BCG scar and positive tuberculin reaction associated with reduced child mortality in West Africa. A non-specific beneficial effect of BCG?

Previous studies have suggested that the bacille Calmette-Guérin (BCG) vaccine may have a non-specific beneficial effect on childhood survival in areas with high mortality. We examined whether BCG-vaccinated children with a BCG scar or a positive tuberculin reaction had better survival than children without such reactions. As part of an ongoing two-dose measles vaccine trial for which children were recruited at 6 months of age, we examined 1813 children for BCG scar at 6 months of age and 813 BCG-vaccinated children were skin-tested for delayed hypersensitivity to tuberculin, tetanus and diphtheria. We found that BCG-vaccinated children with a BCG scar had significantly lower mortality compared with BCG scar-negative children, the mortality ratio in the first 12 months of follow-up being 0.41 (0.25-0.67). BCG-vaccinated children with a positive tuberculin test had a mortality ratio of 0.45 (0.24-0.85) compared with tuberculin negative children. These results were unchanged by control for potential confounders or using different cut-off points for a tuberculin-positive response. Exclusion of dead children who had HIV antibodies did not modify the estimate (mortality rate (MR)=0.46 (0.23-0.94)). After censoring for tuberculosis (TB) exposure at home, the mortality ratios for having a scar and being tuberculin-positive were 0.46 (0.27-0.79) or 0.42 (0.21-0.84), respectively. Children positive to tetanus or diphtheria in the skin test had the same mortality as children not responding to these vaccine-related antigens. Thus, BCG scar and a positive tuberculin reaction were associated with better survival in early childhood in an area with high mortality. Since nothing similar was found for responders to diphtheria-tetanus-pertussis (DTP) vaccine, and the effect could not be explained by protection against tuberculosis, the effect of BCG vaccination could be due to non-specific immune-stimulation protecting against other infections.     

BCG vaccination scar associated with better childhood survival in Guinea-Bissau

BACKGROUND: Recent studies have suggested that Bacille Calmette-Guerin (BCG) vaccination may have a non-specific beneficial effect on infant survival and that a BCG scar may be associated with lower child mortality. No study has previously examined the influence of BCG vaccination on cause of death. METHODS: Two cohorts (A and B) were used to describe the mortality pattern for children with and without BCG scar and to determine specific causes of death. In cohort A (n = 1813), BCG scar was assessed at 6 months of age and as previously described children with a BCG scar had lower mortality over the next 12 months than children with no BCG scar. In cohort B, 1617 children aged 3 months to 5 years of age had their BCG scar status assessed in a household-based survey and mortality was assessed during a 12-month period. Causes of death were determined by verbal autopsy (VA) and related to BCG scar status in a cause-specific hazard function. RESULTS: Controlling for background factors associated with mortality, there was lower mortality for children with a BCG scar than without in cohort B, the mortality ratio (MR) being 0.45 (95% CI 0.21-0.96). Exclusion of children exposed to TB did not have any impact on the result. In a combined analysis of cohorts A and B, the MR was 0.43 (95% CI 0.28-0.65) controlling for background factors. There were no large differences in distribution of the five major causes of death (malaria, pneumonia, acute diarrhoea, chronic diarrhoea, and meningitis/encephalitis) according to BCG scar status in the two cohorts. Having a BCG scar significantly reduced the risk of death from malaria [MR 0.32 (95% CI 0.13-0.76)]. CONCLUSIONS: A BCG scar is a marker of better survival among children in countries with high child mortality. BCG vaccination may affect the response to several major infections including malaria.     

Tuberculin reactivity in a population of schoolchildren with high BCG vaccination coverage.

