NRU :: Browsing by Author "Kitonsa, Peter J."

Browsing by Author "Kitonsa, Peter J."

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Characterization of geographic mobility among participants in facility- and community-based tuberculosis case finding in urban Uganda
(PLoS ONE, 2021) Robsky, Katherine O.; Isooba, David; Nakasolya, Olga; Mukiibi, James; Nalutaaya, Annet; Kitonsa, Peter J.; Kamoga, Caleb; Baik, Yeonsoo; Kendall, Emily A.; Katamba, Achilles; Dowdy, David W.
International and internal migration are recognized risk factors for tuberculosis (TB). Geographic mobility, including travel for work, education, or personal reasons, may also play a role in TB transmission, but this relationship is poorly defined. We aimed to define geographic mobility among participants in facility- and community-based TB case finding in Kampala, Uganda, and to assess associations between mobility, access to care, and TB disease. Methods We included consecutive individuals age �15 years diagnosed with TB disease through either routine health facility practices or community-based case finding (consisting of doorto- door testing, venue-based screening, and contact investigation). Each case was matched with one (for community-based enrollment) or two (health facility enrollment) TB-negative controls. We conducted a latent class analysis (LCA) of eight self-reported characteristics to identify and define mobility; we selected the best-fit model using Bayesian Information Criterion. We assessed associations between mobility and TB case status using multivariable conditional logistic regression. Results We enrolled 267 cases and 432 controls. Cases were more likely than controls to have been born in Kampala (p<0.001); there was no difference between cases and controls for remaining mobility characteristics. We selected a two-class LCA model; the “mobile” class was perfectly correlated with a single variable: travel (>3 km) from residence 2 times per month. Mobility was associated with a 28% reduction in odds of being a TB case (adjusted matched odds ratio 0.72 [95% confidence interval 0.49, 1.06]). Conclusion Frequency of out-of-neighborhood travel is an easily measured variable that correlates closely with predicted mobility class membership. Mobility was associated with decreased risk of TB disease; this may be in part due to the higher socioeconomic status of mobile individuals in this population. However, more research is needed to improve assessment of mobility and understand how mobility affects disease risk and transmission.
A clinical score for identifying active tuberculosis while awaiting microbiological results: Development and validation of a multivariable prediction model in sub- Saharan Africa
(PLoS medicine, 2020) Baik, Yeonsoo; Rickman, Hannah M.; Hanrahan, Colleen F.; Mmolawa, Lesego; Kitonsa, Peter J.; Sewelana, Tsundzukana; Nalutaaya, Annet; Kendall, Emily A.; Lebina, Limakatso; Martinson, Neil; Katamba, Achilles; Dowdy, David W.
In highly resource-limited settings, many clinics lack same-day microbiological testing for active tuberculosis (TB). In these contexts, risk of pretreatment loss to follow-up is high, and a simple, easy-to-use clinical risk score could be useful. Methods and findings We analyzed data from adults tested for TB with Xpert MTB/RIF across 28 primary health clinics in rural South Africa (between July 2016 and January 2018). We used least absolute shrinkage and selection operator regression to identify characteristics associated with Xpert-confirmed TB and converted coefficients into a simple score. We assessed discrimination using receiver operating characteristic (ROC) curves, calibration using Cox linear logistic regression, and clinical utility using decision curves. We validated the score externally in a population of adults tested for TB across 4 primary health clinics in urban Uganda (between May 2018 and December 2019). Model development was repeated de novo with the Ugandan population to compare clinical scores. The South African and Ugandan cohorts included 701 and 106 individuals who tested positive for TB, respectively, and 686 and 281 randomly selected individuals who tested negative. Compared to the Ugandan cohort, the South African cohort was older (41% versus 19% aged 45 years or older), had similar breakdown of biological sex (48% versus 50% female), and had higher HIV prevalence (45% versus 34%). The final prediction model, scored from 0 to 10, included 6 characteristics: age, sex, HIV (2 points), diabetes, number of classical TB symptoms (cough, fever, weight loss,and night sweats; 1 point each), and >14-day symptom duration. Discrimination was moderate in the derivation (c-statistic = 0.82, 95% CI = 0.81 to 0.82) and validation (c-statistic = 0.75, 95% CI = 0.69 to 0.80) populations. A patient with 10% pretest probability of TB would have a posttest probability of 4% with a score of 3/10 versus 43% with a score of 7/10. The de novo Ugandan model contained similar characteristics and performed equally well. Our study may be subject to spectrum bias as we only included a random sample of people without TB from each cohort. This score is only meant to guide management while awaiting microbiological results, not intended as a community-based triage test (i.e., to identify individuals who should receive further testing). Conclusions In this study, we observed that a simple clinical risk score reasonably distinguished individuals with and without TB among those submitting sputum for diagnosis. Subject to prospective validation, this score might be useful in settings with constrained diagnostic resources where concern for pretreatment loss to follow-up is high.
