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BACKGROUND: The aim of this study was to characterize the epidemiology of human seasonal coronaviruses (HCoVs) in southern Malawi. METHODS: We tested for HCoVs 229E, OC43, NL63, and HKU1 using real-time polymerase chain reaction (PCR) on upper respiratory specimens from asymptomatic controls and individuals of all ages recruited through severe acute respiratory illness (SARI) surveillance at Queen Elizabeth Central Hospital, Blantyre, and a prospective influenza-like illness (ILI) observational study between 2011 and 2017. We modeled the probability of having a positive PCR for each HCoV using negative binomial models, and calculated pathogen-attributable fractions (PAFs). RESULTS: Overall, 8.8% (539/6107) of specimens were positive for ≥1 HCoV. OC43 was the most frequently detected HCoV (3.1% [191/6107]). NL63 was more frequently detected in ILI patients (adjusted incidence rate ratio [aIRR], 9.60 [95% confidence interval {CI}, 3.25-28.30]), while 229E (aIRR, 8.99 [95% CI, 1.81-44.70]) was more frequent in SARI patients than asymptomatic controls. In adults, 229E and OC43 were associated with SARI (PAF, 86.5% and 89.4%, respectively), while NL63 was associated with ILI (PAF, 85.1%). The prevalence of HCoVs was similar between children with SARI and controls. All HCoVs had bimodal peaks but distinct seasonality. CONCLUSIONS: OC43 was the most prevalent HCoV in acute respiratory illness of all ages. Individual HCoVs had distinct seasonality that differed from temperate settings.
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Infecciones por Coronavirus , Coronavirus , Estaciones del Año , Humanos , Malaui/epidemiología , Masculino , Adulto , Preescolar , Femenino , Niño , Adolescente , Lactante , Persona de Mediana Edad , Infecciones por Coronavirus/epidemiología , Infecciones por Coronavirus/virología , Adulto Joven , Coronavirus/genética , Coronavirus/aislamiento & purificación , Estudios Prospectivos , Infecciones del Sistema Respiratorio/epidemiología , Infecciones del Sistema Respiratorio/virología , Anciano , Recién NacidoRESUMEN
BACKGROUND: Neonatal mortality remains high in Tanzania at approximately 20 deaths per 1000 live births. Low birthweight, prematurity, and asphyxia are associated with neonatal mortality; however, no studies have assessed the value of combining underlying conditions and vital signs to provide clinicians with early warning of infants at risk of mortality. The aim of this study was to identify risk factors (including vital signs) associated with neonatal mortality in the neonatal intensive care unit (NICU) in Bugando Medical Centre (BMC), Mwanza, Tanzania; to identify the most accurate generalised linear model (GLM) or decision tree for predicting mortality; and to provide a tool that provides clinically relevant cut-offs for predicting mortality that is easily used by clinicians in a low-resource setting. METHODS: In total, 165 neonates were enrolled between November 2019 and March 2020, of whom 80 (48.5%) died. We competed the performance of GLMs and decision trees by resampling the data to create training and test datasets and comparing their accuracy at correctly predicting mortality. RESULTS: GLMs always outperformed decision trees. The best fitting GLM showed that (for standardised risk factors) temperature (OR 0.61, 95% CI 0.40-0.90), birthweight (OR 0.33, 95% CI 0.20-0.52), and oxygen saturation (OR 0.66, 95% CI 0.45-0.94) were negatively associated with mortality, while heart rate (OR 1.59, 95% CI 1.10-2.35) and asphyxia (OR 3.23, 95% 1.25-8.91) were risk factors. To identify the tool that balances accuracy and with ease of use in a low-resource clinical setting, we compared the best fitting GLM with simpler versions, and identified the three-variable GLM with temperature, heart rate, and birth weight as the best candidate. For this tool, cut-offs were identified using receiver operator characteristic (ROC) curves with the optimal cut-off for mortality prediction corresponding to 76.3% sensitivity and 68.2% specificity. The final tool is graphical, showing cut-offs that depend on birthweight, heart rate, and temperature. CONCLUSIONS: Underlying conditions and vital signs can be combined into simple graphical tools that improve upon the current guidelines and are straightforward to use by clinicians in a low-resource setting.
