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WORLD HEALTH ASSEMBLY RESOLUTION ON POLIO ERADICATION, MAY 2012

Wednesday, 6th of June 2012

• WHA RESOLUTION ON POLIO, MAY 2012

 Text below; also at http://apps.who.int/gb/ebwha/pdf_files/WHA65/A65_R5-en.pdf

SIXTY-FIFTH WORLD HEALTH ASSEMBLY WHA65.5

Agenda item 13.10 26 May 2012

 

Poliomyelitis: intensification of the

global eradication initiative

 

The Sixty-fifth World Health Assembly,

 

Having considered the report on poliomyelitis: intensification of the global eradication

initiative;1

 

Recalling resolution WHA61.1 on poliomyelitis: mechanism for management of potential risks to eradication, which requested the Director-General, inter alia, to develop a new strategy to reinvigorate the fight to eradicate poliovirus and to develop appropriate strategies for managing the long-term risks of reintroduction of poliovirus and re-emergence of poliomyelitis, including the eventual cessation of use of oral poliovirus vaccine in routine immunization programmes;

 

Recognizing the need to make rapidly available the necessary financial resources to eradicate the remaining circulating polioviruses and to minimize the risks of reintroduction of poliovirus and reemergence of poliomyelitis after interruption of wild poliovirus transmission;

 

Noting the finding of the Independent Monitoring Board of the Global Polio Eradication

Initiative in its report of October 2011 that “polio simply will not be eradicated unless it receives a higher priority – in many of the polio-affected countries, and across the world”2 and its recommendation in its April 2011 report that the World Health Assembly “considers a resolution to declare the persistence of polio a global health emergency”;

 

Noting the report of the meeting in November 2011 of the Strategic Advisory Group of Experts on immunization at which it stated “unequivocally that the risk of failure to finish global polio eradication constitutes a programmatic emergency of global proportions for public health and is not acceptable under any circumstances”;

 

Recognizing the need for Member States to engage all levels of political and civil society so as to ensure that all children are vaccinated in order to eradicate poliomyelitis;

 

Having noted the current high cost and limited supplies of inactivated polio vaccine that are

hampering the introduction and scaling-up of inactivated polio vaccine, resulting in major

programmatic and financial implications to developing countries;

 

1 Document A65/20.

2 Polio eradication. Weekly epidemiological record, 2012, 87(1):1–16.

 

Noting that the technical feasibility of poliovirus eradication has been proved through the full

application of new strategic approaches;

 

Noting that continuing poliovirus transmission anywhere will continue to pose a risk to

poliomyelitis-free areas until such time as all poliovirus transmission is interrupted globally,

 

1. DECLARES the completion of poliovirus eradication a programmatic emergency for global

public health, requiring the full implementation of current and new eradication strategies, the

institution of strong national oversight and accountability mechanisms for all areas affected by poliovirus, and the application of appropriate vaccination recommendations for all travellers to and from areas affected with poliovirus;1

 

2. URGES Member States with poliovirus transmission to declare such transmission to be a

“national public health emergency” making poliovirus eradication a national priority programme, requiring the development and full implementation of emergency action plans, to be updated every six months, until such time as poliovirus transmission has been interrupted;

 

3. URGES all Member States:

 

(1) to eliminate the unimmunized areas and to maintain very high population immunity

against polioviruses through routine immunization programmes and, where necessary,

supplementary immunization activities;

 

(2) to maintain vigilance for poliovirus importations, and the emergence of circulating

vaccine-derived polioviruses, by achieving and sustaining certification-standard surveillance

and regular risk assessment for polioviruses;

 

(3) to make available urgently the financial resources required for the full and continued

implementation, to the end of 2013, of the necessary strategic approaches to interrupt wild

poliovirus transmission globally, and to initiate planning for the financing to the end of 2018 ofthe polio endgame strategy;

 

(4) to engage in multilateral and bilateral cooperation, including exchanging epidemiological

information, laboratory monitoring data, and carrying out supplementary immunization

activities simultaneously as appropriate;

 

4. REQUESTS the Director-General:

 

(1) to plan for the renewed implementation through 2013 of the approaches to eradicating

wild polioviruses outlined in the Global Polio Eradication Initiative Strategic Plan 2010–2012

and any new tactics that are deemed necessary to complete eradication, including the

enhancement of the existing global polio eradication initiative within the Organization;

 

