Last data update: Apr 29, 2024. (Total: 46658 publications since 2009)
Records 1-30 (of 52 Records) |
Query Trace: Doty J[original query] |
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Co-circulating monkeypox and swinepox viruses, democratic republic of the congo, 2022
Kalonji T , Malembi E , Matela JP , Likafi T , Kinganda-Lusamaki E , Vakaniaki EH , Hoff NA , Aziza A , Muyembe F , Kabamba J , Cooreman T , Nguete B , Witte D , Ayouba A , Fernandez-Nuñez N , Roge S , Peeters M , Merritt S , Ahuka-Mundeke S , Delaporte E , Pukuta E , Mariën J , Bangwen E , Lakin S , Lewis C , Doty JB , Liesenborghs L , Hensley LE , McCollum A , Rimoin AW , Muyembe-Tamfum JJ , Shongo R , Kaba D , Mbala-Kingebeni P . Emerg Infect Dis 2024 30 (4) 761-765 In September 2022, deaths of pigs manifesting pox-like lesions caused by swinepox virus were reported in Tshuapa Province, Democratic Republic of the Congo. Two human mpox cases were found concurrently in the surrounding community. Specific diagnostics and robust sequencing are needed to characterize multiple poxviruses and prevent potential poxvirus transmission. |
Clinical manifestations of an outbreak of monkeypox virus in captive chimpanzees in Cameroon, 2016
Brien SC , LeBreton M , Doty JB , Mauldin MR , Morgan CN , Pieracci EG , Ritter JM , Matheny A , Tafon BG , Tamoufe U , Missoup AD , Nwobegahay J , Takuo JM , Nkom F , Mouiche MMM , Feussom JMK , Wilkins K , Wade A , McCollum AM . J Infect Dis 2024 Monkeypox virus (MPXV) is a re-emerging virus of global concern. An outbreak of Clade I MPXV affected 20 captive chimpanzees in Cameroon in 2016. We describe the epidemiology, virology, phylogenetics, and clinical progression of this outbreak. Clinical signs included exanthema, facial swelling, peri-laryngeal swelling, and eschar. Mpox can be lethal in captive chimpanzees with death likely resulting from respiratory complications. We advise avoiding anesthesia in animals with respiratory signs to reduce the likelihood of death. This outbreak presented a risk to animal care staff. There is a need for increased awareness and a One Health approach to preparation for outbreaks in wildlife rescue centers in primate range states where MPXV occurs. Control measures should include quarantining affected animals, limiting human contacts, surveillance of humans and animals, use of personal protective equipment, and regular decontamination of enclosures. |
One Health Investigation of SARS-CoV-2 Infection and Seropositivity among Pets in Households with Confirmed Human COVID-19 Cases — Utah and Wisconsin, 2020 (preprint)
Goryoka GW , Cossaboom CM , Gharpure R , Dawson P , Tansey C , Rossow J , Mrotz V , Rooney J , Torchetti M , Loiacono CM , Killian ML , Jenkins-Moore M , Lim A , Poulsen K , Christensen D , Sweet E , Peterson D , Sangster AL , Young EL , Oakeson KF , Taylor D , Price A , Kiphibane T , Klos R , Konkle D , Bhattacharyya S , Dasu T , Chu VT , Lewis NM , Queen K , Zhang J , Uehara A , Dietrich EA , Tong S , Kirking HL , Doty JB , Murrell LS , Spengler JR , Straily A , Wallace R , Barton Behravesh C . bioRxiv 2021 2021.04.11.439379 Background Approximately 67% of U.S. households have pets. Limited data are available on SARS-CoV-2 in pets. We assessed SARS-CoV-2 infection in pet cohabitants as a sub-study of an ongoing COVID-19 household transmission investigation.Methods Mammalian pets from households with ≥1 person with laboratory-confirmed COVID-19 were eligible for inclusion from April–May 2020. Demographic/exposure information, oropharyngeal, nasal, rectal, and fur swabs, feces, and blood were collected from enrolled pets and tested by rRT-PCR and virus neutralization assays.Findings We enrolled 37 dogs and 19 cats from 34 of 41 eligible households. All oropharyngeal, nasal, and rectal swabs tested negative by rRT-PCR; one dog’s fur swabs (2%) tested positive by rRT-PCR at the first animal sampling. Among 47 pets with serological results from 30 households, eight (17%) pets (4 dogs, 4 cats) from 6 (20%) households had detectable SARS-CoV-2 neutralizing antibodies. In households with a seropositive pet, the proportion of people with laboratory-confirmed COVID-19 was greater (median 79%; range: 40–100%) compared to households with no seropositive pet (median 37%; range: 13–100%) (p=0.01). Thirty-three pets with serologic results had frequent daily contact (≥1 hour) with the human index patient before the person’s COVID-19 diagnosis. Of these 33 pets, 14 (42%) had decreased contact with the human index patient after diagnosis and none (0%) were seropositive; of the 19 (58%) pets with continued contact, 4 (21%) were seropositive.Interpretations Seropositive pets likely acquired infection from humans, which may occur more frequently than previously recognized. People with COVID-19 should restrict contact with animals.Funding Centers for Disease Control and Prevention, U.S. Department of AgricultureCompeting Interest StatementThe authors have declared no competing interest. |
The CDC domestic mpox response - United States, 2022-2023
McQuiston JH , Braden CR , Bowen MD , McCollum AM , McDonald R , Carnes N , Carter RJ , Christie A , Doty JB , Ellington S , Fehrenbach SN , Gundlapalli AV , Hutson CL , Kachur RE , Maitland A , Pearson CM , Prejean J , Quilter LAS , Rao AK , Yu Y , Mermin J . MMWR Morb Mortal Wkly Rep 2023 72 (20) 547-552 Monkeypox (mpox) is a serious viral zoonosis endemic in west and central Africa. An unprecedented global outbreak was first detected in May 2022. CDC activated its emergency outbreak response on May 23, 2022, and the outbreak was declared a Public Health Emergency of International Concern on July 23, 2022, by the World Health Organization (WHO),* and a U.S. Public Health Emergency on August 4, 2022, by the U.S. Department of Health and Human Services.(†) A U.S. government response was initiated, and CDC coordinated activities with the White House, the U.S. Department of Health and Human Services, and many other federal, state, and local partners. CDC quickly adapted surveillance systems, diagnostic tests, vaccines, therapeutics, grants, and communication systems originally developed for U.S. smallpox preparedness and other infectious diseases to fit the unique needs of the outbreak. In 1 year, more than 30,000 U.S. mpox cases were reported, more than 140,000 specimens were tested, >1.2 million doses of vaccine were administered, and more than 6,900 patients were treated with tecovirimat, an antiviral medication with activity against orthopoxviruses such as Variola virus and Monkeypox virus. Non-Hispanic Black (Black) and Hispanic or Latino (Hispanic) persons represented 33% and 31% of mpox cases, respectively; 87% of 42 fatal cases occurred in Black persons. Sexual contact among gay, bisexual, and other men who have sex with men (MSM) was rapidly identified as the primary risk for infection, resulting in profound changes in our scientific understanding of mpox clinical presentation, pathogenesis, and transmission dynamics. This report provides an overview of the first year of the response to the U.S. mpox outbreak by CDC, reviews lessons learned to improve response and future readiness, and previews continued mpox response and prevention activities as local viral transmission continues in multiple U.S. jurisdictions (Figure). |
