48

Correspondence

THE NATIONAL MEDICAL JOURNAL OF INDIA VOL. 11, NO.1, 1998

An intradermal vaccine protocolagainst hepatitis B in a haemodialysis

population

Among the patients on haemodialysis at the Chris-tian Medical College and Hospital, Veil ore, theprevalence of hepatitis B virus (HBV) is 25%.'·2This is probably true for the rest of India. Despitethe conventional double-dose vaccine protocol,there is a high rate of infection in the early periodof dialysis. J The hepatitis B vaccine has beenadministered intradermally to patients on haerno-dialysis to accelerate seroconversion and protec-tion.' We used a similar intradermal vaccinationprotocol to improve early seroprotection rates.

Forty-four adult patients on maintenancehaemodialysis who did not have markers for HBVinfection and seroprotection, or had not beenpreviously vaccinated, were included in the study.Patients above the age of 60 years, those on shortterm dialysis and those with evidence of sero-protection from HBV infection were excluded.Patients were given acetate dialysis three times aweek for four hours. As part of the pre-transplantprotocol all patients not transfused elsewhere wereadministered a total of 5 transfusions under coverof azathioprine 2 mg/kg for 3 days unless they hadleukopenia, infection or hypersensitivity. None ofthem received erythropoietin.

After informed consent, patients were random-ized using a table of random numbers to the intra-muscular or the intradermal protocol. SUbjects inthe intramuscular group were administered 40 ug(20 ug into each deltoid) of hepatitis B vaccine at0, 4 and 8 weeks. Those in the intradermal groupreceived 6 doses of 20 ug (5 ug at four differentsites in the interscapular region using a tuberculinsyringe with a 26-gauge needle by the same investi-gator) of the same vaccine every week starting ato weeks. The patients were tested for hepatitis Bsurface antigen, and antibodies to hepatitis Bsurface antigen (anti-HBs) and core antigen (HBc)at entry, at monthly intervals for three months orjust before transplantation using commerciallyavailable kits (Abbott Laboratories, Chicago, II,USA). Those with anti-HBs titres of 10 mIU ormore, without other markers of HBV infectionwere categorized as responders. Adverse reac-tions were monitored. The statistical significanceof the difference between the means was calcu-lated by the Student t-test,

There were 24 (I woman; 4 diabetics) and 20patients (3 women) in the intramuscular and intra-dermal groups, respectively. The age, total num-ber of haemodialyses and number of transfusionswere similar in both the groups. Azathioprine wasused to prevent sensitization though variably,depending on leucopenia and the presence ofinfection. The rate of seroprotection at 8 weekswas 21 % in the intramuscular and 60% in the intra-dermal group. The relative risk of not achievingseroprotection was 2.39 times in the intramuscularcompared to the intradermal group and there wasa significantly higher seroprotection at 8 weeks inthose who did not receive azathioprine (59%)compared to those given azathioprine (11%;

TABLEI. Comparison ofseroprotection at 8 weekswith or without azathioprine in the intramuscular(1M) and intradermal (JD) groups

Characteristics 1M routeAza No aza

ID routeAza No aza

No. of patients 13 11 5 15Seroprotected 1* 5* 1* 11 *Infected 8 4 1 2Seronegative 4 3 3 2

i.m. intramuscular i.d. intradermalAza azathioprine ·p<0.05

p<0.05). In the intradermal group the relative riskof not achieving seroprotection with and withoutazathioprine was 1.9 and 1.5 times, respectively.Patients receiving the intradermal vaccine with-out azathioprine had a 9 times better chance ofachieving seroprotection than those given intra-muscular vaccine and azathioprine. There were nosignificant side-effects in both the groups.

Thus, the seroprotection rate in the intradermalgroup was superior to that in the intramusculargroup, and in the azathioprine-free group as com-pared to the azathioprine-treated group, regard-less of the route of vaccination. The highestseroconversion rate was seen in the intradermalgroup without azathioprine (Table I).

Patients on haemodialysis are poor vaccineresponders' though repeated low-dose intrader-mal vaccine achieved complete seroconversion in26 weeks,' the antigens presented by specificepidermal cells causing a macrophage-dependentT cell response."

This intradermal protocol is likely to work bestin a milieu free from transfusions and immunosup-pression, which is possible with erythropoietin.

3 January 1998 L. VincentDepartment of NephrologySt John's Medical College

Bangalore

G. T. JohnDepartment of Nephrology

P. AbrahamDepartment of Virology

C. K. JacobDepartment of Nephrology

Christian Medical College and HospitalVellore

Tamil Nadu

REFERENCESI Gunasekharan v, Kirubakaran MG, Johnny KV, Shastry

JCM, John TJ. Hepatitis B virus infection in a renal unitin India. Indian J Med Res 1979;70: 1-4.

