Tendances de la tuberculose pulmonaire bactériologiquement confirmée et issues thérapeutiques en République Démocratique du Congo : 2007-2017: Trends of bacteriologically confirmed pulmonary tuberculosis and treatment outcomes in Democratic Republic of the Congo: 2007-2017

Context and objective. DR Congo ranks among high burden countries for tuberculosis. However, the real incidence of the disease is unknown. The study aimed to describe the trends in the estimated incidence of the bacteriologically confirmed pulmonary TB and therapeutic outcomes of patients. Methods. A retrospective analysis of data from TB patients recorded during the period of 2007 to 2017 through all the country. Linear regtression model and z-score helped to assess the year to year variations in notification rate and treatment outcomes. Results. A total of 884,458 patients were enrolled including 820,858 new patients (NP TP+) and 63,600 with a previous TB treatment. The increase reached 28.95% during this decade. The annual average inrease was of 2, 41% +/- 3, and 28 % for NP TP+ and of 5, 7% +/-0.26 for default patients. Treatment outcome assessment included 848,163 patients among them, 789, 716 NP TP+ and 58,447 with a previous TB treatment. The success rate was 88% in the former group, of 70% in those with relapse, 64.3% in patients with failure and 67.8% in the group of ancient defaulters. A total of 70,515 (8.3%) patients remained smear positive. Conclusion. The study shows an increase in the incidence of reported TP+ patients with a treatment outcome reaching the WHO’s expectations. However the high proportion of smear positive patients suggests a high risk of further acquired TB resistance. Contexte et objectifs. La République Démocratique du Congo compte parmi les pays à lourd fardeau pour la tuberculose (TB), l’incidence réelle de la maladie n’est pas formellement connue. La présente étude vise à décrire les tendances de l’incidence notifiée des patients atteints de tuberculose pulmonaire bactériologiquement confirmée (TP+) et leurs issues thérapeutiques. Méthodes. Cette étude documentaire, analyse les données des patients diagnostiqués et traités pour tuberculose de 2007 à 2017 en RDC. L’incidence notifiée des patients TP+, le taux d’accroissement annuel, les issues thérapeutiques ont été recherchés. Les variations du nombre de patients sont exprimées par les proportions. Les tendances sont présentées à travers les courbes de régression linéaire. Les issues thérapeutiques sont comparées à l’aide du z-score avec un seuil significatif de p˂ 0,05. Résultats. Au total 884 458 patients TP+ ont été rapportés, dont 820 858 nouveaux patients (NP TP+) et 63 600 déjà traités. Le taux d’accroissement au cours de cette décade était de 28,95%, soit de 66099 en 2007 à 93767 en 2017 pour les NP TP+. L’augmentation annuelle moyenne était de 2,41% +/- 3,28 pour les NP TP+ et de 5,7% +/- 0,26 par an pour les rechutes. La notification des échecs de traitement initial et repris après abandon de traitement ont une tendance à la baisse. L’évaluation thérapeutique de tous les cas cumulés a concerné 848 163 patients dont 789 716 NP TP+ et 58447 en retraitement. Le succès thérapeutique était de 88,0 % pour les NP TP+ et 70,0 % pour les rechutes, de 64,3 % pour les échecs et de 67,8% pour les repris en traitement après abandon. En somme 70 515 (8,3%) patients ont gardé des expectorations positives. Conclusion. Cette étude montre une tendance à la hausse de notification des cas incidents dont l’issue de traitement répond aux standards de l’OMS. En outre, un nombre des personnes demeurent porteurs de germes persistants précurseurs d’une TB pharmacorésistante acquise

Assessment of treatment outcomes of multidrug-resistant tuberculosis patients in D R Congo: A study based on drug regimens used between 2007 to 2017: Évaluation des issues thérapeutiques des patients atteints de la tuberculose à bacilles multi résistants : étude basée sur les régimes de médicaments utilisés en République Démocratique du Congo de 2007 à 2017

