Paradoxical Deterioration During Anti-Tuberculous Therapy in Non-HIV-Infected Patients with Pleural Tuberculosis: A Pragmatic Approach

We report a case of paradoxical deterioration. A male patient diagnosed with pleural tuberculosis, but who was not infected with human immunodeficiency virus (HIV), experienced clinical deterioration 3 weeks after the initiation of anti-tuberculous treatment. After other diagnoses were ruled out, a paradoxical response to treatment was established and the patient was started on systemic corticosteroids. Paradoxical response to treatment should be considered in patients with clinical deterioration after they start on anti-tuberculous treatment.

Endometrial tuberculosis simulating an ovarian cancer

Female genital tuberculosis remains a major health problem in developing countries and is an important cause of infertility. As symptoms, laboratory data and physical fndings are non-specifc, its diagnosis can be diffcult. We describe a case of a 39-year-old woman suffering from peri-umbilical pain and increased abdominal size for one year, anorexia, asthenia, weight loss, occasionally dysuria and dyspareunia, and four months amenorrhea. Laboratory data revealed cancer antigen 125 (CA-125) level of 132.3 U/mL, erythrocyte sedimentation rate of 42 mm/h, and gamma-globulins of 2.66 g/dL. Computer Tomography scan showed loculated ascites. It was initially suspected a carcinomatous origin, but ascites evaluation was negative for malignant cells. Magnetic Resonance Imaging from another hospital showed endometrial heterogeneity. Therefore, an endometrial biopsy was performed demonstrating an infammatory infltrate with giant cells of type Langhans and bacteriological culture identifed Mycobacterium tuberculosis

Thyroid function in multidrug-resistant tuberculosis patients with or without human immunodeficiency virus (HIV) infection before commencement of MDR-TB drug regimen.

Background: Mycobacterium tuberculosis and human immunodeficiency virus (HIV) are known to cause abnormal thyroid function. There is little information on whether HIV infection aggravates alteration of thyroid function in patients with MDRTB. Objectives: This study was carried out to determine if HIV co-infection alters serum levels of thyroid hormones (T3, T4) and thyroid stimulating hormone (TSH) in patients with MDR-TB patients and to find out the frequency of subclinical thyroid dysfunction before the commencement of MDR-TB therapy. Methods: This observational and cross-sectional study involved all the newly admitted patients in MDR-TB Referral Centre, University College Hospital, Ibadan, Nigeria between July 2010 and December 2014. Serum levels of thyroid stimulating hormone (TSH), free thyroxine (fT4) and free triiodothyronine (fT3) were determined using ELISA. Results: Enrolled were 115 patients with MDR-TB, out of which 22 (19.13%) had MDR-TB/HIV co-infection. Sick euthyroid syndrome (SES), subclinical hypothyroidism and subclinical hyperthyroidism were observed in 5 (4.35%), 9 (7.83%) and 2 (1.74%) patients respectively. The median level of TSH was insignificantly higher while the median levels of T3 and T4 were insignificantly lower in patients with MDR-TB/HIV co-infection compared with patients with MDRT-TB only. Conclusion: It could be concluded from this study that patients with MDR-TB/HIV co-infection have a similar thyroid function as patients having MDR-TB without HIV infection before commencement of MDR-TB drug regimen. Also, there is a possibility of subclinical thyroid dysfunction in patients with MDR-TB/HIV co-infection even, before the commencement of MDR-TB therapy.

Profile and treatment outcomes of patients with tuberculosis in Northeastern Ethiopia: a cross sectional study.

