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The varicella-zoster virus (VZV) genome, as with all other human herpesviruses, comprises both unique and repeated regions. In addition, the genome includes six sequences of tandemly repeating short elements termed reiteration regions, designated R1 to R5. The R4 element is duplicated, with one copy each in the terminal repeat short (TRs) and the internal repeat short (IRs) regions. The reiteration regions (R) are an understudied feature of the VZV genome even though three of them (R1, R2 and R3) reside inside the coding regions of important viral genes. R1 is located in ORF11, a tegument protein and the homoolog to herpes simplex virus UL47. R2 is located in ORF 14, which encodes glycoprotein C. R3 is located in ORF22, a component of the viral tegument and the largest gene product encoded by the virus. It is the homolog to herpes simplex virus UL36. R4A is located in the IRs and is duplicated, usually in inverted orientation, as R4B in the TRs. R5 is located in a non-coding region between ORF60 and 61. We developed primers to amplify and Sanger sequence all six reiteration regions, including primers that independently amplify the two copies of R4. We sequenced the reiteration regions from more than 80 genomes for viruses selected from the Kaiser Permanente Herpes Zoster Study, each of which was sampled from patients with well-characterized cases of herpes zoster. Samples were selected to provide a broad representation of VZV clades. The remainder of these genomes were sequenced using the Illumina MiSeq platform.

Aims Describe the pharmacokinetics (PK) of the antiretroviral drugs abacavir and lamivudine in malnourished paediatric patients and relate to viral load outcomes after 12 and 48 weeks of treatment. Methods Severely malnourished human immunodeficiency virus-infected children were randomized to early (within 14 days) or delayed (after nutritional recovery) initiation of antiretroviral treatment (ART) using World Health Organization weight-band dosages. Abacavir and lamivudine concentrations were measured as a secondary objective on day 1 and day 14 and patients were followed-up to week 48. Population PK of abacavir and lamivudine were described using NONMEM. Results In total, 623 abacavir and 627 lamivudine concentrations were collected from 75 paediatric patients aged 0.1-10.8 (median 1.4) years. Abacavir PK was described by a 2-compartment model, patients randomized to early ART showed increased bioavailability of 31%. Apparent clearance (CL/F, L/h/7 kg) of abacavir increased from day 1 to day 14 from 3.33 (95% confidence interval 2.71-4.12) to 5.86 (95% confidence interval 4.78-7.3). A 1-compartment model described lamivudine PK, variability on CL/F was explained by maturation with age, with age at half-matured CL/F being 4 months. For both drugs allometrically scaled total body weight was related to CL/F and apparent volume of distribution. PK exposure did not correlate with virological outcomes or death at 12 or 48 weeks. Conclusion Increases in Abacavir's CL/F between day 1 to day 14, bioavailability and PK variability with early start of ART was found in this cohort of severely malnourished children; however, these changes did not influence virological outcomes. The study supports the use of weight-band dosage tables.

People living within the same household as someone ill with influenza are at increased risk of infection. Here, we use Markov chain Monte Carlo methods to partition the hazard of influenza illness within a cohort into the hazard from the community and the hazard from the household. During the 2013-2014 influenza season, 49 (4.7%) of the 1044 people enrolled in a community surveillance cohort had an acute respiratory illness (ARI) attributable to influenza. During the 2014-2015 influenza season, 50 (4.7%) of the 1063 people in the cohort had an ARI attributable to influenza. The secondary attack rate from a household member was 2.3% for influenza A (H1) during 2013-2014, 5.3% for influenza B during 2013-2014, and 7.6% for influenza A (H3) during 2014-2015. Living in a household with a person ill with influenza increased the risk of an ARI attributable to influenza up to 350%, depending on the season and the influenza virus circulating within the household.

Sickle cell disease (SCD) in Africa has high prevalence, morbidity, and early mortality. Difficulties in reaching parents following infant SCD screening dampen program effectiveness. Text messaging may support initial postscreening parental notification. We explored SCD awareness, and feasibility and acceptability of text messaging about screening follow-up among convenience samples of caretakers with children under 5 years (n=115) at 3 sites: a SCD family conference or 2 general pediatric clinics in urban or rural Uganda. Two thirds of the conference-based participants and 8% at clinic sites had affected children. At the clinics, 64% of caretakers were aware of SCD. In all, 87% claimed current possession of mobile phones; 89% previously had received messages. A sample text on the availability of screening results and need to bring their child to SCD clinic was at least partially understood by 82%. Overall, 52% preferred communication for initial follow-up by telephone over text message. Concerns about texting included phone access, privacy or cost, and readability of messages. Caretakers identified concerns about distance, cost, or preference for another clinic as additional barriers to SCD follow-up. Findings suggest that text messaging to caretakers may be feasible, but less acceptable compared with a telephone call about initial follow-up from newborn SCD screening.

AIM We aimed to assess the receipt of recommended care for young children with sickle cell disease (SCD) in a central SCD clinic in Kampala Uganda, focusing on standard vaccination and antibacterial and antimalarial prophylaxis. METHODS A cross-sectional assessment of immunisation status and timeliness and prescribed antibacterial and antimalarial prophylaxis was performed in a sample with SCD aged ≤71 months in Mulago Hospital SCD Clinic. Government-issued immunisation cards and clinic-issued visit records for prescribed prophylaxis were reviewed. RESULTS Vaccinations were documented by immunisation cards in 104 patients, mean age 31.7 months (range 3-70 months). Only 48 (46.2%) received all doses of each of the four recommended vaccine types, including pneumococcal 10-valent conjugate vaccine (pneumococcal conjugate vaccine (PCV)-10), which became available in 2014. Vaccination completion was associated with younger age and, for polio, maternal employment. PCV-10 series was completed in 54.8% of the sample and in 18.2% of those aged 48-71 months. Of children completing all vaccination types, an average 68.8% were immunised on time, defined as

Ghanaian children (2176) aged, A respiratory pathogen was identified in 59% of Ghanaian children who presented with acute respiratory distress. Rhinovirus and/or enterovirus was identified most commonly. Respiratory syncytial virus and metapneumovirus were detected more frequently in the rainy season than in the dry season.

