Study On Risk Factors Of Tuberculosis Outbreak Among Adolescent Students In Guangdong Area And Intervention Measures

Background and ObjectiveIt is estimated that one third of the world's population(2 billion)is infected with Mycobacterium tuberculosis(MTB),and more than 500 million infected individuals in China,of which 5%?10%will eventually progress to active TB.Students are more susceptible to tuberculosis,accounting for 4.03%of the total number of reported cases,and school populations are particularly vulnerable to epidemic outbreaks of tuberculosis.From December 2014 to June 2015,successive pulmonary tuberculosis outbreaks were reported in three different vocational schools in Guangdong,South China.There are few published reports concerning the incidence of pulmonary tuberculosis among students,and the reports that do exist have mainly focus on disease outbreaks in primary schools,middle schools,and colleges.Few epidemiological studies have focused on an outbreak of pulmonary tuberculosis in a vocational school setting.As a neuroendocrine and immunomodulatory hormone,Vitamin D has been reported in the latest research,among which 1,25(OH)2D3 was found to bind to vitamin D receptor(VDR),further activate VDR signaling,and induce a series of antimicrobial responses such as induction of autophagy,phagolysosomal fusion,release and activation of the antimicrobial peptide cathelicidin,and killing of intracellular Mycobacterium tuberculosis.Many studies have been conducted to verify whether Vitamin D was associated with tuberculosis,however,the results were mixed.Up to this day,there is no study on the relationship between vitamin D deficiency and tuberculosis in Guangdong area,and still no documents on the dynamic changes of plasma IL-37 concentration and cytokines expression for 24 weeks in TB patients after vitamin D intervention.Screening and treatment of latent tuberculosis infection(LTBI)would be one of the necessary tools for global TB control on the basis of the development and outcome of MTB infection.At present,the acceptance rate of preventive treatment(PT)against LTBI is low and the rate of abandonment is high in China,and only a small amount of data on PT tolerance,effectiveness,safety and acceptability under conditions of routine care was reported.In order to propose an effective strategy to prevent tuberculosis outbreaks among adolescent students,we investigate the epidemic of tuberculosis among three vocational schools in Guangdong area,analyze the risk factors of adolescent students in tuberculosis outbreak,investigate the correlation between the level of vitamin D and pulmonary tuberculosis,explore the effects of vitamin D treatment on patients with pulmonary tuberculosis,compare the difference between latent tuberculosis infection patients who received prophylactic treatment and those who did not,and analyze the influencing factors of giving up treatment in adolescent students.MethodsRetrospective epidemiological survey of three consecutive pulmonary tuberculosis outbreaks occurred in three vocational schools of Guangdong area from December 2014 to June 2015 was conducted.In-person interviews with the index case-students were conducted to collect information on the disease onset.Contacts were screened for clinical symptoms,and received a PPD skin test and chest X-ray examination.Those who developed a reactive PPD induration diameter? 15 mm,or displayed papules,blisters,and a normal chest X-ray image were asked to provide 3 sputum specimens(night sputum,morning sputum,and instant sputum)which were microscopically examined and cultured for acid-fast Bacillus.If necessary,a chest CT examination was given to identify new tuberculosis cases in the three vocational schools.Questionnaires were used to analyze the risk factors for tuberculosis among adolescent students during the outbreaks.The plasma 25-hydroxy vitamin D level was detected by electrochemiluminescence to analyze the correlation between decreasing vitamin D level and pulmonary tuberculosis.Oral vitamin D combined with TB drugs were administered in patients with pulmonary tuberculosis,followed up for 6 months,compared with those who did not receive vitamin D,to observe the clinical indicators and immune function of patients with pulmonary tuberculosis,analyzing the therapeutic effect of vitamin D on tuberculosis.PPD test was applied to define latent tuberculosis infection,and patients with high-risk latent infection with a reactive PPD induration diameter? 