Clinical and Imaging Characteristics of Smear Negative Pulmonary Tuberculosis Patients: A Comparative Study.

Background: Prevalence surveys in Ethiopia indicate smear negative pulmonary tuberculosis (SNPTB) taking the major share of the overall TB burden. It has also been a diagnostic dilemma worldwide leading to diagnostic delays and difficulty in monitoring treatment outcomes. This study determines and compares the clinical and imaging findings in SNPTB and smear positive PTB (SPPTB). Methodology. A case-control study was conducted on 313 PTB (173 SNPTB) patients. Data and sputum samples were collected from consented patients. Smear microscopy, GeneXpert, and culture analyses were performed on sputum samples. Data were analyzed using Stata version 17; a P value < 0.05 was considered statistically significant. Results: Of the 173 SNPTB patients, 42% were culture positive with discordances between test results reported by health facilities and Armauer Hansen Research Institute laboratory using concentrated smear microscopy. A previous history of TB and fewer cavitary lesions were significantly associated with SNPTB. Conclusions: Though overall clinical presentations of SNPTB patients resemble those seen in SPPTB patients, a prior history of TB was strongly associated with SNPTB. Subject to further investigations, the relatively higher discrepancies seen in TB diagnoses reflect the posed diagnostic challenges in SNPTB patients, as a higher proportion of these patients are also seen in Ethiopia.

[A case of silicosis complicated with non-tuberculous mycobacterium pulmonary disease].

Non-tuberculosis mycobacterium (NTM) refers to a general term for a large group of mycobacteria, excluding the mycobacterium tuberculosis and mycobacterium leprae, which is an opportunistic pathogen. NTM pulmonary disease and pulmonary tuberculosis have very similar clinical and imaging manifestations. Ordinary sputum tests can not distinguish between mycobacterium tuberculosis and NTM accurately, and it needs to be differentiated through detection methods such as mycobacterium culture medium, high-performance liquid chromatography, and molecular biology. During the diagnosis of occupational pneumoconiosis, a sandblasting and polishing worker's lung CT showed dynamic changes in infiltrating shadows and cavities in the right lung. A sputum drug sensitivity test showed NTM infection, but the patient refused treatment. After 20 months, the CT examination of the lung showed further enlargement of infiltrating shadows and cavities, and NTM bacterial identification showed intracellular mycobacterial infection. Amikacin, moxifloxacin, azithromycin, and ethambutol combined antibacterial treatment were given. Currently, the patient is still under treatment.

Co-infection of Mycobacterium tuberculosis and Mycobacterium leprae Complicated by pulmonary embolism: A rare case report.

A 35-year-old male patient with lepromatous leprosy came to the emergency room (ER) due to breathlessness and chest pain. The patient was diagnosed with pulmonary tuberculosis (TB) after a bronchoscopy and started on antitubercular therapy. However, the patient continued to experience tachycardia and desaturation, and on further evaluation, Computed tomography pulmonary angiography revealed an embolus in the right descending pulmonary artery. The patient was found to have an elevated d-dimer. Further investigation revealed that the cause of the pulmonary thromboembolism (PTE) was the thalidomide medication that the patient was taking for type 2 leprosy reaction. The medication was stopped, and the patient was treated with low-molecular-weight heparin and discharged with apixaban for six months. The patient's condition improved on follow-up. This case is unique due to the rare combination of pulmonary TB, leprosy, and pulmonary embolism brought on by thalidomide administration. Physicians should be aware of the possibility of co-infection of TB and leprosy and the need to rule out thromboembolism when patients are on thalidomide.

Differences in responses to the intracellular macrophage environment between Mycobacterium bovis BCG vaccine strains Moreau and Pasteur.

BACKGROUND: The Bacille Calmette-Guérin (BCG) vaccine comprises a family of strains with variable protective efficacy against pulmonary tuberculosis (TB) and leprosy, partly due to genetic differences between strains. OBJECTIVES: Previous data highlighting differences between the genomes and proteomic profiles of BCG strains Moreau and Pasteur led us to evaluate their behaviour in the macrophage microenvironment, capable of stimulating molecular responses that can impact the protective effect of the vaccine. METHODS: Strain infectivity, viability, co-localisation with acidified vesicles, macrophage secretion of IL-1 and MCP-1 and lipid droplet biogenesis were evaluated after infection. FINDINGS: We found that BCG Moreau is internalised more efficiently, with significantly better intracellular survival up to 96 h p.i., whereas more BCG Pasteur bacilli were found co-localised in acidified vesicles up to 6 h p.i. IL-1ß and MCP-1 secretion and lipid droplet biogenesis by infected macrophages were more prominent in response to BCG Pasteur. MAIN CONCLUSION: Overall, our results show that, compared to Pasteur, BCG Moreau has increased fitness and better endurance in the harsh intracellular environment, also regulating anti-microbial responses (lower IL-1b and MCP-1). These findings contribute to the understanding of the physiology of BCG Moreau and Pasteur in response to the intraphagosomal environment in a THP-1 macrophage model.