Highlights • We investigated risk of acute respiratory illness post-influenza vaccination. • Post-vaccination risk of non-influenza respiratory pathogen was higher in children. • Patient perceptions of illness following influenza vaccination may be supported. • Assessments of potential mechanisms for findings are needed., Background A barrier to influenza vaccination is the misperception that the inactivated vaccine can cause influenza. Previous studies have investigated the risk of acute respiratory illness (ARI) after influenza vaccination with conflicting results. We assessed whether there is an increased rate of laboratory-confirmed ARI in post-influenza vaccination periods. Methods We conducted a cohort sub-analysis of children and adults in the MoSAIC community surveillance study from 2013 to 2016. Influenza vaccination was confirmed through city or hospital registries. Cases of ARI were ascertained by twice-weekly text messages to household to identify members with ARI symptoms. Nasal swabs were obtained from ill participants and analyzed for respiratory pathogens using multiplex PCR. The primary outcome measure was the hazard ratio of laboratory-confirmed ARI in individuals post-vaccination compared to other time periods during three influenza seasons. Results Of the 999 participants, 68.8% were children, 30.2% were adults. Each study season, approximately half received influenza vaccine and one third experienced ≥1 ARI. The hazard of influenza in individuals during the 14-day post-vaccination period was similar to unvaccinated individuals during the same period (HR 0.96, 95% CI [0.60, 1.52]). The hazard of non-influenza respiratory pathogens was higher during the same period (HR 1.65, 95% CI [1.14, 2.38]); when stratified by age the hazard remained higher for children (HR 1·71, 95% CI [1.16, 2.53]) but not for adults (HR 0.88, 95% CI [0.21, 3.69]). Conclusion Among children there was an increase in the hazard of ARI caused by non-influenza respiratory pathogens post-influenza vaccination compared to unvaccinated children during the same period. Potential mechanisms for this association warrant further investigation. Future research could investigate whether medical decision-making surrounding influenza vaccination may be improved by acknowledging patient experiences, counseling regarding different types of ARI, and correcting the misperception that all ARI occurring after vaccination are caused by influenza.

A 2-year-old boy with influenza B infection and rapidly worsening targetoid skin lesions with mucosal involvement was diagnosed with Stevens-Johnson syndrome (SJS) and treated with oseltamivir and intravenous immunoglobulin, with resolution of illness. Subsequent quadrivalent inactivated influenza vaccine was well tolerated. This case highlights the rarity of SJS in the setting of influenza B infection and addresses the safety of administering subsequent influenza vaccines to such individuals.

INTRODUCTION: The feasibility and accuracy of text messaging to monitor events after influenza vaccination throughout pregnancy and the neonatal period has not been studied, but may be important for seasonal and pandemic influenza vaccines and future maternal vaccines. METHODS: This prospective observational study was conducted during 2013–2014 and analyzed in 2015–2016. Enrolled pregnant women receiving inactivated influenza vaccination at a gestational age

A population specific understanding of barriers and facilitators to participation in clinical trials could improve recruitment of elderly and minority populations. We investigated how prior exposure to clinical trials and incentives were associated with likelihood of participation in a vaccine clinical trial through a questionnaire administered to 200 elderly patients in an academic general internal medicine clinic. Wilcoxon signed rank sum test compared likelihood of participation with and without monetary incentives. Logistic regression evaluated characteristics associated with intent to participate in an influenza vaccine trial, adjusted for age, gender, language, and education history. When asked about likelihood of participation if there was monetary compensation, there was a 12.2% absolute increase in those reporting that they would not participate, with a significant difference in the distribution of likelihood before and after mentioning a monetary incentive (Wilcoxon signed rank test, p = 0.001). Those with previous knowledge of clinical trials (54.4%) were more likely to report they would participate vs. those without prior knowledge (OR 2.5, 95% CI [1.2, 5.2]). The study highlights the importance of pre-testing recruitment materials and incentives in key group populations prior to implementing clinical trials. Keywords: Geriatrics, Clinical trials, Research design, Disparities

The majority of influenza related deaths and hospitalizations occur among individuals ≥65 years, yet the national influenza vaccination rate for this group is 63% and is lower in the Hispanic population. Previous studies have described negative predictors of vaccination; however, there is a knowledge gap of how influenza vaccine-specific beliefs affect vaccination rates. We examined the relationship between influenza vaccine health beliefs and vaccination behaviors in a cross sectional sample of 200 primarily Hispanic patients aged ≥65 years in an academic general internal medicine clinic. Participants were asked about perceptions of influenza vaccine effectiveness and safety. Interview responses regarding influenza vaccine concerns were evaluated qualitatively with conventional content analysis. Logistic regression evaluated associations between beliefs and self-reported vaccination the previous year, adjusted for age, gender, and language. Of those approached to complete the questionnaire, 88% participated. Self-reported influenza vaccination rate during the study year was 75%. Only 46.5% endorsed the belief that influenza vaccine is very effective and 47% that it is very safe. Many stated specific concerns about flu vaccine including that it causes side effects/adverse outcomes, is not effective, vaccine components are harmful, and vaccination is not necessary. Belief that the flu shot causes the flu and concern for variability of the flu shot were associated with reduced odds of vaccination (aOR 0.19, 95% CI [0.05, 0.83] and 0.06 [0.006, 0.63] respectively). The patient-perceived distinction between cold, flu, and other symptoms warrants further exploration. This information can be used to develop targeted communication to promote vaccination.

