False-negative result of serum cryptococcal antigen lateral flow assay in an HIV-infected patient with culture-proven cryptococcaemia

The detection of cryptococcal capsular antigen (CrAg) is very sensitive and specific, however false-negative results have been reported, mostly in cerebrospinal fluid. We report the case of an HIV-infected patient with CD4=42 cells/mL, asthenic, negative serum CrAg lateral flow assay (LFA) and culture-proven cryptococcaemia. Despite the high accuracy of LFA, false-negative result is possible. Careful clinical evaluation and close follow-up are relevant

False-negative result of serum cryptococcal antigen lateral flow assay in an HIV-infected patient with culture-proven cryptococcaemia.

The detection of cryptococcal capsular antigen (CrAg) is very sensitive and specific, however false-negative results have been reported, mostly in cerebrospinal fluid. We report the case of an HIV-infected patient with CD4 = 42 cells/mL, asthenic, negative serum CrAg lateral flow assay (LFA) and culture-proven cryptococcaemia. Despite the high accuracy of LFA, false-negative result is possible. Careful clinical evaluation and close follow-up are relevant.

Prospective cohort of AIDS patients screened for cryptococcal antigenaemia, pre-emptively treated and followed in Brazil.

BACKGROUND: Cryptococcal meningitis has a high morbidity and mortality among AIDS population. Cryptococcal antigen (CrAg) detection is considered an independent predictor for meningitis and death. Since 2011, the World Health Organization recommends CrAg screening for people living with HIV/AIDS (PLHAs) with CD4 counts <100-200 cells/µl. Its implementation is still limited in low-middle-income countries. We aimed to estimate the prevalence and predictors of CrAg positivity in PLHAs. We also evaluated outcomes among those who were CrAg-positive. METHODS: Prospective cohort conducted at an infectious diseases hospital, in Brazil. Adults with CD4 <200 cells/µl, without previous cryptococcal disease and regardless of symptoms, were enrolled from 2015 to 2018. CrAg tests were performed by LFA. Lumbar puncture was done in CrAg+ individuals and pre-emptive therapy was offered for those without meningitis. RESULTS: Of 214 individuals recruited, 88% were antiretroviral experienced, of which only 11.6% with viral suppression. Overall, CrAg prevalence was 7.9% (95% CI, 4.7-12.4). In CD4 ≤100 cells/µl group it was 7.5% (95% CI, 4.1-12.6) and 9.1% (95% CI, 3.4-19.0) in the group with CD4 101 to 199 cells/µl (p = 0.17). Prevalence in asymptomatic subjects was 5.3% (95% CI, 1.4-13.1). One among 17 CrAg+ participants had documented meningoencephalitis and no subclinical meningitis was detected. Adherence to pre-emptive treatment was 68.7% (11/16). There were no statistically significant differences in sociodemographic, clinical or laboratory characteristics to predict CrAg positivity. No case of cryptococcal disease was diagnosed among CrAg + subjects, followed by a median of 12 months. CONCLUSIONS: CrAg screening for severely immunosuppressed PLHAs in Brazil yielded a prevalence of 7.9%. No difference was found in the prevalence of CrAg stratified by CD4 values (CD4 <100 versus CD4 101-199 cells/µl). No clinical nor laboratory factors predicted CrAg positivity, corroborating the need for the implementation of universal CrAg screening for PLHAs with CD4 <200 cells/µl in similar settings.

Disseminated histoplasmosis in AIDS patients: an urban disease. Experience in a metropolis in the middle east of Brasil.

