Antibody kinetics between birth and three months of life in healthy infants with natural exposure to Group B streptococcus: A UK cohort study.

INTRODUCTION: Capsular polysaccharide (CPS) serotype-specific Immunoglobulin G (IgG) in cord blood has been proposed as a correlate of protection against invasive Group B Streptococcus (iGBS) disease. Although protective levels are required in infants throughout the window of vulnerability up to 3 months of age, little is known regarding the kinetics of GBS-specific IgG over this period. METHODS: We enrolled 33 healthy infants born to mothers colonized with GBS. We collected cord blood and infant blood samples either at one (21-35 days), two (49-63 days), or three months of age (77-91 days). We measured GBS serotype-specific CPS IgG concentrations and calculated the decay rate using a mixed-effects model. We further explored whether the antibody kinetics were affected by common maternal and infant factors and estimated the correlation between IgG concentration at birth and one, two, and three months of age. RESULTS: The half-life estimate of IgG concentration for homologous and non-homologous GBS serotypes in paired samples with detectable IgG levels at both time points was 27.4 (95 % CI: 23.5-32.9) days. The decay rate did not vary by maternal age (p = 0.7), ethnicity (p = 0.1), gravida (p = 0.1), gestation (p = 0.7), and infant sex (p = 0.1). Predicted IgG titres above the assay lower limit of quantification on day 30 strongly correlated with titres at birth (Spearman correlation coefficient 0.71 [95 % CI: 0.60-0.80]). CONCLUSION: Our results provide a basis for future investigations into the use of antibody kinetics in defining a serocorrelate of protection against late-onset iGBS disease.

Results of the REIV-TOXO national survey on prenatal screening for toxoplasmosis in Spain.

INTRODUCTION: Currently, the status of serological screening for toxoplasmosis in pregnant women in Spain is unknown, and there is no official recommendation. The objective of this study is to show the current practice of gestational screening for toxoplasmosis in hospitals belonging to the Spanish Network for Research on Congenital Toxoplasmosis (REIV-TOXO). METHODS: An electronic survey was sent between April 2021 and September 2021 to investigators from 118 hospitals of REIV-TOXO, representing all Spanish regions. Nine items related to gestational screening for toxoplasmosis were collected. This information was compared with cases of congenital toxoplasmosis (CT) identified in REIV-TOXO to determine if these were diagnosed in the presence of gestational screening. RESULTS: During the study period, serological screening was performed in 53.3% (63/118) hospitals, with variations between regions and even among hospitals within the same region. Testing performed in each trimester was the most common practice (57.7%), followed by a single determination (24.4%). 89.4% of CT cases between January 2015 and September 2021 were diagnosed due to gestational screening. CONCLUSION: The decision to perform gestational screening for toxoplasmosis in Spain is highly heterogeneous, with significant local and regional differences. Despite this, screening still allows the diagnosis of most CT cases. It is urgent to have current epidemiological data to inform decision-making in public health.

Multisystem inflammatory syndrome in children and SARS-CoV-2 variants: a two-year ambispective multicentric cohort study in Catalonia, Spain.

