Three countries endemic for poliovirus

poliovirusI cannot let September pass without noting that 34 years ago this month, I arrived at Columbia University to start my laboratory to do research on poliovirus (pictured). That virus is no longer the sole object of our attention – we are wrapping up some work on poliovirus and our attention has shifted elsewhere. But this is a good month to think about the status of the poliovirus eradication effort.

So far this year 26 cases of poliomyelitis have been recorded – 23 caused by wild type virus, and three caused by vaccine-derived virus. At the same time in 2015 there were 44 reported cases of polio – small progress, but, in the words of Bill Gates, the last one percent is the hardest.

One of the disappointments this year is Nigeria. It was on the verge of being polio-free for one year – the last case of type 1 poliovirus in Nigeria had been recorded in July of 2014. In August the government reported that 2 children developed polio in the Borno State. The genome sequence of the virus revealed that it had been circulating undetected in this region since 2011. Due to threats from militant extremists, it has not been possible for vaccination teams to properly cover this area, and surveillance for polioviruses has also been inefficient. The virus can circulate freely in a poorly immunized population, and as only 1% of infections lead to paralysis, cases of polio might have been missed.

The conclusion from this incident is that the declaration that poliovirus is no longer present in any region is only as good as the surveillance for the virus, which can never be perfect as all sources of infection cannot be covered.

Of the 26 cases of polio recorded so far in 2016, most have been in Afghanistan and Pakistan (9 and 14, respectively). It is quite clear that conflict has prevented vaccination teams from immunizing the population: in Pakistan, militants have attacked polio teams during vaccination campaigns.

Recently 5 of 27 sewage samples taken from different parts of the province of Balochistan in Pakistan have tested positive for poliovirus. Nucleotide sequence analysis revealed that the viruses originated in Afghanistan. The fact that such viruses are present in sewage means that there are still individuals without intestinal immunity to poliovirus in these regions. In response to this finding, a massive polio immunization campaign was planned for the end of September in Pakistan. This effort would involve 6000 teams to reach 2.4 million children. Apparently police will be deployed to protect immunization teams (source: ProMedMail).

The success of the polio eradication program so far has made it clear that if vaccines can be deployed, circulation of the virus can be curtailed. If immunization could proceed unfettered, I suspect the virus would be gone in five years. But can anyone predict whether it will be possible to curtail the violence in Pakistan, Afghanistan, and Nigeria that has limited polio vaccination efforts?

Poliovirus silently (and not so silently) spreads

Poliovirus by Jason RobertsPoliovirus has been found in sewage in Israel. The virus detected is not vaccine-derived poliovirus; it is wild-type 1 poliovirus, the strain that occurs naturally in the wild and which the World Health Organization is trying very hard to eradicate from the planet.

As part of the global effort to eradicate poliovirus, environmental samples from many countries are routinely examined for the presence of the virus. Wild type poliovirus was detected in 30 sewage sample from 10 different sites, collected from 3 February to 30 June 2013 in Israel. No cases of paralytic disease have been detected in that country. This is not a surprising finding because only roughly one in 100 individuals infected with poliovirus develop paralysis.

During poliovirus infection, the virus replicates in the gastrointestinal tract and is shed in the feces. Most of the poliovirus-positive sewage samples were from southern Israel. Finding the virus at multiple sites suggests that the virus has been in the population for an extended period of time and that multiple individuals are shedding virus.

Why is wild type virus circulating in Israel? Poliovirus vaccine coverage in Israel is high but it is never 100%, and non-immunized individuals are hosts for the virus. Another explanation is related the the use of inactivated poliovirus vaccine (IPV) in Israel. Immunization with IPV, which is administered intramuscularly, does not protect the alimentary tract from infection. Therefore poliovirus can replicate in the intestine of immunized individuals, but once the virus reaches the blood its spread is blocked by anti-viral antibodies.

An interesting question is whether there is wild type poliovirus in the United States. I suspect that if we looked for poliovirus in our sewage, we would find it. However we no longer carry out surveillance of sewage for poliovirus and therefore we do not know if it is present.

