Decline in sexually transmitted disease prevalence in female Bolivian sex workers: impact of an HIV prevention project.

OBJECTIVE: To implement an HIV prevention intervention among female commercial sex workers (CSW), and to monitor key outcomes using routinely collected clinical and laboratory data. DESIGN: Cross-sectional and longitudinal analysis of data from an open-enrollment cohort. SETTING: One public sexually transmitted disease (STD) clinic and about 25 brothels in La Paz, Bolivia. PARTICIPANTS: A total of 508 female CSW who work at brothels and attend a public STD clinic. INTERVENTION: Improved STD clinical care, supported by periodic laboratory testing, and behavioral interventions performed by a local non-governmental organization. MAIN OUTCOME MEASURES: Prevalence of gonorrhea, syphilis (reactive plasma reagin titer > or = 1 : 16), genital ulcer disease, chlamydial infection, and trichomoniasis; self-reported condom use in the previous month; and HIV seroprevalence. RESULTS: From 1992 through 1995, prevalence of gonorrhea among CSW declined from 25.8 to 9.9% (P < 0.001), syphilis from 14.9 to 8.7% (P = 0.02), and genital ulcer disease from 5.7 to 1.3% (P = 0.006); trends in prevalence of chlamydial infection and trichomoniasis were not significant. Self-reported condom use during vaginal sex in the past month increased from 36.3 to 72.5% (P < 0.001). In a multivariate analysis, condom use was inversely associated with gonorrhea [odds ratio (OR), 0.63; 95% confidence interval (Cl), 0.41-0.97], syphilis (OR, 0.39; 95% Cl, 0.23-0.64), and trichomoniasis (OR, 0.44; 95% Cl, 0.32-0.71). In 1995, HIV seroprevalence among CSW was 0.1%. CONCLUSION: Effective prevention interventions for female CSW can be implemented through public services and non-governmental organizations while HIV rates are still low, and key outcomes can be monitored using data obtained from periodic screening examinations.

Rotavirus vaccines--from licensure to disease reduction.

Rotavirus infection produces a serious health burden in the United States, causing an estimated > 100,000 hospitalizations and > 100 deaths annually. This health burden is comparable to that for measles, pertussis, mumps, and varicella before vaccines for these diseases were routinely given to children. Rotavirus vaccines have the potential to significantly reduce a serious public health problem in the United States. However, while development and licensure of vaccines is a major breakthrough, it represents only the first step in disease prevention. Vaccines must be recommended by major immunization advisory committees, financed in both the public and private sectors, and successfully integrated into the existing vaccination schedule. Vaccines must reach all targeted children, and monitoring systems must be established or adapted to better determine vaccine safety and disease impact. Reevaluation of disease prevention strategies must be ongoing and fueled by new information on safety and disease reduction.

Morbidity and mortality among low birth weight infants exposed to an intravenous vitamin E product, E-Ferol.

In April 1984, the US FDA was notified of an unusual clinical syndrome consisting of ascites, liver and renal failure, thrombocytopenia, and death among low birth weight infants exposed to an intravenous vitamin E preparation, E-Ferol. The product, which had not been tested for safety prior to marketing, was voluntarily withdrawn from the market in early April. To further investigate the reported associations, the FDA conducted a retrospective cohort study among seven neonatal intensive care units where the product had been used. Standardized abstraction forms were completed for infants admitted to a unit between Nov 1, 1983, and April 30, 1984. Included in the study were 379 infants weighing 2,000 g or less and surviving at least two days; 148 (39%) had been exposed to E-Ferol. Compared with the unexposed infants, the exposed infants were more likely to die and to have ascites, hepatomegaly, thrombocytopenia, and a combination of clinical events similar to the syndrome initially reported. We conclude that the use of E-Ferol in these neonatal intensive care units was associated with increased morbidity and mortality among exposed infants.

Postmarketing surveillance for neurologic adverse events reported after hepatitis B vaccination. Experience of the first three years.