Multisystem inflammatory syndrome in children (MIS-C) is a rare but severe disease temporarily related to SARS-CoV-2. We aimed to describe the epidemiological, clinical, and laboratory findings of all MIS-C cases diagnosed in children < 18 years old in Catalonia (Spain) to study their trend throughout the pandemic. This was a multicenter ambispective observational cohort study (April 2020-April 2022). Data were obtained from the COVID-19 Catalan surveillance system and from all hospitals in Catalonia. We analyzed MIS-C cases regarding SARS-CoV-2 variants for demographics, symptoms, severity, monthly MIS-C incidence, ratio between MIS-C and accumulated COVID-19 cases, and associated rate ratios (RR). Among 555,848 SARS-CoV-2 infections, 152 children were diagnosed with MIS-C. The monthly MIS-C incidence was 4.1 (95% CI: 3.4-4.8) per 1,000,000 people, and 273 (95% CI: 230-316) per 1,000,000 SARS-CoV-2 infections (i.e., one case per 3,700 SARS-CoV-2 infections). During the Omicron period, the MIS-C RR was 8.2 (95% CI: 5.7-11.7) per 1,000,000 SARS-CoV-2 infections, which was significantly lower (p < 0.001) than that for previous variant periods in all age groups. The median [IQR] age of MIS-C was 8 [4-11] years, 62.5% male, and 80.2% without comorbidities. Common symptoms were gastrointestinal findings (88.2%) and fever > 39 °C (81.6%); nearly 40% had an abnormal echocardiography, and 7% had coronary aneurysm. Clinical manifestations and laboratory data were not different throughout the variant periods (p > 0.05).  Conclusion: The RR between MIS-C cases and SARS-CoV-2 infections was significantly lower in the Omicron period for all age groups, including those not vaccinated, suggesting that the variant could be the main factor for this shift in the MISC trend. Regardless of variant type, the patients had similar phenotypes and severity throughout the pandemic. What is Known: • Before our study, only two publications investigated the incidence of MIS-C regarding SARS-CoV-2 variants in Europe, one from Southeast England and another from Denmark. What is New: • To our knowledge, this is the first study investigating MIS-C incidence in Southern Europe, with the ability to recruit all MIS-C cases in a determined area and analyze the rate ratio for MIS-C among SARS-CoV-2 infections throughout variant periods. • We found a lower rate ratio of MISC/infections with SARS-CoV-2 in the Omicron period for all age groups, including those not eligible for vaccination, suggesting that the variant could be the main factor for this shift in the MISC trend.

Social, Academic, and Health Status Impact of Long COVID on Children and Young People: An Observational, Descriptive, and Longitudinal Cohort Study.

There is a lack of evidence of the health impacts due to long COVID among children and young people (CYP). The objective of this study is to determine the main clinical characteristics of long COVID in CYP and to investigate the academic, social, and health status impacts of long COVID in this population. An observational, descriptive, and longitudinal study on CYP who presented COVID-19 symptoms for more than twelve weeks after SARS-CoV-2 infection was performed between December 2020 and May 2021. Fifty CYP were included, with a median age of 14.1 years, 33 (66%) were female, and 17 (34%) had a relative diagnosed with long COVID. Since the initial infection and up to the first visit, CYP had persisting symptoms for a median of 4.1 months, and for 18 (36%) CYP these symptoms persisted for more than 6 months. Fatigue (100%), neurocognitive disorders (74%), muscular weakness (74%), and headache (72%) were the most reported symptoms. A total of 9 (18%) CYP could not attend school, 17 (34%) had a reduced schedule, 33 (66%) showed a decreased school performance, and 68% had stopped extracurricular activities. This preliminary study shows the impact that long COVID has on the health, academic, and social life of CYP.

Factors associated with late presentation for HIV care in adolescents in Spain.

OBJECTIVE: Late presenters (LP) for HIV care are associated with higher morbidity and mortality rates. Our aim was to describe the characteristics associated with LP among adolescents in Spain. Identification of particular features may help in the design of strategies for improvement. METHODS: Late-presenting adolescents diagnosed at 12-19 years of age and enrolled in the Spanish paediatric and adult HIV/AIDS cohorts (CoRIS-CoRISpe) from 2004 to 2019 were selected. LP were defined as those presenting with CD4 count <350 cells/mm3 or an AIDS-defining event in the 6 months following HIV diagnosis. Confirmed low CD4 count in the next 3 months and before antiretroviral treatment initiation defined confirmed LP (cLP). RESULTS: Of 410 adolescents newly diagnosed with HIV, 303 (73.9%) had available data for assessing late presentation. Of these, 34.7% were LP and 23.7% were cLP. The median CD4 count for cLP was 235 cells/mm3 (interquartile range 122-285). In a multivariable analysis, adolescents at the highest risk of late presentation were early adolescents (age 12-14 years; odds ratio [OR] 6.50; 95% confidence interval [CI] 2.61-18.2), middle adolescents (age 15-17 years; OR 1.85; 95% CI 0.92-3.59), and adolescents born abroad (OR 1.71; 95% CI 0.97-3.00), particularly those of African origin (OR 3.08; 95% CI 1.38-6.79). CONCLUSIONS: One-quarter of adolescents presented late for HIV care in Spain. Early adolescents, middle adolescents, and those born abroad presented a sevenfold, twofold, and twofold higher risk of being cLP, respectively. Enhancing the awareness of HIV risk and the access to care, especially for younger and foreign adolescents, could help reduce late presentation and tackle the adolescent HIV epidemic.

