scholarly journals Pathogens detected using a syndromic molecular diagnostic platform in patients hospitalized with severe respiratory illness in South Africa in 2017

Author(s):  
Malefu Moleleki ◽  
Mignon du Plessis ◽  
Kedibone Ndlangisa ◽  
Cayla Reddy ◽  
Anne von Gottberg ◽  
...  

Background Pneumonia continues to be a leading cause of death globally; however, in >50% of cases, an etiological agent is not identified. We describe the use of a multi-pathogen platform, TaqMan array card (TAC) real-time PCR, for the detection of pathogens in patients hospitalized with severe respiratory illness (SRI). Methods We conducted prospective hospital-based surveillance for SRI among patients at two sentinel sites in South Africa between January and December 2017. Patients were included in this study if a blood specimen and at least one respiratory specimen (naso- and oro-pharyngeal (NP/OP) swabs and/or sputum) were available for testing. We tested respiratory specimens for 21 respiratory pathogens and blood samples for nine bacteria using TAC. Pathogen detection was compared by age group and HIV status using the chi-squared test. Results During 2017, 956 patients were enrolled in SRI surveillance, and of these, 637 (67%) patients were included in this study (637 blood, 487 NP/OP and 411 sputum specimens tested). At least one pathogen was detected in 83% (527/637) of patients. Common pathogens detected included H. influenzae (225/637; 35%), S. pneumoniae (224/637; 35%), rhinovirus (144/637; 23%), S. aureus (129/637; 20%), K. pneumoniae (85/637; 13%), M. tuberculosis (75/637; 12%), and respiratory syncytial virus (57/637; 9%). Multiple pathogens (≥2) were co-detected in 57% (364/637) of patients. Conclusion While use of a multi-pathogen platform was useful in the detection of a pathogen in the majority of the patients, pathogen co-detections were common and would need clinical assessment for usefulness in individual-level treatment and management decisions.

Author(s):  
Stefano Tempia ◽  
Jocelyn Moyes ◽  
Adam Cohen ◽  
Sibongile Walaza ◽  
Meredith McMorrow ◽  
...  

Background Estimates of the disease burden associated with different respiratory viruses are severely limited in low- and middle-income countries, especially in Africa. Methods We estimated age-specific numbers and rates of medically and non-medically attended influenza-like illness (ILI) and severe respiratory illness (SRI) that were associated with influenza, respiratory syncytial virus (RSV), rhinovirus, human metapneumovirus, adenovirus, enterovirus and parainfluenza virus types 1-3 after adjusting for the attributable fraction (AF) of virus detection to illness in South Africa during 2013-2015. Rates were reported per 100,000 population. Results The mean annual rates were 51,383 and 4,196 for ILI and SRI, respectively. Of these, 26% (for ILI) and 46% (for SRI) were medically attended. Among outpatients with ILI, rhinovirus had the highest AF-adjusted rate (7,221), followed by influenza (6,443) and adenovirus (1,364); whereas, among inpatients with SRI, rhinovirus had the highest AF-adjusted rate (400), followed by RSV (247) and influenza (130). Rhinovirus (9,424) and RSV (2,026) had the highest AF-adjusted rates among children aged <5 years with ILI or SRI, respectively; whereas rhinovirus (757) and influenza (306) had the highest AF-adjusted rates among individuals aged ≥65 years with ILI or SRI, respectively Conclusions There was a substantial burden of ILI and SRI in South Africa during 2013-2015. Rhinovirus and influenza had a prominent disease burden among patients with ILI. Rhinovirus had the highest burden of illness among patients of any age with SRI, followed by RSV. RSV and influenza were the most prominent causes of SRI in children and the elderly, respectively.


2017 ◽  
Author(s):  
C Langelier ◽  
MS Zinter ◽  
K Kalantar ◽  
GA Yanik ◽  
S Christenson ◽  
...  

