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).

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.

[Description of duplicate records held on the Notifiable Diseases Information System, Brazil, 2008-2009]. / Descrição dos registros repetidos no Sistema de Informação de Agravos de Notificação, Brasil, 2008-2009.

OBJECTIVE: to describe the proportion of duplicate records held on the Brazilian Notifiable Diseases Information System, 2008-2009. METHODS: identification of duplicate records of dengue, leprosy, visceral leishmaniasis and cutaneous leishmaniasis, meningitis and tuberculosis was conducted using Reclink III(r); the proportion of duplicate records was calculated by geographical region, state and municipal population size categories. RESULTS: visceral leishmaniasis (VL) and meningitis had higher proportions of duplicate notification (5.3% and 3.6%, respectively) whilst leprosy had the lowest (0.7%); the states with highest repetitions were Rio Grande do Norte (VL 6.8% and leprosy 5.1%), Rio de Janeiro (tuberculosis 2.5% and meningitis 4.9%) and Goiás (dengue 2.0% and meningitis 7.2%). CONCLUSION: the Northeast region had the highest proportion of duplicate records for four of the six diseases analyzed; with the exception of dengue, percentage repetition was lower in municipalities with larger population size.

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.

[Quality control in the follow-up of pulmonary tuberculosis contacts in Camagüey, Cuba (2008-2011)]. / Control de la calidad del seguimiento de contactos de tuberculosis pulmonar en Camagüey, Cuba (2008-2011).

INTRODUCTION: Tuberculosis is currently a health problem in the municipality of Camagüey. PURPOSE: To assess compliance of guidelines issued by the National Program for the Control of Tuberculosis for the follow-up of contacts of positive cases of pulmonary tuberculosis in the municipality of Camagüey, Cuba. DESIGN: Descriptive cross-sectional design. METHODS: 1,242 contacts resulting from 39 reported cases of tuberculosis during the study period were included in the municipality of Camagüey between 2008 and 2011. Epidemiological surveys and records of reported cases were reviewed. The results were processed and analyzed in SPSS 17.0 statistical software and subsequently presented in tables and graphs. The results were summarized by percentages. The “follow-up form for contacts of pulmonary tuberculosis” was used as main guideline, which was created by experts of the Investigation and Monitoring of Tuberculosis, Acute Respiratory Infections, and Leprosy Workshop of Tropical Medicine Institute Pedro Kourí. RESULTS: Contacts that had an initial examination and four checkups had 96.2% of acceptability. Contacts that had fewer than four checkups showed less than 10% acceptability (3.3%). All contacts were assessed from the outset and were treated, in accordance with program guidelines. CONCLUSION: We found adequate compliance of National Program for the Control of the Tuberculosis guidelines for follow-up of contacts of positive cases of pulmonary tuberculosis. Compliance is greater in younger age groups and in the actively employed (25 to 54 years). This evaluation contributed to identify existing weaknesses in follow-up, such as low interest of this population to undergo appropriate testing in the National Program of Control of Tuberculosis.

INTRODUCCIÓN: La tuberculosis constituye en la actualidad un problema de salud en el municipio de Camagüey. OBJETIVO: Evaluar el cumplimiento de los lineamientos del Programa Nacional para el Control de la Tuberculosis para el seguimiento de los contactos de casos positivos de tuberculosis pulmonar en el municipio de Camagüey, Cuba. DISEÑO: Estudio descriptivo de corte transversal en el municipio de Camagüey entre los años 2008 y 2011. MÉTODOS: Se incluyeron 1.242 contactos resultantes de 39 casos de tuberculosis reportados en el período en estudio. Se revisaron las encuestas epidemiológicas y registros epidemiológicos de los casos reportados. Los resultados se procesaron y analizaron en el software estadístico SPSS 17.0, luego se representaron en tablas y gráficos. Se utilizó el porcentaje como medida de resumen. Se empleó como herramienta guía el “Formulario de seguimiento de los contactos de tuberculosis pulmonar” creado por expertos del grupo de investigación y vigilancia de tuberculosis, infecciones respiratorias agudas y lepra del Instituto de Medicina Tropical Pedro Kourí. RESULTADOS: Los contactos con examen inicial y cuatro controles completados presentaron 96,2% de aceptabilidad; en tanto, los contactos que tuvieron menos de cuatro controles reportaron resultados inferiores a 10% (3,3%). Todos los contactos fueron investigados desde el inicio y se les administró tratamiento de acuerdo a los lineamientos del programa. CONCLUSIÓN: Se observó que hay cumplimiento en los lineamientos del Programa Nacional de Control de la Tuberculosis para el seguimiento de los contactos de casos positivos de tuberculosis pulmonar. Éste es más riguroso en las edades tempranas y laboralmente activas (entre 25 y 54 años). La evaluación contribuyó a la identificación de las debilidades existentes como la poca sensibilidad de la población para someterse a los exámenes correspondientes en el Programa Nacional de Control de la Tuberculosis.