Health and Vaccination Status of Unaccompanied Minors After Arrival in a European Border Country: A Cross-sectional Study (2017-2020).

BACKGROUND: Unaccompanied and separated children (UASC) are a high-risk group for infectious diseases and information on their vaccination status is scarce. Different approaches are used to screen newly arrived minors in Europe. The aim of this study was to describe the health status and serological protection against different vaccine-preventable diseases among UASC to inform public health decision-making. METHODS: Retrospective study of all UASC seen at an international health reference center in Barcelona (Spain) between January 2017 and February 2020. Screening results were analyzed using binary logistic regression with adjustment for symptoms, geographic origin, and time since arrival. RESULTS: We studied 289 UASC (88.9% males; median age, 17 years). At least one infection was diagnosed in 136 minors (47.1%). There was a high prevalence of intestinal parasites (22.8%), latent tuberculosis infection (22.5%), and hepatitis B (5.2%), even in asymptomatic individuals, and especially among UASC from sub-Saharan Africa (odds ratio, 2.5; 95% confidence interval, 1.5-4.0, P < 0.001). We did not observe a significant association between clinical symptoms and the presence of infection or differences in the prevalence of different infections according to number of months since arrival. Protection against hepatitis B virus (36%), measles (80%), and varicella (83%) was suboptimal. CONCLUSIONS: Our results highlight the importance of screening and vaccination programs for UASC arriving in Europe, especially border countries. Protocols should be adjusted according to geographic origin. Absence of symptoms does not necessarily rule out infection, highlighting the importance of screening in asymptomatic minors. These programs are a public health priority and should not be neglected during the current COVID-19 pandemic.

Post COVID-19 Condition in Children and Adolescents: An Emerging Problem.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection became a pandemic in 2020 and by March 2022 had caused more than 479 million infections and 6 million deaths worldwide. Several acute and long-term symptoms have been reported in infected adults, but it remains unclear whether children/adolescents also experience persistent sequelae. Hence, we conducted a review of symptoms and pathophysiology associated with post-coronavirus disease 2019 (post-COVID-19) condition in children and adolescents. We reviewed the scientific literature for reports on persistent COVID-19 symptoms after SARS-CoV-2 infection in both children/adolescents and adults from 1 January 2020 to 31 March 2022 (based on their originality and relevance to the broad scope of this review, 26 reports were included, 8 focused on adults and 18 on children/adolescents). Persistent sequelae of COVID-19 are less common in children/adolescents than in adults, possibly owing to a lower frequency of SARS-CoV-2 infection and to the lower impact of the infection itself in this age group. However, cumulative evidence has shown prolonged COVID-19 to be a clinical entity, with few pathophysiological associations at present. The most common post-COVID-19 symptoms in children/adolescents are fatigue, lack of concentration, and muscle pain. In addition, we found evidence of pathophysiology associated with fatigue and/or headache, persistent loss of smell and cough, and neurological and/or cardiovascular symptoms. This review highlights the importance of unraveling why SARS-CoV-2 infection may cause post-COVID-19 condition and how persistent symptoms might affect the physical, social, and psychological well-being of young people in the future.

