Strengthening the Acute Flaccid Paralysis (AFP) Surveillance Component of the Polio Eradication Initiative through Short Message Service (SMS) Reminders; Experience from Sokoto State, Nigeria 2014.

Eradication of poliomyelitis remains a public health priority due to the paralytic effects of the virus on children and impact on global health system. However, existing gaps in surveillance can hinder eradication. Improved timeliness of identification and reporting of acute flaccid paralysis (AFP) cases with further confirmation of Wild Poliovirus (WPV) in stool samples, can help Nigeria achieve the performance indicators of non-polio AFP rate of ≥ 2/100,000 population aged < 15 years and ≥80% stool sample collection adequacy. To ascertain the awareness of AFP case definition and detection by health care workers and to evaluate the impact of SMS-based reporting on the AFP surveillance system the study was conducted from November 2013 to July 2014. In Sokoto state, 112 health facilities (focal sites) were operational and participated in this study. All AFP focal points for the 112 facilities were included in the study. In addition to AFP focal points, two clinicians per facility where possible, were included in the study. The study focused exclusively on reports from focal sites. The methodology was a one group pretest-posttest design conducted in 3 phases. 1) Pre-intervention Knowledge, Attitude and Practices (KAP) survey, 2) SMS implementation and 3) Post-intervention KAP. Results were analysed using the independent sample t-test to assess the increase in knowledge, attitudes, or practice scores pre- and post- training. The study showed improved knowledge gap of health care workers on AFP surveillance between pre and post intervention. It shows that this approach of improved surveillance will be effective in countries in hard to reach, access compromised or countries/place without sufficient surveillance staff.

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.

Regulatory Aspects of Sabin Type 2 Withdrawal From Trivalent Oral Poliovirus Vaccine: Process and Lessons Learned.

Withdrawal of type 2 oral poliovirus vaccine (OPV) in OPV-using countries required regulatory approval for use of inactivated poliovirus vaccine and bivalent OPV in routine immunization. Worldwide, a variety of mechanisms were used by member states, with some differences in approach observed between inactivated poliovirus vaccine and bivalent OPV. These included acceptance for use of World Health Organization (WHO) prequalified vaccines, registration and licensure pathways, participation in WHO-convened joint reviews of licensing dossiers, as well as pragmatic application of alternatively available mechanisms, when appropriate. Simple but effective tools were used to monitor progress and to record, authenticate, and share information. Essential to achievement of regulatory targets was ongoing communication with key stakeholders, including switch-country national regulatory authorities, vaccine manufacturers, partner organizations, and relevant units within WHO. Understanding of the regulatory environment gained through the OPV switch can be helpful in supporting further stages of the polio end game and other time-sensitive vaccine introduction programs.

Satellite imagery technology in public health: analysis of site catchment areas for assessment of poliovirus circulation in Nigeria and Niger.

Environmental surveillance supplements the surveillance of acute flaccid paralysis by monitoring wastewater for poliovirus circulation. Building on previous work, we analysed wastewater flow to optimise selection and placement of sampling sites with higher digital surface model (DSM) resolution. The newly developed 5-m mesh DSM from the panchromatic, remote-sensing instruments for stereo mapping on-board the Japanese advanced land observing satellite was used to estimate catchment areas and flow of sewage water based on terrain topography. Optimal sampling sites for environmental surveillance were identified to maximise sensitivity to poliovirus circulation. Population data were overlaid to prioritise selection of catchment areas with dense populations. The results for Kano City, Nigeria were compared with an analysis based on existing 30- and 90-m mesh digital elevation model (DEM). Analysis based on 5-m mesh DSM was also conducted for three cities in Niger to prioritise the selection of new sites. The analysis demonstrated the feasibility of using DSMs to estimate catchment areas and population size for programme planning and outbreak response with respect to polio. Alternative sampling points in Kano City that would cover a greater population size have been identified and potential sampling sites in Niger are proposed. Comparison with lower-resolution DEMs suggests that the use of a 5-m mesh DSMs would be useful where the terrain is flat or includes small-scale topographic changes not captured by 30-m data searches.

Poliovirus seroprevalence before and after interruption of poliovirus transmission in Kano State, Nigeria.

