Meghana Sreevatsava

Bio: Meghana Sreevatsava is an academic researcher from World Health Organization. The author has contributed to research in topics: Vaccination & Poliovirus. The author has an hindex of 6, co-authored 7 publications receiving 394 citations.

Fractional Doses of Inactivated Poliovirus Vaccine in Oman

Abstract: Background We conducted a clinical trial of fractional doses of inactivated poliovirus vaccine administered to infants in Oman, in order to evaluate strategies for making the vaccine affordable for use in developing countries. Methods We compared fractional doses of inactivated poliovirus vaccine (0.1 ml, representing one fifth of a full dose) given intradermally with the use of a needle-free jet injector device, with full doses of vaccine given intramuscularly, with respect to immunogenicity and reactogenicity. Infants were randomly assigned at birth to receive either a fractional dose or a full dose of inactivated poliovirus vaccine at 2, 4, and 6 months. We also administered a challenge dose of monovalent type 1 oral poliovirus vaccine at 7 months and collected stool samples before and 7 days after administration of the challenge dose. Results A total of 400 infants were randomized, of whom 373 (93.2%) fulfilled the study requirements. No significant baseline differences between the groups were detected. Thirty days after completion of the three-dose schedule, the rates of seroconversion to types 1, 2, and 3 poliovirus were 97.3%, 95.7%, and 97.9%, respectively, in the fractional-dose group, as compared with 100% seroconversion to all serotypes in the full-dose group (P = 0.01 for the comparison with respect to type 2 poliovirus; results with respect to types 1 and 3 poliovirus were not significant). The median titers were significantly lower in the fractional-dose group than in the full-dose group (P<0.001 for all three poliovirus serotypes). At 7 months, 74.8% of the infants in the fractional-dose group and 63.1% of those in full-dose group excreted type 1 poliovirus (P = 0.03). Between birth and 7 months, 42 hospitalizations were reported, all related to infectious causes, anemia, or falls, with no significant difference between vaccination groups. Conclusions These data show that fractional doses of inactivated poliovirus vaccine administered intradermally at 2, 4, and 6 months, as compared with full doses of inactivated poliovirus vaccine given intramuscularly on the same schedule, induce similar levels of seroconversion but significantly lower titers. (Current Controlled Trials number, ISRCTN17418767.)

Monovalent Type 1 Oral Poliovirus Vaccine in Newborns

Abstract: Background In 1988, the World Health Assembly resolved to eradicate poliomyelitis. Although substantial progress toward this goal has been made, eradication remains elusive. In 2004, the World Health Organization called for the development of a potentially more immunogenic monovalent type 1 oral poliovirus vaccine. Methods We conducted a trial in Egypt to compare the immunogenicity of a newly licensed monovalent type 1 oral poliovirus vaccine with that of a trivalent oral poliovirus vaccine. Subjects were randomly assigned to receive one dose of monovalent type 1 oral poliovirus vaccine or trivalent oral poliovirus vaccine at birth. Thirty days after birth, a single challenge dose of monovalent type 1 oral poliovirus vaccine was administered in all subjects. Shedding of serotype 1 poliovirus was assessed through day 60. Results A total of 530 subjects were enrolled, and 421 fulfilled the study requirements. Thirty days after the study vaccines were administered, the rate of seroconversion to type 1 poliov...

Randomized Trial of Type 1 and Type 3 Oral Monovalent Poliovirus Vaccines in Newborns in Africa