2 Thomas PP, Kirubakaran MG, Jacob CK, Srinivasa NS,Hariharan S, John TJ, et al. Hepatitis B infection in adialysis unit in south India . .I Assoc Physicians India1987;35:284-5.

3 George J, John GT, Jacob CK, Shastry JCM. Activeimmunization against hepatitis infection of a haerno-dialysis population. Natl Med J India 1994;7:115-16.

4 Ono K, Kashiwagi S. 'Complete seroconversion by lowdose intradermal injection of recombinant hepatitis Bvaccine in hemodialysis patients. Nephron 1991 ;58:47-51.

5 Stevens CE, Alter HJ, Taylor PE, Zang EA, Harley EJ,Szmuness W. Hepatitis B vaccine in patients receivinghemodialysis: Immunogenicity and efficacy. N Engl .IMed 1984;311:496-501.

6 Redfield RR, Innis BL. Scott R, Cannon HG, BancroftWHo Clinical evaluation of low-dose intradermallyadministered hepatitis B virus vaccine: A cost reductionstrategy . .lAMA 1985;254:3203-6.

Distribution of vascular lesions inischaemic stroke

This refers to the article 'Distribution of vascularlesions in ischaemic stroke' by Padma et al.' Thelast paragraph which emphasizes that intracranialpathology is high in the Indian population and thatwe have to come to our own conclusions regardingsurgical intervention is very pertinent. This is allthe more so when there is great enthusiasm forsurgical correction. However, I would like to pointout that similar conclusions were arrived at by DrK Sabda Saroop and myself' in a study which wasbased on more than 100 carotid angiographies inthe days when angiography was the gold standardfor cerebrovascular pathology.

I hope such publications in Indian journals willnot be ignored by investigators in India.

21 January 1998 S. ChandrasekharFormer Director

Jawaharlal Nehru Institute of PostgraduateMedical Education and Research

Pondicherry

REFERENCESI Padma MV, Gaikwad S, Jain S, Maheshwari MC,

Mishra NK. Distribution of vascular lesions in ischaemicstroke. Nail Med J India 1997;10:217-20.

2 Sabda Saroop K, Chandrasekhar S. A study of cerebro-vascular occlusive diseases. Neurol India 1975;23:91-9.

Quality of life in cancer: The emergingarbiter

The World Health Organization (WHO) has de-fined quality of life (QOL) as an individual'sperception of his/her position in life in the contextof his/her culture and value systems in which he/she lives and in relation to his/her goals, expecta-tions, standards and concerns. It is a broad-rang-ing concept affected in a complex way by theperson's physical health, psychological state, levelof independence, social relationships and his rela-

CORRESPONDENCE

tionship to salient features of his environment. IAsearly as 1947 the WHO defined health as 'a stateof complete physical, mental arid social well be-ing, and not merely the absence of disease' andyears later set an epidemiological ambition of'Health for All by the year 2000'. Today theemphasis has shifted from 'life expectancy' whichhas shown an increase in morbidity-free life atolder ages, and from indices measuring mortalityand morbidity to 'health expectancy' and 'healthgain'.

In 1948, Karnofsky and Burchenal made theearliest documented effort to evaluate QOL. I Theyfelt that response to chemotherapeutic drugs incancer treatment should be judged not only byobjective measurements of tumour dimensionsbut also by well-being of patients. Visick in thesame year made an effort to measure QOL aftergastric operations.' It was Caiman who 'exposed'a glaring 'gap' in results achieved and resultsexpected named today as 'Caiman's gap'. Hedescribed QOL in an inverse relationship to thesize of the gap between an individual's expecta-tion and the reality ofhislher situation. The smallerthe gap the better the QOL. 4

The need/or QOL measurement in cancerHealth outcome was previously defined as a changein the patient's current and future health status thatcan be attributed to antecedent health care.' Theusual 'outcome' indicators are information onavoidable mortality, morbidity, laboratory inves-tigations, etc. So long as the debate continues as towhether a vegetative state is better or worse thandeath, clinical indicators of outcome are no morevalid" Hence, there is general agreement that inincurable conditions, the thrust of health care shallbe to provide a life worth living-comfortable andfunctional.'

