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Immunity to Streptococcus pyogenes and Common Respiratory Viruses at Age 0 to 4 Years After COVID-19 Restrictions.
Get PDFIMPORTANCE: The upsurge in invasive disease caused by Streptococcus pyogenes among children reported in several European countries during 2022 to 2023 has not been fully explained.
OBJECTIVE: To evaluate whether changes in the circulation of common respiratory pathogens associated with the introduction of nonpharmaceutical interventions (NPIs) during the COVID-19 pandemic were associated with acquisition of immunity to S pyogenes and common respiratory viruses.
DESIGN, SETTING, AND PARTICIPANTS: This cross-sectional study recruited children with suspected infection and afebrile control participants at hospitals in 10 European countries. Data were collected before (September 2016 to March 2020) and after (April 2020 to July 2023) the introduction of NPIs.
MAIN OUTCOMES AND MEASURES: Molecular detection of bacterial and viral pathogens on throat swabs and age-stratified total serum immunoglobin G (IgG) reactivity to S pyogenes cell wall extract from 2 strains, respiratory syncytial virus (RSV), 5 influenza viruses, 4 common cold coronaviruses, and SARS-CoV-2, measured by immunoassay.
RESULTS: Throat swabs from 1942 children aged 0 to 4 years were tested for respiratory pathogens (1449 recruited before introduction of NPIs [median (IQR) age, 19.7 (8.2-38.1) months; 798 (55.1%) male]; 493 recruited after [median (IQR) age, 20.7 (9.7-38.1) months; 269 (54.7%) male]). A decrease in detection of S pyogenes, RSV, common cold coronaviruses, and influenza viruses was observed between March 2020 to July 2021, corresponding to the maximal period of NPIs. Antibodies to S pyogenes were measured in 252 children recruited before NPIs and 200 thereafter. Antibodies to viral antigens were measured in 230 children before NPIs and 92 thereafter. Total IgG to S pyogenes and RSV was significantly lower in children aged 3 to 4 years recruited after NPI introduction compared with those recruited before (S pyogenes emm1 strain: after, 67 participants; median [IQR] 0.13 [0.44-0.44] relative units [RU]; before, 87 participants; median [IQR] 0.35 [0.10-0.65] RU; P = .007. RSV: after, 30 participants; median [IQR] 49.6 [31.1-120.7] mesoscale units [MU]/1000; before, 76 participants; median [IQR] 141.8 [78.1-423.1] MU/1000; P < .001). No such differences were observed for children aged 0 to 2 years or for individual influenza viruses or SARS-CoV-2.
CONCLUSIONS AND RELEVANCE: In this cross-sectional study, there was a significant reduction in serum antibodies to S pyogenes and RSV in children aged 3 to 4 years after introduction of NPIs. Equivalent to approximately a 1-year delay in acquisition of immunity, these data suggest a putative biological basis for the 2022 to 2023 upsurge in severe S pyogenes infections in this age group
Uptake and 24-month Outcomes of Dolutegravir- Versus Lopinavir-based Second-line Antiretroviral Therapy for People With HIV in South Africa: A Retrospective Cohort Study and Emulated Target Trial.
Get PDFBACKGROUND: Aligning with the World Health Organization, South Africa has replaced ritonavir-boosted lopinavir (LPV/r) with dolutegravir (DTG) in second-line antiretroviral therapy (ART) after treatment failure with tenofovir disoproxil fumarate (TDF)/lamivudine or emtricitabine (XTC)/efavirenz (EFV). Initial guidance included special considerations for DTG use among women. METHODS: We analyzed routine deidentified data of adults switched from TDF/XTC/EFV to second-line AZT/XTC/LPV/r, AZT/XTC/DTG, or TDF/XTC/DTG between December 2019 and December 2023 at 108 healthcare facilities in KwaZulu-Natal, South Africa. Among people switched before July 2021, we emulated a target trial comparing 24-month death or loss to follow-up (LTFU), and viremia (>50 copies/mL). We conducted intention-to-treat and per-protocol analyses using weighted logistic regression with bootstrapped CIs. RESULTS: Overall, women were less likely than men to switch to DTG (RR: 0.92 [95% CI: .88, .96]; N = 3649). Of 2321 people switched before July 2021, 915 (39%) switched to AZT/XTC/LPV/r, 415 (18%) to zidovudine (AZT)/XTC/DTG, and 991 (43%) to TDF/XTC/DTG. Median age was 36 years (IQR: 30, 43) and 1364 (59%) were women. In intention-to-treat analyses, the standardized 24-month risk of death or LTFU was similar with AZT/XTC/LPV/r (31%), AZT/XTC/DTG (30%), and TDF/XTC/DTG (34%). The standardized risk of 24-month viremia among those retained in care with a viral load result (N = 1270) was higher with AZT/XTC/LPV/r (50%) than with AZT/XTC/DTG (40%; aRD: -10% [95% CI -19%, -2%]) or TDF/XTC/DTG (39%; aRD: -11% [95% CI -18%, -5%]). Per-protocol analyses gave similar results. CONCLUSIONS: While retention was similar across regimens, viremia was less common on DTG-based ART, supporting current guidelines
Disparate patterns of disease time burden in patients with HCC on immunotherapy or tyrosine kinase inhibitors.
