Last data update: Apr 22, 2024. (Total: 46599 publications since 2009)
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Query Trace: Biggs HM[original query] |
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Etiology of acute lower respiratory illness hospitalizations among infants in 4 countries
Kubale J , Kujawski S , Chen I , Wu Z , Khader IA , Hasibra I , Whitaker B , Gresh L , Simaku A , Simões EAF , Al-Gazo M , Rogers S , Gerber SI , Balmaseda A , Tallo VL , Al-Sanouri TM , Porter R , Bino S , Azziz-Baumgartner E , McMorrow M , Hunt D , Thompson M , Biggs HM , Gordon A . Open Forum Infect Dis 2023 10 (12) ofad580 BACKGROUND: Recent studies explored which pathogens drive the global burden of pneumonia hospitalizations among young children. However, the etiology of broader acute lower respiratory tract infections (ALRIs) remains unclear. METHODS: Using a multicountry study (Albania, Jordan, Nicaragua, and the Philippines) of hospitalized infants and non-ill community controls between 2015 and 2017, we assessed the prevalence and severity of viral infections and coinfections. We also estimated the proportion of ALRI hospitalizations caused by 21 respiratory pathogens identified via multiplex real-time reverse transcription polymerase chain reaction with bayesian nested partially latent class models. RESULTS: An overall 3632 hospitalized infants and 1068 non-ill community controls participated in the study and had specimens tested. Among hospitalized infants, 1743 (48.0%) met the ALRI case definition for the etiology analysis. After accounting for the prevalence in non-ill controls, respiratory syncytial virus (RSV) was responsible for the largest proportion of ALRI hospitalizations, although the magnitude varied across sites-ranging from 65.2% (95% credible interval, 46.3%-79.6%) in Albania to 34.9% (95% credible interval, 20.0%-49.0%) in the Philippines. While the fraction of ALRI hospitalizations caused by RSV decreased as age increased, it remained the greatest driver. After RSV, rhinovirus/enterovirus (range, 13.4%-27.1%) and human metapneumovirus (range, 6.3%-12.0%) were the next-highest contributors to ALRI hospitalizations. CONCLUSIONS: We observed substantial numbers of ALRI hospitalizations, with RSV as the largest source, particularly in infants aged <3 months. This underscores the potential for vaccines and long-lasting monoclonal antibodies on the horizon to reduce the burden of ALRI in infants worldwide. |
Enhanced Contact Investigations for Nine Early Travel-Related Cases of SARS-CoV-2 in the United States (preprint)
Burke RM , Balter S , Barnes E , Barry V , Bartlett K , Beer KD , Benowitz I , Biggs HM , Bruce H , Bryant-Genevier J , Cates J , Chatham-Stephens K , Chea N , Chiou H , Christiansen D , Chu VT , Clark S , Cody SH , Cohen M , Conners EE , Dasari V , Dawson P , DeSalvo T , Donahue M , Dratch A , Duca L , Duchin J , Dyal JW , Feldstein LR , Fenstersheib M , Fischer M , Fisher R , Foo C , Freeman-Ponder B , Fry AM , Gant J , Gautom R , Ghinai I , Gounder P , Grigg CT , Gunzenhauser J , Hall AJ , Han GS , Haupt T , Holshue M , Hunter J , Ibrahim MB , Jacobs MW , Jarashow MC , Joshi K , Kamali T , Kawakami V , Kim M , Kirking HL , Kita-Yarbro A , Klos R , Kobayashi M , Kocharian A , Lang M , Layden J , Leidman E , Lindquist S , Lindstrom S , Link-Gelles R , Marlow M , Mattison CP , McClung N , McPherson TD , Mello L , Midgley CM , Novosad S , Patel MT , Pettrone K , Pillai SK , Pray IW , Reese HE , Rhodes H , Robinson S , Rolfes M , Routh J , Rubin R , Rudman SL , Russell D , Scott S , Shetty V , Smith-Jeffcoat SE , Soda EA , Spitters C , Stierman B , Sunenshine R , Terashita D , Traub E , Vahey GM , Verani JR , Wallace M , Westercamp M , Wortham J , Xie A , Yousaf A , Zahn M . medRxiv 2020 2020.04.27.20081901 Background Coronavirus disease 2019 (COVID-19), the respiratory disease caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), was first identified in Wuhan, China and has since become pandemic. As part of initial response activities in the United States, enhanced contact investigations were conducted to enable early identification and isolation of additional cases and to learn more about risk factors for transmission.Methods Close contacts of nine early travel-related cases in the United States were identified. Close contacts meeting criteria for active monitoring were followed, and selected individuals were targeted for collection of additional exposure details and respiratory samples. Respiratory samples were tested for SARS-CoV-2 by real-time reverse transcription polymerase chain reaction (RT-PCR) at the Centers for Disease Control and Prevention.Results There were 404 close contacts who underwent active monitoring in the response jurisdictions; 338 had at least basic exposure data, of whom 159 had ≥1 set of respiratory samples collected and tested. Across all known close contacts under monitoring, two additional cases were identified; both secondary cases were in spouses of travel-associated case patients. The secondary attack rate among household members, all of whom had ≥1 respiratory sample tested, was 13% (95% CI: 4 – 38%).Conclusions The enhanced contact tracing investigations undertaken around nine early travel-related cases of COVID-19 in the United States identified two cases of secondary transmission, both spouses. Rapid detection and isolation of the travel-associated case patients, enabled by public awareness of COVID-19 among travelers from China, may have mitigated transmission risk among close contacts of these cases.Competing Interest StatementThe authors have declared no competing interest.Funding StatementNo external funding was sought or received.Author DeclarationsAll relevant ethical guidelines have been followed; any necessary IRB and/or ethics committee approvals have been obtained and details of the IRB/oversight body are included in the manuscript.YesAll necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived.YesI understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance).YesI have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable.YesData may be available upon reasonable request. |
