Rickettsioses caused by typhus group rickettsiae have been reported in various African regions. We conducted a cross-sectional survey of 1,227 participants from 9 different sites in the Mbeya region, Tanzania; overall seroprevalence of typhus group rickettsiae was 9.3%. Risk factors identified in multivariable analysis included low vegetation density and highway proximity

Clowes, Petra

Dill, Tatjana

Dobler, Gerhard

Heinrich, Norbert

Hoelscher, Michael

Kroidl, Inge

Löscher, Thomas

Maboko, Leonard

Machibya, Harun

Ntinginya, Elias

Saathoff, Elmar

Emerging Infectious Diseases

PubMed

Tatjana Dill

Gerhard Dobler

Elmar Saathoff

Petra Clowes

Inge Kroidl

Elias Ntinginya

Harun Machibya

Leonard Maboko

Thomas Löscher

Michael Hoelscher

Norbert Heinrich

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High Seroprevalence for Typhus Group Rickettsiae, Southwestern Tanzania

Digital Library of the Tanzania Health Community

High 
Seroprevalence 
for Typhus Group 
Rickettsiae, 
Southwestern 
Tanzania 
Tatjana Dill,1 Gerhard Dobler,1 Elmar Saathoff, 
Petra Clowes, Inge Kroidl, Elias Ntinginya,  
Harun Machibya, Leonard Maboko,  
Thomas Löscher, Michael Hoelscher,  
and Norbert Heinrich
Rickettsioses caused by typhus group rickettsiae have 
been reported in various African regions. We conducted a 
cross-sectional survey of 1,227 participants from 9 different 
sites in the Mbeya region, Tanzania; overall seroprevalence 
of typhus group rickettsiae was 9.3%. Risk factors identified 
in multivariable analysis included low vegetation density 
and highway proximity.
Murine, or endemic, typhus is primarily caused by Rickettsia typhi (typhus group rickettsiae [TGR]) 
and is usually manifest as a benign disease. A systemic 
vasculitis causes a clinical triad of fever, headache, and 
maculopapular rash (1). Because these signs and symptoms 
are nonspecific, the disease is often misdiagnosed or 
overlooked and can frequently be misclassified as malaria 
(2,3). In rare cases, murine typhus can lead to severe 
systemic complications such as acute renal failure, 
interstitial pneumonia, and complications of the central 
nervous system. The case-fatality-rate is <5% (2), in 
contrast to the situation for epidemic, or louse-borne, 
typhus caused by R. prowazekii, which can produce severe 
disease and fatality rates up to 30% if untreated. Serologic 
tests cannot distinguish these 2 infections, however. We 
assume that the antibodies detected in Tanzania in this 
study were caused by R. typhi, because, to our knowledge, 
no severe or epidemic illness compatible with louse-borne 
typhus has been described in the study region.
Murine typhus is found throughout the world, widely 
distributed in subtropical and tropical regions, and is most 
apparent in port cities with large rat populations (2,4), which 
provide a reservoir for the pathogen and its main vector, 
the rat flea (Xenopsylla cheopsis). Additional transmission 
cycles have been described in Texas and California, USA, 
which involved mainly suburban cats and opossums as 
reservoir hosts and the cat flea (Ctenocephalides felis) as 
vector (5). Other yet unknown cycles may exist.
In Tanzania, information on typhus is sparse. A 
seroprevalence study among pregnant women from the port 
city of Dar es Salaam found a seropositivity prevalence 
of 28% (4). In the landlocked northern Tanzanian town 
of Moshi, murine typhus was detected in 0.5% of febrile 
patients (6).
A predictive risk model for endemic typhus based on 
environmental conditions has not been established, but 
because plague is also transmitted by X. cheopsis fleas, 
some of the findings regarding plague transmission might 
also apply to murine typhus. However, no data are available 
on the vector flea C. felis, the predominant flea harvested 
from rodents in a study in Uganda (7).
The Study
 We conducted a cross-sectional seroprevalence study 
among 1,227 persons from the Mbeya region in southwestern 
Tanzania to estimate TGR seroprevalence rates and to 
assess associated sociodemographic and environmental 
risk factors. This study was conducted as a substudy within 
the EMINI (Evaluation and Monitoring the Impact of 
New Interventions) longitudinal cohort study. Briefly, in 
2005 we conducted a census at 9 study sites (Figure) to 
collect baseline data, and 10% of census households were 
chosen by geographically stratified random selection to 
