Implementation of a national reference laboratory for Buruli ulcer disease in Togo.
BACKGROUND
In a previous study PCR analysis of clinical samples from suspected cases of Buruli ulcer disease (BUD) from Togo and external quality assurance (EQA) for local microscopy were conducted at an external reference laboratory in Germany. The relatively poor performance of local microscopy as well as effort and time associated with shipment of PCR samples necessitated the implementation of stringent EQA measures and availability of local laboratory capacity. This study describes the approach to implementation of a national BUD reference laboratory in Togo.


METHODS
Large scale outreach activities accompanied by regular training programs for health care professionals were conducted in the regions "Maritime" and "Central," standard operating procedures defined all processes in participating laboratories (regional, national and external reference laboratories) as well as the interaction between laboratories and partners in the field. Microscopy was conducted at regional level and slides were subjected to EQA at national and external reference laboratories. For PCR analysis, sample pairs were collected and subjected to a dry-reagent-based IS2404-PCR (DRB-PCR) at national level and standard IS2404 PCR followed by IS2404 qPCR analysis of negative samples at the external reference laboratory.


RESULTS
The inter-laboratory concordance rates for microscopy ranged from 89% to 94%; overall, microscopy confirmed 50% of all suspected BUD cases. The inter-laboratory concordance rate for PCR was 96% with an overall PCR case confirmation rate of 78%. Compared to a previous study, the rate of BUD patients with non-ulcerative lesions increased from 37% to 50%, the mean duration of disease before clinical diagnosis decreased significantly from 182.6 to 82.1 days among patients with ulcerative lesions, and the percentage of category III lesions decreased from 30.3% to 19.2%.


CONCLUSIONS
High inter-laboratory concordance rates as well as case confirmation rates of 50% (microscopy), 71% (PCR at national level), and 78% (including qPCR confirmation at external reference laboratory) suggest high standards of BUD diagnostics. The increase of non-ulcerative lesions, as well as the decrease in diagnostic delay and category III lesions, prove the effect of comprehensive EQA and training measures involving also procedures outside the laboratory.
Department of Infectious Diseases and Tropical Medicine, University Hospital, Ludwig-Maximilians-University, Munich, Germany. beissner@lrz.uni-muenchen.de
Marcus
M
Beissner
Kristina Lydia
KL
Huber
Kossi
K
Badziklou
Wemboo Afiwa
WA
Halatoko
Issaka
I
Maman
Felix
F
Vogel
Bawimodom
B
Bidjada
Koffi Somenou
KS
Awoussi
Ebekalisai
E
Piten
Kerstin
K
Helfrich
Carolin
C
Mengele
Jörg
J
Nitschke
Komi
K
Amekuse
Franz Xaver
FX
Wiedemann
Adolf
A
Diefenhardt
Basile
B
Kobara
Karl-Heinz
KH
Herbinger
Abiba Banla
AB
Kere
Mireille
M
Prince-David
Thomas
T
Löscher
Gisela
G
Bretzel
D000293:Adolescent; D000328:Adult; D000368:Aged; D054312:Buruli Ulcer / Q000175:diagnosis* / Q000453:epidemiology; D002648:Child; D002675:Child, Preschool; D019411:Clinical Laboratory Techniques / Q000379:methods* / Q000592:standards*; D005260:Female; D006801:Humans; D008297:Male; D008853:Microscopy / Q000379:methods / Q000592:standards; D008875:Middle Aged; D016133:Polymerase Chain Reaction / Q000379:methods / Q000592:standards; D011785:Quality Assurance, Health Care; D012015:Reference Standards; D014037:Togo / Q000453:epidemiology; D055815:Young Adult