Journal Article > ResearchFull Text
PLOS One. 2015 February 6; Volume 10 (Issue 2); DOI:10.1371/journal.pone.0118191
Orikiriza P, Tibenderana B, Siedner MJ, Mueller YK, Byarugaba F, et al.
PLOS One. 2015 February 6; Volume 10 (Issue 2); DOI:10.1371/journal.pone.0118191
There are limited data on region-specific drug susceptibility of tuberculosis (TB) in Uganda. We performed resistance testing on specimens collected from treatment-naive patients with pulmonary TB in Southwestern Uganda for first and second line anti-TB drugs. We sought to provide data to guide regional recommendations for empiric TB therapy.
Journal Article > CommentaryFull Text
Lancet Public Health. 2018 March 23; Volume 3 (Issue 4); DOI:10.1016/S2468-2667(18)30049-5
Godreuil S, Marcy O, Wobudeya E, Bonnet MMB, Solassol J
Lancet Public Health. 2018 March 23; Volume 3 (Issue 4); DOI:10.1016/S2468-2667(18)30049-5
Journal Article > ResearchFull Text
Int J Tuberc Lung Dis. 2005 October 1
Bonnet MMB, Sizaire V, Kebede YYK, Janin A, Doshetov D, et al.
Int J Tuberc Lung Dis. 2005 October 1
SETTING: After the collapse of the Soviet Union, countries in the region faced a dramatic increase in tuberculosis cases and the emergence of drug resistance. OBJECTIVE: To discuss the relevance of the DOTS strategy in settings with a high prevalence of drug resistance. DESIGN: Retrospective analysis of one-year treatment outcomes of short-course chemotherapy (SCC) and results of drug susceptibility testing (DST) surveys of six programmes located in the former Soviet Union: Kemerovo prison, Russia; Abkhasia, Georgia; Nagorno-Karabagh, Azerbaijan; Karakalpakstan, Uzbekistan; Dashoguz Velayat, Turkmenistan; and South Kazakhstan Oblast, Kazakhstan. Results are reported for new and previously treated smear-positive patients. RESULTS: Treatment outcomes of 3090 patients and DST results of 1383 patients were collected. Treatment success rates ranged between 87% and 61%, in Nagorno-Karabagh and Kemerovo, respectively, and failure rates between 7% and 23%. Any drug resistance ranged between 66% and 31% in the same programmes. MDR rates ranged between 28% in Karakalpakstan and Kemerovo prison and 4% in Nagorno-Karabagh. CONCLUSION: These results show the limits of SCC in settings with a high prevalence of drug resistance. They demonstrate that adapting treatment according to resistance patterns, access to reliable culture, DST and good quality second-line drugs are necessary.
Journal Article > ResearchFull Text
PLOS One. 2011 May 31; Volume 6 (Issue 5); DOI:10.1371/journal.pone.0020175
Bonnet MMB, Gagnidze L, Guerin PJ, Bonte L, Ramsay AR, et al.
PLOS One. 2011 May 31; Volume 6 (Issue 5); DOI:10.1371/journal.pone.0020175
Sputum microscopy is the only diagnostic for tuberculosis (TB) available at peripheral levels of health service in resource-poor countries. Its sensitivity is reduced in high HIV-prevalence settings. Sodium hypochlorite (NaOCl) specimen sedimentation prior microscopy and light-emitting diode (LED)-fluorescence microscopy (FM) can individually improve performance of microscopy. This study aimed to evaluate the performance of combined LED-FM and NaOCl sputum sedimentation for TB detection at peripheral level of health services.
Journal Article > LetterFull Text
Lancet Global Health. 2023 April 1; Volume 11 (Issue 4); e502.; DOI:10.1016/S2214-109X(23)00115-8
Huerga H, Gupta-Wright A, Muyindike WR, Hewison CCH, Casenghi M, et al.
Lancet Global Health. 2023 April 1; Volume 11 (Issue 4); e502.; DOI:10.1016/S2214-109X(23)00115-8
Journal Article > ResearchSubscription Only
Pediatrics. 2023 March 23; Online ahead of print; DOI:10.1542/peds.2022-057912
Bonnet MMB, Nordholm AC, Ssekyanzi B, Byamukama O, Orikiriza P, et al.
