A Reminder of Methylene Blue's Effectiveness in Treating Vasoplegic Syndrome after On-Pump Cardiac Surgery

The inflammatory response induced by cardiopulmonary bypass decreases vascular tone, which in turn can lead to vasoplegic syndrome. Indeed the hypotension consequent to on-pump cardiac surgery often necessitates vasopressor and intravenous fluid support. Methylene blue counteracts vasoplegic syndrome by inhibiting the formation of nitric oxide.We report the use of methylene blue in a 75-year-old man who developed vasoplegic syndrome after cardiac surgery. After the administration of methylene blue, his hypotension improved to the extent that he could be weaned from vasopressors. The use of methylene blue should be considered in patients who develop hypotension refractory to standard treatment after cardiac surgery.     

Assessing the immunogenicity of three different inactivated polio vaccine schedules for use after oral polio vaccine cessation,an open label,phase IV,randomized controlled trial

BackgroundAfter global oral poliovirus vaccine (OPV) cessation, the Strategic Advisory Group of Experts on Immunization (SAGE) currently recommends a two-dose schedule of inactivated poliovirus vaccine (IPV) beginning ≥14-weeks of age to achieve at least 90% immune response. We aimed to compare the immunogenicity of three different two-dose IPV schedules started before or at 14-weeks of age.MethodsWe conducted a randomized, controlled, open-label, inequality trial at two sites in Dhaka, Bangladesh. Healthy infants at 6-weeks of age were randomized into one of five arms to receive two-dose IPV schedules at different ages with and without OPV. The three IPV-only arms are presented: Arm C received IPV at 14-weeks and 9-months; Arm D received IPV at 6-weeks and 9-months; and Arm E received IPV at 6 and 14-weeks. The primary outcome was immune response defined as seroconversion from seronegative (<1:8) to seropositive (≥1:8) after vaccination, or a four-fold rise in antibody titers and median reciprocal antibody titers to all three poliovirus types measured at 10-months of age.FindingsOf the 987 children randomized to Arms C, D, and E, 936 were included in the intention-to-treat analysis. At 10-months, participants in Arm C (IPV at 14-weeks and 9-months) had ≥99% cumulative immune response to all three poliovirus types which was significantly higher than the 77–81% observed in Arm E (IPV at 6 and 14-weeks). Participants in Arm D (IPV at 6-weeks and 9-months) had cumulative immune responses of 98–99% which was significantly higher than that of Arm E (p value < 0.0001) but not different from Arm C.InterpretationResults support current SAGE recommendations for IPV following OPV cessation and provide evidence that the schedule of two full IPV doses could begin as early as 6-weeks.     

Vaccine timeliness and prevalence of undervaccination patterns in children ages 0–19 months,U.S., National Immunization Survey-Child 2017

ObjectivesTypically, early childhood vaccination coverage in the U.S. is measured as the proportion of children by age 24 months who completed recommended vaccine series. However, these measures do not reflect whether vaccine doses were received at the ages recommended by the U.S. Advisory Committee on Immunization Practices, or whether children received vaccines concomitantly, per the ACIP recommended schedule. This study’s objective was to quantify vaccine timeliness and prevalence of specific patterns of undervaccination in U.S. children ages 0–19 months.MethodsUsing 2017 National Immunization Survey-Child data, we calculated days undervaccinated for the combined 7-vaccine series and distinguished undervaccination patterns indicative of parental vaccine hesitancy, such as spreading out vaccines across visits (“shot-limiting”) or starting some but not all recommended vaccine series (“selective vaccination”), from other non-hesitancy patterns, such as missing final vaccine doses or receiving all doses, with some or all late. We measured associations between demographic, socioeconomic and other characteristics with undervaccination patterns using multivariable log-linked binomial regression. Analyses accounted for the complex survey design.ResultsAmong n = 15,333 U.S. children, only 41.2% received all recommended vaccine doses on-time by age 19 months. Approximately 20.9% of children had an undervaccination pattern suggestive of parental vaccine hesitancy, and 36.2% had other undervaccination non-hesitancy patterns. Uninsured children and those with lower levels of maternal education were more likely to exhibit undervaccination patterns suggestive of parental hesitancy. Lower levels of maternal education were also associated with other non-hesitancy undervaccination patterns.ConclusionsMore than half of children in the U.S. are undervaccinated at some point by 19 months of age. Ongoing assessment of vaccine timeliness and immunization schedule adherence could facilitate timely and targeted public health interventions in populations with high levels of undervaccination.     

