Publications
160 results found
Lazarus RP, John J, Shanmugasundaram E, et al., 2017, The effect of probiotics and zinc supplementation on the immune response to oral rotavirus vaccine: A randomized, factorial design, placebo-controlled study among Indian infants, Vaccine, Vol: 36, Pages: 273-279, ISSN: 0264-410X
BackgroundStrategies are needed to improve oral rotavirus vaccine (RV), which provides suboptimal protection in developing countries. Probiotics and zinc supplementation could improve RV immunogenicity by altering the intestinal microbiota and immune function.MethodsInfants 5 weeks old living in urban Vellore, India were enrolled in a randomized, double-blind, placebo-controlled trial with a 4-arm factorial design to assess the effects of daily zinc (5 mg), probiotic (1010 Lactobacillus rhamnosus GG) or placebo on the immunogenicity of two doses of RV (Rotarix®, GlaxoSmithKline Biologicals) given at 6 and 10 weeks of age. Infants were eligible for participation if healthy, available for the study duration and without prior receipt of RV or oral poliovirus vaccine other than the birth dose. The primary outcome was seroconversion to rotavirus at 14 weeks of age based on detection of VP6-specific IgA at ≥20 U/ml in previously seronegative infants or a fourfold rise in concentration.ResultsThe study took place during July 2012 to February 2013. 620 infants were randomized equally between study arms and 551 (88.9%) completed per protocol. Seroconversion was recorded in 54/137 (39.4%), 42/136 (30.9%), 40/143 (28.0%), and 37/135 (27.4%) infants receiving (1) probiotic and zinc, (2) probiotic and placebo, (3) placebo and zinc, (4) two placebos. Seroconversion showed a modest improvement among infants receiving probiotic (difference between groups 1, 2 and 3, 4 was 7.5% (97.5% Confidence Interval (CI): −1.4%, 16.2%), p = 0.066) but not zinc (difference between groups 1, 3 and 2, 4 was 4.4% (97.5% CI: −4.4%, 13.2%), p = 0.272). 16 serious adverse events were recorded, none related to study interventions.ConclusionsZinc or probiotic supplementation did not significantly improve the low immunogenicity of rotavirus vaccine given to infants in a poor urban community in India. A modest effect of combined supplementation deserves further investigation.
Parker EPK, Praharaj I, John J, et al., 2017, Changes in the intestinal microbiota following the administration of azithromycin in a randomised placebo-controlled trial among infants in south India, Scientific Reports, Vol: 7, ISSN: 2045-2322
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 flora may be specific to the age and geographic setting of its recipients.
Li LM, Grassly NC, Fraser C, 2017, Quantifying Transmission Heterogeneity Using Both Pathogen Phylogenies and Incidence Time Series., Molecular Biology and Evolution, Vol: 34, Pages: 2982-2995, ISSN: 1537-1719
Heterogeneity in individual-level transmissibility can be quantified by the dispersion parameter k of the offspring distribution. Quantifying heterogeneity is important as it affects other parameter estimates, it modulates the degree of unpredictability of an epidemic, and it needs to be accounted for in models of infection control. Aggregated data such as incidence time series are often not sufficiently informative to estimate k. Incorporating phylogenetic analysis can help to estimate k concurrently with other epidemiological parameters. We have developed an inference framework that uses particle Markov Chain Monte Carlo to estimate k and other epidemiological parameters using both incidence time series and the pathogen phylogeny. Using the framework to fit a modified compartmental transmission model that includes the parameter k to simulated data, we found that more accurate and less biased estimates of the reproductive number were obtained by combining epidemiological and phylogenetic analyses. However, k was most accurately estimated using pathogen phylogeny alone. Accurately estimating k was necessary for unbiased estimates of the reproductive number, but it did not affect the accuracy of reporting probability and epidemic start date estimates. We further demonstrated that inference was possible in the presence of phylogenetic uncertainty by sampling from the posterior distribution of phylogenies. Finally, we used the inference framework to estimate transmission parameters from epidemiological and genetic data collected during a poliovirus outbreak. Despite the large degree of phylogenetic uncertainty, we demonstrated that incorporating phylogenetic data in parameter inference improved the accuracy and precision of estimates.
