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Year : 2016 | Volume : 4 | Issue : 4 | Page : 238 - 240  


Case Reports
Congenital Rubella and Cytomegalovirus Infection in a New born with Unusual Hematological Features: A Case Report

Col [Dr] Ramanan Duraiswami1, Teena Rajeev 2

1 HOD and Director Laboratory Services, 2 Microbiologist, Fernandez Hospital Hyderabad

Corresponding Author:

Col [Dr] Ramanan Duraiswami

E-mail: daru_r@rediffmail.com

ABSTRACT:

TORCH infections are unique in their pathogenesis and have potentially devastating clinical manifestations. We present a case of concomitant Rubella and CMV infection in a newborn with unusual hematological and immunological features which ended fatally.

Key Words: TORCH infections, CMV infection, Rubella infection

INTRODUCTION:

TORCH infections are unique in their pathogenesis and have potentially devastating clinical manifestations. 1 Despite active immunization programs the incidence of TORCH infections remains high in the Indian population, as a study conducted in Delhi revealed. Kaur et al found an incidence of 93.4 % positivity to one of the TORCH agents in a study of 120 women who attended an antenatal clinic in Delhi [HSV 70 %, toxoplasmosis 11.6 %, rubella 8.3 % and CMV 20.8 %.] 2 Early onset sepsis remains a common and serious problem for neonates, especially pre – term infants, and viruses should be considered in the differential diagnosis. 3 Studies have shown high counts of Nucleated RBC’s [NRBC’S] in patients with TORCH infections. 1, 3 However no mention of markedly elevated levels of mononuclear cells were found.

We present a case of Congenital Rubella Syndrome (CRS) and congenital CMV with unusual hematological and serological features to highlight the need to have a high level of suspicion to detect the condition in time.

CASE REPORT:

33 years old lady with maternal history of G2 P1 A0 L1 delivered a female child by LSCS at 32 weeks of gestation because of non – immune hydrops fetalis at 10:56 hrs on 21 October 2015. The neonate had a birth weight of 1670 grams. APGAR score was 4 at 1 minute, 6 at 5 minutes, and 6 at 10 minutes with resuscitation being required in the form of tube and bag ventilation. The neonate was found to have non – immune hydrops fetalis. Arterial cord pH was 7.297 and Base Excess [BE] was -7.8 mmol/liter. Baby was admitted to NICU in view of non - immune hydrops and poor respiratory efforts.

In view of poor respiratory effort the baby was started on SIMV [Synchronized Intermittent Mandatory Ventilation] mode of ventilation. The baby was shifted to HFO [High Frequency Oscillatory] ventilation as she was not maintaining saturation [SpO2 <70%] even on maximum setting by one hour of life. The baby was found to have low volume pulse, tachycardia and prolonged capillary refill time. She had a palpable liver 3 cm below the right costal margin. 2- D Echo revealed Persistent Pulmonary Hypertension of the Newborn [PPHN]. The baby was started on vasopressors and inotropic drugs. Investigations done on the neonate are summarized in Table 1.

Hyperkalemia was managed with sodium bicarbonate, dextrose insulin drip and calcium gluconate. Partial exchange and double exchange transfusions were done for anemia and hyperbilirubinemia respectively. In spite of all efforts ABG continued to show hypoxemia and worsening metabolic acidosis and refractory shock and was declared dead at 23:10 hrs on 21 October 2015. Maternal blood was sent for TORCH IgG and IgM on 21 October. Tests results revealed the mother to be positive for CMV and Rubella IgG [1.33 [normal =<1.2] and 2.92 [normal = <1.3] whereas other levels of IgG were normal. IgM levels for all five TORCH panel were within normal limits. In view of elevated levels of IgG neonatal blood was sent for five parameters TORCH IgG and IgM panels. Results are summarized in Table 1 and showed elevated levels of IgG for CMV and Rubella in the neonate, matching the maternal findings. Again, TORCH IgM levels were within normal limits.

Kleihauer Betke test for feto – maternal hemorrhage was done and no fetal RBC’s were found in the maternal blood.

Placental histopathology revealed enlarged chorionic villi with dilated vessels many of which showed nucleated RBC’s as well as hematopoietic elements, and inter – villous hemorrhage. Changes were found suggestive of hydrops fetalis. To summarize, a neonate born prematurely at 32 weeks by LSCS to a mother with normal obstetric history and elevated levels of Rubella and CMV IgG was found to have non – immune hydrops fetalis, acidosis, hepatomegaly and jaundice, PPHN, dimorphic anemia and hematological picture of normo blastemia with raised mononuclear cell counts [monocytosis and lymphocytosis]. Elevated levels of CMV and rubella IgG were found in the child corresponding with maternal levels. Elevated lymphocyte and monocyte counts are consistent with a viral infection etiology.

