Lassa Fever

Lassa fever is an illness caused by the Lassa virus, a single-stranded RNA hemorrhagic fever virus from the family Arenaviridae. It is an acute febrile viral illness lasting one to four weeks, and it occurs in West Africa and some areas beyond.

Lassa fever was first described in the 1950s, and the viral particle was identified in 1969 by three missionary nurses who died in Lassa, Nigeria, after caring for an infected obstetrical patient. Lassa fever is one of the hemorrhagic fever viruses, occurring in West African sub-regions in similar areas as the Ebola virus. Sierra Leone, Liberia, Ghana, and Nigeria are most often affected. Surrounding regions are also at risk because the rodents that transmit the virus are very common throughout West through East Africa. There are 100,000 to 300,000 cases of Lassa fever each year in the world. Lassa fever heavily impacts Sierra Leone and Liberia in particular, where it causes an estimated 5,000 deaths and about 10%-16% of admissions to hospitals each year. Deaths are especially common in children. Case fatality is 1% in general (compared to 70% in the Ebola virus). Severe cases have a case fatality of 15%.

An unusually intense outbreak developed in early 2018 in Nigeria with over 300 confirmed positive cases reported in March. Cases were reported in Bauchi, Plateau, Edo, Ondo, and Ebonyi States. Sixteen health workers, at least four of whom died, were diagnosed as of Mar. 4, 2018. Along with high numbers, case fatality rates for this outbreak exceeded 20%. A Weekly Epidemiological Report has been maintained by the Nigeria Centre for Disease Control.

Nigerian Minister of Health, Professor Isaac Adewale, announced that the vaccine against the Lassa virus would be arriving by the end of 2018. Dr. Chikwe Ihekweazu, CEO of the Nigeria Centre for Disease Control, has stressed the important advances of improved awareness and expanded ability to test for Lassa fever virus in recent years. Dr. Ihekweazu has encouraged improved adherence to infection prevention measures and community sanitation efforts to control current and future outbreaks of Lassa fever. Lassa fever has rarely been diagnosed in the U.S. There have been only six diagnosed cases since 1969. The last case was diagnosed in May 2015, in New Jersey by a patient traveling from Liberia. U.S. cases have involved international travelers or immigrants who arrived with the infection after exposure to rodents in West Africa.

Among the scientists who have studied hemorrhagic fever viruses, Dr. Susan P. Fisher-Hoch, Professor of Epidemiology at the University of Texas School of Public Health, worked extensively with the Lassa virus, conducting primate studies and investigating several outbreaks in Nigeria while working with the U.S. Centers for Disease Control and Prevention (CDC). While Deputy Branch Chief of the CDC Special Pathogens Laboratory, Division of Viral Diseases, she supervised the Sierra Leone Lassa Fever Research Unit and published major research articles on Lassa fever vaccines and other hemorrhagic fevers. Many students of epidemiology (the study of how diseases spread) are familiar with the story of her work with her husband, Dr. Joe McCormick, whom she married while he was Chief of, the Special Pathogens Laboratory, Level 4: Virus Hunters of the CDC. Dr. Fisher-Hoch was elected to the Women in Technology International Hall of Fame in 2008 for her extraordinary contributions to science and medicine.

Lassa fever virus is mainly a zoonosis (a disease that is animal-borne or spread to humans from animals). It is spread to people through contact with household items, food, water, or air contaminated with the droppings or urine of infected multimammate rats (Mastomyces natalensis). These rodents live throughout West Africa in homes, and they can shed this virus without being ill. People most often become infected by inhaling air contaminated with aerosols of rodent excretions, swallowing the virus in food or contaminated utensils, preparing and eating multimammate rats (meat of wild or non-domesticated animals, called bush meat or wild meat, which is often prized as a delicacy), and contact with open wounds. Lassa fever virus is believed to be endemic (always present) in Ghana, Sierra Leone, Liberia, and Nigeria. It has also been detected in Ivory Coast, Benin, Guinea, Burkina Faso, Mali, Senegal, Gambia, and Central African Republic. Reporting of cases is not consistent, and the rats are present throughout West, Central, and East Africa, so cases are possible throughout these areas.