Respiratory syncytial virus infection among hospitalized infants in four middle-income countries
Biggs HM , DeGroote NP , Porter RM , Bino S , Marar BI , Gresh L , de Jesus-Cornejo J , Langley G , Thornburg NJ , Peret TCT , Whitaker B , Zhang Y , Wang L , Patel MC , McMorrow M , Campbell W , Hasibra I , Duka E , Al-Gazo M , Kubale J , Sanchez F , Lucero MG , Tallo VL , Azziz-Baumgartner E , Simaku A , Gerber SI . J Pediatric Infect Dis Soc 2023 12 (7) 394-405 BACKGROUND: Understanding respiratory syncytial virus (RSV) global epidemiology is important to inform future prevention strategies. METHODS: Hospitalized infants <1-year-old with acute illness were enrolled prospectively in Albania, Jordan, Nicaragua, and Philippines during respiratory seasons in 2015-2017. Medical chart review, parental interview, and post-discharge follow up were conducted. Respiratory specimens were tested using real-time RT-PCR for RSV. Infant characteristics associated with very severe illness (intensive care unit [ICU] admission or receipt of supplemental oxygen) were assessed using logistic regression to adjust for potential confounders (age, sex, study site, preterm birth). RESULTS: Of 3,634 enrolled hospitalized infants, 1,129 (31%) tested positive for RSV. The median age of RSV-positive infants was 2.7 (IQR: 1.4 to 6.1) months and 665 (59%) were male. Very severe illness in 583 (52%) RSV-positive infants was associated with younger age (aOR 4.1, 95% CI: 2.6-6.5 for 0-2 compared to 9-11-months; p<0.01), , low weight-for-age z-score (aOR 1.9, 95%CI: 1.2-2.8; p<0.01), ICU care after birth (aOR 1.6, 95%CI: 1.0-2.5; p=0.48), and cesarean delivery (aOR 1.4, 95% CI: 1.0-1.8; p=.03). RSV subgroups A and B co-circulated at all sites with alternating predominance by year; subgroup was not associated with severity (aOR 1.0, 95% CI: 0.8-1.4). Nine (0.8%) RSV-positive infants died during admission or within ≤30 days of discharge, of which 7 (78%) were <6-months-old. CONCLUSIONS: RSV was associated with nearly a third of infant acute illness hospitalizations in four middle-income countries during the respiratory season, where, in addition to young age, factors including low weight-for-age might be important predictors of severity. RSV prevention strategies targeting young infants could substantially reduce RSV-associated hospitalizations in middle-income countries. |
Middle East Respiratory Syndrome Coronavirus, Saudi Arabia, 2017-2018
Hakawi A , Rose EB , Biggs HM , Lu X , Mohammed M , Abdalla O , Abedi GR , Alsharef AA , Alamri AA , Bereagesh SA , Al Dosari KM , Ashehri SA , Fakhouri WG , Alzaid SZ , Lindstrom S , Gerber SI , Asiri A , Jokhdar H , Watson JT . Emerg Infect Dis 2019 25 (11) 2149-2151 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. |
Incidence Estimates of Acute Q Fever and Spotted Fever Group Rickettsioses, Kilimanjaro, Tanzania, from 2007 to 2008 and from 2012 to 2014
Pisharody S , Rubach MP , Carugati M , Nicholson WL , Perniciaro JL , Biggs HM , Maze MJ , Hertz JT , Halliday JEB , Allan KJ , Mmbaga BT , Saganda W , Lwezaula BF , Kazwala RR , Cleaveland S , Maro VP , Crump JA . Am J Trop Med Hyg 2021 106 (2) 494-503 Q fever and spotted fever group rickettsioses (SFGR) are common causes of severe febrile illness in northern Tanzania. Incidence estimates are needed to characterize the disease burden. Using hybrid surveillance-coupling case-finding at two referral hospitals and healthcare utilization data-we estimated the incidences of acute Q fever and SFGR in Moshi, Kilimanjaro, Tanzania, from 2007 to 2008 and from 2012 to 2014. Cases were defined as fever and a four-fold or greater increase in antibody titers of acute and convalescent paired sera according to the indirect immunofluorescence assay of Coxiella burnetii phase II antigen for acute Q fever and Rickettsia conorii (2007-2008) or Rickettsia africae (2012-2014) antigens for SFGR. Healthcare utilization data were used to adjust for underascertainment of cases by sentinel surveillance. For 2007 to 2008, among 589 febrile participants, 16 (4.7%) of 344 and 27 (8.8%) of 307 participants with paired serology had Q fever and SFGR, respectively. Adjusted annual incidence estimates of Q fever and SFGR were 80 (uncertainty range, 20-454) and 147 (uncertainty range, 52-645) per 100,000 persons, respectively. For 2012 to 2014, among 1,114 febrile participants, 52 (8.1%) and 57 (8.9%) of 641 participants with paired serology had Q fever and SFGR, respectively. Adjusted annual incidence estimates of Q fever and SFGR were 56 (uncertainty range, 24-163) and 75 (uncertainty range, 34-176) per 100,000 persons, respectively. We found substantial incidences of acute Q fever and SFGR in northern Tanzania during both study periods. To our knowledge, these are the first incidence estimates of either disease in sub-Saharan Africa. Our findings suggest that control measures for these infections warrant consideration. |
Assessment of SARS-CoV-2 Seroprevalence by Community Survey and Residual Specimens, Denver, Colorado, July-August 2020.
