Reduction of diagnostic and treatment delays reduces rifampicin-resistant tuberculosis mortality in Rwanda.

SETTING: In 2005, in response to the increasing prevalence of rifampicin-resistant tuberculosis (RR-TB) and poor treatment outcomes, Rwanda initiated the programmatic management of RR-TB, including expanded access to systematic rifampicin drug susceptibility testing (DST) and standardised treatment.OBJECTIVE: To describe trends in diagnostic and treatment delays and estimate their effect on RR-TB mortality.DESIGN: Retrospective analysis of individual-level data including 748 (85.4%) of 876 patients diagnosed with RR-TB notified to the World Health Organization between 1 July 2005 and 31 December 2016 in Rwanda. Logistic regression was used to estimate the effect of diagnostic and therapeutic delays on RR-TB mortality.RESULTS: Between 2006 and 2016, the median diagnostic delay significantly decreased from 88 days to 1 day, and the therapeutic delay from 76 days to 3 days. Simultaneously, RR-TB mortality significantly decreased from 30.8% in 2006 to 6.9% in 2016. Total delay in starting multidrug-resistant TB (MDR-TB) treatment of more than 100 days was associated with more than two-fold higher odds for dying. When delays were long, empirical RR-TB treatment initiation was associated with a lower mortality.CONCLUSION: The reduction of diagnostic and treatment delays reduced RR-TB mortality. We anticipate that universal testing for RR-TB, short diagnostic and therapeutic delays and effective standardised MDR-TB treatment will further decrease RR-TB mortality in Rwanda.

Risk factors for delay in the diagnosis and treatment of tuberculosis at a referral hospital in Rwanda.

SETTING: Kigali University Hospital, the main referral centre for TB in Rwanda. OBJECTIVE: To evaluate delays in the diagnosis and treatment of tuberculosis (TB) and associated risk factors. DESIGN: Prospective data collection of patients treated for pulmonary TB (PTB) or extra-pulmonary TB (EPTB) between June and September 2006. RESULTS: Of 104 patients with a mean age of 35 years (range 17-84) recruited into the study, 62% were HIV-positive. EPTB was diagnosed in 60 cases. The median total, health care and patient delays were respectively 57, 28 and 25 days. The health system delay before referral was significantly longer than the delay at our institution (18 vs. 6 days, P<0.0001). Risk factors for a longer health system delay at our institution were smear-negative PTB or EPTB (OR 5.12) and a trial of antibiotics (OR 2.96). The latter was also found to significantly prolong total delay (OR 2.85), as did rural residence (OR 4.86). No significant association was found between patient delay and age, sex, profession or health insurance status. CONCLUSION: Smear-negative PTB and EPTB were associated with longer health system delays. A trial of antibiotics significantly increased the health system delay. Its use, recommended by the World Health Organization in case of smear-negative TB and EPTB in developing countries, needs validation at the tertiary health care level.

Integrating tuberculosis and HIV care in rural Rwanda.

SETTING: Rwanda has generalised human immunodeficiency virus (HIV) and tuberculosis (TB) epidemics. The Rwandan Ministry of Health approved a policy on TB-HIV collaborative activities in 2005. The present study is a report on the results of the integrated TB and HIV activities at a rural health care site between July 2005 and June 2006. METHODS: Activities included provider-initiated HIV testing and counselling (PITC) of TB patients and the implementation of a standardised TB screening questionnaire for in-patients on medical wards and HIV-infected out-patients. RESULTS: Of a total 259 TB patients registered, 87% with unknown HIV status or who were HIV-negative accepted PITC. Overall, 48% (125/259) of TB patients were HIV-infected. The proportion of TB patients ever tested for HIV increased from 82% (138/169) in 2004-2005 to 93% (240/259) in 2005-2006 (P < 0.001). Of the 770 in-patients screened for TB, 162 (21%) tested positive, of whom 53 (33%) were diagnosed with TB; 39 (76%) of these were HIV co-infected. Three hundred out-patients with HIV were screened for TB; 80 (27%) tested positive, of whom 11 (14%) were diagnosed with TB. DISCUSSION: Activities integrating TB and HIV were feasible in a rural health care setting. PITC was successful in TB patients and unrecognised TB was common, particularly among HIV-infected in-patients.

Treatment outcome with a short multidrug-resistant tuberculosis regimen in nine African countries.

SETTING: Nine countries in West and Central Africa. OBJECTIVE: To assess outcomes and adverse drug events of a standardised 9-month treatment regimen for multidrug-resistant tuberculosis (MDR-TB) among patients never previously treated with second-line drugs. DESIGN: Prospective observational study of MDR-TB patients treated with a standardised 9-month regimen including moxifloxacin, clofazimine, ethambutol (EMB) and pyrazinamide (PZA) throughout, supplemented by kanamycin, prothionamide and high-dose isoniazid during an intensive phase of a minimum of 4 to a maximum of 6 months. RESULTS: Among the 1006 MDR-TB patients included in the study, 200 (19.9%) were infected with the human immunodeficiency virus (HIV). Outcomes were as follows: 728 (72.4%) cured, 93 (9.2%) treatment completed (81.6% success), 59 (5.9%) failures, 78 (7.8%) deaths, 48 (4.8%) lost to follow-up. The proportion of deaths was much higher among HIV-infected patients (19.0% vs. 5.0%). Treatment success did not differ by HIV status among survivors. Fluoroquinolone resistance was the main cause of failure, while resistance to PZA, ethionamide or EMB did not influence bacteriological outcome. The most important adverse drug event was hearing impairment (11.4% severe deterioration after 4 months). CONCLUSIONS: The study results support the use of the short regimen recently recommended by the World Health Organization. Its high level of success even among HIV-positive patients promises substantial improvements in TB control.

