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What’s the Connection Between Polio Eradication and Primary Immunodeficiency?

Categories: genomics

world map comparing polio from 1988 to 2012 from CDC, Global Health - Polio
A Public Health Role for Human Genetics

Two non-profit foundations with distinct missions recently announced that they are joining forces to support polio eradication. The Bill & Melinda Gates Foundation (BMGF) supports global health programs; the Jeffrey Modell Foundation (JMF) advocates for early diagnosis and treatment of  genetic immunodeficiency disorders. How did these organizations find common cause? 

During the last two decades, surveillance and strategic vaccination campaigns deployed by the Global Polio Eradication Initiative have reduced polio incidence worldwide by 99.8 percent. Wild poliovirus cases are now uncommon, with fewer than 250 new cases reported wordwide during 2012. Endemic transmission is now limited to small areas of just three countries—Afghanistan, Nigeria, and Pakistan.

Oral polio vaccine (OPV) is a live, attenuated vaccine that is used for eradication because it is effective, inexpensive, and easy to administer. When persons with immune deficiencies are directly or indirectly exposed to OPV-related viruses, long-term infections may rarely arise and lead to vaccine-derived polioviruses (VDPVs).

Persons with a genetic primary immunodeficiency disorder (PI, see Box) can carry replicating VDPVs in their intestines and potentially transmit them to their contacts. Reports of such instances are rare and the underlying PI is often detected only after the onset of paralytic polio; however, additional cases have been identified by intensified surveillance and special studies set up by CDC and the World Health Organization (WHO).

A CDC-funded study in Bangladesh recently demonstrated that it is feasible to identify children with PI by screening with a clinical case definition (based on criteria developed by the Jeffrey Modell Foundation), followed by age-specific determination of quantitative immunoglobulin (QIG) levels. Six of the 13 children who met the clinical case definition had QIGs that confirmed the diagnosis of PI. Stool specimens that were obtained from four of these six children tested negative for polio vaccine viruses. The authors recommended expanding surveillance for PI and regularly testing vaccinated persons with PI for poliovirus excretion.

Polio eradication is an important public health priority and an ambitious goal: only one other infectious disease of humans—smallpox—has ever been eradicated from the world’s population. The final push toward polio eradication requires a coordinated, all-out effort by international groups and national governments, public agencies and private foundations. The successful strategy will find synergy between population-based surveillance and case-finding, mass vaccination and clinical screening. Although OPV will be phased out once the goal of polio eradication is reached, any long-term infections in PI patients will require special attention.

British epidemiologist Geoffrey Rose inspired a generation of public health workers when he contrasted population-based with individual risk-based strategies in his essay, “Sick individuals and sick populations”:

The ‘high-risk’ strategy of prevention is an interim expedient, needed in order to protect susceptible individuals, but only for so long as the underlying causes of incidence remain unknown or uncontrollable; if causes can be removed, susceptibility ceases to matter.

The goal of eradicating polio, however, clearly calls for both strategies. Population-wide vaccination programs are delivered by vaccinating individuals—thereby protecting those who are vaccinated, their close contacts, and the whole population through herd immunity. In many areas where wild poliovirus transmission has been interrupted, like Bangladesh, the role of PI in polio eradication has clearly begun to matter. The BGMF has supported polio eradication efforts for years; however, the Jeffrey Modell Foundation is a new partner in a collaboration with CDC, WHO and the Task Force for Global Health that will broaden surveillance for VDPV in persons with PI within the Jeffrey Modell Foundation clinical network. Any long-term VDPV infections that are found are potentially treatable with new antiviral drugs currently under development.

Primary immunodeficiency disorders

Primary immunodeficiency disorders (PI) are inherited (genetic) defects in the immune system.  The term “primary” distinguishes these disorders from acquired causes of immunodeficiency, such as human immunodeficiency virus (HIV) infection or immunosuppression resulting from chemotherapy.

More than 150 different PIs have been described, although fewer than 20 probably account for most cases. PIs are mostly very rare, varying in prevalence among populations; for many types, causative genetic mutations have been identified. Although all PIs increase susceptibility to infection, symptoms range from mild to severe depending on the specific mutations’ effects on immune function.

The International Union of Immunological Societies Expert Committee for Primary Immunodeficiency publishes an updated classification of PIs, grouped according to their most typical immunologic, clinical, and genetic features. Some PIs are features of well-defined syndromes (e.g., ataxia-telangectasia); others have autoinflammatory or autoimmune features. Perhaps the best known PI is severe combined immunodeficiency (SCID), in which the adaptive immune system fails to develop. Other PIs involve defects in innate immunity, immune regulation, or deficiencies in specific components, such as antibodies or complement factors.

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