Potent monoclonal antibody-mediated neutralization of a divergent Hendra virus variant.

Hendra virus (HeV) and Nipah virus (NiV) are deadly zoonotic Henipaviruses (HNVs) responsible for recurrent outbreaks in humans and domestic species of highly fatal (50 to 95%) disease. A HeV variant (HeV-g2) of unprecedented genetic divergence has been identified in two fatally diseased horses, and in two flying fox species in regions of Australia not previously considered at risk for HeV spillover. Given the HeV-g2 divergence from HeV while retaining equivalent pathogenicity and spillover potential, understanding receptor usage and antigenic properties is urgently required to guide One Health biosecurity. Here, we show that the HeV-g2 G glycoprotein shares a conserved receptor tropism with prototypic HeV and that a panel of monoclonal antibodies recognizing the G and F glycoproteins potently neutralizes HeV-g2­ and HeV G/F­mediated entry into cells. We determined a crystal structure of the Fab fragment of the hAH1.3 antibody bound to the HeV G head domain, revealing an antigenic site associated with potent cross-neutralization of both HeV-g2 and HeV. Structure-guided formulation of a tetravalent monoclonal antibody (mAb) mixture, targeting four distinct G head antigenic sites, results in potent neutralization of HeV and HeV-g2 and delineates a path forward for implementing multivalent mAb combinations for postexposure treatment of HNV infections.

Diverse contexts and social factors among young cisgender men and transgender women who sell or trade sex in Bangkok and Pattaya, Thailand: formative research for a PrEP program implementation study.

HIV incidence is high and persistent among cisgender men who have sex with men (MSM) and transgender women (TGW) who have sex with men, particularly among those who sell or trade sex. In preparation for an open-label combination HIV pre-exposure prophylaxis (PrEP) program for these groups, we conducted formative research to explore the context of sex work/trade and factors that affect implementation of PrEP interventions. This study analyzed interviews with 20 young (aged 18-26 years) MSM and TGW who sell/trade sex and three sex work venue managers in Bangkok and Pattaya, Thailand. Participants described diverse contexts of sex work/trade, including in multiple informal and formal sex venues. Several participants reported mobility across provinces and out of the country, which led to intermittent sex work/trade. TGW sex workers reported challenges with access and cost of femininizing hormones and limited employment opportunities. Factors that could facilitate or challenge PrEP program implementation included HIV stigma, the role of venue management in sexual health practice, lack of PrEP knowledge, lower perceived HIV risk, and interest in personal health and wellbeing. Program implementers must consider myriad factors to successfully implement PrEP among young MSM and TGW engaged in sex work or trade in Thailand.

HIV and syphilis prevalence among transgender women and men who have sex with men, Silom Community Clinic, Bangkok, Thailand, 2017-2019.

We assessed HIV and syphilis infection among MSM and TGW attending Silom Community Clinic from 2017 to 2019. Walk-in and referral clients completed a registration application including a question on gender identity. We compared the prevalence of HIV, syphilis, and HIV and syphilis coinfection among TGW and MSM. In a total of 1050 clients, 276 (26.3%) were TGW and 774 (74.7%) were MSM. Among TGW clients, HIV prevalence was 29.8%, syphilis prevalence was 38.4%, and coinfection prevalence was 18.5%. Comparing prevalence among TGW to MSM, the adjusted prevalence ratio (aPR) for HIV was 1.8 (95% CI:1.4-2.3), for syphilis was 1.2 (95% CI:1.0-1.4), and for HIV and syphilis coinfection was 2.1 (95% CI:1.4-2.9). The prevalence of syphilis was higher than HIV among TGW, with a PR of 1.3 (95% CI:1.1-1.6), and among MSM, with a PR of 1.4 (95% CI:1.2-1.7). TGW age 15-21 years had an HIV prevalence of 16.9% and syphilis prevalence of 30.8%. After adjusting for age, referral, and sexual behaviors, TGW remain significantly associated with HIV and syphilis prevalence. There is a substantial burden of HIV and HIV/syphilis co-infection among TGW. HIV/STI prevention are needed for TGW, including linkage to HIV care.

