**2. Etiology/pathogenesis-**

Lassa fever is caused by Lassa fever virus, a member of the family Arenaviridae. It is an enveloped single stranded bi-segmented rna virus Replication for Lassa virus is very rapid, while also demonstrating temporal control in replication. There are two genome segments. The first replication step is transcription of messenger RNA copies of the negative- or minus sense genome. This ensures an adequate supply of viral proteins for subsequent steps of replication, as proteins known as N and L are translated from the mRNA. The positive- or plus-sense genome then makes viral complementary (vcRNA) copies of itself, which are + sense. The vcRNA is a template for producing minus sense progeny but mRNA is also synthesized from it. The mRNA synthesized from vcRNA are translated to make the G (spike) proteins and Z proteins. Thus, with this temporal control, the spike proteins, which are on the outside of the virus particle, are produced last, making the infection more difficult for the host immune system to detect. Nucleotide studies of the genome have shown that Lassa has four lineages: three found in Nigeria and the fourth in Guinea, Liberia, and Sierra

Lassa Fever in the Tropics 111

Lassa fever is endemic in West Africa. However the world is now a global village and the previous geographical gap between the tropics and the developed world has been bridged by international travel. The 6 – 21 days incubation period indicates that a person who contacts Lassa fever in an endemic area in West Africa may travel to a developed country

The prevalence of Lassa fever can be assesed by determining the prevalence of antibodies to Lassa fever in communities. The prevalence of Lassa fever in Nigeria, Guinea and Sierra

The reservoir of infection is mastomys natalensis. It is a species of rodent in the Muridae family. It is also known as the Natal multimammate rat, the common African rat, or the African soft-furred rat. It is found in Angola, Benin, Botswana, Burkina Faso, Burundi, Cameroon, Central African Republic, Chad, Republic of the Congo, Democratic Republic of the Congo, Ivory Coast, Equatorial Guinea, Ethiopia, Gabon, Ghana, Guinea, Guinea-Bissau, Kenya, Lesotho, Malawi, Mali, Mauritania, Mozambique, Namibia, Niger, Nigeria, Rwanda, Senegal, Sierra Leone, Somalia, South Africa, Sudan, Swaziland, Tanzania, Togo, Uganda, Zambia, and Zimbabwe. Its natural habitats are subtropical or tropical dry forests, subtropical or tropical moist lowland forests, dry savanna, moist savanna, subtropical or tropical dry shrubland, subtropical or tropical moist shrubland, arable land, pastureland, rural gardens, urban areas, irrigated land, and seasonally flooded agricultural land. In 1972, the Natal

multimammate Mouse was found to be the natural host of the deadly Lassa fever virus.

Lassa fever is transmitted to humans when they ingest food contaminated by the feces and urine of mastomys natalensis. Once humans are infected, transmission also occurs from human to human through contact with fluid and aerosol secretions in the form of sneezing, sputum, seminal fluid, stool, urine and blood. Vertical transmission through breast milk has

Men are more commonly affected than women. However the case fatality rate is nearly two times higher in women. Men are more likely to buy food from food vendors especially at lunch time while women are more likely to eat personally cooked food. Contamination of food from this source may be responsible for the higher incidence of Lassa fever in men. Although the high case-fatality of Lassa fever is due to delayed cellular immunity, development of partial immunity as a result of frequent exposure to contaminated food may be responsible for the milder forms of the disease and lower case-fatality rate in men. Research is needed to find out whether Lassa fever infection confers partial or full immunity

may be responsible for outbreaks of lassa fever in the dry season.

within the incubation period and cause an epidemic.

Leone can be up to 21%, 55% and 52% respectively.

**3. Epidemiology 3.1 Distribution** 

**3.2 Prevalence** 

**3.3 Reservoir** 

**3.4 Transmission** 

been observed.

**3.5 Host factors** 

on affected people.

drives mastomys natalensis, the reservoir of lassa fever virus, into peoples homes and

Leone. The Nigerian strains seem likely to have been ancestral to the others but further research is required to confirm this.

The Lassa virus gains entry into the host cell by means of the cell-surface receptor the alphadystroglycan (alpha-DG), a versatile receptor for proteins of the extracellular matrix. It shares this receptor with the prototypic arenavirus lymphocytic choriomeningitis virus. Receptor recognition depends on a specific sugar modification of alpha-dystroglycan by a group of glycosyltransferases known as the LARGE proteins. Specific variants of the genes encoding these proteins appear to be under positive selection in West Africa where Lassa is endemic. Alpha-dystroglycan is also used as a receptor by viruses of the New World clade C arenaviruses (Oliveros and Latino viruses). In contrast, the New World areanviruses of clades A and B, which include the important viruses Machupo, Guanarito, Junin, and Sabia in addition to the non pathogenic Amapari virus, use the transferrin receptor 1. A small aliphatic amino acid at the GP1 glycoprotein amino acid position 260 is required for highaffinity binding to alpha-DG. In addition, GP1 amino acid position 259 also appears to be important, since all arenaviruses showing high-affinity alpha-DG binding possess a bulky aromatic amino acid (tyrosine or phenylalanine) at this position.