Molodecky NAL, Blake IM, O'reilly KM, et al., 2017, Risk-factors and short-term projections for serotype-1 poliomyelitis incidence in Pakistan: a spatio-temporal analysis, Plos Medicine, Vol: 14, ISSN: 1549-1676
BackgroundPakistan currently provides a substantial challenge to global polio eradication, having contributed to 73% of reported poliomyelitis in 2015 and 54% in 2016. A better understanding of the risk factors and movement patterns that contribute to poliovirus transmission across Pakistan would support evidence-based planning for mass vaccination campaigns.Methods and findingsWe fit mixed-effects logistic regression models to routine surveillance data recording the presence of poliomyelitis associated with wild-type 1 poliovirus in districts of Pakistan over 6-month intervals between 2010 to 2016. To accurately capture the force of infection (FOI) between districts, we compared 6 models of population movement (adjacency, gravity, radiation, radiation based on population density, radiation based on travel times, and mobile-phone based). We used the best-fitting model (based on the Akaike Information Criterion [AIC]) to produce 6-month forecasts of poliomyelitis incidence. The odds of observing poliomyelitis decreased with improved routine or supplementary (campaign) immunisation coverage (multivariable odds ratio [OR] = 0.75, 95% confidence interval [CI] 0.67–0.84; and OR = 0.75, 95% CI 0.66–0.85, respectively, for each 10% increase in coverage) and increased with a higher rate of reporting non-polio acute flaccid paralysis (AFP) (OR = 1.13, 95% CI 1.02–1.26 for a 1-unit increase in non-polio AFP per 100,000 persons aged <15 years). Estimated movement of poliovirus-infected individuals was associated with the incidence of poliomyelitis, with the radiation model of movement providing the best fit to the data. Six-month forecasts of poliomyelitis incidence by district for 2013–2016 showed good predictive ability (area under the curve range: 0.76–0.98). However, although the best-fitting movement model (radiation) was a significant determinant of poliomyelitis incidence, it did not improve the predictive ability of the multivariable mo
O'Reilly KM, Lamoureux C, Molodecky NA, et al., 2017, An assessment of the geographical risks of wild and vaccine-derived poliomyelitis outbreaks in Africa and Asia, BMC Infectious Diseases, Vol: 17, ISSN: 1471-2334
BackgroundThe international spread of wild poliomyelitis outbreaks continues to threaten eradication of poliomyelitis and in 2014 a public health emergency of international concern was declared. Here we describe a risk scoring system that has been used to assess country-level risks of wild poliomyelitis outbreaks, to inform prioritisation of mass vaccination planning, and describe the change in risk from 2014 to 2016. The methods were also used to assess the risk of emergence of vaccine-derived poliomyelitis outbreaks.MethodsPotential explanatory variables were tested against the reported outbreaks of wild poliomyelitis since 2003 using multivariable regression analysis. The regression analysis was translated to a risk score and used to classify countries as Low, Medium, Medium High and High risk, based on the predictive ability of the score.ResultsIndicators of population immunity, population displacement and diarrhoeal disease were associated with an increased risk of both wild and vaccine-derived outbreaks. High migration from countries with wild cases was associated with wild outbreaks. High birth numbers were associated with an increased risk of vaccine-derived outbreaks.ConclusionsUse of the scoring system is a transparent and rapid approach to assess country risk of wild and vaccine-derived poliomyelitis outbreaks. Since 2008 there has been a steep reduction in the number of wild poliomyelitis outbreaks and the reduction in countries classified as High and Medium High risk has reflected this. The risk of vaccine-derived poliomyelitis outbreaks has varied geographically. These findings highlight that many countries remain susceptible to poliomyelitis outbreaks and maintenance or improvement in routine immunisation is vital.
