In 2012, the Strategic Advisory Group of Experts on Immunization (SAGE) recommended introduction of at least one inactivated poliovirus vaccine (IPV) dose in essential immunization programs. We evaluated systemic humoral and intestinal mucosal immunity of a sequential IPV-bivalent oral poliovirus vaccine (bOPV) schedule compared with a co-administration IPV + bOPV schedule in an open-label, randomized, controlled, non-inferiority, inequality trial in Dhaka, Bangladesh. Healthy infants aged 6 weeks were randomized to either: (A) IPV and bOPV at 6 and bOPV at 10 and 14 weeks (IPV + bOPV-bOPV-bOPV); or (B) IPV at 6 and bOPV at 10 and 14 weeks (IPV-bOPV-bOPV). Of 456 participants enrolled and randomly assigned during May-August 2015, 428 (94%) were included in the modified intention-to-treat analysis (arm A: 211, arm B: 217). Humoral immune responses did not differ at 18 weeks between study arms: type 1 (98% versus 96%; p = 0.42), type 2 (37% versus 39%; p = 0.77), and type 3 (97% versus 93%; p = 0.07). Virus shedding one week after the bOPV challenge dose in arm B was non-inferior to arm A (type 1 difference = -3% [90% confidence interval: -6 - 0.4%]; type 3 difference: -3% [-6 to -0.2%]). Twenty-six adverse events including seven serious adverse events were reported among 25 participants including one death; none were attributed to study vaccines. An IPV-bOPV-bOPV sequential schedule induced comparable systemic humoral immunity to all poliovirus types and types 1 and 3 intestinal mucosal immunity as an IPV + bOPV-bOPV-bOPV co-administration schedule.

BACKGROUND: Type 2 circulating vaccine-derived polioviruses (cVDPV2) from Sabin oral poliovirus vaccines (OPVs) are the leading cause of poliomyelitis. A novel type 2 OPV (nOPV2) has been developed to be more genetically stable with similar tolerability and immunogenicity to that of Sabin type 2 vaccines to mitigate the risk of cVDPV2. We aimed to assess these aspects of nOPV2 in poliovirus vaccine-naive newborn infants. METHODS: In this randomised, double-blind, controlled, phase 2 trial we enrolled newborn infants at the Matlab Health Research Centre, Chandpur, Bangladesh. We included infants who were healthy and were a single birth after at least 37 weeks' gestation. Infants were randomly assigned (2:1) to receive either two doses of nOPV2 or placebo, administered at age 0-3 days and at 4 weeks. Exclusion criteria included receipt of rotavirus or any other poliovirus vaccine, any infection or illness at the time of enrolment (vomiting, diarrhoea, or intolerance to liquids), diagnosis or suspicion of any immunodeficiency disorder in the infant or a close family member, or any contraindication for venipuncture. The primary safety outcome was safety and tolerability after one and two doses of nOPV2, given 4 weeks apart in poliovirus vaccine-naive newborn infants and the primary immunogenicity outcome was the seroconversion rate for neutralising antibodies against type 2 poliovirus, measured 28 days after the first and second vaccinations with nOPV2. Study staff recorded solicited and unsolicited adverse events after each dose during daily home visits for 7 days. Poliovirus neutralising antibody responses were measured in sera drawn at birth and at age 4 weeks and 8 weeks. This study is registered on ClinicalTrials.gov, NCT04693286. FINDINGS: Between Sept 21, 2020, and Aug 16, 2021, we screened 334 newborn infants, of whom three (<1%) were found to be ineligible and one (<1%) was withdrawn by the parents; the remaining 330 (99%) infants were assigned to receive nOPV2 (n=220 [67%]) or placebo (n=110 [33%]). nOPV2 was well tolerated; 154 (70%) of 220 newborn infants in the nOPV2 group and 78 (71%) of 110 in the placebo group had solicited adverse events, which were all mild or moderate in severity. Severe unsolicited adverse events in 11 (5%) vaccine recipients and five (5%) placebo recipients were considered unrelated to vaccination. 306 (93%) of 330 infants had seroprotective maternal antibodies against type 2 poliovirus at birth, decreasing to 58 (56%) of 104 in the placebo group at 8 weeks. In the nOPV2 group 196 (90%) of 217 infants seroconverted by week 8 after two doses, when 214 (99%) had seroprotective antibodies. INTERPRETATION: nOPV2 was well tolerated and immunogenic in newborn infants, with two doses, at birth and 4 weeks, resulting in almost 99% of infants having protective neutralising antibodies. FUNDING: Bill & Melinda Gates Foundation.

