Journal Article > ResearchFull Text
Antimicrob Agents Chemother. 2009 May 26; Volume 53 (Issue 8); 3353-3356.; DOI:10.1128/AAC.00050-09
Feuerriegel S, Cox HS, Zarkua N, Karimovich HA, Braker K, et al.
Antimicrob Agents Chemother. 2009 May 26; Volume 53 (Issue 8); 3353-3356.; DOI:10.1128/AAC.00050-09
The rapid detection of Mycobacterium tuberculosis isolates resistant to second-line drugs is crucial for the institution of appropriate treatment regimens as early as possible. Although molecular methods have successfully been used for the rapid detection of resistance to first-line drugs, there are limited data on mutations that confer resistance to second-line drugs. To address this question, we analyzed Mycobacterium tuberculosis strains resistant to ofloxacin (n = 26) and to capreomycin and/or amikacin (n = 48) from Uzbekistan for variations in target genes (gyrA, gyrB, rrs, and tlyA). Strains susceptible to ofloxacin (n = 49) and capreomycin and/or amikacin (n = 39) were included as controls. Mutations in gyrA or gyrB were found in 96% (25/26 strains) of the ofloxacin-resistant strains, while none of the susceptible strains displayed mutations in those two genes. The most common mutation occurred in gyrA at codon 94 (17/26 strains [65.4%]), followed by mutations at codons 90 and 91. Two strains showed a mutation in gyrB, at codons 485 and 543, respectively; both mutations have not been reported previously. The most frequent mutation in strains resistant to both amikacin and capreomycin was A1401G in rrs (34/40 strains [85.0%]). Three strains had mutations in tlyA, of which two (at codons 18 and 118) were associated with resistance to capreomycin alone. Overall, none of the 10 resistant strains (5 amikacin-resistant and capreomycin-susceptible strains) and none of the 39 susceptible control strains had mutations in the genes investigated. Our results clearly demonstrate the potential of sequence analyses of short regions of relatively few target genes for the rapid detection of resistance to second-line drugs among strains isolated from patients undergoing treatment for multidrug-resistant tuberculosis. The mechanisms that confer amikacin resistance in this setting remain unclear.
Journal Article > ResearchFull Text
PLOS One. 2013 November 6; Volume 8 (Issue 11); e78364.; DOI:10.1371/journal.pone.0078364
Lalor MK, Greig J, Allamuratova S, Althomsons S, Tigay Z, et al.
PLOS One. 2013 November 6; Volume 8 (Issue 11); e78364.; DOI:10.1371/journal.pone.0078364
BACKGROUND
The Médecins Sans Frontières project of Uzbekistan has provided multidrug-resistant tuberculosis treatment in the Karakalpakstan region since 2003. Rates of default from treatment have been high, despite psychosocial support, increasing particularly since programme scale-up in 2007. We aimed to determine factors associated with default in multi- and extensively drug-resistant tuberculosis patients who started treatment between 2003 and 2008 and thus had finished approximately 2 years of treatment by the end of 2010.
METHODS
A retrospective cohort analysis of multi- and extensively drug-resistant tuberculosis patients enrolled in treatment between 2003 and 2008 compared baseline demographic characteristics and possible risk factors for default. Default was defined as missing ≥60 consecutive days of treatment (all drugs). Data were routinely collected during treatment and entered in a database. Potential risk factors for default were assessed in univariate analysis using chi-square test and in multivariate analysis with logistic regression.
RESULTS
20% (142/710) of patients defaulted after a median of 6 months treatment (IQR 2.6-9.9). Factors associated with default included severity of resistance patterns (pre-extensively drug-resistant/extensively drug-resistant tuberculosis adjusted odds ratio 0.52, 95%CI: 0.31-0.86), previous default (2.38, 1.09-5.24) and age >45 years (1.77, 1.10-2.87). The default rate was 14% (42/294) for patients enrolled 2003-2006 and 24% (100/416) for 2007-2008 enrolments (p = 0.001).
CONCLUSIONS
Default from treatment was high and increased with programme scale-up. It is essential to ensure scale-up of treatment is accompanied with scale-up of staff and patient support. A successful first course of tuberculosis treatment is important; patients who had previously defaulted were at increased risk of default and death. The protective effect of severe resistance profiles suggests that understanding disease severity or fear may motivate against default. Targeted health education and support for at-risk patients after 5 months of treatment when many begin to feel better may decrease default.
The Médecins Sans Frontières project of Uzbekistan has provided multidrug-resistant tuberculosis treatment in the Karakalpakstan region since 2003. Rates of default from treatment have been high, despite psychosocial support, increasing particularly since programme scale-up in 2007. We aimed to determine factors associated with default in multi- and extensively drug-resistant tuberculosis patients who started treatment between 2003 and 2008 and thus had finished approximately 2 years of treatment by the end of 2010.
METHODS
A retrospective cohort analysis of multi- and extensively drug-resistant tuberculosis patients enrolled in treatment between 2003 and 2008 compared baseline demographic characteristics and possible risk factors for default. Default was defined as missing ≥60 consecutive days of treatment (all drugs). Data were routinely collected during treatment and entered in a database. Potential risk factors for default were assessed in univariate analysis using chi-square test and in multivariate analysis with logistic regression.
RESULTS
20% (142/710) of patients defaulted after a median of 6 months treatment (IQR 2.6-9.9). Factors associated with default included severity of resistance patterns (pre-extensively drug-resistant/extensively drug-resistant tuberculosis adjusted odds ratio 0.52, 95%CI: 0.31-0.86), previous default (2.38, 1.09-5.24) and age >45 years (1.77, 1.10-2.87). The default rate was 14% (42/294) for patients enrolled 2003-2006 and 24% (100/416) for 2007-2008 enrolments (p = 0.001).
