The seasonal variability in hospitalization for tuberculosis may in part relate to super-imposed bacterial or predisposing respiratory viral infections. We aimed to study the temporal association ...between hospitalization for culture-confirmed pulmonary tuberculosis (PTB), invasive pneumococcal disease (IPD) and influenza virus epidemics in South African children.
We undertook a retrospective analysis which examined seasonal trends, from 2005 to 2008, for hospitalization for culture-confirmed PTB and IPD among children in relation to the influenza epidemics in Soweto, South Africa. Original time-series of the influenza virus epidemics and hospitalization rates for PTB and IPD were decomposed into three components: a trend cycle component, a seasonal component and an irregular component using the X-11 seasonal adjustment method. To compare the seasonality amongst the three series, the trend and irregular components were removed and only seasonal components examined.
Across the study period, the influenza virus epidemics peaked during May to July (winter) months, which was closely followed by an increase in the incidence of hospitalization for IPD (August to October) and PTB (August to November).
Within- and between-year temporal changes associated with childhood TB hospitalization may in part be driven by factors which influence temporal changes in pneumococcal disease, including potential variability in the severity of influenza virus epidemics in temperate climates. The dynamics of the interplay between the host and these infectious agents appears to be complex and multifactorial.
We evaluated memory responses and antibody persistence to diphtheria-toxoid, tetanus-toxoid, whole-cell-pertussis (DTwP), and Hepatitis-B vaccines in HIV-unexposed, HIV-exposed-uninfected and ...HIV-infected children previously randomized to initiate time-limited ART at 6-10 weeks (ART-Immed) or when clinically/immunologically indicated (ART-Def).
All children received DTwP booster at 15-18 months. Antibodies were measured for pertussis-toxoid, filamentous haemagglutinin (FHA), diphtheria-toxoid, tetanus-toxoid, and hepatitis-B prior to booster, 1-2 weeks post-booster and at 24 months of age.
Pre-booster antibody GMC were lower in HIV-infected groups than HIV-unexposed children for all epitopes. Post-booster and at 24 months of age, the ART-Def group had lower GMCs and antibody proportion ≥0.1 IU/ml for tetanus-toxoid and diphtheria-toxoid compared to HIV-unexposed children. At 24 months of age, the ART-Immed group had higher GMCs, and more likely to maintain antibody titres ≥1.0 IU/ml to tetanus-toxoid and diphtheria-toxoid compared to HIV-unexposed children. Compared to HIV-unexposed children, at 15 and 24 months of age, persistence of antibody to HBsAg of ≥10 mIU/ml was similar in the ART-Immed group but lower among the ART-Def group. Antibody kinetics indicated more robust memory responses in HIV-exposed-uninfected than HIV-unexposed children to diphtheria-toxoid and wP.
HIV-infected children not on ART at primary vaccination had poorer memory responses, whereas HIV-exposed-uninfected children mounted robust memory responses.
We propose a Bayesian approach for estimating branching tree mixture models to compare drug-resistance pathways (i.e. patterns of sequential acquisition of resistance to individual antibiotics) that ...are observed among Mycobacterium tuberculosis isolates collected from treatment-naïve and treatment-experienced patients. Resistant pathogens collected from treatment-naïve patients are strains for which fitness costs of resistance were not sufficient to prevent transmission, whereas those collected from treatment-experienced patients reflect both transmitted and acquired resistance, the latter of which may or may not be associated with lower transmissibility. The comparison of the resistance pathways constructed from these two groups of drug-resistant strains provides insight into which pathways preferentially lead to the development of multiple drug resistant strains that are transmissible. We apply the proposed statistical methods to data from worldwide surveillance of drug-resistant tuberculosis collected by the World Health Organization over 13 years.
The high cost of pneumococcal conjugate vaccine (PCV) and local epidemiological factors contributed to evaluating different PCV dosing-schedules. This study evaluated the immunogenicity of ...seven-valent PCV (PCV7) administered at 6-weeks; 14-weeks and 9-months of age.
250 healthy, HIV-unexposed infants were immunized with PCV7 concurrently with other childhood vaccines. Serotype-specific anti-capsular IgG concentrations were measured one-month following the 1(st) and 2(nd) PCV-doses, prior to and two-weeks following the 3(rd) dose. Opsonophagocytic killing assay (OPA) was measured for three serotypes following the 2(nd) and 3(rd) PCV7-doses. Immunogenicity of the current schedule was compared to a historical cohort of infants who received PCV7 at 6, 10 and 14 weeks of age.
