Sandbox ammu WNV green boxes

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Alejandro Lemor, M.D. [2]

Overview

There is currently no specific antiviral pharmacologic therapy indicated for patients with WNV infection, but interferon-alpha-2b or ribavirin have been used. Patients with mild disease may be followed-up as outpatients; whereas patients with severe disease require hospitalization and close monitoring. Current management of infected patients is based on supportive care aimed at symptom relief and prevention of complications.

Medical therapy

  • West nile virus
  • 1.1. Prevention
  • No WNV vaccines are licensed for use in humans. In the absence of a vaccine, prevention of WNV disease depends on community-level mosquito control programs to reduce vector densities, personal protective measures to decrease exposure to infected mosquitoes, and screening of blood and organ donors.
  • Personal protective measures include use of mosquito repellents, wearing long-sleeved shirts and long pants, and limiting outdoor exposure from dusk to dawn. Using air conditioning, installing window and door screens, and reducing peridomestic mosquito breeding sites, can further decrease the risk for WNV exposure.
  • Blood and some organ donations in the United States are screened for WNV infection; health care professionals should remain vigilant for the possible transmission of WNV through blood transfusion or organ transplantation. Any suspected WNV infections temporally associated with blood transfusion or organ transplantation should be reported promptly to the appropriate state health department.
  • 1.2. Treatment
  • There is no specific treatment for WNV disease; clinical management is supportive. Patients with severe meningeal symptoms often require pain control for headaches and antiemetic therapy and rehydration for associated nausea and vomiting. Patients with encephalitis require close monitoring for the development of elevated intracranial pressure and seizures. Patients with encephalitis or poliomyelitis should be monitored for inability to protect their airway. Acute neuromuscular respiratory failure may develop rapidly and prolonged ventilatory support may be required.



Editor-In-Chief: C. Michael Gibson, M.S., M.D. [3]; Associate Editor(s)-in-Chief: Alejandro Lemor, M.D. [4]

Overview

Human vaccines are not available for WNV infection. With the absence of a vaccine, prevention of WNV disease depends on community-level mosquito control programs to reduce vector densities, personal protective measures to decrease exposure to infected mosquitoes, and screening of blood and organ donors.[1]

Primary Prevention

Vaccination

There is no human vaccine available against WNV.[1]

Preventing Mosquito Bites[1]

  • Insect repellent is recommended when going outdoors.
  • Repellents containing DEET, picaridin, IR3535, and some oil of lemon eucalyptus and para-menthane-diol products provide longer-lasting protection.
  • To optimize safety and effectiveness, repellents should be used according to the label instructions.
  • When weather permits, patients should wear long sleeves, long pants, and socks when outdoors.
  • Mosquitoes may bite through thin clothing, so spraying clothes with repellent containing permethrin will give extra protection.
  • Do not apply repellents containing permethrin directly to skin.
  • Do not spray repellent on the skin under your clothing.
  • Take extra care to use repellent and protective clothing from dusk to dawn or consider avoiding outdoor activities during these times.

Integrated Vector Management (IVM)

  • Mosquito abatement programs successfully employ integrated pest management (IPM) principles to reduce mosquito abundance, providing important community services to protect quality of life and public health[2].
  • IVM is based on an understanding of the underlying biology of the arbovirus transmission system, and utilizes regular monitoring of vector mosquito populations and WNV activity levels to determine if, when, and where interventions are needed to keep mosquito numbers below levels which produce risk of human disease, and to respond appropriately to reduce risk when it exceeds acceptable levels.
  • Operationally, IVM is anchored by a monitoring program providing data that describe:
  • Conditions and habitats that produce vector mosquitoes.
  • Abundance of those mosquitoes over the course of a season.
  • WNV transmission activity levels expressed as WNV infection rate in mosquito vectors.
  • Parameters that influence local mosquito populations and WNV transmission.
  • These data inform decisions about implementing mosquito control activities appropriate to the situation, such as:
  • Source reduction through habitat modification.
  • Larval mosquito control using the appropriate methods for the habitat.
  • Adult mosquito control using pesticides applied from trucks or aircraft when established thresholds have been exceeded.
  • Community education efforts related to WNV risk levels and intervention activities.
  • Monitoring also provides quality control for the program, allowing evaluation of:

