Last data update: Jun 20, 2025. (Total: 49421 publications since 2009)
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Query Trace: Aura B[original query] |
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2020 taxonomic update for phylum Negarnaviricota (Riboviria: Orthornavirae), including the large orders Bunyavirales and Mononegavirales.
Kuhn JH , Adkins S , Alioto D , Alkhovsky SV , Amarasinghe GK , Anthony SJ , Avšič-Županc T , Ayllón MA , Bahl J , Balkema-Buschmann A , Ballinger MJ , Bartonička T , Basler C , Bavari S , Beer M , Bente DA , Bergeron É , Bird BH , Blair C , Blasdell KR , Bradfute SB , Breyta R , Briese T , Brown PA , Buchholz UJ , Buchmeier MJ , Bukreyev A , Burt F , Buzkan N , Calisher CH , Cao M , Casas I , Chamberlain J , Chandran K , Charrel RN , Chen B , Chiumenti M , Choi IR , Clegg JCS , Crozier I , da Graça JV , Dal Bó E , Dávila AMR , de la Torre JC , de Lamballerie X , de Swart RL , Di Bello PL , Di Paola N , Di Serio F , Dietzgen RG , Digiaro M , Dolja VV , Dolnik O , Drebot MA , Drexler JF , Dürrwald R , Dufkova L , Dundon WG , Duprex WP , Dye JM , Easton AJ , Ebihara H , Elbeaino T , Ergünay K , Fernandes J , Fooks AR , Formenty PBH , Forth LF , Fouchier RAM , Freitas-Astúa J , Gago-Zachert S , Gāo GF , García ML , García-Sastre A , Garrison AR , Gbakima A , Goldstein T , Gonzalez JJ , Griffiths A , Groschup MH , Günther S , Guterres A , Hall RA , Hammond J , Hassan M , Hepojoki J , Hepojoki S , Hetzel U , Hewson R , Hoffmann B , Hongo S , Höper D , Horie M , Hughes HR , Hyndman TH , Jambai A , Jardim R , Jiāng D , Jin Q , Jonson GB , Junglen S , Karadağ S , Keller KE , Klempa B , Klingström J , Kobinger G , Kondō H , Koonin EV , Krupovic M , Kurath G , Kuzmin IV , Laenen L , Lamb RA , Lambert AJ , Langevin SL , Lee B , Lemos ERS , Leroy EM , Li D , Lǐ J , Liang M , Liú W , Liú Y , Lukashevich IS , Maes P , Marciel de Souza W , Marklewitz M , Marshall SH , Martelli GP , Martin RR , Marzano SL , Massart S , McCauley JW , Mielke-Ehret N , Minafra A , Minutolo M , Mirazimi A , Mühlbach HP , Mühlberger E , Naidu R , Natsuaki T , Navarro B , Navarro JA , Netesov SV , Neumann G , Nowotny N , Nunes MRT , Nylund A , Økland AL , Oliveira RC , Palacios G , Pallas V , Pályi B , Papa A , Parrish CR , Pauvolid-Corrêa A , Pawęska JT , Payne S , Pérez DR , Pfaff F , Radoshitzky SR , Rahman AU , Ramos-González PL , Resende RO , Reyes CA , Rima BK , Romanowski V , Robles Luna G , Rota P , Rubbenstroth D , Runstadler JA , Ruzek D , Sabanadzovic S , Salát J , Sall AA , Salvato MS , Sarpkaya K , Sasaya T , Schwemmle M , Shabbir MZ , Shí X , Shí Z , Shirako Y , Simmonds P , Širmarová J , Sironi M , Smither S , Smura T , Song JW , Spann KM , Spengler JR , Stenglein MD , Stone DM , Straková P , Takada A , Tesh RB , Thornburg NJ , Tomonaga K , Tordo N , Towner JS , Turina M , Tzanetakis I , Ulrich RG , Vaira AM , van den Hoogen B , Varsani A , Vasilakis N , Verbeek M , Wahl V , Walker PJ , Wang H , Wang J , Wang X , Wang LF , Wèi T , Wells H , Whitfield AE , Williams JV , Wolf YI , Wú Z , Yang X , Yáng X , Yu X , Yutin N , Zerbini FM , Zhang T , Zhang YZ , Zhou G , Zhou X . Arch Virol 2020 165 (12) 3023-3072 ![]() In March 2020, following the annual International Committee on Taxonomy of Viruses (ICTV) ratification vote on newly proposed taxa, the phylum Negarnaviricota was amended and emended. At the genus rank, 20 new genera were added, two were deleted, one was moved, and three were renamed. At the species rank, 160 species were added, four were deleted, ten were moved and renamed, and 30 species were renamed. This article presents the updated taxonomy of Negarnaviricota as now accepted by the ICTV. |
Taxonomy of the order Bunyavirales: update 2019.