Co-infection leprosy and tuberculosis: a systematic review.

Leprosy and tuberculosis are endemic in several countries. The aim of this study was to describe factors associated with co-infection among both diseases. A systematic review was carried out, following the Quality of Reporting of Meta-analyses, with the PubMed and Biblioteca Virtual em Saúde (BVS) portals as sources, under eligibility criteria: cross-sectional, cohort, case-control studies or case reports, published in Portuguese, English, French and Spanish, from 2015 to 2020. Studies that dealt with leprosy and tuberculosis not in the context of co-infection were excluded. The initial phase resulted in 1079 articles; 13 went on to a final stage. All were case reports. Thirteen (72.2%) participants were male, aged between 17 and 72 years. Life habits were found in 8 (44.4%) of the articles: 1 (12.5%) reported chronic alcoholism, 1 (12.5%) reported chronic smoking and alcoholism and 1(12.5%) reported chronic smoking, alcoholism and use of illicit drugs. Pathological history was mentioned by 14 (77.8%) patients; 1 (7.1%) reported HIV/AIDS. Three patients (16.6%) described previous history of tuberculosis and/or leprosy. Seven (38.9%) participants reported vaccination with Bacillus Calmette-Guérin. The pulmonary form of tuberculosis predominated and one third of the patients presented resistance to, at least, one tuberculostatic. All cases had multibacillary leprosy. The study did not highlight any comorbidity, and there was no change in the course of the conditions owing to co-infection.

Evaluación del método de Petroff modificado con solución salina para el diagnóstico de micobacterias en el sistema Bact/Alert 3D / Assessment of Petroff method modified with saline solution for the diagnosis of mycobacteria in Bact/Alert 3D system

Introducción: Existen diferentes métodos de descontaminación de muestras pulmonares para el diagnóstico de micobacterias. El Programa Nacional de Control de Tuberculosis recomienda el método de Petroff modificado con solución salina, pero no existen evidencias documentadas que avalen este método. Objetivo: Evaluar el método de Petroff modificado con solución salina para el diagnóstico de micobacterias en el sistema Bact/Alert 3D. Métodos: Se realizó un estudio observacional analítico de pruebas diagnósticas utilizando 100 muestras pulmonares recibidas en el Laboratorio Nacional de Referencia e Investigaciones de Tuberculosis, Lepra y Micobacterias del Instituto Pedro Kourí, abril 2016 enero 2017. La muestra se dividió en 3 alícuotas y se descontaminaron mediante 3 métodos; luego se inocularon en los medios de cultivo sólido y líquido. Se compararon los resultados del cultivo en cuanto: tiempo de detección de crecimiento, tasa de contaminación, por ciento de positividad, además se calcularon indicadores de desempeño. Resultados: Al comparar el método Petroff modificado con solución salina con el Petroff modificado con solución fosfato en Löwenstein Jensen, el tiempo de detección de crecimiento, por ciento de positividad y la tasa de contaminación se comportaron de forma similar y la sensibilidad (93,75 por ciento), concordancia (96,47 por ciento) e índice de Youden (0,91) fueron elevadas. Al compararlo el Petroff modificado con solución salina con el N-Acetil-L-Cisteína, las variables no mostraron diferencias significativas y los Indicadores de Desempeño se comportaron por encima del 93 por ciento, para el medio sólido y líquido. Conclusiones: Los resultados avalan la continuidad del uso del Petroff modificado con solución salina como método de descontaminación de las muestras pulmonares en la red de laboratorios de Cuba y como alternativa en el pretratamiento de las muestras para el medio líquido (Bact/Alert 3D), además constituye un soporte para el Programa Nacional de Control de Tuberculosis(AU)

