TUBERCULOSIS IN PREGNANCY

TB is a dangerous disease in pregnancy, this presentation discusses diagnosis and treatment of this dreaded disease

1. PROF.NARENDRA MALHOTRA M.D., F.I.C.O.G., F.I.C.M.C.H, F.R.C.O.G.,F.I.C.S. Prof. Dubrovnick International University V.P. WAPM(world association of prenatal medicinne ) President ISAR Presiddent Elect ISPAT Sec Gen SAFOG Member FIGO guidelines committee President FOGSI (2008-2009) Dean I.C.M.U. (2008) Director Ian Donald School of Ultrasound National Tech. Advisor for FOGSI-G.O.I.—Mc Arthur Foundation EOC Course Managing Director GLOBAL RAINBOW HEALTH CARE Director ART-RAINBOW –IVF Practicing Obstetrician Gynecologist at Agra. Special Interest in High Risk Obs., Ultrasound, Laparoscopy and Infertility, ART & Genetics Member and Fellow of many Indian and international organisations Awarded best paper and best poster at FOGSI : 5 times, Ethicon fellowship, AOFOG young gyn. award, Corion award, Man of the year award, Best Citizens of India award Over 50 published and 200 presented papers Over 100 guest lectures given in India & Abroad and 24 ORATIONS Organised many workshops, training programmes , travel seminars and conferences Editor 18 books, many chapters, on editorial board of many journals Editor of series of STEP by STEP books Revising editor for Jeatcoate’s Textbook of Gynaecology 7 th and 8 th edition (2015) Very active Sports man, Rotarian and Social worker MALHOTRA NURSING & MATERNITY HOME PVT. LTD. GLOBAL RAINBOW HEALTH CARE,AGRA 84, M.G. Road, Agra-282 010 Phone : (O) 0562-2260275/2260276/2260277, (R) 0562-2260279, (M) 98370-33335; Fax : [phone] www.malhotrahospitals.com,www.rainbow hospitals.org

2. TB and PREGNANCY Narendra Malhotra Jaideep Malhotra Global Rainbow Health Care,India www.rianbowhospitals.org Prerna K eshan,MB B ellad,Parag Biniwala

3. Charlotte Brontë (1816-1855 ) novelist who died at 38 TB in PREGNNACY

4. INTRODUCTION Tuberculosis (TB) and pregnancy are two different types of stresses experienced by women. Their simultaneous presence affects them both physically and mentally. To the concerned physicians, genital tuberculosis presents a diagnostic challenge and management of the underlying disease in a pregnant woman requires great care. Managementof such cases in the context of the Revised National Tuberculosis Programme and the adoption of the Directly Observed Treatment-Short Course (DOTS) needs a strategy.

5. Incidence of TB in pregnancy In 2012 the estimated Global annual incidence of 8.6 million Not many studies have been done in this field. In one study done in some ethnic groups in London it was found to be 1 %. Tuberculosis cases 2.3 million were estimated to have occurred in India .( India accounts for 30% of the burden of all TB cases in the world .) 80% of the patients are in the economically productive age-group of 15– 54 years. In Belgaum District of Karnataka during 2014 till October, 8 out of 3624 Tuberculosis patients a diagnosed are pregnant women . Similar figures from UP/BIHAR/JHARKAND(may be more) In India Tuberculosis is a notifiable Disease

6. Introduction Tuberculosis continues to be a major health issue in a country like India with a large population. Management of Tuberculosis in pregnancy continues to be one of the challenges even to the experienced persons as pregnancy adds many challenges for effective diagnosis and treatment because of the altered situations . One third of the world population and approximately 50% of the Indian adults are infected with Mycobacterium Tuberculosis . In India two deaths occur every three minutes due to Tuberculosis - almost 1000 deaths/day The disease is responsible for killing more women of reproductive age than all the combined causes of maternal mortality

7. TB is a major cause of mortality in pregnancy • Johannesburg: 51% of deaths in HIV positive pregnant women were attributable to TB. •TB was the third leading infectious cause of maternal deaths in Durban at 14.0% and Lusaka at 25% Botswana Grange et al. Tuberculosis in association with HIV/AIDS emerges as a major non-obstetric cause of maternal mortality in Sub-Saharan Africa . IntJ GynaecolObstet . 2010;108:181-183. Black et al. Effect of HIV treatment on maternal mortality at a tertiary center in South Africa: a 5-year audit. ObstetGynecol ,. 2009; 114:292-299, Khan et al. Maternal mortality associated with tuberculosis-HIV-1 co-infection in Durban, South Africa. AIDS. 2001:14:1857-1863

