Hantavirus pulmonary syndrome (HPS) is an infectious disease that is acquired through exposure to rodents carrying the causative virus, the Hantavirus. A few cases have been documented, where the infection was acquired through human to human contact [1] [2].

HPS usually occurs in specific geographical locations, such as north and south America. The disease appears to affect all individuals equally, although men may have a higher incidence rate due to more recurrent exposure to the vector. For the same reason, HPS typically does not present in young children or the elderly.

HPS is one of many syndromes that can arise from Hantavirus infection [3] [4]. The affected organ systems depend on the specific type of Hantavirus an individual has come in contact with. The severity of illness varies greatly between cases, ranging from mild to severe. Furthermore, it demonstrates significantly high case mortality rates, estimated at up to 50%. This syndrome is characterized by severe respiratory compromise. The illness has several stages entailing a prodromal phase, respiratory phase, and convalescent phase. The disease has an incubation period of one week to one month, after which prodromal symptoms manifest.

Prodromal symptoms are often nonspecific and may involve gastrointestinal discomfort, vomiting, headache, and muscle pain [5]. These individuals also experience pyrexia. The typical signs usually last up to 5 days.

Subsequently, the host immune system attacks endothelial cells lining the lungs, displaying viral antigens. This process leads to increased permeability of the endothelium and thus pulmonary edema. The cardiopulmonary phase lasts up to 48 hours and is characterized by the emergence of respiratory findings such as coughing, tachypnea, crepitations, and dyspnea. Patients frequently require mechanical ventilation during this time. Some individuals may develop hypotension and circulatory collapse due to cardiogenic shock, the latter being the main cause of death in HPS [6] [7] [8]. Oliguria is not an uncommon observation during this phase, and in a few cases, may lead to renal failure.

The third stage is preceded by an episode of diuresis and is made evident by the resolution of cardiopulmonary features.

• Fever

  The viral hemorrhagic fevers endemic in the Americas include yellow fever, dengue hemorrhagic fever, the South American hemorrhagic fevers, hantavirus pulmonary syndrome, and hemorrhagic fever with renal syndrome. [ncbi.nlm.nih.gov]

• Chills

  The Maine resident went to a community hospital in early April with a 5-day history of fatigue, decreased appetite, weakness, chills, myalgias, and progressive shortness of breath. On examination, he was hypoxic and tachypneic. [ncbi.nlm.nih.gov]

  Medical Definition of hantavirus pulmonary syndrome : an acute respiratory disease caused by various hantaviruses and characterized initially especially by fever, muscle pain, headache, cough, vomiting, and chills which rapidly progress to pulmonary edema [merriam-webster.com]

  The typical prodrome consists of fever, chills, myalgia, headaches, and gastrointestinal symptoms, and can become complicated by acute respiratory distress syndrome (ARDS), respiratory failure, and shock. The case fatality rate is 35%. [dph.georgia.gov]

  The infection has_symptom fever, has_symptom muscle pain, has_symptom headache, has_symptom cough, has_symptom vomiting, has_symptom chills which rapidly progress to bilateral interstitial pulmonary infiltrates occurrence, pulmonary edema and hypoxia [amp.pharm.mssm.edu]

  Symptoms that almost always occur in the early stages of HPS are: fever, muscle pain, fatigue, headache, chills, nausea, vomiting, diarrhea, abdominal pain, dizziness, and feeling generally ill. [breathebayarea.org]

• Malaise

  Other early symptoms may include gastrointestinal disturbances, headache, chills, and malaise, which may last up to 5 days. The secondary phase is called the cardiopulmonary phase and this includes an acute onset of pulmonary edema. [austincc.edu]

  Other early symptoms include gastrointestinal disturbances, headache, chills, and malaise. 4 Physical findings on initial presentation include fever, tachypnea, and tachycardia, but the remainder of the examination is usually normal. [aafp.org]

  Headache, fever, injected sclerae, malaise, nausea, pain in limbs and back, leukopenia Prolonged mental depression Rare No Sindbis virus infection ( Alphavirus spp.) [nap.edu]

• Turkish

  Of the 5 hamster species, only Turkish hamsters infected with LNV demonstrated signs consistent with HPS and a fatality rate of 43%. [ncbi.nlm.nih.gov]