OBJECTIVE: To investigate the influence of BCG vaccination or revaccination on tuberculin skin test reactivity, in order to guide the correct interpretation of this test in a setting of high neonatal BCG vaccination coverage and an increasing BCG revaccination coverage at school age. METHODS: We conducted tuberculin skin testing and BCG scar reading in 1 148 children aged 7-14 years old in the city of Salvador, Bahia, Brazil. We measured the positive effect of the presence of one or two BCG scars on the proportion of tuberculin skin test results above different cut-off levels (induration sizes of > or = 5 mm, > or = 10 mm, and > or = 15 mm) and also using several ranges of induration size (0, 1-4, 5-9, 10-14, and > or = 15 mm). We also measured the effects that age, gender, and the school where the child was enrolled had on these proportions. RESULTS: The proportion of tuberculin results > or = 10 mm was 14.2% (95% confidence interval (CI) = 8.0%-20.3%) for children with no BCG scar, 21.3% (95% CI = 18.5%-24.1%) for children with one BCG scar, and 45.0% (95% CI = 32.0%-58.0%) for children with two BCG scars. There was evidence for an increasing positive effect of the presence of one and two BCG scars on the proportion of results > or = 5 mm and > or = 10 mm. Similarly, there was evidence for an increasing positive effect of the presence of one and two scars on the proportion of tuberculin skin test results in the ranges of 5-9 mm and of 10-14 mm. The BCG scar effect on the proportion of results > or = 5 mm and > or = 10 mm did not vary with age. There was no evidence for BCG effect on the results > or = 15 mm. CONCLUSIONS: In Brazilian schoolchildren, BCG-induced tuberculin reactivity is indistinguishable, for results under 15 mm, from reactivity induced by Mycobacterium tuberculosis infection. BCG revaccination at school age increases the degree of BCG-induced tuberculin reactivity found among schoolchildren. This information should be taken into account in tuberculin skin test surveys intended to estimate M. tuberculosis prevalence or to assess transmission patterns as well as in tuberculin skin testing of individuals used as an auxiliary tool in diagnosing tuberculosis. Taking this information into consideration is especially important when there is increasing BCG revaccination coverage.     

Non-specific effects of diphtheria tetanus pertussis vaccination on child mortality in Cebu, The Philippines

BACKGROUND: To determine the non-specific effects of diphtheria, tetanus and pertussis (DTP) vaccination and sex on mortality before 30 months of age among those who received Bacille Calmette Guerin (BCG) vaccine in a high mortality area. METHODS: This analysis used a longitudinal study of child survival monitoring the use of primary care services, morbidity and mortality in Metro Cebu, The Philippines. Participants included 14 537 children under 30 months of age who received a BCG vaccination from July 1988 to January 1991. The main outcome measure was all-cause mortality. RESULTS: Mortality before 30 months of age was 57% lower among BCG-vaccinated children who received DTP vaccination than BCG-vaccinated children who did not receive DTP vaccination {hazard ratio (HR) for vaccinated vs unvaccinated 0.43 [95% confidence interval (CI) 0.21-0.88]}. Females had lower mortality rates [HR = 0.19 (0.04-0.86), P = 0.03] than males among DTP-unvaccinated children. The protective effect of DTP vaccination was more pronounced in males [HR 0.32 (0.14-0.73)] than in females [HR 0.86 (0.18-4.23)]. DTP vaccination increased (interaction term P = 0.08) the female-to-male mortality ratio to 0.76 (0.52-1.12). CONCLUSIONS: Among BCG-vaccinated children under 30 months of age, DTP vaccination is associated with improved survival. The increased female-male mortality ratio is associated with reduced mortality among males following DTP vaccination rather than increased mortality among female children.     

