Vaccine wastage in Nigeria: An assessment of wastage rates and related vaccinator knowledge, attitudes and practices.

INTRODUCTION: The introduction of new vaccines highlights concerns about high vaccine wastage, knowledge of wastage policies and quality of stock management. However, an emphasis on minimizing wastage rates may cause confusion when recommendations are also being made to reduce missed opportunities to routinely vaccinate children. This concern is most relevant for lyophilized vaccines without preservatives [e.g. measles-containing vaccine (MCV)], which can be used for a limited time once reconstituted. METHODS: We sampled 54 health facilities within 11 local government areas (LGAs) in Nigeria and surveyed health sector personnel regarding routine vaccine usage and wastage-related knowledge and practices, conducted facility exit interviews with caregivers of children about missed opportunities for routine vaccination, and abstracted vaccine stock records and vaccination session data over a 6-month period to calculate wastage rates and vaccine vial usage patterns. RESULTS: Nearly half of facilities had incomplete vaccine stock data for calculating wastage rates. Among facilities with sufficient data, mean monthly facility-level wastage rates were between 18 and 35% across all reviewed vaccines, with little difference between lyophilized and liquid vaccines. Most (98%) vaccinators believed high wastage led to recent vaccine stockouts, yet only 55% were familiar with the multi-dose vial policy for minimizing wastage. On average, vaccinators reported that a minimum of six children must be present prior to opening a 10-dose MCV vial. Third dose of diphtheria-tetanus-pertussis vaccine (DTP3) was administered in 84% of sessions and MCV in 63%; however, the number of MCV and DTP3 doses administered were similar indicating the number of children vaccinated with DTP3 and MCV were similar despite less frequent MCV vaccination opportunities. Among caregivers, 30% reported being turned away for vaccination at least once; 53% of these children had not yet received the missed dose. DISCUSSION: Our findings show inadequate implementation of vaccine management guidelines, missed opportunities to vaccinate, and lyophilized vaccine wastage rates below expected rates. Missed opportunities for vaccination may occur due to how the health system's contradicting policies may force health workers to prioritize reduced wastage rates over vaccine administration, particularly for multi-dose vials.

Spatial Dynamics and High Risk Transmission Pathways of Poliovirus in Nigeria 2001-2013.

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.

Determinants of routine immunization coverage in Bungudu, Zamfara State, Northern Nigeria, May 2010.

INTRODUCTION: Immunization is a cost-effective public health intervention to reduce morbidity and mortality associated with infectious diseases. The Nigeria Demographic and Health Survey of 2008 indicated that only 5.4% of children aged 12-23 months in Bungudu, Zamfara State were fully immunized. We conducted this study to identify the determinants of routine immunization coverage in this community. METHODS: We conducted a cross-sectional study. We sampled 450 children aged 12-23 months. We interviewed mothers of these children using structured questionnaire to collect data on socio-demographic characteristics, knowledge on immunization, vaccination status of children and reasons for non-vaccination. We defined a fully immunized child as a child who had received one dose of BCG, three doses of oral polio vaccine, three doses of Diptheria-Pertusis-Tetanus vaccine and one dose of measles vaccine by 12 months of age. We performed bivariate analysis and logistic regression using Epi-info software. RESULTS: The mean age of mothers and children were 27 years (standard error (SE): 0.27 year) and 17 months (SE: 0.8 month) respectively. Seventy nine percent of mothers had no formal education while 84% did not possess satisfactory knowledge on immunization. Only 7.6% of children were fully immunized. Logistic regression showed that possessing satisfactory knowledge (Adjusted OR=18.4, 95% CI=3.6-94.7) and at least secondary education (Adjusted OR=3.6, 95% CI=1.2-10.6) were significantly correlated with full immunization. CONCLUSION: The major determinants of immunization coverage were maternal knowledge and educational status. Raising the level of maternal knowledge and increasing maternal literacy level are essential to improve immunization coverage in this community.