Sindhu KNC, Cunliffe N, Peak M, et al., 2017, Impact of maternal antibodies and infant gut microbiota on the immunogenicity of rotavirus vaccines in African, Indian and European infants: protocol for a prospective cohort study, BMJ Open, Vol: 7, ISSN: 2044-6055
Introduction Gastroenteritis is the leading cause of morbidity and mortality among young children living in resource-poor settings, majority of which is attributed to rotavirus. Rotavirus vaccination can therefore have a significant impact on infant mortality. However, rotavirus vaccine efficacy in Sub-Saharan Africa and Southeast Asia is significantly lower than in high-income countries. Maternally derived antibodies, infant gut microbiota and concomitant oral polio vaccination have been proposed as potential reasons for poor vaccine performance in low-income settings. The overall aim of this study is to compare the role of maternally derived antibodies and infant gut microbiota in determining immune response to rotavirus vaccine in high-income and low-income settings, using the same vaccine and a similar study protocol.Methods and analysis The study is an observational cohort in three countries—Malawi, India and UK. Mothers will be enrolled in third trimester of pregnancy and followed up, along with infants after delivery, until the infant completes two doses of oral rotavirus vaccine (along with routine immunisation). The levels of prevaccination maternally derived rotavirus-specific antibodies (IgG) will be correlated with infant seroconversion and antibody titres, 4 weeks after the second dose of rotavirus vaccine. Both within-country and between-country comparisons of gut microbiome will be carried out between children who seroconvert and those who do not. The impact of oral polio vaccine coadministration on rotavirus vaccine response will be studied in Indian infants.Ethics and dissemination Ethical approvals have been obtained from Integrated Research Application System (IRAS, NHS ethics) in UK, College of Medicine Research and Ethics Committee (COMREC) in Malawi and Institutional Review Board (IRB), Christian Medical College, Vellore in India. Participant recruitment and follow-up is ongoing at all three sites. Analysis of data, followed by publicatio
John J, Giri S, Karthikeyan AS, et al., 2016, The duration of intestinal immunity after an inactivated poliovirus vaccine booster dose in children immunized with oral vaccine: a randomized controlled trial, Journal of Infectious Diseases, Vol: 215, Pages: 529-536, ISSN: 0022-1899
Background.In 2014, 2 studies showed that inactivated poliovirus vaccine (IPV) boosts intestinal immunity in children previously immunized with oral poliovirus vaccine (OPV). As a result, IPV was introduced in mass campaigns to help achieve polio eradication.Methods.We conducted an open-label, randomized, controlled trial to assess the duration of the boost in intestinal immunity following a dose of IPV given to OPV-immunized children. Nine hundred healthy children in Vellore, India, aged 1–4 years were randomized (1:1:1) to receive IPV at 5 months (arm A), at enrollment (arm B), or no vaccine (arm C). The primary outcome was poliovirus shedding in stool 7 days after bivalent OPV challenge at 11 months.Results.For children in arms A, B, and C, 284 (94.7%), 297 (99.0%), and 296 (98.7%), respectively, were eligible for primary per-protocol analysis. Poliovirus shedding 7 days after challenge was less prevalent in arms A and B compared with C (24.6%, 25.6%, and 36.4%, respectively; risk ratio 0.68 [95% confidence interval: 0.53–0.87] for A versus C, and 0.70 [0.55–0.90] for B versus C).Conclusions.Protection against poliovirus remained elevated 6 and 11 months after an IPV boost, although at a lower level than reported at 1 month.
Sarkar R, Rose A, Mohan VR, et al., 2016, Study design and baseline results of an open-label cluster randomized community-intervention trial to assess the effectiveness of a modified mass deworming program in reducing hookworm infection in a tribal population in southern India, Contemporary Clinical Trials Communications, Vol: 5, Pages: 49-55, ISSN: 2451-8654
Introduction: Hookworm infection is a leading cause of iron deficiency anemia and malnutrition inresource-poor settings. Periodic mass deworming with anthelminthic drugs remains the cornerstone ofhookworm control efforts worldwide. Reinfection following treatment occurs, reflecting the humanhost's inability to acquire immunity following exposure to an untreated reservoir of infection. Thiscluster randomized trial will evaluate the effectiveness of a modified, population-based, massdeworming strategy in reducing hookworm infection in an endemic southern Indian population.Methods: Forty five tribal villages were randomized into three groups: one received annual treatment;the second received two rounds of treatment at 1-month intervals; and the third received four rounds oftreatment e two rounds 1 month apart at the beginning, followed by another two after 6 months. Stoolsamples collected through cross-sectional parasitological surveys pre- and post-intervention, and at 3-monthly intervals for a period of 1 year were tested for presence of hookworm ova. Long-term effectivenessof treatment will be assessed through another survey conducted 2 years after the last treatmentcycle.Results: From a population of 11,857 individuals, 8681 (73.2%) were found to be eligible and consented toparticipate, out-migration being the primary reason for non-participation. Baseline stool samples wereobtained from 2082 participants, with 18.5% having hookworm infection, although majority were lowintensity infections (<2000 eggs per gram of feces).Discussion: This study will help identify the optimal mass deworming strategy that can achieve thegreatest impact in the shortest period of time, particularly in settings where long-term program sustainabilityis a challenge
Shirreff G, Wadood MZ, Vaz RG, et al., 2016, Estimated Effect of Inactivated Poliovirus Vaccine Campaigns, Nigeria and Pakistan, January 2014-April 2016, Emerging Infectious Diseases, Vol: 23, Pages: 258-263, ISSN: 1080-6040
In 2014, inactivated poliovirus vaccine (IPV) campaigns were implemented in Nigeria and Pakistan after clinical trials showed that IPV boosts intestinal immunity in children previously given oral poliovirus vaccine (OPV). We estimated the effect of these campaigns by using surveillance data collected during January 2014–April 2016. In Nigeria, campaigns with IPV and trivalent OPV (tOPV) substantially reduced the incidence of poliomyelitis caused by circulating serotype-2 vaccine–derived poliovirus (incidence rate ratio [IRR] 0.17 for 90 days after vs. 90 days before campaigns, 95% CI 0.04–0.78) and the prevalence of virus in environmental samples (prevalence ratio [PR] 0.16, 95% CI 0.02–1.33). Campaigns with tOPV alone resulted in similar reductions (IRR 0.59, 95% CI 0.18–1.97; PR 0.45, 95% CI 0.21–0.95). In Pakistan, the effect of IPV+tOPV campaigns on wild-type poliovirus was not significant. Results suggest that administration of IPV alongside OPV can decrease poliovirus transmission if high vaccine coverage is achieved.
