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.

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.

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.

Determination of Lipoprotein Z-Specific IgA in Tuberculosis and Latent Tuberculosis Infection.

Tuberculosis (TB) remains one of the most severe infectious diseases. It is still of paramount importance to establish more accurate, rapid, and efficient diagnostic methods. Since infection with Mycobacterium tuberculosis (M. tb) is largely mediated through the respiratory tract, IgA responses against mycobacterial proteins are worthy of investigation for their potential clinical utility. In this study, the IgA response targeting lipoprotein Z (LppZ) was determined by using a homemade ELISA with plasma of TB patients (N = 125), LTBI individuals (N = 92), healthy controls (HCs) (N = 165), as well as TB patients undergoing anti-TB treatment (N = 9). In parallel the antigen-specific IFN-γ release from PBMCs triggered by LppZ and M. tb-specific ESAT-6 or CFP-10 was detected by using an ELISPOT assay. It was found that the LppZ-specific IgA level was dramatically higher in TB patients than in HCs (p < 0.0001). Compared to that before anti-TB treatment, the LppZ-specific IgA level decreased substantially after 2 months of anti-TB treatment (p = 0.0297) and remained at low levels until the end of the treatment. What is more, pulmonary TB patients exhibited significantly higher LppZ-specific IgA-values than extra-pulmonary TB patients (p = 0.0296). Interestingly, the LppZ-specific IgA-values were negatively correlated to the amounts of IFN-γ released in response to LppZ with statistical significance (r = -0.5806, p = 0.0002). LppZ-specific IgA level was also higher in LTBI individuals than in HCs (p < 0.0001). Additionally there were some PPD+ HC individuals with high LppZ-specific IgA levels but the potential of this assay for identifying leaky LTBI in PPD+ HCs needs to be further investigated through follow-up studies. The sensitivity of detecting TB solely with ESAT-6 or CFP-10-specific IFN-γ release was increased by including the LppZ-specific IgA results, respectively, from 86.11 to 100% and 88.89 to 100%; the sensitivity of screening for LTBI was increased from 80.36 to 83.93% and 57.14 to 69.64%, respectively. The higher LppZ-specific IgA responses in TB and LTBI populations than in controls indicated high immunoreactivity to LppZ upon M. tb infection. Although the assay was not efficient enough for independent application in sero-diagnosis, LppZ-specific IgA might become a complementary biomarker for the improvement of TB and LTBI screening.

Immunoglobulin G response to mammalian cell entry 1A (Mce1A) protein as biomarker of active tuberculosis.

Cell wall components are major determinants of virulence of Mycobacterium tuberculosis and they contribute to the induction of both humoral and cell-mediated immune response. The mammalian cell entry protein 1A (Mce1A), in the cell wall of M. tuberculosis, mediates entry of the pathogen into mammalian cells. Here, we examined serum immunoglobulin levels (IgA, IgM and total IgG) against Mce1A as a potential biomarker for diagnosis and monitoring tuberculosis (TB) treatment response. Serum samples of 39 pulmonary TB patients and 65 controls (15 healthy household contacts, 19 latently infected household contacts, 13 non-TB and 18 leprosy patients) were screened by ELISA. The median levels of all immunoglobulin classes were significantly higher in TB patients when compared with control groups. The positive test results for IgA, IgM and total IgG were 62, 54 and 82%, respectively. For comparison, routine sputum smear examination diagnosed only 26 (67%) of 39 TB cases. Sensitivities of IgA, IgM and IgG test were 59, 51.3 and 79.5%, respectively, while the specificities observed were 77.3, 83.3 and 84.4%, respectively. A significant decrease compared with baseline was also shown after TB treatment. These results suggest that circulating total IgG antibody to Mce1A could be a complementary tool to diagnosis pulmonary TB.