ABSTRACTRATIONALECurrent microbiologic diagnostics often fail to identify the etiology of lower respiratory tract infections (LRTI) in hematopoietic cellular transplant recipients (HCT), which precludes the implementation of targeted therapies.OBJECTIVESTo address the need for improved LRTI diagnostics, we evaluated the utility of metagenomic next generation sequencing (mNGS) of bronchoalveolar lavage (BAL) to detect microbial pathogens in HCT patients with acute respiratory illnesses.METHODSWe enrolled 22 post-HCT adults ages 19-69 years with acute respiratory illnesses who underwent BAL at the University of Michigan between January 2012 and May 2013. mNGS was performed on BAL fluid to detect microbes and simultaneously assess the host transcriptional response. Results were compared against conventional microbiologic assays.MEASUREMENTS & MAIN RESULTSmNGS demonstrated 100% sensitivity for detecting respiratory microbes (human metapneumovirus, respiratory syncytial virus,Stenotrophomonas maltophilia, human herpesvirus 6 and cytomegalovirus) when compared to standard testing. Previously unrecognized LRTI pathogens were identified in six patients for whom standard testing was negative (human coronavirus 229E, human rhinovirus A,Corynebacterium propinquumandStreptococcus mitis); findings were confirmed by independent PCR and 16S rRNA sequencing. Relative to patients without infection, patients with infection had increased expression of immunity related genes (p=0.022) and significantly lower diversity of their respiratory microbiome (p=0.017).CONCLUSIONSCompared to conventional diagnostics, mNGS enhanced detection of pathogens in BAL fluid from HCT patients. Furthermore, our results suggest that combining unbiased microbial pathogen detection with assessment of host gene biomarkers of immune response may hold promise for enhancing the diagnosis of post-HCT respiratory infections.


2017 ◽  
Vol 9 (1) ◽  
Author(s):  
Roger Morbey ◽  
Alex J. Elliot ◽  
Maria Zambon ◽  
Richard Pebody ◽  
Gillian E. Smith

ObjectiveTo improve understanding of the relative burden of differentcausative respiratory pathogens on respiratory syndromic indicatorsmonitored using syndromic surveillance systems in England.IntroductionPublic Health England (PHE) uses syndromic surveillance systemsto monitor for seasonal increases in respiratory illness. Respiratoryillnesses create a considerable burden on health care services andtherefore identifying the timing and intensity of peaks of activity isimportant for public health decision-making. Furthermore, identifyingthe incidence of specific respiratory pathogens circulating in thecommunity is essential for targeting public health interventionse.g. vaccination. Syndromic surveillance can provide early warningof increases, but cannot explicitly identify the pathogens responsiblefor such increases.PHE uses a range of general and specific respiratory syndromicindicators in their syndromic surveillance systems, e.g. “allrespiratory disease”, “influenza-like illness”, “bronchitis” and“cough”. Previous research has shown that “influenza-like illness”is associated with influenza circulating in the community1whilst“cough” and “bronchitis” syndromic indicators in children under 5are associated with respiratory syncytial virus (RSV)2, 3. However, therelative burden of other pathogens, e.g. rhinovirus and parainfluenzais less well understood. We have sought to further understand therelationship between specific pathogens and syndromic indicators andto improve estimates of disease burden. Therefore, we modelled theassociation between pathogen incidence, using laboratory reports andhealth care presentations, using syndromic data.MethodsWe used positive laboratory reports for the following pathogens as aproxy for community incidence in England: human metapneumovirus(HMPV), RSV, coronavirus, influenza strains, invasivehaemophilusinfluenzae, invasivestreptococcus pneumoniae, mycoplasmapneumoniae, parainfluenza and rhinovirus. Organisms were chosenthat were found to be important in previous work2and were availablefrom routine laboratory testing. Syndromic data included consultationswith family doctors (called General Practitioners or GPs), calls to anational telephone helpline “NHS 111” and attendances at emergencydepartments (EDs). Associations between laboratory reports andsyndromic data were examined over four winter seasons (weeks40 to 20), between 2011 and 2015. Multiple linear regression was usedto model correlations and to estimate the proportion of syndromicconsultations associated with specific pathogens. Finally, burdenestimates were used to infer the proportion of patients affected byspecific pathogens that would be diagnosed with different symptoms.ResultsInfluenza and RSV exhibited the greatest seasonal variation andwere responsible for the strongest associated burden on generalrespiratory infections. However, associations were found with theother pathogens and the burden ofstreptococcus pneumoniaewasimportant in adult age groups (25 years and over).The model estimates suggested that only a small proportion ofpatients with influenza receive a specific diagnosis that is coded toan “influenza-like illness” syndromic indicator, (6% for both GPin-hours consultations and for emergency department attendances),compared to a more general respiratory diagnosis. Also, patients withinfluenza calling NHS 111 were more likely to receive a diagnosisof fever or cough than cold/flu. Despite these findings, the specificsyndromic indicators remained more sensitive to changes in influenzaincidence than the general indicators.ConclusionsThe majority of patients affected by a seasonal respiratory pathogenare likely to receive a non-specific respiratory diagnosis. Therefore,estimates of community burden using more specific syndromicindicators such as “influenza-like illness” are likely to be a severeunderestimate. However, these specific indicators remain importantfor detecting changes in incidence and providing added intelligenceon likely causative pathogens.Specific syndromic indicators were associated with multiplepathogens and we were unable to identify indicators that were goodmarkers for pathogens other than influenza or RSV. However, futurework focusing on differences between ages and the relative levels ofa range of pathogens may be able to provide estimates for the mix ofpathogens present in the community in real-time.