8. Who is at risk of TB? Anyone can catch TB, but it is possible that pregnant women have a slightly higher risk of TB. Some people are more at risk than others. These include people who: • Have lived in the same household – or been in prolonged contact – with someone with TB involving the lung/s • Have lived, worked or stayed for a long time in a country with a high rate of TB • Are unable to fight off infection (immunosuppressed) due to illness (such as HIV infection) or treatment (such as therapy for cancer) • Are notably underweight • Are dependent on drugs and alcohol

9. What are the symptoms of TB during pregnancy? The symptoms of tuberculosis in pregnant women can be non-specific. Those that may suggest active TB disease and require further assessment are: • Cough which persists for more than a few weeks • Persistent fever (a high temperature) • Heavy sweating at night • Loss of appetite • Unexplained weight loss • General & unusual sense of tiredness and feeling unwell • Coughing up blood • Persistent swellings in the neck glands (or sometimes other glands)

10. How might TB affect the mother and her baby? • Low birth weight • Prematurity • Congenital TB • Increased neonatal and maternal mortality • Increased pregnancy complications • Abortion • Post partum haemorrhage • Pre- eclampsia

11. Consequences of TB in pregnancy Pregnant women with pulmonary TB who access early appropriate TB treatment do not have an increase in maternal or neonatal complications Therefore it is important to: Prevent TB in pregnancy Diagnose and treat TB in pregnancy

12. Mother & new born A neonate having congenital TB may present with respiratory distress, fever, poor feeding, lethargy, irritability, abdominal distention, lymphadenopathy and hepato -splenomegaly A fetus can get TB infection either by haematogenous spread through umbilical vein to fetal liver or by ingestion or aspiration of infected amniotic fluid. True congenital TB is believed to be rare. The risk to neonate of getting TB infection shortly after the birth is greater

13. Can the mother infect the baby with tuberculosis? A mother can infect her newborn baby if she is infectious; usually this is only the case if she has a cough and is not on treatment . It is very rare for the baby to be born with active TB if their mother has TB. Breastfeeding is encouraged and TB drugs don’t harm the neonate.

14. Diagnosis of TB in pregnancy

15. Suspect Pregnant Woman with cough of ≥2 weeks duration with or without other symptoms . Cough of any duration: If she is a contact of a sputum smear positive case in the family. If she is having haemoptysis. If she is a suspected or confirmed extra pulmonary Tuberculosis case. If she is also infected with HIV. MBB

16. Diagnosis Two samples of sputum (one spot and one in the early morning) are to be collected and examined for Acid Fast Bacilli (AFB) with Zeil-Neelson (ZN) stain Follow RNTCP* diagnostic algorithm mentioned in the next slide Precaution: To cover the abdomen of the pregnant woman with lead apron while taking chest X-ray (if required) *Revised National TB Control Program MBB

17. MBB If cough persists after 10-14 days If one or both + ve Sputum smear + ve TB start ATT X-ray suggestive of active TB Smear – ve TB start ATT If both samples – ve , treat with antibiotics for 10-14 days 2 more samples If One or Both + ve   Refer For chest X-ray X- Ray negative No TB, refer for evaluation Two Sputum Samples If both - ve  

18. Diagnosis dilema Under RNTCP, sputum examination done as per an algorithim is the preferred method for diagnosis of pulmonary TB A chest skiagram (performed after shielding the abdomen) is done if all the 3 sputum smears are negative and symptoms persist despite giving antibiotics for 1-2 weeks. The presence of suggestive radiographic abnormalities and a medical officer’s decision to treat with ATT labels the patient as a ‘smear-negative’ TB case. A pregnant woman with extra-pulmonary TB has constitutional and organ-affection symptoms. Routine haematology and Mantoux test ( not commonly advocated in programme ) along with investigations specific for the site are carried out for the establishment of specific diagnosis. Co-existence of HIV infection should specially lead to a thorough search for any extra-pulmonary tuberculous focus. A mediastinal or retro-peritoneal adenopathy , pleural effusion or parenchymal infiltrate may be detectedin chest skiagram in late course of disease, whereas cavitary lesions could exist in early HIV co-infection.