Kugeler KJ , Podewils LJ , Alden NB , Burket TL , Kawasaki B , Biggerstaff BJ , Biggs HM , Zacks R , Foster MA , Lim T , McDonald E , Tate JE , Herlihy RK , Drobeniuc J , Cortese MM . Public Health Rep 2021 137 (1) 333549211055137 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. |
The genomic epidemiology of multi-drug resistant invasive non-typhoidal Salmonella in selected sub-Saharan African countries.
Park SE , Pham DT , Pak GD , Panzner U , Maria Cruz Espinoza L , von Kalckreuth V , Im J , Mogeni OD , Schütt-Gerowitt H , Crump JA , Breiman RF , Adu-Sarkodie Y , Owusu-Dabo E , Rakotozandrindrainy R , Bassiahi Soura A , Aseffa A , Gasmelseed N , Sooka A , Keddy KH , May J , Aaby P , Biggs HM , Hertz JT , Montgomery JM , Cosmas L , Olack B , Fields B , Sarpong N , Razafindrabe TJL , Raminosoa TM , Kabore LP , Sampo E , Teferi M , Yeshitela B , El Tayeb MA , Krumkamp R , Dekker DM , Jaeger A , Tall A , Gassama A , Niang A , Bjerregaard-Andersen M , Løfberg SV , Deerin JF , Park JK , Konings F , Carey ME , Van Puyvelde S , Ali M , Clemens J , Dougan G , Baker S , Marks F . BMJ Glob Health 2021 6 (8) 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 bla (CTX-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 <5 years in several West African countries. CONCLUSIONS: We identified the circulation of multiple MDR iNTS serovar STs in the sampled sub-Saharan African countries. Investment in the development and deployment of iNTS vaccines coupled with intensified antimicrobial resistance surveillance are essential to limit the impact of these pathogens in Africa. |
Outbreak of Acute Respiratory Illness Associated with Human Adenovirus Type 4 at the U.S. Coast Guard Academy, 2019.
Chu VT , Simon E , Lu X , Rockwell P , Abedi GR , Gardner C , Kujawski SA , Schneider E , Gentile M , Ramsey LA , Liu R , Jones S , Janik C , Siniscalchi A , Landry ML , Christopher J , Lindstrom S , Steiner S , Thomas D , Gerber SI , Biggs HM . J Infect Dis 2021 225 (1) 55-64 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 U.S. 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 PCR testing on patient and environmental samples and whole genome sequencing on a subset of positive patient samples. RESULTS: Among the 1,072 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, 113/228 (50%) cases reported duty restrictions. Of cases with respiratory specimens, 36/50 (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. |
Comparison of Estimated SARS-CoV-2 Seroprevalence through Commercial Laboratory Residual Sera Testing and a Community Survey.
Bajema KL , Dahlgren FS , Lim TW , Bestul N , Biggs HM , Tate JE , Owusu C , Szablewski CM , Drenzek C , Drobeniuc J , Semenova V , Li H , Browning P , Desai R , Epperson M , Jia LT , Thornburg NJ , Edens C , Fry AM , Hall AJ , Schiffer J , Havers FP . Clin Infect Dis 2020 73 (9) e3120-e3123 We compared severe acute respiratory syndrome-related coronavirus-2 seroprevalence estimated from commercial laboratory residual sera and a community household survey in metropolitan Atlanta during April-May 2020 and found these two estimates to be similar (4.94% versus 3.18%). Compared with more representative surveys, commercial sera can provide an approximate measure of seroprevalence. |
Enterovirus D68 infection among hospitalized children with severe acute respiratory illness in El Salvador and Panama, 2012-2013.
