Am. J. Trop. Med. Hyg., 90(6), 2014, pp. 1047–1058
Copyright © 2014 by The American Society of Tropical Medicine and Hygiene
Identification of Risk Factors for Plague in the West Nile Region of Uganda
Rebecca J. Eisen,* Katherine MacMillan, Linda A. Atiku, Joseph T. Mpanga, Emily Zielinski-Gutierrez, Christine B. Graham,
Karen A. Boegler, Russell E. Enscore, and Kenneth L. Gage
Bacterial Diseases Branch, Division of Vector Borne Diseases, National Center for Emerging and Zoonotic Infectious Diseases,
Centers for Disease Control and Prevention, Fort Collins, Colorado; Uganda Virus Research Institute, Entebbe, Uganda
sought to identify risk factors for plague by comparing villages with and without a history of human plague cases within
a model-defined plague focus in the West Nile Region of Uganda. Although rat (Rattus rattus) abundance was similar
inside huts within case and control villages, contact rates between rats and humans (as measured by reported rat bites)
and host-seeking flea loads were higher in case villages. In addition, compared with persons in control villages, persons in
case villages more often reported sleeping on reed or straw mats, storing food in huts where persons sleep, owning dogs
and allowing them into huts where persons sleep, storing garbage inside or near huts, and cooking in huts where persons
sleep. Compared with persons in case villages, persons in control villages more commonly reported replacing thatch
roofing, and growing coffee, tomatoes, onions, and melons in agricultural plots adjacent to their homesteads. Rodent and
flea control practices, knowledge of plague, distance to clinics, and most care-seeking practices were similar between
persons in case villages and persons in control villages. Our findings reinforce existing plague prevention recommen-
dations and point to potentially advantageous local interventions.
Plague is an often fatal, primarily flea-borne rodent-associated zoonosis caused by Yersinia pestis. We
Plague, which is caused by Yersinia pestis, is a primarily
flea-borne rodent-associated zoonosis that was the cause
of three major historical pandemics that claimed millions
of human lives.1Although in modern times human plague
cases still occur sporadically, improved sanitation has lim-
ited the scale of epidemics to focal outbreaks.2Furthermore,
advances in diagnostics and access to appropriate antibiotic
therapy have reduced case-fatality rates.3Despite the decrease
in human plague cases, plague bacteria continue to circulate
in enzootic hosts and their fleas within plague-endemic
regions. Thus, the threat of human infections is still an appre-
ciable concern in disease-endemic countries because of the
high fatality rate of the pathogen for untreated cases and its
Humans are most at risk for exposure to plague bacteria
during epizootics when rodent hosts die in large numbers,
forcing their potentially infectious fleas to abandon their
dying hosts.1As rodent host numbers decrease with the pro-
gression of the epizootic, fleas will occasionally take a blood
meal from humans, thus increasing the risk of human plague
infections. Epizootics are most likely to occur when rodent
and flea numbers are increased;5–7thus, plague prevention
strategies often focus on controlling flea vector and rodent
host populations. In addition to the use of insecticides to
reduce fleas on and off of hosts, prevention recommenda-
tions often include reducing food and harborage for rodents
in the home environment.4,8,9Furthermore, because of the
rapid clinical progression of plague in humans, educating
the public and health care providers of signs of plague and
the need to seek care immediately is advised.9
In recent decades, most human plague cases have been
reported from east and central Africa and Madagascar.10
During 2004–2009, the Democratic Republic of Congo
accounted for 64% of the annual reported incidence of
plague from the African region. All cases were reported
from the Orientale Province, which borders the West Nile
Region of northwestern Uganda.10To aid in better target-
ing plague prevention resources, recent research efforts in
Uganda have sought to define when and where humans
are most at risk for plague in the far eastern edge of this
During August 1999–July 2011, a total of 2,409 suspect
plague cases were reported from the West Nile Region of
Uganda; most cases occurred during September–December,
a time period that corresponds with the primary rainy
season.13Modeling of inter-annual variation showed that
annual plague case counts were negatively associated with
dry season rainfall (December–February) and positively
associated with rainfall immediately preceding the plague
season.13Spatial risk modeling has demonstrated that in the
West Nile Region, plague risk is higher above 1,300 meters
above sea level than below this value. Furthermore, covariates
included in these models suggested that localities that are
generally wetter, but with discontinuous rainfall, pose an
increased risk for plague compared with drier areas.11,12,14
Although existing spatial models performed well in broadly
defining the plague focus, there were many villages within the
focus where human plague cases had not been reported by
clinics during approximately a decade of surveillance. Such an
observation raised the question of whether these disparities in
case counts among villages within the risk area were attribut-
able to differences in access to care, care-seeking behavior or
knowledge of plague, agricultural or food storage practices,
rodent and vector control strategies, or fine-scale ecologic dif-
ferences (e.g., differences in host and flea community struc-
ture). In this study, we sought to identify risk factors for
plague by comparing each of these categories between villages
of similar population size situated within the model-defined
risk area that had or had not reported human plague cases.
