Identification of serologic markers for school-aged children with congenital rubella syndrone

BACKGROUND: Congenital rubella syndrome (CRS) case identification is challenging in older children since laboratory markers of congenital rubella virus (RUBV) infection do not persist beyond age 12 months. METHODS: We enrolled children with CRS born between 1998 and 2003 and compared their immune responses to RUBV with those of their mothers and a group of similarly aged children without CRS. Demographic data and sera were collected. Sera were tested for anti-RUBV immunoglobulin G (IgG), IgG avidity, and IgG response to the 3 viral structural proteins (E1, E2, and C), reflected by immunoblot fluorescent signals. RESULTS: We enrolled 32 children with CRS, 31 mothers, and 62 children without CRS. The immunoblot signal strength to C and the ratio of the C signal to the RUBV-specific IgG concentration were higher (P < .029 for both) and the ratio of the E1 signal to the RUBV-specific IgG concentration lower (P = .001) in children with CRS, compared with their mothers. Compared with children without CRS, children with CRS had more RUBV-specific IgG (P < .001), a stronger C signal (P < .001), and a stronger E2 signal (P ≤ .001). Two classification rules for children with versus children without CRS gave 100% specificity with >65% sensitivity. CONCLUSIONS: This study was the first to establish classification rules for identifying CRS in school-aged children, using laboratory biomarkers. These biomarkers should allow improved burden of disease estimates and monitoring of CRS control programs. Published by Oxford University Press on behalf of the Infectious Diseases Society of America 2014. This work is written by (a) US Government employee(s) and is in the public domain in the US.

Establishing a regional network of academic centers to support decision making for new vaccine introduction in Latin America and the Caribbean: the ProVac experience.

BACKGROUND: The Pan American Health Organization's ProVac Initiative, designed to strengthen national decision making regarding the introduction of new vaccines, was initiated in 2004. Central to realizing ProVac's vision of regional capacity building, the ProVac Network of Centers of Excellence (CoEs) was established in 2010 to provide research support to the ProVac Initiative, leveraging existing capacity at Latin American and Caribbean (LAC) universities. We describe the process of establishing the ProVac Network of CoEs and its initial outcomes and challenges. METHODS: A survey was sent to academic, not-for-profit institutions in LAC that had recently published work in the areas of clinical decision sciences and health economic analysis. Centers invited to join the Network were selected by an international committee on the basis of the survey results. Selection criteria included academic productivity in immunization-related work, team size and expertise, successful collaboration with governmental agencies and international organizations, and experience in training and education. The Network currently includes five academic institutions across LAC. RESULTS: Through open dialog and negotiation, specific projects were assigned to centers according to their areas of expertise. Collaboration among centers was highly encouraged. Faculty from ProVac's technical partners were assigned as focal points for each project. The resulting work led to the development and piloting of tools, methodological guides, and training materials that support countries in assessing existing evidence and generating new evidence on vaccine introduction. The evidence generated is shared with country-level decision makers and the scientific community. CONCLUSIONS: As the ProVac Initiative expands to other regions of the world with support from immunization and public health partners, the establishment of other regional and global networks of CoEs will be critical. The experience of LAC in creating the current network could benefit the formation of similar structures that support evidence-based decisions regarding new public health interventions.

Has the time come to control hepatitis A globally? Matching prevention to the changing epidemiology.

For the first time a global meeting on hepatitis A virus (HAV) infection as vaccine preventable disease was organized at the end of 2007. More than 200 experts from 46 countries gathered to investigate the changing global HAV epidemiology reflecting the increasing numbers of persons at risk for severe clinical disease and mortality from HAV infection. The benefits of childhood and adult hepatitis A (HepA) vaccination strategies and the data needed by individual countries and international health organizations to assess current HepA prevention strategies were discussed. New approaches in preventing HAV infection including universal HepA vaccination were considered. This introductory paper summarizes the major findings of the meeting and describes the changing epidemiology of HAV infections and the impact of HepA vaccination strategies in various countries. Implementation of HepA vaccination strategies should take into account the level of endemicity, the level of the socio-economic development and sanitation, and the risk of outbreaks. A stepwise strategy for introduction of HepA universal immunisation of children was recommended. This strategy should be based on accurate surveillance of cases and qualitative documentation of outbreaks and their control, secure political support on the basis of high-quality results, and comprehensive cost-effectiveness studies. The recognition of the need for increased global attention towards HepA prevention is an important outcome of this meeting.

A new paradigm for international disease control: lessons learned from polio eradication in Southeast Asia.

