Detection of substandard fixed-dose combination tuberculosis drugs using thin-layer chromatography.

SETTING: A convenience sample of 13 fixed-dose combination (FDC) tuberculosis (TB) drugs from 'The Fixed Dose Combination Project' was analysed in laboratories at the University of Botswana and the US Food and Drug Administration (FDA). OBJECTIVE: To determine actual versus stated content of drugs in these FDCs. DESIGN: Chemical analysis was performed using thin-layer chromatography (TLC) as a screening method, and ultraviolet (UV) spectrophotometry or liquid chromatography (LC) as confirmation. FDCs with content outside of 85-115% of stated concentration were defined as substandard. RESULTS: All 13 FDCs contained the stated drugs. However, four (31%) were substandard, including two (15%) with low rifampicin content, one (8%) with excessive rifampicin, and one (8%) with excessive pyrazinamide. Both FDCs with low rifampicin contained four drugs and failed TLC screening. The FDC with excessive rifampicin was not detected by TLC screening. Using UV as the gold standard, the sensitivity of TLC for low rifampicin was 2/2 (100%), and the specificity was 9/10 (90%). CONCLUSION: This study found that 31% of the FDCs in 'The Fixed Dose Combination Project' had substandard content, irrespective of bioavailability. Low rifampicin content, which can be reliably detected by TLC screening, was identified in both four-drug FDC products and is particularly worrisome. TB drugs should be screened for quality using TLC to optimise treatment outcomes and to prevent increases in acquired drug resistance.

Tuberculosis prevention and control activities in the United States: an overview of the organization of tuberculosis services.

After a 20% increase in tuberculosis (TB) cases between 1986 and 1992, TB cases in the United States have declined from 1993 through 1997, an average of 5 to 7 per cent per year. In this paper, we review trends and the current epidemiology of TB in the US, present a brief history of TB control efforts in the country, and present the key strategies for TB control in the US. We describe the current organizational structure of TB services in the US, the role of the private sector in TB control, and how TB control is funded. Finally we discuss the mechanisms by which TB policy is developed. The US model represents a categorical disease program that combines a centralized role of the national government in development of policy, funding, and in the maintenance of national surveillance, and a decentralized role of state and local jurisdictions, which adapt and implement national guidelines and which are responsible for day-to-day program activities. Given the relative success of this combined approach, other countries facing the challenge of maintaining an effective TB control program in the face of increased decentralization of health services may find this description useful.

Survey of physician use of radiography and sputum smear microscopy for tuberculosis diagnosis and follow-up in Botswana.

SETTING: National survey of physician knowledge, attitudes, and practices for tuberculosis (TB) diagnosis and monitoring in Botswana. OBJECTIVE: To assess adherence to national guidelines for TB diagnosis and monitoring. DESIGN: Questionnaires were mailed to all physicians registered with the Ministry of Health. RESULTS: The response rate was 69%. Diagnostic and follow-up practices differed substantially from national recommendations. Senior District Medical Officers (SDMOs) were the most likely to adhere to guidelines on use of sputum examination for diagnosis (87%) and follow-up (50%); private practitioners were the least likely to follow the same guidelines (53% and 10%, respectively). SDMOs were also less likely to use radiographs for diagnosis (27%); the greatest use was seen in government hospital-based physicians (86%). While most SDMOs had received an introduction to the TB programme and had access to the programme manual and recent information on TB, the majority of other practising physicians in the country did not. CONCLUSION: Recommended diagnostic procedures for TB were not being followed by a substantial percentage of physicians. Efforts are being made to inform hospital-based physicians and private practitioners about TB programme policies. Adherence to programme recommendations is vital to strengthen TB control efforts.

Overseas screening for tuberculosis in immigrants and refugees to the United States: current status.

The number of reported cases of tuberculosis (TB) in foreign-born persons in the United States during 1995 was 8,042, 36% of the national total. The overseas screening of immigrants and refugee visa applicants, which relies on a chest radiograph and smear microscopy, is designed to identify future U.S. residents who have active TB or who are at high risk for TB. In this commentary, we summarize current policies and review retrospective evaluations of the screening system currently in place. The system appears to detect most persons who have active TB at the time of screening. However, active TB is actually diagnosed in < 15% of persons who are identified by screening as having suspected TB and who are evaluated in the United States. To improve the system, more sensitive and specific techniques as well as improved means of data transmission to state and local health departments are needed.

