Institute National Of Recherche Biomedicale

Kinshasa, Democratic Republic of the Congo

Institute National Of Recherche Biomedicale

Kinshasa, Democratic Republic of the Congo
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Ngoyi D.M.,Institute National Of Recherche Biomedicale | Pyana P.,Institute National Of Recherche Biomedicale | Boelaert M.,Institute of Tropical Medicine | Llunga M.,Prog. National de Lutte Contre la Trypanosomiase Hum Africaine | And 4 more authors.
Journal of Infectious Diseases | Year: 2010

Background. Clinical management of human African trypanosomiasis requires patient follow-up of 2 years' duration. At each follow-up visit, cerebrospinal fluid (CSF) is examined for trypanosomes and white blood cells (WBCs). Shortening follow-up would improve patient comfort and facilitate control of human African trypanosomiasis. Methods. A prospective study of 360 patients was performed in the Democratic Republic of the Congo. The primary outcomes of the study were cure, relapse, and death. The WBC count, immunoglobulin M level, and specific antibody levels in CSF samples were evaluated to detect treatment failure. The sensitivity and specificity of shortened follow-up algorithms were calculated. Results. The treatment failure rate was 37%. Trypanosomes, a WBC count of 5≥100 cells/μL, and a LATEX/ immunoglobulin M titer of 5≥ 1:16 in CSF before treatment were risk factors for treatment failure, whereas human immunodeficiency virus infection status was not a risk factor. The following algorithm, which had 97.8% specificity and 94.4% sensitivity, is proposed for shortening the duration of follow-up: at 6 months, patients with trypanosomes or a WBC count of 5≤50 cells/μL in CSF are considered to have treatment failure, whereas patients with a CSF WBC count of ≤S5 cells/μL are considered to be cured and can discontinue follow-up. At 12 months, the remaining patients (those with a WBC count of 6-49 cells/μL) need a test of cure, based on trypanosome presence and WBC count, applying a cutoff value of 20 cells/μL. Conclusion. Combining criteria for failure and cure allows follow-up of patients with second-stage human African trypanosomiasis to be shortened to a maximum duration of 12 months. © 2010 by the Infectious Diseases Society of America. All rights reserved.


Buscher P.,Institute of Tropical Medicine | Mertens P.,Coris BioConcept | Leclipteux T.,Coris BioConcept | Gilleman Q.,Coris BioConcept | And 5 more authors.
The Lancet Global Health | Year: 2014

Background: Human African trypanosomiasis (HAT) is a life-threatening infection affecting rural populations in sub-Saharan Africa. Large-scale population screening by antibody detection with the Card Agglutination Test for Trypanosomiasis (CATT)/. Trypanosoma brucei (T b) gambiense helped reduce the number of reported cases of gambiense HAT to fewer than 10 000 in 2011. Because low case numbers lead to decreased cost-effectiveness of such active screening, we aimed to assess diagnostic accuracy of a rapid serodiagnostic test (HAT Sero- K-SeT) applicable in primary health-care centres. Methods: In our case-control study, we assessed participants older than 11 years who presented for HAT Sero- K-SeT and CATT/. T b gambiense at primary care centres or to mobile teams (and existing patients with confirmed disease status at these centres) in Bandundu Province, DR Congo. We defined cases as patients with trypanosomes that had been identified in lymph node aspirate, blood, or cerebrospinal fluid. During screening, we recruited controls without previous history of HAT or detectable trypanosomes in blood or lymph who resided in the same area as the cases. We assessed diagnostic accuracy of three antibody detection tests for gambiense HAT: HAT Sero- K-SeT and CATT/. T b gambiense (done with venous blood at the primary care centres) and immune trypanolysis (done with plasma at the Institute of Tropical Medicine, Antwerp, Belgium). Findings: Between June 6, 2012, and Feb 25, 2013, we included 134 cases and 356 controls. HAT Sero- K-SeT had a sensitivity of 0·985 (132 true positives, 95% CI 0·947-0·996) and a specificity of 0·986 (351 true negatives, 0·968-0·994), which did not differ significantly from CATT/. T b gambiense (sensitivity 95% CI 0·955, 95% CI 0·906-0·979 [128 true positives] and specificity 0·972, 0·949-0·985 [346 true negatives]) or immune trypanolysis (sensitivity 0·985, 0·947-0·996 [132 true positives] and specificity 0·980, 0·960-0·990 [349 true negatives]). Interpretation: The diagnostic accuracy of HAT Sero- K-SeT is adequate for T b gambiense antibody detection in local health centres and could be used for active screening whenever a cold chain and electricity supply are unavailable and CATT/. T b gambiense cannot be done. Funding: European Commission FP7 (NIDIAG, Grant Agreement 260260) and WHO Control of Neglected Tropical Diseases, Innovative and Intensified Disease Management. © 2014 Büscher et al. Open Access article distributed under the terms of CC BY-NC-ND.


