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BMC Infectious Diseases
Published in: BMC Infectious Diseases 1/2010

Open Access 01-12-2010 | Research article

Tracking the transcriptional host response from the acute to the regenerative phase of experimental pneumococcal meningitis

Authors: Matthias Wittwer, Denis Grandgirard, Janine Rohrbach, Stephen L Leib

Published in: BMC Infectious Diseases | Issue 1/2010

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Abstract

Background

Despite the availability of effective antibiotic therapies, pneumococcal meningitis (PM) has a case fatality rate of up to 30% and causes neurological sequelae in up to half of the surviving patients. The underlying brain damage includes apoptosis of neurons in the hippocampus and necrosis in the cortex. Therapeutic options to reduce acute injury and to improve outcome from PM are severely limited.
With the aim to develop new therapies a number of pharmacologic interventions have been evaluated. However, the often unpredictable outcome of interventional studies suggests that the current concept of the pathophysiologic events during bacterial meningitis is fragmentary. The aim of this work is to describe the transcriptomic changes underlying the complex mechanisms of the host response to pneumococcal meningitis in a temporal and spatial context using a well characterized infant rat model.

Methods

Eleven days old nursing Wistar rats were infected by direct intracisternal injection of 2 × 106cfu/ml of Streptococcus pneumoniae. Animals were sacrificed at 1, 3, 10 and 26 days after infection, the brain harvested and the cortex and hippocampus were sampled. The first two time points represent the acute and sub-acute phase of bacterial meningitis, whereas the latter represent the recovery phase of the disease.

Results

The major events in the regulation of the host response on a transcriptional level occur within the first 3 days after infection. Beyond this time, no differences in global gene expression in infected and control animals were detectable by microarray analysis. Whereas in the acute phase of the disease immunoregulatory processes prevail in the hippocampus and the cortex, we observed a strong activation of neurogenic processes in the hippocampal dentate gyrus, both by gene expression and immunohistology starting as early as 3 days after infection.

