Abstract Background There are scarce data on the prevalence and disease presentation of HIV in patients with tuberculosis (TB) and dysglycemia (diabetes [DM] and prediabetes [PDM]), especially in TB-endemic countries. Methods We assessed the baseline epidemiological and clinical characteristics of patients with culture-confirmed pulmonary TB, enrolled in a multicenter prospective cohort in Brazil (RePORT-Brazil) during 2015-2019. Dysglycemia was defined by elevated glycated hemoglobin and stratified as PDM or DM. Additionally, we used data from TB cases obtained through the Brazilian National Notifiable Diseases Information System (SINAN), during 2015-2019. In SINAN, diagnosis of diabetes was based on self-report. Logistic regression models were performed to test independent associations between HIV, dysglycemia status, and other baseline characteristics in both cohorts. Results In the RePORT-Brazil cohort, the prevalence of DM and of PDM was 23.7% and 37.8%, respectively. Furthermore, the prevalence of HIV was 21.4% in the group of persons with TB-dysglycemia and 20.5% in that of patients with TBDM. In the SINAN cohort, the prevalence of DM was 9.2%, and among the TBDM group the prevalence of HIV was 4.1%. Logistic regressions demonstrated that aging was independently associated with PDM or DM in both the RePORT-Brazil and SINAN cohorts. In RePORT-Brazil, illicit drug use was associated with PDM, whereas a higher body mass index (BMI) was associated with DM occurrence. Of note, HIV was not associated with an increased risk of PDM or DM in patients with pulmonary TB in both cohorts. Moreover, in both cohorts, the TBDM-HIV group presented with a lower proportion of positive sputum smear and a higher frequency of tobacco and alcohol users. Conclusion There is a high prevalence of dysglycemia in patients with pulmonary TB in Brazil, regardless of the HIV status. This reinforces the idea that DM should be systematically screened in persons with TB. Presence of HIV does not substantially impact clinical presentation in persons with TBDM, although it is associated with more frequent use of recreational drugs and smear negative sputum samples during TB screening.
The high burden of drug-resistant tuberculosis (TB) is a problem to achieve the goals of the End TB Strategy by 2035. Whether isoniazid monoresistance (Hr) affects anti-TB treatment (ATT) outcomes remains unknown in high-burden countries.
To assess the spatial distribution of TB and malaria incidence, as well as their spatial association with each other, regardless of environmental and socio-economic factors commonly reported as determinants of both disease rates among the municipalities of Amazonas State, Brazil between 2012 and 2015.Through an ecological approach considering municipalities of Amazonas, Brazil, as unit of analysis, a negative binomial regression model was used to assess association between malaria and TB rates, in which the dependent variable was the average municipal tuberculosis incidence rate.Positive associations of overall malaria (β = 0.100 [CI = 0.032, 0.168], P = 0.004), P. vivax malaria (β = 0.115 [CI = 0.036, 0.195], P = 0.005), and P. falciparum malaria (β = 0.389 [CI = -0.0124, 0.791], P = 0.057) with TB rates were found, regardless of the sociodemographic factors included in the study.In the Brazilian Amazon, TB and malaria are spatially associated. Therefore, it is very likely that co-infections also occur in this region, regardless of the HIV status.Evaluer la distribution spatiale de l'incidence de la tuberculose (TB) et du paludisme, ainsi que leur association spatiale, indépendamment des facteurs environnementaux et socioéconomiques communément rapportés comme déterminants des taux des deux maladie dans les municipalités de l'Etat d'Amazonas, au Brésil, entre 2012 et 2015. MÉTHODES: Dans le cadre d'une approche écologique prenant en considération les municipalités d'Amazonas, au Brésil, comme unité d'analyse, un modèle de régression binomiale négatif a été utilisé pour évaluer l'association entre les taux de paludisme et de TB, dans laquelle la variable dépendante était le taux moyen d'incidence municipale de la TB. RÉSULTATS: Des associations positives entre le paludisme en général (β = 0,100 [IC= 0,032 à 0,168], p = 0,004), le paludisme à P. vivax (β = 0,115 [IC: 0,036 à 0,195], p = 0,005) et le paludisme à P. falciparum (β = 0,389 [IC: - 0,0124 à 0,791], p = 0,057) avec des taux de TB ont été retrouvées quels que soient les facteurs sociodémographiques inclus dans l’étude.En Amazonie brésilienne, la TB et le paludisme sont associés spatialement. Par conséquent, il est très probable que des coinfections se produisent également dans cette région, quel que soit le statut VIH.
