A Standard-Based Citywide Health Information Exchange for Public Health in Response to COVID-19: Development Study.

BACKGROUND: Disease surveillance is a critical function of public health, provides essential information about the disease burden and the clinical and epidemiologic parameters of disease, and is an important element of effective and timely case and contact tracing. The COVID-19 pandemic demonstrates the essential role of disease surveillance in preserving public health. In theory, the standard data formats and exchange methods provided by electronic health record (EHR) meaningful use should enable rapid health care data exchange in the setting of disruptive health care events, such as a pandemic. In reality, access to data remains challenging and, even if available, often lacks conformity to regulated standards. OBJECTIVE: We sought to use regulated interoperability standards already in production to generate awareness of regional bed capacity and enhance the capture of epidemiological risk factors and clinical variables among patients tested for SARS-CoV-2. We described the technical and operational components, governance model, and timelines required to implement the public health order that mandated electronic reporting of data from EHRs among hospitals in the Chicago jurisdiction. We also evaluated the data sources, infrastructure requirements, and the completeness of data supplied to the platform and the capacity to link these sources. METHODS: Following a public health order mandating data submission by all acute care hospitals in Chicago, we developed the technical infrastructure to combine multiple data feeds from those EHR systems-a regional data hub to enhance public health surveillance. A cloud-based environment was created that received ELR, consolidated clinical data architecture, and bed capacity data feeds from sites. Data governance was planned from the project initiation to aid in consensus and principles for data use. We measured the completeness of each feed and the match rate between feeds. RESULTS: Data from 88,906 persons from CCDA records among 14 facilities and 408,741 persons from ELR records among 88 facilities were submitted. Most (n=448,380, 90.1%) records could be matched between CCDA and ELR feeds. Data fields absent from ELR feeds included travel histories, clinical symptoms, and comorbidities. Less than 5% of CCDA data fields were empty. Merging CCDA with ELR data improved race, ethnicity, comorbidity, and hospitalization information data availability. CONCLUSIONS: We described the development of a citywide public health data hub for the surveillance of SARS-CoV-2 infection. We were able to assess the completeness of existing ELR feeds, augment those feeds with CCDA documents, establish secure transfer methods for data exchange, develop a cloud-based architecture to enable secure data storage and analytics, and produce dashboards for monitoring of capacity and the disease burden. We consider this public health and clinical data registry as an informative example of the power of common standards across EHRs and a potential template for future use of standards to improve public health surveillance.

Community-Based Testing for SARS-CoV-2 - Chicago, Illinois, May-November 2020.

On May 13, 2020, Chicago established a free community-based testing (CBT) initiative for SARS-CoV-2, the virus that causes COVID-19, using reverse transcription-polymerase chain reaction (RT-PCR). The initiative focused on demographic groups and geographic areas that were underrepresented in testing by clinical providers and had experienced high COVID-19 incidence, including Hispanic persons and those who have been economically marginalized. To assess the CBT initiative, the Chicago Department of Public Health (CDPH) compared demographic characteristics, economic marginalization, and test positivity between persons tested at CBT sites and persons tested in all other testing settings in Chicago. During May 13-November 14, a total of 253,904 SARS-CoV-2 RT-PCR tests were conducted at CBT sites. Compared with those tested in all other testing settings in Chicago, persons tested at CBT sites were more likely to live in areas that are economically marginalized (38.6% versus 32.0%; p<0.001) and to be Hispanic (50.9% versus 20.7%; p<0.001). The cumulative percentage of positive test results at the CBT sites was higher than that at all other testing settings (11.1% versus 7.1%; p<0.001). These results demonstrate the ability of public health departments to establish community-based testing initiatives that reach communities with less access to testing in other settings and that experience disproportionately higher incidences of COVID-19.

Lack of Serologic Evidence of Infection Among Health Care Personnel and Other Contacts of First 2 Confirmed Patients With COVID-19 in Illinois, 2020.

