Strategies to decrease tuberculosis in us homeless populations: a computer simulation model.

CONTEXT: The rate of tuberculosis (TB) among US homeless persons may be 20 times that of the general adult population. Studies suggest that the majority of urban homeless TB cases are attributable to ongoing transmission of TB. Optimal TB-control strategies in both chronically and transiently homeless populations are not known. OBJECTIVE: To examine the effects of TB-control strategies on projected TB cases and deaths in US homeless populations using a computer-based simulation model. DESIGN, SETTING, AND POPULATION: The US general population and a theoretical population of 2 million homeless individuals in 1995 were divided into 18 clinical states based on the risk for or presence of TB and human immunodeficiency virus (HIV) infection in a semi-Markov model. MAIN OUTCOME MEASURES: Prevalence of transiently and chronically homeless individuals with active TB and deaths from TB as a function of public health measures taken to control and eliminate TB, including improvement of treatment effectiveness, improvement in access to treatment, and vaccination with BCG. RESULTS: A 10% increase in access to treatment among homeless persons with active TB produced larger declines in predicted TB cases and deaths after 10 years (cases and deaths among chronically homeless persons decreased 12.5% and 19.8% and among transiently homeless persons dropped 35.9% and 32.4%, respectively) than improvements in the effectiveness of treatment programs (cases and deaths among chronically homeless persons declined 7.2% and 3.1% and among transiently homeless persons dropped 10.9% and 4.1%, respectively). A 10% increase in access to treatment among homeless persons with latent TB infection led to a 6.7% decline in TB among chronically homeless persons and a 5.7% decline among transiently homeless persons, while a 10% improvement in effectiveness of treatment for latent TB infection was associated with declines of 3.0% and 3.3%, respectively. When treatment for latent TB infection was modeled to be the same in vaccinated and nonvaccinated populations, BCG vaccination led to TB case declines of 15.4% and 21.5% in chronically and transiently homeless populations, respectively. CONCLUSIONS: Overcoming barriers faced by homeless individuals in accessing TB treatment programs will be crucial to reducing the burden of TB in this high-risk group. Increased treatment access, improvement in the effectiveness of treatment programs, and BCG vaccination of HIV-negative homeless individuals have the best chance to markedly decrease TB morbidity and mortality.

Pediatric tuberculosis: what needs to be done to decrease morbidity and mortality.

OBJECTIVE: Tuberculosis (TB) control programs have been less successful among children than among adults in the United States. Between 1992 and 1997, the rate of decline of TB cases among 0- to 14-year-old children was less than the rate of decline among any other age group of US-born persons. Because of the higher prevalence of active TB among adults and their higher infectivity, most programs for TB in the United States have targeted adults. The inherent assumption has been that by targeting adults, from whom children may become infected, TB morbidity and mortality among children also will be reduced effectively. METHODS: Using a semi-Markov model that divided the US population into age groups <15 years old and >/=15 years old and into 18 clinical states based on the risk for or presence of TB and human immunodeficiency virus infection, we developed a computer-based simulation model to examine the effect of a range of potential TB control strategies on projected TB cases and deaths in children. We compare the impact of interventions targeted at children with the impact of interventions targeted at adults on pediatric morbidity and mortality. RESULTS: After 10 years, a 5% increase in the number of adults with TB who enter treatment would only lead to a.05% decline in TB cases among children, compared with predicted cases without this intervention. Improving treatment efficacy among those adults who are already receiving treatment for their TB leads to a smaller decline in cases among children of only.003%. In contrast, a 5% increase in the number of children who enter treatment leads to a 25% decline, after 10 years, in the number of TB cases among children and a 16% decline in the number of TB deaths. In the presence of immigration of tuberculin-positive children, the benefit of targeting programs directly at children is magnified. CONCLUSIONS: Marginal changes in programs targeted directly at children are significantly more effective at further reducing pediatric TB morbidity and mortality than the same changes in programs targeted at adults with the indirect goal of reducing spread to children. Marginal increases in the number of children who enter treatment are far more effective at decreasing morbidity and mortality than equivalent marginal increases in treatment effectiveness. Unfortunately, declining insurance coverage and increasing restrictions on services to immigrants have made it harder for those who are at greatest risk of TB to get medical care. Marginal increases in preventive therapy rates substantially reduce future pediatric TB cases and deaths among children with TB infection and human immunodeficiency virus.