Surveillance Programs

  • Effective IVM for WNV prevention relies on a sustained, consistent surveillance program that targets vector species.
  • The objectives are to identify and map larval production sites by season, monitor adult mosquito abundance, monitor vector infection rates, document the need for control based on established thresholds, and monitor control efficacy.
  • Surveillance can be subdivided into three categories based on the objective of the surveillance effort; these are: larval mosquito surveillance, adult mosquito surveillance and WWNV transmission activity.
  • However, the surveillance elements are complementary, and in combination provide the information required for IVM decisions.
Surveillance Programs
Larval Mosquito Surveillance Adult Mosquito Surveillance WNV Transmission Activity
  • Involves identifying and sampling a wide range of aquatic habitats to identify the sources of vector mosquitoes, maintaining a database of these locations, and a record of larval control measures applied to each.
  • This requires trained inspectors to identify larval production sites, collect larval specimens on a regular basis from known larval habitats, and to perform systematic surveillance for new sources.
  • This information is used to determine where and when source reduction or larval control efforts should be implemented.
  • It is used to quantify relative abundance of adult vector mosquitoes, and to describe their spatial distribution.
  • This process also provides specimens for evaluating the incidence of WNV infection in vector mosquitoes.
  • Adult mosquito surveillance programs require standardized and consistent surveillance efforts in order to provide data appropriate for monitoring trends in vector activity, for setting action thresholds, and evaluating control efforts.
  • Various methods are available for monitoring adult mosquitoes and the most frequently method used are the CO2-baited CDC miniature-style light traps for monitoring host-seeking Culex tarsalis (and potential bridge vector species) and gravid traps to monitor Cx. quinquefasciatus, Cx. pipiens and Cx. restuans populations.
  • Adult mosquito surveillance should consist of a series of collecting sites at which mosquitoes are sampled using both gravid and light traps on a regular schedule.
  • Fixed trap sites allow monitoring of trends in mosquito abundance and virus activity over time and are essential for obtaining information to evaluate WNV risk and to guide control efforts.
  • Monitoring WNV transmission activity in the environment before human cases occur is an essential component of an IVM program to reduce WNV risk.
  • Without this information, it is impossible to set thresholds for vector mosquito population management and to take appropriate action before an outbreak is in progress.
  • WNV transmission activity can be monitored by tracking the WNV infection rate in vector mosquito populations, WNV-related avian mortality, seroconversion to WNV in sentinel chickens, seroprevalence/seroconversion in wild birds, and WNV veterinary (primarily horse) cases.
Adapted from West Nile Virus in the United States: Guidelines for Surveillance, Prevention, and Control[3]

