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Objective To assess the effectiveness of a community-based tuberculosis and leprosy intervention in which village health teams and health workers conduct door-to-door tuberculosis screening, targeted screenings and contact tracing. Methods We conducted a before-and-after implementation study in Uganda to assess the effectiveness of the community tuberculosis intervention by looking at reach, outputs, adoption and effectiveness of the intervention. Campaign 1 was conducted in March 2022 and campaign 2 in September 2022. We calculated percentages of targets achieved and compared case notification rates during the intervention with corresponding quarters in the previous year. We also assessed the leprosy screening. Findings Over 5 days, campaign 1 screened 1 289 213 people (2.9% of the general population), of whom 179 144 (13.9%) fulfilled the presumptive tuberculosis criteria, and 4043 (2.3%) were diagnosed with bacteriologically-confirmed tuberculosis; 3710 (91.8%) individuals were linked to care. In campaign 2, 5 134 056 people (11.6% of the general population) were screened, detecting 428 444 (8.3%) presumptive tuberculosis patients and 8121 (1.9%) bacteriologically-confirmed tuberculosis patients; 5942 individuals (87.1%) were linked to care. The case notification rate increased from 48.1 to 59.5 per 100 000 population in campaign 1, with a case notification rate ratio of 1.24 (95% confidence interval, CI: 1.22--1.26). In campaign 2, the case notification rate increased from 45.0 to 71.6 per 100 000 population, with a case notification rate ratio of 1.59 (95% CI: 1.56--1.62). Of the 176 patients identified with leprosy, 137 (77.8%) initiated treatment. Conclusion This community tuberculosis screening initiative is effective. However, continuous monitoring and adaptations are needed to overcome context-specific implementation challenges. [ABSTRACT FROM AUTHOR]

Background: Tuberculosis (TB) is a major public health problem and at 48%, Karamoja in North-Eastern Uganda has the lowest treatment success rate nationally. Addressing the social determinants of TB is crucial to ending TB. This study sought to understand the extent and ways in which socio-economic factors affect TB treatment outcomes in Karamoja.Methods: We conducted a convergent parallel mixed methods study in 10 TB Diagnostic and Treatment Units. The study enrolled former TB patients diagnosed with drug-susceptible TB between April 2018 and March 2019. Unit TB and laboratory registers were reviewed to identify pre-treatment losses to follow-up. Four focus group discussions with former TB patients and 18 key informant interviews with healthcare workers were conducted. Principle component analysis was used to generate wealth quintiles that were compared to treatment outcomes using the proportion test. The association between sociodemographic characteristics and TB treatment outcomes was evaluated using the chi-square test and multiple logistic regression.Results: A total of 313 participants were randomly selected from 1184 former TB patients recorded in the unit TB registers. Of these, 264 were contacted in the community and consented to join the study: 57% were male and 156 (59.1%) participants had unsuccessful treatment outcomes. The wealthiest quintile had a 58% reduction in the risk of having an unsuccessful treatment outcome (adj OR = 0.42, 95% CI 0.18-0.99, p = 0.047). People who were employed in the informal sector (adj OR = 4.71, 95% CI 1.18-18.89, p = 0.029) and children under the age of 15 years who were not in school or employed (adj OR = 2.71, 95% CI 1.11-6.62, p = 0.029) had significantly higher odds of unsuccessful treatment outcome. Analysis of the pre-treatment loss to follow-up showed that 17.2% of patients with pulmonary bacteriologically confirmed TB did not initiate treatment with a higher proportion among females (21.7%) than males (13.5%). Inadequate food, belonging to migratory communities, stigma, lack of social protection, drug stock-outs and transport challenges affected TB treatment outcomes.Conclusions: This study confirmed that low socio-economic status is associated with poor TB treatment outcomes emphasizing the need for multi- and cross-sectoral approaches and socio-economic enablers to optimise TB care. [ABSTRACT FROM AUTHOR]

Background: Successful treatment of tuberculosis leads to clinical and public health benefits such as reduction in transmission, complications, and mortality among patients. However, data are limited on treatment outcomes and the associated factors among persons with bacteriologically confirmed pulmonary (BC-PTB) in rural areas of high dual tuberculosis and Human Immunodeficiency Virus (HIV) burden countries such as Uganda. We investigated factors associated with successful treatment of tuberculosis and mortality among adult persons with BC-PTB in rural eastern Uganda.Methods: We constructed a retrospective cohort of persons with BC-PTB from a routine tuberculosis clinic database in eastern Uganda. We performed bivariate and multivariate analysis. Using a 5% level of significance, we ran a modified Poisson regression analysis to determine factors independently associated with treatment success and mortality rates.Results: We retrieved 1123 records for persons with BC-PTB and the treatment outcomes were distributed as follows: 477(42.5%) cured, 323 (28.0%) treatment completed, 17(1.5%) treatment failed, 81(7.2%) died, 89(7.9%) lost to follow-up, and 136(12.1%) not evaluated. Overall, 800 (81.1%) of the 987 persons with BC-PTB that had treatment outcome, were successfully treated. Successful treatment of tuberculosis was less likely to occur among those with HIV infection (Adjusted risk ratio (aRR), 0.88; 95% Confidence Interval (CI), 0.82-0.95), older than 50 years (aRR, 0.89; 95% CI, 0.81-0.97), or male sex (aRR, 0.92; 95% CI, 0.87-0.98). Mortality was associated with HIV infection (aRR, 4.48; 95% CI, 2.95-6.79), older than 50 years (aRR, 2.93; 95% CI, 1.74-4.92), year of enrollment into treatment after 2015 (aRR, 0.80; 95% CI, 0.66-0.97), and Community-Based Directly Observed Therapy Short Course (aRR, 0.26; 95% CI, 0.13-0.50).Conclusions: Treatment success rate among adult persons with BC-PTB in rural eastern Uganda is suboptimal and mortality rate is high. HIV infection and older age reduce chances of treatment success, and increase mortality rate. Older and HIV infected persons with BC-PTB will require special consideration to optimize treatment success rate and reduce mortality rate. [ABSTRACT FROM AUTHOR]

