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Background Methicillin-resistant Staphylococcus aureus (MRSA) is a serious antimicrobial resistance threat; prevention efforts have focused primarily on healthcare-associated MRSA infections. We assessed progress in MRSA bloodstream infection (BSI) prevention during 2005-2020. Methods MRSA BSI data were from CDC Emerging Infections Program’s active, population-based surveillance for invasive S. aureus in 17 counties in 6 states (sites). A case was defined as isolation of MRSA from a blood culture in a resident of the catchment area. Cases were considered hospital-onset (HO) if the culture was obtained > 3 days after hospitalization, healthcare-associated community-onset (HACO) if the culture was obtained in an outpatient setting or ≤ 3 days after hospitalization in a patient with ≥ 1 prior major healthcare exposures, or otherwise community-associated (CA). Annual incidence was calculated per 100,000 census population for each epidemiologic classification. Results MRSA BSI incidence decreased from 32.2 (per 100,000 population) in 2005 to a nadir of 15.7 in 2016, then increased during 2017-2019 to 17.0 and decreased in 2020 to 16.4. (Figure 1). HACO comprised > 50% of all cases throughout 2005-2020 and mirrored the pattern of overall rates. HO rates decreased from 9.2 to 2.3 during 2005-2013 and fell below CA rates starting in 2012; rates were lowest during 2017-2019 (1.8-2.1) and increased in 2020 to 2.4. CA rates remained 3.0-4.6 throughout the surveillance period; during 2015-2019, rates increased from 3.0 to 4.0, then in 2020 decreased to 3.4. All sites saw decreases in overall MRSA BSI rates by > 50% during 2005-2020, and HACO rates in 2020 were at least 50% of total rates for each site. However, the relative proportion of CA and HO rates during 2020 varied by site (Figure 2), with CA MRSA BSI more than twice as common as HO MRSA BSI in two sites. Figure 1.Incidence rates of methicillin-resistant Staphylococcus aureus bloodstream infection, by epidemiologic classification, in 6 Emerging Infections Program sites, 2005–2020Figure 2.Ratio of incidence (per 100,000 population) of community-associated (CA) to hospital-onset (HO) methicillin-resistant Staphylococcus aureus bloodstream infection, in 6 Emerging Infections Program sites, 2020 Conclusion MRSA BSI rates fell by more than half during the 15-year surveillance period, reflecting substantial declines in HACO and HO cases; however, the recent plateau suggests a need for additional preventive measures that restore previous progress. Increased focus on CA MRSA BSI prevention may be needed in some areas depending on local epidemiology. Disclosures Ghinwa Dumyati, MD, Pfizer: Grant/Research Support William Schaffner, MD, VBI Vaccines: Advisor/Consultant.

We compared severe acute respiratory syndrome coronavirus 2 seroprevalence estimated from commercial laboratory residual sera and a community household survey in metropolitan Atlanta during April and May 2020 and found these 2 estimates to be similar (4.94% vs 3.18%). Compared with more representative surveys, commercial sera can provide an approximate measure of seroprevalence.

Prediction models indicate that melioidosis may be common in parts of East Africa, but there are few empiric data. We evaluated the prevalence of melioidosis among patients presenting with fever to hospitals in Tanzania. Patients with fever were enrolled at two referral hospitals in Moshi, Tanzania, during 2007–2008, 2012–2014, and 2016–2019. Blood was collected from participants for aerobic culture. Bloodstream isolates were identified by conventional biochemical methods. Non–glucose-fermenting Gram-negative bacilli were further tested using a Burkholderia pseudomallei latex agglutination assay. Also, we performed B. pseudomallei indirect hemagglutination assay (IHA) serology on serum samples from participants enrolled from 2012 to 2014 and considered at high epidemiologic risk of melioidosis on the basis of admission within 30 days of rainfall. We defined confirmed melioidosis as isolation of B. pseudomallei from blood culture, probable melioidosis as a ≥ 4-fold rise in antibody titers between acute and convalescent sera, and seropositivity as a single antibody titer ≥ 40. We enrolled 3,716 participants and isolated non-enteric Gram-negative bacilli in five (2.5%) of 200 with bacteremia. As none of these five isolates was B. pseudomallei, there were no confirmed melioidosis cases. Of 323 participants tested by IHA, 142 (44.0%) were male, and the median (range) age was 27 (0–70) years. We identified two (0.6%) cases of probable melioidosis, and 57 (17.7%) were seropositive. The absence of confirmed melioidosis from 9 years of fever surveillance indicates melioidosis was not a major cause of illness.

Molecular data are required to improve our understanding of the epidemiology of leptospirosis in Africa and to identify sources of human infection. We applied molecular methods to identify the infecting Leptospira species and genotypes among patients hospitalized with fever in Tanzania and compared these with Leptospira genotypes detected among animals in Tanzania to infer potential sources of human infection. We performed lipL32 real-time PCR to detect the presence of pathogenic Leptospira in acute-phase plasma, serum, and urine samples obtained from study participants with serologically confirmed leptospirosis and participants who had died with febrile illness. Leptospira blood culture was also performed. In positive specimens, we performed species-specific PCR and compared participant Leptospira secY sequences with Leptospira reference sequences and sequences previously obtained from animals in Tanzania. We detected Leptospira DNA in four (3.6%) of 111 participant blood samples. We detected Leptospira borgpetersenii (one participant, 25.0%), Leptospira interrogans (one participant, 25.0%), and Leptospira kirschneri (one participant, 25.0%) (one [25%] undetermined). Phylogenetic comparison of secY sequence from the L. borgpetersenii and L. kirschneri genotypes detected from participants was closely related to but distinct from genotypes detected among local livestock species. Our results indicate that a diverse range of Leptospira species is causing human infection. Although our analysis suggests a close relationship between Leptospira genotypes found in people and livestock, continued efforts are needed to obtain more Leptospira genetic material from human leptospirosis cases to help prioritize Leptospira species and genotypes for control.

