Medical examiner samples: a source for dengue surveillance

Post-mortem medical examiner samples may be useful for sentinel surveillance of disorders usually detected by antibody determinations on specimens from ill patients or from surveys. We found anti-dengue IgM positivity in 3(23/780) and anti-dengue IgG positivity in 77(597/777) of sera obtained at the Puerto Rico medical examiner (Institute of Forensic Sciences) in December 2000, April 2001, and October 2001. This approach may be a useful alternative for estimating the population prevalence of serologic markers for dengue and other infectious diseases.

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.

La real Expedición filantrópica de la Vacuna de viruela: monarquía y modernidad en 1803 / The real philanthropic expedition of the smallpox vaccine: monarchy and modernity in 1803

Smallpox resulted in the death of 30 % of those who acquired it, so the preventive method discovered by Edward Jenner (London, 1798) spread very quickly. At the request in 1803 of Carlos IV, king of Spain, his government evaluated offers to carry smallpox vaccine to the colonies. The selected proposal, by doctor Francisco Xavier de Balmis, sought to take the lymph to America and Asia in a chain of arm to arm vaccination of foundlings. The Expedition set sail from Corunna on November 30, 1803, stopped in the Canary Isles, Puerto Rico, and Venezuela and after Caracas (1804) split in two groups. Balmis led some members of the Expedition to Cuba and Mexico. For the trip to the Philippines, in 1805, parents lent their children in exchange for economic compensation and the promise that the boys would be returned home. The Expedition returned to Mexico in August, 1807, but Balmis separately took vaccine to China and returned to Spain. Another contingent of the Expedition, under vice-director José Salvany, took vaccine to what we know as Colombia, Ecuador, Peru and Bolivia. His assistant Manuel Grajales reached the Chilean Patagonia in 1811. This article also comments on three principal themes - the institutional management of the scientific project, the conflicts that characterized its course, and the children's experience. The Vaccine Expedition was a brave and humanitarian endeavor, but also an extraordinary sanitary and administrative success. It was not until the twentieth century that a global eradication campaign eliminated smallpox in the world.

The dengue and dengue hemorrhagic fever epidemic in Puerto Rico, 1994-1995.

From June 1, 1994 to May 31, 1995 a total of 24,700 cases of dengue (7.01/1,000 population) were reported to the laboratory-based surveillance system in Puerto Rico (1991-1994, annual average: 2.55/1,000). Dengue virus 2 predominated. The earliest indicator of epidemic activity was the virus isolation rate in May 1994 (14.0% versus 5.7% average). The male-to-female ratio among cases was 1:1.1; 65.4% were younger than 30 years (the 10 to 19 year age group had the highest incidence, 11.8/1,000). At least 5,687 cases (23.0%) showed a hemorrhagic manifestation; 4,662 (18.9%) were hospitalized, and 40 died (0.2%; 10 laboratory-positive). Two cases documented by laboratory were transmitted by unusual routes--intrapartum and through a bone marrow transplant. Among 2,004 hospitalized cases reported by infection control nurses, 139 (6.9%) fulfilled the criteria for dengue hemorrhagic fever (DHF) and another 13 cases (0.6%) had dengue shock syndrome. This epidemic produced the largest number of hospitalizations, DHF cases, and deaths from any dengue epidemic in Puerto Rico. Severity did not change throughout the year. Surveillance capabilities were maintained by temporary, simplified reporting methods, none of which could be recommended as the single method of choice for surveillance; each must be used (on site, or as a service available from a reference laboratory) at the right time in the epidemic cycle. The utility of comparisons of current and previous data underscores the value of long-term surveillance. Our analysis was unable to document whether significantly increased transmission occurred more often in cities where the water supply was rationed or where the local landfill was closed.

Dengue activity in Puerto Rico during an interepidemic period (1995-1997).