Introduction: There are different decontamination methods of pulmonary samples for the diagnosis of mycobacteria. The National Program for the Control of Tuberculosis recommends Petroff method modified with saline solution; but there are not documented evidences that endorse it. Objective: Assess Petroff method modified with saline solution for the diagnosis of mycobacteria in Bact / Alert 3D system. Methods: An observational analytic study of diagnostic tests was conducted; there were used 100 pulmonary samples received in the National Laboratory of References and Researches of Tuberculosis, Leprosy and Mycobacteria of Pedro Kourí Institute, from April 2016 to January 2017. The sample was divided in 3 aliquots and those were decontaminated using 3 methods; then, they were inoculated in the solid and liquid culture means. Cultures´ results were compared according to: growth's detection time, contamination rate, percent of positivity; in addition, performance indicators were calculated. Results: When comparing Petroff method modified with saline solution with Petroff method modified with phosphate solution in Löwenstein Jensen, the growth's detection time, the percent of positivity and the rate of contamination behaved similarly, and sensitivity (93,75percent), concordance (96,47percent) and Youden´s index (0,91) were high. When the Petroff method modified with saline solution was compared with N-Acetil-L- Cisteina, the variables did not show significative differences and the behaviour indicators were over 93percent for the solid and liquid mean. Conclusions: The results endorse the continuity of the use of Petroff method modified with saline solution as a decontamination method of pulmonary samples in the network of Cuban laboratories and as alternative to the pre-treatment of the samples for the liquid mean (Bact/Alert 3D); it also constitutes a support for the National Program for the Control of Tuberculosis(AU)

Concurrent pulmonary tuberculosis and lepromatous leprosy in a newly diagnosed HIV positive patient: a case report.

BACKGROUND: The leprosy-tuberculosis (TB) co-infection is rarely reported in recent times. However, this dual comorbidity is associated with high mortality and major morbidity. Unrecognised leprosy-TB co-infection may predispose affected patients to rifampicin monotherapy and subsequent drug resistance. CASE PRESENTATION: A 35 year old migrant, human immunodeficiency virus (HIV) positive male worker presented with 6 month history of symmetric infiltrative nodular plaques of the face and distal, upper extremities. A few days after initial dermatology presentation, a sputum positive pulmonary tuberculosis diagnosis was made at his base hospital. Subsequent dermatology investigations revealed histology confirmed lepromatous leprosy and a weakly reactive rapid plasma reagin test. The presenting clinical features and laboratory results were suggestive of lepromatous leprosy coexisting with pulmonary tuberculosis in an HIV positive patient. CONCLUSIONS: This case illustrates the occurrence of leprosy with pulmonary tuberculosis in an HIV infected patient and the difficulties in interpreting non-treponemal syphilis tests in these patients. This case also highlights the need for a high index of suspicion for co-infection and the need to exclude PTB prior to initiation of rifampicin containing multi-drug therapy (MDT). Interdisciplinary management and social support are crucial in these patients.

Spectrum of Inborn errors of immunity in a cohort of 90 patients presenting with complications to BCG vaccination in India.

World Health Organisation recommends the practice of BCG vaccination at birth in countries which have a high incidence of tuberculosis and/or high leprosy burden. The BCG vaccination is considered safe for a competent immune system. However, in children with weakened immune systems cause of which can be primary or secondary, the vaccine may lead to side effects which can be localized or disseminated. In this study, we report a spectrum of inborn errors of immunity (IEI) commonly referred to as primary immunodeficiency disorders (PIDs) diagnosed in a large cohort of patients presenting with complications to BCG vaccination from India. Retrospective data analysis of patients referred to ICMR- National Institute of Immunohematology (ICMR-NIIH) for IEI workup between 2007 and 2019 was done. IEI was identified in n = 52/90 (57.7%) patients presenting with BCG complications. Of these, n = 13(14.4%) patients were diagnosed with severe combined immune deficiency, n = 15(16.7%) with chronic granulomatous disease, n = 19(21.1%) with Inborn errors of IFN-γ immunity, n = 4(4.4%) with Combined immunodeficiency and n = 1(1.1%) with Leucocyte Adhesion Deficiency type1. Majority of cases with BCGosis (88%) had an underlying IEI. This study strongly highlights the need for evaluation of patients with BCG complications for underlying IEI. While disseminated BCGosis strongly predicts underlying IEI, even localized persistent adenitis may be a warning sign of underlying IEI. It is also strongly recommended to record a family history of previous sibling death prior to administration of this live vaccine and deferring live vaccine till the diagnosis of IEI is ruled out in cases with a positive family history.