Characteristics of persons refusing oral polio vaccine during the immunization plus days - Sokoto, Nigeria 2011.

INTRODUCTION: Nigeria, the only African country endemic for wild poliovirus, adopted Immunization Plus Days (IPD) to eradicate polio. Refusal of oral polio vaccine (OPV) by heads of households is a significant challenge. In Sokoto state, we determined characteristics of heads of households refusing OPV during IPD in 2011. METHODS: To evaluate reasons for refusals, we conducted a case control study among heads ofhouseholds accepting or refusing OPV vaccine. Noncompliant households were defined as households refusing OPV vaccination in last three rounds of IPDs while compliant households were those accepting vaccination. Interviewers administered a questionnaire to the heads of households to obtain information on socio-demographics, media habits, and knowledge of IPD. RESULTS: Of the 121 (60 cases and 61 controls) interviews, 88 (73%) were from Sokoto north. Noncompliant heads of households were more likely to lack tertiary education (OR = 3.7, 95% CI, 1.6 - 9.2), believe that OPV is not safe (OR = 22, 95% CI, 7.1 - 76), lack access to functional radio (OR = 4.4, 95% CI, 1.4 - 15) and television (OR = 9.4, 95% CI, (1.9 - 63) andget information about IPD from town announcers (OR = 3.9, 95% CI, 1.3 - 12). CONCLUSION: We conclude that noncompliant heads of households compared to compliant heads of households had low level of education, lacked knowledge of immunization, and had negative attitude towards OPV. They get information about OPV from town announcers and lacked access to functional radio and television. We recommended training of town announcers in polio communication and use of key communication messages preceding every round of IPD.

An evaluation of polio supplemental immunization activities in Kano, Katsina, and Zamfara States, Nigeria: lessons in progress.

BACKGROUND: As 1 of 3 remaining poliovirus-endemic countries, Nigeria has become key to the global polio eradication effort. We evaluated supplemental immunization activities, including team performance, communications/mobilization activities, and vaccine acceptance, in 3 high-risk states. METHODS: We used structured survey and observation instruments, document review, and stakeholder interviews. RESULTS: Observations or surveys were conducted at 1697 households. Vaccine acceptance ranged from 87%-94%; among households rejecting polio vaccine, 38% of mothers sought measles vaccine for their children. Teams performed between 4%-42% of assigned tasks. CONCLUSIONS: Acceptance is high but teams have a critical role in surmounting residual vaccine resistance.

Using geographic information systems to track polio vaccination team performance: pilot project report.

The application of geospatial data to public health problems has expanded significantly with increased access to low-cost handheld global positioning system (GPS) receivers and free programs for geographic information systems analysis. In January 2010, we piloted the application of geospatial analysis to polio supplementary immunization activities (SIAs) in northern Nigeria. SIA teams carried GPS receivers to compare hand-drawn catchment area route maps with GPS tracks of actual vaccination teams. Team tracks overlaid on satellite imagery revealed that teams commonly missed swaths of contiguous households and indicated that geospatial data can improve microplanning and provide nearly real-time monitoring of team performance.

Key issues in the persistence of poliomyelitis in Nigeria: a case-control study.

