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Dengue fever

Dengue and dengue hemorrhagic fever (DHF) are acute febrile diseases, found in the tropics, with a geographical spread similar to malaria. Caused by one of four closely related virus serotypes of the genus Flavivirus, family Flaviviridae, each serotype is sufficiently different that there is no cross-protection and epidemics caused by multiple serotypes (hyperendemicity) can occur. Dengue is transmitted to humans by the mosquito Aedes aegypti (rarely Aedes albopictus). more...

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Signs and symptoms

The disease is manifested by a sudden onset of fever, with severe headache, joint and muscular pains (myalgias and arthralgias — severe pain gives it the name break-bone fever) and rashes; the dengue rash is characteristically bright red petechia and usually appears first on the lower limbs and the chest - in some patients, it spreads to cover most of the body. There may also be gastritis with some combination of associated abdominal pain, nausea, vomiting or diarrhoea.

Some cases develop much milder symptoms, which can, when no rash is present, be misdiagnosed as a flu or other viral infection. Thus, travelers from tropical areas may inadvertently pass on dengue in their home countries, having not being properly diagnosed at the height of their illness. Patients with dengue can only pass on the infection through mosquitoes or blood products while they are still febrile.

The classic dengue fever lasts about six to seven days, with a smaller peak of fever at the trailing end of the fever (the so-called "biphasic pattern"). Clinically, the platelet count will drop until the patient's temperature is normal.

Cases of DHF also shows higher fever, haemorrhagic phenomena, thrombocytopenia and haemoconcentration. A small proportion of cases leads to dengue shock syndrome (DSS) which has a high mortality rate.

Diagnosis

The diagnosis of dengue is usually made clinically. The classic picture is high fever with no localising source of infection, a petechial rash with thrombocytopenia and relative leukopenia.

Serology and PCR (polymerase chain reaction) studies are available to confirm the diagnosis of dengue if clinically indicated.

Treatment

The mainstay of treatment is supportive therapy. The patient is encouraged to keep up oral intake, especially of oral fluids. If the patient is unable to maintain oral intake, supplementation with intravenous fluids may be necessary to prevent dehydration and significant hemoconcentration. A platelet transfusion is indicated if the platelet level drops significantly.

Epidemiology

The first epidemics occurred almost simultaneously, in Asia, Africa, and North America in the 1780s. The disease was identified and named in 1779. A global pandemic began in Southeast Asia in the 1950s and by 1975 DHF had become a leading cause of death among children in many countries in that region. Epidemic dengue has become more common since the 1980s - by the late 1990s, dengue was the most important mosquito-borne viral disease affecting humans after malaria, there being around 40 million cases of dengue fever and several hundred thousand cases of dengue hemorrhagic fever each year. In February 2002 there was a serious outbreak in Rio De Janeiro, affecting around one million people but only killing sixteen.

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Dengue fever outbreak in a recreation club, Dhaka, Bangladesh
From Emerging Infectious Diseases, 4/1/04 by Yukiko Wagatsuma

An outbreak of dengue fever occurred among employees of a recreation club in Bangladesh. Occupational transmission was characterized by a 12% attack rate, no dengue among family contacts, and Aedes vectors in club areas. Early recognition of the outbreak likely limited its impact.

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Large outbreaks of dengue fever are rarely reported from occupational or institutional settings (1), probably because a small proportion of Aedes mosquitoes are infected with dengue viruses (2), and in dengue-endemic areas, many adults are immune. Dengue has recently reemerged in Bangladesh; in contrast with the situation in countries where dengue has long been endemic, adults appear to become ill with dengue more often than children (3).

We investigated an outbreak of dengue fever among employees of a Recreation Club for expatriates in Dhaka. The 636-member club, which occupied 92,820 sq ft within a residential area, had 107 employees. Initial cases were evaluated by an embassy physician in early October 2001. Club management requested our investigation to define the magnitude of the outbreak and recommend prevention and control strategies.

The Study

We defined a case of dengue as a febrile illness lasting [greater than or equal to] 3 days during September or October, 2001, with confirmation of dengue infection by presence of antibodies in sera consistent with dengue infection or with presence of dengue viruses in acute-phase sera, detected by reverse transcriptase--polymerase chain reaction (RT-PCR). Cases were identified through occupational absentee logs and through results of initial laboratory testing of acute-phase sera (as ordered by physicians).

Two batches of serum specimens were tested: 18 serum specimens were collected from ill persons by their physicians, and all consenting employees were asked to provide serum specimens 1 month after the outbreak (specimens were collected on November 21, 25, and 26, 2001). Among acute-phase sera, specimens from five patients, collected during the first 5 days of illness, were evaluated for dengue viruses by RT-PCR for serotype-specific dengue viral RNA (4).

Acute- and convalescent-phase sera were tested for immunoglobulin (Ig) G and IgM dengue antibodies through capture enzyme-linked immunosorbent assay (5,6) (MACELISA). Specimens with [greater than or equal to] 40 units of IgG or IgM antibodies were considered positive for dengue infection. Ratios of IgM to IgG antibodies of <1.8 were considered indicative of secondary exposure (i.e., previous exposure to dengue virus), and a ratio of [greater than or equal to] 1.8 was considered suggestive of primary (first-time) exposure (5).

