Browsing by Subject "Drug interactions"

Now showing 1 - 7 of 7
  • Thumbnail Image
    Item
    Open Access
    Drug-associated adverse events and their relationship with outcomes in patients receiving treatment for extensively drug-resistant tuberculosis in South Africa
    (Public Library of Science, 2013) Shean, Karen; Streicher, Elizabeth; Pieterson, Elize; Symons, Greg; van Zyl Smit, Richard; Theron, Grant; Lehloenya, Rannakoe; Padanilam, Xavier; Wilcox, Paul; Victor, Tommie C; van Helden Paul; Groubusch Martin; Warren, Robin; Badri, Motasim; Dheda, Keertan
    BACKGROUND: Treatment-related outcomes in patients with extensively drug-resistant tuberculosis (XDR-TB) are poor. However, data about the type, frequency and severity of presumed drug-associated adverse events (AEs) and their association with treatment-related outcomes in patients with XDR-TB are scarce. METHODS: Case records of 115 South-African XDR-TB patients were retrospectively reviewed by a trained researcher. AEs were estimated and graded according to severity [grade 0 = none; grade 1-2 = mild to moderate; and grade 3-5 = severe (drug stopped, life-threatening or death)]. FINDINGS: 161 AEs were experienced by 67/115(58%) patients: 23/67(34%) required modification of treatment, the offending drug was discontinued in 19/67(28%), reactions were life-threatening in 2/67(3.0%), and 6/67(9.0%) died. ∼50% of the patients were still on treatment at the time of data capture. Sputum culture-conversion was less likely in those with severe (grade 3-5) vs. grade 0-2 AEs [2/27(7%) vs. 24/88(27%); p = 0.02]. The type, frequency and severity of AEs was similar in HIV-infected and uninfected patients. Capreomycin, which was empirically administered in most cases, was withdrawn in 14/104(14%) patients, implicated in (14/34) 41% of the total drug withdrawals, and was associated with all 6 deaths in the severe AE group (renal failure in five patients and hypokalemia in one patient). CONCLUSION: Drug-associated AEs occur commonly with XDR-TB treatment, are often severe, frequently interrupt therapy, and negatively impact on culture conversion outcomes. These preliminary data inform on the need for standardised strategies (including pre-treatment counselling, early detection, monitoring, and follow-up) and less toxic drugs to optimally manage patients with XDR-TB.
  • Thumbnail Image
    Item
    Open Access
    Impact of Anti-Retroviral Treatment and Cotrimoxazole Prophylaxis on Helminth Infections in HIV-Infected Patients in Lambar�n�, Gabon
    (Public Library of Science, 2015) Janssen, Saskia; Hermans, Sabine; Knap, Martijn; Moekotte, Alma; Rossatanga, Elie G; Adegnika, Akim A; Bélard, Sabine; Hänscheid, Thomas; Grobusch, Martin P
    Background: Foci of the HIV epidemic and helminthic infections largely overlap geographically. Treatment options for helminth infections are limited, and there is a paucity of drug-development research in this area. Limited evidence suggests that antiretroviral therapy (ART) reduces prevalence of helminth infections in HIV-infected individuals. We investigated whether ART exposure and cotrimoxazole preventive therapy (CTX-P) is associated with a reduced prevalence of helminth infections. Methodology and Principal Findings: This cross-sectional study was conducted at a primary HIV-clinic in Lambaréné, Gabon. HIV-infected adults who were ART-naïve or exposed to ART for at least 3 months submitted one blood sample and stool and urine samples on 3 consecutive days. Outcome was helminth infection with intestinal helminths, Schistosoma haematobium, Loa loa or Mansonella perstans. Multivariable logistic regression was used to assess associations between ART or CTX-P and helminth infection. In total, 408 patients were enrolled. Helminth infection was common (77/252 [30.5%]). Filarial infections were most prevalent (55/310 [17.7%]), followed by infection with intestinal helminths (35/296 [11.8%]) and S. haematobium (19/323 [5.9%]). Patients on CTX-P had a reduced risk of Loa loa microfilaremia (adjusted odds ratio (aOR) 0.47, 95% CI 0.23-0.97, P = 0.04), also in the subgroup of patients on ART (aOR 0.36, 95% CI 0.13-0.96, P = 0.04). There was no effect of ART exposure on helminth infection prevalence. Conclusions/Significance: CTX-P use was associated with a decreased risk of Loa loa infection, suggesting an anthelminthic effect of antifolate drugs. No relation between ART use and helminth infections was established.