CONCLUSIONS
Default from treatment was high and increased with programme scale-up. It is essential to ensure scale-up of treatment is accompanied with scale-up of staff and patient support. A successful first course of tuberculosis treatment is important; patients who had previously defaulted were at increased risk of default and death. The protective effect of severe resistance profiles suggests that understanding disease severity or fear may motivate against default. Targeted health education and support for at-risk patients after 5 months of treatment when many begin to feel better may decrease default.
Journal Article > ResearchFull Text
J Antimicrob Chemother. 2010 July 1; Volume 65 (Issue 7); DOI:10.1093/jac/dkq120
Plinke C, Cox HS, Zarkua N, Karimovich HA, Braker K, et al.
J Antimicrob Chemother. 2010 July 1; Volume 65 (Issue 7); DOI:10.1093/jac/dkq120
Mechanisms of resistance to ethambutol in Mycobacterium tuberculosis remain inadequately described. Although there is mounting evidence that mutations of codon 306 in embB play a key role, a significant number of phenotypically ethambutol-resistant strains do not carry mutations in this codon. Here, other mutations in the embCAB operon are suggested to be involved in resistance development.
Journal Article > ResearchFull Text
Confl Health. 2012 November 27; Volume 6 (Issue 1); 11.; DOI:10.1186/1752-1505-6-11
Bowden S, Braker K, Checchi F, Wong S
Confl Health. 2012 November 27; Volume 6 (Issue 1); 11.; DOI:10.1186/1752-1505-6-11
BACKGROUND
Prospective surveillance is a recognised approach for measuring death rates in humanitarian emergencies. However, there is limited evidence on how such surveillance should optimally be implemented and on how data are actually used by agencies. This case study investigates the implementation and utilisation of mortality surveillance data by Médecins Sans Frontières (MSF) in eastern Chad. We aimed to describe and analyse the community-based mortality surveillance system, trends in mortality data and the utilisation of these data to guide MSF's operational response.
METHODS
The case study included 5 MSF sites including 2 refugee camps and 3 camps for internally displaced persons (IDPs). Data were obtained through key informant interviews and systematic review of MSF operational reports from 2004-2008.
RESULTS
Mortality data were collected using community health workers (CHWs). Mortality generally decreased progressively. In Farchana and Breidjing refugee camps, crude death rates (CDR) decreased from 0.9 deaths per 10,000 person-days in 2004 to 0.2 in 2008 and from 0.7 to 0.1, respectively. In Gassire, Ade and Kerfi IDP camps, CDR decreased from 0.4 to 0.04, 0.3 to 0.04 and 1.0 to 0.3. Death rates among children under 5 years (U5DR) followed similar trends. CDR and U5DR crossed emergency thresholds in one site, Kerfi, where CDR rapidly rose to 2.1 and U5DR to 7.9 in July 2008 before rapidly decreasing to below emergency levels by September 2008.
DISCUSSION
Mortality data were used regularly to monitor population health status and on two occasions as a tool for advocacy. Lessons learned included the need for improved population estimates and standardized reporting procedures for improved data quality and dissemination; the importance of a simple and flexible model for data collection; and greater investment in supervising CHWs.
CONCLUSIONS
This model of community based mortality surveillance can be adapted and used by humanitarian agencies working in complex settings. Humanitarian organisations should however endeavour to disseminate routinely collected mortality data and improve utilisation of data for operational planning and evaluation. Accurate population estimation continues to be a challenge, limiting the accuracy of mortality estimates.
Prospective surveillance is a recognised approach for measuring death rates in humanitarian emergencies. However, there is limited evidence on how such surveillance should optimally be implemented and on how data are actually used by agencies. This case study investigates the implementation and utilisation of mortality surveillance data by Médecins Sans Frontières (MSF) in eastern Chad. We aimed to describe and analyse the community-based mortality surveillance system, trends in mortality data and the utilisation of these data to guide MSF's operational response.
METHODS
The case study included 5 MSF sites including 2 refugee camps and 3 camps for internally displaced persons (IDPs). Data were obtained through key informant interviews and systematic review of MSF operational reports from 2004-2008.
RESULTS
Mortality data were collected using community health workers (CHWs). Mortality generally decreased progressively. In Farchana and Breidjing refugee camps, crude death rates (CDR) decreased from 0.9 deaths per 10,000 person-days in 2004 to 0.2 in 2008 and from 0.7 to 0.1, respectively. In Gassire, Ade and Kerfi IDP camps, CDR decreased from 0.4 to 0.04, 0.3 to 0.04 and 1.0 to 0.3. Death rates among children under 5 years (U5DR) followed similar trends. CDR and U5DR crossed emergency thresholds in one site, Kerfi, where CDR rapidly rose to 2.1 and U5DR to 7.9 in July 2008 before rapidly decreasing to below emergency levels by September 2008.
DISCUSSION
Mortality data were used regularly to monitor population health status and on two occasions as a tool for advocacy. Lessons learned included the need for improved population estimates and standardized reporting procedures for improved data quality and dissemination; the importance of a simple and flexible model for data collection; and greater investment in supervising CHWs.
CONCLUSIONS
This model of community based mortality surveillance can be adapted and used by humanitarian agencies working in complex settings. Humanitarian organisations should however endeavour to disseminate routinely collected mortality data and improve utilisation of data for operational planning and evaluation. Accurate population estimation continues to be a challenge, limiting the accuracy of mortality estimates.