Training district-level health officers and other mid-level health system managers revealed multiple contextual factors across political, administrative, and social axes affecting tuberculosis (TB) and TB control in Uganda. Individual relationships between local health, political, and media leaders affect efforts to inform the public and provide services, yet greater administrative coordination between national-level logistics, implementing partner funding, and local needs is required. Social challenges to TB control include high population mobility, local industries, poverty with high-density living and social venues, and misinformation about TB. Capitalizing on implementation knowledge and sharing data can overcome social geographic challenges to TB-prevention planning through strategic healthcare capacity-building at the district level. • Local geographic factors, industries, and social patterns contribute to spread of TB. • Reliance on outside funders enables unstable, regionally uneven capacity. • Mid-management capacity-building reduces geographic challenges to TB prevention. • Post-training, inter-district cooperation improved to accommodate patient mobility. • Use of data tables fostered competition, consultation, and collegiality in intervention groups. [ABSTRACT FROM AUTHOR]

Objective To determine the prevalence of chronic respiratory diseases in urban and rural Uganda and to identify risk factors for these diseases. Methods The population-based, cross-sectional study included adults aged 35 years or older. All participants were evaluated by spirometry according to standard guidelines and completed questionnaires on respiratory symptoms, functional status and demographic characteristics. The presence of four chronic respiratory conditions was monitored: chronic obstructive pulmonary disease (COPD), asthma, chronic bronchitis and a restrictive spirometry pattern. Findings In total, 1502 participants (average age: 46.9 years) had acceptable, reproducible spirometry results: 837 (56%) in rural Nakaseke and 665 (44%) in urban Kampala. Overall, 46.5% (698/1502) were male. The age-adjusted prevalence of any chronic respiratory condition was 20.2%. The age-adjusted prevalence of COPD was significantly greater in rural than urban participants (6.1 versus 1.5%, respectively; P < 0.001), whereas asthma was significantly more prevalent in urban participants: 9.7% versus 4.4% in rural participants (P < 0.001). The age-adjusted prevalence of chronic bronchitis was similar in rural and urban participants (3.5 versus 2.2%, respectively; P = 0.62), as was that of a restrictive spirometry pattern (10.9 versus 9.4%; P = 0.82). For COPD, the population attributable risk was 51.5% for rural residence, 19.5% for tobacco smoking, 16.0% for a body mass index < 18.5 kg/m2 and 13.0% for a history of treatment for pulmonary tuberculosis. Conclusion The prevalence of chronic respiratory disease was high in both rural and urban Uganda. Place of residence was the most important risk factor for COPD and asthma. [ABSTRACT FROM AUTHOR]

Background: Xpert MTB/RIF assay is a highly sensitive test for TB diagnosis, but still costly to most low-income countries. Several implementation strategies instead of frontline have been suggested; however with scarce data. We assessed accuracy of different Xpert MTB/RIF implementation strategies to inform national roll-out. Methods: This was a cross-sectional study of 1,924 adult presumptive TB patients in five regional referral hospitals of Uganda. Two sputum samples were collected, one for fluorescent microscopy (FM) and Xpert MTB/RIF examined at the study site laboratories. The second sample was sent to the Uganda Supra National TB reference laboratory for culture using both Lowenstein Jensen (LJ) and liquid culture (MGIT). We compared the sensitivities of FM, Xpert MTB/RIF and the incremental sensitivity of Xpert MTB/RIF among patients negative on FM using LJ and/or MGIT as a reference standard. Results: A total 1924 patients were enrolled of which 1596 (83%) patients had at least one laboratory result and 1083 respondents had a complete set of all the laboratory results. A total of 328 (30%) were TB positive on LJ and /or MGIT culture. The sensitivity of FM was n (%; 95% confidence interval) 246 (63.5%; 57.9–68.7) overall compared to 52 (55.4%; 44.1–66.3) among HIV positive individuals, while the sensitivity of Xpert MTB/RIF was 300 (76.2%; 71.7–80.7) and 69 (71.6%; 60.5–81.1) overall and among HIV positive individuals respectively. Overall incremental sensitivity of Xpert MTB/RIF was 60 (36.5%; 27.7–46.0) and 20 (41.7%; 25.5–59.2) among HIV positive individuals. Conclusion: Xpert MTB/RIF has a higher sensitivity than FM both in general population and HIV positive population. Xpert MTB/RIF offers a significant increase in terms of diagnostic sensitivity even when it is deployed selectively i.e. among smear negative presumptive TB patients. Our results support frontline use of Xpert MTB/RIF assay in high HIV/TB prevalent countries. In settings with limited access, mechanisms to refer smear negative sputum samples to Xpert MTB/RIF hubs are recommended. [ABSTRACT FROM AUTHOR]

Background: The road map for childhood tuberculosis launched in 2013 provided strong renewed efforts focused towards zero deaths due to tuberculosis in children. From 2010, there were efforts to improve childhood tuberculosis diagnosis in Kampala and this study aimed to document the trend and outcome of tuberculosis in children over the period.Methods: This was a retrospective study of tuberculosis data for Kampala city for the period 2011-2015. We extracted data from the unit TB registers in the 52 Diagnostic and treatment units (DTUs) in the Kampala. We report on data for children 0 to 14 years.Results: We accessed 33,221 TB patient records of which 2333 (7.0% 95% CI 6.7 to 7.3) were children. The proportion of children with pulmonary TB was 80% (1870/2333) (95% CI 76.7 to 83.7 and extra-pulmonary TB accounted for 20% (463/2333) (CI 18.3 to 21.5). Among pulmonary TB cases, the clinically diagnosed were 82% (1530/1870) (95% CI 80.0 to 83.5) while the bacteriologically confirmed were 18% (340/1870) (95% CI 16.5 to 20.0). Among the bacteriologically confirmed, 45% (154/340) (95% CI 40.1 to 50.6) were smear positive. During the study period 2011 through 2015, the childhood TB notification rate declined as follows; 105, 76, 72, 88, and 74 per 100,000 respectively. The treatment success rate increased from 78% in 2011 to 83% in 2015.Conclusions: The TB notification rate among children in Kampala city showed a large decline during the period 2011 to 2015. There was a slight improvement in the treatment success rate among the children. [ABSTRACT FROM AUTHOR]