Afghanistan is one of two countries where wild poliovirus (WPV) type 1 remains endemic. We conducted a facility-based cross-sectional survey of antipoliovirus antibodies in children in 14 provinces of Afghanistan. The provinces were selected based on programmatic priorities for polio eradication. Children aged 6-11 and 36-48 months attending outpatient clinics were enrolled in the study. We collected venous blood, isolated serum, and conducted neutralization assays to detect poliovirus neutralizing antibodies. A total of 2086 children from the 14 provinces were enrolled. Among the enrolled children, 44.3% were girls; the median age in the 6-11-month group was 9.4 months, and in the 36-48-month group, it was 41.8 months. The most common spoken language was Pashtu (70.8%). Eighty-two percent of children were fully immunized against all the diseases in the vaccination schedule of Afghanistan. In the children aged 6-11 months, seroprevalence to poliovirus type 1 (PV1) was 96.5% and seroprevalence to poliovirus type 3 (PV3) was 93%; in children aged 36-48 months, seroprevalence to PV1 was 99.5% and to PV3 was 98%. Antipoliovirus antibody prevalence for poliovirus type 2 (PV2) was 70.5% in the younger group compared with 90.9% in the older children. Children from Herat and Laghman provinces had almost 100% seroprevalence to PV1, and other provinces also had high prevalence, ranging from 92.0% to 99.0%. A similar finding was seen for antibodies against PV3, ranging from 88% to 100% by province. On the contrary, antibodies to PV2 were low, ranging from 53% for children in the Khost province to around 89% in Kunduz. There was a cluster of 18 seronegative children in the Nuristan province. Overall, the polio eradication program of Afghanistan has been successful in achieving high seroprevalence of poliovirus neutralizing antibodies in the parts of the country included in this study.

This was a cross-sectional community-based serological survey of polio antibodies assessing the immunogenicity of inactivated poliovirus vaccine (IPV) focusing on poliovirus serotype 2. IPV was administered to 5-month-old children. Type 2 antibody seroprevalence when measured 1 month after IPV administration was >95%. One IPV dose successfully closed the immunity gap.

BACKGROUND: Outbreaks of vaccine-derived poliovirus type 2 (VDPV2) continue to expand across Africa. We conducted a serological survey of polio antibodies in high-polio risk areas of Niger to assess risk of poliovirus outbreaks. METHODS: Children between 1 and 5 years of age were enrolled from structures randomly selected using satellite imaging enumeration in Diffa Province, Niger, in July 2019. After obtaining informed consent, dried blood spot cards were collected. Neutralizing antibodies against 3 poliovirus serotypes were detected using microneutralization assay at the Centers for Disease Control and Prevention. RESULTS: We obtained analyzable data from 309/322 (95.9%) enrolled children. Seroprevalence of polio antibodies was 290/309 (93.9%), 272/309 (88.0%), and 254/309 (82.2%) for serotypes 1, 2, and 3, respectively. For serotypes 1 and 2, the seroprevalence did not significantly change with age (P = .09 and P = .44, respectively); for serotype 3, it increased with age (from 65% in 1-2-year-olds to 91.1% in 4-5-year olds; P < .001). We did not identify any risk factors for type 2 seronegativity. CONCLUSIONS: With type 2 seroprevalence close to 90%, the risk of emergence of new cVDPV2 outbreaks in Niger is low; however, the risk of cVDPV2 importations from neighboring countries leading to local transmission persists. Niger should maintain its outbreak response readiness capacity and further strengthen its routine immunization.

INTRODUCTION: Circulation of poliovirus in neighboring countries and mass population movement places Lebanon at risk of polio and other vaccine-preventable disease outbreaks. Determining population immunity levels is essential for guiding program planning and implementation of targeted supplementary immunization activities (SIAs) in governorates and subpopulations with low seroprevalence. METHODS: A cross-sectional multi-stage cluster survey was conducted during February-December 2016 in all six governorates of Lebanon adapted from the World Health Organization (WHO) recommended Expanded Progamme on Immunization (EPI) methodology. Sera from selected children aged 12-59 months were tested for poliovirus neutralizing antibodies. RESULTS: Of 2,164 children recruited in this study, 1,893 provided sufficient quantity of serum samples for laboratory testing. Seroprevalence for all three poliovirus serotypes was greater than 90% in all six governorates. Poliovirus vaccine coverage with three or more doses, based on vaccination cards or parental recall, ranged between 54.1% for children aged 36-47 months in the North and 83.5% for children aged 48-59 months in Beirut. CONCLUSION: Immunity to polioviruses was high in Lebanon in 2016 following a series of supplementary immunization activities. It is essential to continue strategies that increase vaccination coverage in order to sustain the considerably high immunity levels and prevent reintroduction and transmission of poliovirus. Educating caregivers and training health care workers on the standardized usage of home-based vaccination records is needed to guarantee the accuracy of records on children's vaccination status.