(2) to strengthen accountability and monitoring mechanisms to ensure optimal

implementation of eradication strategies at all levels;

 

(3) to undertake the development, scientific vetting, and rapid finalization of a

comprehensive polio eradication and endgame strategy, and inform Member States of the

 

1 International travel and health. Geneva, World Health Organization, 2012 edition.

 

potential timing of a switch from trivalent to bivalent oral poliovirus vaccine for all routine

immunization programmes; and include budget scenarios to the end of 2018 that include risk

management;

 

(4) to coordinate with all relevant partners, including vaccine manufacturers, to promote the

research, production and supply of vaccines, in particular inactivated polio vaccines, in order to enhance their affordability, effectiveness and accessibility;

 

(5) to continue mobilizing and deploying the necessary financial and human resources for the strategic approaches required through 2013 for wild poliovirus eradication, and for the eventual implementation of a polio endgame strategy to the end of 2018;

 

(6) to report to the Sixty-sixth World Health Assembly and the subsequent two Health

Assemblies, through the Executive Board, on progress in implementing this resolution.

 

Tenth plenary meeting, 26 May 2012

A65/VR/10

 

• IMMUNODEFICIENCY-ASSOCIATED VACCINE-DERIVED POLIOVIRUS TYPE 3 IN INFANT, SOUTH AFRICA, 2011
• EID Journal, June 2012

 

Best viewed at

http://wwwnc.cdc.gov/eid/article/18/6/12-0037_article.htm

 

Dispatch

Nicksy Gumede  , Vongani Muthambi, and Barry D. Schoub

Author affiliations: National Institute for Communicable Diseases National Health Laboratory Service, Johannesburg, South Africa

Abstract

Patients with primary immunodeficiency are prone to persistently excrete Sabin-like virus after administration of live-attenuated oral polio vaccine and have an increased risk for vaccine-derived paralytic polio. We report a case of type 3 immunodeficiency-associated vaccine-derived poliovirus in a child in South Africa who was born with X-linked immunodeficiency syndrome.

Live-attenuated oral polio vaccine (OPV) is still the vaccine of choice for use in developing countries. However, reversion to virulence may occur during OPV replication in humans and may result in the rare cases of vaccine-associated paralytic poliomyelitis in OPV recipients and their close contacts. Two additional OPV-related problems that may affect polio eradication: long-term, persistent infection with OPV-derived viruses in persons with primary humoral immunodeficiencies (so-called immunodeficiency-associated vaccine-derived polioviruses [iVDPVs]); and circulating vaccine-derived polioviruses (VDPV) in areas with low rates of vaccine coverage (1). VDPV strains are defined as follows: 1) strains of types 1 and 3, which have <99% nt sequence identity to the capsid viral protein (VP) 1 coding region of the corresponding Sabin reference strain; and 2) VDPV strains of type 2, which have <99.4% nt sequence identity to the corresponding Sabin reference viral protein 1 (VP1) (1). Circulating VDPVs show marked sequence drift, indicating prolonged replication of the vaccine strain in susceptible human hosts and consequent acquisition of the phenotypic properties of neurovirulence and transmissibility.

Persons born with primary immunodeficiency have been found to be persistently infected with VDPV after exposure to OPV. Immunocompetent persons excrete polio vaccine viruses for up to 2–3 months (2), whereas prolonged excretion of VDPV for 6 months to >10 years has been found in persons with primary humoral immunodeficiency (3–6). The risk for vaccine-associated paralytic poliomyelitis is >3,000-fold higher for these patients (7). We report a case of type 3 iVDPV in a child in South Africa who was born with X-linked immunodeficiency syndrome.

The Patient

The patient, a 10-month-old boy, was born at term on October 28, 2010; X-linked immunodeficiency syndrome was diagnosed after he received 3 scheduled doses of polio vaccine (1 OPV dose at birth and 2 inactivated poliovirus vaccine doses at 10 and 14 weeks). On September 18, 2011, fever developed (38.5°C–40.0°C), and the next day, vomiting and 2 episodes of tonic-clonic convulsions occurred. A lumbar puncture was performed, and testing of cerebrospinal fluid (CSF) showed pleocytosis and mild increase of proteins. His condition deteriorated, and on day 5, acute flaccid paralysis developed, with generalized hypotonia and reduced power and reflexes in all limbs, more marked in the lower limbs. Respiratory distress developed, and some involvement of the facial nerve was manifested by left-sided eye drooping, mouth deviation, and drooling. A lumbar puncture was repeated on day 5, and CSF was positive by PCR for enterovirus and a pleocytosis. Stool samples taken on days 5 and 9 were positive for enterovirus, which was subsequently characterized as poliovirus type 3.