Many infectious diseases lack robust estimates of incidence from endemic areas, and extrapolating incidence when there are few locations with data remains a major challenge in burden of disease estimation. We sought to combine sentinel surveillance with community behavioural surveillance to estimate leptospirosis incidence. We administered a questionnaire gathering responses on established locally relevant leptospirosis risk factors and recent fever to livestock‐owning community members across six districts in northern Tanzania and applied a logistic regression model predicting leptospirosis risk on the basis of behavioural factors that had been previously developed among patients with fever in Moshi Municipal and Moshi Rural Districts. We aggregated probability of leptospirosis by district and estimated incidence in each district by standardizing probabilities to those previously estimated for Moshi Districts. We recruited 286 community participants: Hai District (n = 11), Longido District (59), Monduli District (56), Moshi Municipal District (103), Moshi Rural District (44) and Rombo District (13). The mean predicted probability of leptospirosis by district was Hai 0.029 (0.005, 0.095), Longido 0.071 (0.009, 0.235), Monduli 0.055 (0.009, 0.206), Moshi Rural 0.014 (0.002, 0.049), Moshi Municipal 0.015 (0.004, 0.048) and Rombo 0.031 (0.006, 0.121). We estimated the annual incidence (upper and lower bounds of estimate) per 100,000 people of human leptospirosis among livestock owners by district as Hai 35 (6, 114), Longido 85 (11, 282), Monduli 66 (11, 247), Moshi Rural 17 (2, 59), Moshi Municipal 18 (5, 58) and Rombo 47 (7, 145). Use of community behavioural surveillance may be a useful tool for extrapolating disease incidence beyond sentinel surveillance sites.

Middle East respiratory syndrome coronavirus (MERS-CoV) infection causes a spectrum of respiratory illness, from asymptomatic to mild to fatal. MERS-CoV is transmitted sporadically from dromedary camels to humans and occasionally through human-to-human contact. Current epidemiologic evidence supports a major role in transmission for direct contact with live camels or humans with symptomatic MERS, but little evidence suggests the possibility of transmission from camel products or asymptomatic MERS cases. Because a proportion of case-patients do not report direct contact with camels or with persons who have symptomatic MERS, further research is needed to conclusively determine additional mechanisms of transmission, to inform public health practice, and to refine current precautionary recommendations.

Identifying febrile patients requiring antibacterial treatment is challenging, particularly in low-resource settings. In South-East Asia, C-reactive protein (CRP) has been demonstrated to be highly sensitive and moderately specific in detecting bacterial infections and to safely reduce unnecessary antibacterial prescriptions in primary care. As evidence is scant in sub-Saharan Africa, we assessed the sensitivity of CRP in identifying serious bacterial infections in Tanzania.Samples were obtained from inpatients and outpatients in a prospective febrile illness study at two hospitals in Moshi, Tanzania, 2011-2014. Bacterial bloodstream infections (BSI) were established by blood culture, and bacterial zoonotic infections were defined by ≥4 fold rise in antibody titre between acute and convalescent sera. The sensitivity of CRP in identifying bacterial infections was estimated using thresholds of 10, 20 and 40 mg/l. Specificity was not assessed because determining false-positive CRP results was limited by the lack of diagnostic testing to confirm non-bacterial aetiologies and because ascertaining true-negative cases was limited by the imperfect sensitivity of the diagnostic tests used to identify bacterial infections.Among 235 febrile outpatients and 569 febrile inpatients evaluated, 31 (3.9%) had a bacterial BSI and 61 (7.6%) had a bacterial zoonosis. Median (interquartile range) CRP values were 173 (80-315) mg/l in bacterial BSI, and 108 (31-208) mg/l in bacterial zoonoses. The sensitivity (95% confidence intervals) of CRP was 97% (83%-99%), 94% (79%-98%) and 90% (74%-97%) for identifying bacterial BSI, and 87% (76%-93%), 82% (71%-90%) and 72% (60%-82%) for bacterial zoonoses, using thresholds of 10, 20 and 40 mg/l, respectively.C-reactive protein was moderately sensitive for bacterial zoonoses and highly sensitive for identifying BSIs. Based on these results, operational studies are warranted to assess the safety and clinical utility of CRP for the management of non-malaria febrile illness at first-level health facilities in sub-Saharan Africa.Identifier les patients fébriles nécessitant un traitement antibactérien est un défi, en particulier dans les milieux à faibles ressources. En Asie du Sud-Est, il a été démontré que la protéine C-réactive (CRP) est très sensible et modérément spécifique dans la détection des infections bactériennes et qu'elle réduit en toute sécurité les prescriptions antibactériennes inutiles dans les soins primaires. Comme les données sont rares en Afrique subsaharienne (ASS), nous avons évalué la sensibilité de la CRP dans l'identification des infections bactériennes sévères en Tanzanie. MÉTHODES: Des échantillons ont été obtenus auprès de patients hospitalisés et ambulatoires dans une étude prospective sur les maladies fébriles dans deux hôpitaux à Moshi, en Tanzanie de 2011 à 2014. Les infections bactériennes du sang (IBS) ont été identifiées par la culture du sang et les infections bactériennes zoonotiques ont été définies par une élevation ≥ 4 fois le titre des anticorps entre les sérums en aiguë et en convalescence. La sensibilité de la CRP dans l'identification des infections bactériennes a été estimée en utilisant des seuils de 10, 20 et 40 mg/L. La spécificité n'a pas été évaluée parce que la détermination des résultats faux positifs de la CRP était limitée par le manque de tests de diagnostic pour confirmer les étiologies non bactériennes et parce que la confirmation des vrais cas négatifs était limitée par la sensibilité imparfaite des tests de diagnostic utilisés pour identifier les infections bactériennes. RÉSULTATS: Sur 235 patients ambulatoires fébriles et 569 patients hospitalisés fébriles évalués, 31 (3.9%) avaient une IBS et 61 (7.6%) avaient une zoonose bactérienne. Les valeurs médianes (intervalle interquartile) de la CRP étaient de 173 (80-315) mg/L dans les IBS et de 108 (31-208) mg/L dans les zoonoses bactériennes. La sensibilité (intervalles de confiance à 95%) de la CRP était de 97% (83-99%), 94% (79-98%), 90% (74-97%) pour identifier les IBS et 87% (76-93% ), 82% (71-90%), 72% (60-82%) pour les zoonoses bactériennes, en utilisant des seuils de 10, 20 et 40 mg/L respectivement.La CRP était modérément sensible pour les zoonoses bactériennes et hautement sensible pour l'identification des IBS. Sur la base de ces résultats, des études opérationnelles sont justifiées pour évaluer la sécurité et l'utilité clinique de la CRP pour la prise en charge des maladies fébriles non paludiques dans les établissements de santé de premier niveau en ASS.

We describe the contact investigation for an early confirmed case of coronavirus disease (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), in the United States. Contacts of the case-patient were identified, actively monitored for symptoms, interviewed for a detailed exposure history, and tested for SARS-CoV-2 infection by real-time reverse transcription PCR (rRT-PCR) and ELISA. Fifty contacts were identified and 38 (76%) were interviewed, of whom 11 (29%) reported unprotected face-to-face interaction with the case-patient. Thirty-seven (74%) had respiratory specimens tested by rRT-PCR, and all tested negative. Twenty-three (46%) had ELISA performed on serum samples collected ≈6 weeks after exposure, and none had detectable antibodies to SARS-CoV-2. Among contacts who were tested, no secondary transmission was identified in this investigation, despite unprotected close interactions with the infectious case-patient.