Conclusions

Here we describe the cellular pathways involved in the host response to experimental pneumococcal meningitis in specified disease states and brain regions. With these results we hope to provide the scientific basis for the development of new treatment strategies which take the temporal aspects of the disease into account.
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Literature
1.
Ruckinger S, von Kries R, Siedler A, van der Linden M: Association of serotype of Streptococcus pneumoniae with risk of severe and fatal outcome. Pediatr Infect Dis J. 2009, 28 (2): 118-122. 10.1097/INF.0b013e318187e215.CrossRefPubMed
2.
van de Beek D, de Gans J, McIntyre P, Prasad K: Corticosteroids for acute bacterial meningitis. Cochrane Database Syst Rev. 2007, CD004405-1
3.
Weisfelt M, Hoogman M, van de Beek D, de Gans J, Dreschler WA, Schmand BA: Dexamethasone and long-term outcome in adults with bacterial meningitis. Ann Neurol. 2006, 60 (4): 456-468. 10.1002/ana.20944.CrossRefPubMed
4.
Schuchat A, Robinson K, Wenger JD, Harrison LH, Farley M, Reingold AL, Lefkowitz L, Perkins BA: Bacterial meningitis in the United States in 1995. Active Surveillance Team. N Engl J Med. 1997, 337 (14): 970-976. 10.1056/NEJM199710023371404.CrossRefPubMed
5.
Kastenbauer S, Pfister HW: Pneumococcal meningitis in adults: spectrum of complications and prognostic factors in a series of 87 cases. Brain. 2003, 126 (Pt 5): 1015-1025. 10.1093/brain/awg113.CrossRefPubMed
6.
Ostergaard C, Konradsen HB, Samuelsson S: Clinical presentation and prognostic factors of Streptococcus pneumoniae meningitis according to the focus of infection. BMC Infect Dis. 2005, 5: 93-10.1186/1471-2334-5-93.CrossRefPubMedPubMedCentral
7.
Swartz MN: Bacterial meningitis--a view of the past 90 years. N Engl J Med. 2004, 351 (18): 1826-1828. 10.1056/NEJMp048246.CrossRefPubMed
8.
van de Beek D, Farrar JJ, de Gans J, Mai NT, Molyneux EM, Peltola H, Peto TE, Roine I, Scarborough M, Schultsz C, et al: Adjunctive dexamethasone in bacterial meningitis: a meta-analysis of individual patient data. Lancet Neurol. 2010, 9 (3): 254-263. 10.1016/S1474-4422(10)70023-5.CrossRefPubMedPubMedCentral
9.
Manolidis S, Johnson R: Do corticosteroids prevent hearing loss in pediatric bacterial meningitis? An analysis of the evidence. Ear Nose Throat J. 2006, 85 (9): 586-592.PubMed
10.
Ashburner M, Ball CA, Blake JA, Botstein D, Butler H, Cherry JM, Davis AP, Dolinski K, Dwight SS, Eppig JT, et al: Gene ontology: tool for the unification of biology. The Gene Ontology Consortium. Nat Genet. 2000, 25 (1): 25-29. 10.1038/75556.CrossRefPubMedPubMedCentral
11.
12.
Hashimoto K, Goto S, Kawano S, Aoki-Kinoshita KF, Ueda N, Hamajima M, Kawasaki T, Kanehisa M: KEGG as a glycome informatics resource. Glycobiology. 2006, 16 (5): 63R-70R. 10.1093/glycob/cwj010.CrossRefPubMed
13.
Kanehisa M, Araki M, Goto S, Hattori M, Hirakawa M, Itoh M, Katayama T, Kawashima S, Okuda S, Tokimatsu T, et al: KEGG for linking genomes to life and the environment. Nucleic Acids Res. 2008, D480-484. 36 Database
14.
Bellac CL, Coimbra RS, Christen S, Leib SL: Pneumococcal meningitis causes accumulation of neurotoxic kynurenine metabolites in brain regions prone to injury. Neurobiol Dis. 2006, 24 (2): 395-402. 10.1016/j.nbd.2006.07.014.CrossRefPubMed
15.
Bellac CL, Coimbra RS, Simon F, Imboden H, Leib SL: Gene and protein expression of galectin-3 and galectin-9 in experimental pneumococcal meningitis. Neurobiol Dis. 2007, 28 (2): 175-183. 10.1016/j.nbd.2007.07.005.CrossRefPubMed
16.
Djukic M, Mildner A, Schmidt H, Czesnik D, Bruck W, Priller J, Nau R, Prinz M: Circulating monocytes engraft in the brain, differentiate into microglia and contribute to the pathology following meningitis in mice. Brain. 2006, 129 (Pt 9): 2394-2403. 10.1093/brain/awl206.CrossRefPubMed
