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PubMed2002

Molecular epidemiology and drug resistance of Mycobacterium tuberculosis isolates from Ethiopian pulmonary tuberculosis patients with and without human immunodeficiency virus infection.

We have analyzed the molecular epidemiology and drug resistance of 121 Mycobacterium tuberculosis isolates from consecutive patients with culture-positive pulmonary tuberculosis attending a university hospital outpatient department in Addis Ababa, Ethiopia. Restriction fragment length polymorphism analysis and spoligotyping were used to analyze the DNA fingerprinting patterns. Fifty-one (41.2%) of the isolates were found in 13 clusters with two or more identical DNA patterns. Two such clusters contained 49.0% of all clustered isolates. In a multivariate logistic regression model, human immunodeficiency virus (HIV)-positive serostatus was significantly associated with clustering of isolates for patients of both sexes (odds ratio [OR], 2.55; 95% confidence interval [CI], 1.17 to 5.80). There was a trend toward increased clustering of isolates from tuberculous women residing in Addis Ababa (OR, 2.10; 95% CI, 0.85 to 5.25). In total, 17 of 121 isolates (14.0%) were resistant to one or more of the antituberculosis drugs isoniazid (8.3%), streptomycin (7.4%), rifampin (2.5%), and ethambutol (1.7%). The high rate of drug-resistant isolates (29.6%) coincided with the peak prevalence of HIV infection (77.8%) in patients 35 to 44 years old. The majority (62.5%) of resistant isolates in this group were found within clusters. The simultaneous accumulation of certain bacterial clones in a patient population likely reflects recent transmission. Hence, we conclude that tuberculosis is commonly caused by recent infection with M. tuberculosis in HIV-positive Ethiopian patients. Furthermore, with the rapidly increasing prevalence of HIV infection in Ethiopia, the burden of tuberculosis, including drug-resistant tuberculosis, is likely to increase. Strengthening of classical tuberculosis control measures by promoting active case finding among HIV-positive adults with tuberculosis is warranted to reduce rates of transmission.

Adolescent↗

PubMed2002

Simple and rapid differentiation of Mycobacterium tuberculosis H37Ra from M. tuberculosis clinical isolates through two cytochemical tests using neutral red and nile blue stains.

The attenuated Mycobacterium tuberculosis strain H37Ra is one of the most commonly used controls for M. tuberculosis identification in the clinical laboratory and is a source of false-positive results for M. tuberculosis as a consequence of cross-contamination. Therefore, the ability to discriminate between H37Ra and real clinical isolates has important public health implications. To date, differentiation of H37Ra from M. tuberculosis clinical isolates is possible only by IS6110 genotyping and spoligotyping. In the 1950s, some authors reported that the virulent strain H37Rv and M. tuberculosis clinical isolates were able to fix basic dyes in their anionic forms, while H37Ra was not. We have studied the different techniques described for M. tuberculosis cytochemical staining and have chosen the best of these, introducing certain modifications in order to increase their discriminative power and reproducibility. We describe cytochemical staining of M. tuberculosis cells with neutral red and Nile blue, which differentiates H37Ra from virulent strains. This method could be used as an easy laboratory tool for distinguishing between H37Ra and real M. tuberculosis clinical isolates.

Bacterial Typing Techniques↗

PubMed2003

Genetic biodiversity of Mycobacterium tuberculosis complex strains from patients with pulmonary tuberculosis in Cameroon.

We analyzed DNA polymorphisms in 455 Mycobacterium tuberculosis complex isolates from 455 patients to evaluate the biodiversity of tubercle bacilli in Ouest province, Cameroon. The phenotypic and genotypic identification methods gave concordant results for 99.5% of M. tuberculosis isolates (413 strains) and for 90% of Mycobacterium africanum isolates (41 strains). Mycobacterium bovis was isolated from only one patient. Analysis of regions of difference (RD4, RD9, and RD10) proved to be an accurate and rapid method of distinguishing between unusual members of the M. tuberculosis complex. Whereas M. africanum strains were the etiologic agent of tuberculosis in 56% of cases 3 decades ago, our results showed that these strains now account for just 9% of cases of tuberculosis. We identified a group of closely genetically related M. tuberculosis strains that are currently responsible for >40% of smear-positive pulmonary tuberculosis cases in this region of Cameroon. These strains shared a spoligotype lacking spacers 23, 24, and 25 and had highly related IS6110 ligation-mediated (LM) PCR patterns. They were designated the "Cameroon family." We did not find any significant association between tuberculosis-causing species or strain families and patient characteristics (sex, age, and human immunodeficiency virus status). A comparison of the spoligotypes of the Cameroon strains with an international spoligotype database (SpolDB3) containing 11,708 patterns from >90 countries, showed that the predominant spoligotype in Cameroon was limited to West African countries (Benin, Senegal, and Ivory Coast) and to the Caribbean area.

