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.

Pediatric Bacterial Meningitis Surveillance in Nigeria From 2010 to 2016, Prior to and During the Phased Introduction of the 10-Valent Pneumococcal Conjugate Vaccine.

BACKGROUND: Historically, Nigeria has experienced large bacterial meningitis outbreaks with high mortality in children. Streptococcus pneumoniae (pneumococcus), Neisseria meningitidis (meningococcus), and Haemophilus influenzae are major causes of this invasive disease. In collaboration with the World Health Organization, we conducted longitudinal surveillance in sentinel hospitals within Nigeria to establish the burden of pediatric bacterial meningitis (PBM). METHODS: From 2010 to 2016, cerebrospinal fluid was collected from children <5 years of age, admitted to 5 sentinel hospitals in 5 Nigerian states. Microbiological and latex agglutination techniques were performed to detect the presence of pneumococcus, meningococcus, and H. influenzae. Species-specific polymerase chain reaction and serotyping/grouping were conducted to determine specific causative agents of PBM. RESULTS: A total of 5134 children with suspected meningitis were enrolled at the participating hospitals; of these 153 (2.9%) were confirmed PBM cases. The mortality rate for those infected was 15.0% (23/153). The dominant pathogen was pneumococcus (46.4%: 71/153) followed by meningococcus (34.6%: 53/153) and H. influenzae (19.0%: 29/153). Nearly half the pneumococcal meningitis cases successfully serotyped (46.4%: 13/28) were caused by serotypes that are included in the 10-valent pneumococcal conjugate vaccine. The most prevalent meningococcal and H. influenzae strains were serogroup W and serotype b, respectively. CONCLUSIONS: Vaccine-type bacterial meningitis continues to be common among children <5 years in Nigeria. Challenges with vaccine introduction and coverage may explain some of these finding. Continued surveillance is needed to determine the distribution of serotypes/groups of meningeal pathogens across Nigeria and help inform and sustain vaccination policies in the country.

Pneumonia hospitalizations and mortality in children 3 - 24-month-old in Nigeria from 2013 to 2020: Impact of pneumococcal conjugate vaccine ten valent (PHiD-CV-10).

Pneumococcal conjugate vaccine ten valent (PCV 10) was introduced into Nigeria in three phases. Phase 3 introduction started in August 2016. However, its impact on pneumonia admissions and mortality among vaccinated Nigerian children has not been determined. Data in the period before PCV-10 introduction (3 August 2013-2 August 2016), and after (3 August 2017-2 August 2020) were retrospectively extracted from the medical charts of eligible patients aged 3-24 months with hospitalized radiological pneumonia at the University College Hospital (UCH), Ibadan; National Hospital (NH), Abuja; and Federal Teaching Hospital (FTH), Gombe, allowing for an intervening period of 1 year. Proportions of the patients with hospitalized pneumonia and case fatality rates were determined during both periods. The results were compared using z-test, multiple logistic regression analysis and p < .05 was considered significant. Adjusted pneumonia hospitalization rates between the two periods increased at the NH Abuja (10.7% vs 14.6%); decreased at the UCH, Ibadan (8.7% vs 6.9%); and decreased at the FTH, Gombe (28.5% vs 18.9%). Case fatality rates decreased across all the sites during the post-PCV introduction period: NH Abuja, from 6.6% to 4.4% (p = .106); FTH, Gombe, 11.7% to 7.7% (p = .477); and UCH, Ibadan, 2.0% to 0% (p = .045); but only significant at Ibadan. Overall, proportion of hospitalized pneumonia cases decreased after 3 years of PCV 10 introduction into the National Immunization Programme in Nigeria. The case fatality rate during post-PCV 10 introduction decreased at all the three sites, but this difference was significant at the UCH, Ibadan.

Pneumonia is the commonest killer of Nigerian children aged less than 5 years. Pneumonia vaccine (PCV 10) was introduced into Nigeria Vaccination Program between 2014 and 2016, but up till now the value has not been confirmed. We conducted a retrospective study in which data before and after PCV 10 introduction were compared. The study sites were the University College Hospital (UCH), Ibadan; National Hospital (NH), Abuja; and Federal Teaching Hospital (FTH), Gombe. The data were extracted from the medical charts of eligible patients aged 3­24 months who were admitted for severe pneumonia with evidences on lung radiographs. We found that the proportion of hospitalized pneumonia cases decreased after 3 years of PCV 10 introduction into the National Immunization Program in Nigeria. The death rate during post-PCV 10 introduction decreased at all the three sites, but was only significantly decreased at the UCH, Ibadan.

Intussusception in children under five years of age in Enugu, Nigeria.