Multicentric validation of indigenous molecular test Truenat™ MTB for detection of Mycobacterium tuberculosis in sputum samples from presumptive pulmonary tuberculosis patients in comparison with reference standards.

BACKGROUND & OBJECTIVES: : Early case detection is essential to interrupt transmission and to prevent further spread of tuberculosis (TB) in high endemic settings. Nucleic acid amplification tests (NAATs) with visual read-outs are ideal as point-of-care tests. Truenat™ MTB is an indigenous chip-based NAAT for detection of Mycobacterium tuberculosis, which involves extraction of DNA and real-time polymerase chain reaction (PCR) using portable, automated, battery-operated instruments. The current multicentric study was aimed to evaluate Truenat for detection of MTB in sputum samples obtained from patients with presumptive pulmonary TB with reference to culture as gold standard and Xpert as a comparator. METHODS: : The study was conducted at four sites, namely ICMR-National Institute for Research in Tuberculosis, Chennai; All India Institute of Medical Sciences, New Delhi; ICMR-National JALMA Institute for Leprosy and Other Mycobacterial Diseases, Agra; and National Institute of TB and Respiratory Diseases, New Delhi. Patients suspected to have TB were screened for eligibility. Two sputum samples were collected from each patient. Tests included smear, Xpert and Truenat directly from the sputum sample and culture by Lowenstein-Jensen (L-J) medium and MGIT960 from decontaminated pellets. Sample used for Truenat assay was coded. Resolution of Truenat false positives was done using an in-house PCR with TRC4 primers. RESULTS: : The study enrolled 2419 presumptive TB patients after screening 2465 patients, and 3541 sputum samples were collected from the enrolled patients. Results of 2623 samples were available for analysis. Truenat showed a positivity rate of 48.5 per cent as compared to 37.0 per cent by Xpert. The sensitivities of Truenat and Xpert were was 88.3 and 79.7 per cent, respectively in comparison with culture. INTERPRETATION & CONCLUSIONS: : Truenat MTB identified more positives among culture-confirmed samples than Xpert and had higher sensitivity. In addition, other advantageous operational features of Truenat MTB were identified which would be useful in field settings.

Evaluation of the performance of clinical predictors in estimating the probability of pulmonary tuberculosis among smear-negative cases in Northern Ethiopia: a cross-sectional study.

OBJECTIVES: To evaluate the performance of the predictors in estimating the probability of pulmonary tuberculosis (PTB) when all versus only significant variables are combined into a decision model (1) among all clinical suspects and (2) among smear-negative cases based on the results of culture tests. DESIGN: A cross-sectional study. SETTING: Two public referral hospitals in Tigray, Ethiopia. PARTICIPANTS: A total of 426 consecutive adult patients admitted to the hospitals with clinical suspicion of PTB were screened by sputum smear microscopy and chest radiograph (chest X-ray (CXR)) in accordance with the Ethiopian guidelines of the National Tuberculosis and Leprosy Program. Discontinuation of antituberculosis therapy in the past 3 months, unproductive cough, HIV positivity and unwillingness to give written informed consent were the basis of exclusion from the study. PRIMARY AND SECONDARY OUTCOME MEASURES: A total of 354 patients were included in the final analysis, while 72 patients were excluded because culture tests were not done. RESULTS: The strongest predictive variables of culture-positive PTB among patients with clinical suspicion were a positive smear test (OR 172; 95% CI 23.23 to 1273.54) and having CXR lesions compatible with PTB (OR 10.401; 95% CI 5.862 to 18.454). The regression model had a good predictive performance for identifying culture-positive PTB among patients with clinical suspicion (area under the curve (AUC) 0.84), but it was rather poor in patients with a negative smear result (AUC 0.64). Combining all the predictors in the model compared with only the independent significant variables did not really improve its performance to identify culture-positive (AUC 0.84-0.87) and culture-negative (AUC 0.64-0.69) PTB. CONCLUSIONS: Our finding suggests that predictive models based on clinical variables will not be useful to discriminate patients with culture-negative PTB from patients with culture-positive PTB among patients with smear-negative cases.

Genetic diversity and drug resistance pattern of Mycobacterium tuberculosis strains isolated from pulmonary tuberculosis patients in the Benishangul Gumuz region and its surroundings, Northwest Ethiopia.