Empiric treatment of pulmonary TB in the Xpert era: Correspondence of sputum culture, Xpert MTB/RIF, and clinical diagnoses
(PLoS ONE, 2019) Kendall, Emily A.; Kamoga, Caleb; Kitonsa, Peter J.; Nalutaaya, Annet; Salvatore, Phillip P.; Robsky, Katherine; Nakasolya, Olga; Mukiibi, James; Isooba, David; Cattamanchi, Adithya; Kato-Maeda, Midori; Katamba, Achilles; Dowdy, David W.
Clinical tuberculosis diagnosis and empiric treatment have traditionally been common among patients with negative bacteriologic test results. Increasing availability of rapid molecular diagnostic tests, including Xpert MTB/RIF and the new Xpert Ultra cartridge, may alter the role of empiric treatment. Methods We prospectively enrolled outpatients age > = 15 who were evaluated for pulmonary tuberculosis at three health facilities in Kampala, Uganda. Using sputum mycobacterial culture, interviews, and clinical record abstraction, we estimated the accuracy of clinical diagnosis relative to Xpert and sputum culture and assessed the contribution of clinical diagnosis to case detection. Results Over a period of 9 months, 99 patients were diagnosed with pulmonary tuberculosis and subsequently completed sputum culture; they were matched to 196 patients receiving negative tuberculosis evaluations in the same facilities. Xpert was included in the evaluation of 291 (99%) patients. Compared to culture, Xpert had a sensitivity of 92% (95% confidence interval 83–97%) and specificity of 95% (92–98%). Twenty patients with negative Xpert were clinically diagnosed with tuberculosis and subsequently had their culture status determined; two (10%) were culture-positive. Considering all treated patients regardless of Xpert and culture data completeness, and considering treatment initiations before a positive Xpert (N = 4) to be empiric, 26/101 (26%) tuberculosis treatment courses were started empirically. Compared to sputum smear- or Xpert-positive patients with positive cultures, empiricallytreated, Xpert-negative patients with negative cultures had higher prevalence of HIV (67% versus 37%), shorter duration of cough (median 4 versus 8 weeks), and lower inflammatory markers (median CRP 7 versus 101 mg/L). Conclusion Judged against sputum culture in a routine care setting of high HIV prevalence, the accuracy of Xpert was high. Clinical judgment identified a small number of additional culture-positive cases, but with poor specificity. Although clinicians should continue to prescribe tuberculosis treatment for Xpert-negative patients whose clinical presentations strongly suggest pulmonary tuberculosis, they should also carefully consider alternative diagnoses.
Evaluation of underweight status may improve identification of the highest-risk patients during outpatient evaluation for pulmonary tuberculosis
(PLoS ONE, 2020) Kitonsa, Peter J.; Nalutaaya, Annet; Mukiibi, James; Nakasolya, Olga; Isooba, David; Kamoga, Caleb; Baik, Yeonsoo; Robsky, Katherine; Dowdy, David W.; Katamba, Achilles; Kendall, Emily A.
When evaluating symptomatic patients for tuberculosis (TB) without access to same-day diagnostic test results, clinicians often make empiric decisions about starting treatment. The number of TB symptoms and/or underweight status could help identify patients at highest risk for a positive result. We sought to evaluate the usefulness of BMI assessment and a count of characteristic TB symptoms for identifying patients at highest risk for TB. Methods We enrolled adult patients receiving pulmonary TB diagnoses and a representative sample with negative TB evaluations at four outpatient health facilities in Kampala, Uganda. We asked patients about symptoms of chronic cough, night sweats, chest pain, fever, hemoptysis, or weight loss; measured height and weight; and collected sputum for mycobacterial culture. We evaluated the diagnostic accuracy (for culture-positive TB) of two simple scoring systems: (a) number of TB symptoms, and (b) number of TB symptoms plus one or more additional points for underweight status (body mass index [BMI] � 18.5 kg/m2). Results We included 121 patients with culture-positive TB and 370 patients with negative culture results (44 of whom had been recommended for TB treatment by evaluating clinicians). Of the six symptoms assessed, the median number of symptoms that patients reported was two (interquartile range [IQR]: 1, 3). The median BMI was 20.9 kg/m2 (IQR: 18.6, 24.0), and 118 (24%) patients were underweight. Counting the number of symptoms provided an area
Spatial distribution of people diagnosed with tuberculosis through routine and active case finding: a community-based study in Kampala, Uganda
(Infectious diseases of poverty, 2020) Robsky, Katherine O.; Kitonsa, Peter J.; Mukiibi, James; Nakasolya, Olga; Isooba, David; Nalutaaya, Annet; Salvatore, Phillip P.; Kendall, Emily A.; Katamba, Achilles; Dowdy, David