Medical students' evaluations of curriculum innovations at ten North American medical schools.

The authors recount medical educators' calls in the 1980s to reform general professional medical education by supplementing the standard lecture-lab biomedical curriculum with new biopsychosocial pedagogy and emphases. They then report selected medical students' evaluations of corresponding curriculum reform efforts that were in place by 1990 at eight U.S. and two Canadian medical schools known for being innovators. From interviews conducted in 1992-93 with a group of three to nine medical students at each school, the authors report two findings. First, the students' positive evaluations converged: at all ten schools they invariably appreciated curriculum reform efforts of any sort that encouraged individuation, connection, and diversity. Second, the students' negative evaluations diverged: specifically, those enrolled at the smaller schools with more distinctly teaching-service missions, schools where innovation was more wholesale, even extending across the entire curriculum, objected to curricula that provide too much in the way of new pedagogy and emphases and too little standard instruction; conversely, those enrolled at the larger schools with more comprehensive teaching-research-service missions, schools where innovation must be more piecemeal, often course by course, objected to curricula that provided too little in the way of new pedagogy and emphases and too much standard instruction. Suggesting that the smaller schools studied may be over-supplementing--and the larger schools under-supplementing--standard biomedical with new biopsychosocial pedagogy and emphases, the authors make two recommendations: first, that medical educators at schools of every size and sort contemplating curriculum reform of any scope recognize that medical students invariably appreciate educational opportunities for individuation, connection, and diversity; second, that the same educators, but especially those at the smaller teaching-service medical schools considering more wholesale innovation, recognize that medical students must soon compete for residencies and posts in a rapidly changing health care environment and thus want effective instruction per se, whether it be delivered by a lecturer or a tutor, in class or in tutorial, on a ward or in a clinic. That would be the meaning, they conclude, of student-centered learning, however it were tailored.

The pursuit of global health: the relevance of engagement for developed countries.

The globalisation of the world economy and the consequent increase in commerce, travel, and communication have brought benefits to virtually every country. But these changes also bring risks that cannot be addressed adequately within traditional national borders. These risks include emerging infectious diseases, resulting in part from increased prevalence of drug-resistant pathogens; exposure to dangerous substances, such as contaminated foodstuffs, and banned and toxic substances; and violence, including chemical and bioterrorist attack. By investing in global health, industrialized countries will not only benefit populations in desperate and immediate need of assistance, but also themselves--through protecting their people, improving their economies, and advancing their international interests. This paper describes the rationale for involvement of industrialised countries in global health, and suggests a means for its coordination.

Whose blood is safer? The effect of the stage of the epidemic on screening for HIV.

BACKGROUND: With improvements in HIV antibody test (ELISA) performance, the window of time between infection and seroconversion becomes a major source of error in HIV screening. The authors examined its impact on the false-reassurance rate (FRR). METHODS: Test sensitivity was modeled as the product of two factors: the inherent sensitivity (sensitivity when antibody is present) and the probability that antibody is present in infected blood. A model of HIV and AIDS incidence was used to derive an estimate of the probability of remaining in the seronegative window (pw) among those who are infected. With plausible assumptions, this probability approaches 0.03. The FRR was then estimated as a function of the probability of remaining in the seronegative window, the prevalence of HIV, and the inherent sensitivity of the ELISA test were estimated. RESULTS: The FRRs for two blood donor groups, one with an HIV prevalence of 0.004 and a typical probability of remaining in the seronegative window (pw = 0.03) and the other with a higher prevalence of 0.017 but fewer donors in the window (pw = 0.003), are equal (140 per million donors) if the blood is negative on a single ELISA test. After two negative tests or a single test that can detect antibody more reliably, however, the FRR is much higher in the group with the higher pw (= 120 per million compared with 50 per million), because the greater numbers of donors in the window more than offsets the lower prevalence. CONCLUSION: With improvements in inherent sensitivity of ELISA by virtue of technical progress or retesting, the prevalence of HIV infection may no longer play the critical role in degrading the results of blood screening. As inherent test performance improves, tests are increasingly likely to miss infected blood because of the seronegative-window error rather than because of measurement error. Window error plays a proportionally greater role during the early stages of HIV dissemination in a population where the incidence of new HIV infection is high relative to the incidence of AIDS. These findings may explain, in part, the recent observation that cases of transfusion of contaminated blood often take place in areas where AIDS epidemics have started recently. They also suggest that the traditional strategy of soliciting blood donors from low-prevalence populations may not always be optimal, unless such populations are truly low-risk.

