Lassa fever, also known as Lassa hemorrhagic fever (LHF), is a type of

viral hemorrhagic fever Viral hemorrhagic fevers (VHFs) are a diverse group of animal and human illnesses in which fever and hemorrhage are caused by a viral infection. VHFs may be caused by five distinct families of RNA viruses: the families ''Filoviridae'', ''Flavi ...

caused by the Lassa virus. Many of those infected by the virus do not develop symptoms. When symptoms occur they typically include

fever Fever, also referred to as pyrexia, is defined as having a temperature above the normal range due to an increase in the body's temperature set point. There is not a single agreed-upon upper limit for normal temperature with sources using val ...

, weakness, headaches,

vomiting Vomiting (also known as emesis and throwing up) is the involuntary, forceful expulsion of the contents of one's stomach through the mouth and sometimes the nose. Vomiting can be the result of ailments like food poisoning, gastroenter ...

, and muscle pains. Less commonly there may be

bleeding Bleeding, hemorrhage, haemorrhage or blood loss, is blood escaping from the circulatory system from damaged blood vessels. Bleeding can occur internally, or externally either through a natural opening such as the mouth, nose, ear, urethra, vag ...

from the mouth or

gastrointestinal tract The gastrointestinal tract (GI tract, digestive tract, alimentary canal) is the tract or passageway of the digestive system that leads from the mouth to the anus. The GI tract contains all the major organs of the digestive system, in humans and ...

. The risk of death once infected is about one percent and frequently occurs within two weeks of the onset of symptoms. Of those who survive, about a quarter have

hearing loss Hearing loss is a partial or total inability to hear. Hearing loss may be present at birth or acquired at any time afterwards. Hearing loss may occur in one or both ears. In children, hearing problems can affect the ability to acquire spoken l ...

, which improves within three months in about half of these cases. The

disease A disease is a particular abnormal condition that negatively affects the structure or function of all or part of an organism, and that is not immediately due to any external injury. Diseases are often known to be medical conditions that a ...

is usually initially spread to people via contact with the

urine Urine is a liquid by-product of metabolism in humans and in many other animals. Urine flows from the kidneys through the ureters to the urinary bladder. Urination results in urine being excreted from the body through the urethra. Cellul ...

feces Feces ( or faeces), known colloquially and in slang as poo and poop, are the solid or semi-solid remains of food that was not digested in the small intestine, and has been broken down by bacteria in the large intestine. Feces contain a rela ...

of an infected multimammate mouse. Spread can then occur via direct contact between people. Diagnosis based on symptoms is difficult. Confirmation is by laboratory testing to detect the virus's RNA,

antibodies An antibody (Ab), also known as an immunoglobulin (Ig), is a large, Y-shaped protein used by the immune system to identify and neutralize foreign objects such as pathogenic bacteria and viruses. The antibody recognizes a unique molecule of ...

for the virus, or the virus itself in

cell culture Cell culture or tissue culture is the process by which cells are grown under controlled conditions, generally outside of their natural environment. The term "tissue culture" was coined by American pathologist Montrose Thomas Burrows. This tec ...

. Other conditions that may present similarly include

Ebola Ebola, also known as Ebola virus disease (EVD) and Ebola hemorrhagic fever (EHF), is a viral hemorrhagic fever in humans and other primates, caused by ebolaviruses. Symptoms typically start anywhere between two days and three weeks after becom ...

malaria Malaria is a mosquito-borne infectious disease that affects humans and other animals. Malaria causes symptoms that typically include fever, tiredness, vomiting, and headaches. In severe cases, it can cause jaundice, seizures, coma, or death. ...

typhoid fever Typhoid fever, also known as typhoid, is a disease caused by '' Salmonella'' serotype Typhi bacteria. Symptoms vary from mild to severe, and usually begin six to 30 days after exposure. Often there is a gradual onset of a high fever over severa ...