Control de la calidad del seguimiento de contactos de tuberculosis pulmonar en Camagüey, Cuba (2008-2011) / Quality control in the follow-up of pulmonary tuberculosis contacts in Camaguez, Cuba (2008-2011)

Introducción La tuberculosis constituye en la actualidad un problema de salud en el municipio de Camagüey. ObjetivoEvaluar el cumplimiento de los lineamientos del Programa Nacional para el Control de la Tuberculosis para el seguimiento de los contactos de casos positivos de tuberculosis pulmonar en el municipio de Camagüey, Cuba. DiseñoEstudio descriptivo de corte transversal en el municipio de Camagüey entre los años 2008 y 2011. Métodos Se incluyeron 1.242 contactos resultantes de 39 casos de tuberculosis reportados en el período en estudio. Se revisaron las encuestas epidemiológicas y registros epidemiológicos de los casos reportados. Los resultados se procesaron y analizaron en el software estadístico SPSS 17.0, luego se representaron en tablas y gráficos. Se utilizó el porcentaje como medida de resumen. Se empleó como herramienta guía el “Formulario de seguimiento de los contactos de tuberculosis pulmonar” creado por expertos del grupo de investigación y vigilancia de tuberculosis, infecciones respiratorias agudas y lepra del Instituto de Medicina Tropical Pedro Kourí. Resultados Los contactos con examen inicial y cuatro controles completados presentaron 96,2 por ciento de aceptabilidad; en tanto, los contactos que tuvieron menos de cuatro controles reportaron resultados inferiores a 10 por ciento (3,3 por ciento). Todos los contactos fueron investigados desde el inicio y se les administró tratamiento de acuerdo a los lineamientos del programa.Conclusión Se observó que hay cumplimiento en los lineamientos del Programa Nacional de Control de la Tuberculosis para el seguimiento de los contactos de casos positivos de tuberculosis pulmonar. Éste es más riguroso en las edades tempranas y laboralmente activas (entre 25 y 54 años). La evaluación contribuyó a la identificación de las debilidades existentes como la poca sensibilidad de la población para someterse a los exámenes correspondientes en el Programa Nacional de Control de la Tuberculosis.

Introduction Tuberculosis is currently a health problem in the municipality of Camagüey. Purpose To assess compliance of guidelines issued by the National Program for the Control of Tuberculosis for the follow-up of contacts of positive cases of pulmonary tuberculosis in the municipality of Camagüey, Cuba. Design Descriptive cross-sectional design. Methods1,242 contacts resulting from 39 reported cases of tuberculosis during the study period were included in the municipality of Camagüey between 2008 and 2011. Epidemiological surveys and records of reported cases were reviewed. The results were processed and analyzed in SPSS 17.0 statistical software and subsequently presented in tables and graphs. The results were summarized by percentages. The “Follow-up form for contacts of pulmonary tuberculosis” was used as main guideline, which was created by experts of the Investigation and Monitoring of Tuberculosis, Acute Respiratory Infections, and Leprosy Workshop of Tropical Medicine Institute Pedro Kourí. Results Contacts that had an initial examination and four checkups had 96.2 percent of acceptability. Contacts that had fewer than four checkups showed less than 10 percent acceptability (3.3 percent). All contacts were assessed from the outset and were treated, in accordance with program guidelines. Conclusion We found adequate compliance of National Program for the Control of the Tuberculosis guidelines for follow-up of contacts of positive cases of pulmonary tuberculosis. Compliance is greater in younger age groups and in the actively employed (25 to 54 years). This evaluation contributed to identify existing weaknesses in follow-up, such as low interest of this population to undergo appropriate testing in the National Program of Control of Tuberculosis.

