With the recent case of a child in Kerala who died from Severe Combined Immunodeficiency (SCID) after contracting vaccine-derived poliovirus (VDPV), questions arise about the safety and management of polio vaccination, particularly in immunocompromised individuals. VDPV, which emerges from mutations in the oral polio vaccine (OPV) strain, poses unique challenges compared to wild poliovirus.
The case highlighted the importance of maintaining high vaccination rates and implementing newborn screening for immune deficiencies, particularly in countries using the OPV.
We spoke with Dr P J Harsha, Professor and Head of the Department of Paediatrics at Sri Madhusudan Sai Institute of Medical Sciences and Research, and Dr Pankaj Verma, Senior Consultant in Internal Medicine at Narayana Hospital (Gurugram) who provided insights into the current state of vaccine safety, preventive measures and the latest advancements in antiviral treatments.
What is vaccine-derived poliovirus (VDPV), and how does it differ from wild poliovirus?
Dr P J Harsha: Wild poliovirus is the naturally occurring virus that causes poliomyelitis, a potentially severe and paralytic disease. It exists in three serotypes (types 1, 2, and 3).
Vaccine-derived poliovirus (VDPV), on the other hand, originates from the weakened live poliovirus contained in the oral polio vaccine (OPV). Though OPV is a safe and effective vaccine that has played a critical role in eradicating wild polioviruses globally, in rare cases, the weakened virus can revert to a more virulent form. This occurs when it circulates in under-immunised populations for an extended period or replicates in an individual with a compromised immune system, potentially leading to illness and paralysis.
VDPVs are categorised into three types:
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Circulating VDPVs (cVDPVs): These arise from outbreaks in areas with low OPV coverage.
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Immunodeficiency-associated VDPVs (iVDPVs): These occur in individuals with primary immunodeficiencies.
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Ambiguous VDPVs (aVDPVs): These cannot be classified into either of the first two categories.
OPV is typically administered in the form of oral drops and works by inducing immunity in the gut, which helps stop the spread of the virus. However, VDPVs emerge in situations where insufficient vaccination coverage allows the weakened virus to spread among under-immunised populations.
Can you explain how VDPV was transmitted from an immune-deficient child to his healthy father? (A recent case reported from Kerala) How common is this type of transmission?
Dr P J Harsha: Immunodeficiency-related vaccine-derived polioviruses (iVDPVs) are a rare form of VDPVs that occur in individuals with primary immunodeficiency (PID). While most people with normal immune systems (immunocompetent persons) excrete the vaccine virus for a limited time, those with immunodeficiencies may be unable to clear the virus from their intestines after receiving the oral polio vaccine (OPV). As a result, the virus can replicate in their intestines for an extended period, leading to the excretion of iVDPVs.
In a recent case from Mallapuram district, Kerala, a seven-month-old boy with a severe immunodeficiency disorder received the OPV as part of routine immunisation. Due to his impaired immune response, the child was unable to clear the vaccine virus infection, which typically resolves within six to eight weeks in healthy individuals. Instead, he continued to excrete the virus over a prolonged period. The virus was then transmitted to his father through the faecal-oral route, which is the most common mode of polio transmission, especially among close contacts.
In this incident, an epidemiological investigation was initiated within 48 hours to assess polio immunity in the community and to search for any cases of Acute Flaccid Paralysis. Fortunately, only the child and his father tested positive for the iVDPV type, while others in the community tested negative.
With the child from Kerala succumbing to Severe Combined Immunodeficiency (SCID), how critical is it to implement newborn screening for immune deficiencies in countries using the oral polio vaccine (OPV)?
Dr P J Harsha: Severe Combined Immunodeficiency (SCID) is a rare condition, affecting about 1–3 out of every 100,000 babies. Infants with SCID have severely weakened immune systems, making them highly susceptible to infections. Newborn screening for SCID can be done alongside routine screenings for other conditions in the first few days of life. This screening measures the levels of a T-cell marker using the same dried blood spots collected for other tests. Newborns with low levels of this marker are at higher risk for SCID, but further testing is required to confirm the diagnosis. Without screening, SCID may go undiagnosed for seven months or more after symptoms appear, and some cases may never be identified. Early screening allows for diagnosis and treatment before symptoms develop.
Currently, SCID screening is not part of routine newborn screening in many countries, as the condition is rare. However, the recent case from Kerala, where a child with SCID succumbed after receiving the OPV, highlights the importance of early detection.
In 2022, an exercise by the ICMR-National Institute of Virology, Mumbai, and ICMR-National Institute of Immunohematology, in collaboration with the World Health Organisation, was conducted in two phases. Out of 157 children with Inborn Errors of Immunity (IEI) screened for polio and non-polio enterovirus excretion across the country, one child from Malappuram, Kerala, who had received two doses of OPV, was found to be positive. An epidemiological investigation was promptly initiated, and only the child and his father were found to be positive for iVDPV. Globally, there are very few reports of iVDPV transmission to healthy adults.
