Abstract
Postmortem minimally invasive tissue sampling together with the detailed review of clinical records has been shown to be highly successful in determining the cause of neonatal deaths. ...However, conventional tests including traditional culture methods and nucleic acid amplification tests have periodically proven to be insufficient to detect the causative agent in the infectious deaths. In this study, metagenomic next generation sequencing was used to explore for putative pathogens associated with neonatal deaths in post-mortem blood and lung tissue samples, in Soweto, South Africa. Here we show that the metagenomic sequencing results corroborate the findings using conventional methods of culture and nucleic acid amplifications tests on post-mortem samples in detecting the pathogens attributed in the causal pathway of death in 90% (18/20) of the decedents. Furthermore, metagenomic sequencing detected a putative pathogen, including
Acinetobacter baumannii, Klebsiella pneumoniae, Escherichia coli
, and
Serratia marcescens
, in a further nine of 11 (81%) cases where no causative pathogen was identified. The antimicrobial susceptibility profile was also determined by the metagenomic sequencing for all pathogens with numerous multi drug resistant organism identified. In conclusion, metagenomic sequencing is able to successfully identify pathogens contributing to infection associated deaths on postmortem blood and tissue samples.
Comparisons of histopathological features and microbiological findings between decedents with respiratory symptoms due to SARS-CoV-2 infection or other causes, in settings with high prevalence of HIV ...and Mycobacterium tuberculosis (MTB) infections have not been reported. Deaths associated with a positive ante-mortem SARS-CoV-2 PCR test and/or respiratory disease symptoms at Chris Hani Baragwanath Academic Hospital in Soweto, South Africa from 15th April to 2nd November 2020, during the first wave of the South African COVID-19 epidemic, were investigated. Deceased adult patients had post-mortem minimally-invasive tissue sampling (MITS) performed to investigate for SARS-CoV-2 infection and molecular detection of putative pathogens on blood and lung samples, and histopathology examination of lung, liver and heart tissue. During the study period MITS were done in patients displaying symptoms of respiratory disease including 75 COVID-19-related deaths (COVID+) and 42 non-COVID-19-related deaths (COVID-). The prevalence of HIV-infection was lower in COVID+ (27%) than in the COVID- (64%), MTB detection was also less common among COVID+ (3% vs 13%). Lung histopathology findings showed differences between COVID+ and COVID- in the severity of the morphological appearance of Type-II pneumocytes, alveolar injury and repair initiated by SARS-CoV-2 infection. In the liver necrotising granulomatous inflammation was more common among COVID+. No differences were found in heart analyses. The prevalence of bacterial co-infections was higher in COVID+. Most indicators of respiratory distress syndrome were undifferentiated between COVID+ and COVID- except for Type-II pneumocytes. HIV or MTB infection does not appear in these data to have a meaningful correspondence with COVID-related deaths.
Pneumonia is a major cause of death among adults living with HIV in South Africa, but the etiology of many cases remains unknown. This study evaluated the utility of a nanofluidic qPCR assay to ...detect and serotype Streptococcus pneumoniae in urine samples from patients hospitalized with community-acquired pneumonia (CAP). The nanofluidic qPCR assay was optimized to target 13 pneumococcal serotypes and 4 reference genes. Archived urine samples collected from patients > 15 years of age hospitalized with pneumonia between April 2018 and August 2019 were retrospectively tested using the nanofluidic qPCR assay, BinaxNOW urine antigen test, and standard LytA qPCR. Blood culture was undertaken on a subset of the samples at the discretion of the attending physician. Cohens' Kappa statistics were used to determine the concordance between the methods. Of the 828 adults hospitalized for CAP, urine samples were available in 53% (n = 439). Of those, a random subset of 96 (22%) samples underwent testing. Of the participants included in the final analysis, the mean age was 45.8 years (SD 16.2), 49% (n = 47) were female, 98% (n = 94) were black, and 66% (n = 63) were living with HIV infection. The nanofluidic qPCR method was able to detect PCV13 vaccine strains spiked into urine samples; however, the method failed to detect any pneumococcus in clinical samples. In comparison, 19% of the pneumonia cases were attributed to S. pneumoniae using urine antigen testing. Nanofluidic qPCR is unable to detect and serotype Streptococcus pneumoniae in urine samples of South Africans hospitalized with CAP.