MATERIALS AND METHODS
Description of study site. Our study was conducted in
the plague-endemic counties of Vurra and Okorro, situated
*Address correspondence to Rebecca J. Eisen, Bacterial Diseases
Branch, Division of Vector Borne Diseases, National Center for
Emerging and Zoonotic Infectious Diseases, Centers for Disease
Control and Prevention, PO Box 2087, Fort Collins, CO 80522. E-mail:
in Arua and Zombo Districts, respectively, within the West
Nile Region of northwestern Uganda (Figure 1). Throughout
the two districts, approximately 90% of the population resides
in rural areas, with close to 60% of those persons living in
Ugandan government–defined poverty; more than two-thirds
rely on subsistence farming (i.e., use of traditional seed
strains, livestock breeds, hand tools, and indigenous technical
knowledge) to make a living.15Villagers typically reside in
homesteads comprised of extended families living in multiple
earthen structures (huts) with thatch roofs that are surrounded
by small agricultural plots or other vegetation.
Vurra and Okorro counties straddle the Rift Valley escarp-
ment, resulting in markedly different ecologic conditions
above and below the escarpment. Lower elevation sites are
typically warmer and drier and have sandier soils than sites
above the escarpment.11,13,16Previous studies showed that
human plague cases are more common above the escarpment
than below.11,14Correspondingly, flea species diversity is sig-
nificantly higher above the escarpment within the plague
focus, compared with lower elevation sites outside the focus,
and this has been hypothesized to be important for enzootic
maintenance of Y. pestis.17
Selection of case and control villages. Ten case villages
and five control villages were selected from within areas that
were classified by geographic information system–based sta-
tistical models as posing an increased risk for plague.11In
other words, regardless of case or control status, based on
remotely sensed landscape level features, all villages enrolled
in the study were believed to be ecologically conducive for
plague activity. Ascertainment of village plague case histories
locations within Uganda are shown in the inset.
Locations of case (shaded) and control (unshaded) villages within Vurra and Okoro Counties, West Nile Region, Uganda. County
EISEN AND OTHERS
6. Eisen RJ, Gage KL, 2009. Adaptive strategies of Yersinia pestis
to persist during inter-epizootic and epizootic periods. Vet Res
7. Pham HV, Dang DT, Tran Minh NN, Nguyen ND, Nguyen
TV, 2009. Correlates of environmental factors and human
plague: an ecological study in Vietnam. Int J Epidemiol 38:
8. Gratz NG, 1999. Control of plague transmission. Plague Manual:
Epidemiology, Distribution, Surveillance and Control. Geneva:
World Health Organization, 97–134.
9. Gage KL, 1999. Plague surveillance. Plague Manual: Epide-
miology, Distribution, Surveillance and Control. Geneva: World
Health Organization, 135–165.
10. World Health Organization, 2010. Human plague: review of
regional morbidity and mortality, 2004–2009. Wkly Epidemiol
Rec 85: 40–45.
11. Eisen RJ, Griffith KS, Borchert JN, MacMillan K, Apangu T,
Owor N, Acayo S, Acidri R, Zielinski-Gutierrez E, Winters
AM, Enscore RE, Schriefer ME, Beard CB, Gage KL, Mead
PS, 2010. Assessing human risk of exposure to plague bacteria
in northwestern Uganda based on remotely sensed predictors.
Am J Trop Med Hyg 82: 904–911.
12. MacMillan K, Monaghan AJ, Apangu T, Griffith KS, Mead
PS, Acayo S, Acidri R, Moore SM, Mpanga JT, Enscore
RE, Gage KL, Eisen RJ, 2012. Climate predictors of
the spatial distribution of human plague cases in the
West Nile region of Uganda. Am J Trop Med Hyg 86:
13. Moore SM, Monaghan A, Griffith KS, Apangu T, Mead PS,
Eisen RJ, 2012. Improvement of disease prediction and
modeling through the use of meteorological ensembles: human
plague in Uganda. PLoS ONE 7: e44431.