Vaccination technique, PPD reaction and BCG scarring in a cohort of children born in Guinea-Bissau 2000-2002

The rates of positive tuberculin skin test (TST) reactions and BCG scarring after BCG vaccination vary between studies and populations. Tuberculin reactivity and BCG scarring may be related to better child survival in low-income countries. We therefore studied determinants for TST reaction and scarring in Guinea-Bissau. In a cohort of children born in suburban Bissau from March 2000 to July 2002, we assessed a Mantoux test with Purified protein derivative (PPD) (SSI, 2 T.U.) at 2 (2689 children), 6 (N=2148) and 12 months (N=1638) of age, and BCG scar was assessed at 2 (N=2698) and 6 months (N=2225) of age. In a subgroup of the children the vaccination technique was monitored by direct observation of post-vaccination wheal and route of administration. Three different types of BCG vaccine supplied by the local Extended Programme on Immunization were used. At 6 months of age the rate of PPD reactors (>1mm) after BCG vaccination was 25% and the rate of scarring was 89%. One BCG strain was associated with fewer PPD reactors (OR=0.54 (0.31-0.91)) and BCG scars (OR=0.13 (0.05-0.37)) and larger post-vaccination wheals produced more PPD reactions (OR 1.21 (95% CI 1.02-1.43)) and BCG scars (OR 1.66 (1.24-2.21)). In the multivariable analyses of BCG-vaccinated children assessed at 6 months of age, monitoring of vaccination technique and type of BCG vaccine were important. This was not changed by control for other determinants, including sex, season, vaccination place, birthplace, ethnic group, low birth weight, place of residence, education and civil status of mother. We reason that vaccination technique and BCG strain are important for PPD reaction and scarring in response to BCG vaccination. Considering that these responses are associated with better infant survival, the importance of monitoring vaccination technique and of different BCG strains should be evaluated with respect to infant mortality.     

Risk factors for positive tuberculin skin test in Guinea-Bissau

BACKGROUND: The tuberculin skin test is used for tracing of tuberculosis transmission and identifying individuals in need of prophylactic treatment. METHODS: Using a case-control study design, we recruited 220 smear-positive tuberculosis cases and 223 randomly selected healthy community controls in Bissau, Guinea-Bissau, during 1999-2000. Tuberculin skin tests were performed on family members of cases and controls (n = 1059 and n = 921, respectively). Induration of 10 mm or greater was considered positive. Risk factors were calculated for children (<15 years) and adults separately in multivariate logistic regression analysis. RESULTS: The prevalence of positive tuberculin skin test was 41% in case-contacts compared with 22% in control-contacts, resulting in a prevalence ratio of 1.48 (95% confidence interval = 1.37-1.60). Positive skin tests among case-contacts increased with age for children, as well as with proximity to a case during the night, for both children and adults. A Bacille Calmette Guerin scar increased the likelihood of having a positive tuberculin skin test for adults in case households, but not in other categories of contacts. Among control-contacts the prevalence of positive skin test was associated with older age in children, history of tuberculosis in the family, and a positive tuberculin skin test of the control person. CONCLUSIONS: Risk factors for a positive tuberculin skin test among case- and control-contacts are closely related to tuberculosis exposure. Having a BCG scar did not increase the risk of positive skin test in unexposed individuals. Tuberculin skin testing remains a useful tool for diagnosing tuberculosis infection.     

Evaluation of the tuberculin reaction in health occupation students] .

A cross-sectional study was done at the University of Antioquia, MedellIn, Colombia, to evaluate the response to a tuberculin skin test among students in undergraduate health programs (medicine, odontology, nursing, and bacteriology) as compared to undergraduate students in nonhealth programs. The study included students from the beginning, middle, and end of the university's academic programs. The sample of 490 students included 273 from health programs and 217 from nonhealth programs. Participants were randomly selected using lists provided by the university registrar, for the second semester of 1998. The presence of a BCG vaccination scar was determined, and all the participants were also questioned about TB-related risk factors. Tuberculin skin test reactivity was evaluated by the size of induration 72 hours after intradermal injection of two tuberculin units of purified protein derivative RT 23. There were no differences in tuberculin reactivity between students from the health programs and from the nonhealth programs, irrespective of the academic level. However, there was a significantly higher proportion of positive skin tests among students with a BCG scar. These results suggest that undergraduate health students do not have extensive contact with TB patients or with clinical samples from such patients. Nevertheless, the results do not rule out TB as an occupational risk for health personnel.     

