Conference Material > Abstract
Langendorf C, Nikolay B
Epicentre Scientific Day 2024. 23 May 2024
BACKGROUND
While case confirmation is most of the time not necessary for case management decisions– the measles outbreak response relies on the timely biological confirmation of outbreaks to facilitate a vaccination response. Seroprevalence estimates, on the other hand, can help plan vaccination activities or evaluate them, by quantifying immunization levels in the population. In remote areas where transport of serum or plasma samples is challenging, we ideally would like to use dried blood spots (DBS) which are easy to collect, easy to transport, and theoretically stable in time and temperature. However, the practical use of DBS under field conditions is not as easy as we expect. Based on different examples of measles surveys in the DRC and Niger, we will describe the challenges we are facing regarding interpretation of serology results from DBS for both measles
biological confirmation and seroprevalence surveys.
RESULTS AND DISCUSSION
In the DRC, for biological confirmation , the sensitivity of DBS samples compared to plasma decreases with transport delays and is lower in remote settings. Measles seroprevalence based on DBS was lower than expected, raising questions about the use of the recommended seropositivity threshold and the correlation with seroprotection after vaccination. In Niger, we found that a good quality DBS can be obtain under field conditions, and an adjustment factor for DBS compared to serum is needed but may vary between settings.
CONCLUSION
Serology on DBS is the most acceptable procedure so far for biological confirmation of measles cases and seroprevalence. However, additional investigations are needed to better standardize, test, and interpret DBS samples to help making the most appropriate operational decisions.
While case confirmation is most of the time not necessary for case management decisions– the measles outbreak response relies on the timely biological confirmation of outbreaks to facilitate a vaccination response. Seroprevalence estimates, on the other hand, can help plan vaccination activities or evaluate them, by quantifying immunization levels in the population. In remote areas where transport of serum or plasma samples is challenging, we ideally would like to use dried blood spots (DBS) which are easy to collect, easy to transport, and theoretically stable in time and temperature. However, the practical use of DBS under field conditions is not as easy as we expect. Based on different examples of measles surveys in the DRC and Niger, we will describe the challenges we are facing regarding interpretation of serology results from DBS for both measles
biological confirmation and seroprevalence surveys.
RESULTS AND DISCUSSION
In the DRC, for biological confirmation , the sensitivity of DBS samples compared to plasma decreases with transport delays and is lower in remote settings. Measles seroprevalence based on DBS was lower than expected, raising questions about the use of the recommended seropositivity threshold and the correlation with seroprotection after vaccination. In Niger, we found that a good quality DBS can be obtain under field conditions, and an adjustment factor for DBS compared to serum is needed but may vary between settings.
CONCLUSION
Serology on DBS is the most acceptable procedure so far for biological confirmation of measles cases and seroprevalence. However, additional investigations are needed to better standardize, test, and interpret DBS samples to help making the most appropriate operational decisions.
Journal Article > ReviewFull Text
Health Sci Rep. 4 January 2024; Volume 7 (Issue 1); e1794.; DOI:10.1002/hsr2.1794
Oduoye MO, Fatima E, Muzammil MA, Dave T, Irfan H, et al.
Health Sci Rep. 4 January 2024; Volume 7 (Issue 1); e1794.; DOI:10.1002/hsr2.1794
BACKGROUND AND AIMS
Artificial intelligence (AI) has emerged as a transformative force in laboratory medicine, promising significant advancements in healthcare delivery. This study explores the potential impact of AI on diagnostics and patient management within the context of laboratory medicine, with a particular focus on low‐ and middle‐income countries (LMICs).
METHODS
In writing this article, we conducted a thorough search of databases such as PubMed, ResearchGate, Web of Science, Scopus, and Google Scholar within 20 years. The study examines AI's capabilities, including learning, reasoning, and decision‐making, mirroring human cognitive processes. It highlights AI's adeptness at processing vast data sets, identifying patterns, and expediting the extraction of actionable insights, particularly in medical imaging interpretation and laboratory test data analysis. The research emphasizes the potential benefits of AI in early disease detection, therapeutic interventions, and personalized treatment strategies.