Abudurexiti A , Adkins S , Alioto D , Alkhovsky SV , Avsic-Zupanc T , Ballinger MJ , Bente DA , Beer M , Bergeron E , Blair CD , Briese T , Buchmeier MJ , Burt FJ , Calisher CH , Chang C , Charrel RN , Choi IR , Clegg JCS , de la Torre JC , de Lamballerie X , Deng F , Di Serio F , Digiaro M , Drebot MA , Duan X , Ebihara H , Elbeaino T , Ergunay K , Fulhorst CF , Garrison AR , Gao GF , Gonzalez JJ , Groschup MH , Gunther S , Haenni AL , Hall RA , Hepojoki J , Hewson R , Hu Z , Hughes HR , Jonson MG , Junglen S , Klempa B , Klingstrom J , Kou C , Laenen L , Lambert AJ , Langevin SA , Liu D , Lukashevich IS , Luo T , Lu C , Maes P , de Souza WM , Marklewitz M , Martelli GP , Matsuno K , Mielke-Ehret N , Minutolo M , Mirazimi A , Moming A , Muhlbach HP , Naidu R , Navarro B , Nunes MRT , Palacios G , Papa A , Pauvolid-Correa A , Paweska JT , Qiao J , Radoshitzky SR , Resende RO , Romanowski V , Sall AA , Salvato MS , Sasaya T , Shen S , Shi X , Shirako Y , Simmonds P , Sironi M , Song JW , Spengler JR , Stenglein MD , Su Z , Sun S , Tang S , Turina M , Wang B , Wang C , Wang H , Wang J , Wei T , Whitfield AE , Zerbini FM , Zhang J , Zhang L , Zhang Y , Zhang YZ , Zhang Y , Zhou X , Zhu L , Kuhn JH . Arch Virol 2019 164 (7) 1949-1965 ![]() In February 2019, following the annual taxon ratification vote, the order Bunyavirales was amended by creation of two new families, four new subfamilies, 11 new genera and 77 new species, merging of two species, and deletion of one species. This article presents the updated taxonomy of the order Bunyavirales now accepted by the International Committee on Taxonomy of Viruses (ICTV). |
Reply
Tepper NK , Curtis KM , Champaloux SW . Am J Obstet Gynecol 2018 218 (3) 364-365 We thank Drs Driul and Londero for their interest in our study.1 We agree that thrombogenic mutations may be a contributing factor in migraine-related stroke. We did not adjust for known thrombogenic mutations; however, because combined hormonal contraceptives (CHCs) are not recommended for use by women with known thrombogenic mutations because of safety concerns,2 we expect that there would be only a small number of women with those disorders who use CHCs. Our analysis adjusted for the important confounders mentioned by Drs Driul and Londero, namely age, hypertension, smoking, and obesity as well as others that included diabetes mellitus, ischemic heart disease, and valvular heart disease, while noting the potential for misclassification from the use of healthcare claims data. Because of the use of healthcare claims data, we could not assess migraine or aura frequency. Although there is some evidence that migraine frequency impacts stroke risk,3 it is not clear whether aura frequency is related to stroke risk; these associations warrant further study. | | We agree that the mechanism of ischemic stroke related to migraine with aura is not well understood and probably involves multiple mechanisms.3 The pathways may include cerebral hypoperfusion related to the aura, arterial dissections, patent foramen ovale, or the presence of vascular risk factors.3 Although these complex mechanisms need to be further clarified, migraine with aura is associated independently with an increased risk of ischemic stroke.3 Given that CHCs are also associated with an elevated risk of ischemic stroke, even at lower doses of ethinyl estradiol (including 20 μg),4 and that stroke is a devastating event, concerns remain about the use of CHCs in women who experience migraine with aura. Based on current understanding of mechanisms, it is not clear that there are subgroups of women with migraine with aura (eg, women without a thrombogenic mutation) for whom CHCs would not further elevate the risk of stroke to an unacceptable level.2 In addition, the prevalence of thrombogenic mutations is low, and the cost of screening is high; therefore, screening is not recommended before considering whether to use CHCs.2 | | Future studies are needed on the pathophysiology and magnitude of risk of stroke related to migraine, hormonal contraceptives, and other stroke risk factors. Such research would contribute to better understanding the safety of hormonal contraceptive use among women with migraine. Healthcare providers should counsel women about risks, benefits, and alternatives so that women can make informed decisions about contraceptive method choice. |
A DNA vaccine for Crimean-Congo hemorrhagic fever protects against disease and death in two lethal mouse models.
Garrison AR , Shoemaker CJ , Golden JW , Fitzpatrick CJ , Suschak JJ , Richards MJ , Badger CV , Six CM , Martin JD , Hannaman D , Zivcec M , Bergeron E , Koehler JW , Schmaljohn CS . PLoS Negl Trop Dis 2017 11 (9) e0005908 ![]() Crimean-Congo hemorrhagic fever virus (CCHFV) is a tick-borne virus capable of causing a severe hemorrhagic fever disease in humans. There are currently no licensed vaccines to prevent CCHFV-associated disease. We developed a DNA vaccine expressing the M-segment glycoprotein precursor gene of CCHFV and assessed its immunogenicity and protective efficacy in two lethal mouse models of disease: type I interferon receptor knockout (IFNAR-/-) mice; and a novel transiently immune suppressed (IS) mouse model. Vaccination of mice by muscle electroporation of the M-segment DNA vaccine elicited strong antigen-specific humoral immune responses with neutralizing titers after three vaccinations in both IFNAR-/- and IS mouse models. To compare the protective efficacy of the vaccine in the two models, groups of vaccinated mice (7-10 per group) were intraperitoneally (IP) challenged with a lethal dose of CCHFV strain IbAr 10200. Weight loss was markedly reduced in CCHFV DNA-vaccinated mice as compared to controls. Furthermore, whereas all vector-control vaccinated mice succumbed to disease by day 5, the DNA vaccine protected >60% of the animals from lethal disease. Mice from both models developed comparable levels of antibodies, but the IS mice had a more balanced Th1/Th2 response to vaccination. There were no statistical differences in the protective efficacies of the vaccine in the two models. Our results provide the first comparison of these two mouse models for assessing a vaccine against CCHFV and offer supportive data indicating that a DNA vaccine expressing the glycoprotein genes of CCHFV elicits protective immunity against CCHFV. |
Use of combined hormonal contraceptives among women with migraines and risk of ischemic stroke
