Lassa fever is a zoonotic viral haemorrhagic fever that is endemic to West Africa. It is caused by the Lassa virus, which is named after a small town in Nigeria where the virus was first discovered in 1969 (although the disease has been around far longer than that). The story of that discovery is present in older journals that are unfortunately difficult to access today (Minerva Medicine, 1970; New York State Journal of Medicine, 1992), but an interesting account can be read here (Ms. Laura Wine – a missionary – was apparently the index case who died during the small outbreak that led to the isolation of the virus from one of the nurses that took care of her and was consequently infected – Penny Pinneo: her church, which still exists, also has an online version of the events) that is written by Dr Ibrahim Mamadu, whose hometown is Lassa.

Even though the disease is endemic, there are sporadic seasonal outbreaks, usually between December and June. The largest Lassa fever outbreak to date started on 1st January 2018 in Nigeria, and continues to this date. As of 11th March, there are 1,386 suspected cases with 114 deaths. The map below is from the European Commission’s Directorate-General for European Civil Protection and Humanitarian Aid Operations.

Nigeria-Lassa-2018

The Lassa virus is an arenavirus – single-stranded RNA virus. The primary host is Mastomys natalensis – the multimammate mouse or common African rat. Wikipedia has a rather cute photo of the mouse that has been reproduced numerous times in recent write-ups of Lassa fever, and I repost it below.

Mastomys_natalensis

Years ago, I was taught that this rat was a delicacy and eaten, but that is not true – “bush rats” like the giant pouched rat are hunted and eaten (see this National Geographic YouTube video) but generally, “town rats” like M. natalensis are regarded as pests and disease carriers. Although of course the lines are occasionally blurredOther rodents also harbour the virus in Nigeria, including Rattus rattus (black or ship rat) and Mus musculus (common house mouse), but their role in transmitting the virus is less clear.

Humans become infected on exposure to the rodents’ excreta. Human-to-human transmission can occur as a result of exposure to the body fluids of an infected/symptomatic human, needlestick injuries, and even sexual intercourse, but is uncommon. A multi-national team sequenced 196 Lassa viruses (183 from human clinical samples obtained between 2008 and 2013 from Sierra Leone and Nigeria, 11 from multimammate mice, 2 laboratory viruses) and proposed that the virus probably arose in Nigeria 1,000 years ago, and that human infections occurred from repeated rodent-to-human transmission. The graphical abstract from the Cell paper in 2015 is quaint, and I have taken a screenshot (below).

Cell-Lassa-2015
Screenshot from the 2015 Cell paper on Lassa virus sequencing.

The World Health Organization has a succinct fact sheet on Lassa fever. Only 1 in 5 persons infected with the virus will manifest symptoms of disease. The incubation period is quoted as between 6 and 21 days. Disease onset is gradual, with fever, myalgia and malaise progressing to gastrointestinal symptoms (nausea, vomiting, diarrhoea), proteinuria, hemorrhagic manifestations, and seizures/shock in severe cases. The overall mortality rate is 1% – up to 15-20% of hospitalized cases will die within 14 days of illness. 1/4 of survivors will experience deafness.

Many experts recommend the use of ribavirin early in the course of Lassa fever. It halts virus replication in vitro. There is no real randomized double-blind clinical trial, of course, but in a 1990 paper in the New England Journal of Medicine (behind a paywall), investigators showed that 95% (19 in 20) of patients with Lassa fever survived when treated with ribavirin within 6 days of illness onset, whereas only 45% (27 of 60) of patients who did not receive ribavirin survived their illness. Interestingly, the use of convalescent plasma did not show any benefit whatsoever. There is a case report (2 cases) highlighting survival of Lassa fever after using a combination of ribavirin and favipravir (a Japanese antiviral stockpiled in Japan for influenza), but it is hard to make anything of this given the very small numbers. Post-exposure prophylaxis with ribavirin is controversial, but probably unlikely to be helpful, especially given the high side-effect profile of the drug.

Singapore has been fortunate not to have had any imported cases of Lassa fever to date. The experience around the world suggests (supporting the genomic evidence) that secondary human-to-human transmission of Lassa virus is very rare – even within the healthcare setting with late diagnosis of infection – when standard precautions are applied. In one of the more recent imported cases in Germany, none of 62 contacts were infected despite 33 having had direct exposure to blood and other body fluids, although an undertaker (the index case had died) was infected. It is possible that some of the rats in Singapore may serve as reservoir hosts for the Lassa virus, but even in the unlikely event that this occurs, rat-to-human transmission is likely to be rare.

 

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