We believe that the above picture is consistent with concomitant congenital infections with rubella and CMV transmitted during intra – uterine life. The fact that levels of CMV and rubella IgM were normal in both mother and child is unusual and would seem to suggest a re – activation of both infections in the mother during the pregnancy. We were not able to test the mother and child for viral loads by PCR, which would have confirmed the diagnosis. We report this case because of the acute deterioration of the neonate, the lack of elevated levels of IgM antibodies against CMV and rubella, with elevated levels of IgG antibody to both organisms, and the very high nucleated RBC counts.

DISCUSSION:

Viral infections are major causes of maternal and fetal morbidity and mortality. Infections can develop in the neonate transplacentally, perinatally [from vaginal secretions or blood] or postnatally [from breast milk or other sources]. The clinical manifestations of neonatal infections vary depending on the viral agent and gestational age at exposure. The risk of infection is usually inversely related to the gestational age at acquisition, some resulting in a congenital infection. The risk of primary maternal CMV infection leading to congenital CMV infection is approximately 40%. Approximately 85 – 90 % of infected are asymptomatic at birth; of those who are symptomatic at birth, half will present with isolated findings and the other half with CMV inclusion disease. CMV disease in this group carries a mortality rate of around 30%. 50 – 80% of neonates exposed to rubella within 12 weeks of gestation show signs of congenital infection. The rate of transmission drops dramatically thereafter, such that the risk of congenital infection is very small if infection occurs after 18 weeks of gestation. 4 TORCH infections are unique in their pathogenesis and have potentially devastating clinical effects. TORCH as an acronym stands for Toxoplasmosis, Other [T. Pallidum, Varicella Zoster Virus [VZV], Parvovirus B19], Rubella, Cytomegalovirus [CMV] and Herpes simplex Virus [HSV]. The usual way in which the fetus is infected is by transplacental spread after maternal infection in which the organism circulates in the maternal blood. In most cases the maternal infection is mild but the impact on the fetus is more severe. 1 Because of their relatively low virulence the organisms seldom lead to fetal death beyond the earliest stages of embryogenesis. Since the fetus is essentially a graft of foreign tissue in the uterus, the placenta constitutes a protective immunological barrier that shields the fetus from the mothers’ humoral and cell mediated immune responses.

There are various studies which have documented the incidence of CMV and rubella in Indian population. 5, 6, 7 Singh et al found a positivity rate of 2.8% for rubella IgM and 12.5% for CMV IgM in children. In asymptomatic pregnant women the incidence of rubella IgM positivity was 0.7% and in women with obstetric complications it was 3.4%. IgM antibody positivity for CMV was 7.8% in both groups [asymptomatic pregnant women and women with obstetric complications. 5 Gandhoke et al reported an incidence of 18.75% positivity for CMV IgM in infants and children with congenital infection. 6 Sadik et al found a positivity of 4.65% for Rubella IgM and 29.06% for Rubella IgG and 0% for CMV IgM and 23.25% for CMV IgG in patients with BOH. 7 Most screening programs are based on the detection only of IgM antibodies against CMV and rubella. However, a Brazilian study has recommended the use of IgG antibody screening against TORCH viruses. 8 In our case, both mother and child were negative for CMV and Rubella IgM antibodies but positive for IgG antibodies against infectious agents, which is in agreement with the findings of these authors. Sadik et al also showed a higher incidence of IgG positivity vis a vis IgM positivity in their study. We could not carry out repeat titers of IgG levels of CMV and rubella in our patient because of the early death of the neonate. Fetal erythropoiesis is driven by hypoxia – erythropoietin – NRBC precursors. The number of nucleated RBC’s circulating in the blood of a healthy, full – term infant normally does exceed 8 – 9 per 100 WBC’s counted. 9 Increases in NRBC numbers are seen in intra – uterine hypoxia, maternal diabetes, prematurity, chorioamnionitis, intra – uterine growth restriction [IUGR], preeclampsia and Rh sensitization. Congenital syphilis, toxoplasmosis, CMV, rubella and parvovirus have all been associated with elevated NRBC counts, even up to 500 NRBC’s / 100 WBC’s. 10 Our patient had markedly high NRBC counts, probably because of active hemolysis and extramedullary haemopoiesis, supporting a diagnosis of congenital CMV and rubella infection.