Champaloux SW , Tepper NK , Monsour M , Curtis KM , Whiteman MK , Marchbanks PA , Jamieson DJ . Am J Obstet Gynecol 2016 216 (5) 489 e1-489 e7 BACKGROUND: Migraine with aura and combined hormonal contraceptives are independently associated with an increased risk of ischemic stroke. However, little is known about whether there are any joint effects of migraine and hormonal contraceptives on risk of stroke. OBJECTIVE: To estimate the incidence of stroke in women of reproductive age and examine the association between combined hormonal contraceptive use, migraine type (with or without aura), and ischemic stroke. STUDY DESIGN: This study used a nationwide health care claims database and employed a nested case control study design. Women ages 15-49 years with first-ever stroke during 2006-2012 were identified using the International Classification of Diseases-9th Revision-Clinical Modifications inpatient services diagnosis codes. Four controls were matched to each case based on age. Migraine headache with and without aura was identified using inpatient or outpatient diagnosis codes. Current combined hormonal contraceptive use was identified using the National Drug Code from the pharmacy database. Conditional logistic regression was used to estimate adjusted odds ratios and 95% confidence intervals of ischemic stroke by migraine type and combined hormonal contraceptive use. RESULTS: Between 2006-2012, there were 25,887 ischemic strokes among women ages 15-49, for a cumulative incidence of 11 strokes per 100,000 women. Compared to women with neither migraine nor combined hormonal contraceptive use, the odds ratio of ischemic stroke was highest among women with migraine with aura using combined hormonal contraceptives (odds ratio 6.1, 95% confidence interval 3.1-12.1); odds ratios were also elevated for migraine with aura without combined hormonal contraceptive use (odds ratio 2.7, 95% confidence interval 1.9-3.7), migraine without aura and combined hormonal contraceptive use (odds ratio 1.8, 95% confidence interval 1.1-2.9), and migraine without aura without combined hormonal contraceptive use (odds ratio 2.2, 95% confidence interval 1.9-2.7). CONCLUSION: The joint effect of combined hormonal contraceptives and migraine with aura was associated with a 6-fold increased risk of ischemic stroke compared with neither risk factor. Use of combined hormonal contraceptives did not substantially further increase risk of ischemic stroke among women with migraine without aura. Determining migraine type is critical in assessing safety of combined hormonal contraceptives among women with migraine. |
Safety of hormonal contraceptives among women with migraine: A systematic review
Tepper NK , Whiteman MK , Zapata LB , Marchbanks PA , Curtis KM . Contraception 2016 94 (6) 630-640 BACKGROUND: Migraine is common among women of reproductive age and is associated with an increased risk of ischemic stroke. Combined oral contraceptives (COCs) are also associated with an increased risk of ischemic stroke. Use of hormonal contraception among women with migraine might further elevate the risk of stroke among women of reproductive age. OBJECTIVE: To identify evidence regarding the risk of arterial thromboembolism (stroke or myocardial infarction) among women with migraine who use hormonal contraceptives. METHODS: We searched the PubMed database for all articles published from database inception through January 2016. We included studies that examined women with migraine overall or separated by subtype (with or without aura). Hormonal contraceptives of interest included combined hormonal methods (COCs, patch, and ring) and progestin-only methods (progestin-only pills, injectables, implants, and progestin intrauterine devices). RESULTS: Seven articles met inclusion criteria. All were case-control studies of fair to poor quality reporting on use of COCs or oral contraceptives (OCs) not further described and all reported stroke outcomes. Four studies demonstrated that, among women with migraine (not separated by subtype), COC use was associated with approximately 2-4 times the risk of stroke compared with non-use. The only study to examine specific migraine subtypes found an elevated risk of stroke among women with migraine with aura, and this risk was similar regardless of OC use, although these odds ratios were not reported. Two studies did not report risks among women with migraine and COC use combined, but both found increased risks of stroke with migraine and COC use independently. No evidence was found on other hormonal contraceptives or on risk of myocardial infarction. CONCLUSION: Limited evidence suggests a 2-4 fold increased risk of stroke among women with migraine who use COCs compared with non-use. Additional study is needed on the risks of hormonal contraceptives, including combined and progestin-only methods, among women with different migraine subtypes. |
A Multiplex PCR/LDR Assay for the Simultaneous Identification of Category A Infectious Pathogens: Agents of Viral Hemorrhagic Fever and Variola Virus.
Das S , Rundell MS , Mirza AH , Pingle MR , Shigyo K , Garrison AR , Paragas J , Smith SK , Olson VA , Larone DH , Spitzer ED , Barany F , Golightly LM . PLoS One 2015 10 (9) e0138484 ![]() CDC designated category A infectious agents pose a major risk to national security and require special action for public health preparedness. They include viruses that cause viral hemorrhagic fever (VHF) syndrome as well as variola virus, the agent of smallpox. VHF is characterized by hemorrhage and fever with multi-organ failure leading to high morbidity and mortality. Smallpox, a prior scourge, has been eradicated for decades, making it a particularly serious threat if released nefariously in the essentially non-immune world population. Early detection of the causative agents, and the ability to distinguish them from other pathogens, is essential to contain outbreaks, implement proper control measures, and prevent morbidity and mortality. We have developed a multiplex detection assay that uses several species-specific PCR primers to generate amplicons from multiple pathogens; these are then targeted in a ligase detection reaction (LDR). The resultant fluorescently-labeled ligation products are detected on a universal array enabling simultaneous identification of the pathogens. The assay was evaluated on 32 different isolates associated with VHF (ebolavirus, marburgvirus, Crimean Congo hemorrhagic fever virus, Lassa fever virus, Rift Valley fever virus, Dengue virus, and Yellow fever virus) as well as variola virus and vaccinia virus (the agent of smallpox and its vaccine strain, respectively). The assay was able to detect all viruses tested, including 8 sequences representative of different variola virus strains from the CDC repository. It does not cross react with other emerging zoonoses such as monkeypox virus or cowpox virus, or six flaviviruses tested (St. Louis encephalitis virus, Murray Valley encephalitis virus, Powassan virus, Tick-borne encephalitis virus, West Nile virus and Japanese encephalitis virus). |
