Pulmonary dimorphic fungal infections among HIV/AIDS non-TB patients with chronic cough in Kampala, Uganda.

INTRODUCTION: Dimorphic fungi cause infection following the inhalation of spores into the pulmonary system. In the lower respiratory tract, the conidia transform into yeasts, which are engulfed by alveolar macrophages and may be destroyed without disease manifestation. However, in some immunocompromised individuals, they may persist and cause active fungal disease characterized by formation of granulomas in the infected tissues, which may mimic Mycobacterium tuberculosis (MTB). OBJECTIVE: To determine the prevalence of pulmonary dimorphic fungal infections among HIV/AIDS patients with non-TB chronic cough at Mulago National Referral and Teaching Hospital in Kampala, Uganda. METHODS: Sputum samples were collected from 175 consented HIV/AIDS patients attending the immuno-suppression syndrome (ISS) clinic at the hospital. Upon Xpert MTB/RIF sputum testing, 21 patients tested positive for MTB, and these were excluded from further analysis. The other 154 sputum negative samples were then subjected to PCR for dimorphic fungi at MBN Clinical Laboratories. Singleplex PCR was used to detect the target sequences in selected respective genes of each dimorphic fungal species of interest. DNA amplicons were detected based on gel electrophoresis. RESULTS: Dimorphic fungi were detected in 16.2% (25/154) of the studied population. Of these 9.1% (14/154) had Blastomyces dermatitidis and 7.1% (11/154) had Talaromyces marneffei. The remaining 84% of the studied participants had no dimorphic fungi. Histoplasma capsulatum, Coccidioides immitis and Paracoccidioides brasiliensis were not detected in any of the participants. CONCLUSION: Dimorphic fungi (B. dermatitidis and T. marneffei) were found in 16.2% of the HIV/AIDS patients with non-TB chronic cough in Kampala, Uganda. We recommend routine testing for these pathogens among HIV/AIDS patients with chronic cough.

Current understanding of Bordetella-induced cough.

Typical pathogenic bacteria of the genus Bordetella cause respiratory diseases, many of which are characterized by severe coughing in host animals. In human infections with these bacteria, such as whooping cough, coughing imposes a heavy burden on patients. The pathophysiology of this severe coughing had long been uncharacterized because convenient animal models that reproduce Bordetella-induced cough have not been available. However, rat and mouse models were recently shown as useful for understanding, at least partially, the causative factors and the mechanism of Bordetella-induced cough. Many types of coughs are induced under various physiological conditions, and the neurophysiological pathways of coughing are considered to vary among animal species, including humans. However, the neurophysiological mechanisms of the coughs in different animal species have not been entirely understood, and, accordingly, the current understanding of Bordetella-induced cough is still incomplete. Nevertheless, recent research findings may open the way for the development of prophylaxis and therapeutic measures against Bordetella-induced cough.

Aerosolization of Mycobacterium tuberculosis by Tidal Breathing.

Rationale: Interrupting tuberculosis (TB) transmission requires an improved understanding of how and when the causative organism, Mycobacterium tuberculosis (Mtb), is aerosolized. Although cough is commonly assumed to be the dominant source of Mtb aerosols, recent evidence of cough-independent Mtb release implies the contribution of alternative mechanisms. Objectives: To compare the aerosolization of Mtb bacilli and total particulate matter from patients with TB during three separate respiratory maneuvers: tidal breathing (TiBr), FVC, and cough. Methods: Bioaerosol sampling and Mtb enumeration by live-cell, fluorescence microscopy were combined with real-time measurement of CO2 concentration and total particle counts from 38 patients with GeneXpert-positive TB before treatment initiation. Measurements and Main Results: For all maneuvers, the proportions of particles detected across five size categories were similar, with most particles falling between 0.5-5 µm. Although total particle counts were 4.8-fold greater in cough samples than either TiBr or FVC, all three maneuvers returned similar rates of positivity for Mtb. No correlation was observed between total particle production and Mtb count. Instead, for total Mtb counts, the variability between individuals was greater than the variability between sampling maneuvers. Finally, when modelled using 24-hour breath and cough frequencies, our data indicate that TiBr might contribute more than 90% of the daily aerosolized Mtb among symptomatic patients with TB. Conclusions: Assuming the number of viable Mtb organisms released offers a reliable proxy of patient infectiousness, our observations imply that TiBr and interindividual variability in Mtb release might be significant contributors to TB transmission among active cases.