Get PDFBACKGROUND & AIMS: While cancer survivorship for hepatocellular carcinoma (HCC) has improved, associated disease time burden in patients taking systemic therapies remains poorly understood. In this study, we used days at home (DAH), a patient-centered metric, to compare the disease time burden between patients taking immunotherapies and tyrosine kinase inhibitors (TKIs). METHODS: Patients with HCC receiving systemic therapy from 2008 to 2023 were identified from a population-based cohort. Patients were classified based on the use of immunotherapy (nivolumab, pembrolizumab, atezolizumab, durvalumab, tremelimumab, and ipilimumab; including monotherapies or combinations) or TKIs (lenvatinib, sorafenib, cabozantinib, and regorafenib). The primary outcome was DAH, defined as days alive and not requiring healthcare utilization within the first year of systemic therapy. RESULTS: This study included 4,677 patients (immunotherapy, 578; TKIs, 3,410; both immunotherapy and TKIs, 689). Compared with TKIs, immunotherapy use was associated with higher 1-year overall survival (58.1% vs. 34.2%, respectively, p <0.001) and higher mean DAH (223.1 vs. 183.3 days, respectively, p <0.001). Immunotherapy was associated with fewer days spent on inpatient stays and emergency department attendance, but more days spent on day procedures and investigations (all p <0.01). Immune-related adverse events (irAEs) occurred in 12.3% of patients taking immunotherapy, and independently predicted lower probability of achieving DAH ≥180 days within the first year of therapy (hazard ratio 0.523, 95% CI 0.290-0.942, p = 0.031). Patients taking immunotherapy with irAEs had comparable DAH to patients taking TKIs (p = 0.469). CONCLUSIONS: Immunotherapy was associated with reduced disease time burden in HCC compared with TKIs. However, this benefit was dampened by the occurrence of irAEs. Our data has quality-of-life implications, and could influence patients' treatment decisions. IMPACT AND IMPLICATIONS: This study utilized days at home (DAH), a patient-centered metric, to assess the disease time burden in patients with advanced hepatocellular carcinoma taking systemic therapies. We demonstrated that immunotherapy was associated with higher DAH compared with tyrosine kinase inhibitor treatment, although this benefit was dampened by the occurrence of immune-related adverse events. These findings have quality-of-life implications and can be used for patient counselling
Hip fracture care in Zimbabwe : a cohort-based health economic analysis.
Get PDFAIMS: Hip fractures are a leading cause of morbidity and mortality worldwide, particularly among older people. While early surgical management improves outcomes compared to non-surgical approaches, high costs of surgery pose significant barriers in low- and middle-income countries. A cost-utility analysis of hip fracture management was undertaken in Zimbabwe, to guide resource allocation and policy.
METHODS: Patient-level data were obtained from a prospective cohort of adults aged 40 years and above with acute hip fractures presenting to hospital in Harare (two public; five private) between October 2021 and October 2022. Healthcare resource use and costs in 2023 USD1,676 (95% CI 730 to 2,621) higher per patient. The ICER for the primary analysis was 4,126/QALY gained. The results were sensitive to the exchange rate used to estimate costs.
CONCLUSION: Although patients who underwent surgery for hip fractures had higher costs, they had better health outcomes in terms of QALYs. Targeted improvements in provision of surgical care, particularly in minimizing surgical delays, could improve both patient outcomes and lower healthcare costs
Evaluation of Malaria Parasite Transmission Competency Using a Nanozyme-Based Immunodiagnostic Targeting Female Gamete Antigen Release.