Objectives: The number of SARS-CoV-2 infections is underestimated in surveillance data. Various approaches to assess the seroprevalence of antibodies to SARS-CoV-2 have different resource requirements and generalizability. We estimated the seroprevalence of antibodies to SARS-CoV-2 in Denver County, Colorado, via a cluster-sampled community survey. Methods: We estimated the overall seroprevalence of antibodies to SARS-CoV-2 via a community seroprevalence survey in Denver County in July 2020, described patterns associated with seroprevalence, and compared results with cumulative COVID-19 incidence as reported to the health department during the same period. In addition, we compared seroprevalence as assessed with a temporally and geographically concordant convenience sample of residual clinical specimens from a commercial laboratory. Results: Based on 404 specimens collected through the community survey, 8.0% (95% CI, 3.9%-15.7%) of Denver County residents had antibodies to SARS-CoV-2, an infection rate of about 7 times that of the 1.1% cumulative reported COVID-19 incidence during this period. The estimated infection-to-reported case ratio was highest among children (34.7; 95% CI, 11.1-91.2) and males (10.8; 95% CI, 5.7-19.3). Seroprevalence was highest among males of Black race or Hispanic ethnicity and was associated with previous COVID-19–compatible illness, a previous positive SARS-CoV-2 test result, and close contact with someone who had confirmed SARS-CoV-2 infection. Testing of 1598 residual clinical specimens yielded a seroprevalence of 6.8% (95% CI, 5.0%-9.2%); the difference between the 2 estimates was 1.2 percentage points (95% CI, −3.6 to 12.2 percentage points). Conclusions: Testing residual clinical specimens provided a similar seroprevalence estimate yet yielded limited insight into the local epidemiology of COVID-19 and might be less representative of the source population than a cluster-sampled community survey. Awareness of the limitations of various sampling strategies is necessary when interpreting findings from seroprevalence assessments.

Background Although a human adenovirus (HAdV) vaccine is available for military use, officers-in-training are not routinely vaccinated. We describe an HAdV-associated respiratory outbreak among unvaccinated cadets at the US Coast Guard Academy and its impact on cadet training. Methods We defined a case as a cadet with new onset cough or sore throat during August 1–October 4, 2019. We reviewed medical records and distributed a questionnaire to identify cases and to estimate impact on cadet training. We performed real-time polymerase chain reaction testing on patient and environmental samples and whole genome sequencing on a subset of positive patient samples. Results Among the 1072 cadets, 378 (35%) cases were identified by medical records (n = 230) or additionally by the questionnaire (n = 148). Of the 230 cases identified from medical records, 138 (60%) were male and 226 (98%) had no underlying conditions. From questionnaire responses, 113 of 228 (50%) cases reported duty restrictions. Of cases with respiratory specimens, 36 of 50 (72%) were HAdV positive; all 14 sequenced specimens were HAdV-4a1. Sixteen (89%) of 18 environmental specimens from the cadet dormitory were HAdV-positive. Conclusions The HAdV-4-associated outbreak infected a substantial number of cadets and significantly impacted cadet training. Routine vaccination could prevent HAdV respiratory outbreaks in this population.

BackgroundInvasive nontyphoidal Salmonella (iNTS) is one of the leading causes of bacteraemia in sub-Saharan Africa. Multi-drug resistance (MDR) and further resistance to third generation cephalosporins and fluoroquinolones have emerged in multiple iNTS serotypes. Molecular epidemiological investigations of nontyphoidal Salmonella are needed to better understand the genetic characteristics and transmission dynamics associated with major MDR iNTS serotypes across the continent.MethodsA total of 166 nontyphoidal Salmonella isolates causing invasive disease were collected from a multi-centre study in eight African countries between 2010 and 2014, and whole-genome sequenced to investigate the geographical distribution, antimicrobial genetic determinants and population structure of iNTS serotypes-genotypes. Phylogeographical reconstruction was further conducted in context of the existing genomic framework of iNTS serotypes Typhimurium and Enteritidis. Population-based incidence of MDR-iNTS disease was also estimated.ResultsSalmonella enterica subsp. Enterica serotype Typhimurium (S. Typhimurium) sequence-type (ST) 313 and Salmonella enterica subsp. Enterica serotype Enteritidis (S. Enteritidis) ST11 were predominant, and both exhibited high frequencies of MDR. Salmonella enterica subsp. Enterica serotype Dublin (S. Dublin) ST10 emerged in West Africa. Mutations in the gyrA gene were identified in S. Enteritidis and S. Typhimurium in Ghana; and ST313 carrying blaCTX-M-15 was found in Kenya. Inter-country transmission of MDR ST313 lineage II and the West African Clade of MDR ST11 between Ghana and neighbouring countries including Mali, Burkina Faso, and Nigeria were evident. The incidence of MDR-iNTS disease exceeded 100/100,000-person years-of-observation (PYO) in children aged ConclusionsMultiple MDR iNTS serotypes-sequence types, predominantly S. Typhimurium ST313 and S. Enteritidis ST11, are co-circulating in sub-Saharan Africa with evidence of transmission between West African countries. The development of safe and effective iNTS vaccines coupled with appropriate antimicrobial stewardship and adequate epidemiological monitoring are essential to limit the impact of these pathogens in Africa.

During March 2016–March 2019, a total of 200,936 suspected cases of Middle East respiratory syndrome coronavirus infection were identified in Saudi Arabia; infections were confirmed in 698 cases (0.3% [0.7/100,000 population per year]). Continued surveillance is necessary for early case detection and timely infection control response.

An immunocompetent adult with asthma developed severe human metapneumovirus (HMPV) illness complicated by group A Streptococcus coinfection, progressing to acute respiratory distress syndrome and shock. Several coworkers had less severe HMPV infection. HMPV can cause severe respiratory illness in healthy adults and should be considered as a potential cause of community respiratory outbreaks.