The impact of home-based HIV counseling and testing on care-seeking and incidence of common infectious disease syndromes in rural western Kenya
Bigogo G , Amolloh M , Laserson KF , Audi A , Aura B , Dalal W , Ackers M , Burton D , Breiman RF , Feikin DR . BMC Infect Dis 2014 14 (1) 376 BACKGROUND: In much of Africa, most individuals living with HIV do not know their status. Home-based counseling and testing (HBCT) leads to more HIV-infected people learning their HIV status. However, there is little data on whether knowing one's HIV-positive status necessarily leads to uptake of HIV care, which could in turn, lead to a reduction in the prevalence of common infectious disease syndromes. METHODS: In 2008, Kenya Medical Research Institute (KEMRI) in collaboration with the Centers for Disease Control and Prevention (CDC) offered HBCT to individuals (aged ≥13 years) under active surveillance for infectious disease syndromes in Lwak in rural western Kenya. HIV test results were linked to morbidity and healthcare-seeking data collected by field workers through bi-weekly home visits. We analyzed changes in healthcare seeking behaviors using proportions, and incidence (expressed as episodes per person-year) of acute respiratory illness (ARI), severe acute respiratory illness (SARI), acute febrile illness (AFI) and diarrhea among first-time HIV testers in the year before and after HBCT, stratified by their test result and if HIV-positive, whether they sought care at HIV Patient Support Centers (PSCs). RESULTS: Of 9,613 individuals offered HBCT, 6,366 (66%) were first-time testers, 698 (11%) of whom were HIV-infected. One year after HBCT, 50% of HIV-infected persons had enrolled at PSCs - 92% of whom had started cotrimoxazole and 37% of those eligible for antiretroviral treatment had initiated therapy. Among HIV-infected persons enrolled in PSCs, AFI and diarrhea incidence decreased in the year after HBCT (rate ratio [RR] 0.84; 95% confidence interval [CI] 0.77 - 0.91 and RR 0.84, 95% CI 0.73 - 0.98, respectively). Among HIV-infected persons not attending PSCs and among HIV-uninfected persons, decreases in incidence were significantly lower. While decreases also occurred in rates of respiratory illnesses among HIV-positive persons in care, there were similar decreases in the other two groups. CONCLUSIONS: Large scale HBCT enabled a large number of newly diagnosed HIV-infected persons to know their HIV status, leading to a change in care seeking behavior and ultimately a decrease in incidence of common infectious disease syndromes through appropriate treatment and care. |
Epidemiology of respiratory syncytial virus infection in rural and urban Kenya
Bigogo GM , Breiman RF , Feikin DR , Audi AO , Aura B , Cosmas L , Njenga MK , Fields BS , Omballa V , Njuguna H , Ochieng PM , Mogeni DO , Aol GO , Olack B , Katz MA , Montgomery JM , Burton DC . J Infect Dis 2013 208 Suppl 3 S207-16 ![]() BACKGROUND: Information on the epidemiology of respiratory syncytial virus (RSV) infection in Africa is limited for crowded urban areas and for rural areas where the prevalence of malaria is high. METHODS: At referral facilities in rural western Kenya and a Nairobi slum, we collected nasopharyngeal/oropharyngeal (NP/OP) swab specimens from patients with influenza-like illness (ILI) or severe acute respiratory illness (SARI) and from asymptomatic controls. Polymerase chain reaction assays were used for detection of viral pathogens. We calculated age-specific ratios of the odds of RSV detection among patients versus the odds among controls. Incidence was expressed as the number of episodes per 1000 person-years of observation. RESULTS: Between March 2007 and February 2011, RSV was detected in 501 of 4012 NP/OP swab specimens (12.5%) from children and adults in the rural site and in 321 of 2744 NP/OP swab specimens (11.7%) from those in the urban site. Among children aged <5 years, RSV was detected more commonly among rural children with SARI (odds ratio [OR], 2.0; 95% confidence interval [CI], 1.2-3.3), urban children with SARI (OR, 8.5; 95% CI, 3.1-23.6), and urban children with ILI (OR, 3.4; 95% CI, 1.2-9.6), compared with controls. The incidence of RSV disease was highest among infants with SARI aged <1 year (86.9 and 62.8 episodes per 1000 person-years of observation in rural and urban sites, respectively). CONCLUSIONS: An effective RSV vaccine would likely substantially reduce the burden of respiratory illness among children in rural and urban areas in Africa. |
Association of the CT values of real-time PCR of viral upper respiratory tract infection with clinical severity, Kenya
Fuller JA , Njenga MK , Bigogo G , Aura B , Ope MO , Nderitu L , Wakhule L , Erdman DD , Breiman RF , Feikin DR . J Med Virol 2013 85 (5) 924-32 Quantitative real-time polymerase chain reaction (qRT-PCR) assay of the upper respiratory tract is used increasingly to diagnose lower respiratory tract infections. The cycle threshold (CT) values of qRT-PCR are continuous, semi-quantitative measurements of viral load, although interpretation of diagnostic qRT-PCR results are often categorized as positive, indeterminate, or negative, obscuring potentially useful clinical interpretation of CT values. From 2008 to 2010, naso/oropharyngeal swabs were collected from outpatients with influenza-like illness, inpatients with severe respiratory illness, and asymptomatic controls in rural Kenya. CT values of positive specimens (i.e., CT values < 40.0) were compared by clinical severity category for five viruses using Mann-Whitney U-test and logistic regression. Among children <5 years old we tested with respiratory syncytial virus (RSV), inpatients had lower median CT values (27.2) than controls (35.8, P = 0.008) and outpatients (34.7, P < 0.001). Among children and older patients infected with influenza virus, outpatients had the lowest median CT values (29.8 and 24.1, respectively) compared with controls (P = 0.193 for children, P < 0.001 for older participants) and inpatients (P = 0.009 for children, P < 0.001 for older participants). All differences remained significant in logistic regression when controlling for age, days since onset, and coinfection. CT values were similar for adenovirus, human metapneumovirus, and parainfluenza virus in all severity groups. In conclusion, the CT values from the qRT-PCR of upper respiratory tract specimens were associated with clinical severity for some respiratory viruses. (J. Med. Virol. 85:924-932, 2013. (c) 2013 Wiley Periodicals, Inc.) |