OBJECTIVES: Widespread global transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus causing coronavirus disease 2019 (COVID-19), continues. Many questions remain about asymptomatic or atypical infections and transmission dynamics. We used comprehensive contact tracing of the first 2 confirmed patients in Illinois with COVID-19 and serologic SARS-CoV-2 antibody testing to determine whether contacts had evidence of undetected COVID-19. METHODS: Contacts were eligible for serologic follow-up if previously tested for COVID-19 during an initial investigation or had greater-risk exposures. Contacts completed a standardized questionnaire during the initial investigation. We classified exposure risk as high, medium, or low based on interactions with 2 index patients and use of personal protective equipment (PPE). Serologic testing used a SARS-CoV-2 spike enzyme-linked immunosorbent assay on serum specimens collected from participants approximately 6 weeks after initial exposure to either index patient. The 2 index patients provided serum specimens throughout their illness. We collected data on demographic, exposure, and epidemiologic characteristics. RESULTS: Of 347 contacts, 110 were eligible for serologic follow-up; 59 (17% of all contacts) enrolled. Of these, 53 (90%) were health care personnel and 6 (10%) were community contacts. Seventeen (29%) reported high-risk exposures, 15 (25%) medium-risk, and 27 (46%) low-risk. No participant had evidence of SARS-CoV-2 antibodies. The 2 index patients had antibodies detected at dilutions >1:6400 within 4 weeks after symptom onset. CONCLUSIONS: In serologic follow-up of the first 2 known patients in Illinois with COVID-19, we found no secondary transmission among tested contacts. Lack of seroconversion among these contacts adds to our understanding of conditions (ie, use of PPE) under which SARS-CoV-2 infections might not result in transmission and demonstrates that SARS-CoV-2 antibody testing is a useful tool to verify epidemiologic findings.

Characteristics of Hospitalized Pediatric Coronavirus Disease 2019 Cases in Chicago, Illinois, March-April 2020.

BACKGROUND: To date, no report on coronavirus disease 2019 (COVID-19) pediatric patients in a large urban center with data on underlying comorbidities and coinfection for hospitalized cases has been published. METHODS: This was a case series of Chicago COVID-19 patients aged 0-17 years reported to the Chicago Department of Public Health (CDPH) from March 5 to April 8, 2020. Enhanced case investigation was performed. χ 2 and Wilcoxon 2-sample tests were used to compare characteristics among hospitalized and nonhospitalized cases. RESULTS: During March 5-April 8, 2020, 6369 laboratory-confirmed cases of COVID-19 were reported to CDPH; 64 (1.0%) were among children aged 0-17 years. Ten patients (16%) were hospitalized, and 7 (70%) required intensive care (median length of hospitalization, 4 days [range, 1-14 days]). Reported fever and dyspnea were significantly higher in hospitalized patients than in nonhospitalized patients (9/10 vs 28/54, P = .04 and 7/10 vs 10/54, P = .002, respectively). Hospitalized patients were significantly younger than nonhospitalized patients (median, 3.5 years vs 12 years; P = .03) and all either had an underlying comorbidity or coinfection. Among the 34 unique households with multiple laboratory-confirmed infections, the median number of laboratory-confirmed infections was 2 (range, 2-5), and 31 (91%) households had at least 1 COVID-19-infected adult. For 15 households with available data to assess transmission, 11 (73%) were adult-to-child, 2 (13%) child-to-child, and 2 (13%) child-to-adult. CONCLUSIONS: Enhanced case investigation of hospitalized patients revealed that underlying comorbidities and coinfection might have contributed to severe disease. Given frequency of household transmission, healthcare providers should consider alternative dispositional planning for affected families of children living with comorbidities.

Community Transmission of SARS-CoV-2 at Two Family Gatherings - Chicago, Illinois, February-March 2020.

