Evaluation of the efficacy ofTHE BHARANGYADI GHANAVATI IN VISHAMAJWARA WITH      SPECIAL REFERENCE TO MALARIAL FEVER      ...
D.G.M.AYURVEDIC MEDICAL COLLEGE  POST GRADUATE STUDIES AND RESEARCH CENTER                                 GADAG, 582 103 ...
J.S.V.V. SAMSTHE’S                     D.G.M.AYURVEDIC MEDICAL COLLEGE      POST GRADUATE STUDIES AND RESEARCH CENTER     ...
Declaration by the candidate        I here by declare that this dissertation / thesis entitled “EVALUATION OF THEEFFICACY ...
Copy right                    Declaration by the candidate        I here by declare that the Rajiv Gandhi University of He...
I express my deep gratitude to my guide Dr. V. Varadacharyulu M.D.(Ayu), Professor andH.O.D., for his timely advises and e...
Evaluation of the efficacy of the Bharangyadi           Ghana Vati in Vishamajwara with special                   referenc...
Table of contents               Heading                         Page numberChapter - 1   Introduction                     ...
List of figuresSno                             Figures heading                          Page1     Photograph of Parvateeya...
List of graphsSno                                Graph heading                           Page1     Distribution of patient...
List of tablesSno                                  Table Heading                                  Page1     Showing the Do...
Chapter –1                                                                            Introduction       “               o...
each new class of anti-malarial drugs, is one of most significant threat to the health of peoplein tropical countries. Whi...
usual for this plant to be used in combination with others in the treatment of fevers. In thedevelopment of the new artemi...
The research initiative for traditional anti-malarial methods (RITAM)       To redress this situation, a partnership was e...
Homeopathy, Unani, Yoga & Naturopathy and Siddha systems together called as IndianSystems of Medicine. These systems have ...
randomised clinical trial was conducted in P. vivax malaria patients at the Centre in                           10.collabo...
Chapter -2                                                                          Objectives                      resent...
present in the body. The jwara called as fever may not be a big problem from thecontemporary but as par Ayurveda it is a p...
Chapter -3                                                                 Literary review                           yurve...
Parvateeya Mashaka. Out of these the last Parvateeya Mashaka are more toxic and fatal innature. The symptoms of this type ...
in 165 deaths. WHO declared Australia free of malaria in 1981, however since that time 9patients have contracted locally a...
In the red blood cells the parasites develop into two forms, a sexual and an asexualcycle. The sexual cycle produces male ...
Figure –2                              Geographical distribution of the MalariaHistory of malaria       Malaria or a disea...
treatise, the symptoms of malarial fever were described and attributed to the bites of certaininsects. A number of Roman w...
Differentiation of Species of Malaria (1886)       Camillo Golgi, an Italian neurophysiologist, established that there wer...
malaria transmission was solved. For his discovery, Ross was awarded the Nobel Prize in1902.Discovery of the Transmission ...
USPHS requested and received funds from the U.S. Congress to control malaria in theUnited States. Various activities to in...
Dichloro-diphenyl-trichloroethane (DDT) (1939)       A German chemistry student, Othmer Zeidler, synthesized DDT in 1874, ...
Eradication of Malaria in the United States (1947-1951)       The National Malaria Eradication Program, a co-operative und...
term maintenance of the effort untenable. Completion of the eradication campaign waseventually abandoned to one of control...
implicated. Historians have generally agreed that Romes downfall was due to a combinationof many factors 14.Past and prese...
Malaria Control Operation       The discovery of the insecticide DDT in 1942, by Paul Müller the Nobel PrizeLaureate in Ph...
possible epidemic focal resurgence in receptive areas such as the Mediterranean. Since1976, several new pockets of malaria...
importance. No other country other than India releases a stamp on a Mosquito. The Malariaeradication programme is to be re...
different control and treatment strategies may be necessary. The intricate interactionsbetween host, parasite, and vector ...
The disease Vishamajwara is included under the jwara roga in Ayurveda. Jwara is abroad term, which has versatile meaning. ...
season) and grishma kala (summer season) or in the state of sheeta and ruksha. AtharvaVeda described the following types o...
irregularity manner. He enumerated the Vishamajwara as follows santataka, satataka,anyeduska, triteeyaka and chaturthaka c...
In Amarkosh the bhuta means keetanu. Jejjata considered Vishamajwara astridoshaja in origin. Most of the authors considere...
In the initial stages of the illness, this classical pattern may not be seen because there couldbe multiple groups (broods...
•   Early infection   •   Patients at extremes of age   •   Patients who are immune-compromised (extremes of age, malnouri...
Body ache, backache and joint pains:       These symptoms are fairly common in malaria. These can occur even during thepro...
encephalitis, meningitis, metabolic encephalopathy etc. As a rule of the thumb, malariashould be considered a possibility ...
Chest pain:       Acute retrosternal or precordial pain may be presenting feature of malaria. It mayradiate to the left or...
Jaundice:          Patients may present with history of yellowish discoloration of eyes and urine. Mildjaundice is fairly ...
Hepatosplenomegaly:       Patients can present with enlargement of liver and/or spleen, tender or non-tender,with or witho...
ovale infection, some sporozoites convert to dormant forms called hypnozoites, which cancause disease after months or year...
Figure –5                          Sporogonic and Erythrocytic cycles of Malaria       Rupture of a large number of erythr...
Figure – 6                        Exogenous and Endogenous Phases of MalariaLife cycle of Malaria       The life cycle of ...
Asexual phase in human hostTissue phase       Sporozoites are inoculated by infected mosquito into the host and disappear ...
grow in size to trophozoites absorbing haemoglogin leaving a pigment (haematin orhaemazoin) – a combination of haemoglobin...
salivary glands ready to be inoculated into a new host at the next blood meal. The durationof cycle in the mosquito is kno...
•   Repeated frequent seizures: Even without cerebral malaria, a child can experience       prolonged, frequent convulsion...
absent. Diarrhoea with blood is rare in early typhoid. The signs and symptoms in dysenteryare usually abdominal and remain...
Nidana of Jwara: (Aetiology)       The causative factor may be sarnikristha Nidana (immediate cause) and/orviprakristha Ni...
8. Asatmya Dravya bhojana                          9. Virudha Padartha bhojana (antagonist food)                          ...
Role of bhuta (Keetanu) in Vishamajwara       Susruta believed that Vishamajwara takes place due to agantuka Karana (exter...
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Evaluation of the efficacy of THE BHARANGYADI GHANAVATI IN VISHAMAJWARA WITH SPECIAL REFERENCE TO MALARIAL FEVER By MANGALAVVA .B. PATIL, Department of Kayachikitsa, Post graduate studies and research center D.G. MELMALAGI AYURVEDIC MEDICAL COLLEGE, Gadag - 582 103

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Vishamajwaram kc029 gdg

  1. 1. Evaluation of the efficacy ofTHE BHARANGYADI GHANAVATI IN VISHAMAJWARA WITH SPECIAL REFERENCE TO MALARIAL FEVER By MANGALAVVA .B. PATIL Dissertation submitted to the Rajiv Gandhi University of Health Sciences, Karnataka, Bangalore In partial fulfillment of the degree of Ayurveda Vachaspati M.D. In Kayachikitsa Under the Guidance of Dr. V. Varada Charyulu M.D. (Ayu) (Osm) Dr. R.V.Shettar M.D. (Ayu) Department of Kayachikitsa Post Graduate Studies & Research CenterD.G. MELMALAGI AYURVEDIC MEDICAL COLLEGE, GADAG 2002-2005
  2. 2. D.G.M.AYURVEDIC MEDICAL COLLEGE POST GRADUATE STUDIES AND RESEARCH CENTER GADAG, 582 103 This is to certify that the dissertation entitled “EVALUATION OF THE EFFICACY OFTHE BHARANGYADI GHANAVATI IN VISHAMAJWARA WITH SPECIAL REFERENCETO MALARIAL FEVER” is a bonafide research work done by “MANGALAVVA .B. PATIL”in partial fulfillment of the requirement for the post graduation degree of “AyurvedaVachaspati M.D. (Kayachikitsa)” Under Rajeev Gandhi University of Health Sciences,Bangalore, Karnataka.Dr. R V SHETTAR Dr. V. VARADA CHARYULU M.D. (Ayu) M.D. (Ayu) (Osm)Co- Guide GuideLECTURER IN KAYACHIKITSA Professor & HODDGMAMC, PGS&RC, Gadag Dept. of KayachikitsaDate: PGS&RCPlace: Gadag Date: Place: Gadag
  3. 3. J.S.V.V. SAMSTHE’S D.G.M.AYURVEDIC MEDICAL COLLEGE POST GRADUATE STUDIES AND RESEARCH CENTER GADAG, 582 103 Endorsement by the H.O.D, Principal/ head of the institution This is to certify that the dissertation entitled “EVALUATION OF THE EFFICACY OFTHE BHARANGYADI GHANAVATI IN VISHAMAJWARA WITH SPECIAL REFERENCETO MALARIAL FEVER” is a bonafide research work done by “MANGALAVVA .B. PATIL”under the guidance of Dr. V. VARADA CHARYULU, M.D. (Ayu) (Osm), Professor & HODand Dr. R V SHETTAR, M.D. (Ayu), in partial fulfillment of the requirement for the postgraduation degree of “Ayurveda Vachaspati M.D. (Kayachikitsa)” Under Rajeev GandhiUniversity of Health Sciences, Bangalore, Karnataka.. (Dr. V. Varada charyulu) (Dr. G. B. Patil) Professor & HOD Principal, Dept. of Kayachikitsa DGM Ayurvedic Medical College, PGS&RC Gadag Date: Date: Place: Gadag Place:
  4. 4. Declaration by the candidate I here by declare that this dissertation / thesis entitled “EVALUATION OF THEEFFICACY OF THE BHARANGYADI GHANAVATI IN VISHAMAJWARA WITH SPECIALREFERENCE TO MALARIAL FEVER” is a bonafide and genuine research work carried outby me under the guidance of Dr.V.Varada Charyulu M.D.(Ayu) and Dr. R.V.Shettar, M.D.(Ayu), lecturer in Kayachikitsa, DGMAMC, PGS&RC, Gadag.DatePlace MANGALAVVA .B. PATIL
  5. 5. Copy right Declaration by the candidate I here by declare that the Rajiv Gandhi University of Health Sciences, Karnatakashall have the rights to preserve, use and disseminate this dissertation/ thesis in print orelectronic format for the academic / research purpose.DatePlace MANGALAVVA .B. PATIL© Rajiv Gandhi University of Health Sciences, Karnataka
  6. 6. I express my deep gratitude to my guide Dr. V. Varadacharyulu M.D.(Ayu), Professor andH.O.D., for his timely advises and encouragement in every step of my success. I express my gratefulness to my co-guide Dr R. V. Shettar, M.D (Ayu) lecturer inKayachikitsa, for his time to time help and critical suggestions associated with expert guidance at thecompletion of this dissertation. I express my thankfulness to beloved principal Dr. G. B. Patil, Principal for hisencouragement as well as providing all necessary facilities for this research work. I express my profound sense of acknowledgement to various departments H.O.D.s, teachersand colleagues of sister concern departments along with the ministerial and sub staff of the D.G.M.Ayurvedic Medical College, Gadag. I express my sincere thanks to Dr. K. Shiva Rama Prasad, Dr. Shashidar. H. Doddamani, Dr.Kuber Sankh, Dr. P. Shivaramudu, Dr. M.C. Patil, Dr. Santhosh Belavadi, Dr. Mulkipatil and DrKona. I express my sincere thanks to Mr. Nandakumar for his help in statistical analysis of results. Aspecial thanks on this regard to Dr. Danappagoudar for his valuable support at the preparation of thedrug. I express my deepest gratitude to my beloved parents, Sri B.H.Patil and smt G.B. Patil, andmy husband Sri Shivkumargouda S.Patil, who supported me all the time. I express my sincere thanksto one and all of my relatives and well wishers Dr. D.M.Patil, Dr. Meenakshi, Dr. Shankargouda,Dr. Chetan, Dr. Joshi. D.P, All my colleagues and Harun Kowshik, Smt Valli Shree for their co-operation at all times. At first my sincere thanks to the subjects who co-operated at my dissertation, with out ofthem it would have been not a success.Place: Dr. MANGALAVVA .B. PATILDate: Bharangyadi Ghana Vati in Vishamajwara (malarial fever) 1
  7. 7. Evaluation of the efficacy of the Bharangyadi Ghana Vati in Vishamajwara with special reference to malarial fever Dr. MANGALAVVA .B. PATIL Abstract Vishamajwara vis-à-vis Malaria or a disease resembling malaria has been notedfor more than 4,000 years. Vishamajwara characterised by visamarambha (irregularonset). Dalhana consider bhutas (Keetanu – Parasites) responsible to produceVishamajwara. Cough may be a presenting feature of malaria with severe anaemia canbe a presenting feature of malaria. In Vishamajwara the Doshas are not only localised in Rasa Dhatu like in otherjwara, they spread through Rasa, Rakta, Mansa, Meda, Asthi and Majja to get thedifferent Vishamajwara such as Satata jwara, Santata jwara, Anyedushka jwara,Triteeyak jwara, Chaturthak jwara and Chaturthak jwara. In this trail drug Bharangyadi Ghana Vati, the prime herbs are – Bharangi andKirata Tikta. Panduhara, Jwarahara, Mootrakruchrahara, Hrudrogahara, Tridoshahara,Deepaka, Sangrahi, Rasayana, Panduhara, Kamalahara, Chardihara and AmaharaDravyas are used in the Bharangyadi Ghana Vati. Present study registers 30 patients, out of 68 approached patients. The remaining26 patients of Vishamajwara viz. Malaria, fulfilling the criteria of diagnosis and inclusivecriteria were included in the study. The observation of the jwramukta Lakshana shows that the effect of theBharangyadi Ghana Vati over Vishamajwara vis-à-vis Malaria is admissible.All theparameters except Yakrut Vruddhi and Pleeha Vruddhi show high significance.. Bharangyadi Ghana Vati in Vishamajwara (malarial fever) 2
  8. 8. Table of contents Heading Page numberChapter - 1 Introduction 1 to 6Chapter –2 Objectives 7 to 8Chapter –3 Review of literature 9 to 87Chapter –4 Methodology 88 to 107Chapter –5 Results 108 to 139Chapter –6 Discussion 140 to 157Chapter –7 Conclusion 158 to 163Chapter –8 Summary 164 to 164 Bibliographic References I to X Annex – Case sheet 1 to 6 Bharangyadi Ghana Vati in Vishamajwara (malarial fever) 3
  9. 9. List of figuresSno Figures heading Page1 Photograph of Parvateeya Mashaka 102 Geographical distribution of the Malaria 133 Postal Stamp released by Government of India on the occasion of 24 Malaria control4 Life cycle schematic diagram 375 Sporogonic and Erythrocytic cycles of Malaria 386 Exogenous and Endogenous Phases of Malaria 397 Ingredients of Bharangyadi Ghana Vati 688 Laboratory diagnosis of malaria fever 989 Finished Product of Bharangyadi Ghana Vati 108 List of Flow chartsSno Flow charts heading Page1 Classification of aetiology of Vishamajwara 462 Schematic diagram of Vishamajwara Samprapti 59 Bharangyadi Ghana Vati in Vishamajwara (malarial fever) 4
  10. 10. List of graphsSno Graph heading Page1 Distribution of patients by Age 1092 Distribution of patients by Age- gender 1113 Distribution of patients by Gender 1124 Distribution of patients by Religion 1135 Distribution of patients by Occupation 1156 Economic status distribution Vs Vishamajwara vis-à-vis Malaria 1167 Distribution of patients by Economic status 1178 Distribution of patients by Hygienic Condition 1199 Distribution of patients by Diet 12010 Distribution of patients by presenting complaints 12111 Distribution of patients by Associated features 12312 Distribution of patients by type of Jwara 12413 Distribution of patients by Pranavaha sroto dusti Lakshana 12514 Distribution of patients by Rasavaha sroto dusti Lakshana 12615 Distribution of patients by Annavaha sroto dusti Lakshana 12716 Distribution of patients by Swedavaha sroto dusti Lakshana 12817 Distribution of patients by Nidana 13018 Distribution of patients by Poorva Roopa 13119 Distribution of patients by Jwaramukta Lakshana 13220 Aniyamita Jwara (mean) in Vishamajwara 13321 Graph the temperatures (mean) in Vishamajwara 13522 Distribution of patients by Result in Vishamajwara 137 Bharangyadi Ghana Vati in Vishamajwara (malarial fever) 5
  11. 11. List of tablesSno Table Heading Page1 Showing the Dosha pradhanyata in Malaria 552 Duration and vega in different jwaras 583 Showing the Vishamajwara vishista Lakshana 604 Distribution of patients by Age 1095 Distribution of patients by Age- gender 1106 Distribution of patients by Gender 1127 Distribution of patients by Religion 1138 Distribution of patients by Occupation 1149 Distribution of patients by Economic status 11710 Distribution of patients by Hygienic Condition 11811 Distribution of patients by Diet 11912 Distribution of patients by presenting complaints 12113 Distribution of patients by Associated features 12214 Distribution of patients by type of Jwara 12315 Distribution of patients by Pranavaha sroto dusti Lakshana 12516 Distribution of patients by Rasavaha sroto dusti Lakshana 12617 Distribution of patients by Annavaha sroto dusti Lakshana 12718 Distribution of patients by Swedavaha sroto dusti Lakshana 12819 Distribution of patients by Nidana 12920 Distribution of patients by Poorva Roopa 13021 Distribution of patients by Jwaramukta Lakshana 13222 Evaluation of Subjective Parameters 13323 Evaluation of objective Parameters 13424 Showing the temperatures (mean) in Vishamajwara 13525 Distribution of patients by Result in Vishamajwara 13626 Statistical analysis of the clinical parameters at the end of treatment (21 137 days)27 Statistical analysis of the objective parameters at the end of treatment 138 (21 days)28 Statistical analysis of the clinical parameters at the end of follow-up (36 138 days)29 Describing the pharmacological properties of Bharangyadi Ghana Vati 14530 Describing the Chemical constituents and Indications of individual 146 components of Bharangyadi Ghana Vati Bharangyadi Ghana Vati in Vishamajwara (malarial fever) 6
  12. 12. Chapter –1 Introduction “ osquito makes man Eunuch”, is popular dialogue of the film actor.Fact is that the mosquito really conquers the eco-symphony of the earth and disturbed muchand more of human life. Now a day an average spending of human on mosquito repellentsare sufficient to maintain a family. Asian, African, etc, tropical countries are badly effectedby this small tiny untidy creature and Governments are fallen because of the same. Vishamajwara, a most popular Ayurvedic term in turn of modern medicalterminology co-related to malarial fever, is a protozoan disease caused by genusplasmodium and transmitted to man by certain species of infected female anophelesmosquito. Indias geographic position and climatic conditions are favourable for thetransmission of malaria. Frequently people living in the endemic areas are prone for thisinfection. Out of 300-500 million clinical cases around 100 countries and one million deathsdue to malarial malady are noticed globally. The 38th world health assembly in 1985 recommended that, malaria control shouldbe developed as an integral part of the national primary health care systems. 1-2-3 Vishamajwara is irregular (inconsistent) in its arambha (nature of onsetcommitment), kriya (action production of symptoms) and kala (time of appearance) and 4-5-6possesses anushanga (persistence for long periods) . As on today, the malarial parasitehas developed resistance to chloroquine compounds, which are used vividly for the pastthree decades. The emergence of multiple-drug resistant strains of malaria, which has accompanied Bharangyadi Ghana Vati in Vishamajwara (malarial fever) 1
