ABSTRACT
BACKGROUND: The final endgame strategy of global polio eradication initiative includes switching from trivalent oral poliovirus vaccines (tOPV) to bivalent oral polio vaccine (bOPV), and introduction of inactivated poliovirus vaccine (IPV). This study compares IPV with tOPV week 39 boost in Indian infants. METHODS: Starting 28 March 2012, we enrolled 372 Indian infant-mother pairs from Kolkata, India in an open-label, block-randomized, controlled trial comparing a 39 week tOPV to an IPV boost among infants immunized with three doses of tOPV. The primary outcome was mucosal immunity to poliovirus as measured by fecal polio virus shedding after OPV challenge. The secondary outcome was humoral response as defined by >1:8 titers for neutralizing antibodies at week 40. Seroconversion was measured by change in level of antibody titers from week 18 to week 40. The analyses were performed by both intention-to-treat (ITT) and per-protocol (PP) comparing the occurrences of outcomes between the arms of the study. FINDINGS: Both the study arms provided equivalent mucosal immunity at 52 weeks with a total shedding prevalence of 28%. Vaccination with IPV resulted in significantly higher seroconversion rates for Polio type 2 (p = 0.03) and Polio type 3 (p < 0.01). CONCLUSIONS: This study indicates that an IPV boost at week 39 is equivalent to tOPV in intestinal immunity, and provides higher seroconversion compared to tOPV. The major limitation of the study was the additional OPV doses receive by infants during pulse polio immunization resulted in additional mucosal boosting, diminishing the impact of IPV or tOPV boost at week 39. However, IPV for OPV boost should prove to be a step forward in the global polio eradication initiative to reduce the problem of circulating vaccine-derived poliovirus (cVDPV).
ABSTRACT
Enteroviruses cause a variety of illnesses of the gastrointestinal tract, central nervous system and cardiovascular system. Phylogenetic analysis of VP1 sequences has identified 106 different human enteroviruses classified into four enterovirus species within the genus Enterovirus of the family Picornaviridae. It is likely that not all enterovirus types have been discovered. Between September 2013 and October 2014, stool samples of 6274 apparently healthy children of up to 5 years of age residing in Gorakhpur district, Uttar Pradesh, India were screened for enteroviruses. Virus isolates obtained in RD and Hep-2c cells were identified by complete VP1 sequencing. Enteroviruses were isolated from 3042 samples. A total of 87 different enterovirus types were identified. Two isolates with 71 and 74 % nucleotide sequence similarity to all other known enteroviruses were recognized as novel types. In this paper we report identification and complete genome sequence analysis of these two isolates classified as EV-A114 and EV-A121.
Subject(s)
Enterovirus A, Human/classification , Enterovirus A, Human/genetics , Enterovirus Infections/virology , Genome, Viral , Child, Preschool , Enterovirus A, Human/isolation & purification , Enterovirus B, Human , Enterovirus Infections/epidemiology , Feces/virology , Female , Humans , India/epidemiology , Infant , Male , Phylogeny , RNA, Viral , Sequence Alignment , Sequence Analysis, DNA , Species Specificity , Viral Structural Proteins/geneticsABSTRACT
BACKGROUND & OBJECTIVES: It is important to understand the role of cell surface receptors in susceptibility to infectious diseases. CD155 a member of the immunoglobulin super family, serves as the poliovirus receptor (PVR). Heterozygous (Ala67Thr) polymorphism in CD155 has been suggested as a risk factor for paralytic outcome of poliovirus infection. The present study pertains to the development of a screening test to detect the single nucleotide (SNP) polymorphism in the CD155 gene. METHODS: New primers were designed for PCR, sequencing and SNP analysis of Exon2 of CD155 gene. DNAs extracted from either whole blood (n=75) or cells from oral cavity (n=75) were used for standardization and validation of the SNP assay. DNA sequencing was used as the gold standard method. RESULTS: A new SNP assay for detection of heterozygous Ala67Thr genotype was developed and validated by testing 150 DNA samples. Heterozygous CD155 was detected in 27.33 per cent (41/150) of DNA samples tested by both SNP detection assay and sequencing. INTERPRETATION & CONCLUSIONS: The SNP detection assay was successfully developed for identification of Ala67Thr polymorphism in human PVR/CD155 gene. The SNP assay will be useful for large scale screening of DNA samples.