Comparison of microbial composition of cough swabs and sputum for pathogen detection in patients with cystic fibrosis.

BACKGROUND: With the continued advancement of CFTR modulator therapies there is likely to be a burgeoning population of adult cystic fibrosis (CF) patients unable to expectorate sputum. Consequently, the detection and surveillance of pulmonary colonisation, previously reliant on sputum culture, needs re-examining. We hypothesised that cough swabs analysed with culture-independent analysis of the 16S gene could serve as a surrogate for colonisation of the lower airways. METHODS: Cough swabs and sputum samples were prospectively collected from consecutive adults and children with CF across two sites at regular outpatient appointments. Conventional culture analysis and next generation sequencing were used to compare paired same day samples. RESULTS: Twenty-two adults and 8 paediatric patients provided 75 paired cough swabs and sputum samples. Alpha diversity measures showed increased bacterial richness in sputum, while evenness and Simpson's diveristy index were higher in cough swabs. Within each sampling technique, microbial composition showed greater similarity when considering intra-patient variation. Poor concordance was observed between culture independent cough swabs and culture dependent/independent sputum analysis for specific pathogens, with cough swabs unable to accurately identify commonly associated CF pathogens (AUROCC range: 0.51 to 0.64). CONCLUSION: Culture independent analysis of cough swabs provides an inaccurate diagnosis of lower respiratory tract colonisation and should not be used as a diagnostic test in patients with CF.

Computer-aided X-ray screening for tuberculosis and HIV testing among adults with cough in Malawi (the PROSPECT study): A randomised trial and cost-effectiveness analysis.

BACKGROUND: Suboptimal tuberculosis (TB) diagnostics and HIV contribute to the high global burden of TB. We investigated costs and yield from systematic HIV-TB screening, including computer-aided digital chest X-ray (DCXR-CAD). METHODS AND FINDINGS: In this open, three-arm randomised trial, adults (≥18 years) with cough attending acute primary services in Malawi were randomised (1:1:1) to standard of care (SOC); oral HIV testing (HIV screening) and linkage to care; or HIV testing and linkage to care plus DCXR-CAD with sputum Xpert for high CAD4TBv5 scores (HIV-TB screening). Participants and study staff were not blinded to intervention allocation, but investigator blinding was maintained until final analysis. The primary outcome was time to TB treatment. Secondary outcomes included proportion with same-day TB treatment; prevalence of undiagnosed/untreated bacteriologically confirmed TB on day 56; and undiagnosed/untreated HIV. Analysis was done on an intention-to-treat basis. Cost-effectiveness analysis used a health-provider perspective. Between 15 November 2018 and 27 November 2019, 8,236 were screened for eligibility, with 473, 492, and 497 randomly allocated to SOC, HIV, and HIV-TB screening arms; 53 (11%), 52 (9%), and 47 (9%) were lost to follow-up, respectively. At 56 days, TB treatment had been started in 5 (1.1%) SOC, 8 (1.6%) HIV screening, and 15 (3.0%) HIV-TB screening participants. Median (IQR) time to TB treatment was 11 (6.5 to 38), 6 (1 to 22), and 1 (0 to 3) days (hazard ratio for HIV-TB versus SOC: 2.86, 1.04 to 7.87), with same-day treatment of 0/5 (0%) SOC, 1/8 (12.5%) HIV, and 6/15 (40.0%) HIV-TB screening arm TB patients (p = 0.03). At day 56, 2 SOC (0.5%), 4 HIV (1.0%), and 2 HIV-TB (0.5%) participants had undiagnosed microbiologically confirmed TB. HIV screening reduced the proportion with undiagnosed or untreated HIV from 10 (2.7%) in the SOC arm to 2 (0.5%) in the HIV screening arm (risk ratio [RR]: 0.18, 0.04 to 0.83), and 1 (0.2%) in the HIV-TB screening arm (RR: 0.09, 0.01 to 0.71). Incremental costs were US$3.58 and US$19.92 per participant screened for HIV and HIV-TB; the probability of cost-effectiveness at a US$1,200/quality-adjusted life year (QALY) threshold was 83.9% and 0%. Main limitations were the lower than anticipated prevalence of TB and short participant follow-up period; cost and quality of life benefits of this screening approach may accrue over a longer time horizon. CONCLUSIONS: DCXR-CAD with universal HIV screening significantly increased the timeliness and completeness of HIV and TB diagnosis. If implemented at scale, this has potential to rapidly and efficiently improve TB and HIV diagnosis and treatment. TRIAL REGISTRATION: clinicaltrials.gov NCT03519425.