A Critical Discourse Analysis of an Australian Incarcerated Trans Woman's Letters of Complaint and Self-Advocacy.

This case study provides a critical discourse analysis of 121 letters of complaint and self-advocacy authored by Natasha Keating, a trans woman incarcerated in two Australian male correctional facilities from 2000 to 2007. During her incarceration, Natasha experienced victimization, misgendering, microaggression, and institutional discrimination. Despite this, Natasha embodied and "fought" against the injustices she experienced, whilst seeking to speak for other trans incarcerated persons also silenced and treated with indifference, contributing to changes in the carceral system. This original case study analyzes the discursive strategies Natasha employed to construct and reclaim an affirming self-identity through a deliberate campaign to effect social change and policy concessions within a system designed to curtail self-determination. Through her empathic and impassioned letter-writing approach, leveraging a military metaphor, this novel analysis showcases the significant implications her activism/agentism and determination had in naming and seeking to dismantle the systems of oppression trans incarcerated women experience.

Study protocol of the LARK (TROG 17.03) clinical trial: a phase II trial investigating the dosimetric impact of Liver Ablative Radiotherapy using Kilovoltage intrafraction monitoring.

BACKGROUND: Stereotactic Ablative Body Radiotherapy (SABR) is a non-invasive treatment which allows delivery of an ablative radiation dose with high accuracy and precision. SABR is an established treatment for both primary and secondary liver malignancies, and technological advances have improved its efficacy and safety. Respiratory motion management to reduce tumour motion and image guidance to achieve targeting accuracy are crucial elements of liver SABR. This phase II multi-institutional TROG 17.03 study, Liver Ablative Radiotherapy using Kilovoltage intrafraction monitoring (LARK), aims to investigate and assess the dosimetric impact of the KIM real-time image guidance technology. KIM utilises standard linear accelerator equipment and therefore has the potential to be a widely available real-time image guidance technology for liver SABR. METHODS: Forty-six patients with either hepatocellular carcinoma or oligometastatic disease to the liver suitable for and treated with SABR using Kilovoltage Intrafraction Monitoring (KIM) guidance will be included in the study. The dosimetric impact will be assessed by quantifying accumulated patient dose distribution with or without the KIM intervention. The patient treatment outcomes of local control, toxicity and quality of life will be measured. DISCUSSION: Liver SABR is a highly effective treatment, but precise dose delivery is challenging due to organ motion. Currently, there is a lack of widely available options for performing real-time tumour localisation to assist with accurate delivery of liver SABR. This study will provide an assessment of the impact of KIM as a potential solution for real-time image guidance in liver SABR. TRIAL REGISTRATION: This trial was registered on December 7th 2016 on ClinicalTrials.gov under the trial-ID NCT02984566 .

Hepatic tuberculosis in human immunodeficiency virus co-infected adults: a case series of South African adults.

BACKGROUND: Although Mycobacterium tuberculosis (TB) infection may cause extrapulmonary disease in HIV-infected adults, HIV-associated hepatic TB has been poorly characterized. Our objective was to describe hepatic TB in HIV-infected adults. METHODS: Retrospective study of patients diagnosed with hepatic TB from 2005-2012 at Infectious Diseases Clinic, King Edward VIII Hospital, Durban, South Africa. RESULTS: Among twenty cases of histology-confirmed HIV-associated hepatic TB, median CD4 count was 47 cells/µl (inter-quartile range 27-107 cells/µl) and 75% (15/20) of patients had pre-existing pulmonary TB. The most frequent clinical finding was hepatomegaly (85%). Liver enzyme abnormalities included elevated alkaline phosphatase (median 456 u/L, inter-quartile range 322-1,043 u/L) and gamma-glutamyltransferase (median 422 u/L, inter-quartile range 235-736 u/L). Acid-fast bacilli were cultured from liver tissue in 30% (6/20) of patients; 25% (5/20) identified as TB. With standard anti-TB therapy, liver enzymes improved within six months in 92% (11/12) of patients. One year after diagnosis, twelve patients resolved clinically, two patients developed drug-resistant TB and six patients died. CONCLUSION: In our case series of HIV-infected patients, hepatic TB occurred in patients with severe immunosuppression, who presented with hepatomegaly and abnormal liver enzymes. More than half of patients had resolution of liver function by six months however the 12-month mortality remained high.

