Infection prevention and control and related practices in African neonatal units: The Pan-African neonatal care assessment study (PANCAS).

BACKGROUND: The burden of neonatal mortality is primarily borne by low- and middle-income countries (LMICs), including deaths due to healthcare-associated infections (HAIs). Few studies have assessed infection prevention and control (IP&C) practices in African units caring for small and/or sick newborns aimed to reduce HAIs. METHODS: We performed a mixed-methods study composed of a survey and virtual tour to assess IP&C and related practices. We created a survey composed of multiple-choice and open-ended questions delivered to site respondents via Zoom or video equivalent. Respondents provided a virtual tour of their unit via video and the study team used a checklist to evaluate specific practices. RESULTS: We recruited 45 units caring for small and sick newborns in 20 African countries. Opportunities to optimize hand hygiene, Water, Sanitation and Hygiene (WASH) practices, Kangaroo Mother Care, and IP&C training were noted. The virtual tour offered further understanding of IP&C challenges unique to individual sites. All respondents expressed the need for additional space, equipment, supplies, education, and IP&C staff and emphasized that attention to maternal comfort was important to IP&C success. DISCUSSION: This study identified opportunities to improve IP&C practices using low-cost measures including further education and peer support through learning collaboratives. Virtual tours can be used to provide site-specific assessment and feedback from peers, IP&C specialists and environmental engineering experts.

Burden of neurological and neurocognitive impairment in pediatric sickle cell anemia in Uganda (BRAIN SAFE): a cross-sectional study.

BACKGROUND: Children 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. METHODS: We 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). RESULTS: Mean age was 5.5 ± 2.9 years; 52.3% were male. Mean hemoglobin was 7.3 ± 1.01 g/dl; 76.4% had hemoglobin < 8.0 g/dl. Using established international standards, 14.7% were malnourished, and was more common in children ages 5-12. Overall, 57 (21.5%) subjects had one to three abnormal primary testing. Neurocognitive dysfunction was found in 27, while prior stroke was detected in 15 (5.7%). The most frequent abnormality was elevated TCD velocity 43 (18.1%), of which five (2.1%) were in the highest velocity range of abnormal. Only impaired neurocognitive dysfunction increased with age (OR 1.44, 95%CI 1.23-1.68), p < 0.001). In univariate models, malnutrition defined as wasting (weight-for-height ≤ -2SD), but not sex or hemoglobin, was modestly related to elevated TCD (OR 1.37, 95%CI 1.01-1.86, 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. CONCLUSIONS: The 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.

Assessment of temporally-related acute respiratory illness following influenza vaccination.

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.

Arm Paralysis After Routine Childhood Vaccinations: Application of Advanced Molecular Methods to the Causality Assessment of an Adverse Event After Immunization.

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.

Prescription for antibiotics at drug shops and strategies to improve quality of care and patient safety: a cross-sectional survey in the private sector in Uganda.

OBJECTIVES: The main objective of this study was to assess practices of antibiotic prescription at registered drug shops with a focus on upper respiratory tract infections among children in order to provide data for policy discussions aimed at improving quality of care and patient safety in the private health sector in Uganda. METHODS: A survey was conducted within 57 parishes from August to October 2014 in Mukono District, Uganda. Data was captured on the following variables: drug shop characteristics, training of staff in management of pneumonia, availability of guidelines and basic equipment, available antibiotics, knowledge on treatment of pneumonia in children aged <5 years. The main study outcome was the proportion of private health facilities prescribing an antibiotic. RESULTS: A total of 170 registered drug shops were surveyed between August and October 2014. The majority of drug shops, 93.5% were prescribing antibiotics, especially amoxicillin and trimethoprim-sulfamethoxazole (septrin). The professional qualification of a provider was significantly associated with this practice, p=0.04; where lower cadre staff (nursing assistants and enrolled nurses) overprescribed antibiotics. A third, 29.4% of drug shop providers reported that antibiotics were the first-line treatment for children with diarrhoea; yet the standard guideline is to give oral rehydration salts and zinc tablets. Only few providers, 8.2%, had training on antibiotics, with 10.6% on pneumonia case management. Further to this, 7.1% drug shops had WHO-Integrated Management of Childhood Illness guidelines, and a negligible proportion (<1%) had respiratory timers and baby weighing scales. Although the majority of providers, 82.4%, knew severe signs and symptoms of pneumonia, few, 17.6%, knew that amoxicillin was the first-line drug for treatment of pneumonia in children according to the guidelines. CONCLUSIONS: There is urgent need to regulate drug shop practices of prescribing and selling antibiotics, for the safety of patients seeking care at these outlets.

