Infections Cause Asthma

Since the anti-smoking movement began, the death rates from asthma have more than doubled in every age group above five years. This is despite smoking bans and bullying people to quit smoking, as well as improvements in air pollution. The health establishment grasps at lame explanations such as exposure to cockroaches ( which is nothing new), and to the even lamer story that exposure to infections protects against asthma. They claim that life today is too sanitary to develop children's immune systems, but what about the simultaneous increase in the death rates of the elderly? As usual, the anti-smokers' studies ignore the role of infection in asthma.

Mycoplasmas

"The family Mycoplasmataceae contains two genera that infect humans: Mycoplasma and Ureaplasma, which are usually referred to collectively as mycoplasmas. Although there are many species of mycoplasmas, only four are recognized as human pathogens; Mycoplasma pneumoniae, Mycoplasma hominis, Mycoplasma genitalium, and Ureaplasma urealyticum.... The mycoplasmas are the smallest free-living bacteria. They range from 0.2 - 0.8 micrometers and thus can pass through some filters used to remove bacteria. They have the smallest genome size and, as a result, lack many metabolic pathways and require complex media for their isolation. The mycoplasmas are facultative anaerobes, except for M. pneumoniae, which is a strict aerobe. A characteristic feature that distinguishes the mycoplasmas from other bacteria is the lack of a cell wall. Thus, they can assume multiple shapes including round, pear shaped and even filamentous.... Colonization of the respiratory tract by M. pneumoniae results in the cessation of ciliary movement. The normal clearance mechanisms of the respiratory tract do not function, resulting in contamination of the respiratory tract and the development of a dry cough.... most children are infected from 2 - 5 years of age but disease is most common in children 5-15 years of age." (Bacteriology - Chapter Nineteen. Mycoplasma and Ureaplasma. Dr. Gene Mayer, University of South Carolina School of Medicine. Accessed 12-15-07.)

Mycoplasma pneumoniae and its role as a human pathogen. KB Waites, DF Talkington. Clin Microbiol Rev 2004 Oct;17(4):697-728. Review. "M. pneumoniae infection leads to deterioration of cilia in the respiratory epithelium, both structurally and functionally. Cells may lose their cilia entirely, appear vacuolated, and show a reduction in oxygen consumption, glucose utilization, amino acid uptake, and macromolecular synthesis, ultimately resulting in exfoliation of all or parts of the infected cells (80, 83) These subcellular events can be translated into some of the clinical manifestations of respiratory tract infection that are associated with this organism, such as the persistent, hacking cough that is so commonly associated with M. pneumoniae." "Mycoplasmas have been detected by PCR in airways even when cultures and serological results are negative, suggesting that low numbers of organisms may evade detection by the immune system." "Lung abnormalities, including reduced pulmonary clearance and airway hyperresponsiveness, may persist for weeks to months after an infection with M. pneumoniae."

Chlamydia pneumoniae

Association of Chlamydia pneumoniae (strain TWAR) infection with wheezing, asthmatic bronchitis and adult-onset asthma. DL Hahn, R Dodge, R Golubjatnikov. JAMA 1991;266:225-230. "Nine (47%) of 19 patients with acute C pneumoniae infection had bronchospasm during respiratory illness, and there was a strong quantitative association of C pneumoniae titer with wheezing at the time of enrollment in the study (P = .01). In the matched study, C pneumoniae antibody was significantly associated with asthmatic bronchitis after, but not before, respiratory illness (odds ratio, 7.2; 95% confidence interval, 2.2 to 23.4). Four infected patients had newly diagnosed asthma after illness, and four others had exacerbation of previously diagnosed asthma. There was no serologic evidence of coexisting Mycoplasma pneumoniae, Chlamydia trachomatis, or respiratory viral infection in 96% of patients with asthmatic bronchitis and asthma."

Chlamydial pneumonia and asthma: a potentially important relationship. RC Bone. JAMA 1991 Jul 10;266(2):265. No abstract.

Viruses as precipitants of asthma symptoms. I. Epidemiology. PK Pattemore, SL Johnston, PG Bardin. Clin Exp Allergy 1992 Mar;22(3);325-336. Review.

Chlamydia pneumoniae infection and asthma. DL Hahn. The Lancet 1992 May 9;339:1173-1174. Letter. "I would add another possible explanation that has not received the attention it deserves -- increasing worldwide prevalence of Chlamydia pneumoniae infection." No abstract.

Chlamydia trachomatis infection in children with wheezing simulating asthma. M Bavastrelli, M Midulla, D Rossi, M Salzano. Lancet 1992 May 9;339:1174. Letter. "Our data indicate that wheezing may be another clinical expression of C trachomatis infection and that this organism should be sought as a routine in children who wheeze but have no demonstrable allergy and do not respond to the usual anti-asthmatic medications." No abstract.

Viruses as precipitants of asthma symptoms. II. Physiology and mechanisms. PG Bardin, SL Johnston, PK Pattemore. Clin Exp Allergy 1992 Sep;22(9):809-822. Review. "As most hospital admissions for asthma occur over the winter months and soon after the start of the school terms, spread of viruses through the community to susceptible individuals may be the single most important cause of sustained exacerbations of asthma."

Relationship between viral antibodies and bronchial hyperresponsiveness in 495 unselected children and adolescents. V Backer, CS Ulrick, N Bach-Mortensen, G Glikmann, CH Mordhorst. Allergy 1993 May;48(4):240-247. "Bronchial hyperresponsiveness (BHR) to inhaled histamine was found in 79 (16%) of the subjects, of whom 28 had asthma. Forty-eight subjects (10%) had increased levels of serum IgM antibodies against either parainfluenza, influenza, adenovirus, or respiratory syncytial virus (RSV), reflecting a recently acquired infection. No association between BHR and antibodies against respiratory viruses was found, as 7 (8.9%) of the 79 subjects with BHR and 41 (9.9%) of the 416 subjects without BHR had viral antibodies. Furthermore, no association between degree of bronchial responsiveness and viral antibodies was found."

Another possible risk factor for airway disease. DL Hahn. Chest 1993 Aug;104(2):649. Letter. "In an editorial that also appeared in the March 1992 issue of Chest, Casterline therefore asks, 'Will the real risk factor for airway disease please stand up?' I have a nomination for a possible culprit, who appears to be trying to get up, but will need some prodding from investigators." No abstract.

