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Article ; Online: Molecular control of HIV-1 postintegration latency

Van Lint Carine / Colin Laurence

Retrovirology, Vol 6, Iss 1, p

implications for the development of new therapeutic strategies

2009 Volume 111

Abstract: Abstract The persistence of HIV-1 latent reservoirs represents a major barrier to virus eradication in infected patients under HAART since interruption of the treatment inevitably leads to a rebound of plasma viremia. Latency establishes early after ... ...

Abstract	Abstract The persistence of HIV-1 latent reservoirs represents a major barrier to virus eradication in infected patients under HAART since interruption of the treatment inevitably leads to a rebound of plasma viremia. Latency establishes early after infection notably (but not only) in resting memory CD4 + T cells and involves numerous host and viral trans-acting proteins, as well as processes such as transcriptional interference, RNA silencing, epigenetic modifications and chromatin organization. In order to eliminate latent reservoirs, new strategies are envisaged and consist of reactivating HIV-1 transcription in latently-infected cells, while maintaining HAART in order to prevent de novo infection. The difficulty lies in the fact that a single residual latently-infected cell can in theory rekindle the infection. Here, we review our current understanding of the molecular mechanisms involved in the establishment and maintenance of HIV-1 latency and in the transcriptional reactivation from latency. We highlight the potential of new therapeutic strategies based on this understanding of latency. Combinations of various compounds used simultaneously allow for the targeting of transcriptional repression at multiple levels and can facilitate the escape from latency and the clearance of viral reservoirs. We describe the current advantages and limitations of immune T-cell activators, inducers of the NF-κB signaling pathway, and inhibitors of deacetylases and histone- and DNA- methyltransferases, used alone or in combinations. While a solution will not be achieved by tomorrow, the battle against HIV-1 latent reservoirs is well- underway.
Keywords	Medicine (General) ; R5-920 ; Medicine ; R ; DOAJ:Medicine (General) ; DOAJ:Health Sciences
Subject code	570
Language	English
Publishing date	2009-12-01T00:00:00Z
Publisher	BioMed Central
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: How Often Do Safety Signals Occur by Chance in First-in-Human Trials?

Clayton, Gemma L / Schachter, Asher D / Magnusson, Baldur / Li, Yue / Colin, Laurence

Clinical and translational science

2018 Volume 11, Issue 5, Page(s) 471–476

Abstract: Clinicians working on first-in-human clinical studies need to be able to judge whether safety signals observed on an investigational drug were more likely to have occurred by chance or to have been caused by the drug. We retrospectively reviewed 84 ... ...

Abstract	Clinicians working on first-in-human clinical studies need to be able to judge whether safety signals observed on an investigational drug were more likely to have occurred by chance or to have been caused by the drug. We retrospectively reviewed 84 Novartis studies including 1,234 healthy volunteers receiving placebo to determine the expected incidence of changes in commonly measured laboratory parameters and vital signs, in the absence of any active agent. We calculated the frequency of random incidence of safety signals, focusing on the liver, cardiovascular system, kidney, and pancreas. Using the liver enzyme alanine aminotransferase (ALT) as an example, we illustrate how a predictive model can be used to determine the probability of a given subject to experience an elevation of ALT above the upper limit of the normal range under placebo, conditional on the characteristics of this subject and the study.
MeSH term(s)	Clinical Trials as Topic ; Female ; Healthy Volunteers ; Humans ; Logistic Models ; Male ; Models, Theoretical ; Placebos ; Probability
Chemical Substances	Placebos
Language	English
Publishing date	2018-04-27
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2433157-0
ISSN	1752-8062 ; 1752-8054
ISSN (online)	1752-8062
ISSN	1752-8054
DOI	10.1111/cts.12558
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Article ; Online: The chromatin remodelling protein LSH/HELLS regulates the amount and distribution of DNA hydroxymethylation in the genome.