INTRODUCTION: Tuberculosis (TB) remains a major global public health problem and is the leading cause of death from a single bacterium, Mycobacterium tuberculosis (MTB) complex. The emergence and spread of drug-resistant strains aggravate the problem, especially in tuberculosis high burden countries such as Ethiopia. The supposedly high initial cost of laboratory diagnosis coupled with scarce financial resources has limited collection of information about drug resistance patterns and circulating strains in peripheral and emerging regions of Ethiopia. Here, we investigated drug susceptibility and genetic diversity of mycobacterial isolates among pulmonary tuberculosis patients in the Benishangul Gumuz region and its surroundings in northwest Ethiopia. METHODS AND MATERIAL: In a cross-sectional study, 107 consecutive sputum smear-positive pulmonary tuberculosis (PTB) patients diagnosed at two hospitals and seven health centers were enrolled between October 2013 and June 2014. Sputum samples were cultured at Armauer Hansen Research Institute (AHRI) TB laboratory, and drug susceptibility testing (DST) was performed against Isoniazid, Rifampicin, Ethambutol, and Streptomycin using the indirect proportion method. Isolates were characterized using polymerase chain reaction (PCR)based Region of Difference 9 (RD9) testing and spoligotyping. Statistical analysis was performed using Statistical Package for the Social Sciences (SPSS) for Windows version 24.0. RESULTS: Of 107 acid-fast-bacilli (AFB) smear-positive sputum samples collected, 81.3% (87/107) were culture positive. A PCR based RD9 testing revealed that all the 87 isolates were M. tuberculosis. Of these isolates, 16.1% (14/87) resistance to one or more drugs was observed. Isoniazid monoresistance occurred in 6.9% (6/87). Multidrug resistance (MDR) was observed in two isolates (2.3%), one of which was resistant to all the four drugs tested. Spoligotyping revealed that the majority, 61.3% (46/75) of strains could be grouped into ten spoligotype patterns containing two to 11 isolates each while the remaining 38.7% (29/75) were unique. SIT289 (11 isolates) and SIT53 (nine isolates) constituted 43.5% (20/46) among clustered isolates while 29.3% (22/75) were ''New" to the database. The dominant families were T, 37% (28/75), CAS, 16.0% (12/75), and H, 8% (6/75), adding up to 51.3% (46/75) of all isolates identified. CONCLUSION AND RECOMMENDATIONS: The current study indicates a moderate prevalence of MDR TB. However, the observed high monoresistance to Isoniazid, one of the two proxy drugs for MDR-TB, reveals the hidden potential threat fora sudden increase in MDR-TB if resistance to Rifampicin would increase. Clustered spoligotype patterns suggest ongoing active tuberculosis transmission in the area. The results underscore the need for enhanced monitoring of TB drug resistance and epidemiological studies in this and other peripheral regions of the country using robust molecular tools with high discriminatory power such as the Mycobacterial Interspersed Repetitive Units -Variable Number of Tandem Repeats (MIRU-VNTR) typing and whole-genome sequencing (WGS).

Validation of an indigenous assay for rapid molecular detection of rifampicin resistance in presumptive multidrug-resistant pulmonary tuberculosis patients.

BACKGROUND & OBJECTIVES: There is a need for an affordable, easy, high-sensitivity test usable at the peripheral health facility for diagnosis of drug-resistant (DR) tuberculosis (TB) to interrupt disease transmission. Nucleic acid amplification tests (NAATs) for early detection of DR-TB are ideal to bring testing near to the patient. TruenatTM MTB (Mycobacterium tuberculosis) and TruenatTM MTB-RIF (rifampicin) is an indigenous chip-based real-time polymerase chain reaction (PCR) based test for detection of multidrug-resistant (MDR) TB. The test involves extraction of DNA using automated, battery operated Trueprep instrument and real-time PCR performed on the Truelab analyzer. We report here multicentric validation of Truenat MTB-RIF for detection of DR-TB in suspected DR-TB patients. METHODS: Consecutive patients aged 18-65 yr, with symptoms suggestive of TB and with a history of previous treatment, reporting to the National TB Elimination Programme (NTEP) clinics under four national institutes, namely AIIMS (All India Institute of Medical Sciences, New Delhi), NITRD (National Institute of Tuberculosis and Respiratory Diseases, New Delhi), NIRT (National Institute for Research in Tuberculosis, Chennai) and ICMR-National JALMA Institute for Leprosy and other Mycobacterial Diseases, Agra, were included in the study. Two sputum samples (one spot and one morning) were collected from each patient, after obtaining informed written consent. The samples were subjected to smear, GeneXpert and MGIT 960 culture (and drug susceptibility testing to RIF) (surrogate for MDR-TB) to serve as reference tests. The samples were coded to ensure blinding and subjected to Truenat MTB-RIF. Truenat MTB-RIF Version 1.5 was used for testing 1084 samples for RIF resistance, while Version 2.0 was used to test another 1201 samples. RESULTS: Truenat MTB-RIF Version 1.5 in comparison with comprehensive laboratory reference standards yielded sensitivity and specificity of 76.2 and 94.7 per cent, respectively for the detection of RIF resistance in 1084 samples, collected across four sites. Based on the analysis of discordant samples, Version 2.0 of Truenat was developed by the manufacturer and this was further tested on additional 1201 samples, yielding a sensitivity of 87.5 per cent and specificity of 99.5 per cent. INTERPRETATION & CONCLUSIONS: Multicentric trial of TruenatTM MTB-RIF demonstrated a great potential of this point of care NAAT for detection of MDR-TB. The test would be useful in limited resource settings and inaccessible areas without need for any additional infrastructure.