Pre-exposure prophylaxis with hydroxychloroquine for COVID-19: a double-blind, placebo-controlled randomized clinical trial.

BACKGROUND: Pre-exposure prophylaxis (PrEP) is a promising strategy to break COVID-19 transmission. Although hydroxychloroquine was evaluated for treatment and post-exposure prophylaxis, it is not evaluated for COVID-19 PrEP yet. The aim of this study was to evaluate the efficacy and safety of PrEP with hydroxychloroquine against placebo in healthcare workers at high risk of SARS-CoV-2 infection during an epidemic period. METHODS: We conducted a double-blind placebo-controlled randomized clinical trial in three hospitals in Barcelona, Spain. From 350 adult healthcare workers screened, we included 269 participants with no active or past SARS-CoV-2 infection (determined by a negative nasopharyngeal SARS-CoV-2 PCR and a negative serology against SARS-CoV-2). Participants allocated in the intervention arm (PrEP) received 400 mg of hydroxychloroquine daily for the first four consecutive days and subsequently, 400 mg weekly during the study period. Participants in the control group followed the same treatment schedule with placebo tablets. RESULTS: 52.8% (142/269) of participants were in the hydroxychloroquine arm and 47.2% (127/269) in the placebo arm. Given the national epidemic incidence decay, only one participant in each group was diagnosed with COVID-19. The trial was stopped due to futility and our study design was deemed underpowered to evaluate any benefit regarding PrEP efficacy. Both groups showed a similar proportion of participants experiencing at least one adverse event (AE) (p=0.548). No serious AEs were reported. Almost all AEs (96.4%, 106/110) were mild. Only mild gastrointestinal symptoms were significantly higher in the hydroxychloroquine arm compared to the placebo arm (27.4% (39/142) vs 15.7% (20/127), p=0.041). CONCLUSIONS: Although the efficacy of PrEP with hydroxychloroquine for preventing COVID-19 could not be evaluated, our study showed that PrEP with hydroxychloroquine at low doses is safe. TRIAL REGISTRATION: ClinicalTrials.gov NCT04331834 . Registered on April 2, 2020.

Adverse Events Associated With New Injectable-Free Multidrug-Resistant Tuberculosis Drug Regimens / Efectos adversos asociados a los nuevos tratamientos farmacológicos sin inyectables contra la tuberculosis multirresistente

No disponible

Systematic review of Group B Streptococcal capsular types, sequence types and surface proteins as potential vaccine candidates.

BACKGROUND: 21 million pregnant women worldwide (18%) are estimated to carry Group B Streptococcus (GBS), which is a risk for invasive disease in newborns, pregnant women, and stillbirths. Adults ≥ 60 years or with underlying health conditions are also vulnerable to invasive GBS disease. We undertook systematic reviews on GBS organism characteristics including: capsular polysaccharide (serotype), sequence type (multi-locus sequence types (MLST)), and virulence proteins. We synthesised data by at-risk populations, to inform vaccine development. METHODS: We conducted systematic reviews and meta-analyses to estimate proportions of GBS serotypes for at risk populations: maternal colonisation, invasive disease in pregnant women, stillbirths, infants 0-90 days age, and older adults (≥60 years). We considered regional variation and time trends (2001-2018). For these at-risk population groups, we summarised reported MLST and surface proteins. RESULTS: Based on 198 studies (29247isolates), 93-99% of GBS isolates were serotypes Ia, Ib, II, III, IV and V. Regional variation is likely, but data gaps are apparent, even for maternal colonisation which has most data. Serotype III dominates for infant invasive disease (60%) and GBS-associated stillbirths (41%). ST17 accounted for a high proportion of infant invasive disease (41%; 95%CI: 35-47) and was found almost exclusively in serotype III strains, less present in maternal colonisation (9%; 95%CI:6-13),(4%; 95%CI:0-11) infant colonisation, and adult invasive disease (4%, 95%CI:2-6). Percentages of strains with at least one of alp 1, alp2/3, alpha C or Rib surface protein targets were 87% of maternal colonisation, 97% infant colonisation, 93% infant disease and 99% adult invasive disease. At least one of three pilus islands proteins were reported in all strains. DISCUSSION: A hexavalent vaccine (serotypes Ia, Ib, II, III, IV and V) might provide comprehensive cover for all at-risk populations. Surveillance of circulating, disease-causing target proteins is useful to inform vaccines not targeting capsular polysaccharide. Addressing data gaps especially by world region and some at-risk populations (notably stillbirths) is fundamental to evidence-based decision-making during vaccine design.

