Definition.

Dengue fever (DF) is a worldwide infection caused by 4 related RNA

. viruses of the genus Flavivirus, dengue viruses (DENV) DENV-1, DENV-2, DENV3,
and DENV4. DENV is primarily transmitted to humans through the bite of intected
Aedes aegypti (and less commonly Aedes albopictus or Aedes polynesiensis) mosquitoes.
DENV causes asymptomatic inlection, DE, or a severe syndrome (dengue hemor
rhagic fever [DHF]/dengue shock syndrome [DSS]). The latter is characterized by
systemic capillary leakage, thrombocytopenia, and hypovolemic shock.
I1. Incidence. Denguc is a major public hcalth problem in the tropics and suburopics; an
estimated 50 to 100 million dengue cases occur annualy in more than 1o0 countries,
and 40% of the worlds population lives in areas with DENV transmission. In the United
States, denguc is endcmic in Pucrto Rico, the Virgin lslands, and American Samoa.
Additionally, limited outbreaks with local DENV iransmission have occurred in Texas,
Hawaii, and Florida in the past decade, but no nennatal cases have been reported from
the Cnited States. Millions of US travclers, including children. are at risk. Nconatal
dengue has been described in case reports and case series from outside dhe United
States; therefore, its true incidence worldwide is unknown.
II. Pathophysiology. Viremia is usually detected about 6 ta l8 hours hefore the onset of
symptoms and ends as the fever resolves. Both innate and adaptive immune
responscs seem to play a role in the cearance of infcction. Infcction with 1 of the 4
DENVs (primary infection) provides long- lasting immunity to infection with a virus of
the same serolype; however, immunity to the other denguc serotypes is transient.
dividu-als can subscquently be infected with anotlier denguue serotype (secondary
insection). often with more severe manifestations. DHF can develop with any of the 4
DENVs, but the risk is highest with DENV-2. DHF can usually he distinguished from
DF as it progresses through 3 predictable pathophysiologie phases:
A. Febrile phase: Viremia-driven high fevers.
B. Critical/plasima leak phase: Sudden onset of varying degrees of plasma leak inta
the pleural and abdominal cavities. This phase probably occurs due to endothclial cell
dysfunetion rather than injury.
C. Convalescence or reabsorption phase: Sudden arrest of plasma leak with con-
comitant reahsarption of extravasated plasma and tluids.
Neonates can be inlected through mosquilo bites but also as a verlicał inlection from
the mother. The highest risk period is when the mother hecomes acutely ill with dengue at
or near the time of delivery. It has heen hypothesized that there is an insut. ficicnt level of
protective maternal antibodics (immunoglobulin |lel G) Lransferred to the fetus, and
therefore, the newborn can manifest serious discase. Endothelial damage and plasnma
leakage may enable the vius an easy access across the placental barrier.
 tlearl rate, capillary refill imc, blood pressure, weight, and serum electrolytes should
he checked once or twice a day. Intravenous tluids (colloids and crystalloid) must he
prescrihed as soon as possible, starting typically with normal saline (0.9h sodium
chloride) boluses of 10 to 20 mL/kg to restore perfusion. Total daily luid intake may
vary between 150 and 200 ml./kg/d. Furthermore, extra intravenous sodium chla-ride
may be indicated if shock or hyponatremia (<130 mFq/l.) develops. In cases of severe
thrombocytopenia (<30,000/mm') or serious bleeding. platelet transfusion is
preseribed. Albumin transfusion (1 g/kg every 6-12 hours for 2-1 doses) may be
indicated with severe hypoalbuminemia (<2 g/d1) or when pleural or peritoneal tluid
etfusion is present. Prior to establishing the diagnosis in neonates, antibintics
(amoxicillin, cefotaxime, or gentanicin) are empirically preseribed given the high risk
af hacterial sepsis at this age. Breast feeding is encouraged despite the minimal risk
of transmision via breast milk.
VIll. Prognosis. Neonatal dengue can be potentially lethal. Affected ncwborns should be
carelully observed for a minimum of a 2-wcek period before discharge. Vigilant
monitoring and proper hydration often lead to an uneventful recovery. However, poor
oulcomc may occur; a recent sludy from Lndia thal involved 16 women diagnoscd with
DF (3 had DSS and 8 had DEIF) showed that bleeding manifestations occurred in 7
women, and there were 3 maternal deaths. Perinatal complications from the study
included 3 intrauterine deaths, 6 nursery admissions, and I neonatal death.
L. Preveution. Methods for prevenlion of dengue infeclion in endcmic arcas include
mosquito control and vaccine devclopment. Mosquito control is cffecive but dif
ficult to sustain. Several DENV vaccines are in development, and
1 became com-
mercially available recently; it is licensed in scvcral countries in Latin America and
Southcast Asia. II gained the S
Food and Drug Administration approval in May
2019. CYD.TDV (Dengvaxia) is a prophylactic, tetravalent, live attenuated viral vac.
cine administered to individuals age 9 to 45 years (age 9-16 years in the US) who
have laboratory-confirmed previous dengue infection and living in denguc-
endemic areas. Unfortunately, it is contraindicated in pregnant women hecause it
is a live virus; however, the limited data collected during the clinical trials an
inadvertent immunization of prcgnant women have yiclded no cvidence of harm to
he fetus or pregnant woman.