A newborn infected by Andes virus suggests novel routes of hantavirus transmission: a case report

Abstract

Hantavirus Pulmonary Syndrome (HPS) was described in Argentina in 1995 when Andes virus (ANDV) was firstly characterized. HPS is a zoonotic disease transmitted to humans mainly from rodent reservoirs; however, person-to-person transmission has been well documented for ANDV. HPS is characterized by severe noncardiogenic pulmonary edema resulting in respiratory compromise, with a case-fatality higher than 30%. The aim of the present study was to describe the first newborn case infected with ANDV and to assess possible routes of viral transmission including novel possibilities: intrauterine, perinatal, and breastfeeding infections. At springtime, 30–year-old- pregnant woman, at 34 weeks of gestation, manifested abdominal pain. The symptom was attributed to her 3 previous caesarean scars and an urgent cesarean section was performed. The child was born in full health but was transferred immediately to another specialized care centre. The mother had been discharged from the hospital 48 hours after child birth (Fig. 1) and attended to the neonatal centre to breast-feed her child who before that, was also artificially fed with maternal milk (Fig. 1). Six days following childbirth, she manifested fever and myalgia in her legs. The drastic deterioration of her clinical picture, including respiratory symptoms and elevated hematocrit, leukocytosis and thrombocytopenia, determined her hospitalization, but she rapidly progressed to respiratory failure and died 2 days later. The first manifestation of illness in the child was a sudden thrombocytopenia at day 15 after birth (200,000 to 40,000 cells/mm3 after a few days) and at day 19 respiratory symptoms were developed. Hantavirus infection was suspected, diagnosis and confirmation were performed at the National Reference Laboratory for Hantavirus (NRLH). Subsequent test results were obtained from the National Notifiable Diseases Surveillance System (SISA). The newborn hantavirus infection was confirmed by ELISA, showing titers of 400 (DO 0.51; Cut Off value 0.15) and 1600 (DO 1.32; Cut Off value 0.55) for IgM and IgG respectively, and genomic viral RNA was detected and quantified (5 × 105 RNA copies/ml) in a blood sample of day 26 after his first symptoms. The identified genotype was ANDV-BsA, based on 885 sequenced nucleotides of the viral S-segment. The criterion used to confirm ANDV infection was established by NRLH, which is even stricter than the CDC criterion: a laboratory confirmed case shows IgM and IgG positives. Serum samples from the newborn collected at days 28, 49 and 71 after symptoms onset, showed the declination of IgM titers and remained positive the IgG. The symptoms developed by the mother, particularly her rapid deterioration and death, were typical of HPS cases according to the clinical definition criteria. No samples could be recovered. The patient meets also strong epidemiological components: resident from a rural area in the endemic region; the case occurred in the season when the largest number of HPS cases was usually reported. The possible routes of transmission considered were: intrauterine, at least 16 days before child thrombocytopenia onset; perinatal, during cesarean section, 15 days before, in breastfeeding time and aerosol transmission, both between days 8 to 13. IgM, IgG positives, and the presence of viral genome in blood sample confirmed this infant as the youngest HPS case reported, a relevant finding because it establishes a new vulnerable population to consider. The transmission route that involves reservoir rodents was discarded since the child never left the hospital. Person-to-person transmission was well described and proved. In this mother/newborn couple was one of the hypothesis of transmission, however the short incubation period (8-13 days) was less than the previously described and allow us to consider other possible transmission routes. Viral RNA was found in the breast milk of a SNV infected mother indicating possible infectiousness. More recently, ANDV-genome was detected in breast milk sample of a HPS case in Chile (11th International Conference on Hantaviruses, unpublished data) and the newborn was also reported as a case of HPS. We were not able to obtain these samples, however breast milk and the gastrointestinal route of infection cannot be rule out. Among long lists of viruses that could be transmitted via placenta, there were no evidences of transplacental transmission for Puumala, Dobrava [[1]Hofmann J. Führer A. Bolz M. Waldschläger-Terpe J. Meier M. Lüdders D. et al.Hantavirus infections by Puumala or Dobrava-Belgrade virus in pregnant women.J Clin Virol. 2012; 55: 266-269Crossref PubMed Scopus (11) Google Scholar] or Sin Nombre virus; or vertical transmission of SNV. The four single-case reports that described hemorrhagic fever with renal syndrome in pregnancy in China [[2]Ma R.M. Xiao H. Jing X.T. Lao T.T. Hemorrhagic fever with renal syndrome presenting with intrauterine fetal death. A case report.J Reprod Med. 2003; 48: 661-664PubMed Google Scholar,[3]Ji F. Zhao W. Liu H. Zheng H. Wang S. He C. et al.Hemorrhagic fever with renal syndrome caused by Hantaan virus infection in four pregnant Chinese women.J Med Virol. 2017; Crossref Scopus (2) Google Scholar] and in Korea [[4]Kim B.N. Choi B.D. Hemorrhagic fever with renal syndrome complicated with pregnancy: a case report.Korean J Intern Med. 2006; 21: 150-153Crossref PubMed Scopus (8) Google Scholar] had no molecular evidence available to endorse this route, it will be necessary to study more cases to support intrauterine infection route. Blood contact during cesarean delivery was an opportunity for viral perinatal transmission and this possibility cannot be ruled out. This case report showed evidence of possible transmission routes of hantavirus which should be considered in pregnant women who have compatible epidemiology. The physiology and immunology in pregnancy may lead to variations in the typical presentation and/or the course of HPS. It is noteworthy that an ANDV infected newborn, having an immature immune system, could develop severe adverse effects in the long term, as encephalitis, which was previously described in an adult HPS case [[5]Talamonti L. Padula P.J. Canteli M.S. Posner F. Marczeski F. Weller C. et al.Hantavirus pulmonary syndrome: encephalitis caused by virus Andes.J Neurovirol. 2011; 17: 189-192Crossref PubMed Scopus (10) Google Scholar]. This study was funded by Instituto Nacional de Enfermedades Infecciosas INEI-ANLIS “Dr C. G. Malbran”, Buenos Aires, Argentina. Carla Bellomo encouraged case investigation and has written the manuscript; Daniel Alonso performed the molecular diagnosis, Rocío Coelho and Ayelén Iglesias performed serologic diagnostic; Natalia Periolo carried out the epidemiological investigation and Valeria P Martinez has been directed the work team.