Persistent adenoviral infection and chronic airway obstruction in children. V Macek, J Sorli, S Kopriva, J Marin. Am J Respir Crit Care Med 1994 Jul;150(1):7-10. 34 children aged 14 months to 14 years "who showed an unfavorable response to standard corticosteroid and bronchodilator therapy. Analysis of cytospin preparations of BAL fluid at the light-microscopic level, using a monoclonal antibody to detect adenoviral antigens, demonstrated that capsid protein was present in 31 of 34 (94%) of the children examined. Limited repeat studies within 1 yr showed 6 of 8 (75%) were positive twice when tested on two occasions, and that three were positive in all occasions when sampled three times. Cultures of the BAL fluid were also positive for adenovirus in six of six cultures performed, indicating that the virus was in some cases replicating. Similar studies of control patients without persistent asthma showed no evidence of adenovirus."

Acute acerbations of asthma in adults: role of Chlamydia pneumoniae infection. L Allegra, F Blasi, S Centanni, R Cosentini, F Denti, R Raccanelli, P Tarsia, V Valenti. Eur Respir J 1994 Dec;7(12):2165-2168. Seventy four adult out-patients with a diagnosis of acute exacerbation of asthma. "Fifteen patients (20%) presented seroconversion to at least one of the studied pathogens. Seven were found to be infected by virus, six by C. pneumoniae alone, and one by M. pneumoniae. One more patient showed seroconversion to C. pneumoniae and cytomegalovirus."

Community study of role of viral infections in exacerbations of asthma in 9-11 year old children. SL Johnston, PK Pattemore, G Sanderson, S Smith, F Lampe, L Josephs, P Symington, S O'Toole, SH Myint, DAJ Tyrrell, ST Holgate. BMJ 1995 May 13;310(6989):1225-1229. 108 children. "Viruses were detected in 80% of reported episodes of reduced peak expiratory flow, 80% of reported episodes of wheeze, and in 85% of reported episodes of upper respiratory symptoms, cough, wheeze, and a fall in peak expiratory flow. The median duration of reported falls in peak expiratory flow was 14 days, and the median maximum fall in peak expiratory flow was 81 1/min. The most commonly identified virus type was rhinovirus." Graph of seasonal patterns.

Serology of Chlamydia in relation to asthma and bronchial hyperresponsiveness. E Bjornsson, E Hjelm, C Janson, E Fridell, G Boman. Scand J Infect Dis 1996;28(1):63-69. 122 subjects with asthma vs 75 controls. "For Chlamydia pneumoniae, a relationship was found between current or recent infection and wheezing (odds ratio (OR) 6.0, confidence intervals (CI) 1.3-28) and also between IgA antibodies and bronchial hyperresponsiveness (BHR) (OR 3.3, CI 1.3-8.3). For Chlamydia trachomatis, serological signs of a previous infection were found significantly more often in subjects who reported having had asthma at some time: (OR 3.2, CI 1.4-7.1), asthma during the last year (OR 3.2, CI 1.4-7.1), wheezing during the last year (OR 4.2, CI 1.6-6.6) and in those who had BHR (OR 2.7, CI 1.2-6.1)."

The relationship between upper respiratory infections and hospital admissions for asthma: a time-tend analysis. SL Johnston, PK Pattemore, G Sanderson, S Smith, MJ Campbell, LK Josephs, A Cunningham, BS Robinson, SH Myint, ME Ward, DA Tyrrell, ST Holgate. Am J Respir Crit Care Med 1996 Sep;154(3 Pt 1):654-660. 108 school-age children monitored for 1 year. "Strong correlations were found between the seasonal patterns of upper respiratory infections and hospital admissions for asthma (r = 0.72; p < 0.0001). This relationship was stronger for pediatric (r = 0.68; p < 0.0001) than for adult admissions (r = 0.53; p < 0.01). Upper respiratory infections and admissions for asthma were more frequent during periods of school attendance (87% of pediatric and 84% of total admissions), than during school holiday periods (p < 0.001)."

Influence of viral and bacterial respiratory infections on exacerbations and symptom severity in childhood asthma. SL Johnston. Pediatr Pulmonol Suppl 1997;16:88-89. Review.

Evidence for Chlamydia pneumoniae infection in steroid-dependent asthma. DL Hahn, D Bukstein, A Luskin, H Zeitz. Ann Allergy Asthma Immunol 1998 Jan;80(1):45-49.

Can acute Chlamydia pneumoniae respiratory tract infection initiate chronic asthma? DL Hahn, R McDonald. Ann Allergy Asthma Immunol 1998 Oct;81:339-344.

Detection of mycoplasma pneumoniae in the airways of adults with chronic asthma. M Kraft, GH Cassell, JE Henson, H Watson, J Williamson, BP Marmion, CA Gaydos, RJ Martin. Am J Respir Crit Care Med 1998;158:998-1001. Eighteen asthmatics with chronic, stable asthma and 11 nonasthmatic controls. "M. pneumoniae was detected by PCR in 10 of 18 asthmatics and one of 11 control subjects (p = 0.02). In nine of the 10 patients, the organism was detected in bronchoalveolar lavage or bronchial biopsies. Seven of 18 asthmatics and one of 11 control subjects were also positive for M. fermentans and M. genitalium by PCR. All patients' cultures, EIAs, and serology were negative for M. pneumoniae. All PCR and cultures were negative for C. pneumoniae, and all EIAs for respiratory viruses were negative in all subjects. Nine asthmatics and one control subject exhibited positive serology for C. pneumoniae (p = 0.05)."

Chronic Chlamydia pneumoniae infection and asthma exacerbations in children. AF Cunningham, SL Johnston, SA Julius, FC Lampe, ME Ward. Eur Respir J 1998 Feb;11(2):345-349. One hundred and eight children with asthma symptoms, aged 9-11 yrs. "C. pneumoniae detections were similar between the symptomatic and asymptomatic episodes (23 versus 28%, respectively). Children who reported multiple episodes also tended to remain PCR positive for C. pneumoniae suggesting chronic infection (p< 0.02). C. pneumoniae-specific secretory-IgA antibodies were more than seven times greater in subjects who reported four or more exacerbations in the study compared to those who reported just one (p<0.02)."

Viruses and asthmatic syndromes. E Micillo, P Marcatili, S Palmieri, G Mazzarella. Monaldi Arch Chest Dis 1998 Feb;53(1):88-91. Review.

Mechanisms of asthma exacerbation. SL Johnston. Clin Exp Allergy 1998;28(Suppl 5):181-186. Review.

