POLIOVIRUS OUTBREAKS: THROWING A CURVEBALL INTO THE POLIO-FREE WORLD ENDGAME

By: Putri Permata Sari, Titin Dani Martiwi, Adhella Menur

Brief history of polio, outbreaks, and towards a polio-free world

When we hear “polio” or “poliomyelitis,” we might imagine a child with a small and floppy, one-sided leg, emblematic of the spectrum of disabilities caused by poliovirus infection that has plagued humanity since ancient times. Evidence of polio was identified in an Egyptian painting from 1403 BC, depicting children with limb deformities relying on walking sticks. It wasn’t until 1789 that the English physician Michael Underwood provided the first clinical description, labeling polio as a “debility” of the lower extremities, primarily afflicting children under five. Its most severe consequences were permanent disability and even death, due to paralysis of the breathing muscles. The virus itself was successfully isolated by Karl Landsteiner and Erwin Popper in 1909. In 1931, Sir Macfarlane Burnet and Dame Jean MacNamara identified the three serotypes of the poliovirus: 1, 2, and 3.

By the mid-20th century, poliovirus infections were prevalent worldwide, causing paralysis or death in over half a million people annually. In the United States, localized paralytic poliomyelitis outbreaks began to appear around 1900. Poliovirus outbreaks became increasingly common in the late 19th and early 20th centuries, particularly in summer. One of the most notable early poliovirus outbreaks occurred in New York City in 1916, resulting in thousands of cases and deaths. This outbreak drew widespread attention due to the severity of the disease and fueled public fear. The United States experienced one of its worst poliovirus outbreaks in 1952, with over 50,000 reported cases and thousands of deaths. With no cure and increasing epidemics, a vaccine became urgent. Thomas Weller and Frederick Robbins successfully cultured the poliovirus in 1948, and David Bodian’s description of the three antigenic serotypes in 1952 paved the way for significant progress in vaccine development. Jonas Salk’s inactivated polio vaccine (IPV) in 1955 and Albert Sabin’s oral polio vaccine (OPV) in 1961 marked pivotal milestones, leading to widespread deployment in mass vaccination campaigns. Consequently, the number of polio cases steadily declined, and by 1985, polio had largely disappeared in developed countries. However, in developing countries, polio continued to cripple a child on average every 90 seconds, prompting global commitments and concerted efforts to immunize populations against the poliovirus.

In 1988, the World Health Assembly (WHA) adopted a resolution for the worldwide eradication of polio, marking the launch of the Global Polio Eradication Initiative (GPEI) – a collaborative effort led by various entities, including national governments, the WHO, Rotary International, the US CDC, UNICEF, and later, the Bill & Melinda Gates Foundation and Gavi, the Vaccine Alliance. Since its establishment, the GPEI has made remarkable progress, with a 99.9% reduction in global polio incidence. Wild poliovirus serotypes 2 and 3 (WPV2 and WPV3) were declared eradicated in 2015 and 2019, respectively. However, the endemic transmission of WPV1 persists in Afghani-stan and Pakistan. The endgame effort was also tempered by the emergence of circulating vaccine-derived polioviruses (cVDPVs) from OPV. In 2023, 12 cases of WPV1 in Afghanistan and Pakistan and 374 cases of cVDPV in several countries in Africa and Asia were reported.

To achieve a polio-free world in 2026, the GPEI has re-envisioned the endgame pathway with an urgent call for collective ownership and accountability across the GPEI partnership and with governments, communities, and all other stakeholders. The Polio Eradication Strategy for 2022–2026 outlines the plan for achieving a world free from all polioviruses. Efforts are also focused on transitioning and post-certification initiatives to ensure that the infrastructure established for polio eradication will continue to support broader public health initiatives even after polio is eliminated. The GPEI will transform its approach in each region and country with two elemental goals: Goal One to permanently interrupt all poliovirus transmission in the final WPV-endemic countries of Afghanistan and Pakistan, and Goal Two to stop cVDPV transmission and prevent outbreaks in non-endemic countries. Failure to implement strategic approaches results in continued virus transmission and could lead to a global resurgence of the disease, emphasizing the importance of achieving complete eradication.