Pediatrics. 2023 March 23; Online ahead of print; DOI:10.1542/peds.2022-057912
BACKGROUND AND OBJECTIVES:
Children experience high tuberculosis (TB)-related mortality but causes of death among those with presumptive TB are poorly documented. We describe the mortality, likely causes of death, and associated risk factors among vulnerable children admitted with presumptive TB in rural Uganda.
METHODS:
We conducted a prospective study of vulnerable children, defined as <2 years of age, HIV-positive, or severely malnourished, with a clinical suspicion of TB. Children were assessed for TB and followed for 24 weeks. TB classification and likely cause of death were assessed by an expert endpoint review committee, including insight gained from minimally invasive autopsies, when possible.
RESULTS:
Of the 219 children included, 157 (71.7%) were <2 years of age, 72 (32.9%) were HIV-positive, and 184 (84.0%) were severely malnourished. Seventy-one (32.4%) were classified as “likely tuberculosis” (15 confirmed and 56 unconfirmed), and 72 (32.9%) died. The median time to death was 12 days. The most frequent causes of death, ascertained for 59 children (81.9%), including 23 cases with autopsy results, were severe pneumonia excluding confirmed TB (23.7%), hypovolemic shock due to diarrhea (20.3%), cardiac failure (13.6%), severe sepsis (13.6%), and confirmed TB (10.2%). Mortality risk factors were confirmed TB (adjusted hazard ratio [aHR] = 2.84 [95% confidence interval (CI): 1.19–6.77]), being HIV-positive (aHR = 2.45 [95% CI: 1.37–4.38]), and severe clinical state on admission (aHR = 2.45 [95% CI: 1.29–4.66]).
CONCLUSIONS:
Vulnerable children hospitalized with presumptive TB experienced high mortality. A better understanding of the likely causes of death in this group is important to guide empirical management.
Children experience high tuberculosis (TB)-related mortality but causes of death among those with presumptive TB are poorly documented. We describe the mortality, likely causes of death, and associated risk factors among vulnerable children admitted with presumptive TB in rural Uganda.
METHODS:
We conducted a prospective study of vulnerable children, defined as <2 years of age, HIV-positive, or severely malnourished, with a clinical suspicion of TB. Children were assessed for TB and followed for 24 weeks. TB classification and likely cause of death were assessed by an expert endpoint review committee, including insight gained from minimally invasive autopsies, when possible.
RESULTS:
Of the 219 children included, 157 (71.7%) were <2 years of age, 72 (32.9%) were HIV-positive, and 184 (84.0%) were severely malnourished. Seventy-one (32.4%) were classified as “likely tuberculosis” (15 confirmed and 56 unconfirmed), and 72 (32.9%) died. The median time to death was 12 days. The most frequent causes of death, ascertained for 59 children (81.9%), including 23 cases with autopsy results, were severe pneumonia excluding confirmed TB (23.7%), hypovolemic shock due to diarrhea (20.3%), cardiac failure (13.6%), severe sepsis (13.6%), and confirmed TB (10.2%). Mortality risk factors were confirmed TB (adjusted hazard ratio [aHR] = 2.84 [95% confidence interval (CI): 1.19–6.77]), being HIV-positive (aHR = 2.45 [95% CI: 1.37–4.38]), and severe clinical state on admission (aHR = 2.45 [95% CI: 1.29–4.66]).
CONCLUSIONS:
Vulnerable children hospitalized with presumptive TB experienced high mortality. A better understanding of the likely causes of death in this group is important to guide empirical management.
Journal Article > ResearchAbstract
Pediatr Infect Dis J. 2017 August 2; Volume 37 (Issue 2); 147-152.; DOI:10.1097/INF.0000000000001727
Bonnet MMB, Nansumba M, Bastard M, Orikiriza P, Kyomugasho N, et al.
Pediatr Infect Dis J. 2017 August 2; Volume 37 (Issue 2); 147-152.; DOI:10.1097/INF.0000000000001727
BACKGROUND
Mortality among children with presumptive tuberculosis (TB) empiric TB treatment can be high. We describe the predictors of death among children with presumptive TB, and the relation between treatment and mortality.
