Lassa fever

INTRODUCTION — Lassa fever is a hemorrhagic illness caused by Lassa mammarenavirus virus [1-3]. 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 [4-12]. The animal reservoir is the rodent "multimammate rat" (Mastomys natalensis); transmission to humans occurs via contact with infected rodent urine and feces and via person-to-person contact [4,13]. Lassa virus is a single-stranded RNA virus belonging to the Arenaviridae family and has been classified as a category A bioterrorism agent [14].

Issues specific to Lassa fever will be reviewed here. Issues related to other causes of viral hemorrhagic fever are discussed separately:

●(See "Clinical manifestations and diagnosis of Ebola virus disease" and "Marburg virus".)

●(See "Dengue virus infection: Clinical manifestations and diagnosis".)

●(See "Crimean-Congo hemorrhagic fever".)

●(See "Yellow fever: Epidemiology, clinical manifestations, and diagnosis".)

EPIDEMIOLOGY

Geography — Lassa fever is endemic in parts of West Africa including Guinea, Liberia, Sierra Leone, Nigeria, Benin, Ghana, and Mali [15,16]; other neighboring countries are also at risk as the animal vector is distributed throughout the region. Cases have been reported in Côte d’Ivoire and Burkina Faso, and there is serologic evidence of Lassa virus infection among individuals in Togo [17-26].

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 [17,27]. Within Sierra Leone, seroprevalence rates vary from 8 percent in coastal regions to 52 percent in the Eastern Province [4]. In Guinea, the seroprevalence rate varies from 4 to 55 percent [27-30].

Cases of Lassa fever occur at all times of year; the peak incidence occurs in March, during the transition from dry to wet season [5,31]. In addition, there is a smaller increase in incidence in December, during the middle of the dry season [31].

Lassa virus infection poses a significant healthcare burden in high-incidence regions. In one study examining admissions to two hospitals in Sierra Leone, Lassa fever cases resulted in 10 to 16 percent of medical admissions and 30 percent of all deaths [32].

A large increase in Lassa fever cases occurred in Nigeria between December 2017 and May 2018; there were more than 600 laboratory-confirmed cases with an estimated case-fatality rate of 27 percent [33]. This outbreak raised concern among public health officials regarding emergence of a new or more virulent Lassa virus strain. In a comparison of Lassa virus genomes from more than 100 patients from the 2018 outbreak and more than 90 patients from the two prior seasons, the 2018 Lassa genomes were found to represent a diverse range of viruses previously observed in Nigeria (rather than a single dominant strain), suggesting no clear association between the outbreak and a single virus strain [34]. The reason for the outbreak remains unknown; it may reflect changes in the rodent reservoir population or improved surveillance and heightened public awareness. Since 2018, an increased number of cases have continued to be seen with over 1000 cases in 2020 and 2022 [33,35].

Imported cases of Lassa fever have been described among returned travelers, with a relatively high case fatality rate (>30 percent) [36,37].

Transmission — Modes of Lassa fever transmission include rodent contact and person-to-person contact.

Rodent contact — The primary mode of transmission to humans is via exposure to infected Mastomys rodents; this may occur via direct contact with rodent urine and feces, inhalation of aerosolized rodent excretions, or consumption of infected rodents as a food source [4,13].

Mastomys rodent infestation is associated with households built of poor-quality materials, such as crumbling mud, which facilitates rodent burrows [38]. In one study, residences of patients with Lassa virus infection were 10 times more likely to be infested with Mastomys rodents than residences with no cases [39].

Individuals with a history of routine Mastomys rodent consumption are more than twice as likely to have serologic evidence of Lassa virus infection as individuals who do not consume the rodents [40]. In addition, Mastomys rodent consumption is associated with a fourfold increase in deafness, a common sequela of Lassa fever infection. (See 'Clinical manifestations' below.)

Person-to-person — Person-to-person transmission may occur after exposure to Lassa virus in the blood, urine, feces, or other bodily secretions of an infected individual [41-43]. Lassa virus infection is not thought to spread through casual contact (such as hugging, shaking hands, or sitting near someone) [44]. Individuals with Lassa virus infection are not believed to be contagious prior to onset of symptoms.

