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Antigenic Diversity of Enteroviruses Associated with Nonpolio Acute Flaccid Paralysis, India, 2007–2009 - - Emerging Infectious Disease journal - CDC

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Antigenic Diversity of Enteroviruses Associated with Nonpolio Acute Flaccid Paralysis, India, 2007–2009 - - Emerging Infectious Disease journal - CDC

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Volume 18, Number 11–November 2012


Antigenic Diversity of Enteroviruses Associated with Nonpolio Acute Flaccid Paralysis, India, 2007–2009

C. Durga RaoComments to Author , Prasanna Yergolkar1, and K. Subbanna Shankarappa12
Author affiliations: Author affiliations: Indian Institute of Science, Bangalore, India (C.D. Rao, K.S. Shankarappa); National Institute of Virology–World Health Organization–South East Asia Region Polio Laboratory Network, Victoria Hospital, Bangalore (P. Yergolkar); National Institute of Virology, Bangalore (P. Yergolkar); Victoria Hospital, Bangalore (P. Yergolkar)
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Because of the broadened acute flacid paralysis (AFP) definition and enhanced surveillance, many nonpolio AFP (NP-AFP) cases have been reported in India since 2005. To determine the spectrum of nonpolio enterovirus (NPEV) serotypes associated with NP-AFP from polio-endemic and -free regions, we studied antigenic diversity of AFP-associated NPEVs. Of fecal specimens from 2,786 children with NP-AFP in 1 polio-endemic and 2 polio-free states, 823 (29.5%) were positive for NPEVs in RD cells, of which 532 (64.6%) were positive by viral protein 1 reverse transcription PCR. We identified 66 serotypes among 581 isolates, with enterovirus 71 most frequently (8.43%) detected, followed by enterovirus 13 (7.1%) and coxsackievirus B5 (5.0%). Most strains within a serotype represented new genogropups or subgenogroups. Agents for ≈35.0% and 70.0% of culture-positive and -negative cases, respectively, need to be identified. Association of human enterovirus with NP-AFP requires better assessment and understanding of health risks of NPEV infections after polio elimination.
Acute flaccid paralysis (AFP) is defined as sudden onset of weakness and floppiness in any part of the body in a child <15 a="a" age="age" any="any" href="" in="in" is="is" of="of" or="or" paralysis="paralysis" person="person" polio="polio" suspected="suspected" title="1" whom="whom" years="years">1
). It is a complex and broad clinical syndrome associated with a wide range of microbial and nonmicrobial agents and immune processes; clinical presentations and numbers are influenced by environmental and geographic factors. To cast a wider net for poliovirus detection and to maximize sensitivity so that every poliomyelitis case is detected, in 2005, the Global Poliomyelitis Eradication Initiative adapted AFP as a surveillance tool and broadened the case definition of AFP in India. The expanded case definition of AFP encompasses causes of nonpolio AFP (NP-AFP), including Guillian-Barré syndrome, transverse myelitis and traumatic neuritis, and ambiguous cases (1). With the launch of the Global Poliomyelitis Eradication Initiative in 1988 for effective vaccination, surveillance, and monitoring of wild poliovirus transmission toward the target of polio eradication, the number of wild polio AFP cases declined remarkably from ≈300,000 to 974 in 2010 globally (2). Introduction of Pulse Polio Immunization, in addition to routine administration of oral polio vaccine, effectively interrupted indigenous wild poliovirus transmission and led to a remarkable decline in the number of poliomyelitis cases from ≈35,000 cases annually during 1994–1995 to 66 in 2005 in India. However, during 2006–2009, the number of polio cases hovered at ≈559–874 each year (25), with most cases reported primarily from the 2 northern states of Uttar Pradesh and Bihar, in which wild poliovirus remained endemic. The last case of type 2 wild poliovirus globally occurred in 1999 in India. Introduction of bivalent oral polio vaccine types 1 and 3 resulted in a dramatic decline in wild poliovirus cases to 42 in 2010 and only 1 case reported in January 2011 (25). India is now considered a polio-free nation by the Government of India, National Polio Surveillance Project (NPSP) and by the World Health Organization (WHO)/South-East Asia Regional Office and WHO.
However, analysis of WHO-monitored polio surveillance data on the number of AFP, polio AFP, and NP-AFP cases available at the public domains ( Web Site Icon; Web Site Icon; Web Site Icon) (25) from 1998 through June 2, 2012, in India shows that concomitant with the phenomenal elimination of wild poliovirus transmission in India was an annual increase in the number of reported AFP cases from 2005 to date throughout the country (24). Although 8,103–9,705 were reported during 1998–2003, a total of 55,782 and 60,883 cases were reported during 2010 and 2011, respectively. Through June 2, a total of 20,677 AFP cases were reported in India during 2012, compared with 18,625 during the corresponding period in 2011 (4). This large increase in NP-AFP cases, which represent AFP cases caused by agents other than poliovirus, probably reflects the excellent implementation of the expanded definition of AFP and highly sensitive surveillance and detection methods used by NPSP in India from 2005 onwards, in contrast to the other polio-endemic countries, i.e., Pakistan, Nigeria, and Afghanistan, where the expanded AFP surveillance is not in place (15). The large increase in the NP-AFP rate from 1.45 and 1.97 per 100,000 children during 1998–2003 to 16.20 in 2011 (35) further reflects the excellent operational performance of the expanded AFP surveillance in India.
The genus Enterovirus within the family Picornaviridae comprises a diverse group of 10 species, of which 7 are associated with a wide spectrum of acute and chronic human diseases (6,7). Human enteroviruses (HEVs) are ubiquitous, infecting ≈1 billion persons worldwide. Although the actual incidence of enteroviral diseases is not known, most infections are thought to be asymptomatic, with ≈1% resulting in severe illness with high rates of death, especially in infants and young children (6). The >100 HEV serotypes comprising echoviruses (E), coxsackieviruses A (CAV) and B (CBV), polioviruses, and newer enteroviruses (EV) have been grouped into 4 species—HEV-A, HEV-B, HEV-C, and HEV-D—with poliovirus being part of HEV-C. Recently, rhinoviruses also have been included in the genus Enterovirus (8).
Molecular typing methods based on reverse transcription PCR (RT-PCR) amplification, nucleotide sequencing of the complete or the 3′ portion of the viral protein (VP) 1 gene, and comparison of the derived sequences with those of prototype and variant HEVs in the databases are widely used to identify EV types in clinical samples (9,10). In the current most commonly used molecular typing scheme, homotypic viruses generally share at least 75% nt identity and 85%–88% aa identity in VP1 (9,10).
Although nonpolio enteroviruses (NPEVs) are a major cause of AFP (6,7,11) and NP-AFP cases are being detected in large numbers, detailed knowledge is lacking about the serotypes associated with NP-AFP or other enteroviral diseases in India. We aimed to determine the spectrum of NPEV serotypes associated with NP-AFP from polio-endemic and polio-free regions of India with a view to develop strategies against the so-far unrecognized viral infections.

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