Exploring service user perspectives of behavioural family therapy in early intervention in psychosis.

AIMS: Family intervention (FI) is recommended in national guidance to be offered to all service users accessing an early intervention in psychosis (EIP) team, due to the consistent evidence base in reducing relapse and rehospitalisation rates. However, FI implementation is poor nationally. Although barriers have been identified at the level of staff member and the organisation, there is a paucity of research identifying service user perspectives. METHODS: A qualitative questionnaire design was used to explore service user perspectives of behavioural family therapy (BFT) within a specialist EIP service in northwest England. RESULTS: Most participants contacted reported they lacked knowledge and understanding of BFT, with 54% reporting that this intervention had not been offered to them. This finding was unexpected and is inconsistent with the offer of BFT documentation in their clinical notes. Reasons for accepting BFT included to increase understanding of family members and for them to also be supported. Reasons for declining BFT included a preference for one-to-one interventions and not wanting family involved in their care. CONCLUSIONS: National guidance on FI for psychosis is not reliably being translated to clinical practice, with many participants reporting that they were not offered this intervention. A key factor in accepting or declining an offer of BFT appeared to be whether participants wanted family members to be involved in their care. A lack of understanding of the BFT approach was evident, it is recommended that the offer of FI in psychosis is improved for service users to make an informed decision.

The role of the social determinants of health in outcomes of surgery for low back pain: a systematic review and narrative synthesis.

BACKGROUND CONTEXT: Low back pain is a major cause of morbidity and disability worldwide and is responsible for vast societal impact. Rates of surgical intervention for lumbar spine disorders continue to rise but poor outcomes remain common. Understanding how the social determinants of health (SDH) influence spinal surgical outcomes stands to inform appropriately tailored care practices and lead to better patient outcomes. PURPOSE: To determine the relationships between the SDH and pain, opioid use, disability and work absenteeism following lumbar spine surgery. STUDY DESIGN: Systematic review and narrative synthesis. METHODS: We searched Embase, the Cochrane Library, Medline, and Web of Science from inception to April 21, 2020. Studies eligible for inclusion involved participants receiving lumbar spine surgery and investigated the relationship between at least one SDH and post-surgical pain, opioid use, disability or work absenteeism. We evaluated the risk of bias of included studies and used the PROGRESS-Plus framework to organize a narrative synthesis of findings. RESULTS: Relevant data was extracted from twenty-three studies involving 30,987 adults from 12 countries. A total of 107 relationships between the SDH and post-surgical outcomes were evaluated, 67 in multivariate analyses. Education was investigated in 23 analyses (14 studies): 70% revealed significant independent relationships between lower education and poorer outcomes. Socioeconomic status was investigated in nine analyses (four studies): 67% revealed independent relationships between lower socioeconomic status and poorer outcomes. Gender was investigated in 40 analyses (22 studies): indications that male versus female sex was associated with poorer outcomes were equivocal. Place of residence, race/ethnicity, and social capital were infrequently investigated. CONCLUSIONS: Low educational attainment and low-income status are clear independent contributors to poorer outcomes following lumbar spine surgery. Occupational factors and work context are likely to be influential. Further research is critical to guide best-practice spinal surgery through a health equity lens. STUDY REGISTRATION: PROSPERO registration number CRD42015015778.

Determination of Endovaginal Ultrasound Proficiency and Learning Curve Among Emergency Medicine Trainees.

OBJECTIVES: Performing and interpreting endovaginal ultrasound is an important skill used during the evaluation of obstetric and gynecologic emergencies. This study aims to describe the level of proficiency and confidence achieved after performing 25 endovaginal examinations. METHODS: This is a prospective study at a single urban academic emergency department. Participants performed a minimum of 25 endovaginal ultrasounds under the supervision of a point-of-care ultrasound expert. Anatomical structures were identified by the expert under ultrasound prior to each session. Each examination was scored for agreement of findings between the participant and expert. The data were used to develop a performance curve identifying when proficiency was achieved, where experiential benefit diminished, and when participants felt confident. RESULTS: A total of 1117 endovaginal ultrasound examinations were performed by 50 participants. Agreement after 25 examinations was highest (>95%) for probe insertion and preparation, bladder and uterus identification, and directionality. Agreement was lowest for identification of the ovaries (76%). Experiential benefit plateaus occurred earliest (10 exams) for preparation and insertion followed by bladder identification and directionality. Surprisingly, ovarian experiential benefit plateaued at 16 exams. Participant confidence improved overall and was lowest for the identification of ovaries and abnormal pelvic anatomy. CONCLUSIONS: There is a significant learning curve when performing endovaginal ultrasound. Our data do not support the use of 25 examinations as a minimum standard for identification of the ovaries or abnormal ovarian pathology.

