Fatal avian influenza A(H5N1) infection in a 36‐week pregnant woman survived by her newborn in Sóc Trăng Province, Vietnam, 2012

Background Reports of pregnant women infected with avian influenza are rare. Studies showed that A/H5N1 virus can penetrate the placental barrier and infect the fetus. Of six documented cases, four died and two survivors had a spontaneous abortion. Objectives We report a clinical, outcome and epidemiological characteristics of a 36‐week pregnant woman infected with A/H5N1 and her newborn in Soc Trang province of Vietnam in 2012. Methods Epidemiological and laboratory investigations were conducted. Clinical manifestations, progress, treatment and outcome of the case‐patient and her newborn were collected. Human tracheal aspirate, throat swab and serum specimens were tested for influenza A/H5N1, A/H3N1, A/H1N1pdm09 and B by real‐time RT‐PCR and genome sequencing. Poultry throat and rectal swabs were tested by PCR and virus isolation. Results Case‐patient hospitalized with high fever and cough, and died after onset 6 days. She continuously slaughtered sick poultry 5 days before illness onset. Clinical manifestation showed rapid progressive severe pneumonia. Her tracheal aspirate sample was positive influenza A/H5N1 virus. Her new‐born was delivered by caesarean section with low birth weight and early onset pneumonia, however fully recovered after 16 days treatment. Neonate's throat swabs and paired serum samples tested negative for influenza A/H5N1. Clade 1.1 A/H5N1 virus was detected in poultry samples, was same clade and highly homogenous with the virus was detected in the mother. Conclusions This was the first documented a live birth from a pregnant woman infected with influenza A/H5N1 virus. Intensive studies are needed to better understand mother‐to‐child transmission of influenza A/H5N1 virus.


| BACKG ROU N D
27% and 45% of the entire country respectively. The case fatality rate (CFR) of the Southern region was nearly 1.7 times higher than the CFR in Vietnam. 4 In January 27, 2012, the Sóc Trăng Provincial Preventive Medicine Center was informed about a pregnant patient with suspected avian influenza infection who was admitted to a provincial hospital with high fever and cough. On that day, the Ho Chi Minh City Pasteur Institute (HCMC PI) was also informed about this case.
A day after, the provincial hospital reported that the pregnant patient had died; however, her baby was delivered by cesarean section alive but critically ill.
It was noted that pregnancy associated with A(H5N1) infection is very rare and little is known about A(H5N1) infection during pregnancy. Of the six cases that have been documented, four pregnant women died and two pregnant women who survived had spontaneous abortions. 5 In addition, a recent study showed that the CFR for A(H5N1) infection in pregnant women was 10%-25%, which is much higher than the general population with A(H5N1) infection at 0.3%-1%. 6 This case report describes the epidemiological characteristics, clinical progress and outcome of the Vietnamese pregnant woman (case-patient) and her newborn. Results of the in-depth outbreak investigation to trace the cause of the A(H5N1) infection have been presented.

| ME THODS
We conducted a case study of the clinical characteristics and the outcomes of the case-patient who was pregnant at the time of diagnosis with avian influenza A(H5N1) infection and her newborn baby.
An initial risk assessment was conducted and an in-depth outbreak investigation carried out by a team of epidemiologists, clinicians, virologists and local veterinarians.
The World Health Organization (WHO) guidelines for investigation of human cases of avian influenza A(H5N1) 7 were used to develop investigation tools. The medical records of the case-patient were reviewed and the physicians who cared for the case-patient were also interviewed.
The team collected the epidemiological data of the case-patient and her newborn including the exposure history. Contact tracing was implemented where a list of contacts was developed and for close contacts that were identified were monitored. Contacts were defined as those who had contact with the case-patient eg meeting with the case-patient or had been exposed to the same source eg contact with poultry that was sick or had died such as raising or touching the poultry. Close contact was defined as anyone who  28  8  9  10  11  12  13  14  15  16  17  18  19  20  21  22  23  24  25  26  27  28  29  30  31  1  2  3 Nov -Dec January February

| Clinical course and laboratory data: Casepatient
The case-patient was a 26-year-old rice farmer, without any history of chronic diseases who was pregnant at 36 weeks gestation. She had two antenatal examinations at the second and third trimester with no pregnancy complications noted. The seasonal influenza vaccine was not available in the case-patient's hometown and as a result had not been vaccinated. The case-patient had not visited any poultry outbreak site or live bird market in the 7 days prior to the onset of her symptoms.
The case-patient's hospital course and related information was collected from her medical records. She developed fever and cough on January 22, 2012 and had been treated by a local clinician on the same day. Two days later, she was treated at an outpatient department of a district hospital and then hospitalized at the provincial hospital on January 25, 2012 presenting with cough and high fever.
The admission diagnoses were: pregnancy at 36 weeks gestation; oligohydramnios (amniotic fluid index = 5) and pneumonia. She was treated initially with antibiotics and antipyretics. The doctors then decided to deliver her baby by cesarean section (Figure 1).
On day 2 of hospitalization (January 26, 2012), the patient developed dyspnea. Chest auscultation revealed crackles in her right lung.
Thoracic ultrasound showed pleural effusion of her right lung, and the chest X-ray showed bilateral opacities. Acute respiratory distress syndrome (ARDS) was evident based on the rapid progression from unilateral to bilateral pulmonary infiltrate compared to the chest X-ray image on day 1 (Figure 2). Her oxygen saturation dropped to 80%, requiring intubation and mechanical ventilation.

| DISCUSS IONS
Prior studies have indicated that pregnant women are considered a high-risk population for influenza A(H1N1) pdm09 and avian influenza viruses and are more likely to develop severe complications and to die, especially when infection occurs in the middle and late trimesters. 6,[11][12][13] The case-patient, a 36-week pregnant woman was exposed to sick chickens and was infected with the avian influenza A(H5N1) virus, developed rapid progressive severe pneumonia, lymphopenia, sever hypoxia and increased aminotransferase levels, similar to previously reported avian influenza A(H5N1) patients 6,14,15 Common complications of highly pathogenic avian influenza (HPAI) H5N1 virus infection such as primary pneumonia, respiratory failure due to ARDS, and fatal outcome have been seen and recorded in the case-patient's clinical progress. 16 The case-patient died after 6 days from onset of illness, less than the duration period of 9.8 days reported by Shelan et al. 6 In this case, the case-patient was exposed to poultry 1 to 5 days prior to onset of illness, whereas the number of days between exposure and onset of illness reported by other studies 14  women, should be vaccinated as a priority.
We described the first reported alive newborn baby delivered by cesarean section from a mother (the case-patient) infected with the avian influenza A(H5N1) virus during the third trimester of pregnancy, among 14 other pregnant women infected with A(H5N1), but whose fetuses did not survive regardless of the pregnancy trimester. 6 Previous postmortem studies carried out on pregnant women suggest diffuse systemic dissemination of the A(H5N1) influenza virus including infection in the fetal-placental membranes, 5 suggesting that the A(H5N1) virus could be transmitted from mother to fetus across the placenta. 21 However the newborn baby of this case-patient was negative of the A(H5N1) virus. The severe clinical symptoms that the newborn developed was neonatal respiratory distress syndrome due to intra-amniotic infection, which was highly likely caused by her mother's (the case-patient's) critical condition of viral infection and preterm cesarean delivery at 36 weeks. [22][23][24] Findings from the in-depth investigation and laboratory test re-