The lifetime risk of developing cancer today is30% and there is a 20% risk of cancer being thelife-taker' With a reasonable prospect of cure,patients and doctors are willing to accept theassociated risk of toxicity with less concern forbeneficial effects and QOL. Patients whose livesare prolonged thus, run the risk of bearing not onlythe impact of the 'injury' caused by the disease,but also the 'insult' from medications.

In situations where there is no survival advan-tage, clinicians and patients can choose betweenchemotherapeutic agents' Thus the 'benefit-bur-den' ratio can be balanced and made realistic.

In cancer there is more scope for a multidisci-plinary approach with emphasis on QOL, if theradiation oncologist, medical oncologist, and so-cial worker are allowed 'rightful participation'.Surgical and anaesthetic skills have advanced tosuch great extents that a high-risk patient is virtu-ally non-existent today. In our relentless fightagainst the scourge of malignancy and its recur-rence, the patient whose life is prolonged byexcellence in surgical and anaesthetic skills, ismade to barter his quality oflife to gain quantity.Often patient compliance borders on servitude,and the surgeon's zeal on arrogance. Means justi-fying the end and vice versa provide reciprocatinglicenses for surgical extravaganzas!

In a study which reviewed all clinical studiespublished in six major journals between 1956 and1976, it was found that only in less than 5% anattempt had been made to measure some aspect ofQOL. 10 However, this situation changed and by

1987 there were more than 3000 publicationswhich mentioned QOL." Most studies reportedoutcome only in terms of survival or recurrence,while QOL, although mentioned, was never mea-sured."

Any QOL assessment in cancer patients shouldinclude physical, psychological and social.well-being. Physical well-being should include symp-toms and toxicities such as pain, nausea, fatigue,physical activity including recreation work andself-care. Psychological well-being lays stress onbody image, self-esteem, anger and depressionand social well-being is judged by social activi-ties, participation or isolation and sexual relation-ships."

Commonly used measurement scalesThere are numerous scales, some meant for spe-cific cancers and some for all cancers. All have aquestionnaire, some of which can be completed bythe patient himself and others which need a healthcare giver to complete. The WHO symptom check-list includes 12 categories of treatment-relatedsymptoms: nausea/vomiting, diarrhoea, constipa-tion, haematuria, pulmonary function, fever, al-lergic reactions, skin reactions, hair loss, infec-tion, neurological effects and pain, each beingcoded on a 0-4 index ranging from none or nostatus change to severe." The European Organiza-tion for Research on Treatment of Cancer (EORTC)has a 36- and 30-item version with supplementarydisease-specific items, head and neck cancer be-ing the latest addition to the list." Time withoutsymptoms and toxicity (TWiST) was a conceptintroduced in 1986 and evaluated in breast cancerpatients. 16

Pain measurementSeventy-five per cent of cancer patients havepain. 11 The McGill pain questionnaire is the mostfrequently used measure of pain containing 78adjectives describing pain; it has been found to beuseful as it quantifies pain and is sensitive todifferent treatment methods." The visual ana-logue employs a linear scale with 10 divisionsmarked no pain on one end and worst pain imag-inable on the other end. Patients point on the scaleas to where their pain could be marked and thus itis scored. I.

The emerging mandate today is to balance quan-tity of life and QOL. For that, the QOL in cancerpatients should be audited, such that 'life can beadded to years' as against 'years to life'. There aremany non-biological factors for recovery and out-come such as patient psychology, motivation,coping, socio-economic status, availability ofhealth care and social support networks. Theseneed be addressed so that a uniformity ofQOL canbe expected among cancer patients.

REFERENCES1 Bowling A. Measuring disease: A review of disease

specific quality of life measurement scales.Philadelphia:Buckingham Open University Press,1995:3.

2 Kamofsky DA, Burchenal JH. The clinical evaluationof chemotherapeutic agents against cancer. In: McleodCM (ed), Evaluation of chemotherapeutic agents. NewYork:Columbia University Press, 1949.

3 Visick AH. Measured radical gastrectomy: Review of505 operations for peptic ulcer. Lancet 1948;1:505-8.

4 CaIman KC. Quality of life in cancer patients-Anhypothesis. J Med Ethics 1984;10:124-7.

49

Donabedian A. Explorations in quality assessmentand monitoring. Vols 1--3. Ann Arbor:MI HealthAdministration Press, 1985.

6 Jennett B. Resource allocation for the severely braindamaged. Arch Neurol 1976;33:595-7.

7 Sullivan M. Quality of life assessment in medicine:Concepts, definitions,purposes andbasic tools. NordicPsychiatr 1992;46:79-83.

8 Blackledge G, Lawton F. The ethics and practicalproblems of phase I and II studies. In: Williams CJ(ed). Introducingnewtreatmentsforcancer: Practicalethical and legal problems. Chichester:John Wiley,1992.