Evaluation of tuberculosis control policies using computer simulation.

OBJECTIVE: To develop more effective methods to assess tuberculosis (TB) control strategies so we can meet national goals for the elimination of TB in the United States. DESIGN: Using a semi-Markov model that divided the US population into 3 age groups and 18 clinical states based on disease status and risk for TB and human immunodeficiency virus (HIV) infection, we measured the effects of 5 changes in TB policy, introduced singly and in combination: (1) increased coverage and (2) improved efficacy of preventive therapy, (3) increased coverage and (4) improved efficacy of treatment, and (5) introduction of BCG vaccination. RESULTS: A BCG vaccination program that reached 10% of eligible children and 1% of eligible adults each year would produce a 17% reduction in cases and an 11% decline in deaths over 10 years. Preventive therapy programs among the general population would have little effect on the number of TB cases, but a program targeting HIV-infected patients would reduce HIV-associated TB cases and deaths 14% to 20%. A 10% improvement in the coverage and efficacy of both preventive therapy and treatment, coupled with the BCG vaccination program, would lead to a 47% decline in TB cases and a 50% decline in TB deaths relative to baseline over 10 years. CONCLUSIONS: Improvements in treatment coverage or effectiveness alone are unlikely to reach established national goals for the elimination of TB. These goals can be achieved through a combination of improvements in current programs with targeted preventive therapy and BCG vaccination programs.

The efficacy of bacillus Calmette-Guérin vaccination of newborns and infants in the prevention of tuberculosis: meta-analyses of the published literature.

OBJECTIVE: To quantify the efficacy of vaccination of infants with bacillus Calmette-Guérin (BCG) against tuberculosis. DATA SOURCES: MEDLINE with index terms BCG vaccine, tuberculosis, and human; lists of all known studies provided by experts at the Centers for Disease Control and Prevention, the World Health Organization, and other organizations. STUDY SELECTION: A total of 1264 articles and abstracts were reviewed for details on BCG vaccination, the availability of concurrent vaccinated and unvaccinated groups, and a tuberculosis outcome. Seventy articles were reviewed in depth for method of vaccine allocation used to create comparable groups, age at vaccination of study participants, comparability of surveillance and follow-up of recipient and concurrent control groups in trials, an appropriately defined control group in case-control studies, and outcome measures (tuberculosis cases and/or deaths). Five prospective trials and eleven case-control studies of vaccination during infancy were included in the present analyses. DATA EXTRACTION: We recorded study design, age range of study population, number of patients enrolled, efficacy of vaccine, location of the study, and a series of items to assess the potential for bias in study design, follow-up, and diagnosis. We extracted or computed vaccine efficacy by years since vaccination wherever possible. At least two readers independently extracted data and evaluated data validity. DATA SYNTHESIS: The relative risk (RR) or odds ratio (OR) for tuberculosis in vaccinated versus unvaccinated infants was the measure of vaccine efficacy analyzed. A random-effects method estimated a weighted average RR or OR from data extracted from the trials and case-control studies. The protective effect was then computed by 1-RR or 1-OR. Overall, the protective effect of vaccination against cases of tuberculosis was 0.74 (95% confidence interval [95% CI], 0.62 to 0.83) when estimated from four randomized controlled trials, and 0.52 (95% CI, 0.38 to 0.64) when estimated from nine case-control studies. Five trials reporting deaths from tuberculosis showed a BCG protective effect of 0.65 (95% CI, 0.12 to 0.86), five studies reporting on meningitis showed a protective effect of 0.64 (95% CI, 0.30 to 0.82), and three studies of disseminated tuberculosis showed a protective effect of 0.78 (95% CI, 0.58 to 0.88). Three case-control studies included separate results for laboratory-confirmed cases of tuberculosis. These studies documented a protective effect of 0.83 (95% CI, 0.58 to 0.93). In a random-effects regression model of the nine case-control studies, study validity score explained 15% of the heterogeneity among study-estimated protective effects, suggesting that better studies reported greater efficacy. Three trials and six case-control studies provided some age-specific information that allowed us to examine the duration of BCG efficacy. Most of this evidence suggested that BCG efficacy may persist through 10 years after infant vaccination. CONCLUSION: BCG vaccination of newborns and infants significantly reduces the risk of tuberculosis--by over 50%, on average. Protection has been observed across many populations, study designs, and forms of tuberculosis. Rates of protection against cases that are confirmed by laboratory tests, reflecting reduced error in disease classification and consequently more accurate estimates of BCG efficacy, are highest at 83%.