Background: Data on the epidemiology of tuberculosis and its treatment outcomes were incomplete in the study area and this study was done to fill this gap. Methods: Institution based cross sectional study was conducted from January 2011 to December 2014. A total of 949 TB patients who were on treatment in North Eastern Ethiopia, Eastern Amhara region were included. Data was analyzed using SPSS version 20. Frequency, percentages and means were used to present data. To assess the associations of treatment outcomes with sex, age, type of TB and human immunodeficiency virus (HIV), logistic regression was used. Results: The proportion of smear positive and negative pulmonary TB, and extra pulmonary TB were 187/949 (19.7%), 322/949 (33.9%) and 440/949 (46.4%), respectively. Treatment success rate was 853/949 (89.9%). Smear positive pulmonary TB and TB/HIV co-infections were significantly associated with unsuccessful treatment outcome, P≤ 0.002. Conclusion: Extra pulmonary TB was the most prevalent types of TB followed by smear negative pulmonary TB. Treatment success rate was above the WHO target of 85%. The causes for the high proportion of smear negative PTB and EPTB should be further investigated. Special emphasis should be put on smear positive PTB patients and TB/HIV co-infected patients to decrease unsuccessful treatment outcome and TB transmissions.

Diabetes mellitus among tuberculosis patients: a cross sectional study from Pakistan

Background: The co-occurrence of diabetes mellitus (DM) and tuberculosis (TB) is largely associated with high frequency of morbidity. Objective: To determine the prevalence of DM among TB patients and describe the socio-demographic and behavioral factors associated with TB-DM co-occurrence . Methods: We enrolled 500 TB patients from September, 2014 to August 2015 at four major public sector hospitals of Lahore, Pakistan. A questionnaire was used to collect information regarding associated socio-demographic and behavioral factors of the patients. We monitored the fasting blood sugar of each patient by using a semi automated clinical chemistry analyzer followed by an HbA1c level check of all hyperglycemic patients. Results: The prevalence of TB-DM co-occurrence was 14.8%. The prevalence of TB-DM was higher (62.2%) among males. The >57 year age group had the highest proportion of patients (35.1%), with co-existent TB-DM. Most were illiterate (73.0%) and unemployed (48%). Moreover, among the 74 patients positive for TB-DM had a history of smoking. Age and education level were significantly associated with DM-TB while gender, occupation and smoking were not associated. Conclusion: The study revealed a 14.8% prevalence of DM among TB patients. This was associated with several socio-demographic factors, including age, unemployment, literacy and polluted environment. Thus, poor and unhealthy lifestyles were the factors associated with DM among immunologically compromised individuals due to TB.

Proteína C reactiva, marcador inflamatorio asociado con ANCA en tuberculosis pulmonar

Antecedentes: la proteína C reactiva es uno de los marcadores inflamatorios denominados “reactantes de fase aguda” que se produce en el hígado en respuesta a procesos infecciosos o inflamatorios. En los pacientes con tuberculosis se ha descrito la formación de anticuerpos anticitoplasma de neutrófi los (ANCA). Objetivo: determinar la concentración de proteína C reactiva, evaluar su comportamiento como marcador de la respuesta inflamatoria y analizar su correlación con los ANCA en los pacientes con tuberculosis pulmonar, antes y después de iniciar el tratamiento antifímico. Pacientes: se eligieron pacientes con sospecha de tuberculosis pulmonar. Una vez confirmado el diagnóstico, se obtuvieron las muestras de suero para analizar los datos clínicos y de laboratorios. La determinación de ANCA se realizó con estuches comerciales de inmunofluorescencia y la de proteína C reactiva con ELISA, antes y después de iniciar el tratamiento antifímico. Resultados: se obtuvieron 50 muestras de suero de pacientes con tuberculosis pulmonar. En la primera (94%) y segunda obtención (90%) de los sueros se registró un valor de proteína C reactiva menor de 5 mg/L. El valor promedio de proteína C reactiva fue de 3.05 ± 8.27 mg/L en la primera muestra y de 4.49 ± 11.2 mg/L en la segunda (p = 0.46). Los pacientes positivos a ANCA tuvieron valores más altos de proteína C reactiva en su segunda muestra (p = 0.001). Discusión: existe una asociación entre la proteína C reactiva y la producción de anticuerpos anticitoplasma de neutrófilos en un subgrupo de pacientes con tuberculosis pulmonar. Su significación es incierta, pero quizá desempeñan alguna función patogénica en la respuesta inflamatoria pulmonar.