Orthopoxvirus circulation in an endemic area in Brazil: Investigation of infections in small mammals during an absence of outbreaks
Domingos IJS , Rocha KLS , Graciano JM , Almeida LR , Doty JB , Paglia AP , Oliveira DB , Nakazawa YJ , Trindade GS . Viruses 2023 15 (4) Vaccinia virus (VACV) is the causative agent of an emerging viral zoonosis called bovine vaccinia (BV). Several studies have documented characteristics of VACV infections in Brazil; however, the manner in which this virus is maintained in wildlife remains unknown. This work investigated the presence of viral DNA and anti-orthopoxvirus (OPXV) antibodies in samples collected from small mammals in a VACV-endemic area in Minas Gerais, Brazil, in the absence of current outbreaks. Samples did not show amplification of OPXV DNA in molecular tests. However, 5/142 serum samples demonstrated the presence of anti-OPXV neutralizing antibodies in serological tests. These data reinforce the involvement of small mammals in the natural cycle of VACV, highlighting the need for further ecological studies to better understand how this virus is maintained in nature and to develop measures to prevent BV outbreaks. |
Orthopoxvirus infections in rodents, Nigeria, 2018-2019
Meseko C , Adedeji A , Shittu I , Obishakin E , Nanven M , Suleiman L , Okomah D , Tyakaray V , Kolade D , Yinka-Ogunleye A , Muhammad S , Morgan CN , Matheny A , Nakazawa Y , McCollum A , Doty JB . Emerg Infect Dis 2023 29 (2) 433-434 To investigate animal reservoirs of monkeypox virus in Nigeria, we sampled 240 rodents during 2018-2019. Molecular (real-time PCR) and serologic (IgM) evidence indicated orthopoxvirus infections, but presence of monkeypox virus was not confirmed. These results can be used to develop public health interventions to reduce human infection with orthopoxviruses. |
Epidemiology of human mpox - worldwide, 2018-2021
McCollum AM , Shelus V , Hill A , Traore T , Onoja B , Nakazawa Y , Doty JB , Yinka-Ogunleye A , Petersen BW , Hutson CL , Lewis R . MMWR Morb Mortal Wkly Rep 2023 72 (3) 68-72 Monkeypox (mpox) is a zoonotic disease caused by Monkeypox virus (MPXV), an Orthopoxvirus; the wild mammalian reservoir species is not known. There are two genetic clades of MPXV: clade I and clade II (historically found in central and west Africa, respectively), with only Cameroon reporting both clades (1). Human cases have historically been reported from 1) mostly rural, forested areas in some central and west African countries; 2) countries reporting cases related to population migration or travel of infected persons; and 3) exposure to imported infected mammals (2). The annual number of cases in Africa has risen since 2014 and cumulatively surpassed reports from the previous 40 years for most countries. This reemergence of mpox might be due to a combination of environmental and ecological changes, animal or human movement, the cessation of routine smallpox vaccination since its eradication in 1980, improvements in disease detection and diagnosis, and genetic changes in the virus (2). This report describes the epidemiology of mpox since 1970 and during 2018-2021, using data from national surveillance programs, World Health Organization (WHO) bulletins, and case reports, and addresses current diagnostic and treatment challenges in countries with endemic disease. During 2018-2021, human cases were recognized and confirmed in six African countries, with most detected in the Democratic Republic of the Congo (DRC) and Nigeria. The reemergence and increase in cases resulted in its being listed in 2019 as a priority disease for immediate and routine reporting through the Integrated Disease Surveillance and Response strategy in the WHO African region.* In eight instances, patients with mpox were identified in four countries outside of Africa after travel from Nigeria. Since 2018, introductory and intermediate training courses on prevention and control of mpox for public health and health care providers have been available online at OpenWHO.(†)(,)(§) The global outbreak that began in May 2022(¶) has further highlighted the need for improvements in laboratory-based surveillance and access to treatments and vaccines to prevent and contain the infection, including in areas of Africa with endemic mpox. |
Environmental persistence of monkeypox virus on surfaces in household of person with travel-associated infection, Dallas, Texas, USA, 2021
Morgan CN , Whitehill F , Doty JB , Schulte J , Matheny A , Stringer J , Delaney LJ , Esparza R , Rao AK , McCollum AM . Emerg Infect Dis 2022 28 (10) 1982-1989 In July 2021, we conducted environmental sampling at the residence of a person in Dallas, Texas, USA, who had travel-associated human West African monkeypox virus (MPXV-WA). Targeted environmental swab sampling was conducted 15 days after the person who had monkeypox left the household. Results indicate extensive MPXV-WA DNA contamination, and viable virus from 7 samples was successfully isolated in cell culture. There was no statistical difference (p = 0.94) between MPXV-WA PCR positivity of porous (9/10, 90%) vs. nonporous (19/21, 90.5%) surfaces, but there was a significant difference (p<0.01) between viable virus detected in cultures of porous (6/10, 60%) vs. nonporous (1/21, 5%) surfaces. These findings indicate that porous surfaces (e.g., bedding, clothing) may pose more of a MPXV exposure risk than nonporous surfaces (e.g., metal, plastic). Viable MPXV was detected on household surfaces after at least 15 days. However, low titers (<10(2) PFU) indicate a limited potential for indirect transmission. |
Activity patterns and burrowing ecology of the giant pouched rat (Cricetomys emini) in Tshuapa Province, D. R. Congo
Kalemba LN , Morgan CN , Nakazawa YJ , Mauldin MR , Malekani JM , Doty JB . Mammalia 2022 86 (6) 562-569 Rodents of the genus Cricetomys have been reported to be nocturnal with a bimodal activity pattern and to frequently change burrows. However, no studies to date have examined these ecological aspects with the use of radio-telemetry. Five C. emini were captured and radio-collared to study their activity patterns and burrowing ecology from 9 March to 15 April 2016. Nocturnal activity ranged between the hours of 18:00 and 05:00 with a probable reduction of activities between 20:00-23:00 and around 04:00 with diurnal activity between 06:00 and 17:00 h with a reduction of activity between 11:00 and 14:00. While the present study does confirm nocturnal activity and a bimodal pattern, this study also suggests greater diurnal activity as compared to previous studies. Additionally, data presented here also suggest that C. emini may not change burrows as frequently as previously reported. 2022 Walter de Gruyter GmbH, Berlin/Boston 2022. |
Monkeypox in a Traveler Returning from Nigeria - Dallas, Texas, July 2021.