De Dieuleveult, Maud / Bizet, Martin / Colin, Laurence / Calonne, Emilie / Bachman, Martin / Li, Chao / Stancheva, Irina / Miotto, Benoit / Fuks, François / Deplus, Rachel

Epigenetics

2021 Volume 17, Issue 4, Page(s) 422–443

Abstract: Ten-Eleven Translocation (TET) proteins convert 5-methylcytosine (5mC) to 5-hydroxymethylcytosine (5hmC) leading to a dynamic epigenetic state of DNA that can influence transcription and chromatin organization. While TET proteins interact with complexes ... ...

Abstract	Ten-Eleven Translocation (TET) proteins convert 5-methylcytosine (5mC) to 5-hydroxymethylcytosine (5hmC) leading to a dynamic epigenetic state of DNA that can influence transcription and chromatin organization. While TET proteins interact with complexes involved in transcriptional repression and activation, the overall understanding of the molecular mechanisms involved in TET-mediated regulation of gene expression still remains limited. Here, we show that TET proteins interact with the chromatin remodelling protein lymphoid-specific helicase (LSH/HELLS)
MeSH term(s)	5-Methylcytosine/metabolism ; Animals ; Chromatin Assembly and Disassembly ; Cytosine/metabolism ; DNA/metabolism ; DNA Helicases/metabolism ; DNA Methylation ; Fibroblasts/metabolism ; Genome ; Mice
Chemical Substances	5-Methylcytosine (6R795CQT4H) ; Cytosine (8J337D1HZY) ; DNA (9007-49-2) ; DNA Helicases (EC 3.6.4.-) ; Hells protein, mouse (EC 5.99.-)
Language	English
Publishing date	2021-05-07
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ISSN	1559-2308
ISSN (online)	1559-2308
DOI	10.1080/15592294.2021.1917152
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Article ; Online: HIV-1 chromatin, transcription, and the regulatory protein Tat.

Colin, Laurence / Verdin, Eric / Van Lint, Carine

Methods in molecular biology (Clifton, N.J.)

2013 Volume 1087, Page(s) 85–101

Abstract: Upon integration into the host cell genome, the nucleosomal organization and epigenetic control of the HIV-1 provirus play an active role in its transcriptional regulation. Therefore, characterization of the chromatin changes that occur in the viral ... ...

Abstract	Upon integration into the host cell genome, the nucleosomal organization and epigenetic control of the HIV-1 provirus play an active role in its transcriptional regulation. Therefore, characterization of the chromatin changes that occur in the viral promoter region in response to different cellular stimuli or drug treatments represents an important aspect of our understanding of HIV-1 transcription. Moreover, the viral transactivator Tat protein potently activates HIV-1 transcription by recruiting the cellular positive transcription elongation factor p-TEFb to the TAR element located at the 5' end of all nascent viral transcripts, thereby promoting efficient elongation. This chapter describes two complementary techniques for analyzing chromatin structure. The first technique is called indirect end-labeling and uses DNase I, micrococcal nuclease (MNase) or specific restriction enzymes to provide a view of nucleosome positions and of nucleosome-free regions within genes that are usually associated with transcriptional regulatory elements. The second technique, called chromatin immunoprecipitation (ChIP), provides a detailed analysis of chromatin structure by determining the pattern of histone modification marks in the DNA region of interest and by identifying the transcription factors as well as the components of the transcriptional initiation and elongation machineries that are recruited in vivo to this chromosomal region.
MeSH term(s)	Blotting, Southern ; Chromatin/genetics ; Chromatin/metabolism ; Chromatin Immunoprecipitation ; Deoxyribonuclease I/metabolism ; HIV-1/genetics ; HIV-1/metabolism ; Proviruses/genetics ; Proviruses/metabolism ; Staining and Labeling ; Transcription, Genetic ; Virus Integration ; tat Gene Products, Human Immunodeficiency Virus/metabolism
Chemical Substances	Chromatin ; tat Gene Products, Human Immunodeficiency Virus ; Deoxyribonuclease I (EC 3.1.21.1)
Language	English
Publishing date	2013-10-24
Publishing country	United States
Document type	Journal Article
ISSN	1940-6029
ISSN (online)	1940-6029
DOI	10.1007/978-1-62703-670-2_8
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Article ; Online: Molecular control of HIV-1 postintegration latency: implications for the development of new therapeutic strategies.