Epidemiology, seasonality, and burden of influenza and influenza-like illness in urban and rural Kenya, 2007-2010
Katz MA , Lebo E , Emukule G , Njuguna HN , Aura B , Cosmas L , Audi A , Junghae M , Waiboci LW , Olack B , Bigogo G , Njenga MK , Feikin DR , Breiman RF . J Infect Dis 2012 206 Suppl 1 S53-60 BACKGROUND: The epidemiology and burden of influenza remain poorly defined in sub-Saharan Africa. Since 2005, the Kenya Medical Research Institute and Centers for Disease Control and Prevention-Kenya have conducted population-based infectious disease surveillance in Kibera, an urban informal settlement in Nairobi, and in Lwak, a rural community in western Kenya. METHODS: Nasopharyngeal and oropharyngeal swab specimens were obtained from patients who attended the study clinic and had acute lower respiratory tract (LRT) illness. Specimens were tested for influenza virus by real-time reverse-transcription polymerase chain reaction. We adjusted the incidence of influenza-associated acute LRT illness to account for patients with acute LRT illness who attended the clinic but were not sampled. RESULTS: From March 2007 through February 2010, 4140 cases of acute LRT illness were evaluated in Kibera, and specimens were collected from 1197 (27%); 319 (27%) were positive for influenza virus. In Lwak, there were 6733 cases of acute LRT illness, and specimens were collected from 1641 (24%); 359 (22%) were positive for influenza virus. The crude and adjusted rates of medically attended influenza-associated acute LRT illness were 6.9 and 13.6 cases per 1000 person-years, respectively, in Kibera, and 5.6 and 23.0 cases per 1000 person-years, respectively, in Lwak. In both sites, rates of influenza-associated acute LRT illness were highest among children <2 years old and lowest among adults ≥50 years old. CONCLUSION: In Kenya, the incidence of influenza-associated acute LRT illness was high in both rural and urban settings, particularly among the most vulnerable age groups. |
Additional diagnostic yield of adding serology to PCR in diagnosing viral acute respiratory infections in Kenyan patients 5 years of age and older
Feikin DR , Njenga MK , Bigogo G , Aura B , Gikunju S , Balish A , Katz MA , Erdman D , Breiman RF . Clin Vaccine Immunol 2012 20 (1) 113-4 The role of serology in the setting of PCR-based diagnosis of acute respiratory infections (ARI) is unclear. We found acute- and convalescent-phase paired serologic testing increased the diagnostic yield beyond PCR of naso/oropharyngeal swabs for influenza virus, RSV, human metapneumovirus, adenovirus and parainfluenza viruses, by 0.4%-10.7%. Although still limited for clinical use, serology, along with PCR, can maximize etiologic diagnosis in epidemiologic studies. |
Etiology and incidence of viral and bacterial acute respiratory illness among older children and adults in rural western Kenya, 2007-2010
Feikin DR , Njenga MK , Bigogo G , Aura B , Aol G , Audi A , Jagero G , Muluare PO , Gikunju S , Nderitu L , Balish A , Winchell J , Schneider E , Erdman D , Oberste MS , Katz MA , Breiman RF . PLoS One 2012 7 (8) e43656 BACKGROUND: Few comprehensive data exist on disease incidence for specific etiologies of acute respiratory illness (ARI) in older children and adults in Africa. METHODOLOGY/PRINCIPAL FINDINGS: From March 1, 2007, to February 28, 2010, among a surveillance population of 21,420 persons >5 years old in rural western Kenya, we collected blood for culture and malaria smears, nasopharyngeal and oropharyngeal swabs for quantitative real-time PCR for ten viruses and three atypical bacteria, and urine for pneumococcal antigen testing on outpatients and inpatients meeting a ARI case definition (cough or difficulty breathing or chest pain and temperature >38.0 degrees C or oxygen saturation <90% or hospitalization). We also collected swabs from asymptomatic controls, from which we calculated pathogen-attributable fractions, adjusting for age, season, and HIV-status, in logistic regression. We calculated incidence by pathogen, adjusting for health-seeking for ARI and pathogen-attributable fractions. Among 3,406 ARI patients >5 years old (adjusted annual incidence 12.0 per 100 person-years), influenza A virus was the most common virus (22% overall; 11% inpatients, 27% outpatients) and Streptococcus pneumoniae was the most common bacteria (16% overall; 23% inpatients, 14% outpatients), yielding annual incidences of 2.6 and 1.7 episodes per 100 person-years, respectively. Influenza A virus, influenza B virus, respiratory syncytial virus (RSV) and human metapneumovirus were more prevalent in swabs among cases (22%, 6%, 8% and 5%, respectively) than controls. Adenovirus, parainfluenza viruses, rhinovirus/enterovirus, parechovirus, and Mycoplasma pneumoniae were not more prevalent among cases than controls. Pneumococcus and non-typhi Salmonella were more prevalent among HIV-infected adults, but prevalence of viruses was similar among HIV-infected and HIV-negative individuals. ARI incidence was highest during peak malaria season. CONCLUSIONS/SIGNFICANCE: Vaccination against influenza and pneumococcus (by potential herd immunity from childhood vaccination or of HIV-infected adults) might prevent much of the substantial ARI incidence among persons >5 years old in similar rural African settings. |
Viral and bacterial causes of severe acute respiratory illness among children less than 5 years old in a high malaria prevalence area of western Kenya, 2007-2010