Tuberculosis in sub-Saharan Africa: a regional assessment of the impact of the human immunodeficiency virus and National Tuberculosis Control Program quality.

BACKGROUND: The effect of the human immunodeficiency virus (HIV) epidemic on tuberculosis (TB) has been evaluated for certain countries in sub-Saharan Africa. However, no multi-country comparisons have been performed of the magnitude of the changes in TB case rates and the roles of the HIV epidemic and national TB control program (NTP) quality in these changes. METHODS: We examined trends in TB case rates after 1985 for 20 sub-Saharan African countries, and also from 1975-1984 for 10 of these countries (core countries). Average annual changes in TB case rates after 1985 were stratified by 1992 urban low-risk HIV seroprevalence and by NTP quality, as determined by a survey of international TB experts. RESULTS: Case rates in the core countries decreased by an average of -1.6% per year prior to 1985, but increased by an average of +7.0% per year after 1985 (+7.7% per year after 1985 in all 20 countries). Average annual case rates after 1985 increased approximately twice as fast in countries with high vs low or intermediate HIV seroprevalence ratings. In both the core countries and all 20 countries, the average annual rate of rise in case rates after 1985 decreased as NTP quality rating increased. This relationship persisted even after stratification by HIV seroprevalence rating. CONCLUSIONS: TB case rates have increased in sub-Saharan Africa since 1985. These increases were relatively greater as HIV seroprevalence increased, and relatively lower as NTP quality increased. Improving NTP quality is essential to mitigate the resurgence of TB in the HIV era.

PIP: Specialists in tuberculosis (TB) prevention and control examined trends in TB case rates after 1985 for 20 sub-Saharan African countries and these trends during 1975-84 for 10 of the countries (core countries). They aimed to determine the effect of the HIV epidemic on TB. The 20 countries accounted for 50% of the total population of sub-Saharan Africa and 85% of TB cases. The figures for the core countries were 19% and 27%, respectively. In the core countries, TB case rates fell on average by 1.6% (range, -12.7% to 4.6%) annually before 1985, but increased on average by 7% (range, -2.6% to 18%) thereafter. The TB case rate increased by 7.7% (range, -4.5% to 14.5%) after 1985 in the 20 countries. TB case rates after 1985 increased almost twice as fast in countries with high HIV prevalence ratings when compared to those with low or intermediate HIV prevalence ratings (12.7% vs. 4.6% and 4.5% in core countries and 7.8% and 5.1% in the 20 countries, respectively). In both the core countries and the 20 countries, the annual rate of increase in TB case rates fell as the quality of the national TB control program increased. This held true when the researchers stratified by HIV prevalence. Improving quality had the least impact on the rate of increase in TB case rates in countries with a high HIV seroprevalence. These findings suggest that sub-Saharan African countries should invest in improving the quality of the national TB control program to effect reductions in TB morbidity, even in the face of the HIV epidemic.

Using linked program and birth records to evaluate coverage and targeting in Tennessee's WIC program.

Public health nutrition programs are intended to serve low-income families who are at greater nutritional risk than the general population. Not all persons who are program-eligible are at equal risk, however. It would be desirable to evaluate a program's ability to enroll persons from higher risk backgrounds in the population (coverage) and, conversely, the extent to which those enrolled in this program are at higher risk (targeting). A method for the evaluation of coverage and targeting was developed using data from the Tennessee Women, Infants, and Children Special Supplemental Food Program (WIC) linked with birth certificates. The linked computer file was created by matching the name and date of birth in both record files. The birth records were the common source of information used to characterize the risk background for both the WIC and non-WIC participants. Maternal sociodemographic information on the birth records was used to define the health risk background of each child. The coverage and targeting of "at-risk" children were computed and compared for 50 counties or county-aggregates in Tennessee. Considerable variation in the coverage and targeting rates of at-risk children was observed among Tennessee counties, although the counties within each WIC administrative region tended to have similar coverage and targeting patterns. Using the existing data in linked program and vital records provides a direct evaluation of a program. Coverage and targeting evaluation can be used to detect underserved populations within small geographic areas.