How to detect and diagnose TB

Health workers have four main tools at their disposal for detecting tuberculosis (TB) in patients: clinical symptoms, tuberculin testing, x-ray of the chest, and sputum smear microscopy. The two main detection tools for children are tuberculin skin test and chest x-ray. Signs and symptoms of TB to look for in adults are persistent cough (3 weeks), blood in the sputum, persistent chest pain (1 month), increasing weakness and weight loss, and past history of TB or treatment for cough. TB treatment should not begin until a positive sputum smear is confirmed in cases of pulmonary TB. Health workers should suspect TB if children younger than 5 are in close contact with someone who has confirmed TB, have a strongly positive tuberculin test, and have clinical signs and symptoms. Further tests are usually needed to confirm the diagnosis. In many areas, tests are impossible so health workers need to diagnose TB based on history, physical examination, and clinical symptoms. TB is difficult to diagnose in children because TB is either limited inside the lung or located outside the lungs. Malnourished children with TB usually have a negative tuberculin test. Malnourished children displaying signs of TB or whose X-ray suggests TB should be treated. A recent BCG vaccination can yield a weak positive tuberculin test result. TB signs and symptoms in children are nonspecific. General signs to look for are: unexplained weight loss, anorexia, failure to thrive and gain weight, at least 2 episodes of unexplained fever, swollen lymph nodes (especially in children with HIV), and persistent cough or wheeze (2 weeks). Specific signs depend on the site of infection: whole body, brain or spine, lungs, bones and joints, skin or mucous membranes. This article contains instructions on how to do the tuberculin skin test and sputum smear microscopy.     

Tuberculin reactivity in adults after 50 years of universal bacille Calmette-Guerin vaccination in Taiwan

We aimed to assess whether tuberculin reactivity in adults is affected by bacille Calmette-Guerin (BCG) vaccination after 50 years of universal BCG vaccination with 80-95% coverage. A community-based study on tuberculin reactivity in 619 participants was conducted in February 2000 in Keelung city, Taiwan. Information on BCG vaccination policies and annual risk of infection (ARI) in the underlying population was extracted from consecutive national prevalence surveys relating to the period 1952-1997. Compared with the expected ARI estimate, the standardized morbidity ratio of positive tuberculin response for vaccination in infancy was 2.2 (95% CI 0.3-15.5) for those aged <10 years. The corresponding figures for older age groups ranged from 3.6 (95% CI 2.2-5.9) for those aged 10-12 years to 0.7 (95% CI 0.5-0.9) for those aged 57-67 years. This suggests that the effect of BCG vaccination on positive tuberculin response in adults aged >30 years is probably negligible irrespective of age at vaccination or revaccination and that the tuberculin skin test can be used to diagnose TB in control programmes in countries with moderate or high incidence of TB.     

Annual risk of tuberculous infection in the northern zone of India

OBJECTIVE: To estimate the annual risk of infection with tubercle bacilli in the northern zone of India. METHODS: A community-based cross-sectional tuberculin survey was conducted among children aged 1-9 years who lived in a sample of villages and urban blocks of six selected districts in a defined north zone of India. A two-stage cluster sampling method was used to select rural and urban clusters. A total of 48 624 children in 598 clusters were subjected to tuberculin testing with one tuberculin unit (1 TU) of PPD RT23 stabilized with Tween 80. The maximum transverse diameter of induration was measured about 72 hours after the test. FINDINGS: Among the 48 624 test-read children, 22 064 (45.4%) had a bacille Calmette-Gu rin (BCG) scar. On the basis of the frequency distribution of tuberculin reaction size among 25 816 children without a BCG scar, the prevalence of infection with tubercle bacilli was estimated as 10.3%. The annual risk of infection was computed as 1.9%. The proportion of infected children was significantly higher in urban than rural areas. CONCLUSION: The high rate of tuberculous infection in the north zone of India suggests the need for further intensification of tuberculosis control efforts on a sustained and long-term basis.     