Biggs HM , Nix WA , Zhang J , Rogers S , Clara W , Jara JH , Gonzalez R , Luciani K , Brizuela YS , Estripeaut D , Castillo JM , De Leon T , Corro M , Vergara O , Rauda R , Chong EG , Watson JT , Azziz-Baumgartner E , Gerber SI , Tong S , Dawood FS . Influenza Other Respir Viruses 2020 15 (2) 181-187 We assessed EV-D68 epidemiology and phylogenetics among children aged ≤9 years hospitalized with severe acute respiratory illnesses at five sites in Panama and El Salvador during 2012-2013. Respiratory specimens positive for enterovirus or rhinovirus were tested by real-time RT-PCR for EV-D68, and partial VP1 gene sequences were determined. Of 715 enrolled children, 17 from sites in both countries were EV-D68-positive and commonly had a history of asthma or wheezing. Phylogenetically, 15 of 16 sequences fell into Clade B1, and one into Clade A2. The Central American EV-D68s were closely related genetically to contemporaneous strains from North America, South America, and the Caribbean. |
Molecular Detection and Typing of Pathogenic Leptospira in Febrile Patients and Phylogenetic Comparison with Leptospira Detected among Animals in Tanzania.
Allan KJ , Maze MJ , Galloway RL , Rubach MP , Biggs HM , Halliday JEB , Cleaveland S , Saganda W , Lwezaula BF , Kazwala RR , Mmbaga BT , Maro VP , Crump JA . Am J Trop Med Hyg 2020 103 (4) 1427-1434 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. |
Investigation of melioidosis using blood culture and indirect hemagglutination assay serology among patients with fever, Northern Tanzania
Maze MJ , Elrod MG , Biggs HM , Bonnewell J , Carugati M , Hoffmaster AR , Lwezaula BF , Madut DB , Maro VP , Mmbaga BT , Morrissey AB , Saganda W , Sakasaka P , Rubach MP , Crump JA . Am J Trop Med Hyg 2020 103 (6) 2510-2514 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. |
Enhanced contact investigations for nine early travel-related cases of SARS-CoV-2 in the United States.
Burke RM , Balter S , Barnes E , Barry V , Bartlett K , Beer KD , Benowitz I , Biggs HM , Bruce H , Bryant-Genevier J , Cates J , Chatham-Stephens K , Chea N , Chiou H , Christiansen D , Chu VT , Clark S , Cody SH , Cohen M , Conners EE , Dasari V , Dawson P , DeSalvo T , Donahue M , Dratch A , Duca L , Duchin J , Dyal JW , Feldstein LR , Fenstersheib M , Fischer M , Fisher R , Foo C , Freeman-Ponder B , Fry AM , Gant J , Gautom R , Ghinai I , Gounder P , Grigg CT , Gunzenhauser J , Hall AJ , Han GS , Haupt T , Holshue M , Hunter J , Ibrahim MB , Jacobs MW , Jarashow MC , Joshi K , Kamali T , Kawakami V , Kim M , Kirking HL , Kita-Yarbro A , Klos R , Kobayashi M , Kocharian A , Lang M , Layden J , Leidman E , Lindquist S , Lindstrom S , Link-Gelles R , Marlow M , Mattison CP , McClung N , McPherson TD , Mello L , Midgley CM , Novosad S , Patel MT , Pettrone K , Pillai SK , Pray IW , Reese HE , Rhodes H , Robinson S , Rolfes M , Routh J , Rubin R , Rudman SL , Russell D , Scott S , Shetty V , Smith-Jeffcoat SE , Soda EA , Spitters C , Stierman B , Sunenshine R , Terashita D , Traub E , Vahey GM , Verani JR , Wallace M , Westercamp M , Wortham J , Xie A , Yousaf A , Zahn M . PLoS One 2020 15 (9) e0238342 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. |
Surveillance and testing for Middle East respiratory syndrome coronavirus, Saudi Arabia, March 2016-March 2019
Alzahrani A , Kujawski SA , Abedi GR , Tunkar S , Biggs HM , Alghawi N , Jokhdar H , Assiri AM , Watson JT . Emerg Infect Dis 2020 26 (7) 1571-1574 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. |
Estimated Community Seroprevalence of SARS-CoV-2 Antibodies - Two Georgia Counties, April 28-May 3, 2020.
