Xpert Mycobacterium tuberculosis/Rifampicin-Detected Rifampicin Resistance is a Suboptimal Surrogate for Multidrug-resistant Tuberculosis in Eastern Democratic Republic of the Congo: Diagnostic and Clinical Implications.

BACKGROUND: Rifampicin (RIF) resistance is highly correlated with isoniazid (INH) resistance and used as proxy for multidrug-resistant tuberculosis (MDR-TB). Using MTBDRplus as a comparator, we evaluated the predictive value of Xpert MTB/RIF (Xpert)-detected RIF resistance for MDR-TB in eastern Democratic Republic of the Congo (DRC). METHODS: We conducted a cross-sectional study involving data from new or retreatment pulmonary adult TB cases evaluated between July 2013 and December 2016. Separate, paired sputa for smear microscopy and MTBDRplus were collected. Xpert testing was performed subject to the availability of Xpert cartridges on sample remnants after microscopy. RESULTS: Among 353 patients, 193 (54.7%) were previously treated and 224 (63.5%) were MTBDRplus TB positive. Of the 224, 43 (19.2%) were RIF monoresistant, 11 (4.9%) were INH monoresistant, 53 (23.7%) had MDR-TB, and 117 (52.2%) were RIF and INH susceptible. Overall, among the 96 samples detected by MTBDRplus as RIF resistant, 53 (55.2%) had MDR-TB. Xpert testing was performed in 179 (50.7%) specimens; among these, 163 (91.1%) were TB positive and 73 (44.8%) RIF resistant. Only 45/73 (61.6%) Xpert-identified RIF-resistant isolates had concomitant MTBDRplus-detected INH resistance. Xpert had a sensitivity of 100.0% (95% CI, 92.1-100.0) for detecting RIF resistance but a positive-predictive value of only 61.6% (95% CI, 49.5-72.8) for MDR-TB. The most frequent mutations associated with RIF and INH resistance were S531L and S315T1, respectively. CONCLUSIONS: In this high-risk MDR-TB study population, Xpert had low positive-predictive value for the presence of MDR-TB. Comprehensive resistance testing for both INH and RIF should be performed in this setting.

Challenge to treat pre-extensively drug-resistant tuberculosis in a low-income country: A report of 12 cases.

Setting: Democratic Republic of the Congo is a high-burden TB country. Its capital, Kinshasa, reports annually about one-third of all MDR-TB cases in the country; thus, pre-XDRTB management is warranted. OBJECTIVES: To describe the main challenges in treating pre- XDR TB in this low resources setting and possible solutions. METHOD: This is a retrospective study of all pre-XDR TB patients diagnosed in Kinshasa in 2018. A personalized regimen was applied according to the clinical profile, drug availability, and the Drug susceptibility testing (DST). Treatment was administered by hospitalization during the intensive phase and in ambulatory care in the continuation phase except in emergencies. Monthly follow up included evaluating clinical and bacteriological features, renal and liver functions, QT interval on ECG, and audiometry for those under aminoglycosides. RESULTS: Among the 236 MDR-TB patients identified in 2018, 14 had pre-XDR. Two died before treatment initiation. Of the remaining 12. 75% were male, 50% were aged 25-44 years, 66.7% had previous anti-tuberculosis treatment, 75% had a body mass index < 18.5 kg/m2, and 1 patient was HIV positive. On radiography, all the patients had cavities. The median time from the diagnosis to treatment initiation was 48.5 days (range: 14-105). A favorable outcome occurred in 10 cases (83.3%), one patient died, and anotherwas lost to follow up. Nine (75%) patients reported adverse reactions, which were mild or moderate in 6 cases and severe in 2 cases. The severe reactions were psychosis (1 case) and ototoxicity (1 case). CONCLUSION: Successful pre-XDRTB treatment using the new strategy is possible even in a low-income country. The main challenges are diagnosis access, drug availability and follow-up laboratory facilities. These can be included in a global policy review by the NTP to ensure the sustainability of the strategies implemented.

Outcomes and adverse events of pre- and extensively drug-resistant tuberculosis patients in Kinshasa, Democratique Republic of the Congo: A retrospective cohort study.