Viruses and asthma. SL Johnston. Allergy 1998;53:922-932. Review.

Chlamydia pneumoniae and asthma. PJ Cook, P Davies, W Tunnicliffe, JG Ayres, D Honeybourne, R Wise. Thorax 1998 Apr;53(4):254-259.

Chlamydia pneumoniae and possible relationship to asthma. Serum immunoglobulins and histamine release in patients and controls. FO Larson, S Norn, CH Mordhorst, PS Skov, N Milman, P Clementsen. APMIS 1998 Oct;106(10):928-934.

Viruses and asthma exacerbations. NG Papadopoulos, SL Johnston. Thorax 1998 Nov;53(11):913-914. Review.

Chlamydia pneumoniae and asthma. F Blasi, L Allegra, P Tarsia. Thorax 1998 Dec;53(12):1094. Letter re Cook 1998.

Chlamydia pneumoniae and asthma. DL Hahn. Thorax 1998 Dec;53(12):1095-1096. Letter re Cook 1998.

Bacterial infection as an important triggering factor in bronchial asthma. AK Oehling. J Investig Allergol Clin Immunol 1999 Jan-Feb;9(1):6-13. Review.

PCR detection of viral nucleic acid in fatal asthma: is the lower respiratory tract a reservoir for common viruses? V Macek, A Dakhama, JC Hogg, FH Green, BK Rubin, RG Hegele. Can Respir J 1999 Jan-Feb;6(1):37-43.

Detection of viral, Chlamydia pneumoniae and Mycoplasma pneumoniae infections in exacerbations of asthma in children. F Freymuth, A Vabret, J Brouard, P Toutain, R Verdon, J Petitjean, S Gouarin, J-F Duhamel, B Guillois. J Clin Virol 1999;13:131-139.

The role of viral and atypical bacterial pathogens in asthma pathogenesis. SL Johnston. Pediatric Pulmonol Suppl 1999;18:141-143. Review.

Not an ideal study. DL Hahn. J Family Pract 1999 Mar;48(3):230. (Letter re Smucny). "In addition to relevant clinical variables, I believe that meaningful studies of acute bronchitis must include objective measures of pulmonary function (including reversibility) and [italics] comprehensive evaluation of microbiologic causes for bronchitis; without subgroup analyses based on these variables, I doubt that clinicians will ever have access to the information they need to provide rational antibiotic prescribing for acute bronchitis in otherwise healthy patients." (No abstract).

Treatment of late-onset asthma with fluconazole. GW Ward Jr, JA Woodfolk, ML Hayden, S Jackson, TAE Platts-Mills. J Allergy Clin Immunol 1999 Sep;104(3 Pt 1):541-546. Randomized controlled study of 11 patients. "At the end of the first 5 months of active treatment, there was a highly significant decrease in bronchial sensitivity to Trichophyton (P = .012) and in oral steroid requirement (P = .01). At the end of phase 2, mean peak expiratory flow rates increased in 9 of 11 patients. An improvement in symptoms, peak flow, and steroid use was maintained up to 36 months after starting fluconazole in patients who continued to receive treatment."

New understanding of disease mechanisms: excitement and caution. DA Stempel. J Allergy Clin Immunol 1999 Sep;104(3 Pt 1):524-525. Editorial re Ward 1999.

Community study using a polymerase chain reaction panel to determine the prevalence of common respiratory viruses in asthmatic and nonasthmatic children. JA West, A Dakhama, MA Khan, S Vedal, RG Hegele. J Asthma 1999 Oct;36(7):605-612.

Chlamydia pneumoniae, asthma, and COPD: what is the evidence? DL Hahn. Ann Allergy Asthma Immunol 1999 Oct;83(4):271-292. Review, with CME examination.

Childhood viral infection and the pathogenesis of asthma and chronic obstructive lung disease. JC Hogg. Am J Respir Crit Care Med 1999 Nov;160(5 Pt 2):826-828. Review.

Respiratory infections and asthma. E Micillo, A Bianco, D D'Auria, G Mazzarella, GF Abbate. Allergy 2000;55 Suppl 61:42-45. Review.

Serologic markers for Chlamydia pneumoniae in asthma. DL Hahn, RW Peeling, E Dillon, R McDonald, P Saikku. Ann Allergy Asthma Immunol 2000 Feb;84(2):227-233.

Serological evidence of infection with Chlamydia pneumoniae is related to the severity of asthma. PN Black, R Scicchitano, CR Jenkins, F Blasi, L Allegra, J Wlodarczyk, BC Cooper. Eur Respir J 2000 Feb;15(2):254-259. 619 subjects with asthma (18-60 yrs), by microimmunofluoresence. "The use of high dose inhaled steroids was associated with an increase of 74.1% in the titre of IgG antibodies (p=0.04) and an increase of 70.6% in the titre of IgA antibodies (p=0.0001) when compared with the use of low dose inhaled steroids. There was an inverse association between IgG antibodies and forced expiratory volume in one second (FEV1) as a percentage of predicted in those subjects with elevated IgG and/or IgA (p=0.04). In this group IgA antibodies were also associated with a higher daytime symptom score (p=0.04)."

Lack of correlation between Chlamydia pneumoniae antibody titers and adult-onset asthma. JM Routes, HS Nelson, JA Noda, FT Simon. J Allergy Clin Immunol 2000 Feb;105(2 Pt 1):391-392. 46 asthma patients and 46 age- and sex-matched controls. "Nearly two thirds of control and asthmatic patients had never smoked. There was no significant difference (Fig 1) in the proportion of asthmatic or control subjects with IgG titers against C pneumoniae that would signify acute infection (IgG ≥1:512), indeterminate exposure (1:16 ≥ IgG < 1:512) or seronegativity (IgG <16) (chi-square test, P = .755)."

Viral and bacterial infections in the development and progression of asthma. JE Gem. J Allergy Clin Immunol 2000 Feb;105(2 Pt 2):S497-S502. Review.

Persistence of viruses in the upper respiratory tract of children with asthma. J Marin, D Jeler-Kacar, V Levsiek, V Macek. J Infect 2000 Jul;41(1):69-72. "Conclusions: The persistent presence of viruses in the upper respiratory tract of asthmatic children shows a possible connection between viral infections and asthma."

The role of atypical organisms in asthma. CM Daian, AH Wolff, L Bielory. Allergy Asthma Proc 2000 Mar-Apr;21(2):107-111. Review.