Intra uterine infections are a common cause of Non Immune Hydrops Fetalis [NIHF] [4 – 15%] with parvovirus B19 infection and secondary anemia the most frequent. Fetal toxoplasmosis, syphilis, CMV and Varicella can also present as NIHF, with commonly associated findings of hepatomegaly, splenomegaly or ascites. 11

CONCLUSION:

Patient developed NIHF as a consequence of congenital CMV infection. Our patient had concomitant high levels of IgG antibody to cytomegalovirus and rubella, which we did not find reported elsewhere. We could also not find any reported cases of CMV and Rubella infections with such raised counts of monocytes and lymphocytes.

REFERENCES:

  1. Boyer, SG and Boyer, KM. Update on TORCH infections in the Newborn Infant. Newborn and Infant Nursing Reviews. 2004;4(1). medscape.com/viewarticle/472409_print.
  2. Kaur R, Gupta N, Nair D et al. Screening for TORCH infections in pregnant women: a report from Delhi. Southeast Asian J Trop Med Public Health 1999;30(2):284–6.
  3. Simonsen KA, Anderson – Berry AL, Delair SF and Davies HD. Early onset neonatal sepsis. Clin Microbiol Rev 2014;27[1]:21–47.
  4. Marino T, Isaacs C. Viral infections and pregnancy. 2014. Medscape e – medicine article 235213. http://emedicine.medscape/article/235213-overview.
  5. Singh MP, Arora S, Das A et al. Congenital rubella and cytomegalovirus in and around Chandigarh. Indian J Pathol Microbiol 2009;52[1]:46-
  6. Gandhoke I, Aggarwal R, Lal S et al. Congenital CMV infection in symptomatic infants in Delhi and surrounding areas. Indian J Pediatr 2006;73:1095–7.
  7. Sadik MS, Fatima H, Jamil K et al. Study of TORCH profile in patients with Bad Obstetric History. Biology and Medicine 2012;4(2):95–101.
  8. Neto EC, Rubin R, Schulte J et al. Newborn screening for congenital infectious diseases. Emerging Infectious Diseases 2004;10(6):1069–73.
  9. AxtFliedner R, Ertan K, Hendrik H et al. Neonatal Nucleated Red Blood Cell Counts. J Ultrasound Med 2001;20Delair SF:183–90.
  10. Ingall D, Sanchez PJ. Syphilis. In: Infectious diseases of the fetus and newborn infant. 2001. Eds: Remington, JS, Klein, JO. [WB Saunders, Philadelphia]. 5th Pg 654.
  11. Desilets V, Audibert F. Investigation and Management of non - immune fetal hydrops [SOGC Clinical Practice Guideline]. J Obstet Gynaecol Can 2013;35(10):1–14.

Table 1: Results of investigations on the neonate on 21 Oct 2015

Investigation

Result

Units

Serum Potassium

6.5

mEq/liter

 

10

mEq/liter

PCV

18.7

%

 

45.6

%

Reticulocyte count

14.1

%

Cord TSB

5.4

Mg/dl

X ray chest

Right sided pneumothorax

Haemoglobin

6.2

Gm/dl

RBC count

1.13

Millions/cu mm

MCV

156.7

Femtoliters

MCH

54.9

Picograms

MCHC

33.2

Gm/dl

RDW

27.3

%

TLC

1,02,600

Cells/cu mm

DLC

Neutrophils 16

 

 

Lymphocytes 44

 

 

Eosinophils 06

 

 

Monocytes 34

 

 

Basophils 00

 

Platelet count

1.35

Lakhs/cu mm

Smear evaluation

RBC’s exhibit anisocytosis; macrocytes, microcytes and normocytes noted. NRBC’s 254/100 WBC’s counted.

Corrected TLC 29,000/cu mm; marked increase in mononuclear cells and smear cells seen. Prolymphocytes are observed.

Platelet morphology within normal limits.

 

TORCH IgG PANEL [5 parameters]

Rubella virus IgG Toxoplasma IgG

CMV IgG

HSV 1 &2 IgG

Toxoplasma IgG

2.87 [> 1.3 positive]

WNL

2.86 [> 1.2 positive]

WNL

WNL

Ratio

TORCH IgM PANEL [5 parameters]

All within normal limits

Ratio

 





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