IntroductionMore than 93,000 cases of coronavirus disease (COVID-19) have been reported worldwide. We describe the epidemiology, clinical course, and virologic characteristics of the first 12 U.S. patients with COVID-19.MethodsWe collected demographic, exposure, and clinical information from 12 patients confirmed by CDC during January 20–February 5, 2020 to have COVID-19. Respiratory, stool, serum, and urine specimens were submitted for SARS-CoV-2 rRT-PCR testing, virus culture, and whole genome sequencing.ResultsAmong the 12 patients, median age was 53 years (range: 21–68); 8 were male, 10 had traveled to China, and two were contacts of patients in this series. Commonly reported signs and symptoms at illness onset were fever (n=7) and cough (n=8). Seven patients were hospitalized with radiographic evidence of pneumonia and demonstrated clinical or laboratory signs of worsening during the second week of illness. Three were treated with the investigational antiviral remdesivir. All patients had SARS-CoV-2 RNA detected in respiratory specimens, typically for 2–3 weeks after illness onset, with lowest rRT-PCR Ct values often detected in the first week. SARS-CoV-2 RNA was detected after reported symptom resolution in seven patients. SARS-CoV-2 was cultured from respiratory specimens, and SARS-CoV-2 RNA was detected in stool from 7/10 patients.ConclusionsIn 12 patients with mild to moderately severe illness, SARS-CoV-2 RNA and viable virus were detected early, and prolonged RNA detection suggests the window for diagnosis is long. Hospitalized patients showed signs of worsening in the second week after illness onset.

Summary An outbreak of novel coronavirus (2019-nCoV) that began in Wuhan, China, has spread rapidly, with cases now confirmed in multiple countries. We report the first case of 2019-nCoV infection confirmed in the United States and describe the identification, diagnosis, clinical course, and management of the case, including the patient’s initial mild symptoms at presentation with progression to pneumonia on day 9 of illness. This case highlights the importance of close coordination between clinicians and public health authorities at the local, state, and federal levels, as well as the need for rapid dissemination of clinical information related to the care of patients with this emerging infection.

Background Human adenoviruses (HAdVs) are commonly associated with acute respiratory illness. HAdV outbreaks are well documented in congregate military training settings, but less is known about outbreaks on college campuses. During fall 2018 and spring 2019, 5 United States (US) colleges reported increases in HAdV-associated respiratory illness. Investigations were performed to better understand HAdV epidemiology in this setting. Methods A case was defined as a student at one of the 5 colleges, with acute respiratory illness and laboratory-confirmed HAdV infection during October 2018–December 2018 or March–May 2019. Available respiratory specimens were typed by HAdV type-specific real-time polymerase chain reaction assays, and for a subset, whole genome sequencing was performed. We reviewed available medical records and cases were invited to complete a questionnaire, which included questions on symptom presentation, social history, and absenteeism. Results We identified 168 HAdV cases. Median age was 19 (range, 17–22) years and 102 cases (61%) were male. Eleven cases were hospitalized, 10 with pneumonia; 2 cases died. Among questionnaire respondents, 80% (75/94) missed ≥ 1 day of class because of their illness. Among those with a type identified (79%), HAdV types 4 and 7 were equally detected, with frequency of each varying by site. Genome types 4a1 and 7d were identified, respectively, by whole genome sequence analysis. Conclusions HAdV respiratory illness was associated with substantial morbidity and missed class time among young, generally healthy adults on 5 US college campuses. HAdVs should be considered a cause of respiratory illness outbreaks in congregate settings such as college campuses.

Coronavirus disease 2019 (COVID-19), the respiratory disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), was first identified in Wuhan, China and has since become pandemic. In response to the first cases identified in the United States, close contacts of confirmed COVID-19 cases were investigated to enable early identification and isolation of additional cases and to learn more about risk factors for transmission. Close contacts of nine early travel-related cases in the United States were identified and monitored daily for development of symptoms (active monitoring). Selected close contacts (including those with exposures categorized as higher risk) were targeted for collection of additional exposure information and respiratory samples. Respiratory samples were tested for SARS-CoV-2 by real-time reverse transcription polymerase chain reaction at the Centers for Disease Control and Prevention. Four hundred four close contacts were actively monitored in the jurisdictions that managed the travel-related cases. Three hundred thirty-eight of the 404 close contacts provided at least basic exposure information, of whom 159 close contacts had ≥1 set of respiratory samples collected and tested. Across all actively monitored close contacts, two additional symptomatic COVID-19 cases (i.e., secondary cases) were identified; both secondary cases were in spouses of travel-associated case patients. When considering only household members, all of whom had ≥1 respiratory sample tested for SARS-CoV-2, the secondary attack rate (i.e., the number of secondary cases as a proportion of total close contacts) was 13% (95% CI: 4-38%). The results from these contact tracing investigations suggest that household members, especially significant others, of COVID-19 cases are at highest risk of becoming infected. The importance of personal protective equipment for healthcare workers is also underlined. Isolation of persons with COVID-19, in combination with quarantine of exposed close contacts and practice of everyday preventive behaviors, is important to mitigate spread of COVID-19.

ObjectiveTo investigate a Middle East respiratory syndrome coronavirus (MERS-CoV) outbreak event involving multiple healthcare facilities in Riyadh, Saudi Arabia; to characterize transmission; and to explore infection control implications.DesignOutbreak investigation.SettingCases presented in 4 healthcare facilities in Riyadh, Saudi Arabia: a tertiary-care hospital, a specialty pulmonary hospital, an outpatient clinic, and an outpatient dialysis unit.MethodsContact tracing and testing were performed following reports of cases at 2 hospitals. Laboratory results were confirmed by real-time reverse transcription polymerase chain reaction (rRT-PCR) and/or genome sequencing. We assessed exposures and determined seropositivity among available healthcare personnel (HCP) cases and HCP contacts of cases.ResultsIn total, 48 cases were identified, involving patients, HCP, and family members across 2 hospitals, an outpatient clinic, and a dialysis clinic. At each hospital, transmission was linked to a unique index case. Moreover, 4 cases were associated with superspreading events (any interaction where a case patient transmitted to ≥5 subsequent case patients). All 4 of these patients were severely ill, were initially not recognized as MERS-CoV cases, and subsequently died. Genomic sequences clustered separately, suggesting 2 distinct outbreaks. Overall, 4 (24%) of 17 HCP cases and 3 (3%) of 114 HCP contacts of cases were seropositive.ConclusionsWe describe 2 distinct healthcare-associated outbreaks, each initiated by a unique index case and characterized by multiple superspreading events. Delays in recognition and in subsequent implementation of control measures contributed to secondary transmission. Prompt contact tracing, repeated testing, HCP furloughing, and implementation of recommended transmission-based precautions for suspected cases ultimately halted transmission.

