Immune predictors of oral poliovirus vaccine immunogenicity among infants in south India

Identification of the causes of poor oral vaccine immunogenicity in low-income countries might lead to more effective vaccines. We measured mucosal and systemic immune parameters at the time of vaccination with oral poliovirus vaccine (OPV) in 292 Indian infants aged 6–11 months, including plasma cytokines, leukocyte counts, fecal biomarkers of environmental enteropathy and peripheral blood T-cell phenotype, focused on gut-homing regulatory CD4+ populations. We did not find a distinct immune phenotype associated with OPV immunogenicity, although viral pathogens were more prevalent in stool at the time of immunization among infants who failed to seroconvert (63.9% vs. 45.6%, p = 0.002). Using a machine-learning approach, we could predict seroconversion a priori using immune parameters and infection status with a median 58% accuracy (cross-validation IQR: 50–69%) compared with 50% expected by chance. Better identification of immune predictors of OPV immunogenicity is likely to require sampling of mucosal tissue and improved oral poliovirus infection models

Unravelling mucosal immunity to poliovirus

Comment - No abstrac

Antibiotic Resistance in Streptococcus pneumoniae after Azithromycin Distribution for Trachoma.

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

Population sensitivity of acute flaccid paralysis and environmental surveillance for serotype 1 poliovirus in Pakistan: an observational study

Background To support poliomyelitis eradication in Pakistan, environmental surveillance (ES) of wastewater has been expanded alongside surveillance for acute flaccid paralysis (AFP). ES is a relatively new method of surveillance, and the population sensitivity of detecting poliovirus within endemic settings requires estimation. Methods Data for wild serotype 1 poliovirus from AFP and ES from January 2011 to September 2015 from 14 districts in Pakistan were analysed using a multi-state model framework. This framework was used to estimate the sensitivity of poliovirus detection from each surveillance source and parameters such as the duration of infection within a community. Results The location and timing of poliomyelitis cases showed spatial and temporal variability. The sensitivity of AFP surveillance to detect serotype 1 poliovirus infection in a district and its neighbours per month was on average 30.0% (95% CI 24.8–35.8) and increased with the incidence of poliomyelitis cases. The average population sensitivity of a single environmental sample was 59.4% (95% CI 55.4–63.0), with significant variation in site-specific estimates (median varied from 33.3–79.2%). The combined population sensitivity of environmental and AFP surveillance in a given month was on average 98.1% (95% CI 97.2–98.7), assuming four samples per month for each site. Conclusions ES can be a highly sensitive supplement to AFP surveillance in areas with converging sewage systems. As ES for poliovirus is expanded, it will be important to identify factors associated with variation in site sensitivity, leading to improved site selection and surveillance system performance

The burden of typhoid and paratyphoid in India: systematic review and meta-analysis

BACKGROUND:Typhoid 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. METHODS:We 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. RESULTS:We 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. CONCLUSIONS:Typhoid remains a significant burden in India, particularly among young children, despite apparent declines in prevalence. Infant immunisation with newly-licensed conjugate vaccines could address this challenge

Influence of Enteric Infections on Response to Oral Poliovirus Vaccine: A Systematic Review and Meta-analysis

BACKGROUND: The impaired immunogenicity of oral poliovirus vaccine (OPV) in low-income countries has been apparent since the early field trials of this vaccine. Infection with enteropathogens at the time of vaccination may contribute to this phenomenon. However, the relative influence of these infections on OPV performance remains uncertain. METHODS: We conducted a systematic review to examine the impact of concurrent enteric infections on OPV response. Using random-effects models, we assessed the effects of nonpolio enteroviruses (NPEVs) and diarrhea on the odds of seroconversion and/or vaccine virus shedding. RESULTS: We identified 25 trials in which OPV outcomes were compared according to the presence or absence of enteric infections, the majority of which (n = 17) reported only on NPEVs. Concurrent NPEVs significantly reduced the odds of per-dose seroconversion for type 1 poliovirus (odds ratio [OR] 0.44, 95% confidence interval 0.23-0.84), but not type 2 (OR 0.53 [0.19-1.46]) or type 3 (OR 0.56 [0.27-1.12]). A similar reduction, significant for type 1 poliovirus (OR 0.50 [0.28-0.89]), was observed in the odds of vaccine virus shedding among NPEV-infected individuals. Concurrent diarrhea significantly inhibited per-dose seroconversion overall (OR 0.61 [0.38-0.87]). CONCLUSIONS: Our findings are consistent with an inhibitory effect of concurrent enteric infections on OPV response