SARS-CoV-2, the virus that causes coronavirus disease 2019 (COVID-19), has spread rapidly around the world since it was first recognized in late 2019. Most early reports of person-to-person SARS-CoV-2 transmission have been among household contacts, where the secondary attack rate has been estimated to exceed 10% (1), in health care facilities (2), and in congregate settings (3). However, widespread community transmission, as is currently being observed in the United States, requires more expansive transmission events between nonhousehold contacts. In February and March 2020, the Chicago Department of Public Health (CDPH) investigated a large, multifamily cluster of COVID-19. Patients with confirmed COVID-19 and their close contacts were interviewed to better understand nonhousehold, community transmission of SARS-CoV-2. This report describes the cluster of 16 cases of confirmed or probable COVID-19, including three deaths, likely resulting from transmission of SARS-CoV-2 at two family gatherings (a funeral and a birthday party). These data support current CDC social distancing recommendations intended to reduce SARS-CoV-2 transmission. U.S residents should follow stay-at-home orders when required by state or local authorities.

First known person-to-person transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in the USA.

BACKGROUND: Coronavirus disease 2019 (COVID-19) is a disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), first detected in China in December, 2019. In January, 2020, state, local, and federal public health agencies investigated the first case of COVID-19 in Illinois, USA. METHODS: Patients with confirmed COVID-19 were defined as those with a positive SARS-CoV-2 test. Contacts were people with exposure to a patient with COVID-19 on or after the patient's symptom onset date. Contacts underwent active symptom monitoring for 14 days following their last exposure. Contacts who developed fever, cough, or shortness of breath became persons under investigation and were tested for SARS-CoV-2. A convenience sample of 32 asymptomatic health-care personnel contacts were also tested. FINDINGS: Patient 1-a woman in her 60s-returned from China in mid-January, 2020. One week later, she was hospitalised with pneumonia and tested positive for SARS-CoV-2. Her husband (Patient 2) did not travel but had frequent close contact with his wife. He was admitted 8 days later and tested positive for SARS-CoV-2. Overall, 372 contacts of both cases were identified; 347 underwent active symptom monitoring, including 152 community contacts and 195 health-care personnel. Of monitored contacts, 43 became persons under investigation, in addition to Patient 2. These 43 persons under investigation and all 32 asymptomatic health-care personnel tested negative for SARS-CoV-2. INTERPRETATION: Person-to-person transmission of SARS-CoV-2 occurred between two people with prolonged, unprotected exposure while Patient 1 was symptomatic. Despite active symptom monitoring and testing of symptomatic and some asymptomatic contacts, no further transmission was detected. FUNDING: None.

Opioid Prescribing Patterns Before Fatal Opioid Overdose.

INTRODUCTION: Although opioid prescribing has decreased since 2010, overdose deaths involving illicit opioids have continued to rise. This study explores prescribing patterns before fatal overdose of decedents who died of prescription and illicit opioid overdoses. METHODS: This retrospective cohort study was conducted in 2019 and included all 1,893 Illinois residents who died of an opioid-related overdose in 2016. Each decedent was linked to any existing Prescription Monitoring Program records, calculating weekly morphine milligram equivalents for 52 weeks before overdose. RESULTS: Among the 1,893 fatal opioid overdoses, 309 involved any prescription opioid and 1,461 involved illicit opioids without the involvement of prescription opioids. The death rate because of illicit opioids was 23/100,000 among black residents versus 10.5/100,000 among whites. During the last year of life, 76% of prescription opioid decedents filled any opioid prescription totaling 10.7 prescriptions per decedent, compared with 36% of illicit opioid decedents totaling 2.6 prescriptions per decedent. During the last week of life, 33% of prescription opioid decedents filled an opioid prescription totaling 0.42 prescriptions per decedent, compared with 4% of illicit opioid decedents totaling 0.05 prescriptions per decedent. CONCLUSIONS: Prescribing patterns alone may not be sufficient to identify patients who are at high risk for opioid overdose, especially for those using illicit opioids. Interventions aimed at reducing opioid overdoses should take into account different patterns of opioid prescribing associated with illicit and prescription opioid overdose deaths and be designed around the local characteristics of the opioid overdose epidemic.