Individuals in close contact with patients, including healthcare workers, are at risk for transmission of infection via body fluids and airborne droplets in the absence of appropriate protective measures [11,28,41,45]. Nosocomial outbreaks of Lassa fever have been described, and enhanced precautions must be taken when caring for patients with suspected or confirmed Lassa fever [10,11,46,47]. (See 'Prevention' below.)

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 [5]. Sexual transmission of Lassa fever infection during convalescence has been described [48]. (See 'Sexual transmission' below.)

PATHOGENESIS — Infection with Lassa virus generally occurs via the nasopharyngeal mucosa, where it infects dendritic cells, monocytes, and macrophages [49-51]. Subsequently, the virus spreads to regional lymph nodes before disseminating to virtually all tissues.

Inflammatory cell infiltrate of infected organs tends to be minimal [51,52]; necrosis can occur, particularly in the liver and spleen [50-52]. Hepatic necrosis can be significant, involving up to 40 percent of hepatocytes [51,52]. Splenic necrosis, adrenocortical and pituitary necrosis, interstitial myocarditis, alveolar edema, and renal tubular injury are also common [6,51-53]. Viral infection of endothelial cells in all major organs has been described [52].

Severe disease appears to result from vascular instability and impaired hemostasis [54]. Lassa virus stimulates macrophages and dendritic cells to release soluble mediators resulting in the endothelial dysfunction, insufficient effective circulating intravascular volume, and multiorgan failure [54-57]. This results in pleural effusions and pulmonary edema, ascites, and hemorrhagic manifestations of the gastrointestinal mucosa [6,58]. Hemorrhage has also been associated with a circulating inhibitor of platelet aggregation and thrombocytopenia [59].

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 [41,60,61]. Cell-mediated immunity is predominantly responsible for survival [55,62-64]. Neutralizing antibodies appear after recovery [41,48].

In fatal cases, the cellular response to Lassa virus infection appears to be weak. Lassa virus does not activate monocytes and macrophages to secrete proinflammatory cytokines among fatal cases [65,66]. This virus-induced immunosuppression may allow the Lassa virus to replicate unchecked in fatal cases.

CLINICAL MANIFESTATIONS

Overview — Lassa virus infection is associated with a broad spectrum of clinical manifestations [4]. The incubation period is one to three weeks [6,27,32,67-69]. Individuals with Lassa virus infection are not believed to be contagious prior to onset of symptoms. Most infected individuals (approximately 80 percent) have mild symptoms (low-grade fever, malaise, and headache) and may not seek medical attention.

Disease progresses to more serious signs and symptoms in approximately 20 percent of patients; these include pharyngitis, cough, nausea, vomiting, diarrhea, myalgias, retrosternal chest pain, back pain, and abdominal pain [70]. In severe cases, facial swelling, pulmonary edema, bleeding (from the mouth, nose, vagina, or gastrointestinal tract), and hypotension may develop. Proteinuria may be noted. Shock, seizures, tremor, disorientation, and coma may be seen in the later stages.

The most common 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 [32,71-74]. Onset of hearing loss may occur during acute illness or during convalescence. Hearing may improve after one to three months in approximately half of cases.

Patients who recover generally begin to improve after 8 to 10 days of symptom onset. Some patients have signs of improvement followed by relapse of fever with pulmonary edema.

Poor prognostic factors include the presence of vomiting, sore throat, tachypnea, bleeding, and diarrhea [6,32,41,48]. High-level viremia at presentation (determined by measurement of serum antigen or genomic copies) has been correlated with increased mortality [41,75,76].

Death usually occurs within two 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 [31,32]. Mortality rates can be high (≥50 percent) in the setting of nosocomial outbreaks [47].

Signs and symptoms by organ system — Signs and symptoms are summarized by organ system below.

●Central nervous system – Sensorineural deafness occurs in up to one-third of patients, and it becomes permanent in approximately 18 percent. In severe cases of Lassa virus infection, disorientation, ataxia, and seizures can occur in as many as one-third of patients [27,32,77]. Encephalopathy has been described [78]. It is not clear whether these clinical manifestations reflect direct viral invasion of the central nervous system, an immune response, or metabolic disturbances [79].