Facilitating word retrieval in people with aphasia: an exploration of the relationship between language and neuropsychological processing

Background: The challenge of understanding word retrieval is one that has long been the subject of investigation in aphasia therapy research, and has been confounded by the finding that people with similar patterns of language impairment can respond in different ways to the same therapy approach. Consideration has now turned to factors other than just language processes when planning intervention, including extra-linguistic cognitive processes, and the provision, and type, of feedback given. Aims: To investigate the language and neuropsychological processing abilities of people with aphasia, and to examine how these abilities relate to response to facilitation and feedback. Methods & Procedures: Eight adults with aphasia, aged between 25 and 81, participated in a case series design. A novel battery of language and neuropsychological assessments was administered. Five facilitation studies were carried out, in which the effect on word retrieval at a later point in time was investigated for different linguistic cues and use of feedback. Outcomes & Results: The differences in participants’ profiles enabled significant theoretically-motivated correlations to be identified between several aspects of processing within the areas under investigation: language, facilitation, neuropsychology and feedback. Conclusions & Implications: Assessments of memory and attention show potential for use within a wider battery administered by clinicians. Measures of executive function were less straightforward, due in part to its multifaceted nature; assessments of this domain should therefore be considered on an individual basis with regards to the underlying processes measured. Language skills alone are not able to predict response to facilitation. Facilitation was found to be a robust and valid tool and it is suggested that it may be used as a reliable probe tool to identify appropriate therapy techniques. Clinician-delivered feedback can improve word retrieval for responses that were initially incorrect; promoting self-feedback following correct responses can result in superior delayed naming

Aphasia rehabilitation: Does generalisation from anomia therapy occur and is it predictable? A case series study

Introduction: The majority of adults with acquired aphasia have anomia which can respond to rehabilitation with cues. However, the literature and clinical consensus suggest change is usually limited to treated items. We investigated the effect of an experimentally controlled intervention using progressive cues in the rehabilitation of noun retrieval/production in 16 participants with chronic aphasia. Method: Participants were sub-divided relative to the group according to performance on semantic tasks (spoken/written word to picture matching) and phonological output processing (presence/absence of word length effect and proportion of phonological errors in picture naming) in order to investigate outcome in relation to language profile. Cueing therapy took place weekly for 8 weeks. Results: Intervention resulted in significant improvement on naming treated items for 15/16 participants, with stable performance on control tasks. Change occurred at the point of intervention and not during pre-therapy assessments. We predicted particular patterns of generalisation which were upheld. Only participants classified as having relatively less of a semantic difficulty and more of a phonological output deficit demonstrated generalisation to untreated items. Outcome did not relate to traditional aphasia classification. Conclusion: A cueing hierarchy can improve word retrieval/production for adults with aphasia. In some cases generalisation to untreated items also occurs. The study demonstrates that the results of behavioural testing can be used to guide predictions of recovery with intervention. © 2013 Elsevier Ltd

Therapy for word finding difficulties using phonological and orthographic cues: a clinical application in progress

Semantic therapy for anomia is well established both in research and in clinical practise. Research into phonological therapy is more limited and the results more equivocal. This paper will describe an ongoing clinical study which uses combined phonological and orthographic cues to treat anomia in a case series design. The study includes a single cue and a choice of cue condition, and also assesses the effect of repeated presentation of a picture for naming without cues on word retrieval. The results of therapy for picture naming and for word retrieval in natural conversation will be presented for two participants