Ka Dinga Pepo: Dengue- A Continuing Story for the '90s

ABSTRACT & COMMENTARY

Synopsis: A recent report from the Centers for Disease Control and Prevention, Atlanta, GA, summarized the statistics for imported dengue into the United States for 1996. The good news is that the numbers were down compared to the high incidence rates for 1995. But, remember that dengue is not a reportable disease in the United States, and what we are seeing is a minimum estimate, at best, of dengue activity, which continues to appear fairly close to home.

Source: Centers for Disease Control and Prevention. Imported dengue-United States 1996. MMWR Morb Mortal Wkly Rep 1998;47:544-547.

Since dengue is not a disease that is reported either nationally or in most states, the surveillance maintained by the CDC is a passive laboratory-based system. However, the data presented in this report are of interest to practitioners evaluating ill patients returning from the tropics, particularly those from the Caribbean islands as we approach the winter vacation season for travel to and from North America. Table 1 from this report summarized the data for the 179 suspected and 43 laboratory-diagnosed cases of imported dengue into the United States by state. Serum samples obtained from 179 persons with suspected dengue from 32 states revealed 43 (24%) laboratory-proven cases from 18 states and the District of Columbia. Diagnosis was based upon one of three laboratory criteria: a single high titer of IgG in acute serum, IgM in an early convalescent sample, or isolation of a dengue virus. In five cases, the virus serotypes (DEN-1 or DEN-2 in this report) were identified.

When symptoms, signs, and laboratory values were determined for the 43 persons with laboratory-diagnosed dengue infection, they were fairly classic, including fever (93%), headache (61%), myalgia (57%), rash (57%), and arthralgias (18%). Less commonly reported symptoms included diarrhea, eye pain, skin hemorrhages, jaundice, and depression. Eight patients demonstrated thrombocytopenia (average, 98,000/mm3), and six had depressed white blood cell counts (average, 2550/mm3), with elevated liver function tests in one patient only. None died.

COMMENT BY FRANK J. BIA, MD, MPH

According to the Oxford English Dictionary, the Swahili phrase "Ka dinga pepo" describes a sudden cramp-like seizure originating from an evil spirit or plague, from which we derive the English word, dengue.1 Rigau-Pérez has recently reviewed the fascinating history of these descriptive words used for dengue fever. He documents use of the term "quebranta huesos" (break-bone) as early as 1771 by a physician at the military hospital in San Juan, Puerto Rico, requesting a formal opinion on rum rations for prisoners involved in the construction of the city's forts. He also notes the use of the word "dengue" by Queen Louisa of Spain in her letter of June 12, 1801, to Manuel Godoy, her principal minister, friend, and alleged lover. Since she wrote to Godoy on a daily basis during the Spanish army's invasion of Portugal, her illness was nicely reconstructed and reported by the author. Benjamin Rush also used the term "break-bone fever" to describe the 1780 epidemic of "bilious remitting fever" occurring in Philadelphia that year.

Table 1

Suspected and laboratory-diagnosed cases of imported dengue, by state-United States, 1996

State
Cases
Travel history, if known, of persons with laboratory-diagnosed dengue (serotype, if known)
Suspected Laboratory-diagnosed
Alabama
4
0
Alaska
1
0
Arkansas
0
California
10 
0
Colorado
8
2
India (DEN-2), Malaysia
District of Columbia
5
1
Ivory Coast 
Florida
5
1
Trinidad
Georgia
11
1
Grenadine Islands
Hawaii
6
2
Samoa (two cases)
Illinois
6
0
Indiana
1
0
Maine
1
1
U.S. Virgin Islands (DEN-1)
Maryland
9
6
U.S. Virgin Islands, British Virgin Islands (five cases)
Massachusetts
20
7
U.S. and British Virgin Islands and Puerto Rico, U.S. Virgin Islands, Malaysia, India (two cases)
Michigan
3
0
Minnesota
3
0
Montana
1
0
Nebraska
1
0
New Hampshire
1
0
New Jersey
3
1
India
New Mexico
4
0
New York
18
6
Jamaica, U.S. and British Virgin Islands, Anguilla, India (DEN-2), Trinidad and Tobago
North Carolina
4
2
India, Senegal
Ohio
1
1
Philippines
Oregon
8
1
Burma and Thailand
Pennsylvania
7
3
Puerto Rico and British Virgin Islands, British Virgin Islands (two cases)
Rhode Island
3
3
(DEN-1, two cases)
South Carolina
2
0
Texas
23
2
Honduras, Nigeria
Vermont
2
1
Barbados
Virginia
1
0
Washington
2
1
Southeast Asia
Wisconsin
4
1
Ecuador
Total
179 
43

    Reprinted from: Centers for Disease Control and Prevention. MMWR Morb Mortal Wkly Rep 1998;47:544-547.