Characteristics of Persons Who Report Using Only Nicotine-Containing Products Among Interviewed Patients with E-cigarette, or Vaping, Product Use-Associated Lung Injury - Illinois, August-December 2019.

In 2019, the United States experienced an outbreak of e-cigarette, or vaping, product use-associated lung injury (EVALI) (1). Most EVALI patients have reported using tetrahydrocannabinol (THC)-containing e-cigarette, or vaping, products obtained from informal sources (2,3), and vitamin E acetate in these products has been closely linked with EVALI (4,5). However, some EVALI patients report using only nicotine-containing products. This study compared demographic, product use, and clinical characteristics of EVALI patients in Illinois who reported using only nicotine-containing e-cigarette, or vaping, products with those of patients who reported using any THC-containing products. Among 121 interviewed Illinois EVALI patients, 17 (14%) reported using only nicotine-containing products, including nine (7%) patients who had no indication of any THC use, based on self-report or toxicology testing. Compared with patients who used any THC-containing products, these nine patients were significantly more likely to be older and female and were less likely to experience constitutional symptoms or to have leukocytosis on initial evaluation. Although vitamin E acetate has been strongly linked with EVALI, evidence is not sufficient to rule out the contribution of other chemicals of concern, including chemicals in either THC- or non-THC-containing products, in some reported EVALI cases. The contributing cause or causes of EVALI for patients reporting use of only nicotine-containing products warrants further investigation.

Pulmonary Illness Related to E-Cigarette Use in Illinois and Wisconsin - Final Report.

BACKGROUND: E-cigarettes are battery-operated devices that heat a liquid and deliver an aerosolized product to the user. Pulmonary illnesses related to e-cigarette use have been reported, but no large series has been described. In July 2019, the Wisconsin Department of Health Services and the Illinois Department of Public Health received reports of lung injury associated with the use of e-cigarettes (also called vaping) and launched a coordinated public health investigation. METHODS: We defined case patients as persons who reported use of e-cigarette devices and related products in the 90 days before symptom onset and had pulmonary infiltrates on imaging and whose illnesses were not attributed to other causes. Medical record abstraction and case patient interviews were conducted with the use of standardized tools. RESULTS: There were 98 case patients, 79% of whom were male; the median age of the patients was 21 years. The majority of patients presented with respiratory symptoms (97%), gastrointestinal symptoms (77%), and constitutional symptoms (100%). All case patients had bilateral infiltrates on chest imaging. A total of 95% of the patients were hospitalized, 26% underwent intubation and mechanical ventilation, and two deaths were reported. A total of 89% of the patients reported having used tetrahydrocannabinol products in e-cigarette devices, although a wide variety of products and devices was reported. Syndromic surveillance data from Illinois showed that the mean monthly rate of visits related to severe respiratory illness in June through August of 2019 was twice the rate that was observed in the same months in 2018. CONCLUSIONS: Case patients presented with similar clinical characteristics. Although the definitive substance or substances contributing to injury have not been determined, this initial cluster of illnesses represents an emerging clinical syndrome or syndromes. Additional work is needed to characterize the pathophysiology and to identify the definitive causes.

Risk Factors for E-Cigarette, or Vaping, Product Use-Associated Lung Injury (EVALI) Among Adults Who Use E-Cigarette, or Vaping, Products - Illinois, July-October 2019.