Abstract: Background. The Global Polio Eradication Initiative aims to eradicate wild poliovirus by the end of 2012. Therefore, more-immunogenic polio vaccines, including monovalent oral poliovirus vaccines (mOPVs), are needed for supplemental immunization activities. This trial assessed the immunogenicity of monovalent types 1 and 3, compared with that of trivalent oral poliovirus vaccine (tOPV), in South Africa. Methods. We conducted a blinded, randomized, 4-arm controlled trial comparing the immunogenicity of a single dose of mOPV1 (from 2 manufacturers) and mOPV3 (from 1 manufacturer), given at birth, with the immunogenicity of tOPV. Results. Eight hundred newborns were enrolled; 762 (95%) were included in the analysis. At 30 days after vaccine administration, seroconversion to poliovirus type 1 was 73.4% and 76.4% in the 2 mOPV1 arms, compared with 39.1% in the tOPV arm (P , .0000001), and seroconversion to poliovirus type 3 was 58.0% in the mOPV3 arm, compared with 21.2% in the tOPV arm (P , .0000001). The vaccines were well tolerated, and no adverse events were attributed to trial interventions. Conclusion. A dose of mOPV1 or mOPV3 at birth was superior to that of tOPV in inducing type-specific seroconversion in this sub-Saharan African population. Our results support continued use of mOPVs in supplemental immunization activities in countries where poliovirus types 1 or 3 circulate. Clinical Trials Registration. ISRCTN18107202.

From Emergence to Eradication: The Epidemiology of Poliomyelitis Deconstructed

Abstract: Poliomyelitis has appeared in epidemic form, become endemic on a global scale, and been reduced to near-elimination, all within the span of documented medical history. Epidemics of the disease appeared in the late 19th century in many European countries and North America, following which polio became a global disease with annual epidemics. During the period of its epidemicity, 1900-1950, the age distribution of poliomyelitis cases increased gradually. Beginning in 1955, the creation of poliovirus vaccines led to a stepwise reduction in poliomyelitis, culminating in the unpredicted elimination of wild polioviruses in the United States by 1972. Global expansion of polio immunization resulted in a reduction of paralytic disease from an estimated annual prevaccine level of at least 600,000 cases to fewer than 1,000 cases in 2000. Indigenous wild type 2 poliovirus was eradicated in 1999, but unbroken localized circulation of poliovirus types 1 and 3 continues in 4 countries in Asia and Africa. Current challenges to the final eradication of paralytic poliomyelitis include the continued transmission of wild polioviruses in endemic reservoirs, reinfection of polio-free areas, outbreaks due to circulating vaccine-derived polioviruses, and persistent excretion of vaccine-derived poliovirus by a few vaccinees with B-cell immunodeficiencies. Beyond the current efforts to eradicate the last remaining wild polioviruses, global eradication efforts must safely navigate through an unprecedented series of endgame challenges to assure the permanent cessation of all human poliovirus infections.

Polio vaccination: past, present and future.

Abstract: Live attenuated oral polio vaccine (OPV) and inactivated polio vaccine (IPV) are the tools being used to achieve eradication of wild polio virus. Because OPV can rarely cause paralysis and generate revertant polio strains, IPV will have to replace OPV after eradication of wild polio virus is certified to sustain eradication of all polioviruses. However, uncertainties remain related to IPV's ability to induce intestinal immunity in populations where fecal–oral transmission is predominant. Although substantial effectiveness and safety data exist on the use and delivery of OPV and IPV, several new research initiatives are currently underway to fill specific knowledge gaps to inform future vaccination policies that would assure polio is eradicated and eradication is maintained.

Systematic review of mucosal immunity induced by oral and inactivated poliovirus vaccines against virus shedding following oral poliovirus challenge