Beginning 15 days after the onset of paralysis, intravenous immunoglobulin (National Bioproducts Institute, KwaZulu-Natal, South Africa) with a titer for polio type 3 neutralizing antibodies of 4–8 IU was administered daily for 32 days, followed by alternate days to a total of 43 doses. The patient improved gradually, and strength was regained in all limbs, with the exception of residual paresis in the right lower limb. CSF became negative for poliovirus PCR 2 weeks after immunoglobulin therapy began, and stool excretion of poliovirus ceased on day 70, 55 days after initiation of immunoglobulin therapy.

Extracts of stool specimens were treated with chloroform and cultured on human rhabdomyosarcoma cell line, used for enterovirus isolation, and mouse L cells expressing the human poliovirus receptor, used specifically for poliovirus isolation (8). To distinguish whether the poliovirus isolates were of vaccine or wild origin, real-time PCR tests were performed, targeting the VP1 coding region (9). In addition, to detect mutant and recombinant poliovirus vaccine strains, a vaccine-derived, real-time screening assay was performed (David Kilpatrick, pers. comm.).

All Sabin 3 strains were sequenced at 3 regions of the genome: 5′ untranslated region, VP1, and 3D. The sequence analysis of all viruses revealed a mutation at nt 472 of the 5′ untranslated region (U₄₇₂→C), a critical attenuating mutation feature for Sabin 3. This substitution in the internal ribosomal site restores the original structure of the stem loop and permitting the initiation of translation of the poliovirus RNA template (10,11) The reversion at that site is under strong selection during replication in the human intestine and is associated with the attenuated phenotype in Sabin 3 (12). The VP1 region showed 2 reversions of the capsid determinant; C₂₄₉₃→U appear to be the main determinants of the attenuated phenotype (1), and at position 54 for alanine amino acid mutated to valine (Ala₅₄→Val) that can act as a suppressor of the temperature sensitivity and attenuated phenotype (13). At the 3D region, the sequence analysis showed no recombinant.

Both stool samples showed mixed bases at 12 positions, consistent with the presence of at least 2 main genetic variants in the virus population (Table). Isolates with mixed bases are characteristic of iVDPVs, which suggests the existence of co-replicating poliovirus lineages within immunodeficient patients (1,5).

Figure

 

Figure. . . Neighbor-joining tree of immunodeficiency-associated vaccine-derived poliovirus isolates from infant, South Africa, 2011. The tree was derived from the viral protein (VP) 1 region and rooted at the Sabin 3...

The relationships among the VP1 sequences of the 3 isolates were summarized in a tree constructed by using the neighbor-joining method (14) and rooted to the Sabin 3 sequence (Figure). The iVDVP isolates differed from the Sabin 3 OPV strain at 1.1% and from each other by 1.4% at a VP1 region, similar to the rate of nucleotide sequence evolution in poliovirus as described by Jorba et al. (15). The chronic iVDPV infection could have been initiated by the birth dose. The shallow branches correspond to 2 lineages (A, CSF, and B, stool). The extensive divergence of the two lineages was not surprising as the viruses originated from 2 sources (CSF and stool samples) taken 4 days apart. The VP1 sequence of lineage B was ambiguous at several positions, which suggests the virus population was of mixed variants. All sequences determined in this study were derived from Sabin 3 strain.

Conclusions

Cases of iVDPV are rare; especially rare is type 3. Only ≈50 cases had been reported in the literature as of March 2011 and, to our knowledge, none in sub-Saharan Africa. We characterized 2 separate lineages of type 3 poliovirus in this patient, demonstrating separate evolution of the virus. A relatively rapid clinical and virologic response to intravenous immunoglobulin averted chronic excretion of the virus. Persistent excretion of VDPV in primary immunodeficient patients remains a potential risk to the global eradication of polio, as long as OPV is still used.

Ms Gumede is a medical scientist pursuing a PhD at the University of Pretoria, South Africa. Her research interests include disease epidemiology, clinical research, and polioviruses.

Acknowledgment

We thank the National Institute for Communicable Diseases Polio Working Group for excellent technical assistance and M. Kriel for clinical information.

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