RESULTS
In the realm of laboratory medicine, AI demonstrates remarkable precision in interpreting medical images such as radiography, computed tomography, and magnetic resonance imaging. Its predictive analytical capabilities extend to forecasting patient trajectories and informing personalized treatment strategies using comprehensive data sets comprising clinical outcomes, patient records, and laboratory results. The study underscores the significance of AI in addressing healthcare challenges, especially in resource‐constrained LMICs.
CONCLUSION
While acknowledging the profound impact of AI on laboratory medicine in LMICs, the study recognizes challenges such as inadequate data availability, digital infrastructure deficiencies, and ethical considerations. Successful implementation necessitates substantial investments in digital infrastructure, the establishment of data‐sharing networks, and the formulation of regulatory frameworks. The study concludes that collaborative efforts among stakeholders, including international organizations, governments, and nongovernmental entities, are crucial for overcoming obstacles and responsibly integrating AI into laboratory medicine in LMICs. A comprehensive, coordinated approach is essential for realizing AI's transformative potential and advancing health care in LMICs.
Artificial intelligence (AI) has emerged as a transformative force in laboratory medicine, promising significant advancements in healthcare delivery. This study explores the potential impact of AI on diagnostics and patient management within the context of laboratory medicine, with a particular focus on low‐ and middle‐income countries (LMICs).
METHODS
In writing this article, we conducted a thorough search of databases such as PubMed, ResearchGate, Web of Science, Scopus, and Google Scholar within 20 years. The study examines AI's capabilities, including learning, reasoning, and decision‐making, mirroring human cognitive processes. It highlights AI's adeptness at processing vast data sets, identifying patterns, and expediting the extraction of actionable insights, particularly in medical imaging interpretation and laboratory test data analysis. The research emphasizes the potential benefits of AI in early disease detection, therapeutic interventions, and personalized treatment strategies.
RESULTS
In the realm of laboratory medicine, AI demonstrates remarkable precision in interpreting medical images such as radiography, computed tomography, and magnetic resonance imaging. Its predictive analytical capabilities extend to forecasting patient trajectories and informing personalized treatment strategies using comprehensive data sets comprising clinical outcomes, patient records, and laboratory results. The study underscores the significance of AI in addressing healthcare challenges, especially in resource‐constrained LMICs.
CONCLUSION
While acknowledging the profound impact of AI on laboratory medicine in LMICs, the study recognizes challenges such as inadequate data availability, digital infrastructure deficiencies, and ethical considerations. Successful implementation necessitates substantial investments in digital infrastructure, the establishment of data‐sharing networks, and the formulation of regulatory frameworks. The study concludes that collaborative efforts among stakeholders, including international organizations, governments, and nongovernmental entities, are crucial for overcoming obstacles and responsibly integrating AI into laboratory medicine in LMICs. A comprehensive, coordinated approach is essential for realizing AI's transformative potential and advancing health care in LMICs.
Journal Article > ReviewFull Text
JAC Antimicrob Resist. 17 May 2023; Volume 5 (Issue 3); dlad057.; DOI:10.1093/jacamr/dlad057
Lamrous A, Repetto EC, Depp T, Jimenez C, Chua AC, et al.
JAC Antimicrob Resist. 17 May 2023; Volume 5 (Issue 3); dlad057.; DOI:10.1093/jacamr/dlad057
OBJECTIVES
C-reactive protein (CRP) and procalcitonin (PCT) are widely used biomarkers in high-income countries. However, evidence for their use in low- and middle-income countries (LMICs) is scant. Because many factors, including rates of endemic disease, comorbidities and genetics, may influence biomarkers’ behaviour, we aimed to review available evidence generated in LMICs.
METHODS
We searched the PubMed database for relevant studies within the last 20 years that originated in regions of interest (Africa, Latin America, Middle East, South Asia or South East Asia), and full-text articles involving diagnosis, prognostication and evaluation of therapeutic response with CRP and/or PCT in adults (n = 88) were reviewed and categorized in 12 predefined focus areas.