Written informed consent was taken from each study participant. This study was approved by the ethical review committee of International Centre for Diarrhoeal Disease Research, Bangladesh (ICDDR,B). Interviews with consenting employees were from November 21 through 26, 2002; standardized questionnaires collected sociodemographic information, recent illnesses, febrile illnesses among family members, behaviors and activities, severity of illness, health-seeking behavior, and medications. Detailed information was collected about activities in and around the club. Weight and height were measured; body mass index <20 kg/[m.sup.2] was defined as underweight (7). Data were entered into FoxPro, Version 2.6 (Microsoft Corporation, Redmond, WA) and analyzed using SPSS, Version 10.0 (SPSS Inc., Chicago, IL).

A larval survey was conducted on October 20, 2001. All objects containing water (wet containers) were noted, and water from each was sampled and investigated for presence of larvae (larvae were reared to adult stage for species identification).

One hundred (94%) of 107 employees consented to participate. Dengue fever was confirmed in 13 (12%) of 107 employees, including 12 employees who experienced illness onset within a 10-day period in October (Table 1). One case occurred 10 days earlier (13% attack rate). Twelve (92%) case-employees were male. No severe cases of dengue hemorrhagic fever occurred according to World Health Organization criteria (8), but insufficient data were available to rule out grades 1 and 2. One employee was hospitalized; none died. Eleven other employees had febrile illnesses of [greater than or equal to] 3 days duration in September or October (Figure); however, their dengue serologic assays were negative.

[FIGURE OMITTED]

Ten (77%) participants had dengue antibodies in convalescent-phase sera. Samples from three participants had antibodies present in acute-phase sera only. One patient had dengue virus detected by RT-PCR with PCR pattern consistent with dengue serotype 3 (den-3).

Ratios of IgM to IgG suggested first-time infection among seven (54%) participants and secondary infection in six participants. In addition to the 13 cases of dengue, samples from two employees had dengue antibodies detected during the November serosurvey; the employees had not been ill. One had evidence of primary infection and one of secondary infection on the basis of the IgM/IgG ratio.

In addition to fever in all 13 dengue-positive case-employees (as required by the case definition), 11 (85%) had headache, 5 (39%) had myalgias, and 3 (23%) reported gum bleeding. Nine (69%) patients sought care from clinic or hospital; four persons with dengue did not seek care and reported using medication to alleviate symptoms.

Among 308 family members residing with the 100 employees, 21 (7%) family members were reported to be ill with fever during September and October. The rate (14%) of febrile illnesses among family members was significantly higher among 11 employees with febrile illness with negative dengue assays than among the 13 dengue patients (2%; p = 0.04; Table 2).

The first three dengue cases occurred among security guards. They spent most working hours on the perimeter of the club, particularly around the east and west sides. Overall 3 (23%) of 13 security guards were cases compared with 10 (11%) of 87 other participating employees. Three case-patients (gardener, receptionist, and tennis ball boy) shared significant time, i.e., > 1 hour, with the first three case-patients around the main entrance, as well as within the canteen, west side and laundry room, and changing room areas. Subsequent case-patients represented a wide variety of occupations, and these employees spent time in a variety of locations around the club. The staff did not have living quarters at the club.

Epidemic dengue did not occur among club members. While surveillance was not systematically conducted, 2 (0.3%) of 636 members were known to have had dengue fever during October.

We compared data from case-employees with 76 other employees (noncase-employees) who did not have febrile illnesses during September or October. Age distribution was similar for case-employees (mean 32 years) and noncase-employees (mean 36 years). Differences in sex, duration of employment, body mass index, working hours, time spent indoors or outdoors, medications, or smoking were not significant.

Case-employees (100%) were more likely than noncase-employees (83%) to spend any time within the canteen area during break time (Kendall's [tau], p < 0.01). Case-employees (62%) were also more likely than noncase-employees (33%) to come to the club by walking (odds ratio = 3.3; 95% confidence interval 1.0 to 11.0; p < 0.05). Mosquito repellent use was associated with a slightly reduced likelihood of dengue infection (0% in case-employees and 9% in noncase-employees; Kendall's [tau], p < 0.05).

A total of 23 larvae-positive containers were found among 34 wet containers (container index = 68) (Table 3); 364 larvae (103 Ae. aegypti and 261 Ae. albopictus) were identified in stagnant water covering surface lids of 20 metal drums used for security (to block traffic) at the west perimeter.

Conclusions

Intense focal transmission of dengue viruses occurred within an occupational setting in a community experiencing endemic dengue. Focal intensity is highlighted by a 12% attack rate among employees for a 2-week period, compared with no known cases of dengue among nuclear family members. In other Asian countries where dengue is established and where multiple serotypes circulate, outbreaks of dengue fever in occupational settings are uncommon since adults are usually immune; disease is highest in children (8). Other febrile illnesses were occurring simultaneously among employees; these illnesses were probably caused by another communicable disease, as suggested by a higher attack rate of febrile illnesses among family members of febrile employees who did not have dengue.