Subject(s)
Poliomyelitis/genetics , Poliovirus/genetics , Receptors, Virus/genetics , Sequence Analysis, DNA/methods , Genotype , Heterozygote , Humans , Poliomyelitis/diagnosis , Polymorphism, Single Nucleotide , Receptors, Virus/isolation & purificationABSTRACT
BACKGROUND: The "gold standard" for assessing mucosal immunity after vaccination with poliovirus vaccines consists in measuring virus excretion in stool after challenge with oral poliovirus vaccine (OPV). This testing is time and resource intensive, and development of alternative methods is a priority for accelerating polio eradication. We therefore evaluated circulating antibody-secreting cells (ASCs) as a potential means to evaluate mucosal immunity to poliovirus vaccine. METHODS: 199 subjects, aged 10 years, and previously immunized repeatedly with OPV, were selected. Subjects were assigned to receive either a booster dose of inactivated poliovirus vaccine (IPV), bivalent OPV (bOPV), or no vaccine. Using a micro-modified whole blood-based ELISPOT assay designed for field setting, circulating poliovirus type-specific IgA- and IgG-ASCs, including gut homing α4ß7+ ASCs, were enumerated on days 0 and 7 after booster immunization. In addition, serum samples collected on days 0, 28 and 56 were tested for neutralizing antibody titers against poliovirus types 1, 2, and 3. Stool specimens were collected on day 28 (day of bOPV challenge), and on days 31, 35 and 42 and processed for poliovirus isolation. RESULTS: An IPV dose elicited blood IgA- and IgG-ASC responses in 84.8 to 94.9% of subjects, respectively. In comparison, a bOPV dose evoked corresponding blood ASC responses in 20.0 to 48.6% of subjects. A significant association was found between IgA- and IgG-ASC responses and serum neutralizing antibody titers for poliovirus type 1, 2, 3 (p<0.001). In the IPV group, α4ß7+ ASCs accounted for a substantial proportion of IgA-ASCs and the proportion of subjects with a positive α4ß7+ IgA-ASC response to poliovirus types 1, 2 and 3 was 62.7%, 89.8% and 45.8%, respectively. A significant association was observed between virus excretion and α4ß7+ IgA- and/or IgG-ASC responses to poliovirus type 3 among immunized children; however, only a weak association was found for type 1 poliovirus. DISCUSSION: Our results suggest that virus-specific blood ASCs, especially for type 3 poliovirus, can serve as surrogate of mucosal immunity after vaccination. Further studies are needed to evaluate the duration of such memory responses and to assess the programmatic utility of this whole blood-based mucosal ASC testing for the polio eradication program.
Subject(s)
Antibodies, Viral/immunology , Antibody-Producing Cells/immunology , B-Lymphocytes/immunology , Immunity, Mucosal/immunology , Poliovirus/immunology , Antibodies, Neutralizing/blood , Antibodies, Neutralizing/immunology , Antibodies, Viral/blood , Antibody-Producing Cells/metabolism , B-Lymphocytes/metabolism , Child , Child, Preschool , Feces/virology , Humans , Immunization, Secondary , Immunoglobulin A/blood , Immunoglobulin A/immunology , Immunoglobulin G/blood , Immunoglobulin G/immunology , Infant , Outcome Assessment, Health Care/methods , Poliomyelitis/immunology , Poliomyelitis/prevention & control , Poliomyelitis/virology , Poliovirus/classification , Poliovirus Vaccine, Inactivated/administration & dosage , Poliovirus Vaccine, Inactivated/immunology , Poliovirus Vaccine, Oral/administration & dosage , Poliovirus Vaccine, Oral/immunology , Prognosis , Reproducibility of Results , VaccinationABSTRACT