Travelers to West Africa staying in homes or areas of poor sanitation or crowding, as well as health care and laboratory professionals serving in health care facilities in West Africa, are most at risk. Infection prevention methods are critical to reducing infection of healthcare workers and spread within health facilities.

Those at the highest risk for serious complications and death are pregnant women in their third trimester. Stillbirth or fetal loss occurs in 95% of pregnancies.

Person-to-person spread is possible but is not as frequent as with the Ebola virus. It can rarely occur upon direct contact with saliva, blood, bodily fluids, and mucous membrane or sexual contact. Casual contact of intact skin with intact skin does not transmit the virus. Laboratory workers and health care professionals can become infected through improper infection-control precautions, and patients in rural hospitals have acquired it through the reuse of disposable needles.

No person-to-person spread has been documented in the U.S. from returning travelers.

It is not clear when infected humans are contagious or for how long they are contagious. The presence of the virus in the blood is known to peak four to nine days after symptoms begin. The virus can be transmitted in semen for up to three months.

Lassa fever is one of the hemorrhagic fevers and may appear with signs and symptoms like Ebola or Marburg hemorrhagic fever viruses, and until these viruses are ruled out, suspected cases must be managed with infection control precautions to prevent contact with blood, body fluids, and contaminated surfaces. These include basic hand washing or alcohol-based sanitizing between patients. When working within 3 feet of an affected patient, use of additional barrier personal protective equipment should include an impermeable long-sleeved gown, gloves, and face mask with eye protection. Safe injection practices, safe laboratory handling, and safe mortuary procedures are also important.

It is not clear when infected humans are contagious or for how long, but the virus is cleared from the blood during recovery about three weeks after the onset of symptoms.

The incubation period for Lassa fever is variable, from six days to three weeks. Most people have mild or no symptoms. British researchers suggest the incubation period varies from seven to 10 days and in some people, up to about 21 days.

In those who have symptoms, Lassa fever begins with a flu-like illness:

• fever,
• malaise,
• generalized weakness,
• sore throat (very similar to strep throat and without a runny nose),
• severe headache,
• chest pain (especially behind the breastbone),
• back pain,
• ringing ears, 
• nausea,
• vomiting,
• abdominal pain, and
• diarrhea. 

Hemorrhage is not common in less serious diseases, but the loss of fluid from blood vessels into tissue may occur; this causes facial swelling, reddened whites of the eyes, and fluid around the lungs and heart.

• Dry cough and respiratory distress may occur if the illness involves fluid in the lungs.
• Severe disease may cause encephalitis with confusion, tremors, seizures, and coma.
• Organ failure and shock are often end-stage events.
• Fair-skinned individuals may have a faint rash on the upper body that is not seen in dark-skinned individuals.
• Some bleeding from mucous membranes occurs in severe illnesses.
• Lassa virus infects all tissues, but infection of the liver is especially typical.
• Hepatitis may be mild or severe, and laboratory tests may not reflect the level of injury.

Lassa fever virus often causes deafness, and this complication may be noted in late-stage disease and during recovery periods.

Without laboratory tests, Lassa fever is difficult to differentiate from other infections common to West Africa; however, this requires specialized laboratories and precautions for handling specimens.

• Laboratory tests include enzyme-linked immunosorbent serologic assays (ELISA) for Lassa IgM and IgG antibodies and Lassa antigen. For definitive testing, the virus can be grown in culture in seven to 10 days; a reverse transcriptase polymerase chain reaction (RT-PCR) assay is also available but often limited to research.
• Immunohistochemistry stains performed on tissue specimens can also be used to make a postmortem diagnosis.

