The 2015 represent the deadline for the global tuberculosis (TB) targets set through the Millennium Development Goals (MDG). From 2016 and onward, new goals were set to end the global TB epidemic via implementing new campaign entitled “the End TB Strategy”. The major hurdle to end TB epidemic in several parts of the world is the emergence and spread of drug resistant Mycobacterium tuberculosis (MTB) strains. The better understanding of the actual global burden of drug resistant tuberculosis would feed into better implementing the End TB Strategy. In this article we summarize the current knowledge on the patterns of drug resistance tuberculosis cases in the Middle East countries. These countries are served by the Eastern Mediterranean Regional Office (EMRO), one out of six regional offices of World Health Organization. Middle East countries are characterized by geographic vicinity and population's interaction. However, they are dissimilar in several aspects such as economy and health infrastructures. Regarding economy, countries in this region are ranging from wealthy to very poor. Prevalence of tuberculosis and patterns drug resistance tuberculosis cases are also following variable trends within countries of this region. In almost all Middle East countries, there is under-reporting of drug-resistance tuberculosis cases. There are shortages in the infrastructures and facilities for detecting the pattern of drug-resistance tuberculosis. For instance, sixout of 14 countries have neither in-country capacity nor a linkage with a partner laboratory for second-line drug susceptibility testing and only 4 countries have registered site performing Xpert MTB/RIF.

Objective/background: Despite several studies on health system delay (HSD) among tuberculosis (TB) patients in Nigeria, no study has compared HSD in private and public health facilities. This study assessed the determinants of HSD in public and private health facilities offering the directly observed treatment, short course (DOTS). Methods: A descriptive cross-sectional study was conducted. A total of 470 new smear-positive TB patients aged 14 years and older were consecutively recruited between October 1, 2012, and December 31, 2012, from 34 (23 public and 11 private) DOTS facilities that offered treatment and microscopy services. Mann–Whitney U test and logistic regression were used to assess the determinants of HSD. Results: The median HSD was longer at public DOTS facilities (14 days; interquartile range [IQR] 10–21 days) than private DOTS facilities (12.5 days; IQR 10.0–14.0 days, p = .002). Age and human immunodeficiency virus status were determinants of HSD at the public DOTS facilities, whereas sex and income were determinants of HSD at the private DOTS facilities. TB patients who first visited a nonhospital facility were over four times more likely (odds ratio 4.12; 95% confidence interval 2.25–7.54) to have prolonged HSD than those who first visited the government hospital when they first developed the symptoms of TB after controlling for other factors in the model. Conclusion: Determinants of HSD at the public and private DOTS facilities vary. Strategies to reduce HSD at both public and private DOTS facilities in Lagos State, Nigeria, are urgently needed.

Objective/background: Collection of one spot and one morning sputum specimen is recommended for tuberculosis (TB) drug resistance surveys. This was a retrospective analysis of Mycobacterium tuberculosis cultures isolated from two spot sputum specimens collected from smear positive TB patients in a TB drug resistance survey. It was conducted to understand the value of a second specimen. Methods: A TB drug resistance survey was conducted in the state of Tamil Nadu, India, to estimate the prevalence of drug resistance among new sputum smear-positive (NSP) and previously treated (PT) patients diagnosed in Revised National Tuberculosis Control Program microscopy centers. A total of 2425 patients (1524 NSP and 901 PT cases) were enrolled in the study. From these patients, two spot sputum specimens (C and D) were collected within a period of 2 h. No preservative was added to sputum. The samples were transported at ambient conditions without cold storage to the central laboratory for culture of M. tuberculosis. Culture yield from each sample was computed and analyzed. Results: The proportion of cultures retrieved from C and D specimens among NSP cases (89.3% and 89.7%) and PT cases (90.8% and 90.3%) were similar. The culture grades of C and D samples were comparable (chi-square test, 3560.135; p<.001) and the agreement was moderate (kappa test, 0.454). Conclusion: The findings of the study reveal the adequacy of single spot sputum specimen from smear positive pulmonary TB patients for bacteriological examination in a quality-assured TB laboratory to determine precisely the level of drug resistance in a province of India.

