Modeling Poliovirus Transmission in Pakistan and Afghanistan to Inform Vaccination Strategies in Undervaccinated Subpopulations.

Due to security, access, and programmatic challenges in areas of Pakistan and Afghanistan, both countries continue to sustain indigenous wild poliovirus (WPV) transmission and threaten the success of global polio eradication and oral poliovirus vaccine (OPV) cessation. We fitted an existing differential-equation-based poliovirus transmission and OPV evolution model to Pakistan and Afghanistan using four subpopulations to characterize the well-vaccinated and undervaccinated subpopulations in each country. We explored retrospective and prospective scenarios for using inactivated poliovirus vaccine (IPV) in routine immunization or supplemental immunization activities (SIAs). The undervaccinated subpopulations sustain the circulation of serotype 1 WPV and serotype 2 circulating vaccine-derived poliovirus. We find a moderate impact of past IPV use on polio incidence and population immunity to transmission mainly due to (1) the boosting effect of IPV for individuals with preexisting immunity from a live poliovirus infection and (2) the effect of IPV-only on oropharyngeal transmission for individuals without preexisting immunity from a live poliovirus infection. Future IPV use may similarly yield moderate benefits, particularly if access to undervaccinated subpopulations dramatically improves. However, OPV provides a much greater impact on transmission and the incremental benefit of IPV in addition to OPV remains limited. This study suggests that despite the moderate effect of using IPV in SIAs, using OPV in SIAs remains the most effective means to stop transmission, while limited IPV resources should prioritize IPV use in routine immunization.

Outbreaks of paralytic poliomyelitis during 1996-2012: the changing epidemiology of a disease in the final stages of eradication.

BACKGROUND: Despite substantial progress toward eradication of poliomyelitis, the risk of poliomyelitis outbreaks resulting from virus importations into polio-free areas persists. We reviewed the changing epidemiology of outbreaks in the final stages of the eradication initiative. METHODS: Available literature on outbreaks of poliomyelitis caused by wild polioviruses between 1996 and 2012 was reviewed. RESULTS: During this period, there were 22 outbreaks involving 39 countries. Outbreaks ranged in size from 1 to 1335 cases. These outbreaks caused 4571 cases, representing 21% of all cases reported during this period. Five outbreaks involved multiple countries. In 76% of outbreaks (16/21) with a known age distribution, cases concentrated among children aged <5 years; in 19% (4/21), most cases were among adolescents and adults. The outbreaks among adolescents and adults were associated with higher case-fatality ratios, ranging from 12% in Albania in 1994 to 41% in the Republic of Congo in 2010. The majority of outbreaks were controlled within 6 months with oral poliovirus vaccine. CONCLUSIONS: Importations resulting in epidemic transmission of wild poliovirus caused thousands of cases of paralysis often in countries where poliomyelitis had not occurred for many years. The changing epidemiology, with cases and higher case-fatality ratios among adults, increased the severity of these outbreaks.

Modeling population immunity to support efforts to end the transmission of live polioviruses.

Eradication of wild poliovirus (WPV) types 1 and 3, prevention and cessation of circulating vaccine-derived polioviruses, and achievement and maintenance of a world free of paralytic polio cases requires active risk management by focusing on population immunity and coordinated cessation of oral poliovirus vaccine (OPV). We suggest the need for a complementary and different conceptual approach to achieve eradication compared to the current case-based approach using surveillance for acute flaccid paralysis (AFP) to identify symptomatic poliovirus infections. Specifically, we describe a modeling approach to characterize overall population immunity to poliovirus transmission. The approach deals with the realities that exposure to live polioviruses (e.g., WPV, OPV) and/or vaccination with inactivated poliovirus vaccine provides protection from paralytic polio (i.e., disease), but does not eliminate the potential for reinfection or asymptomatic participation in poliovirus transmission, which may increase with time because of waning immunity. The AFP surveillance system provides evidence of symptomatic poliovirus infections detected, which indicate immunity gaps after outbreaks occur, and this system represents an appropriate focus for controlling disease outbreaks. We describe a conceptual dynamic model to characterize population immunity to poliovirus transmission that helps identify risks created by immunity gaps before outbreaks occur, which provides an opportunity for national and global policymakers to manage the risk of poliovirus and prevent outbreaks before they occur. We suggest that dynamically modeling risk represents an essential tool as the number of cases approaches zero.

Preeradication vaccine policy options for poliovirus infection and disease control.