M. tuberculosis DNA detection in nasopharyngeal mucosa can precede tuberculosis development in contacts.

BACKGROUND: The nasopharynx is a known gateway for some mycobacterial species such as Mycobacterium bovis and M. leprae. M. tuberculosis can cross lymphoepithelial barriers in vitro, but its ability to colonise the nasopharyngeal mucosa in vivo has not been established. OBJECTIVE: To determine if M. tuberculosis can be transiently detected in nasopharyngeal mucosa of tuberculosis (TB) contacts as a preliminary step in the development of tuberculous infection. DESIGN: Exploratory study conducted among asymptomatic household contacts of pulmonary TB cases. A chest X-ray, QuantiFERON(®) TB-Gold or tuberculin skin test and a bilateral nasopharyngeal swab for Xpert(®) MTB/RIF and mycobacterial culture were performed at baseline and repeated 8-12 weeks later. RESULTS: Eighty-nine contacts were enrolled a median of 9 days after the diagnosis of the index case. At baseline, 29.9% were positive for latent tuberculous infection and one subject (1.1%) had a positive Xpert in the nasopharyngeal swab with a normal chest X-ray, negative QuantiFERON and negative induced sputum. After 12 weeks' follow-up, this subject developed a new cough and upper lobe infiltrates and M. tuberculosis grew in sputum. No other cases of active TB were detected at follow-up. CONCLUSION: The detection of M. tuberculosis DNA in the nasopharyngeal mucosa of contacts is an infrequent event that in this instance preceded the development of pulmonary TB. Its pathogenic role requires further investigation.

Diagnosis of tuberculosis based on the detection of a cocktail of mycobacterial antigen 85B, ESAT-6 and cord factor by immuno-PCR.

Attempts were made to enhance the sensitivity of immuno-PCR assay based on the detection of cocktail of mycobacterial antigen 85B (Rv1886c), ESAT-6 (Rv3875) and cord factor (trehalose 6,6'-dimycolate) in pulmonary and extrapulmonary TB patients. Detection of Ag85B was found to be superior to the detection of cocktail in TB patients.

Inoculation site leprosy in a tattoo as a paradoxical reaction following tuberculosis treatment.

We present a patient who developed inoculation site leprosy in a tattoo, which was confirmed by Mycobacterium leprae DNA sequencing of a polymerase chain reaction product from a skin biopsy. His leprosy became manifest as a paradoxical reaction only after 8 weeks of treatment for pulmonary tuberculosis.

Tuberculosis retreatment 'others' in comparison with classical retreatment cases; a retrospective cohort review.

BACKGROUND: Many of the countries in sub-Saharan Africa are still largely dependent on microscopy as the mainstay for diagnosis of tuberculosis (TB) including patients with previous history of TB treatment. The available guidance in management of TB retreatment cases is focused on bacteriologically confirmed TB retreatment cases leaving out those classified as retreatment 'others'. Retreatment 'others' refer to all TB cases who were previously treated but with unknown outcome of that previous treatment or who have returned to treatment with bacteriologically negative pulmonary or extra-pulmonary TB. This study was conducted in 11 regional referral hospitals (RRHs) serving high burden TB districts in Uganda to determine the profile and treatment success of TB retreatment 'others' in comparison with the classical retreatment cases. METHODS: A retrospective cohort review of routinely collected National TB and Leprosy Program (NTLP) facility data from 1 January to 31 December 2010. This study uses the term classical retreatment cases to refer to a combined group of bacteriologically confirmed relapse, return after failure and return after loss to follow-up cases as a distinct group from retreatment 'others'. Distribution of categorical characteristics were compared using Chi-squared test for difference between proportions. The log likelihood ratio test was used to assess the independent contribution of type of retreatment, human immunodeficiency virus (HIV) status, age group and sex to the models. RESULTS: Of the 6244 TB cases registered at the study sites, 733 (11.7%) were retreatment cases. Retreatment 'others' constituted 45.5% of retreatment cases. Co-infection with HIV was higher among retreatment 'others' (70.9%) than classical retreatment cases (53.5%). Treatment was successful in 410 (56.2%) retreatment cases. Retreatment 'others' were associated with reduced odds of success (AOR = 0.44, 95% CI 0.22,0.88) compared to classical cases. Lost to follow up was the commonest adverse outcome (38% of adverse outcomes) in all retreatment cases. Type of retreatment case, HIV status, and age were independently associated with treatment success. CONCLUSION: TB retreatment 'others' constitute a significant proportion of retreatment cases, with higher HIV prevalence and worse treatment success. There is need to review the diagnosis and management of retreatment 'others'.