RESULTS
Overall, results were highly heterogeneous, at times conflicting, and often lacking clinically useful cut-off values. However, most studies demonstrated higher levels of CRP/PCT in patients with bacterial versus other infections. HIV and TB patients had consistently higher levels of CRP/PCT versus controls. In addition, higher CRP/PCT levels at baseline and follow-up in HIV, TB, sepsis and respiratory tract infections were associated with poorer prognosis.
CONCLUSIONS
Evidence generated from LMIC cohorts suggests that CRP and PCT may have potential to become effective clinical guiding tools particularly in respiratory tract infections, sepsis and HIV/TB. However, more studies are needed to define potential scenarios for use and cost-effectiveness. Consensus across stakeholders regarding target conditions, laboratory standards and cut-off values would support the quality and applicability of future evidence.
C-reactive protein (CRP) and procalcitonin (PCT) are widely used biomarkers in high-income countries. However, evidence for their use in low- and middle-income countries (LMICs) is scant. Because many factors, including rates of endemic disease, comorbidities and genetics, may influence biomarkers’ behaviour, we aimed to review available evidence generated in LMICs.
METHODS
We searched the PubMed database for relevant studies within the last 20 years that originated in regions of interest (Africa, Latin America, Middle East, South Asia or South East Asia), and full-text articles involving diagnosis, prognostication and evaluation of therapeutic response with CRP and/or PCT in adults (n = 88) were reviewed and categorized in 12 predefined focus areas.
RESULTS
Overall, results were highly heterogeneous, at times conflicting, and often lacking clinically useful cut-off values. However, most studies demonstrated higher levels of CRP/PCT in patients with bacterial versus other infections. HIV and TB patients had consistently higher levels of CRP/PCT versus controls. In addition, higher CRP/PCT levels at baseline and follow-up in HIV, TB, sepsis and respiratory tract infections were associated with poorer prognosis.
CONCLUSIONS
Evidence generated from LMIC cohorts suggests that CRP and PCT may have potential to become effective clinical guiding tools particularly in respiratory tract infections, sepsis and HIV/TB. However, more studies are needed to define potential scenarios for use and cost-effectiveness. Consensus across stakeholders regarding target conditions, laboratory standards and cut-off values would support the quality and applicability of future evidence.
Conference Material > Abstract
Kaitano R
TB Research Dissemination Workshop, Epicentre Uganda. 29 June 2022
BACKGROUND
There is a growing interest for the use of stool samples as an alternative to respiratory samples for the diagnosis of intrathoracic TB in children unable to produce sputum. Unlike respiratory samples, stool samples require processing before molecular testing. Several groups have already evaluated different processing methods. However, it is difficult to know which method has the best diagnostic accuracy and potential for use at Primary Health Care level, due to the difference in study designs and populations.
METHODS
In this study, we performed a head to head comparison of the diagnostic accuracy and feasibility of four stool processing methods in the same population using the same study methodology. We selected three centrifuge-free simplified methods (Optimized Sucrose flotation (OSF), Stool Processing Kit (SPK) and Simple One Step (SOS)) and one centrifuge-based method (sucrose flotation) with well documented performance used as comparator. Two stool samples and two respiratory samples were collected from children with presumptive TB the Mbarara Regional Referral Hospital (Mbarara, Uganda), Lusaka University Teaching Hospital (Lusaka, Zambia) and the Arthur Davidson Children Hospital (Ndola, Zambia). Stool samples were split in four identical aliquots and processed with the different processing methods. Reference standard was the bacteriological results from respiratory specimens. Laboratory technicians’ perception of the methods was assessed using a self-administered questionnaire at different time points of the study.
RESULTS
Thirty-six children with Ultra or culture positive results from respiratory samples were enrolled to evaluate sensitivity and 140 children with two negative culture results to evaluate specificity of Ultra from stool using the different processing methods. Sensitivity of the different methods ranged between 56% and 69% and specificity was above 95% for all methods. The three centrifuge-free methods were perceived as easy to perform by the laboratory technicians.
CONCLUSION
Simplifying stool processing, regardless of the method used, did not decrease its performance when compared with the centrifuge-based method. All centrifuge free methods were feasible and well accepted by laboratory technicians.