Chlamydia pneumoniae serological status is not associated with asthma in children or young adults. GD Mills, JA Lindeman, JP Fawcett, GP Herbison, MR Sears. Int J Epidemiol 2000 Apr;29(2):280-284. "The study has not, however, addressed the role this organism may play in specific asthmatic subjects or asthma exacerbations."

[Chlamydia pneumoniae infection in patients with acute bronchitis and bronchial asthma]. M Oshima, Y Awaya, T Fujii, Y Kodomari, M Kuwabara. Arerugi 2000 May;49(5):412-419.

Sensitivity to fungal allergens is a risk factor for life-threatening asthma. PN Black, AA Udy, SM Brody. Allergy 2000 May;55(5):501-504.

[Chronic Chlamydia pneumoniae infection in patients with asthma]. J Niedzwiadek, E Mazur, J Chmielewska-Badora, B Gryglicka, I Wegrzyn-Szkutnik, B Chabros, M Koziol-Montewka, J Milanowski. Pneumonol Alergol Pol 2000;68(5-6):255-260.

The role of bacterial infections in asthma. M Kraft. Clin Chest Med 2000 Jun;21(2):301-313. Review.

The role of viruses in development or exacerbation of atopic asthma. J Schwarze, EW Gelfand. Clin Chest Med 2000 Jun;21(2):279-287. Review.

The role of respiratory viruses in acute and chronic asthma. A Tuffaha, JE Gern, RF Lemanske. Clin Chest Med 2000 Jun;21(2):289-300. Review.

Specific and nonspecific obstructive lung disease in childhood: causes of changes in the prevalence of asthma. TA Platts-Mills, MC Carter, PW Heymann. Environ Health Perspect 2000 Aug;108 Suppl 4:725-731. Review.

Chlamydia pneumoniae antibodies and adult-onset asthma. DL Hahn. J Allergy Clin Immunol 2000 Aug;106(2):404. Letter re Routes 2000. "...In any event, I agree with the authors' general conclusions that serologic testing alone will not be clinically useful in selecting asthmatic patients for antimicrobial therapy. Although C pneumoniae IgA antibody testing can be specific (if C trachomatis and C psittaci antigens are used as parallel controls), it is unlikely that IgA is sufficiently sensitive; furthermore, serologic testing cannot identify the location of infection."

[Impact of Chlamydia pneumoniae infections on asthma]. G Jebrak, O Brugiere, ML Uffredi. Presse Med 2000 Sep 9;29(25):1425-1431. Review.

[Percentage of asthmatic patients with acute bronchitis and Chlamydia pneumoniae seropositivity]. J Orfila, P Godard. Presse Med 2000 Sep 9;29(25):1439-1441.

Chlamydia pneumoniae and the lung. MR Hammerschlag. Eur Respir J 2000 Nov;16(5):1001-1007. Comment.

[The role of fungal allergy in bronchial asthma]. K Akiyama. Nippon Ishinkin Gakkai Zasshi 2000;41(3):149-155. Review.

Prevalence of Chlamydia pneumoniae in acute respiratory tract infection and detection of anti-Chlamydia pneumoniae-specific IgE in Japanese childen with reactive airway disease. S Ikezawa. Kurume Med J 2001;48(2):165-170. 411 children with acute respiratory tract infection. "Evidence of infection with C. pneumoniae was detected in 58 children with pneumonia (34.5%), bronchitis (41.4%) and upper respiratory tract infection (24.1%). Twenty-nine (50.0%) out of 58 patients were younger than 5 years old and 18 (31.0%) had wheezing at first visit. A logistic test for anti-C. pneumoniae-specific IgE showed the deference in the fluorescence unit between the patients with C. pneumoniae infection with and without wheezing was statistically significant (Po = 0.02748, to = 2.31891)."

Persistent airflow limitation in adult-onset nonatopic asthma is associated with serologic evidence of Chlamydia pneumoniae infection. A ten Brinke, JT van Dissell, PJ Sterk, AH Zwinderman, KF Rabe, EH Bel. J Allergy Clin Immunol 2001 Mar;107(3):449-454. 32 men and 69 women nonsmokers. "Patients with adult-onset nonatopic asthma and positive IgG antibodies to C pneumoniae had a significantly steeper slope of the regression line compared with the other subgroups of asthmatic patients (P =.001), being indicative of a 4-fold greater estimated decline in postbronchodilator FEV(1)/vital capacity (2.3% vs 0.5% predicted per year of asthma duration)."

A link between chronic asthma and chronic infection. RJ Martin, M Kraft, HW Chu, EA Berns, GH Cassell. J Allergy Clin Immunol 2001 Apr;107(4):595-601. 55 asthma patients vs 11 normal controls. "PCR for Mycoplasma species showed that 23 asthmatic patients had positive test results for M pneumoniae , and an additional 2 had positive test results for either M genitalium or M fermentans... Four subjects had positive results for either M genitalium or M fermentans plus M pneumoniae . Thus 25 of 55 asthmatic patients had positive PCR results for a Mycoplasma species pathogen compared with 1 of 11 control subjects (P = .007). PCR for C pneumoniae demonstrated 7 asthmatic patients with positive test results compared with zero such control subjects (P = .04, Fig 1). Of these 7 asthmatic patients, one had positive results for both C pneumoniae and M pneumoniae . Thus for the 55 asthmatic subjects, 31 (56.4%) had positive results for either Mycoplasma species, Chlamydia species, or both."

Increased frequency of Chlamydia pneumoniae antibodies in patients with asthma. M Gencay, JJ Rudiger, M Tamm, M Soler, AP Perruchoud, M Roth. Am J Respir Crit Care Med 2001 Apr;163(5):1097-1100. 33 adults with a clinical history of asthma, positive methacholine test, and reduced FEV(1), versus 33 age-, sex-, and locality-matched controls. "Chlamydia pneumoniae-specific IgA was detected in 52% of the patients with asthma and in 15% of the healthy control subjects (p < 0.01). Serological evidence of chronic infection with C. pneumoniae (high IgG [> pr = 1:512] and high IgA [> or = 1:40]) was more frequent in patients with asthma (18.2%) compared with control subjects (3.0%) (p < 0.01)."

Host immune response to Chlamydia pneumoniae heat shock protein 60 is associated with asthma. T Huittinen, D Hahn, T Anttila, E Wahlstrom, P Saikku, M Leinonen. Eur Respir J 2001 Jun;17(6):1078-1082. C pneumoniae Hsp60 IgA antibodies were significantly associated with asthma, p = 0.02. "Pulmonary function, as measured by forced expiratory volume in one second, also inversely correlated (r=−0.23, p=0.04) with the quantity of C. pneumoniae Hsp60 IgA antibodies, suggesting an association with the severity of pulmonary obstruction."