  13. 13. each new class of anti-malarial drugs, is one of most significant threat to the health of peoplein tropical countries. While there is widespread agreement that a fresh approach to theprevention and treatment of malaria is urgently needed, solutions have tended to focus onthe development of new classes of drugs. More recently, there has been an emphasis onpromoting combination therapy of existing drugs as a means of preventing resistance. Historically, however, local communities in tropical regions have used local flora asa means of preventing and treating malaria (Kirby, 1997). It can be argued that thesetraditional medicines, based on the use of whole plants with multiple ingredients or ofcomplex mixtures of plant materials, constitute combination therapies that may well combatthe development of resistance to anti-malarial therapy.Resistance, synergism and traditional medicines Medical science is beginning to recognise aspects of synergy, complexity andpotentiation in malaria therapy. At the same time, little significance is as yet being given tothe obvious point that all of the major anti-malarial have been derived from plants, oftenbased on traditional knowledge about the effects of the plants against fever, or specifically,malaria. The call to combine anti-malarials overlooks the fact that combination existed inthe traditional formulations before the process of extraction took place. In view of this, itmust be asked whether any pre-existing synergism, and hence challenge to the developmentof resistance, may have been lost in the process of extraction, isolation and synthesis of newmolecules. For instance, the artemisinin drugs (artesunate, artemehter, dihydroartemisinin) arederived from artemisia annua, used in traditional Chinese medicine as an antipyretic. Anexamination of traditional Chinese medical knowledge and practice would reveal that it was Bharangyadi Ghana Vati in Vishamajwara (malarial fever) 2
  14. 14. usual for this plant to be used in combination with others in the treatment of fevers. In thedevelopment of the new artemisinin drugs, not only has this been overlooked, but thecomplex of alkaloids in the plant itself have been sacrificed for the purpose of isolation of aso-called single active ingredient. Indeed, flavinoids in Artemisia annua, which arestructurally unrelated to the anti-malarial drug artemisinin, enhance the in vitroantiplasmodial activity of artemisinin 7. Elsewhere, synergism has been observed between the alkaloids of the anti-malarialplant Ancistrocladus peltatum. A total alkaloid extract of this plant had far greater anti-parasitic activity than any of the six alkaloids isolated subsequently. In studies on anti-malarial plants from Madagsacar, the alkaloids bisbenzylisoquinoline , novel pavine andbenzyl tetrahydroisoquinolines all were found to potentiate the anti-parasitic activity ofchloroquine in vitro and, in some case, in vivo. Preparations of these plants are currentlybeing tested as adjutants to chloroquine therapy in Madagascar (Kirby, 1997). In Uganda,there is data from clinical case reports that a traditional Ugandan herbal remedy is effectiveagainst malaria. (Bitawha et. al., 1997) Utilisation of traditional medicine is widespread in developing countries and theefficacious of many traditional treatments have been well documented, including in skindisease, malaria and other disorders. Despite growing policy interest in traditional medicine,and the seminal 1997 Dakar meetings on malaria recommending research into herbal anti-malarial, there has been almost no research into the clinical effectiveness of herbal remediesas they are used in real life. Bharangyadi Ghana Vati in Vishamajwara (malarial fever) 3
  15. 15. The research initiative for traditional anti-malarial methods (RITAM) To redress this situation, a partnership was established in December 1999 betweenthe Global Initiative For Traditional Systems (GIFTS) of Health, the Tropical DiseaseResearch Programme of WHO and individual scientists, traditional health practitioners andothers to investigate evaluate and, where appropriate, develop traditional herbal medicines tocombat malaria. It is the Research Initiative for Traditional Anti-malarial Methods (RITAM) Many people live in malarious regions, traditional herbal medicines may be the onlycourse of treatment available. Therefore, research into, promoting and increasing theunderstanding of the nature of crude plant derived medicines are key research priorities.Plants are usually identified for study on the basis of a traditional reputation foreffectiveness, usually for treating or preventing malaria and other fever related conditions. In designing new treatments, drugs and public health programmes in developingcountries, it can be considered unscientific to cast aside traditional knowledge and wisdomafter cursory review, on the assumption that modern methods of analysis and explanation aresuperior. RITAM members have developed four specialist groups to implement a researchstrategy designed to make a significant contribution to malaria control programmes: 1. Policy, advocacy and funding 2. Pre-clinical studies 3. Clinical development 4. Repellence and Vector Control 8 The Indian Systems of Medicine & Homoeopathy is popular in a large number ofStates in the country. There are separate Directorates of ISM&H in 18 States. Ayurveda, Bharangyadi Ghana Vati in Vishamajwara (malarial fever) 4
  16. 16. Homeopathy, Unani, Yoga & Naturopathy and Siddha systems together called as IndianSystems of Medicine. These systems have become part of the culture and traditions of ourcountry 9. Drug resistance to chloroquine in P. falciparum was reported in India for the firsttime from Assam in 1973. Since then the foci of resistance have spread to many more statesall over India. The situation has further deteriorated in the recent past due to parasitebecoming resistant to other available drugs in addition to chloroquine. Sulphadoxine-pyrimethamine, a second line drugs for P. falciparum is not effective for P. vivax malaria.Quinine is still effective but as oral monotherapy it has limited role in mild malaria becauseof 7-day regimen. Mefloquine and artemisinin have specific indications. Therefore, newdrugs and treatment strategies need to be developed as a priority. Development of new drugs involves extensive pre clinical and toxicological studiesfollowed by well-planned clinical trials. At MRC, a number of new drugs have beenscreened in clinical trials for evaluation of safety and efficacy. Based on these data, thedrugs have been registered with Drugs Controller General of India for commercialmarketing and also for use in national programme underAyush-64 Ayush-64 is a combination of four plants namely Alstonia scholaris (aqueous extractof bark–1 part) Picrorhiza kurroa Royle (aqueous extract of rhizome–1 part), Swertia chirata(aqueous extract of whole plant–1 part) and Caesalpinia crista Linn (fine powder of seedpulp–3 parts). The drug was patented by the Central Council of Ayurveda and Siddha and toconfirm the efficacy in well designed scientific trial, open prospective, non-crossover, Bharangyadi Ghana Vati in Vishamajwara (malarial fever) 5
  17. 17. randomised clinical trial was conducted in P. vivax malaria patients at the Centre in 10.collaboration with NAMP Results showed that with Ayush-64 cure rate on Day 28 was48.9% at a dose of 1 g three times a day for 5–7 days as against 100% with chloroquine1500 mg over three days 11. Ayurvedic herbs have an important role in the treatment of malarial fever. Even thechloroquine is a derivative of herbal origin. In the treatment of Vishamajwara many yogashave been explained in Ayurveda. The composition of Bharangyadi Yoga is easily available,low-priced and has no proved adverse effects 12 against malarial fever. Thus the present study has been under taken as “Evaluation of the efficacy of theBharangyadi Ghanavati in Vishamajwara with special reference to malarial fever”. A fewnumbers of clinical trials have been conducted in different Ayurvedic institutes in India,regarding Vishamajwara. These are as follows - Year / scholar Title Institute name1980 M.V. Chari Clinical and experimental study of medicinal Gujrat Ayurveda plants in the treatment of malaria. university, jamnagar.1981 M.V. Chari A double blind clinical trial with ayush. 64 an Do Ayurvedic drug in P. vivax malaria.1981 K.D. Sharma Clinical trial of ayush 64 in case of malaria C.C.R.A.&S. New delhi1982 Kanaka rai dal A study of management of Vishamajwara G.A.U. Jamnagar1982 Jagabandhu Clinical study of panchatikta ghaanabati on G.A.M. Puri. (orissa)das Vishamajwara1985 Kishore panda “therapeutic evaluation of Kiratatikta ghanabati Do on Vishamajwara”1994 B. Baliarsingh “clinical trial on ajajiguda yoga in Do Vishamajwara vis-à-vis malaria1991 Deshmukh 54 Anaetiopathological study on the management Kerala university of vishama jwara with bnuranggadi kwata trivendrum1983 mahant Ushna jwara Governmentdhaneshwar Ayurvedic college hyderabad Bharangyadi Ghana Vati in Vishamajwara (malarial fever) 6
  18. 18. Chapter -2 Objectives resent study bears the following objectives - 1. To evaluate the efficacy of the Bharangyadi Ghanavati in Vishamajwara (Malarial fever) 2. To evaluate the antipyretic properties of Bharangyadi Ghanavati in Vishamajwara (Malarial fever) 3. To evaluate the anti-malarial properties of Bharangyadi Ghanavati in Vishamajwara (Malarial fever) Detailed discussion of above mentioned objectives are as under –1. To evaluate the efficacy of the Bharangyadi Ghana Vati in Vishamajwara (Malarial fever) Many herbal compounds and herbo-mineral compounds are listed in Ayurveda topacify the Jwara, especially Vishamajwara. Ayurveda offers more importance to that of therise of temperature, which is a protective and also pathological identity of the any ailment Bharangyadi Ghana Vati in Vishamajwara (malarial fever) 7