In 1982, the Centers for Disease Control, the Food and Drug Administration, and the manufacturer created a surveillance system to monitor spontaneous reports of adverse events occurring after inoculation with the new plasma-derived hepatitis B vaccine (Heptavax-B, Merck Sharp and Dohme, West Point, PA). In the three years between June 1, 1982 and May 31, 1985, an estimated 850,000 persons received the vaccine. During that period, a total of 41 reports were received for one of the following neurologic adverse events: convulsions (five cases), Bell's palsy (10 cases), Guillain-Barré syndrome (nine cases), lumbar radiculopathy (five cases), brachial plexus neuropathy (three cases), optic neuritis (five cases), and transverse myelitis (four cases). Half of these occurred after the first of three required vaccine doses. There were no deaths. Calculation of the relative risks of these illnesses after hepatitis B vaccination was highly dependent on diagnostic classification of the cases, estimates of the size of the vaccinated population, background incidence of the diseases, and the length and distribution of the hypothetical at-risk interval used in the analysis. Other factors important in judging the results of the study could not be measured, including underreporting. In some analyses, Guillain-Barré syndrome was reported significantly more often than expected (p less than 0.05, Poisson probability distribution). However, no conclusive epidemiologic association could be made between any neurologic adverse event and the vaccine. Even if such an association did exist, the preventive benefits of the vaccine in persons at high risk for hepatitis B would unequivocally outweigh the risk of any neurologic adverse event.

Cardiorespiratory arrests temporally associated with injection of intravenous ampicillin in infants: investigation of a suspected cluster.

In August 1985, the FDA received reports of infants who had cardiorespiratory arrests associated with a widely used IV ampicillin product. The events occurred during July and August 1985 in three hospitals located in different parts of the United States. To assess the possibility of a product defect, an epidemiologic investigation was undertaken to determine whether the suspect ampicillin product was associated with an excess number of serious adverse events among infants in 1985. Because complete ampicillin brand information was unavailable for two of the three hospitals, a nonconcurrent cohort study was conducted to test whether the proportion of serious adverse events among infants who were hospitalized between July 1 and Aug 23, 1985, and exposed to any brand of IV ampicillin was different from the proportion of serious adverse events among infants who were hospitalized during the same time in 1984 and exposed to IV ampicillin. No statistically significant difference was found. A follow-up incidence density study at the hospital for which complete ampicillin brand information was known determined that the suspect ampicillin product was not associated with an increased number of serious adverse events in 1985. No common lots of the suspect ampicillin product were identified at the three hospitals. It was concluded that the suspect ampicillin product was not the cause of the cluster of serious adverse events observed among infants in July and August 1985 based on epidemiologic findings.

Adverse reactions reported following receipt of Haemophilus influenzae type b vaccine: an analysis after 1 year of marketing.

An analysis of adverse reactions occurring after receipt of Haemophilus influenzae type b vaccine and reported to the Food and Drug Administration during the first year of marketing of the product was performed. During the period April 1985 to May 1986, adverse reaction reports on 152 patients, excluding those of vaccine failure and concurrent infection, were received. Several adverse reactions not previously recognized, including convulsions, allergic reactions such as anaphylactoid-like and serum sickness-like reactions, and vomiting were received. The vast majority of adverse reactions were benign. Because there are many biases that result in the reporting of or failure to report an adverse reaction, it is not possible to derive a rate of reactions from these data. Furthermore, causality cannot be inferred from any single report. The data, however, indicate that, in light of widespread use of the vaccine, its use appears to be safe.

National patterns of aspirin use and Reye syndrome reporting, United States, 1980 to 1985.

The number of cases of Reye syndrome reported annually to the Centers for Disease Control declined markedly between 1980 and 1985. In this article, we present pharmaceutical marketing research data that suggest sharp decreases in the use and purchase of children's aspirin between 1980 and 1985. These trends appear to correspond to the decrease in reporting of Reye syndrome cases. Additionally, analysis of physician mentions of aspiring and acetaminophen for treating flu and chickenpox showed statistically significant trends toward decreasing recommendations for the use of aspirin and significant trends toward increasing recommendations for use of acetaminophen. Trends in wholesale purchases of aspirin and acetaminophen by drug stores from 1979 through 1985 demonstrated a significant decline for the 81-mg children's aspirin tablet and an increase in purchases of children's acetaminophen products. Many factors may influence physician and parents' choice of analgesic/antipyretic medication, including information about Reye syndrome. Data suggest that a continuing decline in the use of aspirin for children may be accompanied by a continuing decline in the reported number of Reye syndrome cases.

Fatal hepatic necrosis due to pyrimethamine-sulfadoxine (Fansidar).