BACKGROUND: Extensively drug-resistant tuberculosis (XDR TB) is a very serious form of tuberculosis that is burdened with a heavy mortality toll, especially before the advent of new TB drugs. The Democratic Republic of the Congo (DRC) is among the countries most affected by this new epidemic. METHODS: A retrospective analysis was performed of the records of all patients with pre- and extensively drug-resistant tuberculosis hospitalized from January 1, 2015 to December 31, 2017 and monitored for at least 6 months to one year after the end of their treatment in Kinshasa; an individualized therapeutic regimen with bedaquiline for 20 months was built for each patient. The adverse effects were systematically monitored. RESULTS: Of the 40 laboratory-confirmed patients, 32 (80%) patients started treatment, including 29 preXRB and 3 XDR TB patients. In the eligible group, 3 patients (9.4%) had HIV-TB coinfections. The therapeutic success rate was 53.2%, and the mortality rate was 46.8% (15/32); there were no relapses, failures or losses to follow-up. All coinfected HIV-TB patients died during treatment. The cumulative patient survival rate was 62.5% at 3 months, 53.1% at 6 months and 53.1% at 20 months. The most common adverse events were vomiting, Skin rash, anemia and peripheral neuropathy. CONCLUSION: The new anti-tuberculosis drugs are a real hope for the management of Drug Resistant tuberculosis patient and other new therapeutic combinations may improve favorable outcomes.

Outcomes of a nine-month regimen for rifampicin-resistant tuberculosis up to 24 months after treatment completion in nine African countries.

BACKGROUND: Treatment outcomes of the shorter regimen for rifampicin-resistant tuberculosis are not completely established. We report on these outcomes two years after treatment completion among patients enrolled in an observational cohort study in nine African countries. METHODS: 1,006 patients treated with the nine-month regimen were followed every six months with sputum cultures up to 24 months after treatment completion. The risk of any unfavourable outcome, of failure and relapse, and of death during and after treatment was analysed according to patient's characteristics and initial drug susceptibility by Cox proportional hazard models. FINDINGS: Respectively 67.8% and 57.2% patients had >=1 culture result six months and 12 months after treatment completion. Fourteen relapses were diagnosed. The probability of relapse-free success was 79.3% (95% confidence interval [CI] 76.6-82.0%) overall, 80.9% (95% CI 78.0-84.0%) among HIV-negative and 72.5% (95% CI 66.5-78.9%) among HIV-infected patients. Initial fluoroquinolone (adjusted hazard ratio [aHR] 6.7 [95% CI 3.4-13.1]) and isoniazid resistance (aHR 9.4 [95% CI 1.3-68.0]) were significantly associated with increased risk of failure/relapse and of any unfavourable outcome. INTERPRETATION: The close to 80% relapse-free success indicates the good outcome of the regimen in low-and middle-income settings. Results confirm the lesser effectiveness of the regimen in patients with initial resistance to fluoroquinolones and support the use of high-dose isoniazid, but do not support exclusion of patients for resistance to drugs other than fluoroquinolones. FUNDING: Expertise-France and Agence Française de Développement.

Prevalence, Predictors, and Successful Treatment Outcomes of Xpert MTB/RIF-identified Rifampicin-resistant Tuberculosis in Post-conflict Eastern Democratic Republic of the Congo, 2012-2017: A Retrospective Province-Wide Cohort Study.

BACKGROUND: Multidrug-resistant tuberculosis (MDR-TB) jeopardizes global TB control. The prevalence and predictors of Rifampicin-resistant (RR) TB, a proxy for MDR-TB, and the treatment outcomes with standard and shortened regimens have not been assessed in post-conflict regions, such as the South Kivu province in the eastern Democratic Republic of the Congo (DRC). We aimed to fill this knowledge gap and to inform the DRC National TB Program. METHODS: of adults and children evaluated for pulmonary TB by sputum smear microscopy and Xpert MTB/RIF (Xpert) from February 2012 to June 2017. Multivariable logistic regression, Kaplan-Meier estimates, and multivariable Cox regression were used to assess independent predictors of RR-TB and treatment failure/death. RESULTS: Of 1535 patients Xpert-positive for TB, 11% had RR-TB. Independent predictors of RR-TB were a positive sputum smear (adjusted odds ratio [aOR] 2.42, 95% confidence interval [CI] 1.63-3.59), retreatment of TB (aOR 4.92, 95% CI 2.31-10.45), and one or more prior TB episodes (aOR 1.77 per episode, 95% CI 1.01-3.10). Over 45% of RR-TB patients had no prior TB history or treatment. The median time from Xpert diagnosis to RR-TB treatment initiation was 12 days (interquartile range 3-60.2). Cures were achieved in 30/36 (83%) and 84/114 (74%) of patients on 9- vs 20/24-month MDR-TB regimens, respectively (P = .06). Predictors of treatment failure/death were the absence of directly observed therapy (DOT; adjusted hazard ratio [aHR] 2.77, 95% CI 1.2-6.66) and any serious adverse drug event (aHR 4.28, 95% CI 1.88-9.71). CONCLUSIONS: Favorable RR-TB cure rates are achievable in this post-conflict setting with a high RR-TB prevalence. An expanded Xpert scale-up; the prompt initiation of shorter, safer, highly effective MDR-TB regimens; and treatment adherence support are critically needed to optimize outcomes.

