A pilot study using wearable global positioning system (GPS) dataloggers to compare water contact levels: Schistosoma haematobium infection in pre-school-aged children (PSAC) and their mothers at Barombi Kotto, Cameroon

Background Barombi Kotto, Cameroon serves as a reference location for assessing intervention strategies against Schistosoma haematobium. Methods As part of a pilot study, the whole community was treated with praziquantel, inclusive of pre-school-age children (PSAC) and their mothers. One year later, egg-patent infections were reassessed and water contact patterns of 12 pairs of PSAC and their mothers were measured with global positioning system (GPS) data loggers. Results A substantial reduction in general infection prevalence, from 44.8% to 12.2%, was observed but certain PSAC and mothers continued to have egg-patent infections. Analysis of GPS data demonstrated similar water contact levels between the child and mother groups, although certain individuals were numerical outliers. Conclusions This study shows the potential of GPS data loggers to clarify the at-risk status of PSAC and mothers

Intradermal Administration of Fractional Doses of Inactivated Poliovirus Vaccine: A Dose-Sparing Option for Polio Immunization.

A fractional dose of inactivated poliovirus vaccine (fIPV) administered by the intradermal route delivers one fifth of the full vaccine dose administered by the intramuscular route and offers a potential dose-sparing strategy to stretch the limited global IPV supply while further improving population immunity. Multiple studies have assessed immunogenicity of intradermal fIPV compared with the full intramuscular dose and demonstrated encouraging results. Novel intradermal devices, including intradermal adapters and disposable-syringe jet injectors, have also been developed and evaluated as alternatives to traditional Bacillus Calmette-Guérin needles and syringes for the administration of fIPV. Initial experience in India, Pakistan, and Sri Lanka suggests that it is operationally feasible to implement fIPV vaccination on a large scale. Given the available scientific data and operational feasibility shown in early-adopter countries, countries are encouraged to consider introducing a fIPV strategy into their routine immunization and supplementary immunization activities

The impact of surveillance and other factors on detection of emergent and circulating vaccine derived polioviruses.

Background: Circulating vaccine derived poliovirus (cVDPV) outbreaks remain a threat to polio eradication. To reduce cases of polio from cVDPV of serotype 2, the serotype 2 component of the vaccine has been removed from the global vaccine supply, but outbreaks of cVDPV2 have continued. The objective of this work is to understand the factors associated with later detection in order to improve detection of these unwanted events. Methods: The number of nucleotide differences between each cVDPV outbreak and the oral polio vaccine (OPV) strain was used to approximate the time from emergence to detection. Only independent emergences were included in the analysis. Variables such as serotype, surveillance quality, and World Health Organization (WHO) region were tested in a negative binomial regression model to ascertain whether these variables were associated with higher nucleotide differences upon detection. Results: In total, 74 outbreaks were analysed from 24 countries between 2004-2019. For serotype 1 (n=10), the median time from seeding until outbreak detection was 284 (95% uncertainty interval (UI) 284-2008) days, for serotype 2 (n=59), 276 (95% UI 172-765) days, and for serotype 3 (n=5), 472 (95% UI 392-603) days. Significant improvement in the time to detection was found with increasing surveillance of non-polio acute flaccid paralysis (AFP) and adequate stool collection. Conclusions: cVDPVs remain a risk; all WHO regions have reported at least one VDPV outbreak since the first outbreak in 2000 and outbreak response campaigns using monovalent OPV type 2 risk seeding future outbreaks. Maintaining surveillance for poliomyelitis after local elimination is essential to quickly respond to both emergence of VDPVs and potential importations as low-quality AFP surveillance causes outbreaks to continue undetected. Considerable variation in the time between emergence and detection of VDPVs were apparent, and other than surveillance quality and inclusion of environmental surveillance, the reasons for this remain unclear

Prolonged Excretion of Poliovirus among Individuals with Primary Immunodeficiency Disorder: An Analysis of the World Health Organization Registry.

Individuals with primary immunodeficiency disorder may excrete poliovirus for extended periods and will constitute the only remaining reservoir of virus after eradication and withdrawal of oral poliovirus vaccine. Here, we analyzed the epidemiology of prolonged and chronic immunodeficiency-related vaccine-derived poliovirus cases in a registry maintained by the World Health Organization, to identify risk factors and determine the length of excretion. Between 1962 and 2016, there were 101 cases, with 94/101 (93%) prolonged excretors and 7/101 (7%) chronic excretors. We documented an increase in incidence in recent decades, with a shift toward middle-income countries, and a predominance of poliovirus type 2 in 73/101 (72%) cases. The median length of excretion was 1.3 years (95% confidence interval: 1.0, 1.4) and 90% of individuals stopped excreting after 3.7 years. Common variable immunodeficiency syndrome and residence in high-income countries were risk factors for long-term excretion. The changing epidemiology of cases, manifested by the greater incidence in recent decades and a shift to from high- to middle-income countries, highlights the expanding risk of poliovirus transmission after oral poliovirus vaccine cessation. To better quantify and reduce this risk, more sensitive surveillance and effective antiviral therapies are needed

