Design and implementation of tailored intervention to increase vaccine acceptance in a Somali community in Stockholm, Sweden - based on the Tailoring Immunization Programmes approach.

Objectives: Sweden has had a high and stable vaccination coverage for measles-mumps-rubella (MMR) vaccine (>96%) through the national immunization program (NIP), but coverage rates highlight local pockets of lower vaccination coverage. This project addressed low MMR vaccine acceptance among parents in a Somali community, in Stockholm. The objective of the intervention was to increase vaccine confidence and MMR-vaccine uptake and also to inform practices addressing vaccine acceptance. Study design: This paper describes the design and implementation of a multi-component intervention based on the Tailoring Immunization Programmes (TIP) approach, developed by the WHO European Regional Office. Methods: The theoretical underpinning of TIP is the Capability, Opportunity, and Motivation Model (COM-B model) and Behaviour Change Wheel framework (BCW), adapted for vaccination. The COM-model was used to identify barriers and drivers to vaccination and intervention types. The TIP-phases described in this paper are: pre-TIP (planning), three succeeding TIP phases (situational analysis, formative research, intervention design) and the post-TIP phase (implementation). Results: The situation analysis and formative research revealed that parents feared the MMR vaccine due to autism or that their child would stop talking following vaccination, despite lack of scientific evidence for an association between autism and MMR vaccines. Barriers were linked to their associated COM-B factors and mapped to appropriate intervention types for two target groups: Somali parents and nurses at the Child Health Centres (CHC). Selected intervention types targeting parents were education, persuasion and modelling whereas education and training were selected for CHC nurses. The intervention activities included community engagement for parents, while the activities for nurses focused on improving encounters and dialogue with parents having low vaccine acceptance. Following the intervention design the activities were developed, pilot tested and implemented. Conclusion: This study confirm that the TIP approach is valuable for guiding a stepwise working process for a thorough understanding of barriers and drivers for MMR vaccination among parents in this Somali community. It facilitated the design of a theory and evidence-informed intervention targeting parents and nurses.

Pretreatment HIV drug resistance predicts accumulation of new mutations in ART-naïve Ugandan children.

AIM: To assess the prevalence of pretreatment drug resistance (PDR) and its association with virologic outcomes after 24 weeks of antiretroviral therapy (ART), within an urban cohort of Ugandan children. METHODS: Prospective observational study. Baseline and 24-week assessments of viral load (VL) and genotypic drug resistance to nucleoside reverse transcriptase inhibitors (NRTI) and non-nucleoside reverse transcriptase inhibitors (NNRTI) were performed. RESULTS: Ninety-nine ART-naïve children (3-12 years) initiated efavirenz-based ART 2015-2016 and 18/90 (20%) had baseline NRTI/NNRTI associated drug resistance mutations (DRMs). By 24 weeks, 72/93 (77%) children had VL < 40 copies/mL and a total of 23 children had DRMs. Children with PDR accumulated new DRMs with a mean number (SD) of 1.4 (2.35) new mutations compared to 0.26 (0.98) in 67 children with wild-type virus (P = .003). High pretreatment VL and PDR (number of baseline DRMs) predicted viremia (P = .003; P = .023) as well as acquired drug resistance (P = .02; P = .04). CONCLUSION: Pretreatment drug resistance to NNRTI/NRTI was common among ART-naïve Ugandan children and predicted viremia and new resistance mutations after only 24 weeks of efavirenz-based therapy. PDR may compromise long-term ART outcomes-especially when access to resistance testing and VL monitoring is poor. The long-term importance of PDR for non-NNRTI-based regimens needs further evaluation.

Genetic variants in CYP2B6 and CYP2A6 explain interindividual variation in efavirenz plasma concentrations of HIV-infected children with diverse ethnic origin.

