Andes hantavirus: epidemiology, outbreaks and guidance
The epidemiology, symptoms, diagnosis and management of Andes hantavirus infection.
Epidemiology
Andes virus (ANDV) is a type of hantavirus, within the order Bunyavirales. ANDV infection in humans was first described in 1995 in Argentina, and was identified in Chile later in the same year. ANDV is a cause of hantavirus cardiopulmonary syndrome (HCPS) in South America, which is a potentially fatal, acute medical complication of specific hantavirus infections.
Wild rodents of the family Cricetidae are the natural animal reservoir of ANDV, particularly the long-tailed pygmy rice rat (Oligoryzomys longicaudatus). Humans can acquire ANDV infection by contact with infected rodents or their excreta in South America, principally in Argentina and Chile, and rarely through contact with an infected person.
There are several ANDV hantavirus strains associated with HCPS. Officially classified strains include Castelo dos Sonhos virus, Lechiguanas virus and Orán virus, whilst Araucária virus, Araraquara virus, Bermejo virus, Buenos Aires virus, Juquitiba virus, Paranoá virus and Plata virus are unclassified strains.
In Argentina, cases of ANDV HCPS mostly occur across 4 endemic regions: North (Salta, Jujuy), Centro (Buenos Aires, Santa Fe, and Entre Ríos), Northeast (Misiones) and Patagonia (Neuquén, Río Negro, and Chubut). Within Chile, ANDV infections occur mainly in southern Chile and ANDV infection is endemic in the Región de Los Lagos.
Cases peak in spring and summer, when the number of infected rodents tends to be high and people engage in more outdoor activities, particularly in rural and semi-rural areas. Some years may be associated with an increased risk of exposure, according to factors such as favourable climatic conditions and increases in rodent populations.
Other hantaviruses found in North and South America can cause HCPS, for example Sin Nombre virus in the US and Laguna Negra virus in Paraguay and Bolivia. However, ANDV is the only hantavirus for which human-to-human transmission has been described. Limited human-to-human transmission within families and within healthcare settings has been reported for previous outbreaks in Chile and Argentina.
Rare cases of travel associated ANDV infection have also been reported, including infections in travellers returning to the US and Europe from Argentina and Chile, respectively.
See risk map for HCPS caused by ANDV in southern Argentina.
Transmission
Animal-to-human transmission occurs when people come into contact with infected wild rodents, their droppings or environments contaminated by rodent excreta, whilst in at-risk areas including Chile and Argentina. Infected rodents do not show signs of disease. It is believed that transmission occurs by inhalation of aerosolized virus particles from rodent excreta (or dust containing the excreta), or by touching mucous membranes with hands that have been contaminated by the virus. Rodent bites are a rare but potential route of transmission.
It is unclear how human-to-human transmission of ANDV occurs, but it appears that close contact with an infected person is necessary, and airborne transmission should be considered a possibility. Close contact with infected cases within a household setting has been shown to increase the risk of transmission tenfold and transmission often occurs in family clusters.
Epidemiological studies suggest that human-to-human transmission can occur during the prodromal phase. In late 2018, an outbreak occurred in Chubut province, Argentina. A single suspected symptomatic index case attended a party in Epuyén where secondary transmission is thought to have occurred.
In total there were 34 confirmed cases, including 11 deaths, and 142 people were placed in quarantine. Nosocomial transmission has been described previously in Argentina. For example, in an outbreak that affected 16 individuals (9 deaths and 15 secondary cases), 8 individuals were thought to have been infected in healthcare facilities, including 5 physicians (3 of whom were directly responsible for the clinical care of an ANDV HCPS patient). Three of the physicians and a clinic receptionist died.
Clinical features
The most important complication of ANDV infection is HCPS, which is associated with a high mortality rate. Milder illness without significant cardio-respiratory compromise may also be seen. Illness usually develops 2 to 4 weeks following exposure, but incubation periods as early as 4 days and up to 8 weeks have been described.
Clinical features of ANDV infection include an initial prodrome, which may be an influenza-like or non-specific febrile illness, with fever, chills and myalgia, and sometimes gastrointestinal symptoms. Vomiting, diarrhoea and abdominal pain may be the only initial symptoms in some cases. Conjunctivitis and petechiae may also be present.
Upper respiratory tract signs and symptoms tend to be absent. In progressive illness, the prodromal symptoms worsen and then acute respiratory compromise and hypotension follow quickly, usually heralded by onset of a dry cough. This represents the cardiopulmonary phase, with capillary leakage in the lungs. Abdominal pain may be present and can be severe.
Complications include respiratory failure, acute respiratory distress syndrome, acute pulmonary oedema, shock, coagulopathy and haemorrhage, and cardiac arrhythmias. Neurological complications are uncommon but encephalopathy, encephalitis, meningitis and seizures may occur. The mortality rate is typically 35 to 50%.
