Browsing by Author "Salvatore, Phillip P."

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    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.
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    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.