Trial of roxithromycin in subjects with asthma and serological evidence of infection with Chlamydia pneumoniae. PN Black, F Blasi, CR Jenkins, R Scicchitano, GD Mills, AR Rubinfeld, RE Ruffin, PR Mullins, J Dangain, BC Cooper, DB David, L Allegra. Am J Respir Crit Care Med 2001 Aug 15;164(4):536-541. "Six weeks of treatment with roxithromycin led to improvements in asthma control but the benefit was not sustained."

Activated, cytotoxic CD8(+) T lymphocytes contribute to the pathology of asthma death. S O'Sullivan, L Cormican, JL Faul, S Ichinohe, SL Johnston, CM Burke, LW Poulter. Am J Respir Crit Care Med 2001 Aug 15;164(4):560-564. Seven patients who died an asthma death (AD), seven asthmatic patients who died of unrelated causes (AUC), and seven postmortem cases with no history of lung disease. "The percentage of CD8(+) cells expressing the activation marker CD25 was higher in the AD group than in both the AUC and control groups (11.91 +/- 1.92% versus 3.93 +/- 1.63% and 1.09 +/- 0.56%, respectively (p < 0.001). Perforin expression, a marker of cytotoxicity, was highest in the AD group (9.16 +/- 1.5%) compared with 1.39 +/- 0.9; 1.8 +/- 0.6% in the AUC and control groups respectively (p < 0.001). Expression of interleukin-4 (IL-4) and interferon gamma (IFN-gamma) by CD8(+) T cells was higher in the AD group than the control group (p < 0.05). Furthermore, the IFN-gamma/IL-4 ratio in the AD group was less than half that of the control group (1.46 +/- 0.2 versus 3.2 +/- 0.1; p = 0.02). Using polymerase chain reaction (PCR), viral genome for rhinovirus (RV) was detected in lung tissue from three of the seven cases in the AD group. Two of these cases also had detectable respiratory syncytial virus (RSV). Viral genome for RSV was detected in five of the AUC group and in one of these cases, RV was also detected. No viral genome was detected in the lungs of the control group."

Chlamydia pneumoniae and severity of asthma. HL Von, T Vasankari, K Liippo, E Wahlstrom, M Puolakkainen. Scand J Infect Dis 2002;34(1):22-27. "Severe and moderate asthma were significantly associated with elevated IgA antibody levels to C. pneumoniae suggestive of chronic infection."

Chlamydia pneumoniae immunoglobulin A reactivation and airway inflammation in acute asthma. PA Wark, SL Johnston, JL Simpson, MJ Hensley, PG Gibson. Eur Respir J 2002 Oct;20(4):834-840. "the serological features suggest that Chlamydia pneumoniae reactivation may trigger neutrophilic airway inflammation in acute asthma."

Is asthma an infectious disease?: Thomas A. Neff lecture. RF Lemanske Jr. Chest 2003 Mar;123(3 Suppl):385S-90S. Review. "The data to support a potential role for these agents in asthma is most convincing for C pneumoniae. The major impedance in studying the contribution of this organism to asthma pathogenesis has been the lack of a sensitive, specific, reliable, and convenient diagnostic laboratory test."

Anti-Chlamydia pneumoniae heat shock protein 10 antibodies in asthmatic adults. F Betsou, JM Sueur, J Orfila. FEMS Immunol Med Microbiol 2003 Mar 20;35(2):107-111. In 160 asthmatic adults and 88 non-asthmatic controls, "An association was observed between the presence of anti-Chsp10 antibodies and adult onset asthma."

The development of asthma in children infected with Chlamydia pneumoniae is dependent on the modifying effect of mannose-binding lectin. A Nagy, GT Kozma, M Keszei, A Treszl, A Falus, C Szalai. J Allergy Clin Immunol 2003 Oct;112(4):729-734. 139 children with asthma and 174 healthy controls. "Among asthmatic children carrying variant MBL alleles, there were significantly more patients with positive results for C pneumoniae-specific IgG than among control children with variant MBL genotypes (63.7% vs 40.7% of asthmatic vs control children, respectively; odds ratio adjusted for age and sex, 2.21; 95% CI, 1.10-4.41; P =.02). Infected children with variant MBL alleles were found to have a higher risk of asthma development than infected children with normal MBL genotype. This risk was especially high in children with chronic or recurrent infection (positive results for both IgA and IgG; adjusted odds ratio, 5.38; 95% CI, 1.75-14.36; P =.01), but no increased risk was seen in children with current C pneumoniae infection (positive results for IgM)."

Chlamydia pneumoniae infection and inflammation in adults with asthma. T Savykoski, T Harju, M Paldanius, H Kuitunen, Bloigu, E Wahlstrom, P Rytila, V Kinnula, P Saikku, M Leinonen. Respiration 2004 Mar-Apr;71(2):120-125. Serum and sputum samples from 103 asthma patients and 30 healthy volunteers. "The asthma patients, especially those with moderate asthma, had higher serum IgA antibody levels to CpHsp60 than the healthy controls (test for trend, p = 0.05), whereas antibody levels to CpEB antigen did not differ between the study groups. CRP levels were higher in both asthma groups compared to the control group and moreover, the patients with moderate asthma had higher CRP levels than those with mild asthma (test for trend, p < 0.01). The subjects with a slightly elevated CRP level, defined as > or =1.8 mg/l, had higher CpEB IgA (p = 0.001), CpEB IgG (p = 0.008) and CpHsp60 IgA (p = 0.023) antibody levels in serum compared to the subjects with lower CRP levels."

Seroprevalence of Mycoplasma pneumoniae and Chlamydia pneumoniae in stable asthma and chronic obstructive pulmonary disease. SJ Park, YC Lee, YK Rhee, HB Lee. J Korean Med Sci 2005 Apr;20(2):225-228. "Seroprevalences of M. pneumoniae and C. pneumoniae in the asthma group (11.1% and 8.3%, respectively) were higher than in the control group (4.4% and 2.2%, respectively) without statistical significance. The seroprevalence of M. pneumoniae in the COPD group (16.9%) was significantly higher than in the control group, and the seroprevalence of C. pneumoniae in the COPD group (3.4%) was higher than in the control group without statistical significance." 140 patients in all.

