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International Notes Dengue Type 3 Infection -- Nicaragua and Panama, October-November 1994

The geographic range and incidence of dengue virus activity in the Americas substantially increased from 1980 to 1994. During this period, all dengue activity in the Americas was associated with dengue serotypes 1, 2, and 4 (DEN-1, DEN-2, and DEN-4). On November 25, 1994, the Ministry of Health of Nicaragua announced the isolation of dengue type 3 (DEN-3) from two children hospitalized with minor hemorrhagic manifestations in Managua. Subsequently, DEN-3 virus was isolated from two persons with dengue fever in Panama. These cases represent the first isolation of DEN-3 from autochthonous cases in the Americas since 1977. This report describes these cases and dengue activity in Nicaragua and Panama and summarizes public health activities to control dengue fever in the Americas.

On October 22, 1994, a 5-year-old boy was hospitalized in Managua with symptoms of classic dengue fever (i.e., fever, vomiting, and rash). On October 23, a 10-year-old girl from Managua was hospitalized with similar symptoms. Both children had an uneventful clinical course and recovered. DEN-3 virus was isolated and reisolated (for confirmation) from blood samples from both patients by the Pedro Kouri Institute of Tropical Medicine in Havana. Serologic analyses confirmed that both were primary dengue infections.

DEN-3 virus also was isolated from blood samples of two patients with symptoms of dengue fever in Panama by the Gorgas Memorial Laboratory in Panama City. The first case occurred in the province of Chiriqui (sample collected on October 11) and the second, in the province of Panama (sample collected on November 14). Genetic typing of the initial DEN-3 isolate from Panama at CDC indicated the virus belongs to the Sri Lanka/India genotype, which caused major dengue hemorrhagic fever (DHF) epidemics in Sri Lanka and India during 1989-1992.

During 1994, a countrywide dengue epidemic occurred in Nicaragua (1994 estimated population: 4,300,000). A total of 20,469 dengue cases (4.8 per 1000 population) was reported: the attack rate was highest in the province of Leon (11.9 cases per 1000); the largest number of cases (7631; attack rate: 6.4 per 1000) was reported in Managua. The National Diagnostic and Reference Center documented probable dengue infection (i.e., presence of antiflavivirus immunoglobulin M) in patients from 15 (83%) of the 18 health-care regions. Of the 20,469 reported cases, 1247 (6.1%) had hemorrhagic manifestations; 900 (4.4%) patients were hospitalized. Reviews of medical records at two hospitals indicated that 35 (5.2%) of 676 hospitalized patients met the diagnostic criteria for dengue hemorrhagic fever (DHF). Six cases of suspected DHF were fatal.

In October and November, as the result of increased dengue transmission in Managua, the Ministry of Health initiated a multifaceted response to control Aedes aegypti, the mosquito vector of dengue. This response included ultralow-volume application of insecticides (deltamethrin or cypermethrin); indoor application of mosquito larvicide (temephos {Abate{Registered} * }); and a national, community-based campaign to eliminate mosquito production sites. These activities were supported by efforts to educate the community. By the end of November, the weekly number of reported cases decreased substantially. In late November, an international team sponsored by the Pan American Health Organization (PAHO) traveled to Nicaragua to reinforce laboratory diagnostic capabilities, obtain epidemiologic information, evaluate the severity of disease produced by DEN-3, and assist national authorities in their efforts to control the outbreak.

An outbreak of dengue, which began in July 1994, also occurred in Panama; DEN-1 was the predominant virus serotype isolated. As of December 28, a total of 716 laboratory-diagnosed cases originating from eight of the 13 provinces (attack rate: 27.4 per 100,000 persons) had been reported. Reported by: M Palacio, JJ Amador, F Acevedo, J de los Reyes, A Ramirez, A Gonzalez, G Huelva, Ministry of Health, Managua; R Jimenez, Hospital La Mascota, F Ruiz, Hospital Manolo Morales, Managua; R Cuadra, Hospital Escuela, Leon, Nicaragua. MG Guzman, G Kouri, M Soler, M Alvarez, R Rodriguez, Pedro Kouri Institute of Tropical Medicine, E Martinez, Hospital William Soler, Havana. E Quiroz, V Bayard, C Campos, MO Vasquez, Ministry of Health, Panama. Div of Communicable Disease Prevention and Control, Pan American Health Organization, Washington, DC, and Nicaragua. Dengue Br, Div of Vector-Borne Infectious Diseases, National Center for Infectious Diseases, CDC.

Editorial Note

Editorial Note: Dengue fever is an acute, mosquito-transmitted viral disease characterized by fever, headache, arthralgia, myalgia, rash, nausea, and vomiting. Infections are caused by any of the four virus serotypes. Although most dengue infections result in relatively mild illness, some can produce DHF. Based on the World Health Organization case definition (1), a case of DHF must meet the following criteria: 1) fever, 2) minor or major hemorrhagic manifestations, 3) thrombocytopenia ( less than or equal to 100,000/mm3), and 4) objective evidence of increased capillary permeability (e.g., hemoconcentration {hematocrit increased by greater than or equal to 20%}, pleural effusions {evidenced by chest radiography or other imaging method}, or hypoproteinemia). A case of dengue shock syndrome (DSS) must meet all the criteria for DHF plus hypotension or narrow pulse pressure (less than or equal to 20 mm Hg); the fatality rate for patients with DSS can be as high as 44% (2).