Routine tuberculosis (TB) notifications are geographically heterogeneous, but their utility in predicting the location of undiagnosed TB cases is unclear. We aimed to identify small-scale geographic areas with high TB notification rates based on routinely collected data and to evaluate whether these areas have a correspondingly high rate of undiagnosed prevalent TB. Methods: We used routinely collected data to identify geographic areas with high TB notification rates and evaluated the extent to which these areas correlated with the location of undiagnosed cases during a subsequent community-wide active case finding intervention in Kampala, Uganda. We first enrolled all adults who lived within 35 contiguous zones and were diagnosed through routine care at four local TB Diagnosis and Treatment Units. We calculated average monthly TB notification rates in each zone and defined geographic areas of “high risk” as zones that constituted the 20% of the population with highest notification rates. We compared the observed proportion of TB notifications among residents of these high-risk zones to the expected proportion, using simulated estimates based on population size and random variation alone. We then evaluated the extent to which these high-risk zones identified areas with high burdens of undiagnosed TB during a subsequent community-based active case finding campaign using a chi-square test. Results: We enrolled 45 adults diagnosed with TB through routine practices and who lived within the study area (estimated population of 49 527). Eighteen zones reported no TB cases in the 9-month period; among the remaining zones, monthly TB notification rates ranged from 3.9 to 39.4 per 100 000 population. The five zones with the highest notification rates constituted 62% (95% CI: 47–75%) of TB cases and 22% of the population–significantly higher than would be expected if population size and random chance were the only determinants of zone-to-zone variation (48%, 95% simulation interval: 40–59%). These five high-risk zones accounted for 42% (95% CI: 34–51%) of the 128 cases detected during the subsequent community-based case finding intervention, which was significantly higher than the 22% expected by chance (P < 0.001) but lower than the 62% of cases notified from those zones during the pre-intervention period (P = 0.02). Conclusions: There is substantial heterogeneity in routine TB notification rates at the zone level. Using facilitybased TB notification rates to prioritize high-yield areas for active case finding could double the yield of such casefinding interventions.
The Spectrum of Tuberculosis Disease in an Urban Ugandan Community and Its Health Facilities
(Clinical Infectious Diseases, 2021) Kendall, Emily A.; Kitonsa, Peter J.; Nalutaaya, Annet; Erisa, Caleb; Mukiibi, James; Nakasolya, Olga; Isooba, David; Baik, Yeonsoo; Robsky, Katherine O.; Kato-Maeda, Midori; Cattamanchi, Adithya; Katamba, Achilles; Dowdy, David W.
New, sensitive diagnostic tests facilitate identification and investigation of milder forms of tuberculosis (TB) disease. We used community-based TB testing with the Xpert MTB/RIF Ultra assay (“Ultra”) to characterize individuals with previously undiagnosed TB and compare them to those from the same community who were diagnosed with TB through routine care. Methods. We offered community-based sputum Ultra testing to adult residents of a well-defined area (population 34 000 adults) in Kampala, Uganda, via door-to-door screening and venue-based testing, then used detailed interview and laboratory testing to characterize TB-positive individuals. We compared these individuals to residents diagnosed with pulmonary TB at local health facilities and a representative sample of residents without TB (controls). Results. Of 12 032 residents with interpretable Ultra results, 113 (940 [95% confidence interval {CI}, 780–1130] per 100 000) tested positive, including 71 (63%) positive at the lowest (trace) level. A spectrum of TB disease was observed in terms of chronic cough (93% among health facility–diagnosed cases, 77% among residents with positive community-based Ultra results at levels above trace, 33% among trace-positive community participants, and 18% among TB-negative controls), TB symptom prevalence (99%, 87%, 60%, and 38%, respectively), and C-reactive protein (75th percentile: 101 mg/L, 28 mg/L, 6 mg/L, and 4 mg/L, respectively). Community-diagnosed cases were less likely than health facility–diagnosed cases to have human immunodeficiency virus coinfection or previous TB. The specificity of Ultra was 99.4% (95% CI, 99.2%–99.5%) relative to a single spot sputum culture. Conclusions. People with undiagnosed prevalent TB in the community have different characteristics than those diagnosed with pulmonary TB in health facilities. Newer diagnostic tests may identify a group of people with early or very mild disease. Keywords. active case-finding; Xpert MTB/RIF Ultra; subclinical tuberculosis; prevalent tuberculosis.

Browsing by Author "Kitonsa, Peter J."

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