17.
Koedel U, Merbt UM, Schmidt C, Angele B, Popp B, Wagner H, Pfister HW, Kirschning CJ: Acute brain injury triggers MyD88-dependent, TLR2/4-independent inflammatory responses. Am J Pathol. 2007, 171 (1): 200-213. 10.2353/ajpath.2007.060821.CrossRefPubMedPubMedCentral
18.
Michel U, Gerber J, EOC A, Bunkowski S, Bruck W, Nau R, Phillips DJ: Increased activin levels in cerebrospinal fluid of rabbits with bacterial meningitis are associated with activation of microglia. J Neurochem. 2003, 86 (1): 238-245. 10.1046/j.1471-4159.2003.01834.x.CrossRefPubMed
19.
Brandenburg LO, Varoga D, Nicolaeva N, Leib SL, Wilms H, Podschun R, Wruck CJ, Schroder JM, Pufe T, Lucius R: Role of glial cells in the functional expression of LL-37/rat cathelin-related antimicrobial peptide in meningitis. J Neuropathol Exp Neurol. 2008, 67 (11): 1041-1054. 10.1097/NEN.0b013e31818b4801.CrossRefPubMed
20.
Leib SL, Clements JM, Lindberg RL, Heimgartner C, Loeffler JM, Pfister LA, Täuber MG, Leppert D: Inhibition of matrix metalloproteinases and tumour necrosis factor alpha converting enzyme as adjuvant therapy in pneumococcal meningitis. Brain. 2001, 124 (Pt 9): 1734-1742. 10.1093/brain/124.9.1734.CrossRefPubMed
21.
Gianinazzi C, Grandgirard D, Imboden H, Egger L, Meli DN, Bifrare YD, Joss PC, Täuber MG, Borner C, Leib SL: Caspase-3 mediates hippocampal apoptosis in pneumococcal meningitis. Acta Neuropathol. 2003, 105 (5): 499-507.PubMed
22.
Grandgirard D, Bifrare YD, Pleasure SJ, Kummer J, Leib SL, Täuber MG: Pneumococcal meningitis induces apoptosis in recently postmitotic immature neurons in the dentate gyrus of neonatal rats. Dev Neurosci. 2007, 29 (1-2): 134-142. 10.1159/000096218.CrossRefPubMed
23.
Gerber J, Bottcher T, Bering J, Bunkowski S, Bruck W, Kuhnt U, Nau R: Increased neurogenesis after experimental Streptococcus pneumoniae meningitis. J Neurosci Res. 2003, 73 (4): 441-446. 10.1002/jnr.10682.CrossRefPubMed
24.
Gentleman RC, Carey VJ, Bates DM, Bolstad B, Dettling M, Dudoit S, Ellis B, Gautier L, Ge Y, Gentry J, et al: Bioconductor: open software development for computational biology and bioinformatics. Genome Biol. 2004, 5 (10): R80-10.1186/gb-2004-5-10-r80.CrossRefPubMedPubMedCentral
25.
Gautier L, Cope L, Bolstad BM, Irizarry RA: affy--analysis of Affymetrix GeneChip data at the probe level. Bioinformatics. 2004, 20 (3): 307-315. 10.1093/bioinformatics/btg405.CrossRefPubMed
26.
Ting L, Cowley MJ, Hoon SL, Guilhaus M, Raftery MJ, Cavicchioli R: Normalization and statistical analysis of quantitative proteomics data generated by metabolic labeling. Mol Cell Proteomics. 2009, 8 (10): 2227-2242. 10.1074/mcp.M800462-MCP200.CrossRefPubMedPubMedCentral
27.
Hunter SM, Mansergh FC, Evans MJ: Optimization of minuscule samples for use with cDNA microarrays. J Biochem Biophys Methods. 2008, 70 (6): 1048-1058. 10.1016/j.jprot.2007.11.011.CrossRefPubMed
28.
Benjamini Y, Drai D, Elmer G, Kafkafi N, Golani I: Controlling the false discovery rate in behavior genetics research. Behav Brain Res. 2001, 125 (1-2): 279-284. 10.1016/S0166-4328(01)00297-2.CrossRefPubMed
29.
Falcon S, Gentleman R: Using GOstats to test gene lists for GO term association. Bioinformatics. 2007, 23 (2): 257-258. 10.1093/bioinformatics/btl567.CrossRefPubMed
30.
Culhane AC, Thioulouse J, Perriere G, Higgins DG: MADE4: an R package for multivariate analysis of gene expression data. Bioinformatics. 2005, 21 (11): 2789-2790. 10.1093/bioinformatics/bti394.CrossRefPubMed
31.
