Effectiveness and Safety of an Intravenous Immune Globulin (IVIG) Preparation in Post-exposure Prophylaxis (PEP) Against Measles in Infants

Benno Kohlmaier; Heidemarie Holzmann; Karin Stiasny; Manuel Leitner; Christoph Zurl; Volker Strenger; Michael Kundi; Werner Zenz

doi:10.3389/fped.2021.762793

Effectiveness and Safety of an Intravenous Immune Globulin (IVIG) Preparation in Post-exposure Prophylaxis (PEP) Against Measles in Infants

Front Pediatr. 2021 Dec 2:9:762793. doi: 10.3389/fped.2021.762793. eCollection 2021.

Authors

Benno Kohlmaier¹, Heidemarie Holzmann², Karin Stiasny², Manuel Leitner¹, Christoph Zurl¹, Volker Strenger³, Michael Kundi⁴, Werner Zenz¹

Affiliations

¹ Department of General Pediatrics, Medical University of Graz, Graz, Austria.
² Center for Virology, Medical University of Vienna, Vienna, Austria.
³ Clinical Division of Pediatric Pulmonology and Allergology, Medical University of Graz, Graz, Austria.
⁴ Department of Environmental Health, Center for Public Health, Medical University of Vienna, Vienna, Austria.

Abstract

Background: Administration of measles virus (MV)-specific IgG as post-exposure prophylaxis (PEP) is known to effectively prevent measles. Since the introduction of active immunization against measles, the levels of MV-specific IgG antibodies in the population have dropped. Therefore, the concentration of MV-specific antibodies in immunoglobulin products derived from human plasma donors has declined as the proportion of vaccinated donors has increased. Literature on the effectiveness of PEP with current available immunoglobulins is limited. Here we examine the effectiveness of 400 mg/kg intravenous immunoglobulin (IVIG) (IgVena®, Kendrion) as PEP in infants during a measles outbreak in Austria, 2019. Methods: After exposure to a highly contagious measles patient, identified infants were evaluated for eligibility for IVIG PEP. Infants were tested for measles maternal antibodies, if the result was expected to be available within 72 h after exposure. IVIG was administered to eligible infants with negative maternal IgG antibody levels (n = 11), infants with protective levels but result beyond 72 h (n = 2) and infants not tested for maternal IgG antibodies (n = 52). Telephone enquiries were made asking for measles infection. Effectiveness was calculated using exact logistic regression. Samples of four out of seven used IVIG batches were tested for MV-neutralizing antibody capacity. Results: In 63 (96.9%) of 65 infants PEP with IVIG was administered. The parents of two infants declined IVIG PEP. None of the infants with IVIG PEP got measles or symptoms suggestive for measles, but both infants who did not receive PEP were infected. Effectiveness of IVIG PEP was calculated to be 99.3% (CI 95%: 88.7-100%). No serious adverse event of IVIG treatment was observed. The investigation on MV-neutralizing antibody capacity showed a geometric mean titer ranging from 10.0 to 12.7 IU/ml, resulting in a 1.57-2.26-fold higher concentration than postulated as minimum level for immunity. Conclusions: Our findings suggest that the used IVIG preparation provided an at least non-inferior protection rate compared to IVIG preparations derived from donors before the global introduction of standard active immunization against measles.

Keywords: intravenous immunoglobulins; maternal measles-specific IgG antibodies; measles outbreak control; measles post-exposure prophylaxis; measles virus specific neutralizing antibody.