BACKGROUND & OBJECTIVES: The poliovirus serotype identification and intratypic differentiation by real-time reverse transcription-polymerase chain reaction (rRT-PCR) assay is suitable for serotype mixtures but not for intratypic mixtures of wild and vaccine poliovirus strains. This study was undertaken to develop wild poliovirus 1 and 3 (WPV1 and WPV3) specific rRT-PCR assays for use. METHODS: Specific primers and probes for rRT-PCR were designed based on VP1 sequences of WPV1 and WPV3 isolated in India since 2000. The specificity of the rRT-PCR assays was evaluated using WPV1 and WPV3 of different genetic lineages, non-polio enteroviruses (NPEVs) and mixtures of wild/wild and wild/Sabin vaccine strains. The sensitivity of the assays was determined by testing serial 10-fold dilutions of wild poliovirus 1 and 3 stock suspensions of known titre. RESULTS: No cross-reactivity with Sabin strains, intertypic wild poliovirus isolates or 27 types of NPEVs across all the four Enterovirus species was found for both the wild poliovirus 1 and 3 rRT-PCR assays. All WPV1 and WPV3 strains isolated since 2000 were successfully amplified. The rRT-PCR assays detected 10 4.40 CCID 50 /ml of WPV1 and 10 4.00 CCID 50 /ml of WPV3, respectively either as single isolate or mixture with Sabin vaccine strains or intertypic wild poliovirus. INTERPRETATION & CONCLUSIONS: rRT-PCR assays for WPV1 and WPV3 have been validated to detect all the genetic variations of the WPV1 and WPV3 isolated in India for the last decade. When used in combination with the current rRT-PCR assay testing was complete for confirmation of the presence of wild poliovirus in intratypic mixtures.
Subject(s)
Capsid Proteins/genetics , Poliomyelitis/virology , Poliovirus/isolation & purification , Real-Time Polymerase Chain Reaction/methods , Feces/virology , Humans , India , Poliomyelitis/genetics , Poliomyelitis/immunology , Poliovirus/genetics , Poliovirus Vaccine, Oral/genetics , Poliovirus Vaccine, Oral/isolation & purification , Reverse Transcription/geneticsABSTRACT
BACKGROUND: Polio eradication needs a new routine immunisation schedule--three or four doses of bivalent type 1 and type 3 oral poliovirus vaccine (bOPV) and one dose of inactivated poliovirus vaccine (IPV), but no immunogenicity data are available for this schedule. We aimed to assess immunogenicity of this vaccine schedule. METHODS: We did an open-label, randomised controlled trial in four centres in India. After informed consent was obtained from a parent or legally acceptable representative, healthy newborn babies were randomly allocated to one of five groups: trivalent OPV (tOPV); tOPV plus IPV; bOPV; bOPV plus IPV; or bOPV plus two doses of IPV (2IPV). The key eligibility criteria were: full-term birth (≥37 weeks of gestation); birthweight ≥2·5 kg; and Apgar score of 9 or more. OPV was administered at birth, 6 weeks, 10 weeks, and 14 weeks; IPV was administered intramuscularly at 14 weeks. The primary study objective was to investigate immunogenicity of the new vaccine schedule, assessed by seroconversion against poliovirus types 1, 2, and 3 between birth and 18 weeks in the per-protocol population (all participants with valid serology results on cord blood and at 18 weeks). Neutralisation assays tested cord blood and sera collected at 14 weeks, 18 weeks, 19 weeks, and 22 weeks by investigators masked to group allocation. This trial was registered with the India Clinical Trials Registry, number CTRI/2013/06/003722. FINDINGS: Of 900 newborn babies enrolled between June 13 and Aug 29, 2013, 782 (87%) completed the per-protocol requirements. Between birth and age 18 weeks, seroconversion against poliovirus type 1 in the tOPV group occurred in 162 of 163 (99·4%, 95% CI 96·6-100), in 150 (98·0%, 94·4-99·6) of 153 in the tOPV plus IPV group, in 153 (98·7%, 95·4-99·8) of 155 in the bOPV group, in 155 (99·4%, 96·5-100) of 156 in the bOPV plus IPV group, and in 154 (99·4%, 96·5-100) of 155 in the bOPV plus 2IPV group. Seroconversion against poliovirus type 2 occurred in 157 (96·3%, 92·2-98·6) of 163 