Mosquito Control Activities

  • Integrated efforts to control mosquitoes are implemented to maintain vector populations below thresholds that would facilitate WNV amplification and increase human risk.
  • Efforts to reduce the abundance of WNV-infected biting adult mosquitoes must be quickly implemented to prevent risk levels from increasing to the point of a human disease outbreak.
  • Properly implemented, a program monitoring mosquito abundance and WNV activities in the vector mosquito population will provide a warning of when risk levels are increasing.
  • Because of delays in onset of disease following infection, and delays related to seeking medical care, diagnosis, and reporting of human disease, WNV surveillance based on human case reports lags behind increases in risk and is not sufficiently sensitive to allow timely implementation of outbreak control measures.
  • In outbreak situations, larval control complements adult mosquito control measures by preventing new vector mosquitoes from being produced.
  • Source reduction and larvicide treatments may be inadequate to maintain vector populations at levels sufficiently low to limit virus amplification.
Mosquito Control Activities
Larval Mosquito Control Adult Mosquito Control
  • Objective: To manage mosquito populations before they emerge as adults.
  • This can be an efficient method of managing mosquito populations if the mosquito breeding sites are accessible.
  • Larval control may not attain the levels of mosquito population reduction needed to maintain WNV risk at low levels, and must be accompanied by measures to control the adult mosquito populations as well.
  • Larval control alone is not able to stop WNV outbreaks once virus amplification has reached levels causing human infections.
  • Numerous methods are available for controlling larval mosquitoes.
  • Source reduction is the elimination or removal of habitats that produce mosquitoes. This can range from draining roadside ditches to properly disposing of discarded tires and other trash containers. All sites capable of producing vector mosquitoes must be identified and routinely inspected for the presence of mosquito larvae or pupae.
  • This is difficult to accomplish with the WNV vector species Cx. quinquefasciatus and Cx. pipiens that readily utilize cryptic sites such as storm drainage systems, grey water storage cisterns and storm water runoff impoundments. Vacant housing with unmaintained swimming pools, ponds and similar water features are difficult to identify and contribute a significant number of adult mosquitoes to local populations.
  • Objective: To complement the larval management program by reducing the abundance of adult mosquitoes in an area, thereby reducing the number of eggs laid in breeding sites.
  • It is also intended to reduce the abundance of biting, infected adult mosquitoes in order to prevent them from transmitting WNV to humans and to break the mosquito-bird transmission cycle.
  • In situations where vector abundance is increasing above acceptable levels, targeted pesticides against the adult mosquitoes can assist in maintaining vector abundance below threshold levels.
  • Pesticides for adult mosquito control can be applied from hand-held application devices or from trucks or aircraft. These are useful to manage relatively small areas, but are limited in their capacity to treat large areas quickly during an outbreak.
  • Aerial application of adult mosquito control pesticides is required when large areas must be treated quickly, and can be particularly valuable because controlling WNV vectors such as Cx. quinquefasciatus or Cx. pipiens often requires multiple, closely spaced treatments.
  • Both truck and aerially-applied pesticides for adult mosquitoes control are applied using ultra-low-volume (ULV) technology in which a very small volume of pesticide is applied per acre in an aerosol of minute droplets designed to contain sufficient pesticide to kill mosquitoes that are contacted by the droplets.
Adapted from West Nile Virus in the United States: Guidelines for Surveillance, Prevention, and Control[3]

References

  1. ↑ 1.0 1.1 1.2 "CDC West Nile Virus Prevention & Control".
  2. ↑ Rose RI (2001). "Pesticides and public health: integrated methods of mosquito management". Emerg Infect Dis. 7 (1): 17–23. doi:10.3201/eid0701.700017. PMC 2631680. PMID 11266290.
  3. ↑ 3.0 3.1 "CDC West Nile Virus in the United States: Guidelines for Surveillance, Prevention, and Control" (PDF).


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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [5]; Associate Editor(s)-in-Chief: Alejandro Lemor, M.D. [6]

Overview

Human vaccines against WNV are under development, and they have shown promising results in phase I and II trials. Ribavirin and interferon alfa-2b are currently being studied for the treatment of WNV CNS infections, as both drugs have demonstrated benefit in in vitro studies.

Future or Investigational Therapies

Vaccine

  • Several vaccines are under development for WNV infection, but none has been definitively approved for clinical use. Experimental models in mice and horses have revealed promising results. Phase I and II trials have demonstrated safety and immunogenicity, but further research is still required.[1]
  • The following vaccines are under development:
  • ChimeriVax-WN02[2]
  • Chimeric WN/DEN4-3’delta30[3]
  • Clinical trial VRC303[4][5]
  • WN-80E[6][7]

Pharmacologic Therapy

  • Ribavirin has been administered to patients infected with WNV and have CNS involvement. It has demonstrated inhibition of the virus in human neural cells in vitro.[8][9]
  • Interferon alfa-2b has also shown benefit in in vitro studies against WNV CNS infection.[10]
  • Further studies need to be conducted to determine the efficacy and safety of interferon alfa-2b among patients with WNV infections.

