Dataset Information

Screening Strategies for a Sustainable Endpoint for Gambiense Sleeping Sickness.

ABSTRACT:

Background

Gambiense human African trypanosomiasis ([gHAT] sleeping sickness) is a vector-borne disease that is typically fatal without treatment. Intensified, mainly medical-based, interventions in endemic areas have reduced the occurrence of gHAT to historically low levels. However, persistent regions, primarily in the Democratic Republic of Congo (DRC), remain a challenge to achieving the World Health Organization's goal of global elimination of transmission (EOT).

Methods

We used stochastic models of gHAT transmission fitted to DRC case data and explored patterns of regional reporting and extinction. The time to EOT at a health zone scale (~100 000 people) and how an absence of reported cases informs about EOT was quantified.

Results

Regional epidemiology and level of active screening (AS) both influenced the predicted time to EOT. Different AS cessation criteria had similar expected infection dynamics, and recrudescence of infection was unlikely. However, whether EOT has been achieved when AS ends is critically dependent on the stopping criteria. Two or three consecutive years of no detected cases provided greater confidence of EOT compared with a single year (~66%-75% and ~82%-84% probability of EOT, respectively, compared with 31%-51%).

Conclusions

Multiple years of AS without case detections is a valuable measure to assess the likelihood that the EOT target has been met locally.

SUBMITTER: Castano MS

PROVIDER: S-EPMC7289553 | biostudies-literature | 2020 Jun

REPOSITORIES: biostudies-literature

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Publications

Screening Strategies for a Sustainable Endpoint for Gambiense Sleeping Sickness.

Castaño M Soledad MS Aliee Maryam M Mwamba Miaka Erick E Keeling Matt J MJ Chitnis Nakul N Rock Kat S KS

The Journal of infectious diseases 20200601 Suppl 5

<h4>Background</h4>Gambiense human African trypanosomiasis ([gHAT] sleeping sickness) is a vector-borne disease that is typically fatal without treatment. Intensified, mainly medical-based, interventions in endemic areas have reduced the occurrence of gHAT to historically low levels. However, persistent regions, primarily in the Democratic Republic of Congo (DRC), remain a challenge to achieving the World Health Organization's goal of global elimination of transmission (EOT).<h4>Methods</h4>We u ...[more]

PMID: 31876949

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Project description:ObjectivesRecently, improvements have been made to diagnostics for gambiense sleeping sickness control but their performance remains poorly documented and may depend on specimen processing prior to examination. In a prospective study in the Democratic Republic of the Congo, we compared the diagnostic performance of several parasite detection techniques, immune trypanolysis and of m18S PCR on whole blood stored in a stabilisation buffer or dried on filter paper.MethodsIndividuals with CATT whole blood (WB) titer ?1?4 or with clinical signs indicative for sleeping sickness were examined for presence of trypanosomes in lymph node aspirate (LNA) and/or in blood. Blood was examined with Capillary Centrifugation Technique (CTC), mini-Anion Exchange Centrifugation Technique (mAECT) and mAECT on buffy coat (BC). PCR was performed on whole blood (i) stored in guanidine hydrochloride EDTA (GE) stabilisation buffer and (ii) dried on filter paper, and repeatability and reproducibility were assessed. Immune trypanolysis (TL) was performed on plasma.ResultsA total of 237 persons were included. Among 143 parasitologically confirmed cases, 85.3% had a CATT-WB titre of ?1/8, 39.2% were positive in LNA, 47.5% in CTC, 80.4% in mAECT-WB, 90.9% in mAECT-BC, 95.1% in TL and up to 89.5% in PCR on GE-stabilised blood. PCR on GE-stabilised blood showed highest repeatability (87.8%) and inter-laboratory reproducibility (86.9%). Of the 94 non-confirmed suspects, respectively 39.4% and 23.4% were TL or PCR positive. Suboptimal specificity of PCR and TL was also suggested by latent class analysis.ConclusionThe combination of LNA examination with mAECT-BC offered excellent diagnostic sensitivity. For PCR, storage of blood in stabilisation buffer is to be preferred over filter paper. TL as well as PCR are useful for remote diagnosis but are not more sensitive than mAECT-BC. For TL and PCR, the specificity, and thus usefulness for management of non-confirmed suspects remain to be determined.

Project description:BACKGROUND: Sleeping sickness due to Trypanosoma brucei (T.b.) gambiense is still a major public health problem in some central African countries. Historically, relapse rates around 5% have been observed for treatment with melarsoprol, widely used to treat second stage patients. Later, relapse rates of up to 50% have been recorded in some isolated foci in Angola, Sudan, Uganda and Democratic Republic of the Congo (DRC). Previous investigations are not conclusive on whether decreased sensitivity to melarsoprol is responsible for these high relapse rates. Therefore we aimed to establish a parasite collection isolated from cured as well as from relapsed patients for downstream comparative drug sensitivity profiling. A major constraint for this type of investigation is that T.b. gambiense is particularly difficult to isolate and adapt to classical laboratory rodents. METHODOLOGY/PRINCIPAL FINDINGS: From 360 patients treated in Dipumba hospital, Mbuji-Mayi, D.R. Congo, blood and cerebrospinal fluid (CSF) was collected before treatment. From patients relapsing during the 24 months follow-up, the same specimens were collected. Specimens with confirmed parasite presence were frozen in liquid nitrogen in a mixture of Triladyl, egg yolk and phosphate buffered glucose solution. Isolation was achieved by inoculation of the cryopreserved specimens in Grammomys surdaster, Mastomys natalensis and SCID mice. Thus, 85 strains were isolated from blood and CSF of 55 patients. Isolation success was highest in Grammomys surdaster. Forty strains were adapted to mice. From 12 patients, matched strains were isolated before treatment and after relapse. All strains belong to T.b. gambiense type I. CONCLUSIONS AND SIGNIFICANCE: We established a unique collection of T.b. gambiense from cured and relapsed patients, isolated in the same disease focus and within a limited period. This collection is available for genotypic and phenotypic characterisation to investigate the mechanism behind abnormally high treatment failure rates in Mbuji-Mayi, D.R. Congo.

Dataset Information

Screening Strategies for a Sustainable Endpoint for Gambiense Sleeping Sickness.

Background

Methods

Results

Conclusions

Publications

Screening Strategies for a Sustainable Endpoint for Gambiense Sleeping Sickness.

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