Genetic analysis of wild type poliovirus from Israel suggests that it is related to the strain found in December 2012 in sewers in Cairo, Egypt. That virus in turn is closely related to virus from Pakistan, one of three countries from which wild type poliovirus has not been eradicated (the others are Nigeria and Afghanistan).

There is an ongoing outbreak of poliomyelitis in the Horn of Africa, with 65 cases in Somalia and 8 cases in Kenya. The virus causing that outbreak came from Nigeria. Somalia and Kenya had been free of polio since 2007 and 2011, respectively.

WHO has concluded that the risk of further international spread of wild type poliovirus from Israel as moderate to high. As long as there are individuals who are not immune, there will be a risk of poliovirus infection, in part due to the silent infections caused by the virus.

Petition to ban intelligence involvement in public health campaigns

A petition has been created which asks the Obama Administration to ban intelligence involvement in public health campaigns:

We petition President Obama to amend Executive Order 12333, adding a paragraph after the prohibition on covert action related to US domestic politics. The amendment should ban persons in the intelligence community or acting on their behalf from joining or participating in any activity directly related to the provision of child public health services.

Charles Kenny of the Center for Global Development provides background on the petition.

Deans write to Obama about CIA vaccine scheme in Pakistan

Deans of public health schools in the United States have sent the following letter to President Obama, in which they criticize the use of a vaccination campaign by the Central Intelligence Agency in Pakistan to hunt for Osama bin Laden. I wonder if he will reply.

January 6, 2013

Dear President Obama,

In the first years of the Peace Corps, its director, Sargent Shriver, discovered that the Central Intelligence Agency (CIA) was infiltrating his efforts and programs for covert purposes. Mr. Shriver forcefully expressed the unacceptability of this to the President. His action, and the repeated vigilance and actions of future directors, has preserved the Peace Corps as a vehicle of service for our country’s most idealistic citizens. It also protects our Peace Corps volunteers from unwarranted suspicion, and provides opportunities for the Peace Corps to operate in areas of great need that otherwise would be closed off to them.

In September Save the Children was forced by the Government of Pakistan (GoP) to withdraw all foreign national staff. This action was apparently the result of CIA having used the cover of a fictional vaccination campaign to gather information about the whereabouts of Osama Bin Laden. In fact, Save the Children never employed the Pakistani physician serving the CIA, yet in the eyes of the GoP he was associated with the organization. This past month, eight or more United Nations health workers who were vaccinating Pakistani children against polio were gunned down in unforgivable acts of terrorism. While political and security agendas may by necessity induce collateral damage, we as an open society set boundaries on these damages, and we believe this sham vaccination campaign exceeded those boundaries.

As an example of the gravity of the situation, today we are on the verge of completely eradicating polio. With your leadership, the U.S. is the largest bilateral donor to the Global Polio Eradication Initiative and has provided strong direction and technical assistance as well. Polio particularly threatens young children in the most disadvantaged communities and today has been isolated to just three countries: Afghanistan, Nigeria and Pakistan. Now, because of these assassinations of vaccination workers, the UN has been forced to suspend polio eradication efforts in Pakistan. This is only one example, and illustrates why, as a general principle, public health programs should not be used as cover for covert operations.

Independent of the Geneva Conventions of 1949, contaminating humanitarian and public health programs with covert activities threatens the present participants and future potential of much of what we undertake internationally to improve health and provide humanitarian assistance. As public health academic leaders, we hereby urge you to assure the public that this type of practice will not be repeated.

International public health work builds peace and is one of the most constructive means by which our past, present, and future public health students can pursue a life of fulfillment and service. Please do not allow that outlet of common good to be closed to them because of political and/or security interests that ignore the type of unintended negative public health impacts we are witnessing in Pakistan.

