii that required prolonged mechanical ventilation with high ventilatory parameters. The clinical course of this patient illustrates that apnea can be an early sign of P. carinii infection in small infants. Early diagnosis and specific therapy might prevent morbidity and mortality and also decrease the length of hospitalization

Desensibilización aguda con cotrimoxazol forte en paciente VIH (+) alérgico a sulfas con neumonía por pneunocistis carinii / Acute desensitization with cotrimoxazol forte in HIV (+) patient with allergy to sulfa and pneunocistis carinii pneumonia

Se presenta el caso de un paciente VIH (+), alérgico a sulfas, hospitalizado en 1998 por una neumopatía de predominio intersticial con insuficiencia respiratoria que no respondía al esquema clásico. Se trata del primer caso en nuestro hospital en el que se aplicó la terapia de desensibilización con cotrimoxazol forte, la cual está ampliamente recomendada en la literatura internacional como alternativa en casos de estas características

Is Pneumocystis carinii vertically transmitted to neonatal rats?

Pneumocystis carinii is a pulmonary pathogen of immunocompromised humans or other mammals. Its infection results from activation of organisms involved in latent infection or from new infection through the air. Almost all children are known to be infected within 2 to 4 years of birth, though prenatal transplacental transmission has not yet been demonstrated. In this study we observed experimental P. carinii infection in neonatal rats, thus investigating the possibility of transplacental vertical transmission by Diff-Quik staining of the lung impression smears and in-situ hybridization for lung sections. The positive rate of P. carinii infection in immunosuppressed maternal rats was 100%, but that in normal maternal rats was 0%. Cystic forms of P. carinii were observed in three of six 1-week old neonatal rats born of heavily infected mothers, but none of them was positive by in-situ hybridization. Five weeks after birth, cystic forms were detected in four neonatal rats. In the lobes of the lungs, no predilection site of P. carinii was recognized. Counts of cystic forms on smears and the reactivity of in-situ hybridization in the lungs of neonatal rats were significantly lower than in maternal rats. The present findings suggest that P. carinii is rarely transmitted through the placenta and proliferates less successfully in the lungs of neonatal rats than in mothers.