Background Human coronaviruses (HCoVs) -OC43, -229E, -NL63 and -HKU1 cause upper and lower respiratory tract infections. HCoVs are globally distributed and the predominant species may vary by region or year. Prior studies have shown seasonal patterns of HCoV species and annual variation in species prevalence but national circulation patterns in the US have not yet been described. Objectives To describe circulation patterns of HCoVs -OC43, -229E, -NL63 and -HKU1 in the US. Study design We reviewed real-time reverse transcription polymerase chain reaction (rRT-PCR) test results for HCoV-OC43, -229E, -NL63 and -HKU1 reported to The National Respiratory and Enteric Virus Surveillance System (NREVSS) by U.S. laboratories from July 2014–June 2017. We calculated the total number of tests and percent positive by week. For a subset of HCoV positive submissions with age and sex of the patient available, we tested for differences in age and sex across the four HCoV species using Chi Square and Kruskal Wallace tests. Results 117 laboratories reported 854,575 HCoV tests; 2.2% were positive for HCoV-OC43, 1.0% for HCoV-NL63, 0.8% for HCoV-229E, and 0.6% for HCoV-HKU1. The percentage of positive tests peaked during December – March each year. No significant differences in sex were seen across species, although a significant difference in age distribution was noted. Conclusions Common HCoVs may have annual peaks of circulation in winter months in the US, and individual HCoVs may show variable circulation from year to year. Different HCoV species may be detected more frequently in different age groups. Further years of data are needed to better understand patterns of activity for HCoVs.

We characterized exposures and demographics of Middle East respiratory syndrome coronavirus cases reported to the Saudi Arabia Ministry of Health during July 1–October 31, 2017, and June 1–September 16, 2018. Molecular characterization of available specimens showed that circulating viruses during these periods continued to cluster within lineage 5.

Funder: Swedish International Development Cooperation Agency (SIDA), Funder: Government of Republic of Korea, Funder: US Centers for Disease Control and Prevention, Background: Invasive non-typhoidal Salmonella (iNTS) is one of the leading causes of bacteraemia in sub-Saharan Africa. We aimed to provide a better understanding of the genetic characteristics and transmission patterns associated with multi-drug resistant (MDR) iNTS serovars across the continent. Methods: A total of 166 iNTS isolates collected from a multi-centre surveillance in 10 African countries (2010–2014) and a fever study in Ghana (2007–2009) were genome sequenced to investigate the geographical distribution, antimicrobial genetic determinants and population structure of iNTS serotypes–genotypes. Phylogenetic analyses were conducted in the context of the existing genomic frameworks for various iNTS serovars. Population-based incidence of MDR-iNTS disease was estimated in each study site. Results: Salmonella Typhimurium sequence-type (ST) 313 and Salmonella Enteritidis ST11 were predominant, and both exhibited high frequencies of MDR; Salmonella Dublin ST10 was identified in West Africa only. Mutations in the gyrA gene (fluoroquinolone resistance) were identified in S. Enteritidis and S. Typhimurium in Ghana; an ST313 isolate carrying blaCTX-M-15 was found in Kenya. International transmission of MDR ST313 (lineage II) and MDR ST11 (West African clade) was observed between Ghana and neighbouring West African countries. The incidence of MDR-iNTS disease exceeded 100/100 000 person-years-of-observation in children aged

Human adenoviruses (HAdVs) are nonenveloped, double-stranded DNA viruses in the family Adenoviridae; seven species (A-G) and >60 genotypes are known to cause human infection (1). Clinical manifestations associated with HAdV infection include fever, acute respiratory illness, gastroenteritis, and conjunctivitis. HAdV infection can be severe, particularly among immunocompromised patients, and can cause respiratory failure, disseminated infection, hemorrhagic cystitis, neurologic disease, and death (1,2). Illness tends to occur sporadically and without demonstrated seasonality. Outbreaks of HAdV have been reported globally in communities (3), and in closed or crowded settings, including dormitories, health care settings, and among military recruits, for whom a vaccine against HAdV type 4 (HAdV-4) and HAdV type 7 (HAdV-7) has been developed (4,5). CDC summarized HAdV detections voluntarily reported through the National Adenovirus Type Reporting System (NATRS) after initiation of surveillance in 2014 to describe trends in reported HAdVs circulating in the United States. Reporting laboratories were also encouraged to report available results for specimens collected before surveillance began. Overall, the number of reporting laboratories and HAdV type identifications reported to NATRS has increased substantially from the start of official reporting in 2014 through 2016; this report describes specimens collected during 2003-2016. The most commonly reported HAdV types were HAdV type 3 (HAdV-3) and HAdV type 2 (HAdV-2), although HAdV types reported fluctuated considerably from year to year. In the United States, information on recently circulating HAdV types is needed to inform diagnostic and surveillance activities by clinicians and public health practitioners. Routine reporting to NATRS by all U.S. laboratories with the capacity to type HAdVs could help strengthen this surveillance system.

Background Enterovirus D68 (EV-D68) caused a widespread outbreak of respiratory illness in the United States in 2014, predominantly affecting children. We describe EV-D68 rates, spectrum of illness, and risk factors from prospective, population-based acute respiratory illness (ARI) surveillance at a large US pediatric hospital. Methods Children

Summary Background Since influenza often presents non-specifically in infancy, we aimed to assess the extent to which existing respiratory surveillance platforms might underestimate the frequency of severe influenza disease among infants. Methods The Influenza and Respiratory Syncytial Virus in Infants (IRIS) study was a prospective observational study done at four hospitals in Albania, Jordan, Nicaragua, and the Philippines. We included acutely ill infants aged younger than 1 year admitted to hospital within 10 days or less of illness onset during two influenza seasons (2015–16 and 2016–17) in Albania, Jordan, and Nicaragua, and over a continuous 34 week period (2015–16) in the Philippines. We assessed the frequency of influenza virus infections by real-time RT-PCR (rRT-PCR) and serology. The main study outcome was seroconversion, defined as convalescent antibody titres more than or equal to four-fold higher than acute sera antibody titres, and convalescent antibody titres of 40 or higher. Seroconverison was confirmed by haemagglutination inhibition assay for influenza A viruses, and by hemagglutination inhibition assay and microneutralisation for influenza B viruses. Findings Between June 27, 2015, and April 21, 2017, 3634 acutely ill infants were enrolled, of whom 1943 were enrolled during influenza seasons and had complete acute-convalescent pairs and thus were included in the final analytical sample. Of the 1943 infants, 94 (5%) were influenza-positive by both rRT-PCR and serology, 58 (3%) were positive by rRT-PCR-only, and 102 (5%) were positive by serology only. Seroconversion to at least one of the influenza A or B viruses was observed among 196 (77%) of 254 influenza-positive infants. Of the 254 infants with influenza virus, 84 (33%) only had non-respiratory clinical discharge diagnoses (eg, sepsis, febrile seizures, dehydration, or other non-respiratory viral illness). A focus on respiratory diagnoses and rRT-PCR-confirmed influenza underdetects influenza-associated hospital admissions among infants by a factor of 2·6 (95% CI 2·0–3·6). Findings were unchanged when syndromic severe acute respiratory infection criteria were applied instead of clinical diagnosis. Interpretation If the true incidence of laboratory-confirmed influenza-associated hospital admissions among infants is at least twice that of previous estimates, this substantially increases the global burden of severe influenza and expands our estimates of the preventive value of maternal and infant influenza vaccination programmes. Funding US Centers for Disease Control and Prevention.