19. <5 >100 PCR Culture HPE AFB Stain Bacterial Load Method >1000 The reason genital tuberculosis has such a poor prognosis is our reliance on methods having low sensitivity

20. Sensitivity Mantoux Test ? 50% Laparoscopy 50% AFB-Stain < 5% HPE < 10% Culture <30% PCR > 80%

21. Diagnosis Diagnosis of extra pulmonary Tuberculosis is done by histopathology or FNAC depending upon the site involved . Loss of weight or no weight gain corresponding to the gestational age also is a symptom for screening for Tuberculosis in pregnancy. MBB

22. management

23. Categorization TB Cases Tuberculosis patients are categorized as per RNTCP guidelines as category I (New cases) or category II (Retreatment cases) depending upon the history of previous Anti-tuberculosis treatment received. Pregnant women with Tuberculosis who are taking Anti-tuberculosis treatment for the first time or who have taken Anti-tuberculosis treatment for less than 1 month previously are categorized as new cases MBB

24. Guideline Treatment of tuberculosis in pregnant women and newborn infants

25. KET CRITICAL POINTS The decision to treat tuberculosis (TB) in pregnancy must consider the potential risks to mother and fetus from medication, and the benefits to mother, foetus and the community. The benefits of treating TB in pregnancy are widely considered to outweigh any risk of treatment.  Although small concentrations of anti-TB drugs are excreted in breast milk , treatment for TB is generally not considered a contra-indication to breastfeeding, and is not associated with toxicity to the baby.

26. First-line treatment This guideline endorses the recommendation of the use of standard first-line drug regimens in pregnant women with TB. Isoniazid, rifampicin, pyrazinamide and ethambutol are not contra-indicated in pregnancy, but treatment during pregnancy requires close clinical follow-up, with the monitoring of at least monthly liver function tests due to the higher risk of hepatotoxicity.

27. International guidelines The International Union Against Tuberculosis and Lung Disease ( www.theunion.org ) and the World Health Organization ( www.who.int ) support the use of standard first-line drug regimens in pregnant women with TB. The CDC ( www.cdc.gov ) does not specifically endorse the use of pyrazinamide in pregnancy, citing the absence of detailed teratogenicity data, but states that it can ‘probably be used safely’ during pregnancy. An alternative 9(E)HR regimen is endorsed by the CDC.

28. treatment ATT should be started promptly as untreated disease presents a hazard to the mother and foetus . The same regimens are recommended for use in pregnancy as for the non-pregnant state except for witholding of Streptomycin. Doubts about the use of Pyrazinamide in pregnancy have since been set as rest. Currently , an intermittent regimen (thrice weekly on alternate days) under the DOTS strategy of RNTCP is being increasingly used world-wide for the pregnant women having TB.

29. Case of tb in pregnancy Minimal streaky infiltrate RUL Sputum was smear positive - rare Regimen: Isoniazid, Rifampin, Ethambutol and B6 Pyrazinamide deleted due to pregnancy

30. Treatment of drug-sensitive TB during pregnancy • WHO and International Union against Tuberculosis and Lung Disease support the use of the standard regimen in pregnant women: –rifampicin , isoniazid for six months and ethambutol and pyrazinamide for the first two months (“ rifafour ”)

31. Isoniazid • Pyridoxine (vitamin B6) should be used during pregnancy • Safe in pregnancy : no excess of birth defects have been noted in the babies of pregnant mothers taking rifampicin •Safe in breastfeeding • Hepatitis : some studies suggest higher incidence of drug-induced hepatitis during pregnancy •Isoniazid is considered safe as preventative therapy in the form of IPT

32. Rifampicin • Cytochrome P450 induction can result in clearance of contraceptive hormones and unplanned pregnancy • Safe in pregnancy : no excess of birth defects have been noted in the babies of pregnant mothers taking rifampicin •Safe in breastfeeding

33. Ethambutol • Safe in pregnancy : no excess of birth defects have been noted in the babies of pregnant mothers taking rifampicin. •Safe in breastfeeding

34. Pyrazinamide • No studies of safety in pregnancy: –Extensive clinical experiencesupporting it’s safety –WHO recommends the routine use of PZA in pregnancy

