Congenital Dengue and Myocarditis: A Case Report and Systematic Review of Literature
Infectious Diseases in Clinical Practice: May 2012 - Volume 20 - Issue 3 - p 180–181
Abstract
We report a newborn with congenital dengue infection and cardiomyopathy. Congenital dengue is known to occur owing to vertical transmission of the virus from an infected mother to her baby through the placenta. Dengue-related cardiomyopathy has been reported previously. This is arguably the first time cardiomyopathy is being reported in the context of congenital dengue. A systematic review of literature on congenital dengue as cited in Pubmed is also presented.
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Congenital Dengue and Myocarditis
A Case Report and Systematic Review of Literature
Richa Sharma, DCH, Natwar Parwal, DCH, Nirmal Kumar, MD, and Jacob M. Puliyel, MD
Abstract: We report a newborn with congenital dengue infection and
cardiomyopathy. Congenital dengue is known to occur owing to vertical
transmission of the virus from an infected mother to her baby through
the placenta. Dengue-related cardiomyopathy has been reported previously.
This is arguably the first time cardiomyopathy is being reported in
the context of congenital dengue. A systematic review of literature on
congenital dengue as cited in Pubmed is also presented.
Key Words: congenital dengue, cardiomyopathy
(Infect Dis Clin Pract 2011;00: 00Y00)
Dengue infection is caused by arbovirus pathogens (Flavivirus).
Serologically, there are 4 types of dengue virus. Infection
with one serotype does not confer immunity against infection
with other serotypes. On the other hand, previous dengue infection
(primary dengue) and the developed antibodies predispose
the patient to more severe illness when infected with other
serotypes subsequently (secondary dengue).1 Congenital infection
occurs when the virus is directly transmitted to the baby
through the placenta, and there is insufficient time for protective
antibodies developed in the mother to be transferred to the
baby.2 However ‘‘infection-enhancing antibodies’’ acquired by
the mother from previous Flavivirus infections are passively
transmitted to the baby, and this results in serious manifestations
in the newborn.3 It is reported that although hemorrhagic manifestations
are mainly a feature of secondary dengue infection,
it also manifests in congenital dengue owing to these infectionenhancing
antibodies.4
Cardiomyopathy has been described in adults with dengue
infection.5Y7 Cardiomyopathy, however, has not been previously
reported in congenital dengue to the best of our knowledge. A
systematic review of congenital dengue in PubMed is also
presented.
CASE REPORT
A term 3.2-kg male baby was delivered by AQ1 cesarean birth
with Apgar scores 2, 4, and 4 at 1, 5, and 10 minutes, respectively.
His mother had a history of fever with thrombocytopenia
for 2 days before delivery. Result of her dengue nonstructural
antigen 1 (NS1) test was positive. The mother’s serological test reAQ2
sults were negative for human immunodeficiency virus, HBsAg,
AQ2 and VDRL. The baby developed severe respiratory distress and
bradycardia soon after birth. His peripheral pulses were feeble,
and his blood oxygen saturation fluctuated between 70% and
80% on pulse oximetry. He was centrally cyanosed; had massive
hepatomegaly (liver 4 cm in the right midclavicular line), decreased
air entry in right basal region of the lung, and a systolic
murmur in mitral and tricuspid areas. His dengue nonstructural
antigen 1 test was positive. The first blood sample taken soon
after delivery showed C-reactive protein of 0.45 (positive, 90.5),
and platelet count was 21,000/mL of blood; blood culture was
sterile. A chest x-ray showed cardiomegaly with bilateral pulmonary
infiltrations. An echocardiogram (ECG) done on the unit AQ4
by a pediatrician with special interest in pediatric cardiology
showed massive right atrial and ventricular dilatation with severe
tricuspid regurgitation. Twenty-four hours after birth, the
ECG repeated by a pediatric cardiologist showed cardiomyopa-
thy with dilated left atrium and right ventricle, patent foramen
ovale, small pericardial effusion with right systolic dysfunction,
and moderate tricuspid regurgitation with a pressure gradient of
4 mm Hg. He was given ventilatory assistance, IV fluids, antibiotics,
and blood transfusions. This shock was refractory to ino-
tropes and hydrocortisone. He went on to develop multiple organ
failure (MODS) and died on day 7 of life.
DISCUSSION
Our child, born during the peak of the dengue season in
Delhi India, probably had congenital dengue as evidenced by
symptoms in the mother 2 days before delivery as well as the
dengue antigen positivity in both the mother and the child. Echocardiography
in the newborn with refractory shock suggested
cardiomyopathy.
Dengue virus is known to cause cardiac complication in
children. Salgado et al8 has reported 11 pediatric patients with
myocarditis due to dengue. Sinus node dysfunction with sinus
bradycardia or tachycardia and T-wave inversions on ECG,
pericardial effusion, and diastolic dysfunctions have all been reported.
Promphan et al9 described sinus node dysfunction leading
to bradycardia and hypotension a day after recovery from
DHF in a 13-year-old boy.
Obeyesekere and Hermon10 have listed the diagnostics
criteria for dengue myocarditis:
1. Clinical evidence of myocarditis;
2. Presence of electrocardiographic evidence of myocarditis,
ST segment and T wave changes, and disturbances in conduction
and rhythm;
3. Recent history of denguelike fever;
4. Serological evidence of past dengue infection as revealed
by the presence of antibody in high titer.10
Our neonate with congenital dengue had clinical and echocardiographic
evidence of myocarditis.
The pathogenesis of myocarditis is not clear. It could be
that the virus invades the myocardium and directly damages the
muscle fibers or it may give rise to a hypersensitivity or autoimmune
reaction causing myocardial damage. The altered state
of myocardium may persist long after the initial viral infection
and make it prone to recurrent damage from other agents.10
Salgado et al8 have demonstrated infection of heart tissue in vivo
Copyright @ 2011 Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.
and striated cells in vitro with dengue. It has been proposed that
derangements of calcium storage in infected cells may directly
contribute to presentations of myocarditis.