Feikin DR , Njenga MK , Bigogo G , Aura B , Aol G , Audi A , Jagero G , Muluare PO , Gikunju S , Nderitu L , Winchell JM , Schneider E , Erdman DD , Oberste MS , Katz MA , Breiman RF . Pediatr Infect Dis J 2012 32 (1) e14-9 BACKGROUND: Few comprehensive data exist on the etiology of severe acute respiratory illness (SARI) among African children. METHODS: From March 1, 2007, to February 28, 2010, we collected blood for culture and nasopharyngeal and oropharyngeal swabs for real-time quantitative PCR for ten viruses and three atypical bacteria among children <5 years old with SARI, defined as WHO-classified severe or very severe pneumonia or oxygen saturation <90%, who visited a clinic in rural western Kenya. We collected swabs from controls without febrile or respiratory symptoms. We calculated odds ratios (OR) for infection among cases, adjusting for age and season in logistic regression. We calculated SARI incidence, adjusting for healthcare-seeking for SARI in the community. RESULTS: 2,973 SARI cases were identified (54% inpatient, 46% outpatient), yielding an adjusted incidence of 56 cases per 100 person-years. A pathogen was detected in 3.3% of non-contaminated blood cultures; non-typhi Salmonella (1.9%) and Streptococcus pneumoniae (0.7%) predominated. A pathogen was detected in 84% of nasopharyngeal/oropharyngeal specimens, the most common being rhino/enterovirus (50%), respiratory syncytial virus (RSV, 22%), adenovirus (16%) and influenza viruses (8%). Only RSV and influenza viruses were found more commonly among cases than controls (OR 2.9, 95% CI 1.3-6.7 and OR 4.8, 95% CI 1.1-21, respectively). Incidence of RSV, influenza viruses and S. pneumoniae were 7.1, 5.8 and 0.04 cases per 100 person-years, respectively. CONCLUSIONS: Among Kenyan children with SARI, RSV and influenza virus are the most likely viral causes and pneumococcus the most likely bacterial cause. Contemporaneous controls are important for interpreting upper respiratory tract specimens. |
Secondary household transmission of 2009 pandemic influenza A (H1N1) virus among an urban and rural population in Kenya, 2009-2010
Kim CY , Breiman RF , Cosmas L , Audi A , Aura B , Bigogo G , Njuguna H , Lebo E , Waiboci L , Njenga MK , Feikin DR , Katz MA . PLoS One 2012 7 (6) e38166 BACKGROUND: In Kenya, >1,200 laboratory-confirmed 2009 pandemic influenza A (H1N1) (pH1N1) cases occurred since June 2009. We used population-based infectious disease surveillance (PBIDS) data to assess household transmission of pH1N1 in urban Nairobi (Kibera) and rural Lwak. METHODS: We defined a pH1N1 patient as laboratory-confirmed pH1N1 infection among PBIDS participants during August 1, 2009-February 5, 2010, in Kibera, or August 1, 2009-January 20, 2010, in Lwak, and a case household as a household with a laboratory-confirmed pH1N1 patient. Community interviewers visited PBIDS-participating households to inquire about illnesses among household members. We randomly selected 4 comparison households per case household matched by number of children aged <5. Comparison households had a household visit 10 days before or after the matched patient symptom onset date. We defined influenza-like illnesses (ILI) as self-reported cough or sore throat, and a self-reported fever ≤8 days after the pH1N1 patient's symptom onset in case households and ≤8 days before selected household visit in comparison households. We used the Cochran-Mantel-Haenszel test to compare proportions of ILIs among case and comparison households, and log binomial-model to compare that of Kibera and Lwak. RESULTS: Among household contacts of patients with confirmed pH1N1 in Kibera, 4.6% had ILI compared with 8.2% in Lwak (risk ratio [RR], 0.5; 95% confidence interval [CI], 0.3-0.9). Household contacts of patients were more likely to have ILIs than comparison-household members in both Kibera (RR, 1.8; 95% CI, 1.1-2.8) and Lwak (RR, 2.6; 95% CI, 1.6-4.3). Overall, ILI was not associated with patient age. However, ILI rates among household contacts were higher among children aged <5 years than persons aged ≥5 years in Lwak, but not Kibera. CONCLUSIONS: Substantial pH1N1 household transmission occurred in urban and rural Kenya. Household transmission rates were higher in the rural area. |
The population-based burden of influenza-associated hospitalization in rural western Kenya, 2007-2009
Feikin DR , Ope MO , Aura B , Fuller JA , Gikunju S , Vulule J , Ng'ang'a Z , Njenga MK , Breiman RF , Katz M . Bull World Health Organ 2012 90 (4) 256-263A OBJECTIVE: To estimate the burden and age-specific rates of influenza-associated hospitalization in rural western Kenya. METHODS: All 3924 patients with respiratory illness (defined as acute cough, difficulty in breathing or pleuritic chest pain) who were hospitalized between June 2007 and May 2009 in any inpatient health facility in the Kenyan district of Bondo were enrolled. Nasopharyngeal and oropharyngeal swabs were collected and tested for influenza viruses using real-time reverse transcriptase polymerase chain reaction (RT-PCR). In the calculation of annual rates, adjustments were made for enrolled patients who did not have swabs tested for influenza virus. FINDINGS: Of the 2079 patients with tested swabs, infection with influenza virus was confirmed in 204 (10%); 176, 27 and 1 were found to be RT-PCR-positive for influenza A virus only, influenza B virus only, and both influenza A and B viruses, respectively. Among those tested for influenza virus, 6.8% of the children aged < 5 years and 14.0% of the patients aged ≥ 5 years were found positive. The case-fatality rate among admitted patients with PCR-confirmed infection with influenza virus was 2.0%. The annual rate of hospitalization (per 100,000 population) was 699.8 among patients with respiratory illness and 56.2 among patients with influenza (with 143.7, 18.8, 55.2, 65.1 and 57.3 hospitalized patients with influenza virus per 100,000 people aged < 5, 5-19, 20-34, 35-49 and ≥ 50 years, respectively). CONCLUSION: In a rural district of western Kenya, the rate of influenza-associated hospitalization was highest among children aged less than 5 years. |
Differing burden and epidemiology of non-Typhi Salmonella bacteremia in rural and urban Kenya, 2006-2009