Is tuberculin skin testing useful to diagnose latent tuberculosis in BCG-vaccinated children?

BACKGROUND: The tuberculin skin test (TST) is the most commonly used tool to detect infection with Mycobacterium tuberculosis. We sought to determine whether tuberculin skin testing is useful to detect latent infection by M. tuberculosis in a population that was vaccinated with the Bacille Calmette Guérin (BCG) vaccine. METHODS: We performed a cross-sectional study during October 2000-February 2001, enrolling first and sixth graders from a random, stratified sample of public elementary schools in Orizaba, Veracruz, Mexico. We assessed the relationship between sociodemographic and epidemiological information, BCG scars, and TST reactivity. RESULTS: There were 858 children enrolled in the study with a completed questionnaire and TST result. The prevalence of a positive TST result (> or =10 mm) was 12.4%. Controlling for BCG scar, age, and other characteristics, close contact with pulmonary tuberculosis patients (odds ratio 6.56, 95% confidence interval 2.05-21.07, P = 0.001) was independently associated with TST reactivity. CONCLUSIONS: TST results helped identify children in a BCG-vaccinated population who had recent exposure to persons with pulmonary tuberculosis, were probably infected with M. tuberculosis, and could benefit from treatment for their latent tuberculosis infection.     

Immunization status of internationally adopted children in Italy

An increasing number of internationally adopted children is coming to Italy, and their immunization status is unknown. We evaluated the immunization status of such children in Palermo, Italy. We searched for the presence of a BCG scar in 88 children, 49 boys and 39 girls (mean age 76+/-32 months), most of whom (98%) came from Eastern Europe. Presence of BCG scar was observed in 59 (67.1%) of them, included five children without any pre-adoptive medical records. Twenty-three out of 29 children without any evidence of BCG scar were tested by Mantoux. Seven (30.4%) of 23 were tuberculin positive and diagnosed as having latent tuberculosis infection. We also examined immunization status against poliovirus 1-3, tetanus, diphtheria, pertussis, measles, mumps, rubella and hepatitis B of 70 internationally adopted children and we compared it with the pre-adoptive immunization records of their birth country. Protective titers (>1:8) against poliovirus 1-3, were found respectively in 67.1%, 91.4%, 42.8% of 70 immunized children, and only 38.5% of them had at the same time full protection against all three types of poliovirus. Protective titers against tetanus and diphtheria were found in 91.4% and 95.7% of 70 vaccinated children. Presence of antibodies against pertussis, measles, mumps and rubella was observed respectively in 16 (32.6%) of 49, 40 (62.5%) of 64, 28 (56%) of 50 and 24 (85.7%) of 28 children who had received the vaccine. As regards hepatitis B, only 20 of 29 vaccinated children had detectable hepatitis B surface antibodies, while four of 29 vaccinated and two of 41 not vaccinated children were positive for both hepatitis B surface antibodies and hepatitis B core antibodies. Finally three of 41 not vaccinated children were both hepatitis B surface antigen and hepatitis B core antibodies positive. No relation was found between health status and immunization and between age and antibody positiveness of vaccinated children except for hepatitis B, therefore the youngest immunized children were more likely to be hepatitis B surface antibodies positive. Our data suggest that internationally adopted children should be tested for their immunization status on arrival in the adopting country, because they are not protected in a sufficient way against vaccine-preventable diseases and their pre-adoptive immunization records sometimes are lacking and frequently are scarcely reliable.     