  Laguna Negra Virus Infection Causes Hantavirus Pulmonary Syndrome in Turkish Hamsters (Mesocricetus brandti). [science.gov]

  (Germany) 1996-01-01 Two asymptomatic Turkish sibs are presented, a 4-year-old boy and his 7-year-old sister, with pulmonary alveolar microlithiasis (PAM) confirmed by transbronchial lung biopsy and bronchoalveolar lavage. [worldwidescience.org]

• Intravenous Drugs

  HPS treatment with an experimental antiviral intravenous drug, ribavirin, is under investigation. [ncbi.nlm.nih.gov]

• Cough

  The confirmed case involved a previously healthy young woman who died with signs and symptoms of acute respiratory insufficiency 5 days after presenting fever, myalgia and a dry cough. [ncbi.nlm.nih.gov]

  Prodromal symptoms are flu-like ones, such as fever, cough, myalgia, headache, lethargy, and shortness of breath, which rapidly deteriorates into acute respiratory failure. [en.wikipedia.org]

• Dyspnea

  Temporary exertional dyspnea and reduced expiratory flow are common in early convalescence after HPS but resolves in almost all patients. [ncbi.nlm.nih.gov]

• Tachypnea

  The most common physical findings were tachypnea (100 percent), tachycardia (94 percent), and hypotension (50 percent). [ncbi.nlm.nih.gov]

  The cardiopulmonary phase lasts up to 48 hours and is characterized by the emergence of respiratory findings such as coughing, tachypnea, crepitations, and dyspnea. Patients frequently require mechanical ventilation during this time. [symptoma.com]

  A cough and tachypnea develop before pulmonary edema and signs of hypoxia. Cardiac abnormalities might present such as myocardial depression, and after that the illness usually gets worse. Hospitalization may be required along with ventilation. [microbewiki.kenyon.edu]

  Other early symptoms include gastrointestinal disturbances, headache, chills, and malaise. 4 Physical findings on initial presentation include fever, tachypnea, and tachycardia, but the remainder of the examination is usually normal. [aafp.org]

• Pharyngitis

  Rash, rhinorrhea, pharyngitis, and conjunctivitis are rare in HPS and thus, argue against SNV infection. 13 It is important to note that rash and conjunctivitis are often seen in patients with HPS in South America. [aafp.org]

  Fever, often with shaking chills; severe polyarticular arthralgia; rash with headache, photophobia, retro-orbital pain, sore throat, pharyngitis, nausea, vomiting Arthralgia and myalgia Frequent No Potentially More Prevalent Among Troops in Southwest [nap.edu]

  A systematic review of Andes virus infection in Argentina documented marked conjunctival injection, facial flushing ( rubicundez, in Spanish; this symptom is also found in HFRS), pharyngeal congestion, and petechiae. [academic.oup.com]

  […] deformans) pancreas cancer pancreatitis panic disorder paralysis parkinson's disease paronychia pelvic inflammatory disease (pid) penis cancer pericarditis, acute periodontitis (gum inflammation) peripheral neuropathy (peripheral neuritis) peritonitis pharyngitis [healthse.com]

  He had been diagnosed with streptococcal pharyngitis 2 weeks prior to admission. Given the presence of hemoptysis, bronchoscopy was performed and was consistent with DAH. [science.gov]

• Sore Throat

  Sore throat, runny nose, watery eyes, sneezing and rashes are rarely seen. These symptoms would suggest the illness is due to some other cause. [nasdonline.org]

  throat) stroke (cerebrovascular accident) stye (hordeolum) subarachnoid hemorrhage subconjunctival hemorrhage subdural hemorrhage & hematoma sunburn syphilis tapeworm (taenia saginata) tay-sachs disease tear duct infection or blockage (dacryocystitis [healthse.com]

  Fever, often with shaking chills; severe polyarticular arthralgia; rash with headache, photophobia, retro-orbital pain, sore throat, pharyngitis, nausea, vomiting Arthralgia and myalgia Frequent No Potentially More Prevalent Among Troops in Southwest [nap.edu]

• Vomiting

  In the prodromal stage, HPS presents with flu-like symptoms, nausea, vomiting, and gastrointestinal pain and is often mistaken on the first visit for other infectious diseases or gastroenteritis. [ncbi.nlm.nih.gov]