Background: A recently published Ugandan study on tuberculosis (TB) diagnosis in HIV-positive patients with presumptive smear-negative TB, which showed that out of 90 patients who started TB treatment, 20% (18/90) had a positive Xpert MTB/RIF (Xpert) test, 24% (22/90) had a negative Xpert test, and 56% (50/90) were started without Xpert testing. Although Xpert testing was available, clinicians did not use it systematically. Here we aim to show more objectively the process of clinical decision-making. First, we estimated that pre-test probability of TB, or the prevalence of TB in smear-negative HIV infected patients with signs of presumptive TB in Uganda, was 17%. Second, we argue that the treatment threshold, the probability of disease at which the utility of treating and not treating is the same, and above which treatment should be started, should be determined. In Uganda, the treatment threshold was not yet formally established. In Rwanda, the calculated treatment threshold was 12%. Hence, one could argue that the threshold was reached without even considering additional tests. Still, Xpert testing can be useful when the probability of disease is above the treatment threshold, but only when a negative Xpert result can lower the probability of disease enough to cross the treatment threshold. This occurs when the pre-test probability is lower than the test-treat threshold, the probability of disease at which the utility of testing and the utility of treating without testing is the same. We estimated that the test-treatment threshold was 28%. Finally, to show the effect of the presence or absence of arguments on the probability of TB, we use confirming and excluding power, and a log10 odds scale to combine arguments.Conclusion: If the pre-test probability is above the test-treat threshold, empirical treatment is justified, because even a negative Xpert will not lower the post-test probability below the treatment threshold. However, Xpert testing for the diagnosis of TB should be performed in patients for whom the probability of TB was lower than the test-treat threshold. Especially in resource constrained settings clinicians should be encouraged to take clinical decisions and use scarce resources rationally. [ABSTRACT FROM AUTHOR]

Background: Treatment completion among tuberculosis patients remains low across various regions of Uganda, despite implementation of directly observed treatment short course. This study evaluated the determinants of treatment completion in a rural health sub-district of south western Uganda. Methods: In April 2012, health facility records were reviewed to identify tuberculosis patients who had been initiated on treatment between June 2008 and May 2011, in Rwampara Health Sub-District, south-western Uganda. Out of the 162 patients identified, 128 (79%) were traced and subsequently interviewed during a survey conducted in June 2012. Eleven (6.8%) of the 162 patients died, while 23 (14.2%) could not be traced. A review of records showed that 17 of those that could not be traced completed treatment while the other six did not have definitive records. Results: Treatment completion among the 128 patients interviewed was 89.8%. Pre-treatment counselling (aOR = 24.3, 95% CI: 1.4-26.6, P = 0.03), counselling at the time of submission of sputum during follow up (aOR = 6.8, 95% CI: 1.4-33.7, P = 0.02), and refill of drugs on the exact appointment date (aOR = 13.4, 95% CI: 1.9-93.0, P = 0.01), were independently associated with treatment completion. Conclusions: The level of treatment completion was higher than the national average, with service- related determinants identified as being critical for ensuring treatment completion. These data provide further evidence for the need to provide ongoing counselling support to tuberculosis patients. Enhancing the opportunities for counselling of tuberculosis patients should therefore be rigorously promoted as an approach to increase treatment completion in rural settings. [ABSTRACT FROM AUTHOR]

Background: Estimates of month-2 culture conversion, a proxy indicator of tuberculosis (TB) treatment efficacy in phase-2 trials can vary by culture-type and geographically with lower rates reported among African sites. The sub-study aimed at comparing TB detection rates of different culture media, within and across rifampicin-based regimens (R10, 15 and 20 mg/Kg) over a 6-month treatment follow-up period, and to establish predictors of month-2 culture non-conversion among HIV-negative TB patients enrolled at RIFATOX trial site in Uganda.Methods: Unlike in other Rifatox Trial sites, it is only in Uganda were Lowenstein-Jensen (LJ) and Mycobacteria growth indicator tube (MGIT) were used throughout 6-months for treatment monitoring. Conversion rates were compared at month-2, 4 and 6 across cultures and treatment-type. Binomial regression analysis performed for predictors of month-2 non-conversion.Results: Of the 100 enrolled patients, 45% had converted based on combined LJ and MGIT by month-2, with no significant differences across treatment arms, p = 0.721. LJ exhibited higher conversion rates than MGIT at month-2 (58.4% vs 56.0%, p = 0.0707) and month-4 (98.9% vs 88.4%, p = 0.0391) respectively, more so within the high-dose rifampicin arms. All patients had converted by month-6. Time-to-TB detection (TTD) on MGIT and social service jobs independently predict month-2 non-conversion.Conclusion: The month-2 culture conversion used in phase 2 clinical trials as surrogate marker of treatment efficacy is influenced by the culture method used for monitoring mycobacterial response to TB treatment. Therefore, multi-centric TB therapeutic trials using early efficacy endpoint should use the same culture method across sites. The Time-to-detection of MTB on MGIT prior to treatment and working in Social service jobs bear an increased risk of culture non-conversion at month-2.Trial Registration: ISRCTN ISRCTN55670677 . Registered 09th November 2010. Retrospectively registered. [ABSTRACT FROM AUTHOR]

Background: Microscopic Observation Drug Susceptibility (MODS) and Xpert MTB/Rif (Xpert) are highly sensitive tests for diagnosis of pulmonary tuberculosis (PTB). This study evaluated the cost effectiveness of utilizing MODS versus Xpert for diagnosis of active pulmonary TB in HIV infected patients in Uganda. Methods: A decision analysis model comparing MODS versus Xpert for TB diagnosis was used. Costs were estimated by measuring and valuing relevant resources required to perform the MODS and Xpert tests. Diagnostic accuracy data of the tests were obtained from systematic reviews involving HIV infected patients. We calculated base values for unit costs and varied several assumptions to obtain the range estimates. Cost effectiveness was expressed as costs per TB patient diagnosed for each of the two diagnostic strategies. Base case analysis was performed using the base estimates for unit cost and diagnostic accuracy of the tests. Sensitivity analysis was performed using a range of value estimates for resources, prevalence, number of tests and diagnostic accuracy. Results: The unit cost of MODS was US$ 6.53 versus US$ 12.41 of Xpert. Consumables accounted for 59 % (US$ 3.84 of 6.53) of the unit cost for MODS and 84 % (US$10.37 of 12.41) of the unit cost for Xpert. The cost effectiveness ratio of the algorithm using MODS was US$ 34 per TB patient diagnosed compared to US$ 71 of the algorithm using Xpert. The algorithm using MODS was more cost-effective compared to the algorithm using Xpert for a wide range of different values of accuracy, cost and TB prevalence. The cost (threshold value), where the algorithm using Xpert was optimal over the algorithm using MODS was US$ 5.92. Conclusions: MODS versus Xpert was more cost-effective for the diagnosis of PTB among HIV patients in our setting. Efforts to scale-up MODS therefore need to be explored. However, since other non-economic factors may still favour the use of Xpert, the current cost of the Xpert cartridge still needs to be reduced further by more than half, in order to make it economically competitive with MODS. [ABSTRACT FROM AUTHOR]