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Enfermedades del Recién Nacido , Unidades de Cuidado Intensivo Neonatal , Humanos , Lactante , Mortalidad Infantil , Recién Nacido , Saturación de Oxígeno , Tanzanía/epidemiologíaRESUMEN
Extracellular vesicles (EV) are sub-micron circulating vesicles found in all bodily fluids and in all species so far tested. They have also recently been identified in seawater and it has further been shown that they are released from microorganisms and may participate in interspecies communication in the gut. EV are typically composed of a lipid bilayer formed from the plasma membrane and which encases a cargo that can include genetic material, proteins, and lipids. At least two different processes of formation and release have been described in mammalian cells. The exosome population (50 to 150nm size) are produced via a lyso-endosomal pathway, while microvesicles (100 to 1000nm) are formed by budding of the plasma membrane in a calcium dependent process. Both pathways are highly regulated and appear to be conserved amongst different species. EV release has been shown to be upregulated in a number of human chronic diseases including cardiovascular disease, metabolic disorders, obesity, and cancer; evaluation of their presence in veterinary samples may aid diagnosis in the future. This review will provide insight into the formation of EV and their detection in bodily fluids from different veterinary species and how they may provide a novel addition to the veterinary toolkit of the future.
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Comunicación Celular/fisiología , Vesículas Extracelulares/metabolismo , Animales , Gatos , Bovinos , Perros , CaballosRESUMEN
Background: We characterized the global epidemiology and seasonality of human coronaviruses (HCoVs) OC43, NL63, 229E, and HKU1. Methods: In this systematic review, we searched MEDLINE, EMBASE, Web of Science, SCOPUS, CINAHL, and backward citations for studies published until 1 September 2023. We included studies with ≥12 months of consecutive data and tested for ≥1 HCoV species. Case reports, review articles, animal studies, studies focusing on SARS-CoV-1, SARS-CoV-2, and/or Middle East respiratory syndrome, and those including <100 cases were excluded. Study quality and risk of bias were assessed using Joanna Briggs Institute Critical Appraisal Checklist tools. We reported the prevalence of all HCoVs and individual species. Seasonality was reported for studies that included ≥100 HCoVs annually. This study is registered with PROSPERO, CRD42022330902. Results: A total of 201 studies (1 819 320 samples) from 68 countries were included. A high proportion were from China (19.4%; n = 39), whereas the Southern Hemisphere was underrepresented. Most were case series (77.1%, n = 155) with samples from secondary care (74.1%, n = 149). Seventeen (8.5%) studies included asymptomatic controls, whereas 76 (37.8%) reported results for all 4 HCoV species. Overall, OC43 was the most prevalent HCoV. Median test positivity of OC43 and NL63 was higher in children, and 229E and HKU1 in adults. Among 18 studies that described seasonality (17 from the Northern Hemisphere), circulation of all HCoVs mostly peaked during cold months. Conclusions: In our comprehensive review, few studies reported the prevalence of individual HCoVs or seasonality. Further research on the burden and circulation of HCoVs is needed, particularly from Africa, South Asia, and Central/South America.
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Neonatal bloodstream infections (BSI) can lead to sepsis, with high morbidity and mortality, particularly in low-income settings. The high prevalence of third-generation cephalosporin-resistant organisms (3GC-RO) complicates the management of BSI. Whether BSI is linked to carriage of 3GC-RO, or to acquisition from the hospital environment is important for infection prevention and control, but the relationship remains unclear, especially in low-income settings. At a tertiary hospital in Mwanza, Tanzania, we screened neonatal blood and rectal samples from 200 neonates, and 400 (hospital) environmental samples. We used logistic regression to identify risk factors, and Kolmogorov-Smirnov tests and randomisation analyses to compare distributions of species and resistance patterns to assess potential routes of transmission. We found that BSIs caused by 3GC-RO were frequent (of 59 cases of BSI, 55 were caused by 3GC-RO), as was carriage of 3GC-RO, particularly Escherichia coli, Klebsiella pneumoniae, and Acinetobacter species. In the 28 infants with both a carriage and blood isolate, there were more (4 of 28) isolate pairs of the same species and susceptibility profile than expected by chance (p < 0.05), but most pairs were discordant (24 of 28). Logistic regression models found no association between BSI and carriage with either 3GC-RO or only 3GC-R K. pneumoniae. These analyses suggest that carriage of 3GC-RO is not a major driver of BSI caused by 3GC-RO in this setting. Comparison with environmental isolates showed very similar distributions of species and resistance patterns in the carriage, BSI, and the environment. These similar distributions, a high frequency of Acinetobacter spp. isolations, the lack of strong association between carriage and BSI, together with the high proportion of 3GC-RO in BSI all suggest that these neonates acquire multidrug-resistant carriage and blood isolates directly from the hospital environment.