  19. 19. present in the body. The jwara called as fever may not be a big problem from thecontemporary but as par Ayurveda it is a primary symptom and a disease also some times acomplication. This particular condition needs through emphasis and management. In thisprocess a laboratory identified malarial parasite expression as fever i.e. Vishamajwara isextensively studied and the efficacy of the Bharangyadi Ghana Vati in Vishamajwara isemphasized.2. To evaluate the antipyretic properties of Bharangyadi Ghana Vati in Vishamajwara (Malarial fever) The main aim of the study is to see the antipyretic effect of the selected drug,Bharangyadi Ghana Vati in Vishamajwara. The fever is rise in body temperature. Thisprimary symptom which give the inconvenience is to be forbidden at the earliest to providecomfort to the patient. Thus the antipyretic effect is specially studies under the guide lines ofAyurveda in comparison with that of the contemporary medicine.3. To evaluate the anti-malarial properties of Bharangyadi Ghana Vati in Vishamajwara (Malarial fever) The chosen drug Bharangyadi Ghana Vati is assumed as a best medicament at therelieving the jwara i.e. fever by all means. Its antipyretic effects also a sure thing. But manya times a doubt is raised is whether any Ayurvedic drug acts as anti-microbial, anti-viral oranti-malarial? To achieve the answer for the above raised question and to strengthen theAyurvedic glory to establish Ayurvedic scientific grounds the evaluation of the anti-malarialproperties were under taken as one of the objectives of the study. Bharangyadi Ghana Vati in Vishamajwara (malarial fever) 8
  20. 20. Chapter -3 Literary review yurveda is a perfect science of life and consists of a body of mostremarkable knowledge on the internal mechanism of human health and longevity, onmedicinal herbs and therapeutic roots, on the efficacious treatment of human ills byeradicating from the human system the very sources of their causation. This great medicalscience and humanity’s most ancient and finest preventive school of practical medicine,which has been practised in India, century after century for over four thousand years, byexpert Vaidyas. To those who claim to have a knowledge of this ancient medicinal scienceenriched by the happy results of the researches and advancement made by eminent Vaidyasin succeeding ages, its superior merits over the Western systems of medicine, and itsimmense value, do not need any delineation. Such names of the great pioneers who added tothe development of the science of Ayurveda, as Vagbhata, Madhava, Jivaka and BhavaMishra of Banaras are well known. Ayurveda has a significant name. It is the knowledge of the science, which ensureshealth and longevity. It is in no way inferior to other systems. The Ayurvedic doctors hadvery great influence in the field of medicine. Charaka, Sushruta, Vagbhata, Madhava Nidhanare the well-known scientific books on Indian Medicine. This glorious system of medicinefell into disease owing to lack of State support and facilities for proper study, training andresearch. Susruta, while classifying different insects expands the mosquitoes as five varieties.They are Samudra Mashaka, Parimandala Mashaka, Hasti Mashaka, Krishna Mashaka and Bharangyadi Ghana Vati in Vishamajwara (malarial fever) 9
  21. 21. Parvateeya Mashaka. Out of these the last Parvateeya Mashaka are more toxic and fatal innature. The symptoms of this type resemble with the malarial fever of present discussion 13. Figure –1 Photograph of Parvateeya Mashaka Malaria is a protozoal disease transmitted by the Anopheles mosquito, caused byminute parasitic protozoa of the genus Plasmodium, which infect human and insect hostsalternatively. It is a very old disease and prehistoric man is thought to have suffered frommalaria. It probably originated in Africa and accompanied human migration to theMediterranean shores, India and South East Asia. In the past it used to be common in themarshy areas around Rome and the name is derived from the Italian, (mal-aria) or "bad air";it was also known as Roman fever. Today some 500 million people in Africa, India, SouthEast Asia and South America are exposed to endemic malaria and it is estimated to causetwo and a half million deaths annually, one million of which are children. Fishermen and traders, long before British colonisation, probably introduced thedisease into northern Australia and in the past malaria were not uncommon in the northernparts of the country. In Western Australia an explosive outbreak of falciparum malariaoccurred at Fitzroy Crossing in 1934 which at first was mistaken for influenza and resulted Bharangyadi Ghana Vati in Vishamajwara (malarial fever) 10
  22. 22. in 165 deaths. WHO declared Australia free of malaria in 1981, however since that time 9patients have contracted locally acquired malaria. The so called "airport malaria" has become a problem in recent years. A publicanworking in an establishment close to Londons Heathrow Airport became acutely ill and wasfound to be suffering from falciparum malaria, he had never been out of the country. A ladydriving her car past the same airport became ill with malaria although she too had neverbeen out of the country. Four workers unloading a cargo plane at Amsterdam airport becameinfected with malaria. It is assumed that infected mosquitoes were carried on planes fromAfrica and released at the destination airport. While it was recognised that the Anopheles mosquito played a key role in thetransmission of the disease it was not until 1948 that all the stages in its life cycle wereidentified. The parasite undergoes a development stage in the mosquito and the female of thespecies requires a blood meal to mature her eggs. She bites a human and injects materialfrom her salivary glands, which contains primitive malarial parasites called sporozoites,before feeding. These sporozoites circulate in the blood for a short time and then settle in theliver where they enter the parenchymal cells and multiply; this stage is known as pre-erythrocytic schizogony. After about 12 days there may be many thousands of youngparasites known as merozoites in one liver cell the cell ruptures and the free merozoitesenter red blood cells. The blood stages of the four species of malaria can be seen in thesection on diagnosis. In the case of P. vivax, and P.ovale the liver cycle continues andrequires a course of primaquine to eliminate it. P.falciparum on the other hand does not havea continuing liver cycle. Bharangyadi Ghana Vati in Vishamajwara (malarial fever) 11
  23. 23. In the red blood cells the parasites develop into two forms, a sexual and an asexualcycle. The sexual cycle produces male and female gametocytes, which circulate in the bloodand are taken up by a female mosquito when taking a blood meal. The male and femalegametocytes fuse in the mosquitos stomach and form oöcysts in the wall of the stomach.These oöcysts develop over a period of days and contain large numbers of sporozoites,which move to the salivary glands and are ready to be injected into man when the mosquitonext takes a meal. In the asexual cycle the developing parasites form schizonts in the redblood cells which contain many merozoites, the infected red cells rupture and release a batchof young parasites, merozoites, which invade new red cells. In P.vivax, P.ovale and probablyP.malariae, all stages of development subsequent to the liver cycle can be observed in theperipheral blood. However, in the case of P.falciparum only ring forms and gametocytes areusually present in the peripheral blood. Developing forms appear to stick in the bloodvessels of the large organs such as the brain and restrict the blood flow with seriousconsequences. While all four species have a haemolytic component i.e. when a new brood ofparasites break out of the red blood cell this is usually of little consequence. The exception isfalciparum malaria where the parasites multiply very rapidly and may occupy 30% or moreof the red blood cells causing a very significant level of haemolysis. One reason for this isthat P.falciparum invades red cells of all ages whereas P.vivax and P.ovale prefer youngerred cells, while P.malariae seeks mature red cells. Bharangyadi Ghana Vati in Vishamajwara (malarial fever) 12
  24. 24. Figure –2 Geographical distribution of the MalariaHistory of malaria Malaria or a disease resembling malaria has been noted for more than 4,000 years.From the Italian for "bad air," malaria has probably influenced to a great extent humanpopulations and human history.Ancient History (2700 BCE-340 CE) The symptoms of malaria were described in ancient Chinese medical writings. In2700 BC, several characteristic symptoms of what would later be named malaria weredescribed in the Nei Ching, (The Canon of Medicine. Nei Ching was edited by EmperorHuang Ti). Malaria became widely recognised in Greece by the 4th century BCE, and it wasresponsible for the decline of many of the city-state populations. Hippocrates noted theprincipal symptoms. By the age of Pericles, there were extensive references to malaria in theliterature and depopulation of rural areas was recorded. In the Susruta, a Sanskrit medical Bharangyadi Ghana Vati in Vishamajwara (malarial fever) 13
  25. 25. treatise, the symptoms of malarial fever were described and attributed to the bites of certaininsects. A number of Roman writers attributed malarial diseases to the swamps. In China, during the second century BCE, the Qinghao plant (Artemisia annua L)was described in the medical treatise, 52 Remedies, found in the Mawangdui Tomb. In 340CE, the anti-fever properties of Qinghao were first described by Ge Hong of the East YinDynasty. Chinese scientists isolated the active ingredient of Qinghao in 1971. Known asartemisinin, it is today a very potent and effective anti-malarial drug, especially incombination with other medicines.Quinine (Early 17th Century) Following their arrival in the New World, the Spanish learned of a medicine used forthe treatment of fevers. Spanish Jesuit missionaries in South America learned of a medicinalbark from indigenous Indian tribes. With this bark, the Countess of Chinchón, the wife ofthe Viceroy of Peru, was cured of her fever. The bark from the tree was then called Peruvianbark and the tree was named Cinchona after the countess. The medicine from the bark isnow known as the antimalarial, quinine. Along with artemisinin, quinine is one of the mosteffective antimalarial drugs available today.Discovery of the Malaria Parasite (1880) Charles Louis Alphonse Laveran, a French army surgeon stationed in Constantine,Algeria, was the first to notice parasites in the blood of a patient suffering from malaria.This occurred on the 6th of November 1880. For his discovery, Laveran was awarded theNobel Prize in 1907. Bharangyadi Ghana Vati in Vishamajwara (malarial fever) 14
