From the Journals

Tenofovir didn’t prevent hepatitis B transmission to newborns

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A negative trial with a positive spin

The trial by Jourdain et al. – although described by the authors as negative – “puts down an intriguing marker attesting to the possibility that rapidly phasing in the timely administration of a safe monovalent HBV vaccine within a few hours after birth could contribute to the interruption of mother-to-child transmission and avert preventable HBV infections in childhood,” Geoffrey Dusheiko, MD, wrote in an accompanying editorial (N Engl J Med. 2018;378:952-3).

The World Health Organization supports HBV vaccine schedules of three or four doses, which are usually given as part of a combination immunization protocol beginning at 6 weeks of age. “Currently, HBV vaccination is most frequently administered as a pentavalent or hexavalent vaccine as part of the Expanded Program on Immunization, typically in combination with vaccines against diphtheria, tetanus, pertussis, polio, and Haemophilus influenzae type B,” wrote Dr. Dusheiko. “Paradoxically, support for combination vaccines within an integrated EPI schedule has unwittingly but undesirably shifted thinking and policy away from HBV vaccination at birth. This gap in vaccine strategy is disadvantageous.”

While the study doesn’t support tenofovir for maternal prophylaxis, it does imply value for treating the infant with immune globulin and HBV vaccination soon after birth. Delivering this kind of care globally will be challenging, but it’s entirely feasible, Dr. Dusheiko said.

“It is necessary to analyze regional data to assess the requirements for implementing vaccination at birth, including ... the training of otherwise unskilled birth attendants to deliver monovalent HBV vaccine at the same time as the vaccines against polio and bacille Calmette–Guérin. Importantly, the use of monovalent HBV vaccine would also require governmental or nongovernmental support. HBV vaccination at birth, despite the challenges for poverty-affected countries to deliver vaccination in rural and isolated locales, is feasible.”

Dr. Dusheiko is a hepatologist at the University College London School of Medicine and King’s College Hospital, London.


 

FROM THE NEW ENGLAND JOURNAL OF MEDICINE


Dr. Jourdain and his colleagues noted that the 2% transmission rate in the placebo group is considerably lower than the 7% seen in similar studies and could be related to the rapid postpartum administration of HBV immune globulin and vaccine. If this is the case, prenatal antivirals could be more effective in countries where postpartum treatment is delayed or inconsistent.

“Maternal use of tenofovir may prevent transmissions that would occur when the birth dose is delayed, but its exact timing has not been reported consistently in previous perinatal studies,” the team said.

Another question is whether the stringent, 5-dose infant HBV vaccine series required in Thailand is simply more effective than schedules that have fewer doses or are combined with other vaccines and delivered later.

“It remains unclear whether the administration of more vaccine doses is more efficacious than the administration of the three vaccine doses that is recommended in the United States and by the World Health Organization.”

Dr. Jourdain had no financial disclosures relevant to the study, which was sponsored by the National Institute of Child Health and Human Development.

SOURCE: Jourdain G et al. N Engl J Med. 2018;378:911-23.

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