Randomized Controlled Clinical Trial of Bivalent Oral Poliovirus Vaccine and Inactivated Poliovirus Vaccine in Nigerian Children.

BACKGROUND: We conducted a trial in Nigeria to assess the immunogenicity of the new bivalent oral poliovirus vaccine + inactivated poliovirus vaccine (bOPV+IPV) immunization schedule and gains in type 2 immunity with addition of second dose of IPV. The trial was conducted in August 2016-March 2017, well past the trivalent OPV-bOPV switch in April 2016. METHODS: This was an open-label, 2-arm, noninferiority, multicenter, randomized, controlled trial. We enrolled 572 infants aged ≤14 days and randomized them into 2 arms. Arm A received bOPV at birth, 6, and 10 weeks, bOPV+IPV at week 14, and IPV at week 18. Arm B received IPV each at 6, 10, and 14 weeks and bOPV at 18 weeks of age. RESULTS: Seroconversion rates for poliovirus types 1 and 3, respectively, were 98.9% (95% confidence interval [CI], 96.7-99.8) and 98.1% (95% CI, 88.2-94.8) in Arm A and 89.6% (95% CI, 85.4-93.0) and 98.5% (95% CI, 96.3-99.6) in Arm B. Type 2 seroconversion with 1 dose IPV in Arm A was 72.0% (95% CI, 66.2-77.3), which increased significantly with addition of second dose to 95.9% (95% CI, 92.8-97.9). CONCLUSIONS: This first trial on the new Expanded Program on Immunization (EPI) schedule in a sub-Saharan African country demonstrated excellent immunogenicity against poliovirus types 1 and 3 and substantial/enhanced immunogenicity against poliovirus type 2 after 1 to 2 doses of IPV, respectively.

Trends in Poliovirus Seroprevalence in Kano State, Northern Nigeria.

Background: Kano state has been a protracted reservoir of poliovirus in Nigeria. Immunity trends have been monitored through seroprevalence surveys since 2011. The survey in 2015 was, in addition, intended to assess the impact of use of inactivated poliovirus vaccine (IPV). Methods: It was a health facility based seroprevalence survey. Eligible children aged 6-9, 12-15 and 19-22 months of age brought to the paediatrics outpatient department of Murtala Mohammad Specialist Hospital between 19 October and 6 November 2015, were screened for eligibility. Eligible children were enrolled after parental consent, history taken, physical examination conducted, and a blood sample collected to test for neutralizing antibody titres against the three poliovirus serotypes. Results: Overall, 365 results were available in the three age groups. In the 6-9-month-old age group, the seroprevalence was 73% (95% confidence interval [CI] 64-80%), 83% (95% CI 75-88%), and 66% (95% CI 57-73%) for serotypes 1, 2, and 3, respectively. In the 12-15- and 19-22-month-old age groups, seroprevalence was higher but still remained <90% across serotypes. Seroprevalence to serotypes 1 and 3 in 2015 was similar to 2014; however, for serotype 2 there was a significant improvement. IPV received in supplemental immunization activities was found to be a significant predictor of seropositivity among 6-9-month-old infants for serotypes 1 and 2. Conclusions: Seroprevalence for serotypes 1 and 3 remains low (<80%) in 6-9-month-olds. This poses a significant risk for poliovirus spread if reintroduced into the population. Efforts to strengthen immunization coverage are imperative to secure and sustain high population immunity.

Profile of polio-compatible cases in Nigeria, 2006-2016.

BACKGROUND: The tremendous progress made by Nigeria towards polio eradication has recently suffered a setback with the isolation of circulating vaccine-derived poliovirus (cVDPV) type 2 from environmental samples and confirmation of four wild poliovirus (WPV) cases from acute flaccid paralysis (AFP) cases, with dates of onset of paralysis in July and August 2016. All these viruses were confirmed from the security-challenged northeastern state of Borno. Polio-compatible cases exist in Nigeria, and they indicate surveillance failure. Surveillance, therefore, has to be strengthened for the country to achieve certification. The objective of this paper is to highlight the epidemiological profile and magnitude of polio-compatible cases in Nigeria during the reporting period, as well as immunization and surveillance response activities conducted to close immunity and surveillance gaps. METHODS: We conducted a retrospective review of AFP surveillance performance and polio-compatible cases in Nigeria between 2006 and 2016 from the AFP database at the World Health Organization Country Office. We also reviewed and compared key epidemiological features of polio-compatible cases with those of wild poliovirus cases during the reporting period. RESULTS: The non-polio AFP rate improved from 6.5 in 2006 to 19.5 in 2016. The corresponding figures for stool adequacy rates were 88 and 98%. The total number of polio-compatible cases reported during the reporting period was 888, with the highest number (194) of cases reported in 2006 and the least (24) in 2016. Clusters of polio-compatible cases were reported every year during the reporting period except in 2015. The highest number (65) of polio-compatible cases in clusters was reported in 2006. The key epidemiological features of polio-compatible and wild poliovirus cases were similar. CONCLUSION: AFP surveillance performance has improved significantly during the reporting period. Surveillance gaps still existed as shown by the presence of orphan viruses and polio-compatible cases, and these gaps need to be identified and closed to achieve certification.