The main objective of this study was to assess whether training of private health providers and community sensitization on the importance of effective prompt care seeking and the need for referral could improve treatment of sick children in the private health sector in Uganda. Private providers were trained to diagnose and treat sick children according to the integrated community case management (iCCM) guidelines. In the control arm, routine services were offered. The outcomes were seeking care within 24 hours of onset of symptoms and appropriate case management for malaria, pneumonia, and diarrhea among children aged < 5 years. A total of 10,809 sick children (5,955 in the intervention arm and 4,854 in the control arm) presented for diagnosis and treatment. The percentage seeking care within 24 hours of onset of symptoms was 45.4% (95% CI 36.0-48.8) in the intervention arm versus 43.9% (95% CI 38.1-49.8) in the control arm (P = 0.04). Adherence to malaria rapid diagnostic test (mRDT) results was high, with 1,459 (94.3%) in the intervention arm versus 1,402 (83.0%) in the control arm (P = 0.04). Appropriate treatment of mRDT-positive children with artemisinin-based combination therapy was seen in 93.1% (95% CI 88.5-97.7) in the intervention arm versus 85.1% (95% CI 78.6-91.7) in the control arm (P = 0.03). Adherence to iCCM guidelines was very high: 89.1% of children with diarrhea in the intervention arm and 80.4% in the control arm were given oral rehydration salts and zinc (P = 0.01). Of the children with a respiratory rate > 40 breaths/minute, 1,596 (85.1%) in the intervention arm versus 104 (54.5%) in the control arm were given amoxicillin (P = 0.01). In conclusion, the intervention improved treatment of malaria, pneumonia, and diarrhea because of provider adherence to treatment guidelines. The policy implications of these findings are to initiate a dialogue at district and national levels on how to scale up the intervention in the private sector. NCT02450630 registered with ClinicalTrials.gov: May 9, 2015.

BackgroundChildren with sickle cell anemia (SCA) are highly susceptible to stroke and other manifestations of pediatric cerebral vasculopathy. Detailed evaluations in sub-Saharan Africa are limited.MethodsWe aimed to establish the frequency and types of pediatric brain injury in a cross-sectional study at a large SCA clinic in Kampala, Uganda in a randomly selected sample of 265 patients with HbSS ages 1–12 years. Brain injury was defined as one or more abnormality on standardized testing: neurocognitive impairment using an age-appropriate test battery, prior stroke by examination or transcranial Doppler (TCD) velocities associated with stroke risk in children with SCA (cerebral arterial time averaged mean maximum velocity ≥ 170 cm/second).ResultsMean age was 5.5 ± 2.9 years; 52.3% were male. Mean hemoglobin was 7.3 ± 1.01 g/dl; 76.4% had hemoglobin p p = 0.04). In adjusted models, neurocognitive dysfunction was strongly related to prior stroke (OR 6.88, 95%CI 1.95–24.3,p = .003) and to abnormal TCD (OR 4.37, 95%CI 1.30,p = 0.02). In a subset of 81 subjects who were enriched for other abnormal results, magnetic resonance imaging and angiography (MRI/MRA) detected infarcts and/or arterial stenosis in 52%. Thirteen subjects (25%) with abnormal imaging had no other abnormalities detected.ConclusionsThe high frequency of neurocognitive impairment or other abnormal results describes a large burden of pediatric SCA brain disease in Uganda. Evaluation by any single modality would have underestimated the impact of SCA. Testing the impact of hydroxyurea or other available disease-modifying interventions for reducing or preventing SCA brain effects is warranted.

Background: Adolescents experience high rates of depression, initiation of sexual activity, and substance use. Objectives: To better understand the demographics of adolescents presenting to an adolescent clinic in Uganda, and to elucidate which factors are associated with depressive symptoms, sexual initiation, and substance use. Methods: A retrospective review was performed on intake forms obtained during interviews with adolescents presenting to the Makerere/Mulago Columbia Adolescent Health Clinic (MMCAH) in Kampala, Uganda. Results: Depressive symptoms in adolescents were correlated with having a chronic illness (p=.026), and reported poor quality of home life (p

Background The epidemiology, clinical features, and resource utilization of respiratory syncytial virus (RSV) cases in the community and the hospital are not fully characterized. Methods We identified individuals of all ages with laboratory‐confirmed RSV from two sources, a community cohort undergoing surveillance for acute respiratory infections (ARIs) and hospitalized patients from the same geographic area of New York City between 2013 and 15. The epidemiology, clinical features, and resource utilization (antibiotic/steroid/ribavirin usage, chest X‐rays, respiratory‐support (continuous positive airway pressure [CPAP], mechanical ventilation or extracorporeal membrane oxygenation [ECMO]), and indicators of disease severity (respiratory‐support, and/or ICU admission or death)) were compared among age groups using univariate and bivariate analyses. Results In the community cohort (1777 people with 1805 ARIs), 66(3.7%) tested RSV‐positive (3.8% of

INTRODUCTION: Pain following herpes zoster (HZ) can persist for months and negatively impact quality of life. To evaluate the effect of zoster vaccine live (ZVL) on progression of pain following HZ, we conducted a prospective cohort study of HZ cases at Kaiser Permanente Southern California. METHODS: ZVL vaccinated and unvaccinated members aged ≥60 years with laboratory-confirmed HZ from January 18, 2012 to February 26, 2015 were followed up within 5 days of HZ diagnosis, and at 30, 60, and 90 days after diagnosis. Pain was assessed with the Zoster Brief Pain Inventory (ZBPI) on a 0-10 scale, using cut-points of ≥3, ≥5, and ≥7, with postherpetic neuralgia (PHN) defined as pain ≥3 at 90 days. Log binomial regression was used to estimate adjusted risk ratios (aRRs) and 95% confidence intervals (CIs) associated with pain, comparing vaccinated versus unvaccinated HZ patients. RESULTS: We interviewed 509 vaccinated and 509 unvaccinated HZ patients. ZVL was associated with significantly lower risks of HZ-related pain at all time-points. The risk of PHN in vaccinated and unvaccinated patients, respectively, was 9.2% and 15.4% (aRR= 0.594, 95% CI: 0.413, 0.854); 2.0% and 4.8% of these patients reported pain ≥7 (aRR=0.332, 95% CI: 0.153, 0.721). Irrespective of vaccination, the risk of PHN was lower in adults aged

Adolescents with chronic medical conditions (CMCs), a growing population worldwide, possess a wide array of preventive health care needs. Vaccination is strongly recommended for the vast majority of these adolescents given their increased risk of vaccine preventable infection and associated complications. Not only should they receive routine vaccines, but some also require additional vaccines. Despite these guidelines, evidence suggests that adolescents with CMCs often fail to receive needed vaccines. Many factors contribute to this under-immunization, including lack of knowledge among parents and providers and suboptimal coordination of primary and subspecialty care. This review describes current vaccination recommendations for these adolescents as well as recent data related to infection risk, vaccine efficacy and safety, vaccination coverage, and the unique multilevel factors impacting uptake in this population. It also discusses strategies for improving coverage levels and reducing missed vaccination opportunities, with a particular focus on technology-based interventions.