The polio vaccination story of Pakistan

BackgroundTo describe in chronological detail Pakistan’s decades long battle against poliovirus and evaluate the multiple factors impacting it.Main bodyPakistan’s fight is documented through various published research articles and reports on Pakistan’s progress in eradication of polio published by international agencies involved in elimination of poliovirus worldwide. The socioeconomic, religious, and political factors, violent religious militancy, conspiracy theories resulting in vaccine refusals are documented in detail emphasizing the ups and downs in the fight at different times since 1994 to present. Pakistan and Afghanistan are the only two countries in the world reporting cases caused by wild polio virus type 1 (WPV1) since 2017 and the only two countries that have never stopped the transmission of WPV1 Pakistan needs to work on a war footing to eliminate the disease. The need to act urgently is now being increasingly recognized by the Pakistani Government.ConclusionMany difficulties still remain. Pakistan has reached a critical stage in the fight against polio. The world will not accept any further delay or complacency as there is apprehension around the world that Pakistan may “export” polio to other countries and undermine the worldwide success in eradicating polio.     

Building immunization decision-making capacity within the World Health Organization European Region

A National Immunization Technical Advisory Group (NITAG) is a multi-disciplinary body of national experts that provides evidence-based recommendations to policy-makers, assisting them in making sound immunization policy and programme decisions. The World Health Organization (WHO) Regional Office for Europe is working to strengthen the capacity of newly-established NITAGs and has targeted efforts on low- and middle-income countries. The Regional Office, in collaboration with WHO Headquarters and USA Centers for Disease Control and Prevention (CDC), developed a new training strategy and held training workshops to improve NITAGs’ functioning and ability to make evidence-based recommendations. Feedback from countries that participated in trainings indicated that the updated training materials and interactive approach with follow-up technical support enabled them to align their NITAG charters and processes with WHO recommendations. To ensure continued progress, global and regional partners such as WHO and CDC should continue providing technical support to recently established NITAGs.     

Impact of a multi-component immunization intervention on pneumococcal and herpes zoster vaccinations: A randomized controlled trial of community pharmacies in 2 states

BackgroundThe purpose of this study was to assess the impact of the We Immunize Program on structures, processes, and outcomes of pneumococcal and herpes zoster pharmacy-based immunization services.MethodsPharmacy-technician pairs from 62 Alabama and California community pharmacies participated in a 6-month randomized controlled trial (intervention = 30/control = 32). All received immunization update training; intervention participants also received practical strategies training and monthly telephonic expert feedback. Completion of immunization service structure and process activities were analyzed using Fisher's Exact and one-way Mann-Whitney U tests. The primary outcome, change in number of pneumococcal, herpes zoster, and total vaccine doses administered, was assessed using one-way Wilcoxon signed rank and Mann-Whitney U tests. Associations between program and vaccine doses across time were explored using generalized estimating equations (GEE).ResultsIntervention pharmacies completed more structure (median 12.00 versus 9.00, p = 0.200) and process activities (median 8.00 versus 7.00, p = 0.048) compared to control. Statistically significant increases in the median number of pneumococcal vaccine doses (7.50–12.00 doses, p = 0.007), and total vaccine doses (12.50–28.00 doses, p = 0.014) were seen from baseline to post-intervention within the intervention group. However, these changes were not statistically significant when compared to the control group (pneumococcal p = 0.136, total p = 0.202). Changes in median herpes zoster vaccine doses did not reach significance among intervention (8.50–9.00, p = 0.307) or control (9.00–13.00, p = 0.127) pharmacies.ConclusionsPractical strategies training combined with tailored expert feedback enhanced existing pneumococcal immunization services in community pharmacies.Clinical trial registrationClinicalTrials.gov identifier: NCT02615470.     

Immunization with nontreponemal antigen alters the course of experimental syphilis in the rabbit model