  • Thumbnail Image
    Item
    Open Access
    Predicting and analyzing interactions between Mycobacterium tuberculosis and its human host
    (Public Library of Science, 2013) Rapanoel, Holifidy A; Mazandu, Gaston K; Mulder, Nicola J
    The outcome of infection by Mycobacterium tuberculosis (Mtb) depends greatly on how the host responds to the bacteria and how the bacteria manipulates the host, which is facilitated by protein-protein interactions. Thus, to understand this process, there is a need for elucidating protein interactions between human and Mtb, which may enable us to characterize specific molecular mechanisms allowing the bacteria to persist and survive under different environmental conditions. In this work, we used the interologs method based on experimentally verified intra-species and inter-species interactions to predict human-Mtb functional interactions. These interactions were further filtered using known human-Mtb interactions and genes that are differentially expressed during infection, producing 190 interactions. Further analysis of the subcellular location of proteins involved in these human-Mtb interactions confirms feasibility of these interactions. We also conducted functional analysis of human and Mtb proteins involved in these interactions, checking whether these proteins play a role in infection and/or disease, and enriching Mtb proteins in a previously predicted list of drug targets. We found that the biological processes of the human interacting proteins suggested their involvement in apoptosis and production of nitric oxide, whereas those of the Mtb interacting proteins were relevant to the intracellular environment of Mtb in the host. Mapping these proteins onto KEGG pathways highlighted proteins belonging to the tuberculosis pathway and also suggested that Mtb proteins might use the host to acquire nutrients, which is in agreement with the intracellular lifestyle of Mtb. This indicates that these interactions can shed light on the interplay between Mtb and its human host and thus, contribute to the process of designing novel drugs with new biological mechanisms of action.
  • Thumbnail Image
    Item
    Open Access
    Toward a global view of alcohol, tobacco, cannabis, and cocaine use: findings from the WHO World Mental Health Surveys
    (Public Library of Science, 2008) Degenhardt, Louisa; Chiu, Wai-Tat; Sampson, Nancy; Kessler, Ronald C; Anthony, James C; Angermeyer, Matthias; Bruffaerts, Ronny; Girolamo, Giovanni de; Gureje, Oye; Huang, Yueqin
    Louisa Degenhardt and colleagues report an international survey of 17 countries that finds clear differences in drug use across different regions of the world.
  • Thumbnail Image
    Item
    Open Access
    Translational research for tuberculosis elimination: priorities, challenges, and actions
    (Public Library of Science, 2016) Lienhardt, Christian; Lönnroth, Knut; Menzies, Dick; Balasegaram, Manica; Chakaya, Jeremiah; Cobelens, Frank; Cohn, Jennifer; Denkinger, Claudia M; Evans, Thomas G; Källenius, Gunilla; Kaplan, Gilla; Kumar, Ajay M V; Matthiessen, Line; Mgone, Charles S; Mizrahi, Valerie; Mukadi, Ya-diul; Nguyen, Viet Nhung; Nordström, Anders; Sizemore, Christine F; Spigelman, Melvin; Squire, S Bertel; Swaminathan, Soumya; Helden, Paul D Van; Zumla, Alimuddin; Weyer, Karin; Weil, Diana; Raviglione, Mario
    Christian Lienhardt and colleagues describe the research efforts needed to end the global tuberculosis epidemic by 2035.