Context. Little is known about therapeutic successes in MDR-TB patients under regimens containing second-line molecules. The present study aimed to assess therapeutic outcomes in patients under therapeutic regimens applied in DR Congo. Methods. This historical cohort study has included confirmed MDR-TB patients who received treatment between 2007 and 2017 in 218 TB centers in DR Congo. Treatment outcome and survival at 36 months were analyzed using Zscore and chi square test. Kaplan-Meier method was performed to describe survival and Log Rank test helped in comparing curve based on the therapeutical regimen. Factors associated with therapeutic success and mortality predictors were assessed using multivariate logistic regression and Cox regression analysis, respectively. Results. The therapeutic success in the study group (n=1,724) was 72% (range 68-74%) for all regimen combined. The average death rate was 12.8% although the group of patients receiving Cyclosérine and Ofloxacine was the most affected (16%). The death rate was significantly higher in patients living in urban areas (15.2% versus 14.9%, p = 0.013) and also among MDR-TB/HIV co-infected patients (28.4% vs 15.7%, p<0.001) patients. The median survival of the study group was 722.7 days compared to 601.1 days for MDR-TB/HIV co-infected patients, and 736.7 days for HIV negative patients (p<0.001). Conclusion. Therapeutic successes are significant for the short regimen. However, the death rate remains high when Cycloserine and Ofloxacin are included in the regimen. The predictors of mortality are HIV infection and living in urban areas. Contexte. L’issue thérapeutique de la tuberculose multi résistante (TB-MR) sous les molécules de deuxième intention n’est pas très bien connue. La présente étude a évalué les régimes thérapeutiques appliqués, en termes de succès thérapeutique et de survie. Méthodes. L’étude de cohorte historique a inclu les patients TB-MR confirmés et traités entre 2007 et 2017 dans 218 centres de tuberculose en RD Congo. L’issue thérapeutique et la survie à 36 mois ont été analysées. Le score Z ou le test de chi carré ont comparé des issues. La méthode de Kaplan-Meier a décrit les courbes de survie et le test de Log Rank a comparé la survie en fonction du regime therapeutique. Les facteurs associés au succès thérapeutique et les prédicteurs de mortalité ont été analysés respectivement, par l’analyse multivariée de régression logistique et de Cox. Résultats. Dans le groupe étudié (n=1724), le succès thérapeutique a été de 72% (68-74%) pour l’ensemble des régimes. Le taux était plus élevé pour le régime court (74%) et plus faible pour le régime contenant la Cyclosérine et l’Ofloxacine (68%). La moyenne de décès était de 12,8% ; mais plus élevée dans le groupe sous regime contenant la Cyclosérine et l’Ofloxacine (16%). Le taux de décès était significativement plus élevé en milieu urbain (15,2% versus 14,9 %, p = 0,013) et également chez les sujets co-infectés par la MDR-TB  et le VIH (28.4% vs 15.7%, p <0,001). La survie médiane dans le groupe était de 722,7 jours contre 601,1 jours chez les co-infectés MDR-TB/VIH, et de 736,7 jours) chez les patients VIH négatifs (p<0,001). Conclusion. Les succès thérapeutiques sont acceptables en particulier, pour le régime court ; toutefois, le taux de décès demeure encore très élevé dans le groupe sous Cyclosérine et Ofloxacine. Les prédicteurs de mortalité sont l’infection à VIH et la vie citadine. &nbsp

Falciparum malaria molecular drug resistance in the Democratic Republic of Congo: a systematic review

peer reviewedBackground: Malaria cases were estimated to 207 million in 2013. One of the problems of malaria control is the emergence and spread of Plasmodium falciparum strains that become resistant to almost all drugs available. Monitoring drug resistance is essential for early detection and subsequent prevention of the spread of drug resistance by timely changes of treatment policy. This review was performed to gather all data available on P. falciparum molecular resistance in DR Congo, as baseline for future assessments. Methods: The search for this review was undertaken using the electronic databases PubMed and Google Scholar using the terms “malaria”, “Congo”, “resistance”, “molecular”, “antimalarial”, “efficacy”. Articles were classified based on year of collecting, year of publication, sample size and characteristics, molecular markers analysed and polymorphisms detected. Results: Thirteen articles were included and five genes have been analysed in these studies: pfcrt, pfdhps, pfdhfr, pfmdr1 and K13-propeller. The majority of studies included were not representative of the whole country. Conclusion: This systematic review demonstrates the lack of molecular resistance studies in DRC. Only 13 studies were identified in almost 15 years. The MOH must implement a national surveillance system for monitoring malaria drug resistance and this surveillance should be conducted frequently and country-representative

Predictors of Viral Non-Suppression among Patients Living with HIV under Dolutegravir in Bunia, Democratic Republic of Congo: A Prospective Cohort Study