MoSAIC: Mobile Surveillance for Acute Respiratory Infections and Influenza-Like Illness in the Community.

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 non­medically 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.

Clinical assessment of serious adverse events in children receiving 2009 H1N1 vaccination.

BACKGROUND: Monovalent 2009 H1N1 influenza vaccines were licensed and administered in the United States during the H1N1 influenza pandemic between 2009 and 2013. METHODS: Vaccine Adverse Event Reporting System received reports of adverse events following immunization (AEFI) after H1N1 vaccination. Selected reports were referred to the Centers for Disease Control and Prevention's Clinical Immunization Safety Assessment network for additional review. We assessed causality using modified World Health Organization criteria. RESULTS: There were 3,928 reports of AEFI in children younger than age 18 years after 2009 H1N1 vaccination received by January 31, 2010. Of these, 214 (5.4%) were classified as serious nonfatal and 109 were referred to Clinical Immunization Safety Assessment for further evaluation. Ninety-nine (91%) had sufficient initial information to begin investigation and are described here. The mean age was 8 years (range, 6 months-17 years) and 38% were female. Median number of days between vaccination and symptom onset was 2 (range, -11 days to +41 days). Receipt of inactivated, live attenuated, or unknown type of 2009 H1N1 vaccines was reported by 68, 26 and 5 cases, respectively. Serious AEFI were categorized as neurologic events in 47 cases, as hypersensitivity in 15 cases and as respiratory events in 10 cases. At the time of evaluation, recovery was described as complete (61), partial (16), no improvement (1), or unknown (21). Causality assessment yielded the following likelihood of association with 2009 H1N1 vaccination: 8 definitely; 8 probably; 21 possibly; 43 unlikely; 17 unrelated; and 2 unclassifiable. CONCLUSIONS: Most AEFI in children evaluated were not causally related to vaccine and resolved without sequelae. Detailed clinical assessment of individual serious AEFI can provide reassurance of vaccine safety.

Causality assessment of adverse events reported to the Vaccine Adverse Event Reporting System (VAERS).

UNLABELLED: Adverse events following immunization (AEFI) reported to the national Vaccine Adverse Event Reporting System (VAERS) represent true causally related events, as well as events that are temporally, but not necessarily causally related to vaccine. OBJECTIVE: We sought to determine if the causal relationships between the vaccine and the AEFI reported to VAERS could be assessed through expert review. DESIGN: A stratified random sample of 100 VAERS reports received in 2004 contained 13 fatal cases, 19 cases with non-fatal disabilities, 39 other serious non-fatal cases and 29 non-serious cases. Experts knowledgeable about vaccines and clinical outcomes, reviewed each VAERS report and available medical records. MAIN OUTCOME MEASURES: Modified World Health Organization criteria were used to classify the causal relationship between vaccines and AEFI as definite, probable, possible, unlikely or unrelated. Five independent reviewers evaluated each report. If they did not reach a majority agreement on causality after initial review, the report was discussed on a telephone conference to achieve agreement. RESULTS: 108 AEFIs were identified in the selected 100 VAERS reports. After initial review majority agreement was achieved for 83% of the AEFI and 17% required further discussion. In the end, only 3 (3%) of the AEFI were classified as definitely causally related to vaccine received. Of the remaining AEFI 22 (20%) were classified as probably and 22 (20%) were classified as possibly related to vaccine received; a majority (53%) were classified as either unlikely or unrelated to a vaccine received. CONCLUSIONS: Using VAERS reports and additional documentation, causality could be assessed by expert review in the majority of VAERS reports. Assessment of VAERS reports identified that causality was thought to be probable or definite in less than one quarter of reports, and these were dominated by local reactions, allergic reactions, or symptoms known to be associated with the vaccine administered.

Causality assessment of serious neurologic adverse events following 2009 H1N1 vaccination.

