In a Cross Sectional Study Conducted by Ahmad I. Et Al. in North India, It Was Shown That

In a Cross Sectional Study Conducted by Ahmad I. Et Al. in North India, It Was Shown That

RAJIV GANDHI UNIVERSITY OF HEALTH SCIENCES
KARNATAKA, BANGALORE
ANNEXURE II
PROFORMA FOR REGISTRATION OF SUBJECTS FOR DISSERTATION
1 / NAME OF THE CANDIDATE & ADDRESS / DR. AJAY SANKAR
POSTGRADUATE STUDENT IN PAEDIATRICS
KARNATAKA INSTITUTE OF MEDICAL SCIENCES, HUBLI-580022
2 / NAME OF THE INSTITUTION / KARNATAKA INSTITUTE OF MEDICAL SCIENCES, HUBLI-580022
3 / COURSE OF STUDY AND SUBJECT / MD IN PAEDIATRICS
4 / DATE OF ADMISSION TO THE COURSE / 31ST MAY 2011
5 / TITLE OF TOPIC / IMPACT OF ANTI TUBERCULAR THERAPY ON SERUM ZINC AND ALBUMIN LEVELS IN CHILDREN IN DIFFERENT FORMS OF TUBERCULOSIS IN THE AGE GROUP OF 0-12 YEARS.
6 / BRIEF RESUME OF INTENDED WORK:
6.2 Need for study:
Tuberculosis (TB) continues to be one of the most devastating and widespread infections in the world. Of the 9 million annual TB cases, about 1 million (11%) occur in children (under 15 years of age). Of these childhood cases, 75% occur annually in 22 high burden countries (India tops the list) that together account for 80% of the world’s estimated incident cases.1
Micronutrient deficiencies are probably the most frequent cause of secondary immunodeficiency and infection. Zinc deficiency is known to cause impaired cell mediated immunity (CMI) and compromise neutrophil functions. Since zinc primarily affects CMI, hypozincemia could possibly enhance susceptibility to TB.2
Zinc and albumin are negative markers of acute inflammation. Tuberculosis can induce production of cytokines such as interlukin-6 and tumor necrosis factor- alpha, which may induce fever, hepatic synthesis of acute phase reactant proteins, inhibit the production of serum albumin and cause dramatic shift in the plasma concentration of certain micronutrients.3,4
Zinc is an important micro nutrient, which is involved in many activities, such as metabolic functions, wound healing and immunity.5 A few studies have shown that the serum levels of zinc at the time of diagnosis of active tuberculosis are low.2-7 It has also been observed in many of these studies that the levels of zinc had improved once the patients were started on anti tubercular therapy(ATT).2,7 In one study it was noted that the mean serum zinc level in children with active pulmonary tuberculosis(PTB) was not significantly lower than healthy controls and, did not rise above the initial level, even after the four months of ATT.8
Many studies in adults have reported that, low concentration of serum albumin, at the time of diagnosis of active tuberculosis(TB).3,9-12 Among these some studies have shown improvements in serum albumin after starting ATT.9-11 Low levels of serum albumin were associated with extra pulmonary organ involvement in patients with pulmonary TB.12
Most of the studies on serum zinc and albumin levels were conducted in adults and there are not many Indian studies. Variation in the concentration of essential trace elements was reported in several pathological conditions, their levels in sera of TB patients with or without HIV co-infection and their changes in concentration after therapy is not yet well documented.
Hence this study has been undertaken to determine the impact of ATT on serum zinc and albumin levels in children with different forms of tuberculosis with or without HIV co-infection in the age group of 0-12 years.
