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.
Methodology: 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. Principal Findings:
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.