participate in the 5-year EMINI longitudinal cohort study 
(http://www.mmrp.org/projects/cohort-studies/emini.
html). From these, serum specimens for this substudy were 
selected by stratified disproportionate random sampling 
of stored samples from 17,872 persons who took part in 
the second EMINI survey in 2007. Stratification was done 
for age (7 categories), altitude of residence (2 categories), 
and ownership of domestic mammals (2 categories) and 
resulted in 28 strata of roughly similar size, described in 
detail elsewhere (8). Serum samples were tested for IgG 
against R. typhi by indirect immunofluorescence assay 
(IIFA) with the same batch of a commercially available test 
(Rickettsia typhi Spot IF; Fuller Laboratories, Fullerton, 
 Emerging Infectious Diseases • www.cdc.gov/eid • Vol. 19, No. 2, February 2013 317
Author affiliations: Medical Centre of the University of Munich, 
Munich, Germany (T. Dill, E. Saathoff, P. Clowes, I. Kroidl, T. 
Löscher, M. Hoelscher, N. Heinrich); DZIF German Centre for 
Infection Research–Ludwig Maximilian University of Munich, 
Munich (G. Dobler E. Saathoff, M. Hoelscher, N. Heinrich); 
Bundeswehr Institute of Microbiology, Munich (G. Dobler); NIMR-
Mbeya Medical Research Centre, Mbeya, Tanzania (P. Clowes, 
I. Kroidl, E. Ntinginya, L. Maboko, M. Hoelscher); and Regional 
Medical Office, Mbeya (H. Machibya)
DOI: http://dx.doi.org/10.3201/eid1902.120601 1These authors contributed equally to this article.
CA, USA.). Samples with an IgG titer of >64 or higher were 
regarded as positive; because IIFA for antibody testing 
against rickettsiae has a high sensitivity and specificity, as 
shown by different researchers and with different antigen 
preparations (9). Comparison of the commercial IIFA with 
a commercial ELISA in our laboratory confirmed this 
approach (G. Dobler, unpub. data).
To identify possible risk factors for TGR IgG positivity, 
we analyzed seropositivity as the binary outcome of uni- 
and multivariable Poisson regression models with robust 
variance estimates adjusted for household clustering. 
Initial univariable models for all factors that we deemed 
as possibly related to TGR infection (Table) were used to 
identify variables with a univariable p value <0.1 for further 
multivariable evaluation. Stepwise backward and forward 
regression, the Akaike and Bayesian information criteria, 
and various assessments of model fit were used to identify 
the best multivariable model, in which only variables with 
a multivariable p value <0.1 were retained.
Of the 1,227 analyzed serum specimens, 114 specimens 
(9.3%) were positive for TGR IgG. This finding translates 
into an estimated overall population prevalence of 8.4% 
(95% CI 6.8%–10.1%) when findings are extrapolated 
from our stratified sample to the underlying population of 
the 9 sites by using direct standardization. We found local 
maximum prevalence in the urban sites, Ruanda (17.5%) 
and Iyunga (17.8%), and in semiurban Mlowo (12.5%; 
Figure). The prevalence at other sites ranged from 2.7% to 
10.6%. The highest seropositivity rate was found in the age 
quintile from 42.1 to 55.2 years, with a decline thereafter. 
In univariable analysis, several environmental covariates 
showed a significant inverse association with TGR IgG 
(Table), which included vegetation density, rainfall, 
minimum and night temperatures, whereas population 
density, cattle density, and socioeconomic status were 
positively associated with seropositivity. The geographic 
distribution of seropositive participants (Figure) led us to 
include distance to the nearest highway as a variable in the 
analysis. Distance was found to be inversely associated 
with seropositivity. The final multivariable model included 
age, vegetation density, and distance to the nearest highway 
as significant predictors of TGR IgG. Other factors were 
not included in the multivariable model because their lack 
of multivariable significance.
Although significant in univariable analysis, the 
association of population density, rainfall, socioeconomic 
status, and cattle density became nonsignificant in the 
multivariable model when vegetation density was included 
(p = 0.66 for population density; data not shown). Other 
factors, including sex, livestock ownership, day and night 
average land surface temperatures, and other environmental 
factors, were unrelated to TGR seropositivity.
