Congenital Dengue: A Risk For Pregnant Women Who Travel

Abstract & Commentary

Synopsis: Recent cases from Thailand indicate that children can be born infected by dengue virus. Fever and thrombocytopenia are noted in the first week of life, and death, though unusual, has been reported.

Source: Sirinavin S, et al. Vertical Dengue Infection: Case Reports and Review. Pediatr Infect Dis J. 2004;23:1042-1047.

Dengue fever has been considered primarily a childhood disease in endemic areas. In 2003, however, 40% (3100 of 7760) of Bangkok patients with dengue fever or dengue hemorrhagic fever (DHF) were 15-34 years old.1 This recognized change in ages that are at risk for dengue infection is important for women of childbearing age.

Sirinavin et al describe a new relationship between dengue fever occurring in pregnant adults, that allows for vertical transmission to infants. In this study, they reviewed hospital records of a Bangkok hospital and found 2 dengue infected mother-neonate pairs. The first pair involved a term female born to a 25-year-old, previously healthy mother via repeat caesarean section. This infant was febrile on days of life (DOL) 5-8. On DOL 6, the infant developed hypovolemia, tachycardia, and thrombocytopenia. The patient ultimately had a spontaneous recovery on DOL 9. As part of this infected pair, the mother had fever on post-partum days 1-3. She then recovered without incident after post-partum day 4. Both mother and infant tested positive for dengue IgM antibody. Subsequently, at 2 and a half years of age, the child had a serum titer positive for DEN-2 antibodies and negative for DEN-1, 3 and 4.

The second mother-neonate pair involved a term boy born to a 31-year old mother via primary caesarean section for cephalopelvic disproportion. The infant had fever on DOL 5-9 and also developed a non-petechial rash with thrombocytopenia. The newborn returned to normal health on DOL 13. This mother was febrile during post-partum days 1-6. She experienced thrombocytopenia, but also had pleural effusion and signs of dengue hemorrhagic fever. Both mother and neonate had an uneventful recovery. The mother and infant tested positive for DEN-4 antibody; further studies suggested DEN-4 acute secondary infection for the mother and primary infection for the neonate.

In addition to reporting these 2 new cases to the literature, Sirinavin and colleagues also reviewed the available literature on dengue fever occurring with vertical transmission. They found an additional 15 cases; the first had been reported in 1989. The locations for these additional cases included Tahiti (5), Malaysia (2), Thailand (6), and France (2). Neonatal fever began on day 4 (median, range 1-11) and persisted for a median of 3 (range 1-5) days. Thrombocytopenia developed around day 6 (range 1-11) and persisted for about 6 (range 3-18) days, with lowest platelet counts reaching 5,000 to 75,000 per mm3.

Commentary by Lauren M. McGovern, MD & Philip R. Fischer, MD, DTM&H

Infection with any of the 4 dengue virus serotypes (DEN-1, DEN-2, DEN-3, DEN-4) can lead to dengue fever or DHF. Dengue, a mosquito-born illness, is primarily a disease of the tropics, with its major distribution being similar to that of malaria. The dengue virus life cycle is dependent both upon infected humans and Aedes aegypti, a domestic, day-biting mosquito that prefers feeding on humans. An estimated 2.5 billion people live in areas at risk for epidemic dengue transmission, and approximately 50-100 million cases of dengue fever occur each year; 200,000-500,000 of these represent DHF. Dengue is not uncommon as a cause of fever in returned travelers2 and seems to be occurring more frequently.3 In addition, unusual mucocutaneous, nosocomial transmission of dengue in the United States was recently reported.4

In planning for an international trip, pregnant women face not only their own health challenges, but also the additional issues of attending to the health and safety of unborn children. All exposures, including illnesses, medications, and trauma will likely impact a fetus to varying degrees. Besides some general contraindications to travel, including threatened miscarriages, severe co-morbidities, and coagulopathy disorders, traveling pregnant women must pay particular attention to malaria prevention.