Understanding polio

Poliovirus is a member of the genus Enterovirus, belonging to the Picornaviridae family. Human beings are the only known reservoir of poliovirus infection. The infection spreads through the fecal-oral route, and the virus is disseminated in feces, contributing to its highly contagious nature. The highest amount of virus excretion occurs 2 to 3 days before and up to 1 week after symptoms appear. The virus also presents in urban sewage, which may then serve as a source of direct or indirect transmission through flies or contaminated water used for drinking, bathing, or irrigation. Transmission is remarkably rapid in areas with poor sanitation, especially among children and individuals lacking immunity.

The clinical manifestation of poliovirus infection is categorized based on the severity of symptoms. Approximately 95% are asymptomatic cases. Symptomatic cases may present as mild illness (abortive poliomyelitis), aseptic meningitis (nonparalytic poliomyelitis), and paralytic poliomyelitis. Abortive poliomyelitis, which accounts for 4% to 8% of cases, may lead to symptoms like gastroenteritis, flu-like illness, and mild respiratory problems that usually resolve within a week. Aseptic meningitis accounts for about 1% of clinical cases and is characterized by severe muscle spasms in the neck, back, and lower limbs following a brief prodrome like abortive poliomyelitis. Complete recovery usually occurs within ten days. The most severe manifestation is paralytic poliomyelitis, which affects less than 1% of patients. There are three forms of paralytic poliomyelitis: spinal poliomyelitis (most common), bulbar poliomyelitis (2%), and a combination of the two, bulbospinal poliomyelitis (19%). Bulbar poliomyelitis carries the highest fatality rate due to the involvement of the brain stem. In children, the disease may have a biphasic presentation—a prodromal period followed by a brief symptom-free interval of 7 to 10 days, then the onset of asymmetrical limb flaccid paralysis. While some patients may experience complete recovery, lifelong disability may occur if motor function loss persists beyond 12 months. Post-polio syndrome (PPS) can occur 25 to 40 years after the initial paralytic attack and is characterized by progressive muscular weakness, joint deterioration, and increasing skeletal deformities.

Poliovirus infection can be diagnosed by detecting the virus through culture in cell lines and polymerase chain reaction (PCR) from stool, throat swabs, blood, and cerebrospinal fluid (CSF) samples. A 4-fold rise in serum antibody titer can also confirm the infection. Neutralizing antibodies appear very early in the disease process and persist for life. While there is currently no cure for polio, treatment strategies aim to alleviate symptoms and manage complications. During the acute phase of the illness, medical interventions focus on relieving pain and muscle spasms, ensuring adequate respiratory function and hydration, minimizing the risk of skeletal deformities, and addressing any secondary effects of paralysis. In the recovery phase, physiotherapy, appropriate orthotic devices, and surgical management may improve outcomes.

Polio vaccines and the emergence of vaccine-derived polioviruses

Preventing and eradicating polio is certainly possible with the deployment of polio vaccines to maintain high rates of population immunity. As mentioned above, there are two types of polio vaccines, OPV and IPV, which have their particular advantages and flaws, but both continue to play an essential role in polio control (Table 1).

The OPV has many benefits, but it carries a risk. Sometimes, the weakened polioviruses in the vaccine can genetically mutate to vaccine-derived poliovirus (VDPV) and revert to neurovirulent forms, spread among low-immunized individuals and cause paralysis. There are three types of VDPV, which are: (1) circulating VDPV (cVDPV), which is spread from person to person in a community with a low level of polio immunization coverage; (2) immunodeficiency-associated VDPV (iVDPV), which is isolated from people with primary immunodeficiency disease (PID); and (3) ambiguous VDPV (aVDPV). Among these, cVDPVs pose the most significant public health concern as they resemble wild polioviruses, have the potential to cause outbreaks, and require similar control measures. Since 2000, cVDPV outbreaks have occurred in 18 countries, with the majority (87.1%) associated with type 2 cVDPV. A global resurgence of cVDPV2 began in 2016, linked to the switch from trivalent OPV (tOPV) to bivalent OPV (bOPV) for routine vaccination, creating immunity gaps to type 2 poliovirus. Type 1 cVDPVs (11.1% of cases) caused outbreaks in Hispaniola in 2000–2001 and Indonesia in 2005, while type 3 cVDPVs are relatively rare, accounting for only 1.8% of known cases. Since January 2020, cVDPV has sprung up in more than 50 countries and hampered the endgame of a polio-free world.