Maganga G.D.,World Health Organization | Kapetshi J.,Institute National Of Recherche Biomedicale | Berthet N.,World Health Organization | Berthet N.,French National Center for Scientific Research | And 20 more authors.
New England Journal of Medicine | Year: 2014

Background The seventh reported outbreak of Ebola virus disease (EVD) in the equatorial African country of the Democratic Republic of Congo (DRC) began on July 26, 2014, as another large EVD epidemic continued to spread in West Africa. Simultaneous reports of EVD in equatorial and West Africa raised the question of whether the two outbreaks were linked. Methods We obtained data from patients in the DRC, using the standard World Health Organization clinical-investigation form for viral hemorrhagic fevers. Patients were classified as having suspected, probable, or confirmed EVD or a non-EVD illness. Blood samples were obtained for polymerase-chain-reaction-based diagnosis, viral isolation, sequencing, and phylogenetic analysis. Results The outbreak began in Inkanamongo village in the vicinity of Boende town in Équateur province and has been confined to that province. A total of 69 suspected, probable, or confirmed cases were reported between July 26 and October 7, 2014, including 8 cases among health care workers, with 49 deaths. As of October 7, there have been approximately six generations of cases of EVD since the outbreak began. The reported weekly case incidence peaked in the weeks of August 17 and 24 and has since fallen sharply. Genome sequencing revealed Ebola virus (EBOV, Zaire species) as the cause of this outbreak. A coding-complete genome sequence of EBOV that was isolated during this outbreak showed 99.2% identity with the most closely related variant from the 1995 outbreak in Kikwit in the DRC and 96.8% identity to EBOV variants that are currently circulating in West Africa. Conclusions The current EVD outbreak in the DRC has clinical and epidemiologic characteristics that are similar to those of previous EVD outbreaks in equatorial Africa. The causal agent is a local EBOV variant, and this outbreak has a zoonotic origin different from that in the 2014 epidemic in West Africa. Copyright © 2014 Massachusetts Medical Society.


Ley B.,Institute of Tropical Medicine | Le Hello S.,Institute Pasteur Paris | Lunguya O.,Institute National Of Recherche Biomedicale | Lejon V.,CIRAD - Agricultural Research for Development | And 3 more authors.
Emerging Infectious Diseases | Year: 2014

Infection with Salmonella enterica serotype Typhimurium sequence type (ST) 313 is associated with high rates of drug resistance, bloodstream infections, and death. To determine whether ST313 is dominant in the Democratic Republic of the Congo, we studied 180 isolates collected during 2007-2011; 96% belonged to CRISPOL type CT28, which is associated with ST313.


Mumba Ngoyi D.,University of Kinshasa | Menten J.,Institute of Tropical Medicine | Pyana P.P.,Institute National Of Recherche Biomedicale | Buscher P.,Institute of Tropical Medicine | And 2 more authors.
Tropical Medicine and International Health | Year: 2013

Objectives: Diagnosis of the neurological stage of human African trypanosomiasis is performed by examination of cerebrospinal fluid (CSF) for the presence of trypanosomes and numbers of white blood cells (WBC). Both CSF parameters are also used to assess treatment outcome during follow-up. In view of the importance of CSF examination, and the practical problems encountered with it, we compared the sensitivity of two trypanosome concentration techniques and the repeatability of two cell counting methods, as well as occurrence of systematic differences between them. Methods: Patients were recruited at Dipumba hospital, in Mbuji-Mayi in the Democratic Republic of the Congo. In 94 CSF samples, trypanosome detection was performed with modified single centrifugation (MSC) and double centrifugation (DC). On 189 CSF samples with ≤30 cells/μl, cell counting was performed in duplicate in a Fuchs-Rosenthal counting chamber and in a disposable Uriglass counting chamber. Results: Modified single centrifugation detected trypanosomes in significantly (P < 0.0001) more patients (85) than DC (46). Cell counts did not differ systematically in the two methods. Variability in the differences between duplicate cell counts was significantly higher (P = 0.002) in Uriglass (SD of differences 2.03) than in Fuchs-Rosenthal (SD of differences 1.62). Conclusions: For analysis of CSF in the context of sleeping sickness stage determination and follow-up after treatment, we strongly recommend the MSC for parasite detection and the application of disposable counting chambers. When the first cell count is ≤20 cells/μl, we recommend repeating the counting procedure on the same CSF specimen and taking the average of both countings. © 2013 John Wiley & Sons Ltd.