Mycobacterium tuberculosis infection in First Nations preschool children in Alberta: implications for BCG (bacille Calmette-Guérin) vaccine withdrawal

BACKGROUND: On April 1, 2004, BCG (bacille Calmette-Guérin), a tuberculosis (TB) control vaccine, was discontinued in all but four high-risk communities in Alberta. To confirm the safety of vaccine withdrawal, and for future planning, the annual risk of infection (ARI) was determined in preschool First Nations children. METHODS: First Nations children born into reserve communities in Alberta between April 1, 1998 and March 31, 2004, and still living on reserve in 2004-2005, were identified. Health centre TB histories were validated by cross-referencing the birth cohort with the provincial TB Registry. Children that were not BCG vaccinated and not known to be tuberculin skin test (TST) positive underwent a TST. Birth cohort children were grouped as follows: (i) BCG vaccinated; (ii) BCG non-vaccinated, no TST; (iii) BCG non-vaccinated, TST; (iv) BCG vaccination status unknown. The ARI was calculated and the age and community characteristics of the groups were compared. RESULTS: There were 8447 children in the 6-year birth cohort, 4699 (55.6%) vaccinated, 2696 (31.9%) non-vaccinated, and 1052 (12.5%) whose vaccination status was unknown. Of the non-vaccinated children, 1921 (71.3%) were tested and only 2 were TST positive. No other TST positive, BCG non-vaccinated children were identified in the TB Registry cross-match. The prevalence of infection in 2004-2005 was 0.1% and the ARI was 0.03%. The community risk of TB exposure was comparable in tuberculin-tested and non-tested BCG non-vaccinated children. CONCLUSION: In low BCG-uptake First Nations communities in Alberta, the ARI is low and it is safe to withdraw BCG.     

BCG vaccination among West African infants is associated with less anergy to tuberculin and diphtheria-tetanus antigens.

To examine risk factors for anergy, delayed-type hypersensitivity was assessed among 884 infants participating in a vaccine trial in Guinea-Bissau. The infants were skin-tested at 7.5 months of age with a panel of seven intradermal antigens. Risk factors for anergy to tuberculin or anergy to both the diphtheria and tetanus antigens were determined in relation to Bacillus Calmette-Guérin (BCG) vaccination, diphtheria-tetanus-pertussis (DTP) vaccination, and measles vaccination. We found sick children to be more anergic to tuberculin and diphtheria-tetanus antigens than healthy children (OR=2.49 (95% confidence interval 1.40-4.55)). There was a higher prevalence of anergy to tuberculin in the rainy season than in the dry season (OR=1.67 (1.25-2.23)). Children who had taken antimalarials within the last week had a higher prevalence of anergy to tuberculin (OR=1.41 (1.02-1.92)). BCG vaccination was significantly associated with less anergy to tuberculin and diphtheria-tetanus antigens (OR=0.42 (0.28-0.63), OR=0.77 (0.60-0.99), respectively). Children vaccinated with BCG before 1 month of age were more anergic to tuberculin than children vaccinated after 1 month (OR=1.61 (1.19-2.19)). DTP vaccination was associated with less anergy to diphtheria-tetanus antigens (OR=0.40 (0.32-0.49)), but not to tuberculin. Children with a positive reaction to tuberculin were less likely to be anergic to diphtheria-tetanus antigens (OR=0.36 (0.26-0.49)) than children with a negative tuberculin reaction. Children who were vaccinated with BCG before they received their last DTP vaccine were less anergic to diphtheria-tetanus antigens (OR=0.40 (0.16-0.88)) than other DTP-vaccinated children. In conclusion, current disease, rainy season, age below 1 month of age at the time of BCG vaccination, and administration of chloroquine or quinimax within the last 7 days were risk factors for anergy to tuberculin among 7.5-month-old infants. BCG vaccination and a positive tuberculin reaction were associated with a lower prevalence of anergy to both tuberculin and diphtheria-tetanus. Thus, BCG vaccination may contribute to better cell-mediated immune responses among infants.     