These abstracts are not to be quoted for publication
There is a growing interest for the use of stool samples as an alternative to respiratory samples for the diagnosis of intrathoracic TB in children unable to produce sputum. Unlike respiratory samples, stool samples require processing before molecular testing. Several groups have already evaluated different processing methods. However, it is difficult to know which method has the best diagnostic accuracy and potential for use at Primary Health Care level, due to the difference in study designs and populations.
METHODS
In this study, we performed a head to head comparison of the diagnostic accuracy and feasibility of four stool processing methods in the same population using the same study methodology. We selected three centrifuge-free simplified methods (Optimized Sucrose flotation (OSF), Stool Processing Kit (SPK) and Simple One Step (SOS)) and one centrifuge-based method (sucrose flotation) with well documented performance used as comparator. Two stool samples and two respiratory samples were collected from children with presumptive TB the Mbarara Regional Referral Hospital (Mbarara, Uganda), Lusaka University Teaching Hospital (Lusaka, Zambia) and the Arthur Davidson Children Hospital (Ndola, Zambia). Stool samples were split in four identical aliquots and processed with the different processing methods. Reference standard was the bacteriological results from respiratory specimens. Laboratory technicians’ perception of the methods was assessed using a self-administered questionnaire at different time points of the study.
RESULTS
Thirty-six children with Ultra or culture positive results from respiratory samples were enrolled to evaluate sensitivity and 140 children with two negative culture results to evaluate specificity of Ultra from stool using the different processing methods. Sensitivity of the different methods ranged between 56% and 69% and specificity was above 95% for all methods. The three centrifuge-free methods were perceived as easy to perform by the laboratory technicians.
CONCLUSION
Simplifying stool processing, regardless of the method used, did not decrease its performance when compared with the centrifuge-based method. All centrifuge free methods were feasible and well accepted by laboratory technicians.
These abstracts are not to be quoted for publication
Journal Article > ResearchFull Text
East Afr Med J. 31 March 2017; Volume 6 (Issue 2); 383.; DOI:10.4102/ajlm.v6i2.383
Orikiriza P, Nyehangane D, Atwine D, Kisakye JJ, Kassaza K, et al.
East Afr Med J. 31 March 2017; Volume 6 (Issue 2); 383.; DOI:10.4102/ajlm.v6i2.383
BACKGROUND
To confirm presence of Mycobacterium tuberculosis complex, some tuberculosis culture laboratories still rely on para-nitrobenzoic acid (PNB), a traditional technique that requires sub-culturing of clinical isolates and two to three weeks to give results. Rapid identification tests have improved turnaround times for mycobacterial culture results. Considering the challenges of the PNB method, we assessed the performance of the SD Bioline TB Ag MPT64 assay by using PNB as gold standard to detect M. tuberculosis complex from acid-fast bacilli (AFB) positive cultures.
OBJECTIVES
The aim of this study was to determine the sensitivity, specificity and turnaround time of the SD MPT64 assay for identification of M. tuberculosis complex, in a setting with high prevalence of tuberculosis and HIV.
METHODS
A convenience sample of 690 patients, with tuberculosis symptoms, was enrolled at Epicentre Mbarara Research Centre between April 2010 and June 2011. The samples were decontaminated using NALC-NaOH and re-suspended sediments inoculated in Mycobacterium Growth Indicator Tubes (MGIT) media, then incubated at 37 °C for a maximum of eight weeks. A random sample of 50 known negative cultures and 50 non-tuberculous mycobacteria isolates were tested for specificity, while sensitivity was based on AFB positivity. The time required from positive culture to reporting of results was also assessed with PNB used as the gold standard.
RESULTS
Of the 138 cultures that were AFB-positive, the sensitivity of the SD MPT64 assay was 100.0% [95% CI: 97.3 - 100] and specificity was 100.0% (95% CI, 96.4 - 100). The median time from a specimen receipt to confirmation of strain was 10 days [IQR: 8-12] with SD MPT64 and 24 days [IQR: 22-26] with PNB.