With the circulation of wild poliovirus (WPV) types 1 and 3 continuing more than a decade after the original goal of eradicating all three types of WPVs by 2000, policymakers consider many immunization options as they strive to stop transmission in the remaining endemic and outbreak areas and prevent reintroductions of live polioviruses into nonendemic areas. While polio vaccination choices may appear simple, our analysis of current options shows remarkable complexity. We offer important context for current and future polio vaccine decisions and policy analyses by developing decision trees that clearly identify potential options currently used by countries as they evaluate national polio vaccine choices. Based on a comprehensive review of the literature we (1) identify the current vaccination options that national health leaders consider for polio vaccination, (2) characterize current practices and factors that appear to influence national and international choices, and (3) assess the evidence of vaccine effectiveness considering sources of variability between countries and uncertainties associated with limitations of the data. With low numbers of cases occurring globally, the management of polio risks might seem like a relatively low priority, but stopping live poliovirus circulation requires making proactive and intentional choices to manage population immunity in the remaining endemic areas and to prevent reestablishment in nonendemic areas. Our analysis shows remarkable variability in the current national polio vaccine product choices and schedules, with combination vaccine options containing inactivated poliovirus vaccine and different formulations of oral poliovirus vaccine making choices increasingly difficult for national health leaders.

An outbreak of wild poliovirus in the Republic of Congo, 2010-2011.

BACKGROUND: The Republic of Congo has had no cases of wild poliovirus type 1 (WPV1) since 2000. In October 2010, a neurologist noted an abnormal number of cases of acute flaccid paralysis (AFP) among adults, which were later confirmed to be caused by WPV1. METHODS: Those presenting with AFP underwent clinical history, physical examination, and clinical specimen collection to determine if they had polio. AFP cases were classified as laboratory-confirmed, clinical, or nonpolio AFP. Epidemiologic features of the outbreak were analyzed. RESULTS: From 19 September 2010 to 22 January 2011, 445 cases of WPV1 were reported in the Republic of Congo; 390 cases were from Pointe Noire. Overall, 331 cases were among adults; 378 cases were clinically confirmed, and 64 cases were laboratory confirmed. The case-fatality ratio (CFR) was 43%. Epidemiologic characteristics differed among polio cases reported in Pointe Noire and cases reported in the rest of the Republic of Congo, including age distribution and CFR. The outbreak stopped after multiple vaccination rounds with oral poliovirus vaccine, which targeted the entire population. CONCLUSIONS: This outbreak underscores the need to maintain high vaccination coverage to prevent outbreaks, the need to maintain timely high-quality surveillance to rapidly identify and respond to any potential cases before an outbreak escalates, and the need to perform ongoing risk assessments of immunity gaps in polio-free countries.

New analytic approaches for analyzing and presenting polio surveillance data to supplement standard performance indicators.

BACKGROUND: Sensitive surveillance for acute flaccid paralysis (AFP) allows for rapid detection of polio outbreaks and provides essential evidence to support certification of the eradication of polio. However, accurately assessing the sensitivity of surveillance systems can be difficult due to limitations in the reliability of available performance indicators, including the rate of detection of non-polio AFP and the proportion of adequate stool sample collection. Recent field reviews have found evidence of surveillance gaps despite indicators meeting expected targets. METHODS: We propose two simple new approaches for AFP surveillance performance indicator analysis to supplement standard indicator analysis approaches commonly used by the Global Polio Eradication Initiative (GPEI): (1) using alternative groupings of low population districts in the country (spatial binning) and (2) flagging unusual patterns in surveillance data (surveillance flags analysis). Using GPEI data, we systematically compare AFP surveillance performance using standard indicator analysis and these new approaches. RESULTS: Applying spatial binning highlights areas meeting surveillance indicator targets that do not when analyzing performance of low population districts. Applying the surveillance flags we find several countries with unusual data patterns, in particular age groups which are not well-covered by the surveillance system, and countries with implausible rates of adequate stool specimen collection. CONCLUSIONS: Analyzing alternate groupings of administrative units is a simple method to find areas where traditional AFP surveillance indicator targets are not reliably met. For areas where AFP surveillance indicator targets are met, systematic assessment of unusual patterns ('flags') can be a useful prompt for further investigation and field review.

Patients with Primary Immunodeficiencies Are a Reservoir of Poliovirus and a Risk to Polio Eradication.

Immunodeficiency-associated vaccine-derived polioviruses (iVDPVs) have been isolated from primary immunodeficiency (PID) patients exposed to oral poliovirus vaccine (OPV). Patients may excrete poliovirus strains for months or years; the excreted viruses are frequently highly divergent from the parental OPV and have been shown to be as neurovirulent as wild virus. Thus, these patients represent a potential reservoir for transmission of neurovirulent polioviruses in the post-eradication era. In support of WHO recommendations to better estimate the prevalence of poliovirus excreters among PIDs and characterize genetic evolution of these strains, 635 patients including 570 with primary antibody deficiencies and 65 combined immunodeficiencies were studied from 13 OPV-using countries. Two stool samples were collected over 4 days, tested for enterovirus, and the poliovirus positive samples were sequenced. Thirteen patients (2%) excreted polioviruses, most for less than 2 months following identification of infection. Five (0.8%) were classified as iVDPVs (only in combined immunodeficiencies and mostly poliovirus serotype 2). Non-polio enteroviruses were detected in 30 patients (4.7%). Patients with combined immunodeficiencies had increased risk of delayed poliovirus clearance compared to primary antibody deficiencies. Usually, iVDPV was detected in subjects with combined immunodeficiencies in a short period of time after OPV exposure, most for less than 6 months. Surveillance for poliovirus excretion among PID patients should be reinforced until polio eradication is certified and the use of OPV is stopped. Survival rates among PID patients are improving in lower and middle income countries, and iVDPV excreters are identified more frequently. Antivirals or enhanced immunotherapies presently in development represent the only potential means to manage the treatment of prolonged excreters and the risk they present to the polio endgame.