The United States is experiencing an unprecedented outbreak of e-cigarette, or vaping, product use-associated lung injury (EVALI) (1). All EVALI patients have used e-cigarette, or vaping, products, and most (≥85%) have reported using products containing tetrahydrocannabinol (THC) (2,3), the principal psychoactive component of cannabis. To examine whether e-cigarette, or vaping, product use behaviors differed between adult EVALI patients and adults who use these products but have not developed lung injury, the Illinois Department of Public Health (IDPH) conducted an online public survey during September-October 2019 targeting e-cigarette, or vaping, product users in Illinois. Among 4,631 survey respondents, 94% reported using any nicotine-containing e-cigarette, or vaping, products in the past 3 months; 21% used any THC-containing products; and 11% used both THC-containing products and nicotine-containing products. Prevalence of THC-containing product use was highest among survey respondents aged 18-24 years (36%) and decreased with increasing age. E-cigarette, or vaping, product use behaviors of 66 EVALI patients aged 18-44 years who were interviewed as part of the ongoing outbreak investigation were compared with a subset of 519 survey respondents aged 18-44 years who reported use of THC-containing e-cigarette, or vaping, products. Compared with these survey respondents, EVALI patients had higher odds of reporting exclusive use of THC-containing products (adjusted odds ratio [aOR] = 2.0, 95% confidence interval [CI] = 1.1-3.6); frequent use (more than five times per day) of these products (aOR = 3.1, 95% CI = 1.6-6.0), and obtaining these products from informal sources, such as a dealer, off the street, or from a friend (aOR = 9.2, 95% CI = 2.2-39.4). The odds of using Dank Vapes, a class of largely counterfeit THC-containing products, was also higher among EVALI patients (aOR = 8.5, 95% CI = 3.8-19.0). These findings reinforce current recommendations not to use e-cigarette, or vaping, products that contain THC and not to use any e-cigarette, or vaping, products obtained from informal sources. In addition, because the specific compound or ingredient causing lung injury is not yet known, CDC continues to recommend that persons consider refraining from use of all e-cigarette, or vaping, products while the outbreak investigation continues (1).

E-cigarette Product Use, or Vaping, Among Persons with Associated Lung Injury - Illinois and Wisconsin, April-September 2019.

In July 2019, the Illinois Department of Public Health and the Wisconsin Department of Health Services launched a coordinated epidemiologic investigation after receiving reports of several cases of lung injury in previously healthy persons who reported electronic cigarette (e-cigarette) use, or vaping (1). This report describes features of e-cigarette product use by patients in Illinois and Wisconsin. Detailed patient interviews were conducted by telephone, in person, or via the Internet with 86 (68%) of 127 patients. Overall, 75 (87%) of 86 interviewed patients reported using e-cigarette products containing tetrahydrocannabinol (THC), and 61 (71%) reported using nicotine-containing products. Numerous products and brand names were identified by patients. Nearly all (96%) THC-containing products reported were packaged, prefilled cartridges, and 89% were primarily acquired from informal sources (e.g., friends, family members, illicit dealers, or off the street). In contrast, 77% of nicotine-containing products were sold as prefilled cartridges, and 83% were obtained from commercial vendors. The precise source of this outbreak is currently unknown (2); however, the predominant use of prefilled THC-containing cartridges among patients with lung injury associated with e-cigarette use suggests that they play an important role. While this investigation is ongoing, CDC recommends that persons consider refraining from using e-cigarette, or vaping, products, particularly those containing THC. Given the diversity of products reported and frequency of patients using both THC- and nicotine-containing e-cigarette products, additional methods such as product testing and traceback could help identify the specific cause of this outbreak.

Health Care Utilization of Opioid Overdose Decedents with No Opioid Analgesic Prescription History.

