Environmental mycobacteria in northern Malawi: implications for the epidemiology of tuberculosis and leprosy

Fine, Paul E. M.; Floyd, Sian; Stanford, J. L.; Nkhosa, Prince; Kasunga, A.; Chaguluka, Steven D.; Warndorff, D. K.; Jenkins, Peter; Yates, M.D.; Pönnighaus, J. M.

doi:10.1017/s0950268801005532

Cited by 68 publications

(44 citation statements)

References 17 publications

(14 reference statements)

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“…In fact even a dose as high as 4000 organisms leads to latent non-progressive disease in Mexico City, detectable only by in situ PCR [27]. We suggest that contact with environmental saprophytes in animal facilities in developing countries induces a mixed Th1/Th2 response (mostly Th1), such as that seen in the human population of Malawi [23] and (Dockrell, 8 H., personal communication). A low dose infection may be dealt with by the dominant Th1 component.…”

Section: Discordant Doses Of M Tuberculosis Required To Infect Mice mentioning

confidence: 77%

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Do successful tuberculosis vaccines need to be immunoregulatory rather than merely Th1-boosting?

Rook

Dheda

Zumla

2005

Vaccine

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Tuberculosis vaccine candidates are entering clinical studies in areas where BCG fails. This is a high risk strategy. We suggest that geographical variation in the efficacy of BCG is related to the presence in developing countries of a cross-reactive background Th2-like response, probably attributable to exposure of mother and infant to helminths and environmental mycobacteria. Such Th2-like activity can stop M. tuberculosis from being pushed into a latent state by the Th1 response, impair bactericidal functions and cause toxicity of TNF-α and pulmonary fibrosis. A successful vaccine, rather than driving a Th1 response, might need to suppress this pre-existing subversive Th2-like component.

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Section: Discordant Doses Of M Tuberculosis Required To Infect Mice mentioning

confidence: 77%

“…Presumably contact with cross-reactive environmental mycobacteria would do the same thing in these babies. However these organisms also induce a Th1 response in Malawi that is demonstrably protective [23], and the possible interplay between the Th1 and Th2 components is crucial, and is discussed later.…”

Section: Failure Of Bcg Vaccination In Developing Countriesmentioning

confidence: 99%

Do successful tuberculosis vaccines need to be immunoregulatory rather than merely Th1-boosting?

Rook

Dheda

Zumla

2005

Vaccine

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“…6,20 Thus, some evidence for cross-protection from natural exposure to certain environmental mycobacteria has been associated with the geographic distributions of mycobacterial disease in Malawi. 39 Children who are in contact with individuals with Note: duration of cough is associated with the number of zones involved on chest radiograph (P ϭ .001).…”

Section: Discussionmentioning

confidence: 99%

Risk Factors for Tuberculosis Infection in Children in Contact With Infectious Tuberculosis Cases in The Gambia, West Africa

et al. 2003

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ABSTRACT. Objective. Tuberculosis (TB) infection is highly prevalent in developing countries. As infected children represent a large proportion of the pool from which TB cases will arise, knowledge of the factors that influence TB infection in children are of importance to evaluate transmission of infection in the community and adapt TB control activities. There are limited data on the risk of infection in child populations in developing countries.Methods. We performed a household contact study in The Gambia (West Africa), in which children who were living in contact with individuals who had proven smearpositive pulmonary TB cases were investigated. A questionnaire was addressed to the mother or caregiver of the child to investigate the presence of various risk factors and assess the degree of exposure of the child to the individual with TB within the household. A tuberculin skin test (TST) was performed on each child. TST sizes >5 and 10 mm, respectively, were considered positive.Results. Households of 206 TB cases were visited, and 384 children aged <5 years were examined. The median age was 2, and 48% were girls. The distribution of TST responses followed a bimodal pattern, with 135 (35%) children presenting a palpable induration. Random effects logistic regression analysis demonstrated that the risk of positive TST response in the child increased with the geographic proximity of the child to the individual with TB within the household and with the degree of activities shared with the individual with TB. It was also associated with the clinical severity of the disease in the index case. Nutritional status and presence of a bacille Calmette-Guérin (BCG) scar were not independent risk factors for TST positivity in this population. On multivariate analysis, the effect of geographic proximity to the individual with TB, household size, and duration of cough in the index case persisted for TST responses >5 mm.Conclusions. In a highly endemic country with high BCG vaccination coverage in Africa, TB infection in children who were in contact with individual with infectious TB was directly related to the intensity of exposure of the child to the individual with TB. Our data suggest that a positive TST in a child reflects most probably TB infection rather than previous BCG vaccination. Contact I n 1995, the World Health Organization estimated that at least 180 million children under the age of 15 years were infected with Mycobacterium tuberculosis worldwide and that nearly 170 000 children died of tuberculosis (TB). 1,2 TB infection and disease among children are much more prevalent in developing countries, where resources for TB control are scarce, than in industrialized countries. 3 However, despite the public health importance of the disease, TB is rarely investigated in children, as the diagnosis is difficult in the young age groups and children are usually not infectious. 4 In addition, contact tracing is rarely done in nonindustrialized countries because of lack of resources, and Isoniazid prophylaxis is not sys...

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“…It is commonly thought that nontuberculous mycobacteria, and newly described species in particular, are restricted to developed countries. Again, a shortage of technology may well explain the missed isolation of such problematic microorganisms in developing countries, especially since, when suitable means have been employed, nontuberculous mycobacteria have been detected in these countries too (34,40).…”

Section: Final Remarksmentioning

confidence: 99%

Impact of Genotypic Studies on Mycobacterial Taxonomy: the New Mycobacteria of the 1990s

2003

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The advancement of genetic techniques has greatly boosted taxonomic studies in recent years. Within the genus Mycobacterium, 42 new species have been detected since 1990, most of which were grown from clinical samples. Along with species for which relatively large numbers of strains have been reported, some of the new species of mycobacteria have been detected rarely or even only once. From the phenotypic point of view, among the new taxa, chromogens exceed nonchromogens while the numbers of slowly and rapidly growing species are equivalent. Whereas conventional identification tests were usually inconclusive, an important role was played by lipid analyses and in particular by high-performance liquid chromatography. Genotypic investigations based on sequencing of 16S rRNA gene have certainly made the most important contribution. The investigation of genetic relatedness led to the redistribution of the species previously included in the classically known categories of slow and rapid growers into new groupings. Within slow growers, the intermediate branch related to Mycobacterium simiae and the cluster of organisms related to Mycobacterium terrae have been differentiated; among rapid growers, the group of thermotolerant mycobacteria has emerged. The majority of species are resistant to isoniazid and, to a lesser extent, to rifampin. Many of the new species of mycobacteria are potentially pathogenic, and there are numerous reports of their involvement in diseases. Apart from disseminated and localized diseases in immunocompromised patients, the most frequent infections in immunocompetent people involve the lungs, skin, and, in children, cervical lymph nodes. The awareness of such new mycobacteria, far from being a merely speculative exercise, is therefore important for clinicians and microbiologists

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Environmental mycobacteria in northern Malawi: implications for the epidemiology of tuberculosis and leprosy

Cited by 68 publications

References 17 publications

Do successful tuberculosis vaccines need to be immunoregulatory rather than merely Th1-boosting?

Do successful tuberculosis vaccines need to be immunoregulatory rather than merely Th1-boosting?

Risk Factors for Tuberculosis Infection in Children in Contact With Infectious Tuberculosis Cases in The Gambia, West Africa

Impact of Genotypic Studies on Mycobacterial Taxonomy: the New Mycobacteria of the 1990s

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