Rao AK , Schulte J , Chen TH , Hughes CM , Davidson W , Neff JM , Markarian M , Delea KC , Wada S , Liddell A , Alexander S , Sunshine B , Huang P , Honza HT , Rey A , Monroe B , Doty J , Christensen B , Delaney L , Massey J , Waltenburg M , Schrodt CA , Kuhar D , Satheshkumar PS , Kondas A , Li Y , Wilkins K , Sage KM , Yu Y , Yu P , Feldpausch A , McQuiston J , Damon IK , McCollum AM . MMWR Morb Mortal Wkly Rep 2022 71 (14) 509-516 Monkeypox is a rare, sometimes life-threatening zoonotic infection that occurs in west and central Africa. It is caused by Monkeypox virus, an orthopoxvirus similar to Variola virus (the causative agent of smallpox) and Vaccinia virus (the live virus component of orthopoxvirus vaccines) and can spread to humans. After 39 years without detection of human disease in Nigeria, an outbreak involving 118 confirmed cases was identified during 2017-2018 (1); sporadic cases continue to occur. During September 2018-May 2021, six unrelated persons traveling from Nigeria received diagnoses of monkeypox in non-African countries: four in the United Kingdom and one each in Israel and Singapore. In July 2021, a man who traveled from Lagos, Nigeria, to Dallas, Texas, became the seventh traveler to a non-African country with diagnosed monkeypox. Among 194 monitored contacts, 144 (74%) were flight contacts. The patient received tecovirimat, an antiviral for treatment of orthopoxvirus infections, and his home required large-scale decontamination. Whole genome sequencing showed that the virus was consistent with a strain of Monkeypox virus known to circulate in Nigeria, but the specific source of the patient's infection was not identified. No epidemiologically linked cases were reported in Nigeria; no contact received postexposure prophylaxis (PEP) with the orthopoxvirus vaccine ACAM2000. |
Low SARS-CoV-2 Seroprevalence and No Active Infections among Dogs and Cats in Animal Shelters with Laboratory-Confirmed COVID-19 Human Cases among Employees.
Cossaboom CM , Medley AM , Spengler JR , Kukielka EA , Goryoka GW , Baird T , Bhavsar S , Campbell S , Campbell TS , Christensen D , Condrey JA , Dawson P , Doty JB , Feldpausch A , Gabel J , Jones D , Lim A , Loiacono CM , Jenkins-Moore M , Moore A , Noureddine C , Ortega J , Poulsen K , Rooney JA , Rossow J , Sheppard K , Sweet E , Stoddard R , Tell RM , Wallace RM , Williams C , Barton Behravesh C . Biology (Basel) 2021 10 (9) Human-to-animal and animal-to-animal transmission of SARS-CoV-2 has been documented; however, investigations into SARS-CoV-2 transmission in congregate animal settings are lacking. We investigated four animal shelters in the United States that had identified animals with exposure to shelter employees with laboratory-confirmed COVID-19. Of the 96 cats and dogs with specimens collected, only one dog had detectable SARS-CoV-2 neutralizing antibodies; no animal specimens had detectable viral RNA. These data indicate a low probability of human-to-animal transmission events in cats and dogs in shelter settings with early implementation of infection prevention interventions. |
One Health Investigation of SARS-CoV-2 Infection and Seropositivity among Pets in Households with Confirmed Human COVID-19 Cases-Utah and Wisconsin, 2020.
Goryoka GW , Cossaboom CM , Gharpure R , Dawson P , Tansey C , Rossow J , Mrotz V , Rooney J , Torchetti M , Loiacono CM , Killian ML , Jenkins-Moore M , Lim A , Poulsen K , Christensen D , Sweet E , Peterson D , Sangster AL , Young EL , Oakeson KF , Taylor D , Price A , Kiphibane T , Klos R , Konkle D , Bhattacharyya S , Dasu T , Chu VT , Lewis NM , Queen K , Zhang J , Uehara A , Dietrich EA , Tong S , Kirking HL , Doty JB , Murrell LS , Spengler JR , Straily A , Wallace R , Barton Behravesh C . Viruses 2021 13 (9) Approximately 67% of U.S. households have pets. Limited data are available on SARS-CoV-2 in pets. We assessed SARS-CoV-2 infection in pets during a COVID-19 household transmission investigation. Pets from households with ≥1 person with laboratory-confirmed COVID-19 were eligible for inclusion from April-May 2020. We enrolled 37 dogs and 19 cats from 34 households. All oropharyngeal, nasal, and rectal swabs tested negative by rRT-PCR; one dog's fur swabs (2%) tested positive by rRT-PCR at the first sampling. Among 47 pets with serological results, eight (17%) pets (four dogs, four cats) from 6/30 (20%) households had detectable SARS-CoV-2 neutralizing antibodies. In households with a seropositive pet, the proportion of people with laboratory-confirmed COVID-19 was greater (median 79%; range: 40-100%) compared to households with no seropositive pet (median 37%; range: 13-100%) (p = 0.01). Thirty-three pets with serologic results had frequent daily contact (≥1 h) with the index patient before the person's COVID-19 diagnosis. Of these 33 pets, 14 (42%) had decreased contact with the index patient after diagnosis and none were seropositive; of the 19 (58%) pets with continued contact, four (21%) were seropositive. Seropositive pets likely acquired infection after contact with people with COVID-19. People with COVID-19 should restrict contact with pets and other animals. |
Determination of freedom-from-rabies for small Indian mongoose populations in the United States Virgin Islands, 2019-2020
Browne AS , Cranford HM , Morgan CN , Ellison JA , Berentsen A , Wiese N , Medley A , Rossow J , Jankelunas L , McKinley AS , Lombard CD , Angeli NF , Kelley T , Valiulus J , Bradford B , Burke-France VJ , Harrison CJ , Guendel I , Taylor M , Blanchard GL , Doty JB , Worthington DJ , Horner D , Garcia KR , Roth J , Ellis BR , Bisgard KM , Wallace R , Ellis EM . PLoS Negl Trop Dis 2021 15 (7) e0009536 Mongooses, a nonnative species, are a known reservoir of rabies virus in the Caribbean region. A cross-sectional study of mongooses at 41 field sites on the US Virgin Islands of St. Croix, St. John, and St. Thomas captured 312 mongooses (32% capture rate). We determined the absence of rabies virus by antigen testing and rabies virus exposure by antibody testing in mongoose populations on all three islands. USVI is the first Caribbean state to determine freedom-from-rabies for its mongoose populations with a scientifically-led robust cross-sectional study. Ongoing surveillance activities will determine if other domestic and wildlife populations in USVI are rabies-free. |