Biggs HM , Harris JB , Breakwell L , Dahlgren FS , Abedi GR , Szablewski CM , Drobeniuc J , Bustamante ND , Almendares O , Schnall AH , Gilani Z , Smith T , Gieraltowski L , Johnson JA , Bajema KL , McDavid K , Schafer IJ , Sullivan V , Punkova L , Tejada-Strop A , Amiling R , Mattison CP , Cortese MM , Ford SE , Paxton LA , Drenzek C , Tate JE , CDC Field Surveyor Team , Brown Nicole , Chang Karen T , Deputy Nicholas P , Desamu-Thorpe Rodel , Gorishek Chase , Hanchey Arianna , Melgar Michael , Monroe Benjamin P , Nielsen Carrie F , Pellegrini Gerald JJr , Shamout Mays , Tison Laura I , Vagi Sara , Zacks Rachael . MMWR Morb Mortal Wkly Rep 2020 69 (29) 965-970 Transmission of SARS-CoV-2, the virus that causes coronavirus disease 2019 (COVID-19), is ongoing in many communities throughout the United States. Although case-based and syndromic surveillance are critical for monitoring the pandemic, these systems rely on persons obtaining testing or reporting a COVID-19-like illness. Using serologic tests to detect the presence of SARS-CoV-2 antibodies is an adjunctive strategy that estimates the prevalence of past infection in a population. During April 28-May 3, 2020, coinciding with the end of a statewide shelter-in-place order, CDC and the Georgia Department of Public Health conducted a serologic survey in DeKalb and Fulton counties in metropolitan Atlanta to estimate SARS-CoV-2 seroprevalence in the population. A two-stage cluster sampling design was used to randomly select 30 census blocks in each county, with a target of seven participating households per census block. Weighted estimates were calculated to account for the probability of selection and adjusted for age group, sex, and race/ethnicity. A total of 394 households and 696 persons participated and had a serology result; 19 (2.7%) of 696 persons had SARS-CoV-2 antibodies detected. The estimated weighted seroprevalence across these two metropolitan Atlanta counties was 2.5% (95% confidence interval [CI] = 1.4-4.5). Non-Hispanic black participants more commonly had SARS-CoV-2 antibodies than did participants of other racial/ethnic groups (p<0.01). Among persons with SARS-CoV-2 antibodies, 13 (weighted % = 49.9; 95% CI = 24.4-75.5) reported a COVID-19-compatible illness,* six (weighted % = 28.2; 95% CI = 11.9-53.3) sought medical care for a COVID-19-compatible illness, and five (weighted % = 15.7; 95% CI = 5.1-39.4) had been tested for SARS-CoV-2 infection, demonstrating that many of these infections would not have been identified through case-based or syndromic surveillance. The relatively low seroprevalence estimate in this report indicates that most persons in the catchment area had not been infected with SARS-CoV-2 at the time of the survey. Continued preventive measures, including social distancing, consistent and correct use of face coverings, and hand hygiene, remain critical in controlling community spread of SARS-CoV-2. |
Investigation and Serologic Follow-Up of Contacts of an Early Confirmed Case-Patient with COVID-19, Washington, USA.
Chu VT , Freeman-Ponder B , Lindquist S , Spitters C , Kawakami V , Dyal JW , Clark S , Bruce H , Duchin JS , DeBolt C , Podczervinski S , D'Angeli M , Pettrone K , Zacks R , Vahey G , Holshue ML , Lang M , Burke RM , Rolfes MA , Marlow M , Midgley CM , Lu X , Lindstrom S , Hall AJ , Fry AM , Thornburg NJ , Gerber SI , Pillai SK , Biggs HM . Emerg Infect Dis 2020 26 (8) 1671-1678 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 approximately 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. |
Clinical and virologic characteristics of the first 12 patients with coronavirus disease 2019 (COVID-19) in the United States.
Kujawski SA , Wong KK , Collins JP , Epstein L , Killerby ME , Midgley CM , Abedi GR , Ahmed NS , Almendares O , Alvarez FN , Anderson KN , Balter S , Barry V , Bartlett K , Beer K , Ben-Aderet MA , Benowitz I , Biggs HM , Binder AM , Black SR , Bonin B , Bozio CH , Brown CM , Bruce H , Bryant-Genevier J , Budd A , Buell D , Bystritsky R , Cates J , Charles EM , Chatham-Stephens K , Chea N , Chiou H , Christiansen D , Chu V , Cody S , Cohen M , Conners EE , Curns AT , Dasari V , Dawson P , DeSalvo T , Diaz G , Donahue M , Donovan S , Duca LM , Erickson K , Esona MD , Evans S , Falk J , Feldstein LR , Fenstersheib M , Fischer M , Fisher R , Foo C , Fricchione MJ , Friedman O , Fry A , Galang RR , Garcia MM , Gerber SI , Gerrard G , Ghinai I , Gounder P , Grein J , Grigg C , Gunzenhauser JD , Gutkin GI , Haddix M , Hall AJ , Han GS , Harcourt J , Harriman K , Haupt T , Haynes AK , Holshue M , Hoover C , Hunter JC , Jacobs MW , Jarashow C , Joshi K , Kamali T , Kamili S , Kim L , Kim M , King J , Kirking HL , Kita-Yarbro A , Klos R , Kobayashi M , Kocharian A , Komatsu KK , Koppaka R , Layden JE , Li Y , Lindquist S , Lindstrom S , Link-Gelles R , Lively J , Livingston M , Lo K , Lo J , Lu X , Lynch B , Madoff L , Malapati L , Marks G , Marlow M , Mathisen GE , McClung N , McGovern O , McPherson TD , Mehta M , Meier A , Mello L , Moon SS , Morgan M , Moro RN , Murray J , Murthy R , Novosad S , Oliver SE , O’Shea J , Pacilli M , Paden CR , Pallansch MA , Patel M , Patel S , Pedraza I , Pillai SK , Pindyck T , Pray I , Queen K , Quick N , Reese H , Reporter R , Rha B , Rhodes H , Robinson S , Robinson P , Rolfes MA , Routh JA , Rubin R , Rudman SL , Sakthivel SK , Scott S , Shepherd C , Shetty V , Smith EA , Smith S , Stierman B , Stoecker W , Sunenshine R , Sy-Santos R , Tamin A , Tao Y , Terashita D , Thornburg NJ , Tong S , Traub E , Tural A , Uehara A , Uyeki TM , Vahey G , Verani JR , Villarino E , Wallace M , Wang L , Watson JT , Westercamp M , Whitaker B , Wilkerson S , Woodruff RC , Wortham JM , Wu T , Xie A , Yousaf A , Zahn M , Zhang J . Nat Med 2020 26 (6) 861-868 Data on the detailed clinical progression of COVID-19 in conjunction with epidemiological and virological characteristics are limited. In this case series, we describe the first 12 US patients confirmed to have COVID-19 from 20 January to 5 February 2020, including 4 patients described previously(1-3). Respiratory, stool, serum and urine specimens were submitted for SARS-CoV-2 real-time reverse-transcription polymerase chain reaction (rRT-PCR) testing, viral culture and whole genome sequencing. Median age was 53 years (range: 21-68); 8 patients were male. Common symptoms at illness onset were cough (n = 8) and fever (n = 7). Patients had mild to moderately severe illness; seven were hospitalized and demonstrated clinical or laboratory signs of worsening during the second week of illness. No patients required mechanical ventilation and all recovered. All had SARS-CoV-2 RNA detected in respiratory specimens, typically for 2-3 weeks after illness onset. Lowest real-time PCR with reverse transcription cycle threshold values in the upper respiratory tract were often detected in the first week and SARS-CoV-2 was cultured from early respiratory specimens. These data provide insight into the natural history of SARS-CoV-2. Although infectiousness is unclear, highest viral RNA levels were identified in the first week of illness. Clinicians should anticipate that some patients may worsen in the second week of illness. |
Estimating acute human leptospirosis incidence in northern Tanzania using sentinel site and community behavioural surveillance
Maze MJ , Sharples KJ , Allan KJ , Biggs HM , Cash-Goldwasser S , Galloway RL , de Glanville WA , Halliday JEB , Kazwala RR , Kibona T , Mmbaga BT , Maro VP , Rubach MP , Cleaveland S , Crump JA . Zoonoses Public Health 2020 67 (5) 496-505 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. |
Outbreaks of adenovirus-associated respiratory illness on five college campuses in the United States.
Kujawski SA , Lu X , Schneider E , Blythe D , Boktor S , Farrehi J , Haupt T , McBride D , Stephens E , Sakthivel SK , Bachaus B , Waller K , Bauman L , Marconi A , Lewis R , Dettinger L , Ernst R , Kinsey W , Lindstrom S , Gerber SI , Watson JT , Biggs HM . Clin Infect Dis 2020 72 (11) 1992-1999 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, five U.S. colleges reported increases in HAdV-associated respiratory illness. Investigations were performed to better understand HAdV epidemiology in this setting. METHODS: A case was a student at one of the five 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 PCR 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; two 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 five U.S. college campuses. HAdVs should be considered a cause of respiratory illness outbreaks in congregate settings such as college campuses. |
Persons Evaluated for 2019 Novel Coronavirus - United States, January 2020.
Bajema KL , Oster AM , McGovern OL , Lindstrom S , Stenger MR , Anderson TC , Isenhour C , Clarke KR , Evans ME , Chu VT , Biggs HM , Kirking HL , Gerber SI , Hall AJ , Fry AM , Oliver SE . MMWR Morb Mortal Wkly Rep 2020 69 (6) 166-170 In December 2019, a cluster of cases of pneumonia emerged in Wuhan City in central China's Hubei Province. Genetic sequencing of isolates obtained from patients with pneumonia identified a novel coronavirus (2019-nCoV) as the etiology (1). As of February 4, 2020, approximately 20,000 confirmed cases had been identified in China and an additional 159 confirmed cases in 23 other countries, including 11 in the United States (2,3). On January 17, CDC and the U.S. Department of Homeland Security's Customs and Border Protection began health screenings at U.S. airports to identify ill travelers returning from Wuhan City (4). CDC activated its Emergency Operations Center on January 21 and formalized a process for inquiries regarding persons suspected of having 2019-nCoV infection (2). As of January 31, 2020, CDC had responded to clinical inquiries from public health officials and health care providers to assist in evaluating approximately 650 persons thought to be at risk for 2019-nCoV infection. Guided by CDC criteria for the evaluation of persons under investigation (PUIs) (5), 210 symptomatic persons were tested for 2019-nCoV; among these persons, 148 (70%) had travel-related risk only, 42 (20%) had close contact with an ill laboratory-confirmed 2019-nCoV patient or PUI, and 18 (9%) had both travel- and contact-related risks. Eleven of these persons had laboratory-confirmed 2019-nCoV infection. Recognizing persons at risk for 2019-nCoV is critical to identifying cases and preventing further transmission. Health care providers should remain vigilant and adhere to recommended infection prevention and control practices when evaluating patients for possible 2019-nCoV infection (6). Providers should consult with their local and state health departments when assessing not only ill travelers from 2019-nCoV-affected countries but also ill persons who have been in close contact with patients with laboratory-confirmed 2019-nCoV infection in the United States. |
First Case of 2019 Novel Coronavirus in the United States.