in the tOPV group, 153 (100%, 97·6-100·0) of 153 in the tOPV plus IPV group, 29 (18·7%, 12·9-25·7) of 155 in the bOPV group, 107 (68·6%, 60·7-75·8) of 156 in the bOPV plus IPV group, and in 121 (78·1%, 70·7-84·3) of 155 in the bOPV plus 2IPV group. Seroconversion against poliovirus type 3 was achieved in 147 (90·2%, 84·5-94·3) of 163 in the tOPV group, 152 (99·3%, 96·4-100) of 153 in the tOPV plus IPV group, 151 (97·4%, 93·5-99·3) of 155 in the bOPV group, 155 (99·4%, 96·5-100) of 156 in the bOPV plus IPV group, and 153 (98·7%, 95·4-99·8) of 155 in the bOPV plus 2IPV group. Superiority was achieved for vaccine regimens including IPV against poliovirus type 3 compared with those not including IPV (tOPV plus IPV vs tOPV alone, p=0·0008; and bOPV plus IPV vs bOPV alone, p=0·0153). 12 serious adverse events occurred (six in the tOPV group, one in the tOPV plus IPV group, three in the bOPV group, zero in the bOPV plus IPV group, and two in the bOPV plus 2IPV group), none of which was attributed to the trial intervention. INTERPRETATION: The new vaccination schedule improves immunogenicity against polioviruses, especially against poliovirus type 3. FUNDING: WHO, through a grant from Rotary International (grant number 59735).
Subject(s)
Immunologic Factors/immunology , Poliomyelitis/prevention & control , Poliovirus Vaccine, Inactivated/immunology , Poliovirus Vaccine, Oral/immunology , Antibodies, Viral/blood , Antibody Formation/immunology , Disease Eradication/methods , Female , Humans , Immunization Schedule , Immunologic Factors/administration & dosage , Immunologic Factors/adverse effects , Infant, Newborn , Male , Poliomyelitis/immunology , Poliovirus/immunology , Poliovirus Vaccine, Inactivated/administration & dosage , Poliovirus Vaccine, Inactivated/adverse effects , Poliovirus Vaccine, Oral/administration & dosage , Poliovirus Vaccine, Oral/adverse effects , Seroconversion/physiology , Vaccination/methodsSubject(s)
False Negative Reactions , High-Throughput Screening Assays/standards , Poliomyelitis/diagnosis , Poliovirus Vaccine, Oral/therapeutic use , Poliovirus/genetics , Disease Eradication/trends , Global Health/statistics & numerical data , Global Health/trends , High-Throughput Screening Assays/methods , Humans , Poliomyelitis/prevention & control , Poliovirus/pathogenicity , Poliovirus Vaccine, Oral/pharmacology , Vaccination/adverse effectsABSTRACT
OBJECTIVE: IgG and IgA immunocompetence of children with wild poliovirus poliomyelitis and non-polio acute flaccid paralysis. METHODS: 932 cases of acute flaccid paralysis, reported in 2008-2009, were tested for presence of polio and non-polio enteroviruses according to the WHO standards. Serum IgA and IgG levels were determined by sandwich ELISA. RESULTS: Mean (SD) IgA levels [0.87 (0.62)g/L; n=28] of virologically confirmed poliomyelitis cases were lower than those of virus negative [1.21 (0.83)g/L; n=612] and non-polio Enterovirus positive [1.22 (0.79)g/L; n=240] cases of acute flaccid paralysis. No significant difference was observed in the concentration of IgG among these groups. CONCLUSIONS: IgA plays an important role in protection against poliomyelitis.
Subject(s)
Immunoglobulin A/blood , Immunoglobulin G/blood , Paraplegia/epidemiology , Paraplegia/immunology , Poliomyelitis/epidemiology , Poliomyelitis/immunology , Child, Preschool , Feces/virology , Humans , India/epidemiology , Infant , Infant, Newborn , Poliovirus/immunology , Seroepidemiologic StudiesABSTRACT
We have identified circulation of 3 genogroups of enterovirus (EV) A71 in India. A new genogroup (proposed designation G) was discovered during this study. We isolated genogroups D and G in wide geographic areas but detected subgenogroup C1 only in 1 focus in western India. A systematic nationwide search for EV-A71 is warranted.