Background: The World Health Organization recommends TB infection control (TBIC) in health care facilities. In 2008, the Ministry of Health Uganda initiated efforts to implement TBIC by training of health care workers (HCWs). This study was carried out to assess knowledge and attitudes towards TBIC among HCWs.Methods: We conducted a cross-sectional study among HCWs in health facilities in the districts of Mukono and Wakiso in Uganda, from October 2010 to February 2011. We assessed HCWs' knowledge of basic standards of TB diagnosis, treatment and TBIC and attitudes towards TBIC measures.Results: Twenty four percent of the participants answered correctly all the basic TB knowledge questions. Overall, 62 % of the HCWs were judged to have adequate basic TB knowledge. At multivariable analysis, non-clinical cadres, were more likely to have poor basic TB knowledge, [adjusted odds ratio (aOR) 0.43; 95 % confidence interval (CI) 0.27-0.68)]. Only 7 % of the respondents answered all the questions on TBIC correctly. Almost all the respondents (98 %; 529/541) knew that TB was transmitted through droplet nuclei, while only a third (34 %; 174/532) knew that masks do not protect the wearer from getting TB. Overall, 69 % (355/512) of the HCWs were judged to have adequate TBIC knowledge. At multivariable analysis, non-clinical cadres (aOR 0.61; 95 % CI 0.38-0.98) and having not attended TBIC training, (aOR 0.65; 95 % CI 0.42-0.99), were more likely to have poor TBIC knowledge. More than three quarters (77 %; 410/530) and 63 % (329/522) of the respondents had a high self-efficacy and perceived threat of acquiring TB at work, respectively. Having not attended a TBIC training was significantly associated with a low self-efficacy (aOR 0.52; 95 % CI 0.33-0.81) and low perceived threat of acquiring TB infection at work, (aOR 0.54; 95 % CI 0.36-0.81).Conclusions: Our study finds moderate number of HCWs with correct knowledge and attitudes towards TBIC. Efforts should be put in place to train all HCWs in TBIC, with particular emphasis on the non-clinical staff due to their limited grasp of TBIC measures. [ABSTRACT FROM AUTHOR]

Background: In the absence of a gold standard for the diagnosis of latent tuberculosis (TB) infection (LTBI), the current tests available for the diagnosis of LTBI are limited by their inability to differentiate between LTBI and active TB disease. We investigated IP-10 as a potential biomarker for LTBI among household contacts exposed to sputum positive active TB cases. Methods: Active TB cases and contacts were recruited into a cohort with six months’ follow-up. Contacts were tested for LTBI using QuantiFERON®-TB Gold In-Tube (QFN) assay and the tuberculin skin test (TST). Baseline supernatants from the QFN assay of 237 contacts and 102 active TB cases were analysed for Mycobacterium tuberculosis (MTB) specific and mitogen specific IP-10 responses. Results: Contacts with LTBI (QFN+TST+) had the highest MTB specific IP-10 responses at baseline, compared to uninfected contacts (QFN-TST-) p<0.0001; and active cases, p = 0.01. Using a cut-off of 8,239 pg/ml, MTB specific IP-10 was able to diagnose LTBI with a sensitivity of 87.1% (95% CI, 76.2–94.3) and specificity of 90.9% (95% CI, 81.3–96.6). MTB specific to mitogen specific IP-10 ratio was higher in HIV negative active TB cases, compared to HIV negative latently infected contacts, p = 0.0004. Concentrations of MTB specific IP-10 were higher in contacts with TST conversion (negative at baseline, positive at 6-months) than in those that were persistently TST negative, p = 0.001. Conclusion: IP-10 performed well in differentiating contacts with either latent or active TB from those who were uninfected but was not able to differentiate LTBI from active disease except when MTB specific to mitogen specific ratios were used in HIV negative adults. In addition, IP-10 had the potential to diagnose ‘recent TB infection’ in persons classified as having LTBI using the TST. Such individuals with strong IP-10 responses would likely benefit from chemoprophylaxis. [ABSTRACT FROM AUTHOR]

Objectives Targeting high Tuberculosis (TB) transmission sites may offer a novel approach to TB prevention in sub-Saharan Africa. We sought to characterise TB transmission sites in a rural Ugandan township. Methods We recruited adults starting TB treatment in Tororo, Uganda, over 1 year. Fifty four TB cases provided names of frequent contacts, sites of residence, health care, work and social activities, and two sputum samples. Mycobacterium tuberculosis ( MTB) culture-positive specimens underwent spoligotyping to identify strains with shared genotypes. We visualised TB case social networks, and obtained, mapped and geo-coded global positioning system measures for every location that cases reported frequenting 1 month before treatment. Locations of spatial overlap among genotype-clustered cases were considered potential transmission sites. Results Six distinct genotypic clusters were identified involving 21 of 33 (64%) MTB culture-positive, genotyped cases; none shared a home. Although 18 of 54 (33%) TB cases shared social network ties, none of the genotype-clustered cases shared social ties. Using spatial analysis, we identified potential sites of within-cluster TB transmission for five of six genotypic clusters. All sites but one were healthcare and social venues, including sites of drinking, worship and marketplaces. Cases reported spending the largest proportion of pre-treatment person-time (22.4%) at drinking venues. Conclusions Using molecular epidemiology, geospatial and social network data from adult TB cases identified at clinics, we quantified person-time spent at high-risk locations across a rural Ugandan community and determined the most likely sites of recent TB transmission to be healthcare and social venues. These sites may not have been identified using contact investigation alone. [ABSTRACT FROM AUTHOR]

Community Home-Based Care (CHBC) has evolved in resource-limited settings to fill the unmet needs of people living with HIV/AIDS (PLHA). We compare HIV and tuberculosis (TB) outcomes from the Nsambya CHBC with national averages in Kampala, Uganda. This retrospective observational study compared HIV and TB outcomes from adults and children in the Nsambya CHBC to national averages from 2007 to 2011. Outcomes included numbers of HIV and TB patients enrolled into care, retention, loss to follow-up (LTFU), and mortality among patients on antiretroviral therapy (ART) at 12 months from initiation; new smear-positive TB cure and defaulter rates; and proportion of TB patients tested for HIV. Chi-square test and trends analyses were used to compare outcomes from Nsambya CHBC with national averages. By 2011, approximately 14,000 PLHA had been enrolled in the Nsambya CHBC, and about 4,000 new cases of TB were detected and managed over the study period. Overall, retention and LTFU of ART patients 12 months after initiation, proportion of TB patients tested for HIV, and cure rates for new smear-positive TB scored higher in the Nsambya CHBC compared to national averages. The findings show that Nsambya CHBC complements national HIV and TB management and results in more positive outcomes. [ABSTRACT FROM AUTHOR]