Prevalencia de brucelosis bovina en el periodo 2004-2012 y tuberculosis bovina en el periodo 2006-2012 en hatos lecheros del Cantón Mejía

Brucelosis y tuberculosis bovina son dos enfermedades que causan importantes pérdidas productivas y reproductivas en la ganadería local, nacional e internacional. En el Ecuador, desde hace varios años se viene trabajando en un programa para el control y erradicación de estas dos enfermedades. En el año 2006, por primera vez, siete predios de producción lechera consiguieron la certificación de predio libre de Brucelosis bovina, otorgada por el Servicio Ecuatoriano de Sanidad Animal (SESA) de ese entonces (Paredes 2014, comunicación personal). La Asociación Holstein Friesian del Ecuador (AHFE) inicia en el año 2004 el Programa de Control y Erradicación de Brucelosis bovina y en el año 2006 el Programa de Control y Erradicación de Tuberculosis bovina. Sin embargo, los datos de ambos programas no han sido analizados para determinar el estado de estas dos enfermedades en los periodos comprendidos entre los años 2004 a 2012 y periodo 2006 a 2012, respectivamente.

Transient hyperglycemia in patients with tuberculosis in Tanzania: implications for diabetes screening algorithms.

BACKGROUND: Diabetes mellitus (DM) increases tuberculosis risk while tuberculosis, as an infectious disease, leads to hyperglycemia. We compared hyperglycemia screening strategies in controls and patients with tuberculosis in Dar es Salaam, Tanzania. METHODS: Consecutive adults with tuberculosis and sex- and age-matched volunteers were included in a case-control study between July 2012 and June 2014. All underwent DM screening tests (fasting capillary glucose [FCG] level, 2-hour CG [2-hCG] level, and glycated hemoglobin A1c [HbA1c] level) at enrollment, and cases were tested again after receipt of tuberculosis treatment. Association of tuberculosis and its outcome with hyperglycemia was assessed using logistic regression analysis adjusted for sex, age, body mass index, human immunodeficiency virus infection status, and socioeconomic status. Patients with tuberculosis and newly diagnosed DM were not treated for hyperglycemia. RESULTS: At enrollment, DM prevalence was significantly higher among patients with tuberculosis (n = 539; FCG level > 7 mmol/L, 4.5% of patients, 2-hCG level > 11 mmol/L, 6.8%; and HbA1c level > 6.5%, 9.3%), compared with controls (n = 496; 1.2%, 3.1%, and 2.2%, respectively). The association between hyperglycemia and tuberculosis disappeared after tuberculosis treatment (adjusted odds ratio [aOR] for the FCG level: 9.6 [95% confidence interval {CI}, 3.7-24.7] at enrollment vs 2.4 [95% CI, .7-8.7] at follow-up; aOR for the 2-hCG level: 6.6 [95% CI, 4.0-11.1] vs 1.6 [95% CI, .8-2.9]; and aOR for the HbA1c level, 4.2 [95% CI, 2.9-6.0] vs 1.4 [95% CI, .9-2.0]). Hyperglycemia, based on the FCG level, at enrollment was associated with tuberculosis treatment failure or death (aOR, 3.3; 95% CI, 1.2-9.3). CONCLUSIONS: Transient hyperglycemia is frequent during tuberculosis, and DM needs confirmation after tuberculosis treatment. Performance of DM screening at tuberculosis diagnosis gives the opportunity to detect patients at risk of adverse outcome.