Mitashi P.,Institute of Tropical Medicine | Hasker E.,Institute of Tropical Medicine | Lejon V.,Institute of Tropical Medicine | Kande V.,Programme National de Lutte contre la Trypanosomiase Humaine Africaine | And 3 more authors.
PLoS Neglected Tropical Diseases | Year: 2012

While the incidence of Human African Trypanosomiasis (HAT) is decreasing, the control approach is shifting from active population screening by mobile teams to passive case detection in primary care centers. We conducted a systematic review of the literature between 1970 and 2011 to assess which diagnostic tools are most suitable for use in first-line health facilities in endemic countries. Our search retrieved 16 different screening and confirmation tests for HAT. The thermostable format of the Card Agglutination Test for Trypanosomiasis (CATT test) was the most appropriate screening test. Lateral flow antibody detection tests could become alternative screening tests in the near future. Confirmation of HAT diagnosis still depends on visualizing the parasite in direct microscopy. All other currently available confirmation tests are either technically too demanding and/or lack sensitivity and thus rather inappropriate for use at health center level. Novel applications of molecular tests may have potential for use at district hospital level. © 2012 Mitashi et al.


Van Reet N.,Institute of Tropical Medicine | Van de Vyver H.,University of Munster | Pyana P.P.,Institute of Tropical Medicine | Pyana P.P.,Institute National Of Recherche Biomedicale | And 2 more authors.
PLoS Neglected Tropical Diseases | Year: 2014

Background: Genetic engineering with luciferase reporter genes allows monitoring Trypanosoma brucei (T.b.) infections in mice by in vivo bioluminescence imaging (BLI). Until recently, luminescent T.b. models were based on Renilla luciferase (RLuc) activity. Our study aimed at evaluating red-shifted luciferases for in vivo BLI in a set of diverse T.b. strains of all three subspecies, including some recently isolated from human patients. Methodology/Principal findings: We transfected T.b. brucei, T.b. rhodesiense and T.b. gambiense strains with either RLuc, click beetle red (CBR) or Photinus pyralis RE9 (PpyRE9) luciferase and characterised their in vitro luciferase activity, growth profile and drug sensitivity, and their potential for in vivo BLI. Compared to RLuc, the red-shifted luciferases, CBR and PpyRE9, allow tracking of T.b. brucei AnTaR 1 trypanosomes with higher details on tissue distribution, and PpyRE9 allows detection of the parasites with a sensitivity of at least one order of magnitude higher than CBR luciferase. With CBR-tagged T.b. gambiense LiTaR1, T.b. rhodesiense RUMPHI and T.b. gambiense 348 BT in an acute, subacute and chronic infection model respectively, we observed differences in parasite tropism for murine tissues during in vivo BLI. Ex vivo BLI on the brain confirmed central nervous system infection by all luminescent strains of T.b. brucei AnTaR 1, T.b. rhodesiense RUMPHI and T.b. gambiense 348 BT. Conclusions/Significance: We established a genetically and phenotypically diverse collection of bioluminescent T.b. brucei, T.b. gambiense and T.b. rhodesiense strains, including drug resistant strains. For in vivo BLI monitoring of murine infections, we recommend trypanosome strains transfected with red-shifted luciferase reporter genes, such as CBR and PpyRE9. Red-shifted luciferases can be detected with a higher sensitivity in vivo and at the same time they improve the spatial resolution of the parasites in the entire body due to the better kinetics of their substrate D-luciferin. © 2014 Van Reet et al.


Van Reet N.,Institute of Tropical Medicine | Pyana P.,Institute of Tropical Medicine | Pyana P.,Institute National Of Recherche Biomedicale | Roge S.,Institute of Tropical Medicine | And 2 more authors.
Parasites and Vectors | Year: 2013