Opioid overprescribing is a major driver of the current opioid overdose epidemic. However, annual opioid prescribing in the USA dropped from 782 to 640 morphine milligram equivalents per capita between 2010 and 2015, while opioid overdose deaths increased by 63%. To better understand the role of prescription opioids and health care utilization prior to opioid-related overdose, we analyzed the death records of decedents who died of an opioid overdose in Illinois in 2016 and linked to any existing controlled substance monitoring program (CSMP) and emergency department (ED) or hospital discharge records. We found that of the 1893 opioid-related overdoses, 573 (30.2%) decedents had not filled an opioid analgesic prescription within the 6 years prior to death. Decedents without an opioid prescription were more likely to be black (33.3% vs 20.2%, p < .001), Hispanic (16.3% vs 8.8%, p < .001), and Chicago residents (46.8% vs 25.6%, p < .001) than decedents with at least one filled opioid prescription. Decedents who did not fill an opioid prescription were less likely to die of an overdose involving prescribed opioids (7.3% vs 19.5%, p < .001) and more likely to fatally overdose on heroin (63% vs 50.4%, p < .001) or fentanyl/fentanyl analogues (50.3% vs 41.8%, p = .001). Between 2012 and the time of death, decedents without an opioid prescription had fewer emergency department admissions (2.5 ± 4.2 vs 10.6 ± 15.8, p < .001), were less likely to receive an opioid use disorder diagnosis (41.3% vs 47.5%, p = .052), and were less likely to be prescribed buprenorphine for opioid use disorder treatment (3.3% vs 8.6%, p < .001). Public health interventions have often focused on opioid prescribing and the use of CSMPs as the core preventive measures to address the opioid crisis. We identified a subset of individuals in Illinois who may not be impacted by such interventions. Additional research is needed to understand what strategies may be successful among high-risk populations that have limited opioid analgesic prescription history and low health care utilization.

Increased risk of PTLD in lung transplant recipients with cystic fibrosis.

BACKGROUND: Post-transplant lymphoproliferative disease (PTLD) is an important cause of morbidity and mortality following lung transplantation. Recipients with cystic fibrosis (CF) may have an increased risk of PTLD although the literature is limited to single center cohorts. Our primary aim is to examine PTLD in an adult lung transplant population by utilizing the International Society for Heart and Lung Transplantation Registry. METHODS: We studied 30,598 adult recipients of lung transplants performed between 1999 and 2011. The primary outcome was development of and time to PTLD. In addition to indication for transplant, other predictors examined included Epstein-Barr virus (EBV) and cytomegalovirus (CMV) serostatus, gender, and age. Outcomes were assessed with univariable and multivariable Cox proportional hazard models to obtain hazard ratios (HR). RESULTS: 17% of the cohort had a diagnosis of CF. PTLD developed in 2% of CF recipients compared to 1% for non-CF recipients (p<0.001). Compared to non-CF recipients, CF recipients had higher prevalence of EBV and CMV seronegativity and higher prevalences of high risk EBV and CMV mismatch (D+/R-). There is a significant association between CF and the development of PTLD [HR 1.66 (95% CI 1.30-2.12)]. Stratified multivariable analysis controlling for age revealed EBV negative non-CF recipients have an almost 2 fold increased risk of developing PTLD, whereas EBV negative CF recipients had an almost 6.5 fold increased risk. CONCLUSIONS: CF recipients have a higher risk for PTLD compared to non-CF recipients. Further studies are needed to account for additional risk factors and management in this population post-transplant.

A Synthesis of Hepatitis C prevalence estimates in Sub-Saharan Africa: 2000-2013.

BACKGROUND: Hepatitis C (HCV) is a deleterious virus that can be cured with new, highly effective anti-viral treatments, yet more than 185 million individuals worldwide remain HCV positive (with the vast majority un-diagnosed or untreated). Of importance, HCV is a leading cause of chronic liver disease and liver cancer, especially in Sub-Saharan Africa (SSA) where the prevalence remains high but uncertain due to little population-based evidence of the epidemic. We aimed to synthesize available data to calculate and highlight the HCV disease burden in SSA. METHODS: Weighted random-effects generalized linear mixed models were used to estimate prevalence by risk cohort, African region (Southern, Eastern, Western, and Central Africa), type of assay used, publication year, and whether the estimate included children. A pooled prevalence estimate was also calculated. Multi-variable analyses were limited to cohort and region specific prevalence estimates in the adult population due to limited studies including children. Prevalence estimates were additionally weighted using the known adult population size within each region. RESULTS: We included more than 10 years of data. Almost half of the studies on HCV prevalence in SSA were from the Western region (49 %), and over half of all studies were from either blood donor (25 %) or general population cohorts (31 %). In uni-variable analyses, prevalence was lowest in Southern Africa (0.72 %), followed by Eastern Africa at 3.00 %, Western Africa at 4.14 %, and Central Africa at 7.82 %. Blood donors consistently had the lowest prevalence (1.78 %), followed by pregnant women (2.51 %), individuals with comorbid HIV (3.57 %), individuals from the general population (5.41 %), those with a chronic illness (7.99 %), and those at high risk for infection (10.18 %). After adjusting for the population size in each region, the overall adult prevalence of HCV in SSA rose from 3.82 to 3.94 %. CONCLUSION: This meta-analysis offers a timely update to the HCV disease burden in SSA and offers additional evidence of the burgeoning epidemic. The study highlights the need to account for type of cohort and region variation when describing the HCV epidemic in SSA, the need for more studies that include children, as well as the need to factor in such variations when planning public health interventions.

