Polio: Once Thought Eradicated, Still Smolders On

In this week's meeting of IMMU7630, Dr. JJ Cohen described scenarios where infectious diseases for which effective vaccines are widely available have experienced a resurgence in countries around the world. The most dramatic demonstration of the ramifications of a lapse in vaccination campaigns is that of poliomyelitis. Also this week, NPR aired a three-part series (Parts 1, 2, and 3) on the disease which are succinct, informative, and worth the time to listen. Below you'll find some details from the series and an array of other sources that will hopefully impart a quick overview to a frightening, preventable disease and a few snippets about how its eradication is more complex than one would assume at first blush. 

The Disease 

An "iron lung" ward for the treatment of apnea in which breathing muscles have been paralyzed and pressure is cyclically applied release to the patient's abdomen to sustain respiration.
(Smithsonian Magazine blog)

Source: CDC

Poliomyelitis is caused by an RNA enterovirus (Picornaviridae) which colonizes the gastrointestinal tract and is spread primarily through fecal-oral transmission.  After introduction to the mouth, the virus invades the lymphoid tissues and gastrointestinal (GI) tract and can progress to an infection of the Central Nervous System (CNS) resulting in the characteristic paralysis associated with the disease. According to the Centers for Disease Control and Prevention (CDC), up to 95% of cases* of poliomyelitis are "asymptomatic or inapparent"(1) but patients--mostly children under five--shed the virus in their stool nonetheless. Estimates vary significantly, but approximately 1:50 to 1:1,000 infections lead to paralytic disease. (2)

The World Health Organization (WHO) published incidence of disease in 1988 at ~350,000 patients throughout 125 countries compared to 1352 confirmed cases in 2010, with only four countries classified as "endemic": Nigeria, Chad, Pakistan, and Afghanistan. (3) Unfortunately this essentially preventable childhood disease is growing in numbers once more. 

The Vaccines

The first effective vaccine was developed in 1952 by Jonas Salk who was heralded as a hero in the United States, which was in the throes of panic from a polio outbreak in the 1950's. The Salk vaccine is comprised of all three wild virulent strains of the virus, grown in Green monkey kidney cells (aka "vero" cells) and inactivated with formalin. This inactivated polio virus (IPV) is injected into patients and elicits an IgG response that inhibits viremia (infection of the blood) and protects motor neurons. 

Child receiving oral polio vaccine (NPR Blog)

Licensure for another vaccine came in 1955 from a competing colleague, Albert Sabin, who took advantage of the reduced virulence of the virus that occurred with repeated passages in vitro, through non-human cells, at temperatures below human body temperature (4). His iteration was administered orally and is a "live-attenuated" virus. Today the Sabin Oral Polio Vaccine (OPV) is by far the mostly widely distributed form of the vaccine because of its ease of administration--two drops in the mouth of young children--with three doses given for maximal protection. However, in very rare cases the virus is able to revert to a virulent form and is considered by the Bill and Melinda Gates Foundation to be in need of improvement, even going so far as to have as one of its stated and funded goals the development of a new vaccine: 

Oral polio vaccine, the most widely used vaccine against polio is highly effective. However, in extremely rare instances, the vaccine can cause neurological damage and the weakened poliovirus used in the vaccine can adapt and mutate into a deadlier version that causes polio in the very children it was meant to protect. We are supporting efforts to develop better vaccines that address these challenges. (5)

Polio vaccines have a well-publicized history of missteps and unintended injuries including the early practices now considered ethically bankrupt of challenging prisoners and mental patients with the vaccine in advance of its public administration. Additionally, contamination of the vaccine culture with a known cancer-causing virus, SV40, was identified long after millions of doses of the (Salk) vaccine were administered between 1955 and 1963(6). Retrospective analyses indicate that this co-inoculation did not increase the rate of cancer in individuals overall (7), but it serves as a warning to temper the frenetic pace at which vaccines and indeed all pharmaceuticals are screened and manufactured. 