[Is there a link between chronic chlamydial infection and childhood asthma?] J Tyl. Med Wieku Rozwoj 2004 Apr-Jun;8(2 Pt 2):411-417. "Results were positive for Chlamydia pneumoniae in 7/51 children with asthma compared with 1/36 controls. Specific IgA anti-Chlamydia trachomatis antibodies were detected in 2/51 patients with asthma and in one of the 36 controls. Infected children, more often than asthmatics without specific chlamydial IgA, suffered from more severe forms of asthma and required multiple-drug therapy, but none of the differences appeared statistically significant."

Use of quantitative and objective enzyme immunoassays to investigate the possible association between Chlamydia pneumoniae and Mycoplasma pneumoniae antibodies and asthma.T Tuuminen, I Edelstein, A Punin, N Kislova, L Stratchounski. Clin Microbiol Infect 2004 Apr;10(4):345-348. "Sera from 150 consecutive patients with established asthma and 150 matched controls were examined for Chlamydia pneumoniae IgG and IgA with commercially available enzyme immunoassays (EIAs) detecting immune response solely to surface proteins of elementary bodies. The assays were also modified to measure combined immune response to surface proteins and family-specific lipopolysaccharide antigen. Mycoplasma pneumoniae IgG and IgA were measured with new commercial EIAs utilising P1-enriched protein fraction as an antigen. No statistically significant differences between the patient groups in terms of prevalence or levels of antibodies to either organism were found with these methods."

Mycoplasma pneumoniae and asthma in children. S Biscardi, M Lorrot, E Marc, F Moulin, B Boutonnat-Faucher, C Heilbronner, JL Iniguez, M Chaussain, E Nicand, J Raymond, D Gendrel. Clin Infect Dis 2004 May 15;38(10):1341-1346. "Of 119 patients with previously diagnosed asthma, acute M. pneumoniae infection was found in 24 (20%) and C. pneumoniae infection was found in 4 (3.4%) of the patients during the current exacerbation. Of 51 patients experiencing their first asthma attack, acute M. pneumoniae infection was proven in 26 (50%) of the patients (P<.01) and C. pneumoniae in 4 (8.3%). In the control group of 152 children with stable asthma or rhinitis, 8 (5.2%) had M. pneumoniae infection (P<.005). Of the 29 patients experiencing their first asthma attack and infected with M. pneumoniae or C. pneumoniae, 18 (62%) had asthma recurrences but only 6 (27%) of the 22 patients who did not have such infections had asthma recurrences (P<.05)."

Chlamydophila pneumoniae and Mycoplasma pneumoniae in respiratory specimens of children with chronic lung diseases. N Teig, A Anders, C Schmidt, C Rieger, S Gatermann. Thorax 2005 Nov;60(11):962-966. "We investigated nasal brush specimens and induced sputum from 38 children with stable chronic lung disease (asthma, n = 26; chronic bronchitis n = 12) and from 42 healthy controls for the presence of M pneumoniae or C. pneumoniae DNA by polymerase chain reaction (PCR) using nested primers. RESULTS: None of the controls but 23.6% and 10.5% of the children with lung disease had positive PCR for C pneumoniae (p = 0.001) and M pneumoniae (p = 0.044) respectively."

Bronchial asthma and Chlamydia pneumoniae antibodies in children aged 4-8 years in Olomouc district. F Kopriva, J Szotkowska, M Zapalka. Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub 2005 Dec;149(2):289-291. "In a group of 83 atopic children with chronic cough, IgM and IgG antibodies to C. pneumoniae were demonstrated in 20 children (24 %). Among children with bronchial asthma, positive antibody was present in 29 children (44 %; /p = 0,052/); of this number, 24 (36 %; /p = 0,06/) had IgM and IgG antibodies while 5 children (8 %) had IgA and IgG antibodies against C. pneumoniae. A group of non-atopic children with non-specific symptoms included 38 children (16 %) with antibody positivity; 27 children (11 %) with IgM and IgG antibodies and 11 children (5 %) with IgA and IgG antibodies against C. pneumoniae. CONCLUSIONS. Asthma in children was associated with elevated levels of IgM and IgG antibodies to C. pneumoniae."

The effect of telithromycin in acute exacerbations of asthma. SL Johnston, F Blasi, PN Black, RJ Martin, DJ Farrell, RB Nieman; TELICAST Investigators. N Engl J Med 2006 Apr 13;354(15):1589-1600. Randomized controlled trial in 278 adults with diagnosed asthma, enrolled within 24 hours after an acute exacerbation. "Of the two prespecified primary outcomes, only asthma symptoms showed a significantly greater reduction among patients receiving telithromycin than among those receiving placebo." There was no change in morning peak expiratory flow. "Although 61 percent of patients had evidence of infection with C. pneumoniae, M. pneumoniae, or both, there was no relationship between bacteriologic status and the response to asthma treatment."

[Evaluation of association between an acute attack of childhood bronchial asthma and Chlamydia pneumoniae infection] Y Jiang, XL Liu, FQ Xing, JS Yang, H Tu. Zhongguo Dang Dai Er Ke Za Zhi 2006 Apr;8(2):113-114. "Anti-CP IgM was demonstrated in 22 cases (18.3%) and anti-CP IgG was demonstrated in 32 cases (26.7%) out of the 120 asthmatic patients. The incidence of CP infection in asthmatic children was significantly higher than that in healthy controls (3.7%) (P < 0.01)."

Pathogenic bacteria and viruses in induced sputum or pharyngeal secretions of adults with stable asthma. TH Harju, M Leinonen, J Nokso-Koivisto, T Korhonen, R Räty, Q He, T Hovi, J Mertsola, A Bloigu, P Rytilä, P Saikku. Thorax 2006 Jul;61(7):579-584. "Sputum samples from two of the 30 healthy controls (6.7%), five of 53 patients with mild asthma (9.4%), and eight of 50 with moderate asthma (16.0%) were positive for rhinovirus. Rhinovirus positive asthmatic subjects had more asthma symptoms and lower forced expiratory volume in 1 second (FEV(1)) (79% predicted) than rhinovirus negative cases (93.5% predicted; p = 0.020). Chlamydia pneumoniae PCR was positive in 11 healthy controls (36.6%), 11 mild asthmatics (20.8%), and 11 moderate asthmatics (22%), and PCR positive asthmatics had lower FEV(1)/FVC than negative cases (78.2% v 80.8%, p = 0.023). Bordetella pertussis PCR was positive in 30 cases: five healthy controls (16.7%), 15 mild asthmatics (28.3%), and 10 moderate asthmatics (20%). Bordetella pertussis positive individuals had lower FEV(1)/FVC (77.1% v 80.7%, p = 0.012) and more asthma symptoms than B pertussis negative cases."