The proportion of infants with serotype-specific antibody ≥ 0.35 µg/ml following the 2(nd) PCV7-dose ranged from 84% for 6B to ≥ 89% for other serotypes. Robust antibody responses were observed following the 3(rd) dose. The proportion of children with OPA ≥ 8 for serotypes 9V, 19F and 23F increased significantly following the 3(rd) PCV7-dose to 93.6%; 86.0% and 89.7% respectively. The quantitative antibody concentrations following the 2(nd) PCV7-dose were comparable to that after the 3(rd) -dose in the 6-10-14 week schedule. Geometric mean concentrations (GMCs) following the 3(rd) PCV7-dose were higher for all serotypes in this study compared to the historical cohort.
The studied PCV7 dosing schedule induced good immune responses, including higher GMCs following the 3(rd-)dose at 9-months compared to when given at 14-weeks of age. This may confer longer persistence of antibodies and duration of protection against pneumococcal disease.
To the Editor:
Madhi et al. (May 20 issue)
1
report on the efficacy of vaccination with the recombinant adenoviral vector encoding the spike protein antigen of SARS-CoV-2 (ChAdOx1 nCoV-19) against ...the SARS-CoV-2 B.1.351 (or beta) variant lineage. They commented that in the ENSEMBLE study evaluating the efficacy of the Ad26.COV2.S vaccine, only patients with infection that was confirmed by polymerase-chain-reaction assay who had at least three signs or symptoms of Covid-19 were approved for end-point adjudication. The authors incorrectly concluded that the vaccine efficacy analyses excluded the majority of mild Covid-19 cases. However, all patients with mild or moderate cases . . .
Non-pharmaceutical interventions affected the circulation of and illness due to endemic respiratory pathogens during the COVID-19 pandemic. We investigated the incidence of admissions to hospital for ...overall and specific pathogen-associated lower respiratory tract infection (LRTI) during the COVID-19 pandemic compared with incidence in the pre-pandemic period.
In this observational study, we analysed surveillance data for children younger than 5 years from two public hospitals in Soweto, South Africa, for all-cause LRTI, respiratory syncytial virus (RSV), influenza, human metapneumovirus, and Bordetella pertussis from Jan 1, 2015 to Dec 31, 2022. Data were obtained from an electronic database that includes information for all admissions to the general paediatric wards at the two hospitals, automatically identified by a computer program. We excluded children admitted to hospital with incidental SARS-CoV-2 infection or COVID-19 without LRTI diagnosis. Incidence during COVID-19 pandemic years (2020, 2021, and 2022) were compared with pre-pandemic rates (2015–19).
Overall, there were 42 068 all-cause hospital admissions, including 18 303 all-cause LRTI hospital admissions, from Jan 1, 2015, to Dec 31, 2022, 17 822 (42·4%) of whom were female, 23 893 (57·0%) were male, and 353 (0·8%) had missing data. All-cause LRTI incidence risk ratio (IRR) was 30% lower in 2020 (IRR 0·70, 95% CI 0·67–0·74) and 13% lower in 2021 (0·87, 0·83–0·91), but 16% higher in 2022 (1·16, 1·11–1·21) compared with the pre-pandemic period. Furthermore, compared with the pre-pandemic period, incidence of RSV-associated LRTI (0·52, 0·45–0·58), influenza-associated LRTI (0·05, 0·02–0·11), and pulmonary tuberculosis (0·52, 0·41–0·65) were lower in 2020, with similar trends observed for human-metapneumovirus-associated LRTI, pertussis, and invasive pneumococcal disease (IPD). Compared with the pre-pandemic period, by 2022, RSV-associated LRTI incidence was similar (1·04, 0·95–1·14) and influenza-associated LRTI showed a non-significant increase (1·14, 0·92–1·39), whereas incidence remained lower for tuberculosis (0·79, 0·65–0·94) and IPD (0·51, 0·24–0·99). In 2022, the incidence of COVID-19-associated LRTI hospital admission (65 per 100 000 children younger than 5 years) was lower than pre-pandemic RSV-associated LRTI (0·23, 0·19–0·27) but higher than pre-pandemic influenza-associated LRTI (1·19, 0·97–1·45), although the difference was not significant. All-cause LRTI death in 2022 (57 per 100 000 children younger than 5 years) was 28% higher than in the pre-pandemic period (1·28, 1·03–1·58).