Cenário atual da tuberculose / Current scenario of tuberculosis

Mesmo após 133 anos desde a descoberta do Mycobacterium tuberculosis, a tuberculose continua ser uma das principais causas de morte por doenças infecciosas no mundo, principalmente em países em desenvolvimento.O objetivo deste estudo foi mostrar aspectos relevantes da doença visando uma atualização literária e a busca de um olhar mais atento à problemática da tuberculose no contexto atual. Foram utilizados 130 artigos advindos das bases LILACS, MEDLINE/PUBMED, SCielo, Paho, Biblioteca Cochrane, WHOLIS, IBECS e Scopus, com as principais palavras-chaves selecionadas em terminologia em saúde encontradas no DECS. As espécies pertencentes ao Complexo M. tuberculosis compartilham cerca de 99% de identidade do DNA,com sequências altamente conservadas, mas diferem na distribuição geográfica, patogenicidade e hospedeiros. O mecanismo de resistência clinicamente significativo para rifampicina é uma mutação do gene rpoB, que codifica o alvo desse antibiótico. Há grandes avanços no diagnóstico da TB, com novos instrumentos de biologia molecular e testes rápidos, mas ainda não substituem os métodos clássicos bacteriológicos, apesar de suas conhecidas limitações. Atualmente, a associação de métodos moleculares, principalmente aqueles baseados em reações da PCR tem proporcionado grande impulso nos estudos da epidemiologia molecular do MT. Embora haja uma diminuição do número de casos no mundo, dentre os desafios da doença estão a necessidade de pesquisas na área, envolvimento político para solucionar as questões sociais atribuídas à TB, treinamento permanente dos profissionais e monitoramento de vigilância dos casos para eliminar a doença no cenário mundial.

Even 133 years after the discovery of Mycobacterium tuberculosis, tuberculosis continues to be one of the main causes of death due to infectious diseases worldwide, especially in developing countries. The objective of this study was, after a survey of recent publications, to show issues relevant to the disease and to takea closer look at the tuberculosis problem in the current context. A total of 130 articles were found in the LILACS, MEDLINE/PubMed, SciELO, Paho, Cochrane Library, WHOLIS, IBECS and Scopus databases using the main keywords selected from health terminology of MeSH. Species belonging to the M. tuberculosis complex have highly conserved sequences and share about 99% DNA identity, but differ in their geographic distribution, pathogenicityand host. The clinically significant mechanismof rifampicin resistance is due to a mutation of the rpoB gene which encodes the target of the antibiotic. Great advances in the diagnosis of tuberculosis have occurred, with new molecular biology tools and rapid tests, but without replacing classical bacteriological methods, despite their known limitations. Recently, the association of molecular methods, especially based on PCR, has provided great impetus in molecular epidemiology studies of M. tuberculosis. Although the number of cases in the world has decreased, among the challenges are the need for further research, political involvement to solve social issues linked to tuberculosis, permanent training and the surveillance of cases in order to eliminate the disease on the world stage.

Association of pulmonary tuberculosis and dermatological conditions among patients of a rural medical college hospital.

INTRODUCTION: Pulmonary tuberculosis (PTB) affects a significant proportion of the population. There are many contributory aetiological factors common to tuberculosis (TB) and dermatological conditions. AIM: To study the spectrum of concurrent skin conditions in patients with PTB and to compare with patients having other diseases. METHODS: All patients with PTB admitted to our Institute during the period of the study were included in the study. A comparable number of patients admitted in other departments constituted the control group. All patients were screened for skin diseases. RESULTS: There were 498 patients in each group, matched for age and gender. There were 126 patients with skin conditions in the study group as against 60 patients in the control group. Pityriasis versicolor was the commonest skin condition in both the groups. Whereas acniform eruptions and pruritis were more common in the control group. Pityriasis versicolor, herpes zoster, erythema nodosum and leprosy were significantly more frequent among patients. CONCLUSION: There is a high frequency of concurrent skin diseases in patient with PTB that should be managed along with it.

Childhood tuberculosis in household contacts of newly diagnosed TB patients.