Trend of childhood TB case notification in Lagos, Nigeria, 2011-2014.

BACKGROUND: Childhood tuberculosis (TB) has been neglected by national TB programs in sub-Saharan Africa because of the emphasis on adult smear-positive TB cases. About 80,000 HIV children die from TB, and over 550,000 childhood TB cases occur annually, representing 6% of the global TB burden, making TB an important cause of morbidity and mortality in children. Thus, this study assessed the trend of childhood TB cases notified in Lagos, Nigeria from 2011 to 2014. METHODS: Retrospective data review of childhood TB cases notified to the Lagos State TB and Leprosy Control Programme (LSTBLCP) between January 1, 2011 and December 31, 2014. RESULTS: A total of 2396 children were treated for all forms of TB representing 6.8% of the total 35,305 TB cases notified during the study period. This constituted 1102 (46%) males and 1294 (54%) females. There was a progressive increase in the proportion of children treated for TB from 495 (5.9%) in 2011, 539 (6.4%) in 2012, 682 (7.2%) in 2013 and 680 (7.6%) in 2014. Of the total childhood TB cases notified, 16.3-20% were new sputum pulmonary smear positive; 68.2-74.6% were new sputum pulmonary smear negative; while extra-pulmonary TB accounted for 6.7-10.6%. The case notification rate (CNR) of childhood TB per 100,000 increased from 13.4 in 2011, 14.3 in 2012, 17.7 in 2013 and 17.2 in 2014. CONCLUSION: There was an increase in the case notification rate of TB among children between 2011 and 2014. Efforts should be made to sustain this increasing trend.

Relative value of immunohistochemistry in detection of mycobacterial antigen in suspected cases of tuberculosis in tissue sections.

BACKGROUND: The diagnosis of tuberculosis (TB) depends on identification of the infecting organism. The diagnosis presents as a challenge due to its diverse clinical presentation and low yield of acid-fast bacilli (AFB) in tissue sections. AIM: The aim of the present study is immunohistochemical localization of tubercle bacilli or their components that persist in the granulomas, but have lost the property of staining with acid-fast stain, assess the advantage of immunostaining over conventional Ziehl-Neelsen (ZN) staining and further to study the staining pattern on immunohistochemistry (IHC). MATERIALS AND METHODS: The study population comprised 100 suspected cases of TB. Tissue sections from these were subjected to hematoxylin and eosin, ZN and IHC staining using polyclonal antibody to Mycobacterium tuberculosis followed by a comparative analysis of the results. Cases of lepromatous leprosy were used as a positive control. RESULTS: Acid-fast bacilli were identified by ZN stain in 23% of cases. IHC identified 72% cases. In the present study, IHC had higher sensitivity (95.56%) and negative predictive value (96.43%), but lower specificity (35.06%) and positive predictive value (30.56%) than ZN stain which had the sensitivity, specificity, positive predictive value and negative predictive values of 30.56%, 96.43%, 95.65% and 41.56% respectively. CONCLUSION: Immunohistochemistry is a simple and sensitive technique for localization of tubercle bacilli and their components on tissue sections. It can be easily incorporated in routine histopathology laboratory and serve as an efficient diagnostic adjunct to conventional ZN staining. This will help reduce the practice of prescribing empirical antitubercular treatment based on clinical suspicion alone.