●Head and neck – Cervical lymphadenopathy is a common symptom of Lassa virus infection. Pharyngitis and bilateral conjunctivitis occur in 70 and 40 percent of cases, respectively [31,32,51]. Edema of the head and neck is a distinctive feature of Lassa fever and is seen in approximately 30 percent of hospitalized cases.

●Pulmonary – A dry cough may occur. Pulmonary edema and pleural effusions may develop late in the course of disease [80,81].

●Cardiovascular – Retrosternal chest pain occurs in approximately 70 percent of patients [32]. In one review of electrocardiograms from 32 patients with Lassa fever, 75 percent were abnormal; nonspecific ST and T wave changes were observed in 69 percent of cases [82]. Myocarditis has been observed in some cases of Lassa fever [6,80,81]; nonhuman primate studies have demonstrated that Lassa virus is myocardiotropic, resulting in pulmonary and coronary arteritis as well as perivascular myocarditis [51]. Pericardial effusions have been described infrequently [80].

●Gastrointestinal – Diarrhea and vomiting are common [31,53,72]. In severe cases, abdominal pain is common, likely due to accumulation of fluid in the abdominal cavity [51].

●Renal – Acute renal failure occurs commonly among patients hospitalized with Lassa fever; in one series, it was observed in 28 percent of cases [77].

●Rash – A maculopapular rash may appear on the thorax, face, and upper extremities in less than 5 percent of cases [27]; it may be difficult to see in darker-skinned individuals.

●Hemorrhage – Overt hemorrhage occurs in fewer than 20 percent of patients warranting hospitalization [27,32]. Manifestations generally consist of blood oozing from the mouth, nose, vagina, gastrointestinal tract, and cannulation and injection sites. Occasionally, rectal bleeding occurs. The hemorrhagic component of severe Lassa fever cases appears to be due to endovascular leakage as well as inhibition of platelet aggregation [83]. However, disseminated intravascular coagulation is generally not observed [84].

Pregnancy — Lassa fever is especially severe in late pregnancy; maternal death and/or fetal loss occur in more than 80 percent of cases during the third trimester [85]. Pregnant women are more likely to have severe illness due to Lassa virus infection than nonpregnant women. In a meta-analysis including 276 pregnant women with Lassa fever, the case fatality rate was 34 percent; compared with nonpregnant patients, the relative risk of death for pregnant women was 2.86 [86].

A "swollen baby syndrome" has been described among babies born to women infected during the third trimester; it consists of anasarca, abdominal distension, and bleeding [87]. The fetal case fatality rate is 61.5 to 100 percent [86,87].

Laboratory findings — Laboratory findings associated with Lassa fever infection include:

●Leukopenia – Early in the course of infection, patients generally have a mild leukopenia with a predominant lymphopenia [32,59,67-69,88,89]. Subsequently, patients may develop a leukocytosis with neutrophilia.

●Thrombocytopenia – Mild thrombocytopenia has been observed; the platelet count is rarely below 100,000/microL [83]. Patients with severe Lassa fever have significantly decreased platelet aggregation, which may be due to an inhibitor responsible for decreased platelet function [54,59,83].

●Elevated transaminases and amylase – Both alanine aminotransferase (ALT) and aspartate aminotransferase (AST) are elevated; AST is usually significantly greater than ALT, often at a ratio of 10:1 [88,90]. AST ≥120 international units (IU)/L at the time of presentation has been associated with increased mortality risk [77]. Amylase is frequently elevated as well.

●Coagulation abnormalities – Prothrombin and partial thromboplastic times are usually normal even in severely ill patients [84]. Disseminated intravascular coagulation does not play a significant role in Lassa fever disease (in contrast with some other viral hemorrhagic fevers such as Ebola virus disease).

●Renal abnormalities – Renal insufficiency has been associated with increased risk of mortality due to Lassa fever [77,91]. Proteinuria is common (57 percent of patients in one study) [32].

●Spinal fluid findings – Lassa virus has been isolated from the spinal fluid in a small number of cases [41,71,92]. Spinal fluid analysis in patients with Lassa fever has demonstrated mild to moderate pleocytosis.

Lassa virus can be transmitted via blood and other body fluids; therefore, when possible, routine laboratory testing (such as complete blood cell counts and metabolic panels) should be done via point-of-care equipment rather than in the hospital laboratory. (See 'Prevention' below.)