Cameroon↗

PubMed2005

Distribution of insertion- and deletion-associated genetic polymorphisms among four Mycobacterium tuberculosis phospholipase C genes and associations with extrathoracic tuberculosis: a population-based study.

The Mycobacterium tuberculosis genome contains four phospholipase C (PLC)-encoding genes, designated plcA, plcB, plcC, and plcD, respectively. Each of the four genes contributes to the overall PLC activity of M. tuberculosis. PLC is hypothesized to contribute to M. tuberculosis virulence. Infection of M. tuberculosis strains carrying a truncated plcD gene is associated with the occurrence of extrathoracic tuberculosis. However, whether the other three plc genes are also associated with extrathoracic tuberculosis remains to be assessed. We investigated the insertion- and deletion-associated genetic diversity in all four plc genes among 682 epidemiologically and clinically well-characterized M. tuberculosis clinical isolates using PCR, DNA sequencing, and Southern hybridization. Two hundred sixty-six (39%) of the 682 isolates had an interruption in at least one of the four plc genes, most often associated with an IS6110 insertion. The plcD gene interruption was the most common: it was observed in 233 (34%) of the isolates, compared to 4.7%, 4.1%, and 5.9% for plcA, plcB, and plcC gene interruption, respectively. The association between the plc gene genotypes and disease presentation was adjusted for clustering using generalized estimating equations for both bivariate and multivariate analyses. After controlling for the genotypes of the plcABC genes and the host-related risk factors, interruption in the plcD gene remained significantly associated with extrathoracic tuberculosis (odds ratio, 3.27; 95% confidence interval, 1.32 to 8.14). The data suggest that the plcD gene might play a more important role in the pathogenesis of thoracic TB than it does in the pathogenesis of extrathoracic TB.

Bacterial Proteins↗

PubMed1992

Clinical value of the measurement of Mycobacterium tuberculosis specific antibody in pulmonary tuberculosis.

BACKGROUND: A serological test that could help to diagnose tuberculosis, especially smear negative disease, would contribute to patient management. METHODS: Levels of antibody to distinct antigens of Mycobacterium tuberculosis were assessed for their value in the diagnosis and management of pulmonary tuberculosis. Serum was taken from 52 patients who were smear positive, from 27 patients who were smear negative but with evidence of active tuberculosis (sputum culture positive in 16, response to antituberculosis chemotherapy in 11), from 11 patients with old healed tuberculosis (pre-antibiotic era), and from 39 healthy subjects vaccinated with BCG. RESULTS: In smear positive tuberculosis an enzyme linked immunosorbent assay using a single 38 kDa antigen gave a diagnostic sensitivity of 80% with a 100% specificity. In smear negative pulmonary tuberculosis, however, combination of the 19 kDa antigen, lipoarabinomannan (ML 34 epitope), and hsp 65 (TB 78 epitope) was needed to achieve a sensitivity of 64% with a specificity of 95%. Recurrent and extensive radiographic disease with a poor prognosis was associated with high anti-38 kDa and low anti-14 kDa antibody levels in patients with active disease. Patients with less pulmonary cavitation had high anti-19 kDa titres. Bacteriological relapse during treatment was indicated by a rise in anti-14 kDa (TB68 epitope) antibodies. Four patients with non-tuberculous mycobacterial infection showed no anti-38 kDa antibody. CONCLUSION: Antigen or epitope specific serology may help in the diagnosis, assessment of prognosis, and monitoring of chemotherapy in patients with pulmonary tuberculosis.

Antibodies, Bacterial↗

PubMed2006

Molecular characterisation of Mycobacterium tuberculosis isolates in the First National Survey of Anti-tuberculosis Drug Resistance from Venezuela.