14. Winters AM, Staples JE, Ogen-Odoi A, Mead PS, Griffith
K, Owor N, Babi N, Enscore RE, Eisen L, Gage KL,
Eisen RJ, 2009. Spatial risk models for human plague in
the West Nile Region of Uganda. Am J Trop Med Hyg 80:
15. Lakwo A, Cwinyaai W, Abdallay O, 2008. West Nile Profiling.
Nebbi, Uganda: Agency for Accelerated Regional Development.
16. Monaghan AJ, MacMillan K, Moore SM, Mead PS, Hayden MH,
Eisen RJ, 2012. A regional climatography to support human
plague modeling in the West Nile, Uganda. J Appl Meteorol
Climatol 51: 1201–1221.
17. Eisen RJ, Borchert JN, Mpanga JT, Atiku LA, MacMillan K,
Boegler KA, Montenieri JA, Monaghan A, Gage KL, 2012.
Flea diversity as an element for persistence of plague bacteria
in an East African plague focus. PLoS ONE 7: e35598.
18. Chu MC, 2000. Laboratory Manual of Plague Diagnostics.
Atlanta, GA: Centers for Disease Control and Prevention and
Geneva: World Health Organization, 129.
19. Borchert JN, Eisen RJ, Atiku LA, Delorey MJ, Mpanga JT,
Babi N, Enscore RE, Gage KL, 2012. Efficacy of indoor
residual spraying using lambda-cyhalothrin for controlling
nontarget vector fleas (Siphonaptera) on commensal rats in
a plague endemic region of northwestern Uganda. J Med
Entomol 49: 1027–1034.
20. Delany MJ, 1975. The Rodents of Uganda. Kettering, UK: The
21. Haselbarth E, 1966. Siphonaptera. Zumpt F, ed. The Arthropod
Parasites of Vertebrates in Africa South of the Sahara (Ethiopia
region). Johannesburg, South Africa: South African Institute
of Medical Research, 117–212.
22. Hopkins GH, 1947. Annotated and illustrated keys to the known
fleas of east Africa. Ugandan J 11: 133–191.
23. Hopkins GH, Rothschild M, 1966. An Illustrated Catalogue of
the Rothschild Collection of Fleas (Siphonaptera) in the
British Museum (Natural History): Hystrichopsyllidae. London:
Ballantyne and Company.
24. Smit FG, 1973. Siphonaptera (Fleas). Smith KG, ed. Insects and
other Arthropods of Medical Importance. London: British
Museum of Natural History, 325–371.
25. Nowak RM, 1990. Walker’s Mammals of the World, volume II,
6th edition. Baltimore, MD: The Johns Hopkins University
Press, 1936 pp.
26. Simpson EH, 1949. Measurements of diversity. Nature 163: 688.
27. Bacot AW, Martin CJ, 1914. Observations on the mechanism of
the transmission of plague by fleas. J Hyg 13 (Plague Suppl III):
28. Davis DHS, Heisch RB, McNeil D, Meyer KF, 1968. Serological
survey of plague in rodents and other small mammals in
Kenya. Trans R Soc Trop Med Hyg 62: 838–861.
29. Eisen RJ, Wilder AP, Bearden SW, Montenieri JA, Gage KL,
2007. Early-phase transmission of Yersinia pestis by unblocked
Xenoopsylla cheopis (Siphonaptera: pulicidae) is as efficient
as transmission by blocked fleas. J Med Entomol 44: 678–682.
30. Gratz NG, 1999. Rodent reservoirs and flea vectors of natural
foci of plague. Dennis DT, Gage KL, Gratz NG, Poland JD,
Tikhomirov E, eds. Plauge Manual: Epidemiology, Distribu-
tion, Surveillance and Control. Geneva: World Health Organi-
31. Kilonzo BS, 1976. A survey of rodents and their flea ecto-
parasites in north-eastern Tanzania. E African J Med Res
32. Pollitzer R, 1954. Plague. World Health Organization Monograph
Series No. 22. Geneva: World Health Organization.
33. Velimirovic B, Zikmund V, Herman J, 1969. Plague in the Lake
Edwards focus; the Democratic Republic of Congo, 1960–1966.
Z Tropenmed Parasitol 20: 373–387.
34. Gould LH, Pape J, Ettestad P, Griffith KS, Mead PS, 2008.
Dog-associated risk factors for human plague. Zoonoses
Publ Hlth 55: 448–454.