The role of nontreponemal antibodies in the Treponema pallidum infection course is unclear. We investigated the effect of immunization with nontreponemal antigen on T. pallidum-challenged rabbits. Nontreponemal antigen was injected intravenously into rabbits in the nontreponemal group (n = 12) to elicit antibodies (≥1:64), and normal saline-injected rabbits were used as controls (n = 12). Then, rabbits were challenged with 10⁶ T. pallidum per site along their back. Lesion development was observed, and the injection sites were biopsied for mRNA analysis every week. Six rabbits from both groups were euthanized at 14 d and 28 d. The popliteal lymph nodes were extracted to assess infectivity using a rabbit infectivity test. The maximum lesion diameters were not different between the two groups (12.4 ± 0.9 mm in the nontreponemal group vs. 12.5 ± 1.0 mm in the control group, P = 0.386), but the time to maximum diameter appearance was delayed by approximately 4 d in the nontreponemal group (14.4 ± 1.6 d vs. 10.8 ± 1.9 d, P = 0.000). There were no significant differences in the proportions of lesions (58/60 (96.7%) vs. 59/60 (98.3%), P = 0.500) or ulcers (55/60 (91.7%) vs. 57/60 (95.0%), P = 0.359) between the two groups. An ulcer development delay of 5 d was observed in the nontreponemal group (19.3 ± 2.0 d vs. 14.0 ± 1.8 d, P = 0.000). IL-2 and IFN-γ mRNA expression in the nontreponemal group was significantly higher than that in the control group at 7 d and 14 d post-challenge. flaA mRNA expression and the rabbit infectivity test positive rate were not different between the two groups. Immunization with nontreponemal antigen altered the syphilis course in rabbits, resulting in delayed maximal lesion diameter and ulcer development, but it could not inhibit the spread of T. pallidum from primary lesion sites to viscera.     

Safety evaluation of adverse events following vaccination with Havrix,Engerix-B or Twinrix during pregnancy

BackgroundVaccination of pregnant women against hepatitis A virus (HAV) or hepatitis B virus (HBV) may benefit the mother and the fetus but is not routinely recommended. However, the risk associated with vaccination should be weighed against the risk of HAV or HBV infection. Data on safety profiles after hepatitis A, B or combined AB immunization during pregnancy are limited.MethodsWe searched the GSK Worldwide Safety Database for adverse events (AEs) following immunization of pregnant women with HAV (Havrix, GSK), HBV (Engerix-B, GSK) or the combined hepatitis AB (Twinrix, GSK) vaccine since market authorization through 31 January 2018, covering at least 25 years. AE reports (spontaneous, post-marketing surveillance and clinical trial cases) in the GSK Worldwide Safety Database were identified using a systematic search and were reviewed by clinicians to ascertain pregnancy status at time of vaccination and characterize adverse pregnancy outcomes, including pregnancy-related AEs and AEs in infants regardless of the causality assessment.ResultsOverall, 613, 700 and 363 pregnancies with exposure to Havrix, Engerix-B and Twinrix, respectively, were reported. Of these, 378, 339 and 194 were analyzed. The most frequently identified pregnancy outcomes were live infants (288, 223 and 151), spontaneous abortions (43, 57 and 26) and elective terminations (25, 24 and 9). A total of 19, 29 and 10 cases of congenital anomalies were reported. Of these, 17, 20 and 7 were major birth defects. The most commonly reported pregnancy-related AE and AE in infants were premature delivery (28) and jaundice (11), respectively. No maternal deaths were reported. Congenital anomalies were reported in all recorded infant deaths.ConclusionsThis review did not indicate any concerning pattern of adverse pregnancy outcomes following exposure to any of the 3 vaccines during pregnancy.     

One or two doses of hepatitis A vaccine in universal vaccination programs in children in 2020: A systematic review

BackgroundHepatitis A virus (HAV) is a global health concern as outbreaks continue to occur. Since 1999, several countries have introduced universal vaccination (UV) of children against HAV according to approved two-dose schedules. Other countries have implemented one-dose UV programs since 2005; the long-term impact of this schedule is not yet known.MethodsWe conducted a systematic literature search in four electronic databases for data published between January 2000 and July 2019 to assess evidence for one-dose and two-dose UV of children with non-live HAV vaccines and describe their global impact on incidence, mortality, and severity of hepatitis A, vaccine effectiveness, vaccine efficacy, and antibody persistence.ResultsOf 3739 records screened, 33 peer-reviewed articles and one conference abstract were included. Rapid declines in incidence of hepatitis A and related outcomes were observed in all age groups post-introduction of UV programs, which persisted for at least 14 years for two-dose and six years for one-dose programs according to respective study durations. Vaccine effectiveness was ≥95% over 3–5 years for two-dose programs. Vaccine efficacy was >98% over 0.1–7.5 years for one-dose vaccination. Antibody persistence in vaccinated individuals was documented for up to 15 years (≥90%) and ten years (≥74%) for two-dose and one-dose schedules, respectively.ConclusionExperience with two-dose UV of children against HAV is extensive, demonstrating an impact on the incidence of hepatitis A and antibody persistence for at least 15 years in many countries globally. Because evidence is more limited for one-dose UV, we were unable to draw conclusions on immune response persistence beyond ten years or the need for booster doses later in life. Ongoing epidemiological monitoring is essential in countries implementing one-dose UV against HAV. Based on current evidence, two doses of non-live HAV vaccines are needed to ensure long-term protection.