Unravelling mucosal immunity to poliovirus

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Routine immunization in Pakistan: comparison of multiple data sources and identification of factors associated with vaccination.

Background: Within Pakistan, estimates of vaccination coverage with the pentavalent vaccine, oral polio vaccine (OPV) and measles vaccine (MV) in 2011 were reported to be 74%, 75% and 53%, respectively. These national estimates may mask regional variation. The reasons for this variation have not been explored. Methods: Data from the Multiple Indicator Cluster Surveys (MICS) for Balochistan and Punjab (2010-2011) are analysed to examine factors associated with receiving three or more doses of the pentavalent vaccine and one or more MVs using regression modelling. Pentavalent and OPV estimates from the MICS were compared to vaccine dose histories from surveillance for acute flaccid paralysis (AFP; poliomyelitis) to ascertain agreement. Results: Adjusted coverage of children 12-23 months of age were estimated to be 16.0%, 75.5% and 34.2% in Balochistan and 58.0%, 87.7% and 72.6% in Punjab for the pentavalent vaccine, OPV and MV, respectively. Maternal education, healthcare utilization and wealth were associated with receiving the pentavalent vaccine and the MV. There was a strong correlation of district estimates of vaccination coverage between AFP and MICS data, but AFP estimates of pentavalent coverage in Punjab were biased toward higher values. Conclusions: National estimates mask variation and estimates from individual surveys should be considered alongside other estimates. The development of strategies targeted towards poorly educated parents within low-wealth quintiles that may not typically access healthcare could improve vaccination rates

Key issues in the persistence of poliomyelitis in Nigeria: a case-control study

Background The completion of poliomyelitis eradication is a global emergency for public health. In 2012, more than 50% of the world’s cases occurred in Nigeria following an unanticipated surge in incidence. We aimed to quantitatively analyse the key factors sustaining transmission of poliomyelitis in Nigeria and to calculate clinical effi cacy estimates for the oral poliovirus vaccines (OPV) currently in use. Methods We used acute fl accid paralysis (AFP) surveillance data from Nigeria collected between January, 2001, and December, 2012, to estimate the clinical effi cacies of all four OPVs in use and combined this with vaccination coverage to estimate the eff ect of the introduction of monovalent and bivalent OPV on vaccine-induced serotype-specifi c population immunity. Vaccine effi cacy was determined using a case-control study with CIs based on bootstrap resampling. Vaccine effi cacy was also estimated separately for north and south Nigeria, by age of the children, and by year. Detailed 60-day follow-up data were collected from children with confi rmed poliomyelitis and were used to assess correlates of vaccine status. We also quantitatively assessed the epidemiology of poliomyelitis and programme performance and considered the reasons for the high vaccine refusal rate along with risk factors for a given local government area reporting a case. Findings Against serotype 1, both monovalent OPV (median 32·1%, 95% CI 26·1–38·1) and bivalent OPV (29·5%, 20·1–38·4) had higher clinical effi cacy than trivalent OPV (19·4%, 16·1–22·8). Corresponding data for serotype 3 were 43·2% (23·1–61·1) and 23·8% (5·3–44·9) compared with 18·0% (14·1–22·1). Combined with increases in coverage, this factor has boosted population immunity in children younger than age 36 months to a record high (64–69% against serotypes 1 and 3). Vaccine effi cacy in northern states was estimated to be signifi cantly lower than in southern states (p≤0·05). The proportion of cases refusing vaccination decreased from 37–72% in 2008 to 21–51% in 2012 for routine and supplementary immunisation, and most caregivers cited ignorance of either vaccine importance or availability as the main reason for missing routine vaccinations (32·1% and 29·6% of cases, respectively). Multiple regression analyses highlighted associations between the age of the mother, availability of OPV at health facilities, and the primary source of health information and the probability of receiving OPV (all p<0·05). Interpretation Although high refusal rates, low OPV campaign awareness, and heterogeneous population immunity continued to support poliomyelitis transmission in Nigeria at the end of 2012, overall population immunity had improved due to new OPV formulations and improvements in programme delivery.Funding Bill & Melinda Gates Foundation Vaccine Modeling Initiative, Royal Society.Introduction In May, 2012, after more than 20 years of mass vaccination campaigns, the 65t

Quantity of Vaccine Poliovirus Shed Determines the Titer of the Serum Neutralizing Antibody Response in Indian Children Who Received Oral Vaccine