Histoplasmosis is a fungal disease commonly observed as an opportunistic disease in AIDS patients. It is a neglected disease in many countries, particularly Latin America, including Brazil. It is related with environmental factors, even in urban areas, where the incidence has increased. Implementing a descriptive ecological study, we performed a retrospective chart review for data collected between January 2003 and July 2014 for AIDS patients with histoplasmosis who lived in Goiania. The selected cases were georeferenced to analyse the incidence of histoplasmosis in AIDS patients in the metropolitan area of Goiania. In all, 166 patients (130 men) met the criteria for AIDS and histoplasmosis coinfection. Almost half of the patients (41%) had simultaneous histoplasmosis and AIDS diagnoses. The general mortality was 53% (88 patients). The main symptoms involved the respiratory, gastrointestinal, and cutaneous systems. The distribution of cases included almost all regions of the urban areas, with some predominance in the eastern and western regions close to areas of environmental degradation, contaminated water sources and unplanned urbanisation. In conclusion, coinfection with HIV and disseminated histoplasmosis is common and associated with high mortality rates in our referral hospital for infectious diseases. Despite being considered as having a predominantly rural epidemiology, many patients reported living in urban areas such as Goiânia and Aparecida de Goiânia. Our findings suggest the need for environmental studies to evaluate environmental contamination and possible local risk factors for H. capsulatum infection in addition to serological surveys to determine the prevalence of this infection in the studied cities.

Mycobacterium sherrisii Lung Infection in a Brazilian Patient with Silicosis and a History of Pulmonary Tuberculosis.

Nontuberculous mycobacteria (NTM) diseases became relevant with the emergence and spread of HIV and are also related to lung infection in non-HIV individuals with structural lung diseases. Mycobacterium sherrisii is a NTM first characterized in 2004. Only a few cases have been reported. The aim of this case report is to describe the first detailed case of infection with M. sherrisii in a patient with silicosis and history of pulmonary tuberculosis. A 50-year-old HIV-negative white male, previous smoker, with silicosis and a history of treated pulmonary tuberculosis developed a worsening of cough and expectoration pattern, and two sputum samples were positive for acid-fast bacilli. Presumptive treatment for pulmonary tuberculosis was initiated with rifampin, isoniazid, pyrazinamide, and ethambutol, but, at month 5 of treatment, despite correct medication intake and slight improvement of symptoms, sputum bacilloscopy remained positive. Sputum cultures were positive Mycobacterium sherrisii. Treatment regimen was altered to streptomycin (for 2 months), ethambutol, clarithromycin, rifabutin, and trimethoprim-sulfamethoxazole. M. sherrisii should be considered a possible etiological agent of lung infections in patients with pneumoconiosis and history of tuberculosis.

Herpetic esophagitis in immunocompetent medical student.

Esophagitis caused by herpes simplex virus (HSV) is often documented during periods of immunosuppression in patients infected with human immunodeficiency virus (HIV); it is rare in immunocompetent diagnosed patients. Case reports of herpetic esophagitis in students of health sciences are extremely rare. The disease presents with a clinical picture characterized by acute odynophagia and retrosternal pain without obvious causes and ulcers, evidenced endoscopically in the middistal esophagus. Diagnosis depends on endoscopy, biopsies for pathology studies, and immunohistochemistry techniques. The disease course is often benign; however, treatment with acyclovir speeds the disappearance of symptoms and limits the severity of infection. In this report, we present a case of herpetic esophagitis in an immunocompetent medical student, with reference to its clinical features, diagnosis, and treatment. The disease may have manifested as a result of emotional stress experienced by the patient.

Tuberculosis deaths in a tertiary hospital in Goiânia, Brazil: a descriptive study.

Tuberculosis (TB) remains a serious global public health problem, being the main cause of death in patients with AIDS, and the third cause of death by infectious diseases throughout the world. This is somewhat surprising because TB is a disease that, if treated properly, displays high rates of healing. It is therefore important to characterise these patients to identify target populations for specific measures seeking to reduce TB deaths. We performed a retrospective descriptive study to analyse the cases of TB deaths in a State public hospital, a point of reference for treatment of infectious diseases, located in the Central-West region of Brazil, in the period from January 1st, 2008 to December 31st, 2009. There were 283 diagnosed and reported cases of TB between 2008 and 2009, and 39 recorded deaths occurred, resulting in a lethality index of 14%. The mean age of TB patients was 42 years, and the median age 37 years. Pulmonary TB was the most common form of TB (51.3% of the patients). Of the 39 TB patients who died, 56.4% (n = 22) were co-infected with HIV. The main immediate causes of death were acute respiratory failure (n = 12) and sepsis (n = 8). Anaemia and hypoalbuminaemia were prevalent in this group, and 27 patients required mechanical ventilation. This study found that hospitalized patients who died had the following characteristics: bilateral pulmonary disease, low levels of haemoglobin and haematocrit, albumin, and those co-infected with HIV that were admitted to the ICU required MV. Prospective studies aiming to analyse the risk factors for death from TB are needed to better understand this process.