Thrombocytopaenia is common and may be seen in the prodromal phase. Increases in blood lactate dehydrogenase may be seen initially, followed by increases in blood lactate and liver transaminase levels. There may be evidence of acute renal impairment. Neutrophilic leukocytosis and the presence of immunoblasts in peripheral blood may be seen, particularly in more severe disease.
The resolution of the cardiopulmonary phase can also be rapid (over 24 to 48 hours in some cases), but complete recovery from HCPS can be a protracted process.
Patient assessment
ANDV infection is classed as an airborne high consequence infectious disease (HCID) in England and clinical assessment should be performed by specialist hospital staff, with adherence to strict infection prevention and control precautions (see below) to prevent secondary transmission.
There are currently no agreed case criteria for ANDV infection. Consider ANDV infection in a patient with a relevant travel and exposure history who presents with a compatible illness, particularly severe acute respiratory illness, and the onset of illness was within 8 weeks of a potential exposure.
Visitors to rural areas of Argentina and Chile (for example mountain trekkers and campers) may be at increased risk of ANDV infection, including those who do not report a history of known exposure to rodents and their excreta. ANDV infection is a rare disease and other travel associated and common infections should also be considered in the differential diagnosis.
Any suspected cases in England should be discussed initially with local infection specialists and then with the Imported Fever Service (IFS) (24 hour telephone service: 0844 778 8990). The IFS can advise on whether laboratory testing is indicated. The IFS is also available to clinicians in Scotland, Wales and Northern Ireland. Any suspected cases should be notified immediately to the local Health Protection Team.
Laboratory diagnosis
In the UK, the Rare and Imported Pathogens Laboratory (RIPL) at Public Health England (PHE) Porton Down is the designated diagnostic laboratory. RIPL offers RT-PCR and IgG serological assays for the detection of hantaviruses.
Any suspected case should be discussed with local infection specialists and with the IFS, as above. The IFS can advise on whether laboratory testing is indicated, and if so, will provide advice about the samples types required. IFS will also advise on sample collection precautions and transport requirements.
Treatment
There is no proven, specific treatment for ANDV infection, and there is no preventative vaccine. Treatment is supportive. There is no evidence to support the use of ribavirin or corticosteroids in the treatment of HCPS. Clinical management of confirmed ANDV infection in England must be provided by specialist infectious diseases and critical care teams that are capable of safely managing patients with high consequence infectious diseases.
Patients can deteriorate rapidly and confirmed cases in England should be transferred to an Airborne HCID Treatment Centre quickly, including consideration of whether extracorporeal membrane oxygenation (ECMO) may be required.
Infection prevention and control
Prevention of transmission of infection by airborne and contact routes is required. Since ANDV virus infection is an airborne HCID, strict infection prevention and control (IPC) measures are required when caring for both suspected and confirmed patients.
Appropriate respiratory isolation is essential for suspected and confirmed cases. Enhanced personal protective equipment (PPE) must be used when assessing or providing care to suspected HCID cases in hospitals. Refer to the PHE HCID guidance collection.
Hospital clinicians are advised to follow the same enhanced IPC measures used for suspected and confirmed cases of Middle East respiratory syndrome (MERS). This guidance is available on the PHE website.
Clinical laboratories should be informed in advance of samples submitted from suspected or confirmed diagnosis of ANDV infection, so that they can perform local risk assessments, minimise risk to laboratory workers and, where appropriate, safely perform laboratory tests that are essential to clinical care. ANDV is an ACDP Hazard Group 3 pathogen.
Advice for travellers to endemic areas
Those travelling to endemic areas in Chile and Argentina, particularly rural areas or areas with known active outbreaks, should avoid contact with rodents or areas that may be infested by rodents (for example where rodent droppings are visible). Basic rural accommodation, such as forest cabins and mountain huts, should be aired before use if the accommodation has been left unoccupied for some time.
Cabins and potential campsites in endemic areas should not be used if rodents, rodent droppings or rodent nests or burrows are identified. If use cannot be avoided, disinfect areas that have signs of rodents. If camping, use a ground sheet and camping mat, and sleep on a camping bed if possible. Observe good hand hygiene by washing hands regularly.
Person-to-person transmission is best prevented by avoidance of contact with patients with confirmed or suspected HCPS.
For information about current outbreaks and travel advice, visit the National Travel Health Network and Centre (NaTHNaC) website.
UK risk assessment
Although rodent-associated hantavirus infections occur in the UK, there is no risk of ANDV infection in the UK. It is possible that rare, travel-associated infections may be seen in the UK in travellers returning from Argentina and Chile, although none have been reported to date.
The risk of a case from an outbreak area being imported into the UK is very low if standard precautions are undertaken whilst travelling to an endemic area.