Quality of care plays an important role in the status of tuberculosis (TB) control, by influencing timely diagnosis, treatment adherence, and treatment completion. In this study, we aimed at establishing the quality of TB service care in Kamuli district health care centres using Donabedian structure, process, and outcomes model of health care. A cross-sectional study was conducted in 8 health care facilities, among 20 health care workers and 392 patients. Data was obtained using face-to-face interviews, an observation guide, a check list, and record review of the TB unit and laboratory registers. Data entry and analysis were done using EPI INFO 2008 and STATA 10 versions, respectively. A high number 150 (87.21%) of TB patients were not aware of all the signs to stop TB medication, and 100 (25.51%) patients received laboratory results after a period of 3-5 working days. The major challenges faced by health workers were poor attitude of fellow health workers, patients defaulting treatment, and fear of being infected with TB. One of the worst performance indicators was low percentage of cure. Comprehensive strengthening of the health system focusing on quality of support supervisions, patient follow up, promoting infection control measures, and increasing health staffing levels at health facilities is crucial. [ABSTRACT FROM AUTHOR]

Among patients with HIV-associated tuberculosis, the extent to which recommendations regarding early initiation of antiretroviral therapy are routinely implemented remain unknown. Two Ugandan clinics demonstrated improved rates of antiretroviral therapy initiation in association with changing guidelines and emerging scientific evidenceBackground. We aimed to determine the extent to which emerging evidence and changing guidelines regarding timing of antiretroviral therapy (ART) among human immunodeficiency virus (HIV)–infected patients with tuberculosis influenced “real-world” clinical practice in Uganda.Methods. We evaluated ART-naive, HIV-infected adults starting tuberculosis therapy at 2 HIV clinics in Uganda between 26 August 2006 and 29 September 2012. We used multivariate regression to calculate associations between 4 calendar periods reflecting publication of seminal clinical studies or changes in guidelines and timing of ART after tuberculosis therapy initiation.Results. For patients with CD4 counts <50 cells/µL, the fraction starting ART within 14 and 30 days of initiating tuberculosis therapy increased from 7% to 14% and from 14% to 86% over the period of observation. The fraction of patients with CD4 counts >50 cells/µL starting ART within 60 days increased from 16% to 28%. After adjustment for sociodemographic factors, when comparing the most recent with the earliest calendar period, the rate of ART initiation increased by 4.57-fold (95% confidence interval [CI], 1.76-fold to 11.86-fold) among patients with baseline CD4 counts ≤50 cells/µL and by 5.43-fold (95% CI, 3.16- fold to 9.31-fold) among those with baseline CD4 counts >50 cells/µL.Conclusions. We observed large changes in clinical practice during a period of emerging data and changing guidelines among HIV-infected patients with tuberculosis. Nonetheless, a significant proportion of individuals with higher CD4 cell counts do not start ART within recommended time frames. Targeted dissemination and implementation efforts are still needed to achieve target levels in practice. [ABSTRACT FROM PUBLISHER]

Background: Multidrug resistant and extensively drug resistant tuberculosis (TB) have become major threats to control of tuberculosis globally. The rates of anti-TB drug resistance in Uganda are not known. We conducted a national drug resistance survey to investigate the levels and patterns of resistance to first and second line anti-TB drugs among new and previously treated sputum smear-positive TB cases. Methods: Sputum samples were collected from a nationally representative sample of new and previously treated sputum smear-positive TB patients registered at TB diagnostic centers during December 2009 to February 2011 using a weighted cluster sampling method. Culture and drug susceptibility testing was performed at the national TB reference laboratory. Results: A total of 1537 patients (1397 new and 140 previously treated) were enrolled in the survey from 44 health facilities. HIV test result and complete drug susceptibility testing (DST) results were available for 1524 (96.8%) and 1325 (85.9%) patients, respectively. Of the 1209 isolates from new cases, resistance to any anti-TB drug was 10.3%, 5% were resistant to isoniazid, 1.9% to rifampicin, and 1.4% were multi drug resistant. Among the 116 isolates from previously treated cases, the prevalence of resistance was 25.9%, 23.3%, 12.1% and 12.1% respectively. Of the 1524 patients who had HIV testing 469 (30.7%) tested positive. There was no association between anti-TB drug resistance (including MDR) and HIV infection. Conclusion: The prevalence of anti-TB drug resistance among new patients in Uganda is low relative to WHO estimates. The higher levels of MDR-TB (12.1%) and resistance to any drug (25.3%) among previously treated patients raises concerns about the quality of directly observed therapy (DOT) and adherence to treatment. This calls for strengthening existing TB control measures, especially DOT, routine DST among the previously treated TB patients or periodic drug resistance surveys, to prevent and monitor development and transmission of drug resistant TB. [ABSTRACT FROM AUTHOR]

Background: There is a documented increase of diabetes mellitus in Sub Saharan Africa, a region where tuberculosis is highly endemic. Currently, diabetes mellitus is one of the recognised risk factors of tuberculosis. No study has reported the magnitude of diabetes mellitus among tuberculosis patients in Uganda, one of the countries with a high burden of tuberculosis. Methods: This was a cross-sectional study conducted among 260 consenting adult patients with a confirmed diagnosis of tuberculosis admitted on the pulmonology wards of Mulago national referral and teaching hospital in Kampala, Uganda to determine the prevalence of diabetes mellitus and associated clinical factors. Laboratory findings as well as the socio-demographic and clinical data collected using a validated questionnaire was obtained. Point of care random blood sugar (RBS) testing was performed on all the patients prior to initiation of anti tuberculosis treatment. Diabetes mellitus was diagnosed if the RBS level was = 200mg/dl in the presence of the classical symptoms of diabetes mellitus. Results: The prevalence of diabetes mellitus among the admitted patients with tuberculosis was 8.5%. Only 5 (1.9%) patients with TB had a known diagnosis of diabetes mellitus at enrolment. Majority of the study participants with TB-DM co-infection had type 2 diabetes mellitus (n=20, 90.9%). At bivariate analysis, raised mean ALT concentrations of =80 U/L were associated with DM (OR-6.1, 95% CI 1.4-26.36, p=0.032) and paradoxically, HIV co-infection was protective of DM (OR-0.32, 95% CI 0.13-0.79, P=0.016). The relationship between DM and HIV as well as that with ALT remained statistically significant at multivariate analysis (HIV: OR- 0.17 95%CI 0.06-0.51, p=0.002 and ALT: OR-11.42 95%CI 2.15-60.59, p=0.004) Conclusion: This study demonstrates that diabetes mellitus is common among hospitalized tuberculosis patients in Uganda. The significant clinical predictors associated with diabetes mellitus among tuberculosis patients were HIV co-infection and raised mean serum alanine transaminase concentrations. [ABSTRACT FROM AUTHOR]

