Journal Article > ResearchFull Text
Trop Med Int Health. 1 March 2024; Volume 29 (Issue 3); 192-205.; DOI:10.1111/tmi.13961
Kerschberger B, Vambe D, Schomaker M, Mabhena E, Daka M, et al.
Trop Med Int Health. 1 March 2024; Volume 29 (Issue 3); 192-205.; DOI:10.1111/tmi.13961
OBJECTIVES
Despite declining TB notifications in Southern Africa, TB‐related deaths remain high. We describe patient‐ and population‐level trends in TB‐related deaths in Eswatini over a period of 11 years.
METHODS
Patient‐level (retrospective cohort, from 2009 to 2019) and population‐level (ecological analysis, 2009–2017) predictors and rates of TB‐related deaths were analysed in HIV‐negative and HIV‐coinfected first‐line TB treatment cases and the population of the Shiselweni region. Patient‐level TB treatment data, and population and HIV prevalence estimates were combined to obtain stratified annual mortality rates. Multivariable Poisson regressions models were fitted to identify patient‐level and population‐level predictors of deaths.
RESULTS
Of 11,883 TB treatment cases, 1,302 (11.0%) patients died during treatment: 210/2,798 (7.5%) HIV‐negative patients, 984/8,443 (11.7%) people living with HIV (PLHIV), and 108/642 (16.8%) patients with unknown HIV‐status. The treatment case fatality ratio remained above 10% in most years. At patient‐level, fatality risk was higher in PLHIV (aRR 1.74, 1.51–2.02), and for older age and extra‐pulmonary TB irrespective of HIV‐status. For PLHIV, fatality risk was higher for TB retreatment cases (aRR 1.38, 1.18–1.61) and patients without antiretroviral therapy (aRR 1.70, 1.47–1.97). It decreases with increasing higher CD4 strata and the programmatic availability of TB‐LAM testing (aRR 0.65, 0.35–0.90). At population‐level, mortality rates decreased 6.4‐fold (−147/100,000 population) between 2009 (174/100,000) and 2017 (27/100,000), coinciding with a decline in TB treatment cases (2,785 in 2009 to 497 in 2017). Although the absolute decline in mortality rates was most pronounced in PLHIV (−826/100,000 vs. HIV‐negative: −23/100,000), the relative population‐level mortality risk remained higher in PLHIV (aRR 4.68, 3.25–6.72) compared to the HIV‐negative population.
CONCLUSIONS
TB‐related mortality rapidly decreased at population‐level and most pronounced in PLHIV. However, case fatality among TB treatment cases remained high. Further strategies to reduce active TB disease and introduce improved TB therapies are warranted.
Despite declining TB notifications in Southern Africa, TB‐related deaths remain high. We describe patient‐ and population‐level trends in TB‐related deaths in Eswatini over a period of 11 years.
METHODS
Patient‐level (retrospective cohort, from 2009 to 2019) and population‐level (ecological analysis, 2009–2017) predictors and rates of TB‐related deaths were analysed in HIV‐negative and HIV‐coinfected first‐line TB treatment cases and the population of the Shiselweni region. Patient‐level TB treatment data, and population and HIV prevalence estimates were combined to obtain stratified annual mortality rates. Multivariable Poisson regressions models were fitted to identify patient‐level and population‐level predictors of deaths.
RESULTS
Of 11,883 TB treatment cases, 1,302 (11.0%) patients died during treatment: 210/2,798 (7.5%) HIV‐negative patients, 984/8,443 (11.7%) people living with HIV (PLHIV), and 108/642 (16.8%) patients with unknown HIV‐status. The treatment case fatality ratio remained above 10% in most years. At patient‐level, fatality risk was higher in PLHIV (aRR 1.74, 1.51–2.02), and for older age and extra‐pulmonary TB irrespective of HIV‐status. For PLHIV, fatality risk was higher for TB retreatment cases (aRR 1.38, 1.18–1.61) and patients without antiretroviral therapy (aRR 1.70, 1.47–1.97). It decreases with increasing higher CD4 strata and the programmatic availability of TB‐LAM testing (aRR 0.65, 0.35–0.90). At population‐level, mortality rates decreased 6.4‐fold (−147/100,000 population) between 2009 (174/100,000) and 2017 (27/100,000), coinciding with a decline in TB treatment cases (2,785 in 2009 to 497 in 2017). Although the absolute decline in mortality rates was most pronounced in PLHIV (−826/100,000 vs. HIV‐negative: −23/100,000), the relative population‐level mortality risk remained higher in PLHIV (aRR 4.68, 3.25–6.72) compared to the HIV‐negative population.