Objective/background: The present study was aimed at detecting Mycobacterium bovis in artisanal cheese using real-time quantitative polymerase chain reaction. Methods: One hundred seven cheese samples (250 g) were purchased in 107 commercial establishments including neighborhood grocery stores, bakeries, and open-air markets from 19 municipalities of the state of Pernambuco, Brazil. Ten grams of each cheese sample were macerated with sterile saline solution in a sterile bag and DNA was extracted from 20 mg of the macerated material using the Wizard SV Genomic DNA Purification System. The quantitative polymerase chain reaction amplified a fragment corresponding to the region of difference 4 of M. bovis. Results: Of the 107 samples analyzed, three (2.8%) were positive for M. bovis and their identities were confirmed by sequencing. This is perhaps the first report of the presence of M. bovis in artisanal cheese in the state of Pernambuco, Brazil. Conclusion: The results of the present study highlight the need for improving sanitary measures during the production of artisanal cheese to prevent zoonotic tuberculosis in humans, resulting from the consumption of food contaminated with M. bovis.

Non-tuberculous mycobacteria are increasingly recognized as a cause of infection in both immunocompromised and immunocompetent hosts. Mycobacterium heraklionense is a recently described member of the Mycobacterium terrae complex. Herein we report a case of M. heraklionense chronic flexor tenosynovitis in the hand, managed with surgery and antibiotics.

Objective/background: Nontuberculous mycobacteria (NTM) are not known to be associated with fistula-in-ano. NTM was detected in three fistula-in-ano patients in our series. In this study, related data was reviewed to find the mycobacterial disease in patients in our database. Methods: In this study, 311 consecutive fistula-in-ano patients operated over 2 years were analyzed. The histopathology of anal fistula tract epithelial lining of every operated patient was analyzed and other tests (real-time-polymerase chain reaction [RT-PCR], GeneXpert, and mycobacterial culture) were conducted in patients with high index of suspicion of having mycobacterial disease. Results: Two patients had histopathological features suggestive of mycobacterial disease. Of these, one patient had NTM and the other had Mycobacterium tuberculosis (MTB) on RT-PCR. Four patients had normal histopathology features but tested positive on RT-PCR (2 each for NTM and MTB). Therefore, a total of six patients were tested for mycobacterial disease (3 each for NTM and MTB). Mycobacterium culture was performed in two patients (both NTM) but the result was negative. Five of six patients (NTM = 2, MTB = 3) presented with delayed recurrences after operation (6–18 months after complete healing). Conclusion: NTM can cause fistula-in-ano. It could be an undiagnosed contributory factor in fistula recurrence. Mycobacterial disease (both tuberculous and nontuberculous) may be associated with delayed recurrence of fistula. RT-PCR is highly sensitive and can differentiate between NTM and MTB. It should perhaps be performed in all recurrent and refractory cases.

Objective/background: Tuberculosis (TB) has had a recrudescence in the last few decades in Italy as a result of many factors, among which migration from countries where TB is endemic is one of them. In Sardinia, a major island of Italy, there was no knowledge of the mechanisms of transmission of TB in the immigrant subpopulation and the impact it may have on the native subpopulation and on the community as a whole. Therefore, a molecular epidemiological study was carried out to get a clearer picture of the number and genetic features of Mycobacterium tuberculosis strains isolated from immigrants and from natives in Sardinia. Methods: Two groups of clinical isolates of M. tuberculosis, one collected from immigrants and the other one from Sardinians, were analyzed in this study. The genotyping was executed through the variable number tandem repeat-mycobacterial interspersed repetitive units technique and a first-line antimycobacterial drug-susceptibility test was also carried out. Results: Thirty-six clinical isolates from immigrants and 25 from Sardinians were analyzed. Variable number tandem repeat-mycobacterial interspersed repetitive units technique showed that all of them belonged to different strains and there was a quite high allelic diversity among them. Moreover, data collected allowed the finding of, with a good approximation, the phylogenetic relations among the strains isolated and the best-known phylogenetic groups. Conclusion: The study pointed out that since every strain is different, there was no TB transmission in any of the subpopulations and between immigrants and natives. This showed that the presence of immigrants was not a risk factor for contracting TB in the community.