, and

yellow fever Yellow fever is a viral disease of typically short duration. In most cases, symptoms include fever, chills, loss of appetite, nausea, muscle pains – particularly in the back – and headaches. Symptoms typically improve within five days. ...

. The Lassa virus is a member of the '' Arenaviridae'' family of

virus A virus is a submicroscopic infectious agent that replicates only inside the living cells of an organism. Viruses infect all life forms, from animals and plants to microorganisms, including bacteria and archaea. Since Dmitri Ivanovsk ...

es. There is no

vaccine A vaccine is a biological preparation that provides active acquired immunity to a particular infectious or malignant disease. The safety and effectiveness of vaccines has been widely studied and verified.

. Prevention requires isolating those who are infected and decreasing contact with the mice. Other efforts to control the spread of disease include having a cat to hunt

vermin Vermin ( colloquially varmint(s) or varmit(s)) are pests or nuisance animals that spread diseases or destroy crops or livestock. Since the term is defined in relation to human activities, which species are included vary by region and enterp ...

, and storing food in sealed containers. Treatment is directed at addressing

dehydration In physiology, dehydration is a lack of total body water, with an accompanying disruption of metabolic processes. It occurs when free water loss exceeds free water intake, usually due to exercise, disease, or high environmental temperature. Mil ...

and improving symptoms. The antiviral medication ribavirin has been recommended, but evidence to support its use is weak. Descriptions of the disease date from the 1950s. The virus was first described in 1969 from a case in the town of Lassa, in

Borno State Borno State is a state in the North-East geopolitical zone of Nigeria, bordered by Yobe to the west, Gombe to the southwest, and Adamawa to the south while its eastern border forms part of the national border with Cameroon, its northern borde ...

Nigeria Nigeria ( ), , ig, Naìjíríyà, yo, Nàìjíríà, pcm, Naijá , ff, Naajeeriya, kcg, Naijeriya officially the Federal Republic of Nigeria, is a country in West Africa. It is situated between the Sahel to the north and the Gulf o ...

. Lassa fever is relatively common in

West Africa West Africa or Western Africa is the westernmost region of Africa. The United Nations defines Western Africa as the 16 countries of Benin, Burkina Faso, Cape Verde, The Gambia, Ghana, Guinea, Guinea-Bissau, Ivory Coast, Liberia, Mali ...

including the countries of

Liberia Liberia (), officially the Republic of Liberia, is a country on the West African coast. It is bordered by Sierra Leone to Liberia–Sierra Leone border, its northwest, Guinea to Guinea–Liberia border, its north, Ivory Coast to Ivory Coast� ...

Sierra Leone Sierra Leone,)]. officially the Republic of Sierra Leone, is a country on the southwest coast of West Africa. It is bordered by Liberia to the southeast and Guinea surrounds the northern half of the nation. Covering a total area of , Sierr ...

Guinea Guinea ( ),, fuf, 𞤘𞤭𞤲𞤫, italic=no, Gine, wo, Gine, nqo, ߖߌ߬ߣߍ߫, bm, Gine officially the Republic of Guinea (french: République de Guinée), is a coastal country in West Africa. It borders the Atlantic Ocean to the we ...

, and

Ghana Ghana (; tw, Gaana, ee, Gana), officially the Republic of Ghana, is a country in West Africa. It abuts the Gulf of Guinea and the Atlantic Ocean to the south, sharing borders with Ivory Coast in the west, Burkina Faso in the north, and Tog ...

. There are about 300,000 to 500,000 cases which result in 5,000 deaths a year.