Association between Chlamydia pneumoniae antibodies and wheezing in young children and the influence of sex. E Normann, J Gnarpe, B Wettergren, C Janson, M Wickman, L Nordvall. Thorax 2006 Dec;61(12):1054-1058. In 1581 four-year-olds, "In girls, the occurrence of anti-Cpn IgG was associated with wheezing at the ages of 1, 2, and 4 years (odds ratios (ORs) 3.41 (95% confidence interval (CI) 1.46 to 7.96), 2.13 (95% CI 1.02 to 4.44), and 2.01 (95% CI 1.14 to 3.54), respectively), and even higher ORs were observed for each age category when only high level antibody responses to Cpn were analysed. At the time of blood sampling the association between anti-Cpn IgG and wheezing was restricted to girls without atopic sensitisation (OR 2.39 (95% CI 1.25 to 4.57). No associations with wheezing were detected in boys, in whom IgE sensitisation was inversely associated with the presence of anti-Cpn IgG (OR 0.49 (95% CI 0.26 to 0.90)). CONCLUSIONS: This study suggests an association between evidence of earlier Cpn infection and a history of wheezing in young girls."

Role of viruses and atypical bacteria in asthma exacerbations among children in Oporto (Portugal). M João Silva, C Ferraz, S Pissarra, MJ Cardoso, J Simões, A Bonito Vítor. Allergol Immunopathol (Madr) 2007 Jan-Feb;35(1):4-9. "In 54 eligible children, 37 nasal samples were obtained. Infectious agents were detected in 78 % of the patients. Rhinovirus was detected in 70.3 %, Mycoplasma pneumoniae in 16.2 %, enterovirus in 10.8 %, and Chlamydia pneumoniae in 2.7 %. Coinfection was identified in 21.6 % of the samples. There was no significant correlation between current treatment status, severity of asthma or exacerbations and the isolated agents."

Is there any relationship between asthma and asthma attack in children and atypical bacterial infections; Chlamydia pneumoniae, Mycoplasma pneumoniae and helicobacter pylori. A Annagür, SG Kendirli, M Yilmaz, DU Altintas, A Inal. J Trop Pediatr 2007 Oct;53(5):313-318. "Seventy-nine asthmatic children (46 males, aged 5-15 years) were included in study. The study group was divided into two groups: group 1 consisted of 37 children with asthma attacks and group 2 consisted of 42 children with stable asthma. As a control group we studied 36 healthy children.... Mycoplasma IgM and Chlamidia IgM were positive in 8.1% (3 patients) and 18.9% (7 patients) of group 1 patients, respectively. There was a statistically significant difference for Mycoplasma IgM (p = 0.031) and Chlamidia IgM (p = 0.03) between group1 and other two groups."

Modulation of pulmonary dendritic-cell function during mycobacterial infection. MM Anis, SA Fulton, SM Reba, Y Liu, CV Harding, WH Boom. Infect Immun 2008 Feb;76(2):671-677. "Interestingly, during peak mycobacterial infection, CD11chi MHChi lung DCs had slightly decreased chemotaxis toward the CCR7 ligand CCL21 and less efficiency in activating naive CD4+ T cells than DCs from mice during late-stage infection, when few bacilli are found in the lung."

Chronic Chlamydia pneumoniae infection and bronchial asthma: is there a link? A Agarwal, Y Chander. Indian J Med Microbiol 2008 Oct-Dec;26(4):338-341. 60 adults with a clinical history of asthma and 100 healthy age and sex matched controls. "The IgG anti chlamydial antibody-positivity rate in the patients with bronchial asthma (80%) was significantly higher in all age groups than that in the healthy age and sex matched controls (59%). No significant association was observed for IgA and IgM anti chlamydial antibodies. C. pneumoniae species specific IgG antibody seroprevalence was also found to be significantly higher in all age groups in comparison to controls (61.66% vs 38%)."

Airflow limitation, asthma, and Chlamydia pneumoniae-specific heat shock protein 60. DL Hahn, RW Peeling. Ann Allergy Asthma Immunol 2008 Dec;101(6):614-618. 138 C pneumoniae-exposed primary care patients (86 adult asthmatic cases and 52 nonasthmatic controls), evaluated for seroreactivity against a C pneumoniae-specific hsp60 fragment and against the C trachomatis hsp60 molecule. "Twenty-seven percent of asthmatic patients were C pneumoniae hsp60 seropositive vs 8% of controls (P < .01). Controlling for age, sex, and smoking, C pneumoniae hsp60 seropositivity was associated with lower postbronchodilator forced expiratory volume in 1 second in asthmatic patients (P < .05). No comparable associations were present for C trachomatis hsp60."

Infectious Chlamydia pneumoniae is associated with elevated interleukin-8 and airway neutrophilia in children with refractory asthma. KK Patel, AG Vicencio, Z Du, K Tsirilakis, PS Salva, WC Webley. Pediatr Infect Dis J 2010 Dec;29(12):1093-1098. "Of 18 Bronx samples analyzed, 6 (33%) were PCR-positive for C. pneumoniae, 10 (56%) for C. trachomatis, and 8 (44%) for Mycoplasma 16s DNA. IL-8 from C. pneumoniae-positive samples was 3.3-fold higher compared with negative samples (P = 0.003). There was no difference between patients tested for C. trachomatis or Mycoplasma. Of 84 Massachusetts samples analyzed, 42 (50%) were PCR-positive for C. pneumoniae, 42 (50%) for C. trachomatis, and 13 (16%) for Mycoplasma. IL-8 concentration from C. pneumoniae-positive samples was 10.49-fold higher compared with negative samples (P = 0.0001). As in the Bronx cohort, there were no differences between patients tested for C. trachomatis or Mycoplasma. Lastly, BAL neutrophilia predicted the presence of C. pneumoniae but not Mycoplasma or C. trachomatis."