Tickborne rickettsial diseases continue to cause severe illness and death in otherwise healthy adults and children, despite the availability of low-cost, effective antibacterial therapy. Recognition early in the clinical course is critical because this is the period when antibacterial therapy is most effective. Early signs and symptoms of these illnesses are nonspecific or mimic other illnesses, which can make diagnosis challenging. Previously undescribed tickborne rickettsial diseases continue to be recognized, and since 2004, three additional agents have been described as causes of human disease in the United States: Rickettsia parkeri, Ehrlichia muris-like agent, and Rickettsia species 364D. This report updates the 2006 CDC recommendations on the diagnosis and management of tickborne rickettsial diseases in the United States and includes information on the practical aspects of epidemiology, clinical assessment, treatment, laboratory diagnosis, and prevention of tickborne rickettsial diseases. The CDC Rickettsial Zoonoses Branch, in consultation with external clinical and academic specialists and public health professionals, developed this report to assist health care providers and public health professionals to 1) recognize key epidemiologic features and clinical manifestations of tickborne rickettsial diseases, 2) recognize that doxycycline is the treatment of choice for suspected tickborne rickettsial diseases in adults and children, 3) understand that early empiric antibacterial therapy can prevent severe disease and death, 4) request the appropriate confirmatory diagnostic tests and understand their usefulness and limitations, and 5) report probable and confirmed cases of tickborne rickettsial diseases to public health authorities.

Among students with influenza-like illness at a Pennsylvania college student health center during 2016-2017, 44 (15%) of 288 with respiratory specimens tested positive for human adenovirus (HAdV). HAdV-3, -7, and -4 predominated, and types clustered temporally. HAdV infection should be considered among college students with acute respiratory illness.

What is already known on this topic? Q fever is a zoonotic disease caused by Coxiella burnetii and is usually transmitted through inhalation of air contaminated with animal excreta. The disease is considered to be underdiagnosed because symptoms are nonspecific and can vary from patient to patient, making diagnosis difficult. What is added by this report? During September-October 2014, the New York State Department of Health identified Q fever in five patients with exposure to a treatment known as live cell therapy, an alternative medicine practice involving injections of fetal sheep cells, which is a type of xenotransplantation. Investigation revealed that a group of U.S. residents traveled to Germany twice a year to receive this treatment. What are the implications for public health practice? Clinicians should consider zoonotic diseases, such as Q fever, in patients whose history includes receipt of a treatment known as live cell therapy. International travel for xenotransplantation procedures can facilitate transmission of zoonotic disease.

Background Brucellosis causes substantial morbidity among humans and their livestock. There are few robust estimates of the incidence of brucellosis in sub-Saharan Africa. Using cases identified through sentinel hospital surveillance and health care utilization data, we estimated the incidence of brucellosis in Moshi Urban and Moshi Rural Districts, Kilimanjaro Region, Tanzania, for the periods 2007–2008 and 2012–2014. Methods Cases were identified among febrile patients at two sentinel hospitals and were defined as having either a 4-fold increase in Brucella microscopic agglutination test titres between acute and convalescent serum or a blood culture positive for Brucella spp. Findings from a health care utilization survey were used to estimate multipliers to account for cases not seen at sentinel hospitals. Results Of 585 patients enrolled in the period 2007–2008, 13 (2.2%) had brucellosis. Among 1095 patients enrolled in the period 2012–2014, 32 (2.9%) had brucellosis. We estimated an incidence (range based on sensitivity analysis) of brucellosis of 35 (range 32–93) cases per 100 000 persons annually in the period 2007–2008 and 33 (range 30–89) cases per 100 000 persons annually in the period 2012–2014. Conclusions We found a moderate incidence of brucellosis in northern Tanzania, suggesting that the disease is endemic and an important human health problem in this area.

Background An outbreak of Middle East respiratory syndrome coronavirus (MERS-CoV) in Jordan in 2015 involved a variant virus that acquired distinctive deletions in the accessory open reading frames. We conducted a molecular and seroepidemiologic investigation to describe the deletion variant’s transmission patterns and epidemiology. Methods We reviewed epidemiologic and medical chart data and analyzed viral genome sequences from respiratory specimens of MERS-CoV cases. In early 2016, sera and standardized interviews were obtained from MERS-CoV cases and their contacts. Sera were evaluated by nucleocapsid and spike protein enzyme immunoassays and microneutralization. Results Among 16 cases, 11 (69%) had health care exposure and 5 (31%) were relatives of a known case; 13 (81%) were symptomatic, and 7 (44%) died. Genome sequencing of MERS-CoV from 13 cases revealed 3 transmissible deletions associated with clinical illness during the outbreak. Deletion variant sequences were epidemiologically clustered and linked to a common transmission chain. Interviews and sera were collected from 2 surviving cases, 23 household contacts, and 278 health care contacts; 1 (50%) case, 2 (9%) household contacts, and 3 (1%) health care contacts tested seropositive. Conclusions The MERS-CoV deletion variants retained human-to-human transmissibility and caused clinical illness in infected persons despite accumulated mutations. Serology suggested limited transmission beyond that detected during the initial outbreak investigation.

Little is known about the epidemiology of human brucellosis in sub-Saharan Africa. This hampers prevention and control efforts at the individual and population levels. To evaluate risk factors for brucellosis in northern Tanzania, we conducted a study of patients presenting with fever to two hospitals in Moshi, Tanzania. Serum taken at enrollment and at 4–6 week follow-up was tested by Brucella microagglutination test. Among participants with a clinically compatible illness, confirmed brucellosis cases were defined as having a ≥ 4-fold rise in agglutination titer between paired sera or a blood culture positive for Brucella spp., and probable brucellosis cases were defined as having a single reciprocal titer ≥ 160. Controls had reciprocal titers < 20 in paired sera. We collected demographic and clinical information and administered a risk factor questionnaire. Of 562 participants in the analysis, 50 (8.9%) had confirmed or probable brucellosis. Multivariable analysis showed that risk factors for brucellosis included assisting goat or sheep births (Odds ratio [OR] 5.9, 95% confidence interval [CI] 1.4, 24.6) and having contact with cattle (OR 1.2, 95% CI 1.0, 1.4). Consuming boiled or pasteurized dairy products was protective against brucellosis (OR 0.12, 95% CI 0.02, 0.93). No participants received a clinical diagnosis of brucellosis from their healthcare providers. The under-recognition of brucellosis by healthcare workers could be addressed with clinician education and better access to brucellosis diagnostic tests. Interventions focused on protecting livestock keepers, especially those who assist goat or sheep births, are needed.