6.2. Review of Literature
  1. In a study conducted by Ray M. et al. in Chandigarh, to assess the plasma zinc status in children with tuberculosis and to correlate it with nutritional status, activity and severity of disease in relation to anti tubercular therapy, it was shown that, children with tuberculosis (n=50) had significantly lower plasma zinc level than those without tuberculosis, irrespective of their nutritional status (P < 0.001). There was a significant rise in zinc level at the end of 6 month of ATT (p<0.001), and was concluded that plasma zinc status might prove to be a good objective marker for monitoring the severity of the disease and the response to therapy.2
  2. In a cross sectional study conducted by Ahmad I. et al. in North India, it was shown that the micronutrient status of the adult patients with active pulmonary TB (n=43) was poor compared with healthy subjects. Serum concentrations of zinc were low and were more pronounced in malnourished TB patients. (52.5±19.5µg/dl compared to 85±22.8µg/dl in controls). It was also noted that TB patients had significantly lower levels of serum albumin (2.5±1.2g/dl) than healthy controls (4.0±0.5µg/dl).3
  3. A cross sectional study conducted by Ramakrishnan K. et al. in Madurai on serum zinc and albumin levels in adult pulmonary tuberculosis patients with (n=20) and without HIV(n=20), showed that , the mean level of zinc and albumin were 117.13 ± 4.2 µg/dl and 4.1 ±0.6 g/dl; 53.9 ±8 µg/dl and 2.9 ± 0.4 g/dl; 65.5 ±9.8 µg/dl and 2.9 ±0.4 g/dl among controls(n=20), HIV positive and HIV negative patients with pulmonary tuberculosis (PTB). The parameters were significantly low in active PTB patients irrespective of HIV status, but more so in HIV-positive individuals. These changes may be attributable to nutritional factors, enteropathy and acute phase reactant proteins.5
  4. A study conducted by Mohan G. et al. in adults in Agra, India, has shown that, the average plasma concentration of zinc in healthy volunteers was 96±18µg/dl. In TB patient (n=60), serum zinc levels were 64.14±3.97 µg/dl and 74.31±3.60 µg/dl before and after 4 week of ATT respectively. The serum levels of zinc were significantly lower in patients with TB and had improved with ATT.7
  5. A study conducted in Tehran by Bolooraz MR. et al. that compared plasma zinc levels in 15 children with active pulmonary tuberculosis, 15 malnourished and 15 healthy children, showed that the mean plasma zinc concentration in children with tuberculosis (71.7µg/dl) were not significantly different than the other two groups(72.5 and 76.9 µg/dl). The zinc status of the children with tuberculosis was evaluated after 2 months and 4 months of DOTS therapy. The serum zinc level decreased after 1 month and then recovered to the initial level after 4 months of treatment.8
  6. A study conducted Adedapo KS. et al. in adults in Nigeria has shown that the levels of alpha 2 macroglobulin and albumin were significantly raised in PTB patients on treatment compared with newly diagnosed PTB patients (p=0.05, p=0.01 respectively). The levels of α-2-macroglobulin and albumin were significantly raised in PTB patients on treatment compared with newly diagnosed PTB patients (p=0.05, p=0.01 respectively). The combination of reduced levels of albumin and α-2-macroglobulin may be used to differentiate newly diagnosed PTB and those on chemotherapy.9
  7. A prospective study done by Visser ME. et al. in adults in South Africa has shown that median serum albumin in newly diagnosed TB patients(n=20) before Isoniazid(INH) treatment was initiated was low (median 30.5g/l). After seven days of INH treatment, albumin concentration increased significantly (median 32g/l, p< 0.001.)10
  8. A study conducted by Adebisi SA. et al. in Nigeria in adults with PTB(n=45) has shown that, pre treatment mean serum albumin level was 26.7g/l, while the mean serum albumin of the same patients after completion of six month of treatment rose to 39.97 g/l. There was significant improvement in the serum levels of albumin after six month of treatment.11

6.3 Objectives of study:
Primary Objective: To determine the impact of ATT on serum zinc and albumin levels in different forms of tuberculosis with or without HIV co-infection in the age group 0-12 years.
Secondary Objective: To determine the significance of zinc and albumin as a marker of severity of disease.
7 / MATERIALS AND METHODS:
7.1 Source of data:
Children in the age group 0-12 years who have been diagnosed with any form of TB with or without HIV co-infection from the Out Patient/Inpatient department at Department of Paediatrics, K.I.M.S, Hubli.
7.2 Type of the study:
Prospective hospital based study.
Inclusion Criteria :
Cases are children between the age 0-12 years, who are newly diagnosed tuberculosis with or without HIV co-infection. Controls are healthy children matched for age with no history of TB or any overt illness who are attending OPD. Informed consent will be obtained from the parents before enrolment.
Exclusion Criteria:
  1. Children who have received zinc supplementation in the previous month.
  2. Children who had underwent surgery previous month.
  3. Children with moderate and severe injuries.
  4. Children with acute or chronic, liver, renal, or cardiac diseases.
  5. Children who are on corticostreroids.
  6. Children with neoplasm.
7.3 Methods of collection of data:
The study will be a prospective hospital based study at Department of Paediatrics, K.I.M.S, Hubli.
Study period will be from 1/12/2011 to 30/11/2012
Sample Size:
Since ours is a time bound study, we will enroll all children who fulfill the inclusion/ exclusion criteria during this period.
Diagnosis and Treatment:
Diagnosis of TB will be confirmed as per Revised National Tuberculosis Control Programme (RNTCP) guidelines. The cases will be put on Directly Observed Treatment Short Course Chemotherapy (DOTS) as per RNTCP guidelines.13
Sample collection and Analysis:
For cases, serial estimation of serum zinc and albumin levels will be done at the time of enrolment, and at the end of two months and at the end of six months of ATT. For controls, estimation of serum zinc and albumin will be done at the time of enrolment.