Objectives To investigate whether an unrecognised diagnosis of tuberculosis (TB) at the start of antiretroviral therapy (ART) influences subsequent CD4+ T cell (CD4) count recovery in an urban HIV clinic in Uganda. Methods In a retrospective cohort study, a multivariable polynomial mixed effects model was used to estimate CD4 recovery in the first 96 weeks of ART in two groups of patients: prevalent TB (started ART while on TB treatment), unrecognised TB (developed TB within 6 months after start ART). Results Included were 511 patients with a median baseline CD4 count of 57 cells/mm3 (interquartile range: 22-130), of whom 368 (72%) had prevalent TB and 143 (28%) had unrecognised TB. Compared with prevalent TB, unrecognised TB was associated with lower CD4 count recovery at 96 weeks: −22.3 cells/mm3 (95% confidence interval −43.2 to −1.5, P = 0.036). These estimates were adjusted for gender, age, baseline CD4 count and the use of zidovudine-based regimen. Conclusions Unrecognised TB at the time of ART initiation resulted in impaired CD4 recovery compared with TB treated before ART initiation. More vigilant screening with more sensitive and rapid TB diagnostics prior to ART initiation is needed to decrease the risk of ART-associated TB and sub-optimal immune reconstitution. [ABSTRACT FROM AUTHOR]

Background: In Uganda, isoniazid plus ethambutol is used for 6 months (6HE) during the continuation treatment phase of new tuberculosis (TB) cases. However, the World Health Organization (WHO) recommends using isoniazid plus rifampicin for 4 months (4HR) instead of 6HE. We compared the impact of a continuation phase using 6HE or 4HR on total cost and expected mortality from the perspective of the Ugandan national health system. Methodology/Principal Findings: Treatment costs and outcomes were determined by decision analysis. Median daily drug price was US$0.115 for HR and US$0.069 for HE. TB treatment failure or relapse and mortality rates associated with 6HE vs. 4HR were obtained from randomized trials and systematic reviews for HIV-negative (46% of TB cases; failure/relapse -6HE: 10.4% vs. 4HR: 5.2%; mortality -6HE: 5.6% vs. 4HR: 3.5%) and HIV-positive patients (54% of TB cases; failure or relapse -6HE: 13.7% vs. 4HR: 12.4%; mortality -6HE: 16.6% vs. 4HR: 10.5%). When the initial treatment is not successful, retreatment involves an additional 8-month drug-regimen at a cost of $110.70. The model predicted a mortality rate of 13.3% for patients treated with 6HE and 8.8% for 4HR; average treatment cost per patient was predicted at $26.07 for 6HE and $23.64 for 4HR. These results were robust to the inclusion of MDR-TB as an additional outcome after treatment failure or relapse. Conclusions/Significance: Combination therapy with 4HR in the continuation phase dominates 6HE as it is associated with both lower expected costs and lower expected mortality. These data support the WHO recommendation to transition to a continuation phase comprising 4HR. [ABSTRACT FROM AUTHOR]

Summary [ABSTRACT FROM AUTHOR]

Background: Each year, 10%-20% of patients with tuberculosis (TB) in low- and middle-income countries present with previously treated TB and are empirically started on a World Health Organization (WHO)-recommended standardized retreatment regimen. The effectiveness of this retreatment regimen has not been systematically evaluated.Methods and Findings: From July 2003 to January 2007, we enrolled smear-positive, pulmonary TB patients into a prospective cohort to study treatment outcomes and mortality during and after treatment with the standardized retreatment regimen. Median time of follow-up was 21 months (interquartile range 12-33 months). A total of 29/148 (20%) HIV-uninfected and 37/140 (26%) HIV-infected patients had an unsuccessful treatment outcome. In a multiple logistic regression analysis to adjust for confounding, factors associated with an unsuccessful treatment outcome were poor adherence (adjusted odds ratio [aOR] associated with missing half or more of scheduled doses 2.39; 95% confidence interval (CI) 1.10-5.22), HIV infection (2.16; 1.01-4.61), age (aOR for 10-year increase 1.59; 1.13-2.25), and duration of TB symptoms (aOR for 1-month increase 1.12; 1.04-1.20). All patients with multidrug-resistant TB had an unsuccessful treatment outcome. HIV-infected individuals were more likely to die than HIV-uninfected individuals (p<0.0001). Multidrug-resistant TB at enrollment was the only common risk factor for death during follow-up for both HIV-infected (adjusted hazard ratio [aHR] 17.9; 6.0-53.4) and HIV-uninfected (14.7; 4.1-52.2) individuals. Other risk factors for death during follow-up among HIV-infected patients were CD4<50 cells/ml and no antiretroviral treatment (aHR 7.4, compared to patients with CD4≥200; 3.0-18.8) and Karnofsky score <70 (2.1; 1.1-4.1); and among HIV-uninfected patients were poor adherence (missing half or more of doses) (3.5; 1.1-10.6) and duration of TB symptoms (aHR for a 1-month increase 1.9; 1.0-3.5).Conclusions: The recommended regimen for retreatment TB in Uganda yields an unacceptable proportion of unsuccessful outcomes. There is a need to evaluate new treatment strategies in these patients. [ABSTRACT FROM AUTHOR]

In a prospective randomized, controlled trial in Uganda comparing the efficacy of antiretroviral therapy during tuberculosis therapy with the efficacy of tuberculosis therapy alone in HIV-infected patients with tuberculosis who have a CD4+ cell count 1350 cells/mL, it was found that antiretroviral therapy did not accelerate microbiologic, radiographic, or clinical responses to tuberculosis therapy: 18% of participants had sputum smears positive for Mycobacterium tuberculosis after 5 months of tuberculosis therapy, despite having had negative culture results. [ABSTRACT FROM AUTHOR]