INTRODUCTION: Childhood tuberculosis (TB), although estimated to account for a major proportion of the global TB disease burden, has a lower public health priority. Reliable research and surveillance data on childhood TB is limited in most regions of the world. This study was conducted to assess the burden of childhood TB among the household contacts of new TB patients in Karachi, Pakistan. METHODS: A retrospective analysis of children (<15 years) who were household contacts of new adult TB patients presenting to Marie Adelaide Leprosy Center (MALC) clinics in Karachi during the period of 2008 to 2010 was conducted. RESULTS: Of the household children contacts (n = 6613) screened, 317 were suspected and 121(1.8%) diagnosed with TB. These included 89 (73.6%) with pulmonary and 32 (26.4%) with extra-pulmonary disease. Smear positivity rate in pulmonary cases was 32.6%. Mean age of children diagnosed with TB was 11.7 (± 2.8) years. Within the child-contacts screened, disease was found to be significantly higher among females (2.3%) in comparison to males (1.2%) (p-value <0.01). The commonest relationship of source cases to diagnosed children was the mother (n = 51, 42.1%). The source case was a female for 66.1% (n = 76) of the children. CONCLUSION: A smear positivity rate of 32.6% amongst pulmonary cases suggests their potential to spread disease and emphasizes a need to review the contribution of children in transmission of TB within communities. Greater vulnerability of the female child and considerable role of mother in disease transmission highlights a need to increase focus on females in TB control programs in Pakistan.

Evaluation of a simplified IS6110 PCR for the rapid diagnosis of Mycobacterium tuberculosis in an area with high tuberculosis incidence.

PURPOSE: To assess the diagnostic yield of a simplified IS6110-PCR in an area with high tuberculosis incidence. METHODS: Pulmonary (218) and extrapulmonary (121) samples were collected from 236 patients including smearpositive leprosy patients. All samples were processed to detect acidfast bacilli by microscopy, culture on solid media and PCR. To remove PCR inhibitors, three washing steps of the decontaminated pellet were included before mycobacterial cell lysis by heat treatment. No detergents, enzymes, or chelating agents were used. From the 339 samples, 34 were selected basing on their large volume and were tested by the commercial kit GenoType Mycobacteria Direct (GTMD) (VER 4, Hain Lifescience, Germany) in addition to the tests cited above. RESULTS: The overall sensitivity and specificity of PCR were 93.8 and 98.6% for pulmonary samples, 63.6 and 100% for extrapulmonary samples, respectively. The assay detected MTC in 94.2% of smear positive samples with a positive predictive value of 100%. No inhibition was found among seven samples that were PCR negative but bacteriological confirmed as containing Mycobacterium tuberculosis. No false positive result occurred with samples from leprosy patients. The sensitivities for PCR and GTMD were 81.8 and 75%, respectively. CONCLUSION: PCR could efficiently complement conventional bacteriological tools for the rapid diagnosis of tuberculosis but cannot replace them.

NRAMP1/SLC11A1 gene polymorphisms and host susceptibility to Mycobacterium tuberculosis and M. leprae in South Sulawesi, Indonesia.

Genetic host factor may play an important role in controlling mycobacterial infections such as tuberculosis and leprosy. Natural resistance associated macrophage protein1 (Nramp1, alias Slc11a1) gene has been suggested to an associated gene of the host susceptibility to mycobacterium infection. To determine the association of Nramp1/Slc11a1 with tuberculosis and leprosy, we analyzed using polymerase chain reaction restriction fragment length polymorphisms three variants (D543N, 3'UTR and INT4) of Nramp1/Slc11a1 gene in 58 tuberculosis patients (mean age, 34.0 +/- 13.1), 42 leprosy patients (mean age, 35.0 +/- 14.3) and 198 healthy controls (mean age, 32.0 +/- 12.9) from South Sulawesi, Indonesia. We observed an association of INT4 polymorphism with paucibacillary type of leprosy (p = 0.032, 1df, OR = 2.975, CI = 1.057-8.373), but not to multibacillary type (p = 0.173, 1df, OR = 2.248, CI = 0.682-7.404). No significant association was found in the three variants with tuberculosis in this population.

Delay in tuberculosis case detection in Pwani region, Tanzania. A cross sectional study.