The Democratic Republic of the Congo adopted the integrase inhibitor dolutegravir (DTG) as part of its preferred first-line HIV treatment regimen in 2019. This study aimed to identify predictors of viral non-suppression among HIV-infected patients under a DTG-based regimen in the context of ongoing armed conflict since 2017 in the city of Bunia in the DRC. We conducted a cohort study of 468 patients living with HIV under DTG in all health facilities in Bunia. We calculated the proportion of participants with an HIV RNA of below 50 copies per milliliter. About three in four patients (72.8%) in this cohort had a viral load (VL) of <50 copies/mL after 6–12 months. After controlling for the effect of other covariates, the likelihood of having non-suppression remained significantly lower among the 25–34 age group and self-reported naïve patients with a baseline VL of ≥50 copies/mL. The likelihood of having non-suppression remained significantly higher among those who were at advanced stages of the disease, those with abnormal serum creatinine, those with high baseline HIV viremia over 1000 copies/mL, and the Sudanese ethnic group compared to the reference groups. This study suggests that we should better evaluate adherence, especially among adolescents and economically vulnerable populations, such as the Sudanese ethnic group in the city of Bunia. This suggests that an awareness of the potential effects of DTG and tenofovir is important for providers who take care of HIV-positive patients using antiretroviral therapy (ART), especially those with abnormal serum creatinine levels before starting treatment

Congrès AFMED 2017 : Co-infection VIH-Helminthiases intestinales à Kinshasa (RD Congo) : fréquence et facteurs associés: HIV-Helminthiasis co-infection in Kinshasa (DR Congo): frequency and associated factors

Objectifs. Montrer l‟ampleur des helminthiases intestinales chez les PVVs adultes en milieu de soins à Kinshasa et en identifier les facteurs associés.Méthodes. Étude transversale à visée analytique réalisée dans 8 structures de prise en charge des PVVs à Kinshasa choisies de manière aléatoire. Quatre cent vingt-deux PVVs adultes ont été incluses dans l‟étude selon une approche probabiliste. Un questionnaire pré-testé leur a été administré. Chaque patient avait remis un échantillon de selle conservé dans du formol à 10% pour examen par la méthode de RITCHIE. Les données ont été analysées l‟aide du logiciel SPSS version 21. La régression logistique a servi à identifier les facteurs associés à l‟infection helminthique chez les PVVs.Résultats. Sur 422 PVV, 324 étaient des femmes, soit un sex ratio de 1H/3,3F ; soit 10 H pour 33 F. L‟âge moyen était de 42 ans (ET =10 ans).La fréquence globale des helminthiases intestinales était de 22% (93/422). L‟helminthe le plus retrouvé était Ascaris lumbricoides 44/422 (10,4%) suivi de Trichuris trichiura (Trichocéphale) 33/422 (7,8%), et de Strongyloides stercoralis (Anguillule) 14/422 (3,3%). Ce dernier helminthe était associé à un taux de LT CD4 bas. Aucune infection helminthique mixte n‟a été détectée. Le taux de lymphocytes T CD4 médian était de 388 éléments/mm3 (EIQ : 342-412) pour toutes les PVVs de l‟étude, et 425 éléments/mm3 (EIQ : 373-456) pour les co-infectées, avec comme extrêmes : 13-1421 éléments/mm3. Plus de 70% de PVV étaient atteints d‟infections à faible intensité. Après ajustement, l‟utilisation d‟eau de robinet [OR ajusté 3,62 IC95% (1,04-12,58), p=0,018], la consommation des légumes crus ou fruits frais [OR ajusté 1,80 IC95% (1,11-2,92), p=0,018], la non consommation d‟eau traitée [OR ajusté 2,84 IC95% (1,81-4,72), p=0,018], le non lavage hygiénique des mains après usage de toilettes [OR ajusté 2,65 IC95% (1,14-8,21), p=0,010] et avant de manger [OR ajusté 2,01 IC95% (1,09-6,73), p=0,004] étaient les facteurs associés à l‟helminthiase intestinale.Conclusion. La co-infection VIH-helminthiasiase intestinale est fréquente à Kinshasa. Ascaris lumbrocoides est l‟helminthe le plus retrouvé. L‟immunodépression avancée favorise la strongyloïdose. Les campagnes de sensibilisation sur l‟éducation sanitaire et le déparasitage intermittent de masse chez les PVVs devraient être à envisagés