9 Silverfarb PM, Mauer LH, Crouthamel CS.Psychosocial aspects of neoplastic disease. I:Functional status of breast cancer patients duringdifferent treatment regimens. Am J Psychiatry1980;137:450-5.

10 Bardelli 0, Saracci R. Measuring the quality of life incancer clinical trials: Methods and impact ofcontrolled therapeuttc trials In cancer. Geneva:UnionInternationale Control Ie Cancer Technical ReportSeries. 1978;36:75-94.

I I Aaronson NK, Bullinger M, Ahmedzai S. A modularapproach to quality oflife assessment incancer clinicaltrials. Recent Results Cancer Res 1988;111:231-49.

12 Mosteller F,Gilbert JP, Mcpeek B. Reportingstandardsand research strategies for controlled trials: Agendafor the author. Control Clin Trials 1980;1:37-58.

13 Selby P. Measuring the quality of life of patients withcancer. In: Walker SR, Rosser RM (eds). Qualityof life assessment: Key issues m the 1990s.Dordrecht:Kluwer Academic, 1993.

14 Miller AB, Hoogstraten B, Staquet N, Winkler A.Reporting results of cancer treatment. Cancer1981;47:207-14.

15 Bjordal K, Kaasa S. Psychometric validation of theEORTC core quality of life questionnaire, 30-itemversion and a diagnosis-specific module for head andneck cancer patients. Acta Oncology 1992;31:311-21.

16 Gelber RD, Goldhirsch A. A new end-point for theassessment of adjuvant therapy in postmenopausalwomen with operable breast cancer. J Clin Oncol1986;4:1772-9.

17 Bonica JJ. Cancer pain. In: Bonica JJ (ed). Themanagement of pain. Volume I Philadelphia:Lea andFebiger, 1990:400-60.

18 Melzack R. The McGill pain questionnaire: Majorproperties and scoring methods. Pain 1975;1:277'-99.

19 Valley MA. Pain measurement in pain medicine: Acomprehensive review. In: Prithviraj P (ed). St Louis:Mosby: 36-46.

I January 1998 Cherian M. KoshyRachel Cheri an Koshy

Department of Surgical Oncology andAnaesthesiology

Regional Cancer CentreThiruvananthapuram

Kerala

Supplementary feeding component of theICDS for expectant women

In India the incidence of low birth-weight (LBW:less than 2500 g) is around 30%. I According to aNational Collaborative Study undertaken by theIndian Council of Medical Research Task Force in1990, the extent ofLBW varied between 27% and56% in urban slums and between 33% and 41% inthe rural population. I The surveys carried out by

50

the National Nutrition Monitoring Bureau (NNMB)in 10 states indicate that the dietary intake of ruralwomen ranges between 1600 and 1900 kcal asagainst the Recommended Dietary Intake (RDI) of2175 kcal. About 33% of rural women weighunder 40 kg and 15% are less than 145 cm tall, thecut-off points considered critical' for safe preg-nancy outcome.

Generally, women of low income group, par-ticularly in the rural areas of India, do not makeany additional dietary allowances during preg-nancy.' Thus there is an estimated deficit of about600-1000 kcal per day in the diet of pregnantwomen indicating a need for supplementary feed-ing during pregnancy. The high incidence ofLBW'focused the need for strengthening the Supple-mentary Feeding Programme (SFP) component ofthe Integrated Child Development Scheme (ICDS)as well as during antenatal care. The earlier obser-vations of better maternal nutrition leading tobetter birth-weight of their offspring and a reduc-tion in the incidence ofLBWs with an increase inbody mass index (BMI) of expectant women- alsoemphasizes the need to improve the nutritionalstatus of pregnant women. There is evidence thatthe nutritional supplements given to undernour-ished pregnant women in hospitals even late inpregnancy influenced birth-weight of their in-fants.?

In 1975, the Government of India started theICDS to improve child survival and safe mother-hood. It presently covers about 25 lakh pregnantwomen in nearly 3000 community developmentblocks in the country. The programme providessupplementary nutrition, antenatal check up, im-munization and medical referral service to expect-ant women. However, as in the case of variousother supplementary feeding programmes, par-ticipation of pregnant women in this programmehas not been satisfactory. 8 Therefore, we assessedthe extent of participation of pregnant women inthe SFP of the ICDS and reasons for their lowparticipation. We then introduced remedial mea-sures and studied their impact on the participationof pregnant women in the SFP.