Sincerely,

Pierre M. Buekens, M.D., M.P.H., Ph.D.
Dean, Tulane University School of Public Health and Tropical Medicine*

James W. Curran, M.D., M.P.H.
Dean, Rollins School of Public Health, Emory University*

John R. Finnegan Jr., Ph.D.
Professor and Dean, University of Minnesota School of Public Health*
Chair of the Board, Association of Schools of Public Health*

Julio Frenk, M.D., M.P.H., Ph.D.
Dean and T&G Angelopoulos Professor of Public Health and International Development
Harvard School of Public Health*

Linda P. Fried, M.D., M.P.H.
Dean, Mailman School of Public Health, Columbia University*

Howard Frumkin, M.D., Dr.P.H.
Dean, School of Public Health, University of Washington*

Lynn R. Goldman, M.D., M.P.H.
Professor and Dean, School of Public Health and Health Services, George Washington University*

Jody Heymann, M.D., M.P.P., Ph.D.
Dean, UCLA Fielding School of Public Health*

Michael J. Klag, M.D., M.P.H.
Dean, Johns Hopkins Bloomberg School of Public Health*

Martin Philbert, Ph.D.
Dean, School of Public Health, University of Michigan*

Barbara K. Rimer, Dr.P.H.
Dean and Alumni Distinguished Professor
UNC Gillings School of Global Public Health*

Stephen M. Shortell, Ph.D.
Dean, School of Public Health, University of California Berkeley*

*Institutional affiliation is provided for identification only.

cc:
Regina M. Benjamin, United States Surgeon General
Hillary Rodham Clinton, Secretary of State
Thomas Frieden, Director, Centers for Disease Control and Prevention
Howard Koh, Assistant Secretary of Health
Michael J. Morell, Acting Director of the Central Intelligence Agency
Janet Napolitano, Secretary of Homeland Security
Kathleen Sibelius, Secretary of Health and Human Services

Vaccine-associated poliomyelitis in Pakistan

Poliovirus by Jason RobertsAn outbreak of ten cases of poliomyelitis caused by circulating vaccine-derivied poliovirus type 2 (cVDPV2) is ongoing in Pakistan, centered in the Kila Abdulla/Pishin area of Baluchistan. The same virus strain has spread to the neighboring Kandahar province in Afghanistan, where two paralytic cases have been reported. Vaccine-derived poliomyelitis is a well-known consequence of immunization with the Sabin poliovirus vaccine.

There are three serotypes of poliovirus, each of which causes poliomyelitis. The three vaccine strains developed by Albert Sabin (OPV, oral poliovirus vaccine) contain mutations which prevent them from causing paralytic disease. When the vaccine is taken orally, the viruses replicate in the intestine, and immunity to infection develops. While replicating in the intestinal tract, the vaccine viruses undergo genetic changes. As a consequence, the OPV recipients excrete neurovirulent polioviruses. These so-called vaccine-derived polioviruses (VDPV) can cause poliomyelitis in the recipient of the vaccine or in a contact. During the years that the Sabin poliovirus vaccines were used in the US, cases of poliomyelitis caused by VDPV occurred at a rate of about 1 per 1.4 million vaccine doses, or 7-8 per year. Once the disease was eradicated from the US in 1979, the only cases of polio were caused by VDPVs. For this reason the US switched to the Salk (inactivated) poliovirus vaccine in 2000.

Because VDPVs are excreted in the feces, they can spread in communities. These circulating VDPVs, or cVDPVs, can cause outbreaks of poliomyelitis in under-immunized populations. Examples include outbreaks of poliomyelitis in an Amish community and in Nigeria in 2009 caused by cVDPV2. Nigeria employed trivalent OPV before 2003, the year that this country began a boycott of polio immunization. Because type 2 poliovirus had been eradicated from the globe in 1999, when immunization in Nigeria resumed in 2004, monovalent types 1 and 3 vaccine were used. The source of the VDPV type 2 in Nigeria was the trivalent vaccine used before 2003.

For many years the vaccine used by WHO in the global eradication effort was a trivalent preparation comprising all three serotypes. When type 2 poliovirus was eliminated, many countries began immunizing only against types 1 and 3 poliovirus. As a consequence of this immunization strategy, population immunity to type 2 poliovirus declined. This has likely lead to the emergence of cVDPV2 in Pakistan, together with poor routine immunization coverage.

The resurrection of poliovirus type 2 highlights the difficulties in eradicating a pathogen using a vaccine that can readily mutate to cause the disease that it is designed to prevent. As wild type polioviruses are eliminated, the only remaining polio will be caused by the vaccine. If immunization is then stopped, as planned by WHO, there will likely be outbreaks of polio caused by cVDPV of all three serotypes. The solution to this conundrum is to switch to the inactivated vaccine until cVDPVs disappear from the planet.