Household Air Pollution Is Associated with Chronic Cough but Not Hemoptysis after Completion of Pulmonary Tuberculosis Treatment in Adults, Rural Eastern Democratic Republic of Congo.

Little is known about the respiratory health damage related to household air pollution (HAP) in survivors of pulmonary tuberculosis (PTB). In a population-based cross-sectional study, we determined the prevalence and associated predictors of chronic cough and hemoptysis in 441 randomly selected PTB survivors living in 13 remote health zones with high TB burden in the South Kivu province of the Democratic Republic of Congo (DRC). Trained community and health-care workers administered a validated questionnaire. In a multivariate logistic regression, chronic cough was independently associated with HAP (adjusted odds ratios (aOR) 2.10, 95% CI: 1.10⁻4.00) and PTB treatment >6 months (aOR 3.80, 95% CI: 1.62⁻8.96). Among women, chronic cough was associated with cooking ≥3 h daily (aOR 2.74, 95% CI: 1.25⁻6.07) and with HAP (aOR 3.93, 95% CI: 1.15⁻13.43). Independent predictors of hemoptysis were PTB retreatment (aOR 3.04, 95% CI: 1.04⁻5.09) and ignorance of treatment outcome (aOR 2.24, 95% CI: 1.09⁻4.58) but not HAP (aOR 1.86, 95% CI: 0.61⁻5.62). Exposure to HAP proved a major risk factor for chronic cough in PTB survivors, especially in women. This factor is amenable to intervention.

Profil de sensibilisation aux allergènes des asthmatiques adultes à Kinshasa, RDC : Etude transversale par prick-tests

Contexte. Environ 80% des asthmatiques sont atopiques. La sensibilisation aux allergènes communs présente certaines variabilités environnementales et géographiques. Objectif. Déterminer le profil de sensibilisation aux allergènes communs des asthmatiques adultes de la ville de Kinshasa. Méthodes. De juin 2017 à février 2018, 216 asthmatiques de 18 ans et plus, des 2 sexes, ont été consécutivement recrutés aux Cliniques Universitaires de Kinshasa et dans certaines paroisses et églises de réveil de la ville de Kinshasa. A l'aide d'un questionnaire validé, les variables sociodémographiques ont été précisées. Le prick-test a été réalisé avec cinq extraits commerciaux standardisés de phanères de chien et chat, l'acarien de poussière de maison (Blomia tropicalis, Bt), les moisissures (Alternaria alternata), et le jaune d'œuf. Résultats. L'âge moyen de la population était de 45,23 (ET=17,56) ans, 74% de sexe féminin, 47 % non sensibilisés et 53% sensibilisés à au moins un allergène. Vingt-cinq pourcent étaient monosensibilisées et 27% plurisensibilisées. Le profil de sensibilisation était Blomia tropicalis (72%), phanères de chat (46%), phanères de chien (34%), Alternaria alternata (13%) et jaune d'œuf (11%). Conclusion. Une plurisensibilisation aux allergènes communs chez les asthmatiques dans notre milieu est présente dont le profil dominé par les acariens et les phanères de chats. Des enquêtes futures incluant un plus grand nombre de sujets et recourant à des batteries de tests plus élargies s'imposent en vue d'une définition d'options diagnostiques et thérapeutiques dans notre contexte

Prevalence and determinants of asthma in adults in Kinshasa.