Escape From Monoclonal Antibody Neutralization Affects Henipavirus Fitness In Vitro and In Vivo.

Henipaviruses are zoonotic viruses that can cause severe and acute respiratory diseases and encephalitis in humans. To date, no vaccine or treatments are approved for human use. The presence of neutralizing antibodies is a strong correlate of protection against lethal disease in animals. However, since RNA viruses are prone to high mutation rates, the possibility that these viruses will escape neutralization remains a potential concern. In the present study, we generated neutralization-escape mutants, using 6 different monoclonal antibodies, and studied the effect of these neutralization-escape mutations on in vitro and in vivo fitness. These data provide a mechanism for overcoming neutralization escape by use of cocktails of cross-neutralizing monoclonal antibodies that recognize residues within the glycoprotein that are important for virus replication and virulence.

A systematic review of hepatic tuberculosis with considerations in human immunodeficiency virus co-infection.

BACKGROUND: Mycobacterium tuberculosis (TB) infection of the liver, known as hepatic TB, is an extrapulmonary manifestation of TB. Hepatic TB has become more prevalent, likely as a result of the human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS) epidemic. We sought to review case series to characterize the epidemiology, pathophysiology, clinical features, diagnosis, and treatment of hepatic TB and to comment on the impact of HIV co-infection on these characteristics. METHODS: We conducted a systematic literature search in PubMed and ScienceDirect for articles pertaining to hepatic TB with human subjects from 1960 to July 2013. RESULTS: We obtained data on 618 hepatic TB patients from 14 case series. The most common reported signs and symptoms were hepatomegaly (median: 80%, range: 10-100%), fever (median: 67%, range: 30-100), respiratory symptoms (median: 66%, range: 32-78%), abdominal pain (median: 59.5%, range: 40-83%), and weight loss (median: 57.5%, range: 20-100%). Common laboratory abnormalities were elevated alkaline phosphatase and gamma-glutamyl transferase. Ultrasound and computerized tomography (CT) were sensitive but non-specific. On liver biopsy, smear microscopy for acid-fast bacilli had a median sensitivity of 25% (range: 0-59%), histology of caseating granulomas had a median sensitivity of 68% (range: 14-100%), and polymerase chain reaction for TB had a median sensitivity of 86% (range: 30-100%). Standard anti-tuberculous chemotherapy for 6 to 12 months achieved positive outcomes for nearly all patients with drug-susceptible TB. CONCLUSIONS: Clinicians in TB-endemic regions should maintain a high index of suspicion for hepatic TB in patients presenting with hepatomegaly, fever, respiratory symptoms, and elevated liver enzymes. The most sensitive imaging modality is a CT scan, while the most specific diagnostic modality is a liver biopsy with nucleic acid testing of liver tissue samples. Upon diagnosis, 4-drug anti-TB therapy should promptly be initiated. HIV co-infected patients may have more complex cases and should be closely monitored for complications.

Extracorporeal Membrane Oxygenation for COVID-19 During the Delta and Omicron Waves in North America.