Immunogenicity of a fusion protein containing immunodominant epitopes of Ag85C, MPT51, and HspX from Mycobacterium tuberculosis in mice and active TB infection.

Tuberculosis (TB) remains a major global health problem. The only vaccine against tuberculosis, attenuated Mycobacterium bovis Bacillus Calmette-Guerin (BCG), has demonstrated relatively low efficacy and does not provide satisfactory protection against the disease in adults. More effective vaccines and better therapies are urgently needed to reduce the global spread of TB. This study evaluated the immunogenicity of a recombinant M. tuberculosis Ag85C-MPT51-HspX fusion protein (CMX) in mice and individuals with active tuberculosis. BALB/c mice were immunized with the CMX protein liposome-encapsulated with CpG DNA or with CpGDNA liposome-encapsulated, liposome or saline as negative controls. The immunization produced high levels of anti-CMX -specific IgG1 and IgG2a antibodies and induced an increase in the relative and absolute numbers of specific TCD4 IFN-γ(+) and TNF-α(+) cells in the spleen. Sera from a cohort of individuals with active tuberculosis contained higher levels of IgG and IgM that recognized CMX when compared to healthy individuals. In conclusion, this protein was shown to be immunogenic both in mice and humans.

Mycobacterium tuberculosis and human immunodeficiency virus coinfection in a tertiary care hospital in Midwestern Brazil.

Infection with human immunodeficiency virus (HIV) increases the risk of tuberculosis (TB), and HIV TB coinfection is associated with higher mortality. This study aimed to characterize patients coinfected with Mycobacterium tuberculosis and HIV in a reference centre for cases involving complications or drug resistance in TB. This retrospective cohort study was conducted at a Hospital for Tropical Diseases in the state of Goiás, Midwestern Brazil. Patients' medical records were reviewed between January 2008 and December 2009. Sixty-one cases of TB/HIV coinfection were evaluated, and 54 HIV-seronegative TB cases were selected as controls. The prevalence of TB HIV coinfected patients in 2008/2009 was 23%. Coinfection was more prevalent in men (75.4%), with a mean age of 37.1 years. Pulmonary disease (50.8%) was the most frequent clinical form of TB in coinfected patients, followed by disseminated disease (32.8%). Anaemia, malnutrition and low levels of CD4 T lymphocytes were found in about 80% of coinfected patients. Bilateral pulmonary infiltrates were the most common radiographic finding in coinfected patients (51.8%), and pulmonary cavitation was the rarest event (5.4%). The mortality rate was 2.8 times higher in the TB HIV coinfected group (39.3%) than in TB patients without HIV (18.5%). Actions targeting the TB HIV-coinfected population, based on national and international recommendations, are necessary to improve prognosis and outcomes in TB and HIV infection in the institution.

Clinical data and molecular analysis of Mycobacterium tuberculosis isolates from drug-resistant tuberculosis patients in Goiás, Brazil.

Drug resistance is one of the major concerns regarding tuberculosis (TB) infection worldwide because it hampers control of the disease. Understanding the underlying mechanisms responsible for drug resistance development is of the highest importance. To investigate clinical data from drug-resistant TB patients at the Tropical Diseases Hospital, Goiás (GO), Brazil and to evaluate the molecular basis of rifampin (R) and isoniazid (H) resistance in Mycobacterium tuberculosis. Drug susceptibility testing was performed on 124 isolates from 100 patients and 24 isolates displayed resistance to R and/or H. Molecular analysis of drug resistance was performed by partial sequencing of the rpoB and katGgenes and analysis of the inhA promoter region. Similarity analysis of isolates was performed by 15 loci mycobacterial interspersed repetitive unit-variable number tandem repeat (MIRU-VNTR) typing. The molecular basis of drug resistance among the 24 isolates from 16 patients was confirmed in 18 isolates. Different susceptibility profiles among the isolates from the same individual were observed in five patients; using MIRU-VNTR, we have shown that those isolates were not genetically identical, with differences in one to three loci within the 15 analysed loci. Drug-resistant TB in GO is caused by M. tuberculosis strains with mutations in previously described sites of known genes and some patients harbour a mixed phenotype infection as a consequence of a single infective event; however, further and broader investigations are needed to support our findings.

