Search

To enhance our ability to monitor poliovirus circulation and certify eradication, we evaluated the performance of the bag-mediated filtration system (BMFS) against the two-phase separation (TPS) method for concentrating wastewater samples for poliovirus detection. Sequential samples were collected at two sites in Mexico; one L was collected by grab and ~ 5 L were collected and filtered in situ with the BMFS. In the laboratory, 500 mL collected by grab were concentrated using TPS and the sample contained in the filter of the BMFS was eluted without secondary concentration. Concentrates were tested for the presence of poliovirus and non-poliovirus enterovirus (NPEV) using Global Poliovirus Laboratory Network standard procedures. Between February 16, 2016, and April 18, 2017, 125 pairs of samples were obtained. Collectors spent an average (± standard deviation) of 4.3 ± 2.2 min collecting the TPS sample versus 73.5 ± 30.5 min collecting and filtering the BMFS sample. Laboratory processing required an estimated 5 h for concentration by TPS and 3.5 h for elution. Sabin 1 poliovirus was detected in 37 [30%] samples with the TPS versus 24 [19%] samples with the BMFS (McNemar's mid p value = 0.004). Sabin 3 poliovirus was detected in 59 [47%] versus 49 (39%) samples (p = 0.043), and NPEV was detected in 67 [54%] versus 40 [32%] samples (p < 0.001). The BMFS method without secondary concentration did not perform as well as the TPS method for detecting Sabin poliovirus and NPEV. Further studies are needed to guide the selection of cost-effective environmental surveillance methods for the polio endgame.

Background: Monovalent type 2 oral poliovirus vaccine (mOPV2) and inactivated poliovirus vaccine (IPV) are used to respond to type 2 poliovirus outbreaks. We aimed to assess the effect of two mOPV2 doses on the type 2 immune response by varying the time interval between mOPV2 doses and IPV co-administration with mOPV2., Methods: We did a randomised, controlled, parallel, open-label, non-inferiority, inequality trial at two study clinics in Dhaka, Bangladesh. Healthy infants aged 6 weeks (42-48 days) at enrolment were randomly assigned (1:1:1:1) to receive two mOPV2 doses (each dose consisting of two drops [0·1 mL in total] of about 10 5 50% cell culture infectious dose of type 2 Sabin strain) at intervals of 1 week, 2 weeks, 4 weeks (standard or control group), or 4 weeks with IPV (0·5 mL of type 1 [Mahoney, 40 D-antigen units], type 2 [MEF-1, 8 D-antigen units], and type 3 [Saukett, 32 D-antigen units]) administered intramuscularly with the first mOPV2 dose. We used block randomisation, randomly selecting blocks of sizes four, eight, 12, or 16 stratified by study sites. We concealed randomisation assignment from staff managing participants in opaque, sequentially numbered, sealed envelopes. Parents and clinic staff were unmasked to assignment after the randomisation envelope was opened. Laboratory staff analysing sera were masked to assignment, but investigators analysing data and assessing outcomes were not. The primary outcome was type 2 immune response measured 4 weeks after mOPV2 administration. The primary modified intention-to-treat analysis included participants with testable serum samples before and after vaccination. A non-inferiority margin of 10% and p=0·05 (one-tailed) was used. This trial is registered at ClinicalTrials.gov, number NCT02643368, and is closed to accrual., Findings: Between Dec 7, 2015, and Jan 5, 2016, we randomly assigned 760 infants to receive two mOPV2 doses at intervals of 1 week (n=191), 2 weeks (n=191), 4 weeks (n=188), or 4 weeks plus IPV (n=190). Immune responses after two mOPV2 doses were observed in 161 (93%) of 173 infants with testable serum samples in the 1 week group, 169 (96%) of 177 in the 2 week group, and 176 (97%) of 181 in the 4 week group. 1 week and 2 week intervals between two mOPV2 doses were non-inferior to 4 week intervals because the lower bound of the absolute differences in the percentage of immune responses were greater than -10% (-4·2% [90% CI -7·9 to -0·4] in the 1 week group and -1·8% [-5·0 to 1·5] in the 2 week group vs the 4 week group). The immune response elicited by two mOPV2 doses 4 weeks apart was not different when IPV was added to the first dose (176 [97%] of 182 infants with IPV vs 176 [97%] of 181 without IPV; p=1·0). During the trial, two serious adverse events (pneumonia; one [1%] of 186 patients in the 1 week group and one [1%] of 182 in the 4 week group) and no deaths were reported; the adverse events were not attributed to the vaccines., Interpretation: Administration of mOPV2 at short intervals does not interfere with its immunogenicity. The addition of IPV to the first mOPV2 dose did not improve poliovirus type 2 immune response., Funding: US Centers for Disease Control and Prevention., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