Monitoring Incidence of COVID-19 Cases, Hospitalizations, and Deaths, by Vaccination Status - 13 U.S. Jurisdictions, April 4-July 17, 2021.

COVID-19 vaccine breakthrough infection surveillance helps monitor trends in disease incidence and severe outcomes in fully vaccinated persons, including the impact of the highly transmissible B.1.617.2 (Delta) variant of SARS-CoV-2, the virus that causes COVID-19. Reported COVID-19 cases, hospitalizations, and deaths occurring among persons aged ≥18 years during April 4-July 17, 2021, were analyzed by vaccination status across 13 U.S. jurisdictions that routinely linked case surveillance and immunization registry data. Averaged weekly, age-standardized incidence rate ratios (IRRs) for cases among persons who were not fully vaccinated compared with those among fully vaccinated persons decreased from 11.1 (95% confidence interval [CI] = 7.8-15.8) to 4.6 (95% CI = 2.5-8.5) between two periods when prevalence of the Delta variant was lower (<50% of sequenced isolates; April 4-June 19) and higher (≥50%; June 20-July 17), and IRRs for hospitalizations and deaths decreased between the same two periods, from 13.3 (95% CI = 11.3-15.6) to 10.4 (95% CI = 8.1-13.3) and from 16.6 (95% CI = 13.5-20.4) to 11.3 (95% CI = 9.1-13.9). Findings were consistent with a potential decline in vaccine protection against confirmed SARS-CoV-2 infection and continued strong protection against COVID-19-associated hospitalization and death. Getting vaccinated protects against severe illness from COVID-19, including the Delta variant, and monitoring COVID-19 incidence by vaccination status might provide early signals of changes in vaccine-related protection that can be confirmed through well-controlled vaccine effectiveness (VE) studies.

What do cancer survivors and their health care providers want from a healthy living program? Results from the first round of a co-design project.

PURPOSE: Healthy lifestyles are an important part of cancer survivorship, though survivors often do not adhere to recommended guidelines. As part of the co-design of a new online healthy living intervention, this study aimed to understand cancer survivors', oncology healthcare professionals' (HCP) and cancer non-government organisation (NGO) representatives' preferences regarding intervention content and format. METHODS: Survivors, HCP and NGO representatives participated in focus groups and interviews exploring what healthy living means to survivors, their experience with past healthy living programs and their recommendations for future program content and delivery. Sessions were audio recorded, transcribed verbatim and analysed thematically. RESULTS: Six focus groups and eight interviews were conducted including a total of 38 participants (21 survivors, 12 HCP, 5 NGO representatives). Two overarching messages emerged: (1) healthy living goes beyond physical health to include mental health and adjustment to a new normal and (2) healthy living programs should incorporate mental health strategies and peer support and offer direction in a flexible format with long-term accessibility. There was a high degree of consensus between participant groups across themes. CONCLUSIONS: These findings highlight the need for integration of physical and mental health interventions with flexibility in delivery. Future healthy living programs should investigate the potential for increased program adherence if mental health interventions and a hybrid of delivery options were included.

Imprecise Visual Feedback About Hand Location Increases a Classically Conditioned Pain Expectancy Effect.

We tested the hypotheses that rendering sensory input about hand location imprecise increases a classically conditioned pain expectancy effect, increases generalization of the effect to novel locations and reduces extinction of the effect. Forty healthy volunteers performed movements with their right hand along predefined paths. Each path passed through 2 locations that were defined as either i) the conditioned stimulus (CS+; paired with a painful unconditioned stimulus), or ii) unpaired (CS-). During acquisition phase, participants watched their hand as they moved it. Participants were randomly allocated to an Imprecise group, for whom visual feedback of the hand was offset 30 to 50 mm from its true location, or a Precise group, for whom vision was not disrupted. In the test phase, participants moved their hands to 5 locations-the CS+, CS-, and 3 locations that lay between the 2 ("generalization stimuli"). Our primary hypothesis was supported-pain expectancy was greater at the CS+ location in the Imprecise group than in the Precise group (6.9 [SD = 1.9] vs 5.4 [SD = 2.5], P= .02). Pain expectancies generalized to novel locations similarly in both groups and there was no difference in extinction between groups. Our primary hypothesis was supported but our subsequent hypotheses were not. PERSPECTIVE: We conditioned pain expectancy at a certain location of one hand, even though most participants were unaware of the contingency. Conditioned pain expectancy was greater when sensory information about location was less precise. This adds support to the possibility that associative learning may play a role in the progression of an acute pain episode to a more generalized pain disorder.

