Roland W. Sutter

Current situation and control strategies for resurgence of diphtheria in newly independent states of the former Soviet Union

Since 1990, an epidemic of diphtheria has spread throughout the newly independent states of the former Soviet Union, and by 1995 a total of 47 808 cases were reported. During the early stages of the epidemic, adequate control measures were not taken and vaccine was in short supply; possible contributing factors to the spread of the epidemic are the presence of highly susceptible child and adult populations, socioeconomic instability, population movement, and a deteriorating health infrastructure. Although WHO views the epidemic as an International public-health emergency and, together with UNICEF and the International Red Cross, has formulated a strategy to combat the epidemic, the necessary funds have not been made fully available. Current vaccination recommendations also need to be reviewed to ensure that population immunity will be adequate to prevent any resurgence of diphtheria in Europe and North America.

Successful control of epidemic diphtheria in the states of the former Union of Soviet Socialist Republics: lessons learned.

Epidemic diphtheria reemerged in the Russian Federation in 1990 and spread to all Newly Independent States (NIS) and Baltic States by the end of 1994. Factors contributing to the epidemic included increased susceptibility of both children and adults, socioeconomic instability, population movement, deteriorating health infrastructure, initial shortages of vaccine, and delays in implementing control measures. In 1995, aggressive control strategies were implemented, and since then, all affected countries have reported decreases of diphtheria; however, continued efforts by national health authorities and international assistance are still needed. The legacy of this epidemic includes a reexamination of the global diphtheria control strategy, new laboratory techniques for diphtheria diagnosis and analysis, and a model for future public health emergencies in the successful collaboration of multiple international partners. The reemergence of diphtheria warns of an immediate threat of other epidemics in the NIS and Baltic States and a longer-term potential for the reemergence of vaccine-preventable diseases elsewhere. Continued investment in improved vaccines, control strategies, training, and laboratory techniques is needed.

Search for poliovirus carriers among people with primary immune deficiency diseases in the United States, Mexico, Brazil, and the United Kingdom.

OBJECTIVE To estimate the rate of long-term poliovirus excretors in people known to have B-cell immune deficiency disorders. METHODS An active search for chronic excretors was conducted among 306 persons known to have immunoglobulin G (IgG) deficiency in the United States, Mexico, Brazil, and the United Kingdom, and 40 people with IgA deficiency in the United States. Written informed consent or assent was obtained from the participants or their legal guardians, and the studies were formally approved. Stool samples were collected from participants and cultured for polioviruses. Calculation of the confidence interval for the proportion of participants with persistent poliovirus excretion was based on the binomial distribution. FINDINGS No individuals with long-term excretion of polioviruses were identified. Most participants had received oral poliovirus vaccine (OPV) and almost all had been exposed to household contacts who had received OPV. Polioviruses of recent vaccine origin were transiently found in four individuals in Mexico and Brazil, where OPV is recommended for all children. CONCLUSION Although chronic poliovirus excretion can occur in immunodeficient persons, it appears to be rare.

Vaccine-associated paralytic poliomyelitis in India during 1999: decreased risk despite massive use of oral polio vaccine

OBJECTIVE Vaccine-associated paralytic poliomyelitis (VAPP) is a rare but serious consequence of the administration of oral polio vaccine (OPV). Intensified OPV administration has reduced wild poliovirus transmission in India but VAPP is becoming a matter of concern. METHODS We analysed acute flaccid paralysis (AFP) surveillance data in order to estimate the VAPP risk in this country. VAPP was defined as occurring in AFP cases with onset of paralysis in 1999, residual weakness 60 days after onset, and isolation of vaccine-related poliovirus. Recipient VAPP cases were a subset with onset of paralysis between 4 and 40 days after receipt of OPV. FINDINGS A total of 181 AFP cases met the case definition. The following estimates of VAPP risk were made: overall risk, 1 case per 4.1 to 4.6 million OPV doses administered; recipient risk,1 case per 12.2 million; first-dose recipient risk, 1 case per 2.8 million; and subsequent-dose recipient risk, 1 case per 13.9 million. CONCLUSION On the basis of data from a highly sensitive surveillance system the estimated VAPP risk in India is evidently lower than that in other countries, notwithstanding the administration of multiple OPV doses to children in mass immunization campaigns.