CONCLUSIONS
TB‐related mortality rapidly decreased at population‐level and most pronounced in PLHIV. However, case fatality among TB treatment cases remained high. Further strategies to reduce active TB disease and introduce improved TB therapies are warranted.
Journal Article > ResearchFull Text
Trop Med Int Health. 15 December 2017; Volume 23 (Issue 3); DOI:10.1111/tmi.13025
Bedell RA, van Lettow M, Meaney C, Corbett EL, Chan AK, et al.
Trop Med Int Health. 15 December 2017; Volume 23 (Issue 3); DOI:10.1111/tmi.13025
BACKGROUND:
C-reactive protein (CRP) is an inflammatory biomarker that may identify patients at risk of infections or death. Mortality among HIV-infected persons commencing antiretroviral therapy (ART) is often attributed to tuberculosis (TB) or bloodstream infections (BSI).
METHODS:
In two district hospitals in southern Malawi, we recruited HIV-infected adults with one or more unexplained symptoms present for at least one month (weight loss, fever or diarrhoea) and negative expectorated sputum microscopy for TB. CRP determination for 452 of 469 (96%) participants at study enrolment was analysed for associations with TB, BSI or death to 120 days post-enrolment.
RESULTS:
Baseline CRP was significantly elevated among patients with confirmed or probable TB (52), BSI (50) or death (60) compared to those with no identified infection who survived at least 120 days (269). A CRP value of >10 mg/L was associated with confirmed or probable TB (adjusted odds ratio 5.7; 95% CI 2.6, 14.3; 87% sensitivity) or death by 30 days (adjusted odds ratio 9.2; 95% CI 2.2, 55.1; 88% sensitivity). CRP was independently associated with TB, BSI or death, but the prediction of these endpoints was enhanced by including haemoglobin (all outcomes), CD4 count (BSI, death) and whether ART was started (death) in logistic regression models.
CONCLUSION:
High CRP at the time of ART initiation is associated with TB, BSI and early mortality and so has potential utility for stratifying patients for intensified clinical and laboratory investigation and follow-up. They may also be considered for empirical treatment of opportunistic infections including TB.
C-reactive protein (CRP) is an inflammatory biomarker that may identify patients at risk of infections or death. Mortality among HIV-infected persons commencing antiretroviral therapy (ART) is often attributed to tuberculosis (TB) or bloodstream infections (BSI).
METHODS:
In two district hospitals in southern Malawi, we recruited HIV-infected adults with one or more unexplained symptoms present for at least one month (weight loss, fever or diarrhoea) and negative expectorated sputum microscopy for TB. CRP determination for 452 of 469 (96%) participants at study enrolment was analysed for associations with TB, BSI or death to 120 days post-enrolment.
RESULTS:
Baseline CRP was significantly elevated among patients with confirmed or probable TB (52), BSI (50) or death (60) compared to those with no identified infection who survived at least 120 days (269). A CRP value of >10 mg/L was associated with confirmed or probable TB (adjusted odds ratio 5.7; 95% CI 2.6, 14.3; 87% sensitivity) or death by 30 days (adjusted odds ratio 9.2; 95% CI 2.2, 55.1; 88% sensitivity). CRP was independently associated with TB, BSI or death, but the prediction of these endpoints was enhanced by including haemoglobin (all outcomes), CD4 count (BSI, death) and whether ART was started (death) in logistic regression models.
CONCLUSION:
High CRP at the time of ART initiation is associated with TB, BSI and early mortality and so has potential utility for stratifying patients for intensified clinical and laboratory investigation and follow-up. They may also be considered for empirical treatment of opportunistic infections including TB.
Journal Article > ResearchFull Text
Trop Med Int Health. 1 December 2010; Volume 15 (Issue 12); DOI:10.1111/j.1365-3156.2010.02649.x
Bemelmans M, van den Akker T, Ford NP, Philips M, Zachariah R, et al.
Trop Med Int Health. 1 December 2010; Volume 15 (Issue 12); DOI:10.1111/j.1365-3156.2010.02649.x
Objective To describe how district-wide access to HIV/AIDS care was achieved and maintained in Thyolo District, Malawi. Method In mid-2003, the Ministry of Health and Médecins Sans Frontières developed a model of care for Thyolo district (population 587 455) based on decentralization of care to health centres and community sites and task shifting. Results After delegating HIV testing and counseling to lay counsellors, uptake of testing increased from 1300 tests per month in 2003 to 6500 in 2009. Shifting responsibility for antiretroviral therapy (ART) initiations to non-physician clinicians almost doubled ART enrolment, with a majority of initiations performed in peripheral health centres. By the end 2009, 23 261 people had initiated ART of whom 11 042 received ART care at health-centre level. By the end of 2007, the universal access targets were achieved, with nearly 9000 patients alive and on ART. The average annual cost for achieving these targets was €2.6 per inhabitant/year. Conclusion The Thyolo programme has demonstrated the feasibility of district-wide access to ART in a setting with limited resources for health. Expansion and decentralization of HIV/AIDS service-capacity to the primary care level, combined with task shifting, resulted in increased access to HIV services with good programme outcomes despite staff shortages.
