jawarish amla

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Published 2013-Feb-12; Corrected 2013-Mar-8 DOI: http://dx.doi.org/10.5915/44-1-9988 JIMA: Vol 44, 2012, Page 1 of 9

Original Article

A Pilot Trial of Jawarish Amla as Adjuvant to Anti-Tubercular TreatmentDrugs for Control of Adverse Reactions in DOTS Regime in Pulmonary TB

DOI: http://dx.doi.org/10.5915/44-1-9988

Arish Mohammad Khan Sherwani, MD1 Mohammad Zulkifle, MD2

Rehmatulla, MD3 1Department of Preventative and Social Medicine, National Institute of Unani Medicine, Bangalore, India2Department of Fundamentals of Unani Medicine, National Institute of Unani Medicine, Bangalore, India

3Ministry of Health and Family Welfare, Karnataka State Government, Bangalore, India

Abstract

Background and objectives: One of the greatest challenges of health care systems at the dawn of the21st century is tuberculosis (TB). Drug resistant strains of TB are becoming a global public healthrisk. These strains commonly appear due to faulty therapies. Patients frequently stop treatment dueto the toxicity of anti-tubercular treatment (ATT) drugs. Amla (Emblica officinalis) is a well-knownUnani single drug. Jawarish amla is a Unani compound formulation which is commonly used toadminister amla. This study tested the efficacy of Jawarish amla as an adjuvant to ATT drugs inreducing their side effects.

Methodology: Half of forty eligible pulmonary tuberculosis patients were randomly assigned to Test

(Group B) and the other half to Control (Group A). Six grams of Jawarish amla twice daily wasadministered to the test group, and the same dosage of placebo was administered to control groupalong with directly observed treatment, short course chemotherapy (DOTS) for 60 days. Fisher exacttest and paired t-test were applied for efficacy evaluation. Grading of symptoms was done to assessthe toxicity of ATT and outcome of the adjuvant.

Results and discussion: Significant improvements were observed in almost all subjective andobjective parameters. The exceptions were serum creatine and serum uric acid, which showed non-significant slight elevations within normal limits.

Conclusion: Jawarish amla was ascertained to be safe and effective adjuvant of DOTS in combating theadverse effects of ATT drugs.

Key words: Pulmonary Tuberculosis; Side Effects; Drug Resistance; Herbal Medicine; AdverseReaction; Jawarish Amla

Correspondence should be directed to

Arish Mohammad Khan Sherwani, [email protected]
http://dx.doi.org/10.5915/44-1-9988http://dx.doi.org/10.5915/44-1-9988http://dx.doi.org/10.5915/44-1-9988http://dx.doi.org/10.5915/44-1-9988http://dx.doi.org/10.5915/44-1-9988http://dx.doi.org/10.5915/44-1-9988http://c/Users/User/Documents/JIMA/manuscripts/009988%20Jawarish%20Amla/aris%3ca%20href=%22http:/www.google.com/recaptcha/mailhide/d%3fk=01gFSiJeAj3vZa8Vw4OD18vQ==&c=hvV_2XXRYf-SUNJWG0iqo_XVWunWcgKv_VzOSsqDu9g=%22%20onclick=%22window.open('http:/www.google.com/recaptcha/mailhide/d%3fk/07501gFSiJeAj3vZa8Vw4OD18vQ/75/75/46c/75hvV_2XXRYf-Shttp://c/Users/User/Documents/JIMA/manuscripts/009988%20Jawarish%20Amla/aris%3ca%20href=%22http:/www.google.com/recaptcha/mailhide/d%3fk=01gFSiJeAj3vZa8Vw4OD18vQ==&c=hvV_2XXRYf-SUNJWG0iqo_XVWunWcgKv_VzOSsqDu9g=%22%20onclick=%22window.open('http:/www.google.com/recaptcha/mailhide/d%3fk/07501gFSiJeAj3vZa8Vw4OD18vQ/75/75/46c/75hvV_2XXRYf-Shttp://c/Users/User/Documents/JIMA/manuscripts/009988%20Jawarish%20Amla/aris%3ca%20href=%22http:/www.google.com/recaptcha/mailhide/d%3fk=01gFSiJeAj3vZa8Vw4OD18vQ==&c=hvV_2XXRYf-SUNJWG0iqo_XVWunWcgKv_VzOSsqDu9g=%22%20onclick=%22window.open('http:/www.google.com/recaptcha/mailhide/d%3fk/07501gFSiJeAj3vZa8Vw4OD18vQ/75/75/46c/75hvV_2XXRYf-Shttp://dx.doi.org/10.5915/44-1-9988http://dx.doi.org/10.5915/44-1-9988