Background: Antiretroviral therapy (ART) effectively decreases tuberculosis (TB) incidence long-term, but is associated with high TB incidence rates in the first 6 months. We sought to determine the incidence and the long-term effects of TB during ART on HIV treatment outcome, and the risk factors for incident TB during ART in a large urban HIV clinic in Uganda. Methodology/Principal Findings: Routinely collected longitudinal clinical data from all patients initiated on first-line ART was retrospectively analysed. 5,982 patients were included with a median baseline CD4+ T cell count (CD4 count) of 117 cells/mm³ (interquartile range [IQR]; 42, 182). In the first 2 years, there were 336 (5.6%) incident TB events in 10,710 person-years (py) of follow-up (3.14 cases/100pyar [95% CI 2.82-3.49]); incidence rates at 0-3, 3-6, 6-12 and 12-24 months were 11.25 (9.58-13.21), 6.27 (4.99-7.87), 2.47 (1.87-3.36) and 1.02 (0.80-1.31), respectively. Incident TB during ART was independently associated with baseline CD4 count of <50 cells/mm³ (hazard ratio [HR] 1.84 [1.25-2.70], P = 0.002) and male gender (HR 1.68 [1.34-2.11], P<0.001). After two years on ART, the patients who had developed TB in the first 12 months had a significantly lower median CD4 count increase (184 cells/mm³ [IQR; 107, 258, n = 118] vs 209 cells/mm³ [124, 309, n = 2166], P = 0.01), a larger proportion of suboptimal immune reconstitution according to two definitions (increase in CD4 count <200 cells/mm³: 57.4% vs 46.9%, P = 0.03, and absolute CD4 count <200 cells/mm³: 30.4 vs 19.9%, P = 0.006), and a higher percentage of immunological failure according to the WHO criteria (13.6% vs 6.5%, P = 0.003). Incident TB during ART was independently associated with poor CD4 count recovery and fulfilling WHO immunogical failure definitions. Conclusions/Significance: Incident TB during ART occurs most often within 3 months and in patients with CD4 counts less than 50 cells/mm³. Incident TB during ART is associated with long-term impairment in immune recovery. [ABSTRACT FROM AUTHOR]

Abstract: Aim of the study: Tuberculosis (TB) remains one of the most difficult ailments to control in the world today. The emergence of drug resistant strains has made previously effective and affordable remedies less effective. This has made the search for new medicines from local traditional medicines urgent. The specific objectives of this study were to (1) identify plant species used in the treatment of TB, their methods of preparation and administration, (2) document TB recognition, and (3) document medicine processing and packaging practices by traditional medicine practitioners (TMPs). Methods: We interviewed 32 TMPs from the districts of Kamuli, Kisoro and Nakapiripirit using a guided questionnaire. Results: We documented 88 plant species used to treat TB. Seven of these, Eucalyptus spp., Warburgia salutaris (G. Bertol.) Chiov., Ocimum suave Willd., Zanthoxylum chalybeum Engl., Momordica foetida Schum., Persea americana Mill. and Acacia hockii De Wild. were mentioned by three or more TMPs. Medicines were prepared mostly as mixtures or infrequently as mono-preparations in dosage forms of decoctions and infusions. They were administered orally in variable doses over varying periods of time. The TMPs did not know how to preserve the medicines and packaged them in used water bottles. Almost all TMPs mentioned the most important signs by which TB is recognised. They also knew that TB was a contagious disease spread through poor hygiene and crowding. Conclusions: Local knowledge and practices of treating TB exist in the districts surveyed. This knowledge may be imperfect and TMPs appear to be still experimenting with which species to use to treat TB. There is need to screen among the species mentioned to determine those which are efficacious and safe. The technology of processing, packaging and preserving traditional medicines for the treatment of TB is very basic and needs improving. The TMPs appear to be playing a significant role in primary health care delivery and this lends further justification for the ongoing Uganda government efforts to integrate the allopathic and traditional medicine systems. [Copyright &y& Elsevier]

Tuberculosis (TB) remains a major source of morbidity and mortality in Uganda. This cross-sectional study explores Ugandan women's TB treatment-seeking processes to determine the routes to effective government TB treatment among a sample of urban, semirural, and rural women. This research focuses on women in particular as Ugandan women with tuberculosis must negotiate their treatment paths in a context where women tend to be politically and economically marginalized, with limited control of household resources and senior family members’ health care decisions. The results examine the structural, social, and economic forces similarly guiding treatment seeking across the three research sites and then the specific differences among the settings. The findings suggest that the modest number of nongovernmental health care providers’ diagnoses and referrals, particularly for urban and semirural participants, represents a critical barrier to biomedical TB treatment. Private providers’ diagnosis delays also carry financial and physical costs, which undermine the resources available for subsequent TB treatment and participants’ social and economic well-being. This study indicates that conceptualizations of the political economy of treatment seeking need to more fully acknowledge the dynamic nature of the microlevel political economic context of treatment seeking, including the domino social, economic, and health effects of structurally problematic health care systems. [ABSTRACT FROM AUTHOR]

We studied hepatic transaminases among rural Ugandans initiating highly active antiretroviral therapy (HAART) and assessed the impact of positive serology for hepatitis B surface antigen (HBsAg) and coadministration of therapy for tuberculosis. From July 2003 to December 2004, persons with symptomatic HIV disease or a CD4 count less than 250 cells/mm3 and who had alanine transferase (ALT) or aspartate transferase (AST) less than 5 times the upper limit of normal were started on HAART including nevirapine (96%) or efavirenz (4%). Repository sera from a subset of 596 participants were analyzed for hepatic transaminase levels. A transaminase elevation was present before therapy for 249 (42%) of 596, at 3 months for 140 (25%) of 553, 12 months for 59 (11%) of 520, and 24 months for 67 (13%) of 508. In multivariate analyses, a transaminase elevation at 3 months was associated with male gender (odds ratio [OR], 1.55; 95% confidence interval [CI], 1.02–2.35), body mass index less than 18 kg/m2 (OR, 2.10; 95% CI, 1.34–3.30), transaminase elevation at baseline (OR, 1.97; 95% CI, 1.30–2.99), and treatment for tuberculosis (OR, 4.68; 95% CI, 2.28–9.59). HBsAg status was not associated with transaminase elevations at baseline or while on HAART. The prevalence of hepatic transaminase elevations decreased during non-nucleoside reverse transcriptase inhibitor (NNRTI)-based antiretroviral therapy in this cohort of HIV-infected persons in rural Uganda. [ABSTRACT FROM AUTHOR]

Investigates the safety and efficacy of thiacetazone- and rifampicin-containing regimens for pulmonary tuberculosis among HIV-infected Ugandans. Comparison with alternative regimens; Baseline characteristics of patients according to treatment assignment; Adverse effects of therapy; Patients' response to therapy; Significance of the study in the treatment of HIV.