Colin, Laurence / Van Lint, Carine

Retrovirology

2009 Volume 6, Page(s) 111

Abstract: The persistence of HIV-1 latent reservoirs represents a major barrier to virus eradication in infected patients under HAART since interruption of the treatment inevitably leads to a rebound of plasma viremia. Latency establishes early after infection ... ...

Abstract	The persistence of HIV-1 latent reservoirs represents a major barrier to virus eradication in infected patients under HAART since interruption of the treatment inevitably leads to a rebound of plasma viremia. Latency establishes early after infection notably (but not only) in resting memory CD4+ T cells and involves numerous host and viral trans-acting proteins, as well as processes such as transcriptional interference, RNA silencing, epigenetic modifications and chromatin organization. In order to eliminate latent reservoirs, new strategies are envisaged and consist of reactivating HIV-1 transcription in latently-infected cells, while maintaining HAART in order to prevent de novo infection. The difficulty lies in the fact that a single residual latently-infected cell can in theory rekindle the infection. Here, we review our current understanding of the molecular mechanisms involved in the establishment and maintenance of HIV-1 latency and in the transcriptional reactivation from latency. We highlight the potential of new therapeutic strategies based on this understanding of latency. Combinations of various compounds used simultaneously allow for the targeting of transcriptional repression at multiple levels and can facilitate the escape from latency and the clearance of viral reservoirs. We describe the current advantages and limitations of immune T-cell activators, inducers of the NF-kappaB signaling pathway, and inhibitors of deacetylases and histone- and DNA- methyltransferases, used alone or in combinations. While a solution will not be achieved by tomorrow, the battle against HIV-1 latent reservoirs is well- underway.
MeSH term(s)	Antiretroviral Therapy, Highly Active ; Epigenesis, Genetic/drug effects ; Gene Expression Regulation, Viral/drug effects ; HIV Infections/drug therapy ; HIV Infections/virology ; HIV-1/drug effects ; HIV-1/physiology ; Histone Deacetylase Inhibitors/therapeutic use ; Host-Pathogen Interactions/drug effects ; Humans ; Lymphocyte Activation/drug effects ; Virus Integration ; Virus Latency/drug effects
Chemical Substances	Histone Deacetylase Inhibitors
Language	English
Publishing date	2009-12-04
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ISSN	1742-4690
ISSN (online)	1742-4690
DOI	10.1186/1742-4690-6-111
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Article ; Online: A Multicentre, Double-Blind, Placebo-Controlled, Parallel-Group Study to Evaluate the Efficacy, Safety, and Tolerability of the S1P Receptor Agonist KRP203 in Patients with Moderately Active Refractory Ulcerative Colitis.

Radeke, Heinfried H / Stein, Jürgen / Van Assche, Gert / Rogler, Gerhard / Lakatos, Peter L / Muellershausen, Florian / Moulin, Pierre / Jarvis, Philip / Colin, Laurence / Gergely, Peter / Kruis, Wolfgang

Inflammatory intestinal diseases

2020 Volume 5, Issue 4, Page(s) 180–190

Abstract: Background and aims: KRP203 is a potent oral agonist of the sphingosine-1-phosphate receptor subtype 1 that induces the sequestration of peripheral lymphocytes, thereby potentially reducing the number of activated lymphocytes circulating to the ... ...