According to manufacturers, inactivated poliovirus vaccines (IPVs) are freeze sensitive and require storage between 2°C and 8°C, whereas oral poliovirus vaccine requires storage at -20 °C. Introducing IPV into ongoing immunization services might result in accidental exposure to freezing temperatures and potential loss of vaccine potency. To better understand the effect of freezing IPVs, samples of single-dose vaccine vials from Statens Serum Institut (VeroPol) and multi-dose vaccine vials from Sanofi Pasteur (IPOL) were exposed to freezing temperatures mimicking what a vaccine vial might encounter in the field. D-antigen content was measured to determine the in vitro potency by ELISA. Immunogenicity testing was conducted for a subset of exposed IPVs using the rat model. Freezing VeroPol had no detectable effect on in vitro potency (D-antigen content) in all exposures tested. Freezing of the IPOL vaccine for 7 days at -20 °C showed statistically significant decreases in D-antigen content by ELISA in poliovirus type 1 (p < 0.0001) and type 3 (p = 0.048). Reduction of poliovirus type 2 potency also approached significance (p = 0.062). The observed loss in D-antigen content did not affect immunogenicity in the rat model. Further work is required to determine the significance of the loss observed and the implications for vaccine handling policies and practices., (Copyright © 2018. Published by Elsevier Ltd.)

Background: More than 99% of poliovirus infections are non-paralytic and therefore, not detected by acute flaccid paralysis (AFP) surveillance. Environmental surveillance (ES) can detect circulating polioviruses from sewage without relying on clinical presentation. With extensive ES and continued circulation of polioviruses, Pakistan presents a unique opportunity to quantify the impact of ES as a supplement to AFP surveillance on overall completeness and timeliness of poliovirus detection., Methods: Genetic, geographic and temporal data were obtained for all wild poliovirus (WPV) isolates detected in Pakistan from January 2011 through December 2013. We used viral genetics to assess gaps in AFP surveillance and ES as measured by detection of 'orphan viruses' (≥1.5% different in VP1 capsid nucleotide sequence). We compared preceding detection of closely related circulating isolates (≥99% identity) detected by AFP surveillance or ES to determine which surveillance system first detected circulation before the presentation of each polio case., Findings: A total of 1,127 WPV isolates were detected by AFP surveillance and ES in Pakistan from 2011-2013. AFP surveillance and ES combined exhibited fewer gaps (i.e., % orphan viruses) in detection than AFP surveillance alone (3.3% vs. 7.7%, respectively). ES detected circulation before AFP surveillance in nearly 60% of polio cases (200 of 346). For polio cases reported from provinces conducting ES, ES detected circulation nearly four months sooner on average (117.6 days) than did AFP surveillance., Interpretation: Our findings suggest ES in Pakistan is providing earlier, more sensitive detection of wild polioviruses than AFP surveillance alone. Overall, targeted ES through strategic selection of sites has important implications in the eradication endgame strategy.