Background: Childhood tuberculosis (TB) diagnoses often lack microbiologic confirmation and require empiric treatment. Barriers to empiric treatment include concern for poor outcomes and adverse effects. We thus determined the outcomes of empiric TB treatment from a retrospective cohort of children at a national referral hospital in Kampala, Uganda from 2010 to 2015.Methods: Children were diagnosed clinically and followed through treatment. Demographics, clinical data, outcome and any adverse events were extracted from patient charts. A favorable outcome was defined as a child completing treatment with clinical improvement. We performed logistic regression to assess factors associated with loss to follow up and death.Results: Of 516 children, median age was 36 months (IQR 15-73), 55% (95% CI 51-60%) were male, and HIV prevalence was 6% (95% CI 4-9%). The majority (n = 422, 82, 95% CI 78-85%) had a favorable outcome, with no adverse events that required treatment discontinuation. The most common unfavorable outcomes were loss to follow-up (57/94, 61%) and death (35/94, 37%; overall mortality 7%). In regression analysis, loss to follow up was associated with age 10-14 years (OR 2.38, 95% CI 1.15-4.93, p = 0.02), HIV positivity (OR 3.35, 95% CI 1.41-7.92, p = 0.01), hospitalization (OR 4.14, 95% CI 2.08-8.25, p < 0.001), and living outside of Kampala (OR 2.64, 95% CI 1.47-4.71, p = 0.001). Death was associated with hospitalization (OR 4.57, 95% CI 2.0-10.46, p < 0.001), severe malnutrition (OR 2.98, 95% CI 1.07-8.27, p = 0.04), baseline hepatomegaly (OR 4.11, 95% CI 2.09-8.09, p < 0.001), and living outside of Kampala (OR 2.41, 95% CI 1.17-4.96, p = 0.02).Conclusions: Empiric treatment of child TB was effective and safe, but treatment success remained below the 90% target. Addressing co-morbidities and improving retention in care may reduce unfavorable outcomes. [ABSTRACT FROM AUTHOR]

Background: According to the traditional tuberculosis (TB) treatment paradigm, the initial doses of treatment rapidly kill most Mycobacterium tuberculosis (Mtb) bacilli in sputum, yet many more months of daily treatment are required to eliminate a small, residual subpopulation of drug-tolerant bacilli. This paradigm has recently been challenged following the discovery that up to 90% of Mtb bacilli in sputum are culturable only with growth-factor supplementation. These "differentially culturable" bacilli are hypothesized to be more drug-tolerant than routinely culturable bacilli. This hypothesis implies an alternative paradigm in which TB treatment does not rapidly reduce the total Mtb population but only the small, routinely culturable subpopulation. To evaluate these competing paradigms, we developed a culture-independent method for quantifying the viable fraction of Mtb bacilli in sputum during treatment.Methods: We used GeneXpert MTB/RIF to quantify Mtb DNA in sputa collected longitudinally from Ugandan adults taking standard 4-drug treatment for drug-susceptible pulmonary TB. We modeled GeneXpert cycle thresholds over time using nonlinear mixed-effects regression. We adjusted these models for clearance of DNA from killed-but-not-yet-degraded bacilli, assuming clearance half-lives ranging from 0 to 1.25 days. We used a convolution integral to quantify DNA from viable bacilli only, and converted cycle thresholds to Mtb genomic equivalents. We replicated our results in a South African cohort.Results: We enrolled 41 TB patients in Uganda. Assuming a DNA-clearance half-life of 0 days, genomic equivalents of viable sputum bacilli decreased by 0.22 log/day until 8.8 days, then by 0.07 log/day afterwards. Assuming a DNA-clearance half-life of 1.25 days, genomic equivalents of viable bacilli decreased by 0.36 log/day until 5.0 days, then by 0.06 log/day afterwards. By day 7, viable Mtb had decreased by 97.2-98.8%. We found similar results for 19 TB patients in South Africa.Discussion: Using a culture-independent method, we found that TB treatment rapidly eliminates most viable Mtb in sputum. These findings are incompatible with the hypothesis that differentially culturable bacilli are drug-tolerant.Conclusions: A culture-independent method for measuring viable Mtb in sputum during treatment corroborates the traditional TB treatment paradigm in which a rapid bactericidal phase precedes slow, elimination of a small, residual bacillary subpopulation. [ABSTRACT FROM AUTHOR]

Background: Appraisal delay is the time a patient takes to consider a symptom as not only noticeable, but a sign of illness. The study's objective was to determine the association between appraisal delay in seeking tuberculosis (TB) treatment and geographic distance measured by network travel (driving and pedestrian) time (in minutes) and distance (Euclidean and self-reported) (in kilometers) and to identify other risk factors from selected covariates and how they modify the core association between delay and distance.Methods: This was part of a longitudinal cohort study known as the Kawempe Community Health Study based in Kampala, Uganda. The study enrolled households from April 2002 to July 2012. Multivariable interval regression with multiplicative heteroscedasticity was used to assess the impact of time and distance on delay. The delay interval outcome was defined using a comprehensive set of 28 possible self-reported symptoms. The main independent variables were network travel time (in minutes) and Euclidean distance (in kilometers). Other covariates were organized according to the Andersen utilization conceptual framework.Results: A total of 838 patients with both distance and delay data were included in the network analysis. Bivariate analyses did not reveal a significant association of any distance metric with the delay outcome. However, adjusting for patient characteristics and cavitary disease status, the multivariable model indicated that each minute of driving time to the clinic significantly (p = 0.02) and positively predicted 0.25 days' delay. At the median distance value of 47 min, this represented an additional delay of about 12 (95% CI: [3, 21]) days to the mean of 40 days (95% CI: [25, 56]). Increasing Euclidean distance significantly predicted (p = 0.02) reduced variance in the delay outcome, thereby increasing precision of the mean delay estimate. At the median Euclidean distance of 2.8 km, the variance in the delay was reduced by more than 25%.Conclusion: Of the four geographic distance measures, network travel driving time was a better and more robust predictor of mean delay in this setting. Including network travel driving time with other risk factors may be important in identifying populations especially vulnerable to delay. [ABSTRACT FROM AUTHOR]