Ribavirin given intravenously and early in the course of illness is an effective treatment, in addition to supporting fluid and electrolytes, oxygenation, and blood pressure. In the only study to evaluate it in 1986, this treatment reduced mortality from 50% to 5% if given early in serious illness. Adverse effects include hemolytic anemia (rupture of red blood cells) if infused too quickly.

Other than acute illness, the most common complication or an after-effect of Lassa fever is hearing loss, which has been observed during recovery in 20%-30% of cases. Because most Lassa fever viral infections cause no symptoms, and because people with acute deafness have been shown to have high antibody levels to Lassa virus, suggesting recent infection, Lassa fever virus is believed to be a common cause of sudden deafness in affected areas.

Pregnant women, especially in the third trimester, are at risk for serious disease. Spontaneous abortion occurs in 95% of infections with Lassa fever.

The prognosis of Lassa fever is generally good, considering that many individuals in affected areas have antibodies to Lassa fever and do not recall illness. Most illness is mild and does not require hospitalization. Of those hospitalized from the community with Lassa fever, up to 15% die. Mortality may be up to 65% in cases of hospital-associated transmission, perhaps because patients do not seek or receive correct treatment until late into illness.

There is no vaccine available as yet against Lassa fever. In light of the especially severe 2018 outbreak, the World Health Organization and several global public health entities are working to develop an effective vaccine.

Oral ribavirin given as prophylaxis or preventive treatment has been studied in a limited fashion during an outbreak, with no evidence of transmission; however, only 40% of the small number of participants completed treatment due to side effects from ribavirin that included weakness, dizziness, headache, and nausea.

There is no clear-cut data to support the routine use of oral ribavirin as prophylaxis at this time, and suitable large trials have not been feasible, thus this use will have to rely on experience in the field over time.

The most important preventive method against Lassa fever outbreaks is to eliminate rodent habitats by improving sanitation, safe food storage and preparation, and clean water access. The public must be taught about limiting consumption or safely preparing bush meat by careful use of gloves and thorough cooking. This measure also helps to prevent other hemorrhagic fever outbreaks, such as the Ebola virus.

In healthcare facilities, suspected cases require strict infection control precautions to prevent contact with blood, body fluids, and contaminated surfaces around infected patients. Hand hygiene requires washing with soap and water and/or using alcohol-based sanitizer between patients. When working within 3 feet of a patient, barrier personal protective equipment should include an impermeable long-sleeved gown, gloves that cover the sleeves, and a face mask with eye protection from splashes. Safe injection practices require the use of disposable rather than reusable needles. Similar personal protective measures are needed for safe laboratory handling and safe mortuary services.

Civil unrest and inadequate health care resources often have limited research on the prevention and control of Lassa fever in West Africa. The Mano River Union Lassa Fever Network (MRU LFN) was established in 2004 to assist in developing national and regional surveillance, diagnosis, treatment, control, and prevention. This network includes local governments, the World Health Organization, Tulane University, the United Nations, the United States Office of Foreign Disaster Assistance (OFDA), and the U.S. Army Medical Research Institute of Infectious Diseases (USAMRIID).

In 2010, Tulane University was awarded a five-year $15 million grant by the National Institute of Health toward developing prevention, treatments, and a vaccine for Lassa and other hemorrhagic fevers. The Viral Hemorrhagic Fever Consortium was established from this contract and brings together Tulane, Scripps Research Institute, Broad Institute, Harvard University, University of California at San Diego, University of Texas Medical Branch, Autoimmune Technologies LLC, Corgenix Medical Corporation, Kenema Government Hospital in Nigeria, and Irrua Specialist Teaching Hospital in Nigeria. In 2017, the National Institutes of Health awarded Tulane University more than $12 million to test a promising drug against the Lassa fever virus, as well as to develop a vaccine based on a recently discovered key antibody target on the surface of the virus.

More information about Lassa fever may be found at the websites of the World Health Organization (http://www.who.int/mediacentre/factsheets/fs179/en/) and the Centers for Disease Control and Prevention (http://www.cdc.gov/vhf/lassa/index.html).