BACKGROUND: Delay in Tuberculosis (TB) case detection may worsen the disease and increase TB transmission. It is also a challenge to the National TB and Leprosy control Program (NTLP). METHODS: We conducted a cross sectional study in four out of six districts in Pwani region to estimate the extent and factors responsible for delay in TB case detection in Pwani region. Delays were divided into patient, health facility and total delay. RESULTS: We enrolled a total of 226 smear positive TB patients. Out of 226 patient's results were available for 206. The majority (66.5%) of the patients were males. Mean age for males and females were 37.3 and 33.7 years respectively. Mean (SD) total delay was 125.5 (98.5) days (median 90). Out of 206 patients, 79 (38.35%) delayed to seek TB health care. Health facility delay was observed among 121 (58.7%) patients.Risk factors for delay was poor knowledge that chest pain may be a TB symptom (OR = 2.9; 95%CI 1.20- 7.03) and the belief that TB is always associated with HIV/AIDS (OR = 2.7; 95%CI 1.39-5.23). Risk for delay was low among patients who first presented to a government health facility (OR = 0.3; 95%CI 0.12- 0.71) and those presenting with chest pain (OR = 0.2; 95%CI 0.10-0.61). CONCLUSION: There is a considerable delay in TB case detection in Pwani mainly contributed by patients. Risk factors for delay include misconception about TB/HIV and poor knowledge of TB symptoms.

What has Karonga taught us? Tuberculosis studied over three decades.

This paper summarises tuberculosis (TB) research over almost 30 years in Karonga District, northern Malawi, an area typical of much of rural Africa. The dominant factor has been the human immunodeficiency virus (HIV), which arrived in the district about 1980, leading to an increase in TB incidence to a peak of approximately 65 smear-positive pulmonary cases per 100000 population in 2000. Tuberculin surveys indicate annual risks of Mycobacterium tuberculosis infection of approximately 1%; thus, most of the population is uninfected and at risk of primary infection and disease. Molecular epidemiological studies demonstrate that about two thirds of TB arises from recent infection, but recognisable recent contact is responsible for only about 10% of disease. By 2001, 57% of TB was directly attributable to HIV, implying that it would have declined were it not for HIV. HIV infection increases the risk of TB most among young adults, and greatly increases the risk of recurrence from new infection after treatment. Mortality rates in the HIV-infected are high, but there is no association of HIV with drug resistance. Other risk factors with relatively smaller effects include age and sex, contact, several genetic polymorphisms and area. Neither one nor two doses of the bacille Calmette-Guérin (BCG) vaccine provides protection against adult pulmonary TB, despite protecting against leprosy. Skin test surveys, cohort studies and comparative immunological studies with the UK suggest that exposure to environmental mycobacteria provides some protection against TB and that BCG's failure is attributable partly to this widespread heterologous exposure masking effects of the vaccine. Drug resistance has remained constant (<10%) over more than 20 years. Immunotherapy with M. vaccae provided no benefits, but treatment of HIV-positive patients with cotrimoxazole reduced mortality. The Karonga programme illustrates the value of long-term population-based studies to investigate the natural history of TB and to influence TB control policy. Current studies focus on immunological markers of infection, disease and protection, and on elucidating the impact of antiretroviral treatment on TB incidence at population level.

Potential of Mw as a prophylactic vaccine against pulmonary tuberculosis.

