Science - USA (2019-01-04)

INSIGHTS | PERSPECTIVES

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By Nahid Bhadelia

L

assa fever is a viral hemorrhagic fever

prevalent in West Africa that has been

gaining international attention as an

emerging infectious disease with the

potential to cause epidemics ( 1 ). Con-

firmed and suspected cases of Lassa

fever have been steadily rising in Nigeria

over the past 3 years. Laboratory-confirmed

cases have increased from 106 in 2016 to 143

in 2017 and had already reached 562 by No-

vember 2018 ( 2 ). Part of defining the scope of

the problem is trying to assess whether this

is a true increase in the number of people af-

flicted by the infection, due to either changes

in the virus itself or the geographical spread

of the vector (rodents of the Mastomys spp.),

or a reflection of higher rates of detection

and diagnosis secondary to the increased

attention and interest of clinicians and labo-

ratorians ( 1 ). Lassa fever outbreaks illustrate

the issues associated with the response and

management of emerging infectious diseases:

How do you plan the public health, clinical,

and community responses to a disease while

you are still learning about the epidemiology,

pathophysiology, and the ecological factors

contributing to the spread of the pathogen?

On page 74 of this issue, Kafetzopoulou et

al. ( 3 ) present the results of a rapid genomic

study of Lassa virus (LASV) from the cases

of 2018, which have improved understanding

of how the disease has been spreading in Ni-

geria and have led to informed and targeted

disease-control strategies. The study also fur-

ther describes the use of a new and compact

genomic sequencing device, which may start

playing a larger role in defining other emerg-

ing infectious disease outbreaks in real time.

The device generates exponentially longer

reads of genetic material than traditional

sequencing and offers some remarkable

advantages over existing next-generation

sequencing platforms ( 4 ). To date, sequenc-

ing the genomes of organisms has been like

printing individual pages of a novel in the

wrong order (many of which end with the

same words and phrases) and trying to put

the story together with guess work. The de-

vice allows researchers to instead print out

whole chapters, making it easier to get a

sense of the bigger picture. In the biological

world, longer reads of genomic information

also provide invaluable information about

structural variations and epigenetic modifi-

cations between individual organisms. How-

ever, with longer reads comes greater error

rates, which appear to improve with repeated

reads of the same genetic material, as long as

it is of high-enough quality and quantity ( 5 ).

With its compact size, portability, and quick

turnaround time, the device can be rapidly

deployed in outbreak areas where laboratory

capacity may not exist for genomic sequenc-

ing and when samples cannot be exported

out of the country for analysis ( 4 ). Its uses

include not only sequencing to evaluate vi-

ral evolution and chains of transmission but

also, as the authors highlight, identification

of multiple cocirculating viruses in patient

samples. The technology has already been

used in outbreaks with other pathogens, in-

cluding Ebola virus ( 6 ).

Kafetzopoulou et al. used this technology

to compare the phylogenetic differences be-

tween the strains of viruses from 120 con-

firmed LASV samples from Nigeria from

the spring of 2018. With the increase in the

number of total cases as well as clusters of

cases in recent years, one of the concerns has

been whether the virus has changed, allow-

ing Lassa fever to transmit between humans

more easily. By examining the level of genetic

diversity between viruses in each of the dif-

ferent samples, alongside epidemiological

information about the cases, the authors

demonstrated that most of the viral genomes

were different enough from each other that

they had to have come from humans infected

by different rodents, rather than from those

infected through transmission from other

humans (which would have greater shared

phylogenetic homology). Another recent

study from the current outbreak of Lassa fe-

ver in Nigeria has drawn similar conclusions

using more traditional genetic sequencing

technology ( 7 ).

Despite the critical epidemiological clues

provided by both studies, it is helpful to keep

in mind that the narrative of Lassa fever is

driven by where the testing for the disease

occurs. Owing to the high number of asymp-

tomatic cases and the nonspecific symptoms

mimicking myriads of infectious diseases in

the region in patients who actually become

sick, establishing the true burden of Lassa

fever in Nigeria and other West African coun-

tries has been near impossible ( 8 ). The dis-

ease is mainly spread through contact with

the urine and feces of multimammate rats in

the household setting, a human-vector inter-

face that happens mostly in poor communi-

ties and in rural areas. Unfortunately, these

are also communities with considerably less

access to health care, and, because diagnos-

tic testing for Lassa fever is only available

at a handful of reference laboratories, it is

thought that many suspected patients are

either never tested or only tested after a de-

lay ( 9 ). Conversely, ~80% of suspected cases

tested in 2018 were actually negative for

Lassa fever ( 2 ).

Because of a lack of access to laboratory

testing, a sizeable portion of the world’s

population, particularly in resource-limited

areas, is simply treated on the basis of symp-

tomatology for common infectious diseases

such as malaria or cholera rather than tested

on presentation to confirm the underlying di-

agnosis ( 10 ). This paradigm allows emerging

infectious diseases to circulate in populations

without initial detection. Hence, the real test

of emerging microbial detection techniques

will be how accurate, affordable, and amena-

ble to widespread use they are and whether

they can test both for common endemic in-

fectious diseases as well as rarer pathogens

of high concern, such as viral hemorrhagic

fevers. To get the true sense of the disease

burden and deaths from these emerging in-

fectious diseases, to really solve the problem

of Lassa fever, we still need diagnostic tech-

nologies closer to the point of care, and ev-

erywhere patients get sick. j

REFERENCES

1. L. Roberts, Science 359 , 1201 (2018).


2. Nigeria Centre for Disease Control, “Weekly epidemiologi-
   cal report: Epi week 1, week 46” (2018).


3. L. E. Kafetzopoulou et al., Science 363 , 74 (2019).


4. H. Lu et al., Genom. Proteom. Bioinf. 14 , 265 (2016).


5. A. D. Tyler et al., Sci. Rep. 8 , 10931 (2018).


6. J. Quick et al., Nature 530 , 228 (2016).


7. K. J. Siddle et al., N. Engl. J. Med. 379 , 1745 (2018).


8. C. Houlihan, R. Behrens, BMJ 358 , j2986 (2017).


9. R. S. Dhillon et al., Lancet Infect. Dis. 18 , 601 (2018).


10. A. M. Caliendo et al., Clin. Infect. Dis. 57 (suppl. 3), S139
    (2013).

10.1126/science.aav8958

INFECTIOUS DISEASE

Understanding Lassa fever

Genomics study informs about Lassa fever epidemiology

Section of Infectious Diseases, Boston University

School of Medicine and National Emerging Infectious Diseases

Laboratories, Boston University, Boston, MA, USA.

Email: [email protected]

LASV (blue) is spread by rat urine and droppings and

infects humans through ingestion or inhalation.

30 4 JANUARY 2019 • VOL 363 ISSUE 6422

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