Tabu C , Breiman RF , Ochieng B , Aura B , Cosmas L , Audi A , Olack B , Bigogo G , Ongus JR , Fields P , Mintz E , Burton D , Oundo J , Feikin DR . PLoS One 2012 7 (2) e31237 BACKGROUND: The epidemiology of non-Typhi Salmonella (NTS) bacteremia in Africa will likely evolve as potential co-factors, such as HIV, malaria, and urbanization, also change. METHODS: As part of population-based surveillance among 55,000 persons in malaria-endemic, rural and malaria-nonendemic, urban Kenya from 2006-2009, blood cultures were obtained from patients presenting to referral clinics with fever ≥38.0 degrees C or severe acute respiratory infection. Incidence rates were adjusted based on persons with compatible illnesses, but whose blood was not cultured. RESULTS: NTS accounted for 60/155 (39%) of blood culture isolates in the rural and 7/230 (3%) in the urban sites. The adjusted incidence in the rural site was 568/100,000 person-years, and the urban site was 51/100,000 person-years. In both sites, the incidence was highest in children <5 years old. The NTS-to-typhoid bacteremia ratio in the rural site was 4.6 and in the urban site was 0.05. S. Typhimurium represented >85% of blood NTS isolates in both sites, but only 21% (urban) and 64% (rural) of stool NTS isolates. Overall, 76% of S. Typhimurium blood isolates were multi-drug resistant, most of which had an identical profile in Pulse Field Gel Electrophoresis. In the rural site, the incidence of NTS bacteremia increased during the study period, concomitant with rising malaria prevalence (monthly correlation of malaria positive blood smears and NTS bacteremia cases, Spearman's correlation, p = 0.018 for children, p = 0.16 adults). In the rural site, 80% of adults with NTS bacteremia were HIV-infected. Six of 7 deaths within 90 days of NTS bacteremia had HIV/AIDS as the primary cause of death assigned on verbal autopsy. CONCLUSIONS: NTS caused the majority of bacteremias in rural Kenya, but typhoid predominated in urban Kenya, which most likely reflects differences in malaria endemicity. Control measures for malaria, as well as HIV, will likely decrease the burden of NTS bacteremia in Africa. |
Risk factors for hospitalized seasonal influenza in rural Western Kenya
Ope MO , Katz MA , Aura B , Gikunju S , Njenga MK , Ng'ang'a Z , Vulule J , Breiman RF , Feikin DR . PLoS One 2011 6 (5) e20111 BACKGROUND: Risk factors for influenza hospitalization in Africa are unknown, including the role of HIV. METHODS: We conducted a case-control study of risk factors for hospitalized seasonal influenza among persons in rural western Kenya, a high HIV prevalence area, from March 2006- August 2008. Eligible cases were ≥five years old, admitted to health facilities with respiratory symptoms, and had nasopharyngeal/oropharyngeal swab specimens that tested positive for influenza A or B by real-time reverse transcription-PCR. Three randomly selected age-, sex- and neighborhood-matched controls were enrolled per case. A structured questionnaire was administered and home-based HIV testing was performed. Risk factors were evaluated using conditional logistic regression. RESULTS: A total of 64 cases (38 with influenza A and 26 with influenza B) and 190 controls were enrolled. The median age was 16 years (range 5-69 years). Among cases, 24.5% were HIV-infected versus 12.5% of controls (p = 0.004). Among persons ≥18 years old, 13 (59%) of 22 tested cases were HIV-positive compared with 15 (24%) of 62 tested controls (p = 0.005). In multivariable analysis, HIV-infection was associated with hospitalization due to influenza [adjusted Odds Ratio (aOR) 3.56, 95% CI 1.25-10.1]. The mean CD4 count among HIV-infected cases and controls was similar (399 vs. 387, respectively, p = 0.89). Chronic lung disease (aOR 6.83, 95% CI 1.37-34.0) was also associated with influenza hospitalization in multivariable analysis. Active pulmonary tuberculosis was associated with influenza hospitalization in bivariate, but not multivariable, analysis. CONCLUSIONS: People with HIV infection and chronic lung disease were at increased risk of hospitalized influenza in rural Kenya. HIV infection is common in many parts of sub-Saharan Africa. Influenza vaccine might prevent severe influenza in these risk groups. |
The burden of common infectious disease syndromes at the clinic and household level from population-based surveillance in rural and urban Kenya
Feikin DR , Olack B , Bigogo GM , Audi A , Cosmas L , Aura B , Burke H , Njenga MK , Williamson J , Breiman RF . PLoS One 2011 6 (1) e16085 BACKGROUND: Characterizing infectious disease burden in Africa is important for prioritizing and targeting limited resources for curative and preventive services and monitoring the impact of interventions. METHODS: From June 1, 2006 to May 31, 2008, we estimated rates of acute lower respiratory tract illness (ALRI), diarrhea and acute febrile illness (AFI) among >50,000 persons participating in population-based surveillance in impoverished, rural western Kenya (Asembo) and an informal settlement in Nairobi, Kenya (Kibera). Field workers visited households every two weeks, collecting recent illness information and performing limited exams. Participants could access free high-quality care in a designated referral clinic in each site. Incidence and longitudinal prevalence were calculated and compared using Poisson regression. RESULTS: Incidence rates resulting in clinic visitation were the following: ALRI - 0.36 and 0.51 episodes per year for children <5 years and 0.067 and 0.026 for persons ≥5 years in Asembo and Kibera, respectively; diarrhea - 0.40 and 0.71 episodes per year for children <5 years and 0.09 and 0.062 for persons ≥5 years in Asembo and Kibera, respectively; AFI - 0.17 and 0.09 episodes per year for children <5 years and 0.03 and 0.015 for persons ≥5 years in Asembo and Kibera, respectively. Annually, based on household visits, children <5 years in Asembo and Kibera had 60 and 27 cough days, 10 and 8 diarrhea days, and 37 and 11 fever days, respectively. Household-based rates were higher than clinic rates for diarrhea and AFI, this difference being several-fold greater in the rural than urban site. CONCLUSIONS: Individuals in poor Kenyan communities still suffer from a high burden of infectious diseases, which likely hampers their development. Urban slum and rural disease incidence and clinic utilization are sufficiently disparate in Africa to warrant data from both settings for estimating burden and focusing interventions. |
Health-seeking patterns among participants of population-based morbidity surveillance in rural western Kenya: implications for calculating disease rates
