Lassa Fever

Lassa Fever

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  LASSA FEVER
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  INTRODUCTION  Lassa feveris a hemorrhagic illness caused by Lassa virus.  Lassa fever was first recognized in Lassa, Nigeria, in 1969 and is endemic to West Africa; there are approximately 300,000 cases and 5000 deaths annually.  Lassa virus is a single-stranded RNA virus belonging to the Arenaviridae family and has been classified as a category A bioterrorism agent
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  EPIDEMIOLOGY  Lassa feveris endemic in parts of West Africa including Guinea, Liberia, Sierra Leone, Nigeria, Benin, Ghana, and Mali  The prevalence of Lassa virus infections varies within endemic areas; the incidence is highest in the forested regions of West Africa where Guinea, Liberia, and Sierra Leone share a border.  Cases of Lassa fever occur at all times of year; the peak incidence occurs in March, during the transition from dry to wet season. In addition, there is a smaller increase in incidence in December, during the middle of the dry season.  Imported cases of Lassa fever have been described among returned travelers, with a relatively high case fatality rate (>30 percent)
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  TRANSMISSION  The primarymode of transmission to humans is via exposure to infected Mastomys rodents via direct contact with rodent urine and feces, inhalation of aerosolized rodent excretions, or consumption of infected rodents as a food source  Mastomys rodent infestation is associated with households built of poor-quality materials, such as crumbling mud, which facilitates rodent burrows.  Person-to-person transmission may occur after exposure to Lassa virus in the blood, urine, feces, or other bodily secretions of an infected individual.  Risk for person-to-person transmission of Lassa virus persists after recovery; the virus is shed in the urine for three to nine weeks and in the semen for up to three months . RODENT CONTACT PERSON-TO-PERSON CONTACT
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  TRANSMISSION Reservoir Mastomys rats Primary human infections Secondaryhuman infections  The virus maintains itself in Mastomys rat population  Virus is present in urine and feces of infected rats 80 to 90 % of humans are infected through:  Food or household items contaminated by infected rat urine and feces.  Direct contact while handling Mastomys rats (food source)  Secondary human-to- human transmission occurs through direct contact with the blood secretions, organs or other body fluids of infected persons
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  PATHOGENESIS  Transmission occursvia the nasopharyngeal mucosa, where it infects dendritic cells, monocytes, and macrophages. Subsequently, the virus spreads to regional lymph nodes before disseminating to virtually all tissues.  Inflammatory cell infiltrate of infected organs tends to be minimal; necrosis can occur, particularly in the liver and spleen. Hepatic necrosis can be significant, involving up to 40 percent of hepatocytes. Splenic necrosis, adrenocortical and pituitary necrosis, interstitial myocarditis, alveolar edema, and renal tubular injury are also common.Severe disease appears to result from vascular instability and impaired hemostasis.  Lassa virus stimulates macrophages and dendritic cells to release soluble mediators resulting in the endothelial dysfunction, insufficient effective circulating intravascular volume, and multiorgan failure. This results in pleural effusions and pulmonary edema, ascites, and hemorrhagic manifestations of the gastrointestinal mucosa. Hemorrhage has also been associated with a circulating inhibitor of platelet aggregation and thrombocytopenia.  Among survivors, Lassa virus levels peak between days 4 and 9 of illness, and serum viral RNA can be detected for up to three weeks after recovery. Cell-mediated
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  CLINICAL MANIFESTATIONS  Theincubation period is 1 to 3 weeks.  Most infected individuals (approx. 80%) have mild symptoms (low-grade fever, malaise, and headache) and may not seek medical attention.  Disease progresses to more serious signs and symptoms in approx. 20% of patients; these include pharyngitis, cough, nausea, vomiting, diarrhea, myalgias, retrosternal chest pain, back pain, and abdominal pain.  In severe cases, facial swelling, pulmonary edema, bleeding (from the mouth, nose, vagina, or GI tract), and hypotension may develop. Proteinuria may be noted.  Shock, seizures, tremor, disorientation, and coma may be seen in the later stages.
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   The mostcommon complication of Lassa fever is deafness, which occurs in up to one-third of patients and may develop in the setting of mild or severe illness. Hearing may improve after 1 to 3 months in approximately half of cases.  Patients who recover generally begin to improve after 8 to 10 days of symptom onset. Poor prognostic factors include the presence of vomiting, sore throat, tachypnea, bleeding, and diarrhea.  Death usually occurs within 2 weeks after onset of symptoms in fatal cases. Approximately 1 percent of Lassa virus infections result in death; among hospitalized patients, case-fatality rates range from 15 to 30 percent. Mortality rates can be high (≥50 percent) in the setting of nosocomial outbreaks.