METHODS
A prospective cohort of children with presumptive TB who underwent clinical assessment, chest radiograph, tuberculin skin test and sputum bacterial tests for TB was followed up for 3 months. TB diagnosis was based on mycobacterial, clinical and radiologic findings. Predictors of deaths were determined using cox regression model.
RESULTS
Of 360 children included in the analysis, 31.4% were younger than 2 years; 31.6% were HIV infected and 11.3% were severely malnourished. One hundred forty (38.9%) were diagnosed with TB, 18 (13%) of whom were bacteriologically confirmed. At 3 months of follow up, 25 of 360 (6.9%) children had died: 15 of 140 (10.7%) were receiving TB treatment versus 10 of 220 (4.5%) were not receiving treatment (P = 0.025). Severely malnourished children [adjusted hazard ratio (aHR), 9.86; 95% confidence interval (CI): 3.11-31.23] and those with chest radiographs suggestive of TB (aHR, 4.20; 95% CI: 0.93-19.01) were more likely to die. Children receiving empiric TB treatment had an increased risk of death (aHR, 2.37; 95% CI: 1.01-5.55) compared with children without treatment after adjustment for age, sex, HIV status and Bacillus Calmette-Guérin (BCG) vaccination.
CONCLUSIONS
The high mortality in children receiving empirically TB treatment highlights the difficulty in diagnosing childhood TB, the increased likelihood of starting treatment in critically ill children and in children with chronic disease, and the possibility of misdiagnosis. It strengthens the need to invest further in early TB detection and diagnosing nonsevere illness.
Mortality among children with presumptive tuberculosis (TB) empiric TB treatment can be high. We describe the predictors of death among children with presumptive TB, and the relation between treatment and mortality.
METHODS
A prospective cohort of children with presumptive TB who underwent clinical assessment, chest radiograph, tuberculin skin test and sputum bacterial tests for TB was followed up for 3 months. TB diagnosis was based on mycobacterial, clinical and radiologic findings. Predictors of deaths were determined using cox regression model.
RESULTS
Of 360 children included in the analysis, 31.4% were younger than 2 years; 31.6% were HIV infected and 11.3% were severely malnourished. One hundred forty (38.9%) were diagnosed with TB, 18 (13%) of whom were bacteriologically confirmed. At 3 months of follow up, 25 of 360 (6.9%) children had died: 15 of 140 (10.7%) were receiving TB treatment versus 10 of 220 (4.5%) were not receiving treatment (P = 0.025). Severely malnourished children [adjusted hazard ratio (aHR), 9.86; 95% confidence interval (CI): 3.11-31.23] and those with chest radiographs suggestive of TB (aHR, 4.20; 95% CI: 0.93-19.01) were more likely to die. Children receiving empiric TB treatment had an increased risk of death (aHR, 2.37; 95% CI: 1.01-5.55) compared with children without treatment after adjustment for age, sex, HIV status and Bacillus Calmette-Guérin (BCG) vaccination.
CONCLUSIONS
The high mortality in children receiving empirically TB treatment highlights the difficulty in diagnosing childhood TB, the increased likelihood of starting treatment in critically ill children and in children with chronic disease, and the possibility of misdiagnosis. It strengthens the need to invest further in early TB detection and diagnosing nonsevere illness.
Journal Article > ResearchFull Text
Int J Tuberc Lung Dis. 2007 September 1
Bonnet MMB, Ramsay AR, Gagnidze L, Githui W, Guerin PJ, et al.
Int J Tuberc Lung Dis. 2007 September 1
SETTING: Urban health clinic, Nairobi. OBJECTIVE: To evaluate the impact on tuberculosis (TB) case detection and laboratory workload of reducing the number of sputum smears examined and thresholds for diagnosing positive smears and positive cases. DESIGN: In this prospective study, three Ziehl-Neelsen stained sputum smears from consecutive pulmonary TB suspects were examined blind. The standard approach (A), > or = 2 positive smears out of 3, using a cut-off of 10 acid-fast bacilli (AFB)/100 high-power fields (HPF), was compared with approaches B, > or = 2 positive smears (> or = 4 AFB/100 HPF) out of 3, one of which is > or = 10 AFB/100 HPF; C, > or = 2 positive smears (> or = 4 AFB/100 HPF) out of 3; D, > or = 1 positive smear (> or = 10 AFB/100 HPF) out of 2; and E, > or = 1 positive smear (> or = 4 AFB/100 HPF) out of 2. The microscopy gold standard was detection of at least one positive smear (> or = 4 AFB/100 HPF) out of 3. RESULTS: Among 644 TB suspects, the alternative approaches detected from 114 (17.7%) (approach B) to 123 cases (19.1%) (approach E) compared to 105 cases (16.3%) for approach A (P < 0.005). Sensitivity ranged between 82.0% (105/128) for A and 96.1% (123/128) for E. The single positive smear approaches reduced the number of smears by 36% compared to approach A. CONCLUSION: Reducing the number of specimens and the positivity threshold to define a positive case increased the sensitivity of microscopy and reduced laboratory workload.