Exacerbating the polio situation in Pakistan was the murder in the past week of nine immunization workers in several provinces. The Taliban, which carried out the executions, accused them of being spies. This accusation originates from the CIA operation in 2011 in which a Pakistani doctor ran an immunization program in Abbottabad in an attempt to obtain DNA samples from the Bin Laden family. As a result of this violence, immunization campaigns in Balochistan have been suspended. Coupled with the previous refusal of many parents to have their children immunized, this action makes it likely that poliovirus will spread more extensively in the country, making eradication even more difficult.

Poliovirus image courtesy of Jason Roberts.

Can India remain polio-free?

global polio 2012India has been free of polio for over one year. This is a remarkable accomplishment, considering that just 30 years ago the country recorded 200,000 cases of the disease annually, or one every three minutes. With polio endemic in two neighboring countries, Pakistan and Afghanistan, and in the more distant Nigeria (figure), can India remain free of the disease? According to Shahnaz Wazir Ali, the Pakistani Prime Minister’s focal person for polio, there is little risk for export of the virus from Pakistan:

The likeliness of polio virus being exported to India from Pakistan is very low, and historically, it has not happened. Those who travel from India to Pakistan are mostly adults. There are rarely any babies. So the chances are low.

It is correct that polio has not traveled from Pakistan to India during the modern era of virus detection (1980 to the present). However, the same genotypes of types 1 and 3 poliovirus have circulated in both countries, implying sharing of viruses some time in recent history. Therefore Ali cannot conclude that export of virus to India ‘has not happened’.

Poliovirus continues to circulate in Pakistan, which shares a border with India: there were 198 cases in that country in 2011, the most of any in the world, and 16 cases so far in 2012. Remember that most poliovirus infections are asymptomatic, so the number of paralytic cases is far lower than the actual number of infections. The ratio of paralytic cases to infections varies according to the viral serotype: 1:200, 1:1800, and 1:1200 for types 1, 2, and 3 respectively. Furthermore, poliovirus has been known to spread from Pakistan from other countries. An outbreak of polio in Xinjiang, China, in 2011 was caused by virus imported from Sindh, Pakistan. There were 21 paralytic cases caused by poliovirus type 1, over half of which occurred in individuals 19-53 years old. The outbreak was halted by immunization but the region remains at risk for importation from Pakistan.

Poliovirus also continues to circulate in Afghanistan, which lies on the northwestern border of Pakistan. Eighty cases of paralytic disease were reported in this country in 2011, and 7 so far in 2012. It has been difficult to control polio in the southern provinces of Kandahar and Helmand due to ongoing armed activities. There is active migration between the southern regions of Afghanistan and Pakistan which has lead to a steady exchange of polioviruses between the two countries.

There many other examples of polio spread from one country to another in recent years. Following cessation of polio immunization in 2003, virus spread from Nigeria to many countries in Africa as well as to Indonesia. From India poliovirus has spread to Nepal, Angola (2005 and 2007), and Tajikistan and then to Russia (2010), in all cases causing substantial outbreaks of the disease.

The message is clear: poliovirus spreads easily among countries, and it is often spread by infected adults, not children. Because poliovirus infection is frequently asymptomatic, such spread cannot be detected by simply examining travelers for signs of paralysis.

For these reasons I am skeptical of Ali’s reassurance that the virus is not likely to spread from Pakistan to India. If adults mainly travel from India to Pakistan, as she says, they could well be infected and import the virus back home before it is detected. Furthermore, adults could bring the virus to India from other countries where poliovirus continues to circulate, although that is not Pakistan’s concern.

Because Pakistan remains a major reservoir of poliovirus, it is a good sign that the country is acknowledging the possibility that they might export the virus to India. The best way to avoid this scenario would be to intensify their immunization programs and eliminate the virus. Apparently Ali has been speaking with Indian officials to learn how they accomplished this goal:

We got to know what actually took India to become polio-free. We have understood the scale and efforts that we require to make Pakistan polio-free.