Efeitos adversos no tratamento da tuberculose / Adverse effects in the treatment of tuberculosis

Objetivo: Analisar ocorrências de efeitos adversos relacionados a medicamentos no tratamento de tuberculose e sua associação com variáveis clínicas e desfecho. Método: Estudo transversal com 63 casos de tuberculose tratados no Ambulatório de Tuberculose e Hanseníase de São José do Rio Preto, São Paulo, no período de 2010 a 2015. Utilizou-se análise de frequência e teste qui-quadrado com correção de Monte Carlo. Resultados: Os efeitos adversos iniciaram-se antes do terceiro mês de tratamento; efeitos menores foram mais frequentes, com predomínio de irritação gástrica. Houve associação entre conduta médica e efeitos adversos (p = 0,009). Conclusão: Efeitos adversos causados pelos medicamentos podem prejudicar o desfecho clínico devido ao risco de abandono do tratamento. Profissionais de saúde devem estar atentos aos sinais e sintomas relacionados aos efeitos adversos, implementando condutas necessárias para neutralizar ou diminuir as queixas, visando adesão ao tratamento e cura da doença. (AU)

Objective: To analyze occurrences of drug-related adverse effects in treatment of tuberculosis and its association with clinical variables and outcome. Method: Cross-sectional study with 63 cases of tuberculosis treated at Tuberculosis and Leprosy Outpatient Clinic of São José do Rio Preto, São Paulo, from 2010 to 2015. We used frequency analysis and chi-square test with Monte Carlo correction. Results: Adverse effects started before the third month of treatment; effects were more frequent, with predominance of gastric irritation. There was association between medical conduct and adverse effects (p=0.009). Conclusion: Adverse effects caused by medications may impair the clinical outcome due to risk of treatment withdrawal. Health professionals should be alert to signs and symptoms related to adverse effects, implementing the necessary behaviors to neutralize or reduce complaints, aiming adherence to treatment and cure of the disease. (AU)

Objetivo: Analizar los efectos adversos relacionados con medicamentos en tratamiento de la tuberculosis y su asociación con variables clínicas y desenlace. Método: Estudio transversal con 63 casos de tuberculosis tratados en Ambulatorio de Tuberculosis y Hanseniasis de São José Rio Preto, São Paulo, en período de 2010 a 2015. Se utilizó análisis de frecuencia y prueba chi-cuadrado con corrección de Monte Carlo. Los efectos adversos se iniciaron antes del tercer mes de tratamiento; los efectos menores fueron más frecuentes, con predominio de irritación gástrica. Se observó asociación entre conducta médica y efectos adversos (p=0,009). Resultados: Los efectos adversos causados por medicamentos pueden perjudicar el resultado clínico debido al riesgo de abandono del tratamiento. Conclusiones: Los profesionales de salud deben estar atentos a los signos y síntomas relacionados con efectos adversos, implementando conductas necesarias para neutralizar o disminuir las quejas, visando adhesión al tratamiento y cura de la enfermedad. (AU)

Tuberculosis control activities in the private and public health sectors of Kenya from 2013 to 2017: how do they compare?