Clinical outcomes for patients with severe acute respiratory failure caused by different variants of the coronavirus disease 2019 (COVID-19) supported with extracorporeal membrane oxygenation (ECMO) are incompletely understood. Clinical characteristics, pre-ECMO management, and hospital mortality at 90 days for adults with COVID-19 who received venovenous ECMO (VV-ECMO) at North American centers during waves predominated by Delta (August 16 to December 12, 2021) and Omicron (January 31 to May 31, 2022) severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants were compared in a competing risks framework. One thousand seven hundred and sixty-six patients (1,580 Delta, 186 Omicron) received VV-ECMO for COVID-19 during the Delta- and Omicron-predominant waves in North American centers. In the unadjusted competing risks model, no significant difference was observed in risk of hospital mortality at 90 days between patients during the Delta- versus Omicron-predominant wave (subhazard ratio [sHR], 0.94; 95% confidence interval [CI], 0.74-1.19), but patients supported with VV-ECMO during the Omicron-predominant wave had a significantly lower adjusted risk of hospital mortality at 90 days (subhazard ratio, 0.71; 95% CI, 0.51-0.99). Patients receiving VV-ECMO during the Omicron-predominant wave had a similar unadjusted risk of hospital mortality at 90 days, but a significantly lower adjusted risk of hospital mortality at 90 days than those receiving VV-ECMO during the Delta-predominant wave.

Data quality assessment of the Enhanced Gonococcal Antimicrobial Surveillance Programme (EGASP), Thailand, 2015-2021.

BACKGROUND: Quality assessments of gonococcal surveillance data are critical to improve data validity and to enhance the value of surveillance findings. Detecting data errors by systematic audits identifies areas for quality improvement. We designed and implemented an internal audit process to evaluate the accuracy and completeness of surveillance data for the Thailand Enhanced Gonococcal Antimicrobial Surveillance Programme (EGASP). METHODS: We conducted a data quality audit of source records by comparison with the data stored in the EGASP database for five audit cycles from 2015-2021. Ten percent of culture-confirmed cases of Neisseria gonorrhoeae were randomly sampled along with any cases identified with elevated antimicrobial susceptibility testing results and cases with repeat infections. Incorrect and incomplete data were investigated, and corrective action and preventive actions (CAPA) were implemented. Accuracy was defined as the percentage of identical data in both the source records and the database. Completeness was defined as the percentage of non-missing data from either the source document or the database. Statistical analyses were performed using the t-test and the Fisher's exact test. RESULTS: We sampled and reviewed 70, 162, 85, 68, and 46 EGASP records during the five audit cycles. Overall accuracy and completeness in the five audit cycles ranged from 93.6% to 99.4% and 95.0% to 99.9%, respectively. Overall, completeness was significantly higher than accuracy (p = 0.017). For each laboratory and clinical data element, concordance was >85% in all audit cycles except for two laboratory data elements in two audit cycles. These elements significantly improved following identification and CAPA implementation. DISCUSSION: We found a high level of data accuracy and completeness in the five audit cycles. The implementation of the audit process identified areas for improvement. Systematic quality assessments of laboratory and clinical data ensure high quality EGASP surveillance data to monitor for antimicrobial resistant Neisseria gonorrhoeae in Thailand.

Perceived Feasibility and Acceptability of HIV Prevention Research With Daily Oral PrEP Among Young Transgender Women (YTGW) Who Sell or Trade Sex in Bangkok and Pattaya, Thailand.

Young transgender women (YTGW) who sell or trade sex have among the highest HIV incidence rates in Thailand. Using qualitative methods, we assessed perceived acceptability, feasibility, and optimal design of a combination HIV prevention intervention including PrEP for YTGW. Key informant interviews were conducted during July 2016-July 2018 with 21 YTGW, aged 18-26 years, who sold sex and resided in Bangkok or Pattaya, Thailand. Grounded theory and content analysis were used for data analysis. Most YTGW interviewed reported high interest in HIV prevention research and believed participation in it supported sexual health. However, participants perceived HIV studies as complicated and time-consuming. Regarding PrEP, participants suggested more PrEP options beyond daily oral PrEP and expressed concerns related to perceived side effects of PrEP, including interaction with gender-affirming hormone therapy. Improving PrEP knowledge, being able to self-assess HIV risk, and reducing HIV/PrEP stigma could increase interest in research and PrEP uptake among YTGW.

