Comparison of paediatric infectious disease deaths in public sector health facilities using different data sources in the Western Cape, South Africa (2007-2021).

BACKGROUND: Routinely collected population-wide health data are often used to understand mortality trends including child mortality, as these data are often available more readily or quickly and for lower geographic levels than population-wide mortality data. However, understanding the completeness and accuracy of routine health data sources is essential for their appropriate interpretation and use. This study aims to assess the accuracy of diagnostic coding for public sector in-facility childhood (age < 5 years) infectious disease deaths (lower respiratory tract infections [LRTI], diarrhoea, meningitis, and tuberculous meningitis [TBM]) in routine hospital information systems (RHIS) through comparison with causes of death identified in a child death audit system (Child Healthcare Problem Identification Programme [Child PIP]) and the vital registration system (Death Notification [DN] Surveillance) in the Western Cape, South Africa and to calculate admission mortality rates (number of deaths in admitted patients per 1000 live births) using the best available data from all sources. METHODS: The three data sources: RHIS, Child PIP, and DN Surveillance are integrated and linked by the Western Cape Provincial Health Data Centre using a unique patient identifier. We calculated the deduplicated total number of infectious disease deaths and estimated admission mortality rates using all three data sources. We determined the completeness of Child PIP and DN Surveillance in identifying deaths recorded in RHIS and the level of agreement for causes of death between data sources. RESULTS: Completeness of recorded in-facility infectious disease deaths in Child PIP (23/05/2007-08/02/2021) and DN Surveillance (2010-2013) was 70% and 69% respectively. The greatest agreement in infectious causes of death were for diarrhoea and LRTI: 92% and 84% respectively between RHIS and Child PIP, and 98% and 83% respectively between RHIS and DN Surveillance. In-facility infectious disease admission mortality rates decreased significantly for the province: 1.60 (95% CI: 1.37-1.85) to 0.73 (95% CI: 0.56-0.93) deaths per 1000 live births from 2007 to 2020. CONCLUSION: RHIS had accurate causes of death amongst children dying from infectious diseases, particularly for diarrhoea and LRTI, with declining in-facility admission mortality rates over time. We recommend integrating data sources to ensure the most accurate assessment of child deaths.

Dysregulation of the renin-angiotensin system during lung ischemia-reperfusion injury.

UNLABELLED: Aim/Purpose of the Study: Activation of the renin-angiotensin system leading to increased angiotensin-(1-7) (Ang-(1-7)) and decreased angiotensin 2 (Ang 2) levels may be a new therapeutic approach to reduce acute lung injury. Prolylcarboxypeptidase (PRCP) and prolyloligopeptidase (PREP) are capable of hydrolyzing Ang 2 into Ang-(1-7). However, their relation with circulating Ang 2 levels after lung ischemia-reperfusion injury (LIRI) has never been explored. This study determines whether the activity and expression of PRCP and PREP in plasma and lung tissue is related to circulating Ang 2 levels in a murine model of LIRI. MATERIALS AND METHODS: LIRI in Swiss mice (6 animals per group) was induced by temporary left lung hilar clamping (1 h) followed by 0, 1 or 24 h of reperfusion. Animals in the sham group received thoracotomy only. PRCP activity was measured via RP-HPLC, PREP activity using a fluorogenic substrate and plasma Ang 2 levels via ELISA. Western blotting was used to determine the PRCP and PREP protein expression profiles in left lung tissue. RESULTS: Plasma Ang 2 levels significantly rise after lung ischemia and remain increased after 1 h and 24 h of reperfusion compared to the sham group. While a significant decrease in plasma PREP activity was found after 24 h of reperfusion, a transient increase in plasma PRCP activity was observed after ischemia. However, no correlation with plasma Ang 2 levels could be demonstrated. The activity profiles of PRCP and PREP and the protein expression of PRCP in the lung tissues remained unchanged after LIRI. CONCLUSIONS: LIRI causes a dysregulation of circulating Ang 2 levels and plasma PREP activity, although no direct link between both phenomena could be shown. The activity profile of pulmonary PRCP and PREP was not significantly changed after LIRI, which implies a minor role for local PRCP and PREP in the ischemic lung itself.

Lower respiratory tract infection admissions and deaths among children under 5 years in public sector facilities in the Western Cape Province, South Africa, before and during the COVID-19 pandemic (2019 - 2021).