Poliovirus outbreaks and government responses in Indonesia

The journey towards polio eradication in Indonesia has been long and challenging. The government has committed to providing free polio vaccines, including IPV (given twice before one year) and OPV (given four times at 1, 2, 3, and 4 months of age). However, in 2021, the national average OPV vaccination rate was only 80.2% (target 95%). Alarmingly, 19 out of 34 provinces had vaccination coverage lower than the national average, with West Papua and Aceh having the lowest coverage rates (West Papua: 43.3% of 19,200 and Aceh: 50.9% of 101,520 infants born). The WHO assesses the polio risk to be high at the national level due to low polio vaccination coverage in some provinces in Indonesia. The population is susceptible to poliovirus type 2 after switching from tOVP to bOPV in 2016, combined with low uptake of IPV, sub-optimal acute flaccid paralysis (AFP) surveil-lance capacity, and vaccine hesitancy among the at-risk population. Additionally, in some regions, there are still issues with open defecation, diapers discharged to the river, and children playing in contaminated rivers, increasing the risk of polio transmission.

When there’s a poliovirus outbreak, two main strategies are used: (1) Outbreak Response Immunization (ORI): this involves giving OPV to all children and toddlers at risk of being exposed to the virus, especially in the area where the case was found and nearby. Vaccines are administered as soon as possible (within 3×24 hours), no later than the first week, regardless of the child’s immunization status; (2) Mopping Up: this strategy covers a broader area by administering OPV to all children under five years, regardless of their immunization status. Mopping Up is carried out nationwide namely National Immunization Week (Pekan Imunisasi Nasional/ PIN) or in specific provinces namely Sub-National Immunization Week (Sub-PIN) or supplementary immunization activities (SIA). Recent outbreaks of cVDPV2 underscore the importance of maintaining high levels of routine vaccination coverage everywhere to reduce the risk and consequences of poliovirus circulation. It’s also crucial to ensure quality AFP surveillance for early detection.

The primary responses to recent cVDPV2 outbreaks have included enhancing AFP case finding and surveillance, routine immunization, Sub-PIN/ SIA campaigns with novel OPV2 (nOPV2; more genetically stable) and promoting proper hygiene and sanitation practices. Great news! The polio vaccination coverage during the Sub-PIN/ SIA in Central Java, Yogyakarta, and East Java provinces has surpassed 95%. This vaccination campaign was conducted in two rounds (January 15th to 21st, 2024 and February 19th to 25th, 2024) targeted 8.6 million children 0-7 years. This high coverage is a significant achievement in the fight against polio. It inspires us to strive for even greater success in expanding routine polio immunization coverage across all provinces in Indonesia. By ensuring that more children receive the necessary vaccinations, we can effectively protect them from the threat of polio and contribute to a healthier future for all towards polio-free world in 2026.

Concluding remarks

Poliovirus outbreaks are like throwing a curveball into the polio-free world endgame. For every child para-lyzed by poliovirus infection, there are approximately 200 asymptomatic cases, meaning that a single reported case is just the tip of the iceberg. As long as polio exists in any country, even polio-free nations remain at risk. Enhanced AFP surveillance is crucial for early detection and intervention in polio cases. Eradicating polio will also require discontinuing OPV to prevent a resurgence of VDPVs in a polio-free world. New, safe, and effective polio vaccines, such as currently developed poliovirus virus-like particles (VLPs) and new-generation IPV, are urgently needed. However, until the new vaccines are available, conventional and novel OPVs must continue to be used. Sequential immunizations with IPV and OPV have been proven to increase population immunity and stop the spread of cVDPV.

Acknowledging the significant progress made in the fight against polio is essential. To date, an estimated 16 million people today are walking who would otherwise have been paralyzed by the disease, and more than 1.5 million people are alive whose lives would otherwise have been lost. The GPEI stated: “Achieving and sustaining a polio-free world has proven harder – and taken longer – than anyone could have imagined. But making history is never easy, and we are confident that together we can eradicate a second human disease after smallpox from this earth and build stronger, more resilient health systems along the way.”

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