Subject(s)
Enterovirus A, Human/genetics , Hand, Foot and Mouth Disease/virology , Adolescent , Adult , Aged , Capsid Proteins/genetics , Child , Evolution, Molecular , Female , Genetic Variation , Hand, Foot and Mouth Disease/epidemiology , Humans , India/epidemiology , Male , Middle Aged , Molecular Typing , Paralysis/epidemiology , Paralysis/virology , Phylogeny , Sequence Analysis, DNAABSTRACT
BACKGROUND: Moradabad district in Uttar Pradesh reported the highest number of paralytic polio cases in India during 2001-2007. We conducted a study in Moradabad in 2007 to assess seroprevalence against poliovirus types 1, 2, and 3 in children 6-12 and 36-59 months of age to guide future strategies to interrupt wild poliovirus transmission in high-risk areas. METHODS: Children attending 10 health facilities for minor illnesses who met criteria for study inclusion were eligible for enrollment. We recorded vaccination history, weight, and length and tested sera for neutralizing antibodies to poliovirus types 1, 2, and 3. RESULTS: Poliovirus type 1, 2, and 3 seroprevalences were 88% (95% confidence interval [CI], 84%-91%), 70% (95% CI, 66%-75%), and 75% (95% CI, 71%-79%), respectively, among 467 in the younger age group (n=467), compared with 100% (95% CI, 99%-100%), 97% (95% CI, 95%-98%), and 93% (91%-95%), respectively, among 447 children in the older age group (P<.001 for all serotypes). CONCLUSIONS: This seroprevalence study provided extremely useful information that was used by the program in India to guide immunization policies, such as optimizing the use of different OPV formulations in vaccination campaigns and strengthening routine immunization services. Similar surveys in populations at risk should be performed at regular intervals in countries where the risk of persistence or spread of indigenous or imported wild poliovirus is high.
Subject(s)
Antibodies, Viral/blood , Poliomyelitis/epidemiology , Poliomyelitis/prevention & control , Poliovirus Vaccine, Oral/immunology , Antibodies, Neutralizing/blood , Child, Preschool , Female , Humans , India/epidemiology , Infant , Male , Poliovirus Vaccine, Oral/administration & dosage , Seroepidemiologic StudiesABSTRACT
INTRODUCTION: The objectives of this survey were to assess the seroprevalence of antibodies to poliovirus types 1 and 3 and the impact of bivalent (types 1 and 3) oral poliovirus vaccine (bOPV) use in immunization campaigns in northern India. METHODS: In August 2010, a 2-stage stratified cluster sampling method identified infants aged 6-7 months in high-risk blocks for wild poliovirus infection. Vaccination history, weight and length, and serum were collected to test for neutralizing antibodies to poliovirus types 1, 2, and 3. RESULTS: Seroprevalences of antibodies to poliovirus types 1, 2, and 3 were 98% (95% confidence interval [CI], 97%-99%), 66% (95% CI, 62%-69%), and 77% (95% CI, 75%-79%), respectively, among 664 infants from Bihar and 616 infants from Uttar Pradesh. Infants had received a median of 3 bOPV doses and 2 monovalent type 1 OPV (mOPV1) doses through campaigns and 3 trivalent OPV (tOPV) doses through routine immunization. Among subjects with 0 tOPV doses, the seroprevalences of antibodies to type 3 were 50%, 77%, and 82% after 2, 3, and 4 bOPV doses, respectively. In multivariable analysis, malnutrition was associated with a lower seroprevalence of type 3 antibodies. CONCLUSIONS: This study confirmed that replacing mOPV1 with bOPV in campaigns was successful in maintaining very high population immunity to type 1 poliovirus and substantially decreasing the immunity gap to type 3 poliovirus.