Radiation therapy for ventricular arrhythmias.

Ventricular arrhythmias (VA) can be life-threatening arrhythmias that result in significant morbidity and mortality. Catheter ablation (CA) is an invasive treatment modality that can be effective in the treatment of VA where medications fail. Recurrence occurs commonly following CA due to an inability to deliver lesions of adequate depth to cauterise the electrical circuits that drive VA or reach areas of scar responsible for VA. Stereotactic body radiotherapy is a non-invasive treatment modality that allows volumetric delivery of energy to treat circuits that cannot be reached by CA. It overcomes the weaknesses of CA and has been successfully utilised in small clinical trials to treat refractory VA. This article summarises the current evidence for this novel treatment modality and the steps that will be required to bring it to the forefront of VA treatment.

Approach to the Physiologically Challenging Endotracheal Intubation in the Intensive Care Unit.

Endotracheal intubation for airway management is a common procedure in the ICU. Intubation may be difficult due to anatomic airway abnormalities but also due to physiologic derangements that predispose patients to cardiovascular collapse during the procedure. Results of studies demonstrate a high incidence of morbidity and mortality associated with airway management in the ICU. To reduce the likelihood of complications, medical teams must be well versed in the general principles of intubation and be prepared to manage physiologic derangements while securing the airway. In this review, we present relevant literature on the approach to endotracheal intubation in the ICU and provide pragmatic recommendations relevant to medical teams performing intubations in patients who are physiologically unstable.

High PrEP uptake, adherence, persistence and effectiveness outcomes among young Thai men and transgender women who sell sex in Bangkok and Pattaya, Thailand: findings from the open-label combination HIV prevention effectiveness (COPE) study.

Background: Daily oral pre-exposure prophylaxis (PrEP) is effective in preventing HIV infection, but no study has evaluated combination prevention interventions with PrEP for transgender women (TGW) and men who have sex with men (MSM) who sell sex. Methods: The Combination Prevention Effectiveness (COPE) study was a community-based, non-randomized implementation study in Bangkok and Pattaya, Thailand. Participants were HIV-negative MSM and TGW aged 18-26 years who reported exchanging sex with men in the prior 12 months and who met 2014 U.S. Public Health Service PrEP eligibility criteria. The intervention included quarterly HIV testing, semiannual testing for sexually transmitted infections, provision of condoms with lubricant, and the opportunity to initiate or end daily oral PrEP use at any time during study participation. Participants taking PrEP received monthly adherence counseling and short message service reminders. The primary outcome was HIV incidence rate ratio (IRR) on PrEP vs. not on PrEP. Secondary outcomes were PrEP initiation, PrEP use at 12 months, and PrEP adherence. Findings: From October 2017 to August 2019, 846 participants were enrolled: 531 (62.8%) immediately initiated PrEP; 104 (12.3%) subsequently initiated PrEP, and 211 (24.9%) never initiated PrEP. Among those initiating PrEP within 30 days of enrollment; 85.9% were on PrEP at the 12-months. When taking PrEP, participants reported adherent PrEP use at 94.2% of quarterly assessments. Ten HIV seroconversions occurred without PrEP use (incidence rate [IR] = 3.42 per 100 person-years [PY]; 95% CI = 1.64-6.30), while zero cases occurred with PrEP use (IR = 0.0 per 100PY; 95% CI = 0.0-0.62), with IRR = 0.0 (95% CI = 0.0-0.22; p < 0.001). Interpretation: Young Thai MSM and TGW who exchange sex can have high PrEP uptake, persistence and adherence, and low HIV incidence when offered in supportive community-based settings. Funding: U.S. National Institute of Allergy and Infectious Diseases; Centers for Disease Control and Prevention.