The impact of surveillance and other factors on detection of emergent and circulating vaccine derived polioviruses [version 3; peer review: 2 approved, 1 approved with reservations]

Background: Circulating vaccine derived poliovirus (cVDPV) outbreaks remain a threat to polio eradication. To reduce cases of polio from cVDPV of serotype 2, the serotype 2 component of the vaccine has been removed from the global vaccine supply, but outbreaks of cVDPV2 have continued. The objective of this work is to understand the factors associated with later detection in order to improve detection of these unwanted events. Methods: The number of nucleotide differences between each cVDPV outbreak and the oral polio vaccine (OPV) strain was used to approximate the time from emergence to detection. Only independent emergences were included in the analysis. Variables such as serotype, surveillance quality, and World Health Organization (WHO) region were tested in a negative binomial regression model to ascertain whether these variables were associated with higher nucleotide differences upon detection. Results: In total, 74 outbreaks were analysed from 24 countries between 2004-2019. For serotype 1 (n=10), the median time from seeding until outbreak detection was 572 (95% uncertainty interval (UI) 279-2016), for serotype 2 (n=59), 276 (95% UI 172-765) days, and for serotype 3 (n=5), 472 (95% UI 392-603) days. Significant improvement in the time to detection was found with increasing surveillance of non-polio acute flaccid paralysis (AFP) and adequate stool collection. Conclusions: cVDPVs remain a risk; all WHO regions have reported at least one VDPV outbreak since the first outbreak in 2000 and outbreak response campaigns using monovalent OPV type 2 risk seeding future outbreaks. Maintaining surveillance for poliomyelitis after local elimination is essential to quickly respond to both emergence of VDPVs and potential importations as low-quality AFP surveillance causes outbreaks to continue undetected. Considerable variation in the time between emergence and detection of VDPVs were apparent, and other than surveillance quality and inclusion of environmental surveillance, the reasons for this remain unclear

A pilot study using wearable global positioning system data loggers to compare water contact levels:Schistosoma haematobium infection in pre-school-age children (PSAC) and their mothers at Barombi Kotto, Cameroon

Background: Barombi Kotto, Cameroon serves as a reference location for assessing intervention strategies against Schistosoma haematobium. Methods: As part of a pilot study, the whole community was treated with praziquantel, inclusive of preschool- age children (PSAC) and their mothers. One year later, egg-patent infections were reassessed and water contact patterns of 12 pairs of PSAC and their mothers were measured with global positioning system (GPS) data loggers. Results: A substantial reduction in general infection prevalence, from 44.8% to 12.2%, was observed but certain PSAC and mothers continued to have egg-patent infections. Analysis of GPS data demonstrated similar water contact levels between the child and mother groups, although certain individuals were numerical outliers. Conclusions: This study shows the potential of GPS data loggers to clarify the at-risk status of PSAC and mothers. © 2018 The Author(s)

Vaccine schedules and the effect on humoral and intestinal immunity against poliovirus: a systematic review and network meta-analysis.

BACKGROUND: The eradication of wild and vaccine-derived poliovirus requires the global withdrawal of oral poliovirus vaccines (OPVs) and replacement with inactivated poliovirus vaccines (IPVs). The first phase of this effort was the withdrawal of the serotype 2 vaccine in April 2016, with a switch from trivalent OPVs to bivalent OPVs. The aim of our study was to produce comparative estimates of humoral and intestinal mucosal immunity associated with different routine immunisation schedules. METHODS: We did a random-effect meta-analysis with single proportions and a network meta-analysis in a Bayesian framework to synthesise direct and indirect data. We searched MEDLINE and the Cochrane Library Central Register of Controlled Trials for randomised controlled trials published from Jan 1, 1980, to Nov 1, 2018, comparing poliovirus immunisation schedules in a primary series. Only trials done outside western Europe or North America and without variation in age schedules (ie, age at administration of the vaccine) between study groups were included in the analyses, because trials in high-income settings differ in vaccine immunogenicity and schedules from other settings and to ensure consistency within the network of trials. Data were extracted directly from the published reports. We assessed seroconversion against poliovirus serotypes 1, 2, and 3, and intestinal immunity against serotype 2, measured by absence of shedding poliovirus after a challenge OPV dose. FINDINGS: We identified 437 unique studies; of them, 17 studies with a maximum of 8279 evaluable infants were eligible for assessment of humoral immunity, and eight studies with 4254 infants were eligible for intestinal immunity. For serotype 2, there was low between-trial heterogeneity in the data (τ=0·05, 95% credible interval [CrI] 0·009-0·15) and the risk ratio (RR) of seroconversion after three doses of bivalent OPVs was 0·14 (95% CrI 0·11-0·17) compared with three doses of trivalent OPVs. The addition of one or two full doses of an IPV after a bivalent OPV schedule increased the RR to 0·85 (0·75-1·0) and 1·1 (0·98-1·4). However, the addition of an IPV to bivalent OPV schedules did not significantly increase intestinal immunity (0·33, 0·18-0·61), compared with trivalent OPVs alone. For serotypes 1 and 3, there was susbstantial inconsistency and between-trial heterogeneity between direct and indirect effects, so we only present pooled estmates on seroconversion, which were at least 80% for serotype 1 and at least 88% for serotype 3 for all vaccine schedules. INTERPRETATION: For WHO's polio eradication programme, the addition of one IPV dose for all birth cohorts should be prioritised to protect against paralysis caused by type 2 poliovirus; however, this inclusion will not prevent transmission or circulation in areas with faecal-oral transmission. FUNDING: UK Medical Research Council

