学位論文内容の要旨（ Summary of dissertation）

博士の専攻分野の名称

博士（医 学）（Degree conferred: Doctor of Philosophy）

氏名

チンイェリィ・ウワフォー・オコリ（Name of recipient: Chinyere Nwafor-Okoli）

学位論文題名
Leptospirosis infection among febrile patients at the University of Peradeniya teaching Hospital in
Sri Lanka: Clinical, epidemiological and laboratory investigations（スリランカ・キャンディ市の大学病院における発熱外来患者を対象としたレプトスピラ症に関する研究：臨床的・疫学的・生化学的アプローチ）

Background and Objectives
Leptospirosis is a globally important zoonosis which has been recognized as an emerging
infectious disease, especially in the tropical countries including Sri Lanka. The discovery of
Leptospira was done 100 years ago but the understanding of its pathogenesis is still very poor andhas subsequently hampered the development of new intervention strategies. A variety of wild anddomestic animals form the natural reservoirs for pathogenic Leptospira. Leptospirosis is transmitted
to humans by direct contact with reservoir animals or by exposure to environmental surface water orsoil that is contaminated with their urine. Clinical symptoms of leptospirosis are protean leading todifficult diagnosis. Serological diagnosis is often used for confirmation of cases of leptospirosis andmicroscopic agglutination test (MAT) has been the gold standard.
The incidence of leptospirosis based on notifiable cases was 35.7 per 100,000 in 2008. In
Kandy District, infections were reported to have also risen from 147 in 2007 to 501 in 2008. To help
formulate local intervention, the study describes the socio-demographic characteristics and thecirculating leptospiral serogroups and serovars among the clinically diagnosed cases; deduces theleptospiral species among laboratory-confirmed positive cases; and examines the characteristics
between laboratory-confirmed positive and negative cases.
Methods
Patients were identified by physicians according to the surveillance case definition of theEpidemiology Unit of the Ministry of Health Sri Lanka from 1 April 2009 to 31 March 2010. We
interviewed 97 patients clinically diagnosed with Leptospirosis and requested for blood samples
from these cases. We examined serum samples for distribution of serovars using microscopic
agglutination test (MAT) with a battery of representative leptospiral serogroups; and polymerase
chain reaction test (PCR) was applied to the serum samples to detect flaB gene. Data were analyzed
by SPSS version 14 and χ2 test was employed for the test of significance.

Results
Among others, the 97 clinically diagnosed cases were mostly men (92.8%); nearly two-thirds
were 35 years of age or older and had secondary or higher education (61.8%); half were farmers orlaborers; and more than half were acute cases (57.7%). Of these 97 cases, 17 (17.5%) wereMAT-confirmed positives, while 80 (82.5%) were negatives. The predominant serogroups among theconfirmed positives were Sejroe and Tarassovi. Of 8 (8.2%) PCR-positives detected among 97
clinical cases, 1 PCR-positive occurred in the serum with MAT titre >200 but the remaining
PCR-positives (7) were observed among those with MAT-negative. The 7 leptospiral species among
8 PCR-positives were L. interrogans. Having a pet (dog) seemed to be statistically associated withlaboratory-confirmed positives.
Discussion
This study was undertaken in Kandy District, Sri Lanka for the purpose of collecting
epidemiological and laboratory evidence on the socio-demographic profile of clinically diagnosed
cases; the serogroups, serovars and species related to Leptospirosis; and the specific characteristics
of laboratory confirmation status. Data are intended to help formulate strategies for the local control
and prevention measures. Local data that are germane to the efficacious implementation of thesemeasures, while critical, are sparse.
Our research findings suggest that Leptospira infection appears to be relatively common in
Kandy District as borne out by our survey/clinical examination, and laboratory results. Ourlaboratory evidence particularly on serogroups (i.e., Sejroe and Tarassovi), is partly consistent withthe findings from the same study site and source. All these studies have revealed Sejroe as the mostpredominant serogroup in humans and dairy cattle, suggesting that the reservoir of human
Leptospirosis in Kandy is the smallholder dairy cattle. This information is useful for local control
and prevention efforts.
Positive rate of the results by MAT also depends, to some degree, specimen-collection time
during clinical course and chronic state of the infections. Further research is needed to validate thisfinding using, for examples, pairs of sera and/or serial blood samples of clinically diagnosed patients.
Anyhow, in these circumstances, the choice of an appropriate assay(s) is not only critical but also
vital in confirming Leptospira infections particularly in endemic areas like Sri Lanka.
Due to, among others, resource limitations and technical/logistical difficulties, clinicaldiagnosis and surveillance case definition do not accompany laboratory confirmation in Sri Lanka.
The protean clinical manifestations of Leptospirosis tend to masquerade a true picture of
Leptospirosis including fever and other signs and symptoms which are also common in many
communicable diseases prevalent in Sri Lanka, such as dengue fever and hanta virus infections.
Therefore, it is essential to employ laboratory support to confirm and/or differentiate Leptospirosis
from other febrile diseases especially prevalent in the area.
Conclusions
Leptospirosis is relatively common in Kandy District and the most common leptospiral species
is L. interrogans. The laboratory results by MAT and PCR depend on the time of blood collection
after onset of fever. Laboratory-confirmed positives seem to be associated with those who playedwith a dog. Further studies are warranted for choice and development of appropriate assay methods
as well as identification of potential reservoirs in the region.