Abstract	Background and aims: KRP203 is a potent oral agonist of the sphingosine-1-phosphate receptor subtype 1 that induces the sequestration of peripheral lymphocytes, thereby potentially reducing the number of activated lymphocytes circulating to the gastrointestinal tract. Methods: We conducted a multicentre, double-blind, placebo-controlled, parallel-group, proof-of-concept study to evaluate the efficacy, safety, and tolerability of KRP203 in patients with moderately active 5-aminosalicylate-refractory ulcerative colitis (UC). Patients were randomly assigned to receive 1.2 mg KRP203 or placebo daily for 8 weeks. Primary efficacy variable was clinical remission, defined as partial Mayo Score 0-1 and modified Baron Score 0-1 with rectal bleeding subscore 0. Results: KRP203 was safe and well tolerated overall. The most common adverse events (AEs) were gastrointestinal disorders and headache. Importantly, no KRP203-related cardiac AEs were reported. Total peripheral lymphocytes and selectively affected lymphocyte subtypes decreased, causing marked decreases in naive and central memory CD4+ and CD8+ T cells, and also in B cells. Clinical remission occurred in 2/14 (14%) patients under KRP203, compared with 0/8 (0%) under placebo. Conclusions: Overall, KRP203 was safe and well tolerated by patients with UC. Importantly, no cardiac AEs were reported. Although KRP203 did not meet the minimum clinically relevant threshold for efficacy, the results may suggest that KRP203 treatment is superior to placebo. However, in this small study population, the difference was insignificant. Based on these data, studies with an improved design and a larger population should be considered.
Language	English
Publishing date	2020-08-21
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2817967-5
ISSN	2296-9365 ; 2296-9403
ISSN (online)	2296-9365
ISSN	2296-9403
DOI	10.1159/000509393
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Article ; Online: A Novel Anti-CD40 Monoclonal Antibody, Iscalimab, for Control of Graves Hyperthyroidism-A Proof-of-Concept Trial.

Kahaly, George J / Stan, Marius Nicolae / Frommer, Lara / Gergely, Peter / Colin, Laurence / Amer, Ahmed / Schuhmann, Imelda / Espie, Pascal / Rush, James S / Basson, Craig / He, Yanling

The Journal of clinical endocrinology and metabolism

2019 Volume 105, Issue 3

Abstract: Context: The CD40-CD154 co-stimulatory pathway plays an important role in the pathogenesis of Graves disease (GD) by promoting autoreactive B-cell activation.: Objective: Evaluate efficacy and safety of a human, blocking, nondepleting anti-CD40 ... ...

Abstract	Context: The CD40-CD154 co-stimulatory pathway plays an important role in the pathogenesis of Graves disease (GD) by promoting autoreactive B-cell activation. Objective: Evaluate efficacy and safety of a human, blocking, nondepleting anti-CD40 monoclonal antibody, iscalimab, in hyperthyroid patients with GD. Design: Open-label, phase II proof-of-concept study. Setting: Multicenter. Patients: Fifteen with GD. Intervention: Patients received 5 doses of iscalimab at 10 mg/kg intravenously over 12 weeks. Main outcome measures: Thyroid-related hormones and autoantibodies, plasma soluble CD40, free CD40 on B cells, soluble CXCL13, pharmacokinetics, and safety were assessed. Results: The iscalimab intervention resulted in complete CD40 engagement for up to 20 weeks. A clinical response and biochemical euthyroidism was observed in 7 of 15 (47%) patients. Free and total triiodothyronine and thyroxine normalized in 7 patients who did not receive any rescue medication with antithyroid drugs (ATD), and 2/15 (13.3%) showed normal thyrotropin. Six (40%) patients required ATD. Four of 7 responders relapsed after treatment completion. Serum concentrations of thyrotropin receptor autoantibodies (TSH-R-Ab) significantly declined in all patients (mean 15.3 IU/L vs 4.0 IU/L, 66% reduction; P < 0.001) and TSH-R-Ab levels normalized in 4 (27%). Thyroperoxidase and thyroglobulin autoantibodies significantly decreased in responders. Iscalimab rapidly reduced serum CXCL13 concentrations (P < 0.001). Twelve (80.0%) patients reported at least 1 adverse event (AE). All treatment-related AE were mild or moderate and resolved by end of the study. Conclusion: Iscalimab was generally safe and clinically effective in a subgroup of hyperthyroid GD patients. The potential therapeutic benefit of iscalimab should be further tested.
MeSH term(s)	Adult ; Aged ; Antibodies, Monoclonal/pharmacokinetics ; Antibodies, Monoclonal/therapeutic use ; CD40 Antigens/antagonists & inhibitors ; CD40 Antigens/immunology ; Female ; Follow-Up Studies ; Humans ; Hyperthyroidism/drug therapy ; Hyperthyroidism/immunology ; Male ; Middle Aged ; Prognosis ; Proof of Concept Study ; Thyroid Function Tests ; Tissue Distribution ; Young Adult
Chemical Substances	Antibodies, Monoclonal ; CD40 Antigens ; iscalimab (0628T707D0)
Language	English
Publishing date	2019-09-10
Publishing country	United States
Document type	Clinical Trial, Phase II ; Journal Article ; Multicenter Study
ZDB-ID	3029-6
ISSN	1945-7197 ; 0021-972X
ISSN (online)	1945-7197
ISSN	0021-972X
DOI	10.1210/clinem/dgz013
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Article ; Online: Bioequivalence of canakinumab liquid pre-filled syringe and reconstituted lyophilized formulations following 150 mg subcutaneous administration: a randomized study in healthy subjects.