BACKGROUND: Large numbers of tuberculosis (TB) patients seek care from private for-profit providers. This study aimed to assess and compare TB control activities in the private for-profit and public sectors in Kenya between 2013 and 2017. METHODS: We conducted a retrospective cross-sectional study using routinely collected data from the National Tuberculosis, Leprosy and Lung Disease Program. RESULTS: Of 421 409 patients registered and treated between 2013 and 2017, 86 894 (21%) were from the private sector. Data collection was less complete in the private sector for nutritional assessment and follow-up sputum smear examinations (p<0.001). The private sector notified less bacteriologically confirmed TB (43.1% vs 52.6%; p<0.001) and had less malnutrition (body mass index <18.5 kg/m2; 36.4% vs 43.3%; p<0.001) than the public sector. Rates of human immunodeficiency virus (HIV) testing and antiretroviral therapy initiation were >95% and >90%, respectively, in both sectors, but more patients were HIV positive in the private sector (39.6% vs 31.6%; p<0.001). For bacteriologically confirmed pulmonary TB, cure rates were lower in the private sector, especially for HIV-negative patients (p<0.001). The private sector had an overall treatment success of 86.3% as compared with the public sector at 85.7% (p<0.001). CONCLUSIONS: The private sector is performing well in Kenya although there are programmatic challenges that need to be addressed.

Performance of diagnostic tests for pulmonary tuberculosis in indigenous populations in Brazil: the contribution of Rapid Molecular Testing.

OBJECTIVE: To evaluate the accuracy of rapid molecular testing as a diagnostic tool and estimate the incidence of smear-positive pulmonary tuberculosis among the indigenous population. METHODS: This is an epidemiological study based on secondary data. We calculated the incidence of smear-positive pulmonary tuberculosis between January 1st, 2011 and December 31, 2016, and the performance of bacilloscopy and rapid molecular testing in diagnosing pulmonary tuberculosis compared to sputum culture (standard test). RESULTS: We included 4,048 cases of indigenous people with respiratory symptoms who provided sputum samples for analysis. Among them, 3.7%, 6.7%, and 3.7% had positive results for bacilloscopy, sputum culture, and rapid molecular testing, respectively. The mean incidence of pulmonary tuberculosis was 269.3/100 thousand inhabitants. Rapid molecular testing had 93.1% sensitivity and 98.2% specificity, compared to sputum culture. Bacilloscopy showed 55.1% sensitivity and 99.6% specificity. CONCLUSIONS: Rapid molecular testing can be useful in remote areas with limited resources and a high incidence of tuberculosis, such as indigenous villages in rural regions of Brazil. In addition, the main advantages of rapid molecular testing are its easy handling, fast results, and the possibility of detecting rifampicin resistance. Together, these attributes enable the early start of treatment, contributing to reduce the transmission in communities recognized as vulnerable to infection and disease.

Co-existence of mycobacterial infections: is it an emerging issue with retroviral infections?

We report a 46-year-old woman presenting with leprosy, HIV and active pulmonary tuberculosis (TB). It is advisable to screen for each one of TB, HIV and leprosy patients, especially when an extra feature emerges. Particularly in a leprosy case, if TB remains undiagnosed, the development of rifampicin resistance secondary to monotherapy in leprosy is a major concern.

Performance of diagnostic tests for pulmonary tuberculosis in indigenous populations in Brazil: the contribution of Rapid Molecular Testing / Desempenho de testes para o diagnóstico de tuberculose pulmonar em populações indígenas no Brasil: a contribuição do Teste Rápido Molecular

ABSTRACT Objective: To evaluate the accuracy of rapid molecular testing as a diagnostic tool and estimate the incidence of smear-positive pulmonary tuberculosis among the indigenous population. Methods: This is an epidemiological study based on secondary data. We calculated the incidence of smear-positive pulmonary tuberculosis between January 1st, 2011 and December 31, 2016, and the performance of bacilloscopy and rapid molecular testing in diagnosing pulmonary tuberculosis compared to sputum culture (standard test). Results: We included 4,048 cases of indigenous people with respiratory symptoms who provided sputum samples for analysis. Among them, 3.7%, 6.7%, and 3.7% had positive results for bacilloscopy, sputum culture, and rapid molecular testing, respectively. The mean incidence of pulmonary tuberculosis was 269.3/100 thousand inhabitants. Rapid molecular testing had 93.1% sensitivity and 98.2% specificity, compared to sputum culture. Bacilloscopy showed 55.1% sensitivity and 99.6% specificity. Conclusions: Rapid molecular testing can be useful in remote areas with limited resources and a high incidence of tuberculosis, such as indigenous villages in rural regions of Brazil. In addition, the main advantages of rapid molecular testing are its easy handling, fast results, and the possibility of detecting rifampicin resistance. Together, these attributes enable the early start of treatment, contributing to reduce the transmission in communities recognized as vulnerable to infection and disease.

