Measures to prevent and treat Nipah virus disease: research priorities for 2024-29.

Nipah virus causes highly lethal disease, with case-fatality rates ranging from 40% to 100% in recognised outbreaks. No treatments or licensed vaccines are currently available for the prevention and control of Nipah virus infection. In 2019, WHO published an advanced draft of a research and development roadmap for accelerating development of medical countermeasures, including diagnostics, therapeutics, and vaccines, to enable effective and timely emergency response to Nipah virus outbreaks. This Personal View provides an update to the WHO roadmap by defining current research priorities for development of Nipah virus medical countermeasures, based primarily on literature published in the last 5 years and consensus opinion of 15 subject matter experts with broad experience in development of medical countermeasures for Nipah virus or experience in the epidemiology, ecology, or public health control of outbreaks of Nipah virus. The research priorities are organised into four main sections: cross-cutting issues (for those that apply to more than one category of medical countermeasures), diagnostics, therapeutics, and vaccines. The strategic goals and milestones identified in each section focus on key achievements that are needed over the next 6 years to ensure that the necessary tools are available for rapid response to future outbreaks of Nipah virus or related henipaviruses.

Lassa fever research priorities: towards effective medical countermeasures by the end of the decade.

In 2016, WHO designated Lassa fever a priority disease for epidemic preparedness as part of the WHO Blueprint for Action to Prevent Epidemics. One aspect of preparedness is to promote development of effective medical countermeasures (ie, diagnostics, therapeutics, and vaccines) against Lassa fever. Diagnostic testing for Lassa fever has important limitations and key advancements are needed to ensure rapid and accurate diagnosis. Additionally, the only treatment available for Lassa fever is ribavirin, but controversy exists regarding its effectiveness. Finally, no licensed vaccines are available for the prevention and control of Lassa fever. Ongoing epidemiological and behavioural studies are also crucial in providing actionable information for medical countermeasure development, use, and effectiveness in preventing and treating Lassa fever. This Personal View provides current research priorities for development of Lassa fever medical countermeasures based on literature published primarily in the last 5 years and consensus opinion of 20 subject matter experts with broad experience in public health or the development of diagnostics, therapeutics, and vaccines for Lassa fever. These priorities provide an important framework to ensure that Lassa fever medical countermeasures are developed and readily available for use in endemic and at-risk areas by the end of the decade.

World Health Organization Methodology to Prioritize Emerging Infectious Diseases in Need of Research and Development.

The World Health Organization R&D Blueprint aims to accelerate the availability of medical technologies during epidemics by focusing on a list of prioritized emerging diseases for which medical countermeasures are insufficient or nonexistent. The prioritization process has 3 components: a Delphi process to narrow down a list of potential priority diseases, a multicriteria decision analysis to rank the short list of diseases, and a final Delphi round to arrive at a final list of 10 diseases. A group of international experts applied this process in January 2017, resulting in a list of 10 priority diseases. The robustness of the list was tested by performing a sensitivity analysis. The new process corrected major shortcomings in the pre-R&D Blueprint approach to disease prioritization and increased confidence in the results.

Influenza prevention in nursing homes: Great significance of seasonal variability and spatio-temporal pattern.

OBJECTIVE: This work evaluated seasonal variations and spatio-temporal pattern of respiratory tract infections (RTI) in geriatric nursing homes in order to improve effective surveillance, prevention, control and management of RTI. METHODS: Prospective surveillance of RTI (Low Respiratory Tract infections and Influenza Like Illnesses) was conducted in 11 sites in Alsace over a 10-year period with clinical case definitions and rapid tests (Immunoassay) to identify influenza virus. RESULTS: Influenza national epidemic was a period at high risk of RTI in nursing homes with variable impacts depending on the seasonal period. 2004-2005, 2008-2009, 2011-2012 and 2012-2013 were the periods with the highest impacts. The higher risk was not well understood during these four influenza epidemics and outbreaks occurred in numerous nursing homes despite the alerts and surveillance. CONCLUSION: Information about seasonal variability and spatio-temporal patterns of the RTI during the national epidemic periods is essential for the nursing homes in order to help the health care workers and the visitors to understand the risk for the residents and then to improve the implementation of the control and prevention measures.