BACKGROUND: The COVID-19 pandemic resulted in the implementation of strict public health and social measures (PHSMs) (including mobility restrictions, social distancing, mask-wearing and hand hygiene), limitations on non-essential healthcare services, and public fear of COVID-19 infection, all of which potentially affected transmission and healthcare use for other diseases such as lower respiratory tract infections (LRTIs). OBJECTIVE: To determine changes in LRTI hospital admissions and in-facility mortality in children aged <5 years in the Western Cape Province during the pandemic. METHODS: We conducted a retrospective analysis of LRTI admissions and in-facility deaths from January 2019 to November 2021. We estimated changes in rates and trends of LRTI admissions during the pandemic compared with pre-pandemic period using interrupted time series analysis, adjusting for key characteristics. RESULTS: There were 36 277 children admitted for LRTIs during the study period, of whom 58% were male and 51% were aged 28 days - 1 year. COVID-19 restrictions were associated with a 13% step reduction in LRTI admissions compared with the pre-COVID-19 period (incidence rate ratio (IRR) 0.87, 95% confidence interval (CI)) 0.80 - 0.94). The average LRTI admission trend increased on average by 2% per month during the pandemic (IRR 1.02, 95% CI 1.02 - 1.04). CONCLUSIONS: The COVID-19 surges and their associated measures were linked to declining LRTI admissions and in-facility deaths, likely driven by a combination of reduced infectious disease transmission and reduced use of healthcare services, with effects diminishing over time. These findings may inform future pandemic response policies.

Ciprofloxacin versus trimethoprim/sulfamethoxazole for prophylaxis of bacterial infections in bone marrow transplant recipients: a randomized, controlled trial.

PURPOSE: To compare the efficacy and safety of ciprofloxacin (CIP) and trimethoprim/sulfamethoxazole (TMS) for the prevention of bacterial infections in patients who received bone marrow transplantation (BMT) for the treatment of solid and hematopoietic neoplasms. PATIENTS AND METHODS: Adult inpatients about to undergo BMT for lymphoma, leukemia, or solid tumors were enrolled onto a prospective, randomized, double-blinded, controlled trial that compared CIP (750 mg orally twice per day) with TMS (160 mg trimethoprim and 800 mg sulfamethoxazole orally twice per day). Subjects were stratified before randomization according to tumor and BMT type. Prophylaxis was begun within 96 hours of initiation of the BMT preparative regimen and continued until the onset of fever, signs or symptoms of infection, serious adverse effects, or recovery of the absolute granulocyte count (AGC) to > or = to 400/microL. RESULTS: Seventy-five CIP recipients and 71 TMS recipients were assessable for efficacy. No difference was noted between the two groups in occurrence of fever during neutropenia, time to onset of first fever, or overall infection rates. Ten bacteremias occurred in CIP recipients versus six in TMS recipients (P = .43). Ten episodes of Clostridium difficile enterocolitis occurred in TMS recipients versus no episodes in CIP recipients (P = .001). Four infections caused by gram-negative bacilli, including one bacteremia, occurred in TMS recipients versus none in CIP recipients (P = .06). No differences were noted in the incidence of rash or organ toxicity. TMS recipients had longer durations of granulocytopenia at AGC levels < or = to 500/microL and < or = to 100/microL than did CIP recipients (P = .08 for both comparisons). Mean peak and trough serum levels of CIP decreased significantly between weeks 1 and 2 of prophylaxis. CONCLUSION: CIP and TMS were equally safe and effective in the prevention of bacterial infections in BMT patients when the overall infection rate was used as the principal end point. TMS prophylaxis was associated with a higher incidence of C difficile enterocolitis and infections caused by gram-negative bacilli, as well as a trend toward prolongation of granulocytopenia.

Prophylaxis of bacterial infections with ciprofloxacin in patients undergoing bone marrow transplantation.

Twenty-six oncology patients, 25 of whom received bone marrow transplants, were enrolled in a prospective, randomized, double-blinded, placebo-controlled trial assessing the efficacy of ciprofloxacin, 750 mg p.o. b.i.d., for preventing bacterial infections during prolonged neutropenia. Treatment was begun within 48 hr of initiation of chemotherapy and continued until the absolute granulocyte count recovered to greater than or equal to 500/microliters, or until the onset of fever (greater than or equal to 38.3 degrees C). Seven evaluable subjects received ciprofloxacin, and 11 received placebo. Risk factors for infection were comparable in both groups. Fever occurred in all study subjects, but onset was delayed in ciprofloxacin recipients (median = 6 days after the fall of the absolute granulocyte count to less than or equal to 500/microliters vs. 3 days for placebo recipients, P = 0.01). No clinically or microbiologically documented infections occurred in ciprofloxacin recipients vs. 10 infections in placebo recipients (5 bacteremias, 4 skin/soft tissue infections, 1 urinary tract infection, P = 0.0003). Ciprofloxacin recipients required fewer days of therapeutic antimicrobials (median: 28 antibiotic-days vs. 49, P0.02). The bioavailability of ciprofloxacin appeared comparable to that found in previously published studies of normal volunteers and patients not receiving chemotherapy. Adverse effects and colonization by ciprofloxacin-resistant microorganisms were monitored, but the sample sizes were too small to permit meaningful conclusions about these safety parameters. Ciprofloxacin appears to be effective for preventing bacterial infections in neutropenic patients. Additional trials are needed to establish the optimal dose of ciprofloxacin and to compare its safety and efficacy with those of currently used prophylactic regimens.