Public health investigations can require intensive collaboration between numerous governmental and nongovernmental organizations. We describe an investigation involving several governmental and nongovernmental partners that was successfully planned and performed in an organized, comprehensive, and timely manner with several governmental and nongovernmental partners.

During September–November 2014, the New York State Department of Health (NYSDOH) was notified of five New York state residents who had tested seropositive for Coxiella burnetii, the causative agent of Q fever. All five patients had symptoms compatible with Q fever (e.g., fever, fatigue, chills, and headache) and a history of travel to Germany to receive a medical treatment called "live cell therapy" (sometimes called "fresh cell therapy") in May 2014. Live cell therapy is the practice of injecting processed cells from organs or fetuses of nonhuman animals (e.g., sheep) into human recipients. It is advertised to treat a variety of health conditions. This practice is unavailable in the United States; however, persons can travel to foreign locations to receive injections. Local health departments interviewed the patients, and NYSDOH notified CDC and posted a report on CDC’s Epidemic Information Exchange to solicit additional cases. Clinical and exposure information for each patient was reported to the Robert Koch Institute in Germany, which forwarded the information to local health authorities. A Canada resident who also received live cell therapy in May 2014 was diagnosed with Q fever in July 2014. Clinicians should be aware of health risks, such as Q fever and other zoonotic diseases, among patients with a history of receiving treatment with live cell therapy products.

Background. The epidemiology of Salmonella Typhi and invasive nontyphoidal Salmonella (NTS) differs, and prevalence of these pathogens among children in sub-Saharan Africa may vary in relation to malaria transmission intensity. Methods. We compared the prevalence of bacteremia among febrile pediatric inpatients aged 2 months to 13 years recruited at sites of high and low malaria endemicity in Tanzania. Enrollment at Teule Hospital, the high malaria transmission site, was from June 2006 through May 2007, and at Kilimanjaro Christian Medical Centre (KCMC), the low malaria transmission site, from September 2007 through August 2008. Automated blood culture, malaria microscopy with Giemsa-stained blood films, and human immunodeficiency virus testing were performed. Results. At Teule, 3639 children were enrolled compared to 467 at KCMC. Smear-positive malaria was detected in 2195 of 3639 (60.3%) children at Teule and 11 of 460 (2.4%) at KCMC (P < .001). Bacteremia was present in 336 of 3639 (9.2%) children at Teule and 20 of 463 (4.3%) at KCMC (P < .001). NTS was isolated in 162 of 3639 (4.5%) children at Teule and 1 of 463 (0.2%) at KCMC (P < .001). Salmonella Typhi was isolated from 11 (0.3%) children at Teule and 6 (1.3%) at KCMC (P = .008). With NTS excluded, the prevalence of bacteremia at Teule was 5.0% and at KCMC 4.1% (P = .391). Conclusions. Where malaria transmission was intense, invasive NTS was common and Salmonella Typhi was uncommon, whereas the inverse was observed at a low malaria transmission site. The relationship between these pathogens, the environment, and the host is a compelling area for further research.

Leptospirosis and human immunodeficiency virus (HIV) infection are prevalent in many areas, including northern Tanzania, yet little is known about their interaction.We enrolled febrile inpatients at two hospitals in Moshi, Tanzania, over 1 year and performed HIV antibody testing and the microscopic agglutination test (MAT) for leptospirosis. Confirmed leptospirosis was defined as ≥ four-fold rise in MAT titer between acute and convalescent serum samples, and probable leptospirosis was defined as any reciprocal MAT titer ≥ 800.Confirmed or probable leptospirosis was found in 70 (8.4%) of 831 participants with at least one serum sample tested. At total of 823 (99.0%) of 831 participants had HIV testing performed, and 203 (24.7%) were HIV infected. Among HIV-infected participants, 9 (4.4%) of 203 had confirmed or probable leptospirosis, whereas among HIV-uninfected participants 61 (9.8%) of 620 had leptospirosis. Leptospirosis was less prevalent among HIV-infected as compared to HIV-uninfected participants [odds ratio (OR) 0.43, p=0.019]. Among those with leptospirosis, HIV-infected patients more commonly presented with features of severe sepsis syndrome than HIV-uninfected patients, but differences were not statistically significant. Among HIV-infected patients, severe immunosuppression was not significantly different between those with and without leptospirosis (p=0.476). Among HIV-infected adolescents and adults, median CD4 percent and median CD4 count were higher among those with leptospirosis as compared to those with other etiologies of febrile illness, but differences in CD4 count did not reach statistical significance (p=0.015 and p=0.089, respectively).Among febrile inpatients in northern Tanzania, leptospirosis was not more prevalent among HIV-infected patients. Although some indicators of leptospirosis severity were more common among HIV-infected patients, a statistically significant difference was not demonstrated. Among HIV-infected patients, those with leptospirosis were not more immunosuppressed relative to those with other etiologies of febrile illness.

Background This multi-country prospective study of infants aged

Background The sole report of annual leptospirosis incidence in continental Africa of 75–102 cases per 100,000 population is from a study performed in August 2007 through September 2008 in the Kilimanjaro Region of Tanzania. To evaluate the stability of this estimate over time, we estimated the incidence of acute leptospirosis in Kilimanjaro Region, northern Tanzania for the time period 2012–2014. Methodology and Principal Findings Leptospirosis cases were identified among febrile patients at two sentinel hospitals in the Kilimanjaro Region. Leptospirosis was diagnosed by serum microscopic agglutination testing using a panel of 20 Leptospira serovars belonging to 17 separate serogroups. Serum was taken at enrolment and patients were asked to return 4–6 weeks later to provide convalescent serum. Confirmed cases required a 4-fold rise in titre and probable cases required a single titre of ≥800. Findings from a healthcare utilisation survey were used to estimate multipliers to adjust for cases not seen at sentinel hospitals. We identified 19 (1.7%) confirmed or probable cases among 1,115 patients who presented with a febrile illness. Of cases, the predominant reactive serogroups were Australis 8 (42.1%), Sejroe 3 (15.8%), Grippotyphosa 2 (10.5%), Icterohaemorrhagiae 2 (10.5%), Pyrogenes 2 (10.5%), Djasiman 1 (5.3%), Tarassovi 1 (5.3%). We estimated that the annual incidence of leptospirosis was 11–18 cases per 100,000 population. This was a significantly lower incidence than 2007–08 (p, Author Summary Leptospirosis is an infectious disease that causes a fever. It can be severe or fatal. Understanding how many people get leptospirosis helps to determine priorities in allocating resources for disease diagnosis, treatment, and prevention. There are few data about leptospirosis incidence in sub-Saharan African countries. The only mainland estimate is from northern Tanzania for the years 2007–08. To see if leptospirosis incidence had changed since 2007–08, we measured leptospirosis incidence in the same location in 2012–2014. To do this, we systematically approached people at two hospitals in the Kilimanjaro Region and tested them for leptospirosis. We adjusted the number of identified cases of leptospirosis found at the hospitals to account for people with fever who did not come to hospital for testing and care. We also adjusted for imperfect testing methods. We found that the number of people who developed leptospirosis annually had dropped from 75–102 cases per 100,000 people during 2007–08 to 11–18 cases per 100,000 people during 2012–14. Also, the subtype of leptospirosis responsible for the most cases during 2007–08 was not present during 2012–14. The number of people developing leptospirosis was not stable, highlighting the value of measuring how commonly leptospirosis occurs over several years.