Integrating sepsis management recommendations into clinical care guidelines for district hospitals in resource-limited settings: the necessity to augment new guidelines with future research.

Several factors contribute to the high mortality attributed to severe infections in resource-limited settings. While improvements in survival and processes of care have been made in high-income settings among patients with severe conditions, such as sepsis, guidelines necessary for achieving these improvements may lack applicability or have not been tested in resource-limited settings. The World Health Organization's recent publication of the Integrated Management of Adolescent and Adult Illness District Clinician Manual provides details on how to optimize management of severely ill, hospitalized patients in such settings, including specific guidance on the management of patients with septic shock and respiratory failure without shock. This manuscript provides the context, process and underpinnings of these sepsis guidelines. In light of the current deficits in care and the limitations associated with these guidelines, the authors propose implementing these standardized best practice guidelines while using them as a foundation for sepsis research undertaken in, and directly relevant to, resource-limited settings.

The use of a mobile laboratory unit in support of patient management and epidemiological surveillance during the 2005 Marburg Outbreak in Angola.

BACKGROUND: Marburg virus (MARV), a zoonotic pathogen causing severe hemorrhagic fever in man, has emerged in Angola resulting in the largest outbreak of Marburg hemorrhagic fever (MHF) with the highest case fatality rate to date. METHODOLOGY/PRINCIPAL FINDINGS: A mobile laboratory unit (MLU) was deployed as part of the World Health Organization outbreak response. Utilizing quantitative real-time PCR assays, this laboratory provided specific MARV diagnostics in Uige, the epicentre of the outbreak. The MLU operated over a period of 88 days and tested 620 specimens from 388 individuals. Specimens included mainly oral swabs and EDTA blood. Following establishing on site, the MLU operation allowed a diagnostic response in <4 hours from sample receiving. Most cases were found among females in the child-bearing age and in children less than five years of age. The outbreak had a high number of paediatric cases and breastfeeding may have been a factor in MARV transmission as indicated by the epidemiology and MARV positive breast milk specimens. Oral swabs were a useful alternative specimen source to whole blood/serum allowing testing of patients in circumstances of resistance to invasive procedures but limited diagnostic testing to molecular approaches. There was a high concordance in test results between the MLU and the reference laboratory in Luanda operated by the US Centers for Disease Control and Prevention. CONCLUSIONS/SIGNIFICANCE: The MLU was an important outbreak response asset providing support in patient management and epidemiological surveillance. Field laboratory capacity should be expanded and made an essential part of any future outbreak investigation.

Studies needed to address public health challenges of the 2009 H1N1 influenza pandemic: insights from modeling.

In light of the 2009 influenza pandemic and potential future pandemics, Maria Van Kerkhove and colleagues anticipate six public health challenges and the data needed to support sound public health decision making.

Pandemic potential of a strain of influenza A (H1N1): early findings.

A novel influenza A (H1N1) virus has spread rapidly across the globe. Judging its pandemic potential is difficult with limited data, but nevertheless essential to inform appropriate health responses. By analyzing the outbreak in Mexico, early data on international spread, and viral genetic diversity, we make an early assessment of transmissibility and severity. Our estimates suggest that 23,000 (range 6000 to 32,000) individuals had been infected in Mexico by late April, giving an estimated case fatality ratio (CFR) of 0.4% (range: 0.3 to 1.8%) based on confirmed and suspected deaths reported to that time. In a community outbreak in the small community of La Gloria, Veracruz, no deaths were attributed to infection, giving an upper 95% bound on CFR of 0.6%. Thus, although substantial uncertainty remains, clinical severity appears less than that seen in the 1918 influenza pandemic but comparable with that seen in the 1957 pandemic. Clinical attack rates in children in La Gloria were twice that in adults (<15 years of age: 61%; >/=15 years: 29%). Three different epidemiological analyses gave basic reproduction number (R0) estimates in the range of 1.4 to 1.6, whereas a genetic analysis gave a central estimate of 1.2. This range of values is consistent with 14 to 73 generations of human-to-human transmission having occurred in Mexico to late April. Transmissibility is therefore substantially higher than that of seasonal flu, and comparable with lower estimates of R0 obtained from previous influenza pandemics.

New opportunities for field research on the pathogenesis and treatment of Lassa fever.