When is hilar uptake of 67Ga-citrate indicative of residual disease after CHOP chemotherapy?

UNLABELLED: The purpose of this study was to evaluate the prevalence and characterize the patterns of hilar uptake (HU) on 67Ga-citrate imaging after cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) chemotherapy regimens for non-Hodgkin's lymphoma (NHL), to differentiate hilar lymphoma (HL) from HU of benign etiology. METHODS: A total of 930 studies (698 planar, 232 thoracic SPECT) was reviewed retrospectively in 100 NHL patients (29 low-grade, 60 intermediate-grade, and 11 high-grade) treated with CHOP and followed up longitudinally with serial gallium studies (planar: median, 7; range, 3-16 studies in 100 patients; SPECT: median, 1; range, 0-11 studies in 72 patients) over a median duration of 36 mo (range, 6-112 mo) from diagnosis. Clinical outcome and size changes over time on correlative CT and/or radiographs were used to evaluate benign versus malignant changes within the hila. RESULTS: HU after CHOP was present in 79% of patients (90% confidence interval [CI], 71%-85%), with 33% showing HU on SPECT alone. Once present, HU persisted for a median of 27 mo (range, 2-84 mo) from onset. The prevalence of HU and HL at various time points was as follows: baseline HU, 52% with HL 60%; mid-CHOP HU, 59% with HL2%; post-CHOP HU, 52% with HL6%; follow-up HU, 76% with HL 9%. HU of benign etiology was not significantly correlated with CHOP dosage. HU was symmetric in 90% of patients (90% CI, 82%-95%) and less intense than the original disease in 89% of patients (90% CI, 80%-95%), and these features were highly predictive of benign etiology (negative predictive value [NPV], 98.6% if symmetric; NPV, 96.5% if less than original disease; NPV, 100% if both present). Asymmetric HU equal in intensity to the original disease, however, was highly predictive of HL (positive predictive value [PPV], 87.5% if asymmetric; PPV, 85.7% if equal to original disease; PPV, 100% if both present). CONCLUSION: HU after CHOP is common (overall incidence, 79%), often seen only on SPECT, and most likely of benign etiology when symmetric and less intense than the original disease. Asymmetric HU that equals the intensity of the original disease, however, is a possible indicator for HL.

SEPT5_v2 is a parkin-binding protein.

Mutations in parkin are associated with various inherited forms of Parkinson's disease (PD). Parkin is a ubiquitin ligase enzyme that catalyzes the covalent attachment of ubiquitin moieties onto substrate proteins destined for proteasomal degradation. The substrates of parkin-mediated ubiquitination have yet to be completely identified. Using a yeast two-hybrid screen, we isolated the septin, human SEPT5_v2 (also known as cell division control-related protein 2), as a putative parkin-binding protein. SEPT5_v2 is highly homologous to another septin, SEPT5, which was recently identified as a target for parkin-mediated ubiquitination. SEPT5_v2 binds to parkin at the amino terminus and in the ring finger domains. Several lines of evidence have validated the putative link between parkin and SEPT5_v2. Parkin co-precipitates with SEPT5_v2 from human substantia nigra lysates. Parkin ubiquitinates SEPT5_v2 in vitro, and both SEPT5_v1 and SEPT5_v2 accumulate in brains of patients with ARJP, suggesting that parkin is essential for the normal metabolism of these proteins. These findings suggest that an important relationship exists between parkin and septins.

Angular distributions of s-subshell electrons in open-shell atoms: 3s photoionization of atomic chlorine

A determination of the angular distribution parameter beta of the atomic chlorine 3s photoelectrons over the photon-energy range from 29 to 70 eV has been carried out using electron spectrometry in conjunction with synchrotron radiation. Our results confirm the basic theoretical predictions that beta, for s-subshell photoionization in open-shell atoms, is in general term and photon-energy dependent, in contrast to closed-shell atoms where beta is always 2 nonrelativistically. However, our measurements of beta for the Cl+ 3s((1,3)P) channels demonstrate that significant details are not handled well by simple Hartree-Fock theory.

Infection of human B lymphocytes with MMR vaccine induces IgE class switching.

Circulating immunoglobulin E (IgE) is one of the characteristics of human allergic diseases including allergic asthma. We recently showed that infection of human B cells with rhinovirus or measles virus could lead to the initial steps of IgE class switching. Since many viral vaccines are live viruses, we speculated that live virus vaccines may also induce IgE class switching in human B cells. To examine this possibility, we selected the commonly used live attenuated measles mumps rubella (MMR) vaccine. Here, we show that infection of a human IgM(+) B cell line with MMR resulted in the expression of germline epsilon transcript. In addition, infection of freshly prepared human PBLs with this vaccine resulted in the expression of mature IgE mRNA transcript. Our data suggest that a potential side effect of vaccination with live attenuated viruses may be an increase in the expression of IgE.