Pyrimethamine-sulfadoxine has been associated with severe and fatal cutaneous reactions as well as transient liver damage. We report the case of a patient who died of progressive hepatic failure caused by pyrimethamine-sulfadoxine administration. In addition, we summarize reports made to the Food and Drug Administration since 1982 that focus on hepatotoxic reactions to pyrimethamine-sulfadoxine. We suggest that fatal hepatic injury can occur after treatment with pyrimethamine-sulfadoxine and that physicians who prescribe the drug should be aware of this possibility.

Prospective surveillance of Haemophilus influenzae type b disease in Dallas County, Texas, and in Minnesota.

Among children less than 12 years of age residing in Dallas County, Texas, and in the state of Minnesota we conducted prospective, active surveillance of invasive Haemophilus influenzae disease. During 18 months, 616 cases were identified, of which 600 were caused by type b organisms. The annual incidence of disease was significantly greater in Dallas than in Minnesota (109 v 68/100,000 children younger than 5 years of age, P less than .001) and was greater in Dallas, even when rates for white children in the two regions were compared (P less than .001). Other regional differences were observed. In Dallas, a larger proportion of cases were in children attending day-care centers (27% compared with 12% in Minnesota, P less than .001) and more patients attended day care for greater than 40 h/wk (56% compared with 30% in Minnesota, P less than .001). Outer membrane protein subtyping of isolates revealed that in Dallas 6U isolates were associated significantly with cases in black children who attended day care. In Minnesota, but not in Dallas, isolates with subtype 1H were associated significantly with cases in children in day care. These data indicate that there are regional differences in the epidemiology of type b Haemophilus disease that may relate to differences in strains, day-care practices, or other unknown cultural or environmental factors. Finally, because only 15% of systemic Haemophilus disease in these regions occurred in children in the age groups recommended for vaccination (24 to 59 months), the new Haemophilus type b polysaccharide vaccine is expected to have a limited impact on the overall incidence of disease.

The risk of subsequent transmission of Hemophilus influenzae type B disease among children in day care. Results of a two-year statewide prospective surveillance and contact survey.

To determine the risk of Hemophilus influenzae type b disease among children attending day-care facilities who were exposed to a primary case of invasive hemophilus disease, we conducted a two-year (August 1982 through July 1984) statewide prospective study involving active surveillance for H. influenzae disease and a 60-day follow-up of the children's day-care contacts. We identified 185 patients with primary invasive hemophilus type b disease who were under six years of age and who attended a total of 195 day-care facilities (centers or private homes). There were 4102 children in attendance at these day-care facilities when the primary cases occurred; 4034 (98 percent) were followed for 60 days or more after the onset of illness in the patients with primary disease. A total of 2612 children were considered classroom contacts of the patients with primary disease, because they were cared for in the same home or the same room in a larger facility, but they were not siblings of the index patients. Of these classroom contacts, 370 from 0 to 23 months of age and 716 from 24 to 47 months of age did not receive rifampin chemoprophylaxis. We could confirm no subsequent H. influenzae disease among contacts. Our results suggest that the risk of subsequent hemophilus disease in contacts of patients in day-care facilities is significantly lower than that previously reported for siblings and day-care contacts.

Adverse respiratory and cardiovascular events attributed to timolol ophthalmic solution, 1978-1985.

Between September 1978 and December 1985, 450 case reports of serious respiratory and cardiovascular events and 32 case reports of death attributed to ophthalmic timolol were received by the United States Food and Drug Administration and the National Registry of Drug-Induced Ocular Side Effects. Two hundred sixty-seven patients (55%) experienced a cardiac arrhythmia or a bronchospasm-related event. The median age was 68 years (n = 365). Fifty-five percent of the patients were women and 45% were men (n = 41). Of the 212 persons for whom medical history was provided, 129 (61%) had respiratory disease, 65 (31%) had cardiovascular disease, 13 (6%) had other illnesses, and five (2%) had no underlying illness. Of the 318 patients for whom data on duration of drug use were available 106 (33%) experienced their adverse event within one week of beginning timolol therapy: 73 (23%) had their events on the first day of therapy. Of 192 patients for whom information was available 177 (92%) improved after the drug was discontinued.

Severe cutaneous reactions among American travelers using pyrimethamine-sulfadoxine (Fansidar) for malaria prophylaxis.