Pons-Salort M, Molodecky NA, O'Reilly KM, et al., 2016, Population immunity against serotype-2 poliomyelitis Leading up to the global withdrawal of the oral poliovirus vaccine: spatio-temporal modelling of surveillance data, Plos Medicine, Vol: 13, ISSN: 1549-1676
BackgroundGlobal 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 FindingsIn 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 <36 mo old identified with non-polio acute flaccid paralysis (AFP) reported through polio surveillance, information on immunisation activities with different oral poliovirus vaccine (OPV) formulations, and serotype-specific estimates of the efficacy of these OPVs against poliomyelitis. District immunity estimates were spatio-temporally smoothed using a Bayesian hierarchical framework. Coverage estimates for immunisation activities were also obtained, allowing for heterogeneity within and among districts. Forward projections of immunity, based on these estimates and planned immunisation activities, were produced through to April 2016 using a cohort model.Estimated population immunity was negatively correlated with the probability of VDPV2 poliomyelitis being reported in a district. In Nigeria and Pakistan, declines in immunity during 2008–2009 and 2012–2013, respectively, were associated with outbreaks of VDPV2. Immunity has since improved in both countries as a result of increased use of trivalent OPV, and projections generally indicated sustained or improved immunity in April 2016, such that the majority of districts (99% [95% uncertainty interval 97%–100%] in Nigeria and 84% [95% uncertainty interval 77%–91%] in Pakistan) had >70
Mangal TD, Aylward RB, Shuaib F, et al., 2016, Spatial dynamics and high risk transmission pathways of poliovirus in Nigeria 2001-2013, PLOS ONE, Vol: 11, Pages: 1-14, ISSN: 1932-6203
The polio eradication programme in Nigeria has been successful in reducing incidence to just six confirmed cases in 2014 and zero to date in 2015, but prediction and management of future outbreaks remains a concern. A Poisson mixed effects model was used to describe poliovirus spread between January 2001 and November 2013, incorporating the strength of connectivity between districts (local government areas, LGAs) as estimated by three models of human mobility: simple distance, gravity and radiation models. Potential explanatory variables associated with the case numbers in each LGA were investigated and the model fit was tested by simulation. Spatial connectivity, the number of non-immune children under five years old, and season were associated with the incidence of poliomyelitis in an LGA (all P < 0.001). The best-fitting spatial model was the radiation model, outperforming the simple distance and gravity models (likelihood ratio test P < 0.05), under which the number of people estimated to move from an infected LGA to an uninfected LGA was strongly associated with the incidence of poliomyelitis in that LGA. We inferred transmission networks between LGAs based on this model and found these to be highly local, largely restricted to neighbouring LGAs (e.g. 67.7% of secondary spread from Kano was expected to occur within 10 km). The remaining secondary spread occurred along routes of high population movement. Poliovirus transmission in Nigeria is predominantly localised, occurring between spatially contiguous areas. Outbreak response should be guided by knowledge of high-probability pathways to ensure vulnerable children are protected.