Chioato, Andrea / Noseda, Emanuele / Colin, Laurence / Matott, Ralph / Skerjanec, Andrej / Dietz, Albert J

Clinical drug investigation

2013 Volume 33, Issue 11, Page(s) 801–808

Abstract: Background: Canakinumab is a human anti-interleukin-1beta antibody approved for the treatment of cryopyrin associated periodic syndrome currently formulated as a lyophilized powder requiring reconstitution. A new formulation (solution for injection as ... ...

Abstract	Background: Canakinumab is a human anti-interleukin-1beta antibody approved for the treatment of cryopyrin associated periodic syndrome currently formulated as a lyophilized powder requiring reconstitution. A new formulation (solution for injection as pre-filled syringe) has been developed to avoid reconstitution. Objective: The objective of this study was to evaluate the bioequivalence of pre-filled syringe and reconstituted formulations following 150 mg administration in healthy subjects. Methods: This was an open-labeled, randomized, single dose, parallel-group study in 130 healthy subjects, followed for 120 days. Subjects received a single subcutaneous injection of 150 mg canakinumab after either reconstitution or in pre-filled syringe formulation, followed by pharmacokinetics/pharmacodynamics evaluations and safety assessments. The main outcome measure for the study was the pharmacokinetic bioequivalence of the two formulations, which was concluded if the 90% confidence intervals for the ratios of AUC(last) (area under the serum concentration-time curve from time zero to time of last measurable concentration) and C(max) (maximum serum concentration) were entirely contained within the interval, 0.80-1.25. Results: The arithmetic mean values for the exposure parameters C(max) and AUC(last) were similar for the two formulations. The geometric mean ratio (pre-filled syringe vs. lyophilized form) of C(max) and AUC(last) were 0.99 and 1.01. The associated 90% confidence intervals were 0.90 to 1.08 and 0.94 to 1.09, respectively. Most common adverse events were headache and nasopharyngitis. Neutropenia occurred in 2 cases (reported as serious adverse events). No deaths occurred. Conclusion: The 150 mg liquid pre-filled syringe and lyophilized formulations of canakinumab are bioequivalent.
MeSH term(s)	Antibodies, Monoclonal/administration & dosage ; Antibodies, Monoclonal/pharmacokinetics ; Antibodies, Monoclonal, Humanized ; Freeze Drying ; Humans ; Injections, Subcutaneous ; Interleukin-1beta/metabolism ; Reference Values ; Syringes ; Therapeutic Equivalency
Chemical Substances	Antibodies, Monoclonal ; Antibodies, Monoclonal, Humanized ; Interleukin-1beta ; canakinumab (37CQ2C7X93)
Language	English
Publishing date	2013-09-12
Publishing country	New Zealand
Document type	Journal Article ; Randomized Controlled Trial ; Research Support, Non-U.S. Gov't
ZDB-ID	1220136-4
ISSN	1179-1918 ; 0114-2402 ; 1173-2563
ISSN (online)	1179-1918
ISSN	0114-2402 ; 1173-2563
DOI	10.1007/s40261-013-0127-4
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Article ; Online: A randomized, placebo-controlled trial of canakinumab in patients with peripheral artery disease.