Clinical data and molecular analysis of Mycobacterium tuberculosi isolates from drug-resistant tuberculosis patients in Goiás, Brazil

Drug resistance is one of the major concerns regarding tuberculosis (TB) infection worldwide because it hampers control of the disease. Understanding the underlying mechanisms responsible for drug resistance development is of the highest importance. To investigate clinical data from drug-resistant TB patients at the Tropical Diseases Hospital, Goiás (GO), Brazil and to evaluate the molecular basis of rifampin (R) and isoniazid (H) resistance in Mycobacterium tuberculosis. Drug susceptibility testing was performed on 124 isolates from 100 patients and 24 isolates displayed resistance to R and/or H. Molecular analysis of drug resistance was performed by partial sequencing of the rpoB and katGgenes and analysis of the inhA promoter region. Similarity analysis of isolates was performed by 15 loci mycobacterial interspersed repetitive unit-variable number tandem repeat (MIRU-VNTR) typing. The molecular basis of drug resistance among the 24 isolates from 16 patients was confirmed in 18 isolates. Different susceptibility profiles among the isolates from the same individual were observed in five patients; using MIRU-VNTR, we have shown that those isolates were not genetically identical, with differences in one to three loci within the 15 analysed loci. Drug-resistant TB in GO is caused by M. tuberculosis strains with mutations in previously described sites of known genes and some patients harbour a mixed phenotype infection as a consequence of a single infective event; however, further and broader investigations are needed to support our findings.

Splenic rupture in dengue hemorrhagic fever: report of a case and review.

Dengue is currently the most important arboviral disease in the world, particularly in tropical countries in which the environmental conditions favor the development and proliferation of the mosquito vector. Dengue hemorrhagic fever presents in two phases: an initial phase, which is characterized by sudden onset of fever and a variety of nonspecific signs and symptoms, and a critical phase, which is characterized by the recovery from fever and development of hemorrhagic symptoms and circulatory insufficiency. This report documents a case of splenic rupture in a patient with dengue hemorrhagic fever who developed hypovolemic shock and subsequently died. Although splenic rupture is a known complication of other acute infections, it is a rare complication of dengue; therefore, it may be misdiagnosed. In the case described here, the poor outcome mainly resulted from the sudden onset of complications; the patient died of splenic rupture less than 24 h after admission, and the cause of death was confirmed at necropsy.

Limitations of the BCG vaccine and new prophylaxis strategies against human tuberculosis / Limitações da vacina BCG e novas estratégias profiláticas contra tuberculose humana

A atual vacina contra a tuberculose, o BCG (Bacilo Calmette Guérin), uma vacina atenuada, derivada do Mycobacterium bovis, apesar de proteger as crianças contra a enfermidade, falha na proteção contra a tuberculose pulmonar ativa em adultos, principalmente em países onde a doença é endêmica. Uma nova vacina para tuberculose deve proteger várias categorias de indivíduos, como crianças, adultos, idosos e imunocomprometidos. Sendo assim, uma característica importante a se considerar é a seguridade vacinal para todas as classes de imunizados. Esta revisão propõe apresentar as novas estratégias de vacinação, tais como subunidades vacinais, vacinas de DNA, vacinas com micro-organismos e vetores vivos e discutir as aplicações dessas novas estratégias no controle e erradicação da tuberculose.