The study was carried out in 15 villages inRanga Reddy district, near Hyderabad where ICDSwas being implemented. In the study area, all 40 Ipregnant women in the second and third trimesterswere contacted, and a questionnaire was adminis-

THE NATIONAL MEDICAL JOURNAL OF INDIA VOL. 11, NO.1, 1998

tered to evaluate their participation in and percep-tions about the ongoing SFP of the ICDSprogramme. Each pregnant woman beneficiaryreceived asupplementof'Upma' (asavouryprepa-ration of com soya mix and salad oil) supplied byCARE providing about 500 kcal of energy. Spe-cific reasons for non-participation were elicitedfrom those women who were eligible to receivethe supplement, but were not participating in theprogramme.

Only 34% of the eligible beneficiaries werereportedly participating in the supplementaryprogramme. The main causes for poor participa-tion were poor palatability of the recipe (31%),distribution of the supplement at an inconvenienttime (22%), ignorance of the need for additionalfood (24%) and not a felt need (27%) in case ofwomen belonging to the higher socio-economicgroup.

The following remedial measures were thenimplemented in four of the selected villages whichhad 96 pregnant women:I The palatability of the recipe was improved by

adding locally available non-starchy vege-tables, with an additional cost of Rs 2 per dayper Anganwadi centre.

2 Distributing the supplement separately to thepregnant women before they actually left fortheir daily work at around 9 a.m. instead ofserving it at 12 noon along with the childbeneficiaries.

3 Nutrition and health education to pregnantwomen to create awareness about the need foradditional food during pregnancy.

Out of the 96 pregnant women, 69 (72%) par-ticipated in the SFP of the ICDS, thus showingsignificant improvement (p<O.OOI) in the compli-ance rate of pregnant women. The additional costof modified supplement increased from Rs 1.30 toRs 1.50 per woman per day.

The National Nutrition Policy of the Govern-ment of India approved by Parliament in 1993'aims at bringing down the incidence of LBW to10% by AO 2000. One of the means to achieve thisobjective can be strengthening ofthe SFP compo-nent of the ICDS. However, it is necessary toincrease the participation of pregnant women inthe SFP in areas where the ICDS is in operation. Amanagement information system based on monthlyprogress reports can be effectively built to

strengthen the SFP component of the ICDS, espe-cially with regard to pregnant women. The cost ofremedial measures implemented in the currentstudy will be about Rs 40 000 for a period of 100days per ICDS Project.

ACKNOWLEDGEMENTSWe thank the Director, National Institute ofNutri-tion, Hyderabad, for encouragement throughoutthe study. We are also grateful to the ICDS func-tionaries for their cooperation and pregnant moth-ers for participating in the study.

REFERENCESI Reddy V, Prahlad Rao N, Sastry JG, Kasinath K.

Nutrition trends in India. Hyderabad:National Instituteof Nutrition, 1993:39.

2 Indian Council of Medical Research Task Force. ANatianal Collaborative Study of identification of high.risk families. mothers and outcome of their offspringwith particular reference to the problem of maternalnutrition. low birth-weight. perinatal and infantmorbidity and mortality in rural and urban slumcommunities. New Delhi:Indian Council of MedicalResearch, 1990.

3 GowrinathSastryJ, PrahladRaoN. 'Extensionstrategiesfor safe motherhood'. Paper presented at the NationalSeminaron Innovative Strategiesof ExtensionforRuralDevelopment of S.V. University, Tirupati.

4 Women and nutrition in India. In: Gopalan C, Kaur S(eds). Nutrition in pregnancy. New Delhi:NutritionFoundation of India, Special Publication, 1989, SeriesNo. 5:155.

5 Annual Report. National Institute of Nutrition.Hyderabad:lndian Council of MedicalResearch, 1988-90:8-9.

6 NadamuniNaidu A, Prahlad Rao N. Bodymass index-A measureofthe nutritionalstatus in Indianpopulations.EurJ Clin Nutr 1994;48:SI31-40.

7 Srikantia SG, Iyengar L. Effect of nutrient supplementsin pregnancy on birth weight of new born. Proceedingsof the Nutrition Society of India No. II, 1972.

8 Rameshwar Sarma KV, Prahlad Rao N. Strengtheningnutritionprogrammesforwomen.IASSIQuarterly Oct-Dec 1992.

9 National Nutrition Policy. Department of Women andChild Welfare, Governmentof India,New Delhi, 1993.

4 January 1998 K. V. Rameshwar SarmaD. Hanumantha Rao

K. DamayanthiM. Ravindranath

National Institute of NutritionHyderabad

Andhra Pradesh