The limited, highly localized cVDPV outbreak in 2006 in the neighboring villages of Hongwei and Yongping highlights the risks of cVDPV emergence and spread in small, isolated populations with critical immunity gaps. In this outbreak, the key risk group (n
≈ 250) was children aged 5 to 10 years, among whom the rates of OPV coverage were <30%. Younger children had high rates of OPV coverage, and older persons had acquired immunity from the intensive mass immunization campaigns of the 1990s and some had acquired immunity from natural WPV infection before 1993 (23
). If the potential paralytic attack rate of the cVDPV was similar to that of WPV1 (~1 paralytic case per 200 infections in nonimmune children) (28
) and most of the susceptible children in the two communities were exposed, then the expected paralytic case count would be ~1.
We cannot be certain that the cVDPV actually emerged from an OPV dose given in Hongwei or Yongping because the cVDPV appears to have been in circulation for ~10 months before appearance of the index AFP case. However, the inaccessibility of these communities makes local emergence likely. The lack of paved roads restricts the mobility of the local population and limits outside contact, and the rugged mountain paths were a barrier both to the delivery of quality routine immunization services and to virus dissemination. The absence of polio cases elsewhere in Guangxi, where the province-wide coverage rates for three doses of OPV is ~95% (48
), is consistent with local emergence.
The observation that all isolates were S1/S2/S1/S3 recombinants sharing common recombination junctions is also consistent with limited VDPV circulation. Although vaccine/vaccine recombinants of Sabin 1 are relatively infrequent (16
), it is likely that the recombination occurred in the original tOPV recipient. Spread of the vaccine progeny was sufficiently limited that no subsequent recombination with various species C human enteroviruses (HEVs-C) was observed. This is in distinct contrast to the serial recombination with HEVs-C that is typically found during circulation of most cVDPVs (18
) and WPVs (24
). The likelihood of recombination with HEV-C increases with the frequency of poliovirus and HEV-C infections. Although the HEV-C carriage rate in Hongwei and Yongping in 2005 to 2006 is unknown, the VDPV was likely circulating throughout the 2005 enterovirus season, and close contact among infected school-age children and poor conditions of sanitation and hygiene may have facilitated virus transmission. Thus, vaccine/nonvaccine recombinants probably would have emerged had there been widespread VDPV circulation. The absence of HEV-C recombinants from among the Guangxi cVDPVs and the nonrecombinant type 1 cVDPVs from the 2004 Guizhou outbreak (23
) demonstrates that recombination with HEVs-C is not required for cVDPV emergence and spread in the early phases of outbreaks.
Phylogenetic analysis has provided insights into the minimum period of cVDPV circulation in small, isolated communities. In a previous study, circulation of a type 1 VDPV in a rural undervaccinated community in Minnesota (population, ~161) was estimated to have been at least 3 to 4 months, whereas it was ~12 months in the villages of Hongwei and Yongping (combined populations, ~4,300). In Minnesota, the estimate of the circulation time may have been reduced by the small sample size (n = 5), whereas in Guangxi, circulation was likely halted by the strong immunization response.
It is of interest that the recent small VDPV outbreaks in China and Minnesota were associated with type 1. In contrast, the large and prolonged VDPV outbreaks in Egypt (46
) and Nigeria (9
) were associated with type 2. One possible explanation is that the substantially higher paralytic attack rate for poliovirus type 1 than for type 2 (28
) favors earlier detection of AFP cases associated with type 1 infection, especially in small populations. Moreover, emergence of type 2 cVDPVs probably requires wider gaps in tOPV coverage because of the greater tendency of type 2 vaccine virus to spread to unvaccinated contacts (2
). For unknown reasons, outbreaks of type 3 cVDPV infections appear to be rare (9
Because of its large population, high population densities, numerous communities with poor sanitation, and large areas with subtropical and tropical climates, China is potentially at high risk of cVDPV emergence. China has mitigated those risks with high rates of routine OPV coverage nationwide (estimated in 2004 to be 93.8% for three or more doses of OPV among children aged 1 to 3 years [29
]), sensitive AFP surveillance, comprehensive and definitive laboratory testing, and a rapid immunization response following detection of VDPVs. Since 1997, of the 18 different VDPVs isolated from AFP patients in China (>130,000 specimens have been screened), only 3 have been associated with outbreaks (23
). Both the Guangxi and the Guizhou outbreaks were detected before circulation was widespread, were associated with very few AFP cases, and were halted by large effective immunization responses launched within 2 to 3 months of appearance of the first AFP case. Immediately following the detection of VDPV from the March AFP case in Guangxi, intensive screening for VDPVs was initiated by provincial and national-level polio laboratories.
Our findings reinforce the point that geographic isolation and limited outside contact do not protect against polio and that cVDPVs can emerge in any location where OPV is used at low rates of coverage (1
). Therefore, it is critical that high rates of polio vaccine coverage and sensitive AFP and poliovirus surveillance be maintained in all countries to mitigate the risks of poliovirus transmission.