Extensively drug-resistant tuberculosis: a case report and literature review

Extensively drug-resistant tuberculosis (XDR-TB) is an emerging health problem that threatens tuberculosis (TB) control worldwide, since suitable treatment for this disease has not yet been found. We report a case of secondary pulmonary XDR-TB in a 54-year-old, HIV-negative male from Goiânia, Brazil. The patient had long-standing pulmonary tuberculosis (nine years) with extensive bilateral lung damage and had been treated with multiple antituberculosis drugs (self-administered) before XDR-TB diagnosis. The strain of Mycobacterium tuberculosis was resistant to R- rifampicin, H-isoniazid, E-ethambutol, Eto-ethionamide, Ofx-ofloxacin, and Am-amikacin. This patient died with multiple organ failure due to sepsis secondary to bacterial pneumonia.

Cellular responses to MPT-51, GlcB and ESAT-6 among MDR-TB and active tuberculosis patients in Brazil.

Multi-drug resistant pulmonary tuberculosis (MDR-TB) may result from either insufficiency of the host cellular immune response or mycobacterial mechanisms of resistance. Mycobacterium tuberculosis-specific CD8+ and CD4+ T lymphocytes from MDR-TB patients are poorly studied. The aim of this study was to evaluate CD4+IFN-gamma+, CD4+IL-10+, CD8(+)IFN-gamma+ and CD8+IL-10+ cell populations by flow cytometry in non-resistant TB and multi-drug resistant tuberculosis (MDR-TB) patients from mid-central Brazil after stimulation with MPT-51, GlcB and ESAT-6 recombinant antigens from M. tuberculosis in comparison to tuberculin skin test negative (TST) healthy individuals. Non-resistant TB patients present specific cellular responses (CD4 and CD8, both IFN-gamma and IL-10) to GlcB, MPT-51 and ESAT-6; while MDR-TB patients present only CD8+IFN-gamma+ responses to ESAT-6 and CD8+IL-10+ responses to GlcB and ESAT-6. The results show that MDR-TB patients present impaired specific CD4 IFN-gamma and IL-10 responses and increased/normal specific CD8 IFN-gamma and IL-10 responses. This suggests an important role for CD8 function in these patients.

Multidrug-resistant tuberculosis: case reports study in a central state of Brazil.

Multidrug-resistant tuberculosis (MDR-TB) is an emerging and worrisome health problem that threatens tuberculosis (TB) control worldwide. The clinical management of MDR-TB is a complex issue associated with the use of multiple drugs for a long period, usually accompanied by side effects and high costs. The objective of this work was to relate cases of MDR-TB occurring in Goiás, a central state of Brazil. We related five cases of MDR-TB, three women and two men. All were pulmonary cases. Three were in their second treatment and two in their first treatment. Surgical pulmonary resection was performed in one case. One death occurred. Lack of adherence, gastric intolerance to anti-TB drugs and poor clinical management were the main aspects related to the emergent resistance. A revision of the main clinical aspects of this disease was performed.

Multidrug-resistant tuberculosis: case reports study in a central state of Brazil

Multidrug-resistant tuberculosis (MDR-TB) is an emerging and worrisome health problem that threatens tuberculosis (TB) control worldwide. The clinical management of MDR-TB is a complex issue associated with the use of multiple drugs for a long period, usually accompanied by side effects and high costs. The objective of this work was to relate cases of MDR-TB occurring in Goiás, a central state of Brazil. We related five cases of MDR-TB, three women and two men. All were pulmonary cases. Three were in their second treatment and two in their first treatment. Surgical pulmonary resection was performed in one case. One death occurred. Lack of adherence, gastric intolerance to anti-TB drugs and poor clinical management were the main aspects related to the emergent resistance. A revision of the main clinical aspects of this disease was performed.

Extensively drug-resistant tuberculosis: a case report and literature review.

Extensively drug-resistant tuberculosis (XDR-TB) is an emerging health problem that threatens tuberculosis (TB) control worldwide, since suitable treatment for this disease has not yet been found. We report a case of secondary pulmonary XDR-TB in a 54-year-old, HIV-negative male from Goiânia, Brazil. The patient had long-standing pulmonary tuberculosis (nine years) with extensive bilateral lung damage and had been treated with multiple antituberculosis drugs (self-administered) before XDR-TB diagnosis. The strain of Mycobacterium tuberculosis was resistant to R- rifampicin, H-isoniazid, E-ethambutol, Eto-ethionamide, Ofx-ofloxacin, and Am-amikacin. This patient died with multiple organ failure due to sepsis secondary to bacterial pneumonia.

