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Case history
A 38-year-old pregnant woman was admitted with vomiting and general body itching in Ndala hospital, Tabora region, Western Tanzania. The fundal height corresponded to a gestational age of 30 weeks. Malaria and syphilis tests were negative, the haemoglobin count was 12.4 g/ dl, and urinalysis showed only haematuria. Following admission, she was unable to eat and drink with excessive vomiting and shortness of breath. She progressively suffered from tremors and was becoming increasingly restless, febrile and afraid to drink water. When asked, a bite of an unknown animal five months before was reported, increasing suspicion of rabies. The patient was treated with diazepam and promethazine. The first dose of antenatal corticosteroid therapy was administered to promote lung maturation of the foetus in anticipation of possible preterm birth. While staff and relatives were still contemplating whether to perform a caesarean section to try and save at least the baby, the mother died, together with her unborn baby, two days after admission.

Background

Around 30,000 to 70,000 people worldwide die of rabies each year, most often acquired by bites of rabid dogs causing transmission of the virus from the dog’s saliva. If left untreated, infection rates vary between 38% and 57% and depend on the severity and location of the wound and virus titre in the saliva. When symptoms start to develop, mortality reaches 100%. Human rabies deaths are preventable through local treatment of the wound, followed by prompt administration of Post Exposure Prophylaxis (PEP) with the anti-rabies vaccine, with or without rabies immune globulin (RIG); see Table 1. [1,2]

The woman we presented did not receive PEP although she was bitten by a dog, maybe due to lack of knowledge or money. We will focus on some dilemmas regarding rabies in pregnancy. Will the foetus benefit from premature delivery by caesarean section or would vaginal delivery be better? What is known about the risk of the baby also becoming infected? Moreover, how safe is PEP in pregnant women and newborns?

The rabies virus

Rabies is caused by several different species of viruses (Genus Lyssavirus). After amplification near the site of contamination, the virus migrates centrally to the peripheral motor and sensory nerves until it reaches the spinal cord and brain, causing acute encephalitis. [3] Time of incubation varies from one week to six months. [2]

Passive and active immunisation

Post-exposure immunisation reduces the risk of rabies when the treatment is given before clinical signs of rabies develop. Prophylaxis should be given as soon as possible after exposure. The rabies vaccine induces protective virus-neutralising antibodies within approximately 7-10 days (active immunisation). The rabies immune globulin (RIG) provides immediate virus-neutralising antibodies until protective antibodies are generated in response to the vaccine (passive immunisation), which may be necessary when contamination of the virus is near to the central nervous system, resulting in a short incubation period. [4] In Ndala hospital, human RIG is not available; only rabies vaccine is. Rabies PEP is safe for pregnant and breastfeeding women as well as for newborns. [1,5,6] Studies found no increased risk of spontaneous abortions, premature births or foetal abnormalities among pregnant women after receiving PEP. [1]

Mother-to-child transmission

The exact risk of vertical transmission of rabies is unclear, but mother-to-child transmission has rarely been reported. The most important risk for the baby is the death of the mother before labour. Rabies virus is not present in the blood, and risk of contamination of the baby’s mucosa by maternal infectious fluids and tissue seems limited. [7]

There are multiple reports describing cases of healthy babies being born, irrespective of mode of birth, from pregnant women with rabies. [1,5,6,7,8,9,10,11] In most cases, either the mother, the baby or both received PEP (vaccine and humane RIG when available).

However, in one study four pregnant women with rabies and their babies appeared to not have received PEP due to fear that PEP might harm the foetus. Three of these women delivered successfully by caesarean section, and one baby died due to non-rabies related complications. [1] Some studies also described the status of the mothers after delivery. In every reported case, the mother had passed away. [8,9,11]. An interesting Turkish article mentioned a term woman who was bitten by a dog 34 days earlier. [12] 40 hours after vaginal delivery the baby died suddenly. Rabies was confirmed in both the mother and baby. This is the first case reporting human rabies acquired by placental transmission.

The above indicates that the delivery of a healthy neonate from a rabid mother is possible. The route of delivery does not seem to be a determinant for the neonatal outcome. It cannot be excluded that the foetus can be contaminated by the placenta, vaginal secretions of infected maternal tissues although many reports conclude that the neonates remain healthy after receiving PEP.

Practical dilemmas

If the diagnosis is correct, the mother will surely die. This raises concerns on the (long term) chances if the neonate is born without rabies, especially in case of suspected prematurity. In general, the prognosis of a neonate after maternal death is poor. An analysis in Ethiopia indicated that in case of maternal death, the infant was much more likely to die than to survive. [13]

After symptoms of rabies appear, death by rabies will follow in a few days. Vaginal delivery might not be quick enough. Caesarean section is quicker but exposes health care workers to a higher risk of rabies infection.

Prevention of rabies is a superior strategy. The use of PEP and RIG appears to be safe in pregnant women and newborns. If a pregnant woman might have been exposed to rabies, prophylaxis needs to be administered as soon as possible. Health education campaigns need to focus on education of pregnant women and local health workers to inform them of the importance of timely prophylaxis and its safety. In our case, the prognosis of both the mother and the foetus was poor because the rabies was already symptomatic and prematurity was predicted. Retrospectively, a caesarean section would have put health staff at risk with little chance of saving the baby.

Co-authors
CHOBO STEVE PAUL, MD
St. Joseph’s Mission Hospital, Ndala-Tabora, Tanzania.

ROB MOOIJ, MD
Medical doctor international health and tropical medicine, gynaecologist in training, Jeroen Bosch Ziekenhuis, ‘s Hertogenbosch. Former medical officer (2010-2013) Ndala Hospital, Tanzania.

References

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  2. The United Republic of Tanzania, Ministry of Health and Social Welfare. Standard treatment guidelines and national essential medicines list for Tanzania Mainland. July 2013, fourth edition.
  3. UpToDate. Clinical manifestations and diagnosis of rabies. [Internet]. Available from: https://www.uptodate.com/contents/clinical-manifestations-and-diagnosis-of-rabies. [Accessed October 1st, 2018].
  4. UpToDate. Rabies immune globulin and vac-cine. [Internet]. Available from: https://www.uptodate.com/contents/rabies-immune-globulin-and-vaccine. [Accessed October 1st, 2018].
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