Safety assessment in primary Mycobacterium tuberculosis smear microscopy centres in Blantyre Malawi: a facility based cross sectional survey

Introduction Tuberculosis (TB) is caused by Mycobacterium tuberculosis and is transmitted mainly through aerosolization of infected sputum which puts laboratory workers at risk in spite of the laboratory workers’ risk of infection being at 3 to 9 times higher than the general public. Laboratory safety should therefore be prioritized and optimized to provide sufficient safety to laboratory workers. Objective To assess the safety for the laboratory workers in TB primary microscopy centres in Blantyre urban. Methodology TB primary microscopy centers in Blantyre urban were assessed in aspects of equipment availability, facility layout, and work practice, using a standardized WHO/AFRO ISO 15189 checklist for the developing countries which sets the minimum safety score at ≥80%. Each center was graded according to the score it earned upon assessment. Results Only one (1) microscopy center out nine (9) reached the minimum safety requirement. Four (4) centers were awarded 1 star level, four (4) centers were awarded 2 star level and only one (1) center was awarded 3 star level. Conclusion In Blantyre urban, 89% of the Tuberculosis microscopy centers are failing to provide the minimum safety to the laboratory workers. Government and other stake holders should be committed in addressing the safety challenges of TB microscopy centres in the country to ensure safety for the laboratory workers. Recommendations It is recommended that the study be conducted at the regional or national level for both public and private laboratories in order to have a general picture of safety in Tb microscopy centres possibly across the country.

Tuberculosis de la glándula parótida

Hoy en día la tuberculosis es una de las más importantes infecciones reemergentes en el mundo. Hasta un 20% de las formas de presentación son extratorácicas. Sin embargo, la presencia de tuberculosis a nivel parotídeo es infrecuente incluso en países subdesarrollados, donde la incidencia de esta enfermedad es mayor. Presentamos un paciente de 83 años que acude por tumoración en región parotídea de 4 semanas de evolución sin antecedentes personales. La exploración clínica revela una masa en cola de parótida izquierda de aproximadamente 3 × 2 cm, no dolorosa a la palpación y sin evidencia de adenopatías a nivel cervical. Tras el estudio radiológico y punción con aguja fina, no se obtienen datos concluyentes, por lo que se procede a realizar exéresis. Se envía muestra para estudio de PCR, se confirma diagnóstico de tuberculosis parotídea. Tras recibir quimioterapia antituberculosa complementaria, el paciente es dado de alta por remisión de la enfermedad.

A molecular platform for the diagnosis of multidrug-resistant and pre-extensively drug-resistant tuberculosis based on single nucleotide polymorphism mutations present in Colombian isolates of Mycobacterium tuberculosis

Developing a fast, inexpensive, and specific test that reflects the mutations present in Mycobacterium tuberculosis isolates according to geographic region is the main challenge for drug-resistant tuberculosis (TB) control. The objective of this study was to develop a molecular platform to make a rapid diagnosis of multidrug-resistant (MDR) and extensively drug-resistant TB based on single nucleotide polymorphism (SNP) mutations present in the rpoB, katG, inhA, ahpC, and gyrA genes from Colombian M. tuberculosis isolates. The amplification and sequencing of each target gene was performed. Capture oligonucleotides, which were tested before being used with isolates to assess the performance, were designed for wild type and mutated codons, and the platform was standardised based on the reverse hybridisation principle. This method was tested on DNA samples extracted from clinical isolates from 160 Colombian patients who were previously phenotypically and genotypically characterised as having susceptible or MDR M. tuberculosis. For our method, the kappa index of the sequencing results was 0,966, 0,825, 0,766, 0,740, and 0,625 for rpoB, katG, inhA, ahpC, and gyrA, respectively. Sensitivity and specificity were ranked between 90-100% compared with those of phenotypic drug susceptibility testing. Our assay helps to pave the way for implementation locally and for specifically adapted methods that can simultaneously detect drug resistance mutations to first and second-line drugs within a few hours.