Holshue ML , DeBolt C , Lindquist S , Lofy KH , Wiesman J , Bruce H , Spitters C , Ericson K , Wilkerson S , Tural A , Diaz G , Cohn A , Fox L , Patel A , Gerber SI , Kim L , Tong S , Lu X , Lindstrom S , Pallansch MA , Weldon WC , Biggs HM , Uyeki TM , Pillai SK . N Engl J Med 2020 382 (10) 929-936 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. |
Sensitivity of C-reactive protein for the identification of patients with laboratory-confirmed bacterial infections in northern Tanzania
Althaus T , Lubell Y , Maro VP , Mmbaga BT , Lwezaula B , Halleux C , Biggs HM , Galloway RL , Stoddard RA , Perniciaro JL , Nicholson WL , Doyle K , Olliaro P , Crump JA , Rubach MP . Trop Med Int Health 2019 25 (3) 291-300 OBJECTIVE: Identifying febrile patients requiring antibacterial treatment is challenging, particularly in low-resource settings. In Southeast 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. METHODS: 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 titer 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 etiologies and because ascertaining true negative cases was limited by the imperfect sensitivity of the diagnostic tests used to identify bacterial infections. RESULTS: 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%), 90% (74-97%) for identifying bacterial BSI, and 87% (76-93%), 82% (71-90%), 72% (60-82%) for bacterial zoonoses, using thresholds of 10, 20 and 40mg/L respectively. CONCLUSION: CRP 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. |
Severe human metapneumovirus and group A Streptococcus pneumonia in an immunocompetent adult
Biggs HM , Van Beneden CA , Kurkjian K , Kobayashi M , Peret TCT , Watson JT , Schneider E , Gerber SI , Ravishankar J . Clin Infect Dis 2019 70 (12) 2712-2714 An immunocompetent adult with asthma developed severe human metapneumovirus (HMPV) illness complicated by group A Streptococcus coinfection, progressing to ARDS 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. |
Underdetection of laboratory-confirmed influenza-associated hospital admissions among infants: a multicentre, prospective study
Thompson MG , Levine MZ , Bino S , Hunt DR , Al-Sanouri TM , Simoes EAF , Porter RM , Biggs HM , Gresh L , Simaku A , Khader IA , Tallo VL , Meece JK , McMorrow M , Mercado ES , Joshi S , DeGroote NP , Hatibi I , Sanchez F , Lucero MG , Faouri S , Jefferson SN , Maliqari N , Balmaseda A , Sanvictores D , Holiday C , Sciuto C , Owens Z , Azziz-Baumgartner E , Gordon A . Lancet Child Adolesc Health 2019 3 (11) 781-794 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. |
Adenovirus-associated influenza-like illness among college students, Pennsylvania, USA
Biggs HM , Lu X , Dettinger L , Sakthivel S , Watson JT , Boktor SW . Emerg Infect Dis 2018 24 (11) 2117-2119 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. |
Scope and extent of healthcare-associated Middle East respiratory syndrome coronavirus transmission during two contemporaneous outbreaks in Riyadh, Saudi Arabia, 2017.
Alanazi KH , Killerby ME , Biggs HM , Abedi GR , Jokhdar H , Alsharef AA , Mohammed M , Abdalla O , Almari A , Bereagesh S , Tawfik S , Alresheedi H , Alhakeem RF , Hakawi A , Alfalah H , Amer H , Thornburg NJ , Tamin A , Trivedi S , Tong S , Lu X , Queen K , Li Y , Sakthivel SK , Tao Y , Zhang J , Paden CR , Al-Abdely HM , Assiri AM , Gerber SI , Watson JT . Infect Control Hosp Epidemiol 2019 40 (1) 79-88 OBJECTIVE: To 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. DESIGN: Outbreak investigation. SETTING: Cases 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. METHODS: Contact 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. RESULTS: In 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. CONCLUSIONS: We 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. |
The phylogeography and incidence of multi-drug resistant typhoid fever in sub-Saharan Africa.