Steroid resistance

Latent adenoviral infection modifies the steroid response in allergic lung inflmmation. K Yamada, WM Elliott, S Hayashi, R Brattsand, C Roberts, TZ Vitalis, JC Hogg. J Allergy Clin Immunol 2000 Nov;106(5):844-851. Guinea pigs with latent adenoviral (n = 12) or sham (n = 12) infections. "Latent adenoviral infection increased CD8+ cells in the airway wall and CD8+ cells, macrophages, B cells, and CD4+ cells in the lung parenchyma. Ovalbumin challenge, on the other hand, increased eosinophils, macrophages, B cells, and CD4+ cells in both the airway wall and lung parenchyma independent of the effect of latent adenoviral infection. In the sham-infected groups steroid treatment caused the expected reduction in the eosinophilic infiltrate induced by OA challenge in the airways without affecting the other cells. In the presence of both latent adenoviral infection and OA challenge, steroid treatment had no effect on allergen-induced eosinophilia but reduced CD8+ cells in the airways and CD8+ cells, CD4+ cells, and B cells in the parenchyma."

Interactions between allergic inflammation and respiratory viral inflammations. PC Avila. J Allergy Clin Immunol 2000 Nov;106(5):829-831. Editorial re Yamada.

Molecular mechanisms of decreased steroid responsiveness induced by latent adenoviral infection in allergic lung inflammation. K Yamada, WM Elliott, R Brattsand, A Valeur, JC Hogg, S Hayashi. J Allergy Clin Immunol 2002 Jan;109(1):35-42. In this guinea pig study, latent adenovirus infection inhibited the anti-inflammatory effects of glucocorticoids.

Pertussis (whooping cough) causes persistent cough in children and adults

Anti-smoker studies never take this infection into consideration. The official incidence figures are up to 80 times too low, so this is an important source of confounding.

Bordetella pertussis, Bordetella parapertussis, Mycoplasma pneumoniae, Chlamydia pneumoniae and persistent cough in children. HO Hallander, J Gnarpe, H Gnarpe, P Olin. Scand J Infect Dis 1999;31(3):281-286. "The most common single agent was B. pertussis, representing 56%(64/115), with a median cough period of 51 d, followed by M. pneumoniae 26%(30/115), 23 d, C. pneumoniae 17% (19/115), 26 d, and B. parapertussis 2% (2/115). For co-infections, the median duration of cough was about 60 d. Spasmodic cough for 21 d or more (clinical WHO criteria for pertussis) was present in 82% (41/50) of infections with B. pertussis as single agent, 38% (17/45) with B. parapertussis, 38% (5/13) with C. pneumoniae, 26% (5/19) with M. pneumoniae and 30%(17/56) in cases where no aetiology was found. In children with cough for more than 100 d (n = 78) using all vaccine arms, B. pertussis was responsible in 83% (65/78), in 21%(16/78) together with other agents."

Molecular aspects of Bordetella pertussis pathogenesis. C Locht. Int Microbiol 1999 Sep;2(3):137-144. Review.

Bordetella pertussis and chronic cough in adults. NH Birkeback, M Kristiansen, T Seefeldt, J Degn, A Moller, I Heron, PL Andersen, JK Moller, L Ostergard. Clin Infect Dis 1999 Nov;29(5):1239-1242. 201 patients who had a cough for 2-12 weeks and no pulmonary disease. "Four patients were B. pertussis culture-positive; 11 (including the culture-positive patients) were B. pertussis PCR-positive; and 33, including 10 of the 11 PCR-positive patients, had serological evidence of recent B. pertussis infection."

Serological evidence of pertussis in patients presenting with cough at a general practice in Birmingham. E Miller, DM Fleming, LA Ashworth, DA Mabbett, JE Vurdien, TS Elliott. Commun Dis Public Health 2000 Jun;3(2):132-134. "Fifty-eight cases of pertussis in this population and time period was equivalent to an annual incidence of 330 per 100,000, whereas statutory notifications of pertussis in England and Wales suggest an incidence of less than 4 per 100,000 in the same period."

Frequency of serologic evidence of Bordetella infections and mixed infections with other respiratory pathogens in university students with cough illnesses. LA Jackson, JD Cherry, SP Wang, JT Grayston. Clin Infect Dis 2000 Jul;31(1):3-6. "Our findings indicate that bordetella infections are common in young adults with cough illnesses (incidence, 9%), and a surprising number of these are mixed infections with other respiratory pathogens."

Costs of illness due to Bordetella pertussis in families. LH Lee, ME Pichichero. Arch Fam Med 2000 Nov-Dec;9(10):989-996. Sixty-nine families (87 individuals). "A family member required an average of 1.6 visits before (range, 0-7 visits) and after (range, 0-9 visits) pertussis was diagnosed; children younger than 1 year needed 2.5 and 2 visits, respectively. Symptomatic improvement occurred after a mean of 31 days (range, 4-134 days) after pertussis diagnosis and full recovery after a mean of 66 days (range, 5-383 days). Adults experienced the longest recovery time (median, 93 days) compared with other age groups. The average medical costs for an infant, child, adolescent, and adult were $2822, $308, $254, and $181, respectively. Parents lost an average of 6 workdays (range, 1-35 days) to care for an ill child; for these parents, costs associated with work loss averaged $767 per family. An average of 1.7 and 0.7 lost workdays accrued to bring an ill child to a physician's office and the emergency department, respectively. A majority (58%) of parents working while family members were ill with pertussis reported decreased work productivity ranging from 25% to 99%. Work-related costs contributed more than 60% of the overall costs of pertussis." The average cost was $2115 per family.

Pertussis is a frequent cause of prolonged cough illness in adults and adolescents. LD Senzilet, SA Halperin, JS Spika, M Alagaratnam, A Morris, B Smith. Clin Infect Dis 2001 Jun 15;32(12):1691-1697. 48/442 patients (19.9%) with prolongued cough illness had laboratory-confirmed or laboratory evidence of pertussis involvement.

Changes in genetic diversity of the Bordetella pertussis population in the United Kingdom between 1920 and 2006 reflect vaccination coverage and emergence of a single dominant clonal type. DJ Litt, SE Neal, NK Fry. J Clin Microbiol 2009 Mar;47(3):680-688. "genetic diversity of the bacterial population decreased during periods of high vaccine coverage. However, it was elevated between 1977 and 1986, when vaccine coverage in the United Kingdom was low and epidemics occurred. A high proportion of MLVA types during this epidemic period were novel, and the prnA(2) and prnA(3) alleles were seen for the first time in the United Kingdom. MLVA-27 appeared in 1982, was codominant during the 1998-to-2001 period, and comprised approximately 70% of isolates during both the 2002-to-2004 and the 2005-to-2006 periods."

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cast 01-11-11