Signs and symptoms

Onset of symptoms is typically 7 to 21 days after exposure. In 80% of those who are infected few or no symptoms occur. These mild symptoms may include fever, tiredness, weakness, and headache. In 20% of people more severe symptoms such as bleeding gums, breathing problems, vomiting, chest pain, or dangerously low blood pressure may occur. Long term complications may include

. In those who are

pregnant Pregnancy is the time during which one or more offspring develops ( gestates) inside a woman's uterus (womb). A multiple pregnancy involves more than one offspring, such as with twins. Pregnancy usually occurs by sexual intercourse, but ca ...

miscarriage Miscarriage, also known in medical terms as a spontaneous abortion and pregnancy loss, is the death of an embryo or fetus before it is able to survive independently. Miscarriage before 6 weeks of gestation is defined by ESHRE as biochemica ...

may occur in 95% of child-bearing women. Lassa fever can be difficult to distinguish clinically from other viral hemorrhagic fevers, such as

Ebola virus disease Ebola, also known as Ebola virus disease (EVD) and Ebola hemorrhagic fever (EHF), is a viral hemorrhagic fever in humans and other primates, caused by ebolaviruses. Symptoms typically start anywhere between two days and three weeks after becom ...

. A combination of

pharyngitis Pharyngitis is inflammation of the back of the throat, known as the pharynx. It typically results in a sore throat and fever. Other symptoms may include a runny nose, cough, headache, difficulty swallowing, swollen lymph nodes, and a hoa ...

, pain behind the sternum, presence of excess protein in the urine and fever can indicate Lassa fever with higher specificity. In cases in which death occurs, this typically occurs within 14 days of onset. About 1% of all Lassa virus infections result in death. Approximately 15%-20% of those who have required hospitalization for Lassa fever die. The risk of death is greater in those who are pregnant. A "Swollen baby syndrome" may occur in newborns, infants and toddlers with pitting edema, abdominal distension and bleeding.

Cause

Virology

Lassa virus is a member of the Arenaviridae, a family of negative-sense, single-stranded

RNA viruses ''Orthornavirae'' is a kingdom of viruses that have genomes made of ribonucleic acid (RNA), those genomes encoding an RNA-dependent RNA polymerase (RdRp). The RdRp is used to transcribe the viral RNA genome into messenger RNA (mRNA) and to ...

. Specifically it is an old world arenavirus, which is enveloped, single-stranded, and bi-segmented RNA. This virus has both a large and a small genome section, with four lineages identified to date: Josiah (Sierra Leone), GA391 (Nigeria), LP (Nigeria) and strain AV.

Spread

Lassa virus commonly spreads to humans from other animals, specifically the '' Natal multimammate mouse'' or African rat, also called the Natal multimammate rat (''Mastomys natalensis''). This is probably the most common mouse in equatorial Africa, common in human households and eaten as a delicacy in some areas. The multimammate mouse can quickly produce a large number of offspring, tends to colonize human settlements, increasing the risk of rodent-human contact, and is found throughout the west, central and eastern parts of the African continent. Once the mouse has become a carrier, it will excrete the virus throughout the rest of its lifetime through feces and urine creating ample opportunity for exposure. The virus is probably transmitted by contact with the feces or urine of animals accessing

grain A grain is a small, hard, dry fruit ( caryopsis) – with or without an attached hull layer – harvested for human or animal consumption. A grain crop is a grain-producing plant. The two main types of commercial grain crops are cereals and legum ...

stores in residences. No study has proven presence in breast milk, but the high level of viremia suggests it may be possible. Individuals who are at a higher risk of contracting the infection are those who live in rural areas where Mastomys are discovered, and where sanitation is not prevalent. Infection typically occurs by direct or indirect exposure to animal excrement through the respiratory or gastrointestinal tracts. Inhalation of tiny particles of infectious material (aerosol) is believed to be the most significant means of exposure. It is possible to acquire the infection through broken

skin Skin is the layer of usually soft, flexible outer tissue covering the body of a vertebrate animal, with three main functions: protection, regulation, and sensation. Other animal coverings, such as the arthropod exoskeleton, have different ...

or mucous membranes that are directly exposed to infectious material. Transmission from person to person has been established, presenting a disease risk for healthcare workers. The virus is present in urine for between three and nine weeks after infection, and it can be transmitted in

semen Semen, also known as seminal fluid, is an organic bodily fluid created to contain spermatozoa. It is secreted by the gonads (sexual glands) and other sexual organs of male or hermaphroditic animals and can fertilize the female ovum. Sem ...

for up to three months after becoming infected.