Geographic latitude and the efficacy of bacillus Calmette-Guérin vaccine.

In a meta-analysis of the efficacy of BCG vaccine for preventing tuberculosis, study sites at a greater distance from the equator were associated with a higher efficacy. In a random-effects regression analysis of prospective studies, geographic latitude alone accounted for 41% of the between-study variance. Many factors that vary with latitude may influence the effectiveness of BCG vaccine by modifying the susceptibility of human hosts, the pathogenecity of the organism, or host-agent interactions. These factors include socioeconomic conditions, genetic composition of the population, climate, exposure to sunlight, diet and nutrition, presence of nontuberculous mycobacteria in the environment, completeness of surveillance and follow-up in studies of BCG vaccine, virulence of locally prevalent strains of Mycobacterium tuberculosis, and storage and viability of BCG vaccine. This paper describes the biological plausibility, epidemiologic evidence, and other scientific data bearing on the influence of these factors on the efficacy of BCG vaccine.

Efficacy of BCG vaccine in the prevention of tuberculosis. Meta-analysis of the published literature.

OBJECTIVE: To quantify the efficacy of BCG vaccine against tuberculosis (TB). DATA SOURCES: MEDLINE with index terms BCG vaccine, tuberculosis, and human. Experts from the Centers for Disease Control and Prevention and the World Health Organization, among others, provided lists of all known studies. STUDY SELECTION: A total of 1264 articles or abstracts were reviewed for details on BCG vaccination, concurrent vaccinated and unvaccinated groups, and TB outcome; 70 articles were reviewed in depth for method of vaccine allocation used to create comparable groups, equal surveillance and follow-up for recipient and concurrent control groups, and outcome measures of TB cases and/or deaths. Fourteen prospective trials and 12 case-control studies were included in the analysis. DATA EXTRACTION: We recorded study design, age range of study population, number of patients enrolled, efficacy of vaccine, and items to assess the potential for bias in study design and diagnosis. At least two readers independently extracted data and evaluated validity. DATA SYNTHESIS: The relative risk (RR) or odds ratio (OR) of TB provided the measure of vaccine efficacy that we analyzed. The protective effect was then computed by 1-RR or 1-OR. A random-effects model estimated a weighted average RR or OR from those provided by the trials or case-control studies. In the trials, the RR of TB was 0.49 (95% confidence interval [CI], 0.34 to 0.70) for vaccine recipients compared with nonrecipients (protective effect of 51%). In the case-control studies, the OR for TB was 0.50 (95% CI, 0.39 to 0.64), or a 50% protective effect. Seven trials reporting tuberculous deaths showed a protective effect from BCG vaccine of 71% (RR, 0.29; 95% CI, 0.16 to 0.53), and five studies reporting on meningitis showed a protective effect from BCG vaccine of 64% (OR, 0.36; 95% CI, 0.18 to 0.70). Geographic latitude of the study site and study validity score explained 66% of the heterogeneity among trials in a random-effects regression model. CONCLUSION: On average, BCG vaccine significantly reduces the risk of TB by 50%. Protection is observed across many populations, study designs, and forms of TB. Age at vaccination did not enhance predictiveness of BCG efficacy. Protection against tuberculous death, meningitis, and disseminated disease is higher than for total TB cases, although this result may reflect reduced error in disease classification rather than greater BCG efficacy.