Journal Article > ResearchAbstract
J Clin Microbiol. 2019 October 16
Ardizzoni E, Orikiriza P, Ssuuna C, Nyehangane D, Gumsboga M, et al.
J Clin Microbiol. 2019 October 16
Background: Xpert MTB/RIF (Xpert) and culture are the most reliable methods for tuberculosis diagnosis but are still poorly accessible in many low resource countries. We aimed to assess the effect of OMNIgene® SPUTUM (OM-S) and ethanol in preserving sputum for Xpert and OM-S for mycobacteria growth indicator tube (MGIT) testing over a period of 15 and 8 days respectively.
Methods: Sputum were collected from newly diagnosed smear-positive patients. For Xpert, pooled samples were split into 5 aliquots: 3 for Xpert on day 0, 7 and 15 days without additive and 2 with either OM-S or ethanol at day 15. For MGIT, 2 aliquots were tested without preservative and 2 with OM-S at 0 and 8 days.
Results: A total of 48 and 47 samples were included in the analysis for Xpert and culture. With Xpert, using Day 0 as reference, untreated samples stored for 7 and 15 days showed concordance of 45/46 (97.8%) and 46/48 (95.8%). For samples preserved with OM-S or ethanol for 15 days compared with untreated samples processed at day 0 or after 15 days, OM-S concordance was 46/48(95.8%) and 47/48(97.9%), while ethanol was 44/48 (91.7%) and 45/48 (93.8%). With MGIT, concordance between untreated and OM-S treated samples was 21/41(51.2%) at Day 0 and 21/44(47.7%) at day8.
Conclusions: Xpert equally detected TB in OM-S treated and untreated samples up to 15 days but showed slightly lower detection in ethanol treated samples. Among OM-S treated samples, MGIT positivity was significantly lower compared to untreated samples at both time-points.
Methods: Sputum were collected from newly diagnosed smear-positive patients. For Xpert, pooled samples were split into 5 aliquots: 3 for Xpert on day 0, 7 and 15 days without additive and 2 with either OM-S or ethanol at day 15. For MGIT, 2 aliquots were tested without preservative and 2 with OM-S at 0 and 8 days.
Results: A total of 48 and 47 samples were included in the analysis for Xpert and culture. With Xpert, using Day 0 as reference, untreated samples stored for 7 and 15 days showed concordance of 45/46 (97.8%) and 46/48 (95.8%). For samples preserved with OM-S or ethanol for 15 days compared with untreated samples processed at day 0 or after 15 days, OM-S concordance was 46/48(95.8%) and 47/48(97.9%), while ethanol was 44/48 (91.7%) and 45/48 (93.8%). With MGIT, concordance between untreated and OM-S treated samples was 21/41(51.2%) at Day 0 and 21/44(47.7%) at day8.
Conclusions: Xpert equally detected TB in OM-S treated and untreated samples up to 15 days but showed slightly lower detection in ethanol treated samples. Among OM-S treated samples, MGIT positivity was significantly lower compared to untreated samples at both time-points.
Journal Article > LetterFull Text
Am J Respir Crit Care Med. 2016 October 15; Volume 194 (Issue 8); 1028-1029.; DOI:10.1164/rccm.201605-1080LE
Varaine FFV, Guglielmetti L, Huerga H, Bonnet MMB, Kiria N, et al.
Am J Respir Crit Care Med. 2016 October 15; Volume 194 (Issue 8); 1028-1029.; DOI:10.1164/rccm.201605-1080LE