GA

Gabriela Añez Aguilera

Centro Nacional de Enfermedades Tropicales

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Roxana Loayza Mafayle

Centro Nacional de Enfermedades Tropicales

Jimmy Revollo Guzmán

Centro Nacional de Enfermedades Tropicales

Joel M. Montgomery

Centers for Disease Control and Prevention

Shannon Whitmer

Centers for Disease Control and Prevention

Kamalesh Kumar Patel

Indiana University School of Medicine

Trevor Shoemaker

Centers for Disease Control and Prevention

Maria Morales-Betoulle

Centers for Disease Control and Prevention

Stuart T. Nichol

Centers for Disease Control and Prevention

Caitlin M. Cossaboom

Centers for Disease Control and Prevention

E. Gil Colque

Centro Nacional de Enfermedades Tropicales

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Centro Nacional de Enfermedades Tropicales

Centers for Disease Control and Prevention

National Center for Emerging and Zoonotic Infectious Diseases

National Institutes of Health

Ministerio de Salud

Inserm

Institut de Recherche pour le Développement

École des Hautes Études en Santé Publique

The Centers

Aix-Marseille Université

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Detection and characterization of a novel strain of Chapare virus during an outbreak of viral hemorrhagic fever in Bolivia, 2019

International Journal of Infectious Diseases (2020)

Maria Morales-Betoulle Roxana Loayza Mafayle Cinthia Avila Caitlin M. Cossaboom Sebastián Sasías

Background: Bolivian hemorrhagic fever is caused by Machupo virus (MACV), which was first isolated and characterized in 1963, and has since caused sporadic outbreaks with notable re-emergence in 2007 in the Beni region. A novel New World arenavirus, Chapare virus (CHAPV), was identified as the etiology for one fatal case of hemorrhagic fever, now known as Chapare hemorrhagic fever (CHHF), in 2004 in Cochabamba. No CHHF cases have been identified since. In June 2019, the Bolivian Epidemiology Services in Caranavi reported three hemorrhagic fever cases of unknown etiology. Specimens from two of the cases tested negative at the Bolivian Center for Tropical Diseases (CENETROP) for MACV, Dengue, and Yellow Fever virus. Because a viral hemorrhagic fever was suspected, human specimens were sent to the Viral Special Pathogens Branch, Centers for Disease Control and Prevention (USA) for further testing and identification in the Biosafety Level-4 (BSL4) lab. Methods and materials: Using a combination of next generation sequencing and virus isolation, we were able to identify and characterize the virus circulating in Caranavi as a strain of Chapare virus. Based on the initial sequencing data, we designed primers and probes to develop specific real-time RT-PCR assays for the S and L segments of the virus. Results: In collaboration with the Pan American Health Organization, we deployed the assays to CENETROP and provided training for specimen processing. We detected CHAPV RNA in a variety of human (blood, serum, tracheal aspirates, urine, semen) and rodent specimens associated with the outbreak. Conclusion: Since Machupo and Chapare viruses are BSL4 agents they require special biosafety precautions and inactivation methods during specimen processing. Molecular techniques are preferred when handling viral hemorrhagic fever specimens in laboratories that do not have BSL4. Our approach of initial characterization in CDC's BSL4 lab and then deployment of the molecular assays for continued testing in Bolivia has been successful to detect the presence of viral RNA in survivors, identify potential rodent reservoirs, and build local capacity for rapid diagnosis and response to future suspect CHHF cases. This work demonstrates that international partnerships can aid urgent public health responses and highlights the need to enhance laboratory capacity in Bolivia.

Ebola Hemorrhagic Fever

Viral hemorrhagic fever

Etiology

Arenavirus

Veterinary virology

10.1016/j.ijid.2020.11.124

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Citations (2)

Re-emergence of Chapare hemorrhagic fever in Bolivia, 2019

International Journal of Infectious Diseases (2020)