  26. 26. Differentiation of Species of Malaria (1886) Camillo Golgi, an Italian neurophysiologist, established that there were at least twoforms of the disease, one with tertian periodicity (fever every other day) and one withquartan periodicity (fever every third day). He also observed that the forms produceddiffering numbers of merozoites (new parasites) upon maturity and that fever coincided withthe rupture and release of merozoites into the blood stream. He was awarded a Nobel Prizein Medicine for his discoveries in neurophysiology in 1906.Naming of Human Malaria Parasites (1890,1897) The Italian investigators Giovanni Batista Grassi and Raimondo Filetti firstintroduced the names Plasmodium vivax and P. malariae for two of the malaria parasitesthat affect humans in 1890. Laveran had believed that there was only one species, Oscillariamalariae. An American, William H. Welch, reviewed the subject and, in 1897, he named themalignant tertian malaria parasite, P. falciparum. There were many arguments against theuse of this name, however, the use was so extensive in the literature that a change back tothe name given by Laveran was no longer thought possible. In 1922, John William WatsonStephens described the fourth human malaria parasite, P. ovale.Discovery That Mosquitoes Transmit Malaria Parasites (1897-1898) On August 20th, 1897, Ronald Ross, a British officer in the Indian Medical Service,was the first to demonstrate that malaria parasites could be transmitted from infectedpatients to mosquitoes. In further work with bird malaria, Ross showed that mosquitoescould transmit malaria parasites from bird to bird. This necessitated a sporogonic cycle (thetime interval during which the parasite developed in the mosquito). Thus, the problem of Bharangyadi Ghana Vati in Vishamajwara (malarial fever) 15
  27. 27. malaria transmission was solved. For his discovery, Ross was awarded the Nobel Prize in1902.Discovery of the Transmission of the Human Malaria Parasites (1898-1899) Led by Giovanni Batista Grassi, a team of Italian investigators, which includedAmico Bignami and Giuseppe Bastianelli, collected Anopheles claviger mosquitoes and fedthem on malarial patients. The complete sporogonic cycle of Plasmodium falciparum, P.vivax, and P. malariae was demonstrated. In 1899, mosquitoes infected by feeding on apatient in Rome were sent to London where they fed on two volunteers, both of whomdeveloped benign tertian malaria.The Panama Canal (1905-1910) The construction of the Panama Canal was made possible only after yellow fever andmalaria were controlled in the area. These two diseases were a major cause of death anddisease among workers in the area. In 1906, there were over 26,000 employees working onthe Canal. Of these, over 21,000 were hospitalised for malaria at some time during theirwork. By 1912, there were over 50,000 employees, and the number of hospitalised workershad decreased to approximately 5,600. Through the leadership and efforts of WilliamCrawford Gorgas, Joseph Augustin Le Prince, and Samuel Taylor Darling, yellow fever waseliminated and malaria incidence markedly reduced through an integrated program of insectand malaria control.The U.S. Public Health Service (USPHS) and Malaria (1914-1942) During the U.S. military occupation of Cuba and the construction of the PanamaCanal at the turn of the 20th century, U.S. officials made great strides in the control ofmalaria and yellow fever. In 1914 Henry Rose Carter and Rudolph H. von Ezdorf of the Bharangyadi Ghana Vati in Vishamajwara (malarial fever) 16
  28. 28. USPHS requested and received funds from the U.S. Congress to control malaria in theUnited States. Various activities to investigate and combat malaria in the United Statesfollowed from this initial request and reduced the number of malaria cases in the UnitedStates. The USPHS established malaria control activities around military bases in themalarious regions of the southern United States to allow soldiers to train year round.The U.S. Tennessee Valley Authority (TVA) - The Integration of Malaria Control withEconomic Development (1933) U.S. President Franklin D. Roosevelt signed a bill that created the TVA on May 18,1933. The law gave the federal government a centralised body to control the Tennesseerivers potential for hydroelectric power and improve the land and waterways fordevelopment of the region. An organised and effective malaria control program stemmedfrom this new authority in the Tennessee River valley. Malaria affected 30 percent of thepopulation in the region when the TVA was incorporated in 1933. The Public Health Serviceplayed a vital role in the research and control operations and 1947 essentially eliminated thedisease. Controlling water levels and insecticide applications reduced Mosquito breedingsites.Chloroquine (1934, 1946) A German, Hans Andersag discovered chloroquine, in 1934 at Bayer I.G.Farbenindustrie A.G. laboratories in Eberfeld, Germany. He named his compound resochin.Through a series of lapses and confusion brought about during the war, chloroquine wasfinally recognised and established as an effective and safe anti-malarial in 1946 by Britishand U.S. scientists. Bharangyadi Ghana Vati in Vishamajwara (malarial fever) 17
  29. 29. Dichloro-diphenyl-trichloroethane (DDT) (1939) A German chemistry student, Othmer Zeidler, synthesized DDT in 1874, for histhesis. Paul Müller in Switzerland did not discover the insecticidal property of DDT until1939. Various militaries in WWII utilised the new insecticide initially for louse-bornetyphus. DDT was used for malaria control at the end of WWII after it had proven effectiveagainst malaria-carrying mosquitoes by British, Italian, and American scientists. Müller wonthe Nobel Prize for Medicine in 1948.Malaria Control in War Areas (MCWA) (1942-1945) MCWA was established to control malaria around military training bases in thesouthern United States and its territories, where malaria was still problematic. Many of thebases were established in areas where mosquitoes were abundant. MCWA aimed to preventreintroduction of malaria into the civilian population by mosquitoes that would have fed onmalaria-infected soldiers, in training or returning from endemic areas. During theseactivities, MCWA also trained state and local health department officials in malaria controltechniques and strategies.CDC and Malaria (1946-present) CDCs mission to combat malaria began at its inception on July 1, 1946. TheCommunicable Disease Centre, as CDC was first known, stemmed from MCWA. Thus,much of the early work done by CDC was concentrated on the control and eradication ofmalaria in the United States. With the successful reduction of malaria in the United States,the CDC switched its malaria focus from eradication efforts to prevention, surveillance, andtechnical support both domestically and internationally. This is still the focus of CDCsMalaria Branch today. Bharangyadi Ghana Vati in Vishamajwara (malarial fever) 18
  30. 30. Eradication of Malaria in the United States (1947-1951) The National Malaria Eradication Program, a co-operative undertaking by state andlocal health agencies of 13 Southeastern states and the CDC, originally proposed by LouisLaval Williams, commenced operations on July 1, 1947. By the end of 1949, over 4,650,000house-spray applications had been made. In 1947, 15,000 malaria cases were reported. By1950, only 2,000 cases were reported. By 1951, malaria was considered eradicated from theUnited States.Eradication Efforts Worldwide: Success and Failure (1955-1978) With the success of DDT, the advent of less toxic, more effective synthetic anti-malarials, and the enthusiastic and urgent belief that time and money were of the essence,the World Health Organisation (WHO) submitted at the World Health Assembly in 1955 anambitious proposal for the eradication of malaria world wide. Eradication efforts began andfocused on house spraying with residual insecticides, anti-malarial drug treatment, andsurveillance, and would be carried out in 4 successive steps: preparation, attack,consolidation, and maintenance. Successes included eradication in nations with temperateclimates and seasonal malaria transmission. Some countries such as India and Sri Lanka hadsharp reductions in the number of cases, followed by increases to substantial levels afterefforts ceased. Other nations had negligible progress (such as Indonesia, Afghanistan, Haiti,and Nicaragua). Some nations were excluded completely from the eradication campaign(most of sub-Saharan Africa). The emergence of drug resistance, widespread resistance toavailable insecticides, wars and massive population movements, difficulties in obtainingsustained funding from donor countries and lack of community participation made the long- Bharangyadi Ghana Vati in Vishamajwara (malarial fever) 19