Population immunity to polioviruses in the context of a large-scale wild poliovirus type 1 outbreak in Tajikistan, 2010.

BACKGROUND: A serosurvey to evaluate population immunity to polioviruses (PVs) in the context of the importation-related wild PV1 outbreak in Tajikistan in 2010 (461 confirmed cases among children and young adults) was conducted. METHODS: Serum specimens from a nationwide sample of 1-24 year-old persons selected through stratified cluster sampling (n=2447) were tested for neutralizing antibodies to all three PV types. Samples with titers<1:8 were considered seronegative. The serosurvey was conducted during the interval after mOPV1 supplementary immunization activities (SIAs) and before tOPV SIAs (targeting ages ≤ 15 years) implemented to control the outbreak. In the absence of pre-outbreak specimens, results for PV3 were used as a proxy for pre-outbreak PV1 immunity patterns. RESULTS: Overall, PV1 seroprevalence was 98.9%, PV2 seroprevalence was 98.8%, and PV3 seroprevalence was 86.9%. PV1 and PV2 seroprevalence exceeded 95% in all age groups and regions. PV3 seroprevalence was <90% in all age groups and regions, except 15-19 year-olds (91.7%) and Dushanbe (90.0%). PV3 seroprevalence was lowest among 1-4 (82.7%) and 5-9 (84.4%) year-olds, particularly among 1-4 year-olds in Kurgan-Tube (76.3%) and RRS (80.0%) regions. Birth cohorts immunized only through routine services (ages, 1-7 years) had lower PV3 seroprevalence than birth cohorts targeted by the SIAs during 1995-2002 (8-19 years): 82.5% versus 89.3%, p<0.001. CONCLUSIONS: Suboptimal (<90%) PV3 seroprevalence across wide age range suggests the outbreak resulted from accumulation of susceptibles due to suboptimal coverage over a long time period, particularly in the birth cohorts immunized only through routine services and in areas where the outbreak began (Kurgan-Tube and RRS). High PV1 seroprevalence indicates that mOPV1 SIAs with expanded target age (≤ 15 years) succeeded in closing the immunity gap and ongoing WPV1 transmission is unlikely. To accelerate outbreak control in areas which have been polio-free for long time, expanding SIA target age should be considered.

Seroepidemiology of diphtheria and tetanus among children and young adults in Tajikistan: nationwide population-based survey, 2010.

BACKGROUND: Tajikistan had a major diphtheria outbreak (≈ 10,000 cases) in the 1990 s, which was controlled after nationwide immunization campaigns with diphtheria-tetanus toxoid in 1995 and 1996. Since 2000, only 52 diphtheria cases have been reported. However, in coverage surveys conducted in 2000 and 2005, diphtheria-tetanus-pertussis vaccine coverage was lower than administratively reported estimates raising concerns about potential immunity gaps. To further assess population immunity to diphtheria in Tajikistan, diphtheria antibody testing was included in a large-scale nationwide serosurvey for vaccine-preventable diseases conducted in connection with a poliomyelitis outbreak in 2010. In addition, the serosurvey provided an opportunity to assess population immunity to tetanus. METHODS: Residents of all regions of Tajikistan aged 1-24 years were included in the serosurvey implemented during September-October 2010. Participants were selected through stratified cluster sampling. Specimens were tested for diphtheria antibodies using a Vero cell neutralization assay and for tetanus antibodies using an anti-tetanus IgG ELISA. Antibody concentrations ≥ 0.1 IU/mL were considered seropositive. RESULTS: Overall, 51.4% (95% CI, 47.1%-55.6%) of participants were seropositive for diphtheria and 78.9% (95% CI, 74.7%-82.5%) were seropositive for tetanus. The lowest percentages of seropositivity for both diseases were observed among persons aged 10-19 years: diphtheria seropositivity was 37.1% (95% CI, 31.0%-43.7%) among 10-14 year-olds, and 35.3% (95% CI, 29.9%-41.1%) among 15-19 year-olds; tetanus seropositivity in respective age groups was 65.3% (95% CI, 58.4%-71.6%) and 70.1% (95% CI, 64.5%-75.2%). CONCLUSIONS: Population immunity for diphtheria in Tajikistan is low, particularly among 10-19 year-olds. Population immunity to tetanus is generally higher than for diphtheria, but is suboptimal among 10-19 year-olds. These findings highlight the need to improve routine immunization service delivery, and support a one-time supplementary immunization campaign with diphtheria-tetanus toxoid among birth cohorts aged 1-19 years in 2010 (3-21 years in 2012) to close immunity gaps and prevent diphtheria outbreaks.