Caitlin M. Cossaboom A Ramírez Carla Romero Maria Morales-Betoulle Guerra Vega

Background: Chapare virus (CHAPV), causative agent of Chapare hemorrhagic fever (CHHF), is a rodent–borne virus of the genus Mammarenvirus, family Arenaviridae. The only previously confirmed case of CHHF was a 2004 fatality in an agricultural worker in Cochabamba, Bolivia with limited epidemiological information. Case description: In June 2019, the Bolivian Ministry of Health reported a hemorrhagic fever cluster of unknown etiology. Case one, 65-year-old agricultural worker, presented in Caranavi Municipality on 1 May reporting eight days of fever, myalgia, retro-orbital pain, abdominal pain, and vomiting progressing to include gingival hemorrhage. He died on 12 May, suspected of severe dengue. Case two, 25-year-old medical intern, attended to case one on 11 May, developed identical symptoms on 20 May, transferred to a referral hospital in La Paz on 2 June, and died two days later. Case three, 22-year-old agricultural worker, spent the night in the hospital with case one on 11 May and developed identical symptoms with maculo-papular rash and irritability on 29 May. On 3 June, he was transferred from Caranavi to La Paz and discharged on 30 June. Two healthcare workers, cases four and five, had contact with case two during transfer on 2 June and endoscopy on 4 June, and developed fever, arthromyalgia, and malaise on 18 June that progressed to gingival hemorrhage. Case four, 48-year-old ambulance worker, eventually recovered, while case five, 42-year-old gastroenterologist, died on 10 July. Discussion: Specimens from cases two and three were shipped to the Centers for Disease Control and Prevention in Atlanta, Georgia, USA where next generation sequencing identified a novel strain of Chapare virus. A novel real-time RT-PCR assay was developed that detected CHAPV RNA in specimens (blood, saliva, tracheal aspirates, urine, and/or semen) from four cases. Case one remains probable as no specimens were available. CHAPV RNA was detected in blood, saliva, urine, and semen of the two survivors following recovery. We report a confirmed outbreak of CHHF in Bolivia. Novel disease characteristics are described including human-to-human transmission, incubation period, and viral persistence in bodily fluids following recovery. Conclusion: This investigation highlights the need for enhanced surveillance, public awareness, and improved identification and prevention of CHHF.

myalgia

Irritability

Malaise

Etiology

Melena

10.1016/j.ijid.2020.11.073

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Citations (2)

A Novel Approach Using Transcomplementing Adenoviral Vectors for Gene Therapy of Adrenocortical Cancer

Hormone and Metabolic Research (2002)

Gernot W. Wolkersdörfer S. Bornstein James N. Higginbotham Naoki Hiroi J.J. Vaquero

Current therapies for adrenocortical carcinomas do not improve the life expectancy of patients. In this study, we tested whether a gene-transfer therapy based upon a suicide gene/prodrug system would be effective in an animal model of the disease. We employed E4- and E1A/B-depleted, herpes simplex virus-thymidine kinase-expressing adenoviral mutants that transcomplement each other within tumor cells, hereby improving transgene delivery and efficacy by viral replication in situ. Transcomplementation of vectors increased the fraction of transduced of tumor cells. This increase was accompanied by greater tumor volume reduction compared to non-transcomplementing approaches. Survival time improved with non-replicating vectors plus GCV compared to controls. However, transcomplementation/replication of vectors led to a further significant increment in anti-tumor activity and survival time (p < 0.02). In treated animals, we observed a high number of apoptotic nuclei both adjacent to and distant from injection sites and sites of viral oncolysis. Ultrastructural analyses exhibited nuclear inclusion bodies characteristic of virus production in situ, and provided further evidence that this therapy induced apoptotic cell death within tumor cells. We conclude that the efficacy of suicide gene therapy is significantly amplified by viral replication and, in combination with GCV, significantly reduces tumor burden and increases survival time.

Suicide gene

Thymidine kinase

10.1055/s-2002-33255

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Citations (16)

Viral aetiology influenza like illnesses in Santa Cruz, Bolivia (2010–2012)

Virology Journal (2014)

Julie Delangue Yelin Roca Sanchez Géraldine Piorkowski Maël Bessaud Cécile Baronti

Acute respiratory infections represent a serious public health issue worldwide but virological aetiologies of Influenza Like Illnesses (ILIs) remain largely unknown in developing countries. This study represents the first attempt to characterise viral aetiologies of ILIs in Bolivia. It was performed in Santa Cruz city from January 2010 to September 2012, based on 564 naso-pharyngeal swabs collected in a National Reference Laboratory and real-time PCR techniques, viral cultures and phylogenetic analyses. 50.2% of samples were positive for at least one virus with influenza viruses (Flu A: ~15%; Flu B: ~9%), rhinoviruses (~8%), coronaviruses (~5%) and hRSV (~4%) being the most frequently identified. The pattern of viral infections varied according to age groups. The elucidation rate was the highest (>60%) amongst patients under 10 yo and the lowest (<40%) amongst patients ≥60 yo. Nearly 3% of samples showed dual viral infections. Epidemiological peaks were associated with a predominant virus but generally included 30-50% of infections by different viruses. Unexpectedly, the frequency of influenza in the 0–4 yo population was very low and a complete hRSV eclipse occurred in 2011. Genetic analyses indicated that distinct evolutionary lineages of Flu A(H1N1)pdm2009, Flu A/H3N2 and Flu B have co-circulated in Bolivia in the study period, originating from Central and North America, Europe, Asia and Australia. Our results emphasise the requirement for a reinforced epidemiological and genetic follow-up of influenza and other ILIs in Bolivia to further inform the preparation of vaccines used in the region, guide vaccination campaigns and improve the medical management of patients.

Pandemic

Etiology

Influenza-like illness

10.1186/1743-422x-11-35

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Citations (11)