In 1982, the fixed combination of pyrimethamine and sulfadoxine (Fansidar) became available in the United States, and was recommended for use in travelers at risk of acquiring chloroquine-resistant Plasmodium falciparum. Prior to that time, no reports of severe cutaneous reactions had appeared in the medical literature despite widespread use for more than 8 years in both Europe and malarious areas of the developing world. In the fall of 1984, the Centers for Disease Control received reports of 4 cases of toxic epidermal necrolysis (including 3 fatalities) among Americans who had used pyrimethamine-sulfadoxine (PYR/SDX) for the prevention of malaria. Subsequent investigation into severe cutaneous reactions associated with the use of this drug by American travelers detected 24 cases of erythema multiforme, Stevens-Johnson syndrome, or toxic epidermal necrolysis. Twenty-three of the 24 patients concurrently used chloroquine. Seven patients died. No risk factors in the development of these reactions other than the use of PYR/SDX could be identified. Among American travelers, we estimate that these reactions occur in 1 per 5,000-8,000 users, and that fatal reactions occur in 1 per 11,000-25,000 users. This higher than expected incidence necessitates that the use of PYR/SDX for the prevention of malaria be reconsidered. In the United States it is now recommended that the routine weekly use of the drug be reserved for those travelers at highest risk of acquiring chloroquine-resistant P. falciparum, when alternate prophylactic regimens are not deemed appropriate.

Liver involvement in the sulfone syndrome.

A patient being treated with dapsone developed a hypersensitivity reaction with typical features of the "sulfone syndrome," including fever, malalse, and hepatitis. All abnormalities rapidly reversed with discontinuance of the dapsone regimen and institution of prednisone therapy. Hepatic involvement may be a prominent feature of the sulfone syndrome and may be of the hepatocellular or cholestatic type. Based on our review of the Food and Drug Administration reports, this syndrome appears to be relatively uncommon, but physicians need to recognize that expression of this syndrome may be incomplete. More clinical data are necessary to better define the incidence and pathogenesis of sulfone-induced liver disease.

Results of nationwide screening of blood and plasma for antibodies to human T-cell lymphotrophic III virus, type III.

From April 22 to July 28, and from October 7 to November 3, 1985 the American Red Cross, the Council of Community Blood Centers, the American Association of Blood Banks, and the American Blood Resources Association provided the Food and Drug Administration with data at 2-week intervals on human T-lymphotropic virus type III (HTLV-III) test kit results at blood and plasma collection centers. Reports were received from over 150 blood collection centers that screened 2,502,829 units of blood for antibody to HTLV-III by enzyme-linked immunosorbent assay (ELISA) during nine 2-week surveillance intervals. Of these, 25,324 or 1.01 percent were initially reactive and 8443 or 0.34 percent were repeatedly reactive. The repeatedly reactive rate for women was 0.33 percent and for men 0.30 percent. Data for source plasma was collected at 275 locations and tested at eight central laboratories showed that for 2,603,652 units screened (which may represent multiple collections from the same donor) 3978 or 0.15 percent were repeatedly reactive. Screening results from both blood and plasma collection centers varied over time and among kits.

Comparison of the enzyme immunoassay, immunodiffusion, and complement fixation tests in detecting antibody in human serum to the A antigen of Blastomyces dermatitidis.

Using a new enzyme immunoassay (EIA) and standard immunodiffusion (ID) and complement fixation techniques for antibody to the A antigen of Blastomyces dermatitidis, we tested serum from 27 patients with blastomycosis diagnosed histopathologically or by culture; 20 with diagnoses made during 1981 through 1983 (Group A) and 7 during 1974 through 1976 (Group B). We also studied 30 control subjects with Mycoplasma pneumoniae infection (17 subjects), histoplasmosis (6 subjects), coccidioidomycosis (1 subject) and no known disease (6 subjects). Detectable antibody by all 3 tests was present more often for Group A than for Group B, possibly because of delay in testing. Enzyme immunoassay was the most sensitive test; a 1:8 or greater titer was present in acute-phase serum of all Group A patients tested, and a 1:64 or greater titer was associated with disseminated disease (p = 0.003). A positive ID was also more common in disseminated (88%) than in localized (33%) disease. Enzyme immunoassay titers of 1:16 were present in 4 control subjects, 3 with histoplasmosis. The 100% predictive values of a negative EIA and positive ID suggest that these tests are useful for serologic screening (EIA) and serologic confirmation (ID) of suspected blastomycosis, particularly in disseminated disease. Enzyme immunoassay titers of 1:32 or greater strongly support the diagnosis and titers of 1:16 or less may indicate localized disease or be nonspecific. None of the serologic tests predicted disease progression or reactivation.