INTRODUCTION: In September 2015, Nigeria was removed from the list of polio-endemic countries after more than 12months had passed since the detection of last wild poliovirus case in the country on 24 July 2014. We are presenting here a report of two polio seroprevalence surveys conducted in September 2013 and October 2014, respectively, in the Kano state of northern Nigeria. METHODS: Health facility based seroprevalence surveys were undertaken at Murtala Mohammad Specialist Hospital, Kano. Parents or guardians of children aged 6-9months, 36-47months, 5-9years and 10-14years in 2013 and 6-9months and 19-22months (corresponding to 6-9months range at the time of 2013 survey) in 2014 presenting to the outpatient department, were approached for participation, screened for eligibility and asked to provide informed consent. A questionnaire was administered and a blood sample collected for polio neutralization assay. RESULTS: Among subjects aged 6-9months in the 2013 survey, seroprevalence was 58% (95% confidence interval [CI] 51-66%) to poliovirus type 1, 42% (95% CI 34-50%) to poliovirus type 2, and 52% (95% CI 44-60%) to poliovirus type 3. Among children 36-47months and older, seroprevalence was 85% or higher for all three serotypes. In 2014, seroprevalence in 6-9month infants was 72% (95% CI 65-79%) for type 1, 59% (95% CI 52-66%) for type 2, and 65% (95% CI 57-72%) for type 3 and in 19-22months, 80% (95% CI 74-85%), 57% (49-63%) and 78% (71-83%) respectively. Seroprevalence was positively associated with history of increasing oral poliovirus vaccine doses. CONCLUSIONS: There was significant improvement in seroprevalence in 2014 over the 2013 levels indicating a positive impact of recent programmatic interventions. However the continued low seroprevalence in 6-9month age is a concern and calls for improved immunization efforts to sustain the polio-free Nigeria.

Role of Serial Polio Seroprevalence Studies in Guiding Implementation of the Polio Eradication Initiative in Kano, Nigeria: 2011-2014.

BACKGROUND: Nigeria was one of 3 polio-endemic countries before it was de-listed in September 2015 by the World Health Organization, following interruption of transmission of the poliovirus. During 2011-2014, Nigeria conducted serial polio seroprevalence surveys (SPS) in Kano Metropolitan Area, comprising 8 local government areas (LGAs) in Kano that is considered very high risk (VHR) for polio, to monitor performance of the polio eradication program and guide the program in the adoption of innovative strategies. METHODS: Study subjects who resided in any of the 8 local government areas of Kano Metropolitan Area and satisfied age criteria were recruited from patients at Murtala Mohammed Specialist Hospital (Kano) for 3 seroprevalence surveys. The same methods were used to conduct each survey. RESULTS: The 2011 study showed seroprevalence values of 81%, 75%, and 73% for poliovirus types 1, 2, and 3, respectively, among infants aged 6-9 months age. Among children aged 36-47 months, seroprevalence values were greater (91%, 87%, and 85% for poliovirus types 1, 2, and 3, respectively).In 2013, the results showed that the seroprevalence was unexpectedly low among infants aged 6-9 months, remained high among children aged 36-47 months, and increased minimally among children aged 5-9 years and those aged 10-14 years. The baseline seroprevalence among infants aged 6-9 months in 2014 was better than that in 2013. CONCLUSIONS: The results from the polio seroprevalence surveys conducted in Kano Metropolitan Area in 2011, 2013, and 2014 served to assess the trends in immunity and program performance, as well as to guide the program, leading to various interventions being implemented with good effect, as evidenced by the reduction of poliovirus circulation in Kano.

Immunogenicity of a new routine vaccination schedule for global poliomyelitis prevention: an open-label, randomised controlled trial.

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).

Cluster lot quality assurance sampling: effect of increasing the number of clusters on classification precision and operational feasibility.