References

  1. ↑ Brandler, Samantha; Tangy, Frederic (2013). "Vaccines in Development against West Nile Virus". Viruses. 5 (10): 2384–2409. doi:10.3390/v5102384. ISSN 1999-4915.
  2. ↑ Bruno Guy, Farshad Guirakhoo, Veronique Barban, Stephen Higgs, Thomas P. Monath & Jean Lang (2010). "Preclinical and clinical development of YFV 17D-based chimeric vaccines against dengue, West Nile and Japanese encephalitis viruses". Vaccine. 28 (3): 632–649. doi:10.1016/j.vaccine.2009.09.098. PMID 19808029. Unknown parameter |month= ignored (help)
  3. ↑ Marina De Filette, Sebastian Ulbert, Mike Diamond & Niek N. Sanders (2012). "Recent progress in West Nile virus diagnosis and vaccination". Veterinary research. 43: 16. doi:10.1186/1297-9716-43-16. PMID 22380523.
  4. ↑ Julie E. Ledgerwood, Theodore C. Pierson, Sarah A. Hubka, Niraj Desai, Steve Rucker, Ingelise J. Gordon, Mary E. Enama, Steevenson Nelson, Martha Nason, Wenjuan Gu, Nikkida Bundrant, Richard A. Koup, Robert T. Bailer, John R. Mascola, Gary J. Nabel & Barney S. Graham (2011). "A West Nile virus DNA vaccine utilizing a modified promoter induces neutralizing antibody in younger and older healthy adults in a phase I clinical trial". The Journal of infectious diseases. 203 (10): 1396–1404. doi:10.1093/infdis/jir054. PMID 21398392. Unknown parameter |month= ignored (help)
  5. ↑ Julie E. Martin, Theodore C. Pierson, Sarah Hubka, Steve Rucker, Ingelise J. Gordon, Mary E. Enama, Charla A. Andrews, Qing Xu, Brent S. Davis, Martha Nason, Michael Fay, Richard A. Koup, Mario Roederer, Robert T. Bailer, Phillip L. Gomez, John R. Mascola, Gwong-Jen J. Chang, Gary J. Nabel & Barney S. Graham (2007). "A West Nile virus DNA vaccine induces neutralizing antibody in healthy adults during a phase 1 clinical trial". The Journal of infectious diseases. 196 (12): 1732–1740. doi:10.1086/523650. PMID 18190252. Unknown parameter |month= ignored (help)
  6. ↑ Susan I. Jarvi, Darcy Hu, Kathleen Misajon, Beth-Ann Coller, Teri Wong & Michael M. Lieberman (2013). "Vaccination of captive nene (Branta sandvicensis) against West Nile virus using a protein-based vaccine (WN-80E)". Journal of wildlife diseases. 49 (1): 152–156. doi:10.7589/2011-12-363. PMID 23307381. Unknown parameter |month= ignored (help)
  7. ↑ Michael M. Lieberman, Vivek R. Nerurkar, Haiyan Luo, Bruce Cropp, Ricardo Jr Carrion, Melissa de la Garza, Beth-Ann Coller, David Clements, Steven Ogata, Teri Wong, Tim Martyak & Carolyn Weeks-Levy (2009). "Immunogenicity and protective efficacy of a recombinant subunit West Nile virus vaccine in rhesus monkeys". Clinical and vaccine immunology : CVI. 16 (9): 1332–1337. doi:10.1128/CVI.00119-09. PMID 19641099. Unknown parameter |month= ignored (help)
  8. ↑ I. Jordan, T. Briese, N. Fischer, J. Y. Lau & W. I. Lipkin (2000). "Ribavirin inhibits West Nile virus replication and cytopathic effect in neural cells". The Journal of infectious diseases. 182 (4): 1214–1217. doi:10.1086/315847. PMID 10979920. Unknown parameter |month= ignored (help)
  9. ↑ S. Ia Loginova, S. V. Borisevich, Iu A. Pashchenko & V. P. Bondarev (2009). "[Ribavirin prophylaxis and therapy of experimental West Nile fever]". [[Antibiotiki i khimioterapiia = Antibiotics and chemoterapy [sic] / Ministerstvo meditsinskoi i mikrobiologicheskoi promyshlennosti SSSR]]. 54 (11–12): 17–20. PMID 20583562.
  10. ↑ Anderson, John F. (2002). "Efficacy of Interferon -2b and Ribavirin Against West Nile Virus In Vitro". Emerging Infectious Diseases. 8 (1): 107–108. doi:10.3201/eid0801.010252. ISSN 1080-6040.


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