Approximately 10% of the global tuberculosis (TB) burden is in children. Identification, diagnosis, and early treatment of Mycobacterium tuberculosis infection (TBI) is critical to prevent progression to TB in children. The risk of TB, including severe disease, is highest in children <5 years old. We evaluated the cascade of TBI care among child and adolescent TB contacts to identify factors associated with losses in the cascade.Close contacts ≤ 18 years old of pulmonary TB patients enrolled between 2015 and 2019 in a multi-centre Brazilian cohort were followed for up to 24 months and classified according to age groups: <5 years, 5-9 years, 10-14 years and 15-18 years. Data on clinical investigation, radiographic examination, IGRA testing at baseline and 6 months, initiation and completion of TB preventive treatment (TPT) were collected. Multivariable regression analyses identified factors associated with TBI and losses in the cascade of care in children and adolescents.Among 1795 TB contacts initially identified, 530 (29·5%) were ≤18 years old. Losses for all steps in the cascade were especially high in children <5 years old (88%) because at this age all contacts are recommended to initiate TPT. As a proportion of all children, completion of TPT was low (between 10% and 13%) in all age-groups. Furthermore, multivariable regression revealed that younger age of contacts and TB index cases who were female, had pulmonary cavities, and persistent cough were independently associated with losses in the cascade of care among persons ≤18 years old.Losses in the TBI cascade were the highest among children <5 years, which was the group at highest risk for TB among the four age groups. The findings highlight the need to improve screening, initiation, and completion of TPT of young children who are close contacts of people with TB in Brazil.National Institutes of Allergy and Infectious Diseases.
Hemophagocytic lymphohistiocytosis (HLH) is a disorder that occurs due to unsuitable monocyte activation in a variety of infections. In human immunodeficiency virus (HIV) infections, patients with advanced immunossupression associated with opportunistic infections are at increased risk of developing HLH. We describe a clinical case of a 33-year-old male student diagnosed with HIV who was hospitalized for investigation of asthenia and dyspnea, accompanied by adynamia, decreased motor force in the left leg, dysphagia, and dysfluency. His general condition was regular, he was pale, feverish, and had normal cardiac and pulmonary auscultation. Physical examination revealed ulcerated lesions in the perianal region and hepatosplenomegaly without palpable lymph node enlargement. Laboratory parameters showed pancytopenia, a slight increase in liver function accompanied by high lactate dehydrogenase, and hiperferritinemia. The initial diagnosis was disseminated histoplasmosis, thus amphotericin B deoxycholate was empirically prescribed while waiting on myeloculture and blood cultures for fungi and mycobacteria. Other clinical procedures were blood transfusion, resumption of antiretroviral therapy (ART) and secondary prophylaxis. Myeloculture blood cultures of fungi and mycobacteria were negative. Patient evolved well in relation to the initial complaints and showed partial clinical and laboratory improvement. However, 23 days after hospitalization, he developed a febrile episode accompanied by chills and a convulsive crisis. The patient was transferred to the intensive unit care and developed septic shock and respiratory failure. He died 25 days after the onset of the condition. After the postmortem examination, histopathology revealed countless rounded fungal structures compatible with Histoplasma sp., which were observed in the peripancreatic lymph node, liver, and spleen, in addition to hemophagocytosis in the splenic parenchyma. We thus conclude that when the patient met criteria for HLH, such as fever, hepatosplenomegaly, hiperferritinemia, and pancytopenia, the evolution was fast due to the aggressive and rapidly fatal nature of HLH, despite anti-fungal and corticoid treatment. Therefore, this case report reinforces the need to consider hemophagocytic syndrome in patients with HIV and disseminated histoplasmosis, especially where histoplasmosis is highly endemic, in order for the treatment be started early when there is high clinical suspicion.
Abstract Background Interferon-gamma release assay (IGRA) has emerged as a useful tool in identifying latent tuberculosis infection (LTBI). This assay can be performed through testing platforms, such as QuantiFERON-TB Gold Plus (QFT ® -Plus). This in vitro test has been incorporated by several guidelines worldwide and has recently been considered for the diagnosis of LTBI by the World Health Organization (WHO). The possibility of systematically implementing IGRAs such as QFT ® -Plus in centers that perform LTBI screening has been accelerated by the decreased availability of tuberculin skin testing (TST) in several countries. Nevertheless, the process to implement IGRA testing in routine clinical care has many gaps. Methods The study utilized the expertise acquired by the laboratory teams of the Regional Prospective Observational Research in Tuberculosis (RePORT)-Brazil consortium during study protocol implementation of LTBI screening of TB close contacts. Results RePORT-Brazil includes clinical research sites from Brazilian cities and is the largest multicenter cohort of TB close contacts to date in the country. Operational and logistical challenges faced during IGRA implementation in all four study laboratories are described, as well as the solutions that were developed and led to the successful establishment of IGRA testing in RePORT-Brazil. Conclusions The problems identified and resolved in this study can assist laboratories implementing IGRAs, in addition to manufacturers of IGRAs providing effective technical support. This will facilitate the implementation of IGRA testing in countries with a high TB burden, such as Brazil. Importance The interferon-gamma release assay (IGRA) has emerged as a useful tool in identifying persons with latent tuberculosis infection (LTBI). Although the implementation of IGRAs is of utmost importance, to our knowledge, there is scarce information on identification of logistical and technical challenges of systematic screening of for LTBI on a large scale. Thus, the problems identified and resolved in this study can assist laboratories implementing IGRAs, in addition to manufacturers of IGRAs providing effective technical support. This will facilitate the implementation of IGRA testing in countries with a high TB burden, such as Brazil.