A systematic review of the literature looking for reported
cases of congenital dengue in Pubmed was performed using the
search criteria: ((‘‘congenital’’[Subheading] OR ‘‘congenital’’
[All Fields]) AND (‘‘dengue’’[MeSH Terms] OR ‘‘dengue’’[All
Fields])) AND (Case Reports[ptyp] AND ‘‘infant, newborn’’
[MeSH Terms]). Four case reports were found. The papers were
retrieved and reviewed. The symptoms in the mothers and the
newborn and tests used for diagnosis AQ7T1 are tabulated in Table 1.
CLINICAL MANIFESTATIONS OF NEONATAL
DENGUE INFECTION
In all the cases of neonatal dengue caused by vertical transmission,
fever was detected. All the neonates manifested a rash.
Other manifestations include hepatomegaly,11,13 respiratory distress,
4 pleural infiltrates,13 and pleural effusion.13 The laboratory
manifestations consisted of thrombocytopenia and raised
AQ8 liver enzymes.12 Diagnosis of 2 patients was based on PCR, and
both were of serotype 2.11,12 The diagnosis of 2 other patients
was based on 4-fold rise in antibody IgM titers.4,13 All 4 patients
recovered from their illness. None of the cases of congenital
dengue had evidence of myocarditis. In our case, there were features
suggestive of myocarditis and shock, which was refractory
to inotropes.
Cardiomyopathy seems to be a novel complication of congenital
dengue fever. One must have a high index of suspicion
and be vigilant for this potentially serious complication.
REFERENCES
1. Gubler DJ. Dengue and dengue hemorrhagic fever. Clin Microbiol Rev.
1988;11:480.
2. Perret C, Chanthavanich P, Pengsaa K. Dengue infection during
pregnancy and transplacental antibody transfer in Thai mothers.
J Infect. 2005;51:287Y293.
3. Kilkis SC, Nimmannitya S, Nisaliak A, et al. Evidence that maternal
dengue antibodies are important in the development of dengue
hemorrhagic fever in infants. Am J Trop Med Hyg. 1988;411Y419. AQ9
4. Fatimil LE, Mollah AH, Ahmed S, et al. Vertical transmission of
dengue: first case report from Bangladesh. Southeast Asian J
Trop Med Public Health. 2003;34:800Y803. Review. Erratum in:
Southeast Asian J Trop Med Public Health. 2004;35:494.
5. Lee IK, Lee WH, Liu JW, et al. Acute myocarditis in dengue
hemorrhagic fever: a case report and review of cardiac complications
in dengue-affected patients. Int J Infect Dis. 2010;14:e919Ye220.
6. Lee CH, Teo C, Low AF. Fulminant dengue myocarditis masquerading
as acute myocardial infarction. Int J Cardiol. 2009;136:e69Ye71.
7. Kularatne SA, Pathirage MM, Kumarasiri PV, et al. Cardiac
complications of a dengue fever outbreak in Srilanka, 2005.
Trans R Soc Trop Med Hyg. 2007;101:804Y808.
8. Salgado DM, Eltit JM, Mansfield K, et al. Heart and skeletal muscles
are targets of dengue virus infection. Pediatr Infect Dis J.
2010;29:238Y242.
9. Promphan W, Sopontammarak S, Pruekprasert P, et al. Dengue
myocarditis. Southeast Asian J Trop Med Public Health. 2004;35:61.
10. Obeyesekere I, Hermon Y. Arbovirus heart disease: myocarditis and
cardiomyopathy following dengue and chikungunya feverVa follow-up
study. Am Heart J. 1973:186Y194. AQ9
11. Witayathawornwong P. Parturient and perinatal dengue hemorrhagic fever.
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TABLE 1. Symptoms in Mothers and Newborns and Tests Used
Citation Pregnant Women’s Symptoms Newborn Symptoms Outcome Diagnostic Test
1 Witayathawornwong11
(Thailand) 2003
Fever, 5 days; thrombocytopenia
and pleural effusion;
postpartum anemia
Fever, 2 days (48 h of life);
thrombocytopenia; pleural
effusion; hepatomegaly
Recovered Dengue virus
type 2 by PCR
2 Fatimil et al,4 (Bangladesh) 2003 Fever, intense body ache,
tourniquet test +, bilateral
mild pleural effusions
with hepatomegaly
Fever, respiratory distress Recovered IgM and IgG for
dengue with
4-fold rise of IgM
3 Janjindamai and Pruekprasert,12
(Thailand) 2003
Acute dengue Fever, convalescent rash,
elevated SGOT and SGPT
Recovered Dengue virus
type 2 by PCR
4 Bugna et al13 (Poland) 2010 Fever, thrombocytopenia, rashes Fever, thrombocytopenia,
erythematous rashes,
hepatomegaly, bilateral
pleural infiltrates,
mild pleural effusion
Recovered Dengue IgM
and IgG
Sharma et al Infectious Diseases in Clinical Practice & Volume 00, Number 00, Month 2011
2 www.infectdis.com * 2011 Lippincott Williams & Wilkins
REVIEW ARTICLE
Infectious Diseases in Clinical Practice & Volume 00, Number 00, Month 2011 www.infectdis.com 1
Copyeditor: Wilma Q. Sabueto
From the Department of Pediatrics, St Stephen’s Hospital, Tis Hazari, New
Delhi, India.
Correspondence to: Richa Sharma, St Stephen’s Hospital, Tis Hazari,
Delhi 110054 India. E-mail: Richa.dr.sharma@gmail.com.