Jay Wenger

New Strategies for the Elimination of Polio from India

The feasibility of global polio eradication is being questioned as a result of continued transmission in a few localities that act as sources for outbreaks elsewhere. Perhaps the greatest challenge is in India, where transmission has persisted in Uttar Pradesh and Bihar despite high coverage with multiple doses of vaccine. We estimate key parameters governing the seasonal epidemics in these areas and show that high population density and poor sanitation cause persistence by not only facilitating transmission of poliovirus but also severely compromising the efficacy of the trivalent vaccine. We analyze strategies to counteract this and show that switching to monovalent vaccine may finally interrupt virus transmission.

Protective efficacy of a monovalent oral type 1 poliovirus vaccine: a case-control study

BACKGROUNDnA high-potency monovalent oral type 1 poliovirus vaccine (mOPV1) was developed in 2005 to tackle persistent poliovirus transmission in the last remaining infected countries. Our aim was to assess the efficacy of this vaccine in India.nnnMETHODSnWe estimated the efficacy of mOPV1 used in supplementary immunisation activities from 2076 matched case-control pairs of confirmed cases of poliomyelitis caused by type 1 wild poliovirus and cases of non-polio acute flaccid paralysis in India. The effect of the introduction of mOPV1 on population immunity was calculated on the basis of estimates of vaccination coverage from data for non-polio acute flaccid paralysis.nnnFINDINGSnIn areas of persistent poliovirus transmission in Uttar Pradesh, the protective efficacy of mOPV1 was estimated to be 30% (95% CI 19-41) per dose against type 1 paralytic disease, compared with 11% (7-14) for the trivalent oral vaccine. 76-82% of children aged 0-23 months were estimated to be protected by vaccination against type 1 poliovirus at the end of 2006, compared with 59% at the end of 2004, before the introduction of mOPV1.nnnINTERPRETATIONnUnder conditions where the efficacy of live-attenuated oral poliovirus vaccines is compromised by a high prevalence of diarrhoea and other infections, a dose of high-potency mOPV1 is almost three times more effective against type 1 poliomyelitis disease than is trivalent vaccine. Achieving high coverage with this new vaccine in areas of persistent poliovirus transmission should substantially improve the probability of rapidly eliminating transmission of the disease.

Introduction of Hib conjugate vaccines in the non-industrialized world: experience in four 'newly adopting' countries.

Hib conjugate vaccines are widely used in the industrialized world, but are just now beginning to be introduced into other countries. To identify factors facilitating rapid global introduction, we evaluated the decision-making process, mode of introduction, effectiveness, and impact on the immunization program of Hib conjugate vaccine introduction in four non- industrialized countries through site visits and use of a standardized questionnaire. The key promoters of Hib introduction were the pediatric community and ministries of health. Local surveillance and severity data were critical in the decision to adopt Hib vaccine. Assistance with surveillance, introduction guidelines, educational material, tenders, and funding is needed to accelerate wider adoption.

Mucosal Immunity after Vaccination with Monovalent and Trivalent Oral Poliovirus Vaccine in India

BACKGROUNDnPersistent wild-poliovirus transmission, particularly in India, has raised questions about the degree of mucosal immunity induced by oral poliovirus vaccine (OPV) in tropical countries.nnnMETHODSnExcretion of vaccine poliovirus after challenge with OPV was measured in stool samples collected from children identified by the acute flaccid paralysis surveillance program in India during 2005-2007. The effectiveness of trivalent and monovalent OPV against excretion of each poliovirus type was estimated.nnnRESULTSnVaccine poliovirus was isolated from 4994 (5.2%) of 96,641 children with 2 stool samples. The relative odds of excreting challenge poliovirus among children with 5 reported previous doses of trivalent OPV compared with 0 previous doses was 0.24 (95% confidence interval [CI], 0.12-0.45), 0.08 (95% CI, 0.04-0.14), and 0.40 (95% CI, 0.19-0.85) for serotypes 1, 2, and 3, respectively, but the relative odds increased to 0.62 (95% CI, 0.44-0.88), 0.44 (95% CI, 0.20-0.99), and 0.66 (95% CI, 0.41-1.06), respectively, in the northern states of Uttar Pradesh and Bihar. In these 2 states, the relative odds of excretion of serotype 1 was 0.32 (95% CI, 0.26-0.41) after 5 doses of type 1 monovalent OPV.nnnCONCLUSIONSnThe mucosal immunity induced by OPV in India varies by location, serotype, and vaccine formulation. These findings have implications for global eradication and the potential role played by inactivated vaccine in this setting.