INTRODUCTION: intussusception is the invagination of a segment of the bowel into a distal segment. It occurs predominantly in infants worldwide. Following documentation of increased incidence after introduction of the first rotavirus vaccine (Rotashield, Wyeth-Lederle), it has become a standard recommendation to maintain surveillance for intussusception as newer rotavirus vaccines are introduced into EPI. Nigeria plans to introduce rotavirus vaccine in 2020. Pre-vaccine introduction surveillance will serve as a baseline to understand the epidemiology of intussusception in Nigeria. METHODS: from 2013 to 2017, prospective enrolment of under five children with intussusception was done following the WHO protocol and using the WHO case report form. Only children who met the Pan American Health Organization/World Health Organization (PAHO/WHO) protocol case definition for intussusception were enrolled. These children were monitored until discharge or death. Clinical features and outcome were recorded in the case report form. RESULTS: a total of 63 cases were enrolled, with age range of 3 to 42 months (median: 6 months, IQR: 5-9 months). Majority were within 4-6 months and 96% were < 12 months old. There were 41 males and 22 females (male to female ratio of 1.9:1). Duration of symptoms before presentation ranged from 2 hours to 15 days (median: 72 hours). Fifty-seven patients had abdominal ultrasound and 52 patients (83%) had surgery. Case fatality rate was 9% and duration of hospitalization ranged from 1 to 30 days (median 10 days, IQR 8-15 days). CONCLUSION: intussusception occurred most commonly in infants but well beyond the proposed age for rotavirus vaccination in the population studied. Late presentation and surgical intervention were common. This data provides a good baseline description of the epidemiology of intussusception.

Etiology of Pediatric Meningitis in West Africa Using Molecular Methods in the Era of Conjugate Vaccines against Pneumococcus, Meningococcus, and Haemophilus influenzae Type b.

Despite the implementation of effective conjugate vaccines against the three main bacterial pathogens that cause meningitis, Streptococcus pneumoniae, Haemophilus influenzae type b (Hib), and Neisseria meningitidis serogroup A, the burden of meningitis in West Africa remains high. The relative importance of other bacterial, viral, and parasitic pathogens in central nervous system infections is poorly characterized. Cerebrospinal fluid (CSF) specimens were collected from children younger than 5 years with suspected meningitis, presenting at pediatric teaching hospitals across West Africa in five countries including Senegal, Ghana, Togo, Nigeria, and Niger. Cerebrospinal fluid specimens were initially tested using bacteriologic culture and a triplex real-time polymerase chain reaction (PCR) assay for N. meningitidis, S. pneumoniae, and H. influenzae used in routine meningitis surveillance. A custom TaqMan Array Card (TAC) assay was later used to detect 35 pathogens including 15 bacteria, 17 viruses, one fungus, and two protozoans. Among 711 CSF specimens tested, the pathogen positivity rates were 2% and 20% by the triplex real-time PCR (three pathogens) and TAC (35 pathogens), respectively. TAC detected 10 bacterial pathogens, eight viral pathogens, and Plasmodium. Overall, Escherichia coli was the most prevalent (4.8%), followed by S. pneumoniae (3.5%) and Plasmodium (3.5%). Multiple pathogens were detected in 4.4% of the specimens. Children with human immunodeficiency virus (HIV) and Plasmodium detected in CSF had high mortality. Among 220 neonates, 17% had at least one pathogen detected, dominated by gram-negative bacteria. The meningitis TAC enhanced the detection of pathogens in children with meningitis and may be useful for case-based meningitis surveillance.

Health-Care Workers' Perspectives on Ebola Virus Vaccine: A Focus Group and In-Depth Interview Interventional Study.

Health-care workers (HCWs) will require Ebola virus vaccine (EVV) when it is introduced because of the high risk of exposure to the disease. Evaluations of factors that facilitate or limit vaccine uptake are critical for a successful vaccine program. Nigerian HCWs were interviewed to evaluate their knowledge, levels of acceptance, determinants of acceptance, and willingness to pay for EVV. The significance level was set at P ≤ 0.05. None of the 193 participating HCWs had correct knowledge of EVV; 34.7% (67/193) of workers thought that EVV was an extract of the serum of Ebola virus patients. About 77.3% (51/66) of workers in a region that reported Ebola cases (Lagos) were willing to be vaccinated, compared with 4.7% (3/61) in Enugu and 13.6% (9/66) in Abia (P = 0.0001). After health education, the proportion of HCWs willing to receive EVV increased (P = 0.006) except for doctors (P < 0.1). The percentage of HCWs willing to pay for EVV was 86.4%, 72.1%, and 59% in Lagos, Enugu, and Abia, respectively. The workers had fears about EVV based on nonfactual assumptions. Therefore, the EVV introduction strategy should include a strong awareness campaign with adequate explanation about the content of EVV.

Neonatal infections: Case definition and guidelines for data collection, analysis, and presentation of immunisation safety data.

Maternal vaccination is an important area of research and requires appropriate and internationally comparable definitions and safety standards. The GAIA group, part of the Brighton Collaboration was created with the mandate of proposing standardised definitions applicable to maternal vaccine research. This study proposes international definitions for neonatal infections. The neonatal infections GAIA working group performed a literature review using Medline, EMBASE and the Cochrane collaboration and collected definitions in use in neonatal and public health networks. The common criteria derived from the extensive search formed the basis for a consensus process that resulted in three separate definitions for neonatal blood stream infections (BSI), meningitis and lower respiratory tract infections (LRTI). For each definition three levels of evidence are proposed to ensure the applicability of the definitions to different settings. Recommendations about data collection, analysis and presentation are presented and harmonized with the Brighton Collaboration and GAIA format and other existing international standards for study reporting.