Low back pain and the social determinants of health: a systematic review and narrative synthesis.

The social determinants of health (SDH) are known to differentially impact outcomes from many noncommunicable diseases; however, their potential role in low back pain (LBP) is poorly defined. This review endeavours to comprehensively inform the field of their relevance. Our research question was: "How do the broad range of SDH and chronic LBP (CLBP) relate?" The primary aim of this review was to synthesise evidence of relationships between SDH and the frequency or severity of CLBP. Secondary aims were to identify relationships between SDH and LBP-related disability, work absenteeism, and opioid prescription. We included studies involving adult participants that evaluated relationships between one or more of the SDH and CLBP frequency or LBP outcomes (beyond 3 months). Two reviewers screened studies, extracted data, and assessed risk of bias. We synthesized the results narratively and applied PROGRESS to organise our findings. Database searches identified 7018 records. Forty-one studies were included, containing data from 2,161,617 adults from 17 countries. Twenty-four percent and 19% of the relationships included were classified as having a high risk of bias due to confounding and missing data, respectively. We reported 166 relationships representing the majority of the PROGRESS domains. An array of independent and interdependent relationships between the SDH and CLBP were identified with the strongest evidence for associations related to educational attainment and socioeconomic status. Our findings suggest that greater recognition of the contribution of SDH to disparities in LBP outcomes is warranted and this has the potential to usefully inform strategies to impact burden.

Availability and advertising of electronic cigarettes in two Russian cities following implementation of comprehensive tobacco advertising restrictions.

INTRODUCTION: Electronic cigarettes (e-cigarettes) continue to gain popularity globally. Jurisdictions with comprehensive tobacco control policies, which limit the use and availability of combustible tobacco products but do not regulate e-cigarettes (as in Russia), may be vulnerable to the expansion of the e-cigarette market. METHODS: Using McNemar's test conducted in STATA, this observational study assessed changes between 2014 and 2016 in the availability of e-cigarettes across 239 retail outlets in Moscow and St Petersburg. Also, this study characterized the presence of retail advertising and promotion of e-cigarettes in 2016. RESULTS: Between 2014 and 2016, the availability and display of e-cigarettes increased within traditional tobacco product retail venues (27.6% in 2014 vs 51.9% in 2016; p<0.01). CONCLUSIONS: Observations indicate that there has been an increase in the proportion of retailers selling and displaying e-cigarettes.

Point-of-Sale Tobacco Advertising and Display Bans: Policy Evaluation Study in Five Russian Cities.

BACKGROUND: The tobacco industry uses point-of-sale (POS) advertising, promotion, and product display to increase consumption of its products among current users, to attract new consumers, and to encourage former customers to resume tobacco use. As part of a comprehensive tobacco control effort, Russia-having one of the highest tobacco use prevalence rates in the world-enacted legislation that banned tobacco POS advertising, effective November 15, 2013, and banned the display of tobacco and the sale of cigarettes in kiosks, effective June 1, 2014. OBJECTIVE: The objective of the study was to evaluate the implementation of the national law by assessing the state of POS advertising, promotion, and product display, and sales in kiosks across Russia. METHODS: Two waves of observations were conducted to measure compliance with the POS restrictions: wave 1 took place in April-May 2014 after the advertising ban was in effect and again in August-September 2014 after the display ban and elimination of tobacco sales in kiosks came into effect. Observations were conducted by local trained staff that traveled to 5 populous cities in different regions of Russia (Moscow, St. Petersburg, Kazan, Ekaterinburg, and Novosibirsk). Staff followed a published POS evaluation protocol and used mobile phones to collect data. Observations were conducted in a roughly equal number of supermarket chains, convenience stores, and kiosks. Observed items included advertising at POS, product displays, and cigarette sales in kiosks. RESULTS: Observations were made in 780 venues in wave 1 and in 779 revisited venues in wave 2. In wave 1, approximately a third of supermarkets and convenience stores (34.2%, 184/538) were advertising cigarettes using light boxes, and over half of observed venues (54.3%, 292/538) had signage such as banners or shelf liners that used colors or images related to cigarette brands. Product displays were common in wave 1. In wave 2, compliance with advertising restrictions was very good: there were virtually no light boxes (1.0%, 5/489); banners or shelf liners were observed in 30.5% (149/489) of supermarkets/convenience stores; approximately 7.4% (36/489) of venues were still displaying products in a powerwall. In wave 2, 41.3% (100/242) of kiosks continued to sell tobacco. CONCLUSIONS: Russia's compliance with POS bans was excellent. Remaining compliance issues are largely with the use of cigarette brand colors or images used in banners or shelf liners; this type of infraction is more difficult to enforce as inspectors need to be deeply familiar with tobacco industry products and marketing practices. A sizable proportion of kiosks continue to sell tobacco post restrictions.