Conclusions 
In contrast to results of a recent study of febrile patients 
from inland northern Tanzania (6), site-specific seropositivity 
prevalences of up to 17.8% in our study suggest that TGR 
contributes substantially to febrile illness in some areas of 
the Mbeya region. Our study provides data on environmental 
risk factors for TGR seropositivity, which might be useful 
DISPATCHES
318 Emerging Infectious Diseases • www.cdc.gov/eid • Vol. 19, No. 2, February 2013
Figure. Study sites in Tanzania, 
showing positivity and negativity 
for IgG against Rickettsia typhi 
displayed in Voronoi polygons. 
Every polygon represents 1 
household. Numbers in parentheses 
indicate site prevalence.
High Seroprevalence for Typhus Group Rickettsiae
to inform a predictive model for disease occurrence. The 
inverse association of vegetation density with seropositivity 
has been described for plague in Uganda, a disease that 
is also transmitted by the rat flea (X. cheopsis) (10). That 
study and early laboratory data suggest that dryness is not 
the driving factor behind the link between vegetation and 
disease transmission, because increasingly dry conditions 
in the laboratory adversely affect vector lifespan (11). In 
our study, rainfall was not significantly associated with 
seropositivity in the multivariable model. The urbanity of a 
settlement, expressed by population density and closeness to 
highways, may still be a relevant factor through providing 
more favorable habitats for the mammal reservoir hosts, and 
sparse vegetation could just be a proxy for urbanization. 
The positive univariable association of seropositivity with 
socioeconomic status appears to be a product of the higher 
socioeconomic status in urbanized communities. Our results 
suggest that TGR incidence may increase with deforestation 
and increasing urbanization. Additional research is needed 
to detect the pathogen in acute infection and to describe the 
local transmission cycle to validate the identified risk factors 
prospectively. We further hypothesize that remote sensing 
data could be used to design a model for prediction of R. 
typhi infection, which could be used to direct public health 
interventions in the future.
Acknowledgments
We thank the study participants as well as Wolfram 
Mwalongo, Weston Assisya, and the EMINI field and laboratory 
teams for their support during this study.
The EMINI study was funded by 2 grants from the European 
Union (SANTE/2004/078-545/130 and SANTE/2006/129-931). 
This serology substudy was supported by the German Federal 
Ministry of Education and Research (BMBF), grant no. 01KA0903. 
The funders had no role in study design, data collection and analysis, 
decision to publish, or preparation of the manuscript.
Ms Dill is studying for her medical doctorate at the Medical 
Centre of the University of Munich. Her research interests include 
arthropod-borne diseases and zoonotic diseases.
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Table. Covariates associated with seropositivity for typhus group rickettsiae, Mbeya region, southwestern Tanzania, 2007* 
Covariate/stratum 
No. specimens 
(% positive)  
Univariable†‡ 
 
Multivariable†§ 
PR (95% CI) p value PR (95% CI) p value 
Age, y        
 5–<13.6 245 (5.3) 1 –  1 (–) – 
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Minimum ambient temperature, °C 1,227 (9.3) 0.92 (0.87–0.97) 0.004    
Average day land surface temperature, °C 1,227 (9.3) 1.37 (0.71–2.63) 0.351    
Average night land surface temperature, °C 1,227 (9.3) 0.61 (0.38–0.99) 0.044    
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Address for correspondence: Norbert Heinrich, Medical Centre of the 
University of  Munich (LMU), Leopoldstr. 5, 80802 Munich, Germany; 
email: heinrich@lrz.uni-muenchen.de
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320 Emerging Infectious Diseases • www.cdc.gov/eid • Vol. 19, No. 2, February 2013


High Seroprevalence for Typhus Group rickettsiae, southwestern Tanzania.

Clinical and laboratory features of murine typhus in central Tunisia: a report of seven cases.

Rickettsioses and the international traveler. Clin Infect Dis.

When is “malaria” malaria? The different burdens of malaria infection, malaria disease, and malarialike illnesses.

High Seroprevalence for Typhus Group rickettsiae, southwestern Tanzania.

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