Expert Review on Poliovirus Immunity and Transmission

Successfully managing risks to achieve wild polioviruses (WPVs) eradication and address the complexities of oral poliovirus vaccine (OPV) cessation to stop all cases of paralytic poliomyelitis depends strongly on our collective understanding of poliovirus immunity and transmission. With increased shifting from OPV to inactivated poliovirus vaccine (IPV), numerous risk management choices motivate the need to understand the tradeoffs and uncertainties and to develop models to help inform decisions. The U.S. Centers for Disease Control and Prevention hosted a meeting of international experts in April 2010 to review the available literature relevant to poliovirus immunity and transmission. This expert review evaluates 66 OPV challenge studies and other evidence to support the development of quantitative models of poliovirus transmission and potential outbreaks. This review focuses on characterization of immunity as a function of exposure history in terms of susceptibility to excretion, duration of excretion, and concentration of excreted virus. We also discuss the evidence of waning of host immunity to poliovirus transmission, the relationship between the concentration of poliovirus excreted and infectiousness, the importance of different transmission routes, and the differences in transmissibility between OPV and WPV. We discuss the limitations of the available evidence for use in polio risk models, and conclude that despite the relatively large number of studies on immunity, very limited data exist to directly support quantification of model inputs related to transmission. Given the limitations in the evidence, we identify the need for expert input to derive quantitative model inputs from the existing data.

Review and Assessment of Poliovirus Immunity and Transmission: Synthesis of Knowledge Gaps and Identification of Research Needs

With the intensifying global efforts to eradicate wild polioviruses, policymakers face complex decisions related to achieving eradication and managing posteradication risks. These decisions and the expanding use of inactivated poliovirus vaccine (IPV) trigger renewed interest in poliovirus immunity, particularly the role of mucosal immunity in the transmission of polioviruses. Sustained high population immunity to poliovirus transmission represents a key prerequisite to eradication, but poliovirus immunity and transmission remain poorly understood despite decades of studies. In April 2010, the U.S. Centers for Disease Control and Prevention convened an international group of experts on poliovirus immunology and virology to review the literature relevant for modeling poliovirus transmission, develop a consensus about related uncertainties, and identify research needs. This article synthesizes the quantitative assessments and research needs identified during the process. Limitations in the evidence from oral poliovirus vaccine (OPV) challenge studies and other relevant data led to differences in expert assessments, indicating the need for additional data, particularly in several priority areas for research: (1) the ability of IPV-induced immunity to prevent or reduce excretion and affect transmission, (2) the impact of waning immunity on the probability and extent of poliovirus excretion, (3) the relationship between the concentration of poliovirus excreted and infectiousness to others in different settings, and (4) the relative role of fecal-oral versus oropharyngeal transmission. This assessment of current knowledge supports the immediate conduct of additional studies to address the gaps.

Polio eradication initiative in Africa: influence on other infectious disease surveillance development

BackgroundThe World Health Organization (WHO) and partners are collaborating to eradicate poliomyelitis. To monitor progress, countries perform surveillance for acute flaccid paralysis (AFP). The WHO African Regional Office (WHO-AFRO) and the U.S Centers for Disease Control and Prevention are also involved in strengthening infectious disease surveillance and response in Africa. We assessed whether polio-eradication initiative resources are used in the surveillance for and response to other infectious diseases in Africa.MethodsDuring October 1999-March 2000, we developed and administered a survey questionnaire to at least one key informant from the 38 countries that regularly report on polio activities to WHO. The key informants included WHO-AFRO staff assigned to the countries and Ministry of Health personnel.ResultsWe obtained responses from 32 (84%) of the 38 countries. Thirty-one (97%) of the 32 countries had designated surveillance officers for AFP surveillance, and 25 (78%) used the AFP resources for the surveillance and response to other infectious diseases. In 28 (87%) countries, AFP program staff combined detection for AFP and other infectious diseases. Fourteen countries (44%) had used the AFP laboratory specimen transportation system to transport specimens to confirm other infectious disease outbreaks. The majority of the countries that performed AFP surveillance adequately (i.e., non polio AFP rate = 1/100,000 children aged <15 years) in 1999 had added 1–5 diseases to their AFP surveillance program.ConclusionsDespite concerns regarding the targeted nature of AFP surveillance, it is partially integrated into existing surveillance and response systems in multiple African countries. Resources provided for polio eradication should be used to improve surveillance for and response to other priority infectious diseases in Africa.