BACKGROUND: Molecular typing of Mycobacterium tuberculosis strains has become a valuable tool in the epidemiology of tuberculosis (TB) by allowing detection of outbreaks, tracking of epidemics, identification of genotypes and transmission events among patients who would have remained undetected by conventional contact investigation. This is the first genetic biodiversity study of M. tuberculosis in Venezuela. Thus, we investigated the genetic patterns of strains isolated in the first survey of anti-tuberculosis drug-resistance realised as part of the Global Project of Anti-tuberculosis Drug Resistance Surveillance (WHO/IUATLD). RESULTS: Clinical isolates (670/873) were genotyped by spoligotyping. The results were compared with the international spoligotyping database (SpolDB4). Multidrug resistant (MDR) strains (14/18) were also analysed by IS6110-RFLP assays, and resistance to isoniazid and rifampicin was characterised. Spoligotyping grouped 82% (548/670) of the strains into 59 clusters. Twenty new spoligotypes (SITs) specific to Venezuela were identified. Eight new inter-regional clusters were created. The Beijing genotype was not found. The genetic network shows that the Latin American and Mediterranean family constitutes the backbone of the genetic TB population-structure in Venezuela, responsible of >60% of total TB cases studied. MDR was 0.5% in never treated patients and 13.5% in previously treated patients. Mutations in rpoB gene and katG genes were detected in 64% and 43% of the MDR strains, respectively. Two clusters were found to be identical by the four different analysis methods, presumably representing cases of recent transmission of MDR tuberculosis. CONCLUSION: This study gives a first overview of the M. tuberculosis strains circulating in Venezuela during the first survey of anti-tuberculosis drug-resistance. It may aid in the creation of a national database that will be a valuable support for further studies.

Antitubercular Agents↗

PubMed1992

Detection of Mycobacterium tuberculosis in clinical samples from patients with tuberculosis or other pulmonary diseases by polymerase chain reaction.

Polymerase chain reaction (PCR) using primers targeting the IS6110 repetitive sequence was employed to detect Mycobacterium tuberculosis in 228 samples from patients with tuberculosis or other pulmonary diseases and controls, and the results were compared with culture and clinical findings. None of culture negative samples from 17 healthy controls were PCR positive. Of 109 active tuberculosis patients under chemotherapy, 88 (80.7%) were PCR positive and were significantly higher than 63 (57.8%) positive by culture. Fifty-nine (93.7) of 63 culture positive and 29 (63.0%) of 46 culture negative specimens contained M. tuberculosis detectable by PCR. In 41 specimens from inactive tuberculosis patients who visited to the chest clinic because of chest problems, 16 (39.0%) also gave PCR positive results. In addition, 14 (46.7%) of 30 specimens submitted for M. tuberculosis culture from patients with pulmonary diseases were PCR positive. Presumptive diagnosis of these PCR positive patients was bronchitis, pneumonia, bronchial asthma, etc. Therefore, this study suggests that PCR is sensitive and specific in detecting M. tuberculosis in clinical specimens. However, the interpretation of the PCR results in specimens from patients with pulmonary diseases should be done cautiously in areas with a high prevalence of tuberculosis.

Base Sequence↗

PubMed2002

[Tuberculosis and HIV infection: experience of the national tuberculosis prevention program in Djibouti: 1990-1996].

Based on analysis of data collected from the national tuberculosis prevention program in Djibouti between 1990 and 1996, the authors analyzed the relationship between HIV infection and tuberculosis. The study cohort comprised a total of 22,000 patients including 14,000 with documented HIV infection. Although HIV infection probably worsened the situation, it was neither the only nor the main factor involved in the resurgence of tuberculosis. Demographic growth, higher population density, and increasing poverty as well as the quality of the national tuberculosis prevention program must be taken into account. The incidence of smear-negative tuberculosis was not significantly higher in HIV-infected patients (incidence of smear positive cases, > 92%). Extrapulmonary tuberculosis especially of pleural involvement was more common (15% versus 9.4%). Treatment was effective in HIV-infected patients. If directly observed (DOT) therapy was used, there was no risk of emergence of multidrug-resistant tuberculosis strains. Drug side-effects associated with the protocols used in Djibouti were not greater in HIV-infected patients. Most additional mortality observed in HIV-infected tuberculosis patients (10.5% versus 2%) was due to progression of HIV infection.

Adolescent↗

PubMed2002

[Tuberculosis in children less than 11 years old: primary resistance and dominant genetic variants of Mycobacterium tuberculosis in Antananarivo].

