Standardizing case definitions for monitoring the safety of maternal vaccines globally: GAIA definitions, a review of progress to date.

In 2014, the Global Alignment on Immunization safety Assessment in pregnancy consortium (GAIA) was formed, with the goal of developing a harmonized, globally-concerted approach to actively monitor the safety of vaccines in pregnancy. A total of 26 standardized definitions for the classification of adverse events have been developed. The aim of this review was to identify and describe studies undertaken to assess the performance of these definitions. A literature search was undertaken to identify published studies assessing the performance of the definitions, and reference lists were snowballed. Data were abstracted by two investigators and a narrative review of the results is presented. Four studies that have evaluated 13 GAIA case definitions (50%) were identified. Five case definitions have been assessed in high-income settings only. Recommendations have been made by the investigators to improve the performance of the definitions. These include ensuring consistency across definitions, removal of the potential for ambiguity or variations in interpretation and ensuring that higher-level criteria are acceptable at lower levels of confidence. Future research should prioritize the key case definitions that have not been assessed in low- and middle-income settings, as well as the 13 that have not undergone any validation.

Applicability of the GAIA Maternal and Neonatal Outcome Case Definitions for the Evaluation of Adverse Events Following Vaccination in Pregnancy in High-income Countries.

BACKGROUND: The Brighton Collaboration Global Alignment of Immunization Safety in Pregnancy (GAIA) project developed case definitions for the assessment of adverse events in mothers and infants following maternal immunization. This study evaluated the applicability of these definitions to data collected in routine clinical care and research trial records across 7 sites in high-resource settings. METHODS: Data collection forms were designed and used to retrospectively abstract the key elements of the GAIA definitions from records for 5 neonatal and 5 maternal outcomes, as well as gestational age. Level of diagnostic certainty was assessed by the data abstractor and an independent clinician, and then verified by Automated Brighton Case logic. The ability to assign a level of diagnostic certainty for each outcome and the positive predictive value (PPV) for their respective ICD-10 codes were evaluated. RESULTS: Data from 1248 case records were abstracted: 624 neonatal and 622 maternal. Neonatal outcomes were most likely to be assessable and assigned by the level of diagnostic certainty. PPV for preterm birth, low birth weight, small for gestational age and respiratory distress were all above 75%. Maternal outcomes for preeclampsia and fetal growth restriction showed PPV over 80%. However, microcephaly (neonatal outcome) and dysfunctional labor (maternal outcome) were often nonassessable, with low PPVs. CONCLUSIONS: The applicability of GAIA case definitions to retrospectively ascertain and classify maternal and neonatal outcomes was variable among sites in high-resource settings. The implementation of the case definitions is largely dependent on the type and quality of documentation in clinical and research records in both high- and low-resource settings. While designed for use in the prospective evaluation of maternal vaccine safety, the GAIA case definitions would likely need to be specifically adapted for observational studies using alternative sources of data, linking various data sources and allowing flexibility in the ascertainment of the elements and levels of certainty of the case definition.

'Do I, don't I?' A qualitative study addressing parental perceptions about seeking healthcare during the COVID-19 pandemic.

BACKGROUND: Paediatric emergency departments have seen reduced attendance during the COVID-19 pandemic. Late paediatric presentations may lead to severe illness and even death. Maintaining provision of healthcare through a pandemic is essential. This qualitative study aims to identify changing care-seeking behaviours in child health during the pandemic and ascertain parental views around barriers to care. METHODS: Semistructured interviews were conducted with caregivers of children accessing acute paediatric services in a hospital in North-West London. Thematic content analysis was used to derive themes from the data, using a deductive approach. RESULTS: From interviews with 15 caregivers an understanding was gained of care-seeking behaviours during the pandemic. Themes identified were; influencers of decision to seek care, experience of primary care, other perceived barriers, experiences of secondary care, advice to others following lived experience. Where delays in decision to seek care occurred this was influenced predominantly by fear, driven by community perception and experience and media portrayal. Delays in reaching care were focused on access to primary care and availability of services. Caregivers were happy with the quality of care received in secondary care and would advise friends to seek care without hesitation, not to allow fear to delay them. CONCLUSION: A pandemic involving a novel virus is always a challenging prospect in terms of organisation of healthcare provision. This study has highlighted parental perspectives around access to care and care-seeking behaviours which can inform us how to better improve service functioning during such a pandemic and beyond into the recovery period.

Molecular Epidemiology of Group A Streptococcus Infections in The Gambia.