Clinical and epidemiologic findings from enhanced monkeypox surveillance in Tshuapa Province, Democratic Republic of the Congo during 2011-2015
Whitehouse ER , Bonwitt J , Hughes CM , Lushima RS , Likafi T , Nguete B , Kabamba J , Monroe B , Doty JB , Nakazawa Y , Damon I , Malekani J , Davidson W , Wilkins K , Li Y , Radford KW , Schmid DS , Pukuta E , Muyamuna E , Karhemere S , Tamfum JM , Okitolonda EW , McCollum AM , Reynolds MG . J Infect Dis 2021 223 (11) 1870-1878 BACKGROUND: Monkeypox is a poorly described emerging zoonosis endemic to Central and Western Africa. METHODS: Using surveillance data from Tshuapa Province, Democratic Republic of the Congo during 2011-2015, we evaluated differences in incidence, exposures, and clinical presentation of PCR-confirmed cases by sex and age. RESULTS: We report 1,057 confirmed cases. Average annual incidence was 14·1 per 100,000 (95% CI: 13·3-15·0). Incidence was higher in males (incidence rate ratio [IRR] males: females: 1·21, 95% CI 1·07-1·37), except among 20-29-year-old (IRR: 0·70, 95% CI: 0·51-0·95). Females aged 20-29 years also reported a high frequency of exposures (26·2%) to people with monkeypox-like symptoms. Highest incidence was among 10-19-year-old males, the cohort reporting the highest proportion of animal exposures (37·5%). Incidence was lower among those presumed to have received smallpox vaccination versus those presumed unvaccinated. No differences were observed by age group in lesion count or lesion severity score. CONCLUSIONS: Monkeypox incidence was twice that reported during 1980-1985, an increase possibly linked to declining immunity provided by smallpox vaccination. The high proportion of cases attributed to human exposures suggests changing exposure patterns. Cases were distributed across age and sex, suggesting frequent exposures that follow socio-cultural norms. |
Pharmacokinetics and efficacy of a potential smallpox therapeutic, brincidofovir, in a lethal monkeypox virus animal model
Hutson CL , Kondas AV , Mauldin MR , Doty JB , Grossi IM , Morgan CN , Ostergaard SD , Hughes CM , Nakazawa Y , Kling C , Martin BE , Ellison JA , Carroll DD , Gallardo-Romero NF , Olson VA . mSphere 2021 6 (1) Smallpox, caused by Variola virus (VARV), was eradicated in 1980; however, VARV bioterrorist threats still exist, necessitating readily available therapeutics. Current preparedness activities recognize the importance of oral antivirals and recommend therapeutics with different mechanisms of action. Monkeypox virus (MPXV) is closely related to VARV, causing a highly similar clinical human disease, and can be used as a surrogate for smallpox antiviral testing. The prairie dog MPXV model has been characterized and used to study the efficacy of antipoxvirus therapeutics, including recently approved TPOXX (tecovirimat). Brincidofovir (BCV; CMX001) has shown antiviral activity against double-stranded DNA viruses, including poxviruses. To determine the exposure of BCV following oral administration to prairie dogs, a pharmacokinetics (PK) study was performed. Analysis of BCV plasma concentrations indicated variability, conceivably due to the outbred nature of the animals. To determine BCV efficacy in the MPXV prairie dog model, groups of animals were intranasally challenged with 9 × 10(5) plaque-forming units (PFU; 90% lethal dose [LD(90)]) of MPXV on inoculation day 0 (ID0). Animals were divided into groups based on the first day of BCV treatment relative to inoculation day (ID-1, ID0, or ID1). A trend in efficacy was noted dependent upon treatment initiation (57% on ID-1, 43% on ID0, and 29% on ID1) but was lower than demonstrated in other animal models. Analysis of the PK data indicated that BCV plasma exposure (maximum concentration [C (max)]) and the time of the last quantifiable concentration (AUC(last)) were lower than in other animal models administered the same doses, indicating that suboptimal BCV exposure may explain the lower protective effect on survival.IMPORTANCE Preparedness activities against highly transmissible viruses with high mortality rates have been highlighted during the ongoing coronavirus disease 2019 (COVID-19) pandemic. Smallpox, caused by variola virus (VARV) infection, is highly transmissible, with an estimated 30% mortality. Through an intensive vaccination campaign, smallpox was declared eradicated in 1980, and routine smallpox vaccination of individuals ceased. Today's current population has little/no immunity against VARV. If smallpox were to reemerge, the worldwide results would be devastating. Recent FDA approval of one smallpox antiviral (tecovirimat) was a successful step in biothreat preparedness; however, orthopoxviruses can become resistant to treatment, suggesting the need for multiple therapeutics. Our paper details the efficacy of the investigational smallpox drug brincidofovir in a monkeypox virus (MPXV) animal model. Since brincidofovir has not been tested in vivo against smallpox, studies with the related virus MPXV are critical in understanding whether it would be protective in the event of a smallpox outbreak. |
Laboratory infection of novel Akhmeta virus in CAST/EiJ mice