  31. 31. term maintenance of the effort untenable. Completion of the eradication campaign waseventually abandoned to one of control.Fall of Roman Empire because of Malaria Could ancient childrens burial ground contain clues about how one of the worldsgreatest empires came to an end? Andrew Thompson explores the theory that malaria wasthe silent killer responsible for the fall of Rome. A British scientist proved conclusively that the most dangerous type of malaria was akiller in imperial Rome. The scientist relied on the latest DNA techniques that arerevolutionising the understanding of the role of disease in ancient times. The malarial DNAfrom a Roman site, dating from around AD 450, is the oldest definite evidence of malaria inhistory. The finding of malaria was a remarkable and complicated piece of detective work,which spanned the last ten years. At its height, the Roman Empire stretched from Scotland in the NorthernHemisphere to the deserts of Africa in the south. The empire lasted for over 500 years,although its eastern part, the Byzantine Empire, lasted for several more centuries. When theempire collapsed, hordes of barbarian armies, including the infamous Vandal pirates invadedItaly throughout the fifth century AD. Rome was transformed from a bustling city ofmillions to a provincial town of a few thousand, surrounded by swamps. The anarchy of theDark Ages had begun. Although there has been no shortage of theories, it has never been clear why Romebecame so vulnerable to foreign invaders at this time. Political instability, the collapse offood supplies to Rome, and even the infamous lead in the water supplies have all been Bharangyadi Ghana Vati in Vishamajwara (malarial fever) 20
  32. 32. implicated. Historians have generally agreed that Romes downfall was due to a combinationof many factors 14.Past and present of Malaria Mosquitoes probably originated in Africa (along with mankind), and fossils ofmosquitoes up to 30 million years old, show that the malaria vector, the malaria mosquito,was present well before the earliest history. Hippocrates, a physician born in ancient Greece,today regarded as the "Father of Medicine", was the first to describe the manifestations ofthe disease, and relate them to the time of year and to where the patients lived. Before this,the supernatural was blamed. The association with stagnant waters (breeding grounds for theAnopheles mosquito) led the Romans to begin drainage programs, the first interventionagainst malaria. The first recorded treatment dates back to 1600, when the bitter bark of the Cinchonatree in Peru was used by the native Peruvian Indians. By 1649, the bark was available inEngland, as "Jesuits powder," so that those suffering from "agues" might benefit from thechemical substance quinine, which it contained. Not until 1889 was the protozoal (singlecelled parasite) cause of malaria discovered by Alphonse Laveran working in Algeria, andonly in 1897 was the Anopheles mosquito demonstrated to be the vector for the disease byRonald Ross 15. It was the army surgeon, Ronald Ross, who undertook the experimental testing of themosquito-theory, proposed by both Laveran and the investigator, Patrick Manson. Thesolution came from India, while Ross was commissioned in the Indian Medical Service, andin the late 1890s the mosquito hypothesis could be established. Bharangyadi Ghana Vati in Vishamajwara (malarial fever) 21
  33. 33. Malaria Control Operation The discovery of the insecticide DDT in 1942, by Paul Müller the Nobel PrizeLaureate in Physiology or Medicine, 1948, and its first use in Italy in 1944, made the idea ofglobal eradication of malaria seem possible. Subsequently, widespread systematic controlmeasures such as spraying with DDT, coating marshes with paraffin (to kill Anophelesmosquito larvae), draining stagnant water, and the widespread use of nets and cheap,effective drugs such as chloroquine were implemented - with impressive results. Despiteinitial success, there was a complete failure to eradicate malaria in many countries due to anumber of factors. Although technical difficulties such as mosquito and parasite drugresistance have played a part, the main failure to reduce the disease is probably due to socialand political factors preventing efficient application of control measures. Despite the setbacks, up until 1969, when the global eradication policy was finallyabandoned, the following European countries had managed to completely eradicate endemicmalaria by interrupting transmission: Hungary, Bulgaria, Romania, Yugoslavia, Spain,Poland, Italy, Netherlands and Portugal. From the early 1970s, the malaria situation has slowly and progressively deterioratedand reduced control measures between 1972 and 1976, due to financial constraints, led to amassive 2-3 fold increases in cases globally. Spraying never truly eradicated the mosquitoesanywhere, and the reduction in the more persistent P. vivax infections were much less thanfor P. falciparum - though the latter returned in much greater strength as control measureswaned. The growing interchange of populations between countries where malaria isprevalent and malaria free countries is responsible for the continuous increase in the numberof imported malaria cases in European countries, and causes serious concern because of Bharangyadi Ghana Vati in Vishamajwara (malarial fever) 22
  34. 34. possible epidemic focal resurgence in receptive areas such as the Mediterranean. Since1976, several new pockets of malaria transmission have evolved, and a WHO 1980 reportrecommended that countries, which had become non-malarious should maintain at least onemalaria vigilance unit. The World Health Organization (WHO) warned about increased risk of vector-borne diseases such as malaria and dengue fever across tsunami-affected areas in SoutheastAsia. Nearly four weeks after the disaster struck the region on 26 December, theorganization is strengthening its disease surveillance, as stagnant water conditions createconditions for mosquito vectors to multiply to sufficient levels to potentially cause severepublic health problems. Most affected countries in the region are endemic for dengue fever and malariaexcept the Maldives, which has no malaria cases but does have dengue cases. With the onsetof the rainy season, particularly in Indonesia and Sri Lanka, a rise in the cases can beexpected at this time of the year 16. According to the World Health Organisation, the following statistics reveal thespread of malaria in the world. Africa: Ninety-seven million cases of malaria a year. Thetropical region’s leading killer of children claims five percent under five. Latin America:One million cases a year. The settlement of people in mosquito-infested rain forests in Brazilhas exposed millions to the disease. Asia: Nine million cases a year. New, hard-to-treatstrains are rapidly gaining ground 17.Malaria control – philately It is fantasising for a researcher to observe in various angles, the topic chosen. TheMalaria, a disease caused by an insect placed it self in the philately because of its Bharangyadi Ghana Vati in Vishamajwara (malarial fever) 23
  35. 35. importance. No other country other than India releases a stamp on a Mosquito. The Malariaeradication programme is to be recollected and on the occasion 4 Annas (25 Paise) stamp isreleased by the Indian Postal Department is shown below. Figure – 3 Postal Stamp released by Government of India on the occasion of Malaria controlEpidemiology Malaria is primarily a disease of the tropics and subtropics and is widespread in hothumid regions of Africa, Asia and South and Central America. The disease was alsocommon in many temperate areas including the USA, Europe and northern Eurasia andAsia, but has been eradicated. In many areas, which previously had malaria under control, 18.are experiencing resurgence The four human malarial species exhibit an overlappinggeographical distribution (Box). P. vivax and P. falciparum are the most commonlyencountered species with P. vivax being the most wisespread geographically. Mixedinfections are common in endemic areas. "Everything about malaria is so moulded by localconditions that it becomes a thousand epidemiological puzzles." Hackett (1937) The above quote emphasises the complexity of malaria and the many facets thedisease exhibits. Different communities will experience different malaria and consequently Bharangyadi Ghana Vati in Vishamajwara (malarial fever) 24
  36. 36. different control and treatment strategies may be necessary. The intricate interactionsbetween host, parasite, and vector are the major factors in this epidemiological complexity. The fundamental problem of developing drugs for tropical diseases are too expensivefor widespread use of poor countries. Ayurveda may contribute a lot for the utilisation of ourown resources. The Ayurvedic method of treatment in Vishamajwara has been claimedeffective either in single/compound drug therapy. Sudarsana Churna has been used for thetreatment of Vishamajwara since Sarangadhara period (1400 A.D). Even the contemporaryAyurvedic practices the same is considered as very effective and potent treatment modalityin Vishamajwara of “all types”. It also claimed to be effective any kind of jwara includingmalarial fever as diagnosed by modern clinical-parasitology. Vishamajwara, literally meaning irregular fever, is very vast. It may be remittenttype or intermittent type as keetanu (micro-organisms) have been incriminated as one of thecauses of Vishamajwara. The major cardinal symptoms of Vishamajwara i.e. Fever withchill and rigor have been observed to be present in other disease including Malaria, which isa protozoal disease caused by plasmodia group of organism and transmitted to manprimarily by certain species of infected female anopheles mosquitoes 19.Jwara (fever) and Vishamajwara (Malaria) Ayurveda mentioned jwara as the synonym of the disease or a febrile condition.“From among all disorders fever deserves to be described fist, it being the foremost of allsomatic diseases”. Charaka mentioned jwara afflicts body, mind and sense organs, regulatesthe well being of life. Chakrapani described jwara as “jwarayati santapayati” i.e. diseaseassociated with burning manifestation is known as jwara 20-21. Bharangyadi Ghana Vati in Vishamajwara (malarial fever) 25