Are neighbourhoods of tuberculosis cases a high-risk population for active intervention? A protocol for tuberculosis active case finding.

BACKGROUND: Indonesia has the second largest tuberculosis (TB) burden globally. Attempts to scale-up TB control efforts have focused on TB households. However, in most high burden settings, considerable Mycobacterium tuberculosis (Mtb) transmission occurs outside TB households. A better understanding of transmission dynamics in an urban setting in Indonesia will be crucial for the TB Control Program in scaling up efforts towards elimination of TB in a more targeted way. Therefore, the study aims to measure TB prevalence and incidence in household contacts and neighbourhoods in the vicinity of known TB cases and to assess their genomic and epidemiological relatedness. METHODS AND ANALYSIS: Individuals (~1000) living in the same household as a case diagnosed with pulmonary TB (n = 250) or in a neighbouring household (~4500 individuals) will be screened for TB symptoms and by chest x-ray. Two sputum samples will be collected for microbiological analysis from anyone with a productive cough. Any person found to have TB will be treated by the National TB Control Program. All those with no evidence of TB disease will have a repeat screen at 12 months. Whole-genome sequencing (WGS) and social network analysis (SNA) will be conducted on Index cases and contacts diagnosed with TB.

High TB burden and low notification rates in the Philippines: The 2016 national TB prevalence survey.

SETTING: The 3rd national tuberculosis (TB) survey in the Philippines in 2007 reported a significant decline in the prevalence of TB. Since then, more significant investments for TB control have been made, yet TB burden estimates from routine surveillance data remain relatively stable. OBJECTIVE: To estimate the prevalence of bacteriologically confirmed pulmonary TB in the Philippines amongst individuals aged ≥15 years in 2016. DESIGN: In March-December 2016, we conducted a population-based survey with stratified, multi-stage cluster sampling of residents in 106 clusters aged ≥15 years. Survey participants were screened for TB by symptom-based interview and digital chest X-ray. Those with cough ≥2 weeks and/or haemoptysis and/or chest X-ray suggestive of TB were requested to submit 2 sputum specimens for Xpert MTB/RIF, direct sputum smear microscopy using LED fluorescent microscopy, and mycobacterial solid culture (Ogawa method). Bacteriologically confirmed pulmonary TB was defined as MTB culture positive and/or Xpert positive. RESULTS: There were 46,689 individuals interviewed, and 41,444 (88.8%) consented to a chest X-ray. There were 18,597 (39.8%) eligible for sputum examination and 16,242 (87.3%) submitted at least one specimen. Out of 16,058 sputum-eligible participants, 183 (1.1%) were smear-positive. There were 466 bacteriologically confirmed TB cases: 238 (51.1%) Xpert positive, 69 (14.8%) culture positive, and 159 (34.1%) positive by both Xpert and culture. The estimated TB prevalence per 100,000 population aged ≥15 years was 434 (95% CI: 350-518) for smear-positive TB, and 1,159 (95% CI: 1,016-1,301) for bacteriologically confirmed TB. CONCLUSION: This nationally representative survey found that the TB burden in the Philippines in 2016 was higher than estimated from routine TB surveillance data. There was no evidence of a decline in smear and culture positive TB from the 2007 survey despite significant investments in TB control. New strategies for case-finding and patient-centered care must be intensified and expanded.