Parker EPK, Grassly NC, 2016, Unravelling mucosal immunity to poliovirus, The Lancet Infectious Diseases, Vol: 16, Pages: 1310-1311, ISSN: 1474-4457
Kaliappan SP, Venugopal S, Giri S, et al., 2016, Factors determining anti-poliovirus type 3 antibodies among orally immunised Indian infants, Vaccine, Vol: 34, Pages: 4979-4984, ISSN: 1873-2518
BackgroundAmong the three poliovirus serotypes, the lowest responses after vaccination with trivalent oral polio vaccine (tOPV) are to serotype 3. Although improvements in routine immunisation and supplementary immunisation activities have greatly increased vaccine coverage, there are limited data on antibody prevalence in Indian infants.MethodsChildren aged 5–11 months with a history of not having received inactivated polio vaccine were screened for serum antibodies to poliovirus serotype 3 (PV3) by a micro-neutralisation assay according to a modified World Health Organization (WHO) protocol. Limited demographic information was collected to assess risk-factors for a lack of protective antibodies. Student’s t-test, logistic regression and multilevel logistic regression (MLR) model were used to estimate model parameters.ResultsOf 8454 children screened at a mean age of 8.3 (standard deviation [SD]-1.8) months, 88.1% (95% confidence interval (CI): 87.4–88.8) had protective antibodies to PV3. The number of tOPV doses received was the main determinant of seroprevalence; the maximum likelihood estimate yields a 37.7% (95% CI: 36.2–38.3) increase in seroprevalence per dose of tOPV. In multivariable logistic regression analysis increasing age, male sex, and urban residence were also independently associated with seropositivity (Odds Ratios (OR): 1.17 (95% CI: 1.12–1.23) per month of age, 1.27 (1.11–1.46) and 1.24 (1.05–1.45) respectively).ConclusionSeroprevalence of antibodies to PV3 is associated with age, gender and place of residence, in addition to the number of tOPV doses received. Ensuring high coverage and monitoring of response are essential as long as oral vaccines are used in polio eradication.
Parker EPK, Grassly NC, 2016, Polio vaccination: preparing for a change of routine (vol 388, pg 107, 2016), LANCET, Vol: 388, Pages: E2-E2, ISSN: 0140-6736
Pons-Salort M, Burns CC, Lyons H, et al., 2016, Preventing Vaccine-Derived Poliovirus Emergence during the Polio Endgame, PLOS Pathogens, Vol: 12, ISSN: 1553-7366
Reversion and spread of vaccine-derived poliovirus (VDPV) to cause outbreaks of poliomyelitis is a rare outcome resulting from immunisation with the live-attenuated oral poliovirus vaccines (OPVs). Global withdrawal of all three OPV serotypes is therefore a key objective of the polio endgame strategic plan, starting with serotype 2 (OPV2) in April 2016. Supplementary immunisation activities (SIAs) with trivalent OPV (tOPV) in advance of this date could mitigate the risks of OPV2 withdrawal by increasing serotype-2 immunity, but may also create new serotype-2 VDPV (VDPV2). Here, we examine the risk factors for VDPV2 emergence and implications for the strategy of tOPV SIAs prior to OPV2 withdrawal. We first developed mathematical models of VDPV2 emergence and spread. We found that in settings with low routine immunisation coverage, the implementation of a single SIA increases the risk of VDPV2 emergence. If routine coverage is 20%, at least 3 SIAs are needed to bring that risk close to zero, and if SIA coverage is low or there are persistently "missed" groups, the risk remains high despite the implementation of multiple SIAs. We then analysed data from Nigeria on the 29 VDPV2 emergences that occurred during 2004-2014. Districts reporting the first case of poliomyelitis associated with a VDPV2 emergence were compared to districts with no VDPV2 emergence in the same 6-month period using conditional logistic regression. In agreement with the model results, the odds of VDPV2 emergence decreased with higher routine immunisation coverage (odds ratio 0.67 for a 10% absolute increase in coverage [95% confidence interval 0.55-0.82]). We also found that the probability of a VDPV2 emergence resulting in poliomyelitis in >1 child was significantly higher in districts with low serotype-2 population immunity. Our results support a strategy of focused tOPV SIAs before OPV2 withdrawal in areas at risk of VDPV2 emergence and in sufficient number to raise population immuni
Parker EPK, Grassly NC, 2016, Polio vaccination: preparing for a change of routine, Lancet, Vol: 388, Pages: 9-15, ISSN: 1474-547X
Grassly NC, Praharaj I, Babji S, et al., 2016, The effect of azithromycin on the immunogenicity of oral poliovirus vaccine: a double-blind randomised placebo-controlled trial in seronegative Indian infants, Lancet Infectious Diseases, Vol: 16, Pages: 905-914, ISSN: 1473-3099