Tuberculosis during childhood is often due to Mycobacterium tuberculosis primo-infection. Tuberculosis is highly prevalent in Madagascar and most people are infected during childhood. Our objectives were to evaluate the primary resistance of M. tuberculosis and to determine the genotypes responsible for recent infection in the population. Thus we studied 142 isolated strains from 97 children (66 with pulmonary tuberculosis and 31 with extra-pulmonary tuberculosis) recruited in different health centers in Antananarivo from 1997 to 2000. Excepting one strain resistant to isoniazide, all strains were susceptible to the four antibiotics (streptomycin, isoniazid, ryfampicin and ethambutol). This result confirms the low rate of primary resistance reported during the two surveys in 1994-1995 and 1999-2000. 67 strains of 1997-2000 were typed with the genetic marker IS6110, 44 has been assigned to 13 clusters containing each 2 to 8 similar strains. Some IS6110 clusters have already been reported in 1994-1995. Some genotypes observed in 1994-1995 seemed to have disappeared in 1997-2000. (As the rate of the frequency of some genetic variants according to the period are more likely due to a difference in strain virulence). Since there is minimal antibiotic resistance versus M. tuberculosis in Madagascar, one can not explain the appearance or disappearance of certain variants because of drug resistance. Rather, this is due to the virulence of the various M. tuberculosis strains.

Age Distribution↗

PubMed2003

[Molecular epidemical characteristics of Mycobacterium tuberculosis strains from the nationwide random survey for the epidemiology of tuberculosis in China, 2000].

OBJECTIVE: To explore the epidemical distribution characteristics of Mycobacterium tuberculosis isolated from China. METHODS: The M. tuberculosis strains were gained by multi-stratified grouping random sampling method from the nationwide random survey for the epidemiology of tuberculosis in China, 2000, and analyzed by IS6110-based RFLP and DR-based Spoligotyping DNA fingerprinting. These fingerprinting patterns were transferred into digital data and compared each other, and clustered by Gel compar4.1 Software. The clustering values in different TB patients were compared by chi(2) test and the risk factors for recent transmission were calculated by Odd Ratios. RESULTS: Two hundreds and four of 402 M. tuberculosis strains from this survey were determined to be "Beijing Genotype" M. Tuberculosis strain by DNA fingerprinting analysis. Three clusters M. tuberculosis strains sharing identical fingerprint pattern were found, including one cluster belong to a same family. There were significant difference between female and male, and younger (< 40 years old) and elder (>or= 40 years old) (P < 0.05). Odds Ratio 1 showed youth [1.68 95% CI (1.01 - 2.80)] and male [2.04 95% CI (1.07 - 3.96)], but Odds Ratio 2 showed youth [0.3 95% CI (0.2 - 0.44)] and male [4.96 95% CI (2.77 - 9.00)]. CONCLUSION: M. tuberculosis strains of Beijing Genotype are prevailing in China at present. Male and elder were shown to be significant risk factors for recent transmission. The infection source of M. tuberculosis could be traced by DNA fingerprinting.

Adult↗

PubMed1992

[Detection of Mycobacterium tuberculosis in sputum specimens of pulmonary tuberculosis by DNA amplification].

The PCR was used to detect M. tuberculosis DNA sequences in uncultured clinical specimens. Two oligonucleotide primers with 20 bp each amplified target template DNA of M. tuberculosis. Amplified DNA product was 245 bp which was identified by agarose gel electrophoresis. The sensitivity of detection of M. tuberculosis genomic DNA and bacteria suspension by PCR was lpg and 13 viable bacteria cell/ml, respectively. In specificity experiments, only M. tuberculosis, M. bovis and BCG were positive by PCR, but all other 14 Mycobacterium tested, including streptomyces lividans and E. coli plasmid PUC19 were negative. The sensitivity of detection of M. tuberculosis by PCR was determined by comparing the fast-acid staining and culture on total 54 sputum specimens of pulmonary tuberculosis and 12 nontuberculosis lung disease. The positive rate of PCR in pulmonary tuberculosis were 37.0%, culture method showed only 14.8%, fast-acid staining were 16.7%. Nontuberculosis lung disease were negative. The results show that DNA amplification is a superior method with high degree of sensitivity and specificity for rapid diagnosis of pulmonary tuberculosis.