Double-stranded RNA regulates IL-4 expression.

dsRNA, as genomic fragment, replicative intermediate, or stem and loop structure in cells infected by viruses, can act to signal the immune system of the presence of viral infections. Although most viral infections are associated with strong Th1 immune responses, Th2-type responses have also been observed. In this study, we characterize the effects of dsRNA on the induction of Th2 responses in human lymphocytes. We report that in addition to the well-known Th1-inducing capabilities of dsRNA, treatment of human lymphocytes with low concentrations of dsRNA (0.1-1 microg/ml) leads to the expression of the prototypic Th2 cytokine IL-4. This induction was accompanied with the concentration-dependent activation of NF-kappaB and NF-AT2 but not NF-AT1. In addition, dsRNA can directly activate an IL-4 promoter-driven chloramphenicol acetyltransferase reporter gene in transiently transfected Jurkat cells. These results are the first demonstration of a non-TCR-associated activator of NF-AT in human cells and suggest that dsRNA directly influences IL-4 gene expression through its effect on NF-AT activation. Our data provide support for the idea that dsRNA at low concentrations in vivo may induce a Th2-dominant response that is not optimal for protective immunity to the virus.

Phosphatase 2A participates in interferon-gamma's induced upregulation of C1 inhibitor mRNA expression.

C1 inhibitor (C1 INH) is the major inhibitor of the proteolytically active subcomponents of C1, kallikrein, activated forms of factor XII, and factor XIa in plasma. We determined the mechanism(s) how interferon-gamma (IFN-gamma) regulates C1 INH mRNA expression in HepG2 cells. Cycloheximide or anisomycin treatment alone did not increase C1 INH mRNA nor did it potentiate C1 INH mRNA expression after IFN-gamma stimulation. C1 INH mRNA levels on Northern blot from untreated and IFN-gamma-treated cells did not change for more than 20 hours after actinomycin D treatment. Actinomycin D and 5,6-dichloro-1-beta-ribofuranosylbenzimidazole abolished IFN-gamma-induced C1 INH mRNA expression. Relatively more C1 INH mRNA precursor (heterogeneous nuclear RNA [hnRNA]) was detected in total RNA from IFN-gamma-treated HepG2 cells than unstimulated cells. Treatment of HepG2 cells with the phosphatase 1 and 2A inhibitors, okadaic acid (> or = 50 nmol/L) and calyculin (> or = 25 nmol/L), decreased IFN-gamma's ability to upregulated C1 INH mRNA. The phosphatase 2A inhibitor, cantharidin (> or = 10 micromol/L), also blocked the IFN-gamma induction of the C1 INH gene. In HepG2 cells total phosphatase 2A activity was significantly increased by C6 ceramide but not IFN-gamma. However, C6 ceramide itself did not increase C1 INH mRNA expression. These data indicate that phosphatase 2A is required to dephosphorylate a substrate in order for IFN-gamma to induce the transcriptional upregulation of C1 INH mRNA, but phosphatase 2A is not a direct stimulator of C1 INH gene expression.

Uptake of radiolabeled somatostatin analog is detectable in patients with metastatic foci of sarcoma.

BACKGROUND: Somatostatin receptors are present on many types of epithelial tumors, and ligands targeting these receptors are used to treat patients with neuroendocrine malignancies. Preclinical studies have demonstrated the presence of somatostatin receptors on a variety of mesenchymal tumors by in vitro receptor autoradiography. The use of radiolabeled somatostatin analogs to assess the presence of somatostatin receptors in vivo has been established, but use of this technique to evaluate human sarcomas has not been reported previously. METHODS: Seventeen patients (13 females and 4 males) with metastatic sarcoma underwent imaging via somatostatin-receptor scintigraphy. Scans were performed using indium -111 pentetreotide. Planar studies and single photon emission computed tomography imaging were performed at 4 and 24 hours, and results of scintigraphy were correlated with computed tomography findings. RESULTS: Twelve of 17 scans showed increased uptake in regions of known metastatic disease. There was no apparent correlation with scan positivity and patient age, histology, site of disease, or duration of diagnosis. CONCLUSIONS: Seventy-one percent of patients with advanced soft-tissue sarcomas had positive scintigraphy scans demonstrating tumor expression of somatostatin receptors subtype 2 in vivo. Imaging with indium-111 pentetreotide could be studied as an adjunct to conventional imaging modalities for assessment of sarcoma patients. Further research is needed to determine the prognostic implications of somatostatin receptor subtype 2 positivity, including larger studies to evaluate any potential correlation with metastatic behavior and other clinical outcomes.