Tuberculosis contact tracing among children and adolescents, Brazil

OBJECTIVE: To detect tuberculosis (TB) disease or infection among contacts of pulmonary TB patients. METHODS: Cross-sectional study in a Primary Healthcare unit in Rio de Janeiro (Brazil) with 184 child and adolescent contacts of pulmonary TB patients between March 1995 and March 1997. Subjects underwent clinical evaluation, chest radiographs, and tuberculin skin tests (TST); sputum smears were performed whenever possible. TB cases found were submitted to treatment and infected patients to chemoprophylaxis. Tuberculin converters, who tested positive for TST eight weeks after an initial negative result, received chemoprophylaxis. RESULTS: The sample included 98 boys and 86 girls; age ranged from 0 to 15 years; 26.9% were malnourished according to the Gomez criteria. Concerning the source of infection, 170 cases (92.4%) had household contacts, of which 66.5% were the child's parents. BCG vaccination was verified in 98.4% of children, and 14.7% of children had been revaccinated. Strong TST reactions were observed in 110/181 children. Seventy-six children (41.3%) were considered as infected by M. tuberculosis and 25 cases (13.6%) of TB were detected, of which seven (28%) were asymptomatic. There was greater occurrence of disease when the contact lived with more than one source of infection (p=0.02). CONCLUSIONS: The detection of TB disease and infection was high in the studied population. Contact control must be emphasized, for it allows for the diagnosis of TB in children who are still asymptomatic, in addition to identifying infected subjects who may profit from chemoprophylaxis.     

The effect of Bacille Calmette-Guérin vaccine on tuberculin reactivity in indigenous children from communities with high prevalence of tuberculosis

The Bacille Calmette-Guérin (BCG) vaccine is the most widely used vaccine in the world, however it may cause problems for the appropriate interpretation of the tuberculin skin test (TST). We assessed the diagnostic value of latent infection in vaccinated and unvaccinated indigenous children from communities that have a very high prevalence of adult tuberculosis (TB). A total of 997 children under 15 years old and classified in age groups (0-1.9, 2-5, 6-9 and 10-15 years old) were randomly selected and given TSTs using the Mantoux technique. TST induration values of vaccinated children (n=724) were compared with those of children unvaccinated (n=273). BCG vaccination was not an important cause of false-positive TST, except in communities with a low prevalence of active TB. In conclusion, the results suggested that a history of BCG vaccination on TST+ response after 10 years of vaccination was statistically insignificant but whether at earlier age TST+ reflects most probably the degree of exposure to TB cases than BCG vaccination should be clarified in the future.     

BCG vaccine effectiveness in preventing tuberculosis and its interaction with human immunodeficiency virus infection

BACKGROUND: To explore Bacillus Calmette-Guérin vaccine (BCG) as a protective factor against tuberculosis (TB) and how human immunodeficiency virus (HIV) infection modifies the effect of BCG on TB. METHODS: Two matched case-control studies were conducted. One study compared TB cases and controls who were HIV positive. The second compared TB cases and controls who were HIV negative. The study population consisted of 88 TB cases and 88 controls among HIV-positive individuals and 314 TB cases and 310 controls among HIV-negative individuals. Cases were new TB diagnoses, confirmed by either bacteriology, pathology, radiology or clinical response to treatment; controls were selected from people without TB symptoms and who sought medical attention in the same institution where a case was enrolled. BCG was assessed by the presence of a typical scar. RESULTS: The level of protection against all clinical forms of TB was 22% among HIV positive individuals (odds ratio [OR] = 0.78, 95% CI : 0.48-1.26) and 26% among HIV negatives (OR = 0.74, 95% CI : 0.52-1.05). There was a significant difference (P = 0.002) in the level of protection against extrapulmonary TB (ETB) between HIV-negative (OR = 0.54, 95% CI : 0.32-0.93) and HIV-positive individuals (OR = 1.36, 95% CI : 0.72-2.57). CONCLUSION: BCG has a modest protective effect against all forms of TB independent of HIV status, and BCG confers protection against extrapulmonary TB among HIV-negative individuals. However, HIV infection seems to abrogate the protective effect of BCG against extrapulmonary TB. Our data support the public health importance of BCG vaccine in the prevention of extrapulmonary TB among immunocompetent individuals.     