Journal Article > ResearchAbstract
Trop Med Int Health. 29 July 2012; Volume 17 (Issue 9); 1163-1170.; DOI:10.1111/j.1365-3156.2012.03048
Khader A, Zachariah R
Trop Med Int Health. 29 July 2012; Volume 17 (Issue 9); 1163-1170.; DOI:10.1111/j.1365-3156.2012.03048
Recording and reporting systems borrowed from the DOTS framework for tuberculosis control can be used to record, monitor and report on chronic disease. In a primary healthcare clinic run by UNRWA in Amman, Jordan, serving Palestine refugees with hypertension, we set out to illustrate the method of cohort reporting for persons with hypertension by presenting on quarterly and cumulative case finding, cumulative and 12-month analysis of cohort outcomes and to assess how these data may inform and improve the quality of hypertension care services.
Journal Article > ResearchFull Text
Trop Med Int Health. 6 March 2016; Volume 21 (Issue 5); 603-609.; DOI:10.1111/tmi.12688
Kosack CS, Nick S
Trop Med Int Health. 6 March 2016; Volume 21 (Issue 5); 603-609.; DOI:10.1111/tmi.12688
OBJECTIVE
To evaluate the diagnostic accuracy of the OraQuick HCV rapid antibody test from OraSure and the Multisure HCV antibody assay from MP Biomedicals.
METHODS
Five seropanels from patients, intravenous drug users and blood donors with and without HCV infection were used on the two rapid immunochromatographic tests. Sensitivity, specificity and predictive values were calculated. In addition, seropanels from 10 seroconverters were used to assess early identification of HCV infection. The study was undertaken in a laboratory at Paul Ehrlich Institute in Germany.
RESULTS
Panel 1 contained of 55 positive and 25 negative samples. The OraQuick HCV test had a sensitivity of 100% (95% CI: 93.5-100) and a specificity of 100% (95% CI: 86.3-100). The Multisure HCV test had a sensitivity of 100% (95% CI: 93.5-100) and a specificity of 96% (95% CI: 79.6-99.9). Panel 2 consisted of 193 pre-characterised anti-HCV-positive patient samples. The OraQuick HCV test identified 191 samples correctly and the Multisure HCV 192. The sensitivity was 99.0% (95% CI: 96.3-99.9) for the OraQuick HCV test and 99.5% (95% CI: 97.1-100) for the Multisure HCV test. Panel 3 was composed of seroconversion samples of 10 patients. The OraQuick HCV test detected all of these 10 infections while the Multisure HCV test detected six and was indeterminate on 2. Panel 4 included 53 anti-HCV negative blood samples from blood donors. Both tests correctly identified all 53. Panel 5 consisted of 26 samples of HCV/HIV co-infected patients. The sensitivity of the OraQuick HCV test was 65.2% (95% CI: 42.8-82.8) after 20 min and 73.9% (95% CI: 51.3-88.9) after 40 min of incubation. The Multisure HCV test had a sensitivity of 96.2% (95% CI: 80.4-99.9).
CONCLUSION
This evaluation revealed good sensitivity for both rapid screening assays. The detection of seroconverters, however, was lower in the MutiSure HCV test. Therefore the MultiSure test should be used with hesitation in high incidence settings. The OraQuick gave HCV false-negative results in almost 25% of the HIV-positive sera. Therefore may the OraQuick be less suited in HIV prevalent areas.
To evaluate the diagnostic accuracy of the OraQuick HCV rapid antibody test from OraSure and the Multisure HCV antibody assay from MP Biomedicals.
METHODS
Five seropanels from patients, intravenous drug users and blood donors with and without HCV infection were used on the two rapid immunochromatographic tests. Sensitivity, specificity and predictive values were calculated. In addition, seropanels from 10 seroconverters were used to assess early identification of HCV infection. The study was undertaken in a laboratory at Paul Ehrlich Institute in Germany.