2018 ◽  
Vol 5 (suppl_1) ◽  
pp. S377-S378
Author(s):  
Mila M Prill ◽  
Lindsay Kim ◽  
Sibyl Wilmont ◽  
Brett L Whitaker ◽  
Xiaoyan Lu ◽  
...  

Abstract Background Residents of pediatric chronic care facilities (PCCFs) are vulnerable to acute respiratory infections (ARIs) due to their underlying medical conditions and infection control challenges in congregate living. Methods We conducted active, prospective surveillance for ARIs (defined as ≥2 new signs/symptoms of respiratory illness) among all residents in three PCCFs near New York City from December 7, 2016 to May 7, 2017. The parents/guardians of some residents also provided consent for research specimen collection at the start of the study. In that subset, nasopharyngeal swabs were obtained ≤4 days of ARI symptom onset and weekly for 4 weeks of follow-up to assess viral shedding. Influenza, respiratory syncytial virus (RSV), rhinovirus (RV), coronavirus (229E, NL63, OC43, HKU1), parainfluenzavirus (PIV 1–4), metapneumovirus (MPV), adenovirus (AdV), bocavirus (BoV), enterovirus, parechovirus, and M. pneumoniae were tested by the Fast Track Diagnostics Respiratory Pathogens 21 real-time RT-PCR panel. Results Subset with research specimen collection: Among 79 residents (aged 0–20 years, median = 8), 60 ARIs were reported in 37 (47%) residents. Swabs were obtained at illness onset for 53/60 ARI episodes; among these, there were 25 single-virus detections and five co-detections. An additional 33 single- and five co-detections occurred in 175 follow-up swabs (table). Molecular typing of 32 RV+ specimens identified 13 RV types. All residents: During the 2016–2017 influenza season, 308/322 (96%) age-eligible residents received influenza vaccine and 168/364 (46%) received prophylactic antivirals for influenza exposures. Although influenza was not detected in research swabs, it was detected in 3/200 tests conducted for clinical purposes. Conclusion ARIs were common among residents of three PCCFs, and a variety of respiratory viruses were detected. The rarity of influenza may reflect strong infection control practices in these facilities, including vaccination and prophylactic use of antivirals. Disclosures All authors: No reported disclosures.


2019 ◽  
Vol 69 (12) ◽  
pp. 2208-2211
Author(s):  
Meredith L McMorrow ◽  
Stefano Tempia ◽  
Sibongile Walaza ◽  
Florette K Treurnicht ◽  
Jocelyn Moyes ◽  
...  

Abstract From 2011 through 2016, we conducted surveillance for severe respiratory illness in infants. Human immunodeficiency virus exposure significantly increased the risk of respiratory syncytial virus (RSV)–associated hospitalization in infants aged <5 months. More than 60% of RSV-associated hospitalizations occurred in the first 4 months of life and may be preventable through maternal vaccination or birth-dose monoclonal antibody.


2017 ◽  
Vol 145 (9) ◽  
pp. 1922-1932 ◽  
Author(s):  
R. A. MORBEY ◽  
S. HARCOURT ◽  
R. PEBODY ◽  
M. ZAMBON ◽  
J. HUTCHISON ◽  
...  

SUMMARYSeasonal respiratory illnesses present a major burden on primary care services. We assessed the burden of respiratory illness on a national telehealth system in England and investigated the potential for providing early warning of respiratory infection. We compared weekly laboratory reports for respiratory pathogens with telehealth calls (NHS 111) between week 40 in 2013 and week 29 in 2015. Multiple linear regression was used to identify which pathogens had a significant association with respiratory calls. Children aged <5 and 5–14 years, and adults over 65 years were modelled separately as were time lags of up to 4 weeks between calls and laboratory specimen dates. Associations with respiratory pathogens explained over 83% of the variation in cold/flu, cough and difficulty breathing calls. Based on the first two seasons available, the greatest burden was associated with respiratory syncytial virus (RSV) and influenza, with associations found in all age bands. The most sensitive signal for influenza was calls for ‘cold/flu’, whilst for RSV it was calls for cough. The best-fitting models showed calls increasing a week before laboratory specimen dates. Daily surveillance of these calls can provide early warning of seasonal rises in influenza and RSV, contributing to the national respiratory surveillance programme.