A Vaccine Against Group B Streptococcus: Recent Advances.

Group B streptococcus (GBS) causes a high burden of neonatal and infant disease globally. Implementing a vaccine for pregnant women is a promising strategy to prevent neonatal and infant GBS disease and has been identified as a priority by the World Health Organisation (WHO). GBS serotype-specific polysaccharide - protein conjugate vaccines are at advanced stages of development, but a large number of participants would be required to undertake Phase III clinical efficacy trials. Efforts are therefore currently focused on establishing serocorrelates of protection in natural immunity studies as an alternative pathway for licensure of a GBS vaccine, followed by Phase IV studies to evaluate safety and effectiveness. Protein vaccines are in earlier stages of development but are highly promising as they might confer protection irrespective of serotype. Further epidemiological, immunological and health economic studies are required to enable the vaccine to reach its target population as soon as possible.

Developing a serocorrelate of protection against invasive group B streptococcus disease in pregnant women: a feasibility study.

BACKGROUND: Group B streptococcus is the leading cause of infection in infants. Currently, intrapartum antibiotic prophylaxis is the major strategy to prevent invasive group B streptococcus disease. However, intrapartum antibiotic prophylaxis does not prevent maternal sepsis, premature births, stillbirths or late-onset disease. Maternal vaccination may offer an alternative strategy. Multivalent polysaccharide protein conjugate vaccine development is under way and a serocorrelate of protection is needed to expedite vaccine licensure. OBJECTIVES: The ultimate aim of this work is to determine the correlate of protection against the major group B streptococcus disease-causing serotypes in infants in the UK. The aim of this feasibility study is to test key operational aspects of the study design. DESIGN: Prospective cohort study of pregnant women and their infants in a 6-month period (1 July to 31 December 2018). SETTING: Five secondary and tertiary hospitals from London and South England. National iGBS disease surveillance was conducted in all trusts in England and Wales. PARTICIPANTS: Pregnant women aged ≥ 18 years who were delivering at one of the selected hospitals and who provided consent during the study period. There were no exclusion criteria. INTERVENTIONS: No interventions were performed. MAIN OUTCOME MEASURES: (1) To test the feasibility of collecting serum at delivery from a large cohort of pregnant women. (2) To test the key operational aspects for a proposed large serocorrelates study. (3) To test the feasibility of collecting samples from those with invasive group B streptococcus. RESULTS: A total of 1823 women were recruited during the study period. Overall, 85% of serum samples were collected at three sites collecting only cord blood. At the two sites collecting maternal, cord and infant blood samples, the collection rate was 60%. A total of 614 women were screened for group B streptococcus with a colonisation rate of 22% (serotype distribution: 30% III, 25% Ia, 16% II, 14% Ib, 14% V and 1% IV). A blood sample was collected from 34 infants who were born to colonised women. Maternal and infant blood and the bacterial isolates for 15 newborns who developed invasive group B streptococcal disease during the study period were collected (serotype distribution: 29% III, 29% II, 21% Ia, 7% Ib, 7% IV and 7% V). LIMITATIONS: Recruitment and sample collection were dependent on the presence of research midwives rather than the whole clinical team. In addition, individualised consent limited the number of women who could be approached each day, and site set-up for the national surveillance study and the limited time period of this feasibility study limited recruitment of all eligible participants. CONCLUSIONS: We have verified the feasibility of collecting and processing rectovaginal swabs and blood samples in pregnant women, as well as samples from those with invasive group B streptococcal disease. We have made recommendations for the recruitment of cases within the proposed GBS3 study and for controls both within GBS3 and as an extension of this feasibility study. FUTURE WORK: A large case-control study comparing specific immunoglobulin G levels in mothers whose infants develop invasive group B streptococcal disease with those in colonised mothers whose infants do not develop invasive group B streptococcal disease is recommended. TRIAL REGISTRATION: Current Controlled Trials ISRCTN49326091; IRAS project identification number 246149/REC reference number 18/WM/0147. FUNDING: This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 23, No. 67. See the NIHR Journals Library website for further project information.