CONCLUSION
The SD MPT64 assay is comparable to PNB for identification of M. tuberculosis complex and reduces the time to detection.
To confirm presence of Mycobacterium tuberculosis complex, some tuberculosis culture laboratories still rely on para-nitrobenzoic acid (PNB), a traditional technique that requires sub-culturing of clinical isolates and two to three weeks to give results. Rapid identification tests have improved turnaround times for mycobacterial culture results. Considering the challenges of the PNB method, we assessed the performance of the SD Bioline TB Ag MPT64 assay by using PNB as gold standard to detect M. tuberculosis complex from acid-fast bacilli (AFB) positive cultures.
OBJECTIVES
The aim of this study was to determine the sensitivity, specificity and turnaround time of the SD MPT64 assay for identification of M. tuberculosis complex, in a setting with high prevalence of tuberculosis and HIV.
METHODS
A convenience sample of 690 patients, with tuberculosis symptoms, was enrolled at Epicentre Mbarara Research Centre between April 2010 and June 2011. The samples were decontaminated using NALC-NaOH and re-suspended sediments inoculated in Mycobacterium Growth Indicator Tubes (MGIT) media, then incubated at 37 °C for a maximum of eight weeks. A random sample of 50 known negative cultures and 50 non-tuberculous mycobacteria isolates were tested for specificity, while sensitivity was based on AFB positivity. The time required from positive culture to reporting of results was also assessed with PNB used as the gold standard.
RESULTS
Of the 138 cultures that were AFB-positive, the sensitivity of the SD MPT64 assay was 100.0% [95% CI: 97.3 - 100] and specificity was 100.0% (95% CI, 96.4 - 100). The median time from a specimen receipt to confirmation of strain was 10 days [IQR: 8-12] with SD MPT64 and 24 days [IQR: 22-26] with PNB.
CONCLUSION
The SD MPT64 assay is comparable to PNB for identification of M. tuberculosis complex and reduces the time to detection.
Journal Article > ResearchFull Text
J Infect Dis. 25 May 2016; Volume 215 (Issue 1); 64–69.; DOI:10.1093/infdis/jiw206
Muehlenbachs A, de la Rosa Vazquez O, Bausch DG, Schafer IJ, Paddock C, et al.
J Infect Dis. 25 May 2016; Volume 215 (Issue 1); 64–69.; DOI:10.1093/infdis/jiw206
Here we describe clinicopathologic features of EVD in pregnancy. One woman infected with Sudan virus in Gulu, Uganda in 2000 had a stillbirth and survived, and another woman with Bundibugyo virus had a livebirth with maternal and infant death in Isiro, the Democratic Republic of the Congo in 2012. Ebolavirus antigen was seen in the syncytiotrophoblast and placental maternal mononuclear cells by immunohistochemistry, and no antigen was seen in fetal placental stromal cells or fetal organs. In the Gulu case, ebolavirus antigen localized to malaria pigment-laden macrophages. These data suggest trophoblast infection may be a mechanism of transplacental ebolavirus transmission.
Journal Article > ReviewFull Text
Clin Chem Lab Med. 16 March 2012; Volume 50 (Issue 7); 1221-1227.; DOI:10.1515/cclm-2011-0618
Kosack CS
Clin Chem Lab Med. 16 March 2012; Volume 50 (Issue 7); 1221-1227.; DOI:10.1515/cclm-2011-0618
In medical humanitarian assistance, the diagnosis of diseases plays a crucial role. Laboratory investigations are one of the main diagnostic tools utilized in Médecins Sans Frontières' (MSF) programs. Currently MSF supports and/or operates more than 130 laboratories in approximately 45 countries. The variety of analysis offered depends largely on the context of the program and the availability of context adapted tools and ranges from sophisticated laboratories specializing in tuberculosis culture to small laboratories within a primary health care program or operating as mobile clinics. The largest laboratories in MSF are found in programs with the main objective to diagnose, treat and monitor patients with tuberculosis and/or human immunodeficiency virus. Other MSF programs are either disease-specific (e.g., malaria, Chagas, kala azar or visceral leishmaniasis, sleeping sickness, malnutrition, sexually transmitted infections) or are integrated in primary or secondary health care structures.