35. Treatment C ategory I-Needs DOTS regimen (Directly Observed Treatment and short course) 2H 3 R 3 Z 3 E 3 / 4H 3 R 3 Where numbers 2 and 4 are the months of treatment and prefex 3 denotes the number of the doses in a week . H-INH (Isoniazid) R- Refampicin , Z- pyrazinamide, E- Ethambutol S- Streptomycin. MBB

36. Treatment For first two months (intensive phase) four antibiotic are given. They are ---- Rifampicin 450 mg INH 600 mg Pyrazinamide 1500 mg Ethambutal 1200 mg If the weight of the patient at the time of initiation of the treatment is 60 kg or more, or increases to 60 kg or more, during the course of the treatment an additional dose of Rifampicin of 150 mg is to be added. The Doses are given on three days in a week; (on Monday, Wednesday, Friday or Tuesday, Thursday, Saturday as the DOT* days .) *Directly O bserved Treatment MBB

37. Side/adverse effects of ATT drugs Rifampicin : Red/orange coloured urine and tears, nausea, vomiting, Jaundice INH : Burning in the hands and feet, nausea, vomiting, jaundice, pruritis ( Peripheral neuritis) Ethambutal : Retrobulbar neuritis may occur. Pyrazinamide : May produce G. I upset, arthralgia, Hypperuraecimia and hepatitis. Streptomycin : may cause vertigo, ototoxiaty and nephrotoxicity (Contraindicated in Pregnancy) Note:In all cases of jaundice anti Tuberculosis drugs should be stopped immediately and the patients should be referred for evaluation. MBB

38. Treatment The treatment is domiciliary based where, the doses are given at the DOT centre by a DOT provider who keeps the drug box reserved for the patient. The serious patients are admitted in the hospital till they are recovered and become fit to take treatment in the home . During the intensive Phase all the 3 doses in a week are directly observed by the DOT provider, Whereas in the continuation phase first dose of the weekly doses is directly observed and the remaining 2 doses are given to the patient for consumption in her house. MBB

39. Treatment- regimen for cat II patients 2H 3 R 3 Z 3 E 3 S 3 / 1 H 3 R 3 Z 3 E 3 / 5H 3 R 3 E 3 : Category II patients (retreatment cases who have taken Anti-tuberculosis treatment earlier for at least 1 month) the pregnant woman with tuberculosis is treated with the same regimen of RNTCP as for the non-pregnant woman with Tuberculosis, ( except that Injection streptomycin is withheld till the woman delivers) The intensive phase treatment is of 3 months duration and the continuation phase is of 5 months. In the intensive phase of 3 months streptomycin is given for the first two months only( non-pregnant). MBB

40. Please note The intensive phase of treatment in both cat I and cat II patients can be extended for one more month if the follow up sputum after intensive phase is positive for AFB . While treating Tuberculous meningitis (TBM), streptomycin is to be used in place of ethambutol after delivery in new cases during the intensive phase (H 3 R 3 Z 3 S 3 instead of H 3 R 3 Z 3 E 3 ). The continuation phase of treatment for patients with Tuberculosis meningitis or spinal Tuberculosis is for 7 months - total duration of treatment will be of 9 months. Steroids as adjunctive therapy may be useful in patients with Tuberculosis pericarditis and meningeal Tuberculosis , with an initial high dose tapered down gradually over 6 - 8 weeks. MBB

41. Also Note The patient is regularly followed up by the treating doctor In pulmonary - follow up sputum smear examinations are done regularly Extra Pulmonary - assessed by regular clinical examination . A woman under Anti Tuberculosis treatment can breast feed her infant taking the precaution of cough hygiene i.e she should cover her mouth and nose with a cloth while breast feeding. P ractitioners who undertake to treat a patient with tuberculosis must not only prescribe standard regimen but also have the means to assess adherence to regimen and address poor adherence in order to ensure that treatment is completed. MBB

42. TB,HIV and Pregnanacy HIV and Tuberculosis are inextricably linked. Their effect is even more deadly in pregnancy; when they may contribute significantly to maternal morbidity and mortality. Over 50% of maternal mortality occurring in mothers with Tuberculosis in pregnancy is due to co-infection with HIV The treatment is also complicated by the challenges of adherence, polypharmacy and overlapping side effects of anti-Tuberculosis and Anti-Retroviral Treatment (ART) drugs . Follow NACO guidelines 2013 (NATIONAL AIDS CONTROL ORGANISATION) MBB