Objective/background: Nontuberculous mycobacteria (NTM) infection associated with pulmonary and extrapulmonary disease has been increasing globally. Despite an increase in incidence rate of NTM infection, its prevalence, species diversity, and circulation pattern in India is largely unknown. This study sought to investigate the overall burden and diversity of NTM among both pulmonary and extrapulmonary clinical isolates from a Northern Indian population. Methods: The study was conducted in the Department of Microbiology, from January 2013 to December 2015. A total of 4620 clinical samples were collected from patients suspected to have pulmonary and extrapulmonary tuberculosis. Preliminary diagnosis was performed using Ziehl–Neelsen staining followed by liquid culture in BacT/ALERT three-dimensional system. A total of 906 positive cultures obtained were differentiated as either NTM or Mycobacterium tuberculosis complex using a biochemical and MPT64 antigen test. Further identification of NTM species was confirmed with a line probe assay. Results: Out of 906 cultures isolates, 263 (29.0%) were confirmed as NTM and 643 (71.0%) were identified as Mycobacterium tuberculosis complex. A total of 79.4% of the NTM were recovered from pulmonary and 18.2% from extrapulmonary specimens. The diversity of NTM species was high (13 species) and predominated by Mycobacterium abscessus (31.3%) followed by Mycobacterium fortuitum (22%), Mycobacterium intracellulare (13.6%), Mycobacterium chelonae (9.1%), however, M. abscessus and M. fortuitum were the predominant species in both types of clinical isolates. Men (60.4%) and older patients aged greater than 55 years were the predominated risk group for NTM infection. Conclusion: The high prevalence and species diversity of NTM suggests the need for immediate and accurate characterization of NTM for proper treatment and management of patients.

Objective: To determine the performance of FDA vital staining method in detecting viability of acid fast bacilli in comparison with culture and also its correlation with conventional drug susceptibility testing results for isoniazid and rifampicin. Design: The study was conducted from Jan 2014 to June 2015. Sputum samples of patients taking either Cat I or Cat II anti-TB treatment were tested by Ziehl Neelsen and FDA staining, culture and susceptibility to rifampicin and isoniazid at the end of intensive phase. Results: Of the 100 ZN positive specimens, 74 were FDA positive of which 70 were reported positive by both the readers. All specimens having higher grades (2+ and 3+) by ZN were positive by FDA staining. 87.88% of 1+ and 45% of scanty smears were positive by FDA staining. MTB was isolated in 75 specimens of which 72 were positive by FDA. Two culture negative specimens were FDA positive. FDA staining had sensitivity and specificity of 96% and 92% respectively. 70.66% of the total culture isolates were MDRTB strains. 2.66% strains demonstrated monoresistance to each of INH and rifampicin. Conclusion: FDA microscopy can be used as a simple and rapid TB treatment monitoring tool in resource limited settings to identify those patients requiring immediate culture and DST test.

Objective/background: Detection of mutations in the quinolone resistance-determining region (QRDR) of the gyrA gene could determine resistance to fluoroquinolone antituberculosis drugs. The aim of this study was to detect mutations in QRDRs. Methods: From 184 clinical isolates of Mycobacterium tuberculosis, ofloxacin resistance was proven in 42 isolates using the proportion method. The molecular basis of resistance to ofloxacin were investigated by the determination of mutations in the QRDR region of the gyrA gene. Extracted DNA fragments of 194bp from the gyrA gene were amplified and an automatic DNA sequencer was used for the sequencing process. Results: Molecular genetic analysis of 42 resistant M. tuberculosis strains demonstrated that they belong to Principal Genetic Group (PGG) 1 in 19 cases (45.2±10.9%), to PGG2 in 15 cases (35.7±10.5%), and to PGG3 in eight cases (19.0±8.4%). Isolates from PGG1 were dominant among resistant isolates (p<.05). It was found that 24 (57%) resistant isolates carried mutations at codon 94 with five different amino acid changes: D94A (n = 11), D94G (n = 3), D94T (n = 4), D94A (n = 4), and D94Y (n = 2). The remaining 18 (43%) isolates had mutations in codon A90V (GCG → GTG) and S91P (TCG → CCG). Five isolates had two mutations in codons 90 and 94. There was no difference between mutations at these two codons in resistant isolates of the two countries (p<.001). There was no polymorphism observed in codon 95 in any of the ofloxacin-susceptible isolates. Conclusion: It was concluded that the determination of nucleotide sequences of QRDRs can be used as a molecular test for the rapid detection of ofloxacin resistance. Furthermore, frequencies in gyrA codons in Belarus and Iran were similar, therefore it is not of geographical concern for the two countries.