Evaluation of screening strategies for pulmonary tuberculosis among hospitalized patients in a low-burden setting: cost-effectiveness of GeneXpert MTB/RIF compared to smear microscopy.

OBJECTIVE: Hospitalized patients undergoing evaluation for pulmonary tuberculosis (TB) require airborne isolation while testing for Mycobacterium tuberculosis (MTB) to reduce risk of nosocomial transmission. GeneXpert MTB/RIF (Xpert) is more rapid and accurate than sputum smear microscopy, but it is not routinely used to 'rule out' infectious pulmonary TB among hospitalized patients in the United States. We sought to evaluate the diagnostic performance and cost-effectiveness of Xpert-based TB evaluation. METHODS: We conducted a retrospective cohort study of hospitalized adults evaluated for pulmonary TB at a large academic medical center in New York from 2010 to 2017. Using propensity score matching, we compared hospital length-of-stay among patients undergoing conventional smear-based TB evaluation to a control group with non-TB pneumonia. We performed a probabilistic cost-effectiveness analysis to compare Xpert-based versus conventional TB evaluation. RESULTS: In total 1,421 patients were evaluated for TB with airborne isolation and sputum testing; mycobacterial culture was positive for MTB in 49 (3.4%). Conventional TB evaluation was associated with an increase of 4.4 hospital days compared to propensity-matched controls. Xpert-based testing strategies dominated conventional TB evaluation with a cost savings of $5,947 (95% CI, $1,156-$12,540) and $4,445 (95% CI, $696-$9,526) per patient depending on the number of Xpert tests performed (1 vs 2, respectively) and assumptions about the reduction of length of stay achieved. CONCLUSIONS: In the evaluation of hospitalized patients for pulmonary TB, Xpert-based testing has superior diagnostic performance and is likely cost-effective compared to smear microscopy due to reduced hospital length-of-stay associated with more rapid test results.

Architecture and antigenicity of the Nipah virus attachment glycoprotein.

Nipah virus (NiV) and Hendra virus (HeV) are zoonotic henipaviruses (HNVs) responsible for outbreaks of encephalitis and respiratory illness. The entry of HNVs into host cells requires the attachment (G) and fusion (F) glycoproteins, which are the main targets of antibody responses. To understand viral infection and host immunity, we determined a cryo-electron microscopy structure of the NiV G homotetrameric ectodomain in complex with the nAH1.3 broadly neutralizing antibody Fab fragment. We show that a cocktail of two nonoverlapping G-specific antibodies neutralizes NiV and HeV synergistically and limits the emergence of escape mutants. Analysis of polyclonal serum antibody responses elicited by vaccination of macaques with NiV G indicates that the receptor binding head domain is immunodominant. These results pave the way for implementing multipronged therapeutic strategies against these deadly pathogens.

HLA-B∗46 associates with rapid HIV disease progression in Asian cohorts and prominent differences in NK cell phenotype.

Human leukocyte antigen (HLA) alleles have been linked to HIV disease progression and attributed to differences in cytotoxic T lymphocyte (CTL) epitope representation. These findings are largely based on treatment-naive individuals of European and African ancestry. We assessed HLA associations with HIV-1 outcomes in 1,318 individuals from Thailand and found HLA-B∗46:01 (B∗46) associated with accelerated disease in three independent cohorts. B∗46 had no detectable effect on HIV-specific T cell responses, but this allele is unusual in containing an HLA-C epitope that binds inhibitory receptors on natural killer (NK) cells. Unbiased transcriptomic screens showed increased NK cell activation in people with HIV, without B∗46, and simultaneous single-cell profiling of surface proteins and transcriptomes revealed a NK cell subset primed for increased responses in the absence of B∗46. These findings support a role for NK cells in HIV pathogenesis, revealed by the unique properties of the B∗46 allele common only in Asia.

Transactional sex, HIV and health among young cisgender men and transgender women who have sex with men in Thailand.