BACKGROUND: The completion of poliomyelitis eradication is a global emergency for public health. In 2012, more than 50% of the world's cases occurred in Nigeria following an unanticipated surge in incidence. We aimed to quantitatively analyse the key factors sustaining transmission of poliomyelitis in Nigeria and to calculate clinical efficacy estimates for the oral poliovirus vaccines (OPV) currently in use. METHODS: We used acute flaccid paralysis (AFP) surveillance data from Nigeria collected between January, 2001, and December, 2012, to estimate the clinical efficacies of all four OPVs in use and combined this with vaccination coverage to estimate the effect of the introduction of monovalent and bivalent OPV on vaccine-induced serotype-specific population immunity. Vaccine efficacy was determined using a case-control study with CIs based on bootstrap resampling. Vaccine efficacy was also estimated separately for north and south Nigeria, by age of the children, and by year. Detailed 60-day follow-up data were collected from children with confirmed poliomyelitis and were used to assess correlates of vaccine status. We also quantitatively assessed the epidemiology of poliomyelitis and programme performance and considered the reasons for the high vaccine refusal rate along with risk factors for a given local government area reporting a case. FINDINGS: Against serotype 1, both monovalent OPV (median 32.1%, 95% CI 26.1-38.1) and bivalent OPV (29.5%, 20.1-38.4) had higher clinical efficacy than trivalent OPV (19.4%, 16.1-22.8). Corresponding data for serotype 3 were 43.2% (23.1-61.1) and 23.8% (5.3-44.9) compared with 18.0% (14.1-22.1). Combined with increases in coverage, this factor has boosted population immunity in children younger than age 36 months to a record high (64-69% against serotypes 1 and 3). Vaccine efficacy in northern states was estimated to be significantly lower than in southern states (p≤0.05). The proportion of cases refusing vaccination decreased from 37-72% in 2008 to 21-51% in 2012 for routine and supplementary immunisation, and most caregivers cited ignorance of either vaccine importance or availability as the main reason for missing routine vaccinations (32.1% and 29.6% of cases, respectively). Multiple regression analyses highlighted associations between the age of the mother, availability of OPV at health facilities, and the primary source of health information and the probability of receiving OPV (all p<0.05). INTERPRETATION: Although high refusal rates, low OPV campaign awareness, and heterogeneous population immunity continued to support poliomyelitis transmission in Nigeria at the end of 2012, overall population immunity had improved due to new OPV formulations and improvements in programme delivery. FUNDING: Bill & Melinda Gates Foundation Vaccine Modeling Initiative, Royal Society.

Epidemiology of rotavirus diarrhea among children younger than 5 years in Enugu, South East, Nigeria.

BACKGROUND: Severe rotavirus diarrhea in children is a major cause of morbidity globally and mortality in developing countries. It is estimated to be responsible for >453,000 deaths in children <5 years of age globally and 232,000 in the African region. The aim of the current study was to determine the prevalence of rotavirus gastroenteritis among hospitalized children <5 years of age in Enugu and to support awareness and advocacy efforts for the introduction of rotavirus vaccines in Nigeria. METHODS: World Health Organization-standardized case forms were used to collect data from eligible children with non-bloody diarrhea from October 2010 to September 2012. Data collected included socio-demographic and clinical information. Stool samples were obtained from recruited children and tested for rotavirus antigen using the Oxoid Prospect ELISA Kit (Basingstoke, United Kingdom). RESULTS: Of the 615 diarrhea stool samples collected, 344 (56%) were positive for human rotavirus. Of the 344 positive samples, 329 (96%) were children <2 years of age, while 247 (77%) were <1 year of age. Peak rotavirus season occurred during the cold dry months of December to April during which 95% of all cases occurred. CONCLUSIONS: This study found a relatively high incidence of severe rotavirus-associated diarrhea disease in Nigeria and infants were the most affected. It highlights the urgent need for introduction of rotavirus vaccine into the national immunization program and the need to adequately equip health facilities to enable them administer intravenous fluids to severe diarrhea patients to reduce morbidity and mortality.

Multiple independent emergences of type 2 vaccine-derived polioviruses during a large outbreak in northern Nigeria.