DNA Probes↗

PubMedDate not supplied

Hepatic tuberculosis in absence of disseminated abdominal tuberculosis.

Liver involvement in tuberculosis in absence of miliary tuberculosis is rare. This study was performed to analyse the spectrum and response to treatment of hepatic tuberculosis in the absence of miliary abdominal tuberculosis. Retrospective analysis of seven cases of hepatic tuberculosis without miliary abdominal tuberculosis who presented at the single tertiary referral center were analyzed. All patients presented with fever and hepatomegaly. Five of them had pain in upper abdomen and vomiting. HIV serology was positive in one patient. All patients had normocytic normochromic anaemia, raised erythrocyte sedimentation rate (Mean 65). Mild elevation of liver enzymes and low albumin (Mean 2.4 gm%) with reversal of albumin globulin ratio (Mean 0.6) were seen in all. Two had jaundice. Prothrombin time was normal in all and lactate dehydrogenase values were elevated in all (Mean 794 IU/L). On ultrasonography, 2 had multiple hypodense lesion, 1 had coarse echotexture of liver, 1 had hyperechoic pattern and 3 had just hepatomegaly. Complete resolution of liver lesions on treatment with 4-drug anti-tuberculosis drug chemotherapy was seen. In conclusion, liver tuberculosis has protean manifestations with nonspecific alteration of liver function tests and is best diagnosed on liver biopsy. Overall response to therapy is satisfactory.

Adolescent↗

PubMed2006

[Establishment of the guinea pig model of synovial tuberculosis of knee joint by mycobacterium tuberculosis H37Rv infection].

OBJECTIVE: To explore how to establish the guinea pig model of synovial tuberculosis of knee joint by mycobacterium tuberculosis H37Rv infection. METHODS: Two doses (1 x 10(7)/mL, 50 microL and 100 microL) of Mycobacterium strains were injected into the knee joint of the guinea pig that had been immunized and allergized with Freund's complete adjuvant six weeks previously. The pathological changes of the synovial membrane, cartilage and bone after infection of mycobacterium tuberculosis were investigated. At the same time, the synovial membrane tissues and culture for the mycobacterium tuberculosis were collected and examined. RESULTS: After the infection of mycobacterium tuberculosis H37Rv, the knee joint of guinea pig became swollen, but the interference to the whole conditions of the guinea pig was slight in both infection groups. The tissue sections of the synovial membrane showed tubercle and caseous necrosis of the knee joint in both groups. The mycobacterium tuberculosis could be detected by using Ziehl-neelsen stain and the culture from the synovial membrane of the knee joint. CONCLUSION: By injecting suitable dosage of mycobacterium H37Rv strains into the joint of the immunized and allergized guinea pig, we have established the guinea pig model of synovial tuberculosis that is pathologically similar to synovial tuberculosis in humans, so it is fit for use in the diagnostic studies and pathological researches.

Animals↗

PubMed2004

Sociocultural aspects of tuberculosis: a literature review and a case study of immigrant tuberculosis.

The resurgence of tuberculosis in recent years has obliged us to reconsider the existing explanations of the disease. Whereas biomedical literature tends to explain tuberculosis in terms of biological factors (e.g., bacterial infection), social scientists have examined various cultural, environmental, and politico-economic factors. In this paper, sociocultural approaches to tuberculosis are reviewed according to their emphasis on cultural, environmental, and politico-economic factors. Then how the public health establishment considers biological, cultural, environmental and politico-economic factors will be examined through a case study of immigrant tuberculosis. While public health facilities emphasize biological factors in the control of immigrant tuberculosis, an ethnographic study of tuberculosis among Chinese immigrants in New York City provides detailed contexts that illustrate the cultural, environmental, and politico-economic forces shaping tuberculosis and supports an emerging theorization of tuberculosis that encompasses a heterogeneous collection of factors. Finally, a number of implications for public health interventions will be discussed.

China↗

PubMed2003

Susceptibility to tuberculosis: a locus on mouse chromosome 19 (Trl-4) regulates Mycobacterium tuberculosis replication in the lungs.