Background. Lack of a gold standard for identifying bacterial and viral etiologies of pneumonia has limited evaluation of C-reactive protein (CRP) for identifying bacterial pneumonia. We evaluated ...the sensitivity and specificity of CRP for identifying bacterial vs respiratory syncytial virus (RSV) pneumonia in the Pneumonia Etiology Research for Child Health (PERCH) multicenter case-control study. Methods. We measured serum CRP levels in cases with World Health Organization–defined severe or very severe pneumonia and a subset of community controls. We evaluated the sensitivity and specificity of elevated CRP for "confirmed" bacterial pneumonia (positive blood culture or positive lung aspirate or pleural fluid culture or polymerase chain reaction PCR) compared to "RSV pneumonia" (nasopharyngeal/oropharyngeal or induced sputum PCR-positive without confirmed/suspected bacterial pneumonia). Receiver operating characteristic (ROC) curves were constructed to assess the performance of elevated CRP in distinguishing these cases. Results. Among 601 human immunodeficiency virus (HIV)–negative tested controls, 3% had CRP ≥40 mg/L. Among 119 HIV-negative cases with confirmed bacterial pneumonia, 77% had CRP ≥40 mg/L compared with 17% of 556 RSV pneumonia cases. The ROC analysis produced an area under the curve of 0.87, indicating very good discrimination; a cut-point of 37.1 mg/L best discriminated confirmed bacterial pneumonia (sensitivity 77%) from RSV pneumonia (specificity 82%). CRP ≥100 mg/L substantially improved specificity over CRP ≥40 mg/L, though at a loss to sensitivity. Conclusions. Elevated CRP was positively associated with confirmed bacterial pneumonia and negatively associated with RSV pneumonia in PERCH. CRP may be useful for distinguishing bacterial from RSV-associated pneumonia, although its role in discriminating against other respiratory viral-associated pneumonia needs further study.
BACKGROUND:The detection of human rhinoviruses (HRV) is highly prevalent in children with pneumonia, bronchiolitis, acute asthma and croup; however, there is also evidence that HRV is common in ...asymptomatic individuals. The majority of studies on the role of different HRV serotypes during acute respiratory tract infections episodes have limited sample size to fully characterize the epidemiology of HRV infection, including those from low-middle income countries, where the burden of childhood respiratory disease is greatest.
METHODS:We systematically reviewed HRV clinical and molecular epidemiology in low- and middle-income countries in Africa and Southeast Asia before November 2015.
RESULTS:We identified 31 studies, which included data from 13 African and 6 Southeast Asian countries, emphasizing the gaps in knowledge surrounding HRV infections. HRV was one of the most prevalent respiratory viruses detected during childhood respiratory disease (13%–59%); however, many studies could not determine the attributable role of HRV in the pathogenesis of acute respiratory infections due to high prevalence of detection among asymptomatic individuals (6%–50%). A meta-analysis showed no significant difference in the prevalence of HRV identification between children of different age groups; or between children with severe disease compared with asymptomatic children.
CONCLUSIONS:These data highlight the need for large-scale surveillance projects to determine the attributable etiologic role of HRV in respiratory disease.
The pathogenesis of human rhinovirus (HRV) during severe respiratory disease remains undefined; thus, we aimed to explore the relationship between the HRV molecular subtyping results obtained during ...severe and asymptomatic childhood infections. Nasopharyngeal/oropharyngeal swabs from children (1 to 59 months of age) hospitalized with pneumonia and from age-frequency-matched controls were collected between August 2011 and August 2013. Swabs were tested for respiratory pathogens, including HRV, using quantitative real-time PCR assays. HRV-positive samples were sequenced for phylogenetic analysis by targeting the 5' noncoding region (5'NCR). Our data showed that there were no differences in the prevalence of HRV detection among cases and controls (21% versus 20%,
0.693); however, among children 13 to 59 months old, HRV detection was more often case associated (21% versus 16%;
0.009), with the results mainly driven by HRV-C (12% versus 7%;
0.001). Overall, there were no differences in the results of molecular subtyping of the HRV species prevalence among cases (for HRV-A, 48%; for HRV-B, 7%; for HRV-C, 45%) and controls (for HRV-A, 45%; for HRV-B, 10%; for HRV-C, 45%
0.496). Those with pneumonia and HRV-C were older (12.1 versus 9.4 months,
0.033) and more likely to present with wheeze (35% versus 25%,
0.031) than those with HRV-A cases. Thus, the rate of HRV detection was high, with similar degrees of genetic diversity among cases and controls, confounding the interpretation of the presence of HRV in nasopharyngeal samples for attribution of a causal role in the pathogenesis of severe pneumonia in infants. However, among children 13 to 59 months of age, HRV detection, in particular, HRV-C detection, was associated with case status, especially among children with wheezing disease.
