Journal Article > ResearchAbstract Only
Ann Glob Health. 2015 March 12; Volume 81 (Issue 1); 7.; DOI:10.1016/j.aogh.2015.02.529
Kemigisha E, Katawera V, Mwanga-Amumpaire J
Ann Glob Health. 2015 March 12; Volume 81 (Issue 1); 7.; DOI:10.1016/j.aogh.2015.02.529
BACKGROUND
TB contributes to increased morbidity and mortality in children with vulnerable immune systems such as the severely malnourished, HIV infected or the infants. Clinical features might be poor predictors of active TB infection especially in children with severe malnutrition. This study determined the prevalence; estimated additional yield of TB cases on routine screening compared to targeted screening approach and studied the clinical predictors of tuberculosis disease in children between 2 months and 5 years with severe acute malnutrition.
METHODS
A cross sectional study of newly admitted children with severe malnutrition aged between 2 months and 5 years was conducted between March and September 2014 at Mbarara Regional Referral Hospital. Written informed consent was obtained from guardians. A detailed history, general physical examination, and investigations which included specimen collection by gastric, nasopharyngeal and or lymph node aspirate methods, as well as TST and CXR were done. Children were classified according to level of certainty of TB diagnosis as “confirmed”, “probable”, “possible”or “TB unlikely”. The proportional yield by routine screening and subgroup of targeted screening was determined. Logistic regression was done to determine independent predictors of TB.
FINDINGS
A total of 172 children had complete TB evaluation. The prevalence of confirmed/probable TB (TB cases) was 6.4% (11/172); Of the 11 TB cases, 4 were confirmed; 3 of whom had a positive smear, Xpert/MTB/RIF and culture results while 1 had a smear positive result only. Although, there was no statistical difference in TB yield between targeted and routine screening of TB in this population (p-value>0.05), there were 4 more TB cases identified through routine screening. Severe wasting, cervical lymphadenopathy and age group below 1 year had a statistically significant association with tuberculosis (p¼0.0002).
INTERPRETATION
We found a high prevalence of TB cases using NIH criteria, but low rates of Xpert/culture-confirmed TB among severely malnourished hospitalized children. Due to very unspecific presentation of TB in this population, evidenced by lack of statistical associations with documented predictors of TB, routine screening of all severely malnourished children for TB may offer clinical benefits
TB contributes to increased morbidity and mortality in children with vulnerable immune systems such as the severely malnourished, HIV infected or the infants. Clinical features might be poor predictors of active TB infection especially in children with severe malnutrition. This study determined the prevalence; estimated additional yield of TB cases on routine screening compared to targeted screening approach and studied the clinical predictors of tuberculosis disease in children between 2 months and 5 years with severe acute malnutrition.
METHODS
A cross sectional study of newly admitted children with severe malnutrition aged between 2 months and 5 years was conducted between March and September 2014 at Mbarara Regional Referral Hospital. Written informed consent was obtained from guardians. A detailed history, general physical examination, and investigations which included specimen collection by gastric, nasopharyngeal and or lymph node aspirate methods, as well as TST and CXR were done. Children were classified according to level of certainty of TB diagnosis as “confirmed”, “probable”, “possible”or “TB unlikely”. The proportional yield by routine screening and subgroup of targeted screening was determined. Logistic regression was done to determine independent predictors of TB.
FINDINGS
A total of 172 children had complete TB evaluation. The prevalence of confirmed/probable TB (TB cases) was 6.4% (11/172); Of the 11 TB cases, 4 were confirmed; 3 of whom had a positive smear, Xpert/MTB/RIF and culture results while 1 had a smear positive result only. Although, there was no statistical difference in TB yield between targeted and routine screening of TB in this population (p-value>0.05), there were 4 more TB cases identified through routine screening. Severe wasting, cervical lymphadenopathy and age group below 1 year had a statistically significant association with tuberculosis (p¼0.0002).
INTERPRETATION
We found a high prevalence of TB cases using NIH criteria, but low rates of Xpert/culture-confirmed TB among severely malnourished hospitalized children. Due to very unspecific presentation of TB in this population, evidenced by lack of statistical associations with documented predictors of TB, routine screening of all severely malnourished children for TB may offer clinical benefits
Journal Article > ResearchFull Text
MBMC Microbiol. 2014 October 7; Volume 14 (Issue 1); DOI:10.1186/s12866-014-0259-6
Katawera V, Siedner MJ, Boum Y II
MBMC Microbiol. 2014 October 7; Volume 14 (Issue 1); DOI:10.1186/s12866-014-0259-6
BackgroundThe resazurin microtiter assay (classic REMA), a colorimetric liquid culture-based drug susceptibility assay for Mycobacterium tuberculosis (MTB), has been endorsed by the World Health Organization. The assay requires 8-16 days to obtain results, delaying management of drug resistant tuberculosis patients. A modified REMA which allows results in as little as 24 hours for bacterial strains, has been developed and validated using Staphylococcus aureus, but has not yet been evaluated for MTB. Therefore we assessed the performance of the modified REMA for rifampicin (RIF) and isoniazid (INH) susceptibility, using the classic REMA as the reference standard. We also compared simplicity (from the technicians¿ point of view), time taken to obtain results (rank-sum testing), specificity and Kappa statistics of the two methods.ResultsThe modified REMA, which is a one-step procedure, was found to be simpler to perform and results were obtained in a significantly shorter time (5 versus 9 days, p¿<¿0.0001) compared to the classic REMA due to addition of indicator and strain at the same time. The specificity of the modified REMA was low {46.8% (35.5% - 58.4%) for RIF and 13.9% (7.2% - 23.5%) for INH}. Kappa statistics were 16.0% for RIF and 2.0% for INH. Low specificity and kappa statistics are due to indicator reduction by the strains before complete drug activity.ConclusionAlthough modified REMA is faster and simpler compared to classic REMA, it is not reliable for MTB drug susceptibility testing.
