Study shows vaccine-derived poliovirus in infant with severe immunodeficiency

By Tarun Sai LomteSep 13 2022Reviewed by Aimee Molineux

In a recent study published in Morbidity and Mortality Weekly Report, researchers identified type 3 vaccine-derived poliovirus (VDPV) in an infant.

The oral poliovirus vaccine (OPV) has been effective against poliomyelitis due to its ability to elicit intestinal and humoral immune responses. Sabin vaccine is a live attenuated poliovirus that stimulates the immune system by replicating in the intestine, thereby inducing immune responses against the vaccine strain.

OPV mutations due to protracted replication in under-vaccinated communities and immunodeficient individuals could result in neurovirulent, genetically divergent VDPVs. OPVs also cause vaccine-associated paralytic poliomyelitis (VAPP). Identifying polioviruses in circulation depends on acute flaccid paralysis (AFP) and wastewater/sewage surveillance.

Immunodeficiency-associated VDPV (iVDPV), integrated AFT, and environmental surveillance are pivotal to achieving the global eradication of polio. The first case of iVDPV was detected in the United Kingdom in 1962, and 149 iVDPV cases have been reported globally until May 2020. Most iVDPV patients develop paralysis before being diagnosed with immune deficiency and are mainly identified via AFP surveillance.

The Chinese Center for Disease Control and Prevention (CCDC) initiated a pilot iVDPV surveillance program in 2021, per the recommendations of the World Health Organization, to expand poliovirus surveillance among individuals with primary immunodeficiency disorder (PID). Five pediatric hospitals participated and provided stool specimens of infants newly diagnosed with PID or combined immunodeficiency disorder.

The study and findings

In the present study, researchers reported the identification of an infant with VDPV. A child admitted to Children’s Hospital of Chongqing Medical University was newly diagnosed with PID in March 2022. CCDC and relevant authorities investigated this case. The patient was a one-year-old boy from Guizhou province.

Initially, the patient was hospitalized at six months of life due to persistent diarrhea, diffuse red papules, fevers, and lymphadenitis. The subject was diagnosed with severe combined immunodeficiency (SCID) due to heterozygous mutations in the zeta chain of T cell receptor-associated protein kinase 70 (ZAP70) gene.

Lymph node culture and biopsy revealed disseminated mycobacterial infection. The boy was administered with a Bacillus Calmette-Guérin (BCG) vaccine shorty after birth. Further, the infant received two doses of inactivated polio vaccine (IPV) two and three months after birth and the first dose of bivalent OPV (bOPV) at four months of age.

Shortly after bOPV administration, the infant had left axillary lymphadenitis, eventually involving right axillary, cervical, and occipital lymph nodes. Later, the boy developed pneumonia due to infection with Klebsiella pneumoniae and Pneumocystis yersini. The patient died of respiratory failure at the age of 13 months.

Stool specimens of the infant collected in February and March 2022 were tested for poliovirus. Four isolates were identified as type 3 poliovirus. Molecular sequencing showed that the isolates had 15 shared nucleotide substitutions and differed from the type 3 Sabin vaccine strain by 22 to 24 nucleotides.

Conclusions

Infants with PID are affected by various hereditary disorders, resulting in immune dysfunction and developmental defects. As such, live vaccines are contraindicated in this population due to the disease risk. Although prenatal screening could identify PIDs, diagnosis/identification requires consultations with specialists such as clinical immunologists. Children with PID might be vaccinated with BCG/OPV before being diagnosed, increasing the risk of iVDPV and disseminated tuberculosis.

Overall, the patient’s death precluded additional stool sampling and further characterization of viral mutations. Notably, the patient did not develop paralysis. That a non-paralyzed iVDPV patient was identified in the pilot PID study emphasizes the development of an action plan for surveillance of iVDPV in China.