43. TB,HIV and Pregnanacy Effavirenz is contraindicated before the 13 th week of gestational age While the risk of toxicity due to the use of didanozine and stavudine is significantly increased in pregnancy . Rifampicin may cause a reduction in the serum concentration of effavirenz . Neverepin which is alternative to the use of effavirenz also exhibits some drug interaction with rifampicin . Rifampicin may lead to the reduction of serum concentration of neverepin by as much as 50%. To circumvent this problem rifabutin another rifampicin that is as effective as rifampicin may be used. MBB

44. TB,HIV and Pregnanacy The pregnant women with Tuberculosis and HIV should receive Tuberculosis treatment as per RNTCP regimen along with ART ART should be initiated as soon as possible within 8 weeks of initiation of Tuberculosis treatment irrespective of their CD4 cell count. The drugs used in ART for pregnant women are Tenofovir (TDF), Lamivudile (3TC) single pill (300 Mg + 300 Mg) and Effavirenz (600 Mg) per day. The treatment is lifelong. For HIV exposed infant Neverepin 25ml (10 mg per ml), 3 bottles per child up to 6 weeks should be given and may be extended to 12 weeks if the mother has received ART later than 24 weeks of gestational age . MBB

45. Multi Drug Resistant Tuberculosis Definition : Multi Drug Resistant ( MDR ) TB : defined as resistance to isoniazid and rifampicin with or without resistance to other anti-tuberculosis drugs . Extensively Drug Resistant ( XDR) TB: defined as resistance to isoniazid and rifampicin ( i.e MDR Tuberculosis) + resistance to any of the fluoroquinolones and any one of the second line injectable drugs ( Amikacin , Kanamycin or Capreomycin ) MBB

46. MDR TB into 3 categories:A,B&C Criteria-A All treatment failures of new Tuberculosis cases . Smear positive previously treated cases who remain smear positive at 4 th month of treatment. All pulmonary Tuberculosis cases who are contacts of known MDR Tuberculosis case.   Criteria-B, in addition to criteria A; All smear positive previously treated pulmonary Tuberculosis cases at diagnosis. Any smear positive follow up result in new or previously treated cases. Criteria-c, in addition to criteria B; All smear Negative previously treated pulmonary Tuberculosis cases at diagnosis. HIV Tuberculosis co-infected cases at diagnosis.   MBB

47. Options for treatment of DR-TB during pregnancy Need to consider risks and benefits for the mother and fetus. –Option 1: Stop or delay MDR-TB treatment –Option 2: Terminate the pregnancy –Option 3: Continue treatment while pregnant

48. Show of hands Option 1: Stop or delay MDR-TB treatment Option 2: Terminate the pregnancy Option 3: Continue treatment while pregnant

49. Recommendations • Provide individualized care based on risks and benefits to the patient and foetus •The patient should be involved in therapeutic decisions •Pregnancy should not be terminated because of DR-TB infection

50. MDR- TB The treatment of MDR Tuberculosis in India has been started from 2009 there is limited experience in treating pregnant women with MDR Tuberculosis . During 2013 in India 23289 MDR cases were diagnosed. The death rate among MDR Tuberculosis is around 20% as compared to drug sensitive Tuberculosis which is around 5%. MBB

51. MDR- TB All women of child bearing age who are receiving MDR Tuberculosis therapy should be advised to use birth control measures because of potential risk to both mother and the fetus . Use of barrier methods, Intra Uterine Device, or DMPA (Depot Medroxy progesterone Acetate) are recommended MBB

52. Basic RNTCP regimen for MDR TB 6(9) Km Lvx Eto C S Z E /18 Lvx Eto C S E [Reserve / substitute drugs: PAS, Mfx , Cm ] ( Km – Kanamycin, Lvx - Levofloxacin, Eto - Ethionamide , C s – Cycloserine , Z- Pyrazinamide, E- Ethambutol , PAS- Para amino salicylic acid, Mfx – Moxifloxacin , Cm- Capreomycin ) The figures denote the number of months of treatment MBB