Leib SL, Heimgartner C, Bifrare YD, Loeffler JM, Täuber MG: Dexamethasone aggravates hippocampal apoptosis and learning deficiency in pneumococcal meningitis in infant rats. Pediatr Res. 2003, 54 (3): 353-357. 10.1203/01.PDR.0000079185.67878.72.CrossRefPubMed
32.
Leib SL, Leppert D, Clements J, Täuber MG: Matrix metalloproteinases contribute to brain damage in experimental pneumococcal meningitis. Infect Immun. 2000, 68 (2): 615-620. 10.1128/IAI.68.2.615-620.2000.CrossRefPubMedPubMedCentral
33.
Tauber SC, Stadelmann C, Spreer A, Bruck W, Nau R, Gerber J: Increased expression of BDNF and proliferation of dentate granule cells after bacterial meningitis. J Neuropathol Exp Neurol. 2005, 64 (9): 806-815. 10.1097/01.jnen.0000178853.21799.88.CrossRefPubMed
34.
Koedel U, Angele B, Rupprecht T, Wagner H, Roggenkamp A, Pfister HW, Kirschning CJ: Toll-like receptor 2 participates in mediation of immune response in experimental pneumococcal meningitis. J Immunol. 2003, 170 (1): 438-444.CrossRefPubMed
35.
Koedel U, Rupprecht T, Angele B, Heesemann J, Wagner H, Pfister HW, Kirschning CJ: MyD88 is required for mounting a robust host immune response to Streptococcus pneumoniae in the CNS. Brain. 2004, 127 (Pt 6): 1437-1445. 10.1093/brain/awh171.CrossRefPubMed
36.
Butovsky O, Ziv Y, Schwartz A, Landa G, Talpalar AE, Pluchino S, Martino G, Schwartz M: Microglia activated by IL-4 or IFN-gamma differentially induce neurogenesis and oligodendrogenesis from adult stem/progenitor cells. Mol Cell Neurosci. 2006, 31 (1): 149-160. 10.1016/j.mcn.2005.10.006.CrossRefPubMed
37.
Biber K, Neumann H, Inoue K, Boddeke HW: Neuronal 'On' and 'Off' signals control microglia. Trends Neurosci. 2007, 30 (11): 596-602. 10.1016/j.tins.2007.08.007.CrossRefPubMed
38.
Klein M, Paul R, Angele B, Popp B, Pfister HW, Koedel U: Protein expression pattern in experimental pneumococcal meningitis. Microbes Infect. 2006, 8 (4): 974-983. 10.1016/j.micinf.2005.10.013.CrossRefPubMed
39.
Lie DC, Colamarino SA, Song HJ, Desire L, Mira H, Consiglio A, Lein ES, Jessberger S, Lansford H, Dearie AR, et al: Wnt signalling regulates adult hippocampal neurogenesis. Nature. 2005, 437 (7063): 1370-1375. 10.1038/nature04108.CrossRefPubMed
40.
van Rossum D, Hanisch UK: Microglia. Metab Brain Dis. 2004, 19 (3-4): 393-411. 10.1023/B:MEBR.0000043984.73063.d8.CrossRefPubMed
41.
Walther M, Kuklinski S, Pesheva P, Guntinas-Lichius O, Angelov DN, Neiss WF, Asou H, Probstmeier R: Galectin-3 is upregulated in microglial cells in response to ischemic brain lesions, but not to facial nerve axotomy. J Neurosci Res. 2000, 61 (4): 430-435. 10.1002/1097-4547(20000815)61:4<430::AID-JNR9>3.0.CO;2-3.CrossRefPubMed
42.
Bonaguidi MA, McGuire T, Hu M, Kan L, Samanta J, Kessler JA: LIF and BMP signaling generate separate and discrete types of GFAP-expressing cells. Development. 2005, 132 (24): 5503-5514. 10.1242/dev.02166.CrossRefPubMed
43.
Leib SL, Täuber MG: Pathogenesis of bacterial meningitis. Infect Dis Clin North Am. 1999, 13 (3): 527-548. 10.1016/S0891-5520(05)70093-3. v-viCrossRefPubMed
44.
Leppert D, Lindberg RL, Kappos L, Leib SL: Matrix metalloproteinases: multifunctional effectors of inflammation in multiple sclerosis and bacterial meningitis. Brain Res Brain Res Rev. 2001, 36 (2-3): 249-257. 10.1016/S0165-0173(01)00101-1.CrossRefPubMed
45.
Koedel U, Scheld WM, Pfister HW: Pathogenesis and pathophysiology of pneumococcal meningitis. Lancet Infect Dis. 2002, 2 (12): 721-736. 10.1016/S1473-3099(02)00450-4.CrossRefPubMed
46.
Takeda K, Akira S: Roles of Toll-like receptors in innate immune responses. Genes Cells. 2001, 6 (9): 733-742. 10.1046/j.1365-2443.2001.00458.x.CrossRefPubMed
47.
Kim YS, Kim SS, Cho JJ, Choi DH, Hwang O, Shin DH, Chun HS, Beal MF, Joh TH: Matrix metalloproteinase-3: a novel signaling proteinase from apoptotic neuronal cells that activates microglia. J Neurosci. 2005, 25 (14): 3701-3711. 10.1523/JNEUROSCI.4346-04.2005.CrossRefPubMed