In 1994, outbreaks of dengue were reported from Brazil, Costa Rica, Dominican Republic, Haiti, Mexico, Puerto Rico, and Venezuela. In Nicaragua, an outbreak in 1992 was localized in Leon province and associated with DEN-2 and DEN-4 viruses; an outbreak in June and July 1993 was focused in Leon and adjacent Chinandega province, but no virus was isolated. A limited outbreak of DEN-2 (14 laboratory-confirmed cases) occurred in Panama City in 1993 and was the first recorded outbreak of dengue in Panama since 1942.

DEN-3 was first isolated in the Americas (in Puerto Rico) in 1963 (3) and subsequently caused epidemics in Jamaica and the eastern Caribbean during that year (4). Although DEN-3 has been isolated from international travelers returning to the Americas from other geographic regions (5), this serotype was last isolated in the region (in Puerto Rico) in 1977 (6). The identification of autochthonous transmission of DEN-3 in two countries in the Americas (Nicaragua and Panama) in 1994 has important implications for public health because most residents of urban areas in the American tropics are susceptible to this serotype. In particular, all persons in the American tropics who are aged less than 16 years (approximately one third of the population of Latin America) and all persons living in Ae. aegypti-infested areas who were not infected with DEN-3 during 1963-1978 are at risk for infection with this virus. The appearance of DEN-3 also may increase the risk for DHF resulting from secondary, heterotypic infection (7) or from the introduction of a particularly virulent genotype of DEN-3 (8).

The international response to the outbreak in Nicaragua was specified by a contingency plan developed by health agencies in 1993 to address the potential for reintroduction of DEN-3 into the Americas. This plan highlighted the importance of effective, laboratory-based surveillance programs for dengue and DHF in the Americas. Because of increased DEN-3 activity in other regions and repeated detection of DEN-3 in travelers returning to the Americas, PAHO alerted member countries of these events during April-May 1994 and recommended actions to follow after the identification of an autochthonous case of DEN-3. These actions include prompt investigation to define the magnitude and distribution of the DEN-3 virus in the country and, if the distribution is determined to be limited and circumscribed, efforts to eradicate mosquitoes in the affected area.

PAHO recently published a document for the prevention and control of dengue in the Americas (9), which includes a detailed emergency plan for the control of epidemic dengue and DHF. During 1992-1994, these guidelines were presented by PAHO to national representatives of Ae. aegypti-infested countries in the Americas. In addition, during 1994, PAHO teams reviewed national dengue-control programs in selected countries and assisted national authorities in preparing or updating contingency plans for outbreaks.

Health-care providers should consider dengue in the differential diagnosis of all patients who have symptoms compatible with dengue and who reside in or have visited any tropical areas. When dengue is suspected, the patient's blood pressure, hematocrit, and platelet count should be monitored for evidence of hypotension, hemoconcentration, and thrombocytopenia. Acetaminophen products are recommended for management of fever because of the anticoagulant properties of acetylsalicylic acid (i.e., aspirin). Acute- and convalescent-phase serum samples should be obtained for viral isolation and serodiagnosis.

Suspected dengue cases should be reported to the state or territorial health department; the report should include a clinical summary, dates of onset of illness and blood collection, and other epidemiologic information (e.g., a detailed travel history with dates and location of travel). Serum samples should be sent for confirmation through state health department laboratories to CDC's Dengue Branch, Division of Vector-Borne Infectious Diseases, National Center for Infectious Diseases, 2 Calle Casia, San Juan, PR 00921-3200; telephone (809) 766-5181; fax (809) 766-6596.


  1. World Health Organization. Dengue hemorrhagic fever: diagnosis, treatment, and control. Geneva: World Health Organization, 1986.

  2. Tassniyom S, Vasanawathana S, Chirawatkul A, Rojanasuphot S. Failure of high-dose methylprednisolone in established dengue shock syndrome: a placebo-controlled, double-blind study. Pediatrics 1993;92:111-5.

  3. Russell PK, Buescher EL, McCown JM, Ordonez J. Recovery of dengue viruses from patients during epidemics in Puerto Rico and East Pakistan. Am J Trop Med Hyg 1966;15:573-9.

  4. Ehrenkranz NJ, Ventura AK, Cuadrado RR, Pond WL, Porter JE. Pandemic dengue in Caribbean countries and the southern United States: past, present, and potential problems. N Engl J Med 1971;285:1460-9.

  5. Rigau-Perez JG, Gubler DJ, Vorndam AV, Clark GG. Dengue surveillance -- United States, 1986-1992. In: CDC surveillance summaries (July). MMWR 1994;43(no. SS-2):7-19.

  6. Gubler DJ. Dengue and dengue hemorrhagic fever in the Americas. P R Health Sci J 1987;6: 107-11.

  7. Halstead SB. Pathogenesis of dengue: challenges to molecular biology. Science 1988;239: 476-81.

  8. Lanciotti RS, Lewis JG, Gubler DJ, Trent DW. Molecular evolution and epidemiology of DEN-3 virus. J Gen Virol 1994;75:65-75.

  9. Pan American Health Organization. Dengue and dengue hemorrhagic fever in the Americas: guidelines for prevention and control of dengue and dengue hemorrhagic fever in the Americas. Washington, DC: Pan American Health Organization, 1994; scientific publication no. 548.

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