Objective/background: Most tuberculosis cases in children are primary infection, with difficult and imprecise diagnosis mainly based on the existence of mediastinal lymphadenopathy. Here, we investigated the characteristics of mediastinal lymphadenopathy in lung computed tomography (CT) scans of children with tuberculosis. Methods: This cross-sectional study was performed on 75 children with tuberculosis referred to Masih Daneshvari Hospital in Tehran, Iran, from 2009 to 2013. Their medical records were investigated, and CT-scan characteristics were extracted by a radiologist. Results: Mean±standard deviation age of cases was 11.2±4.6 years. CT-scan results indicated 94.7% of cases had lymphadenopathy, with lower paratracheal, upper paratracheal, hilar, and subcarinal forms observed in 81.7%, 69.1%, 53.5%, and 47.9% of cases as the most involved stations in lymph nodes, respectively. In 74.6% of patients with mediastinal lymphadenopathy, perilymph node fat inflammation (matting) was observed, with 52.11% exhibiting conglomeration. Bronchial pressure was observed in 4.23% of children with tuberculosis, and bilateral-, right-, and left-parenchymal involvement was observed in 42.7%, 25.3%, and 8% of these cases, respectively. Left- and right-pleural effusion and calcification was reported in 6.7%, 12%, and 5.6% of patients, respectively. Additionally, nearly 80% of patients exhibited mediastinal lymphadenopathy and lung-parenchyma involvement simultaneously. Lung-parenchyma involvement was significantly correlated with subcarinal (p<.001), hilar (p<.001), subaortic (p = .030), lower paratracheal (p = .037), and axillary (p = .006) stations. Conclusion: Situation of mediastinal lymphadenopathy and its synchronicity with lung-parenchyma involvement can help in differential diagnosis of pulmonary tuberculosis from other lung diseases.

Objective/background: Viral hepatitis, particularly hepatitis B virus (HBV) and hepatitis C virus (HCV), infections and tuberculosis (TB) are a global public health concern. Co-infection with HBV or HCV among TB patients may potentiate the risk of hepatotoxicity induced by anti-TB drugs. Hence, the aim of this study was to identify the prevalence of HBV and HCV among TB patients included in the Duhok National Tuberculosis Program (NTP). Methods: The Duhok NTP Center is a specialized institution in Duhok City, Iraq, concerned with management and follow-up of TB patients. A cross-sectional study was conducted at the center between June 2015 and May 2016. All documented TB patients were analyzed on the basis of socio-demographic and other characteristics. Thereafter, all patients underwent screening for hepatitis B surface antigen (HBsAg), anti-HCV, and anti-HIV using enzyme-linked immunosorbent assay (ELISA). The results obtained were analyzed by entering the data in binary format into a Microsoft Excel spreadsheet. A p value of <.05 was considered to be statistically significant. Results: Two-hundred fourteen documented TB patients were recruited in this study, with 127 (59.3%) males and 87 (40.7%) females. The mean age of the patients was 40.34 years (±20.29). Of the total number of patients, four cases (1.8%) were HBsAg-positive and one case (0.9%) was positive for anti-HCV. The variables significantly associated with HBV were history of surgical dental procedure [odds ratio (OR), 0.04; 95% confidence interval (CI), −0.01 to 0.04; p = .03], and nationality (OR, 13.67; 95% CI, 0.46–210.85; p = .007). Conclusion: The prevalence of HBV and HCV co-infection among TB patients in this study was low. This may be explained by the low rate of blood transfusion among the patients, the very low prevalence of HIV infections in Kurdistan, the negative history of injection drug use, and adherence to universal infection-control measures, including vaccination for HBV. Both history of dental intervention and belonging to a Syrian population were independent risk factors for HBV/TB co-infection.