Acute flaccid paralysis (AFP) surveillance intensification for polio certification in Kaduna state, Nigeria: lessons learnt, 2015-2016.

BACKGROUND: Nigeria has made remarkable progress in its current efforts to interrupt wild poliovirus transmission despite the re-emergence of wild poliovirus in 2016. The gains made in Nigeria have been achieved through concerted efforts by governments at all levels, traditional leaders, health workers, caregivers, and development partners. The efforts have involved an elaborate plan, coordination, and effective implementation of routine immunization services, supplemental immunization activities, and acute flaccid paralysis (AFP) surveillance. METHODS: We conducted the following activities to strengthen AFP surveillance in Kaduna state: a monetary reward for all AFP cases reported by health workers or community informants and verified as "true" AFP by a World Health Organization (WHO) cluster coordinator; training and sensitization of surveillance officers, clinicians, and community informants; recruitment of more personnel and expansion of the surveillance network; and the involvement of special populations (nomadic, hard-to-reach, and border communities) and caregivers in stool sample collection. The paired t test was used to evaluate the impact of the different initiatives implemented in Kaduna state to intensify AFP surveillance in 2016. RESULTS: There was increased annualized non-polio AFP rate (ANPAFPR) in 21 out of 23 Local Government Areas (LGAs) of Kaduna state 6 months after implementation of different initiatives to intensify AFP surveillance. The AFP reported by the special population increased in 15 out of 23 LGAs. Statistical analyses of mean scores of ANPAFPR before and after the interventions using the paired t test revealed a significant difference in mean scores: mean = 19.7 (standard deviation (SD) = 16.1) per 100,000 < 15 years old in July-December 2015, compared with 38.0 (SD = 21.6) per 100,000 < 15 years old in January-June 2016 (p < 0.05). Likewise, analysis of silent wards using the paired t test showed a significant difference in mean scores: mean = 4.0 (SD = 2.1) in July-December 2015 compared with 2.4 (SD = 1.8) in January-June 2016 (p < 0.05). CONCLUSION: The different initiatives implemented in 23 LGAs of Kaduna state to intensify AFP surveillance may be responsible for the significant improvement in the AFP surveillance performance indicators in 2016.

Towards an effective poliovirus laboratory containment strategy in Nigeria.

BACKGROUND: The Global Commission for the Certification of the Eradication of Poliomyelitis will declare the world free of wild poliovirus transmission when no wild virus has been found in at least 3 consecutive years, and all laboratories possessing wild poliovirus materials have adopted appropriate measures of containment. Nigeria has made progress towards poliomyelitis eradication with the latest reported WPV type 1 on 21 Aug 2016 after 2 years without any case. This milestone achievement was followed by an inventory of biomedical laboratories completed in November 2015 with the destruction of all identified infectious materials. This paper seeks to describe the poliovirus laboratory containment process in Nigeria on which an effective containment system has been built to minimize the risk of virus re-introduction into the population from the laboratories. METHODS: A national survey of all biomedical facilities, as well as an inventory of laboratories from various sectors, was conducted from June-November 2015. National Task Force (NTF) members and staff working on polio administered an on-site questionnaire in each facility. Laboratory personnel were sensitized with all un-needed materials destroyed by autoclaving and incineration. All stakeholders were also sensitized to continue the destruction of such materials as a requirement for phase one activities. RESULTS: A total of 20,638 biomedical facilities were surveyed with 9575 having laboratories. Thirty laboratories were found to contain poliovirus or potentially infectious materials. The 30 laboratories belonged to the ministries of health, education, defence and private organizations. CONCLUSIONS: This article is amongst the first in Africa that relates poliovirus laboratory containment in the context of the tOPV-bOPV switch in alignment with the Global Action Plan III. All identified infectious materials were destroyed and personnel trained to continue to destroy subsequent materials, a process that needs meticulous monitoring to mitigate the risk of poliovirus re-introduction to the population.

Strategies for Improving Polio Surveillance Performance in the Security-Challenged Nigerian States of Adamawa, Borno, and Yobe During 2009-2014.

