Addressing the drug-resistant tuberculosis challenge through implementing a mixed model of care in Uganda.

Worldwide, Drug-resistant Tuberculosis (DR-TB) remains a big problem; the diagnostic capacity has superseded the clinical management capacity thereby causing ethical challenges. In Sub-Saharan Africa, treatment is either inadequate or lacking and some diagnosed patients are on treatment waiting lists. In Uganda, various health system challenges impeded scale-up of DR-TB care in 2012; only three treatment initiation facilities existed, with only 41 of the estimated 1010 RR-TB/MDR-TB cases enrolled on treatment yet 300 were on the waiting list and there was no DR-TB treatment scale-up plan. To scale up care, the National TB and leprosy Program (NTLP) with partners rolled out a DR-TB mixed model of care. In this paper, we share achievements and outcomes resulting from the implementation of this mixed Model of DR-TB care. Routine NTLP DR-TB program data on treatment initiation site, number of patients enrolled, their demographic characteristics, patient category, disease classification (based on disease site and human immunodeficiency virus (HIV) status), on co-trimoxazole preventive therapy (CPT) and antiretroviral therapy (ART) statuses, culture results, smear results and treatment outcomes (6, 12, and 24 months) from 2012 to 2017 RR-TB/MDR-TB cohorts were collected from all the 15 DR-TB treatment initiation sites and descriptive analysis was done using STATA version 14.2. We presented outcomes as the number of patient backlog cleared, DR-TB initiation sites, RR-TB/DR-TB cumulative patients enrolled, percentage of co-infected patients on the six, twelve interim and 24 months treatment outcomes as per the Uganda NTLP 2016 Programmatic Management of drug-resistant Tuberculosis (PMDT) guidelines (NTLP, 2016). Over the period 2013-2015, the RR-TB/MDR-TB Treatment success rate (TSR) was sustained between 70.1% and 74.1%, a performance that is well above the global TSR average rate of 50%. Additionally, the cure rate increased from 48.8% to 66.8% (P = 0.03). The Uganda DR-TB mixed model of care coupled with early application of continuous improvement approaches, enhanced cohort reviews and use of multi-disciplinary teams allowed for rapid DR-TB program expansion, rapid clearance of patient backlog, attainment of high cumulative enrollment and high treatment success rates. Sustainability of these achievements is needed to further reduce the DR-TB burden in the country. We highly recommend this mixed model of care in settings with similar challenges.

Early versus delayed initiation of highly active antiretroviral therapy for HIV-positive adults with newly diagnosed pulmonary tuberculosis (TB-HAART): a prospective, international, randomised, placebo-controlled trial.

BACKGROUND: WHO guidelines recommend early initiation of antiretroviral therapy (ART) irrespective of CD4 cell count for all patients with tuberculosis who also have HIV, but evidence supporting this approach is poor quality. We assessed the effect of timing of ART initiation on tuberculosis treatment outcomes for HIV-positive patients with CD4 counts of 220 cells per µL or more. METHODS: We did this randomised, placebo-controlled trial between Jan 1, 2008, and April 31, 2013 at 26 treatment centres in South Africa, Tanzania, Uganda, and Zambia. We enrolled HIV-positive patients with culture-confirmed tuberculosis who had tolerated 2 weeks of tuberculosis short course chemotherapy. Participants were randomly allocated (1:1) to early ART (starting after 2 weeks of tuberculosis treatment) or delayed ART (placebo, then starting ART at the end of 6 months of tuberculosis treatment). Randomisation was computer generated, with permuted blocks of size eight, and stratified by CD4 count (220-349 cells per µL vs ≥350 cells per µL). Patients and investigators were masked to treatment allocation until completion of 6-months' tuberculosis treatment, after which the study was open label. The primary endpoint was a composite of failure of tuberculosis treatment, tuberculosis recurrence, and death within 12 months of starting tuberculosis treatment in the modified intention-to-treat population. Secondary endpoints included mortality. The study is registered with controlled-trials.com (ISRCTN77861053). FINDINGS: We screened 13,588 patients and enrolled 1675: 834 assigned early ART, 841 delayed ART. The primary endpoint was reached by 65 (8·5%) of 767 patients in the early ART group versus 71 (9·2%) of 771 in the delayed ART group (relative risk [RR] 0·91, 95% CI 0·64-1·30; p=0·9). Of patients with a CD4 cell count of 220-349 cells per µL, 26 (7·9%) of 331 patients versus 33 (9·6%) of 342 reached the primary endpoint (RR 0·80, 95% CI 0·46-1·39; p=0·6). For those with 350 cells per µL or more, 39 (8·9%) of 436 versus 38 (8·9%) of 429 reached the primary endpoint (RR 1·01, 95% CI 0·63-1·62; p=0·4). Mortality did not differ significantly between treatment groups (RR 1·4, 95% CI 0·8-2·3; p=0·23). Grade 3 and 4 adverse events occurred in 149 (18%) of 834 patients assigned early ART versus 174 (21%) of 841 assigned delayed ART (p=0·37). 87 (10%) of 834 versus 84 (10%) of 841 had immune reconstitution inflammatory syndrome (p=0·56). INTERPRETATION: ART can be delayed until after completion of 6 months of tuberculosis treatment for HIV-positive patients with tuberculosis who have CD4 cell counts greater than 220 cells per µL. WHO guidelines should be updated accordingly. FUNDING: USAID, Zambia Ministry of Health, Tanzania Commission for Science and Technology, WHO-TDR.

Ebola haemorrhagic fever outbreak in Masindi District, Uganda: outbreak description and lessons learned.

BACKGROUND: Ebola haemorrhagic fever (EHF) is infamous for its high case-fatality proportion (CFP) and the ease with which it spreads among contacts of the diseased. We describe the course of the EHF outbreak in Masindi, Uganda, in the year 2000, and report on response activities. METHODS: We analysed surveillance records, hospital statistics, and our own observations during response activities. We used Fisher's exact tests for differences in proportions, t-tests for differences in means, and logistic regression for multivariable analysis. RESULTS: The response to the outbreak consisted of surveillance, case management, logistics and public mobilisation. Twenty-six EHF cases (24 laboratory confirmed, two probable) occurred between October 21st and December 22nd, 2000. CFP was 69% (18/26). Nosocomial transmission to the index case occurred in Lacor hospital in Gulu, outside the Ebola ward. After returning home to Masindi district the index case became the origin of a transmission chain within her own extended family (18 further cases), from index family members to health care workers (HCWs, 6 cases), and from HCWs to their household contacts (1 case). Five out of six occupational cases of EHF in HCWs occurred after the introduction of barrier nursing, probably due to breaches of barrier nursing principles. CFP was initially very high (76%) but decreased (20%) due to better case management after reinforcing the response team. The mobilisation of the community for the response efforts was challenging at the beginning, when fear, panic and mistrust had to be countered by the response team. CONCLUSIONS: Large scale transmission in the community beyond the index family was prevented by early case identification and isolation as well as quarantine imposed by the community. The high number of occupational EHF after implementing barrier nursing points at the need to strengthen training and supervision of local HCWs. The difference in CFP before and after reinforcing the response team together with observations on the ward suggest a critical role for intensive supportive treatment. Collecting high quality clinical data is a priority for future outbreaks in order to identify the best possible FHF treatment regime under field conditions.