From 1995 to 1997 dengue was reported in Puerto Rico at an average annual rate of 1.75/1,000 population, compared to 6.73 in 1994, an epidemic year. Dengue virus serotypes 1 (DEN-1), -2, and -4 were isolated each year, with DEN-2 predominating in 1995 and 1996, and DEN-4 in 1997. From 1995 through 1997 incidence was highest (0.61-0.77/1,000) in persons under 30 years of age; males and females were equally affected. Among positive cases, 28.3% to 37.9% were hospitalized; 28.9% to 35.2% had hemorrhagic manifestations; at least 1.1% to 1.6% fulfilled the criteria for dengue hemorrhagic fever/dengue shock syndrome; and 0.2% to 0.3% died. Neither hurricane preparations (1995) nor widespread floods (1996) seem to have affected dengue incidence. Most municipalities with the highest laboratory-diagnosed dengue rates in 1995 were in the eastern foothills of the central mountains, an area relatively spared by the 1994 epidemic. In the next two years, at least half of the municipalities with the highest laboratory-diagnosed dengue rates were in the west. The most intense municipal outbreak of this period (DEN-2, Villalba, 1995, rate of 11.67/1,000) is described to highlight the importance of local conditions and epidemiologic history in determining the risk of dengue.

[Bailey K. Ashford, more in his remembrance]. / Bailey K. Ashford, más allá de sus memorias.

The military physician Bailey K. Ashford (Washington, D. C., September 18, 1873--San Juan, Puerto Rico, November 1, 1934) is mostly remembered for having identified in 1899 the cause of fatal anemia prevalent among Puertorican peasants, but he was also a distinguished investigator of other diseases, and organizer of mass medical services, in peace and in war. In spite of Ashford's own sober statements, the great influence of his scientific work in Puerto Rico and the impact of his personality in patients and colleagues have helped cast him as a mythical figure. His personal archives (kept at the library of the University of Puerto Rico's Medical Sciences Campus) make clear that his autobiography presents only a selection among the episodes that would form a complete biography.

A dengue outbreak among camp participants in a Caribbean island, 1995.

BACKGROUND: Dengue, a mosquito-transmitted viral disease, is a risk for visitors in tropical and subtropical areas. Several participants in a community-assistance program in Tortola, British Virgin Islands, in August, 1995, reported dengue-like symptoms either before or soon after leaving the island. METHODS: We conducted a retrospective cohort study to determine the extent of the outbreak, risk factors for illness, and the proportion of inapparent infections. Program participants were interviewed by telephone or mail, and asked to submit a serum sample for dengue diagnosis. A clinically-diagnosed case of dengue was defined as a person with fever and two or more of the following: headache, retro-orbital pain, myalgia, arthralgia, rash, or hemorrhagic manifestations. Serum specimens were tested for virus isolation, polymerase chain reaction (PCR), plaque-reduction neutralization (PRNT) or anti-dengue IgM and IgG antibody. RESULTS: Thirty-two (97%) of the 33 program participants responded; 21 of the 32 (66%) provided at least one serum sample for study. The median age was 17 years; 20 (62%) were women. Of 32 respondents, 22 (69%) met the clinical case definition for dengue: 15 of them (68%) had a positive IgM antibody response and 7 did not submit a serum sample. Dengue 1 virus (DEN-1) was identified by PCR in one case and all 11 positive PRNT results. No asymptomatic infections were identified. No respondent used effective mosquito repellent, and only 2 (6%) used bednets. CONCLUSIONS: A DEN-1 outbreak with a high attack rate (69%) occurred in a group of young short-term community aid workers. There were no asymptomatic infections documented. Participants' rare use of bednets or effective mosquito repellent highlights the importance of providing travelers to tropical areas with information about dengue fever and the recommended precautions to protect against infection.

[Health in Puerto Rico in the 20th century]. / La salud en Puerto Rico en el siglo XX.

The evolution in physical condition, life expectancy at birth, and access to preventive and curative services rapidly improved the quality of life of Puerto Ricans in the twentieth century. The population quadrupled to almost 4 million inhabitants and the crude mortality rate fell from 38 per thousand in 1900 to 7.7 per thousand in 1997, with its most dramatic change (18.6 to 6.7) occurring from 1941 to 1960. The great promoters of health were the general increase in socioeconomic level, improvements in infrastructure, and vaccines; its great scourges were infectious diseases (from hookworm to AIDS) and social dislocations, such as the war of 1917 (accompanied by epidemics and hunger) or the present war between illicit drug distributors. This article summarizes the events in the century related to health and its political and economic contexts, the developments in public health structures and health care, professional education, volunteer organizations, campaigns against infectious diseases, chronic causes of mortality, and environmental problems. Bringing the capacity to defend public health to the level of sophistication available for clinical care is one of the vital challenges of the twenty-first century for Puerto Rico.

Hospitalizations for suspected dengue in Puerto Rico, 1991-1995: estimation by capture-recapture methods. The Puerto Rico Association of Epidemiologists.