The Backlash to Vaccination

"The world is getting tantalizingly close to eradicating the polio virus. Although 11 countries reported cases of polio in 2011, the virus has turned up in only four countries so far this year." Source: GPEI (NPR Blog)

In 1988 the WHO established the Global Polio Eradication Initiative (GPEI) to eradicate poliomyelitis by the year 2000**. Although complete eradication has remained elusive, great strides were made towards this ambitious goal in the years that followed. In October of 2003, a "final push" was intended in the northern African nation of Nigeria where 45% of the world's cases occurred at that time. Unfortunately, in the predominantly Muslim northern states of Kano, Zamfara, and Kaduna, the effort was purportedly impeded by religious and political leaders: 

In an article reported by News24.com, a South African online news Web site, Sule Ya'u Sule, speaking for the governor of Kano, is quoted as saying: “Since September 11, the Muslim world is beginning to be suspicious of any move from the Western world…Our people have become really concerned about polio vaccine” [(News 24)]. In the same article, Datti Ahmed, a Kano-based physician who heads a prominent Muslim group, the Supreme Council for Sharia in Nigeria (SCSN), is quoted as saying that polio vaccines were “corrupted and tainted by evildoers from America and their Western allies.” Ahmed went on to say: “We believe that modern-day Hitlers have deliberately adulterated the oral polio vaccines with anti-fertility drugs and…viruses which are known to cause HIV and AIDS” [(News 24)].(8)

The other countries currently in the throes of active polio outbreaks (Chad, Pakistan, and Afghanistan--particularly the border region) are areas embroiled in extensive military conflict. As mentioned above, children must receive three doses of the OPV in order to be formally protected. This proves extremely challenging logistically even in the most developed areas; complicating matters is the necessity for the live virus vaccine to be transported and stored under refrigerated conditions (11). 

In addition to poor living conditions, some leaders in these countries have openly rejected the massive influx of vaccines and "vaccine workers" who have descended on their territories in ways reminiscent of Nigeria's opposition almost a decade previous (9). The suspicions are not altogether unfounded. Indeed, the CIA acknowledged that an agent posed as a vaccine administrator to gain access to relatives of Osama bin Ladin in 2011(10 "CIA defends running vaccine program to find bin Ladin", Washington Post, July 2011.) Also for context, one should consider that the aforementioned Kano province had previous murky experiences with drug manufacturer Pfizer in 1996: 

"They were there to conduct a quickly organized randomized trial of orally administered Trovan (trovafloxacin), which had not yet been tested in children or approved in the United States. They enrolled 200 children in the trial, stayed in Kano for several weeks, and then left. Pfizer has maintained that it had done everything correctly and with adequate permission, and that the children’s deaths or long-term symptoms were the result of their being gravely ill." (12)-(from "How a U.S. Court Case Explains Problems Eradicating Polio", Wired Magazine, Aug 2011)

The resulting lawsuits "..sent the Nigerian complaints all the way to the US Supreme Court and back.." (12) and at minimum muddied the waters in terms of public relations with the local peoples. 

An attack on a medical doctor in Pakistan in July of this year (13) also brought into sharp focus the uphill battle being waged by aid workers. The attack came in direct response to instructions from various Taliban leaders to oppose the vaccination campaign.(14) The seemingly endless escalation of distrust of America and her allies in the West seem to indicate that the polio situation might be trending in the wrong direction. 

Despite bold statements---(to reiterate the quote shared by JJ in the syllabus: "...it is time to close the book on infectious diseases, declare the war against pestilence won." (William H. Stewart, United States Surgeon General, 1967))---and vigorous pursuit of bastions of poliovirus pockets throughout the world, infectious diseases will always be compounded and outbreaks exacerbated by the pesky details of politics, religion, and personal freedoms. 

Notes: 

* When the virus establishes an infection, replicates in the GI tract, invades the bloodstream but does not progress to CNS infection, it is termed "abortive poliomyeltis" and presents with non-specific symptoms in the respiratory and GI tract. This accounts for 4-6% of infections according to the CDC.  

**Informally, and perhaps for discussion: 

Reasons why Polio is the quintessential candidate for eradication through vaccination: 

1) The virus does not mutate as rapidly as other infectious diseases (only three virulent serotypes have been identified)

2) Poliovirus is transmitted through fecal-oral route (traditional water-treatment methods, chlorine, UV, etc., are extremely effective at destroying the virus)

3) There is no natural host besides humans (e.g.: it is not contracted by other mammals nor is it vector-borne) 

4) Both the Salk (IPV) and Sabin (OPV) vaccines have a high efficacy when administered correctly.