Epidemiology of type 2 vaccine-derived poliovirus outbreaks between 2016 and 2020.

The number and geographic breadth of circulating vaccine-derived poliovirus type 2 (cVDPV2) outbreaks detected after the withdrawal of type 2 containing oral polio vaccine (April 2016) have exceeded forecasts.Using Acute Flaccid Paralysis (AFP) investigations and environmental surveillance (ES) data from the Global Polio Laboratory Network, we summarize the epidemiology of cVDPV2 outbreaks. Between 01 January 2016 to 31 December 2020, a total of 68 unique cVDPV2 genetic emergences were detected across 34 countries. The cVDPV2 outbreaks have been associated with 1596 acute flaccid paralysis cases across four World Health Organization regions: 962/1596 (60.3%) cases occurred in African Region; 619/1596 (38.8%) in the Eastern Mediterranean Region; 14/1596 (0.9%) in Western-Pacific Region; and 1/1596 (0.1%) in the European Region. As the majority of the cVDPV2 outbreaks have been seeded through monovalent type 2 oral poliovirus vaccine (mOPV2) use in outbreak responses, the introduction of the more stable novel oral poliovirus vaccine will be instrumental in stopping emergence of new cVDPV2 lineages

Update on Immunodeficiency-Associated Vaccine-Derived Polioviruses - Worldwide, July 2018-December 2019.

Since establishment of the Global Polio Eradication Initiative* in 1988, polio cases have declined >99.9% worldwide; extensive use of live, attenuated oral poliovirus vaccine (OPV) in routine childhood immunization programs and mass campaigns has led to eradication of two of the three wild poliovirus (WPV) serotypes (types 2 and 3) (1). Despite its safety record, OPV can lead to rare emergence of vaccine-derived polioviruses (VDPVs) when there is prolonged circulation or replication of the vaccine virus. In areas with inadequate OPV coverage, circulating VDPVs (cVDPVs) that have reverted to neurovirulence can cause outbreaks of paralytic polio (2). Immunodeficiency-associated VDPVs (iVDPVs) are isolated from persons with primary immunodeficiency (PID). Infection with iVDPV can progress to paralysis or death of patients with PID, and excretion risks seeding cVDPV outbreaks; both risks might be reduced through antiviral treatment, which is currently under development. This report updates previous reports and includes details of iVDPV cases detected during July 2018-December 2019 (3). During this time, 16 new iVDPV cases were reported from five countries (Argentina, Egypt, Iran, Philippines, and Tunisia). Alongside acute flaccid paralysis (AFP) surveillance (4), surveillance for poliovirus infections among patients with PID has identified an increased number of persons excreting iVDPVs (5). Expansion of PID surveillance will facilitate early detection and follow-up of iVDPV excretion among patients with PID to mitigate the risk for iVDPV spread. This will be critical to help identify all poliovirus excretors and thus achieve and maintain eradication of all polioviruses

Prolonged Excretion of Poliovirus among Individuals with Primary Immunodeficiency Disorder: An Analysis of the World Health Organization Registry

Individuals with primary immunodeficiency disorder may excrete poliovirus for extended periods and will constitute the only remaining reservoir of virus after eradication and withdrawal of oral poliovirus vaccine. Here, we analyzed the epidemiology of prolonged and chronic immunodeficiency-related vaccine-derived poliovirus cases in a registry maintained by the World Health Organization, to identify risk factors and determine the length of excretion. Between 1962 and 2016, there were 101 cases, with 94/101 (93%) prolonged excretors and 7/101 (7%) chronic excretors. We documented an increase in incidence in recent decades, with a shift toward middle-income countries, and a predominance of poliovirus type 2 in 73/101 (72%) cases. The median length of excretion was 1.3 years (95% confidence interval: 1.0, 1.4) and 90% of individuals stopped excreting after 3.7 years. Common variable immunodeficiency syndrome and residence in high-income countries were risk factors for long-term excretion. The changing epidemiology of cases, manifested by the greater incidence in recent decades and a shift to from high- to middle-income countries, highlights the expanding risk of poliovirus transmission after oral poliovirus vaccine cessation. To better quantify and reduce this risk, more sensitive surveillance and effective antiviral therapies are needed