Mycobacterium w (Mw), is a cultivable, non-pathogenic mycobacterium and has been tried extensively as an immunomodulator in leprosy. This has been found to be safe and has shown beneficial immunoprophylactic effect in population based, double blind placebo controlled trials in North India. These effects were also observed in the vaccine trials in South India. Keeping in view these beneficial effects and its earlier reported protective effect against tuberculosis in animals, its protective efficacy was evaluated in a rural population of about 28,948 people belonging to 272 villages in Ghatampur, Kanpur (India). The population was vaccinated with two doses (1st dose of 1x10(9) heat killed organisms followed 6 months later with a 2nd dose of 5x10(8) organisms) of Mw 10-13 years ago originally to investigate its effect against leprosy. The vaccine/placebo was given to healthy contacts of leprosy patients who had no evidence of suffering from tuberculosis. Incidence and prevalence of pulmonary tuberculosis in the present study was assessed in a blind manner by an active field survey and also retrospectively by history of anti tuberculosis treatment received by the patient in the intervening period (since vaccination), which was also corroborated by scrutinizing the medical records. Diagnosis was confirmed by standard clinical and bacteriological criteria. A total of 69 patients were diagnosed to be suffering from pulmonary tuberculosis during the survey which included 17 new sputum smear positive cases and 52 previously partially treated but still active pulmonary tuberculosis cases. The difference in the new sputum positive cases between the vaccinated (5/17) and placebo groups (12/17) was significant at 5% level of significance for 1 tailed test (Z>1.64). As 75% (52/69) of the cases had been diagnosed as suffering from pulmonary tuberculosis but had not taken adequate therapy all the cases diagnosed during the intervening period were recorded and re-analysis done. The differences are more significant at 1% level of significance for 1 tail test (Z>2.59) when all cases were analysed as a group. A small proportion 12.85% (total number=3036) of the contacts in the study population had BCG scars. On analysis of results on protection against tuberculosis in this group, BCG did provide protection against tuberculosis (p<0.01). In the placebo group the prevalence of tuberculosis was 1.11% which reduced to 0.70% for those who received Mw vaccine (p<0.01) which further decreased to 0.53% in those who had BCG scars and received Mw. These results thus provide evidence suggesting protective efficacy of Mw against pulmonary tuberculosis and that Mw merits investigation in future prospective immunoprophylactic trials along with other candidates for protection against pulmonary tuberculosis.

Humoral response to Mycobacterium tuberculosis antigens in patients with tuberculosis in the Gambia.

OBJECTIVE: To determine and compare the sensitivity and specificity of four common mycobacterial antigens with three RD-1 region antigens in the serological diagnosis of active pulmonary tuberculosis (PTB) in the Gambia. DESIGN: Serum from 300 Gambians (100 with active PTB, 100 of their household contacts, and 100 community controls) was tested using an ELISA method to detect antibodies to seven mycobacterial antigens (three encoded in the RD-1 region [ESAT-6, CFP-10 and Rv3871] and four common [38 kDa, GLU-S, 19 kDa and 14 kDa]). Individuals with active TB were recruited from one of the National Leprosy and TB Control Program clinics in the western region of the Gambia, and neighborhood controls were an age-matched individual living within five houses of the case. RESULTS: The sensitivity of the RD-1 antigens ranged from 34% to 67%, while specificity ranged from 51% to 71%. The sensitivity of the common antigens ranged from 24% to 75% and specificity from 26% to 75%. CONCLUSION: In countries with high rates of TB, such as the Gambia, the clinical utility of serological testing to diagnose active TB remains limited, even with newer antigens encoded in the RD-1 region of Mycobacterium tuberculosis.

Impact of scarcity of automobile fuel on attendance at a referral centre for tuberculosis in Nigeria.

BACKGROUND: Tuberculosis in its pulmonary and extra-pulmonary form is still a common finding in the developing world. This study was to investigate the impact of a period of scarcity of automobile fuel in the Niger-Delta area of Nigeria on attendance at a Tuberculosis Referral Centre in Igbogene, Yenagoa, Bayelsa State. METHODS: Data was collected on attendance before, during and after the scarcity. This Tuberculosis and Leprosy Control Centre is run by a German non-governmental organization. (NGO), and the State's Ministry of Health. No user fee is charged. RESULTS: During the period of scarcity of automobile fuel, the total 12-months attendance of males decreased to 25.1% of that before the advent of scarcity. Attendance rose in the post-scarcity period, but reached only 78.5% of the pre-scarcity level. For females, the 12 months attendance during the scarcity period reduced to 75.3% of the pre-scarcity level. The 12-months attendance by females rose in the post-scarcity period to 109.2% above the pre-scarcity level. There was no evidence of an increase in attendance over the course of the period of automobile fuel scarcity among either males or females. CONCLUSION: The scarcity of automobile fuel which usually translated to an increase in cost of transportation probably increased the number of untreated tuberculosis patients in the population with potential serious long term health implications. The provision of vehicles as well as facility for storage of automobile fuel to this referral Centre by either the NGO or the Ministry of Health is suggested. This would allow the Centre carry out domiciliary service to these patients.