BACKGROUND: Oral poliovirus vaccine is less immunogenic and effective in low-income countries than in high-income countries, similarly to other oral vaccines. The high prevalence of intestinal pathogens and associated environmental enteropathy has been proposed to explain this problem. Because administration of an antibiotic has the potential to resolve environmental enteropathy and clear bacterial pathogens, we aimed to assess whether antibiotics would improve oral poliovirus vaccine immunogenicity. METHODS: We did a double-blind, randomised, placebo-controlled trial of the effect of azithromycin on the immunogenicity of serotype-3 monovalent oral poliovirus vaccine given to healthy infants living in 14 blocks of Vellore district, India. Infants were eligible to participate if they were 6-11 months old, available for the study duration, and lacked serum neutralising antibodies to serotype-3 poliovirus. Infants were randomly assigned (1:1) at enrolment to receive oral 10 mg/kg azithromycin or placebo once daily for 3 days, followed by serotype-3 monovalent oral poliovirus vaccine on day 14. The primary outcome was detection of serum neutralising antibodies to serotype-3 poliovirus at a dilution of one in eight or more on day 35 and was assessed in the per-protocol population (ie, all those who received azithromycin or placebo, oral poliovirus vaccine, and provided a blood sample according to the study protocol). Safety outcomes were assessed in all infants enrolled in the study. The trial is registered with the Clinical Trials Registry India, number CTRI/2014/05/004588. FINDINGS: Between Aug 5, 2014, and March 21, 2015, 754 infants were randomly assigned: 376 to receive azithromycin and 378 to placebo. Of these, 348 (93%) of 376 in the azithromycin group and 357 (94%) of 378 infants in the placebo group completed the study per protocol. In the azithromycin group, 175 (50%) seroconverted to serotype-3 poliovirus compared with 192 (54%) in the placebo group (risk rati
John J, Van Aart CJC, Grassly NC, 2016, The burden of typhoid and paratyphoid in India: systematic review and meta-analysis, PLOS Neglected Tropical Diseases, Vol: 10, ISSN: 1935-2735
BackgroundTyphoid is an important public health challenge for India, especially with the spread of antimicrobial resistance. The decision about whether to introduce a public vaccination programme needs to be based on an understanding of disease burden and the age-groups and geographic areas at risk.MethodsWe searched Medline and Web of Science databases for studies reporting the incidence or prevalence of typhoid and paratyphoid fever confirmed by culture and/or serology, conducted in India and published between 1950 and 2015. We used binomial and Poisson mixed-effects meta-regression models to estimate prevalence and incidence from hospital and community studies, and to identify risk-factors.ResultsWe identified 791 titles and abstracts, and included 37 studies of typhoid and 18 studies of paratyphoid in the systematic review and meta-analysis. The estimated prevalence of laboratory-confirmed typhoid and paratyphoid among individuals with fever across all hospital studies was 9.7% (95% CI: 5.7–16.0%) and 0.9% (0.5–1.7%) respectively. There was significant heterogeneity among studies (p-values<0.001). Typhoid was more likely to be detected among clinically suspected cases or during outbreaks and showed a significant decline in prevalence over time (odds ratio for each yearly increase in study date was 0.96 (0.92–0.99) in the multivariate meta-regression model). Paratyphoid did not show any trend over time and there was no clear association with risk-factors. Incidence of typhoid and paratyphoid was reported in 3 and 2 community cohort studies respectively (in Kolkata and Delhi, or Kolkata alone). Pooled estimates of incidence were 377 (178–801) and 105 (74–148) per 100,000 person years respectively, with significant heterogeneity between locations for typhoid (p<0.001). Children 2–4 years old had the highest incidence.ConclusionsTyphoid remains a significant burden in India, particularly among young children, despite apparen
Lopman BA, Grassly NC, 2016, Editorial Commentary: Pediatric Norovirus in Developing Countries: A Picture Slowly Comes Into Focus, Clinical Infectious Diseases, Vol: 62, Pages: 1218-1220, ISSN: 1537-6591
Blake IM, Chenoweth P, Okayasu H, et al., 2016, Faster Detection of Poliomyelitis Outbreaks to Support Polio Eradication, Emerging Infectious Diseases, Vol: 22, Pages: 449-456, ISSN: 1080-6040
As the global eradication of poliomyelitis approaches the final stages, prompt detection of new outbreaks is critical to enable a fast and effective outbreak response. Surveillance relies on reporting of acute flaccid paralysis (AFP) cases and laboratory confirmation through isolation of poliovirus from stool. However, delayed sample collection and testing can delay outbreak detection. We investigated whether weekly testing for clusters of AFP by location and time, using the Kulldorff scan statistic, could provide an early warning for outbreaks in 20 countries. A mixed-effects regression model was used to predict background rates of nonpolio AFP at the district level. In Tajikistan and Congo, testing for AFP clusters would have resulted in an outbreak warning 39 and 11 days, respectively, before official confirmation of large outbreaks. This method has relatively high specificity and could be integrated into the current polio information system to support rapid outbreak response activities.