Journal Article > ResearchFull Text
Int J Tuberc Lung Dis. 2016 August 1; Volume 20 (Issue 8); 1113-1117.; DOI:10.5588/ijtld.15.0691
Atwebembeire J, Orikiriza P, Bonnet MMB, Atwine D, Katawera V, et al.
Int J Tuberc Lung Dis. 2016 August 1; Volume 20 (Issue 8); 1113-1117.; DOI:10.5588/ijtld.15.0691
SETTING
Although it is now widely used for tuberculosis (TB) diagnosis, Xpert® MTB/RIF availability remains inadequate in low-resource settings. Moreover, its accuracy in testing stored samples from non-expectorating patients has not been evaluated.
OBJECTIVE
To assess the performance of Xpert in frozen samples of induced sputum (IS) and sputum from string test (ST) from non-expectorating individuals with presumed TB.
DESIGN
This was a laboratory-based study of 377 ST and IS samples collected between March 2010 and March 2013 at a referral hospital in Uganda. Samples were decontaminated, centrifuged and cultured, and the resultant samples were frozen at −20°C before Xpert evaluation.
RESULTS
TB was detected in ST and IS samples from 19/163 (11.7%) children and 63/201 (29.4%) adults using culture. Xpert sensitivity in frozen sediments from children was 37.5% (95%CI 8.5–75.5) in ST and 41.7% (95%CI 15.2–72.3) in IS samples, with specificities of respectively 100% (95%CI 94.9–100) and 98.6% (95%CI 92.7–100). In adults, sensitivity was respectively 50% (95%CI 31.3–68.7) and 48.5% (95%CI 30.8–66.4) in ST and IS samples, with specificities of respectively 100% (95%CI 95.5–100) and 98.6% (95%CI 92.4–100).
CONCLUSION
Given these results, and particularly the high specificity, the use of Xpert on frozen ST and IS sediment samples from both children and adults is promising.
Although it is now widely used for tuberculosis (TB) diagnosis, Xpert® MTB/RIF availability remains inadequate in low-resource settings. Moreover, its accuracy in testing stored samples from non-expectorating patients has not been evaluated.
OBJECTIVE
To assess the performance of Xpert in frozen samples of induced sputum (IS) and sputum from string test (ST) from non-expectorating individuals with presumed TB.
DESIGN
This was a laboratory-based study of 377 ST and IS samples collected between March 2010 and March 2013 at a referral hospital in Uganda. Samples were decontaminated, centrifuged and cultured, and the resultant samples were frozen at −20°C before Xpert evaluation.
RESULTS
TB was detected in ST and IS samples from 19/163 (11.7%) children and 63/201 (29.4%) adults using culture. Xpert sensitivity in frozen sediments from children was 37.5% (95%CI 8.5–75.5) in ST and 41.7% (95%CI 15.2–72.3) in IS samples, with specificities of respectively 100% (95%CI 94.9–100) and 98.6% (95%CI 92.7–100). In adults, sensitivity was respectively 50% (95%CI 31.3–68.7) and 48.5% (95%CI 30.8–66.4) in ST and IS samples, with specificities of respectively 100% (95%CI 95.5–100) and 98.6% (95%CI 92.4–100).
CONCLUSION
Given these results, and particularly the high specificity, the use of Xpert on frozen ST and IS sediment samples from both children and adults is promising.
Journal Article > ResearchFull Text
Sci Rep. 2016 June 10; Volume 6 (Issue 1); DOI:10.1038/srep27792
Djaout K, Singh VK, Boum Y II, Katawera V, Becker HF, et al.
Sci Rep. 2016 June 10; Volume 6 (Issue 1); DOI:10.1038/srep27792
There is an urgent need to identify new treatments for tuberculosis (TB), a major infectious disease caused by Mycobacterium tuberculosis (Mtb), which results in 1.5 million deaths each year. We have targeted two essential enzymes in this organism that are promising for antibacterial therapy and reported to be inhibited by naphthoquinones. ThyX is an essential thymidylate synthase that is mechanistically and structurally unrelated to the human enzyme. DNA gyrase is a DNA topoisomerase present in bacteria and plants but not animals. The current study set out to understand the structure-activity relationships of these targets in Mtb using a combination of cheminformatics and in vitro screening. Here, we report the identification of new Mtb ThyX inhibitors, 2-chloro-3-(4-methanesulfonylpiperazin-1-yl)-1,4-dihydronaphthalene-1,4-dione) and idebenone, which show modest whole-cell activity and appear to act, at least in part, by targeting ThyX in Mtb.
Journal Article > ResearchFull Text
BMC Research Notes. 2014 October 22; Volume 7 (Issue 1); DOI:10.1186/1756-0500-7-746
Omoding D, Katawera V, Siedner MJ, Boum Y II
BMC Research Notes. 2014 October 22; Volume 7 (Issue 1); DOI:10.1186/1756-0500-7-746
Point-of-care tests have the capacity to improve healthcare delivery by reducing costs and delay associated with care. A novel point-of-care immunochromatographic test for dual diagnosis of both HIV and syphilis by detecting IgG, IgM and IgA antibodies to HIV, and specific and recombinant Treponema pallidum antigens has recently been developed, but has not been evaluated in rural field settings. We evaluated the performance of the SD Bioline Syphilis/HIV Duo (Duo) assay at a healthcare center in rural Uganda.