Subject(s)
Antibodies, Viral/blood , Poliomyelitis/epidemiology , Poliomyelitis/prevention & control , Poliovirus/immunology , Antibodies, Neutralizing/blood , Cross-Sectional Studies , Female , Humans , India/epidemiology , Infant , Infant, Newborn , Male , Poliovirus Vaccines/administration & dosage , Poliovirus Vaccines/immunology , Seroepidemiologic Studies , Vaccination/methodsABSTRACT
Inactivated poliovirus vaccine (IPV) is efficacious against paralytic disease, but its effect on mucosal immunity is debated. We assessed the efficacy of IPV in boosting mucosal immunity. Participants received IPV, bivalent 1 and 3 oral poliovirus vaccine (bOPV), or no vaccine. A bOPV challenge was administered 4 weeks later, and excretion was assessed 3, 7, and 14 days later. Nine hundred and fifty-four participants completed the study. Any fecal shedding of poliovirus type 1 was 8.8, 9.1, and 13.5% in the IPV group and 14.4, 24.1, and 52.4% in the control group by 6- to 11-month, 5-year, and 10-year groups, respectively (IPV versus control: Fisher's exact test P < 0.001). IPV reduced excretion for poliovirus types 1 and 3 between 38.9 and 74.2% and 52.8 and 75.7%, respectively. Thus, IPV in OPV-vaccinated individuals boosts intestinal mucosal immunity.
Subject(s)
Disease Eradication , Intestinal Mucosa/immunology , Poliomyelitis/prevention & control , Poliovirus Vaccine, Inactivated/administration & dosage , Poliovirus Vaccine, Oral/administration & dosage , Poliovirus/immunology , Adult , Antibodies, Viral/blood , Antibodies, Viral/immunology , Child , Child, Preschool , Feces/virology , Female , Humans , Immunity, Mucosal , Immunization, Secondary , India/epidemiology , Infant , Intestinal Mucosa/virology , Male , Middle Aged , Poliomyelitis/epidemiology , Poliomyelitis/immunology , Poliovirus/isolation & purification , Prevalence , Virus Shedding/immunologyABSTRACT
Hospital-based rotavirus surveillance was carried out in Mumbai during 2005-2009. An isolate (B08299) with a rare genotype combination (G11P[25]) was detected. The present study was undertaken to characterize the complete genome of the isolate. B08299 exhibited a G11-P[25]-I12-R1-C1-M1-A1-N1-T1-E1-H1 genotype constellation. Phylogenetic analysis of the 11 gene segments of B08299 revealed that the VP2 and NSP5 genes of B08299 had a human origin, while the VP6 gene represented an I12 genotype of obscure origin. The remaining six genes formed a lineage distinct from human and porcine rotaviruses within genotype 1. Analysis of the structural and non-structural genes suggested that B08299 has evolved by gene reassortment. Our findings provide further evidence that interspecies transmission is an important mechanism involved in the evolution and genetic diversity of human rotaviruses in nature.
Subject(s)
Genome, Viral , RNA Viruses/genetics , RNA, Viral/genetics , Recombination, Genetic , Rotavirus Infections/virology , Rotavirus/genetics , Sequence Analysis, DNA , Animals , Child, Preschool , Cluster Analysis , Evolution, Molecular , Genotype , Humans , India , Infant , Male , Molecular Sequence Data , Phylogeny , RNA Viruses/isolation & purification , Rotavirus/classification , Rotavirus/isolation & purificationABSTRACT
BACKGROUND: Protection against paralytic poliomyelitis is provided mainly by antibody mediated host defense. Despite intensive oral polio vaccine (OPV) immunization campaigns wild poliovirus transmission could not be stopped in Uttar Pradesh (UP) and Bihar states of India by the end of 2010. The objective of our study was to quantitate serum IgG and IgA in children of western UP, India, to determine the prevalence of antibody immunodeficiency. METHODS: A cross-sectional survey for IgG and IgA concentrations in serum samples from healthy children and children with acute flaccid paralysis (AFP), up to the age of 5 years, was performed using sandwich ELISA. RESULTS: The overall mean IgG concentration for 1882 children of western UP, India, was 10.57 ± 4.53 (SD) g/L and mean IgA concentration for 979 children was 1.2 ± 0.818 g/L. Two 7-month-old female children had IgG levels below 2 g/L and there was an absence of neutralizing polio antibodies. The mean serum IgG level of children with AFP (n=979) was lower than levels observed in healthy children (n=903). The proportion of children with IgG levels below 2 g/L and IgA levels below 0.07 g/L was 0.7% in both healthy children and AFP cases. CONCLUSIONS: There was no abnormal prevalence of immunodeficiency in children in western UP which could have delayed achieving the eradication of polio in the state. The immunoglobulin levels reported here may be used as age-specific normal values for Indian children.