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II patients [sic] as suggested by DOTS strategy andensuring adherence to a full course of treatment is[sic] the key to curing TB patients and preventingthe emergence of drug resistance. 6

A pharmacologically multi-potent herbaladjuvant drug which can also combat the adverseeffects of DOTS chemotherapy and improve thepatient's compliance with DOTS would be of vitalimportance. Jawarish amla as an adjuvant therapymay increase the efficiency of DOTS therapy,reduce the number of drug resistance cases andside effects as well as reverse the consequencesand rejuvenate body power. A recent study oawarish amla showed potential to provide

protection against toxic effects ocyclophosphamide in tumour bearing mice.7 Thusa study using Jawarish amla, an Unani adjuvantcompound formulation, has been undertaken toevaluate its efficacy in combating the side effectsof ATT drugs, reversing the adverse consequencesof DOTS therapy, boosting general immunity andfacilitating a complete recovery from TB.

Table 1 includes a list of all Unani medicalterms used in this paper.

Materials and MethodsThe present study was designed as a single-

blinded randomized controlled, concurrentparallel, comparative, adjuvant clinical trial,conducted at the National Institute of UnaniMedicine (NIUM) Hospital, Bangalore, to evaluate

the efficacy of Jawarish amla as an adjuvant incombating the side effects of ATT among patientsof pulmonary TB on DOTS regime. The studyduration was from March 2010 to March 2011.

All pulmonary tuberculosis patients on DOTS,age between 15-60 years and patients of either sexwere eligible for inclusion in the study. Patientsdiagnosed with diabetes mellitus, HIV/AIDS orhormonal disorders patients on corticosteroidtherapy extra pulmonary tuberculosis patients, patients with severe disability and patients not

IntroductionAbout one third of the world population, about

two billion people, is infected with tubercle bacilli.It is estimated that about nine million peopledevelop tuberculosis every year. By 2020, another200 million people are expected to become sick,and about 70 million will die from tuberculosis(TB). TB has been a major communicable tragedy for centuries and is the prime cause of morbidityand mortality in patients with humanimmunodeficiency virus (HIV)/Acquired ImmuneDeficiency Syndrome (AIDS).1,2,3 It is estimated that2.5 million people are infected with HIV in India.Considering 40% of the total population of India is

infected with Mycobacterium tuberculosis, anestimated 1 million persons are co-infected withTB and HIV. HIV is the most powerful risk factorfor the progression of TB infection to TB disease. Itis also the leading cause of death in People Livingwith HIV/AIDS (PLHA).

Under directly observed treatment, shortcourse chemotherapy (DOTS), the patient isobserved while taking medication. Thisobservation helps ensure that the correct dosageof the drug is taken at the right time. It alsoascertains that the patient does not stop thetreatment midway. When used properly, a courseof DOTS cures over 80% of patients, striking asignificant blow against TB worldwide.

A number of dropouts are recorded, mainlybecause of the side effects of the anti tubercular

treatment (ATT) drugs used in DOTS. Isoniazidcauses peripheral neuropathy and hepatitis.Rifampicin causes loss of appetite, nausea andhepatitis. Ethambutol causes visual disturbances(poor vision and color perception). Pyrazinamidecauses hepatitis and arthritis. The toxicity of drugsis the major reason for defaulting from treatment,which the Revised National Tuberculosis ControlProgramme defines as not taking anti-TB drugs for2 months or more consecutively. 4,5 Effective useof first line drugs in every category I and category
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awarish is derived from the Persian word gowarish,which means the granular semisolid that tends tostay longer in the gastrointestinal tract to enhanceits digestive power and to potentiate liver.

Administration of Conventional DOTS and Adjuvant

Regime Patient-friendly boxes were prepared. They

consisted of two kinds of pouches for intensive orinitial phase (12 blisters) and continuous phase (48blisters) of treatment. The pouches wereadministered for six or eight months at thepatients primary health centers (PHCs), which arethe community health centers or nearby hospitals

to which patients would come three times perweek during the initial phase and once weeklyduring the continuous phase. PHCs are generallyone to two kilometers from the patients homes.

During the initial two month intensive phase,patients swallowed the drugs under thesupervision of the doctors and drug providers atthe time of their thrice weekly visits. In thesubsequent continuous phase of TB treatment,

patients received seven-day blister packs at theirPHCs, and, after taking the initial days dose at thePHC, take the remaining six days of medicine ontheir own.

