Four-year safety follow-up of the tetravalent dengue vaccine efficacy randomized controlled trials in Asia and Latin America.

OBJECTIVE: Our objective was to describe the risk of hospital admission for virologically confirmed dengue (VCD) and the risk of clinically severe hospitalized VCD occurring up to 4 years after the first dose (years 1 to 4) in three randomized clinical trials comparing tetravalent dengue vaccine with placebo. METHODS: The relative risks (RR) for hospitalized VCD from first dose to year 4 were estimated by year and age-group in individual and combined studies. RESULTS: Overall, from Year 1 to Year 4, 233 and 228 participants had at least one episode of hospitalized VCD in the vaccinated (n = 22 603) and placebo (n = 11 301) groups, respectively (RR = 0.511, 95% CI 0.42-0.62). Among these, 48 and 47 cases, respectively, were classified as clinically severe. In children aged ≥9 years, 88 and 136 participants had at least one episode of hospitalized VCD in the vaccinated (n = 17 629) and placebo (n = 8821) groups, respectively (RR = 0.324; 95% CI 0.24-0.43). In vaccinated participants aged <9 years, particularly in those aged 2-5 years, there were more hospitalized VCD cases compared with the control participants in Year 3 but not in Year 4. The overall RR in those aged <9 years for Year 1 to Year 4 was 0.786 (95% CI 0.60-1.03), with a higher protective effect in the 6-8 year olds than in the 2-5 year olds. CONCLUSIONS: The overall benefit-risk remained positive in those aged ≥9 years up to year 4, although the protective effect was lower in years 3 and 4 than in years 1 and 2.

Leptospirosis among patients presenting with dengue-like illness in Puerto Rico.

Leptospirosis is difficult to distinguish from dengue fever without laboratory confirmation. Sporadic cases/clusters of leptospirosis occur in Puerto Rico, but surveillance is passive and laboratory confirmation is rare. We tested for leptospirosis using an IgM ELISA on sera testing negative for dengue virus IgM antibody and conducted a case-control study assessing risk factors for leptospirosis, comparing clinical/laboratory findings between leptospirosis (case-patients) and dengue patients (controls). Among 730 dengue-negative sera, 36 (5%) were positive for leptospirosis. We performed post mortem testing for leptospirosis on 12 available specimens from suspected dengue-related fatalities; 10 (83%) tested positive. Among these 10 fatal cases, pulmonary hemorrhage and renal failure were the most common causes of death. We enrolled 42 case-patients and 84 controls. Jaundice, elevated BUN, hyperbilirubinemia, anemia, and leukocytosis were associated with leptospirosis (p < .01 for all). Male sex, walking in puddles, rural habitation, and owning horses were independently associated with leptospirosis. Epidemiological, clinical, and laboratory criteria may help distinguish leptospirosis from dengue and identify patients who would benefit from early antibiotic treatment.

Increase of leptospirosis in dengue-negative patients after a hurricane in Puerto Rico in 1996 [correction of 1966].