Capture-recapture estimations compare the results of 2 or more independent surveillance systems for the same event, and by measuring the degree of overlap between them, provide an estimate of the total number of events, and therefore the completeness of ascertainment in each system. The Puerto Rico Department of Health and the Dengue Branch of the Centers for Disease Control and Prevention (CDC) monitor dengue activity in Puerto Rico through 2 distinct surveillance systems: diagnostic specimens from patients with suspected dengue and infection control nurses' reports on patients hospitalized for suspected dengue. The patient listings from these systems were used in a 2-sample, capture-recapture calculation to estimate the total number of persons with suspected dengue hospitalized from 1991 to 1995. The laboratory positivity rate for suspected dengue cases who submitted appropriately timed serum samples in those years ranged from 72.1% to 81.2%. The laboratory-based (diagnostic sample) surveillance system (routinely used to monitor hospitalizations for suspected dengue) detected an average of 1,197 hospitalized cases during non-epidemic years, and 4,329 cases during the epidemic year of 1994. The detection rate of this system averaged 42% of the numbers derived by the capture-recapture method. In non-epidemic years, an estimated average of 2,791 patients (range = 1,553-3,481) was estimated to have been hospitalized with a clinical diagnosis of dengue, compared with 9,479 during 1994. These results demonstrate the under-detection inherent in passive surveillance systems for hospitalized cases of suspected dengue, and illustrate the value of capture-recapture techniques to better estimate the true incidence of hospitalizations for this disease.

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.

Surveillance for an emerging disease: dengue hemorrhagic fever in Puerto Rico, 1988-1997. Puerto Rico Association of Epidemiologists.

Surveillance for emerging diseases is critically dependent on four factors: reporting methods, case definition, laboratory diagnosis, and knowledge of the disease among health-care professionals. The dengue hemorrhagic fever (DHF) surveillance system in Puerto Rico collects patient data from three sources: dengue case investigation (DCI) forms sent with diagnostic samples, clinical reports from hospital infection control nurses (ICNs), and hospital records. Recruitment of ICN reporting produced a marked increase in notifications (67 to 294). Hospital records of possible DHF cases showed that tests for ascertaining diagnosis (e.g., blood in stool, serum albumin) were frequently not performed. DCI and ICN reports underestimated severity. After hospital record review, the ratio of total DHF cases to cases detected by surveillance was approximately 3:1, whether using clinical criteria or using clinical and dengue laboratory diagnosis. An important determinant for the low sensitivity (28.4%) and high specificity (96.5%) of the surveillance system was the World Health Organization (WHO) clinical definition for DHF. In spite of such limitations, DHF surveillance data in Puerto Rico provide abundant, reliable information for monitoring disease trends. These methods may be applied to other situations to define the characteristics and incidence trends of emerging infections.

An evaluation of modified case definitions for the detection of dengue hemorrhagic fever. Puerto Rico Association of Epidemiologists.

The case definition for dengue hemorrhagic fever (DHF) requires fever, platelets < or = 100,000/mm3, any hemorrhagic manifestation, and plasma leakage evidenced by hemoconcentration > or = 20%, pleural or abdominal effusions, hypoproteinemia or hypoalbuminemia. We evaluated the specificity and yield of modified DHF case definitions and the recently proposed World Health Organization criteria for a provisional diagnosis of DHF, using a data base of laboratory-positive and laboratory-negative reports of hospitalizations for suspected dengue in Puerto Rico, 1994 to 1996. By design, all modifications had 100% sensitivity. More liberal criteria for plasma leakage were examined: 1) adding as evidence a single hematocrit > or = 50% (specificity 97.4%); 2) accepting hemoconcentration > or = 10% (specificity 90.1%); and 3) accepting either hematocrit > or = 50% or hemoconcentration > or = 10% (specificity 88.8%). The new DHF cases identified by these definitions (and percent laboratory positive) were 25 (100.0%), 95 (90.5%), and 107 (91.6%), respectively. In contrast, the provisional diagnosis of DHF (fever and hemorrhage, and one or more of platelets < or = 100,000/mm3, or hemoconcentration > or = 20%, or at least a rising hematocrit [redefined quantitatively as a 5% or greater relative change]) showed a specificity of 66.8%, and identified 318 new DHF cases, of which 282 (88.7%) were laboratory-positive. Very small changes in the criteria may result in a large number of new cases. The modification that accepted either hematocrit > or = 50% or hemoconcentration > or = 10% had acceptable specificity, while doubling the detection of DHF-compatible, laboratory-positive severe cases, but "provisional diagnosis" showed even lower specificity, and may produce inflated DHF incidence figures. Modified case definitions should be prospectively evaluated with patients in a health-care facility before they are recommended for widespread use.