All study participants from the various PHCscame to NIUM to receive the supply of adjuvantdrug of either Jawarish amla or placebo, given infifteen-day dose packs. Placebo of adjuvant drug

was a sweet and morphologically similar,semisolid paste of similar color made by starchand sugar, given with the same dose of 6 grams,twice daily for two months. The adjuvant drug wastaken 6 grams twice daily for two months aftermeal at their home. The Jawarish amla wasprepared fresh and distributed at NIUM every twoweeks to the patients during the two-month studyperiod.

All clinically suspected outpatients andinpatients of NIUM with history of cough for more

willing to give consent were excluded from thestudy.

Ethical clearance was obtained from theinstitutional ethical committee for biomedicalsciences at the National Institute of UnaniMedicine (NIUM), Bangalore. There were 54

enrolled patients. Of the fourteen cases who couldnot complete the study, one patient of the placebogroup died without any known immediate cause.Ten others dropped out from the study within onemonth of the trial. Three patients of the test groupwho came from other places returned to theirhomes for completion of DOTS therapy as theywere unable to in Bangalore until the completion

of the DOTS regime. Fourteen cases did notcomplete the study. The remaining 40 patientswere equally randomized and matched into TestGroup B, DOTS plus adjuvant drug, and ControlGroup A, DOTS plus adjuvant placebo, by table ofrandom numbers calculated by Stat Trek'sRandom Number Generator.

Selection Criteria for Adjuvant Drug

The fruit amla is used for many ailments,particularly in South India. It is easily availableand cheap. Retrolective survey of ancientliterature and scientific studies revealed that amla (Emblica officinalis) is an antipyretic, hepato-protective, appetizer, anti-tussive, nervine tonic,antihemorrhagic, anti-inflammatory drug 7 whichstrengthens the vital organs and stomach and

enhances vision. It is also a good blood purifierwhich inhibits production of morbid balgham and sauda. Amla is a well known Unani single drug. Amla is the richest source of natural heat stablevitamin C. It is a powerful antioxidant and boostsimmunity. It restores vitality and rejuvenates allof the vital organs.9

Jawarish amla is a sweet, semi-solid andgranular unani compound formulation. Its chiefingredient is amla (Emblica officinalis), whichis processed in cow milk and sugar. The term


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Table 1. Unani Medical TermsEnglish and/or Latin Transliteration

Indian Gooseberry (Phyllanthus emblica, syn.

Emblica officinalis)Amla

Sweet, semi-solid and granular preparation ofUnani compound formulation

Jawarish

Gastric ulcer quruhul meda

Hyperacidity umuzatul meda

Headache uda

Biliary Diarrhea ishl-e afrav

Pulmonary tuberculosis Diqq-e revi

Phlegm (humor) Balgham

Black bile or melancholy (humor) Sauda

than two weeks were investigated for pulmonaryKochs. Eligible patients were enrolled into thestudy with their written consent. All clinicallysuspect patients had chest x-rays (PA views) atNIUM. Two sputum samples (early morning andspot) were collected and sent to the designated

microscopic centre, Leggere PHC, for acid-fastbacilli (AFB) examination as a routine diagnosticprocedure. All diagnosed cases of pulmonarytuberculosis were advised to come for two weekfollowup and adjuvant, Jawarish Amla or placebo, was prescribed, 6 grams twice daily for twomonths.

In India, patients diagnosed with TB andprescribed DOTS are provided with DOTStreatment cards. Each card contains a unique TBnumber and enables tracking of associated lab

results and other case-related information. Allpatients DOTS treatment cards were verifiedbefore enrolling in the study. The cards werephotocopied and retained for authenticity.

Investigations were carried out for diagnosis,exclusion and assessment of the objective

parameters in various treatment groups.Investigations done in every case includedcomplete hemogram, erythrocyte sedimentationrate, fasting blood glucose, serum creatinine,serum uric acid, alanine aminotransferase (ALT),aspartate aminotransferase (AST), serum alkalinephosphatase (ALP), serum total bilirubin, HIV I &II, chest x-ray PA view and sputum smear test forAFB.

Investigations for objective evaluation wereassessed at zero days (before starting) and on


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60thday (after completion) of the treatment atNIUM. Investigations for exclusion and diagnosticcriteria were taken at pre-treatment assessment.Sputum for AFB was examined before treatmentand after completion of initial phase andcontinuous phase in the patien ts respective

health centers at regular standard intervals as aprotocol of DOTS.