Gambhir M, Grassly NC, Burton MJ, et al., 2015, Estimating the Future Impact of a Multi-Pronged Intervention Strategy on Ocular Disease Sequelae Caused by Trachoma: A Modeling Study, Ophthalmic Epidemiology, Vol: 22, Pages: 394-402, ISSN: 1744-5086
Purpose: Trachoma control programs are underway in endemic regions worldwide. They are based on the SAFE strategy (Surgery for trichiasis, Antibiotic distribution, Facial cleanliness, and Environmental improvement). Although much is known about the effect of community-wide treatment with antibiotics on the prevalence of Chlamydia trachomatis, the impact of the SAFE strategy on severe ocular disease sequelae (the main focus of the Global Elimination of blinding Trachoma by 2020 program) remains largely unknown.Methods: We use a mathematical model to explore the impact of each of the components of the SAFE strategy, individually and together, on disease sequelae, arising from repeat infection and subsequent conjunctival scarring. We ask whether two elimination goals, to reduce the prevalence of trachomatous trichiasis to 1 per 1000 persons, and the incidence of corneal opacity to 1 per 10,000 persons per annum, are achievable, and which combinations of interventions have the greatest impact on these indicators.Results: In high prevalence communities (here, >20% infection of children aged 1–9 years), a combination of efforts is needed to bring down sustainably the prevalence and incidence of ocular disease sequelae.Conclusion: The mass delivery of antibiotics is highly beneficial for the clearance of infection, inflammation and prevention of subsequent scarring, but needs to be supplemented with sustained reductions in transmission and surgery to consider realistically the elimination of blindness by the year 2020.
O'Reilly KM, cori A, Durry E, et al., 2015, A new method to estimate the coverage of mass vaccination campaigns against poliomyelitis from surveillance data., American Journal of Epidemiology, Vol: 182, Pages: 961-970, ISSN: 1476-6256
Mass vaccination campaigns with the oral poliovirus vaccine targeting children aged <5 years are a critical component of the global poliomyelitis eradication effort. Monitoring the coverage of these campaigns is essential to allow corrective action, but current approaches are limited by their cross-sectional nature, nonrandom sampling, reporting biases, and accessibility issues. We describe a new Bayesian framework using data augmentation and Markov chain Monte Carlo methods to estimate variation in vaccination coverage from children's vaccination histories investigated during surveillance for acute flaccid paralysis. We tested the method using simulated data with at least 200 cases and were able to detect undervaccinated groups if they exceeded 10% of all children and temporal changes in coverage of ±10% with greater than 90% sensitivity. Application of the method to data from Pakistan for 2010–2011 identified undervaccinated groups within the Balochistan/Federally Administered Tribal Areas and Khyber Pakhtunkhwa regions, as well as temporal changes in coverage. The sizes of these groups are consistent with the multiple challenges faced by the program in these regions as a result of conflict and insecurity. Application of this new method to routinely collected data can be a useful tool for identifying poorly performing areas and assisting in eradication efforts.
Ho DK, Sawicki C, Grassly N, 2015, Antibiotic Resistance in Streptococcus pneumoniae after Azithromycin Distribution for Trachoma., Journal of Tropical Medicine, Vol: 2015, ISSN: 1687-9694
Trachoma is caused by Chlamydia trachomatis and is a leading cause of blindness worldwide. Mass distribution of azithromycin (AZM) is part of the strategy for the global elimination of blinding trachoma by 2020. Although resistance to AZM in C. trachomatis has not been reported, there have been concerns about resistance in other organisms when AZM is administered in community settings. We identified studies that measured pneumococcal prevalence and resistance to AZM following mass AZM provision reported up to 2013 in Medline and Web of Science databases. Potential sources of bias were assessed using the Cochrane Risk of Bias Tool. A total of 45 records were screened, of which 8 met the inclusion criteria. We identified two distinct trends of resistance prevalence, which are dependent on frequency of AZM provision and baseline prevalence of resistance. We also demonstrated strong correlation between the prevalence of resistance at baseline and at 2-3 months (r = 0.759). Although resistance to AZM in C. trachomatis has not been reported, resistance to this commonly used macrolide antibiotic in other diseases could compromise treatment. This should be considered when planning long-term trachoma control strategies.
Parker EP, Molodecky NA, Pons-Salort M, et al., 2015, Impact of inactivated poliovirus vaccine on mucosal immunity: implications for the polio eradication endgame., Expert Review of Vaccines, Vol: 14, Pages: 1113-1123, ISSN: 1744-8395
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.