RESULTS
Panel 1 contained of 55 positive and 25 negative samples. The OraQuick HCV test had a sensitivity of 100% (95% CI: 93.5-100) and a specificity of 100% (95% CI: 86.3-100). The Multisure HCV test had a sensitivity of 100% (95% CI: 93.5-100) and a specificity of 96% (95% CI: 79.6-99.9). Panel 2 consisted of 193 pre-characterised anti-HCV-positive patient samples. The OraQuick HCV test identified 191 samples correctly and the Multisure HCV 192. The sensitivity was 99.0% (95% CI: 96.3-99.9) for the OraQuick HCV test and 99.5% (95% CI: 97.1-100) for the Multisure HCV test. Panel 3 was composed of seroconversion samples of 10 patients. The OraQuick HCV test detected all of these 10 infections while the Multisure HCV test detected six and was indeterminate on 2. Panel 4 included 53 anti-HCV negative blood samples from blood donors. Both tests correctly identified all 53. Panel 5 consisted of 26 samples of HCV/HIV co-infected patients. The sensitivity of the OraQuick HCV test was 65.2% (95% CI: 42.8-82.8) after 20 min and 73.9% (95% CI: 51.3-88.9) after 40 min of incubation. The Multisure HCV test had a sensitivity of 96.2% (95% CI: 80.4-99.9).
CONCLUSION
This evaluation revealed good sensitivity for both rapid screening assays. The detection of seroconverters, however, was lower in the MutiSure HCV test. Therefore the MultiSure test should be used with hesitation in high incidence settings. The OraQuick gave HCV false-negative results in almost 25% of the HIV-positive sera. Therefore may the OraQuick be less suited in HIV prevalent areas.
Journal Article > CommentaryFull Text
Trop Med Int Health. 10 August 2011; Volume 16 (Issue 11); DOI:10.1111/j.1365-3156.2011.02863.x
Tayler-Smith K, Zachariah R, Manzi M, Kizito W, Vandenbulcke A, et al.
Trop Med Int Health. 10 August 2011; Volume 16 (Issue 11); DOI:10.1111/j.1365-3156.2011.02863.x
Journal Article > ResearchFull Text
Trop Med Int Health. 1 January 2008; Volume 13 (Issue 1); DOI:10.1111/j.1365-3156.2007.01978.x
Guthmann JP, Pittet A, Lesage A, Imwong M, Lindegardh N, et al.
Trop Med Int Health. 1 January 2008; Volume 13 (Issue 1); DOI:10.1111/j.1365-3156.2007.01978.x
OBJECTIVE: To assess the efficacy of chloroquine in the treatment of Plasmodium vivax malaria in in Dawei District, southern Myanmar. METHODS: Enrolled patients at Sonsinphya clinic >6 months of age were assessed clinically and parasitologically every week for 28 days. To differentiate new infections from recrudescence, we genotyped pre- and post-treatment parasitaemia. Blood chloroquine was measured to confirm resistant strains. RESULTS: Between December 2002 and April 2003, 2661 patients were screened, of whom 252 were included and 235 analysed. Thirty-four per cent (95% CI: 28.1-40.6) of patients had recurrent parasitaemia and were considered treatment failures. 59.4% of these recurrences were with a different parasite strain. Two (0.8%) patients with recurrences on day 14 had chloroquine concentrations above the threshold of 100 ng/ml and were considered infected with chloroquine resistant parasites. 21% of failures occurred during the first 3 weeks of follow-up: early recurrence and median levels of blood chloroquine comparable to those of controls suggested P. vivax resistance. CONCLUSIONS: Plasmodium vivax resistance to chloroquine seems to be emerging in Dawei, near the Thai-Burmese border. While chloroquine remains the first-line drug for P. vivax infections in this area of Myanmar, regular monitoring is needed to detect further development of parasite resistance.
Journal Article > ResearchFull Text
Trop Med Int Health. 1 August 2004; Volume 9 (Issue 8); DOI:10.1111/j.1365-3156.2004.01266.x
Robays J, Ebeja Kadima A, Lutumba P, Miaka mia Bilenge C, Kande Betu Ku Mesu V, et al.