BACKGROUND: Adverse events occurring after vaccination are routinely reported to the Vaccine Adverse Event Reporting System (VAERS). We studied serious adverse events (SAEs) of a neurologic nature reported after receipt of influenza A (H1N1) 2009 monovalent vaccine during the 2009-2010 influenza season. Investigators in the Clinical Immunization Safety Assessment (CISA) network sought to characterize these SAEs and to assess their possible causal relationship to vaccination. METHODS: Centers for Disease Control and Prevention (CDC) and Food and Drug Administration (FDA) physicians reviewed all SAE reports (as defined by the Code of Federal Regulations, 21CFR§314.80) after receipt of H1N1 vaccine reported to VAERS between October 1, 2009 and March 31, 2010. Non-fatal SAE reports with neurologic presentation were referred to CISA investigators, who requested and reviewed additional medical records and clinical information as available. CISA investigators assessed the causal relationship between vaccination and the event using modified WHO criteria as defined. RESULTS: 212 VAERS reports of non-fatal serious neurological events were referred for CISA review. Case reports were equally distributed by gender (50.9% female) with an age range of 6 months to 83 years (median 38 years). The most frequent diagnoses reviewed were: Guillain-Barré Syndrome (37.3%), seizures (10.8%), cranial neuropathy (5.7%), and acute disseminated encephalomyelitis (3.8%). Causality assessment resulted in classification of 72 events as "possibly" related (33%), 108 as "unlikely" related (51%), and 20 as "unrelated" (9%) to H1N1 vaccination; none were classified as "probable" or "definite" and 12 were unclassifiable (6%). CONCLUSION: The absence of a specific test to indicate whether a vaccine component contributes to the pathogenesis of an event occurring within a biologically plausible time period makes assessing causality difficult. The development of standardized protocols for providers to use in evaluation of adverse events following immunization, and rapid identification and follow-up of VAERS reports could improve causality assessment.

Overview of the Clinical Consult Case Review of adverse events following immunization: Clinical Immunization Safety Assessment (CISA) network 2004-2009.

BACKGROUND: In 2004 the Clinical Consult Case Review (CCCR) working group was formed within the CDC-funded Clinical Immunization Safety Assessment (CISA) Network to review individual cases of adverse events following immunizations (AEFI). METHODS: Cases were referred by practitioners, health departments, or CDC employees. Vaccine Adverse Event Reporting System (VAERS) searches and literature reviews for similar cases were performed prior to review. After CCCR discussion, AEFI were assessed for a causal relationship with vaccination and recommendations regarding future immunizations were relayed back to the referring physicians. In 2010, surveys were sent to referring physicians to determine the utility and effectiveness of the CCCR service. RESULTS: CISA investigators reviewed 76 cases during 68 conference calls between April 2004 and December 2009. Almost half of the cases (35/76) were neurological in nature. Similar AEFI for the specific vaccines received were discovered for 63 cases through VAERS searches and for 38 cases through PubMed searches. Causality assessment using the modified WHO criteria resulted in classifying 3 cases as definitely related to vaccine administration, 12 as probably related, 16 as possibly related, 18 as unlikely related, 10 as unrelated, and 17 had insufficient information to assign causality. The physician satisfaction survey was returned by 30 (57.7%) of those surveyed and a majority of respondents (93.3%) felt that the CCCR service was useful. CONCLUSIONS: The CCCR provides advice about AEFI to practitioners, assigns potential causality, and contributes to an improved understanding of adverse health events following immunizations.

Understanding the role of human variation in vaccine adverse events: the Clinical Immunization Safety Assessment Network.

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.

Impact of the Advisory Committee on Immunization Practices' 4-day grace period in a low-income community.

BACKGROUND: In 2002, the Advisory Committee on Immunization Practices (ACIP) recommended vaccine doses administered < or = 4 days before the minimum age or interval be counted as valid. The study objective was to assess the impact of the 4-day grace period on the need for revaccination and associated costs in a low-income community, compared to standard practice (i.e., repeating all doses that fall outside current ACIP guidelines). METHODS: From 1999 to 2001, semi-annual immunization assessments of 8293 randomly selected children, aged 19-35 months, were conducted at a 16-practice network serving an underserved community in New York City. Outcome measures were rates of antigen-specific invalid doses and number of children needing revaccination, with and without the 4-day grace period. Revaccination costs were based on the Vaccines for Children (VFC) price list. RESULTS: The 4-day grace period reduced the number of children needing revaccination from 17.1% to 12.0%, a drop of 30%. The rates of invalid doses decreased from 1.9% to 1.3%, a drop of 33%. Invalid doses for hepatitis B (HepB)-2 decreased by two thirds (69.7%); for diphtheria-tetanus-acellular pertussis (DTaP)-1, Haemophilus influenzae type b (Hib)-1 and Hib-3 by half (44.9%-50.0%); for Polio-1, Polio-2, Polio-3, and measles-mumps-rubella (MMR) by one third (31.6%-33.3%); and for DTaP-2, DTaP-3, HepB-3, and varicella by nearly one quarter (20.0%-24.0%). At these rates, revaccinating 100,000 children younger than age 3 years would cost 213,588 dollars per year, compared to 152,539 dollars with the 4-day grace period, in vaccine costs alone. CONCLUSIONS: In a low-income community, ACIP's 4-day grace period made a significant impact on the number of children requiring revaccination and on revaccination costs. However, the number of children needing revaccination remains high.