Malaria in pregnancy causes significant morbidity and mortality for both the mother and the fetus.5 Expectant mothers are advised to take appropriate chemoprophylaxis, if possible, and to protect themselves from potentially infective mosquito bites. Malaria-transmitting Anopheles mosquitoes, unlike Aedes, typically bite at night. The different mosquito behaviors and relationships to infectivity are significant for the pregnant traveler. The complications of malaria during pregnancy are so well known that many pregnant travelers are advised to avoid evening mosquito bites. However, they could potentially ignore daytime protection, the highest time of risk for acquiring infections with dengue virus.

Sirinavin and colleagues discuss several cases of dengue virus infection in expectant mothers with vertical transmission to their fetuses. Since dengue virus infection is not an isolated childhood disease, severe perinatal complications (maternal and neonatal) must be considered and avoided. The risk for vertical transmission of dengue virus needs to be reviewed with women who are traveling to dengue endemic areas during pregnancy, and appropriate counsel must be provided.

Interestingly, 6 of 17 newborns with congenital dengue infection in Sirinavin and colleagues’ review had been delivered operatively. It is possible that this rate of operative delivery was higher than routine for those areas, but it is not known if dengue was transmitted prior to or during the delivery process.

Currently there is no chemoprophylaxis against dengue fever, and the best protection against dengue infection is avoidance of mosquito bites. Dengue can be prevented by utilizing basic mosquito bite prevention. Pregnant travelers can avoid insect bites by wearing loose-fit clothing that covers the body. Bed nets, use of permethrin on clothing and nets, and application of DEET-containing repellents to exposed skin are also important measures. The recommendations for DEET use in pregnant women do not differ from those for non-pregnant adults. Women choosing lower concentrations of DEET must increase the frequency of application if staying outdoors for long periods.6

There is new evidence of risk for another vertically-transmitted infection which could be relevant to women traveling during pregnancy. Researchers in Japan have identified Helicobacter pylori in stools of 30% (15 of 50) of tested newborns. While follow-up testing 24 months later on 8 of the positive children did not reveal persistent infection,7 there have been concerns generated from The Gambia that early H. pylori colonization may be associated with a poor growth history later in infancy.8

Thus, new information supports even greater attention to prevention of travel-related infections during pregnancy. Beyond risks for pregnant women, children are also at risk of febrile illness due to congenitally acquired dengue, as well as for reduced subsequent growth following acquisition of H. pylori infection. Pregnant women who choose to travel internationally should be vigilant about avoidance of insect bites and about food and water hygiene.

Lauren M. McGovern, MD, is a resident in the Department of Pediatric and Adolescent Medicine at the Mayo Clinic, Rochester, MN.

References

1. Dengue Hemorrhagic Fever Surveillance Report. Disease Control Division, Health Department. Bangkok, Thailand: Bangkok Metropolitan Administration; 2003, as cited in the source article by Sirinavin et al.

2. Shaw MT, et al. Illness in Returned Travellers Presenting at GeoSentinel Sites in New Zealand. Aust N Z J Public Health. 2003;27:82-86.

3. Frank C, et al. Increase in Imported Dengue, Germany, 2001-2002. Emerg Infect Dis. 2004;10:903-906.

4. Chen LH, et al. Transmission of Dengue Virus Without a Mosquito Vector: Nosocomial Mucocutaneous Transmission and Other Routes of Transmission. Clin Infect Dis. 2004;23:1042-1047.

5. Fischer PR. Malaria and Newborns. J Trop Pediatr. 2003;49:132-134.

6. Fradin MS, et al. Comparative Efficacy of Insect Repellents Against Mosquito Bites. N Engl J Med. 2002;347:13-18.

7. Fujimura S, et al. Detection of Helicobacter pylori in the Stools of Newborn Infants. Pediatr Infect Dis J. 2004;23:1055-1056.

8. Thomas JE, et al. Early Helicobacter pylori Colonization: The Association With Growth Faltering in The Gambia. Arch Dis Child. 2004;89:1149-1154.