Russell, Kerry S / Yates, Denise P / Kramer, Christopher M / Feller, Andrea / Mahling, Ping / Colin, Laurence / Clough, Timothy / Wang, Tianke / LaPerna, Lucy / Patel, Alpa / Lawall, Holger / Shennak, Mustafa M / Fulmer, James / Nikol, Sigrid / Smith, William B / Müller, Oliver J / Ratchford, Elizabeth V / Basson, Craig T

Vascular medicine (London, England)

2019 Volume 24, Issue 5, Page(s) 414–421

Abstract: Extensive atherosclerotic plaque burden in the lower extremities often leads to symptomatic peripheral artery disease (PAD) including impaired walking performance and claudication. Interleukin-1β (IL-1β) may play an important pro-inflammatory role in the ...

Abstract	Extensive atherosclerotic plaque burden in the lower extremities often leads to symptomatic peripheral artery disease (PAD) including impaired walking performance and claudication. Interleukin-1β (IL-1β) may play an important pro-inflammatory role in the pathogenesis of this disease. Interruption of IL-1β signaling was hypothesized to decrease plaque progression in the leg macrovasculature and improve the mobility of patients with PAD with intermittent claudication. Thirty-eight patients (mean age 65 years; 71% male) with symptomatic PAD (confirmed by ankle-brachial index) were randomized 1:1 to receive canakinumab (150 mg subcutaneously) or placebo monthly for up to 12 months. The mean vessel wall area (by 3.0 T black-blood magnetic resonance imaging (MRI)) of the superficial femoral artery (SFA) was used to measure plaque volume. Mobility was assessed using the 6-minute walk test. Canakinumab was safe and well tolerated. Markers of systemic inflammation (interleukin-6 and high-sensitivity C-reactive protein) fell as early as 1 month after treatment. MRI (32 patients at 3 months; 21 patients at 12 months) showed no evidence of plaque progression in the SFA in either placebo-treated or canakinumab-treated patients. Although an exploratory endpoint, placebo-adjusted maximum and pain-free walking distance (58 m) improved as early as 3 months after treatment with canakinumab when compared with placebo. Although canakinumab did not alter plaque progression in the SFA, there is an early signal that it may improve maximum and pain-free walking distance in patients with symptomatic PAD. Larger studies aimed at this endpoint will be required to definitively demonstrate this.
MeSH term(s)	Aged ; Anti-Inflammatory Agents/adverse effects ; Anti-Inflammatory Agents/therapeutic use ; Antibodies, Monoclonal, Humanized/adverse effects ; Antibodies, Monoclonal, Humanized/therapeutic use ; Biomarkers/blood ; Double-Blind Method ; Exercise Tolerance/drug effects ; Female ; Germany ; Humans ; Inflammation Mediators/blood ; Intermittent Claudication/blood ; Intermittent Claudication/diagnosis ; Intermittent Claudication/drug therapy ; Intermittent Claudication/physiopathology ; Jordan ; Male ; Middle Aged ; Peripheral Arterial Disease/blood ; Peripheral Arterial Disease/diagnosis ; Peripheral Arterial Disease/drug therapy ; Peripheral Arterial Disease/physiopathology ; Proof of Concept Study ; Prospective Studies ; Recovery of Function ; Time Factors ; Treatment Outcome ; United States
Chemical Substances	Anti-Inflammatory Agents ; Antibodies, Monoclonal, Humanized ; Biomarkers ; Inflammation Mediators ; canakinumab (37CQ2C7X93)
Language	English
Publishing date	2019-07-05
Publishing country	England
Document type	Journal Article ; Multicenter Study ; Randomized Controlled Trial ; Research Support, Non-U.S. Gov't
ZDB-ID	1311628-9
ISSN	1477-0377 ; 1358-863X
ISSN (online)	1477-0377
ISSN	1358-863X
DOI	10.1177/1358863X19859072
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Article ; Online: Epidemiology of pharyngitis as reported by Zambian school children and their families: implications for demand-side interventions to prevent rheumatic heart disease.

