Advocacy for neonates: Will respiratory syncytial virus monoclonal antibodies and maternal vaccine be made available in India?

INTRODUCTION

This case series is representative of a sincere request towards procurement of the recently approved maternal vaccine and monoclonal antibody against respiratory syncytial virus (RSV) in India. The burden of RSV-related morbidity is globally high.^[1] Ongoing research to develop prevention methods has led to the approval of two evidence-based strategies that are yet to enter this country.^[2,3] We describe here our experience with infected neonates who required intensive care through the season of RSV in 2023. To re-admit neonates who have gone home after several weeks of intensive care only to acquire a severe RSV lower respiratory infection (LRI) is heart-wrenching.

Epidemiological studies describe several million RSV-related lower respiratory infections.^[1] In a recent review of 12 studies, including 5969 children, that analysed risk factors for LRI in low-middle income countries (LMIC), authors reported a significantly higher risk of respiratory infections requiring in‐hospital care (0.5%–27.7%) in preterm neonates.^[4] There were no studies from India included in this report. Other authors, too, highlight that preventive strategies for RSV must be given high priority.^[5,6] We audited the de-identified data of affected neonates retrospectively. Therefore, no informed consent was sought.

CASE REPORT

From August 2023, among the 187 young infants who presented to the Neonatology outpatient services or emergency room with features suggestive of viral respiratory illnesses, we admitted nine neonates to the ICU. Sixteen others were admitted to non-ICU rooms for symptomatic treatment since they required monitoring for feeding and posttussive vomiting. The others were managed on an outpatient basis with close follow-up, either physically or by synchronous video teleconsultation. Fifteen infants’ families preferred to follow up and receive therapy in hospitals close to their homes.

Polymerase chain reaction (PCR) for respiratory viruses in a nasopharyngeal swab is sent only for those requiring intensive care (unit protocol). This allows for optimised use of antibiotics and reduces the cost of additional testing. In the admitted cohort, all nine tested positive for RSV. Two were extreme preterm with bronchopulmonary dysplasia and 6 were late preterm. Six had predominantly severe cough and chest signs; 5 preterm neonates presented with apnea as well.

All required non-invasive respiratory supports at some point during hospital stay. All of the preterm infants were ventilated, 2 of these needed high-frequency ventilation for up to 3 weeks. Median Interquartile range (IQR) age at presentation and duration of hospital stay was 30 (24–58) days and 18 (7–37) days, respectively. One infant was readmitted for the resurgence of a worrying cough. We had treated 4 with oral ribavirin and inhaled steroids, as there was a very slow response to supportive measures. Fortunately, all survived.

DISCUSSION

We report a rate of 4.8% requirement for intensive care and a 13% hospitalisation rate in infants <2 months of age for viral respiratory illness in 3 months. Indian hospital and community-based reports of RSV infection rates in children range up to 54% and 15%, respectively.^[7] Seasonal variations are known, these are, however, spread over several months. Other authors from different regions of India showed an incidence rate of up to 62.5%, with a high disease burden in children under five years.^[5] We describe nine neonates who were seriously ill and needed intensive care. Kalane et al. has reported 14 neonates who required hospitalisation related to RSV.^[8]

RSV infection has been implicated in LRI, neurological complications, and long-term predilection to asthma.^[9] Basic science research from 10 states in India has identified genotypes through phylogenetic analyses. In spite of the authors describing the very high burden of RSV disease in the country, we have no methods of prevention available here yet. Palivizumab is a short-acting monoclonal antibody derived from recombinant technology. This has been in use for several decades in high-income countries. The hospitalisation rate decreased significantly in those with comorbidities. Problems identified were low compliance due to the need for monthly injections and prohibitive costs.^[10] Gupta et al. concluded that infants at high risk of RSV pneumonia would still be at risk of acquiring other more common viral and bacterial infections and deemed the intervention cost-ineffective in India.^[11] Times have changed since, and we beg to differ. With the improved survival of extreme preterm neonates and the approval of effective methods of prevention, we would have to re-consider this statement.

Nirsevimab, a recently developed recombinant monoclonal antibody, can be given as a single intramuscular dose for preterm infants at high risk of RSV. Approved in 2023, the three amino acid substitutions in fragment crystallisable (FC) region increase Immunoglobulin G (IgG) affinity for the human Fc receptor, allowing recirculation. This results in a longer half-life and high potency. The safety profile is good, and evidence supports reduced medically attended RSV in term and high-risk preterm infants.^[2]

One can understand the scientific logic that supports vaccination during pregnancy for the passive transfer of antibodies to infants who are too young to receive vaccines themselves for diseases like influenza, pertussis, and COVID-19. A vaccine for RSV based on glycoprotein F has been approved for pregnant mothers. Since administration is recommended between 32 and 36 weeks gestation, extreme preterms would miss out.^[3] Moreover, with larger households having potential contacts for infection (elder siblings), maternal vaccination would not be wholly preventive.^[12]

Hence, the neonatology community might strategize a staged implementation. For high-risk infant groups like preterm and those with chronic cardiorespiratory illnesses, Nirsevimab would be required as a single dose (duration of action of 5 months) given at birth or before the baby’s first RSV season. If the baby remains “susceptible” or at high risk, another dose is advisable before the second season he/she is exposed to.^[13] It would mean that a schedule of 1 or 2 doses is advised for high-risk infants.

The costs vary based on the strategies used. In some countries, universal prophylaxis is given. Others are based on the severity of the RSV season or in high-risk neonates only. A recent cost-based review concluded that compared to placebo or palivizumab, nirsevimab was consistently less costly and more clinically efficacious (in terms of hospital admissions and in-patient/ICU care). However, the results varied depending immunisation program, parameters used to assess clinical efficacy, and the local price of nirsevimab.^[14]

Hence, generalising the findings may not be prudent. Local or regional data of efficacy and costs may be required to systematically assess cost–effectiveness. If indeed we were to study immunogenicity, efficacy, and clinical protection aspects systematically, the products would have to first be made available in the country. There would be a compelling reason to work towards maternal vaccination for wider protection.

CONCLUSION

RSV poses a risk to neonates, and some require prolonged intensive care support.

It is time we are at par with high-income countries with regard to the availability of advanced medications, along with increasing expertise and improved outcomes in neonatal care. Implementation of evidence-based measures for RSV infection would require cognizance of disease burden and preventive strategies. Programmatic changes and coordination with the pharmaceutical industry are necessary. We appeal that the near future will hold hope for these drugs to be available in India.