Background: To estimate the prevalence of genital tuberculosis in women with idiopathic chronic pelvic pain on laparoscopy, correlate laparoscopic findings with microbiological and histological diagnosis of tuberculosis and assess the response to anti tubercular treatment (ATT) in these cases. Method: In a prospective cohort study, fifty women with idiopathic chronic pelvic pain were enrolled. Diagnostic laparoscopy was done in all women and fluid from pouch of Douglas and/or saline washings were sent for acid fast bacilli (AFB) smear, conventional and rapid culture and DNA polymerase chain reaction (PCR) analysis for diagnosis of genital TB. The results of these tests were analyzed and agreement with laparoscopy was assessed using Kappa statistics. Pain scores using visual analogue scale were compared before and after treatment. Results: Pelvic pathology was present in 44 (88%) women of idiopathic chronic pelvic pain, with a 34% prevalence rate of genital tuberculosis. Pelvic inflammation was associated with positive peritoneal fluid PCR (n = 4) and AFB culture (n = 3). Acid fast bacilli PCR had substantial agreement (kappa statistics = 0.716) with visual findings at laparoscopy. There was a significant reduction in pain scores after treatment. Conclusion: Genital tuberculosis contributes to one-third cases of chronic pelvic pain. Pelvic inflammation is an early feature of genital TB and peritoneal fluid PCR has the best co-relation with laparoscopic findings of genital tuberculosis.

Objective/background: Generating epidemiological data on multidrug-resistant tuberculosis (MDR-TB) is essential to assess the magnitude and trends of anti-TB drug resistance. This study determined the prevalence of MDR-TB among presumptive MDR cases referred to a TB referral laboratory in the Tigray region of Ethiopia. Methods: A retrospective cross-sectional study was conducted on 262 culture-positive presumptive MDR-TB samples submitted to the Tigray Regional Research Laboratory for MDR testing between January 2013 and August 2014. Relevant data were recorded using a structured recording format. Results: Out of 262 Mycobacterium tuberculosis isolates, 143 (54.6%) were MDR, 28 (10.7%) were resistant to rifampicin only, and 19 (7.3%) were resistant to isoniazid only. The prevalence of MDR-TB among newly infected cases was 66.7% (8/12) and that among previously treated cases was 54.1% (97/179). Of the variables tested, being a male was found to be associated with the development of MDR-TB (p = .003). Conclusion: More than half of the presumptive MDR cases referred to the Tigray Regional Research Laboratory were MDR. The prevalence was high in both newly infected and previously treated cases. Hence, re-enforcing the TB prevention methods, and strengthening the directly observed treatment short-course (DOTS) strategy and the capacity of laboratories to undertake drug susceptibility testing (DST) in the region are imperative in order to curb the emergence and transmission of MDR-TB.

Background: The mce4 operon is one of the four mce operons with eight genes ( yrbE4A , yrbE4B , mce4A, mce4B, mce4C, mce4D, mce4E and mce4F) of Mycobacterium tuberculosis. It expresses in the later phase of infection and imports cholesterol for long term survival of the bacilli. To cause latent infection, M. tuberculosis undergoes metabolic reprogramming of its genes to survive in the hostile environment like low availability of oxygen and nutrition depletion inside the host. Objective: To analyze real time expression profile of mce4 operon under various stress conditions. Methods: M. tuberculosis H37Rv was exposed to surface stress (0.1% SDS for 30 min and 90 min in late log and stationary phase of culture), hypoxia (5, 10, 15 and 20 days) and grown in the presence of either glycerol or cholesterol as sole source of carbon. The expression profile of genes of mce4 operon was analyzed by real time PCR. Results: Surface stress induced expression of mce4C and yrbE4B in late log phase on 30 min and 90 min exposure respectively. The SDS exposure for 30 min induced mce4C, mce4D and mce4F in stationary phase. All eight genes were induced significantly on 10th and 15th days of hypoxia and in the presence of cholesterol. Conclusion: Hypoxia and cholesterol are potent factors for the expression of mce4 operon of M. tuberculosis.