OBJECTIVES: This study evaluated the impact of international coordination on polio eradication in Southeast Asia. METHODS: Active surveillance systems for acute flaccid paralysis were assessed. Analyses focused on surveillance proficiency and polio incidence. RESULTS: Ten countries coordinated activities. Importations occurred and were rapidly contained in China and Myanmar. Countries that have been free of indigenous polio transmission for at least 3 years include Sri Lanka, Indonesia, Myanmar, and Thailand. In the remaining endemic countries--India, Nepal, and Bangladesh--poliovirus transmission has been substantially reduced; however, these countries still harbor the world's largest polio reservoir. CONCLUSIONS: Unprecedented international coordination in Southeast Asia resulted in dramatic progress in polio eradication and serves as a paradigm for control of other infectious diseases such as malaria and tuberculosis.

Surveillance for polio eradication: current status and lessons learnt--India, 1999.

With the launch of the Universal Immunisation Programme in India in 1985, childhood immunisation was provided to children in all districts of the country in a phased manner by 1990. Surveillance for vaccine preventable diseases (VPD) including polio was started at the same time with monthly reporting from the districts to the Ministry of Health and Family Welfare (MOHFW), Government of India (GOI). In 1995, the Pulse Polio Immunisation (PPI) campaign was launched with the objective of polio eradication. Prior to 1997, surveillance for polio was directed at finding clinical polio cases by passive reporting from health facilities. There was no active surveillance for all cases of acute flaccid paralysis (AFP). In 1996, a scheme for the surveillance of AFP was drawn up. With the support of the Danish and US governments and Rotary International, 59 surveillance medical officers (SMOs) were hired, trained, and posted throughout the country in October 1997 to establish active surveillance of AFP. The number of SMOs was increased to 108 in August 1999. The SMOs along with their government counterparts established 10,069 reporting units nationwide by the end of November 1999 reporting weekly the occurrence of AFP cases to the district, state, and national levels; timely case investigation and collection of stool specimens from AFP cases; linkages to support the polio laboratory network; and extensive training of government counterparts. Data reported to the national level is analysed and put on an internet website which is updated every two weeks. Annualised rates of reported non-polio AFP have increased from 0.22 per 100,000 children aged < 15 years in 1997 to 1.57 in 1999. The number of polio cases associated with isolation of wild poliovirus decreased from 1404 in the third trimester of 1998 to 664 in the third trimester of 1999, yet widespread transmission of wild polioviruses persists throughout the country.

Poliomyelitis surveillance: the model used in India for polio eradication.

Poliomyelitis surveillance in India previously involved the passive reporting of clinically suspected cases. The capacity for detecting the disease was limited because there was no surveillance of acute flaccid paralysis (AFP). In October 1997, 59 specially trained Surveillance Medical Officers were deployed throughout the country to establish active AFP surveillance; 11,533 units were created to report weekly on the occurrence of AFP cases at the district, state and national levels; timely case investigation and the collection of stool specimens from AFP cases was undertaken; linkages were made to support the polio laboratory network; and extensive training of government counterparts of the Surveillance Medical Officers was conducted. Data reported at the national level are analysed and distributed weekly. Annualized rates of non-polio AFP increased from 0.22 per 100,000 children aged under 15 years in 1997 to 1.39 per 100,000 in 1999. The proportion of cases with two adequate stools collected within two weeks of the onset of paralysis increased from 34% in 1997 to 68% in 1999. The number of polio cases associated with the isolation of wild poliovirus decreased from 211 in the first quarter of 1998 to 77 in the first quarter of 1999. Widespread transmission of wild poliovirus types 1 and 3 persists throughout the country; type 2 occurs only in Bihar and Uttar Pradesh. In order to achieve polio eradication in India during 2000, extra national immunization days and house-to-house mopping-up rounds should be organized.

Eradication of wild poliovirus from the Americas: acute flaccid paralysis surveillance, 1988-1995.

In May 1985, the Pan American Health Organization proposed the goal of interruption of wild poliovirus transmission in the Western Hemisphere. An important component of the polio eradication strategy was conducting surveillance for cases of acute flaccid paralysis. Reported cases were thoroughly investigated, including the collection of stool samples for testing for the presence of wild poliovirus. The last patient with poliomyelitis due to wild poliovirus in the Americas had onset of paralysis on 23 August 1991 in Peru. Since then, >9000 cases of acute flaccid paralysis have been reported and thoroughly investigated; none has been confirmed as paralytic poliomyelitis due to wild poliovirus. On 29 September 1994, the International Commission for the Certification of Poliomyelitis Eradication declared the Americas to be polio-free.

Polio eradication in the World Health Organization South-East Asia Region by the year 2000: midway assessment of progress and future challenges.