Acute encephalopathy and chronic neurological damage after pertussis vaccine.

In August 1991, the Institute of Medicine released a report entitled Adverse Effects of Pertussis and Rubella Vaccines, which examined, among others, the relation between immunization with whole-cell diphtheria-tetanus-pertussis (DTP) vaccine and both acute encephalopathy and chronic neurological damage. The committee reviewed information from a wide range of both professional and lay sources and found that the evidence is consistent with a possible causal relation between DTP vaccine and acute encephalopathy, although it is insufficient to establish causality. The range of excess risk of acute encephalopathy following DTP immunization is consistent with that estimated from the National Childhood Encephalopathy Study: 0.0 to 10.5 cases per million immunizations. The committee concluded that the evidence is insufficient to indicate either the presence or absence of a causal relationship between DTP vaccine and permanent neurological damage. The evaluative methods used by the committee are briefly described and the evidence underlying its conclusions presented.

Chronic arthritis after rubella vaccination.

In August 1991 the Institute of Medicine released a report entitled "Adverse Effects of Pertussis and Rubella Vaccines" that examined, among other relations, the relation between immunization with the RA 27/3 rubella vaccine strain and chronic arthritis. The committee spent 20 months reviewing a wide range of information sources including case series and individual case reports published in peer-reviewed journals and reported by vaccine manufacturers; unpublished case reports from physicians, parents, and other concerned persons; epidemiological studies; and laboratory studies. There were no animal studies available. The committee found that the evidence is consistent with a causal relation between the RA 27/3 rubella vaccine strain and chronic arthritis in adult women, although the evidence is limited in scope. Proving that rubella vaccination can cause chronic arthritis will require a better understanding of pathogenetic mechanisms and additional well-designed studies. We briefly describe the committee's evaluative methods and present the evidence underlying its conclusion.

Adverse events following pertussis and rubella vaccines. Summary of a report of the Institute of Medicine.

In August 1991, the Institute of Medicine released a report entitled Adverse Effects of Pertussis and Rubella Vaccines, which examined 18 adverse events in relation to diphtheria-tetanus-pertussis (DTP) vaccine and four adverse events in relation to the currently used rubella vaccine strain, RA 27/3. The committee spent 20 months reviewing a wide range of information sources, including case series and individual case reports, both published and unpublished, epidemiologic studies, studies in animals, and other laboratory studies. The committee found that the evidence indicates a causal relation between DTP vaccine and anaphylaxis and between the pertussis component of DTP vaccine and extended periods of inconsolable crying or screaming. The committee also reported that the evidence indicates a causal relation between the rubella vaccine and acute arthritis in adult women. The committee found the available evidence weaker but still consistent with a causal relation between DTP vaccine and two conditions--acute encephalopathy and hypotonic, hyporesponsive episodes--and between rubella vaccine and chronic arthritis in adult women. Estimated incidence rates of these adverse events following vaccination are provided, where possible. The committee found that the evidence does not indicate a causal relation between the DTP vaccine and infantile spasms, hypsarrhythmia, Reye's syndrome, and sudden infant death syndrome. The committee found insufficient evidence to indicate either the presence or absence of a causal relation between DTP vaccine and chronic neurologic damage, aseptic meningitis, erythema multiforme or other rash, Guillain-Barré syndrome, hemolytic anemia, juvenile diabetes, learning disabilities and attention-deficit disorder, peripheral mononeuropathy, or thrombocytopenia, and between rubella vaccine and radiculoneuritis and other neuropathies or thrombocytopenic purpura. The committee's evaluative methods are briefly described and a summary of research needs is provided.