RESUMO Objetivo: Avaliar a acurácia do teste rápido molecular como ferramenta diagnóstica e estimar a incidência de casos pulmonares positivos entre a população indígena. Métodos: Estudo epidemiológico baseado em dados secundários. Foi calculada a incidência de casos de tuberculose pulmonar positiva entre 1° de janeiro de 2011 e 31 de dezembro de 2016, e o desempenho da baciloscopia e do teste rápido molecular no diagnóstico de tuberculose pulmonar, em comparação à cultura de escarro (teste padrão). Resultados: Foram incluídos 4.048 casos de indígenas considerados sintomáticos respiratórios, que forneceram amostras de escarro para análise. Destes, 3,7%, 6,7% e 3,7% apresentaram resultados positivos para baciloscopia, cultura e teste rápido molecular, respectivamente. A incidência média de tuberculose pulmonar foi de 269,3/100 mil habitantes. A sensibilidade do teste rápido molecular, em relação à cultura, foi 93,1% e a especificidade foi 98,2%. A baciloscopia apresentou sensibilidade 55,1% e especificidade 99,6%. Conclusões: O teste rápido molecular pode ser útil em áreas remotas, com recursos limitados e incidência de tuberculose elevada, como as aldeias indígenas nas áreas rurais do país. Ademais, o teste rápido molecular apresenta como principais vantagens o fácil manuseio, os resultados rápidos e a possibilidade de identificar a resistência à rifampicina. Em conjunto, esses atributos facilitam o início do tratamento precoce, contribuindo para reduzir a transmissão em comunidades reconhecidamente vulneráveis à infecção e à doença.

Complement Component C1q as Serum Biomarker to Detect Active Tuberculosis.

Background: Tuberculosis (TB) remains a major threat to global health. Currently, diagnosis of active TB is hampered by the lack of specific biomarkers that discriminate active TB disease from other (lung) diseases or latent TB infection (LTBI). Integrated human gene expression results have shown that genes encoding complement components, in particular different C1q chains, were expressed at higher levels in active TB compared to LTBI. Methods: C1q protein levels were determined using ELISA in sera from patients, from geographically distinct populations, with active TB, LTBI as well as disease controls. Results: Serum levels of C1q were increased in active TB compared to LTBI in four independent cohorts with an AUC of 0.77 [0.70; 0.83]. After 6 months of TB treatment, levels of C1q were similar to those of endemic controls, indicating an association with disease rather than individual genetic predisposition. Importantly, C1q levels in sera of TB patients were significantly higher as compared to patients with sarcoidosis or pneumonia, clinically important differential diagnoses. Moreover, exposure to other mycobacteria, such as Mycobacterium leprae (leprosy patients) or BCG (vaccinees) did not result in elevated levels of serum C1q. In agreement with the human data, in non-human primates challenged with Mycobacterium tuberculosis, increased serum C1q levels were detected in animals that developed progressive disease, not in those that controlled the infection. Conclusions: In summary, C1q levels are elevated in patients with active TB compared to LTBI in four independent cohorts. Furthermore, C1q levels from patients with TB were also elevated compared to patients with sarcoidosis, leprosy and pneumonia. Additionally, also in NHP we observed increased C1q levels in animals with active progressive TB, both in serum and in broncho-alveolar lavage. Therefore, we propose that the addition of C1q to current biomarker panels may provide added value in the diagnosis of active TB.

Coinfection of leprosy and tuberculosis.

Leprosy and tuberculosis (TB) are endemic to India, however, their coinfection is not frequently encountered in clinical practice. Here, we report a 32-year-old female patient who presented with a history of high-grade intermittent fever, cough and painless skin lesions since a month, along with bilateral claw hand (on examination). The haematological profile was suggestive of anaemia of chronic disease, chest radiograph showed consolidation, sputum smears were positive for Mycobacterium tuberculosis, and skin slit smear confirmed leprosy. The patient was prescribed WHO recommended multidrug therapy for multibacillary leprosy with three drugs. Additionally, prednisolone was added to her regimen for 2 weeks to treat the type 2 lepra reaction. For treatment of TB, she was placed on the standard 6-month short course chemotherapy. She was lost to follow-up, and attempts were made to contact her. Later, it came to our notice that she had discontinued medications and passed away 3 months after diagnosis.