Background. The potential to strengthen routine immunization (RI) services through supplementary immunization activities (SIAs) is an important benefit of global measles and rubella elimination and ...polio eradication strategies. However, little evidence exists on how best to use SIAs to strengthen RI. As part the 2012 Nepal measles-rubella and polio SIA, we developed an intervention package designed to improve RI processes and evaluated its effect on specific RI process measures. Methods. The intervention package was incorporated into existing SIA activities and materials to improve healthcare providers' RI knowledge and practices throughout Nepal. In 1 region (Central Region) we surveyed the same 100 randomly selected health facilities before and after the SIA and evaluated the following RI process measures: vaccine safety, RI planning, RI service delivery, vaccine supply chain, and RI data recording practices. Data collection included observations of vaccination sessions, interviews with the primary healthcare provider who administered vaccines at each facility, and administrative record reviews. Pair-matched analytical methods were used to determine whether statistically significant changes in the selected RI process measures occurred over time. Results. After the SIA, significant positive changes were measured in healthcare provider knowledge of adverse events following immunization (11% increase), availability of RI microplans (+17%) and maps (+12%), and awareness of how long a reconstituted measles vial can be used before it must be discarded (+14%). For the SIA, 42% of providers created an SIA high-risk villages list, and >50% incorporated this information into RI outreach session site planning. Significant negative changes occurred in correct knowledge of measles vaccination contraindications (−11%), correct definition for a measles outbreak (−21%), and how to treat a child with a severe adverse event following immunization (−10%). Twenty percent of providers reported cancelling ≥1 RI sessions during the SIA. Many RI process measures were at high proportions (>90%) before the SIA and remained high afterward, including proper vaccine administration techniques, proper vaccine waste management, and availability of vaccine carriers and vaccine registers. Conclusions. Focusing on activities that are easily linked between SIAs and RI services, such as using SIA high-risk village list to strengthen RI microplanning and examining ways to minimize the impact of an SIA on RI session scheduling, should be prioritized when implementing SIAs.
All-trans-retinoic acid (RA) is known to induce terminal granulocytic differentiation and cell cycle arrest of HL-60 cells. Responding to an RA-induced cytosolic signaling machine, c-Raf translocates ...to the nucleus, providing propulsion for RA-induced differentiation. This novel mechanism is not understood, but presumably reflects c-Raf binding with nuclear gene regulatory proteins. RRD-251 is a small molecule that prevents the interaction of c-Raf and RB, the retinoblastoma tumor suppressor protein. The involvement of c-Raf and RB in RA-induced differentiation motivates interest in the effects of combined RA and RRD-251 treatment on leukemic cell differentiation. We demonstrate that RRD-251 enhances RA-induced differentiation. Mechanistically, we find that nuclear translocated c-Raf associates with pS608 RB. RA causes loss of pS608 RB, where cells with hypophosphorylated S608 RB are G0/G1 restricted. Corroborating the pS608 RB hypophosphorylation, RB sequestration of E2F increased with concomitant loss of cdc6 expression, which is known to be driven by E2F. Hypophosphorylation of S608 RB releases c-Raf from RB sequestration to bind other nuclear targets. Release of c-Raf from RB sequestration results in enhanced association with GSK-3 which is phosphorylated at its S21/9 inhibitory sites. c-Raf binding to GSK-3 is associated with dissociation of GSK-3 and RARα, thereby relieving RARα of GSK-3 inhibition. RRD-251 amplifies each of these RA-induced events. Consistent with the posited enhancement of RARα transcriptional activity by RRD-251, RRD-251 increases the RARE-driven CD38 expression per cell. The RA/c-Raf/GSK-3/RARα axis emerges as a novel differentiation regulatory mechanism susceptible to RRD-251, suggesting enhancing RA-effects with RRD-251 in therapy.
Since special efforts are necessary to vaccinate people living far from fixed vaccination posts, decision makers are interested in knowing the economic value of such efforts.
Using our immunization ...geospatial information system platform and a measles compartment model, we quantified the health and economic value of a 2-dose measles immunization outreach strategy for children <24 months of age in Kenya who are geographically hard-to-reach (i.e., those living outside a specified catchment radius from fixed vaccination posts, which served as a proxy for access to services).
When geographically hard-to-reach children were not vaccinated, there were 1427 total measles cases from 2016 to 2020, resulting in $9.5 million ($3.1–$18.1 million) in direct medical costs and productivity losses and 7504 (3338–12,903) disability-adjusted life years (DALYs). The outreach strategy cost $76 ($23–$142)/DALY averted (compared to no outreach) when 25% of geographically hard-to-reach children received MCV1, $122 ($40-$226)/DALY averted when 50% received MCV1, and $274 ($123-$478)/DALY averted when 100% received MCV1.
Outreach vaccination among geographically hard-to-reach populations was highly cost-effective in a wide variety of scenarios, offering support for investment in an effective outreach vaccination strategy.