Journal Article > ReviewFull Text
Lancet Infect Dis. 1 August 2018; Volume 18 (Issue 8); E248-E258.; DOI:10.1016/S1473-3099(18)30093-8
Ombelet S, Ronat JB, Walsh T, Yansouni CP, Cox J, et al.
Lancet Infect Dis. 1 August 2018; Volume 18 (Issue 8); E248-E258.; DOI:10.1016/S1473-3099(18)30093-8
Low-resource settings are disproportionately burdened by infectious diseases and antimicrobial resistance. Good quality clinical bacteriology through a well functioning reference laboratory network is necessary for effective resistance control, but low-resource settings face infrastructural, technical, and behavioural challenges in the implementation of clinical bacteriology. In this Personal View, we explore what constitutes successful implementation of clinical bacteriology in low-resource settings and describe a framework for implementation that is suitable for general referral hospitals in low-income and middle-income countries with a moderate infrastructure. Most microbiological techniques and equipment are not developed for the specific needs of such settings. Pending the arrival of a new generation diagnostics for these settings, we suggest focus on improving, adapting, and implementing conventional, culture-based techniques. Priorities in low-resource settings include harmonised, quality assured, and tropicalised equipment, consumables, and techniques, and rationalised bacterial identification and testing for antimicrobial resistance. Diagnostics should be integrated into clinical care and patient management; clinically relevant specimens must be appropriately selected and prioritised. Open-access training materials and information management tools should be developed. Also important is the need for onsite validation and field adoption of diagnostics in low-resource settings, with considerable shortening of the time between development and implementation of diagnostics. We argue that the implementation of clinical bacteriology in low-resource settings improves patient management, provides valuable surveillance for local antibiotic treatment guidelines and national policies, and supports containment of antimicrobial resistance and the prevention and control of hospital-acquired infections.
Journal Article > ResearchFull Text
Pan Afr Med J. 31 December 2017; Volume 30; 44.; DOI:10.11604/pamj.2018.30.44.14663
Yambasu EE, Reid AJ, Owiti P, Manzi M, Sia Murray MJ, et al.
Pan Afr Med J. 31 December 2017; Volume 30; 44.; DOI:10.11604/pamj.2018.30.44.14663
INTRODUCTION
Transmissible blood-borne infections are a serious threat to blood transfusion safety in West African countries; and yet blood remains a key therapeutic product in the clinical management of patients. Sierra Leone screens blood donors for blood-borne infections but has not implemented prevention of mother-to-child transmission for hepatitis B. This study aimed to describe the overall prevalence of hepatitis B and C, HIV and syphilis among blood donors in Sierra Leone in 2016 and to compare the differences between volunteer versus family replacement donors, as well as urban versus rural donors.
METHODS
Retrospective, cross-sectional study from January-December 2016 in five blood bank laboratories across the country. Routinely-collected programme data were analyzed; blood donors were tested with rapid diagnostic tests-HBsAg for HBV, anti-HCV antibody for HCV, antibodies HIV1&2 for HIV and TPHA for syphilis.
RESULTS
There were 16807 blood samples analysed, with 80% from males; 2285 (13.6%) tested positive for at least one of the four pathogens. Overall prevalence was: 9.7% hepatitis B; 1.0% hepatitis C; 2.8% HIV; 0.8% syphilis. Prevalence was higher among samples from rural blood banks, the difference most marked for hepatitis C. The proportion of voluntary donors was 12%. Family replacement donors had a higher prevalence of hepatitis B, C and HIV than volunteers.
CONCLUSION
A high prevalence of blood-borne pathogens, particularly hepatitis B, was revealed in Sierra Leone blood donors. The study suggests the country should implement the prevention of mother-to-child transmission of hepatitis B and push to recruit more volunteer, non-remunerated blood donors.