Azithromycin use and outcomes in severe sepsis patients with and without pneumonia.

PURPOSE: Studies investigating the association between macrolides and outcomes in both pulmonary and nonpulmonary critically ill patients are limited. We aimed to examine the association between azithromycin use and clinical outcomes in severe sepsis patients with and without pneumonia receiving mechanical ventilation. MATERIALS AND METHODS: A retrospective cohort of 105 patients admitted to an adult intensive care unit (ICU) with severe sepsis in an urban university hospital were included in the study. Multivariable linear regression was performed to assess the relationship between azithromycin use and the following outcomes: 28-day ICU-free days and 28-day ventilator-free days. RESULTS: In univariate analysis, patients receiving azithromycin had nearly 6 more ICU-free days on average than did patients not receiving azithromycin (P = .005). The increased ICU-free days remained in multivariable analysis adjusting for age, sex, race, ICU type, and presence of shock (P = .005). In stratified analysis examining the association of azithromycin use in severe sepsis patients without pneumonia (n = 74), the results were similar to the full cohort. CONCLUSION: Azithromycin was associated with more ICU-free days in severe sepsis patients with and without pneumonia. Further investigations are warranted to better elicit the association of macrolide use on clinical outcomes in severe sepsis patients, especially those without pneumonia.

Next-Generation Sequencing Reveals Frequent Opportunities for Exposure to Hepatitis C Virus in Ghana.

Globally, hepatitis C Virus (HCV) infection is responsible for a large proportion of persons with liver disease, including cancer. The infection is highly prevalent in sub-Saharan Africa. West Africa was identified as a geographic origin of two HCV genotypes. However, little is known about the genetic composition of HCV populations in many countries of the region. Using conventional and next-generation sequencing (NGS), we identified and genetically characterized 65 HCV strains circulating among HCV-positive blood donors in Kumasi, Ghana. Phylogenetic analysis using consensus sequences derived from 3 genomic regions of the HCV genome, 5'-untranslated region, hypervariable region 1 (HVR1) and NS5B gene, consistently classified the HCV variants (n = 65) into genotypes 1 (HCV-1, 15%) and genotype 2 (HCV-2, 85%). The Ghanaian and West African HCV-2 NS5B sequences were found completely intermixed in the phylogenetic tree, indicating a substantial genetic heterogeneity of HCV-2 in Ghana. Analysis of HVR1 sequences from intra-host HCV variants obtained by NGS showed that three donors were infected with >1 HCV strain, including infections with 2 genotypes. Two other donors share an HCV strain, indicating HCV transmission between them. The HCV-2 strain sampled from one donor was replaced with another HCV-2 strain after only 2 months of observation, indicating rapid strain switching. Bayesian analysis estimated that the HCV-2 strains in Ghana were expanding since the 16th century. The blood donors in Kumasi, Ghana, are infected with a very heterogeneous HCV population of HCV-1 and HCV-2, with HCV-2 being prevalent. The detection of three cases of co- or super-infections and transmission linkage between 2 cases suggests frequent opportunities for HCV exposure among the blood donors and is consistent with the reported high HCV prevalence. The conditions for effective HCV-2 transmission existed for ~ 3-4 centuries, indicating a long epidemic history of HCV-2 in Ghana.