We aimed to assess the receipt of recommended care for young children with sickle cell disease (SCD) in a central SCD clinic in Kampala Uganda, focusing on standard vaccination and antibacterial and antimalarial prophylaxis.A cross-sectional assessment of immunisation status and timeliness and prescribed antibacterial and antimalarial prophylaxis was performed in a sample with SCD aged ≤71 months in Mulago Hospital SCD Clinic. Government-issued immunisation cards and clinic-issued visit records for prescribed prophylaxis were reviewed.Vaccinations were documented by immunisation cards in 104 patients, mean age 31.7 months (range 3-70 months). Only 48 (46.2%) received all doses of each of the four recommended vaccine types, including pneumococcal 10-valent conjugate vaccine (pneumococcal conjugate vaccine (PCV)-10), which became available in 2014. Vaccination completion was associated with younger age and, for polio, maternal employment. PCV-10 series was completed in 54.8% of the sample and in 18.2% of those aged 48-71 months. Of children completing all vaccination types, an average 68.8% were immunised on time, defined as60 days beyond the recommended age. Only 17 (13.5%) children were both fully and timely vaccinated. In an overlapping sample of 147 children, with a mean age of 38.4 months (4-70 months), 81.6% had ≥1 documented prescription for penicillin and/or antimalarial prophylaxis.Standardised vaccination and antibacterial and antimalarial protective measures for young children at this central SCD clinic were incomplete, especially PCV-10 for age ≥24 months, and often late. Child age, but not general maternal demographics, were associated with vaccination and chemoprophylaxis. Clinic-based oversight may improve timely uptake of these preventative measures.

Background Studies have investigated a possible association between family history of HZ and the occurrence of HZ. However, the results were inconclusive and susceptible to bias. We evaluated this association in an elderly population. Methods The matched case-control study conducted at Kaiser Permanente Southern California in 2012-2015 included 656 incident HZ patients ≥60 whose skin lesion tested positive for varicella zoster virus by polymerase chain reaction. Half of the HZ patients were vaccinated with zoster vaccine as achieved by stratified sampling. The controls were randomly selected and 1:1 matched to the cases on sex, age (±1year), and zoster vaccination (±3 months of the case's vaccination date). Conditional logistic regression was used to estimate the odds ratio (OR) and 95% confidence interval (CI). Results Having any blood relative with a history of HZ was associated with a slightly increased risk of HZ (adjusted OR=1.37, 95% CI 1.05–1.79). The adjusted OR associated with having one and two categories of first-degree blood relatives with a history of HZ was 1.30 (95% CI: 0.97–1.73) and 2.53 (95% CI: 1.17–5.44), respectively. Conclusions Our results suggested a weak association between the development of HZ and a positive family history of HZ among the elderly population.

Background Surveillance of influenza-like illness (ILI) in the United States is primarily conducted through medical settings despite a significant burden of non-medically attended ILI. Objectives To assess consistency between surveillance for respiratory viruses in outpatient and community settings using ILI surveillance from the Centers for Disease Control and Prevention Influenza Incidence Surveillance Project (IISP) and the Mobile Surveillance for Acute Respiratory Infections (ARI) and Influenza-Like Illness in the Community (MoSAIC) Study. Methods The Influenza Incidence Surveillance Project conducts ILI surveillance in 3 primary care clinics in New York City, and MoSAIC conducts community-based ILI/ARI surveillance through text messaging among a cohort of New York City residents. Both systems obtain respiratory specimens from participants with ILI/ARI and test for multiple pathogens. We conducted a retrospective review of ILI cases in IISP and MoSAIC from January 2013 to May 2015 with descriptive analyses of clinical and laboratory data. Results Five-hundred twelve MoSAIC and 669 IISP participants met an ILI criteria (fever with cough or sore throat) and were included. Forty percent of MoSAIC participants sought care; the majority primary care. Pathogens were detected in 63% of MoSAIC and 70% of IISP cases. The relative distribution of influenza and other respiratory viruses detected was similar; however, there were statistically significant differences in the frequency that were not explained by care seeking. Conclusions Outpatient and community-based surveillance in the one found similar timing and relative distribution of respiratory viruses, but community surveillance in a single neighborhood may not fully capture the variations in ILI etiology that occur more broadly.

Background Using text messaging for vaccine safety monitoring, particularly for non-medically attended events, would be valuable for pandemic influenza and emergency vaccination program preparedness. We assessed the feasibility and acceptability of text messaging to evaluate fever and wheezing post-influenza vaccination in a prospective, observational, multi-site pediatric study. Methods Children aged 2–11 years old, with an emphasis on children with asthma, were recruited during the 2014–2015 influenza season from three community-based clinics in New York City, and during the 2014–2015 and 2015–2016 seasons from a private practice in Fall River, Massachusetts. Parents of enrolled children receiving quadrivalent live attenuated (LAIV4) or inactivated influenza vaccine (IIV4) replied to text messages assessing respiratory symptoms (day 3 and 7, then weekly through day 42), and temperature on the night of vaccination and the next seven nights (day 0–7). Missing data were collected via diary (day 0–7 only) and phone. Phone confirmation was obtained for both presence and absence of respiratory symptoms. Reporting rates, fever (T ≥ 100.4 °F) frequency, proportion of wheezing and/or chest tightness reports captured via text message versus all sources (text, phone, diary, electronic health record) and parental satisfaction were assessed. Results Across both seasons, 266 children were analyzed; 49.2% with asthma. Parental text message response rates were high (>70%) across sites. Overall, fever frequency was low (day 0–2: 4.1% [95% confidence interval (CI) 2.3–7.4%]; d3–7: 6.7% [95% CI 4.1–10.8%]). A third (39.2%) of parents reported a respiratory problem in their child, primarily cough. Most (88.2%) of the 52 wheezing and/or chest tightness reports were by text message. Most (88.1%) participants preferred text messaging over paper reporting. Conclusions Text messaging can provide information about pediatric post-vaccination fever and wheezing and was viewed positively by parents. It could be a helpful tool for rapid vaccine safety monitoring during a pandemic or other emergency vaccination program. Trial registration: clinicaltrials.gov Identifier: NCT02295007 .