BACKGROUND: Epidemiological data on asthma among adults in sub-Saharan Africa are sparse. OBJECTIVE: To determine the prevalence of and factors associated with asthma among adults in Kinshasa. METHODS: A previously validated asthma questionnaire was administered to an adult population aged ≥18 years in urban and peri-urban suburbs of Kinshasa. A random stratified multi-stage sampling plan was used to select the study participants. Logistic regression was used to identify factors associated with asthma. RESULTS: The mean age of respondents was 36.7 (SD 15.36) years, 75% lived in an urban environment, and 57% were women. The prevalence of asthma-ever was 6.9% (95% CI: 5.4-8.4). Among asthmatic patients, intermittent asthma was estimated at 75.7% and severe asthma at 9.3%. Family atopy (OR: 3.97; 95% CI: 2.42-6.50; p<0.001), and the presence of a cat in the house (OR: 1.82; 95% CI: 1.01-3.28; p = 0.045) were associated with self-reported asthma. CONCLUSION: Asthma is relatively frequent in adults in Kinshasa, a prevalence similar to those reported elsewhere in Africa. Family atopy and the presence of a cat in the house could be the most common determinants to be confirmed with national survey in order to design guidelines for the control of asthma.

Obesity and diabetes mellitus association in rural community of Katana, South Kivu, in Eastern Democratic Republic of Congo: Bukavu Observ Cohort Study Results.

BACKGROUND: Factual data exploring the relationship between obesity and diabetes mellitus prevalence from rural areas of sub-Saharan Africa remain scattered and are unreliable. To address this scarceness, this work reports population study data describing the relationship between the obesity and the diabetes mellitus in the general population of the rural area of Katana (South Kivu in the Democratic Republic of the Congo). METHODS: A cohort of three thousand, nine hundred, and sixty-two (3962) adults (>15 years old) were followed between 2012 and 2015 (or 4105 person-years during the observation period), and data were collected using the locally adjusted World Health Organization's (WHO) STEPwise approach to Surveillance (STEPS) methodology. The hazard ratio for progression of obesity was calculated. The association between diabetes mellitus and obesity was analyzed with logistic regression. RESULTS: The diabetes mellitus prevalence was 2.8 % versus 3.5 % for obese participants and 7.2 % for those with metabolic syndrome, respectively. Within the diabetes group, 26.9 % had above-normal waist circumference and only 9.8 % were obese. During the median follow-up period of 2 years, the incidence of obesity was 535/100,000 person-years. During the follow-up, the prevalence of abdominal obesity significantly increased by 23 % (p <0.0001), whereas the increased prevalence of general obesity (7.8 %) was not significant (p = 0.53). Finally, diabetes mellitus was independently associated with age, waist circumference, and blood pressure but not body mass index. CONCLUSION: This study confirms an association between diabetes mellitus and abdominal obesity but not with general obesity. On the other hand, the rapid increase in abdominal obesity prevalence in this rural area population within the follow-up period calls for the urgent promoting of preventive lifestyle measures.

Childhood Tuberculosis in a Sub-Saharan Tertiary Facility: Epidemiology and Factors Associated with Treatment Outcome.

Childhood tuberculosis (TB) is a diagnostic challenge in developing countries, and patient outcome can be influenced by certain factors. We report the disease course, clinical profile and factors associated with treatment outcome in a tertiary facility of Kinshasa. Documentary and analytical studies were conducted using clinical and exploratory data for children aged up to 15 years who were admitted to the University Clinics of Kinshasa for TB. Data are presented as frequencies and averages, and binary and logistic regression analyses were performed. Of 283 children with TB, 82 (29.0%) had smear-negative TB, 40 (14.1%) had smear-positive TB, 159 (56.1%) had extra-pulmonary TB (EPTB), 2 (0.7%) had multidrug-resistant TB (MDR-TB), 167 (59.0%) completed treatment, 30 (10.6%) were cured, 7 (2.5%) failed treatment, 4 (1.4%) died, 55 (19.4%) were transferred to health centers nearest their home, and 20 (7.0%) were defaulters. In the binary analysis, reported TB contacts (p = 0.048), type of TB (p = 0.000), HIV status (p = 0.050), Ziehl-Nielsen test result (p = 0.000), Lowenstein culture (p = 0.004) and chest X-ray (p = 0.057) were associated with outcome. In the logistic regression, none of these factors was a significant predictor of outcome. Tertiary level care facilities must improve the diagnosis and care of patients with childhood TB, which justifies the development of alternative diagnostic techniques and the assessment of other factors that potentially affect outcome.