Bigogo G , Audi A , Aura B , Aol G , Breiman RF , Feikin DR . Int J Infect Dis 2010 14 (11) e967-73 BACKGROUND: Calculation of disease rates in developing countries using facility-based surveillance is affected by patterns of health utilization. We describe temporal patterns in health care seeking by syndrome as part of population-based morbidity surveillance in rural western Kenya. METHODS: From July 2006 to June 2008, health utilization data were collected from 27,171 participants at biweekly home visits and at Lwak Hospital, the designated referral clinic where free care provided by dedicated study clinical staff was available. Ill persons were asked if and where they sought care. Proportions seeking care for children and adults with fever, acute respiratory infection (ARI), acute lower respiratory infection (ALRI), and diarrhea were compared by Chi-square test. Care-seeking by distance was evaluated by logistic regression. RESULTS: While care-seeking outside the home was common for all syndromes (>50%), only 18-38% of care-seeking was to health facilities. Children were more likely than adults to visit health facilities for all syndromes. Of ill persons visiting Lwak Hospital, 45-54% had previously sought care elsewhere, mostly from informal drug sellers, and 11-24% with fever, ARI, or ALRI had already taken an antimalarial or antibiotic. The distance from the participant's home to Lwak Hospital was the most common reason (71%) for ill participants not seeking care there. The likelihood of visiting Lwak decreased with increasing distance of residence (p<0.001) and fluctuated significantly over the study period. CONCLUSIONS: Even in a study setting where free and reliable care is offered, health utilization is affected by other factors, such as distance. Health utilization data in population-based surveillance are important in adjusting disease rates. |
High rate of pneumococcal bacteremia in a prospective cohort of older children and adults in an area of high HIV prevalence in rural western Kenya
Feikin DR , Jagero G , Aura B , Bigogo GM , Oundo J , Beall BW , Karani A , Morpeth S , Njenga MK , Breiman RF . BMC Infect Dis 2010 10 186 BACKGROUND: Although causing substantial morbidity, the burden of pneumococcal disease among older children and adults in Africa, particularly in rural settings, is not well-characterized. We evaluated pneumococcal bacteremia among 21,000 persons > or =5 years old in a prospective cohort as part of population-based infectious disease surveillance in rural western Kenya from October 2006-September 2008. METHODS: Blood cultures were done on patients meeting pre-defined criteria--severe acute respiratory illness (SARI), fever, and admission for any reason at a referral health facility within 5 kilometers of all 33 villages where surveillance took place. Serotyping of Streptococcus pneumoniae was done by latex agglutination and quellung reaction and antibiotic susceptibility testing was done using broth microdilution. We extrapolated incidence rates based on persons with compatible illnesses in the surveillance population who were not cultured. We estimated rates among HIV-infected persons based on community HIV prevalence. We projected the national burden of pneumococcal bacteremia cases based on these rates. RESULTS: Among 1,301 blood cultures among persons > or =5 years, 52 (4%) yielded pneumococcus, which was the most common bacteria isolated. The yield was higher among those > or =18 years than 5-17 years (6.9% versus 1.6%, p < 0.001). The highest yield was for inpatients with SARI (10%), compared with SARI outpatients (3%) and acute febrile outpatients (1%). Serotype 1 pneumococcus was most common (42% isolates) and 71% were serotypes included in the 10-valent pneumococcal conjugate vaccine (PCV10). Non-susceptibility to beta-lactam antibiotics was low (<5%), but to trimethoprim-sulfamethoxazole was high (>95%). The crude rate of pneumococcal bacteremia was 129/100,000 person-years, and the adjusted rate was 419/100,000 person-years. Nineteen (61%) of 31 patients with HIV results were HIV-positive. The adjusted rate among HIV-infected persons was 2,399/100,000 person-years (Rate ratio versus HIV-negative adults, 19.7, 95% CI 12.4-31.1). We project 58,483 cases of pneumococcal bacteremia will occur in Kenyan adults in 2010. CONCLUSIONS: Pneumococcal bacteremia rates were high among persons > or =5 years old, particularly among HIV-infected persons. Ongoing surveillance will document if expanded use of highly-active antiretroviral treatment for HIV and introduction of PCV10 for Kenyan children (anticipated in late 2010) result in substantial secondary benefits by reducing pneumococcal disease in adults. |
Relation of candidate genes that encode for endothelial function to migraine and stroke: the stroke prevention in young women study
Macclellan LR , Howard TD , Cole JW , Stine OC , Giles WH , O'Connell JR , Wozniak MA , Stern BJ , Mitchell BD , Kittner SJ . Stroke 2009 40 (10) e550-7 ![]() BACKGROUND AND PURPOSE: Migraine with aura is a risk factor for ischemic stroke, but the mechanism by which these disorders are associated remains unclear. Both disorders exhibit familial clustering, which may imply a genetic influence on migraine and stroke risk. Genes encoding for endothelial function are promising candidate genes for migraine and stroke susceptibility because of the importance of endothelial function in regulating vascular tone and cerebral blood flow. METHODS: Using data from the Stroke Prevention in Young Women study, a population-based case-control study including 297 women aged 15 to 49 years with ischemic stroke and 422 women without stroke, we evaluated whether polymorphisms in genes regulating endothelial function, including endothelin-1 (EDN), endothelin receptor type B (EDNRB), and nitric oxide synthase-3 (NOS3), confer susceptibility to migraine and stroke. RESULTS: EDN SNP rs1800542 and rs10478723 were associated with increased stroke susceptibility in whites (OR, 2.1; 95% CI, 1.1-4.2 and OR, 2.2; 95% CI, 1.1-4.4; P=0.02 and 0.02, respectively), as were EDNRB SNP rs4885493 and rs10507875, (OR, 1.7; 95% CI, 1.1-2.7 and OR, 2.4; 95% CI, 1.4-4.3; P=0.01 and 0.002, respectively). Only 1 of the tested SNP (NOS3 rs3918166) was associated with both migraine and stroke. CONCLUSIONS: In our study population, variants in EDN and EDNRB were associated with stroke susceptibility in white but not in black women. We found no evidence that these genes mediate the association between migraine and stroke. |
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