Replication of oral poliovirus vaccine (OPV) in the intestine (ie, vaccine take) is associated with seroconversion and protection against poliomyelitis. We used quantitative polymerase chain reaction analysis to measure vaccine shedding in 300 seronegative infants aged 6–11 months and in 218 children aged 1–4 years 7 days after administration of monovalent or bivalent OPV. We found that the quantity of shedding correlated with the magnitude of the serum neutralizing antibody response measured 21 or 28 days after vaccination. This suggests that the immune response to OPV is on a continuum, rather than an all-or-nothing phenomenon, that depends on efficient vaccine virus replication

The effect of mass immunisation campaigns and new oral poliovirus vaccines on the incidence of poliomyelitis in Pakistan and Afghanistan, 2001–11: a retrospective analysis

SummaryBackgroundPakistan and Afghanistan are two of the three remaining countries yet to interrupt wild-type poliovirus transmission. The increasing incidence of poliomyelitis in these countries during 2010–11 led the Executive Board of WHO in January, 2012, to declare polio eradication a “programmatic emergency for global public health”. We aimed to establish why incidence is rising in these countries despite programme innovations including the introduction of new vaccines.MethodsWe did a matched case-control analysis based on a database of 46 977 children aged 0–14 years with onset of acute flaccid paralysis between Jan 1, 2001, and Dec 31, 2011. The vaccination history of children with poliomyelitis was compared with that of children with acute flaccid paralysis due to other causes to estimate the clinical effectiveness of oral poliovirus vaccines (OPVs) in Afghanistan and Pakistan by conditional logistic regression. We estimated vaccine coverage and serotype-specific vaccine-induced population immunity in children aged 0–2 years and assessed their association with the incidence of poliomyelitis over time in seven regions of Afghanistan and Pakistan.FindingsBetween Jan 1, 2001, and Dec 31, 2011, there were 883 cases of serotype 1 poliomyelitis (710 in Pakistan and 173 in Afghanistan) and 272 cases of poliomyelitis serotype 3 (216 in Pakistan and 56 in Afghanistan). The estimated clinical effectiveness of a dose of trivalent OPV against serotype 1 poliomyelitis was 12·5% (95% CI 5·6–18·8) compared with 34·5% (16·1–48·9) for monovalent OPV (p=0·007) and 23·4% (10·4–34·6) for bivalent OPV (p=0·067). Bivalent OPV was non-inferior compared with monovalent OPV (p=0·21). Vaccination coverage decreased during 2006–11 in the Federally Administered Tribal Areas (FATA), Balochistan, and Khyber Pakhtunkhwa in Pakistan and in southern Afghanistan. Although partially mitigated by the use of more effective vaccines, these decreases in coverage resulted in lower vaccine-induced population immunity to poliovirus serotype 1 in FATA and Balochistan and associated increases in the incidence of poliomyelitis.InterpretationThe effectiveness of bivalent OPV is comparable with monovalent OPV and can therefore be used in eradicating serotype 1 poliomyelitis whilst minimising the risks of serotype 3 outbreaks. However, decreases in vaccination coverage in parts of Pakistan and southern Afghanistan have severely limited the effect of this vaccine.FundingPoliovirus Research subcommittee of WHO, Royal Society, and Medical Research Council

Impact of inactivated poliovirus vaccine on mucosal immunity: implications for the polio eradication endgame.

The polio eradication endgame aims to bring transmission of all polioviruses to a halt. To achieve this aim, it is essential to block viral replication in individuals via induction of a robust mucosal immune response. Although it has long been recognized that inactivated poliovirus vaccine (IPV) is incapable of inducing a strong mucosal response on its own, it has recently become clear that IPV may boost immunity in the intestinal mucosa among individuals previously immunized with oral poliovirus vaccine. Indeed, mucosal protection appears to be stronger following a booster dose of IPV than oral poliovirus vaccine, especially in older children. Here, we review the available evidence regarding the impact of IPV on mucosal immunity, and consider the implications of this evidence for the polio eradication endgame. We conclude that the implementation of IPV in both routine and supplementary immunization activities has the potential to play a key role in halting poliovirus transmission, and thereby hasten the eradication of polio

Population Immunity against Serotype-2 Poliomyelitis Leading up to the Global Withdrawal of the Oral Poliovirus Vaccine: Spatio-temporal Modelling of Surveillance Data.