The presence of a booster phenomenon among contacts of active pulmonary tuberculosis cases: a retrospective cohort

Background  

Assuming a higher risk of latent tuberculosis (TB) infection in the population of Rio de Janeiro, Brazil, in October of 1998 the TB Control Program of Clementino Fraga Filho Hospital (CFFH) routinely started to recommend a two-step tuberculin skin test (TST) in contacts of pulmonary TB cases in order to distinguish a boosting reaction due to a recall of delayed hypersensitivity previously established by infection with Mycobacterium tuberculosis (M.tb) or BCG vaccination from a tuberculin conversion. The aim of this study was to assess the prevalence of boosted tuberculin skin tests among contacts of individuals with active pulmonary tuberculosis (TB).     

Tuberculosis screening in private physicians' offices, Pennsylvania, 1996

OBJECTIVE: To assess tuberculin skin testing practices of physicians after community-wide screening of 1400 children exposed to a pediatrician with active tuberculosis (TB). DESIGN: A self-administered questionnaire. SETTING: Medium-sized city in eastern Pennsylvania. PARTICIPANTS: Pediatricians and family practitioners seeing pediatric patients. MAIN OUTCOME MEASURES: Percentages of physicians who followed published recommendations for placement and reading of TB skin tests published by the American Academy of Pediatrics (AAP) and the Centers for Disease Control and Prevention (CDC). RESULTS: Questionnaires were completed by 60/80 (75%) physicians. The 60 physicians had practiced a mean of 17 years (range 3-38 years), and only one did not do TB skin testing for pediatric patients. The 59 physicians doing TB skin testing reported routinely tuberculin testing more than 900 children per month. Only 8/59 (14%) physicians followed published guidelines for placement and reading of tuberculin tests. Those physicians screened 158 (17%) of the pediatric patients undergoing TB skin testing in a typical month. CONCLUSION: In this community where a highly publicized TB case prompted massive pediatric screening, most physicians seeing children in private practice do not follow standard TB skin testing guidelines. Increased understanding of how private-practice physicians learn about and decide to use recommended standards are needed if tuberculin tests are to be correctly performed and TB appropriately diagnosed.     

Vaccinia scars associated with better survival for adults. An observational study from Guinea-Bissau

BACKGROUND: Live vaccines including BCG and measles may have non-targeted beneficial effects on childhood survival in areas with high mortality. The authors therefore undertook a survey of vaccinia scars to evaluate subsequent mortality. SUBJECTS: Based on a population census, a cohort of 1893 adults in urban Guinea-Bissau was examined in 1998 and followed until 2002. MAIN OUTCOME MEASURE: All cause mortality, excluding accidents. RESULTS: The median age of vaccinia vaccinations had been 16-18 years. Adults with a vaccinia scar had a mortality ratio (MR) of 0.60 (0.41-0.87) compared to those without any scar. The effect was stronger for women. Mortality decreased with each additional vaccinia scar (MR=0.73 (0.56-0.95)). Among 502 individuals with information on HIV infection, the age-adjusted HIV-2 prevalence was 2.45 (1.06-5.65) for those with a vaccinia scar. Control for district, ethnic group, schooling, place of birth, quality of housing and HIV status had little effect on the estimate. Since vaccinia and BCG scars could have been confused, mortality for adults with vaccinia and/or BCG scar was compared to those without, the MR being 0.61 (0.41-0.89). CONCLUSION: Known cultural or socio-economic factors possibly associated with access to vaccination had no influence on the mortality ratio for having a vaccinia scar. Hence, vaccinia vaccination may have a prolonged beneficial effect on adult survival.