Rapid Diagnosis of Rhabdomyolysis with Point-of-Care Ultrasound.

It is important to rapidly diagnosis and treat rhabdomyolysis in order to decrease morbidity and mortality. To date there are no reports in the emergency medicine literature on the use of point-of-care ultrasound in the diagnosis of rhabdomyolysis. This unique case describes how ultrasound was used in the emergency department (ED) to quickly diagnose and treat rhabdomyolysis prior to confirmation with an elevated serum creatine kinase. When coupled with a high index of suspicion, ultrasound can be one of the most portable, readily available, low cost, and minimally invasive techniques for making a rapid diagnosis of rhabdomyolysis in the ED.

The Development and Piloting of a Mobile Data Collection Protocol to Assess Compliance With a National Tobacco Advertising, Promotion, and Product Display Ban at Retail Venues in the Russian Federation.

BACKGROUND: Tobacco control policies that lead to a significant reduction in tobacco industry marketing can improve public health by reducing consumption of tobacco and preventing initiation of tobacco use. Laws that ban or restrict advertising and promotion in point-of-sale (POS) environments, in the moment when consumers decide whether or not to purchase a tobacco product, must be correctly implemented to achieve the desired public health benefits. POS policy compliance assessments can support implementation; however, there are challenges to conducting evaluations that are rigorous, cost-effective, and timely. Data collection must be discreet, accurate, and systematic, and ideally collected both before and after policies take effect. The use of mobile phones and other mobile technology provide opportunities to efficiently collect data and support effective tobacco control policies. The Russian Federation (Russia) passed a comprehensive national tobacco control law that included a ban on most forms of tobacco advertising and promotion, effective November 15, 2013. The legislation further prohibited the display of tobacco products at retail trade sites and eliminated kiosks as a legal trade site, effective June 1, 2014. OBJECTIVE: The objective of the study was to develop and test a mobile data collection protocol including: (1) retailer sampling, (2) adaptation of survey instruments for mobile phones, and (3) data management protocols. METHODS: Two waves of observations were conducted; wave 1 took place during April-May 2014, after the advertising and promotion bans were effective, and again in August-September 2014, after the product display ban and elimination of tobacco sales in kiosks came into effect. Sampling took place in 5 Russian cities: Moscow, St. Petersburg, Novosibirsk, Yekaterinburg, and Kazan. Lack of access to a comprehensive list of licensed tobacco retailers necessitated a sampling approach that included the development of a walking protocol to identify tobacco retailers to observe. Observation instruments were optimized for use on mobile devices and included the collection of images/photos and the geographic location of retailers. Data were uploaded in real-time to a remote ("cloud-based") server accessible via Internet and verified with the use of a data management protocol that included submission of daily field notes from the research team for review by project managers. RESULTS: The walking protocol was a practical means of identifying 780 relevant retail venues in Russia, in the absence of reliable sampling resources. Mobile phones were convenient tools for completing observation checklists discretely and accurately. Daily field notes and meticulous oversight of collected data were critical to ensuring data quality. CONCLUSIONS: Mobile technology can support timely and accurate data collection and also help monitor data quality through the use of real-time uploads. These protocols can be adapted to assess compliance with other types of public health policies.

A review of smoking policies in airports around the world.