Background Some studies have found a higher frequency of fever with trivalent live attenuated influenza vaccine (LAIV) than with inactivated influenza vaccine (IIV), but quadrivalent LAIV has not been assessed. Understanding fever is important for safety reviews and for parents and providers. In addition, there have been only a limited number of studies in which text messaging was used for vaccine adverse-event (AE) surveillance. Methods We conducted a prospective observational study in 3 community clinics in New York City to assess post-influenza vaccination fever in 24- to 59-month-olds during the 2013-2014 season. Enrolled families of children who received quadrivalent LAIV (LAIV4) or IIV (trivalent IIV3 or quadrivalent IIV4) replied to text messages that assessed their temperature on vaccination night and the next 10 nights (days 0 to 10); missing data were collected via telephone and a diary. We compared frequencies of fever (temperature ≥ 100.4°F) according to vaccine group on days 0 to 2 and 3 to 10 by using χ2 and multivariate log-binomial regression adjusted for age, previous influenza vaccination, and vaccine coadministration. We also assessed outcomes using all sources versus only text messages. Results Most (84.1% [n = 540]) eligible parents enrolled. Fever frequencies on days 0 to 2 did not differ between LAIV4 and any IIV (3.8% vs 5.7%, respectively; adjusted relative risk [aRR] [95% confidence interval], 0.60 [0.25-1.46]), between LAIV4 and IIV4 (4.2% vs 7.1%, respectively; aRR, 0.58 [0.19-1.72]), or between IIV4 and IIV3 (7.1% vs 6.0%, respectively; aRR, 1.02 [0.30-3.46]). The findings were similar when all data sources versus text-message data alone were used. There were no significant differences on days 3 to 10. Conclusions Postvaccination fever frequencies were low overall and did not differ according to influenza vaccine type during the 2013-2014 influenza season. The similarity of results when data were limited to text messages lends support to its use for surveillance of vaccine adverse events.

This observational study aimed to describe immunopathogenesis and treatment outcomes in children with and without severe acute malnutrition (SAM) and HIV-infection. We studied markers of microbial translocation (16sDNA), intestinal damage (iFABP), monocyte activation (sCD14), T-cell activation (CD38, HLA-DR) and immune exhaustion (PD1) in 32 HIV-infected children with and 41 HIV-infected children without SAM prior to initiation of antiretroviral therapy (ART) and cross-sectionally compared these children to 15 HIV-uninfected children with and 19 HIV-uninfected children without SAM. We then prospectively measured these markers and correlated them to treatment outcomes in the HIV-infected children at 48 weeks following initiation of ART. Plasma levels of 16sDNA, iFABP and sCD14 were measured by quantitative real time PCR, ELISA and Luminex, respectively. T cell phenotype markers were measured by flow cytometry. Multiple regression analysis was performed using generalized linear models (GLMs) and the least absolute shrinkage and selection operator (LASSO) approach for variable selection. Microbial translocation, T cell activation and exhaustion were increased in HIV-uninfected children with SAM compared to HIV-uninfected children without SAM. In HIV-infected children microbial translocation, immune activation, and exhaustion was strongly increased but did not differ by SAM-status. SAM was associated with increased mortality rates early after ART initiation. Malnutrition, age, microbial translocation, monocyte, and CD8 T cell activation were independently associated with decreased rates of CD4% immune recovery after 48 weeks of ART. SAM is associated with increased microbial translocation, immune activation, and immune exhaustion in HIV-uninfected children and with worse prognosis and impaired immune recovery in HIV-infected children on ART.

We report whole-genome sequences (WGSs) for four varicella-zoster virus (VZV) samples from a shingles study conducted by Kaiser Permanente of Southern California. Comparative genomics and phylogenetic analysis of all published VZV WGSs revealed that strain KY037798 is in clade IX, which shall henceforth be designated clade 9. Previously published single nucleotide polymorphisms (SNP)-based genotyping schemes fail to discriminate between clades 6 and VIII and employ positions that are not clade-specific. We provide an updated list of clade-specific positions that supersedes the list determined at the 2008 VZV nomenclature meeting. Finally, we propose a new targeted genotyping scheme that will discriminate the circulating VZV clades with at least a twofold redundancy. Genotyping strategies using a limited set of targeted SNPs will continue to provide an efficient ‘first pass’ method for VZV strain surveillance as vaccination programmes for varicella and zoster influence the dynamics of VZV transmission.

Academic tertiary referral hospital in Durban, South Africa. To describe the incidence and diagnostic challenges of tuberculosis (TB) in human immunodeficiency virus (HIV) infected children with severe acute malnutrition (SAM). Post-hoc analysis of a randomised controlled trial that enrolled antiretroviral therapy naive, HIV-infected children with SAM. Trial records and hospital laboratory results were explored for clinical diagnoses and bacteriologically confirmed cases of TB. Negative binomial regression was used to explore associations with confirmed cases of TB, excluding cases where the clinical diagnosis was not supported by microbiological confirmation. Of 82 children enrolled in the study, 21 (25.6%) were diagnosed with TB, with bacteriological confirmation in 8 cases. Sputum sampling (as opposed to gastric washings) was associated with an increased risk of subsequent diagnosis of TB (adjusted relative risk [aRR] 1.134, 95%CI 1.02-1.26). Culture-proven bacterial infection during admission was associated with a reduced risk of TB (aRR 0.856, 95%CI 0.748-0.979), which may reflect false-negative microbiological tests secondary to empiric broad-spectrum antibiotics. TB is common in HIV-infected children with SAM. While microbiological confirmation of the diagnosis is feasible, empiric treatment remains common, possibly influenced by suboptimal testing and false-negative TB diagnostics. Rigorous microbiological TB investigation should be integrated into the programmatic management of HIV and SAM.