15 mm,or with papules,blisters,were divided into treatment group and control group according to the principle of voluntary.The treatment group was given isoniazid combined with rifampicin for preventive treatment for 3 months and followed up for a period of 2 years so as to compare the difference between these two groups.Logistic regression analysis of the factors related to those students who gave up treatment was conducted to screen out the influencing factors.Results8100 staff and students were screened in three vocational schools,41 cases of active pulmonary tuberculosis were found.Among them,28 cases of pulmonary tuberculosis were found in school A,which were defined as pulmonary tuberculosis outbreak;8 cases of pulmonary tuberculosis were found in school B,which were defined as sporadic pulmonary tuberculosis;and 5 cases of pulmonary tuberculosis were found in school C,which were defined as pulmonary tuberculosis outbreak.Of the 41 cases,37 were type ?,1 was type ?,and 3 were type ? combined with type ?.There were no type ? and type ? cases.The survey found that there were five major risk factors for pulmonary tuberculosis among students during the outbreak of pulmonary tuberculosis in vocational schools,namely,close contact with patients with active pulmonary tuberculosis,students from rural areas,often staying up to-late all night,low body mass index and too little monthly living expenses.Further investigation found that two factors might account this finding:(1)vocational schools in China have a tuition-free enrollment system,the majority of students come from rural areas in which the economic conditions and living standards of the families are relatively low;(2)the entrance requirements for vocational schools are often relatively low,which may be associated with the relatively low academic performance of their students,and peer influence is vulnerable to the bad habit.Vitamin D test results showed that the vitamin D levels in patients with active pulmonary tuberculosis were significantly lower than the healthy persons with close contact,especially those of sputum positive or cavities shown on chest images had much lower vitamin D levels.Univariate and multivariate logistic regression analysis showed that vitamin D deficiency and rural origins were the risk factors of pulmonary tuberculosis.Female and the age-increasing were the risk factors for vitamin D deficiency.Compared to the group without vitamin D,the group with combination of TB drugs and vitamin D for TB patients showed that there was no change in sputum-negative conversion rate or total effective rate of chest radiographs,but it could improve clinical symptoms and increase body weight,and the lesions in the lungs were more stable.Further observations about the changes of cytokines found that the concentrations of IL-37,IFN-?,TNF-? and IL-6 decreased in both groups after treatment,while the concentrations of IL-4 and IL-10 increased at first and then decreased,and the changes in Vitamin D group were more significant(P<0.05),which maybe resulted from regulating the expression of pro-inflammatory cytokines IFN-?,TNF-?,IL-6 and anti-inflammatory cytokines IL-4 and IL-10 through IL-37,indicating all of them participate in the regulation of inflammatory reaction of pulmonary tuberculosis.348 cases of high-risk latent infections were divided into treatment group with 151 cases and control group with 197 cases.The results showed that the average annual incidence of the treatment group was 0.66%,while it was 4.57%in the control group(?2=8.243,P=0.004),the protection rate of preventive treatment of tuberculosis was 85.6%.With a 43.0%treatment completion rate,the incidence of adverse reactions was 9.9%,of which 1.3%was hepatotoxicity.And there are 283 patients who had gave up treatment.Univariate and multivariate Logistic regression analysis about those who gave up treatment showed that the influencing factors were TB discrimination,non-tuberculosis physicians'different opinions to tuberculosis treatment,worrying about adverse drug reactions and parents with low educational levels.ConclusionsChina is one of the countries with a high burden of tuberculosis in the world.Tuberculosis among adolescent students has an important impact on the incidence of tuberculosis the whole population,and creating an effective outbreak strategy has become an urgent task.Close contact with persons who have active pulmonary tuberculosis,students from rural areas,often staying up to-late night,low living expenses per month and low body mass index are risk factors for the incidence of tuberculosis in vocational schools,and targeted these risk factors would reduce the incidence of tuberculosis among students.The vitamin D levels in active pulmonary TB patients in Guangzhou area are insufficient,which was correlated to the incidence of tuberculosis,exogenous supplementation of vitamin D is likely to reduce the incidence of tuberculosis.Although there was no change in sputum-negative conversion rate or total effective rate of chest radiographs in TB patients after oral vitamin D,the clinical symptoms of these patients improved and body weight increased,and the pulmonary lesions became more stable,so that vitamin D could be used as adjuvant treatment of TB.Prophylactic treatment of latent infection patients during the outbreak of tuberculosis can effectively reduce the incidence of pulmonary tuberculosis,the incidence of side effects of prophylactic treatment is low,generally reversible.Overcoming the psychological barrier is the key factor to improve treatment compliance.Targeted prevention and control strategies can reduce the incidence of tuberculosis in adolescent students in Guangdong area.