A 44-year-old woman with long-standing common variable immunodeficiency who was receiving intravenous immune globulin suddenly had paralysis of all four limbs and the respiratory muscles, resulting ...in death. Type 2 vaccine-derived poliovirus was isolated from stool. The viral capsid protein VP1 region had diverged from the vaccine strain at 12.3% of nucleotide positions, and the two attenuating substitutions had reverted to the wild-type sequence. Infection probably occurred 11.9 years earlier (95% confidence interval CI, 10.9 to 13.2), when her child received the oral poliovirus vaccine. No secondary cases were identified among close contacts or 2038 screened health care workers. Patients with common variable immunodeficiency can be chronically infected with poliovirus, and poliomyelitis can develop despite treatment with intravenous immune globulin.
Background. To monitor immunization-system strengthening in the Polio Eradication Endgame Strategic Plan 2013–2018 (PEESP), the Global Polio Eradication Initiative identified 1 indicator: 10% annual ...improvement in third dose of diphtheria-tetanus-pertussis–containing vaccine (DTP3) coverage in polio high-risk districts of 10 polio focus countries. Methods. A multiagency team, including staff from the African Region, developed a comprehensive list of outcome and process indicators measuring various aspects of the performance of an immunization system. Results. The development and implementation of the dashboard to assess immunization system performance allowed national program managers to monitor the key immunization indicators and stratify by high-risk and non–high-risk districts. Discussion. Although only a single outcome indicator goal (at least 10% annual increase in DTP3 coverage achieved in 80% of high-risk districts) initially existed in the endgame strategy, we successfully added additional outcome indicators (eg, decreasing the number of DTP3-unvaccinated children) as well as program process indicators focusing on cold chain, stock availability, and vaccination sessions to better describe progress on the pathway to raising immunization coverage. Conclusion. When measuring progress toward improving immunization systems, it is helpful to use a comprehensive approach that allows for measuring multiple dimensions of the system.
Background. In 2013, the World Health Organization's (WHO's) Strategic Advisory Group of Experts (SAGE) recommended that all 126 countries using only oral polio vaccine (OPV) introduce at least 1 ...dose of inactivated polio vaccine (IPV) into their routine immunization schedules by the end of 2015. In many countries, the addition of IPV would necessitate delivery of multiple injectable vaccines (hereafter, "multiple injections") during a single visit, with infants receiving IPV alongside pentavalent vaccine (which covers diphtheria, tetanus, and whole-cell pertussis; hepatitis B; and Haemophilus influenzae type b) and pneumococcal vaccine. Unanticipated concerns emerged from countries over acceptability of multiple injections, sites of administration, and safety. We contextualized the issues surrounding multiple injections by documenting concerns associated with administration of ≥3 injections, existing evidence in the published literature, and findings of a systematic review on administration practices and techniques. Methods. Concerns associated with multiple-injection visits were documented from meetings and personal communications with immunization program managers. Published literature on the acceptability of multiple injections by providers and caregivers was summarized, and a systematic review of the literature on administration practices was completed on the following topics: spacing between injection sites (ie, vaccine spacing), site of injection, route of injection, and procedural preparedness. WHO and United Nations Children's Fund data from 2013–2015 were used to assess multiple-injection visits included in national immunization schedules. Results. Healthcare provider and caregiver attitudes and practices indicated concerns about infant pain, potential adverse effects, and uncertainty about vaccine effectiveness with multiple-injection visits. Published literature reinforced the record of safety and acceptance of the recommended schedule of IPV by the SAGE, but the evidence was largely from developed countries. Parental acceptance of multiple injections was associated with a positive provider recommendation to the caregiver. Findings of the systematic review identified that the intramuscular route is preferred over the subcutaneous route for vaccine administration and that the vastus lateralis muscle is preferred over the deltoid muscle for intramuscular injections. Recommendations on vaccine spacing and procedural preparedness were based on practical necessities, but comparative evidence was not identified. During 2013–2015, 85 countries added IPV to their immunization schedules, 46 (55%) of which adopted a schedule resulting in 3 injectable vaccines being administered in a single visit. Conclusion. The multiple-injection experience identified gaps in guidance for future vaccine introductions. Global partner organizations quickly mobilized to assess, document, and communicate the existing global experience on multiple-injection visits. This evidence-based approach provided reassurance to opinion leaders, health workers, and professional societies, thus encouraging uptake of IPV as a second or third injection in an accelerated manner globally.
Community health workers (CHWs) play an integral role in Sierra Leone's health systems strengthening efforts. Our goal was to understand CHWs' experiences of providing immunization and malaria ...prevention services in urban settings and explore opportunities to optimize their contributions to these services.