Unlike many viral hemorrhagic fevers (VHFs), Lassa fever (LF) is not a rare disease that emerges only as sporadic cases or in outbreak form. Although surveillance is inadequate to determine the true incidence, up to 300,000 infections and 5000 deaths from LF are estimated to occur yearly. The highest incidence is in the "Mano River Union (MRU) countries" of Sierra Leone, Liberia, and Guinea. Although civil unrest in this region over the past two decades has impeded capacity building and research, new-found peace in recent years presents new opportunities. In 2004, the Mano River Union Lassa Fever Network (MRU LFN) was established to assist MRU countries in the development of national and regional surveillance, diagnosis, treatment, control, and prevention of LF. Here, we review the present literature on treatment and pathogenesis of LF and outline priorities for future research in the field made possible by the improved research capacity of the MRU LFN.

Hantavirus infection: a review and global update.

Hantaviruses have the potential to cause two different types of diseases in human: hemorrhagic fever with renal syndrome (HFRS) and hantavirus pulmonary syndrome (HPS). HFRS, initially described clinically at the turn of the 20th century, occurs endemically in the Asian and European continents, while HPS, recognized as a clinical entity since 1993, represents the prototype of emerging diseases occurring in the Western hemisphere. Approximately 150,000 to 200,000 cases of HFRS are hospitalized each year world wide, with most of the cases occurring in the developing countries. The case fatality rate of HFRS varies from <1% to 12% depending on the viruses. Although HPS is much smaller in number than HFRS, with approximately 200 HPS cases per year in the Americas, the average case fatality rate is 40%. The reported cases of hantaviral infection is increasing in many countries and new hantavirus strains have been increasingly identified worldwide, which constitutes a public health problem of increasing global concern. Hantaviral infection might be underestimated due to its asymptomatic and non-specific mild infection, and the lack of simple standardized laboratory diagnostics in hospitals, especially in the developing countries. This review summarizes the current knowledge on virology, epidemiology, clinical manifestation, laboratory diagnostics, treatment and prevention of hantaviruses and hantaviral infections.

Outbreaks of filovirus hemorrhagic fever: time to refocus on the patient.

In the 40 years since the recognition of filoviruses as agents of lethal human disease, there have been no specific advances in antiviral therapies or vaccines and few clinical studies on the efficacy of supportive care. On 20 September 2006, experts from 14 countries representing 68 institutions integrally involved in the response to outbreaks of filovirus hemorrhagic fever gathered at the National Microbiology Laboratory of the Public Health Agency of Canada in Winnipeg to discuss possible remedies for this grim situation, in a unique workshop entitled "Marburg and Ebola Hemorrhagic Fever: Feasibility of Prophylaxis and Therapy." A summary of the opportunities for and challenges to improving treatment of filovirus hemorrhagic fevers is presented here.

WHO Rapid Advice Guidelines for pharmacological management of sporadic human infection with avian influenza A (H5N1) virus.

Recent spread of avian influenza A (H5N1) virus to poultry and wild birds has increased the threat of human infections with H5N1 virus worldwide. Despite international agreement to stockpile antivirals, evidence-based guidelines for their use do not exist. WHO assembled an international multidisciplinary panel to develop rapid advice for the pharmacological management of human H5N1 virus infection in the current pandemic alert period. A transparent methodological guideline process on the basis of the Grading Recommendations, Assessment, Development and Evaluation (GRADE) approach was used to develop evidence-based guidelines. Our development of specific recommendations for treatment and chemoprophylaxis of sporadic H5N1 infection resulted from the benefits, harms, burden, and cost of interventions in several patient and exposure groups. Overall, the quality of the underlying evidence for all recommendations was rated as very low because it was based on small case series of H5N1 patients, on extrapolation from preclinical studies, and high quality studies of seasonal influenza. A strong recommendation to treat H5N1 patients with oseltamivir was made in part because of the severity of the disease. Similarly, strong recommendations were made to use neuraminidase inhibitors as chemoprophylaxis in high-risk exposure populations. Emergence of other novel influenza A viral subtypes with pandemic potential, or changes in the pathogenicity of H5N1 virus strains, will require an update of these guidelines and WHO will be monitoring this closely.