The high cost and low efficacy of weekly viral cultures for pregnant women with recurrent genital herpes: a reappraisal.

The use of weekly cultures to prevent neonatal infection among infants of pregnant women who have histories of genital herpes has been controversial since a decision analysis study in 1983 suggested that this strategy was not cost-effective and would avert relatively few cases of neonatal herpes simplex virus infection. Using more recent and better data, the authors reanalyzed this approach to reducing neonatal herpes infection. The reanalysis revealed that a national screening program would prevent only 1.8 cases of neonatal herpes in the United States annually, at a cost of more than 37 million dollars per case averted. The program would cost nearly 7 million dollars per quality-adjusted life year gained when only infant deaths are taken into consideration. When maternal deaths from excess cesarean deliveries are taken into account, over 44 million dollars would be spent for every quality-adjusted life-year gained. On the basis of the strategy's limited benefits and low cost-effectiveness, the authors support the American College of Obstetrics and Gynecology's position of abandoning the recommendation for weekly prenatal herpes cultures.

Feeding practices and growth in Yemeni children.

A nutritional survey in the Tihama region of Yemen allowed an analysis of the relationship between infant feeding practices and the growth of children 3-23 months of age. The survey was conducted in 1979 on a representative sample of 364 preschool children 3-23 months of age. After adjustment for demographic and socioeconomic factors, breast feeding was found to be associated with higher weight-for-length and weight-for-age. The strongest beneficial effect of breast feeding on weight-for-length was seen at 3-6 months, a weaker effect at 7-12 months, and essentially no effect over 12 months of age. A higher weight-for-age was seen in breast-fed infants 3-6 months of age only. Introducing other foods was associated with higher weight-for-length only in children 13-23 months of age. Neither breast feeding nor introducing other foods was associated with length-for-age. Infant feeding practices appear to be associated with weight gain, but not linear growth in Yemeni infants.

Comparing the prevalence of smoking in pregnant and nonpregnant women, 1985 to 1986.

The 1990 health objectives for the nation state that pregnant women should be only half as likely to smoke as nonpregnant women. To assess progress toward meeting this objective, we used cross-sectional data from the 26 states in the Behavioral Risk Factor Surveillance System in 1985 and 1986. We compared the prevalence of self-reported smoking among pregnant (N = 836) and nonpregnant (N = 18,025) women aged 18 to 45 years. Overall, pregnant women were 70% as likely to be current smokers as nonpregnant women (prevalence ratio, 0.7; 95% confidence interval, 0.6 to 0.8), while blacks showed the largest pregnancy-associated reduction in the prevalence of smoking (prevalence ratio, 0.5; 95% confidence interval, 0.3 to 0.9). Most of the difference in smoking prevalence occurred not because pregnant women were less likely to have ever smoked, but because pregnant women were more likely to have quit smoking than nonpregnant women. However, unmarried pregnant white women were 40% more likely to smoke than their nonpregnant counterparts (prevalence ratio, 1.4; 95% confidence interval, 1.1 to 1.7). We conclude from this analysis that the 1990 health objective for smoking among pregnant women is unlikely to be achieved. Clinicians providing care to pregnant women need to pay increased attention to smoking cessation.

Preventing neonatal herpes. The value of weekly viral cultures in pregnant women with recurrent genital herpes.

To reduce the occurrence of neonatal herpes, laboratory screening with viral cultures during the last four to eight weeks of pregnancy has been recommended as a way to recognize women with subclinical herpes infection at delivery. Screening efforts have focused on a group of high-risk women, especially those with recurrent genital herpes infection. Using the technique of decision analysis, we examined the benefits, risks, and costs of viral culture screening for women with recurrent genital herpes. In a cohort of 3.6 million women, we estimate that screening would avert 11.3 neonatal deaths and 3.7 cases of severe retardation, but 3.3 women would die as a result of cesarean deliveries necessitated by culture results. Weekly viral cultures would diagnose one fourth of women with subclinical recurrent infection at delivery. The cost per case averted would be approximately $1.8 million. Future screening recommendations should consider not only the number of cases averted but also the effectiveness of screening and the costs in both maternal lives and medical care dollars.