PURPOSE: To examine how recent sex work is identified and the HIV risk factors and service needs among Thai cisgender men who have sex with men (MSM) and transgender women (TGW) who exchange sex. METHODS: MSM and TGW in Bangkok and Pattaya who exchanged sex in the last year (n = 890) were recruited through social media, outreach, and word-of-mouth. Recent sex exchange was based on the primary question, "In the last 30 days, have you sold or traded sex"; secondary questions (regarding income source and client encounters) were also investigated. RESULTS: Overall, 436 (48%) participants engaged in sex work in the last 30 days; among those, 270 (62%) reported exchanging sex by the primary question, and 160 (37%) based on secondary questions only. Recent sex exchange was associated with gonorrhea, syphilis, discussing PrEP with others, and using condoms, alcohol, methamphetamine, amyl nitrate, and Viagra. Exchanging sex based on secondary questions only was associated with being in a relationship, social media recruitment, less recent anal intercourse, and not discussing PrEP. CONCLUSIONS: Thai MSM and TGW who exchange sex need regular access to HIV/STI prevention, testing, and treatment services, and multiple approaches to assessing sex work will help identify and serve this diverse and dynamic population.

A novel model of lethal Hendra virus infection in African green monkeys and the effectiveness of ribavirin treatment.

The henipaviruses, Hendra virus (HeV) and Nipah virus (NiV), are emerging zoonotic paramyxoviruses that can cause severe and often lethal neurologic and/or respiratory disease in a wide variety of mammalian hosts, including humans. There are presently no licensed vaccines or treatment options approved for human or veterinarian use. Guinea pigs, hamsters, cats, and ferrets, have been evaluated as animal models of human HeV infection, but studies in nonhuman primates (NHP) have not been reported, and the development and approval of any vaccine or antiviral for human use will likely require efficacy studies in an NHP model. Here, we examined the pathogenesis of HeV in the African green monkey (AGM) following intratracheal inoculation. Exposure of AGMs to HeV produced a uniformly lethal infection, and the observed clinical signs and pathology were highly consistent with HeV-mediated disease seen in humans. Ribavirin has been used to treat patients infected with either HeV or NiV; however, its utility in improving outcome remains, at best, uncertain. We examined the antiviral effect of ribavirin in a cohort of nine AGMs before or after exposure to HeV. Ribavirin treatment delayed disease onset by 1 to 2 days, with no significant benefit for disease progression and outcome. Together our findings introduce a new disease model of acute HeV infection suitable for testing antiviral strategies and also demonstrate that, while ribavirin may have some antiviral activity against the henipaviruses, its use as an effective standalone therapy for HeV infection is questionable.

A neutralizing human monoclonal antibody protects against lethal disease in a new ferret model of acute nipah virus infection.

Nipah virus is a broadly tropic and highly pathogenic zoonotic paramyxovirus in the genus Henipavirus whose natural reservoirs are several species of Pteropus fruit bats. Nipah virus has repeatedly caused outbreaks over the past decade associated with a severe and often fatal disease in humans and animals. Here, a new ferret model of Nipah virus pathogenesis is described where both respiratory and neurological disease are present in infected animals. Severe disease occurs with viral doses as low as 500 TCID(50) within 6 to 10 days following infection. The underlying pathology seen in the ferret closely resembles that seen in Nipah virus infected humans, characterized as a widespread multisystemic vasculitis, with virus replicating in highly vascular tissues including lung, spleen and brain, with recoverable virus from a variety of tissues. Using this ferret model a cross-reactive neutralizing human monoclonal antibody, m102.4, targeting the henipavirus G glycoprotein was evaluated in vivo as a potential therapeutic agent. All ferrets that received m102.4 ten hours following a high dose oral-nasal Nipah virus challenge were protected from disease while all controls died. This study is the first successful post-exposure passive antibody therapy for Nipah virus using a human monoclonal antibody.