Live attenuated varicella vaccine is recommended for healthy individuals who are susceptible to varicella. Although the vaccine is safe, effective, and used worldwide, serious adverse events have been reported, mainly in immunocompromised patients who subsequently recovered. Here, we describe the fatality of an immunocompromised patient who received the varicella vaccine. His medical history provides a cautionary lens through which to view the decision of when vaccination is appropriate. A middle-aged man with non-Hodgkin lymphoma received chemotherapy and a stem cell transplant. He was vaccinated 4 years post-transplantation, despite diagnosis of a new low-grade lymphoma confined to the lymph nodes. Within 3 months of vaccination, he developed recurrent rashes with fever, malaise, weakness, hepatitis, weight loss, and renal failure. The syndrome was eventually determined to be associated with persistent disseminated zoster caused by the vaccine virus. This case illustrates a circumstance when a live viral vaccine should not be used.

Surveillance for acute respiratory infection (ARI) and influenza-like illness (ILI) relies primarily on reports of medically attended illness. Community surveillance could mitigate delays in reporting, allow for timely collection of respiratory tract samples, and characterize cases of non–medically attended ILI representing substantial personal and economic burden. Text messaging could be utilized to perform longitudinal ILI surveillance in a community-based sample but has not been assessed. We recruited 161 households (789 people) in New York City for a study of mobile ARI/ILI surveillance, and selected reporters received text messages twice weekly inquiring whether anyone in the household was ill. Home visits were conducted to obtain nasal swabs from persons with ARI/ILI. Participants were primarily female, Latino, and publicly insured. During the 44-week period from December 2012 through September 2013, 11,282 text messages were sent. In responses to 8,250 (73.1%) messages, a household reported either that someone was ill or no one was ill; 88.9% of responses were received within 4 hours. Swabs were obtained for 361 of 363 reported ARI/ILI episodes. The median time from symptom onset to nasal swab was 2 days; 65.4% of samples were positive for a respiratory pathogen by reverse-transcriptase polymerase chain reaction. In summary, text messaging promoted rapid ARI/ILI reporting and specimen collection and could represent a promising approach to timely, community-based surveillance.

Background: Children with sickle cell anemia (SCA) are highly susceptible to stroke, impaired neurocognitive function and other manifestations of pediatric cerebral vasculopathy. Detailed multifaceted evaluations of children with SCA in sub-Saharan Africa are limited, including neurocognitive testing. Methods: We aimed to establish the prevalence and types of neurocognitive dysfunction in a cross-sectional study in a randomly selected sample of patients with HbSS ages 1-12 years at a large SCD clinic in Kampala, Uganda. Neurocognitive function was assessed by Mullen Scales of Early Learning (ages 1-4) and Kaufman Assessment Battery for Children, 2nd edition (ages 5-12) using linguistically validated local translations (John CC, Pediatrics 2008; Bangirana P., Clin Infect Dis. 2014). The Behavioral Rating Inventory for Executive Function was used to assess executive function. Children also underwent standardized stroke examination (PedsNIHSS) and transcranial Doppler ultrasound (TCD) for measuring stroke risk by arterial velocities in pediatric SCD. Results: Experienced testers performed neurocognitive assessment in 242 participants: 100 (41%) ages of 1-4 years and 142 ages 5-12 years (58.7%). Mean age was 5.44 ±2.9 years; 51.6% were male. Mean hemoglobin was 7.3 ±1.02 g/dl; 76.5% had hemoglobin Conclusion: In children with SCA, executive function was the most common impairment. Overall, only 11% of the SCA children had impaired neurocognitive function. The major predictors of impairment were age, prior stroke and elevated TCD arterial velocity. These abnormalities were highly prevalent in the sample, and identifies significant disease-associated morbidity. Disease-modifying therapy should be assessed for improved neuropsychological function in these children. Disclosures No relevant conflicts of interest to declare.

Background: Children with sickle cell anemia (SCA) are highly susceptible to stroke and other manifestations of pediatric cerebral vasculopathy. Detailed evaluations of children with SCA in sub-Saharan Africa are limited, especially magnetic resonance imaging and angiography (MRI/MRA). In a sample of Ugandan children receiving care at the Mulago Hospital sickle cell clinic in Kampala and were not on disease-modifying therapy, we examined the range of MR imaging findings, and how those findings correlated with standardized demographic, clinical, neurological and neurocognitive assessments. Methods: From within a larger sample of 265 participants with HbSS ages 1-12 years not taking disease-modifying therapy and enrolled in the BRAIN SAFE study, a sub-sample of 81 underwent non-contrast MRI/MRA on a 1.5 Telsa scanner. Participants also underwent 3 standardized assessments: neurocognitive testing by experienced testers using the Mullen Scales of Early Learning (for ages 1-4 years) or Kaufman Assessment Battery for Children, 2nd edition (for ages 5-12) (abnormal z-score of -2 or lower), stroke examination (PedsNIHSS) and transcranial Doppler ultrasound (TCD) using criteria for pediatric SCA. Participants undergoing MRI/MRA intentionally included 29 without any abnormal findings. MRI scans included T1- and T2- weighted images, T2 FLAIR and MRA three-dimensional time-of-flight technique. MR scans were interpreted by clinical and research methods, the latter per SWiTCH protocol (Helton, Blood 2014). Adjudication of differing reads was performed by a blinded third neuroradiologist. Results: A total of 81 children with SCA were examined by MRI/MRA. Mean age was 6.48 ± 2.75 years; 50.6% were male. Mean hemoglobin was 7.26±0.90 g/dl; 75% had hemoglobin Conclusion: High prevalence of pediatric cerebral vasculopathy was found on MR scanning. Despite clinical evidence suggesting abnormal neuropsychological testing or a prior stroke, not all of the children who had clinical evidence of neurological disorders had MRI evidence of a stroke. Additionally, a number with no evidence of stroke had infarct(s) on MRI, so-called "silent stroke." The strongest predictors of an abnormal MRI reading included having a detectable stroke or an abnormal TCD. MR imaging is a critical aspect of evaluating cerebral vasculopathy in this patient population, and will be an important measure when prospectively assessing impact in a treatment trial. Disclosures No relevant conflicts of interest to declare.