Molecular epidemiological data on Group A Streptococcus (GAS) infection in Africa is scarce. We characterized the emm-types and emm-clusters of 433 stored clinical GAS isolates from The Gambia collected between 2004 and 2018. To reduce the potential for strain mistyping, we used a newly published primer for emm-typing. There was considerable strain diversity, highlighting the need for vaccine development offering broad strain protection.

Barriers and facilitators to neonatal health and care-seeking behaviours in rural Cambodia: a qualitative study.

OBJECTIVES: Neonatal mortality remains persistently high in low-income and middle-income countries. In Cambodia, there is a paucity of data on the perception of neonatal health and care-seeking behaviours at the community level. This study aimed to identify influencers of neonatal health and healthcare-seeking behaviour in a rural Cambodian province. DESIGN: A qualitative study using focus group discussions and thematic content analysis. SETTING: Four health centres in a rural province of Northern Cambodia. PARTICIPANTS: Twenty-four focus group discussions were conducted with 85 community health workers in 2019. RESULTS: Community health workers recognised an improvement in neonatal health over time. Key influencers to neonatal health were identified as knowledge, sociocultural behaviours, finances and transport, provision of care and healthcare engagement. Most influencers acted as both barriers and facilitators, with the exception of finances and transport that only acted as a barrier, and healthcare engagement that acted as a facilitator. CONCLUSION: Understanding health influencers and care-seeking behaviours is recognised to facilitate appropriate community health programmes. Key influencers and care-seeking behaviours have been identified from rural Cambodia adding to the current literature. Where facilitators have already been established, they should be used as building blocks for continued change.

Elizabethkingia anophelis Infection in Infants, Cambodia, 2012-2018.

We describe 6 clinical isolates of Elizabethkingia anophelis from a pediatric referral hospital in Cambodia, along with 1 isolate reported from Thailand. Improving diagnostic microbiological methods in resource-limited settings will increase the frequency of reporting for this pathogen. Consensus on therapeutic options is needed, especially for resource-limited settings.

Acute rheumatic fever and rheumatic heart disease in resource-limited settings.

Poststreptococcal complications, such as acute rheumatic fever (ARF) and rheumatic heart disease (RHD), are common in resource-limited settings, with RHD recognised as the most common cause of paediatric heart disease worldwide. Managing these conditions in resource-limited settings can be challenging. We review the investigation and treatment options for ARF and RHD and, most importantly, prevention methods in an African setting.

Do maternal factors influence neonatal thyroid status in the extreme premature infant?

BACKGROUND: In early pregnancy, maternal transfer of thyroxine (T4) significantly contributes to the foetal T4 requirements. Interruption of the maternal transfer of T4 may lead to inadequate T4 exposure, potentially leading to neurodevelopmental deficits. AIM: To determine if maternal factors are associated with the thyroid hormone status of extremely premature infants during the first five days of life. METHOD: This prospective study looked at 117 mothers and their extremely premature babies (born before 28 weeks' gestation). The relationship between neonatal thyroid hormone status and maternal factors (gestation, route of delivery, exogenous maternal glucocorticoid administration, maternal free T4 (FT4), presence or absence of maternal chorioamnionitis, maternal smoking status, maternal body mass index (BMI) index, maternal thyroid peroxidase antibody status (TPO) and maternal haemoglobin levels) were evaluated. Multiple linear regression was used to study independent factors affecting neonatal thyroid function. RESULTS: Mean gestational age was 25(+5) ± 1.3 weeks (range 22(+0) to 27(+6)). Neonatal FT4 strongly correlated with gestation, with a greater severity of hypothyroxinaemia associated with lower gestation (r = 0.6, p < 0.0001). Multiple regression found gestation to be the only independent factors affecting thyroid status (beta coefficient = 0.08, p = 0.01), and no maternal factors were found to be associated with neonatal thyroid status. CONCLUSION: Neonatal thyroid status in extreme preterm infants is independently affected by gestation and not maternal factors such as route of delivery, exogenous maternal glucocorticoid administration, third trimester maternal FT4, presence or absence of chorioamnionitis, smoking status, BMI, TPO status or haemoglobin levels. The severity of neonatal hypothyroxinaemia increases with lower gestational age.

Spontaneous extradural aerocele following cardiopulmonary resuscitation - an unrecognised complication.

We present a case report of a 61-year-old gentleman who had a cardiac arrest and was delivered cardiopulmonary resuscitation (CPR) by a bystander. After resuscitation, he regained cardiac output and was breathing spontaneously. CT scan of the head showed spontaneous right frontal extradural aerocele with fracture of the posterior wall of the frontal sinus with no sign of head injury. We discuss the pathophysiology of this unrecognised complication due to CPR.