Grassly NC, 2015, New vaccine strategies to finish polio eradication, LANCET INFECTIOUS DISEASES, Vol: 15, Pages: 864-865, ISSN: 1473-3099
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- Citations: 2
Pons Salort M, Parker E, Grassly N, 2015, The epidemiology of non-polio enteroviruses: recent advances and outstanding questions, Current Opinion in Infectious Diseases, Vol: 28, Pages: 479-487, ISSN: 1473-6527
Purpose of reviewThere are over 100 serotypes of human enteroviruses, which cause a spectrum ofillnesses, including meningitis, encephalitis, paralysis, myocarditis and rash.Increasing incidence of hand-foot-and-mouth disease in the Asia-Pacific and recentoutbreaks of enterovirus-associated disease, such as severe respiratory illness in theUnited States in 2014, highlight the threat of these viruses to human health.Recent findingsWe describe recent outbreaks of human enteroviruses and summarise knowledgegaps regarding their burden, spectrum of diseases and epidemiology.SummaryReported outbreaks of respiratory, neurological, skin and eye diseases associatedwith human enteroviruses have increased in frequency and size in recent years.Improved molecular diagnostics and genetic sequence analysis are beginning toreveal the complex dynamics of individual serotypes and genotypes, and theircontribution to these outbreaks. However, the biological mechanisms underlying theiremergence and transmission dynamics remain elusive. They are likely to involvechanges in the virus, such as fitness, antigenicity, virulence or tropism, and in thehuman population, such as levels of sanitation and of homo- and heterotypicimmunity. Improvements in surveillance, serological surveys and detailed geneticand antigenic characterisation of viral populations would help to elucidate thesemechanisms. This will be important for the design of outbreak control and vaccinedevelopment strategies.
Grassly NC, Kang G, Kannpmann B, 2015, Biological challenges to effective vaccines in the developing world, PHILOSOPHICAL TRANSACTIONS OF THE ROYAL SOCIETY B-BIOLOGICAL SCIENCES, Vol: 370, ISSN: 0962-8436
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- Citations: 20
Grassly NC, 2014, Immunogenicity and Effectiveness of Routine Immunization With 1 or 2 Doses of Inactivated Poliovirus Vaccine: Systematic Review and Meta-analysis, JOURNAL OF INFECTIOUS DISEASES, Vol: 210, Pages: S439-S446, ISSN: 0022-1899
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- Citations: 45
John J, Giri S, Karthikeyan AS, et al., 2014, Effect of a single inactivated poliovirus vaccine dose on intestinal immunity against poliovirus in children previously given oral vaccine: an open-label, randomised controlled trial, The Lancet, Vol: 384, Pages: 1505-1512, ISSN: 0140-6736
BackgroundIntestinal immunity induced by oral poliovirus vaccine (OPV) is imperfect and wanes with time, permitting transmission of infection by immunised children. Inactivated poliovirus vaccine (IPV) does not induce an intestinal mucosal immune response, but could boost protection in children who are mucosally primed through previous exposure to OPV. We aimed to assess the effect of IPV on intestinal immunity in children previously vaccinated with OPV.MethodsWe did an open-label, randomised controlled trial in children aged 1–4 years from Chinnallapuram, Vellore, India, who were healthy, had not received IPV before, and had had their last dose of OPV at least 6 months before enrolment. Children were randomly assigned (1:1) to receive 0·5 mL IPV intramuscularly (containing 40, 8, and 32 D antigen units for serotypes 1, 2, and 3) or no vaccine. The randomisation sequence was computer generated with a blocked randomisation procedure with block sizes of ten by an independent statistician. The laboratory staff did blinded assessments. The primary outcome was the proportion of children shedding poliovirus 7 days after a challenge dose of serotype 1 and 3 bivalent OPV (bOPV). A second dose of bOPV was given to children in the no vaccine group to assess intestinal immunity resulting from the first dose. A per-protocol analysis was planned for all children who provided a stool sample at 7 days after bOPV challenge. This trial is registered with Clinical Trials Registry of India, number CTRI/2012/09/003005.FindingsBetween Aug 19, 2013, and Sept 13, 2013, 450 children were enrolled and randomly assigned into study groups. 225 children received IPV and 225 no vaccine. 222 children in the no vaccine group and 224 children in the IPV group had stool samples available for primary analysis 7 days after bOPV challenge. In the IPV group, 27 (12%) children shed serotype 1 poliovirus and 17 (8%) shed serotype 3 poliovirus compared with 43 (19%) and 57 (26%) in the no vac
Parker EPK, Kampmann B, Kang G, et al., 2014, Influence of Enteric Infections on Response to Oral Poliovirus Vaccine: A Systematic Review and Meta-analysis, JOURNAL OF INFECTIOUS DISEASES, Vol: 210, Pages: 853-864, ISSN: 0022-1899
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- Citations: 58
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