Assessment of Plasmodium falciparum anti-malarial drug resistance markers in pfk13-propeller, pfcrt and pfmdr1 genes in isolates from treatment failure patients in Democratic Republic of Congo, 2018–2019

Background: The national policy for malaria treatment of the Democratic Republic of Congo recommends two first-line artemisinin-based combinations for the treatment of uncomplicated malaria: artesunate-amodiaquine and artemether-lumefantrine. This study investigated the presence of markers associated with resistance to the current first-line artemisinin-based combination therapy (ACT) in isolates of Plasmodium falciparum from treatment failure patients in the Democratic Republic of Congo. Methods: From November 2018 to November 2019, dried blood spots were taken from patients returning to health centres for fever within 28 days after an initial malaria treatment in six sentinel sites of the National Malaria Control Programme across Democratic Republic of Congo. The new episode of malaria was first detected by a rapid diagnostic test and then confirmed by a real-time PCR assay to define treatment failure. Fragments of interest in pfk13 and pfcrt genes were amplified by conventional PCR before sequencing and the Pfmdr1 gene copy number was determined by a TaqMan real-time PCR assay. Results: Out of 474 enrolled patients, 364 (76.8%) were confirmed positive by PCR for a new episode of P. falciparum malaria, thus considered as treatment failure. Of the 325 P. falciparum isolates obtained from 364 P. falciparum-positive patients and successfully sequenced in the pfk13-propeller gene, 7 (2.2%) isolates carried non-synonymous mutations, among which 3 have been previously reported (N498I, N554K and A557S) and 4 had not yet been reported (F506L, E507V, D516E and G538S). Of the 335 isolates successfully sequenced in the pfcrt gene, 139 (41.5%) harboured the K76T mutation known to be associated with chloroquine resistance. The SVMNT haplotype associated with resistance to amodiaquine was not found. None of the isolates carried an increased copy number of the pfmdr1 gene among the 322 P. falciparum isolates successfully analysed

Biennial surveillance of Plasmodium falciparum anti-malarial drug resistance markers in Democratic Republic of Congo, 2017 and 2019

Background: Because of the loss of chloroquine (CQ) effectiveness, the Democratic Republic of Congo (DRC)’s malaria treatment policy replaced CQ by sulfadoxine–pyrimethamine (SP) as first‑line treatment of uncomplicated malaria in 2003, which in turn was replaced by artemisinin‑based combination therapies (ACT) in 2005. The World Health Organization (WHO) recommends monitoring of anti‑malarial drug resistance every 2 years. The study aimed to provide baseline data for biennial molecular surveillance of anti‑malarial drug resistance by comparing data from a study conducted in 2019 to previously published data from a similar study conducted in 2017 in the DRC. Methods: From July to November 2019, a cross‑sectional study was conducted in ten sites which were previously selected for a similar study conducted in 2017 across the DRC. P. falciparum malaria was diagnosed by a rapid diagnostic test (RDT) or by microscopy and dried blood samples (DBS) were taken from patients who had a positive test. Segments of interest in pfcrt and pfk13 genes were amplified by conventional PCR before sequencing. Results: Out of 1087 enrolled patients, 906 (83.3%) were PCR‑confirmed for P. falciparum. Like in the 2017‑study, none of the mutations known to be associated with Artemisinine (ART) resistance in Southeast Asia was detected. How‑ ever, non‑synonymous (NS) mutations with unknown functions were observed among which, A578S was detected in both 2017 and 2019‑studies. The overall prevalence of pfcrt‑K76T mutation that confers CQ‑resistance was 22.7% in 2019‑study compared to 28.5% in 2017‑study (p‑value = 0.069), but there was high variability between sites in the two studies. Like in 2017‑study, the pfcrt 72–76 SVMNT haplotype associated with resistance to amodiaquine was not detected. Conclusion: The study reported, within 2 years, the non‑presence of molecular markers currently known to be associated with resistance to ART and to AQ in P. falciparum isolated in the DRC. However, the presence of polymorphisms with as‑yet unknown functions was observed, requiring further characterization. Moreover, an overall decrease in the prevalence of CQ‑resistance marker was observed in the DRC, but this prevalence remained highly variable from region to regio