Case finding of tuberculosis among mining communities in Ghana.

BACKGROUND: Data on active TB case finding activities among artisanal gold mining communities (AMC) is limited. The study assessed the yield of TB cases from the TB screening activities among AMC in Ghana, the factors associated with TB in these communities and the correlation between the screening methods and a diagnosis of TB. METHODS: We conducted secondary data analyses of NTP program data collected from TB case finding activities using symptom screening and mobile X-ray implemented in hard to reach AMC. Yield of TB cases, number needed to screen (NNS) and the number needed to test (NNT) to detect a TB case were assessed and logistic regression were conducted to assess factors associated with TB. The performance of screening methods chest X-ray and symptoms in the detection of TB cases was also evaluated. RESULTS: In total 10,441 people from 78 communities in 24 districts were screened, 55% were female and 60% (6,296) were in the aged 25 to 54 years. Ninety-five TB cases were identified, 910 TB cases per 100,000 population screened; 5.6% of the TB cases were rifampicin resistant. Being male (aOR 5.96, 95% CI 3.25-10.92, P < 0.001), a miner (aOR 2.70, 95% CI 1.47-4.96, P = 0.001) and age group 35 to 54 years (aOR 2.27, 95% CI 1.35-3.84, P = 0.002) were risk factors for TB. NNS and NNT were 110 and 24 respectively.; Cough of any duration had the strongest association with X-ray suggestive of TB with a correlation coefficient of 0.48. Cough was most sensitive for a diagnosis of TB; sensitivity of 86.3% (95% CI 79.4-93.2) followed by X-ray, sensitivity 81.1% (95% CI 71.7-88.4). The specificities of the symptoms and X-rays ranged from 80.2% (cough) to 97.3% (sputum). CONCLUSION: The high risk of TB in the artisanal mining communities and in miners in this study reinforces the need to target these populations with outreach programs particularly in hard to reach areas. The diagnostic value of cough highlights the usefulness of symptom screening in this population that may be harnessed even in the absence of X-ray to identify those suspected to have TB for further evaluation.

Effect of congenital heart disease on the recurrence of cough variant asthma in children.

BACKGROUND: The research into the recurrence of cough variant asthma (CVA) in congenital heart disease (CHD) are few in number. The purpose of this study is to investigate the effect of CHD on the risk of the recurrence of CVA. METHODS: This study was a retrospective cohort study of 489 children with CVA aged between one and 14 years, of whom 67 had CHD complicated with CVA and 134 had CVA without CHD at a ratio of 1:2 according to age, sex and index year. The adjusted hazard ratio (aHR) of CVA recurrence in both the CHD cohort and the non-CHD cohort was determined by multivariate analysis using the Cox proportional hazard regression model. RESULTS: Adjusting for CHD classification, Mycoplasma pneumonia (MP) infection and immunoglobulin E (IgE) sensitization, the recurrence hazard of CVA in the complex congenital heart disease (CCHD) group (aHR = 3.281; 95% CI 1.648-6.530; P < 0.01) was significantly higher than that in the simple congenital heart disease group (aHR = 2.555; 95% CI 1.739-3.752; P < 0.01). Further, children with IgE sensitization (aHR = 2.172; 95% CI 1.482-3.184; P < 0.01) had a higher recurrence hazard of CVA than those without IgE sensitization, and children with MP infection (aHR = 1.777; 95% CI 1.188-2.657; P < 0.01) had a higher recurrence hazard of CVA than those without the MP infection. CONCLUSION: The hazard of recurrent CVA is higher in children with CHD, especially in the CCHD children. In addition, those children with IgE sensitization or a MP infection had an increased hazard of recurrent CVA.

Capture and visualization of live Mycobacterium tuberculosis bacilli from tuberculosis patient bioaerosols.