The mouse DBA/2 (D2) strain is very susceptible to infection with virulent Mycobacterium tuberculosis, whereas C57BL/6 (B6) is much more resistant. Infection of D2 and B6 mice with M. tuberculosis H37Rv by the respiratory route is biphasic: during the first 3 weeks, there is rapid bacterial growth in the lung of both strains, whereas beyond this point replication stops in B6 but continues in D2, causing rapidly fatal pulmonary disease. To identify the genes regulating growth of M. tuberculosis in the lungs of these two strains, 98 informative (B6 x D2) F2 mice were infected by the respiratory route with M. tuberculosis H37Rv (2 x 102 colony-forming units), and the extent of bacterial replication in the lungs at 90 days was used as a quantitative measure of susceptibility in a whole-genome scan. Quantitative trait locus mapping identified a major locus on chromosome 19 (Tuberculosis resistance locus-4, Trl-4; logarithm of odds 5.6), which regulated pulmonary replication of M. tuberculosis and accounted for 25% of the phenotypic variance. B6 alleles at Trl-4 were inherited in an incompletely dominant fashion and associated with reduced bacterial replication. An additional effect of a locus (Trl-3), previously shown to affect survival to i.v. infection with M. tuberculosis, was also noted. F2 mice homozygous for B6 alleles at both Trl-3 and Trl-4 were as resistant as B6 parents, whereas mice homozygous for D2 alleles were as susceptible as D2 parents. These results suggest a strong genetic interaction between Trl-3 and Trl-4 in regulating pulmonary replication of M. tuberculosis.

Animals↗

PubMed2003

The world-wide increase in tuberculosis: how demographic changes, HIV infection and increasing numbers in poverty are increasing tuberculosis.

After more than a century of decline, in the mid 1980s tuberculosis began to increase in some developed countries. Health care workers were then forced to look to the developing world, where they found tuberculosis to be out of control, in many countries. It is now appreciated that tuberculosis is not only increasing globally but is likely to do so beyond the next decade for three principal reasons. First, demographically as the expected population increase will be greatest in areas of the world where tuberculosis is most prevalent, particularly middle Africa and South Asia. Secondly, the increase of HIV, which renders the host uniquely susceptible to tuberculosis, is occurring in the same areas of the world and is already causing an increase in tuberculosis case rates of up to tenfold. Thirdly, as more and more people are forced to live in poverty, where poor nutrition and crowded conditions lead to the spread of tuberculosis, the disease risk will be compounded. Sound medical management, particularly the use of the five components of directly observed therapy, will relieve the situation. But until world conditions of poverty and HIV spread are addressed, it is unlikely that tuberculosis can be controlled.

Global Health↗

PubMed1986

Tuberculosis and renal transplantation--observations from an endemic area of tuberculosis.

Ninety-five renal transplant recipients from an endemic area of tuberculosis were investigated to find out the prevalence and course of tuberculosis in pre- and post-transplant periods. Eleven patients had tuberculosis in the pre-transplant period - pulmonary (2), pleural (2), miliary (1), abdominal (2), lymph node (5) and pericardial (1). They were transplanted after antituberculous therapy of 3 to 6 months with satisfactory results. The anti-tuberculous treatment was usually continued for 2 years. Only one of the above 11 patients had evidence of tuberculosis in the post-transplant period. Nine patients developed tuberculosis for the first time in the post-transplant period - pulmonary (4), pleural (1), miliary (1), lymph node (4) and pericardial (1). There was no mortality due to tuberculosis. Thorough search for tuberculosis is mandatory both during pre-transplant assessment and post-transplant follow-up in areas of endemic tuberculosis.

Adult↗

PubMed1999

Community contribution to tuberculosis care in countries with high tuberculosis prevalence: past, present and future.

Effective tuberculosis control requires the collaboration of many partners. There is increasing interest in harnessing the contribution of communities to effective ambulatory tuberculosis control, as part of national tuberculosis programme activities. Understanding the lessons learned from the 1980s about community participation in Primary Health Care is important in understanding how communities may contribute specifically to tuberculosis care. Most of the published experience of community contribution to tuberculosis care is quite recent, small scale, and reports non-standardised results of effectiveness of tuberculosis treatment. There has been little attention to the issues of cost-effectiveness and acceptability. A multi-national collaborative project is underway in sub-Saharan Africa, coordinated by the World Health Organization, and aims at evaluating in a standardised way the effectiveness, cost-effectiveness and acceptability of community contribution to tuberculosis care. This should pave the way towards the development of international policy guidelines, to promote community contribution to tuberculosis care in ways which are effective, cost-effective and acceptable.

Africa South of the Sahara↗