48.
Haynes SE, Hollopeter G, Yang G, Kurpius D, Dailey ME, Gan WB, Julius D: The P2Y12 receptor regulates microglial activation by extracellular nucleotides. Nat Neurosci. 2006, 9 (12): 1512-1519. 10.1038/nn1805.CrossRefPubMed
49.
Elward K, Gasque P: "Eat me" and "don't eat me" signals govern the innate immune response and tissue repair in the CNS: emphasis on the critical role of the complement system. Mol Immunol. 2003, 40 (2-4): 85-94. 10.1016/S0161-5890(03)00109-3.CrossRefPubMed
50.
Colonna M: TREMs in the immune system and beyond. Nat Rev Immunol. 2003, 3 (6): 445-453. 10.1038/nri1106.CrossRefPubMed
51.
Takahashi K, Prinz M, Stagi M, Chechneva O, Neumann H: TREM2-transduced myeloid precursors mediate nervous tissue debris clearance and facilitate recovery in an animal model of multiple sclerosis. PLoS Med. 2007, 4 (4): e124-10.1371/journal.pmed.0040124.CrossRefPubMedPubMedCentral
52.
Takahashi K, Rochford CD, Neumann H: Clearance of apoptotic neurons without inflammation by microglial triggering receptor expressed on myeloid cells-2. J Exp Med. 2005, 201 (4): 647-657. 10.1084/jem.20041611.CrossRefPubMedPubMedCentral
53.
Griffiths M, Neal JW, Gasque P: Innate immunity and protective neuroinflammation: new emphasis on the role of neuroimmune regulatory proteins. Int Rev Neurobiol. 2007, 82: 29-55. full_text.CrossRefPubMed
54.
Michaelidis TM, Lie DC: Wnt signaling and neural stem cells: caught in the Wnt web. Cell Tissue Res. 2008, 331 (1): 193-210. 10.1007/s00441-007-0476-5.CrossRefPubMed
55.
Zhu Y, Culmsee C, Klumpp S, Krieglstein J: Neuroprotection by transforming growth factor-beta1 involves activation of nuclear factor-kappaB through phosphatidylinositol-3-OH kinase/Akt and mitogen-activated protein kinase-extracellular-signal regulated kinase1,2 signaling pathways. Neuroscience. 2004, 123 (4): 897-906. 10.1016/j.neuroscience.2003.10.037.CrossRefPubMed
56.
Krieglstein K, Strelau J, Schober A, Sullivan A, Unsicker K: TGF-beta and the regulation of neuron survival and death. J Physiol Paris. 2002, 96 (1-2): 25-30. 10.1016/S0928-4257(01)00077-8.CrossRefPubMed
57.
Chen S, Luo D, Streit WJ, Harrison JK: TGF-beta1 upregulates CX3CR1 expression and inhibits fractalkine-stimulated signaling in rat microglia. J Neuroimmunol. 2002, 133 (1-2): 46-55. 10.1016/S0165-5728(02)00354-5.CrossRefPubMed
58.
Bottner M, Krieglstein K, Unsicker K: The transforming growth factor-betas: structure, signaling, and roles in nervous system development and functions. J Neurochem. 2000, 75 (6): 2227-2240. 10.1046/j.1471-4159.2000.0752227.x.CrossRefPubMed
59.
Unsicker K, Krieglstein K: TGF-betas and their roles in the regulation of neuron survival. Adv Exp Med Biol. 2002, 513: 353-374.CrossRefPubMed
60.
Docagne F, Nicole O, Gabriel C, Fernandez-Monreal M, Lesne S, Ali C, Plawinski L, Carmeliet P, MacKenzie ET, Buisson A, et al: Smad3-dependent induction of plasminogen activator inhibitor-1 in astrocytes mediates neuroprotective activity of transforming growth factor-beta 1 against NMDA-induced necrosis. Mol Cell Neurosci. 2002, 21 (4): 634-644. 10.1006/mcne.2002.1206.CrossRefPubMed
61.
Letamendia A, Labbe E, Attisano L: Transcriptional regulation by Smads: crosstalk between the TGF-beta and Wnt pathways. J Bone Joint Surg Am. 2001, 83-A (Suppl 1 Pt 1): S31-39.PubMed
62.
Hopwood B, Tsykin A, Findlay DM, Fazzalari NL: Microarray gene expression profiling of osteoarthritic bone suggests altered bone remodelling, WNT and transforming growth factor-beta/bone morphogenic protein signalling. Arthritis Res Ther. 2007, 9 (5): R100-10.1186/ar2301.CrossRefPubMedPubMedCentral