The studys parameters were subjective andobjective. The subjective parameters were theadverse reactions the patients reported. Adversereactions severity was classified as minor, majorand other. The minor reactions were nausea,vomiting, anorexia, abdominal pain, itching, rash,

oint pain, and burning sensation in feet. Themajor reactions were jaundice, constipation, skinrash and flu syndrome. Other side effects werebitter taste, angina, diarrhea, sweating, insomniaand body pain.10,11 Before starting treatment, eachsign and symptom was recorded in the case reportform for their grades at the initial visit. Anyworsening or improvement in parameters wasnoted down at every follow-up visit until the end

of the treatment.The liver function tests alanine

aminotransferase (ALT), aspartateaminotransferase (AST), alkaline phosphatase andtotal bilirubin and the renal function tests serumcreatinine and serum uric acid are objectiveparameters of DOTS toxicity.4,12,13,14 These testswere administered for efficacy evaluation of

adjuvant drug.After 60 days of the treatment, the pre- andpost- treatment values of different parameters(subjective and objective) were analyzed andsubjected to comparisons and statistical analysisto evaluate the efficacy of the treatment. Patientscompliance to treatment and improvements inadverse reactions to the ATT treatment and insigns and symptoms of tuberculosis were closelywatched throughout the study.

Paired t-test was applied to analyze the intra

group comparison of pre- and post-treatmentvariables, and unpaired t-test and Fisher exact testwas applied to compare inter groups aftertreatment variables. SAS 9.2, SPSS 15.0, Stata 10.1,MedCalc 9.0.1, Systat 12.0 and R environmentver.2.11.1 were used for the analysis of the data.

Results on continuous measurements arepresented on mean SD (range) and results oncategorical measurements were presented inNumber (%). Significant figures were stated as p 0.05.

The safety of the treatment was assessedclinically at every visit of follow up anddiscontinuation of study medication was the

prime tool of safety measure. However, there wasno such consequence observed which hadnegative impact on our study.

ResultsEfficacy evaluation of Jawarish Amla on SubjectiveParameters

The minor side effects of the incidence ofnausea (p


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significant. Pre- and post-treatment values werewithin normal ranges. (Tables 2 and 3)

Over the course of treatment, average ALTdecreased in Group B, but the decrease was notstatistically significant. ALT in Group A showed asignificant increase (p=0.005) pre- and post-treatment. Group Bs ALT values were significantlylower after treatment than those of Group A(p=0.008) (Table 4).

Group As AST values increased significantlypre- and post-treatment (p=0.001). The decrease inGroup Bs AST values was not statisticallysignificant. Group Bs AST values weresignificantly lower after treatment than those of

Group A (p=0.009) (Table 4).Group As alkaline phosphatase values did not

increase significantly pre- and post-treatment.The decrease in Group Bs alkaline phosphatasevalues was statistically significant (p=0.036). GroupBs alkaline phosphatase values were significantlylower after treatment than those of Group A(p=0.029) (Table 4).

Group As total bilirubin values increasedsignificantly pre- and post-treatment (p=0.002).The change in Group Bs total bilirubin values wasnot statistically significant. Group Bs totalbilirubin values were not significantly lower aftertreatment than those of Group A (Table 4).

DiscussionThe significantly lower incidence of nausea

(p


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in test group in comparison to control group.The test drug in this study was safe and

effective in checking the adverse effects of ATTdrugs used in DOTS therapy. It may thus be anexcellent adjuvant to DOTS in the communitymanagement of pulmonary tuberculosis (diqq-erevi). This adjuvant therapy should be selected forstudy involving a large sample size. If the resultsof this study are confirmed, it should then beimplemented in Indias Revised NationalTuberculosis Control Programme (RNTCP) forchecking the adverse reaction of DOTS andefficacy improvement.

AcknowledgementWe gratefully acknowledge the former NIUM

Director, Professor M.A. Jafri, for his kindpermission and providing other necessaryfacilities in carrying out the trial. We are alsoindebted to Health and Family WelfareDepartment, Karnataka State and immenselythankful to the designated microscopic centre(DMC), Leggere PHC staff for their continuous co-operation throughout this work. We also owegratitude to Dr. K. P. Suresh, Scientist(Biostatistics), National Institute of AnimalNutrition and Physiology (NIAN & P), Bangalore,for his help in statistical evaluation for this study.

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