Morgan CN , Matheny AM , Nakazawa YJ , Kling C , Gallardo-Romero N , Seigler L , Barbosa Costa G , Hutson C , Maghlakelidze G , Olson V , Doty JB . Viruses 2020 12 (12) Akhmeta virus is a zoonotic Orthopoxvirus first identified in 2013 in the country of Georgia. Subsequent ecological investigations in Georgia have found evidence that this virus is widespread in its geographic distribution within the country and in its host-range, with rodents likely involved in its circulation in the wild. Yet, little is known about the pathogenicity of this virus in rodents. We conducted the first laboratory infection of Akhmeta virus in CAST/EiJ Mus musculus to further characterize this novel virus. We found a dose-dependent effect on mortality and weight loss (p < 0.05). Anti-orthopoxvirus antibodies were detected in the second- and third-highest dose groups (5 × 10(4) pfu and 3 × 10(2) pfu) at euthanasia by day 10, and day 14 post-infection, respectively. Anti-orthopoxvirus antibodies were not detected in the highest dose group (3 × 10(6) pfu), which were euthanized at day 7 post-infection and had high viral load in tissues, suggesting they succumbed to disease prior to mounting an effective immune response. In order of highest burden, viable virus was detected in the nostril, lung, tail, liver and spleen. All individuals tested in the highest dose groups were DNAemic. Akhmeta virus was highly pathogenic in CAST/EiJ Mus musculus, causing 100% mortality when ≥3 × 10(2) pfu was administered. |
Four new species of the Hylomyscus anselli group (Mammalia: Rodentia: Muridae) from the Democratic Republic of Congo and Tanzania
Kerbis Peterhans JC , Hutterer R , Doty JB , Malekani JM , Moyer DC , Krásová J , Bryja J , Banasiak RA , Demos TC . Bonn Zoological Bulletin 2020 69 (1) 55-83 As in many other small mammal groups from the Afrotropics, the number of species recognized within the genus Hylomyscus has increased considerably over the past dozen years. The last comprehensive review (2005) of the genus recognized eight species. Since that time, nine additional species have been elevated from synonymy (n = 4) or described as new (n = 5). Here we describe four additional new species supported by morphological and molecular evidence, all collected by the late William Stanley. Two of the new taxa are sympatric and come from the poorly known left bank (direction source to mouth) of the Congo River. One of these (Hylomyscus pygmaeus sp. nov.) is easily recognized, as it is tiny and significantly smaller than any known species of the genus; the second new species (Hylomyscus thornesmithae sp. nov.) is also small, and syntopic with the first. The third new species (Hylomyscus stanleyi sp. nov.), from the SW corner of Tanzania, is quite large and had been previously included within the hypodigm of Hylomyscus anselli following its recognition from within the synonymy of Hylomyscus denniae. The fourth species (Hylomyscus mpungamachagorum sp. nov.) is from Mahale Mountains National Park, western Tanzania. Our study reveals a much higher species diversity of the genus than previously known, providing insights into additional Afrotropical and Afromontane centers of endemism that require further exploration. |
Exportation of Monkeypox virus from the African continent.
Mauldin MR , McCollum AM , Nakazawa YJ , Mandra A , Whitehouse ER , Davidson W , Zhao H , Gao J , Li Y , Doty J , Yinka-Ogunleye A , Akinpelu A , Aruna O , Naidoo D , Lewandowski K , Afrough B , Graham V , Aarons E , Hewson R , Vipond R , Dunning J , Chand M , Brown C , Cohen-Gihon I , Erez N , Shifman O , Israeli O , Sharon M , Schwartz E , Beth-Din A , Zvi A , Mak TM , Ng YK , Cui L , Lin RTP , Olson VA , Brooks T , Paran N , Ihekweazu C , Reynolds MG . J Infect Dis 2020 225 (8) 1367-1376 BACKGROUND: The largest West African monkeypox outbreak began September 2017, in Nigeria. Four individuals traveling from Nigeria to the UK (2), Israel, and Singapore became the first human monkeypox cases exported from Africa, and a related nosocomial transmission event in the UK became the first confirmed human-to-human monkeypox transmission event outside of Africa. METHODS: Epidemiological and molecular data for exported and Nigerian cases were analyzed jointly to better understand the exportations in the temporal and geographic context of the outbreak. RESULTS: Isolates from all travelers and a Bayelsa case shared a most recent common ancestor and traveled to Bayelsa, Delta, or Rivers states. Genetic variation for this cluster was lower than would be expected from a random sampling of genomes from this outbreak, but data did not support direct links between travelers. CONCLUSIONS: Monophyly of exportation cases and the Bayelsa sample, along with the intermediate levels of genetic variation suggest a small pool of related isolates is the likely source for the exported infections. This may be the result of the level of genetic variation present in monkeypox isolates circulating within the contiguous region of Bayelsa, Delta, and Rivers states, or another more restricted, yet unidentified source pool. |
IMVAMUNE and ACAM2000 provide different protection against disease when administered postexposure in an intranasal monkeypox challenge prairie dog model
Keckler MS , Salzer JS , Patel N , Townsend MB , Nakazawa YJ , Doty JB , Gallardo-Romero NF , Satheshkumar PS , Carroll DS , Karem KL , Damon IK . Vaccines (Basel) 2020 8 (3) The protection provided by smallpox vaccines when used after exposure to Orthopoxviruses is poorly understood. Postexposu re administration of 1st generation smallpox vaccines was effective during eradication. However, historical epidemiological reports and animal studies on postexposure vaccination are difficult to extrapolate to today's populations, and 2nd and 3rd generation vaccines, developed after eradication, have not been widely tested in postexposure vaccination scenarios. In addition to concerns about preparedness for a potential malevolent reintroduction of variola virus, humans are becoming increasingly exposed to naturally occurring zoonotic orthopoxviruses and, following these exposures, disease severity is worse in individuals who never received smallpox vaccination. This study investigated whether postexposure vaccination of prairie dogs with 2nd and 3rd generation smallpox vaccines was protective against monkeypox disease in four exposure scenarios. We infected animals with monkeypox virus at doses of 10(4) pfu (2× LD(50)) or 10(6) pfu (170× LD(50)) and vaccinated the animals with IMVAMUNE(®) or ACAM2000(®) either 1 or 3 days after challenge. Our results indicated that postexposure vaccination protected the animals to some degree from the 2× LD(50), but not the 170× LD(5) challenge. In the 2× LD(50) challenge, we also observed that administration of vaccine at 1 day was more effective than administration at 3 days postexposure for IMVAMUNE(®), but ACAM2000(®) was similarly effective at either postexposure vaccination time-point. The effects of postexposure vaccination and correlations with survival of total and neutralizing antibody responses, protein targets, take formation, weight loss, rash burden, and viral DNA are also presented. |