In this community-based cohort study of 275 primarily low-income, urban households in New York City, overall 2013-2014 influenza vaccine effectiveness (VE) was 62.5% (95% confidence interval, 21.7%-82.0%). VE point estimates were highest against 2009 H1N1 and for those who were vaccinated in 2013-2014 but not in 2012-2013.

Human parainfluenza virus type 3 (HPIV3) is a common cause of upper and lower respiratory tract illness in infants and young children. Live-attenuated cold-adapted HPIV3 vaccines have been evaluated in infants but a suitable interval for administration of a second dose of vaccine has not been defined.HPIV3-seronegative children between the ages of 6 and 36 months were randomized 2:1 in a blinded study to receive two doses of 10⁵ TCID₅₀ (50% tissue culture infectious dose) of live-attenuated, recombinant cold-passaged human PIV3 vaccine (rHPIV3cp45) or placebo 6 months apart. Serum antibody levels were assessed prior to and approximately 4-6 weeks after each dose. Vaccine virus infectivity, defined as detection of vaccine-HPIV3 in nasal wash and/or a≥4-fold rise in serum antibody titer, and reactogenicity were assessed on days 3, 7, and 14 following immunization.Forty HPIV3-seronegative children (median age 13 months; range 6-35 months) were enrolled; 27 (68%) received vaccine and 13 (32%) received placebo. Infectivity was detected in 25 (96%) of 26 evaluable vaccinees following doses 1 and 9 of 26 subject (35%) following dose 2. Among those who shed virus, the median duration of viral shedding was 12 days (range 6-15 days) after dose 1 and 6 days (range 3-8 days) after dose 2, with a mean peak log₁₀ viral titer of 3.4 PFU/mL (SD: 1.0) after dose 1 compared to 1.5 PFU/mL (SD: 0.92) after dose 2. Overall, reactogenicity was mild, with no difference in rates of fever and upper respiratory infection symptoms between vaccine and placebo groups.rHPIV3cp45 was immunogenic and well-tolerated in seronegative young children. A second dose administered 6 months after the initial dose was restricted in those previously infected with vaccine virus; however, the second dose boosted antibody responses and induced antibody responses in two previously uninfected children.

Background: In Uganda, referral of sick children seeking care at public health facilities is poor and widely reported. However, studies focusing on the private health sector are scanty. The main objective of this study was to assess referral practices for sick children seeking care at private health facilities in order to explore ways of improving treatment and referral of sick children in this sector. Methods: A survey was conducted from August to October 2014 in Mukono district, central Uganda. Data was collected using a structured questionnaire supplemented by Focus Group Discussions and Key Informant interviews with private providers and community members. Results: A total of 241 private health facilities were surveyed; 170 (70.5%) were registered drug shops, 59 (24.5%) private clinics and 12 (5.0%) pharmacies. Overall, 104/241 (43.2%) of the private health facilities reported that they had referred sick children to higher levels of care in the two weeks prior to the survey. The main constraints to follow referral advice as perceived by caretakers were: not appreciating the importance of referral, gender-related decision-making and negotiations at household level, poor quality of care at referral facilities, inadequate finances at household level; while the perception that referral leads to loss of prestige and profit was a major constraint to private providers. Conclusion: In conclusion, the results show that referral of sick children at private health facilities faces many challenges at provider, caretaker, household and community levels. Thus, interventions to address constraints to referral of sick children are urgently needed.

BACKGROUND: The epidemiology and clinical features of human coronaviruses (HCoVs) in children are not fully characterized. METHODS: A retrospective study of children with HCoV detected by reverse-transcriptase polymerase chain reaction (RT-PCR) was performed for a community cohort and a children’s hospital in the same community from January 2013 to December 2014. The RT-PCR assay detected HCoV 229E, HKU1, NL63, and OC43 in nasal swabs from symptomatic children ≤18 years. Factors associated with increased severity of illness in hospitalized children were assessed by multivariable logistic regression. RESULTS: Human coronavirus was detected in 261 children, 49 and 212 from the community and hospital, respectively. The distribution of HCoV types and seasonal trends were similar in the community and hospital. Community cases were older than hospitalized cases (median age, 4.4 versus 1.7 years, respectively; P < .01), and a minority of community cases (26.5%) sought medical attention. Among the hospitalized children with HCoV detected, 39 (18.4%) received respiratory support and 24 (11.3%) were admitted to the pediatric intensive care unit (PICU). Age

Routine childhood immunizations have resulted in great reductions in vaccine-preventable infectious diseases. Vaccine-related adverse events, albeit rare, can be of significant consequence. Although anaphylaxis, or type I hypersensitivity, is recognized as a potential reaction after vaccination, delayed type hypersensitivity or type IV reactions are less so. We present a case of persistent subcutaneous nodules and sterile abscesses in the setting of delayed type hypersensitivity to aluminum, confirmed by patch testing and recurrence on re-exposure. We review sources of aluminum in common immunizations, principles for treatment, and strategies for management of future vaccinations for this patient.

Post-licensure surveillance for adverse events following immunizations (AEFI) can identify rare complications of vaccinations and rigorous vaccine adverse event causality assessments can help to identify possible causal relationships. We report the development of arm paralysis after varicella vaccination in a 1-year-old child. Paralysis was initially presumed to be due to vOka because of the temporal relationship between vaccination and onset of arm weakness; however, molecular studies identified wild-type varicella zoster virus VZV (WT-VZV) in the CSF, leading the authors to conclude that WT-VZV was the probable cause. This case illustrates the complexity of assessing AEFI causality, and the importance of careful and complete evaluations when determining the most likely cause of an AEFI.