Diagnosis

A range of laboratory investigations are performed, where possible, to diagnose the disease and assess its course and complications. The confidence of a diagnosis can be compromised if laboratory tests are not available. One comprising factor is the number of febrile illnesses present in Africa, such as

that could potentially exhibit similar symptoms, particularly for non-specific manifestations of Lassa fever. In cases with

abdominal pain Abdominal pain, also known as a stomach ache, is a symptom associated with both non-serious and serious medical issues. Common causes of pain in the abdomen include gastroenteritis and irritable bowel syndrome. About 15% of people have a m ...

, in countries where Lassa is common, Lassa fever is often misdiagnosed as

appendicitis Appendicitis is inflammation of the appendix. Symptoms commonly include right lower abdominal pain, nausea, vomiting, and decreased appetite. However, approximately 40% of people do not have these typical symptoms. Severe complications of a r ...

and

intussusception Intussusception may refer to: * Intussusception (medical disorder) Intussusception is a medical condition in which a part of the intestine folds into the section immediately ahead of it. It typically involves the small bowel and less commonly ...

which delays treatment with the antiviral ribavirin. In West Africa, where Lassa is most common, it is difficult to diagnose due to the absence of proper equipment to perform testing. The FDA has yet to approve a widely validated laboratory test for Lassa, but there are tests that have been able to provide definitive proof of the presence of the LASV virus. These tests include cell cultures, PCR, ELISA antigen assays, plaque neutralization assays, and immunofluorescence essays. However, immunofluorescence essays provide less definitive proof of Lassa infection. An

ELISA The enzyme-linked immunosorbent assay (ELISA) (, ) is a commonly used analytical biochemistry assay, first described by Eva Engvall and Peter Perlmann in 1971. The assay uses a solid-phase type of enzyme immunoassay (EIA) to detect the presen ...

test for antigen and

Immunoglobulin M Immunoglobulin M (IgM) is one of several isotypes of antibody (also known as immunoglobulin) that are produced by vertebrates. IgM is the largest antibody, and it is the first antibody to appear in the response to initial exposure to an antig ...

antibodies give 88% sensitivity and 90% specificity for the presence of the infection. Other laboratory findings in Lassa fever include lymphocytopenia (low white blood cell count),

thrombocytopenia Thrombocytopenia is a condition characterized by abnormally low levels of platelets, also known as thrombocytes, in the blood. It is the most common coagulation disorder among intensive care patients and is seen in a fifth of medical patients a ...

(low platelets), and elevated aspartate transaminase levels in the blood. Lassa fever virus can also be found in

cerebrospinal fluid Cerebrospinal fluid (CSF) is a clear, colorless body fluid found within the tissue that surrounds the brain and spinal cord of all vertebrates. CSF is produced by specialised ependymal cells in the choroid plexus of the ventricles of the ...

Prevention

Control of the '' Mastomys'' rodent population is impractical, so measures focus on keeping rodents out of homes and food supplies, encouraging effective personal hygiene, storing grain and other foodstuffs in rodent-proof containers, and disposing of garbage far from the home to help sustain clean households. Gloves, masks, laboratory coats, and goggles are advised while in contact with an infected person, to avoid contact with blood and body fluids. These issues in many countries are monitored by a department of

public health Public health is "the science and art of preventing disease, prolonging life and promoting health through the organized efforts and informed choices of society, organizations, public and private, communities and individuals". Analyzing the det ...

. In less developed countries, these types of organizations may not have the necessary means to effectively control outbreaks.

Vaccine

There is no

for humans as of 2019. Researchers at the United States Army Medical Research Institute of Infectious Diseases facility had a promising vaccine candidate in 2002. They have developed a replication-competent vaccine against Lassa virus based on recombinant vesicular stomatitis

vectors expressing the Lassa virus glycoprotein. After a single

intramuscular injection Intramuscular injection, often abbreviated IM, is the injection of a substance into a muscle. In medicine, it is one of several methods for parenteral administration of medications. Intramuscular injection may be preferred because muscles hav ...