  • Thumbnail Image
    Item
    Open Access
    Treatment-seeking for tuberculosis-suggestive symptoms: a reflection on the role of human agency in the context of universal health coverage in Malawi
    (Public Library of Science, 2016) Kumwenda, Moses; Desmond, Nicola; Hart, Graham; Choko, Augustine; Chipungu, Geoffrey A; Nyirenda, Deborah; Shand, Tim; Corbett, Elizabeth L; Chikovore, Jeremiah
    Tuberculosis (TB) is highly infectious and one of the leading killers globally. Several studies from sub-Saharan Africa highlight health systems challenges that affect ability to cope with existing disease burden, including TB, although most of these employ survey-type approaches. Consequently, few address community or patient perspectives and experiences. At the same time, understanding of the mechanisms by which the health systems challenges translate into seeking or avoidance of formal health care remains limited. This paper applies the notion of human agency to examine the ways people who have symptoms suggestive of TB respond to and deal with the symptoms vis-à-vis major challenges inherent within health delivery systems. Empirical data were drawn from a qualitative study exploring the ways in which notions of masculinity affect engagement with care, including men's well-documented tendency to delay in seeking care for TB symptoms. The study was carried out in three high-density locales of urban Blantyre, Malawi. Data were collected in March 2011 -March 2012 using focus group discussions, of which eight (mixed sex = two; female only = three; male only = three) were with 74 ordinary community members, and two (both mixed sex) were with 20 health workers; and in-depth interviews with 20 TB patients (female = 14) and 20 un-investigated chronic coughers (female = eight). The research process employed a modified version of grounded theory. Data were coded using a coding scheme that was initially generated from the study aims and subsequently progressively amended to incorporate concepts emerging during the analysis. Coded data were retrieved, re-read, and broken down and reconnected iteratively to generate themes. A myriad of problems were described for health systems at the primary health care level, centring largely on shortages of resources (human, equipment, and drugs) and unprofessional conduct by health care providers. Participants consistently pointed out how the problems could drive patients from promptly reporting symptoms at primary healthcare centres. The accounts suggest that in responding to illness symptoms including those suggestive of TB, patients navigate their options taking into cognisance past and current experiences with formal health systems. Understanding and factoring in the mediating role of such 'agency' is critical when implementing efforts to promote timely response to TB-suggestive symptoms.
  • Thumbnail Image
    Item
    Open Access
    Use of anti-retroviral therapy in tuberculosis patients on second-line anti-TB regimens: a systematic review
    (Public Library of Science, 2012) Arentz, Matthew; Pavlinac, Patricia; Kimerling, Michael E; Horne, David J; Falzon, Dennis; Schünemann, Holger J; Royce, Sarah; Dheda, Keertan; Walson, Judd L
    Introduction: Use of antiretroviral therapy (ART) during treatment of drug susceptible tuberculosis (TB) improves survival. However, data from HIV infected individuals with drug resistant TB are lacking. Second line TB drugs when combined with ART may increase drug interactions and lead to higher rates of toxicity and greater noncompliance. This systematic review sought to determine the benefit of ART in the setting of second line drug therapy for drug resistant TB. Methods: We included individual patient data from studies that evaluated treatment of drug-resistant tuberculosis in HIV-1 infected individuals published between January 1980 and December of 2009. We evaluated the effect of ART on treatment outcomes, time to smear and culture conversion, and adverse events. Results: Ten observational studies, including data from 217 subjects, were analyzed. Patients using ART during TB treatment had increased likelihood of cure (hazard ratio (HR) 3.4, 95% CI 1.6–7.4) and decreased likelihood of death (HR 0.4, 95% CI 0.3–0.6) during treatment for drug resistant TB. These associations remained significant in patients with a CD4 less than 200 cells/mm3 and less than 50 cells/mm3, and when correcting for drug resistance pattern. Limitations: We identified only observational studies from which individual patient data could be drawn. Limitations in study design, and heterogeneity in a number of the outcomes of interest had the potential to introduce bias. Discussion: While there are insufficient data to determine if ART use increases adverse drug interactions when used with second line TB drugs, ART use during treatment of drug resistant TB appears to improve cure rates and decrease risk of death. All individuals with HIV appear to benefit from ART use during treatment for TB.