1999 ◽  
Vol 20 (12) ◽  
pp. 812-815 ◽  
Author(s):  
Paul J. Drinka ◽  
Stefan Gravenstein ◽  
Elizabeth Langer ◽  
Peggy Krause ◽  
Peter Shult

AbstractObjective:To compare mortality following isolation of influenza A to mortality following isolation of other respiratory viruses in a nursing home.Setting:The Wisconsin Veterans Home, a 688-bed skilled nursing facility for veterans and their spouses.Participants:All residents with respiratory viral isolates obtained between 1988 and 1999.Design:Thirty-day mortality was determined following each culture-proven illness.Results:Thirty-day mortality following isolation of viral respiratory pathogens was 4.7% (15/322) for influenza A 5.4% (7/129) for influenza B; 6.1% (3/49) for parainfluenza type 1; 0% (0/26) for parainfluenza types 2,3, and 4; 0% (0/26) for respiratory syncytial virus (RSV); and 1.6% (1/61) for rhinovirus.Conclusions:Mortality following isolation of certain other respiratory viruses may be comparable to that following influenza A (although influenza A mortality might be higher without vaccination and antiviral agents). The use of uniform secretion precautions for all viral respiratory illness deserves consideration in nursing homes.


2021 ◽  
Author(s):  
Cheryl Cohen ◽  
Meredith L. McMorrow ◽  
Neil A. Martinson ◽  
Kathleen Kahn ◽  
Florette K. Treurnicht ◽  
...  

AbstractPurposeThe PHIRST study (Prospective Household cohort study of Influenza, Respiratory Syncytial virus, and other respiratory pathogens community burden and Transmission dynamics in South Africa) aimed to estimate the community burden of influenza and respiratory syncytial virus (RSV) including the incidence of infection, symptomatic fraction, and disease severity, and to assess household transmission. We further aimed to estimate the impact of HIV infection and age on disease burden and transmission, and to assess the burden of Bordetella pertussis and Streptococcus pneumoniae.ParticipantsWe enrolled 1684 individuals in 327 randomly selected households in two sites (rural Agincourt subdistrict, Mpumalanga Province and urban Jouberton Township, North West Province) over 3 consecutive influenza and RSV seasons. A new cohort of households was enrolled each year. Eligible households included those with >2 household members where ≥80% of household members provided consent (and assent for children aged 7-17 years). Enrolled household members were sampled with nasopharyngeal swabs twice weekly during the RSV and influenza seasons of the year of enrolment. Serology samples were collected at enrolment and before and after the influenza season annually.Findings to dateThere were 122,113 potential individual follow-up visits over the 3 years, and participants were interviewed for 105,783 (87%) of these. Out of 105,683 nasopharyngeal swabs from follow-up visits, 1,258 (1%), 1,026 (1%), 273 (<1%), 38,829 (37%) tested positive on PCR for influenza viruses, respiratory syncytial virus, pertussis and pneumococcus respectively.Future plansFuture planned analyses include analysis of influenza serology results and RSV burden and transmission. Households enrolled in the PHIRST study during 2016-2018 were eligible for inclusion in a study of SARS-CoV-2 transmission initiated in July 2020. This study uses similar testing frequency and household selection methods to assess the community burden of SARS-CoV-2 infection and the role of asymptomatic infection in virus transmission.RegistrationClinical trials.gov NCT02519803Article summaryStrengths and limitations of this studyPHIRST was conducted in urban and rural African settings with high HIV prevalence, allowing assessment of the effect of HIV on community burden and transmission dynamics of respiratory pathogens.Households were selected randomly to provide a representative sample of the community. Twice weekly sampling from each cohort of individuals for 6-10 months irrespective of symptoms allows estimation of community burden, household secondary infection risk, and serial interval including asymptomatic or paucisymptomatic episodes.Polymerase chain reaction testing of >100,000 nasopharyngeal swab samples for multiple pathogens (influenza, respiratory syncytial virus, pertussis and Streptoccocus pneumonia) allows detailed examination of disease burden and transmission and pathogen interactionsPHIRST was not powered to assess severe outcomes (i.e. hospitalisation and death).We only examined four pathogens, but other micro-organisms may be important. Samples have been stored which could allow us to implement broader multi-pathogen testing in the future.


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