35. Mann JM, Martone WJ, Boyce JM, Kaufmann AF, Barnes
AM, Weber NS, 1979. Endemic human plague in New
Mexico: risk factors associated with infection. J Infect Dis
36. MacMillan K, Enscore RE, Ogen-Odoi A, Borchert JN, Babi N,
Amatre G, Atiku LA, Mead PS, Gage KL, Eisen RJ, 2011.
Landscape and residential variables associated with plague-
endemic villages in the West Nile region of Uganda. Am J
Trop Med Hyg 84: 435–442.
37. Laudisoit A, Neerinckx S, Makundi RH, Leirs H, Krasnov
BR, 2009. Are local plague endemicity and ecological char-
acteristics of vectors and reservoirs related? A case study
in north-east Tanzania. Curr Zool 55: 200–211.
38. Amatre G, Babi N, Enscore RE, Ogen-Odoi A, Atiku LA, Akol
A, Gage KL, Eisen RJ, 2009. Flea diversity and infestation
prevalence on rodents in a plague-endemic region of Uganda.
Am J Trop Med Hyg 81: 718–724.
39. Orach SO, 2003. Plague Outbreaks: the Gender and Age Perspec-
tive in Okoro County, Nebbi District, Uganda. Nebbi, Uganda:
Agency for Accelerated Regional Development.
40. Davis S, Trapman P, Leirs H, Begon M, Heesterbeek JAP, 2008.
The abundance threshold for plague as a critical percolation
phenomenon. Nature 454: 634–637.
41. Msangi AS, 1975. The surveillance of rodent populations in east
Africa in relation to plague endemicity. Dar Salam University
Sci J 1: 8–20.
42. Njunwa KJ, Mwaiko GL, Kilonzo BS, Mhina JI, 1989. Seasonal
patterns of rodents, fleas and plague status in the Western
Usambara Mountains, Tanzania. Med Vet Entomol 3: 17–22.
43. Kilonzo BS, Mvena ZSK, Machangu RS, Mbise TJ, 1997. Pre-
liminary observations on factors responsible for long persis-
tence and continued outbreaks of plague in Lushoto district,
Tanzania. Acta Trop 68: 215–227.
44. Belmain SR, Meyer AN, Penicela L, Xavier R, Jones SC, Zhai
J, Robinson WH, eds., 2002. Population management of
rodent pests through intensive trapping inside rural house-
holds in Mozambique. Jones SC, Zhai J, Robinson WH, eds.
Proceedings of the Fourth International Conference on Urban
45. Kingdon J, 1974. East African Mammals: An Atlas of Evolution
in Africa: Hares and Rodents. London: The University of
46. Eisen RJ, Enscore RE, Atiku LA, Zielinski-Gutierrez E,
Mpanga JT, Kajik E, Andama V, Mungujakisa C, Tibo E,
MacMillan K, Borchert JN, Gage KL, 2013. Evidence that
rodent control strategies ought to be improved to enhance
food security and reduce the risk of rodent-borne illnesses
within subsistence farming villages in the plague-endemic West
Nile region, Uganda. Int J Pest Manage 59: 259–270.
PLAGUE IN UGANDA
47. Hirst LF, 1953. The Conquest of Plague: A Study of the Evolu-
tion of Epidemiology. Oxford, UK: Carendon Press.
48. Laudisoit A, Leirs H, Makundi RH, Van Dongen S, Davis S,
Neerinckx S, Deckers J, Libois R, 2007. Plague and the
human flea, Tanzania. Emerg Infect Dis 13: 687–693.
49. Rust MK, Dryden MW, 1997. The biology, ecology, and man-
agement of the cat flea. Annu Rev Entomol 42: 451–473.
50. Eisen RJ, Borchert JN, Holmes JL, Amatre G, Van Wyk K,
Enscore RE, Babi N, Atiku LA, Wilder AP, Vetter SM,
Bearden SW, Montenieri JA, Gage KL, 2008. Early-phase
transmission of Yersinia pestis by cat fleas (Ctenocephalides
felis) and their potential role as vectors in a plague-endemic
region of Uganda. Am J Trop Med Hyg 78: 949–956.
51. Graham CB, Borchert JN, Black WC, Atiku LA, Mpanga JT,
Boegler KA, Moore SM, Gage KL, Eisen RJ, 2013. Blood
meal identification in off-host cat fleas (Ctenocephalides felis)
from a plague-endemic region of Uganda. Am J Trop Med
Hyg 88: 381–389.
EISEN AND OTHERS