In the South-East Asia Region (SEAR) of WHO, paralytic poliomyelitis has decreased from 25,711 cases in 1988 to 3304 cases in 1995, representing an 87% reduction. By 1995, in 6 of 10 member countries--India, Bangladesh, Myanmar, Nepal, Indonesia, and Democratic People's Republic of Korea--polio remained endemic. Two countries, Sri Lanka and Thailand, appear close to polio eradication, and 2, Bhutan and Maldives, reported no cases during 1989-1995. Although reported rates of acute flaccid paralysis and the percentage of cases virologically investigated are low in some countries, no isolates of wild poliovirus type 2 have been reported outside India since 1993. By the end of 1996, all 8 countries in which polio is endemic will have conducted national immunization days for polio eradication. The major challenge for polio eradication in SEAR will be strengthening surveillance, because national immunization days alone cannot eradicate polio.

Evaluation of mass pulse immunization with oral polio vaccine in Delhi: is pre-registration of children necessary?

Delhi was the fourth State in India to conduct mass immunization of children (Pulse Polio Immunization) of the < 3 year age group with Oral Polio Vaccine (OPV) as a strategy towards the eradication of poliomyelitis. This study attempted to evaluate the immunization coverage achieved and the channels of communication which were effective in increasing coverage in three high risk areas of Delhi during October 1994. The overall immunization coverage was 89%. Information sources like enumeration visits, posters, television, radio and schools statistically correlated with the Pulse Polio Immunization (PPI) outcome. However, the cost of enumeration was high. Other less expensive channels of communication appeared to be equally effective. Only 11% of the children surveyed were not immunized with PPI OPV. The major reasons why some children did not receive OPV was that parents were "not informed" or they were "too busy".

Risk of vaccine-associated paralytic poliomyelitis in Latin America, 1989-91.

A major factor influencing the success of poliomyelitis eradication in the Americas was the reliance on mass immunization campaigns with oral poliovirus vaccine (OPV). As global poliomyelitis eradication activities accelerate and campaign vaccine delivery strategies are applied elsewhere, it is critical to determine whether the risk of vaccine-associated paralytic poliomyelitis (VAPP) is altered when routine delivery strategies are supplemented with mass immunization campaigns. We analysed all 6043 cases of acute flaccid paralysis (AFP) reported in Latin America over the period 1989-91 in order to estimate the risk of VAPP. The overall risk was estimated to be one case per 1.5-2.2 million doses of OPV administered, compared with one case per 1.4 million doses administered in England and Wales (1985-91) and with one case per 2.5 million net doses distributed in the USA (1980-89). These data suggest that to eradicate poliomyelitis globally, strategies that rely on mass immunization campaigns to supplement routine delivery services, as recommended by WHO, do not appear to alter significantly the risk of VAPP.

PIP: Mass immunization campaigns with oral poliovirus vaccine (OPV) played a major role in eradicating poliomyelitis in the Americas. The authors analyzed all 6043 cases of acute flaccid paralysis (AFP) reported in Latin America during 1989-91 to estimate the risk of vaccine-associated paralytic poliomyelitis (VAPP). The overall risk was estimated to be one case per 1.5-2.2 million doses of OPV administered, compared with one case per 1.4 million doses administered in England and Wales during 1985-91 and with one case per 2.5 million net doses distributed in the US over 1980-89. The data suggest that strategies which rely upon mass immunization campaigns to supplement routine delivery services, as recommended by the World Health Organization to eradicate poliomyelitis globally, do not significantly change the risk of VAPP.

Lessons from Cuba: mass campaign administration of trivalent oral poliovirus vaccine and seroprevalence of poliovirus neutralizing antibodies.

The immunogenicity of trivalent oral poliovirus vaccine (TOPV), which is less effective in tropical than in temperate areas, may potentially be improved in several ways, including increasing the number of doses. Little information is available on TOPV when more than 6 doses are given. The situation in Cuba provides a unique opportunity to relate the seroprevalence of neutralizing antibodies to the dose of TOPV because Cuba has not reported culture-confirmed poliomyelitis since 1973 and TOPV is only administered in twice yearly 1-week mass immunization campaigns. Sera from 2000 children nationwide were studied for neutralizing antibody among children who received 0, 2, 4, 6 and 8 doses of TOPV. These doses were administered in the period 1989-91, when TOPV (from the USSR) was being used with 500,000, 200,000, and 300,000 median tissue-culture-infecting doses (TCID50) for types 1, 2 and 3, respectively--the 5:2:3 formulation. Seroprevalence of neutralizing antibody after two TOPV doses was 91.5% for type 1, 90.8% for type 2, and 45.9% for type 3. Seroprevalence of type-3 neutralizing antibody after 6 doses remained low (73.4%), but increased to 83.5% after 8 doses (P < 0.05). Although 16.5% of the children remained unprotected for type-3 infection even after 8 doses, mass campaign immunization strategies were sufficient to eradicate the transmission of wild poliovirus in Cuba. Because the seroprevalence of type-1 neutralizing antibody was high (91.5%) after two campaign doses, additional studies using different formulations are needed to determine whether simultaneous improvement in the type-3 response to two campaign doses can be achieved.