Characteristics of acute pneumonia in human immunodeficiency virus-infected children and association with long term mortality risk. National Institute of Child Health and Human Development Intravenous Immunoglobulin Clinical Trial Study Group.

OBJECTIVE: To describe the epidemiologic, clinical, radiologic, laboratory and treatment characteristics of acute pneumonia and its association with mortality in HIV-infected children. METHODS: Data were collected during a trial of intravenous immunoglobulin (IVIG) for infection prophylaxis (1988 to 1991); CD4+ percentage was measured and HIV RNA was assessed on stored sera collected at baseline and every 3 months. Mortality was recorded during the trial and updated through 1996. All reported physician-diagnosed pneumonia episodes underwent blinded review for trial endpoint classification as acute (new radiologic findings and presence of clinical symptoms) or nonacute. RESULTS: On blinded clinical trial endpoint review of all reported pneumonia episodes (n = 281), only 47% were classified as acute. One hundred thirty-one episodes of acute pneumonia were reported in 93 children (47 in 31 IVIG and 84 in 62 placebo patients, P < 0.01). The incidence of acute pneumonia was 24 episodes per 100 patient years. Findings associated with an acute bacterial process were uncommon (leukocytosis > or =15000/mm3 in 21% and fever > or =103 degrees F in 32% of episodes). Multiple acute episodes occurred in 34% of the children and were associated with increased risk of mortality in a univariate analysis (risk ratio, 2.1; 95% confidence interval, 1.3 to 3.4, P = 0.002), but in a multivariate model only baseline HIV RNA copy number and CD4+ percentage remained independently associated with mortality (relative risk, 2.0 and 1.4, respectively, P < 0.001). CONCLUSION: Acute pneumonia was a common occurrence in HIV-infected children and was associated with long term mortality risk. Multiple episodes of acute pneumonia likely represent a marker of progressive disease and immunologic dysfunction rather than being causally associated with increased long term mortality.

Epidemic leptospirosis associated with pulmonary hemorrhage-Nicaragua, 1995.

In October 1995, epidemic "hemorrhagic fever," without jaundice or renal manifestations, was reported in rural Nicaragua following heavy flooding; 2259 residents were evaluated for nonmalarial febrile illnesses (cumulative incidence, 6.1%) and 15 (0.7%) died with pulmonary hemorrhage. A case-control study found that case-patients were more likely than controls to have ever walked in creeks (matched odds ratio [MOR], 15.0; 95% confidence interval [CI], 1.7-132.3), have household rodents (MOR, 10.4; 95% CI, 1.1-97.1), or own dogs with titers >/=400 to Leptospira species (MOR, 23.4; 95% CI, 3.6-infinity). Twenty-six of 51 case-patients had serologic or postmortem evidence of acute leptospirosis. Leptospira species were isolated from case-patients and potential animal reservoirs. This leptospirosis epidemic likely resulted from exposure to flood waters contaminated by urine from infected animals, particularly dogs. Leptospirosis should be included in the differential diagnosis for nonmalarial febrile illness, particularly during periods of flooding or when pulmonary hemorrhage occurs.

Dengue and dengue haemorrhagic fever.

The incidence and geographical distribution of dengue have greatly increased in recent years. Dengue is an acute mosquito-transmitted viral disease characterised by fever, headache, muscle and joint pains, rash, nausea, and vomiting. Some infections result in dengue haemorrhagic fever (DHF), a syndrome that in its most severe form can threaten the patient's life, primarily through increased vascular permeability and shock. The case fatality rate in patients with dengue shock syndrome can be as high as 44%. For decades, two distinct hypotheses to explain the mechanism of DHF have been debated-secondary infection or viral virulence. However, a combination of both now seems to be the plausible explanation. The geographical expansion of DHF presents the need for well-documented clinical, epidemiological, and virological descriptions of the syndrome in the Americas. Biological and social research are essential to develop effective mosquito control, medications to reduce capillary leakage, and a safe tetravalent vaccine.