  Medical Definition of hantavirus pulmonary syndrome : an acute respiratory disease caused by various hantaviruses and characterized initially especially by fever, muscle pain, headache, cough, vomiting, and chills which rapidly progress to pulmonary edema [merriam-webster.com]

  Nausea, vomiting, acute shock, and hypotension may occur in this stage. The following stage is the oliguric, and kidney function improves in the stage that follows, the diuretic stage. [microbewiki.kenyon.edu]

  The infection has_symptom fever, has_symptom muscle pain, has_symptom headache, has_symptom cough, has_symptom vomiting, has_symptom chills which rapidly progress to bilateral interstitial pulmonary infiltrates occurrence, pulmonary edema and hypoxia [amp.pharm.mssm.edu]

  Some people also get headaches, dizziness, vomiting, or diarrhea. After about four to ten days, people who are sick with hantavirus infection begin to cough and have shortness of breath. [wcsv.org]

• Nausea

  In the prodromal stage, HPS presents with flu-like symptoms, nausea, vomiting, and gastrointestinal pain and is often mistaken on the first visit for other infectious diseases or gastroenteritis. [ncbi.nlm.nih.gov]

  Signs of hantavirus infection usually occur within one to five weeks after exposure, and include fever, muscle aches, dizziness, nausea, difficulty breathing, and coughing. [directorsblog.health.azdhs.gov]

  Symptoms include abrupt onset of fever, chills, weakness, nausea, vomiting, and abdominal pain followed by difficulty breathing. HPS can be rapidly fatal if not identified and treated promptly. [foundation.chestnet.org]

  Symptoms that almost always occur in the early stages of HPS are: fever, muscle pain, fatigue, headache, chills, nausea, vomiting, diarrhea, abdominal pain, dizziness, and feeling generally ill. [breathebayarea.org]

  Key symptoms and signs to watch for (especially with a history of rodent exposure) include: Fever greater than 101 F, chills, body aches, headaches Nausea and vomiting and abdominal pain New rash (faint red spots) A dry cough followed by rapid onset of [lung.org]

• Diarrhea

  The second phase lasts 2 to 8 days and includes rapid development of fever, dry cough, body aches, headaches, diarrhea, and abdominal pain. Heart and lung failure can develop during this phase. [lung.org]

  Some people also get headaches, dizziness, vomiting, or diarrhea. After about four to ten days, people who are sick with hantavirus infection begin to cough and have shortness of breath. [wcsv.org]

  Symptoms that almost always occur in the early stages of HPS are: fever, muscle pain, fatigue, headache, chills, nausea, vomiting, diarrhea, abdominal pain, dizziness, and feeling generally ill. [breathebayarea.org]

  F), tiredness, muscle aches, headaches, dizziness, chills, and stomach problems (nausea, vomiting, diarrhea, and pain). Later symptoms are coughing and difficulty breathing, which are caused by fluid buildup in the lungs. [phpa.health.maryland.gov]

  Symptoms such as fever, headache, muscle aches, nausea, vomiting, chills, diarrhea and dizziness may occur up to 6 weeks after exposure to infected mice or mice urine, saliva or droppings. [hnhu.org]

• Abdominal Pain

  The second phase lasts 2 to 8 days and includes rapid development of fever, dry cough, body aches, headaches, diarrhea, and abdominal pain. Heart and lung failure can develop during this phase. [lung.org]

  Symptoms include abrupt onset of fever, chills, weakness, nausea, vomiting, and abdominal pain followed by difficulty breathing. HPS can be rapidly fatal if not identified and treated promptly. [foundation.chestnet.org]

  Symptoms that almost always occur in the early stages of HPS are: fever, muscle pain, fatigue, headache, chills, nausea, vomiting, diarrhea, abdominal pain, dizziness, and feeling generally ill. [breathebayarea.org]

  Early symptoms include: Fatigue Fever Muscle aches in large muscle groups Headache Dizziness Chills Nausea and vomiting Diarrhea Abdominal pain 4-10 days after initial symptoms begin, more severe symptoms occur: Coughing Shortness of breath Lungs filling [gethealthycarsoncity.org]

  Some individuals may experience more serious symptoms such as vomiting, dizziness, abdominal pain followed by coughing, shortness of breath and difficulty breathing. [simcoemuskokahealth.org]