Unlike most enveloped viruses which use clathrin coated pits for cellular entry and bind to their receptors in a pH dependent fashion, Lassa and lymphocytic choriomeningitis virus instead use an endocytotic pathway independent of clathrin, caveolin, dynamin and actin. Once within the cell the viruses are rapidly delivered to endosomes via vesicular trafficking albeit one that is largely independent of the small GTPases Rab5 and Rab7. On contact with the endosome pH-dependent membrane fusion occurs mediated by the envelope glycoprotein.

Lassa virus will infect almost every tissue in the human body. It starts with the mucosa, intestine, lungs and urinary system, and then progresses to the vascular system.

#### **2.1 Predisposing factors**


Leone. The Nigerian strains seem likely to have been ancestral to the others but further

The Lassa virus gains entry into the host cell by means of the cell-surface receptor the alphadystroglycan (alpha-DG), a versatile receptor for proteins of the extracellular matrix. It shares this receptor with the prototypic arenavirus lymphocytic choriomeningitis virus. Receptor recognition depends on a specific sugar modification of alpha-dystroglycan by a group of glycosyltransferases known as the LARGE proteins. Specific variants of the genes encoding these proteins appear to be under positive selection in West Africa where Lassa is endemic. Alpha-dystroglycan is also used as a receptor by viruses of the New World clade C arenaviruses (Oliveros and Latino viruses). In contrast, the New World areanviruses of clades A and B, which include the important viruses Machupo, Guanarito, Junin, and Sabia in addition to the non pathogenic Amapari virus, use the transferrin receptor 1. A small aliphatic amino acid at the GP1 glycoprotein amino acid position 260 is required for highaffinity binding to alpha-DG. In addition, GP1 amino acid position 259 also appears to be important, since all arenaviruses showing high-affinity alpha-DG binding possess a bulky

Unlike most enveloped viruses which use clathrin coated pits for cellular entry and bind to their receptors in a pH dependent fashion, Lassa and lymphocytic choriomeningitis virus instead use an endocytotic pathway independent of clathrin, caveolin, dynamin and actin. Once within the cell the viruses are rapidly delivered to endosomes via vesicular trafficking albeit one that is largely independent of the small GTPases Rab5 and Rab7. On contact with the endosome pH-dependent membrane fusion occurs mediated by the envelope

Lassa virus will infect almost every tissue in the human body. It starts with the mucosa,

Use of rat meat as a source of protein by people in some communities; contamination of

Traditional autopsy, where the operator may injure himself with scalpel and contaminate

 Forceful ingestion of water used in bathing a dead husband, by a widow suspected to be involved in his death. In many communities, family members may be forced to drink

 Corrupt practices by staple food producers, which involve drying garri (cassava flour) in the open air in the daytime and sometimes at night. This enables all types of rat including mastomys natalensis to contaminate the flour with their excreta. This constitutes a public health hazard when the infected garri is sold to consumers in the market. The common

 Many other types of staple foods are also processed in the open sun, which is the major natural drier. These include rice, plantain chips, yam chips and cassava chips, which are processed into rice flour, plantain flour, yam flour, and raw cassava flour. Though these are also processed into staple foods such as tuwo shinkafa, plantain based amala, yam based amala and lafun respectively, the amount of heat involved in processing them into edible pastes, may be enough to denature lassa fever virus, which is heat labile. Bush burning of savannahs may be carried out by meat-hungry youths, during the dry season, in order to be able to have access to rodents and other animals. This habit often

the injury with the blood of the deceased, who may have died of Lassa fever

water used in bathing dead relatives in order to prove their innocence.

habit of eating garri soaked in water may favor Lassa fever infection.

intestine, lungs and urinary system, and then progresses to the vascular system.

aromatic amino acid (tyrosine or phenylalanine) at this position.

research is required to confirm this.

glycoprotein.

**2.1 Predisposing factors** 

exposed food by rat feces and urine;

drives mastomys natalensis, the reservoir of lassa fever virus, into peoples homes and may be responsible for outbreaks of lassa fever in the dry season.