[Hypertension in the adult Congolese population of Southern Kivu: Results of the Vitaraa Study]. / Hypertension artérielle chez l'adulte Congolais du Sud Kivu : résultats de l'étude Vitaraa.

OBJECTIVE: To assess the prevalence of cardiovascular risk factors in adult urban and rural Congolese subjects. METHODS: We obtained anthropometric data and information on life habits and medical history in 699 people ≥ 20 years, 444 in an urban, 255 in a rural setting. We determined the body mass index and recorded two blood pressure measurements that were averaged for analysis. Hypertension was BP ≥ 140/90mmHg, awareness and/or use of antihypertensive treatment. Diabetes mellitus was self-reported diagnosis or a casual glycemia ≥ 200mg/dL. We assessed the probability of hypertension in stepwise multiple logistic analysis, and awareness, and control of hypertension. RESULTS: We found higher (P<0.001) prevalence in the urban than the rural subjects for hypertension (41.4% vs 38.1%), diabetes (4.9% vs 3.2%), overweight/obesity (37.6% vs 16.5%), abdominal obesity (30.9% vs 12.9%), use of alcohol (45% vs 17.6%) and smoking (11.6% vs 1.2%). Hypertension was associated (P<0.05) to aging in 51.3%, overweight/obesity in 54.5%, diabetes in 69%, abdominal obesity in 63.8%, low physical activity in 42.4%, to stress in urban environment in 43.2% and professional position (executives: 53.2%, workers: 38.6%). Of these hypertensive subjects, 57.5% were unaware, 30.5% were treated, with control achieved in only 13.6% (17.4% women vs 6.9% men; P<0.01). In the logistic model, the probability of hypertension increased with age (OR for age>55 years: 2.35; P<0.001), overweight/obesity (2.22; P<0.001) and diabetes mellitus (2.67; P<0.05). CONCLUSIONS: Our results indicate a heavy burden of uncontrolled risk factors in the Congolese population the potential complications of which run at a high mortality rate. They highlight the need for reasonable prevention measures at the population level.

[Hypertension, insulin resistance and chronic kidney disease in type 2 diabetes patients from South Kivu, DR Congo]. / Hypertension artérielle, insulinorésistance et maladie rénale chronique dans un groupe de diabétiques de type 2 du Sud-Kivu, RD Congo.

OBJECTIVE: To assess the frequency and determinants of high blood pressure (HBP) in a group of type 2 black diabetics living in the east of Democratic Republic of Congo. METHODOLOGY: The medical records of 98 diabetic patients followed at the General Reference Hospital in Bukavu between 2005 and 2007 were collected and analyzed. Hypertension was defined as blood pressure≥140/90mmHg. Insulin sensitivity (HOMA S; %) was determined with the HOMA model, with insulin resistance (IR) representing HOMA S(-1) and defined from HOMA S values<50%). Patients were phenotyped regarding their cardiometabolic profile using metabolic syndrome criteria (minus that for HBP). The probability of hypertension was assessed by multiple logistic regression. RESULTS: There was an overall high prevalence of HBP (59.6%) and of chronic kidney disease (66%) contrasting with a low frequency of insulin resistance (5.2%) and obesity (18.6%). In addition, hypertension was not associated with insulin resistance [regression of SBP by % S: regression coefficient, 0.007 (-0.090-0.104) mmHg; correlation coefficient, 0.00; p = 0.89], [regression of DBP by % S: -0.004 (-0.053-0.045) mmHg; 0.00; 0.87]. There was no significant difference in prevalence of metabolic syndrome changed between hypertensive and normotensive patients [38.6% versus 33.3%, p = 0.60]. In multivariate analysis, overweight [OR adjusted = 3.20 (95%: 1.19-8.61), p = 0.02] and CKD [2.49 (0,98-6.34; 0.05] were found as major determinants of hypertension. CONCLUSION: The metabolic syndrome is poorly predictive of an absolute decrease in insulin sensitivity in a type 2 diabetes population, in which the prevalence of hypertension was high, and that of insulin resistance low. Overweight independently of insulin resistance and chronic kidney disease common in type 2 diabetes in Sub-Saharan Africa in which the disease is poorly controlled may play a major role in the determinism of hypertension.