OBJECTIVE: To review smoking policies of major international airports, to compare these policies with corresponding incountry tobacco control legislation and to identify areas of improvement for advancing smoke-free policy in airports. METHODS: We reviewed smoking policies of 34 major international airports in five world regions, and collected data on current national and subnational legislation on smoke-free indoor places in the corresponding airport locations. We then compared airport smoking policies with local legislation. Additionally, we collected anecdotal information concerning smoking rules and practices in specific airports from an online traveller website. RESULTS: We found that 52.9% of the airports reviewed had indoor smoking rooms or smoking areas; smoking policy was unknown or unstated for two airports. 55.9% of the airports were located in countries where national legislation allowed designated smoking rooms and areas, while 35.3% were in smoke-free countries. Subnational legislation restricted smoking in 60% of the airport locations, while 40% were smoke-free. 71.4% of the airport locations had subnational legislation that allowed smoke-free laws to be more stringent than at the national level, but only half of these places had enacted such laws. CONCLUSIONS: Despite the increasing presence of smoke-free places and legal capacity to enact stricter legislation at the local level, airports represent a public and occupational space that is often overlooked in national or subnational smoke-free policies. Secondhand smoke exposure in airports can be reduced among travellers and workers by implementing and enforcing smoke-free policies in airports. Additionally, existing information on smoke-free legislation lacks consistent terminology and definitions, which are needed to inform future tobacco control policy within airports and in the law.

Bridging the health security divide: department of defense support for the global health security agenda.

In 2011, President Obama addressed the United Nations General Assembly and urged the global community to come together to prevent, detect, and fight every kind of biological danger, whether a pandemic, terrorist threat, or treatable disease. Over the past decade, the United States and key international partners have addressed these dangers through a variety of programs and strategies aimed at developing and enhancing countries' capacity to rapidly detect, assess, report, and respond to acute biological threats. Despite our collective efforts, however, an increasingly interconnected world presents heightened opportunities for human, animal, and zoonotic diseases to emerge and spread globally. Further, the technical capabilities required to develop biological agents into a weapon are relatively low. The launch of the Global Health Security Agenda (GHSA) provides an opportunity for the international community to enhance the linkages between the health and security sectors, accelerating global efforts to prevent avoidable epidemics and bioterrorism, detect threats early, and respond rapidly and effectively to biological threats. The US Department of Defense (DoD) plays a key role in achieving GHSA objectives through its force health protection, threat reduction, and biodefense efforts at home and abroad. This article focuses on GHSA activities conducted in the DoD Office of the Assistant Secretary of Defense for Nuclear, Chemical, and Biological Defense.

A rightward shift in the visuospatial attention vector with healthy aging.

The study of lateralized visuospatial attention bias in non-clinical samples has revealed a systematic group-level leftward bias (pseudoneglect), possibly as a consequence of right hemisphere (RH) dominance for visuospatial attention. Pseudoneglect appears to be modulated by age, with a reduced or even reversed bias typically present in elderly participants. It has been suggested that this shift in bias may arise due to disproportionate aging of the RH and/or an increase in complementary functional recruitment of the left hemisphere (LH) for visuospatial processing. In this study, we report rightward shifts in subjective midpoint judgment relative to healthy young participants whilst elderly participants performed a computerized version of the landmark task (in which they had to judge whether a transection mark appeared closer to the right or left end of a line) on three different line lengths. This manipulation of stimulus properties led to a similar behavioral pattern in both the young and the elderly: a rightward shift in subjective midpoint with decreasing line length, which even resulted in a systematic rightward bias in elderly participants for the shortest line length (1.98° of visual angle, VA). Overall performance precision for the task was lower in the elderly participants regardless of line length, suggesting reduced landmark task discrimination sensitivity with healthy aging. This rightward shift in the attentional vector with healthy aging is likely to result from a reduction in RH resources/dominance for attentional processing in elderly participants. The significant rightward bias in the elderly for short lines may even suggest a reversal of hemisphere dominance in favor of the LH/right visual field under specific conditions.

RIG-I enhanced interferon independent apoptosis upon Junin virus infection.