Subject(s)
Communicable Disease Control/organization & administration , Immunization Programs/organization & administration , Immunoglobulin A/blood , Immunoglobulin G/blood , Poliomyelitis/immunology , Poliovirus/immunology , Child, Preschool , Cross-Sectional Studies , Enzyme-Linked Immunosorbent Assay , Female , Humans , India/epidemiology , Infant , Male , Poliomyelitis/epidemiology , Poliomyelitis/prevention & control , Poliovirus Vaccine, Oral , Population Surveillance , PrevalenceABSTRACT
Most circulating strains of Human enterovirus 71 (EV-A71) have been classified primarily into three genogroups (A to C) on the basis of genetic divergence between the 1D gene, which encodes the VP1 capsid protein. The aim of the present study was to provide further insights into the diversity of the EV-A71 genogroups following the recent description of highly divergent isolates, in particular those from African countries, including Madagascar. We classified recent EV-A71 isolates by a large comparison of 3,346 VP1 nucleotidic sequences collected from GenBank. Analysis of genetic distances and phylogenetic investigations indicated that some recently-reported isolates did not fall into the genogroups A-C and clustered into three additional genogroups, including one Indian genogroup (genogroup D) and 2 African ones (E and F). Our Bayesian phylogenetic analysis provided consistent data showing that the genogroup D isolates share a recent common ancestor with the members of genogroup E, while the isolates of genogroup F evolved from a recent common ancestor shared with the members of the genogroup B. Our results reveal the wide diversity that exists among EV-A71 isolates and suggest that the number of circulating genogroups is probably underestimated, particularly in developing countries where EV-A71 epidemiology has been poorly studied.
Subject(s)
Enterovirus A, Human/genetics , Enterovirus A, Human/isolation & purification , Evolution, Molecular , Genetic Variation , Viral Proteins/genetics , Africa , Base Sequence , Bayes Theorem , Genotype , Humans , Madagascar , Models, Genetic , Phylogeny , Time FactorsABSTRACT
BACKGROUND & OBJECTIVES: Polioviruses are the causative agent of paralytic poliomyelitis. Attenuated polioviruses (Sabin oral poliovirus vaccine strains) do not replicate efficiently in neurons as compared to the wild type polioviruses and therefore do not cause disease. This study was aimed to investigate the differential host immune response to wild type 1 poliovirus (wild PV) and Sabin attenuated type 1 poliovirus (Sabin PV) in cultured human neuronal cells. METHODS: By using flow cytometry and real time PCR methods we examined host innate immune responses and compared the role of toll like receptors (TLRs) and cytoplasmic RNA helicases in cultured human neuronal cells (SK-N-SH) infected with Sabin PV and wild PV. RESULTS: Human neuronal cells expressed very low levels of TLRs constitutively. Sabin PV infection induced significantly higher expression of TLR3, TLR7 and melanoma differentiation-associated protein-5 (MDA-5) m-RNA in neuronal cells at the beginning of infection (up to 4 h) as compared to wild PV. Further, Sabin PV also induced the expression of interferon α/ß at early time point of infection. The induced expression of IFN α/ß gene by Sabin PV in neuronal cells could be suppressed by inhibiting TLR7. INTERPRETATION & CONCLUSIONS: Neuronal cell innate immune response to Sabin and wild polioviruses differ significantly for TLR3, TLR7, MDA5 and type 1 interferons. Effects of TLR7 activation and interferon production and Sabin virus replication in neuronal cells need to be actively investigated in future studies.