Rapid Assessment Tool for Haemophilus influenzae type b Disease in Developing Countries

Haemophilus influenzae type b disease prevalence in children provides estimates of national disease prevalence.

Early detection and response to meningococcal disease epidemics in sub-Saharan Africa: appraisal of the WHO strategy

OBJECTIVEnTo assess the sensitivity, specificity and predictive value positive of the WHO threshold strategy for detecting meningococcal disease epidemics in sub-Saharan Africa and to estimate the impact of the strategy on an epidemic at district level.nnnMETHODSnData on meningitis cases at the district level were collected weekly from health ministries, WHO country and regional offices, and nongovernmental organizations in countries where there were epidemics of meningococcal disease in 1997. An epidemic was defined as a cumulative district attack rate of at least 100 cases per 100,000 population from January to May, the period of epidemic risk. The sensitivity, specificity and predictive value positive of the WHO threshold rate were calculated, and curves of sensitivity against (1 - specificity) were compared with alternatively defined threshold rates and epidemic sizes. The impact of the WHO strategy on a district epidemic was estimated by comparing the numbers of epidemic cases with cases estimated to have been prevented by vaccination.nnnFINDINGSnAn analysis was made of 48 198 cases reported in 174 districts in Benin, Burkina Faso, the Gambia, Ghana, Mali, Niger, and Togo. These cases were 80.3% of those reported from Africa to WHO during the 1997 epidemic period. District populations ranged from 10,298 to 573,908. The threshold rate was crossed during two consecutive weeks in 69 districts (39.7%) and there were epidemics in 66 districts (37.9%). Overall, the sensitivity of the threshold rate for predicting epidemics was 97%, the specificity was 95%, and the predictive value positive was 93%. Taken together, these values were equivalent or better than the sensitivity, specificity and predictive value positive of alternatively defined threshold rates and epidemics, and remained high regardless of district size. The estimated number of potential epidemic cases decreased by nearly 60% in the age group targeted for vaccination in one district where the guidelines were followed in a timely manner.nnnCONCLUSIONnThe use of the WHO strategy was sensitive and specific for the early detection of meningococcal disease epidemics in countries of sub-Saharan Africa during 1997 and had a substantial impact on a district epidemic. Nevertheless, the burden of meningococcal disease in these countries remains formidable and additional control measures are needed.

Vaccines for the developing world: current status and future directions.

Developing country infectious disease problems differ substantially from those in the industrialized world, and a major effort must be made to devote necessary resources to development of vaccines for the bulk of human infectious disease suffering. At the same time, the political will must be mobilized, at international and national levels, to obtain the financial support and backing to provide these vaccines for children. Finally, efforts must be made to take advantage of new technologies now being developed which address many of the logistic and programmatic challenges faced by developing country immunization programme delivery systems.

Estimating the Haemophilus influenzae type b (Hib) disease burden and the impact of Hib vaccine in Fiji.

AIMSnTo estimate Haemophilus influenzae type b (Hib) disease burden in Fiji in children under the age of 5 years (under-5s) prior to vaccine introduction. To compare estimates from WHOs Hib rapid assessment tool (RAT), with that from decline in disease after vaccine introduction.nnnMETHODSnLaboratory data (meningitis), hospitalization and mortality data (pneumonia and meningitis) before and after Hib vaccine introduction were collected. The RAT protocol provides two independent estimates of pre-vaccine disease burden (one based on meningitis incidence laboratory data and the other based on mortality statistics). A third estimate uses the decline in disease following vaccine introduction.nnnRESULTSnThe decline in meningitis hospitalizations implies a pre-vaccine Hib meningitis incidence of 66 per 100,000 in under-5s. This compares with a pre-vaccine RAT estimate of Hib meningitis incidence of 84 per 100,000 (for 1992-1993). The RAT estimated the total annual pre-vaccine Hib burden (meningitis plus pneumonia) at 476 cases and 36 deaths per year (meningitis incidence method) and 70 cases and 5 deaths (child mortality method). Hib vaccine led to declines of 32% (95% confidence interval (CI)=11-48%), and 78% (95% CI=22-94%) for all under-5s meningitis hospitalizations and deaths, respectively. There was no similar consistent decline in pneumonia hospitalizations or deaths after vaccine introduction, except for a statistically significant reduction in pneumonia mortality in children aged under 1 year.nnnCONCLUSIONSnHib disease constitutes an important burden on the health of Pacific children that can be rapidly reduced with Hib vaccine. In this setting, routine morbidity statistics (comparing pre-and post-vaccine) provided an estimate of Hib meningitis burden which is broadly similar to that of the Hib RAT, suggesting that both might be valid ways to estimate Hib meningitis incidence. However, Hib pneumonia burden could not be estimated from routine statistics.