Leptospirosis has rarely been reported in Puerto Rico, although in the period from 1948 to 1952, 208 cases of leptospirosis and an island-wide seroprevalence of antibody to Leptospira of 14% were documented. In Puerto Rico in October 1996, following rainfall and a period of flooding generated by Hurricane Hortense, serum specimens of 4 patients with suspected dengue fever that were negative for dengue tested positive for Leptospira-specific IgM antibodies in a dipstick assay. Subsequently, we used an island-wide dengue laboratory-based surveillance system to determine the increase in leptospirosis after hurricane-generated floods. All anti-dengue IgM-negative patients (n = 142) with disease onset from August 8 to October 6, 1996 from prehurricane and posthurricane groups were investigated for leptospirosis. Laboratory-confirmed leptospirosis cases were defined as microscopic agglutination test titers > or = 1 :400 to 1 or more serovars, or positive immunohistochemistry in autopsy tissues. Four (6%) of 72 prehurricane and 17 (24%) of 70 posthurricane patients had laboratory-confirmed cases of leptospirosis (relative risk [RR] = 4.4, 95% confidence interval [CI] = 1.6-12.4). The mean age of case-patients was 34 years (range = 13-64). Eighteen (86%) of 21 confirmed case-patients were males, including one patient who died (31 years old). Patients were located in 18 (38%) of 48 municipalities that submitted serum samples. Clinical features significantly associated with leptospirosis were eye pain (RR = 1.5, 95% CI = 1.3-1.9), joint pain (RR = 1.4, 95% CI = 1.1-1.6), diarrhea (RR = 1.7, 95% CI = 1.2-2.5), and jaundice (RR = 3.3, 95% CI = 1.5-7.2). This study demonstrates the utility of a dengue laboratory-based surveillance system for the detection of an increase of leptospirosis, which most likely would have gone unrecognized. Leptospirosis is treatable with antibacterial agents; knowledge of this diagnosis may significantly reduce morbidity and mortality.

A deviation bar chart for detecting dengue outbreaks in Puerto Rico.

OBJECTIVES: A Centers for Disease Control and Prevention deviation bar chart (Statistical Software for Public Health Surveillance) and laboratory-based surveillance data were evaluated for their utility in detecting dengue outbreaks in Puerto Rico. METHODS: A significant increase in dengue incidence was defined as an excess of suspected cases of more than 2 SDs beyond the mean for all 4-week periods from April through June (the period of lowest seasonal incidence), 1989 through 1993. An outbreak was defined as a cumulative annual rate of reported dengue greater than 3 per 1000 population. RESULTS: Retrospective application of the system to 1994 data showed agreement with previous analyses. In 1995 and 1996, 36.4% and 27.3%, respectively, of municipalities with a significant increase in reports for 2 or more consecutive weeks before the first week of September had an outbreak, compared with 9.0% (in 1995, P = .042) and 6.0% (in 1996, P = .054) of towns without a significant increase. The system showed sensitivity near 40%, specificity near 89%, and accuracy in classifying municipalities near 84%. CONCLUSIONS: This method provides a statistically based, visually striking, specific, and timely signal for dengue control efforts.

Prevalence of hepatitis B, hepatitis C, and human immunodeficiency virus infection among women attending prenatal clinics in San Juan, Puerto Rico, from 1989-1990.

OBJECTIVE: To evaluate the prevalence of hepatitis B virus (HBV), hepatitis C virus (HCV), and human immunodeficiency virus (HIV) among pregnant women in Puerto Rico. METHODS: An anonymous serosurvey was conducted in four prenatal clinics in San Juan, Puerto Rico, involving women presenting consecutively for their first prenatal visit. RESULTS: Nineteen of 997 pregnant women (1.9%, 95% confidence interval [CI] 1.2-3.0) tested positive for HCV antibody (anti-HCV), and eight (0.8%, 95% CI 0.4-1.6) were HIV seropositive. Of the 992 women for whom serum samples were tested for HBV markers, 91 (9.2%, 95% CI 7.5-11.2) had evidence of past or current HBV infection, and four (0.4%, 95% CI 0.1-1.1) were HBV carriers. The age-specific HBV prevalence ranged from 4.1% among women 15-19 years old to 18.5% among those at least 30 years old (P < .001, chi 2 test for trend). Anti-HCV prevalence was also higher among women at least 30 years old compared to younger women (3.1 versus 1.9%; prevalence ratio 1.6, 95% CI 0.6-4.9), although the difference was not statistically significant. Anti-HCV prevalence was higher among women with past or current HBV infection than among women who were not infected (7.7 versus 1.3%; prevalence ratio 5.8, 95% CI 2.3-14.3). CONCLUSIONS: The prevalence of chronic HBV and HCV infection among pregnant women tested in San Juan, Puerto Rico, is comparable to that among pregnant women in the United States. The prevalence of HIV infection among pregnant women in San Juan is higher than among childbearing women in the United States.