Group B streptococcus is often carried by healthy women and usually causes no problems. Group B streptococcus may be passed from mother to child, primarily through the birth canal, and, in rare cases, can cause serious disease (i.e. pneumonia, sepsis or meningitis) and even death in babies. It may be possible to prevent group B streptococcus disease in babies by giving a vaccine to pregnant women. The reason for vaccinating the mother is so that she can pass on protection (antibodies) during the pregnancy to her baby. A vaccine is currently being developed against group B streptococcus that aims to boost this protection. To help vaccine development progress faster, we need to find out how much antibody is actually needed to protect babies from group B streptococcus disease. A large study is needed to address this question; therefore, we have performed a feasibility study to assess the practicalities of performing this large study. Specifically, we will assess (1) women's willingness to participate in a swabbing and cord blood study, (2) the ability to collect swabs and cord blood once recruited, (3) the ability to identify group B streptococcus disease in this population and (4) the laboratory processing of samples. We recruited 1823 pregnant women from five maternity units in England in a 6-month period: 22% of all women delivering at all sites and 74% of those women who were approached. In three hospitals, cord blood samples from 85% of 1201 women were collected. In two hospitals, we collected 60% of maternal blood samples, 53% of cord blood samples and 99% of swabs from the vagina and rectum from 622 women. A total of 22% of these women carried group B streptococcus in their vagina or gut and we collected blood samples from 34 healthy babies born to these women. During the study, we collected samples from 15 babies who had developed severe group B streptococcus disease; four babies were born to women participating in the study and the rest were identified through national surveillance. In conclusion, we have verified the feasibility of collecting and processing swabs from the vagina and rectum and blood samples in pregnant women, as well as samples from babies who developed group B streptococcus disease. In addition, we have identified a number of strategies that could be adopted in a future study in order to increase recruitment and sample collection.

Group B Streptococcus: Trials and Tribulations.

Group B Streptococcus (GBS) is estimated to have caused 319,000 cases of neonatal disease resulting in 90,000 infant deaths globally in 2015. It is also associated with maternal sepsis, preterm births, stillbirths and neonatal encephalopathy. There is a significant burden of neurologic impairment among survivors of infant GBS disease. Intrapartum antibiotic prophylaxis strategies have reduced the incidence of newborn early-onset GBS (occurring days 0-6) in some settings, but they are not feasible in many low and middle-income countries. A maternal vaccine given to pregnant women to stimulate passive transplacental transfer of protective antibodies has the potential to reduce maternal disease, adverse pregnancy outcomes and newborn disease. Phase I and II vaccine studies are occurring, but conducting phase III efficacy studies of a GBS vaccine candidate would require very large numbers due to the relatively low incidence of invasive GBS disease. It has therefore been proposed that alternative pathways to vaccine licensure should be explored, for example, through use of a regulatory approved correlate of protection and safety evaluation in mothers, fetuses and infants. These studies would then be followed-up with post-licensure phase IV studies in which vaccine effectiveness is evaluated.