Musuku, John / Lungu, Joyce C / Machila, Elizabeth / Jones, Catherine / Colin, Laurence / Schwaninger, Sherri / Musonda, Patrick / Tadmor, Brigitta / Spector, Jonathan M / Engel, Mark E / Zühlke, Liesl J

BMC infectious diseases

2017 Volume 17, Issue 1, Page(s) 473

Abstract: Background: Prompt and appropriate treatment of streptococcal pharyngitis decreases the risk of acute rheumatic fever and rheumatic heart disease (RHD). Understanding public perceptions and behaviors related to sore throat is fundamental to inform ... ...

Abstract	Background: Prompt and appropriate treatment of streptococcal pharyngitis decreases the risk of acute rheumatic fever and rheumatic heart disease (RHD). Understanding public perceptions and behaviors related to sore throat is fundamental to inform health programs aimed at eliminating new cases of RHD in endemic regions. We sought to describe the epidemiology of pediatric pharyngitis and its treatment, as reported by children and their parents or guardians in Lusaka, Zambia. Methods: This was a cross-sectional investigation using interviews and written surveys, nested in a school-based RHD prevalence study. Students and their parents were asked to report number of sore throats in the previous 12 months, treatment received, and type and place of treatment. A focused history and physical examination to detect pharyngitis was conducted and children were referred for follow-up as indicated. Results: A total of 3462 students from 47 schools participated in the study, along with their parents or guardians. Six hundred and fifty eight (19%) parents/guardians reported their child had at least one sore throat in the previous year, and 835 (24%) of students reported at least one sore throat in the same time period. Girls were reported to have pharyngitis 50% more often than boys, and also made up two-thirds of the total students treated. Approximately two-thirds of children who had at least one episode of pharyngitis during the previous year were also reported to have received some form of treatment. The majority of treatments were received in government clinics (36.6%) and at home (26.3%). Half of treatments included an antibiotic. Nineteen students (0.5%) had clinically-apparent pharyngitis at screening. Conclusion: Pharyngitis is common among school-aged children and adolescents in Zambia, with females reporting significantly more sore throat episodes than males. Parents/guardians have variable knowledge about the frequency of sore throat in their children, and management of pharyngitis may be suboptimal for many children since more than a quarter were reported to have received treatment without skilled assessment. These results provide insight into current perceptions and practices related to sore throat in Zambia and will be used to design public awareness activities aimed at reducing RHD.
MeSH term(s)	Adolescent ; Adult ; Anti-Bacterial Agents/therapeutic use ; Child ; Child, Preschool ; Cross-Sectional Studies ; Female ; Humans ; Male ; Pharyngitis/drug therapy ; Pharyngitis/epidemiology ; Pharyngitis/microbiology ; Rheumatic Fever/etiology ; Rheumatic Fever/prevention & control ; Rheumatic Heart Disease/epidemiology ; Rheumatic Heart Disease/prevention & control ; Schools/statistics & numerical data ; Young Adult ; Zambia/epidemiology
Chemical Substances	Anti-Bacterial Agents
Language	English
Publishing date	2017-07-06
Publishing country	England
Document type	Journal Article
ISSN	1471-2334
ISSN (online)	1471-2334
DOI	10.1186/s12879-017-2563-x
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