Since 2005, a large poliomyelitis outbreak associated with type 2 circulating vaccine-derived poliovirus (cVDPV2) has occurred in northern Nigeria, where immunization coverage with trivalent oral poliovirus vaccine (tOPV) has been low. Phylogenetic analysis of P1/capsid region sequences of isolates from each of the 403 cases reported in 2005 to 2011 resolved the outbreak into 23 independent type 2 vaccine-derived poliovirus (VDPV2) emergences, at least 7 of which established circulating lineage groups. Virus from one emergence (lineage group 2005-8; 361 isolates) was estimated to have circulated for over 6 years. The population of the major cVDPV2 lineage group expanded rapidly in early 2009, fell sharply after two tOPV rounds in mid-2009, and gradually expanded again through 2011. The two major determinants of attenuation of the Sabin 2 oral poliovirus vaccine strain (A481 in the 5'-untranslated region [5'-UTR] and VP1-Ile143) had been replaced in all VDPV2 isolates; most A481 5'-UTR replacements occurred by recombination with other enteroviruses. cVDPV2 isolates representing different lineage groups had biological properties indistinguishable from those of wild polioviruses, including efficient growth in neuron-derived HEK293 cells, the capacity to cause paralytic disease in both humans and PVR-Tg21 transgenic mice, loss of the temperature-sensitive phenotype, and the capacity for sustained person-to-person transmission. We estimate from the poliomyelitis case count and the paralytic case-to-infection ratio for type 2 wild poliovirus infections that ∼700,000 cVDPV2 infections have occurred during the outbreak. The detection of multiple concurrent cVDPV2 outbreaks in northern Nigeria highlights the risks of cVDPV emergence accompanying tOPV use at low rates of coverage in developing countries.

Measles resurgence following a nationwide measles vaccination campaign in Nigeria, 2005-2008.

INTRODUCTION: From 1990 through 2008, routine immunization coverage of measles vaccine in Nigeria ranged from 35% to 70%. Nigeria conducted a nationwide measles vaccination campaign in 2 phases during 2005-2006 that targeted children aged 9 months to 14 years; in 2008, a nationwide follow-up campaign that targeted children aged 9 months to 4 years was conducted in 2 phases. Despite these efforts, measles cases continued to occur. METHODS: This is a descriptive study that reviewed the measles immunization coverage data from administrative, World Health Organization, United Nations Children's Fund, survey, and supplemental immunization activities data. Measles surveillance data were analyzed from case-based surveillance reports. RESULTS: Confirmed measles cases increased from 383 in 2006 to 2542 in 2007 and to 9510 in 2008. Of the confirmed cases in 2008, 717 (30%) occurred in children <2 years of age, 1145 (48%) in children 2-4 years of age, and 354 (14%) were in children 5-14 years of age. In 2008, the measles case fatality rate was 1.2%. CONCLUSIONS: Suboptimal routine coverage and the wide interval between the catch-up and follow-up campaigns likely led to an accumulation of children susceptible to measles.

Outbreak of type 2 vaccine-derived poliovirus in Nigeria: emergence and widespread circulation in an underimmunized population.

Wild poliovirus has remained endemic in northern Nigeria because of low coverage achieved in the routine immunization program and in supplementary immunization activities (SIAs). An outbreak of infection involving 315 cases of type 2 circulating vaccine-derived poliovirus (cVDPV2; >1% divergent from Sabin 2) occurred during July 2005-June 2010, a period when 23 of 34 SIAs used monovalent or bivalent oral poliovirus vaccine (OPV) lacking Sabin 2. In addition, 21 "pre-VDPV2" (0.5%-1.0% divergent) cases occurred during this period. Both cVDPV and pre-VDPV cases were clinically indistinguishable from cases due to wild poliovirus. The monthly incidence of cases increased sharply in early 2009, as more children aged without trivalent OPV SIAs. Cumulative state incidence of pre-VDPV2/cVDPV2 was correlated with low childhood immunization against poliovirus type 2 assessed by various means. Strengthened routine immunization programs in countries with suboptimal coverage and balanced use of OPV formulations in SIAs are necessary to minimize risks of VDPV emergence and circulation.

Implications of a circulating vaccine-derived poliovirus in Nigeria.