The vector for dengue is the urban mosquito, Aedes aegypti, which is found in and around houses, making this environment, rather than rural mosquito exposure, important in the epidemiology of dengue infection. In the urban residential environs, the vector bites during early morning and late afternoon, when activity around the household is generally high. Protection against mosquito bites is paramount in the prevention of infection, but travelers must be made aware of these behavior differences between vectors that transmit dengue and those that transmit malaria. The latter are Anopheline species, which are more likely to be encountered at dusk in rural areas. There are four dengue virus serotypes, but no vaccine exists for any of them at present. Although the southeastern United States harbors Aedes aegypti during the summer months, dengue transmission in the United States is rare. Rather, this CDC report underscores the travel history, which was available for 37 of 43 documented cases. Nineteen infections were likely acquired in the Caribbean islands, 11 in Asia, three in Africa, two in the Pacific islands, and one each in Central and South America. With a short incubation period of only 4-7 days (range, 3-14 days), the Caribbean traveler may become ill while on vacation or within a short time following return to North America. Travelers who become ill more than two weeks following their return are unlikely to have dengue.

Rossi et al have underscored the ease with which the incidence of dengue might be underestimated in their analysis of the laboratory diagnosis of acute dengue fever during the United Nations mission to Haiti, 1995 and 1996.2 Using dengue virus isolation in tissue culture as the gold standard and comparing the IgM capture ELISA, they were able to isolate dengue virus from 161 of 379 acute samples using cell culture and detected IgM antibodies in 93 of 414 acute sera. However, the acute IgM antibody assay had a sensitivity of only 13% when compared with virus isolation as the standard. In other words, compared with virus isolation, the IgM capture assay detected only 13% of cases confirmed by virus isolation (21 of 161). The use of a single acute serum and the detection of IgM antibody alone was not sensitive enough (13%) for reliably obtaining a presumptive diagnosis of dengue. Although all 25 primary dengue patients, for whom the initial serology was negative and additional samples were available for testing, appeared to show a detectable IgM response by day five, it took 18 days for all patients to develop an IgG response. In addition, anti-dengue antibodies appear to interfere with virus isolation, and infectious virus was more likely to be isolated from seronegative than seropositive sera. The authors determined that using both virus isolation and the detection of virus-reactive IgM antibodies increased sensitivity to 45% in their study for the presumptive diagnosis of acute dengue fever. These results are particularly important to consider when aggressive follow-up with convalescent sera is not possible. For the travel medicine practitioner, the message is clearly that serology performed on a single acute sample will markedly underestimate the incidence of dengue. The incidence of dengue in the Caribbean is likely to be much higher than the numbers indicate, if based upon serology alone.

None of the patients reported in the CDC summary died, since most cases of dengue are not life-threatening, showing relatively mild disease manifestations. If dengue shock syndrome (DSS) occurs, the fatality rate may exceed 40%. This syndrome would be characterized by fever, thrombocytopenia, hemorrhage, and increased vascular permeability causing hematocrit elevations, hypoalbuminemia, and pleural/abdominal effusions. DSS differs from simple dengue fever in that it occurs almost exclusively in children who are under age 15. It begins no differently than dengue fever but progresses through several stages of circulatory failure to profound shock. The pathogenesis of DSS is not entirely clear, but a nearly universal prerequisite seems to be a previous dengue infection. Why? Current theory invokes immune enhancement. Dengue virus targets the mononuclear phagocytic cell population. After infection with one serotype of dengue, there appears to be a period of cross-protection against other serotypes of dengue virus. However, once neutralizing antibody levels fall to non-neutralizing levels, infection with a different serotype may actually result in enhanced penetration of dengue virus into target cells. This may be due to complexing of such non-neutralizing antibodies and their potential to promote virus entry into mononuclear cells. The result may be more infected cells and, therefore, more severe disease. The theory is useful in understanding pathogenesis, but others have pointed out that it does not explain why certain strains of virus are more likely to cause DSS, nor why it is so rarely seen in adults.3

With this in mind, the major issue is not the evolution of dengue fever into DSS for the travel medicine specialist, but rather distinguishing the illness from malaria, measles, leptospirosis, HIV seroconversion, and EBV-associated mononucleosis in addition to other viral hemorrhagic fevers. Diagnosis can be aided by contacting CDC's Dengue Branch, Division of Vector-Borne Infectious Diseases, National Center for Infectious Diseases, 2 Calle Casia, San Juan, PR 00921-3200; telephone (787) 766-6596.

Treatment of this self-limited illness includes bed rest, hydration, and control of fevers with acetaminophen rather than aspirin or other nonsteroidal anti-inflammatory agents, which themselves have anticoagulant properties.

References

    1. Rigau-Pèrez JG. Am J Trop Med Hyg 1998;59:272-274.

    2. Rossi CA, et al. Am J Trop Med Hyg 1998;59:275-278.

    3. Pile JC, Wagner KF. Infect Dis Pract Clin 1997;21:17-20.