• Hypotension

  The most common physical findings were tachypnea (100 percent), tachycardia (94 percent), and hypotension (50 percent). [ncbi.nlm.nih.gov]

  The illness takes a severe turn when hypotension and respiratory distress appear suddenly. A cough and tachypnea develop before pulmonary edema and signs of hypoxia. [microbewiki.kenyon.edu]

  None of the surviving patients had severe hypotension. Hypotension did not appear to be a direct consequence of hypoxia, since several patients with adequate oxygenation had progressive hypotension. [nejm.org]

  Some individuals may develop hypotension and circulatory collapse due to cardiogenic shock, the latter being the main cause of death in HPS. Oliguria is not an uncommon observation during this phase, and in a few cases, may lead to renal failure. [symptoma.com]

• Tachycardia

  The most common physical findings were tachypnea (100 percent), tachycardia (94 percent), and hypotension (50 percent). [ncbi.nlm.nih.gov]

  Other early symptoms include gastrointestinal disturbances, headache, chills, and malaise. 4 Physical findings on initial presentation include fever, tachypnea, and tachycardia, but the remainder of the examination is usually normal. [aafp.org]

  paroxysmal tachycardia) heatstroke or heat exhaustion (sunstroke; heat prostration) heel spur (calcaneal spur) hemophilia hemorrhoids (piles) hepatitis, viral hepatoma (malignant liver tumor; hepatocellular carcinoma) hernia herpangina herpes, genital [healthse.com]

• Chest Pain

  A previously healthy 29-year-old male presented to the emergency department with pleuritic chest pain, nonproductive cough, and dyspnea. He was treated empirically for community acquired pneumonia and discharged to home. [ncbi.nlm.nih.gov]

  On June 7, an adolescent boy aged 14 years went to a Washington emergency department with a 5-day history of shortness of breath, chest pain, cough, and fever. [jamanetwork.com]

  Late symptoms of HPS symptoms occur about four to 10 days after the early symptoms and include coughing, chest pain, and shortness of breath that can become severe. [medicinenet.com]

  Patients (N 840) had chest pain, dyspnea, nondiagnostic ECGs, and no obvious diagnosis. [science.gov]

• Refractory Shock

  shock despite fluid resuscitation, and vasoactive medications. [ncbi.nlm.nih.gov]

  Both patients developed adult respiratory distress syndrome and refractory shock. A patient died and another one recovered 12 days later. [science.gov]

  Both patients developed adult respiratory distress syndrome and refractory shock. [worldwidescience.org]

• Petechiae

  The hemorrhagic part of the disease name comes from petechiae, hematuria, and melena that may develop in more severe cases. [microbewiki.kenyon.edu]

  This is followed by flushing, then petechiae. The disease progresses to hemorrhage (gastrointestinal, subconjunctival) and hemodynamic instability, occasionally progressing to shock. [web.archive.org]

  A systematic review of Andes virus infection in Argentina documented marked conjunctival injection, facial flushing ( rubicundez, in Spanish; this symptom is also found in HFRS), pharyngeal congestion, and petechiae. [academic.oup.com]

  However, in this group of patients we also observed conjuntival injection in 10/25 (42%), facial flushing in 8/25 (33%), pharyngeal congestion in 7/25 (29%) and petechiae in 3/25 (12%). [science.gov]

• Myalgia

  The confirmed case involved a previously healthy young woman who died with signs and symptoms of acute respiratory insufficiency 5 days after presenting fever, myalgia and a dry cough. [ncbi.nlm.nih.gov]

• Arthralgia

  Clinical Presentation: Hantavirus pulmonary syndrome infection often presents as a "flu-like" illness, with fever, intense headache, myalgia, nausea and other gastrointestinal symptoms; this is followed by cough, shortness of breath, dizziness, sweats and arthralgia [tbdhu.com]

  Fever, often with shaking chills; severe polyarticular arthralgia; rash with headache, photophobia, retro-orbital pain, sore throat, pharyngitis, nausea, vomiting Arthralgia and myalgia Frequent No Potentially More Prevalent Among Troops in Southwest [nap.edu]

  Persons with acute brucellosis develop high daily fevers, arthralgia and hepatosplenomegaly. [iloencyclopaedia.org]