Magnitude and diversity of immune response to vaccinia virus is dependent on route of administration
Hughes LJ , Townsend MB , Gallardo-Romero N , Hutson CL , Patel N , Doty JB , Salzer JS , Damon IK , Carroll DS , Satheshkumar PS , Karem KL . Virology 2020 544 55-63 Historic observations suggest that survivors of smallpox maintained lifelong immunity and protection to subsequent infection compared to vaccinated individuals. Although protective immunity by vaccination using a related virus (vaccinia virus (VACV) strains) was the key for smallpox eradication, it does not uniformly provide long term, or lifelong protective immunity (Heiner et al., 1971). To determine differences in humoral immune responses, mice were inoculated with VACV either systemically, using intranasal inoculation (IN), or locally by an intradermal (ID) route. We hypothesized that sub-lethal IN infections may mimic systemic or naturally occurring infection and lead to an immunodominance reaction, in contrast to localized ID immunization. The results demonstrated systemic immunization through an IN route led to enhanced adaptive immunity to VACV-expressed protein targets both in magnitude and in diversity when compared to an ID route using a VACV protein microarray. In addition, cytokine responses, assessed using a Luminex(R) mouse cytokine multiplex kit, following IN infection was greater than that stemming from ID infection. Overall, the results suggest that the route of immunization (or infection) influences antibody responses. The greater magnitude and diversity of response in systemic infection provides indirect evidence for anecdotal observations made during the smallpox era that survivors maintain lifelong protection. These findings also suggest that systemic or disseminated host immune induction may result in a superior response, that may influence the magnitude of, as well as duration of protective responses. |
Asymptomatic orthopoxvirus circulation in humans in the wake of a monkeypox outbreak among chimpanzees in Cameroon
Guagliardo SAJ , Monroe B , Moundjoa C , Athanase A , Okpu G , Burgado J , Townsend MB , Satheshkumar PS , Epperson S , Doty JB , Reynolds MG , Dibongue EE , Etoundi GA , Mathieu E , McCollum AM . Am J Trop Med Hyg 2019 102 (1) 206-212 Monkeypox virus is a zoonotic Orthopoxvirus (OPXV) that causes smallpox-like illness in humans. In Cameroon, human monkeypox cases were confirmed in 2018, and outbreaks in captive chimpanzees occurred in 2014 and 2016. We investigated the OPXV serological status among staff at a primate sanctuary (where the 2016 chimpanzee outbreak occurred) and residents from nearby villages, and describe contact with possible monkeypox reservoirs. We focused specifically on Gambian rats (Cricetomys spp.) because it is a recognized possible reservoir and because contact with this species was common enough to render sufficient statistical power. We collected one 5-mL whole blood specimen from each participant to perform a generic anti-OPXV ELISA test for IgG and IgM antibodies and administered a questionnaire about prior symptoms of monkeypox-like illness and contact with possible reservoirs. Our results showed evidence of OPXV exposures (IgG positive, 6.3%; IgM positive, 1.6%) among some of those too young to have received smallpox vaccination (born after 1980, n = 63). No participants reported prior symptoms consistent with monkeypox. After adjusting for the education level, participants who frequently visited the forest were more likely to have recently eaten Gambian rats (OR: 3.36, 95% CI: 1.91-5.92, P < 0.001) and primate sanctuary staff were less likely to have touched or sold Gambian rats (OR: 0.23, 95% CI: 0.19-0.28, P < 0.001). The asymptomatic or undetected circulation of OPXVs in humans in Cameroon is likely, and contact with monkeypox reservoirs is common, raising the need for continued surveillance for human and animal disease. |
Characterization of Monkeypox virus dissemination in the black-tailed prairie dog (Cynomys ludovicianus) through in vivo bioluminescent imaging
Weiner ZP , Salzer JS , LeMasters E , Ellison JA , Kondas AV , Morgan CN , Doty JB , Martin BE , Satheshkumar PS , Olson VA , Hutson CL . PLoS One 2019 14 (9) e0222612 Monkeypox virus (MPXV) is a member of the genus Orthopoxvirus, endemic in Central and West Africa. This viral zoonosis was introduced into the United States in 2003 via African rodents imported for the pet trade and caused 37 human cases, all linked to exposure to MPXV-infected black-tailed prairie dogs (Cynomys ludovicianus). Prairie dogs have since become a useful model of MPXV disease, utilized for testing of potential medical countermeasures. In this study, we used recombinant MPXV containing the firefly luciferase gene (luc) and in vivo imaging technology to characterize MPXV pathogenesis in the black-tailed prairie dog in real time. West African (WA) MPXV could be visualized using in vivo imaging in the nose, lymph nodes, intestines, heart, lung, kidneys, and liver as early as day 6 post infection (p.i.). By day 9 p.i., lesions became visible on the skin and in some cases in the spleen. After day 9 p.i., luminescent signal representing MPXV replication either increased, indicating a progression to what would be a fatal infection, or decreased as infection was resolved. Use of recombinant luc+ MPXV allowed for a greater understanding of how MPXV disseminates throughout the body in prairie dogs during the course of infection. This technology will be used to reduce the number of animals required in future pathogenesis studies as well as aid in determining the effectiveness of potential medical countermeasures. |
Isolation and characterization of Akhmeta virus from wild caught rodents ( Apodemus spp.) in Georgia.
