# Presentation: 066392

## Lassa Fever

- Special Pathogens Branch
- NCID/DVRD
- CDC

## General Facts

- Viral hemorrhagic fever caused by the *Arenavirus *Lassa
- Transmitted from rodents to humans
- Discovered in Nigeria, 1969
- Endemic in portions of West Africa
- Seasonal clustering: Late rainy and early dry season
- Affects all age groups and both sexes

## Arenaviridae

- Name derived from “arenosus” (Latin “sandy”) describing appearance of virions on examination by electron microscopy
- Enveloped virus, round or pleomorphic, 50-300 nm in diameter
- Single-stranded genome divided into 2 RNA segments:  small (~3.4 kb) and large (~7.1 kb)
- 2 genes on each segment, arranged in unique “ambisense” orientation, encoding 5 proteins
- Inactivated by:
- heating to 56oC
- pH<5.5 or >8.5
- UV/gamma irradiation
- detergents

## Arenaviridae

- Arenaviruses associated with human disease
- _Virus_		_Origin of Name_	_Year_	 	_Distribution_
- Lassa		Town, Nigeria	1969		West Africa
- Junin		Town, Argentina**	**1957		South America
- Machupo	River, Bolivia	1962		South America
- Guanarito	Area, Venezuela	1989		South America
- Sabia		Town, Brazil	1990		South America
- LCMV		Clinical disease	1933		Worldwide

## Lassa Virus

- Image source:  C.S. Goldsmith and M. Bowen (CDC).

## Epidemiology

- Endemic in areas of West Africa, including Nigeria, Liberia, Sierra Leone, and Guinea
- Estimated 300,000-500,000 infections/year, with 5000 deaths
- Rodent-to-human transmission (the “multimammate rat”, *Mastomys* species-complex)
- Secondary human-to-human transmission with the potential for nosocomial outbreaks with high case-fatality

## Known Distribution of Mastomys

***MASTOMYS***
**DISTRIBUTION**

**LASSA  1969**

## Rodent Reservoir

*Mastomys* species complex
- Taxonomy still unclear
*M. huberti*: more common in peridomestic habitat
*M. erytholeucus*: more common in brush habitat
- Others

## Transmission

- Rodent-to-human:
- Inhalation of aerosolized virus
- Ingestion of food or materials contaminated by infected rodent excreta
- Catching and preparing *Mastomys* as a food source

## Transmission

- Human-to-human:
- Direct contact with blood, tissues, secretions or excretions of infected humans
- Needle stick or cut
- Inhalation of aerosolized virus

## Pathogenesis

- Endothelial cell damage/capillary leak
- Platelet dysfunction
- Suppressed cardiac function
- Cytokines and other soluble mediators of shock and inflammation

## Clinical Aspects

- Incubation period of 5-21 days
- Gradual onset of fever, headache, malaise and other non-specific signs and symptoms
- Pharyngitis, myalgias, retro-sternal pain, cough and gastrointestinal symptoms typically seen
- A minority present with classic symptoms of bleeding, neck/facial swelling and shock
- Case fatality of hospitalized cases: 15-20%
- Particularly severe in pregnant women and their offspring
- Deafness a common sequela

## Clinical Signs and Symptoms

**0**

**10**

**20**

**30**

**40**

**50**

**60**

**70**

**80**

**90**

**100**

**Swollen Neck or Face**

**Bleeding**

**Deafness**

**Conjunctivitis/Sub-conjunctival**

**Hemorrhage**

**Abdominal Pain/Tenderness**

**Cough**

**Dizziness**

**Retro-sternal Pain**

**Headache**

**Fever**

**Arthralgias/Myalgias**

**Sore throat/Pharyngitis**

**Weakness**

**Vomiting**

**Diarrhea**

**Chills**

**Lymphadenopgathy**

**Confusion**

**Percent**

## Lassa Fever in Pregnancy

- Increased maternal mortality in third trimester (>30%)
- Increased fetal and neonatal mortality (>85%)
- Increased level of viremia in pregnant women
- Placental infection
- Evacuation of uterus improves mother’s chance of survival

## Sensorineural Hearing Deficit in Lassa Fever

- Typically appears during early convalescence
- Not related to severity of acute illness
- Occurs in one-third of cases
- May be bilateral or unilateral
- May persist for life in up to one-third of those affected

## Lassa Fever in Children and Infants

- Significant cause of pediatric hospitalizations in some areas of West Africa
- Signs and symptoms most often similar to adults
- “Swollen Baby Syndrome”
- 		- Edema/Anasarca
- 		- Abdominal distension
- 		- Bleeding
- 		- Poor prognosis

## Differential Diagnosis of Lassa Fever

- Malaria
- Typhoid fever
- Streptococcal pharyngitis
- Leptospirosis

- Bacterial sepsis
- Bacterial meningitis
- Arboviral infection
- Anicteric hepatitis
- Enterovirus infection
- Bacterial or viral conjuctivitis

## Diagnostics

- Clinical diagnosis often difficult
- ELISA (Enzyme-linked immunosorbent assays) for antigen, IgM, and IgG
- As research tools:
- Virus isolation
- Immunohistochemistry (for post-mortem diagnosis)
- RT-PCR (Reverse transcription-polymerase chain reaction)

## Treatment

- Supportive measures
- Ribavirin
- Most effective when started within the first 6 days of illness
- Major toxicity:  mild hemolysis and suppression of erythropoesis. Both reversible
- Presently contraindicated in pregnancy, although may be warranted if mother’s life at risk
- Does not appear to reduce incidence or severity of deafness

## Associated with Poor Prognosis in Lassa Fever

- High viremia
- Serum AST level >150 IU/L
- Bleeding
- Encephalitis
- Edema
- Third trimester of pregnancy

## Prevention and Control

- Village-based programs for rodent control and avoidance
- Hospital training programs to avoid nosocomial spread:  barrier nursing manual
- Diagnostic technology transfer
- Specific antiviral chemotherapy (ribavirin)

## Rodent Control

- Proper storage of food in rodent-proof containers
- Cleaning around homes
- Trapping and killing rodents with proper and safe disposal of carcasses
- Avoid rodents as a food source

## Natural history of disease

Where it came from
How clinical course progresses
Whom it affects

Diagnosis: Clinical/Laboratory

Immunopathogenesis

Treatment

Rodent population dynamics

Prevention and control

Collaboration between CDC/SPB and the Guinean Institute for Research and Applied Biology

- Where it came from
- How clinical course progresses
- Whom it affects
- Diagnosis: Clinical/Laboratory
- Immunopathogenesis
- Treatment
- Rodent population dynamics
- Prevention and control
- Collaboration between CDC/SPB and the Guinean Institute for Research and Applied Biology

- Ongoing Lassa Fever Research in Guinea, West Africa