Background: Namibia experienced a large measles outbreak starting in 2009, with 38% of reported cases in adults, including women of reproductive age. Population immunity was assessed among pregnant women to determine whether immunization activities were needed in adults to achieve measles elimination in Namibia., Methods: A total of 1708 and 2040 specimens sampled from Namibian pregnant women aged 15-44 years who were included in the 2008 and 2010 National HIV Sentinel Survey, respectively, were tested for measles immunoglobulin G antibody. The proportion of women seropositive overall and by 5-year age strata was determined, and factors associated with seropositivity were analyzed by logistic regression, including age, facility type, gravidity, HIV status, and urban/rural setting. Seropositivity in 2008 versus 2010 was compared., Results: In both analysis years, measles seropositivity was lower in 15-19-year-olds (77%) and 20-24-year-olds (85-87%) and higher in 25-44-year-olds (90-94%) (2008, p<0.001; 2010, p<0.001). Overall measles seropositivity did not differ between 2008 (87%) and 2010 (87%) (p=0.7). HIV status did not affect seropositivity., Conclusions: Late in a large measles outbreak, 13% of pregnant women in Namibia, and almost one in four 15-19-year-old pregnant women, remained susceptible to measles. In Namibia, immunization campaigns with measles-containing vaccine should be considered for adults., (Published by Elsevier Ltd.)

Background: The level of rubella susceptibility among women of reproductive age in Namibia is unknown. Documenting the risk of rubella will help estimate the potential burden of disease in Namibian women and the risk of congenital rubella syndrome (CRS) in infants, and will guide strategies for the introduction of rubella vaccine., Methods: A total of 2044 serum samples from pregnant Namibian women aged 15-44 years were tested for rubella immunoglobulin G antibody; the samples were obtained during the 2010 National HIV Sentinel Survey. The proportion of women seropositive for rubella was determined by 5-year age strata, and factors associated with seropositivity were analyzed by logistic regression, including age, gravidity, HIV status, facility type, and urban/rural status., Results: Overall rubella seroprevalence was 85% (95% confidence interval (CI) 83-86%). Seroprevalence varied by age group (83-90%) and health district (71-100%). In the multivariable model, women from urban residences had higher odds of seropositivity as compared to women from rural residences (odds ratio 1.40, 95% CI 1.09-1.81)., Conclusions: In the absence of a routine rubella immunization program, the high level of rubella seropositivity suggests rubella virus transmission in Namibia, yet 15% of pregnant Namibian women remain susceptible to rubella. The introduction of rubella vaccine will help reduce the risk of rubella in pregnant women and CRS in infants., (Published by Elsevier Ltd.)

Background: A globally-coordinated phase out of all type 2 containing oral polio vaccine (OPV) is planned for April 2016 during which bivalent 1+3 OPV (bOPV) will replace trivalent OPV (tOPV) in routine immunization schedules and campaigns. Diarrhea impairs the immune response to tOPV, but the effect of diarrhea on bOPV is unknown., Methods: Infants aged 6 weeks to 11 months, who had received <3 doses of OPV and had mild-moderate diarrhea or no diarrhea, were recruited at five health facilities in Nepal. Neutralizing antibody titers to poliovirus types 1 and 3 were measured before and 28 days after bOPV administration. The effect of diarrhea and other factors on seroconversion or boosting in antibody titers to poliovirus was assessed by multivariable analysis., Results: Infants with diarrhea, versus those without diarrhea, had reduced response for poliovirus types 1 (56% [87/156] vs 66% [109/164]) and 3 (34% [70/209] vs 52% [122/236]). After adjusting for other factors, infants with diarrhea had significantly reduced response for type 3 (odds ratio [OR]=0.44, 95% CI 0.29-0.68), as did infants with >5 loose stools per day (OR=0.36, 95% CI 0.21-0.62)., Conclusions: Diarrhea reduced the immune response to bOPV. Provision of additional doses of polio vaccine is necessary to maintain high population immunity in areas with high prevalence of diarrheal disease., Clinical Trial Registry: This study is registered at clinicaltrials.gov as NCT01559636., (Published by Elsevier Ltd.)