Endemic human coronaviruses (HCoV) are capable of causing a range of diseases from the common cold to pneumonia. We evaluated the epidemiology and seasonality of endemic HCoVs in children ...hospitalized with clinical pneumonia and among community controls living in countries with a high HIV burden, namely South Africa and Zambia, between August 2011 to October 2013. Nasopharyngeal/oropharyngeal swabs were collected from all cases and controls and tested for endemic HCoV species and 12 other respiratory viruses using a multiplex real-time PCR assay. We found that the likelihood of detecting endemic HCoV species was higher among asymptomatic controls than cases (11% vs. 7.2%; 95% CI: 1.2–2.0). This was however only observed among children > 6 months and was mainly driven by the Betacoronavirus endemic species (HCoV-OC43 and –HKU1). Endemic HCoV species were detected through the year; however, in Zambia, the endemic Betacoronavirus species tended to peak during the winter months (May–August). There was no association between HIV status and endemic HCoV detection.
In pregnant women, antibodies against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein cross the placenta and can be detected in cord-blood at the time of delivery. We ...measured SARS-CoV-2 full-length antispike IgG in blood samples collected from women living with HIV (WLWHIV) and without HIV when presenting for labour, and from paired cord-blood samples. Antispike IgG was measured in maternal blood at delivery on the Luminex platform. Cord-blood samples from newborns of women in with detectable antispike IgG were analysed. The IgG geometric mean concentrations (GMCs) and the percentage of cord-blood samples with detectable antispike IgG were compared between WLWHIV and without HIV. A total of 184 maternal and cord-blood pairs were analysed, including 47 WLWHIV and 137 without HIV. There was no difference in antispike GMCs between WLWHIV and without HIV 157 binding antibody units (BAU)/ml vs. 187 BAU/ml; P = 0.17). Cord-blood samples from newborns of WLWHIV had lower GMCs compared with those without HIV (143 vs. 205 BAU/ml; P = 0.033). Cord-to-maternal blood antibody ratio was 1.0 and similar between the two HIV groups. In WLWHIV, those who were 30 years old or less had lower cord-to-maternal blood antibody ratio (0.75 vs. 1.10; P = 0.037) and their newborns had lower cord-blood GMCs (94 vs. 194 BAU/ml; P = 0.04) compared with the older women. Independently of maternal HIV infection status, there was efficient transplacental transfer of antispike antibodies. The GMCs in cord-blood from newborns of WLWHIV were lower than those in HIV-unexposed newborns.
We investigated Omicron infections among healthcare workers (HCW) presenting with symptoms of SARS-CoV-2 infection and evaluated the protective effect of vaccination or prior infection. Between 24 ...November and 31 December 2021, HCW in Johannesburg, South Africa, were tested for SARS-CoV-2 infection by Nucleic Acid Amplification Test (NAAT). Blood samples collected either at the symptomatic visit or in the 3 months prior, were tested for spike protein immunoglobulin G (IgG). Overall, 433 symptomatic HCW were included in the analysis, with 190 (43.9%) having an Omicron infection; 69 (16.7%) were unvaccinated and 270 (62.4%) received a single dose of the Ad26.COV.2 vaccine. There was no difference in the odds of identifying Omicron between unvaccinated and Ad26.COV.2 vaccinated HCW (adjusted odds ratio (aOR) 0.81, 95% confidence interval (CI): 0.46, 1.43). One-hundred and fifty-four (35.3%) HCW had at least one SARS-CoV-2 NAAT-confirmed prior infection; these had lower odds of Omicron infection compared with those without past infection (aOR 0.55, 95%CI: 0.36, 0.84). Anti-spike IgG concentration of 1549 binding antibody unit/mL was suggestive of significant reduction in the risk of symptomatic Omicron infection. We found high reinfection and vaccine breakthrough infection rates with the Omicron variant among HCW. Prior infection and high anti-spike IgG concentration were protective against Omicron infection.
Abstract
From April to September 2020, we investigated severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections in a cohort of 396 healthcare workers (HCWs) from 5 departments at Chris ...Hani Baragwanath Hospital, South Africa. Overall, 34.6% of HCWs had polymerase chain reaction–confirmed SARS-CoV-2 infection (132.1 95% confidence interval, 111.8–156.2 infections per 1000 person-months); an additional 27 infections were identified by serology. HCWs in the internal medicine department had the highest rate of infection (61.7%). Among polymerase chain reaction–confirmed cases, 10.4% remained asymptomatic, 30.4% were presymptomatic, and 59.3% were symptomatic.
PDF