Get PDFPreventing malaria parasite transmission to the mosquito vector is a key elimination challenge that could benefit from a diagnostic test that can identify transmission-competent individuals. Only sexual parasite forms, called gametocytes, which activate into gametes (gametogenesis) upon mosquito uptake or blood sampling are responsible for transmission. Herein, we devised a nanozyme-based immunoassay to detect the Plasmodium falciparum female gametocyte activation antigen PfG377, which is released during gametogenesis. Initial validation of our nanozyme assay with cultured parasites demonstrated that levels of PfG377 were higher in supernatants of activated versus nonactivated cultures and those treated with transmission blocking drugs. To define the field potential of this approach, patient samples from a clinical transmission-focused trial were used, including those receiving treatment with the gametocytocidal drug primaquine (PQ) that sterilizes gametocytes and blocks transmission. PQ-treated patient samples showed significantly lower signals of PfG377 2 days after treatment, consistent with an inability of PQ-treated gametocytes to activate and release antigen upon blood sampling. This study serves as a pathfinder for field transmission rapid diagnostics to detect transmission-competent individuals, which could help revive malaria elimination strategies
Behavioural shifts of bats during urban music festivals
Get PDFThe impact on wildlife of large‐scale outdoor music events held in urban green spaces remains poorly understood. Bats are a taxon of focus for evening events, because of their protected status, nocturnality, sensitivity to artificial lighting, and reliance on sound for navigation and foraging. While experimental field studies have singly demonstrated the effects of artificial night‐time lighting and noise on bat activity, studies made during actual music events, associated with unusually high levels of both artificial lighting and noise, are lacking.
In this study, we deployed passive acoustic detectors within an urban parkland to monitor bat activity over a 23‐night period, during which two large weekend concert events were held. Nine bat species were recorded. Activity minutes were calculated for all bats and some species groups, and the effect of concerts, alongside several abiotic variables, were measured.
Total bat activity was not depressed on concert nights, but total bat activity was reduced during concert hours compared with the same times on nights without concerts. This was significant at the species level for
Pipistrellus pipistrellus
and
Myotis
species, with the latter also showing a marginally significant delay in peak activity on concert nights. We suggest that the reduction and delay in bat activity observed during concerts may impair bat foraging success with potential implications for fitness.
Solutions.
We propose practical solutions to reduce these risks, such as a better‐informed placement and timing of urban outdoor concerts away from important bat habitats and outside the breeding season
Global medium-term research priority setting for seasonal malaria chemoprevention: results from an eDelphi study.
Get PDFINTRODUCTION: Seasonal malaria chemoprevention (SMC) with sulfadoxine-pyrimethamine and amodiaquine (SPAQ) has been delivered in sub-Saharan Africa since 2014, reaching over 40 million children in 2022. New questions are emerging related to SMC's sustainability, integration with other interventions and introduction to new regions. Meanwhile, new WHO malaria guidelines have substantially increased flexibility for tailoring malaria strategies to local contexts. The SMC Alliance, bringing together researchers and implementers, commissioned a consultation to identify medium-term SMC research priorities. METHODS: The consultation was conducted online from September 2022 to September 2023 using the eDelphi methodology. An initial list of 46 research priorities was compiled during a workshop with SMC implementers. The wider expert consultation comprised three waves of online surveys available in English, French and Portuguese. Respondents rated research priorities on their importance, feasibility and degree to which they had already been addressed; responses determined elimination or retention of research priorities after each survey wave. Respondents suggested their own research priorities for rating. We also collected anonymised data on respondents' characteristics. A final ranking exercise was conducted to reach consensus on a top 10 list of research priorities. RESULTS: A total of 67 unique respondents residing in 20 countries provided 96 survey responses. The surveys achieved balanced representation of respondents by gender, country of residence and professional background. Of the 25 research priorities retained for ranking, the highest-ranked included 'evaluate duration of prophylactic protection offered by SPAQ and other SMC medicines' and 'evaluate the effect of integrating SMC with other malaria prevention interventions on development of antimalarial resistance'. CONCLUSIONS: Research priorities related to sustainability, antimalarial resistance, integration with other interventions and improving quality of SMC delivery featured prominently among the highest-ranked research priorities. It is hoped the results of this consultation can encourage research uptake, guide new research and inform programme adaptation
Not one but two: cross-sectional associations among repeat pregnancy, maternal mental health and child cognitive outcomes among adolescent and young mothers in South Africa.
