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Incidence of tuberculosis and the predictive value of ELISPOT and Mantoux tests in Gambian case contacts.

Hill PC, Jackson-Sillah DJ, Fox A, Brookes RH, de Jong BC, Lugos MD, Adetifa IM, Donkor SA, Aiken AM, Howie SR, Corrah T, McAdam KP, Adegbola RA - PLoS ONE (2008)

Bottom Line: Of these, 6 pairs were concordant and 3 were discordant. 2.5% of non-progressors were HIV positive compared to 12% of progressors (HR 6.2; 95% CI 1.7-22.5; p = 0.010). 25 secondary cases had initial Mantoux results, 14 (56%) were positive ; 21 had initial ELISPOT results, 11 (52%) were positive; 15 (71%) of 21 tested were positive by one or the other test.ELISPOT positive contacts, and those with discordant results, had a similar rate of progression to those who were Mantoux positive.These data do not support the replacement of the Mantoux test by an ELISPOT test in The Gambia or similar settings.

View Article: PubMed Central - PubMed

Affiliation: Bacterial Diseases Programme, Medical Research Council (MRC) Laboratories, Banjul, The Gambia. pandmhill@hotmail.com

ABSTRACT

Background: Studies of Tuberculosis (TB) case contacts are increasingly being utilised for understanding the relationship between M. tuberculosis and the human host and for assessing new interventions and diagnostic tests. We aimed to identify the incidence rate of new TB cases among TB contacts and to relate this to their initial Mantoux and ELISPOT test results.

Methods and findings: After initial Mantoux and ELISPOT tests and exclusion of co-prevalent TB cases, we followed 2348 household contacts of sputum smear positive TB cases. We visited them at 3 months, 6 months, 12 months, 18 months and 24 months, and investigated those with symptoms consistent with TB. Those who were diagnosed separately at a government clinic had a chest x-ray. Twenty six contacts were diagnosed with definite TB over 4312 person years of follow-up (Incidence rate 603/100,000 person years; 95% Confidence Interval, 370-830). Nine index and secondary case pairs had cultured isolates available for genotyping. Of these, 6 pairs were concordant and 3 were discordant. 2.5% of non-progressors were HIV positive compared to 12% of progressors (HR 6.2; 95% CI 1.7-22.5; p = 0.010). 25 secondary cases had initial Mantoux results, 14 (56%) were positive ; 21 had initial ELISPOT results, 11 (52%) were positive; 15 (71%) of 21 tested were positive by one or the other test. Of the 6 contacts who had concordant isolates with their respective index case, 4 (67%) were Mantoux positive at recruitment, 3 (50%) were ELISPOT positive; 5 (83%) were positive by one or other of the two tests. ELISPOT positive contacts, and those with discordant results, had a similar rate of progression to those who were Mantoux positive. Those negative on either or both tests had the lowest rate of progression.

Conclusions: The incidence rate of TB disease in Gambian TB case contacts, after screening for co-prevalent cases, was 603/100,000 person years. Since initial ELISPOT test and Mantoux tests were each positive in only just over half of cases, but 71% were positive by one or other test, positivity by either might be the best indication for preventive treatment. These data do not support the replacement of the Mantoux test by an ELISPOT test in The Gambia or similar settings.

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Related in: MedlinePlus

Timing of presentation for diagnosis of incident TB cases after exposure to their respective index case.
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pone-0001379-g002: Timing of presentation for diagnosis of incident TB cases after exposure to their respective index case.

Mentions: Figure 2 shows the period from enrolment to the time when the contact first became a TB suspect: 14 were diagnosed in the first 6 months after the co-prevalent window period, the other 12 were distributed over the next 17 months. Table 1 shows the characteristics of those who progressed to disease versus those who did not. Progressors had a similar gender and ethnicity split than those who did not progress. Interestingly there was not a strong relationship with sleeping proximity to a TB case. As expected, while only 2.5% of non-progressors were HIV positive, 12% (3 of 24) progressors were HIV positive at recruitment. This difference was significant in the univariable (HR 6.0; 95% CI 1.8–20.0; p = 0.020) and multivariable analysis (HR 6.2; 95% CI 1.7–22.5; p = 0.010), and accounted for some of the age difference between progressors and non-progressors. No information was available regarding the level of immunosuppression of the HIV positive progressors. BCG scar was not significantly associated with protection against progression to disease.