Trop Med Int Health. 1 August 2004; Volume 9 (Issue 8); DOI:10.1111/j.1365-3156.2004.01266.x
BACKGROUND: Increasing numbers of human African trypanosomiasis (HAT) cases have been reported in urban residents of Kinshasa, Democratic Republic Congo since 1996. We set up a case-control study to identify risk factors for the disease. METHODS: All residents of the urban part of Kinshasa with parasitologically confirmed HAT and presenting for treatment to the city's specialized HAT clinics between 1 August, 2002 and 28 February, 2003 were included as cases. We defined the urban part as the area with contiguous habitation and a population density >5000 inhabitants per square kilometre. A digital map of the area was drawn based on a satellite image. For each case, two serologically negative controls were selected, matched on age, sex and neighbourhood. Logistic regression models were fitted to control for confounding. RESULTS: The following risk factors were independently associated with HAT: travel, commerce and cultivating fields in Bandundu, and commerce and cultivating fields in the rural part of Kinshasa. No association with activities in the city itself was found. DISCUSSION: In 2002, the emergence of HAT in urban residents of Kinshasa appears mainly linked to disease transmission in Bandundu and rural Kinshasa. We recommend to intensify control of these foci, to target HAT screening in urban residents to people with contact with these foci, to increase awareness of HAT amongst health workers in the urban health structures and to strengthen disease surveillance.
Journal Article > ResearchAbstract
Trop Med Int Health. 25 July 2012; Volume 17 (Issue 5); 1302-8.; DOI:10.1111/j.1365-3156.2012.03069.x
Lin YD, Li L, Mi F, Du J, Dong Y, et al.
Trop Med Int Health. 25 July 2012; Volume 17 (Issue 5); 1302-8.; DOI:10.1111/j.1365-3156.2012.03069.x
OBJECTIVE
There is a high burden of both diabetes (DM) and tuberculosis (TB) in China, and as DM increases the risk of TB and adversely affects TB treatment outcomes, there is a need for bidirectional screening of the two diseases. How this is best performed is not well determined. In this pilot project in China, we aimed to assess the feasibility and results of screening DM patients for TB within the routine healthcare setting of five DM clinics.
METHOD
Agreement on how to screen, monitor and record was reached in May 2011 at a national stakeholders meeting, and training was carried out for staff in the five clinics in July 2011. Implementation started in September 2011, and we report on 7 months of activities up to 31 March 2012. DM patients were screened for TB at each clinic attendance using a symptom-based enquiry, and those positive to any symptom were referred for TB investigations.
RESULTS
In the three quarters, 72% of 3174 patients, 79% of 7196 patients and 68% of 4972 patients were recorded as having been screened for TB, resulting in 7 patients found who were already known to have TB, 92 with a positive TB symptom screen and 48 of these newly diagnosed with TB as a result of referral and investigation. All patients except one were started on anti-TB treatment. TB case notification rates in screened DM patients were several times higher than those of the general population, were highest for the five sites combined in the final quarter (774/100 000) and were highest in one of the five clinics in the final quarter (804/100 000) where there was intensive in-house training, special assignment of staff for screening and colocation of services.
CONCLUSION
This pilot project shows that it is feasible to carry out screening of DM patients for TB resulting in high detection rates of TB. This has major public health and patient-related implications.
There is a high burden of both diabetes (DM) and tuberculosis (TB) in China, and as DM increases the risk of TB and adversely affects TB treatment outcomes, there is a need for bidirectional screening of the two diseases. How this is best performed is not well determined. In this pilot project in China, we aimed to assess the feasibility and results of screening DM patients for TB within the routine healthcare setting of five DM clinics.
METHOD
Agreement on how to screen, monitor and record was reached in May 2011 at a national stakeholders meeting, and training was carried out for staff in the five clinics in July 2011. Implementation started in September 2011, and we report on 7 months of activities up to 31 March 2012. DM patients were screened for TB at each clinic attendance using a symptom-based enquiry, and those positive to any symptom were referred for TB investigations.
RESULTS
In the three quarters, 72% of 3174 patients, 79% of 7196 patients and 68% of 4972 patients were recorded as having been screened for TB, resulting in 7 patients found who were already known to have TB, 92 with a positive TB symptom screen and 48 of these newly diagnosed with TB as a result of referral and investigation. All patients except one were started on anti-TB treatment. TB case notification rates in screened DM patients were several times higher than those of the general population, were highest for the five sites combined in the final quarter (774/100 000) and were highest in one of the five clinics in the final quarter (804/100 000) where there was intensive in-house training, special assignment of staff for screening and colocation of services.
CONCLUSION
This pilot project shows that it is feasible to carry out screening of DM patients for TB resulting in high detection rates of TB. This has major public health and patient-related implications.
Journal Article > LetterFull Text
Trop Med Int Health. 30 May 2013; Volume 18 (Issue 8); DOI:10.1111/tmi.12133
Zachariah R, Reid AJ, Van der Bergh R, Dahmane A, Kosgei RJ, et al.
Trop Med Int Health. 30 May 2013; Volume 18 (Issue 8); DOI:10.1111/tmi.12133