Tuberculosis (TB) causes 1 in 3 deaths among people living with HIV (PLHIV). Diagnosing and treating latent tuberculosis infection (LTBI) is critical to reducing TB incidence and mortality. Blood-based screening tests (e.g., QuantiFERON-TB Gold Plus (QFT+)) and shorter-course TB preventive therapy (TPT) regimens such as 3HP (3 months weekly isoniazid-rifapentine) hold significant promise to improve TB outcomes. We qualitatively explored barriers and solutions to optimizing QFT+ and 3HP among PLHIV in three cities in Brazil. We conducted 110 in-depth interviews with PLHIV, health care providers (HCP) and key informants (KI). Content analysis was conducted including the use of case summaries and comparison of themes across populations and contexts. LTBI screening and treatment practices were dependent on HCP’s perceptions of whether they were critical to improving TB outcomes. Many HCP lacked a strong understanding of LTBI and perceived the current TPT regimen as complicated. HCP reported that LTBI screening and treatment were constrained by clinic staffing challenges. While PLHIV generally expressed willingness to consider any test or treatment that doctors recommended, they indicated HCP rarely discussed LTBI and TPT. TB testing and treatment requests were constrained by structural factors including financial and food insecurity, difficulties leaving work for appointments, stigma and family responsibilities. QFT+ and 3HP were viewed by all participants as tools that could significantly improve the LTBI cascade by avoiding complexities of TB skin tests and longer LTBI treatment courses. QFT+ and 3HP were perceived to have challenges, including the potential to increase workload on over-burdened health systems if not implemented alongside improved supply chains, staffing, and training, and follow-up initiatives. Multi-level interventions that increase understanding of the importance of LTBI and TPT among HCP, improve patient-provider communication, and streamline clinic-level operations related to QFT+ and 3HP are needed to optimize their impact among PLHIV and reduce TB mortality.
Tuberculosis (TB) remains a major plague of humanity. People with TB (PWTB) are commonly anemic. Here, we assessed whether the severity of anemia in PWTB prior to anti-TB treatment (ATT) was a risk factor for an unfavorable outcome.
The interferon gamma release assay (IGRA) has emerged as a useful tool for identifying latent tuberculosis infection (LTBI). This assay can be performed through testing platforms such as the QuantiFERON-TB Gold Plus (QFT-Plus) assay. This in vitro test has been incorporated into several guidelines worldwide and has recently been considered by the World Health Organization (WHO) for the diagnosis of LTBI. The possibility of systematically implementing IGRAs such as the QFT-Plus assay in centers that perform LTBI screening has been accelerated by the decreased availability of the tuberculin skin test (TST) in several countries. Nevertheless, the process to implement IGRA testing in routine clinical care has many gaps. The study utilized the expertise acquired by the laboratory teams of the Regional Prospective Observational Research in Tuberculosis (RePORT)-Brazil consortium during study protocol implementation of LTBI screening of tuberculosis (TB) close contacts. RePORT-Brazil includes clinical research sites from Brazilian cities and is the largest multicenter cohort of TB close contacts in the country to date. Operational and logistical challenges faced during IGRA implementation in all study laboratories are described, as well as the solutions that were developed and led to the successful establishment of IGRA testing in RePORT-Brazil. The descriptions of the problems identified and resolved in this study can assist laboratories implementing IGRAs, in addition to manufacturers of IGRAs providing effective technical support. This will facilitate the implementation of IGRA testing in countries with large TB burdens, such as Brazil. IMPORTANCE The IGRA has emerged as a useful tool for identifying persons with LTBI. Although the implementation of IGRAs is of utmost importance, to our knowledge there is scarce information on the identification of logistical and technical challenges for systematic screening for LTBI on a large scale. Thus, the descriptions of the problems identified and resolved in this study can assist laboratories implementing IGRAs, in addition to manufacturers of IGRAs providing effective technical support. This will facilitate the implementation of IGRA testing in countries with large TB burdens, such as Brazil.
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