53. Special adjustments to the standard MDR TB Regimen In case of intolerance to Kanamycin substitute with capreomycin or PAS. In case of intolerance to any oral drugs PAS is the substitute. Baseline Levofloxacin and Kanamycin resistance ( i.e XDR Tuberculosis) should lead to referral for diagnosis of XDR Tuberculosis. All drugs should be given as single daily doses under directly observed treatment (DOT) MBB

54. Management of MDR TB during Pregnancy The gestational age (GA). If GA is <20 weeks, the women is advised MTP, For not willing for MTP or if GA is >20 weeks the risk to the mother and the Fetus needs to be explained before starting the treatment. For patients with GA <12 weeks, Km and Ethionamide are omitted & PAS is added. For patients with GA >12 weeks, Km is replaced with PAS, and after delivery, PAS may be replaced with Km and continued until the end of Intensive phase. Duration of treatment: At least 6 months of intensive phase treatment (IP) may be extended up to 9 months in patients who have a positive culture result at 4 th month of treatment . Minimum 18 months of continuation phase treatment (CP) should be given following IP. MBB

55. Regimen for XDR Tuberculosis Intensive phase IP: (6 – 12 months) consists of 7 drugs- Capreomycin , PAS, Moxifloxacin , High dose INH, Clofazimine , Linezolid and Amoxyclav . Continuation phase CP: (18 months) Consist of 6 drugs - PAS, Moxifloxacin , High dose INH, Clofazimine , Linezolid and Amoxyclav . Duration of treatment: 24- 30 months, with 6-12 months of IP and 18months of CP. RNTCP has a policy against empirical treatment of MDR/XDR Tuberculosis without microbiological confirmation from an RNTCP certified laboratory. MBB

56. Recommendations • There is limited evidence, but clinical experience has shown that terizidone , moxifloxacin , and PAS may be used safely in pregnant patients • During the first 20 weeks of pregnancy, avoid the injectable if possible. –Exception: if the risk of mortality is high, an injectable agent should be used. –Which injectable: Capreomycin or Kanamycin? • Ethionamide : Not enough data to confirm the safety or risk

57. Conclusion MDR / XDR • The best way to deal with DR-TB and pregnancy is to prevent it. •DR-TB treatment programs must provide integrated contraceptive services –Depo-Provera can be provided at 3 month intervals during clinic visits •Pregnancies should not be terminated because of DR-TB •We need more data! Especially in the management of HIV and DR-TB co-infection

58. Adverse effect of ATT on Fetus First line anti-tuberculosis drugs except streptomycin are safe. Streptomycin and Kanamycin may produce congenital deafness in the fetus. Ethionamide and PAS may cause various types of congenital defects. MBB

59. Side effects of second line ATT drugs Ethionamide and PAS may cause G.I. disturbances. Kanamycin may cause nephrotoxicity. Use of Cycloserine may induce suicidal tendency, psychosis and increase in the number of seizures. MBB

60. Warning It is well known that poor treatment practices breed drug resistance. Good treatment is a pre-requisite to the prevention of emergence of MDR Tuberculosis . Implementation of a good quality DOTS programme is the first priority for Tuberculosis control . And prevention of emergence of MDR Tuberculosis in the community is more imperative rather than its treatment . Each MDR case costs more than 20 times the cost of a drug susceptible Tuberculosis case. Therefore basic Tuberculosis diagnostic and treatment services should be prioritized implemented and adhered strictly. MBB

61. Summary Diagnosis and treatment of Tuberculosis during pregnancy is a real challenge . Pregnancy is not a contraindication for treatment of tuberculosis. Good quality treatment is a prerequisite to the prevention of emergence of drug resistance. Treatment must be adhered/ensured . Special precautions are essential in extra pulmonary, recurrent and other types of Tuberculosis (MDR and XDR). Co-morbid conditions (like HIV) really affect the success of treatment. Proper counselling, supervision and reassurance play a key role in the success of the treatment. MBB

62. Conclusion In spite of the side effects mentioned above the pregnant women tolerate the primary anti Tuberculosis drugs reasonably well . And drugs (except streptomycin) under RNTCP DOTS can be safely given to pregnant women with tuberculosis Proper Counseling , reassurrance , supervision are key to the successful treatment MBB

63. LET’S FIGHT T.B. TOGETHER AND SAVE MOTHERS FROM DIEING 24 TH MARCH WORLD T.B. DAY Thank you for giving me this oppurtunity