  37. 37. The disease Vishamajwara is included under the jwara roga in Ayurveda. Jwara is abroad term, which has versatile meaning. If we analyse the etymological derivation of theterm we see that the word jwara is derived from the “jr” or “jya”. The jr. indicates vayohanior loss of life span. It indicates the state of cellular destruction produces more temperature. 22 Vishamajwara characterised by visamarambha (irregular onset) visama kriya 23(alternative feeling of hot and cold) and visamakala (irregular duration of sufferings) ofjwara. Susruta believed this to be caused by agantuka Karana or parahetu (external factor) 24.This parahetu is more cleared by commentator Dalhana as bhutabhisanga. Bhutabhisanga 25can be correlated with parasitic infection as discussed in modern medicine.History and background of VishamajwaraVAIDAIC PERIOD: Jwara is the term originated by the anger of Rudra. Rudra is known as god ofdestruction in Hindu mythology. Jwara is the king of all diseases and known by differentterms in various animals also i.e. Pakala for the jwara of elephants and abhitapan for horses’etc. Vishamajwara is the varieties of jwara, which can be identified by its peculiarity ofvisamata (irregularity) 26. The description of Vishamajwara was known from ancient era. In “UPANISHAD”(400B.C) visamajwara is described as “TAKMAN”. It is described that the jwara havingdahana and shosana properties, which attacks like fire (Agni) and they’re by the patient runslike a mad. For it’s relief chanting of mantras has been described to pray God 27. Atharva Veda has also described Vishamajwara causes that in the body like Agni (fire)patients feels very much uneasiness and sometime comes in the state of pralapa (delirium)and die. The attack of triteeyaka and santatajwara follows in sarat (autumn), varsa (rainy Bharangyadi Ghana Vati in Vishamajwara (malarial fever) 26
  38. 38. season) and grishma kala (summer season) or in the state of sheeta and ruksha. AtharvaVeda described the following types of Vishamajwara 28. These are - 1. Triteeyaka 2. Chaturthaka 3. Satataka 4. Sharada 5. Grishmika 6. Varsakalika Atharva-Veda is also described that takman is a periodic fever manifested with rigor,trembling and pain particularly in head. It is accompanied by debility and cough and ends inpallor or yellow-ness. It is endemic in particular places like Manjavan, Mahavrsa, Gandhara,Anga and Magadha 29. It is a clear picture of Vishamajwara of malarial origin. Sayana calls it sitajwara.,sitajanka (chill fever) 30 and kricchra jivanakrit (making life troubled). Whitney translates itas ‘fever’31.Synonyms in Vedas The synonyms of jwara are tapah, shushmi, Shoka, abhishoka, rudraha, papma,amarthya vigadh, vyangah, sheersha, parbheta and sochi etc. mentioned in the Veda are saidto be developed due to rudrakopa 32.Samhita & Sangraha kala Wide description of Vishamajwara is found in Samhita granthas like, Charaka,sushrut, bhela, harita, kashyapa, Madhava, sarangadhara, bhavaprakash, yogaratnaka etc.Kashyapa considered that in the Vishamajwara specific properties of jwara are found in a Bharangyadi Ghana Vati in Vishamajwara (malarial fever) 27
  39. 39. irregularity manner. He enumerated the Vishamajwara as follows santataka, satataka,anyeduska, triteeyaka and chaturthaka considering the days of its onset. According toKashyapa the aetiology lies as - if one takes exercise, heavy meal, unsuitable diet, excessdrinking of water or milk, blackgram preparation, recent curd, paste of tila, village animalflesh, virudhahara (incompatible food), day sleeping and takes much food before thedigestion during the period of jwara temperature goes on rising and attains the stage ofVishamajwara. He also described not to take Kashaya during the Amavastha orTarunavastha of jwara etc. which may leads to Vishamajwara 33. Bhaluki considered that thejwara that comes with cold or hot stage with temperature rise or low is uncertain inVishamajwara 34. 35 Charaka described that all the Vishamajwara are tridoshaja in origin. Susrutaconsidered that the Vishamajwara occurs due to Tridosha but Vata is the dominant Dosha.He considered the Agantuka Karana (external cause) of which bhutabhishanga constituteone of the variety in the main aetiology for Vishamajwara 36. Vagbhata defined Vishamajwara, as the jwara is irregular in respect to its onset,suffering and symptoms. The mandagni during adanakala is one of the important causes ofVishamajwara. He also advocated if an emaciated patient who takes irregular diet duringconvalescent period in spite of residual of small quantity of Dosha may causesVishamajwara 37. 38 According to Hareeta the Vishamajwara is five types such as vataja, ekaikajwara,dwahieka jwara, triahika jwara, chaturthakjwara. Chakrapani opinions, the poisonous insectsmay be considered under the word bhuta. Dalhana consider bhutas responsible to produceVishamajwara. Madhavkara 39 views as bhuta plays an important role for Vishamajwara too. Bharangyadi Ghana Vati in Vishamajwara (malarial fever) 28
  40. 40. In Amarkosh the bhuta means keetanu. Jejjata considered Vishamajwara astridoshaja in origin. Most of the authors considered five types of Vishamajwara.Bhavamishra and Madhavakara have included pralepaka jwara also in the group ofVishamajwara.Clinical Features of Malaria Fever is the commonest reason for hospital attendance in rural India. In recent past,Malaria was the main reason for fever. Even today, probably malaria may rank first.Outbreaks of fever are regularly reported from health workers and health institutions. Now-a-days after malaria, dengue fever has become important cause of fever outbreaks 40. Malaria is a febrile illness characterised by fever and related symptoms. However itis very important to remember that malaria is not a simple disease of fever, chills and rigors.In fact, in a malarious area, it can present with such varied and dramatic manifestations thatmalaria may have to be considered as a differential diagnosis for almost all the clinicalproblems! Malaria is a great imitator and trickster, particularly in areas where it is endemic. All the clinical features of malaria are caused by the erythrocytic schizogony in theblood. The growing parasite progressively consumes and degrades intracellular proteins,principally haemoglobin, resulting in formation of the malarial pigment and hemolysis ofthe infected red cell. This also alters the transport properties of the red cell membrane, andthe red cell becomes more spherical and less deformable. The rupture of red blood cells bymerozoites releases certain factors and toxins (such as red cell membrane lipid, glycosylphosphatidyl inositol anchor of a parasite membrane protein), which could directly inducethe release of cytokines such as TNF and interleukin-1 from macrophages, resulting in chillsand high grade fever. This occurs once in 48 hours, corresponding to the erythrocytic cycle. Bharangyadi Ghana Vati in Vishamajwara (malarial fever) 29
  41. 41. In the initial stages of the illness, this classical pattern may not be seen because there couldbe multiple groups (broods) of the parasite developing at different times, and as the diseaseprogresses, these broods synchronise and the classical pattern of alternate day fever isestablished. It has been observed that in primary attack of malaria, the symptoms mayappear with lesser degree of parasitemia or even with sub-microscopic parasitemia.However, in subsequent attacks and relapses, a much higher degree of parasitemia is neededfor onset of symptoms. Further, there may be great individual variations with regard to thedegree of parasitemia required to induce the symptoms. The first symptoms of malaria after the pre-patent period (period betweeninoculation and symptoms, the time when the sporozoites undergo schizogony in the liver)are called the primary attack. It is usually atypical and may resemble any febrile illness. Asthe disease gets established, the patient starts getting relapse of symptoms at regularintervals of 48-72 hours. The primary attack may spontaneously abort in some patients andthe patient may suffer from relapses of the clinical illness periodically after 8-10 days owingto the persisting blood forms of the parasite. These are called as short term relapses(recrudescences). Some patients will get long term relapses after a gap of 20-60 days ormore and these are due to the reactivation of the hypnozoites in the liver in case of vivax andovale malaria. In falciparum and malariae infections, recrudescences can occur due topersistent infection in the blood.Atypical featuresIn an endemic area, malaria often presents with atypical manifestations.Atypical features are more common in the following situations: • Falciparum malaria Bharangyadi Ghana Vati in Vishamajwara (malarial fever) 30
  42. 42. • Early infection • Patients at extremes of age • Patients who are immune-compromised (extremes of age, malnourished, AIDS, tuberculosis, cancers, on immunosuppressive therapy etc.) • Patients on chemoprophylaxis for malaria • Patients who have had recurrent attacks of malaria • Patients with end stage organ failure • Last but not the least, pregnancy.Atypical fever: In an endemic area, it is rather unusual to find cases with typical fever pattern. Somepatients may not have fever at all and may present with other symptoms listed below. Manypresent with fever of various patterns - low grade to high grade, with or without chills,intermittent to continuous, or even as cases of prolonged fever. In the initial stages of theillness, fever may be quotidian, with more than one spike per day and this is due to thedevelopment of multiple broods of the parasite. As the disease progresses, these broods getsynchronised and the fever tends to be more uniform. However in cases of P. falciparummalaria and mixed infections, this pattern of multiple spikes may continue.Headache: Headache may be a presenting feature of malaria, with or without fever. It can beunilateral or bilateral. Some times the headache could be so intense that it may mimic intra-cranial infections or intra-cranial space occupying lesions. It may also mimic migraine,sinusitis etc. Presence of projectile vomiting, papilloedema, neck stiffness and focalneurological signs would suggest other possibilities. Bharangyadi Ghana Vati in Vishamajwara (malarial fever) 31