Background: The provision of several doses of monovalent type 1 oral poliovirus vaccine (mOPV1) and bivalent OPV1 and 3 (bOPV) vaccines through campaigns is essential to stop the circulation of remaining wild polioviruses. Our study aimed to assess the shortening of intervals between campaigns with bOPV and mOPV1 and to assess the immunogenicity of bOPV in routine immunisation schedules., Methods: We did an open-label, non-inferiority, five-arm, randomised controlled trial in Bangladesh. We recruited healthy infants aged 6 weeks at 42 immunisation clinics and randomly assigned them (with blocks of 15, three per group) to receive a short three-dose schedule of bOPV (bOPV short) or mOPV1 (mOPV1 short) with the first dose given at age 6 weeks, the second at age 8 weeks, and the third at age 10 weeks; or to a standard three-dose schedule of bOPV (bOPV standard) or mOPV1 (mOPV1 standard) or trivalent OPV (tOPV standard) with the first dose given at age 6 weeks, the second at 10 weeks, and the third at age 14 weeks. The primary outcome was the proportion of infants with antibody seroconversion for type 1, type 2, and type 3 polioviruses. The primary, modified intention-to-treat analysis included all patients who had testable serum samples before and after receiving at least one OPV dose. We used a 10% margin to establish non-inferiority for bOPV groups versus mOPV1 groups in seroconversion for type 1 poliovirus, and for bOPV1 short versus bOPV1 standard for types 1 and 3. This trial is registered at ClinicalTrials.gov, number NCT01633216, and is closed to new participants., Findings: Between May 13, 2012, and Jan 21, 2013, we randomly assigned 1000 infants to our study groups. 927 completed all study visits and were included in the primary analysis. Seroconversion for type-1 poliovirus was recorded in 183 (98%, 95% CI 95-100) of 186 infants given bOPV short, 179 (97%, 94-99) of 184 given bOPV standard, 180 (96%, 92-98) of 188 given mOPV short, 178 (99%, 97-100) of 179 given mOPV1 standard, and 175 (92%, 87-96) of 190 given tOPV standard. Seroconversion for type 2 was noted in 16 infants (9%, 5-14) on bOPV short, 29 (16%, 11-22) on bOPV standard, 19 (10%, 7-15) on mOPV short, 33 (18%, 13-25) on mOPV1 standard, and 182 (96%, 92-98) on tOPV standard. Seroconversion for type 3 was noted in 175 infants (94%, 90-97) on bOPV short, 176 (96%, 92-98) on bOPV standard, 18 (10%, 6-15) on mOPV short, 25 (14%, 10-20) on mOPV1 standard, and 167 (88%, 83-92) on tOPV standard. The short schedules for mOPV1 and bOPV elicited a non-inferior antibody response compared with the bOPV standard schedule. 104 adverse events were reported in 100 infants during follow up. 36 of these events needed admission to hospital (32 were pneumonia, two were vomiting or feeding disorders, one was septicaemia, and one was diarrhoea with severe malnutrition). One of the infants admitted to hospital for pneumonia died 5 days after admission. No adverse event was attributed to the vaccines., Interpretation: Our trial showed that three doses of mOPV1 or bOPV with a short schedule of 2 week intervals between doses induces an immune response similar to that obtained with the standard schedule of giving doses at 4 week intervals. These findings support the use of these vaccines in campaigns done at short intervals to rapidly increase population immunity against polioviruses to control outbreaks or prevent transmission in high-risk areas., Funding: Centers for Disease Control and Prevention and UNICEF., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Background: The effect of transport temperature on the viability of poliovirus in stool specimens from paralyzed cases has not been tested. Quality assurance of programmatic indicators will be necessary in the final phase of polio eradication., Objective: To estimate the effect of time at elevated temperatures on wild poliovirus titers in stool specimens., Methods: We exposed aliquots of pooled wild poliovirus type 1 specimens to elevated temperatures (27 °C, 31 °C, and 35 °C) for varying time periods up to 14 days. We determined the virus titer of these aliquots and created decay curves at each temperature to estimate the relationship between time at temperature and virus titer., Results: We found significantly different slopes of decay at each temperature. The negative slopes increased as the temperature increased., Conclusions: While poliovirus in stool remains relatively stable at moderately elevated temperature, transport at higher temperatures could impact sample integrity and virus isolation results., (Published by Elsevier Inc.)