Doty JB , Maghlakelidze G , Sikharulidze I , Tu SL , Morgan CN , Mauldin MR , Parkadze O , Kartskhia N , Turmanidze M , Matheny A , Davidson W , Tang S , Gao J , Li Y , Upton C , Carroll DS , Emerson GL , Nakazawa Y . J Virol 2019 93 (24) In 2013, a novel orthopoxvirus was detected in skin lesions of two cattle herders from the Kakheti region of Georgia (country), this virus was named Akhmeta virus. Subsequent investigation of these cases revealed that small mammals in the area had serological evidence of orthopoxvirus infections, suggesting their involvement in the maintenance of these viruses in nature. In October 2015, we began a longitudinal study assessing the natural history of orthopoxviruses in Georgia. As part of this effort, we trapped small mammals near Akhmeta (n=176) and Gudauri (n=110). Here, we describe the isolation and molecular characterization of Akhmeta virus from lesion material and pooled heart and lung samples collected from five wood mice (Apodemus uralensis and A. flavicollis) in these two locations. The genomes of Akhmeta virus obtained from rodents group into 2 clades; one clade represented by viruses isolated from A. uralensis samples, and one clade represented by viruses isolated from A. flavicollis samples. These genomes also display several presumptive recombination events for which gene truncation and identity has been examined.Importance Akhmeta virus is a unique Orthopoxvirus that was described in 2013 from the country of Georgia. This paper presents the first isolation of this virus from small mammal (Rodentia; Apodemus spp.) samples and the molecular characterization of those isolates. The identification of the virus in small mammals is an essential component to understanding of the natural history of this virus and its transmission to human populations; and could guide public health interventions in Georgia. Akhmeta virus genomes harbor evidence suggestive of recombination with a variety of other orthopoxviruses; this has implications for the evolution of orthopoxviruses, their ability to infect mammalian hosts, and their ability to adapt to novel host species. |
Analgesia during monkeypox virus experimental challenge studies in prairie dogs (Cynomys ludovicianus)
Hutson CL , Gallardo-Romero N , Carroll DS , Salzer JS , Ayers JD , Doty JB , Hughes CM , Nakazawa Y , Hudson P , Patel N , Keckler MS , Olson VA , Nagy T . J Am Assoc Lab Anim Sci 2019 58 (4) 485-500 Because human patients with monkeypox virus (MPXV) infection report painful symptoms, it is reasonable to assume that animals infected with MPXV experience some degree of pain. Understanding whether and how analgesics affect MPXV disease progression is crucial when planning in vivo challenge experiments. In the current study, we challenged prairie dogs with a low dose (4 x10(3) pfu) of MPXV and treated with meloxicam (NSAID) or buprenorphine (opioid); control animals did not receive analgesia or received analgesia without MPXV challenge. Subsets of animals from each group were serially euthanized during the course of the study. Disease progression and viral kinetics were similar between groups, but MXPVinfected, meloxicam-treated animals showed increasing trends of morbidity and mortality compared with other groups. Differences between no-analgesia MPXV-infected control animals and MPXV-infected animals treated with buprenorphine were minimal. The findings in the current study allow more informed decisions concerning the use of analgesics during experimental MPXV challenge studies, thereby improving animal welfare. In light of these findings, we have modified our pain scale for this animal model to include the use of buprenorphine for pain relief when warranted after MPXV challenge. |
Outbreak of human monkeypox in Nigeria in 2017-18: a clinical and epidemiological report.
Yinka-Ogunleye A , Aruna O , Dalhat M , Ogoina D , McCollum A , Disu Y , Mamadu I , Akinpelu A , Ahmad A , Burga J , Ndoreraho A , Nkunzimana E , Manneh L , Mohammed A , Adeoye O , Tom-Aba D , Silenou B , Ipadeola O , Saleh M , Adeyemo A , Nwadiutor I , Aworabhi N , Uke P , John D , Wakama P , Reynolds M , Mauldin MR , Doty J , Wilkins K , Musa J , Khalakdina A , Adedeji A , Mba N , Ojo O , Krause G , Ihekweazu C . Lancet Infect Dis 2019 19 (8) 872-879 BACKGROUND: In September, 2017, human monkeypox re-emerged in Nigeria, 39 years after the last reported case. We aimed to describe the clinical and epidemiological features of the 2017-18 human monkeypox outbreak in Nigeria. METHODS: We reviewed the epidemiological and clinical characteristics of cases of human monkeypox that occurred between Sept 22, 2017, and Sept 16, 2018. Data were collected with a standardised case investigation form, with a case definition of human monkeypox that was based on previously established guidelines. Diagnosis was confirmed by viral identification with real-time PCR and by detection of positive anti-orthopoxvirus IgM antibodies. Whole-genome sequencing was done for seven cases. Haplotype analysis results, genetic distance data, and epidemiological data were used to infer a likely series of events for potential human-to-human transmission of the west African clade of monkeypox virus. FINDINGS: 122 confirmed or probable cases of human monkeypox were recorded in 17 states, including seven deaths (case fatality rate 6%). People infected with monkeypox virus were aged between 2 days and 50 years (median 29 years [IQR 14]), and 84 (69%) were male. All 122 patients had vesiculopustular rash, and fever, pruritus, headache, and lymphadenopathy were also common. The rash affected all parts of the body, with the face being most affected. The distribution of cases and contacts suggested both primary zoonotic and secondary human-to-human transmission. Two cases of health-care-associated infection were recorded. Genomic analysis suggested multiple introductions of the virus and a single introduction along with human-to-human transmission in a prison facility. INTERPRETATION: This study describes the largest documented human outbreak of the west African clade of the monkeypox virus. Our results suggest endemicity of monkeypox virus in Nigeria, with some evidence of human-to-human transmission. Further studies are necessary to explore animal reservoirs and risk factors for transmission of the virus in Nigeria. FUNDING: None. |
Field identification key and guide for bats of the United States of America
Morgan CN , Ammerman LK , Demere KD , Doty JB , Nakazawa YJ , Mauldin MR . Occas Pap Tex Tech Univ Mus 2019 360 Bats are the second most speciose lineage of mammals with more than 1,300 recognized species. Overall, bats are extremely ecologically and morphologically diverse, making them of interest to a wide variety of biologists. Bats are also known reservoirs for an assortment of zoonotic diseases, including rabies, for which they are commonly tested if identified as sick, behaving abnormally, or in instances where there has been a significant human exposure. In these cases, proper identification of bat species is important to public health experts as it will inform future testing procedures and management practices, as well as broaden our understanding of rabies virus bat variant distributions and disease ecology. Despite the multiple disciplines interested in bats, no key has been developed which includes all species found within the United States. For this reason, a dichotomous key and bat identification guide, designed to differentiate bats to species level, has been developed. This document can be used by people with a variety of backgrounds to morphologically identify bats quickly and accurately using only a scale, a ruler, and attention to detail. |