, test primates have survived lethal challenge, while showing no clinical symptoms.

Treatment

Treatment is directed at addressing

and improving symptoms. All persons suspected of Lassa fever infection should be admitted to isolation facilities and their body fluids and excreta properly disposed of.

Medications

The antiviral medication ribavirin has been recommended, but evidence to support its use is weak. Some evidence has found that it may worsen outcomes in certain cases. Fluid replacement, blood transfusions, and medication for low blood pressure may be required. Intravenous

interferon Interferons (IFNs, ) are a group of signaling proteins made and released by host cells in response to the presence of several viruses. In a typical scenario, a virus-infected cell will release interferons causing nearby cells to heighten th ...

therapy has also been used.

Pregnancy

When Lassa fever infects pregnant women late in their third trimester, inducing delivery is necessary for the mother to have a good chance of survival. This is because the virus has an affinity for the placenta and other highly vascular tissues. The fetus has only a one in ten chance of survival no matter what course of action is taken; hence, the focus is always on saving the life of the mother. Following delivery, women should receive the same treatment as other people with Lassa fever.

Prognosis

About 15–20% of hospitalized people with Lassa fever will die from the illness. The overall case fatality rate is estimated to be 1%, but during

epidemic An epidemic (from Greek ἐπί ''epi'' "upon or above" and δῆμος ''demos'' "people") is the rapid spread of disease to a large number of patients among a given population within an area in a short period of time. Epidemics of infectious ...

s, mortality can climb as high as 50%. The mortality rate is greater than 80% when it occurs in pregnant women during their third trimester; fetal death also occurs in nearly all those cases. Abortion decreases the risk of death to the mother. Some survivors experience lasting effects of the disease, and can include partial or complete deafness. Because of treatment with ribavirin, fatality rates have declined.

Epidemiology

file:Lassa fever Outbreak Distribution Map.svg, 350px, Lassa fever distribution. Countries reporting continued spread of disease and outbreaks in blue. Countries reporting a few cases, periodic isolation of virus, or serological evidence of infection in green. Countries with unknown status in grey. There are about 300,000 to 500,000 cases which result in 5,000 deaths a year. One estimate places the number as high as 3 million cases per year. Estimates of Lassa fever are complicated by the lack of easy-available diagnosis, limited public health surveillance infrastructure, and high clustering of incidence near high intensity sampling. The infection affects females 1.2 times more than males. The age group predominantly infected is 21–30 years.

Geography

Lassa high risk areas are near the western and eastern extremes of West Africa. As of 2018, the Lassa belt includes Guinea, Nigeria, Sierra Leone and Liberia. As of 2003, 10-16% of people in Sierra Leone and Liberia admitted to hospital had the virus. The case fatality rate for those who are hospitalized for the disease is about 15-20%. Research showed a twofold increase risk of infection for those living in close proximity to someone with infection symptoms within the last year. The high risk areas cannot be well defined by any known biogeographical or environmental breaks except for the multimammate rat, particularly Guinea (

Kindia Kindia ( N’ko: ߞߌ߲ߘߌߦߊ߫) is the fourth largest city in Guinea, lying about 85 miles northeast of the nation's capital, Conakry. Its estimated population in 2008 was 181,126. Kindia serves as the capital and largest city of Kindia Prefect ...

Faranah Faranah ( N’ko: ߝߙߊߣߊ߫߫) is a town and sub-prefecture in central Guinea, lying by the River Niger. As of 2014 it had a population of 78,108 people. The town is mainly inhabited by the Malinke people. History Sékou Touré was born i ...

and Nzérékoré regions), Liberia (mostly in Lofa,

Bong A bong (also known as a water pipe) is a filtration device generally used for smoking cannabis, tobacco, or other herbal substances. In the bong shown in the photo, the gas flows from the lower port on the left to the upper port on the right. ...