Junin virus (JUNV) is the etiological agent of Argentine hemorrhagic fever (AHF), a human disease with a high case-fatality rate. It is widely accepted that arenaviral infections, including JUNV infections, are generally non-cytopathic. In contrast, here we demonstrated apoptosis induction in human lung epithelial carcinoma (A549), human hepatocarcinoma and Vero cells upon infection with the attenuated Candid#1 strain of, JUNV as determined by phosphatidylserine (PS) translocation, Caspase 3 (CASP3) activation, Poly (ADP-ribose) polymerase (PARP) cleavage and/or chromosomal DNA fragmentation. Moreover, as determined by DNA fragmentation, we found that the pathogenic Romero strain of JUNV was less cytopathic than Candid#1 in human hepatocarcinoma and Vero, but more apoptotic in A549 and Vero E6 cells. Additionally, we found that JUNV-induced apoptosis was enhanced by RIG-I signaling. Consistent with the previously reported role of RIG-I like helicase (RLH) signaling in initiating programmed cell death, we showed that cell death or DNA fragmentation of Candid#1-infected A549 cells was decreased upon siRNA or shRNA silencing of components of RIG-I pathway in spite of increased virus production. Similarly, we observed decreased DNA fragmentation in JUNV-infected human hepatocarcinoma cells deficient for RIG-I when compared with that of RIG-I-competent cells. In addition, DNA fragmentation detected upon Candid#1 infection of type I interferon (IFN)-deficient Vero cells suggested a type I IFN-independent mechanism of apoptosis induction in response to JUNV. Our work demonstrated for the first time apoptosis induction in various cells of mammalian origin in response to JUNV infection and partial mechanism of this cell death.

Potent inhibition of Junín virus infection by interferon in murine cells.

The new world arenavirus Junín virus (JUNV) is the causative agent of Argentine hemorrhagic fever, a lethal human infectious disease. Adult laboratory mice are generally resistant to peripheral infection by JUNV. The mechanism underlying the mouse resistance to JUNV infection is largely unknown. We have reported that interferon receptor knockout mice succumb to JUNV infection, indicating the critical role of interferon in restricting JUNV infection in mice. Here we report that the pathogenic and vaccine strains of JUNV were highly sensitive to interferon in murine primary cells. Treatment with low concentrations of interferon abrogated viral NP protein expression in murine cells. The replication of both JUNVs was enhanced in IRF3/IRF7 deficient cells. In addition, the vaccine strain of JUNV displayed impaired growth in primary murine cells. Our data suggested a direct and potent role of host interferon response in restricting JUNV replication in mice. The defect in viral growth for vaccine JUNV might also partially explain its attenuation in mice.

Endothelial cell permeability and adherens junction disruption induced by junín virus infection.

Junín virus (JUNV) is endemic to the fertile Pampas of Argentina, maintained in nature by the rodent host Calomys musculinus, and the causative agent of Argentine hemorrhagic fever (AHF), which is characterized by vascular dysfunction and fluid distribution abnormalities. Clinical as well as experimental studies implicate involvement of the endothelium in the pathogenesis of AHF, although little is known of its role. JUNV has been shown to result in productive infection of endothelial cells (ECs) in vitro with no visible cytopathic effects. In this study, we show that direct JUNV infection of primary human ECs results in increased vascular permeability as measured by electric cell substrate impedance sensing and transwell permeability assays. We also show that EC adherens junctions are disrupted during virus infection, which may provide insight into the role of the endothelium in the pathogenesis of AHF and possibly, other viral hemorrhagic fevers.

Epidemiology and pathogenesis of Bolivian hemorrhagic fever.

The etiologic agent of Bolivian hemorrhagic fever (BHF), Machupo virus (MACV) is reported to have a mortality rate of 25-35%. First identified in 1959, BHF was the cause of a localized outbreak in San Joaquin until rodent population controls were implemented in 1964. The rodent Calomys collosus was identified as the primary vector and reservoir for the virus. Multiple animal models were considered during the 1970s with the most human-like disease identified in Rhesus macaques but minimal characterization of the pathogenesis has been published since. A reemergence of reported BHF cases has been reported in recent years, which necessitates the further study and development of a vaccine to prevent future outbreaks.

Rescue of a recombinant Machupo virus from cloned cDNAs and in vivo characterization in interferon (αß/γ) receptor double knockout mice.

Machupo virus (MACV) is the etiological agent of Bolivian hemorrhagic fever (BHF), a reemerging and neglected tropical disease associated with high mortality. The prototypical strain of MACV, Carvallo, was isolated from a human patient in 1963, but minimal in vitro and in vivo characterization has been reported. To this end, we utilized reverse genetics to rescue a pathogenic MACV from cloned cDNAs. The recombinant MACV (rMACV) had in vitro growth properties similar to those of the parental MACV. Both viruses caused similar disease development in alpha/beta and gamma interferon receptor knockout mice, including neurological disease development and high mortality. In addition, we have identified a novel murine model with mortality and neurological disease similar to BHF disease reported in humans and nonhuman primates.