Poliomyelitis Eradication: Progress, Challenges for the End Game, and Preparation for the Post-Eradication Era

In 1988, the World Health Assembly resolved to eradicate poliomyelitis globally by the year 2000. Dramatic progress toward this goal has occurred: three of the six WHO regions (Region of the Americas, European Region, and Western Pacific Region) are now polio free; and the number of polio-endemic countries decreased from over 125 in 1988 to 30 in 1999. Intensified efforts currently are underway to reach the target as soon as possible after 2000 in the three remaining polio-endemic WHO regions (African Region, Eastern Mediterranean Region, and South-East Asia Region). Even in polio-endemic regions, many countries are already polio free as the geographic extent of poliovirus shrinks while others. especially those experiencing conflict and war, pose substantial challenges to implementing the proven polio eradication strategies. Increasing attention and research now are devoted to the certification of polio eradication in the polio-free regions (that will include the first phase of implementing the Global Plan of Action for the laboratory containment of wild poliovirus) and formulating a policy for stopping all polio vaccination once eradication, containment, and global certification have been achieved. This report outlines the progress toward polio eradication and highlights some of the remaining issues and challenges that must be addressed before polio becomes a disease that future generations know only by history.

Immunogenicity of Tetanus-Diphtheria Toxoids (Td) among Ukrainian Adults: Implications for Diphtheria Control in the Newly Independent States of the Former Soviet Union

After 30 years of control, epidemic diphtheria returned to the Soviet Union in 1990. To develop control strategies, the immunogenicity of the tetanus and diphtheria toxoids (Td) vaccine was assessed. Workers who were 18-67 years old received two Td immunizations separated by 30 days. A neutralization assay determined diphtheria antitoxin (DAT) on enrollment and on days 7, 30, 60, and 425. On enrollment, 43.0% of 488 workers had DAT <0.1 IU/mL. After one dose, 88.5% had DAT >/=0.1 IU/mL, after two doses, 92.2% had >/=0.1 IU/mL and >90% of participants <30 or >/=50 years of age attained >/=1.0 IU/mL; however, only 78.4% of those who were 30-39 years old and 51.8% of those who were 40-49 years old achieved >/=1.0 IU/mL after two doses. To control the epidemic in Ukraine, one Td dose should be administered to virtually the entire population (persons 30-49 years old require three doses of Td for optimal individual protection and to maximize population immunity).

Evaluation of a Single Dose of Diphtheria-Tetanus Toxoids among Adults in Odessa, Ukraine, 1995: Immunogenicity and Adverse Reactions

Epidemic diphtheria spread to Ukraine in 1991, where it peaked in 1995 with >5,000 reported cases. To refine epidemic control strategies, immunogenicity of a tetanus-diphtheria toxoids vaccine (Td) containing 2 limits of flocculation (Lf) diphtheria toxoid was evaluated. During a mass vaccination campaign, adults at a clinic in Odessa received one dose of Td. At enrollment, 57.2% of 341 study participants had levels of diphtheria antitoxin (DAT) >/=0.1 IU/mL. Thirty and 180 days after receiving one dose of Td, 91.5% and 84.5% of the participants, respectively, had DAT levels >/=0.1 IU/mL. However, among 40- to 49-year-old participants, only 78.8% and 73.8% had DAT levels >/=0.1 IU/mL at 30 and 180 days, respectively. This study suggests that one dose of 2 Lf diphtheria toxoid is highly effective in raising DAT to protective levels in most adults; however, the study also shows that certain age groups, particularly persons 40-49 and, to a lesser degree, 30-39 years old may require additional doses or a complete three-dose primary vaccination series for optimal protection against diphtheria.