Procedure:
Two samples of whole blood will be collected in two separate vacutainers, one for zinc estimation and one for albumin estimation, which will then be centrifuged at 3000 rpm. The sera will be separated and then analyzed. The estimation of serum zinc and albumin will be done by calorimetric method at Department of Biochemistry, K.I.M.S, Hubli.
7.4 Does the study require any investigation to be conducted on patients or animals specify.
Yes
Serum Zinc and Albumin levels will be done for cases and controls.
A complete haemogram, Chest X ray, Mantoux test and other appropriate investigations will be done for controls.
7.5 Has the ethical clearance been obtained from ethical committee of your Institution in case of 7.4?
Yes
7.6 Statistical Analysis
Results will be analyzed by using appropriate statistical methodologies.
LIST OF REFERENCES
  1. Guidance for national tuberculosis programmes on the management of tuberculosis in children. WHO/HTM/TB/2006.371.[Cited 2010 Aug 3]. Available from: URL:
  2. Ray M, Kumar L, Prasad B. Plasma zinc status in Indian childhood tuberculosis: Impact of antituberculosis therapy. Int J Tuberc Lung Dis. 1998; 2: 719-725.
  3. Ahmad I, Srivastava V, Prasad R, Yusuf M, Safia, Saleem M, et al. Deficiency of Micronutrient Status in Pulmonary Tuberculosis Patients in North India. Biomedical Research. 2011; 22: 449-454.
  4. Beisel WR. Metabolic responses of the host to infection. In:Textbook of Pediatric Diseases (Feign.R.D and Cherry.J.D., eds). Saunders, Philadelphia,PA.1998; PP. 54-69. WB.
  5. Ramakrishnan K, Shenbagarathai R, Kavitha K, Uma A, Balasubramaniam R, Thirumalaikolundusubramanian P. Serum zinc and albumin levels in pulmonary tuberculosis patients with and without HIV. Jpn J Infect Dis. 2008; 61: 202-204.
  6. Kassu A, Yabutani T, Mahmud ZH, Mohammad A, Nguyen N, Huong BTM, et al. Alterations in serum levels of trace elements in tuberculosis and HIV infections. European Journal of Clinical Nutrition. 2005; 60: 580-586.
  7. Mohan G, Kulshreshtha S, Dayal R, Singh M, Sharma P. Effect of Therapy on Serum Zinc and Copper in Primary Complex of Children. Biol Trace Elem Res. 2007; 118: 184-190.
  8. Bolooraz MR, Khalizade S, Milanifer AR, Milanifar AR, Safavi A, Velagati AA. Impact of anti-tuberculosis therapy on plasma zinc status in childhood tuberculosis. East Mediterr Health J. 2007; 13: 1078-1084.
  9. Adedapo K S, Arinola OG, Ige OM, Adedapo ADA, Salimonu LS. Combination of Reduced Levels of Serum Albumin and Αlpha-2-Macroglobulin Differentiates Newly Diagnosed Pulmonary Tuberculosis Patients from Patients on Chemotherapy. African Journal of Biomedical Research. 2006; 9:169-172
  10. Visser ME, Texeira-Swiegelaar C, Maartens G. The short-term effects of anti-tuberculosis therapy on plasma pyridoxine levels in patients with pulmonary tuberculosis. Int J Tuberc Lung Dis. 2004; 8: 260-262.
  11. Adebisi SA, Oluboyo PO, Oladipo OO. The usefulness of serum albumin and urinary creatinine as biochemical indices for monitoring the nutritional status of Nigerians with pulmonary tuberculosis. Niger Postgrad Med J. 2003;10: 247-250.
  12. Kim MJ, Kim H-R, Hwang SS, Kim YW, Han SK, Shim Y-S, et al. Prevalence and Its Predictors of Extrapulmonary Involvement in Patients with Pulmonary Tuberculosis. J Korean Med Sci. 2009; 24: 237-241
  13. Chauhan LS, Arora VK. “Management of pediatric tuberculosis under Revised National Tuberculosis Control Programme”. The Indian J pediatr. 2004; 71: 341-343.

8
9 / SIGNATURE OF CANDIDATE
10 / REMARKS OF THE GUIDE / It is possible to do this project work at KIMS, Hubli.
11 / NAME & DESIGNATION
11.1 GUIDE / DR. VINOD. H. RATAGERI
ASSOCIATE PROFESSOR
DEPARTMENT OF PAEDIATRICS
K.I.M.S, HUBLI
11.2 SIGNATURE
11.3 CO-GUIDE
11.4 SIGNATURE
11.5 HEAD OF THE DEPARTMENT / DR.T.A.SHEPUR
PROFESSOR & HEAD, DEPARTMENT OF PEDIATRICS, KIMS, HUBLI.
11.6 SIGNATURE
12 / 12.1 REMARKS OF CHAIRMAN AND PRINCIPAL
12.2 SIGNATURE
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