DIAGNOSIS — The diagnosis of Lassa fever should be suspected in individuals with suggestive signs and symptoms (these include fever, malaise, headache, pharyngitis, cough, nausea, vomiting, diarrhea, myalgia, chest pain, or hearing loss) in the setting of relevant epidemiologic exposure (residence in or travel to an endemic area with exposure to Mastomys rodents and/or symptomatic individuals with known or suspected Lassa fever in the past three months, or unprotected sexual contact with a person who meets these criteria). Patients being evaluated for Lassa fever should be isolated. (See 'Prevention' below.)

The World Health Organization case definition for suspected acute Lassa fever is summarized in the (table 1). Administration of empiric treatment with ribavirin is reasonable for patients in endemic areas with symptoms strongly suggestive of Lassa fever, prior to diagnostic confirmation. (See 'Treatment' below.)

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 [60,61,93,94]. In addition, the genetic heterogeneity within and between the lineages makes the molecular diagnosis of Lassa virus difficult [95,96].

The diagnosis of 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 [97]. 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 [48,76,98]. In one study, Lassa virus serology had sensitivity and specificity of 88 and 90 percent, respectively [48]. There is variation among Lassa virus lineages, and some assays may not have equal sensitivity for each lineage [99]. In addition, there is some cross-reactivity between Lassa fever virus, lymphocytic choriomeningitis virus, and New World arenaviruses such as Tacaribe virus [13]. 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, and culture should be performed only in high-containment laboratories. 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 as described in the following section. (See 'Differential diagnosis' below.)

DIFFERENTIAL DIAGNOSIS — The differential diagnosis of Lassa fever virus infection includes [100]:

●Other viral hemorrhagic fevers:

•Ebola and Marburg virus – Both Ebola and Marburg virus are causes of viral hemorrhagic fevers endemic to West Africa with symptoms and signs similar to those caused by Lassa virus. The diagnosis of Ebola or Marburg virus is established via reverse-transcription polymerase chain reaction (RT-PCR) in blood or other body fluids. (See "Clinical manifestations and diagnosis of Ebola virus disease" and "Marburg virus".)

•Dengue – Dengue is an acute febrile illness accompanied by fever, headache, retro-orbital pain, and marked muscle and joint pain. Hemorrhagic manifestations and thrombocytopenia can also occur. The virus is transmitted by Aedes aegypti mosquitoes, which have broad epidemiologic distribution. The diagnosis of dengue fever is established via serologic testing. (See "Dengue virus infection: Clinical manifestations and diagnosis".)

•Crimean-Congo hemorrhagic fever – Crimean-Congo hemorrhagic fever (CCHF) is a zoonotic disease caused by a virus transmitted by ticks and characterized by fever and hemorrhage; it is endemic in parts of Africa, the Middle East, Asia, and southeastern Europe. The diagnosis is established via RT-PCR or serology. (See "Crimean-Congo hemorrhagic fever".)

•Yellow fever – Yellow fever is a mosquito-borne viral hemorrhagic fever endemic to tropical regions of South America and sub-Saharan Africa. It is characterized by acute infection with nonspecific symptoms, followed by a period of remission and a subsequent episode of illness with hepatic and renal dysfunction. The diagnosis is established via serology or RT-PCR. (See "Yellow fever: Epidemiology, clinical manifestations, and diagnosis".)

●Malaria – Malaria is the most common diagnosis in ill travelers returning from West Africa; it is a mosquito-borne illness with nonspecific clinical manifestations including fever, malaise, headache, anorexia, nausea, vomiting, abdominal pain, diarrhea, arthralgias, and myalgias. The diagnosis is established via rapid diagnostic testing or blood smear. (See "Malaria: Clinical manifestations and diagnosis in nonpregnant adults and children" and "Laboratory tools for diagnosis of malaria".)

●Typhoid – Typhoid fever is common in areas where Lassa fever is endemic. Clinical manifestations of typhoid fever include abdominal pain, fever, and chills; classic manifestations include relative bradycardia, pulse-temperature dissociation, and "rose spots" (faint salmon-colored macules on the trunk and abdomen). Typhoid is diagnosed by identifying the organism in blood cultures. (See "Enteric (typhoid and paratyphoid) fever: Epidemiology, clinical manifestations, and diagnosis".)