BACKGROUND: Approximately 2.6 million children live with HIV globally, and efavirenz (EFV) is one of the most widely used antiretroviral agents for HIV treatment in children and adults. There are concerns about the appropriateness of current EFV dosing and it has been discussed whether EFV dosing should be adapted according to genotype in children as suggested for adults. AIM: To investigate if pediatric EFV dosing should be guided by genetic variation in drug metabolizing enzymes rather than by body weight. METHOD: EFV plasma concentrations measured for clinical purposes from all children less than 18 years old at Karolinska University Hospital, Stockholm, Sweden, treated with EFV were collected retrospectively. They were genotyped for eleven polymorphisms in genes coding for drug-metabolizing enzymes and P-glycoprotein, of potential importance for EFV disposition. Data on country of origin, sex, age, weight, HIV RNA, viral resistance patterns, CD4 cells, adherence to treatment, subjective health status and adverse events were collected from their medical records. RESULTS: Thirty-six patients and 182 (mean 5 samples/patient) EFV plasma concentration measurements from children of African, Asian and Latin American origin were included. EFV plasma concentration varied 21-fold between measurements (n = 182) (0.85-19.3 mg/L) and 9-fold measured as mean EFV plasma concentration across the subjects (1.55-13.4 mg/L). A multivariate mixed-effects restricted maximum likelihood regression model, including multiple gene polymorphisms, identified CYP2B6*6 T/T (p < 0.0005), CYP2B6*11 G/G (p < 0.0005), CYP2A6*9 A/C (p = 0.001) genotypes, age at treatment initiation (p = 0.002) and time from treatment initiation (p < 0.0005) as independent factors significantly related to loge concentration/(dose/weight). The contribution of the model to the intra- and interindividual variation were 6 and 75%, respectively (Bryk/Raudenbush R-squared level). CONCLUSION: Genetic polymorphisms in CYP2B6 and CYP2A6 explained a significant proportion of variability in EFV plasma concentration in HIV-infected children in a multi-ethnic outpatient clinic. Knowledge about individual variants in key drug metabolizing enzyme genes could improve clinical safety and genotype directed dosing could achieve more predictable EFV plasma concentrations in HIV-infected children.

Intrathecal chemoprophylaxis after HSCT in children.

At present, the literature on the efficacy and risks of i.t. chemotherapy to children after HSCT is scarce. Current practices to reduce the risk of leukemic relapse in the CNS after HSCT differ between centers of transplantation. We compared 74 patients (56 ALL/18 AML), who received i.t. therapy post-HSCT with 46 patients (36 ALL/10 AML) who did not receive post-HSCT i.t. therapy. The patients were transplanted at the University Children's Hospital, Uppsala or the Karolinska University Hospital, Huddinge, two Swedish transplantation units with different routines concerning i.t. therapy after HSCT. The primary end-point was the number of isolated CNS relapses. Secondary end-points were other types of relapse, death, and neurological complications. There was no statistically significant difference in the incidence of CNS relapses between the groups (p > 0.05). I.t. therapy did not reduce the overall incidence of isolated CNS relapse or mortality. Our study did not demonstrate a protective effect of i.t. therapy indicating that post-HSCT i.t. therapy may only be of limited use in the treatment of acute childhood leukemia. We conclude that with the risks present, i.t. therapy should be carefully evaluated, and only considered in high-risk cases.

Acute neurological complications after hematopoietic stem cell transplantation in children.

Children undergoing hematopoietic stem cell transplantation (HSCT) may develop toxicity-related neurological complications (NC). Known risk factors include total body irradiation (TBI) and the use of busulfan or cyclosporine A, but other risk factors might also be of importance. The medical records of 144 children (0-18 yr) who underwent their first HSCT at Karolinska University Hospital (Huddinge) between 1995 and 2002 were reviewed retrospectively concerning pretransplantation parameters and clinical course during the first 3 months after HSCT. Sibling donors were used in 49 transplantations, unrelated donors in 88 and haploidentical donors in seven cases. Nineteen patients (13%) developed NC within the first 3 months after HSCT. A significant association was seen between pretransplant viral status, defined as a higher number of positive herpes group viral serologies in the recipient before transplantation, and NC (p = 0.04). A significant association was also seen for CMV-positive recipients and NC (p = 0.01) as well as for disturbances in serum levels of sodium, potassium and calcium and NC. No association was found between sex, age at HSCT, underlying disease, previous neurological symptoms, the conditioning regimen, GVHD, donor type and NC. Number of positive herpes group viral serologies in the recipient before transplantation and certain electrolyte disturbances may contribute to neurological complications after HSCT.