Interrupting transmission is an attractive anti-tuberculosis (TB) strategy but it remains underexplored owing to our poor understanding of the events surrounding transfer of Mycobacterium tuberculosis (Mtb) between hosts. Determining when live, infectious Mtb bacilli are released and by whom has proven especially challenging. Consequently, transmission chains are inferred only retrospectively, when new cases are diagnosed. This process, which relies on molecular analyses of Mtb isolates for epidemiological fingerprinting, is confounded by the prolonged infectious period of TB and the potential for transmission from transient exposures. We developed a Respiratory Aerosol Sampling Chamber (RASC) equipped with high-efficiency filtration and sampling technologies for liquid-capture of all particulate matter (including Mtb) released during respiration and non-induced cough. Combining the mycobacterial cell wall probe, DMN-trehalose, with fluorescence microscopy of RASC-captured bioaerosols, we detected and quantified putative live Mtb bacilli in bioaerosol samples arrayed in nanowell devices. The RASC enabled non-invasive capture and isolation of viable Mtb from bioaerosol within 24 hours of collection. A median 14 live Mtb bacilli (range 0-36) were isolated in single-cell format from 90% of confirmed TB patients following 60 minutes bioaerosol sampling. This represented a significant increase over previous estimates of transmission potential, implying that many more organisms might be released daily than commonly assumed. Moreover, variations in DMN-trehalose incorporation profiles suggested metabolic heterogeneity in aerosolized Mtb. Finally, preliminary analyses indicated the capacity for serial image capture and analysis of nanowell-arrayed bacilli for periods extending into weeks. These observations support the application of this technology to longstanding questions in TB transmission including the propensity for asymptomatic transmission, the impact of TB treatment on Mtb bioaerosol release, and the physiological state of aerosolized bacilli.

Recognition and Management of Protracted Bacterial Bronchitis in Australian Aboriginal Children: A Knowledge Translation Approach.

BACKGROUND: Chronic wet cough in children is the hallmark symptom of protracted bacterial bronchitis (PBB) and if left untreated can lead to bronchiectasis, which is prevalent in Indigenous populations. Underrecognition of chronic wet cough by parents and clinicians and underdiagnosis of PBB by clinicians are known. RESEARCH QUESTION: We aimed to improve recognition and management of chronic wet cough in Aboriginal children using knowledge translation (KT), a methodologic approach that can be adapted for use in Indigenous contexts to facilitate effective and sustained translation of research into practice. STUDY DESIGN AND METHODS: A mixed-methods KT study undertaken at a remote-based Aboriginal primary medical service (February 2017 to December 2019). Our KT strategy included the following: (1) culturally secure (ie, ensuring Aboriginal people are treated regarding their unique cultural needs and differences) knowledge dissemination to facilitate family health seeking for chronic wet cough in children, and (2) an implementation strategy to facilitate correct diagnosis and management of chronic wet cough and PBB by physicians. RESULTS: Post-KT, health seeking for chronic wet cough increased by 184% (pre = eight of 630 children [1.3%], post = 23 of 636 children [3.6%]; P = .007; 95% CI, 0.7%-4.0%). Physician proficiency in management of chronic wet cough improved significantly as reflected by improved chronic cough-related quality of life (P < .001; 95% CI, 0.8-3.0) and improved physician assessment of cough quality (P < .001; 95% CI, 10.4%-23.0%), duration (P < .001; 95% CI, 11.1%-24.1%), and appropriate antibiotic prescription (P = .010; 95% CI, 6.6%-55.7%). INTERPRETATION: Health seeking for children with chronic wet cough can be facilitated through provision of culturally secure health information. Physician proficiency in the management of PBB can be improved with KT strategies which include training in culturally informed management, leading to better health outcomes. Comprehensive strategies that include both families and health systems are required to ensure that chronic wet cough in children is detected and optimally managed.

Cough-independent production of viable Mycobacterium tuberculosis in bioaerosol.

