ABSTRACT Gain-of-function mutations in the STAT1 gene have been initially associated with chronic mucocutaneous candidiasis. However, further research has shown that STAT1 GOF variants may increase susceptibility to infection by other intracellular pathogens. This report describes the first case of disseminated leishmaniasis associated with a STAT1 GOF mutation in a pediatric patient who did not have chronic mucocutaneous candidiasis. The patient was a four-year-old boy presenting with fever, severe asthenia, hepatosplenomegaly, pancytopenia, and liver failure. Bone marrow aspirate revealed hemophagocytosis and Leishmania parasites. Treatment consisted primarily of liposomal amphotericin B, as per the Hemophagocytic Lymphohistiocytosis 2004 protocol. After eight weeks of treatment, the patient did not improve and was submitted to diagnostic splenectomy. Activated macrophages and nodular spleen necrosis secondary to the visceral leishmaniasis were detected. Unfortunately, the patient died in the second week after splenectomy due to overwhelming systemic infection. DNA sequencing revealed a pathogenic (p. R274Q) GOF mutation in STAT1.

ABSTRACT OBJECTIVE: To verify the effectiveness of screening for tuberculosis (TB) on all-cause mortality and tuberculosis cases in newly diagnosed HIV-infected patients through a clinical algorithm based on recommendations of the World Health Organization. METHODS: From March 2014 to April 2016, a pragmatic randomized clinical trial was conducted with newly diagnosed and TB-free HIV-infected adults undergoing antiretroviral therapy for up to one month at a major tertiary hospital for HIV in the state of Pernambuco, Brazil. Participants were randomized into intervention and control groups using an automatically-generated random list, and followed-up for at least 6 months. The intervention group was screened for TB at hospital admission and at every follow-up visit through a series of questions addressing TB-related symptoms (cough, fever, night sweating, and weight loss). Patients presenting with any of these symptoms were referred to a pulmonologist and underwent sputum smear microscopy, sputum culture, and rapid molecular testing (GeneXpert). When at least one test result came back positive, TB treatment was initiated. In turn, if patients tested negative but presented with severe clinal symptoms, TB preventive treatment was initiated. Screening for TB was not performed systematically in the control group. The primary outcome assessed in this study was death from all causes, and secondary outcomes included sensitivity and specificity of this screening test, as well as its detection time. RESULTS: This study evaluated 581 patients, 377 in the intervention group (64.9%) and 204 in the control group (35.1%). In total, 36 patients died during the follow-up period. Of these, 26 (6.9%) were from the intervention group, reaching a cumulative mortality coefficient of 69 per 1,000 inhabitants, and 10 (4.9%) from the control group (p = 0.341), with a cumulative mortality coefficient of 49 per 1,000 inhabitants (p = 0.341).

ABSTRACT OBJECTIVE: To verify the effectiveness of screening for tuberculosis (TB) on all-cause mortality and tuberculosis cases in newly diagnosed HIV-infected patients through a clinical algorithm based on recommendations of the World Health Organization. METHODS: From March 2014 to April 2016, a pragmatic randomized clinical trial was conducted with newly diagnosed and TB-free HIV-infected adults undergoing antiretroviral therapy for up to one month at a major tertiary hospital for HIV in the state of Pernambuco, Brazil. Participants were randomized into intervention and control groups using an automatically-generated random list, and followed-up for at least 6 months. The intervention group was screened for TB at hospital admission and at every follow-up visit through a series of questions addressing TB-related symptoms (cough, fever, night sweating, and weight loss). Patients presenting with any of these symptoms were referred to a pulmonologist and underwent sputum smear microscopy, sputum culture, and rapid molecular testing (GeneXpert). When at least one test result came back positive, TB treatment was initiated. In turn, if patients tested negative but presented with severe clinal symptoms, TB preventive treatment was initiated. Screening for TB was not performed systematically in the control group. The primary outcome assessed in this study was death from all causes, and secondary outcomes included sensitivity and specificity of this screening test, as well as its detection time. RESULTS: This study evaluated 581 patients, 377 in the intervention group (64.9%) and 204 in the control group (35.1%). In total, 36 patients died during the follow-up period. Of these, 26 (6.9%) were from the intervention group, reaching a cumulative mortality coefficient of 69 per 1,000 inhabitants, and 10 (4.9%) from the control group (p = 0.341), with a cumulative mortality coefficient of 49 per 1,000 inhabitants (p = 0.341).