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  SYMPTOMS  CNS –Sensorineural deafness occurs in up to 1/3 of patients, and it becomes permanent in approximately 18%. In severe cases of Lassa virus infection, disorientation, ataxia, and seizures can occur in as many as one-third of patients  Head and neck – Cervical lymphadenopathy is a common symptom of Lassa virus infection. Pharyngitis and bilateral conjunctivitis occur in 70 and 40% of cases, respectively. Edema of the head and neck is a distinctive feature of Lassa fever and is seen in approx. 30% of hospitalized cases.  Pulmonary – A dry cough may occur. Pulmonary edema and pleural effusions may develop late in the course of disease  Cardiovascular – Retrosternal chest pain occurs in approximately 70% of patients. Myocarditis has been observed in some cases of Lassa fever
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   GI –Diarrhea and vomiting are common. In severe cases, abdominal pain is common, likely due to fluid accumulation  Renal – Acute renal failure occurs in 28% of cases  Rash – A maculopapular rash may appear on the thorax, face, and upper extremities in less than 5% of cases.  Hemorrhage –Manifestations generally consist of blood oozing from the mouth, nose, vagina, GI tract, and cannulation and injection sites due to endovascular leakage as well as inhibition of platelet aggregation
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  DIAGNOSIS  The diagnosisof Lassa fever should be suspected in individuals with suggestive signs and symptoms in the setting of relevant epidemiologic exposure.  Administration of empiric treatment with ribavirin is reasonable for patients in endemic areas with symptoms strongly suggestive of Lassa fever, prior to diagnostic confirmation.  The preferred test for diagnosis of Lassa fever is serum reverse-transcription polymerase chain reaction; however, this is rarely used in regions where Lassa fever is endemic because it requires expensive equipment and technical expertise .  In addition, the genetic heterogeneity within and between the lineages makes the molecular diagnosis of Lassa virus difficult.
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   The diagnosisof Lassa fever in some endemic regions may be established via serum enzyme-linked immunosorbent serologic assay, which can detect immunoglobulin (Ig)M and IgG antibodies and Lassa antigen. Antigen is typically detectable at the time of symptom onset. However, if initial testing is negative, but a high index of suspicion for Lassa fever remains, the test should be repeated in 24 to 48 hours.  Serum IgM is detectable 10 to 21 days after symptom onset; serum IgG is detectable approximately 21 days after symptom onset .  Enzyme-linked immunosorbent serologic and antigen assays take 4 to 18 hours to perform depending on the individual platform used.  Lassa virus may be cultured from blood, urine, or throat washings, but these are not routine clinical diagnostic tools. A postmortem diagnosis may be established via immunohistochemistry performed on formalin-fixed tissue specimens.  Diagnostic evaluation of patients with suspected Lassa fever infection should also include diagnostic testing for malaria, blood cultures, and evaluation for other infections
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  LAB FINDINGS  Leukopenia–Patients generally have a mild leukopenia in the early stages. Subsequently, patients may develop a leukocytosis with neutrophilia.  Thrombocytopenia – Mild thrombocytopenia has been observed. Patients with severe Lassa fever have significantly decreased platelet aggregation  Elevated transaminases and amylase – Both alanine aminotransferase (ALT) and aspartate aminotransferase (AST) are elevated; AST is usually significantly greater than ALT. Amylase is frequently elevated as well.  Renal abnormalities – Renal insufficiency has been associated with increased risk of mortality due to Lassa fever. Proteinuria is common  Spinal fluid findings – Lassa virus has been isolated from the spinal fluid in a small number of cases. Spinal fluid analysis in patients with Lassa fever has demonstrated mild to moderate pleocytosis.
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  TREATMENT  It consistsprimarily of supportive care, including maintenance of oxygenation and blood pressure. Fluid replacement is important although care must be taken to avoid volume overload due to the risk of capillary leak and renal dysfunction. Aspirin and NSAIDs should be avoided because these agents can adversely affect clotting.  In addition to supportive care, it is suggested to administer ribavirin for all symptomatic patients with a confirmed diagnosis of Lassa fever.  Ribavirin has been reported to be most effective when given within the first six days after onset of symptoms  Intravenous (IV) administration is preferred because higher serum concentrations can be achieved than with oral formulations  Loading dose 30 mg/kg (maximum 2 g), followed by 15 mg/kg (maximum 1 g) every six hours for four days, followed by 7.5 mg/kg (maximum 500 mg) every eight hours for six days
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  PREVENTION  There isno vaccine for prevention of Lassa virus infection. Preventive measures include avoiding Mastomys rodents and minimizing risk of person-to-person transmission  Patients with known or suspected Lassa fever should be managed in healthcare facilities whenever possible; community-based care should be avoided to minimize the risk of person- to-person transmission. Patients with signs and symptoms of infection should be considered contagious, even if the clinical manifestations are mild  Blood and body fluid specimens from patients with suspected Lassa fever infection should be considered highly infectious and handled with extreme caution.  The body of a deceased patient should not be returned to family members; it should be placed in a sealed body bag and trained personnel in PPE should handle and bury the body.  Individuals should wait at least three months following resolution of Lassa fever infection before unprotected sex.