  Ron M; Wells, Athol U 2006-03-01 Hypocomplementaemic urticarial vasculitis syndrome (HUVS) is a rare disorder characterised by complement activation and the presence of C1q precipitins together with a syndrome of urticarial vasculitis, angioedema, arthralgia [science.gov]

• Back Pain

  There is severe abdominal, joint and back pain, and possibly, nausea and vomiting. Within 1-5 days after symptoms start, a person will develop a cough, shortness of breath and difficulty breathing due to fluid build-up in the lungs. [nasdonline.org]

  pain (sciatica) balanitis baldness, pattern, male & female barotitis media (barotrauma) bed-wetting (enuresis) bell's palsy bladder tumor blastomycosis (north american blastomycosis; gilchrist's disease) blepharitis blood poisoning (septicemia; septic [healthse.com]

  Case report: A 45-year-old Danish woman living in an area endemic for Hanta virus, without prior medical history, was admitted because of lower back pain radiating to the left hip, fever, headache, nausea, and malaise. [science.gov]

  Leptospirosis-Associated Severe Pulmonary Hemorrhagic Syndrome with Lower Back Pain as an Initial Symptom DEFF Research Database (Denmark) SÃ ndergaard, Mads Madsen; tursunovic, Amela; Thye-Roenn, Peter 2016-01-01 BACKGROUND Leptospirosis is a zoonosis [worldwidescience.org]

• Suggestibility

  Immunoreactivity analysis of white blood cell lysates suggests that some circulating PB are virus-specific but we also observed a significant increase of reactivity against virus-unrelated antigens, which suggests a possible bystander effect by polyclonal [ncbi.nlm.nih.gov]

• Headache

  Infected patients suffer from fatigue, fever, and muscle aches often accompanied by headaches, dizziness and gastrointestinal problems in the weeks following exposure. [en.wikipedia.org]

  The most common prodromal symptoms were fever and myalgia (100 percent), cough or dyspnea (76 percent), gastrointestinal symptoms (76 percent), and headache (71 percent). [ncbi.nlm.nih.gov]

  The second phase lasts 2 to 8 days and includes rapid development of fever, dry cough, body aches, headaches, diarrhea, and abdominal pain. Heart and lung failure can develop during this phase. [lung.org]

• Dizziness

  Infected patients suffer from fatigue, fever, and muscle aches often accompanied by headaches, dizziness and gastrointestinal problems in the weeks following exposure. [en.wikipedia.org]

  Signs of hantavirus infection usually occur within one to five weeks after exposure, and include fever, muscle aches, dizziness, nausea, difficulty breathing, and coughing. [directorsblog.health.azdhs.gov]

  Some people also get headaches, dizziness, vomiting, or diarrhea. After about four to ten days, people who are sick with hantavirus infection begin to cough and have shortness of breath. [wcsv.org]

  Symptoms that almost always occur in the early stages of HPS are: fever, muscle pain, fatigue, headache, chills, nausea, vomiting, diarrhea, abdominal pain, dizziness, and feeling generally ill. [breathebayarea.org]

  F), tiredness, muscle aches, headaches, dizziness, chills, and stomach problems (nausea, vomiting, diarrhea, and pain). Later symptoms are coughing and difficulty breathing, which are caused by fluid buildup in the lungs. [phpa.health.maryland.gov]

Upon presentation, baseline blood tests, as well as more specific laboratory testing should be carried out. Often requested laboratory studies include:

• Complete blood count (CBC), urea and electrolytes, peripheral smear, and arterial blood gas analysis (ABGA).
• Immunochemistry.
• Serology.
• PCR (polymerase chain reaction).

CBC may reveal low platelets and elevated white blood cells, with an unusually high proportion of immature cells [9]. Serum lactate dehydrogenase (LDH) is also high. Other parameters may reflect the distributive shock experienced in Hantavirus pulmonary syndrome [6] [7]. One such finding is hemoconcentration. A peripheral blood smear, in addition to the above, may reveal the presence of atypical immune cells, as well as immunoblasts [9]. Once these findings are observed, HPS can be diagnosed.

Imaging studies are usually carried out in the form of a chest radiograph. Signs of pulmonary edema that may be visualized include increased hilar markings, diffuse bilateral infiltrates, Kerley B lines, and peribronchial thickening. The cardiac silhouette is of normal size, and pleural effusions might also be present.

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