The mc2-CMX vaccine induces an enhanced immune response against Mycobacterium tuberculosis compared to Bacillus Calmette-Guérin but with similar lung inflammatory effects

Although the attenuated Mycobacterium bovis Bacillus Calmette-Guérin (BCG) vaccine has been used since 1921, tuberculosis (TB) control still proceeds at a slow pace. The main reason is the variable efficacy of BCG protection against TB among adults, which ranges from 0-80%. Subsequently, the mc2-CMX vaccine was developed with promising results. Nonetheless, this recombinant vaccine needs to be compared to the standard BCG vaccine. The objective of this study was to evaluate the immune response induced by mc2-CMX and compare it to the response generated by BCG. BALB/c mice were immunised with both vaccines and challenged with Mycobacterium tuberculosis (Mtb). The immune and inflammatory responses were evaluated by ELISA, flow cytometry, and histopathology. Mice vaccinated with mc2-CMX and challenged with Mtb induced an increase in the IgG1 and IgG2 levels against CMX as well as recalled specific CD4+ T-cells that produced T-helper 1 cytokines in the lungs and spleen compared with BCG vaccinated and challenged mice. Both vaccines reduced the lung inflammatory pathology induced by the Mtb infection. The mc2-CMX vaccine induces a humoral and cellular response that is superior to BCG and is efficiently recalled after challenge with Mtb, although both vaccines induced similar inflammatory reductions.

Effects of the encapsulation of usnic acid into liposomes and interactions with antituberculous agents against multidrug-resistant tuberculosis clinical isolates

Mycobacterium tuberculosis (Mtb) has acquired resistance and consequently the antibiotic therapeutic options available against this microorganism are limited. In this scenario, the use of usnic acid (UA), a natural compound, encapsulated into liposomes is proposed as a new approach in multidrug-resistant tuberculosis (MDR-TB) therapy. Thus the aim of this study was to evaluate the effect of the encapsulation of UA into liposomes, as well as its combination with antituberculous agents such as rifampicin (RIF) and isoniazid (INH) against MDR-TB clinical isolates. The in vitro antimycobacterial activity of UA-loaded liposomes (UA-Lipo) against MDR-TB was assessed by the microdilution method. The in vitro interaction of UA with antituberculous agents was carried out using checkerboard method. Minimal inhibitory concentration values were 31.25 and 0.98 μg/mL for UA and UA-Lipo, respectively. The results exhibited a synergistic interaction between RIF and UA [fractional inhibitory concentration index (FICI) = 0.31] or UA-Lipo (FICI = 0.28). Regarding INH, the combination of UA or UA-Lipo revealed no marked effect (FICI = 1.30-2.50). The UA-Lipo may be used as a dosage form to improve the antimycobacterial activity of RIF, a first-line drug for the treatment of infections caused by Mtb.

Drug resistance and genetic diversity of Mycobacterium tuberculosis in Luanda, Angola: a molecular epidemiological perspective

Poster presented at the 36th Annual Congress of the European Society of Mycobacteriology. Riga, Latvia, 28 June - 1 July 2015

Protein expression of Myt272-3 recombinant clone and in silico prediction of a possible vaccine candidate against Mycobacterium tuberculosis

Purpose: To investigate the expression of Myt272-3 recombinant protein and also to predict a possible protein vaccine candidate against Mycobacterium tuberculosis . Methods: Myt272-3 protein was expressed in pET30a+-Myt272-3 clone. The purity of the protein was determined using Dynabeads® His-Tag Isolation & Pulldown. Protein sequence was analysed in silico using bioinformatics software for the prediction of allergenicity, antigenicity, MHC-I and MHC-II binding, and B-cell epitope binding. Results: The candidate protein was a non-allergen with 15.19 % positive predictive value. It was also predicted to be antigenic, with binding affinity to MHC-I and MHC-II, as well as B-cell epitope binding. Conclusion: The predicted results obtained in this study provide a guide for practical design of a new tuberculosis vaccine.