BACKGROUND: To assess the quality of supplementary immunization activities (SIAs), the Global Polio Eradication Initiative (GPEI) has used cluster lot quality assurance sampling (C-LQAS) methods since 2009. However, since the inception of C-LQAS, questions have been raised about the optimal balance between operational feasibility and precision of classification of lots to identify areas with low SIA quality that require corrective programmatic action. METHODS: To determine if an increased precision in classification would result in differential programmatic decision making, we conducted a pilot evaluation in 4 local government areas (LGAs) in Nigeria with an expanded LQAS sample size of 16 clusters (instead of the standard 6 clusters) of 10 subjects each. RESULTS: The results showed greater heterogeneity between clusters than the assumed standard deviation of 10%, ranging from 12% to 23%. Comparing the distribution of 4-outcome classifications obtained from all possible combinations of 6-cluster subsamples to the observed classification of the 16-cluster sample, we obtained an exact match in classification in 56% to 85% of instances. CONCLUSIONS: We concluded that the 6-cluster C-LQAS provides acceptable classification precision for programmatic action. Considering the greater resources required to implement an expanded C-LQAS, the improvement in precision was deemed insufficient to warrant the effort.

Affordable inactivated poliovirus vaccine: strategies and progress.

After polio eradication is achieved, the use of live-attenuated oral poliovirus vaccine (OPV) must be discontinued because of the inherent risk of the Sabin strains to revert to neurovirulence and reacquire greater transmissibility that could potentially result in the reestablishment of polio transmission. In 2008, the World Health Assembly mandated that the World Health Organization establish a strategy for developing more-affordable inactivated poliovirus vaccine (IPV) options for low-income countries. In 2012, the Strategic Advisory Group of Experts (SAGE) on Immunization recommended universal IPV introduction as a risk-mitigation strategy before the phased cessation of OPV (starting with Sabin type 2) and emphasized the need for affordable IPV options. In 2013, SAGE reiterated the importance of attaining the long-term target price of IPV at approximately $0.5 per immunizing dose and encouraged accelerated efforts to develop lower-cost IPV options. This article outlines the 4-pronged approach that is being pursued to develop affordable options and provides an update on the current status and plans to make IPV affordable for developing-country use.

Monitoring service delivery for universal health coverage: the Service Availability and Readiness Assessment.

OBJECTIVE: To describe the Service Availability and Readiness Assessment (SARA) and the results of its implementation in six countries across three continents. METHODS: The SARA is a comprehensive approach for assessing and monitoring health service availability and the readiness of facilities to deliver health-care interventions, with a standardized set of indicators that cover all main programmes. Standardized data-collection instruments are used to gather information on a defined set of selected tracer items from public and private health facilities through a facility sample survey or census. Results from assessments in six countries are shown. FINDINGS: The results highlight important gaps in service delivery that are obstacles to universal access to health services. Considerable variation was found within and across countries in the distribution of health facility infrastructure and workforce and in the types of services offered. Weaknesses in laboratory diagnostic capacities and gaps in essential medicines and commodities were common across all countries. CONCLUSION: The SARA fills an important information gap in monitoring health system performance and universal health coverage by providing objective and regular information on all major health programmes that feeds into country planning cycles.

Mapping cis-acting regulatory variation in recombinant congenic strains.

We present an integrated approach for the enriched detection of genes subject to cis-acting variation in the mouse genome. Gene expression profiling was performed with lung tissue from a panel of recombinant congenic strains (RCS) derived from A/J and C57BL/6J inbred mouse strains. A multiple-regression model measuring the association between gene expression level, donor strain of origin (DSO), and predominant strain background identified over 1,500 genes (P < 0.05) whose expression profiles differed according to the DSO. This model also identified over 1,200 genes whose expression showed dependence on background (P < 0.05), indicating the influence of background genetic context on transcription levels. Sequences obtained from 1-kb segments of 3'-untranslated regions identified single nucleotide polymorphisms in 64% of genes whose expression levels correlated with DSO status, compared with 29% of genes that displayed no association (P < 0.01, Fisher exact test). Allelic imbalance was identified in 50% of genes positive for expression-DSO association, compared with 22% of negative genes (P < 0.05, Fisher exact test). Together, these results demonstrate the utility of RCS mice for identifying the roles of proximal genetic determinants and background genetic context in determining gene expression levels. We propose the use of this integrated experimental approach in multiple tissues from this and other RCS panels as a means for genome-wide cataloging of genetic regulatory mechanisms in laboratory strains of mice.