BACKGROUND: Caring for young children is a known risk factor for cytomegalovirus (CMV) infection mainly through exposure to their saliva and urine. In a previous study, 36 CMV-seropositive children 2 mo. to 4 years old were categorized as CMV shedders (n = 23) or non-shedders (n = 13) based on detection of CMV DNA in their saliva and urine. The current study evaluated the presence of CMV on surfaces in homes of the children. METHODS: Study staff made 4 visits to homes of the 36 enrolled children over 100 days. Saliva was collected by swabbing the mouth and urine was collected on filter paper inserted into diapers. In addition, five surface specimens were collected: three in contact with children's saliva (spoon, child's cheek, washcloth) and two in contact with children's urine (diaper changing table, mother's hand). Samples were tested by PCR and viral culture to quantify the presence of CMV DNA and viable virus. RESULTS: A total of 654 surface samples from 36 homes were tested; 136 were CMV DNA positive, 122 of which (90%) were in homes of the children shedding CMV (p < 0.001). Saliva-associated samples were more often CMV positive with higher viral loads than urine-associated samples. The higher the CMV viral load of the child in the home, the more home surfaces that were PCR positive (p = 0.01) and viral culture positive (p = 0.05). CONCLUSIONS: The main source for CMV on surfaces in homes was saliva from the child in the home. Higher CMV viral loads shed by children correlated with more viable virus on surfaces which could potentially contribute to viral transmission.

BACKGROUND: To better understand potential transmission risks from contact with the body fluids of children, we monitored the presence and amount of CMV shedding over time in healthy CMV-seropositive children. METHODS: Through screening we identified 36 children from the Atlanta, Georgia area who were CMV-seropositive, including 23 who were shedding CMV at the time of screening. Each child received 12 weekly in-home visits at which field workers collected saliva and urine. During the final two weeks, parents also collected saliva and urine daily. RESULTS: Prevalence of shedding was highly correlated with initial shedding status: children shedding at the screening visit had CMV DNA in 84% of follow-up saliva specimens (455/543) and 28% of follow-up urine specimens (151/539); those not shedding at the screening visit had CMV DNA in 16% of follow-up saliva specimens (47/303) and 5% of follow-up urine specimens (16/305). Among positive specimens we found median viral loads of 82,900 copies/mL in saliva and 34,730 copies/mL in urine (P=0.01), while the viral load for the 75th percentile was nearly 1.5 million copies/mL for saliva compared to 86,800 copies/mL for urine. Younger age was significantly associated with higher viral loads, especially for saliva (P<0.001). Shedding prevalence and viral loads were relatively stable over time. All children who were shedding at the screening visit were still shedding at least some days during weeks 11 and 12, and median and mean viral loads did not change substantially over time. CONCLUSIONS: Healthy CMV-seropositive children can shed CMV for months at high, relatively stable levels. These data suggest that behavioral prevention messages need to address transmission via both saliva and urine, but also need to be informed by the potentially higher risks posed by saliva and by exposures to younger children.

BACKGROUND: Congenital cytomegalovirus (CMV) is the leading infectious cause of birth defects in the United States. To better understand factors that may influence CMV transmission risk, we compared viral and immunological factors in healthy children and their mothers. METHODS: We screened for CMV IgG antibodies in a convenience sample of 161 children aged 0-47 months from the Atlanta, Georgia metropolitan area, along with 32 mothers of children who screened CMV-seropositive. We assessed CMV shedding via PCR using saliva collected with oral swabs (children and mothers) and urine collected from diapers using filter paper inserts (children only). RESULTS: CMV IgG was present in 31% (50/161) of the children. Half (25/50) of seropositive children were shedding in at least one fluid. The proportion of seropositive children who shed in saliva was 100% (8/8) among the 4-12 month-olds, 64% (9/14) among 13-24 month-olds, and 40% (6/15) among 25-47 month-olds (P for trend=0.003). Seropositive mothers had a lower proportion of saliva shedding (21% [6/29]) than children (P<0.001). Among children who were shedding CMV, viral loads in saliva were significantly higher in younger children (P<0.001); on average, the saliva viral load of infants (i.e., <12 months) was approximately 300 times that of two year-olds (i.e., 24-35 months). Median CMV viral loads were similar in children's saliva and urine but were 10-50 times higher (P<0.001) than the median viral load of the mothers' saliva. However, very high viral loads (> one million copies/mL) were only found in children's saliva (31% of those shedding); children's urine and mothers' saliva specimens all had fewer than 100,000 copies/mL. Low IgG avidity, a marker of primary infection, was associated with younger age (p=0.03), higher viral loads in saliva (p=0.02), and lower antibody titers (p=0.005). CONCLUSIONS: Young CMV seropositive children, especially those less than one year-old may present high-risk CMV exposures to pregnant women, especially via saliva, though further research is needed to see if this finding can be generalized across racial or other demographic strata.