Dengue viruses are transmitted by infected mosquitoes during feeding, which may occur several times a day, for a 1- to 4-week lifetime (9). The larval survey showed that Aedes mosquitoes were present in working areas. High concentrations of Aedes larvae in water on security drum surfaces may have provided a mechanism for this outbreak. The first three cases were among security guards who were often in close proximity with the security drums. The guards also spent time inside the club (eating, praying, changing clothes, and taking breaks). The security guards may have been exposed to dengue while on patrol outside of the club, and once infected, transmitted dengue viruses to adult Aedes mosquitoes feeding on them while they spent time inside the club. Mosquitoes, thus infected, were able to quickly infect other employees working or resting within the club, perhaps within the staff canteen, resulting in a burst of illnesses. The end of intense transmission coincided with recognition of the outbreak, aggressive use of insecticides, and removal of breeding sites.

The outbreak likely resulted from conditions which promoted rapid transmission of dengue viruses, such as high vector density and many susceptible (nonimmune) people within close quarters. Primary infection among seven cases supports the notion that dengue has recently emerged in Bangladesh. No club members were case-patients, reflecting the importance of duration of exposure in risk for transmission.

Early recognition of the outbreak may have helped limit its impact (10). Institutional or systematic monitoring of suspected cases, i.e., surveillance, supported by prompt laboratory confirmation, may help to contain such outbreaks. Integrating and targeting vector control as soon as a cluster of cases is detected can suppress transmission and minimize numbers of cases.

Acknowledgments

We acknowledge the assistance of Kimberly Ottwell and the ICDDR,B Dengue Scientific Working Group; Rajib Chowdhury, Shirin Sultana, and Tanjin Akter for assisting in interviews and entomological assessment; Rabindranath Sarker for blood collection; Mahmuda Khatun for technical assistance with laboratory assays; and the Armed Forces Research Institute of Medical Sciences for providing training and reagents for serologic studies.

The work was supported by the United States Agency for International Development.

References

(1.) Lyerla R, Rigau-Perez JG, Vorndam AV, Reiter P, George AM, Potter IM, et al. A dengue outbreak among camp participants in a Caribbean island, 1995. J Travel Med 2000;7:59-63.

(2.) Chang Yk, Pang FY. Dengue virus infection in field populations of female Aedes aegypti and Aedes albopictus in Singapore. Trop Med Int Health 2002:322-30.

(3.) Rahman M, Rahman K, Siddque AK, Shoma S, Kamal AHM, Ali KS, et al. First outbreak of dengue hemorrhagic fever, Bangladesh. Emerg Infect Dis 2002;8:738-40.

(4.) Lanciotti RS, Calisher CH, Gubler DJ, Chang GJ, Vorndam AV. Rapid detection and typing of dengue viruses from clinical samples by using reverse transcriptase-polymerase chain reaction. J Clin Microbiol 1992;30:545-51.

(5.) Vaughn DW, Nisalak A, Solomon T, Kalayanarooj S, Nguyen MD, Kneen R, et al. Rapid serologic diagnosis of dengue virus infection using a commercial capture ELISA that distinguishes primary and secondary infections. Am J Trop Med Hyg 1999;60:693-8.

(6.) Innis BL, Nisalak A, Nimmannitya S, Kusalerdchariya S, Chongswasdi V, Suntayakorn S, et al. An enzyme-linked immunosorbent assay to characterize dengue infections where dengue and Japanese encephalitis co-circulate. Am J Trop Med Hyg 1989;40:418-27.

(7.) Promoting healthy weights: a discussion paper. Ottawa, Canada: Health Services and Promotion Branch, Health and Welfare; 1988.

(8.) World Health Organization. Dengue haemorrhagic fever: diagnosis, treatment, prevention and control. 2nd ed. Geneva: The Organization; 1997.

(9.) Costero A, Edman JD, Clark GG, Kittayapong P, Scott TW. Survival of starved Aedes aegypti (Diptera: Culicidae) in Puerto Rico and Thailand. J Med Entomol 1999;36:272-6.

(10.) Wang CH, Chang NT, Wu HH, Ho CM. Integrated control of the dengue vector Aedes aegypti in Liu-Chiu village, Ping-Tung County, Taiwan. J Am Mosq Control Assoc 2000;16:93-9.

Dr. Wagatsuma is an assistant scientist in the department of International Health, Bloomberg School of Public Health, Johns Hopkins University. She has been based at ICDDR,B for more than 3 years. Before that, she conducted infectious disease research in Africa for more than 10 years.

Address for correspondence: Robert Breiman, ICDDR,B: Centre for Health and Population Research, Mohakhali, GPO Box 128, Dhaka-1000, Bangladesh; fax: 880-2-8823963; email: breiman@icddrb.org

Yukiko Wagatsuma, * Robert F. Breiman, * Anowar Hossain, * and Mahbubur Rahman *

* ICDDR,B--Centre for Health and Population Research, Dhaka, Bangladesh

COPYRIGHT 2004 U.S. National Center for Infectious Diseases
COPYRIGHT 2004 Gale Group

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