BACKGROUND: The largest recorded outbreak of a circulating vaccine-derived poliovirus (cVDPV), detected in Nigeria, provides a unique opportunity to analyze the pathogenicity of the virus, the clinical severity of the disease, and the effectiveness of control measures for cVDPVs as compared with wild-type poliovirus (WPV). METHODS: We identified cases of acute flaccid paralysis associated with fecal excretion of type 2 cVDPV, type 1 WPV, or type 3 WPV reported in Nigeria through routine surveillance from January 1, 2005, through June 30, 2009. The clinical characteristics of these cases, the clinical attack rates for each virus, and the effectiveness of oral polio vaccines in preventing paralysis from each virus were compared. RESULTS: No significant differences were found in the clinical severity of paralysis among the 278 cases of type 2 cVDPV, the 2323 cases of type 1 WPV, and the 1059 cases of type 3 WPV. The estimated average annual clinical attack rates of type 1 WPV, type 2 cVDPV, and type 3 WPV per 100,000 susceptible children under 5 years of age were 6.8 (95% confidence interval [CI], 5.9 to 7.7), 2.7 (95% CI, 1.9 to 3.6), and 4.0 (95% CI, 3.4 to 4.7), respectively. The estimated effectiveness of trivalent oral polio vaccine against paralysis from type 2 cVDPV was 38% (95% CI, 15 to 54%) per dose, which was substantially higher than that against paralysis from type 1 WPV (13%; 95% CI, 8 to 18%), or type 3 WPV (20%; 95% CI, 12 to 26%). The more frequent use of serotype 1 and serotype 3 monovalent oral polio vaccines has resulted in improvements in vaccine-induced population immunity against these serotypes and in declines in immunity to type 2 cVDPV. CONCLUSIONS: The attack rate and severity of disease associated with the recent cVDPV identified in Nigeria are similar to those associated with WPV. International planning for the management of the risk of WPV, both before and after eradication, must include scenarios in which equally virulent and pathogenic cVDPVs could emerge.

Effectiveness of immunization against paralytic poliomyelitis in Nigeria.

BACKGROUND: The number of cases of paralytic poliomyelitis has declined in Nigeria since the introduction of newly licensed monovalent oral poliovirus vaccines and new techniques of vaccine delivery. Understanding the relative contribution of these vaccines and the improved coverage to the decline in incident cases is essential for future planning. METHODS: We estimated the field efficacies of monovalent type 1 oral poliovirus vaccine and trivalent oral poliovirus vaccine, using the reported number of doses received by people with poliomyelitis and by matched controls as identified in Nigeria's national surveillance database, in which 27,379 cases of acute flaccid paralysis were recorded between 2001 and 2007. Our estimates of vaccine coverage and vaccine-induced immunity were based on the number of doses received by children listed in the database who had paralysis that was not caused by poliovirus. RESULTS: The estimated efficacies per dose of monovalent type 1 oral poliovirus vaccine and trivalent oral poliovirus vaccine against type 1 paralytic poliomyelitis were 67% (95% confidence interval [CI], 39 to 82) and 16% (95% CI, 10 to 21), respectively, and the estimated efficacy per dose of trivalent oral poliovirus vaccine against type 3 paralytic poliomyelitis was 18% (95% CI, 9 to 26). In the northwestern region of Nigeria, which reported the majority of cases during the study period, coverage with at least one dose of vaccine increased from 59 to 78%. Between 2005 and 2007, vaccine-induced immunity levels among children under the age of 5 years more than doubled, to 56%. CONCLUSIONS: The higher efficacy of monovalent type 1 oral poliovirus vaccine (four times as effective as trivalent oral poliovirus vaccine) and the moderate gains in coverage dramatically increased vaccine-induced immunity against serotype 1 in northern Nigeria. Further increases in coverage in Nigerian states with infected populations are required to achieve the levels of vaccine-induced immunity associated with the sustained elimination achieved in other parts of the country.