PHOTO: KATE HAMPSONscience.org SCIENCEent localities at different times.
A previous study from the same
area sequenced R. lyssavirus
isolates from a subset of cases
and placed them in a phylogeo-
graphic framework that veri-
fied the existence of genetically
identifiable lineages ( 2 ). Similar
rabies transmission chains have
been identified in the Central Af-
rican Republic ( 3 ).
Canine rabies provides a clear
example of a virulent pathogen,
which is inevitably fatal because
dogs do not naturally develop
immunity, endemically persist-
ing because transmission and
infection are spatially segregated
into a metapopulation ( 4 , 5 ). In
a rabies metapopulation, local
flare-ups in places with denser
dog populations burn themselves
out, but rabid dogs disperse
while transmitting the virus and
starting new local outbreaks.
With rabies prevalence being
low across the region of north-
ern Tanzania, rabies infections
cannot at that scale be predicted
from dog densities. Disaggregat-
ing the region into individual
lineages at the scale of 1 km^2 reveals locally
subdivided and temporally separated infec-
tion dynamics. Furthermore, dynamics are
density-dependent at the local scale, with ra-
bies persisting in the region asynchronously
and endemically as a metapopulation with
multiple independent chains of transmission.
Localized contagion and outbreaks of dis-
ease are not new to the human experience.
This was observed in Medieval Europe dur-
ing the Black Death (plague) era that be-
gan in 1347 AD and caused local outbreaks
for three centuries. The advice “Fuge cito,
vade longe, redetarde” (flee quickly, go far,
return slowly) was commonly given when
outbreaks flared up. Plague (Yersinia pestis)
is a zoonotic, flea-borne bacterial pathogen
of ground-dwelling rodents that catastrophi-
cally spilled over to humans in at least three
large-scale epidemics dating back to 550 AD.
Plague does not persist as an epidemic hu-
man disease and now recurs only in places
where competent rodent hosts and their
fleas are uncontrolled in human proximity
( 6 ). Persistence in rodent host populations,
however, depends on metapopulation dy-
namics ( 7 – 9 ). For example, plague outbreaks
among prairie dog colonies on the Great
Plains of the United States sporadically cause
local extinctions of prairie dog towns, which
are then recolonized ~4 to 5 years after the
epidemic wanes ( 8 ). Plague retains high viru-
lence and, in the time since its introduction
into North America in the early 1900s, has
drastically reduced overall prairie dog abun-
dance. Despite high local mortality, plague
has not caused overall extinction of prairie
dogs from the grasslands. Like rabies, plague
persists endemically and is usually undetect-
able between outbreaks in prairie dog towns.
Does rabies endemism in dogs in Tanzania
represent a general phenomenon of patho-
gen persistence? Rabies in Tanzania is in
many ways a distinct example, with trans-
mission directly from dog to dog, no wild an-
imal reservoir, a long serial interval between
infections (up to several hundred days), and
infections that are nonimmunizing and in-
evitably fatal. Other pathogens have a diver-
sity of transmission modes (directly among
hosts, vector-borne, or from animal or envi-
ronmental reservoirs), differences in serial
infection intervals (time from transmission
to a host until the onset of symptoms), and
heterogeneity of transmission patterns (su-
perspreaders) and can elicit variable im-
mune responses. All of these factors can af-
fect persistence and endemism. Further, in
host-pathogen systems in the wild, observing
infection dynamics through contact tracing,
accurately estimating host abundance, eval-
uating host immunity, and detecting move-
ments of infected hosts without bias is much
more difficult ( 10 ).
What is generalizable is that pathogen
transmission is scale-dependent and thatmost host populations are sub-
divided and are not well mixed
at large scales. Ecological in-
teractions, including pathogen
transmission patterns, gener-
ally occur locally ( 10 – 12 ), and
epidemiological studies that
aggregate data to large spatial
scales can result in spurious
conclusions ( 13 ). Mancy et al.
tested alternative spatial scales
in their model, with the local
scale of 1 km^2 providing the best
fit to the rabies prevalence data.
After 2 years of the CO-
VID-19 pandemic, a transi-
tion to endemism and the
end of widespread infection
chains and less obtrusive pub-
lic health measures may be in
reach. Widespread vaccination
should lessen disease and slow
emergence of new viral vari-
ants. The likelihood, however,
is that severe acute respiratory
syndrome coronavirus 2 (SARS-
CoV-2) will not entirely burn
out but will slide into endemic
persistence in localized chains
of transmission. But endemic
persistence still carries health
risks in local populations. In Tanzania dur-
ing the 2002 to 2016 period, more than 1000
humans were bitten by rabid dogs, with 44
rabies deaths ( 1 ). Vaccination of dogs has
been implemented but not at high enough
levels to stop transmission and eradicate
R. lyssavirus. Even in the modern vaccina-
tion era, several early-childhood diseases
(measles, mumps, rubella, and whooping
cough) and the dengue virus persist in lo-
cal transmission chains that escape detec-
tion without regular surveillance ( 14 , 15 ).
Although endemism is more desirable than
an epidemic, it is not the end of disease but
a new and alternative challenge. jREFERENCES AND NOTES- R. Mancy et al., Science 376 , 512 (2022).
- K. Brunker et al., Mol. Ecol. 27 , 773 (2018).
- H. Bourhy et al., PLOS Pathog. 12 , e1005525 (2016).
- G. Hess, Ecology 77 , 1617 (1996).
- B. Grenfell, J. Harwood, Trends Ecol. Evol. 12 , 395 (1997).
- K. L. Gage, M. Y. Kosoy, Annu. Rev. Entomol. 50 , 505
(2005). - M. J. Keeling, C. A. Gilligan, Nature 407 , 903 (2000).
- S. Davis et al., Science 304 , 736 (2004).
- D. J. Salkeld et al., Bioscience 66 , 118 (2016).
- J. Antonovics, Philos. Trans. R. Soc. Lond. B Biol. Sci. 372 ,
20160087 (2017). - J. F. Addicott et al., Oikos 49 , 340 (1987).
- J. N. Thompson, The Geographic Mosaic of Coevolution
(Univ. Chicago Press, 2005). - D. J. Salkeld, M. F. Antolin, EcoHealth 17 , 4 (2020).
- C. J. E. Metcalf, K. Hampson, A. J. Tatem, B. T. Grenfell, O.
N. Bjørnstad, PLOS ONE 8 , e74696 (2013). - H. Salje et al., Science 355 , 1302 (2017).
10.1126/science.abo7428INSIGHTS | PERSPECTIVES
Canine rabies was tracked in
tens of thousands of domestic
dogs in northern Tanzania to
understand the persistence of
endemic disease.454 29 APRIL 2022 • VOL 376 ISSUE 6592