Transmissible blood-borne infections are a serious threat to blood transfusion safety in West African countries; and yet blood remains a key therapeutic product in the clinical management of patients. Sierra Leone screens blood donors for blood-borne infections but has not implemented prevention of mother-to-child transmission for hepatitis B. This study aimed to describe the overall prevalence of hepatitis B and C, HIV and syphilis among blood donors in Sierra Leone in 2016 and to compare the differences between volunteer versus family replacement donors, as well as urban versus rural donors.
METHODS
Retrospective, cross-sectional study from January-December 2016 in five blood bank laboratories across the country. Routinely-collected programme data were analyzed; blood donors were tested with rapid diagnostic tests-HBsAg for HBV, anti-HCV antibody for HCV, antibodies HIV1&2 for HIV and TPHA for syphilis.
RESULTS
There were 16807 blood samples analysed, with 80% from males; 2285 (13.6%) tested positive for at least one of the four pathogens. Overall prevalence was: 9.7% hepatitis B; 1.0% hepatitis C; 2.8% HIV; 0.8% syphilis. Prevalence was higher among samples from rural blood banks, the difference most marked for hepatitis C. The proportion of voluntary donors was 12%. Family replacement donors had a higher prevalence of hepatitis B, C and HIV than volunteers.
CONCLUSION
A high prevalence of blood-borne pathogens, particularly hepatitis B, was revealed in Sierra Leone blood donors. The study suggests the country should implement the prevention of mother-to-child transmission of hepatitis B and push to recruit more volunteer, non-remunerated blood donors.
Journal Article > ResearchFull Text
Antimicrob Agents Chemother. 24 March 2014; Volume 58 (Issue 6); 3182-90.; DOI:10.1128/AAC.02379-13
Bhatt NB, Barau C, Amin A, Baudin E, Meggi B, et al.
Antimicrob Agents Chemother. 24 March 2014; Volume 58 (Issue 6); 3182-90.; DOI:10.1128/AAC.02379-13
This is a substudy of the Agence Nationale de Recherches sur le Sida et les Hépatites Virales (ANRS) Comparison of Nevirapine and Efavirenz for the Treatment of HIV-TB Co-infected Patients (ANRS 12146-CARINEMO) trial, which assessed the pharmacokinetics of rifampin or isoniazid with or without the coadministration of nonnucleoside reverse transcriptase inhibitor-based HIV antiretroviral therapy in HIV-tuberculosis-coinfected patients in Mozambique. Thirty-eight patients on antituberculosis therapy based on rifampin and isoniazid participated in the substudy (57.9% males; median age, 33 years; median weight, 51.9 kg; median CD4(+) T cell count, 104 cells/μl; median HIV-1 RNA load, 5.5 log copies/ml). The daily doses of rifampin and isoniazid were 10 and 5 mg/kg of body weight, respectively. Twenty-one patients received 200 mg of nevirapine twice a day (b.i.d.), and 17 patients received 600 mg of efavirenz once a day (q.d.) in combination with lamivudine and stavudine from day 1 until the end of the study. Blood samples were collected at regular time-dosing intervals after morning administration of a fixed-dose combination of rifampin and isoniazid. When rifampin was administered alone, the median maximum concentration of drug in serum (Cmax) and the area under the concentration-time curve (AUC) at steady state were 6.59 mg/liter (range, 2.70 to 14.07 mg/liter) and 27.69 mg · h/liter (range, 11.41 to 109.75 mg · h/liter), respectively. Concentrations remained unchanged when rifampin was coadministered with nevirapine or efavirenz. When isoniazid was administered alone, the median isoniazid Cmax and AUC at steady state were 5.08 mg/liter (range, 1.26 to 11.51 mg/liter) and 20.92 mg · h/liter (range, 7.73 to 56.95 mg · h/liter), respectively. Concentrations remained unchanged when isoniazid was coadministered with nevirapine; however, a 29% decrease in the isoniazid AUC was observed when isoniazid was combined with efavirenz. The pharmacokinetic parameters of rifampin and isoniazid when coadministered with nevirapine or efavirenz were not altered to a clinically significant extent in these severely immunosuppressed HIV-infected patients. Patients experienced favorable clinical outcomes. (This study has been registered at ClinicalTrials.gov under registration no. NCT00495326.).