BACKGROUND: Symptoms of infectious respiratory illnesses are often assumed to drive transmission. However, production and release of Mycobacterium tuberculosis (Mtb) bioaerosols is poorly understood. We report quantitation of Mtb exhaled during specific respiratory manoeuvres. METHODS: Direct capture of nascent bioaerosol particles and indirect collection of aged particles was performed in 10 healthy subjects. Indirect and direct capture of exhaled viable Mtb bacilli was compared in 38 PTB patients and directly captured viable Mtb during cough and bronchiole-burst manoeuvres in 27 of the PTB patients. RESULTS: Direct sampling of healthy subjects captured larger bioaerosol volumes with higher proportions of 2-5 µm particles than indirect sampling. Indirect sampling identified viable Mtb in 92.1% (35 of 38) of PTB patients during 60-min relaxed breathing, median bacillary count 7.5 (IQR: 3.25-19). Direct sampling for 10-min identified Mtb in 97.4% (37 of 38) of PTB patients with higher bacilli counts (p < 0.001), median 24.5 (IQR:11.25-37.5). A short 5-min sampling regimen of 10 coughs or 10 bronchiole-burst manoeuvres yielded a median of 11 (IQR: 4-17) and 11 (IQR: 7-17.5) Mtb bacilli, respectively (p = 0.53). CONCLUSIONS: Peripheral lung bioaerosol released through deep exhalations alone contained viable Mtb suggesting non-cough transmission is possible in PTB.

Pseudomonas laryngeal perichondritis: unexpected diagnosis.

A 57-year-old male chronic smoker with underlying diabetes mellitus presented with dysphonia associated with cough, dysphagia and reduced effort tolerance of 3 months' duration. Videoendoscope finding revealed bilateral polypoidal and erythematous true and false vocal fold with small glottic airway. The patient was initially treated as having tuberculous laryngitis and started on antituberculous drug. However, no improvement was observed. CT of the neck showed erosion of thyroid cartilage, which points to laryngeal carcinoma as a differential diagnosis. However, the erosion was more diffuse and appeared systemic in origin. The diagnosis of laryngeal perichondritis was made when the histopathological examination revealed features of inflammation, and the tracheal aspirate isolated Pseudomonas aeruginosa The patient made a good recovery following treatment with oral ciprofloxacin.

Zhisou powder in treatment of postinfectious cough: A protocol for systematic review and meta-analysis.

BACKGROUND: The pathogensis of postinfectious cough (PIC) is unkown, unsatisfactory clinical curative effects of conventional western medicine have been shown. Zhisou powder (ZP) is one of the most common prescriptions in traditional Chinese medicine for the treatment of PIC. However, the effects and safety also remain uncertain. We aim to systematically review the effectiveness and safety of ZP for PIC. METHODS: We will search the following databases: PubMed, Embase, Cochrane Library, MEDLINE, the China National Knowledge Infrastructure , the Chinese Biomedical Literature Database, Cqvip Database, and Wanfang Data. The studies published from the inception of the database to May 2020 will be retrieved. The randomized controlled trials on ZP for PIC will be included. The primary outcomes were cough relief rate and cough resolution rate. We will perform the analyses using RevMan V.5.3 software. RESULTS: This study will provide high-quality evidence of ZP for PIC in the effectiveness and safety. CONCLUSIONS: This systematic review will assess whether ZP is an effective and safe prescription for PIC.

A 52-Year-Old Man With an 11-Month History of Fever, Cough, Chest Pain, Pleural Effusion, and Left Lung Atelectasis.

CASE PRESENTATION: A 52-year-old man was referred to our hospital for cough, fever, chest pain, and progressive dyspnea. He has worked as a full-time security staff at a community center and was in a normal state of health until 11 months prior to referral when he began experiencing cough, expectoration, a high-grade fever (up to 39.7°C), chills, and left chest pain. He visited the local hospital several times with suspected lung cancer. Bronchoscopy showed chronic inflammatory changes in his bronchi. He was given a course of antibiotics, but his fever had not subsided. The patient had visited a bamboo rat farm and consumed bamboo rat meat one year previously. He had never smoked.

Transformative Approach To Investigate the Microphysical Factors Influencing Airborne Transmission of Pathogens.