Subject(s)
Interferons/biosynthesis , Neurons/metabolism , Poliovirus/physiology , Toll-Like Receptors/biosynthesis , Cells, Cultured , Humans , Neurons/cytologyABSTRACT
BACKGROUND: The eradication of wild-type polioviruses in areas with efficient fecal-oral transmission relies on intestinal mucosal immunity induced by oral poliovirus vaccine (OPV). Mucosal immunity is thought to wane over time but the rate of loss of protection has not been examined. METHODS: We examined the degree and duration of intestinal mucosal immunity in India by measuring the prevalence of vaccine poliovirus in stool samples collected 4-28 days after a "challenge" dose of OPV among 47 574 children with acute flaccid paralysis reported during 2005-2009. RESULTS: Previous vaccination with OPV was protective against excretion of vaccine poliovirus after challenge, but the odds of excretion increased significantly with the time since the child was last exposed to an immunization activity (odds ratio, 1.39 [95% confidence interval .99-1.97], 2.04 [1.28-3.25], and 1.31 [1.00-1.70] comparing ≥6 months with 1 month ago for serotypes 1, 2, and 3, respectively). Vaccine administered during the high season for enterovirus infections (April-September) was significantly less likely to result in excretion, especially in northern states (odds ratio, 0.57 [95% confidence interval, .50-.65], 0.58 [.41-.81], and 0.48 [.40-.57] for serotypes 1, 2, and 3). CONCLUSIONS: Infection with OPV (vaccine "take") is highly seasonal in India and results in intestinal mucosal immunity that appears to wane significantly within a year of vaccination.
Subject(s)
Intestinal Mucosa/immunology , Poliomyelitis/immunology , Poliomyelitis/prevention & control , Poliovirus Vaccine, Oral/immunology , Poliovirus/immunology , Child, Preschool , Feces/virology , Female , Humans , Immunity, Mucosal/immunology , India , Infant , Logistic Models , Male , Poliomyelitis/virology , Poliovirus/isolation & purification , Poliovirus/physiology , Seasons , Time Factors , Vaccination , Virus SheddingABSTRACT
BACKGROUND: On the basis of studies from developed countries, the case-fatality ratio (CFR) of poliomyelitis generally ranges from 2%-5% among children <5 years of age to 10%-30% among adults. However, little information is available for poliomyelitis-related CFR in developing countries. We conducted a study to determine the CFR in India, 1 of the 4 remaining countries with endemic wild poliovirus (WPV) circulation, during outbreaks of WPV infection during 2002 and 2006 and during the inter-epidemic years of 2003-2005. METHODS: We conducted a descriptive analysis with use of data from the acute flaccid paralysis surveillance system in India. Variables analyzed included age, caregiver-reported vaccination status, date of paralysis onset, laboratory results, final case classification, and survival outcome. Our analysis also accounted for surveillance changes that occurred in 2005, impacting case definitions and final classification. RESULTS: In 2006, 45 deaths occurred among 676 WPV cases in India, yielding a CFR of 6.7%. By comparison, in 2002, there were 66 deaths among 1600 reported WPV cases (CFR, 4.2%) and during 2002-2005, CFR was 1.5%-5.2%. All 45 deaths were among 644 (95%) WPV cases in children aged <5 years (CFR, 7.0%). Among those who died, 33 (73%) were children aged <2 years (CFR, 7.1%). CONCLUSIONS: The CFR among children aged <2 years in India is high compared with previously published CFRs for young children, in part because of improved case finding through enhanced surveillance techniques. Fatal cases emphasize the lethal nature of the disease and the importance of achieving polio eradication in India.
Subject(s)
Poliomyelitis/epidemiology , Child, Preschool , Cluster Analysis , Developing Countries/statistics & numerical data , Geography , Humans , India/epidemiology , Infant , Poliomyelitis/mortality , Poliovirus/geneticsABSTRACT
BACKGROUND: A 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. METHODS: We 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. FINDINGS: In 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. INTERPRETATION: Under 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.
Subject(s)
Immunization Programs/statistics & numerical data , Paraplegia/prevention & control , Poliomyelitis/prevention & control , Poliovirus Vaccines/immunology , Population Surveillance/methods , Case-Control Studies , Child, Preschool , Humans , India/epidemiology , Infant , Logistic Models , Paraplegia/epidemiology , Paraplegia/immunology , Poliomyelitis/epidemiology , Poliomyelitis/immunology , Poliovirus Vaccines/classificationABSTRACT
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.