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Bacteriemia , Sepsis , Antibacterianos/farmacología , Antibacterianos/uso terapéutico , Bacteriemia/microbiología , Bacterias , Cefalosporinas/farmacología , Atención a la Salud , Escherichia coli , Hospitales , Humanos , Lactante , Recién Nacido , Klebsiella pneumoniae , Sepsis/microbiología , Tanzanía/epidemiologíaRESUMEN
The proportions and similarities of extended-spectrum ß-lactamase (ESBL) producing K. pneumoniae (ESBL-KP) and E. coli (ESBL-EC) carrying multiple ESBL genes is poorly known at our setting. This study investigated the existence of multiple ESBL genes (blaCTX-M, blaTEM, and blaSHV) among ESBL-KP and ESBL-EC concurrently isolated from clinical, colonization, and contamination samples from neonatology units in Mwanza-Tanzania. Twenty and 55 presumptive ESBL-EC and ESBL-KP, respectively, from a previous study archived at -80 °C were successfully recovered for this study. Isolates were screened and confirmed for production of ESBLs by phenotypic methods followed by multiplex PCR assay to determine ESBL genes. All (100%) and 97.3% of presumptive ESBL isolates were phenotypically confirmed by Clinical and Laboratory Standards Institute (CLSI) and modified double-disc synergy methods, respectively. About 93.3% (70/75) of phenotypically confirmed ESBL isolates had at least one ESBL gene, whereby for 62.9% (44/70), all ESBL genes (blaCTX-M, blaTEM, and blaSHV) were detected. Eight pairs of ESBL bacteria show similar patterns of antibiotics susceptibility and ESBL genes. ESBL-KP and ESBL-EC, concurrently isolated from clinical, colonization and contamination samples, harbored multiple ESBL genes. Further, eight pairs of ESBL isolates had similar patterns of antibiotics susceptibility and ESBL genes, suggesting transmission of and/or sharing of mobile genetic elements (MGEs) among ESBL-KP and ESBL-EC.
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BACKGROUND: Multidrug resistance (MDR) is a major clinical problem in tertiary hospitals in Tanzania and jeopardizes the life of neonates in critical care units (CCUs). To better understand methods for prevention of MDR infections, this study aimed to determine, among other factors, the role of MDR-Gram-negative bacteria (GNB) contaminating neonatal cots and hands of mothers as possible role in transmission of bacteremia at Bugando Medical Centre (BMC), Mwanza, Tanzania. METHODS: This cross-sectional, hospital-based study was conducted among neonates and their mothers in a neonatal intensive care unit and a neonatology unit at BMC from December 2018 to April 2019. Blood specimens (n = 200) were sub-cultured on 5% sheep blood agar (SBA) and MacConkey agar (MCA) plates. Other specimens (200 neonatal rectal swabs, 200 maternal hand swabs and 200 neonatal cot swabs) were directly inoculated on MCA plates supplemented with 2 µg/ml cefotaxime (MCA-C) for screening of GNB resistant to third generation cephalosporins, r-3GCs. Conventional biochemical tests, Kirby-Bauer technique and resistance to cefoxitin 30 µg were used for identification of bacteria, antibiotic susceptibility testing and detection of MDR-GNB and screening of potential Amp-C beta lactamase producing GNB, respectively. RESULTS: The prevalence of culture confirmed bacteremia was 34.5% of which 85.5% were GNB. Fifty-five (93.2%) of GNB isolated from neonatal blood specimens were r-3GCs. On the other hand; 43% of neonates were colonized with GNB r-3GCs, 32% of cots were contaminated with GNB r-3GCs and 18.5% of hands of neonates' mothers were contaminated with GNB r-3GCs. The prevalences of MDR-GNB isolated from blood culture and GNB r-3GCs isolated from neonatal colonization, cots and mothers' hands were 96.6, 100, 100 and 94.6%, respectively. Significantly, cyanosis (OR[95%CI]: 3.13[1.51-6.51], p = 0.002), jaundice (OR[95%CI]: 2.10[1.07-4.14], p = 0.031), number of invasive devices (OR[95%CI]: 2.52[1.08-5.85], p = 0.031) and contaminated cot (OR[95%CI]: 2.39[1.26-4.55], p = 0.008) were associated with bacteremia due to GNB. Use of tap water only (OR[95%CI]: 2.12[0.88-5.09], p = 0.040) was protective for bacteremia due to GNB. CONCLUSION: High prevalence of MDR-GNB bacteremia and intestinal colonization, and MDR-GNB contaminating cots and mothers' hands was observed. Improved cots decontamination strategies is crucial to limit the spread of MDR-GNB. Further, clinical presentations and water use should be considered in administration of empirical therapy whilst awaiting culture results.