63.
Bifrare YD, Kummer J, Joss P, Täuber MG, Leib SL: Brain-derived neurotrophic factor protects against multiple forms of brain injury in bacterial meningitis. J Infect Dis. 2005, 191 (1): 40-45. 10.1086/426399.CrossRefPubMed
64.
de Gans J, van de Beek D: Dexamethasone in adults with bacterial meningitis. N Engl J Med. 2002, 347 (20): 1549-1556. 10.1056/NEJMoa021334.CrossRefPubMed
65.
Peltola H, Roine I, Fernandez J, Zavala I, Ayala SG, Mata AG, Arbo A, Bologna R, Mino G, Goyo J, et al: Adjuvant glycerol and/or dexamethasone to improve the outcomes of childhood bacterial meningitis: a prospective, randomized, double-blind, placebo-controlled trial. Clin Infect Dis. 2007, 45 (10): 1277-1286. 10.1086/522534.CrossRefPubMed
66.
Zysk G, Bruck W, Gerber J, Bruck Y, Prange HW, Nau R: Anti-inflammatory treatment influences neuronal apoptotic cell death in the dentate gyrus in experimental pneumococcal meningitis. J Neuropathol Exp Neurol. 1996, 55 (6): 722-728. 10.1097/00005072-199606000-00006.CrossRefPubMed
67.
Spreer A, Gerber J, Hanssen M, Schindler S, Hermann C, Lange P, Eiffert H, Nau R: Dexamethasone increases hippocampal neuronal apoptosis in a rabbit model of Escherichia coli meningitis. Pediatr Res. 2006, 60 (2): 210-215. 10.1203/01.pdr.0000227553.47378.9f.CrossRefPubMed
68.
Smith E, Coetzee GA, Frenkel B: Glucocorticoids inhibit cell cycle progression in differentiating osteoblasts via glycogen synthase kinase-3beta. J Biol Chem. 2002, 277 (20): 18191-18197. 10.1074/jbc.M109708200.CrossRefPubMed
69.
Smith E, Frenkel B: Glucocorticoids inhibit the transcriptional activity of LEF/TCF in differentiating osteoblasts in a glycogen synthase kinase-3beta-dependent and -independent manner. J Biol Chem. 2005, 280 (3): 2388-2394. 10.1074/jbc.M406294200.CrossRefPubMed
70.
Wang FS, Lin CL, Chen YJ, Wang CJ, Yang KD, Huang YT, Sun YC, Huang HC: Secreted frizzled-related protein 1 modulates glucocorticoid attenuation of osteogenic activities and bone mass. Endocrinology. 2005, 146 (5): 2415-2423. 10.1210/en.2004-1050.CrossRefPubMed
71.
Ohnaka K, Tanabe M, Kawate H, Nawata H, Takayanagi R: Glucocorticoid suppresses the canonical Wnt signal in cultured human osteoblasts. Biochem Biophys Res Commun. 2005, 329 (1): 177-181. 10.1016/j.bbrc.2005.01.117.CrossRefPubMed
72.
Ohnaka K, Taniguchi H, Kawate H, Nawata H, Takayanagi R: Glucocorticoid enhances the expression of dickkopf-1 in human osteoblasts: novel mechanism of glucocorticoid-induced osteoporosis. Biochem Biophys Res Commun. 2004, 318 (1): 259-264. 10.1016/j.bbrc.2004.04.025.CrossRefPubMed
73.
Wexler EM, Geschwind DH, Palmer TD: Lithium regulates adult hippocampal progenitor development through canonical Wnt pathway activation. Mol Psychiatry. 2008, 13 (3): 285-292. 10.1038/sj.mp.4002093.CrossRefPubMed
74.
Mostany R, Valdizan EM, Pazos A: A role for nuclear beta-catenin in SNRI antidepressant-induced hippocampal cell proliferation. Neuropharmacology. 2008, 55 (1): 18-26. 10.1016/j.neuropharm.2008.04.012.CrossRefPubMed
Metadata
Title
Tracking the transcriptional host response from the acute to the regenerative phase of experimental pneumococcal meningitis
Authors
Matthias Wittwer
Denis Grandgirard
Janine Rohrbach
Stephen L Leib
Publication date
01-12-2010
Publisher
BioMed Central
Published in
BMC Infectious Diseases / Issue 1/2010
Electronic ISSN: 1471-2334
DOI
https://doi.org/10.1186/1471-2334-10-176

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WHO estimates that half of all patients worldwide are non-adherent to their prescribed medication. The consequences of poor adherence can be catastrophic, on both the individual and population level.

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