BACKGROUND: The security-challenged states of Adamawa, Borno, and Yobe bear most of the brunt of the Boko Haram insurgency in Nigeria. The security challenge has led to the killing of health workers, destruction of health facilities, and displacement of huge populations. To identify areas of polio transmission and promptly detect possible cases of importation in these states, polio surveillance must be very sensitive. METHODS: We conducted a retrospective review of acute flaccid paralysis surveillance in the security-compromised states between 2009 and 2014, using the acute flaccid paralysis database at the World Health Organization Nigeria Country Office. We also reviewed the reports of surveillance activities conducted in these security-challenged states, to identify strategies that were implemented to improve polio surveillance. RESULTS: Environmental surveillance was implemented in Borno in 2013 and in Yobe in 2014. All disease surveillance and notification officers in the 3 security-challenged states now receive annual training, and the number of community informants in these states has dramatically increased. Media-based messaging (via radio and television) is now used to sensitize the public to the importance of surveillance, and contact samples have been regularly collected in both states since 2014. CONCLUSIONS: The strategies implemented in the security-challenged states improved the quality of polio surveillance during the review period.

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.

Contribution of Environmental Surveillance Toward Interruption of Poliovirus Transmission in Nigeria, 2012-2015.

BACKGROUND: Cases of paralysis caused by poliovirus have decreased by >99% since the 1988 World Health Assembly's resolution to eradicate polio. The World Health Organization identified environmental surveillance (ES) of poliovirus in the poliomyelitis eradication strategic plan as an activity that can complement acute flaccid paralysis (AFP) surveillance. This article summarizes key public health interventions that followed the isolation of polioviruses from ES between 2012 and 2015. METHODS: The grap method was used to collect 1.75 L of raw flowing sewage every 2-4 weeks. Once collected, samples were shipped at 4 °C to a polio laboratory for concentration. ES data were then used to guide program implementation. RESULTS: From 2012 to 2015, ES reported 97 circulating vaccine-derived polioviruses (cVDPV2) and 14 wild polioviruses. In 2014 alone, 54 cVDPV type 2 cases and 1 WPV type 1 case were reported. In Sokoto State, 58 cases of AFP were found from a search of 9426 households. A total of 2 252 059 inactivated polio vaccine and 2 460 124 oral polio vaccine doses were administered to children aged <5 year in Borno and Yobe states. CONCLUSIONS: This article is among the first from Africa that relates ES findings to key public health interventions (mass immunization campaigns, inactivated polio vaccine introduction, and strengthening of AFP surveillance) that have contributed to the interruption of poliovirus transmission in Nigeria.

Survey of poliovirus antibodies in Borno and Yobe States, North-Eastern Nigeria.

BACKGROUND: Nigeria remains one of only three polio-endemic countries in the world. In 2016, after an absence of 2 years, wild poliovirus serotype 1 was again detected in North-Eastern Nigeria. To better guide programmatic action, we assessed the immunity status of infants and children in Borno and Yobe states, and evaluated the impact of recently introduced inactivated poliovirus vaccine (IPV) on antibody seroprevalence. METHODS AND FINDINGS: We conducted a facility-based study of seroprevalence to poliovirus serotypes 1, 2 and 3 among health-seeking patients in two sites each of Borno and Yobe States. Enrolment was conducted amongst children 6-9 and 36-47 months of age attending the paediatrics outpatient department of the selected hospitals in the two states between 11 January and 5 February 2016. Detailed demographic and immunization history of the child was taken and an assessment of the child's health and nutritional state was conducted via physical examination. Blood was collected to test for levels of neutralizing antibody titres against the three poliovirus serotypes. The seroprevalence in the two age groups, potential determinants of seropositivity and the impact of one dose of IPV on humoral immunity were assessed. A total of 583 subjects were enrolled and provided sufficient quantities of serum for testing. Among 6-9-month-old infants, the seroprevalence was 81% (74-87%), 86% (79-91%), and 72% (65-79%) in Borno State, and 75% (67-81%), 74% (66-81%) and 69% (61-76%) in Yobe States, for serotypes-1, 2 and 3, respectively. Among children aged 36-47 months, the seroprevalence was >90% in both states for all three serotypes, with the exception of type 3 seroprevalence in Borno [87% (80-91%)]. Median reciprocal anti-polio neutralizing antibody titers were consistently >900 for serotypes 1 and 2 across age groups and states; with lower estimates for serotype 3, particularly in Borno. IPV received in routine immunization was found to be a significant determinant of seropositivity and anti-polio neutralizing antibodies among 6-9-month-old infants for serotypes 1 and 3, but demonstrated a non-significant positive association for serotype 2. Children receiving IPV through SIAs demonstrated significantly higher anti-polio neutralizing antibodies for serotypes 1 and 3. CONCLUSIONS: The seroprevalence to poliovirus remains suboptimal in both Borno and Yobe States in Nigeria. The low seroprevalence facilitated the continued transmission of both wild serotype 1 and serotype 2 circulating vaccine-derived poliovirus detected in Borno State in 2016. Further efforts are necessary to improve the immunity status of these populations to ensure sufficient population immunity to interrupt transmission.

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.