Abstract: Inactivated poliovirus vaccine (IPV) may be used in mass vaccination campaigns during the final stages of polio eradication. It is also likely to be adopted by many countries following the coordinated global cessation of vaccination with oral poliovirus vaccine (OPV) after eradication. The success of IPV in the control of poliomyelitis outbreaks will depend on the degree of nasopharyngeal and intestinal mucosal immunity induced against poliovirus infection. We performed a systematic review of studies published through May 2011 that recorded the prevalence of poliovirus shedding in stool samples or nasopharyngeal secretions collected 5–30 days after a “challenge” dose of OPV. Studies were combined in a meta-analysis of the odds of shedding among children vaccinated according to IPV, OPV, and combination schedules. We identified 31 studies of shedding in stool and four in nasopharyngeal samples that met the inclusion criteria. Individuals vaccinated with OPV were protected against infection and shedding of poliovirus in stool samples collected after challenge compared with unvaccinated individuals (summary odds ratio [OR] for shedding 0.13 (95% confidence interval [CI] 0.08–0.24)). In contrast, IPV provided no protection against shedding compared with unvaccinated individuals (summary OR 0.81 [95% CI 0.59–1.11]) or when given in addition to OPV, compared with individuals given OPV alone (summary OR 1.14 [95% CI 0.82–1.58]). There were insufficient studies of nasopharyngeal shedding to draw a conclusion. IPV does not induce sufficient intestinal mucosal immunity to reduce the prevalence of fecal poliovirus shedding after challenge, although there was some evidence that it can reduce the quantity of virus shed. The impact of IPV on poliovirus transmission in countries where fecal-oral spread is common is unknown but is likely to be limited compared with OPV.

Intradermal delivery of vaccines: potential benefits and current challenges

Abstract: Delivery of vaccine antigens to the dermis and/or epidermis of human skin (i.e. intradermal delivery) might be more efficient than injection into the muscle or subcutaneous tissue, thereby reducing the volumes of antigen. This is known as dose-sparing and has been demonstrated in clinical trials with some, but not all, vaccines. Dose-sparing could be beneficial to immunization programmes by potentially reducing the costs of purchase, distribution and storage of vaccines; increasing vaccine availability and effectiveness. The data obtained with intradermal delivery of some vaccines are encouraging and warrant further study and development; however significant gaps in knowledge and operational challenges such as reformulation, optimizing vaccine presentation and development of novel devices to aid intradermal vaccine delivery need to be addressed. Modelling of the costs and potential savings resulting from intradermal delivery should be done to provide realistic expectations of the potential benefits and to support cases for investment. Implementation and uptake of intradermal vaccine delivery requires further research and development, which depends upon collaboration between multiple stakeholders in the field of vaccination.

Multiple Independent Emergences of Type 2 Vaccine-Derived Polioviruses during a Large Outbreak in northern Nigeria

Abstract: Since 2005, a large poliomyelitis outbreak associated with type 2 circulating vaccine-derived poliovirus (cVDPV2) has occurred in northern Nigeria, where immunization coverage with trivalent oral poliovirus vaccine (tOPV) has been low. Phylogenetic analysis of P1/capsid region sequences of isolates from each of the 403 cases reported in 2005 to 2011 resolved the outbreak into 23 independent type 2 vaccine-derived poliovirus (VDPV2) emergences, at least 7 of which established circulating lineage groups. Virus from one emergence (lineage group 2005-8; 361 isolates) was estimated to have circulated for over 6 years. The population of the major cVDPV2 lineage group expanded rapidly in early 2009, fell sharply after two tOPV rounds in mid-2009, and gradually expanded again through 2011. The two major determinants of attenuation of the Sabin 2 oral poliovirus vaccine strain (A 481 in the 5′-untranslated region [5′-UTR] and VP1-Ile 143 ) had been replaced in all VDPV2 isolates; most A 481 5′-UTR replacements occurred by recombination with other enteroviruses. cVDPV2 isolates representing different lineage groups had biological properties indistinguishable from those of wild polioviruses, including efficient growth in neuron-derived HEK293 cells, the capacity to cause paralytic disease in both humans and PVR-Tg21 transgenic mice, loss of the temperature-sensitive phenotype, and the capacity for sustained person-to-person transmission. We estimate from the poliomyelitis case count and the paralytic case-to-infection ratio for type 2 wild poliovirus infections that ∼700,000 cVDPV2 infections have occurred during the outbreak. The detection of multiple concurrent cVDPV2 outbreaks in northern Nigeria highlights the risks of cVDPV emergence accompanying tOPV use at low rates of coverage in developing countries.