Park SE , Pham DT , Boinett C , Wong VK , Pak GD , Panzner U , Espinoza LMC , von Kalckreuth V , Im J , Schutt-Gerowitt H , Crump JA , Breiman RF , Adu-Sarkodie Y , Owusu-Dabo E , Rakotozandrindrainy R , Soura AB , Aseffa A , Gasmelseed N , Keddy KH , May J , Sow AG , Aaby P , Biggs HM , Hertz JT , Montgomery JM , Cosmas L , Fields B , Sarpong N , Razafindrabe TJL , Raminosoa TM , Kabore LP , Sampo E , Teferi M , Yeshitela B , El Tayeb MA , Sooka A , Meyer CG , Krumkamp R , Dekker DM , Jaeger A , Poppert S , Tall A , Niang A , Bjerregaard-Andersen M , Valborg Løfberg S , Seo HJ , Jeon HJ , Deerin JF , Park J , Konings F , Ali M , Clemens JD , Hughes P , Sendagala JN , Vudriko T , Downing R , Ikumapayi UN , Mackenzie GA , Obaro S , Argimon S , Aanensen DM , Page A , Keane JA , Duchene S , Dyson Z , Holt KE , Dougan G , Marks F , Baker S . Nat Commun 2018 9 (1) 5094 There is paucity of data regarding the geographical distribution, incidence, and phylogenetics of multi-drug resistant (MDR) Salmonella Typhi in sub-Saharan Africa. Here we present a phylogenetic reconstruction of whole genome sequenced 249 contemporaneous S. Typhi isolated between 2008-2015 in 11 sub-Saharan African countries, in context of the 2,057 global S. Typhi genomic framework. Despite the broad genetic diversity, the majority of organisms (225/249; 90%) belong to only three genotypes, 4.3.1 (H58) (99/249; 40%), 3.1.1 (97/249; 39%), and 2.3.2 (29/249; 12%). Genotypes 4.3.1 and 3.1.1 are confined within East and West Africa, respectively. MDR phenotype is found in over 50% of organisms restricted within these dominant genotypes. High incidences of MDR S. Typhi are calculated in locations with a high burden of typhoid, specifically in children aged <15 years. Antimicrobial stewardship, MDR surveillance, and the introduction of typhoid conjugate vaccines will be critical for the control of MDR typhoid in Africa. |
Multihospital Outbreak of a Middle East Respiratory Syndrome Coronavirus Deletion Variant, Jordan: A Molecular, Serologic, and Epidemiologic Investigation.
Payne DC , Biggs HM , Al-Abdallat MM , Alqasrawi S , Lu X , Abedi GR , Haddadin A , Iblan I , Alsanouri T , Al Nsour M , Sheikh Ali S , Rha B , Trivedi SU , Rasheed MAU , Tamin A , Lamers MM , Haagmans BL , Erdman DD , Thornburg NJ , Gerber SI . Open Forum Infect Dis 2018 5 (5) ofy095 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. |
Incidence of human brucellosis in the Kilimanjaro Region of Tanzania in the periods 2007-2008 and 2012-2014
Carugati M , Biggs HM , Maze MJ , Stoddard RA , Cash-Goldwasser S , Hertz JT , Halliday JEB , Saganda W , Lwezaula BF , Kazwala RR , Cleaveland S , Maro VP , Rubach MP , Crump JA . Trans R Soc Trop Med Hyg 2018 112 (3) 136-143 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. |
Risk factors for human acute leptospirosis in northern Tanzania
Maze MJ , Cash-Goldwasser S , Rubach MP , Biggs HM , Galloway RL , Sharples KJ , Allan KJ , Halliday JEB , Cleaveland S , Shand MC , Muiruri C , Kazwala RR , Saganda W , Lwezaula BF , Mmbaga BT , Maro VP , Crump JA . PLoS Negl Trop Dis 2018 12 (6) e0006372 INTRODUCTION: Leptospirosis is a major cause of febrile illness in Africa but little is known about risk factors for human infection. We conducted a cross-sectional study to investigate risk factors for acute leptospirosis and Leptospira seropositivity among patients with fever attending referral hospitals in northern Tanzania. METHODS: We enrolled patients with fever from two referral hospitals in Moshi, Tanzania, 2012-2014, and performed Leptospira microscopic agglutination testing on acute and convalescent serum. Cases of acute leptospirosis were participants with a four-fold rise in antibody titers, or a single reciprocal titer >/=800. Seropositive participants required a single titer >/=100, and controls had titers <100 in both acute and convalescent samples. We administered a questionnaire to assess risk behaviors over the preceding 30 days. We created cumulative scales of exposure to livestock urine, rodents, and surface water, and calculated odds ratios (OR) for individual behaviors and for cumulative exposure variables. RESULTS: We identified 24 acute cases, 252 seropositive participants, and 592 controls. Rice farming (OR 14.6), cleaning cattle waste (OR 4.3), feeding cattle (OR 3.9), farm work (OR 3.3), and an increasing cattle urine exposure score (OR 1.2 per point) were associated with acute leptospirosis. CONCLUSIONS: In our population, exposure to cattle and rice farming were risk factors for acute leptospirosis. Although further data is needed, these results suggest that cattle may be an important source of human leptospirosis. Further investigation is needed to explore the potential for control of livestock Leptospira infection to reduce human disease. |
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