Country-specific studies in Africa have indicated that Plasmodium falciparum is associated with invasive nontyphoidal Salmonella (iNTS) disease. We conducted a multicenter study in 13 sites in Burkina Faso, Ethiopia, Ghana, Guinea-Bissau, Kenya, Madagascar, Senegal, South Africa, Sudan, and Tanzania to investigate the relationship between the occurrence of iNTS disease, other systemic bacterial infections, and malaria. Febrile patients received a blood culture and a malaria test. Isolated bacteria underwent antimicrobial susceptibility testing, and the association between iNTS disease and malaria was assessed. A positive correlation between frequency proportions of malaria and iNTS was observed (P = .01; r = 0.70). Areas with higher burden of malaria exhibited higher odds of iNTS disease compared to other bacterial infections (odds ratio [OR], 4.89; 95% CI, 1.61-14.90; P = .005) than areas with lower malaria burden. Malaria parasite positivity was associated with iNTS disease (OR, 2.44; P = .031) and gram-positive bacteremias, particularly Staphylococcus aureus, exhibited a high proportion of coinfection with Plasmodium malaria. Salmonella Typhimurium and Salmonella Enteritidis were the predominant NTS serovars (53/73; 73%). Both moderate (OR, 6.05; P = .0001) and severe (OR, 14.62; P < .0001) anemia were associated with iNTS disease. A positive correlation between iNTS disease and malaria endemicity, and the association between Plasmodium parasite positivity and iNTS disease across sub-Saharan Africa, indicates the necessity to consider iNTS as a major cause of febrile illness in malaria-holoendemic areas. Prevention of iNTS disease through iNTS vaccines for areas of high malaria endemicity, targeting high-risk groups for Plasmodium parasitic infection, should be considered.

Chikungunya spread throughout the Dominican Republic (DR) after the first identified laboratory-confirmed cases were reported in April 2014. In June 2014, a U.S.-based service organization operating in the DR reported chikungunya-like illnesses among several staff. We assessed the incidence of chikungunya virus (CHIKV) and dengue virus (DENV) infection and illnesses and evaluated adherence to mosquito avoidance measures among volunteers/staff deployed in the DR who returned to the United States during July-August 2014. Investigation participants completed a questionnaire that collected information on demographics, medical history, self-reported illnesses, and mosquito exposures and avoidance behaviors and provided serum for CHIKV and DENV diagnostic testing by reverse transcription polymerase chain reaction and IgM enzyme-linked immunosorbent assay. Of 102 participants, 42 (41%) had evidence of recent CHIKV infection and two (2%) had evidence of recent DENV infection. Of the 41 participants with evidence of recent CHIKV infection only, 39 (95%) reported fever, 37 (90%) reported rash, and 37 (90%) reported joint pain during their assignment. All attended the organization's health trainings, and 89 (87%) sought a pretravel health consultation. Most (∼95%) used insect repellent; however, only 30% applied it multiple times daily and < 5% stayed in housing with window/door screens. In sum, CHIKV infections were common among these volunteers during the 2014 chikungunya epidemic in the DR. Despite high levels of preparation, reported adherence to mosquito avoidance measures were inconsistent. Clinicians should discuss chikungunya with travelers visiting areas with ongoing CHIKV outbreaks and should consider chikungunya when diagnosing febrile illnesses in travelers returning from affected areas.

Tickborne rickettsial diseases continue to cause severe illness and death in otherwise healthy adults and children, despite the availability of low-cost, effective antibacterial therapy. Recognition early in the clinical course is critical because this is the period when antibacterial therapy is most effective. Early signs and symptoms of these illnesses are nonspecific or mimic other illnesses, which can make diagnosis challenging. Previously undescribed tickborne rickettsial diseases continue to be recognized, and since 2004, three additional agents have been described as causes of human disease in the United States: Rickettsia parkeri, Ehrlichia muris-like agent, and Rickettsia species 364D. This report updates the 2006 CDC recommendations on the diagnosis and management of tickborne rickettsial diseases in the United States and includes information on the practical aspects of epidemiology, clinical assessment, treatment, laboratory diagnosis, and prevention of tickborne rickettsial diseases. The CDC Rickettsial Zoonoses Branch, in consultation with external clinical and academic specialists and public health professionals, developed this report to assist health care providers and public health professionals to 1) recognize key epidemiologic features and clinical manifestations of tickborne rickettsial diseases, 2) recognize that doxycycline is the treatment of choice for suspected tickborne rickettsial diseases in adults and children, 3) understand that early empiric antibacterial therapy can prevent severe disease and death, 4) request the appropriate confirmatory diagnostic tests and understand their usefulness and limitations, and 5) report probable and confirmed cases of tickborne rickettsial diseases to public health authorities.

BACKGROUND Salmonella enterica serovar Typhi is a predominant cause of bloodstream infections in sub-Saharan Africa (SSA). Increasing numbers of S. Typhi with resistance to ciprofloxacin have been reported from different parts of the world. However, data from SSA are limited. In this study, we aimed to measure the ciprofloxacin susceptibility of S. Typhi isolated from patients with febrile illness in SSA. METHODS Febrile patients from 9 sites within 6 countries in SSA with a body temperature of ≥38.0°C were enrolled in this study. Blood samples were obtained for bacterial culture, and Salmonella isolates were identified biochemically and confirmed by multiplex polymerase chain reaction (PCR). Antimicrobial susceptibility of all Salmonella isolates was performed by disk diffusion test, and minimum inhibitory concentrations (MICs) against ciprofloxacin were measured by Etest. All Salmonella isolates with reduced susceptibility to ciprofloxacin (MIC > 0.06 µg/mL) were screened for mutations in quinolone resistance-determining regions in target genes, and the presence of plasmid-mediated quinolone resistance (PMQR) genes was assessed by PCR. RESULTS A total of 8161 blood cultures were performed, and 100 (1.2%) S. Typhi, 2 (