Incidence of tuberculosis and the predictive value of ELISPOT and Mantoux tests in Gambian case contacts.

Hill PC, Jackson-Sillah DJ, Fox A, Brookes RH, de Jong BC, Lugos MD, Adetifa IM, Donkor SA, Aiken AM, Howie SR, Corrah T, McAdam KP, Adegbola RA - PLoS ONE (2008)

Timing of presentation for diagnosis of incident TB cases after exposure to their respective index case.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2147055&req=5

pone-0001379-g002: Timing of presentation for diagnosis of incident TB cases after exposure to their respective index case.
Mentions: Figure 2 shows the period from enrolment to the time when the contact first became a TB suspect: 14 were diagnosed in the first 6 months after the co-prevalent window period, the other 12 were distributed over the next 17 months. Table 1 shows the characteristics of those who progressed to disease versus those who did not. Progressors had a similar gender and ethnicity split than those who did not progress. Interestingly there was not a strong relationship with sleeping proximity to a TB case. As expected, while only 2.5% of non-progressors were HIV positive, 12% (3 of 24) progressors were HIV positive at recruitment. This difference was significant in the univariable (HR 6.0; 95% CI 1.8–20.0; p = 0.020) and multivariable analysis (HR 6.2; 95% CI 1.7–22.5; p = 0.010), and accounted for some of the age difference between progressors and non-progressors. No information was available regarding the level of immunosuppression of the HIV positive progressors. BCG scar was not significantly associated with protection against progression to disease.

Bottom Line: Of these, 6 pairs were concordant and 3 were discordant. 2.5% of non-progressors were HIV positive compared to 12% of progressors (HR 6.2; 95% CI 1.7-22.5; p = 0.010). 25 secondary cases had initial Mantoux results, 14 (56%) were positive ; 21 had initial ELISPOT results, 11 (52%) were positive; 15 (71%) of 21 tested were positive by one or the other test.ELISPOT positive contacts, and those with discordant results, had a similar rate of progression to those who were Mantoux positive.These data do not support the replacement of the Mantoux test by an ELISPOT test in The Gambia or similar settings.

View Article: PubMed Central - PubMed

Affiliation: Bacterial Diseases Programme, Medical Research Council (MRC) Laboratories, Banjul, The Gambia. pandmhill@hotmail.com

ABSTRACT

Background: Studies of Tuberculosis (TB) case contacts are increasingly being utilised for understanding the relationship between M. tuberculosis and the human host and for assessing new interventions and diagnostic tests. We aimed to identify the incidence rate of new TB cases among TB contacts and to relate this to their initial Mantoux and ELISPOT test results.

Methods and findings: After initial Mantoux and ELISPOT tests and exclusion of co-prevalent TB cases, we followed 2348 household contacts of sputum smear positive TB cases. We visited them at 3 months, 6 months, 12 months, 18 months and 24 months, and investigated those with symptoms consistent with TB. Those who were diagnosed separately at a government clinic had a chest x-ray. Twenty six contacts were diagnosed with definite TB over 4312 person years of follow-up (Incidence rate 603/100,000 person years; 95% Confidence Interval, 370-830). Nine index and secondary case pairs had cultured isolates available for genotyping. Of these, 6 pairs were concordant and 3 were discordant. 2.5% of non-progressors were HIV positive compared to 12% of progressors (HR 6.2; 95% CI 1.7-22.5; p = 0.010). 25 secondary cases had initial Mantoux results, 14 (56%) were positive ; 21 had initial ELISPOT results, 11 (52%) were positive; 15 (71%) of 21 tested were positive by one or the other test. Of the 6 contacts who had concordant isolates with their respective index case, 4 (67%) were Mantoux positive at recruitment, 3 (50%) were ELISPOT positive; 5 (83%) were positive by one or other of the two tests. ELISPOT positive contacts, and those with discordant results, had a similar rate of progression to those who were Mantoux positive. Those negative on either or both tests had the lowest rate of progression.

Conclusions: The incidence rate of TB disease in Gambian TB case contacts, after screening for co-prevalent cases, was 603/100,000 person years. Since initial ELISPOT test and Mantoux tests were each positive in only just over half of cases, but 71% were positive by one or other test, positivity by either might be the best indication for preventive treatment. These data do not support the replacement of the Mantoux test by an ELISPOT test in The Gambia or similar settings.

Show MeSH
Related in: MedlinePlus