Epidemiologic and ecologic investigations of monkeypox, Likouala Department, Republic of the Congo, 2017
Doshi RH , Guagliardo SAJ , Doty JB , Babeaux AD , Matheny A , Burgado J , Townsend MB , Morgan CN , Satheshkumar PS , Ndakala N , Kanjingankolo T , Kitembo L , Malekani J , Kalemba L , Pukuta E , N'Kaya T , Kangoula F , Moses C , McCollum AM , Reynolds MG , Mombouli JV , Nakazawa Y , Petersen BW . Emerg Infect Dis 2019 25 (2) 281-289 Monkeypox, caused by a zoonotic orthopoxvirus, is endemic in Central and West Africa. Monkeypox has been sporadically reported in the Republic of the Congo. During March 22-April 5, 2017, we investigated 43 suspected human monkeypox cases. We interviewed suspected case-patients and collected dried blood strips and vesicular and crust specimens (active lesions), which we tested for orthopoxvirus antibodies by ELISA and monkeypox virus and varicella zoster virus DNA by PCR. An ecologic investigation was conducted around Manfouete, and specimens from 105 small mammals were tested for anti-orthopoxvirus antibodies or DNA. Among the suspected human cases, 22 met the confirmed, probable, and possible case definitions. Only 18 patients had available dried blood strips; 100% were IgG positive, and 88.9% (16/18) were IgM positive. Among animals, only specimens from Cricetomys giant pouched rats showed presence of orthopoxvirus antibodies, adding evidence to this species' involvement in the transmission and maintenance of monkeypox virus in nature. |
Monkeypox re-emergence in Africa: a call to expand the concept and practice of One Health
Reynolds MG , Doty JB , McCollum AM , Olson VA , Nakazawa Y . Expert Rev Anti Infect Ther 2019 17 (2) 129-139 INTRODUCTION: Monkeypox is a re-emerging viral zoonosis that occurs naturally in heavily-forested regions of West and Central Africa. Inter-human transmission of monkeypox virus, although limited, drives outbreaks, particularly in household and healthcare settings. But the available evidence suggests that without repeated zoonotic introductions, human infections would eventually cease to occur. Therefore, interrupting virus transmission from animals to humans is key to combatting this disease. Such efforts, however, are hindered by an incomplete understanding of the maintenance and transmission dynamics of the virus in its natural reservoir host(s). Areas covered: Herein we review laboratory and field studies examining the susceptibility of various animal taxa to monkeypox virus infection, and note the competence of various species to serve as reservoirs or transmission hosts. In addition, we discuss early socio-ecologic theories of monkeypox virus transmission in rural settings and review current modes of ecologic investigation-including ecologic niche modeling, and ecologic sampling-in light of their potential to identify specific animal species and features of the environment that are associated with heightened risk for human disease. Expert opinion: The role of disease ecology and scientific research in ongoing disease prevention efforts should be reinforced, particularly for wildlife-associated zoonoses such as monkeypox. Such efforts alongside those aimed at nurturing 'One Health' collaborations may ultimately hold the greatest promise for reducing human infections with this pathogen. |
Notes from the Field: Responding to an outbreak of monkeypox using the One Health approach - Nigeria, 2017-2018
Eteng WE , Mandra A , Doty J , Yinka-Ogunleye A , Aruna S , Reynolds MG , McCollum AM , Davidson W , Wilkins K , Saleh M , Ipadeola O , Manneh L , Anebonam U , Abdulkareem Z , Okoli N , Agenyi J , Dan-Nwafor C , Mahmodu I , Ihekweazu C . MMWR Morb Mortal Wkly Rep 2018 67 (37) 1040-1041 On September 22, 2017, a suspected human case of monkeypox was reported to the Nigeria Centre for Disease Control (NCDC) from Bayelsa State in southern Nigeria. Because monkeypox had not been reported in Nigeria since 1978 (1), the case raised national and international concern. A multisectoral, international outbreak investigation was undertaken to identify sources and risk factors, establish surveillance, and enhance preparedness. A suspected case was defined as the sudden onset of fever, followed by a vesiculopustular rash primarily on the face, palms, and soles. A confirmed case was any suspected case with laboratory confirmation (by serology, molecular detection of viral DNA, or virus isolation). A probable case was a suspected case epidemiologically linked to a confirmed case. As of February 25, 2018, a total of 228 suspected cases (including 89 confirmed and three probable cases) had been investigated in 24 of Nigeria’s 36 states and the Federal Capital Territory. Six deaths (6.7%) were recorded among the 89 confirmed cases. The outbreak has not been declared over, and NCDC continues to collect data to develop a baseline level for this disease, which had not been reported in 40 years and now might be endemic to Nigeria. Given the zoonotic nature of the disease, this outbreak has required a robust One Health outbreak collaboration among human, animal, and environmental health institutions. |
Demonstration of efficient vertical and venereal transmission of dengue virus type-2 in a genetically diverse laboratory strain of Aedes aegypti.
Sanchez-Vargas I , Harrington LC , Doty JB , Black WC4th , Olson KE . PLoS Negl Trop Dis 2018 12 (8) e0006754 Aedes aegypti is the primary mosquito vector of dengue viruses (DENV; serotypes 1-4). Human-mosquito transmission cycles maintain DENV during epidemics but questions remain regarding how these viruses survive when human infections and vector abundance are minimal. Aedes mosquitoes can transmit DENV within the vector population through two alternate routes: vertical and venereal transmission (VT and VNT, respectively). We tested the efficiency of VT and VNT in a genetically diverse laboratory (GDLS) strain of Ae. aegypti orally infected with DENV2 (Jamaica 1409). We examined F1 larvae from infected females generated during the first and second gonotrophic cycles (E1 and E2) for viral envelope (E) antigen by amplifying virus in C6/36 cells and then performing an indirect immunofluorescence assay (IFA). RT-PCR/nested PCR analyses confirmed DENV2 RNA in samples positive by IFA. We observed VT of virus to larvae and adult male progeny and VNT of virus to uninfected virgin females after mating with males that had acquired virus by the VT route. We detected no DENV2 in 30 pools (20 larvae/pool) of F1 larvae following the first gonotrophic cycle, suggesting limited virus dissemination at 7 days post-infection. DENV2 was detected by IFA in 27 of 49 (55%) and 35 of 51 (68.6%) F1 larval pools (20 larvae/pool) from infected E2 females that received a second blood meal without virus at 10 or 21 days post-infection (E2-10d-F1 and E2-21-F1), respectively. The minimum filial infection rates by IFA for E2-10d-F1 and E2-21d-F1 mosquitoes were 1:36 and 1:29, respectively. The VNT rate from E2-10d-F1 males to virgin (uninfected) GDLS females was 31.6% (118 of 374) at 8 days post mating. Twenty one percent of VNT-infected females receiving a blood meal prior to mating had disseminated virus in their heads, suggesting a potential pathway for virus to re-enter the human-mosquito transmission cycle. This is the first report of VNT of DENV by male Ae. aegypti and the first demonstration of sexual transmission in Aedes by naturally infected males. Our results demonstrate the potential for VT and VNT of DENV in nature as mechanisms for virus maintenance during inter-epidemic periods. |
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