Background: New compounds for the treatment of human African trypanosomiasis (HAT) are urgently required. Trypanosoma brucei (T.b.) gambiense is the leading cause of HAT, yet T.b. gambiense is often not the prime target organism in drug discovery. This may be attributed to the difficulties in handling this subspecies and the lack of an efficient viability assay to monitor drug efficacy. Methods. In this study, a T.b. gambiense strain, recently isolated in the D.R. Congo, was made bioluminescent by transfection with Renilla luciferase (RLuc) without altering its in vitro and in vivo growth characteristics. A luminescent multiplex viability assay (LMVA), based on measurement of the Renilla luciferase activity and the ATP content of the cells within the same experiment, was investigated as an alternative to the standard fluorimetric resazurin viability assay for drug sensitivity testing of T.b. gambiense. Results: In a 96-well format, the RLuc transfected strain showed a detection limit of 2 × 104 cells ml-1 for the Renilla luciferase measurement and 5 × 103 cells ml -1 for the ATP measurement. Both assays of the LMVA showed linearity up to 106 cells ml-1 and correlated well with the cell density during exponential growth of the long slender bloodstream forms. The LMVA was compared to the fluorimetric resazurin viability assay for drug sensitivity testing of pentamidine, eflornithine, nifurtimox and melarsoprol with both the wild type and the RLuc transfected population. For each drug, the IC50 value of the RLuc population was similar to that of the wild type when determined with either the fluorimetric resazurin method or the LMVA. For eflornithine, nifurtimox and melarsoprol we found no difference between the IC50 values in both viability assays. In contrast, the IC 50 value of pentamidine was higher when determined with the fluorimetric resazurin method than in both assays of the LMVA. Conclusions: LMVA has some advantages for viability measurement of T.b. gambiense: it requires less incubation time for viability detection than the fluorimetric resazurin assay and in LMVA, two sensitive and independent viability assays are performed in the same experiment. © 2013 Van Reet et al.; licensee BioMed Central Ltd.


Lejon V.,Institute of Tropical Medicine | Ngoyi D.M.,Institute National Of Recherche Biomedicale | Boelaert M.,Institute of Tropical Medicine | Buscher P.,Institute of Tropical Medicine
PLoS Neglected Tropical Diseases | Year: 2010

Background: Cure after treatment for human African trypanosomiasis (HAT) is assessed by examination of the cerebrospinal fluid every 6 months, for a total period of 2 years. So far, no markers for cure or treatment failure have been identified in blood. Trypanosome-specific antibodies are detectable in blood by the Card Agglutination Test for Trypanosomiasis (CATT). We studied the value of a normalising, negative post-treatment CATT result in treated Trypanosoma brucei (T.b.) gambiense sleeping sickness patients as a marker of cure. Methodology/Principal Findings: The CATT/T.b. gambiense was performed on serum of a cohort of 360 T.b. gambiense patients, consisting of 242 primary and 118 retreatment cases. The CATT results during 2 years of post-treatment follow-up were studied in function of cure or treatment failure. At inclusion, sensitivity of CATT was 98% (234/238) in primary cases and only 78% (91/117) in retreatment cases. After treatment, the CATT titre decreased both in cured patients and in patients experiencing treatment failure. Conclusions/Significance: Though CATT is a good test to detect HAT in primary cases, a normalising or negative CATT result after treatment for HAT does not indicate cure, therefore CATT cannot be used to monitor treatment outcome. © 2010 Lejon et al.


Pyana Pati P.,Institute National Of Recherche Biomedicale | Van Reet N.,Institute of Tropical Medicine | Mumba Ngoyi D.,Institute National Of Recherche Biomedicale | Ngay Lukusa I.,Institute National Of Recherche Biomedicale | And 2 more authors.
PLoS Neglected Tropical Diseases | Year: 2014

Forty five T.b. gambiense strains were used. Forty one were isolated from patients that were cured or relapsed after melarsoprol treatment in Mbuji-Mayi. In vivo drug sensitivity tests provide evidence of reduced melarsoprol sensitivity in these strains. This reduced melarsoprol sensitivity was not attributable to mutations in TbAT1. However, in all these strains, irrespective of the patient treatment outcome, the two aquaglyceroporin (AQP) 2 and 3 genes are replaced by chimeric AQP2/3 genes that may be associated with resistance to pentamidine and melarsoprol. The 4 T.b. gambiense strains isolated in Masi-Manimba contain both wild-type AQP2 and a different chimeric AQP2/3. These findings suggest that the reduced in vivo melarsoprol sensitivity of the Mbuji-Mayi strains and the high relapse rates in that sleeping sickness focus are caused by mutations in the AQP2/AQP3 locus and not by mutations in TbAT1.Sleeping sickness caused by Trypanosoma brucei (T.b.) gambiense constitutes a serious health problem in sub-Sahara Africa. In some foci, alarmingly high relapse rates were observed in patients treated with melarsoprol, which used to be the first line treatment for patients in the neurological disease stage. Particularly problematic was the situation in Mbuji-Mayi, East Kasai Province in the Democratic Republic of the Congo with a 57% relapse rate compared to a 5% relapse rate in Masi-Manimba, Bandundu Province. The present study aimed at investigating the mechanisms underlying the high relapse rate in Mbuji-Mayi using an extended collection of recently isolated T.b. gambiense strains from Mbuji-Mayi and from Masi-Manimba.We conclude that mutations in the TbAQP2/3 locus of the local T.b. gambiense strains may explain the high melarsoprol relapse rates in the Mbuji-Mayi focus but other factors must also be involved in the treatment outcome of individual patients. © 2014 Pyana Pati et al.

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