Emerging outbreaks of airborne pathogenic infections worldwide, such as the current severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic, have raised the need to understand parameters affecting the airborne survival of microbes in order to develop measures for effective infection control. We report a novel experimental strategy, TAMBAS (tandem approach for microphysical and biological assessment of airborne microorganism survival), to explore the synergistic interactions between the physicochemical and biological processes that impact airborne microbe survival in aerosol droplets. This innovative approach provides a unique and detailed understanding of the processes taking place from aerosol droplet generation through to equilibration and viability decay in the local environment, elucidating decay mechanisms not previously described. The impact of evaporation kinetics, solute hygroscopicity and concentration, particle morphology, and equilibrium particle size on airborne survival are reported, using Escherichia coli MRE162 as a benchmark system. For this system, we report that (i) particle crystallization does not directly impact microbe longevity, (ii) bacteria act as crystallization nuclei during droplet drying and equilibration, and (iii) the kinetics of size and compositional change appear to have a larger effect on microbe longevity than the equilibrium solute concentration.IMPORTANCE A transformative approach to identify the physicochemical processes that impact the biological decay rates of bacteria in aerosol droplets is described. It is shown that the evaporation process and changes in the phase and morphology of the aerosol particle during evaporation impact microorganism viability. The equilibrium droplet size was found to affect airborne bacterial viability. Furthermore, the presence of Escherichia coli MRE162 in a droplet does not affect aerosol growth/evaporation but influences the dynamic behavior of the aerosol by processing the culture medium prior to aerosolization, affecting the hygroscopicity of the culture medium; this highlights the importance of the inorganic and organic chemical composition within the aerosolized droplets that impact hygroscopicity. Bacteria also act as crystallization nuclei. The novel approach and data have implications for increased mechanistic understanding of aerosol survival and infectivity in bioaerosol studies spanning the medical, veterinary, farming, and agricultural fields, including the role of microorganisms in atmospheric processing and cloud formation.

Signs and symptoms do not predict, but may help rule out acute Q fever in favour of other respiratory tract infections, and reduce antibiotics overuse in primary care.

BACKGROUND: From early 2009, the Dutch region of South Limburg experienced a massive outbreak of Q fever, overlapping with the influenza A(H1N1)pdm09 pandemic during the second half of the year and affecting approximately 2.9% of a 300,000 population. Acute Q fever shares clinical features with other respiratory conditions. Most symptomatic acute infections are characterized by mild symptoms, or an isolated febrile syndrome. Pneumonia was present in a majority of hospitalized patients during the Dutch 2007-2010 Q fever epidemic. Early empiric doxycycline, guided by signs and symptoms and patient history, should not be delayed awaiting laboratory confirmation, as it may shorten disease and prevent progression to focalized persistent Q fever. We assessed signs' and symptoms' association with acute Q fever to guide early empiric treatment in primary care patients. METHODS: In response to the outbreak, regional primary care physicians and hospital-based medical specialists tested a total of 1218 subjects for Q fever. Testing activity was bimodal, a first "wave" lasting from March to December 2009, followed by a second "wave" which lasted into 2010 and coincided with peak pandemic influenza activity. We approached all 253 notified acute Q fever cases and a random sample of 457 Q fever negative individuals for signs and symptoms of disease. Using data from 140/229(61.1%) Q fever positive and 194/391(49.6%) Q fever negative respondents from wave 1, we built symptom-based models predictive of Q-fever outcome, validated against subsets of data from wave 1 and wave 2. RESULTS: Our models had poor to moderate AUC scores (0.68 to 0.72%), with low positive (4.6-8.3%), but high negative predictive values (91.7-99.5%). Male sex, fever, and pneumonia were strong positive predictors, while cough was a strong negative predictor of acute Q fever in these models. CONCLUSION: Whereas signs and symptoms of disease do not appear to predict acute Q fever, they may help rule it out in favour of other respiratory conditions, prompting a delayed or non-prescribing approach instead of early empiric doxycycline in primary care patients with non-severe presentations. Signs and symptoms thus may help reduce the overuse of antibiotics in primary care during and following outbreaks of Q fever.