In 2018, we conducted an exploratory qualitative assessment in the Western Area Urban district, which covers most of the capital city of Freetown. We purposively selected diverse health facilities (i.e., type, ownership, setting) and recruited CHWs through their supervisors. We conducted eight focus group discussions (FGD) with CHWs, which were audio-recorded. The topics explored included participants' background, responsibilities and priorities of urban CHWs, sources of motivation at work, barriers to CHWs' immunization and malaria prevention activities, and strategies used to address these barriers. The local research team transcribed and translated FGDs into English; then we used qualitative content analysis to identify themes.
Four themes emerged from the qualitative content analysis: (1) pride, compassion, recognition, and personal benefits are important motivating factors to keep working as CHWs; (2) diverse health responsibilities and competing priorities result in overburdening of CHWs; (3) health system- and community-level barriers negatively affect CHWs' activities and motivation; (4) CHWs use context-specific strategies to address challenges in their work but require further support.
Focused support for CHWs is needed to optimize their contributions to immunization and malaria prevention activities. Such interventions should be coupled with systems-level efforts to address the structural barriers that negatively affect CHWs' overall work and motivation, such as the shortage of work supplies and the lack of promised financial support.
There is limited understanding of the potential impact of information sources on vaccination attitudes and behaviors in low-income countries. We examined how exposure to immunization information ...sources may be associated with vaccination uptake in Sierra Leone.
In 2019, a household survey was conducted using multistage cluster sampling to randomly select 621 caregivers of children aged 12-23 months in 4 districts in Sierra Leone. We measured exposure to various sources of immunization information and 2 outcomes: (1) vaccination confidence using an aggregate score (from 12 Likert items, informed by previously validated scale) that was dichotomized into a binary variable; (2) uptake of the third dose of diphtheria-pertussis-tetanus-hepatitis B-
type-b-pentavalent vaccine (penta-3) based on card record or through caregiver recall when card was unavailable. Associations between information sources and the outcomes were examined using modified Poisson regression with robust variance estimator.
Weighted estimate for penta-3 uptake was 81% (75.2%-85.5%). The likelihood of uptake of penta-3 was significantly greater when caregiver received information from health facilities (adjusted prevalence ratio aPR=1.26, 95% confidence interval CI=1.1, 1.5), faith leaders (aPR=1.16, 95% CI=1.1, 1.3), and community health workers (aPR=1.13, 95% CI=1.003, 1.3). Exposure to greater number of information sources was associated with high penta-3 uptake (aPR=1.05, 95% CI=1.02, 1.1).
Immunization information received during health facility visits and through engagement with religious leaders may enhance vaccination uptake. Assessments to understand context-specific information dynamics should be prioritized in optimizing immunization outcomes.
Objective
This study aimed to examine whether 1‐month BMI improvement is predictive of superior 6‐ and 12‐month BMI changes in a national sample of youth in pediatric weight management treatment.
...Methods
Participants were 4‐ to 18‐year‐olds from the Pediatric Obesity Weight Evaluation Registry, a prospective study collecting data from 31 pediatric weight management programs across the United States. Response at 1 month was defined as ≥ 3% BMI reduction; success at 6 and 12 months was defined as ≥ 5% BMI reduction from baseline. Analyses used linear and logistic regression with robust variance estimation.
Results
Primary analyses were completed with 687 participants (mean age 12.2 years). One‐month responders demonstrated significant improvements in BMI compared with nonresponders at 6 months (BMI, −2.05 vs. 0.05; %BMI, −5.81 vs. 0.23; P < 0.001 for all) and 12 months (BMI, −1.87 vs. 0.30; %BMI, −5.04 vs. 1.06; P < 0.001 for all). The odds of success for 1‐month responders were 9.64 (95% CI: 5.85‐15.87; P < 0.001) times that of nonresponders at 6 months and 5.24 (95% CI: 2.49‐11.02; P < 0.001) times that of nonresponders at 12 months.
Conclusions
In treatment‐seeking youth with obesity, early BMI reduction was significantly associated with greater long‐term BMI reduction. Nonresponders may benefit from early treatment redirection or intensification.
Background. Albania introduced inactivated polio vaccine (IPV) into its immunization system in May 2014, increasing the maximum recommended number of injectable vaccines given in a single visit from ...2 to 3. Methods. Health-care providers and caregivers were interviewed at 42 health facilities in Albania to assess knowledge, attitudes, and practices regarding injectable vaccine administration. Immunization register data were abstracted from December 2014 to July 2015 at the same facilities to explore the number of injectable vaccines children received during their 2- and 4-month visits. Results. The majority of children (87%) identified in the record review at either their 2- or 4-month immunization visit received all 3 injectable vaccines in a single visit. Almost all children who did not receive the vaccines in a single visit were subsequently fully immunized, most within a 2-week period. Over half of caregivers whose children got 3 or more injectable vaccines in a single visit reported being only comfortable with 1 or 2 injectable vaccines in a single visit. Conclusions. Despite most caregivers expressing hesitation regarding children receiving multiple injectable vaccines in a single visit, most children received vaccines according to the recommended schedule. Almost all children eventually received all recommended vaccines.
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