Dengue fever is an acute febrile illness caused by
four serotypes of Dengue virus and in older children characterized by
biphasic fever, myalgia, arthralgia, rash and leuco-penia. Dengue
hemorrhagic fever (DHF) is characterized by hemoconcentration,
abnor-mality of hemostasis and in severe cases by a fluid & protein
losing shock syndrome (Dengue Shock Syndrome, DSS). This arthropod born
virus is transmitted by a day time biting mosquito Aedes aegypti.
There is no cross protection between the 4 dengue serotype but there is
cross reaction(1). The disease usually establishes a pattern of epidemic
activity every 2-5 years. DHF and DSS are usually confined to children
with a modal age at hospitalization of 4-6 years(2). Only 9% of the
cases in a recent epidemic in Delhi were infants and the youngest child
was 3-month-old(3). We are reporting 4 cases of DSS in neonatal period
seen during recent epidemic of dengue fever in Rajasthan
(August-November, 2001).
Case 1
A 28-day-old term neonate was admitted with fever,
refusal to feed and excessive cry for two days. There was no history of
rash, convulsion or bleeding from any site. On examination the heart
rate was 150/min, respiratory rate 48/min, temperature 38.5ºC per axilla
with normal perfusion. Neonatal reflexes were poor. The neonate was
treated with a presumptive diagnosis of neonatal septicemia with
parenteral cefotaxime and amikacin. Investigation revealed hemoglobin 13
g%, total leukocyte count 6300/mm3, DLC (N24L70M6), platelet count 1
Lakh/mm3 and negative serum C-reactive protein. The following day baby
was in shock. As there was ongoing dengue epidemic the case was
investigated for it. Investigation revealed hemoglobin 14g%, platelet
count 36000/mm3, SGOT 1386U/L, SGPT 1858 U/L, Stool for occult blood
positive and positive serum IgG and IgM for dengue. Mother also had
positive IgG and IgM for dengue. The shock was managed with appropriate
fluid and dopamine. Baby improved within 72 hours and was discharged
after 10 days.
Case 2
A four day old term male neonate was admitted with
fever, lethargy and refusal to feed for two days. There was no history
of rash, convulsion or bleeding from any site. Maternal history was
non-contributory. On examination baby had normal heart rate, respiratory
rate, temperature and peripheral perfusion but was lethargic. The
neonate was managed with a presumptive diagnosis of neonatal septicemia.
Initial investigations were normal except for a positive C-reactive
protein. The next day baby was in shock with bleeding per rectum.
Investigation revealed platelet count 50,000/mm3, prothrombin time 18
seconds and normal PTTK. Serology for dengue (IgG and IgM) was positive.
Chest X-ray revealed right side pleural effusion. He was treated
with appropriate fluid manage-ment and platelet rich plasma. Baby
improved and discharged after 7 days.
Case 3
A 34 week premature neonate presented on day seven of
life with shock, rectal bleeding, progressive distension of abdomen and
increasing pallor. The baby had thrombo-cytopenia and weakly positive
IgG and negative IgM for dengue. Five day later IgG and IgM for dengue
were positive. Despite aggressive management of shock baby deteriorated
and expired on day 20 of life.
Case 4
A full term baby was admitted on day four of life
with history of delayed cry after birth, seizures and unconsciousness.
On examination baby had altered sensorium with subcostal and
intercostals retraction, bilateral crepitations and wheezing. The baby
had a positive serum C-reactive protein. On day 11 baby developed shock.
Investigation revealed low platelet count and positive IgM for dengue.
There has history of fever in last trimester in mother and investigation
showed IgM and IgG for dengue positive in mother serum. Baby improved
with supportive management.
Discussion
Dengue virus infection results in a spectrum of
disease. On one end is dengue fever characterized by fever, myalgia,
arthralgia, leucopenia and lymphadenopathy, while on the other end is
DHF characterized by hemorrhage and shock syndrome(4). The disease and
particularly severe DHF/DSS form has a predeliction for pediatric age
group with a modal age at hospitalization of 4-6 years(2).
According to WHO criteria, for defining DHF the
following must all be present (a) fever, (b) hemorrhagic
tendency (c) thrombo-cytopenia (d) evidence of plasma
leakage, manifested by either a rise in the hematocrit equal to or
greater than 20% above average for age, sex and population or signs of
plasma leakage such as pleural effusion, ascites and hypoprotienemia.
For defining DSS all of the above four criteria for DHF plus evidence of
circulatory failure manifested by rapid and weak pulse, narrow pulse
pressure (less than 20 mmHg), hypotension for age or cold, clammy skin
must be present(2).
DHF/DSS occurs with higher frequency in two
immunologically defined groups: children who have experienced a previous
dengue infection, and infants with waning levels of maternal dengue
antibody. Various studies reported its rarity in early infancy and
neonatal period(2).
In 1996 epidemic in Delhi, 23% cases of DHF/DSS was
in 0-3 years age group and the youngest child was 3-months-old(3).
Another study of the same epidemic reported a four months old infants as
the youngest patient(5). In Calcutta epidemic in 1990, no case of DHF/DSS
was reported in infancy(6). Recently, we came across four cases of DSS
in newborn period. Presence of IgM antibodies in a neonate can be
detected by day 5 of life in postnatally acquired illness(2).
DHF/DSS is uncommon in children below 1 year who are
usually exposed to infection by dengue virus for the first time.
However, if the mother is previously infected by dengue virus and hence
has already developed antibody against that virus the infant may have
placentally transmitted antibodies and may develop DHF after the first
infection by dengue virus of antigenically different type(6). So
presence of shock and hemorrhagic manifestation seen during neonatal
period can be attributed to passively transferred circulating antibodies
from the mother. This can be explained on the basis of immune
enhancement theory also. According to this theory DHF/DSS occurs as a
result of enhanced replication of virus in presence of preexisting
antibody against another dengue serotype(6). Most cases have been noted
to occur when dengue type 2 infects either (1) a baby with maternal
antibody against dengue or (2) a child with serological evidence of
having been infected during the previous 5 years with a hetrogenus
dengue serotypes(6-8).
Some authors have suggested that viral virulence is a
risk factor for DHF/DSS inde-pendent of pre-infection antibody
status(8). Therefore, cases of DHF/DSS in earlier age group could also
be due to increased virulence of virus during the present epidemic.
In Delhi epidemic the cause of low incidence of DHF/DSS
in infants may be because the epidemic was controlled in a very short
time and thus secondary infection rate was low, but 2001 epidemic in
Rajasthan lasted for about 4 months and thus mother infected during
earlier period of epidemic gave birth to babies who were subsequently
infected in later period of epidemic and developed DHF/DSS. One must
think for DHF/DSS in a neonate presenting with short duration pyrexia,
bleeding disorder and shock.
Contributors: SPC drafted and designed the paper.
RK & JK searched literature and manage patients under guidance of SPC.
SPC will be guarantor for the paper.
Competing interests: None.
Funding: None.