●Travelers' diarrhea – Travelers' diarrhea typically occurs during travel or within 10 days after returning; clinical manifestations include watery diarrhea, malaise, anorexia, and abdominal cramps. It is important to differentiate patients with travelers' diarrhea from those with a more systemic syndrome associated with other symptoms. The diagnosis of travelers' diarrhea is established via stool and/or blood cultures. (See "Travelers' diarrhea: Treatment and prevention".)

●Sepsis due to bacterial infection – Patients with sepsis due to bacterial infection typically present with fever, hypotension, disorientation, and/or respiratory failure. The diagnosis is established via blood culture. (See "Gram-negative bacillary bacteremia in adults".)

●Influenza – Clinical manifestations of influenza and Lassa fever include fever, headache, myalgias, and malaise; rhinorrhea is commonly associated with influenza but does not generally occur in the setting of Lassa fever infection. Influenza can occur year-round in the tropics; the preferred diagnostic test is RT-PCR. (See "Seasonal influenza in adults: Clinical manifestations and diagnosis".)

●Streptococcal pharyngitis – Clinical manifestations of streptococcal pharyngitis include sore throat, particularly when swallowing; fever is often present and may occur in association with headache or malaise. Patients may note anterior neck pain related to lymphadenopathy. The diagnosis is established via throat culture or rapid antigen testing. (See "Evaluation of acute pharyngitis in adults".)

●Meningococcal meningitis – Clinical manifestations of meningococcal disease include fever, headache, nausea, vomiting, and myalgias. A purpuric rash may occur. The diagnosis is established via analysis of cerebrospinal fluid or blood cultures. (See "Clinical manifestations of meningococcal infection" and "Diagnosis of meningococcal infection".)

●Leptospirosis – Clinical manifestations of leptospirosis include abrupt onset of fever, rigors, myalgias, and headache. Conjunctival suffusion is a distinguishing feature. Animal reservoirs include rodents and domestic animals. The diagnosis is established via serologic testing. (See "Leptospirosis: Epidemiology, microbiology, clinical manifestations, and diagnosis".)

TREATMENT

Supportive care — Treatment of Lassa fever consists primarily 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 nonsteroidal anti-inflammatory drugs should be avoided because these agents can adversely affect clotting.

Ribavirin — In addition to supportive care, we suggest administering ribavirin for all symptomatic patients with a confirmed diagnosis of Lassa fever. Empiric treatment with ribavirin is reasonable for patients in endemic areas with symptoms strongly suggestive of the illness. Our recommendations are generally in agreement with expert guidelines [101].

●Timing – Ribavirin has been reported to be most effective when given within the first six days after onset of symptoms [90].

●Dose – Intravenous (IV) administration is preferred because higher serum concentrations can be achieved than with oral formulations. Oral ribavirin is acceptable if IV ribavirin is not available [49,90,102].

•IV ribavirin: 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 [42].

An alternative dosing strategy (100 mg/kg on day 1, 25 mg/kg on days 2 to 5, and 12.5 mg/kg on days 6 to 10) is used at a single institution, and efficacy and safety data are not available [103].

•Oral ribavirin: 35 mg/kg (maximum 2.5 g), followed by 15 mg/kg (maximum 1 g) every six hours for four days, followed by 15 mg/kg (maximum 1 g) every eight hours for six days.

The optimal oral dosing regimen is unknown. Given the lower serum levels of oral ribavirin compared with IV ribavirin, it is reasonable to use higher doses (as summarized above), although no pharmacologic or efficacy data are available.

●Side effects – Side effects include hemolytic anemia, which is reversible, and rigors during infusion [90,104]. Rigors can be ameliorated by judicious prehydration and pretreatment with diphenhydramine (25 to 50 mg orally or IV) administered 30 minutes prior to ribavirin.

We recommend monitoring renal function and hemoglobin concentration daily during treatment. If symptomatic anemia develops, transfusion of blood products should be considered. If renal insufficiency occurs, ribavirin dosages may require adjustment based on the specific manufacturer's recommendations. Ribavirin-associated hemolytic anemia has been found to worsen underlying cardiac disease and has sometimes lead to myocardial infarction so caution is necessary when deciding whether to administer it to patients with known cardiac disease.