PIP: During December 1991-January 1992 in Cuba, health workers took blood samples from a nationwide sample of 2000 children aged 0-3 who received 0, 2, 4, 6, and 8 doses of trivalent oral poliovirus vaccine (TOPV) to determine the seroprevalence of poliovirus neutralizing antibodies for types 1, 2, and 3. Specifically, researchers wanted to learn whether TOPV becomes more effective as the number of doses increases. Since 1973, Cuba has conducted two mass immunization campaigns each year in February and April. During 1970-91, Cuba used a USSR-produced poliovirus vaccine that had 500,000, 200,000, and 300,000 median tissue-culture-infecting doses for types 1, 2, and 3, respectively. Wild poliovirus has not been transmitted in Cuba since 1973 (as of August 1993), indicating that the mass immunization campaigns without routine vaccine delivery have eradicated poliomyelitis in Cuba. The seroprevalence of poliovirus neutralizing antibodies for type 1 increased significantly between 2 and 4 doses (91.5% vs. 96.5%; p = 0.05), thereafter the increases were small and insignificant. The seroprevalence of poliovirus neutralizing antibodies for type 2 increased significantly between 2 and 4 doses (90.8% vs. 97.2%), with small insignificant increases thereafter. Two doses of TOPV induced a response against poliovirus type 3 in only 45.9% of cases. At 4 doses and 8 doses, it did increase significantly from the previous dose (71.2% and 83.5%, respectively; p 0.05). Further studies using other vaccine formulations would allow persons involved in global eradication efforts to determine whether two campaign doses can improve the immunogenicity of the type 3 poliovirus while also improving that of the type 1 poliovirus.

Direct detection of wild poliovirus circulation by stool surveys of healthy children and analysis of community wastewater.

Cartagena, Colombia, was one of the last cities in the Americas known to have endemic poliomyelitis. After 3 cases were identified in 1991, two approaches for detecting continued silent transmission of wild polioviruses within a high-risk community were used: stool surveys of healthy children and virologic analysis of community sewage. Wild type 1 polioviruses were isolated from 8% of the children studied and from 21% of sewage samples. The proportions of wild polioviruses, vaccine-related polioviruses, and nonpolio enteric viruses were similar for both approaches. Wild poliovirus sequences were also amplified directly from processed sewage samples by the polymerase chain reaction using primer pairs specific for the indigenous type 1 genotype. The last reported cases associated with wild polioviruses in the Americas occurred in Colombia (8 April 1991) and Peru (23 August 1991). Direct sampling for wild polioviruses in high-risk communities can provide further evidence that eradication of the indigenous wild polioviruses has been achieved in the Americas.

Strategies for poliomyelitis eradication in developing countries.

Oral polio vaccine (OPV) delivered only through routine services does not appear to interrupt wild virus transmission in the developing countries. The experience in the Americas, which despite intensive surveillance has not confirmed any cases of paralytic poliomyelitis due to wild poliovirus since 23 August 1991, has shown the necessity of delivery of additional doses of OPV through mass campaigns targeted at all children under five years of age regardless of their previous immunization status and in special mop-up operations targeted at this same age group in areas categorized as at high risk of virus transmission, such as those that harbored the virus in the recent past. High-risk areas were determined by empirical observations, which were subsequently confirmed by molecular epidemiology which indicated the presence of several "reservoirs" that helped maintain transmission over several years. During mop-ups, OPV is delivered house by house. This paper discusses the rationale for the utilization of these strategies and outlines the phases for their preparation and evaluation, with illustrations from recent experiences with the last cases of paralytic poliomyelitis in the Americas.

Patient-care directives and infection control: the potential conflict of interest during epidemics in long-term care facilities.

Patient-care directives in long-term care facilities ensure that the aggressiveness of diagnostic and therapeutic interventions accurately reflects the desires of the patient. The results of our investigation of two outbreaks of fatal respiratory illness in long-term care facilities illustrate how patient-care directives may have delayed response to the outbreaks. Despite a cluster of deaths in each facility, staff delayed collection of laboratory specimens until patients with no directives restricting the medical workup became ill. Directives focus on the needs of the individual patient and family, but when an outbreak occurs, they may conflict with community needs. The challenge for the infection control practitioner is to recognize when community needs outweigh individual desires so that appropriate laboratory investigations can identify the cause of the illness.