Metastatic cancer to the stomach.

BACKGROUND: Metastases in the stomach are rare. The increased use of esophagogastroduodenoscopy (EGD), associated with better treatment results for malignancies, requires them to be acknowledged. The aim of this study was to describe a series of cases of metastasis to the stomach, their primary sites, clinical and endoscopic features, treatment, and results. METHODS: Twenty cases were diagnosed between December 1999 and January 2004. Their analysis included symptomatology, macroscopic presentation, time from diagnosis of the primary tumor to the detection of the gastric metastasis, treatment approach, and survival. RESULTS: The primary sites were the esophagus, skin, lung, cervix, breast, sigmoid colon, and testis. The symptom most frequently requiring EGD was upper gastrointestinal bleeding. Ten patients showed concomitant metastases to other organs. The mean time between diagnosis of the primary tumor and diagnosis of gastric metastasis was 16 months (range, 0 to 56 months). Only seven patients were given some form of treatment after diagnosis of the gastric metastasis. The median survival was 4.75 months. Overall survival during the first year was 20% and survival was nil at 2 years. CONCLUSIONS: Gastric metastasis marks advanced disease and the prognosis is poor. New advances in diagnosis and treatment are required for better results.

Co-infeccao pelo virus da imunodeficiencia humana (HIV) e o Mycobacterium leprae: aspectos imunologicos e caracterizacao anatomopatologica e imunofenotipica de lesoes de pele / ?

O aumento de susceptibilidade a infecções por micobactérias, notadamente Mycobacterium avium e Mycobacterium tuberculosis, é uma conseqüência bem conhecida da infecção pelo Vírus da Imnudeficiência Humana (HIV) refletindo em maior morbi/letalidade nos pacientes co-infectados. À medida que o HIV se dissemina em regiões tropicais e subtropicais endêmicas para a hanseníase, como é o caso do Brasil, os efeitos do HIV na hanseníase deveriam ser aparentes. No entanto, várias questões, como as listadas, ainda não estão totalmente esclarecidas. A infecção pelo HIV: constitui fa or de risco para a hanseníase? Agravaria a hanseníase pré-existente? Altera a progressão da resposta imune para o Mycobacterium leprae e as manifestações da doença levando a amior incidência de formas multibacilares? Altera a histoarquitetura e a compisição celular da pele? Favorece maior número de reações tipo 2? Representa fator de risco para incapacidades? Infuência o tratamento MDT-hansênico? Aumenta a letalidade? Relatos de casos isolados ou pequenas casuísticas de pacientes co-infectados descritos indicam que a interação HIV-M. leprae é incerta, pouco conhecida e representa um enigma do ponto de vista imunológico. A imunidade celular, gradativamente comprometida na infecção pelo HIV, representa o mecanismo protetor crucial para ambos patógenos. Embora pudéssemos prever um resultado desfavorável à medida que a imunossupressão se instala e a imunidade celular diminui, não está definido até que ponto a infecção por um patógeno influencia o curso da outra infecção. No contexto de uma região de alta endemicidade para a hanseníase e média endemicidade para o HIV, como é o Estado de Goiás, o presente estudo se propôs a avaliar a situação de co-infecção HIV-M. leprae entre os pacientes atendidos no centro de referência HAA/HDT. Dezoito pacientes co-infectados, atendidos no HAA/HDT, Goiânia, Goiás, no período de 1986 a 2001, que assinaram consentimento informado, tiveram biópsias de lesões de pele disponíveis para a análise histopatológica (HE e Fite-Faraco) e imunofenotípica (imuno-histoquímica). Utilizaram-se os critérios de classificação de Ridley-Jopling. A metade das biópsias analisadas era de pacientes virgens de tratamento e as demais, de pacientes em tratamento (n=3), em lesão residual pós tratamento (n=3) e nos casos de retratamento (n=3). Contagens de linfócitos T CD8+ periféricos (Citometria de Fluxo, FACSCount, BD) e valores de carga viral (NASBA, Organon), obtidos