Results of a national survey on drug resistance among pulmonary tuberculosis patients in Rwanda.

BACKGROUND: One of the principal objectives of tuberculosis (TB) control is to minimise the emergence of drug resistance. The first national survey was conducted in Rwanda to determine the prevalence of M. tuberculosis drug resistance. METHODS: Sputum samples were collected from all new and retreatment cases in the health districts from November 2004 to February 2005. Drug susceptibility testing of isolates against first-line drugs was performed by the proportion method. RESULTS: Of 616 strains from new cases, 6.2% were resistant to isoniazid, 3.9% to rifampicin and 3.9% were multidrug-resistant TB. Among 85 strains from previously treated cases, the prevalence of resistance was respectively 10.6%, 10.6% and 9.4% (MDR-TB strains). Eight MDR cases showed additional resistance to ethambutol and streptomycin. CONCLUSION: The level of MDR-TB among TB patients in Rwanda is high. The main reasons of this emergence of MDR-TB can be attributed to the disorganisation of the health system, migration of the population during the 1994 civil war and poor success rates, with a high number of patients transferred out and lost to follow-up. On the other hand, the use of treatment regimens administered twice weekly during the continuation phase could be another important factor and merit further investigations.

[Primary and acquired resistance to antituberculous drugs in strains of Mycobacterium tuberculosis isolated in Rwanda]. / Résistance primaire et acquise aux antituberculeux des souches de Mycobacterium tuberculosis isolées au Rwanda.

This study was undertaken within the framework of a surveillance project on the resistance of Mycobacterium tuberculosis to first-line antituberculosis drugs in four provinces of Rwanda with a high prevalence of tuberculosis (TB). The purpose was to determine the prevalence of primary and acquired resistance of M. tuberculosis to major antituberculosis drugs. A cohort of patients (n=710) with pulmonary TB documented by positive microscopic examinations of exhaustive samples was recruited at 7 treatment centers. Sputum samples were cultured on Löwenstein-Jensen and Coletsos media. Sensitivity to antituberculosis drugs was tested using a BACTEC 460 radiometric system. M. tuberculosis was isolated in 644 of the 710 patients (90.7%). A total of 296 out of 573 tested for HIV infection (51.7%) were positive. Primary resistance to one, two, three or four antituberculosis drugs was observed in 3.5%, 2.9%, 1.4% and 5.7% respectively. The prevalence of acquired resistance to antituberculosis drugs was 11.2%. Primary monoresistance to streptomycin was the most prevalent (2.3%) followed by resistance to ethambutol (1%). The combined rate of multiresistance was 11.6% with 7% involving new cases and 25.5% involving retreatment. This study showed that the rates of primary and acquired resistance to first-line antituberculosis drugs were high and that TB was associated with HIV infection. The National TB Control Program must implement measures to coordinate diagnosis and management of TB and HIV infection.

The effect of household poverty on tuberculosis.

pSETTING: Households in Malawi, Mongolia, Myanmar, the Philippines, Rwanda, Tanzania, Viet Nam and Zambia.OBJECTIVE To assess the relationship between household socio-economic level, both relative and absolute, and individual tuberculosis (TB) disease. DESIGN: We analysed national TB prevalence surveys from eight countries individually and in pooled multicountry models. Socio-economic level (SEL) was measured in terms of both relative household position and absolute wealth. The outcome of interest was whether or not an individual had TB disease. Logistic regression models were used to control for putative risk factors for TB disease such as age, sex and previous treatment history. RESULTS: Overall, a strong and consistent association between household SEL and individual TB disease was not found. Significant results were found in four individual country models, with the lowest socio-economic quintile being associated with higher TB risk in Mongolia, Myanmar, Tanzania and Viet Nam. CONCLUSIONS: TB prevalence surveys are designed to assess prevalence of disease and, due to the small numbers of cases usually detected, may not be the most efficient means of investigating TB risk factors. Different designs are needed, including measuring the SEL of individuals in nested case-control studies within TB prevalence surveys or among TB patients seeking treatment in health care facilities.

Tuberculosis may be underestimated in Rwandan women.

BACKGROUND AND HYPOTHESIS: The majority of adult tuberculosis (TB) cases reported to the surveillance system in Rwanda are male. If this results from detection mechanisms that are less sensitive to TB in women, notified cases should be more severe in women than in men. METHODS: We analysed the 2006 series of TB cases among persons aged ≥ 15 years in Huye District and Kigali. Severe TB was defined as disease leading to death, or extra-pulmonary or disseminated TB. RESULTS: Of 1673 cases identified, 40% involved women, who were younger than men (65% vs. 54% aged <35 years). Overall severity was similar in both sexes. Considering age <35 years, women were at higher risk of severe TB than men, although the difference was not statistically significant. Smear-negative pulmonary TB (SNPTB), and human immunodeficiency virus (HIV) infection were more frequent in women than in men (59% vs. 42%, P < 0.001). For women with smear-positive pulmonary TB (SPPTB), the risk of death was twice that among men (adjusted hazard ratio 1.8; 95%CI 1.0-3.2). CONCLUSIONS: Among female TB patients, the higher risk of death with SPPTB, the higher frequency of SNPTB and the higher prevalence of HIV infection suggest that the passive system of case detection may underestimate the burden of TB in Rwandan women.