The higher incidence of all-cause LRTI admissions to hospital in 2022 compared with the pre-pandemic period is partly due to ongoing COVID-19 admission to hospital, and could worsen if other endemic respiratory pathogens revert to pre-pandemic incidence. Interventions, including the introduction of vaccines for people who are pregnant that aim to prevent RSV and possibly COVID-19 in young children, are warranted.
The Bill & Melinda Gates Foundation.
Chronic subdural hematoma (CSDH) is a commonly encountered neurosurgical pathology that frequently requires operative intervention. With an increasing ageing demographic, more elderly and comorbid ...patients will present with symptomatic CSDH. This study evaluated clinical and radiologic factors to create a scoring system to aid prognostication.
A cohort of patients undergoing evacuation of CSDH at a single institution was established from 2010 to 2015. Primary endpoint was a dichotomized score on a modified Rankin Scale score at 1-year follow-up (favorable outcome score 0–1; unfavorable outcome score 2–6). Logistic regression analyses were performed to model determinants related to outcome. A prediction rule for diagnosing poor postoperative prognosis with unfavorable modified Rankin Scale score was developed with the obtained results.
Logistic regression analyses showed that age >75 years, midline shift >10 mm, and hematoma thickness >30 mm were significantly associated with unfavorable outcome (age >75 years: odds ratio OR 0.01, 95% confidence interval CI 0.001–0.01; midline shift 11–20 mm: OR 0.18, 95% CI 0.04–0.88; midline shift >20 mm: OR 0.03, 95% CI 0.002–0.41; hematoma thickness >30 mm: OR 0.07, 95% CI 0.01–0.46). A scoring system was designed using the final fitted multivariate model. A minimum score of 3 is feasible, indicating worst prognosis, and maximum score of 13 is feasible, indicating best prognosis. A score of ≥9 showed favorable outcome. Receiver operating characteristic curves were constructed to predict favorable versus unfavorable outcomes with the sensitivity analysis yielding an excellent model discrimination with an area under curve of 0.95, 95% CI 0.92–0.98.
A scoring system has been devised to predict outcome, which can aid in the necessity of surgery in certain patient demographics.
BACKGROUND:Children with cancer are immunocompromised with increased susceptibility to infections. We evaluated the burden of tuberculosis in children with cancer.
METHODS:Children with cancer were ...enrolled and screened for Mycobacterium tuberculosis infection using the tuberculin skin test and enzyme-linked immune absorbent spot (T-SPOT.TB; Oxford Immunotec Ltd, Oxford, United Kingdom). Children with physician-suspected tuberculosis were investigated for M. tuberculosis using microscopy and culture on sputum or gastric washings.
RESULTS:We enrolled 169 children; 10.7% were living with HIV. The tuberculin skin test was positive in 2.9% of patients, who were treated for tuberculosis and excluded from further analysis. The enzyme-linked immune absorbent spot (T-SPOT.TB) was either negative or indeterminate in the first 100 children screened. The incidence of tuberculosis was 7.6 per 100 child-years; 35.3% were culture-confirmed. Tuberculosis was diagnosed at a mean of 5.5 months from cancer diagnosis. A greater proportion of children living with HIV (44.4%) developed tuberculosis than those without (17.2%; adjusted P = 0.042). Children treated for high-risk acute lymphoblastic leukemia, advanced stage non-Hodgkin lymphoma and acute myeloid leukemia (P = 0.009) and those with a higher exposure-period (per 100 child-years) to corticosteroids courses (350 vs. 29.4; P < 0.001) had a higher incidence of tuberculosis. Twenty-six of 34 children (76.5%) with tuberculosis died; multiple infections were identified at the time of death.
CONCLUSIONS:Screening children for tuberculosis infection at cancer diagnosis was of limited value. The high rate of tuberculosis and poor outcomes emphasize the need for a high index of suspicion to diagnose tuberculosis and consideration for antituberculosis treatment, especially for those with identified risk factors.
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