Our recommendations are based on a single report of small trials in patients in Sierra Leone with confirmed Lassa fever and serum aspartate aminotransferase levels (AST) ≥150 international units (IU)/L at the time of admission in the late 1970s and early 1980s [90]. IV or oral ribavirin for 10 days resulted in lower case fatality rates than no treatment (19, 14, and 55 percent, respectively) and the case fatality rate was lowest (5 percent) in patients who received IV ribavirin within the first six days of illness.

After publication, the data set used in the Sierra Leone study was re-evaluated, which led some experts to question the validity of the findings [105-109]. Additionally, systematic reviews, a meta-analysis, and post-hoc analyses of the Sierra Leone dataset have suggested that ribavirin may actually increase mortality in patients with an AST <150 IU/L, although these analyses mostly rely on the Sierra Leone publication. Nonetheless, based on these concerns, some experts withhold ribavirin for individual patients with mild to no symptoms and an AST <150 IU/L.

The specific mechanism of action of ribavirin in the treatment of Lassa fever is unclear. Reduction in markers of cell damage suggests that it may have an anti-inflammatory effect, whereas pharmacokinetic studies question its anti-viral efficacy at recommended dosages [110].

Ribavirin may be difficult to obtain in certain regions and shortages have been known to occur. Under these circumstances, we recommend seeking out clinical trials utilizing other antivirals. If direct participation is not possible, we recommend requesting compassionate use authorization from the manufacturer.

Empiric treatment for other infections — The patient should be evaluated for other infections as described above, including malaria, typhoid, and secondary bacterial infection; antimicrobial therapy should be tailored accordingly. If malaria cannot be ruled out in a timely manner, empiric treatment for malaria is warranted. (See 'Differential diagnosis' above and "Treatment of uncomplicated falciparum malaria in nonpregnant adults and children" and "Treatment of severe malaria".)

MONITORING RESPONSE — Improvement manifests as resolution of fever, transaminitis, and other clinical manifestations and generally occurs 8 to 10 days after onset of symptoms.

We suggest monitoring serum Lassa antigen levels to monitor response (we check it on days 2, 3, 4, 7, and 10 of illness). In our experience, antigenemia almost always resolves by day 10.

PREVENTION — Thus far, there is no vaccine for prevention of Lassa virus infection [111]. Preventive measures include avoiding Mastomys rodents and minimizing risk of person-to-person transmission.

Post-exposure prophylaxis is warranted for contacts of patients with known or suspected Lassa fever infection who have risk factors for transmission; this is discussed further below.

Avoiding rodents — Residents of and travelers to areas where Mastomys rodents are endemic should store food in rodent-proof containers, trap rodents in and around homes, and avoid using rodents as a food source [44].

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.

Infection control — The approach to infection control for preventing transmission of Lassa fever virus is similar to the approach for preventing transmission of other viral hemorrhagic fevers such as Ebola virus disease [112]. (See "Treatment and prevention of Ebola virus disease", section on 'Infection control precautions during acute illness'.)

Patients being evaluated or treated for Lassa fever infection in healthcare facilities should be isolated. Handwashing is of the utmost importance, and care should include enhanced precautions (including standard, contact, and droplet precautions as well as correct use of appropriate personal protective equipment [PPE]). PPE consists of gloves, gown, mask, goggles, and foot coverings; the equipment should be put on and removed under the supervision of a trained monitor to minimize risk of contamination. (See "Infection prevention: Precautions for preventing transmission of infection".)

Blood and body fluid specimens from patients with suspected Lassa fever infection should be considered highly infectious and handled with extreme caution. Routine laboratory tests (such as complete blood cell counts and metabolic panels) should be done via point-of-care tools rather than in the hospital laboratory. Medical equipment should be sterilized, and soiled linens should be handled as potentially hazardous material.

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. Family members should not open the body bag or clean the body of a deceased patient with Lassa fever.

Sexual transmission — Sexual transmission of Lassa fever infection during convalescence has been described [48]. Individuals should wait at least three months following resolution of Lassa fever infection before unprotected sex.

Post-exposure prophylaxis — Post-exposure prophylaxis (PEP) is warranted for contacts of patients with known or suspected Lassa fever infection with risk factors for transmission; these include penetrating needle stick injury, exposure of mucous membranes or broken skin to blood or body fluids, and participation in procedures involving exposure to bodily fluids or respiratory secretions without use of PPE [113].