Expanding IEI surveillance could facilitate the early detection and follow-up of iVDPV excretion, reducing the risk of its spread. However, the cost of implementing SCID and other immunodeficiency disorder screenings for the entire population would be significantly higher compared to targeted IEI surveillance.
What measures can be taken to prevent the spread of VDPV, especially in households with immune-deficient individuals?
Dr Pankaj Verma: I emphasize the critical importance of vaccinations in preventing the spread of vaccine-derived poliovirus (VDPV), especially in households with immune-deficient people. First and foremost, ensuring complete immunization with the inactivated polio vaccine (IPV) is vital, as it significantly reduces the risk of VDPV transmission. Hygiene plays a crucial role as well—strict handwashing practices, safe food handling, and proper sanitation can prevent the virus from spreading through contaminated surfaces or food. For households with immunocompromised members, it’s essential to limit contact with people who have recently received the oral polio vaccine (OPV), as they could shed the virus. Regular health check-ups and prompt reporting of any symptoms are also key.”
What are the current advancements in antiviral treatments for poliovirus, and how might these impact the management of iVDPV cases, especially in immunodeficient patients?
Dr P J Harsha: As per the Global Polio Eradication Initiative (GPEI), there are three primary scenarios where polio antiviral drugs might be used:
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Treatment of Immunodeficient Individuals Excreting Poliovirus
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Preventive Treatment for Exposed Individuals: This includes those who may have been exposed to poliovirus through unintentional laboratory exposure or other means
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Use in Communities Exposed to cVDPV Outbreaks: In the post-eradication era, antiviral drugs could be used in conjunction with inactivated polio vaccines (IPV) to manage outbreaks of circulating vaccine-derived poliovirus (cVDPV).
In 2006, the Poliovirus Antivirals Initiative was established with the goal of identifying safe and effective antiviral drugs that could prevent, reduce, or stop poliovirus shedding in immunodeficient individuals who received the oral polio vaccine (OPV). Several drug candidates were evaluated, including capsid inhibitors and protease inhibitors.
Pocapavir (V-073) emerged as the lead candidate. It has undergone clinical testing in adults, demonstrating that the treatment is safe and significantly accelerates virus clearance. However, during trials in a clinical isolation facility, issues such as the emergence of drug resistance and continued virus transmission were observed.
To address these challenges, the Poliovirus Antivirals Initiative is currently developing a combination therapy that includes Pocapavir and another drug candidate, V-7404. V-7404 works through a different mechanism (protease inhibition), which is intended to reduce the likelihood of resistance developing.
Given the rarity of iVDPV transmission to healthy people, how should public health guidelines adapt to prevent similar cases, particularly in households with immunocompromised members?
Dr Pankaj Verma: It’s important to emphasize that while iVDPV (immunodeficiency-related vaccine-derived poliovirus) transmission to healthy individuals is exceedingly rare, public health guidelines must still evolve to remove any potential risks. Given that immunocompromised individuals are more vulnerable, households with such members should receive targeted guidance. This could include heightened awareness about the potential risks associated with live attenuated vaccines, ensuring timely and complete vaccination for all household contacts, and considering alternative vaccine options where appropriate. Public health protocols should also incorporate regular screening for immunodeficiencies before administering oral polio vaccines, alongside increased surveillance in communities with known cases of immunodeficiency. Prevention remains our most effective tool in safeguarding both individual and public health.
What are the implications of this case for countries like India that rely on oral polio vaccines?
Dr P J Harsha: The use of Oral Polio Vaccine (OPV) in India carries the risk of Vaccine-Derived Poliovirus (VDPV), particularly due to the type 2 component of the vaccine. Recognising this risk, the Global Polio Eradication and Endgame Strategic Plan 2013–2018 recommended the phased withdrawal of OPV, starting with the type 2 component, and the introduction of Inactivated Poliovirus Vaccine (IPV), which is a killed vaccine. India, along with other Southeast Asian countries, has already begun this transition.
The switch from trivalent OPV (tOPV) to bivalent OPV (bOPV) was anticipated to reduce immunity against poliovirus type 2, potentially increasing the risk of new circulating VDPV (cVDPV) type 2 outbreaks post-switch. To mitigate this risk, it was recommended that IPV be introduced, which India has already initiated. Additionally, it was advised that all type 2 poliovirus materials or potentially infectious materials be destroyed or contained according to WHO’s Global Action Plan III.
However, there have been global constraints in IPV supply due to challenges in scaling up IPV manufacturing. To address the short supply, India adopted an alternative immunisation schedule in April 2016, administering two fractional doses of IPV intradermally instead of a single full dose, as recommended by the WHO.