Epidemiology of meningitis due to Haemophilus influenzae type b in children in Bulgaria: a prospective, population-based surveillance study

OBJECTIVEnTo assess the incidence of meningitis caused by Haemophilus influenzae type b (Hib) among children in Bulgaria and to provide evidence for an informed decision on the use of Hib vaccines in Bulgaria.nnnMETHODSnFrom 1 July 1997 to 31 December 1999, active surveillance for meningitis was conducted in six regions. For children with suspected meningitis, a cerebrospinal fluid (CSF) specimen was sent for cytology, chemistry, latex agglutination testing, culture and sensitivity.nnnFINDINGSnDuring the 2.5-year study period, surveillance was conducted among 138 249 children aged <5 years - a sample representing 40% of all Bulgarian children in this age group. Overall, 285 children with suspected meningitis were identified. In eight children, clinical symptoms of meningitis resolved rapidly before a CSF specimen could be obtained. Of the remaining 277 children, 121 (44%) were classified as having probable bacterial meningitis on the basis of a CSF examination. An organism was identified for 88 (73%) of the 121 cases with probable bacterial meningitis. There were 21 cases of Hib, giving a mean annual incidence of 6.1 Hib meningitis cases per 100 000 children <5 years; the case-fatality rate was 10%. Nearly 60% of Hib isolates were resistant to one or more antibiotics, but they were not resistant to third-generation cephalosporins.nnnCONCLUSIONnOn the basis of these findings, Hib conjugate vaccines have been included in the list of vaccines recommended for children by the Bulgarian Ministry of Health. The recommended initial treatment for paediatric bacterial meningitis has been changed to third-generation cephalosporins.

Improving polio vaccination during supplementary campaigns at areas of mass transit in India.

BackgroundIn India, children who are traveling during mass immunization campaigns for polio represent a substantial component of the total target population. These children are not easily accessible to health workers and may thus not receive vaccine. Vaccination activities at mass transit sites (such as major intersections, bus depots and train stations), can increase the proportion of children vaccinated but the effectiveness of these activities, and factors associated with their success, have not been rigorously evaluated.MethodsWe assessed data from polio vaccination activities in Jyotiba Phule Nagar district, Uttar Pradesh, India, conducted in June 2006. We used trends in the vaccination results from the June activities to plan the timing, locations, and human resource requirements for transit vaccination activities in two out of the seven blocks in the district for the July 2006 supplementary immunization activity (SIA). In July, similar data was collected and for the first time vaccination teams also recorded the proportion of children encountered each day who were vaccinated (a new monitoring system).ResultsIn June, out of the 360,937 total children vaccinated, 34,643 (9.6%) received vaccinations at mass transit sites. In the July SIA, after implementation of a number of changes based on the June monitoring data, 36,475 children were vaccinated at transit sites (a 5.3% increase). Transit site vaccinations in July increased in the two intervention blocks from 18,194 to 21,588 (18.7%) and decreased from 16,449 to 14,887 (9.5%) in the five other blocks. The new monitoring system showed the proportion of unvaccinated children at street intersection transit sites in the July campaign decreased from 24% (1,784/7,405) at the start of the campaign to 3% (143/5,057) by the end of the SIA, consistent with findings from the more labor-intensive post-vaccination coverage surveys routinely performed by the program.ConclusionsAnalysis of vaccination data from transit sites can inform program management changes leading to improved outcomes in polio immunization campaigns. The number of vaccinated children encountered should be routinely recorded by transit teams and may provide a useful, inexpensive alternative mechanism to assess program coverage.