Get PDFBACKGROUND: Globally, adolescent mothers and their children have poorer health outcomes. However, little is known regarding having multiple children as an adolescent. Analyses explore associations between having multiple versus single children on young mothers' mental health and having a sibling and child development outcomes for their children. Furthermore, maternal age when having a second child (eg, multipara adolescent or multipara adolescent-adult pregnancy) is examined in relation to maternal and child outcomes. METHODS: Data are drawn from a cohort of young mothers (n=1017; 10-24 years) and their children (0-68 months) residing in the Eastern Cape Province, South Africa. Effects of having multiple versus single children on maternal mental health and child cognitive outcomes (assessed using the Mullen Scales of Early Learning) were explored using hierarchical regression models. We examined associations among primipara adolescent motherhood, multipara adolescent motherhood and multipara adolescent-adult motherhood, and child cognitive development scores. RESULTS: Poor maternal mental health was elevated among multipara mothers. Multipara mothers were more likely to report higher parental stress scores and lower social support scores (p=0.002-0.038). Child cognitive development scores were higher in children born to multipara mothers (those with a sibling (B=6.75, 95% CI 1.00 to 12.51, p=0.021)); younger child age (B=-0.56, 95% CI -0.68 to -0.44, p=<0.001) and formal childcare attendance (B=3.58, 95% CI 0.03 to 7.13, p=0.048) were also identified as positive predictors of higher cognitive development scores. First-born children of multipara adolescent mothers appeared to perform equally well to children born to primipara mothers (children without siblings), while first-born children of multipara adolescent-adult mothers seemed to benefit strongly from having siblings (B=14.31, 95% CI 4.18 to 24.44, p=0.006). CONCLUSIONS: Having multiple children was associated with poorer maternal mental health. Delaying a second pregnancy until adulthood may have benefits, as sibling effects were found to be positively associated with child cognitive development scores. Formal childcare support was associated with positive child outcomes. Findings highlight the need to focus on repeat adolescent pregnancy, improve social, psychological and family planning support among young mothers with a focus on birth timing and spacing, early childhood care provision and support for young families
Are childcare settings' food menus fit for purpose? A qualitative analysis in England.
Get PDFChildcare settings have a central role in feeding pre-school-aged infants and children. One of the ways in which childcare settings plan nutritious, balanced, and varied meals and snacks for preschool-aged infants and children (0-5 years) is through the use of a menu. Nevertheless, international studies indicate an overwhelming heterogeneity in uptake of menus, as well as use and format, with variable details of food and drinks provided. Thus, in the context of a nationally representative survey on food provision in early years settings in England, we invited respondents to upload sample menus. Of the 322 settings that completed the survey, 56 submitted menus (17.4%). Five were excluded because the attachment was either not a menu or was illegible. Data contained in the 51 readable menus was extracted into an Excel spreadsheet designed deductively from available guidance on menus and inductively based on patterns emerging from the menus themselves. The menus demonstrated great variations in depth of information, completeness and clarity. Breakfasts, snacks, and beverages were often excluded from menus or the information about them was unclear. Menus also sometimes contained dishes with names that were unclear. Early years settings are expected to promote healthy eating, but their ability to do so is shaped by wider structural factors. Thus while childcare settings can play a crucial role in the health promotion of young children during a time of vital development, the wider policy context and challenges faced by childcare settings and families must be addressed
Metabolic dysfunction impairs Mycobacterium tuberculosis-specific cytokine and chemokine responses in latent tuberculosis and type 2 diabetes mellitus.
Get PDFType 2 diabetes mellitus (DM) is associated with impaired host immune responses, increasing the risk for latent tuberculosis (TB) infection (LTBI). This study investigated how DM and associated metabolic dysfunction alter Mycobacterium tuberculosis (Mtb)-specific cytokine and chemokine responses. We analysed a cohort of 164 participants with and without DM and/or LTBI. Mtb-specific cytokine/chemokine responses were measured in QuantiFERON-TB Gold-Plus supernatants using a 17-plex Luminex assay to quantify Th1, Th2, Th17, inflammatory and regulatory responses. DM was associated with decreased Mtb-specific IFN-γ, TNF, IL-12, IP-10 and MIP-1α, with increased IFN-α compared to non-DM, suggesting impairment of Th1 and inflammatory pathways. Additionally, pre-DM was not associated with altered cytokine/chemokine responses, but subtle changes in IL-10, GM-CSF, MIP-1β, and IL-1β may suggest early indicators of immune dysregulation. Poorly controlled DM was associated with increased IL-4 and IFN-α, indicating a shift toward Th2 and inflammatory responses. Compared to borderline high, high total cholesterol levels, indicating dyslipidaemia, were associated with decreased IFN-γ, TNF and IL-2, suggesting impaired Th1 immunity. These findings imply that metabolic disturbances may compromise Mtb-specific immune responses, potentially increasing TB infection susceptibility. Optimising glycaemic and lipid control may be crucial for restoring immune balance and improving TB outcomes in patients with DM-associated metabolic dysfunction