Acceptability and Willingness-to-Pay for a Hypothetical Ebola Virus Vaccine in Nigeria.

BACKGROUND: Ebola virus disease is a highly virulent and transmissible disease. The largest recorded fatality from Ebola virus disease epidemic is ongoing in a few countries in West Africa, and this poses a health risk to the entire population of the world because arresting the transmission has been challenging. Vaccination is considered a key intervention that is capable of arresting further spread of the disease and preventing future outbreak. However, no vaccine has yet been approved for public use, although various recombinant vaccines are undergoing trials and approval for public use is imminent. Therefore, this study aimed to determine the acceptability of and willingness-to-pay for Ebola virus vaccine by the public. METHODS: The study was a community-based cross-sectional qualitative and quantitative interventional study conducted in two communities, each in two states in Nigeria. An interviewer-administered questionnaire was used to collect information on respondents' knowledge of the Ebola virus, the ways to prevent the disease, and their preventive practices, as well as their acceptability of and willingness-to-pay for a hypothetical vaccine against Ebola virus disease. The association between acceptability of the vaccine and other independent variables were evaluated using multivariate regression analysis. RESULTS: Ebola virus disease was considered to be a very serious disease by 38.5% of the 582 respondents (224/582), prior to receiving health education on Ebola virus and its vaccine. Eighty percent (80%) accepted to be vaccinated with Ebola vaccine. However, among those that accepted to be vaccinated, most would only accept after observing the outcome on others who have received the vaccine. More than 87.5% was willing to pay for the vaccine, although 55.2% was of the opinion that the vaccine should be provided free of charge. CONCLUSION: The level of acceptability of Ebola virus vaccine among respondents was impressive (though conditional), as well as their willingness to pay for it if the vaccine is not publicly funded. In order to achieve a high uptake of the vaccine, information and education on the vaccine should be extensively shared with the public prior to the introduction of the vaccine, and the vaccine should be provided free of charge by government.

Parental acceptance of inactivated polio vaccine in Southeast Nigeria: a qualitative cross-sectional interventional study.

BACKGROUND: The introduction of inactivated polio vaccines (IPV) is imminent. In view of the Polio Eradication and Endgame Strategic Plan 2013-2018, parental acceptance of IPV will be important for achieving universal coverage. In view of the imminent introduction of IPV, it is only reasonable to assess the awareness and acceptance of IPV, so that necessary socio-anthropological measures would be put in place. This study is aimed at determining the level of awareness and acceptance of IPV by parents. METHODS: A cross-sectional study involving 408 parents that brought their children for immunization. Structured-questionnaire was to collect data on the parent's demographic characteristics, awareness and acceptance of IPV. The independent factors that may affect parental acceptability of IPV were evaluated using linear regression analysis. RESULTS: About 53% of the parents had no knowledge of vaccine content and 84.1% had not heard of IPV, and 40.2% were willing to accept IPV. However, with post-intervention (IPV) health education, the level of acceptance of IPV increased to 95.6% and the difference was statistically significant (p=0.0001). 35.3% expressed fear for IPV, and 61.8% cited fear for pain (61.8%). In the rating scale of 1 to 5, doctors (4.7), Nurses (4.0) and staff of the Ministry of Health (4.0) were rated high as reliable media to inform them about a new vaccine. The logistic regression revealed only educational level of mothers (p-value=0.048) was the only significant factor associated with acceptability of IPV. CONCLUSION: The parents' knowledge on vaccine was poor, as well as IPV acceptability (pre health education). But the acceptability was improved with provision of extra information. Although most still preferred OPV, and with improvement in pain management, acceptability of IPV can be improved further. Clear policies and strategies should be immediately developed and implementation of pre-introduction awareness/sensitization on IPV should be commenced.

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.

Neonatal infections: case definition and guidelines for data collection, analysis, and presentation of immunisation safety data

A vacinação materna é uma importante área de pesquisa e requer definições e padrões de segurança apropriados e internacionalmente comparáveis. O grupo GAIA, parte da Brighton Collaboration, foi criado com o mandato de propor definições padronizadas aplicáveis ​​à pesquisa de vacinas maternas. Este estudo propõe definições internacionais para infecções neonatais. O grupo de trabalho GAIA de infecções neonatais realizou uma revisão de literatura utilizando Medline, EMBASE e a colaboração Cochrane e coletou definições em uso em redes neonatais e de saúde pública. Os critérios comuns derivados da pesquisa extensiva formaram a base para um processo de consenso que resultou em três definições separadas para infecções da corrente sanguínea neonatal (BSI), meningite e infecções do trato respiratório inferior (ITRI). Para cada definição, três níveis de evidência são propostos para assegurar a aplicabilidade das definições a diferentes configurações. Recomendações sobre coleta, análise e apresentação de dados são apresentadas e harmonizadas com o formato Colaboração de Brighton e GAIA e outros padrões internacionais existentes para relatórios de estudo.