BACKGROUND: Global withdrawal of serotype-2 oral poliovirus vaccine (OPV2) took place in April 2016. This marked a milestone in global polio eradication and was a public health intervention of unprecedented scale, affecting 155 countries. Achieving high levels of serotype-2 population immunity before OPV2 withdrawal was critical to avoid subsequent outbreaks of serotype-2 vaccine-derived polioviruses (VDPV2s). METHODS AND FINDINGS: In August 2015, we estimated vaccine-induced population immunity against serotype-2 poliomyelitis for 1 January 2004-30 June 2015 and produced forecasts for April 2016 by district in Nigeria and Pakistan. Population immunity was estimated from the vaccination histories of children 70% population immunity among children <36 mo old. Districts with lower immunity were clustered in northeastern Nigeria and northwestern Pakistan. The accuracy of immunity estimates was limited by the small numbers of non-polio AFP cases in some districts, which was reflected by large uncertainty intervals. Forecasted improvements in immunity for April 2016 were robust to the uncertainty in estimates of baseline immunity (January-June 2015), vaccine coverage, and vaccine efficacy. CONCLUSIONS: Immunity against serotype-2 poliomyelitis was forecasted to improve in April 2016 compared to the first half of 2015 in Nigeria and Pakistan. These analyses informed the endorsement of OPV2 withdrawal in April 2016 by the WHO Strategic Advisory Group of Experts on Immunization

Expression Profiling the Temperature-Dependent Amphibian Response to Infection by Batrachochytrium dendrobatidis

Amphibians are experiencing a panzootic of unprecedented proportions caused by the emergence of Batrachochytrium dendrobatidis (Bd). However, all species are not equally at risk of infection, and risk is further modified by environmental variables, specifically temperature. In order to understand how, and when, hosts mount a response to Bd we analysed infection dynamics and patterns of gene expression in the model amphibian species Silurana (Xenopus) tropicalis. Mathematical modelling of infection dynamics demonstrate the existence of a temperature-dependent protective response that is largely independent of the intrinsic growth-rate of Bd. Using temporal expression-profiling by microarrays and qRT-PCR, we characterise this response in the main amphibian lymphoid tissue, the spleen. We demonstrate that clearance of Bd at the host-optimal temperature is not clearly associated with an adaptive immune response, but rather is correlated with the induction of components of host innate immunity including the expression of genes that are associated with the production of the antimicrobial skin peptide preprocareulein (PPCP) as well as inflammatory responses. We find that adaptive immunity appears to be lacking at host-optimal temperatures. This suggests that either Bd does not stimulate, or suppresses, adaptive immunity, or that trade-offs exist between innate and adaptive limbs of the amphibian immune system. At cold temperatures, S. tropicalis loses the ability to mount a PPCP-based innate response, and instead manifests a more pronounced inflammatory reaction that is characterised by the production of proteases and higher pathogen burdens. This study demonstrates the temperature-dependency of the amphibian response to infection by Bd and indicates the influence that changing climates may exert on the ectothermic host response to pathogens

Estimating Household and Community Transmission of Ocular Chlamydia trachomatis

Trachoma is a major cause of blindness worldwide and results from ocular infection with the bacterium Chlamydia trachomatis. Mass distribution of antibiotics in communities is part of the strategy to eliminate blindness due to trachoma. Targeted treatment of infected households could be more efficient, but the success of such a strategy will depend on the extent of transmission of infection between members of the same household and between members of the community. In this work, we estimated the magnitude of household and community transmission in four populations, two from The Gambia and two from Tanzania. We found that, in general, transmission of the bacteria within households is very efficient. In three of the four populations, persistent infection within households was predicted by the high level of household transmission (a phenomenon observed in longitudinal studies of trachoma). In all of the studied populations, individuals who live in households with more individuals contribute more to the number of new infections in the community than those who live with fewer individuals. Further studies are required to identify and examine household-targeted approaches to treatment

Changes in the intestinal microbiota following the administration of azithromycin in a randomised placebo-controlled trial among infants in south India.

Macrolides are among the most widely prescribed antibiotics worldwide. However, their impact on the gut's bacterial microbiota remains uncertain. We characterised the intestinal microbiota in 6-11 month-old infants in India who received a 3-day course of azithromycin or placebo during a randomised trial of oral poliovirus vaccine immunogenicity (CTRI/2014/05/004588). In 60 infants per study arm, we sequenced the V4 region of the bacterial 16S rRNA gene in stool samples collected before and 12 days after finishing treatment. We also tested for the presence of common bacterial, viral, and eukaryotic enteropathogens in the same samples using real-time PCR in a Taqman array card (TAC) format. Azithromycin induced a modest decline in microbiota richness and a shift in taxonomic composition driven by a reduction in the relative abundance of Proteobacteria and Verrucomicrobia (specifically Akkermansia muciniphila). The former phylum includes pathogenic strains of Escherichia coli and Campylobacter spp. that declined in prevalence based on the TAC assay. These findings differ from previous observations among older children and adults in Europe and North America, suggesting that the effects of azithromycin on the bacterial microbiota may be specific to the age and geographic setting of its recipients