BACKGROUND: Private facilities are the first place of care seeking for many sick children. Involving these facilities in child health interventions may provide opportunities to improve child welfare. The objective of this study was to assess the potential of rural and urban private facilities in diagnostic capabilities, operations and human resource in the management of malaria, pneumonia and diarrhoea.METHODS: A survey was conducted in pharmacies, private clinics and drug shops in Mukono district in October 2014. An assessment was done on availability of diagnostic equipment for malaria, record keeping, essential drugs for the treatment of malaria, pneumonia and diarrhoea; the sex, level of education, professional and in-service training of the persons found attending to patients in these facilities. A comparison was made between urban and rural facilities. Univariate and bivariate analysis was done.RESULTS: A total of 241 private facilities were assessed with only 47 (19.5 %) being in rural areas. Compared to urban areas, rural private facilities were more likely to be drug shops (OR 2.80; 95 % CI 1.23-7.11), less likely to be registered (OR 0.31; 95 % CI 0.16-0.60), not have trained clinicians, less likely to have people with tertiary education (OR 0.34; 95 % CI 0.17-0.66) and less likely to have zinc tablets (OR 0.38; 95 % CI 0.19-0.78). In both urban and rural areas, there was low usage of stock cards and patient registers. About half of the facilities in both rural and urban areas attended to at least one sick child in the week prior to the interview.CONCLUSION: There were big gaps between rural and urban private facilities with rural ones having less trained personnel and less zinc tablets' availability. In both rural and urban areas, record keeping was low. Child health interventions need to build capacity of private facilities with special focus on rural areas where child mortality is higher and capacity of facilities lower.

Sickle cell disease (SCD) is associated with high mortality for children under 5 years of age in sub-Saharan Africa. Newborn sickle screening program and enhanced capacity for SCD treatment are under development to reduce disease burden in Uganda and elsewhere in the region. Based on an international stakeholder meeting and a family-directed conference on SCD in Kampala in 2015, and interviews with parents, multinational experts, and other key informants, we describe health care, community, and family perspectives in support of these initiatives. Key stakeholder meetings, discussions, and interviews were held to understand perspectives of public health and multinational leadership, patients and families, as well as national progress, resource needs, medical and social barriers to program success, and resources leveraged from HIV/AIDS. Partnering with program leadership, professionals, patients and families, multinational stakeholders, and leveraging resources from existing programs are needed for building successful programs in Uganda and elsewhere in sub-Saharan Africa.

The Clinical Immunization Safety Assessment (CISA) Network is a collaboration between the Centers for Disease Control and Prevention (CDC) and 6 academic medical centers to provide support for immunization safety assessment and research. The CISA Network was established by the CDC in 2001 with 4 primary goals: (1) develop research protocols for clinical evaluation, diagnosis, and management of adverse events following immunization (AEFI); (2) improve the understanding of AEFI at the individual level, including determining possible genetic and other risk factors for predisposed people and subpopulations at high risk; (3) develop evidence-based algorithms for vaccination of people at risk of serious AEFI; and (4) serve as subject-matter experts for clinical vaccine-safety inquiries. CISA Network investigators bring in-depth clinical, pathophysiologic, and epidemiologic expertise to assessing causal relationships between vaccines and adverse events and to understanding the pathogenesis of AEFI. CISA Network researchers conduct expert reviews of clinically significant adverse events and determine the validity of the recorded diagnoses on the basis of clinical and laboratory criteria. They also conduct special studies to investigate the possible pathogenesis of adverse events, assess relationships between vaccines and adverse events, and maintain a centralized repository for clinical specimens. The CISA Network provides specific clinical guidance to both health care providers who administer vaccines and those who evaluate and treat patients with possible AEFI. The CISA Network plays an important role in providing critical immunization-safety data and expertise to inform vaccine policy-makers. The CISA Network serves as a unique resource for vaccine-safety monitoring efforts conducted at the CDC.

Background. Because of ongoing outbreaks of varicella, a second dose of varicella vaccine was added to the routine immunization schedule for children in June 2006 by the Centers for Disease Control and Prevention. Methods. We assessed the effectiveness of 2 doses of varicella vaccine in a case-control study by identifying children ≥4 years of age with varicella confirmed by polymerase chain reaction assay and up to 2 controls matched by age and pediatric practice. Effectiveness was calculated using exact conditional logistic regression. Results. From July 2006 to January 2010, of the 71 case subjects and 140 matched controls enrolled, no cases (0%) vs 22 controls (15.7%) had received 2 doses of varicella vaccine, 66 cases (93.0%) vs 117 controls (83.6%) had received 1 dose, and 5 cases (7.0%) vs 1 control (0.7%) did not receive varicella vaccine (P

Objectives: The aim of this study was to investigate the possible effects of antiretroviral therapy (ART) in utero on cardiac development and function in human immunodeficiency virus (HIV)–negative...

Although varicella vaccine is given to clinically stable human immunodeficiency virus (HIV)-infected children, its effectiveness is unknown. We assessed its effectiveness by reviewing the medical records of closely monitored HIV-infected children, including those receiving highly active antiretroviral therapy (HAART) between 1989 and 2007. Varicella immunization and development of varicella or herpes zoster were noted. Effectiveness was calculated by subtracting from 1 the rate ratios for the incidence rates of varicella or herpes zoster in vaccinated versus unvaccinated children. The effectiveness of the vaccine was 82% (95% confidence interval [CI], 24%-99%; P = .01) against varicella and was 100% (95% CI, 67%-100%; P.001) against herpes zoster. When the analysis was controlled for receipt of HAART, vaccination remained highly protective against herpes zoster.

Traditional surveillance for respiratory viruses relies on symptom detection and laboratory detection during medically attended encounters for acute respiratory infection/influenza-like illness (ARI/ILI). Ecological momentary reporting using text messages is a novel method for surveillance. This study compares respiratory viral activity detected through longitudinal community-based surveillance using text message responses for sample acquisition and testing to respiratory viral activity obtained from hospital laboratory data from the same community. We demonstrate a significant correlation between community- and hospital laboratory-based surveillance for most respiratory viruses, although the relative proportions of viruses detected in the community and hospital differed significantly.