Objective/background: Tuberculosis (TB) is a major health problem. The aim of this study was to examine the pattern of TB in Aswan Chest Hospital, Aswan, Egypt. Methods: This cross-sectional study was carried out using medical records from the TB registry in Aswan Chest Hospital. The investigated variables included demographic characteristics, type of TB infection, and affected organs. All data were coded and statistically analyzed. Results: The average age of the 557 patients infected with TB was 40.31±18.87 years; 58.2% of the cases were men and 41.8% were women. In both sexes, the highest number of TB patients was from the reproductive age groups. During the 5-year study period, the highest percentage of cases were new cases and the highest frequency of cases was during 2011 and the lowest frequency was during 2015. Pulmonary TB cases showed a sharp decline; however, there was a decrease in extrapulmonary TB cases during 2012 and 2013, with a slight rise in 2014 and 2015. Of the pulmonary TB cases, 82.5% were smear-positive TB. Conclusion: There was a decline in the total number of TB cases across the studied years and the most studied cases were pulmonary smear-positive and new cases. Younger people represented a large percentage of reported cases.

Penile tuberculosis (TB) is an uncommon variety of genitourinary TB. It is either primary (via local spread) or secondary (spread of infection from other organs). We encountered a case of rapidly growing penile ulceration, resembling carcinoma. Biopsy revealed the classic picture of TB, which responded well to antitubercular treatment.

Osteoarticular tuberculosis is a rare type of tuberculosis. The spine is the most frequent location, while peripheral locations in the limbs are rare. We report a case of tuberculous osteoarthritis of the metatarsophalangeal joint of the first ray of the foot in a 48-year-old woman. The patient presented with painful swelling of the dorsum of the big toe, insidiously evolving for 6 months. Diagnosis was obtained with histological study after surgical biopsy. Antitubercular chemotherapy for 12 months promoted healing. Through this clinical case the authors describe the epidemiological, diagnostic features, and treatment of osteoarticular tuberculosis and discuss the causes of delayed diagnosis often encountered in these exceptional locations and differential diagnoses, gout in particular, for this particular case.

A variant of the protein tyrosine phosphatase nonreceptor type 22 (PTPN22) gene is known to be associated with susceptibility to autoimmune diseases and bacterial infections as it acts as an important regulator of T-cell activation. The objective of this study was to evaluate whether PTPN22-C1858T polymorphism is associated with the resistance to pulmonary tuberculosis (PTB). Single-nucleotide polymorphism of PTPN22-C1858T (rs2476601) was genotyped in 124 patients with PTB and 130 healthy controls from India using restriction fragment length polymorphism and direct sequencing of the amplified DNA. The frequencies of genotypes CC, CT, and TT were 100%, 0%, and 0%, respectively, in PTB; and 99.2%, 0.8% and 0%, respectively, in healthy control individuals. These values did not differ significantly between the patients and controls. The mutant allele C1858T was found to be a rare allele in Indian population.

Nontuberculous mycobacterial (NTM) adenitis of the head and neck region is well-described in healthy children, most commonly presenting under the age of 5 years. Extracervicofacial NTM adenitis is less common. We present a case of NTM inguinal adenitis in a 2-year-old girl, followed by a systematic review of the literature.

The sternal localization of bone and joint tuberculosis (TB) is rare, has an insidious clinical presentation, and usually affects young adults living in endemic areas. Mycobacterium africanum causes a relevant proportion of human TB in West Africa and in migrants from endemic countries. Here, we report two cases of sternal osteomyelitis due to M. africanum in migrants.

Genital tract tuberculosis is usually secondary to extragenital tuberculosis. The upper genital tract is usually involved; involvement of cervix and vulva is very uncommon. We present two such rare cases of vulval and cervical tuberculosis diagnosed on histopathology and treated with antitubercular chemotherapy.

Pericardial tuberculosis (TB) is rare, but has particularly severe complications and a high mortality rate when not treated. Prompt treatment of pericardial TB is important and can be life-saving. We report a 13-year-old girl with massive pericardial effusion and negative workup for TB, who was empirically treated with an excellent response.