, and Nimba counties), Nigeria (in about 10 of 36 states) and Sierra Leone (typically from

Kenema Kenema is the third largest city in Sierra Leone (after Freetown and Bo), and the largest city in the country's Eastern Province. It is the capital of Kenema District and a major economic center of the Eastern Province. At the 2015 national cen ...

and Kailahun districts). It is less common in the Central African Republic, Mali, Senegal and other nearby countries, and less common yet in Ghana and the Democratic Republic of the Congo. Benin had its first confirmed cases in 2014, and Togo had its first confirmed cases in 2016. As of 2013, the spread of Lassa outside of West Africa had been very limited. Twenty to thirty cases had been described in Europe, as being caused by importation through infected individuals. These cases found outside of West Africa were found to have a high fatality risk because of the delay of diagnosis and treatment due to being unaware of the risk associated with the symptoms. Imported cases have not manifested in larger epidemics outside of Africa due to a lack of human to human transmission in hospital settings. An exception had occurred in 2003 when a healthcare worker became infected before the person showed clear symptoms.

Nigeria

2018 outbreak

An outbreak of Lassa fever occurred in Nigeria during 2018 and spread to 18 of the country's states; it was the largest outbreak of Lassa recorded. On 25 February 2018, there were 1081 suspected cases and 90 reported deaths; 317 of the cases and 72 deaths were confirmed as Lassa which increased to a total of 431 reported cases in 2018.

2019 outbreak

The total cases in Nigeria in 2019 was 810 with 167 deaths, the largest case fatality rate(23.3%) until then.

2020 outbreak

The epidemic started from the second week of the January. By the tenth week the total number of cases has risen to 855 and deaths to 144, the case fatality rate of 16.8%.

2021 Outbreak

On the 8th of December 2021, the Nigeria Centre for Disease Control (NCDC) was notified of the death of two persons from Lassa fever.

2022 Outbreak

The epidemic took a new form, from 3 to 30 January 2022, 211 laboratory confirmed Lassa fever cases including 40 deaths (case fatality ratio: 19%) have been cumulatively reported in 14 of the 36 Nigerian states and the Federal Capital Territory across the country. In total from January until March, 132 deaths have been reported with a case fatality rate (CFR) of 19.1% which is lower than the CFR for the same period in 2021 (21.0%).

Liberia

Lassa fever is endemic in Liberia. From 1 January 2017 through 23 January 2018, 91 suspected cases were reported from six counties: Bong, Grand Bassa, Grand Kru, Lofa, Margibi, and Nimba. Thirty-three of these cases were laboratory confirmed, including 15 deaths (case fatality rate for confirmed cases = 45.4%). In February 2020, a total of 24 confirmed cases with nine associated deaths has been reported from nine health districts in six counties. Grand Bossa and Bong counties account for 20 of the confirmed cases.

History

The disease was identified in Nigeria in 1969. It is named after the town of Lassa, where it was discovered. A prominent expert in the disease, Aniru Conteh, died from the disease.

Research

The Lassa virus is one of several viruses identified by WHO as a likely cause of a future epidemic. They therefore list it for urgent research and development to develop new diagnostic tests, vaccines, and medicines. In 2007,

SIGA Technologies SIGA Technologies, Inc. is an American pharmaceutical company founded in 1995, currently based in New York City, which develops and sells pharmaceutical solutions for the antiviral treatment of smallpox, monkeypox, cowpox, and vaccinia complicatio ...

, studied a medication in

guinea pig The guinea pig or domestic guinea pig (''Cavia porcellus''), also known as the cavy or domestic cavy (), is a species of rodent belonging to the genus '' Cavia'' in the family Caviidae. Breeders tend to use the word ''cavy'' to describe the ...

with Lassa fever. Work on a vaccine is continuing, with multiple approaches showing positive results in animal trials.