Post-exposure prophylaxis consists of ribavirin administered via 35 mg/kg orally as a loading dose (maximum dose 2.5 g), followed by 15 mg/kg orally (maximum dose 1 g) every eight hours for 10 days [90,114-117].

Patients receiving post-exposure prophylaxis should be monitored closely for 21 days; those who develop fever (temperature ≥38.3°C) should begin treatment with intravenous ribavirin while awaiting diagnostic testing for Lassa fever infection. (See 'Treatment' above.)

SUMMARY AND RECOMMENDATIONS

●Epidemiology – Lassa fever is a viral hemorrhagic fever caused by Lassa virus that is endemic to West Africa. Approximately 300,000 cases and 5000 deaths occur annually. (See 'Geography' above.)

●Transmission – The primary mode of transmission is via exposure to infected Mastomys rodents by direct contact with rodent urine or feces, inhalation of aerosolized rodent excretions, or consumption of infected rodents as a food source. (See 'Rodent contact' above.)

Person-to-person transmission may occur after exposure to blood, urine, feces, or other bodily secretions from an infected individual. It is not spread through casual contact. (See 'Person-to-person' above.)

●Clinical manifestations – The incubation period is one to three weeks. Approximately 80 percent of cases are mild (low-grade fever, malaise, and headache). (See 'Clinical manifestations' above.)

Clinical manifestations of more severe illness include pharyngitis, cough, nausea, vomiting, diarrhea, myalgias, retrosternal chest pain, back pain, and abdominal pain. Disease may progress to facial swelling, pulmonary edema, bleeding (from the mouth, nose, vagina, or gastrointestinal tract), and hypotension. (See 'Clinical manifestations' above.)

Recovery typically begins 8 to 10 days after onset of symptoms. Overall mortality is approximately 1 percent; mortality for hospitalized patients is 15 to 30 percent. The most common complication among survivors is deafness, which occurs in up to one-third of patients. (See 'Clinical manifestations' above.)

●Clinical suspicion – Lassa fever should be suspected in individuals with typical signs and symptoms in the setting of potential rodent exposure in endemic areas or in individuals having had close contact with an infected person. The World Health Organization case definition is summarized in the table (table 1). (See 'Diagnosis' above.)

●Diagnostic tests – Diagnosis is usually established via detection of IgM and IgG antibodies and Lassa antigen in serum. Polymerase chain reaction (PCR) is preferred but is rarely used in regions where Lassa fever is endemic. (See 'Diagnosis' above.)

Testing for other endemic infections, including malaria, typhoid, and secondary bacterial infections, should also be performed.

●Treatment

•Supportive care – This is the mainstay of treatment, 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 nonsteroidal anti-inflammatory drugs should be avoided because they can adversely affect clotting. (See 'Treatment' above.)

•Ribavirin – We suggest intravenous (IV) ribavirin for all patients (Grade 2C). However, some experts withhold ribavirin for individual patients with mild to no symptoms and an aminotransferase level (AST) <150 international units (IU)/L because of concern of toxicity. If IV ribavirin is not available, oral ribavirin is an alternative. Dosing is summarized above. (See 'Treatment' above.)

•Empiric treatment of other illnesses – If malaria cannot be ruled out in a timely manner, empiric treatment for malaria is warranted. (See "Treatment of uncomplicated falciparum malaria in nonpregnant adults and children" and "Treatment of severe malaria".)

●Prevention – Measures include avoiding rodents and isolation of potentially infected individuals. In healthcare facilities, enhanced precautions (standard, contact, and droplet) should be followed, and all blood and bodily fluids should be handled with extreme caution. (See 'Prevention' above and 'Infection control' above.)

•Post-exposure prophylaxis – We suggest post-exposure prophylaxis (PEP) with oral ribavirin for close contacts of patients with known or suspected Lassa fever infection and risk factors for transmission (Grade 2C). Risk factors include penetrating needle stick, exposure of mucous membranes or broken skin to blood or body fluids, and participation in procedures involving exposure to bodily fluids or respiratory secretions without use of personal protective equipment (PPE). (See 'Post-exposure prophylaxis' above.)