  43. 43. Body ache, backache and joint pains: These symptoms are fairly common in malaria. These can occur even during theprodromal period and at that stage these are generally ignored and diagnosis of malaria isimpossible owing to lack of peripheral parasitemia. They are also common accompanimentsof the malaria paroxysm. Sometimes, malaria may present only with these symptoms,particularly in cases of recurrent malaria.Dizziness, vertigo: Some patients may present with dizziness or vertigo, with or without fever. Theymay also have associated vomiting and/or diarrhoea. This may mimic labyrinthitis,Mennieres disease, vertebro-basilar insufficiency etc. Rarely patients may present withswaying and cerebellar signs. Drugs like chloroquine, quinine, mefloquine and halofantrinecan also cause dizziness, vertigo, and tinnitus.Altered behaviour, acute psychosis: Patients may present with altered behaviour, mood changes, hallucinosis or evenacute psychosis, with or without fever. Malaria may be detected accidentally in such casesand they improve completely with anti malarial therapy. Altered behaviour may also be dueto high grade fever or drugs. Antimalarial drugs like chloroquine, quinine, mefloquine andhalofantrine can cause restlessness, hallucinations, confusion, delirium or even frankpsychosis.Altered sensorium: Patients with P. falciparum malaria may present with altered sensorium due to severeinfection, hypoglycemia, electrolyte imbalance due to vomiting or diarrhoea (particularly theelderly), hyperpyrexia, subclinical convulsions etc. Differential diagnosis will include acute Bharangyadi Ghana Vati in Vishamajwara (malarial fever) 32
  44. 44. encephalitis, meningitis, metabolic encephalopathy etc. As a rule of the thumb, malariashould be considered a possibility in all cases of acute neuropsychiatric syndromes and incases of proven malaria, other possibilities should be considered in the presence ofpapilloedema, increasesd ICT, neck stiffness and focal deficits.Convulsions, coma: Patients with cerebral malaria present with generalised seizures and deepunarousable coma. Sometimes one single fit can precipitate deep, unarousable coma. Thesecould also be due to hypoglycemia and all patients presenting with these manifestationsshould be administered 25-50% dextrose immediately. Drugs like chloroquine, quinine,mefloquine and halofantrine may also trigger convulsions.Cough: Cough may be a presenting feature of malaria, particularly P. falciparum infection.Patient may have pharyngeal congestion and features of mild bronchitis. Patients who havepersistent cough and/or fever even after clearance of parasitemia should be evaluated forsecondary bacterial pneumonias/ bronchopneumonia and bronchitis.Breathlessness: In severe falciparum malaria, patients may present with history of breathlessness,due to either severe anemia or non-cardiogenic pulmonary oedema. Secondary respiratorytract infections and lactic acidosis are other rarer causes for tachypnoea and/orbreathlessness in these patients. Patients with pre-existing cardio-vascular or pulmonarycompromise may deteriorate or even die if they suffer from severe malaria. Bharangyadi Ghana Vati in Vishamajwara (malarial fever) 33
  45. 45. Chest pain: Acute retrosternal or precordial pain may be presenting feature of malaria. It mayradiate to the left or right shoulder tips or arms. It is due to rapid increase in the splenic sizeand perisplenitis. This pain may mimic acute myocardial infarction, pleurisy, neuralgia etc.Coupled with breathlessness, sweating and hypotension (algid malaria), the picture will veryclosely resemble that of acute MI.Acute abdomen: Patients can present with acute abdominal pain, guarding and rigidity, mimickingbowel perforation, acute appendicitis, acute cholecystitis, ureteric colic etc.Weakness: Sometimes patients may present with history of weakness, malaise and prostration.On examination they may have significant pallor, hypotension, dehydration etc. Algidmalaria may present like this and the patient may not have fever at all. Chloroquine is alsoknown to cause profound muscular weakness and a new disease called macrophagicmyofaciitis has been described in patients receiving chloroquine.Vomiting and diarrhoea: Malaria can present as a case of acute gastroenteritis with profuse vomiting andwatery diarrhoea (Choleraic form). Vomiting is very common in malaria and is due to highgrade fever, the disease itself or even drugs. Vomiting may pose problems in administeringantimalarial treatment. These could also be due to drugs like chloroquine and due tosecondary bacterial or amebic colitis. Bharangyadi Ghana Vati in Vishamajwara (malarial fever) 34
  46. 46. Jaundice: Patients may present with history of yellowish discoloration of eyes and urine. Mildjaundice is fairly common in malaria and may be seen in 20-40% of the cases. Deeperjaundice with serum bilirubin of more than 3 mg/dL is seen in severe P. falciparum malariaand is associated with anemia, hyperparasitemia and malarial hepatitis with elevated serumenzymes. Malaria must be considered as a differential diagnosis for all cases of jaundice in amalarious area.Pallor: Severe anemia can be a presenting feature of malaria. It is usually normocyticnormochromic. It may pose special problems in pregnancy and in children. Pre-existingnutritional anemia may be aggravated by malaria.Puffiness of lids: Occasionally patients may present with puffiness of lids, with or without renaldysfunction.Secondary infections: Malaria produces significant immune suppression and this can result in secondaryinfections. Common among them are pneumonia, aspiration bronchopneumonia (in theelderly), urinary tract infection, colitis etc. Meningitis and enteric fever have also beenreported. In falciparum malaria, severe infection can lead to septicaemic shock (algidmalaria). Persistence of fever, neutrophilic leucocytosis and focal signs of infection shouldalways alert the clinician to this possibility of secondary infections. Bharangyadi Ghana Vati in Vishamajwara (malarial fever) 35
  47. 47. Hepatosplenomegaly: Patients can present with enlargement of liver and/or spleen, tender or non-tender,with or without fever. Rapid enlargement of spleen or liver in malaria can cause acute painin the abdomen or chest. Generally, organomegaly is noticed in the second week of malarialillness. However, in cases of relapse or recrudescence, it may be present earlier. Also, inimmune compromised patients splenomegaly may be absent. In pregnancy, particularlysecond half, splenomegaly may be smaller or an enlarged spleen may regress in size due toimmune suppression. Although splenomegaly is a cardinal sign of malaria, absence ofsplenomegaly does not rule out the possibility of malaria.Combinations of the above: Patients can frequently present with various combinations of the above mentionedsymptoms and signs, further confusing the picture. This list is not exhaustive and malaria may present in many other ways. In all theabove listed situations, patients may not have associated fever, thus confusing the picture. Insome, fever may follow these symptoms. Therefore, one should not wait for the typicalsymptoms of malaria to get a blood test done; it is always better to do a smear wheneverreasonable doubt exists.Pathophysiology of Malaria: The bite of an infected mosquito introduces asexual forms of the parasite, calledsporozoites, into the bloodstream. Sporozoites enter the hepatocytes and form schizonts,which are also asexual forms. Schizonts undergo a process of maturation and multiplicationknown as preerythrocytic or hepatic schizogony. In Plasmodium vivax and Plasmodium Bharangyadi Ghana Vati in Vishamajwara (malarial fever) 36
  48. 48. ovale infection, some sporozoites convert to dormant forms called hypnozoites, which cancause disease after months or years. Preerythrocytic schizogony takes 6-16 days, and results in the host cell bursting andreleasing thousands of merozoites into the blood. Merozoites enter the erythrocytes andinitiate another asexual reproductive cycle, known as erythrocytic schizogony. The parasitepasses successively through the stages of trophozoite and schizont, ultimately giving rise toseveral merozoites. On maturation of these merozoites, the erythrocyte ruptures, releasingthe merozoites and multiple antigenic and pyrogenic substances into the bloodstream. Thesemerozoites again infect new erythrocytes. After a few cycles of this erythrocytic schizogony,some merozoites differentiate into the sexual forms: the male and female gametocytes. Amosquito that takes a blood meal from a patient with gametocytemia acquires these sexualforms and plays host to the sexual stage of the plasmodial life cycle. Figure – 4 Life cycle schematic diagram Bharangyadi Ghana Vati in Vishamajwara (malarial fever) 37
  49. 49. Figure –5 Sporogonic and Erythrocytic cycles of Malaria Rupture of a large number of erythrocytes at the same time releases a large amountof pyrogens, which causes the paroxysms of malarial fever. The periodicity of malarial feverdepends on the time required for the erythrocytic cycle and is definite for each species.Plasmodium malariae needs 72 hours for each cycle, leading to the name quatrain malaria.The other 3 species each take 48 hours for one cycle and cause fever on alternate days(tertian malaria). However, this periodicity requires all the parasites to be developing andreleasing simultaneously; if this synchronization is absent, periodicity is not observed 41. Bharangyadi Ghana Vati in Vishamajwara (malarial fever) 38
  50. 50. Figure – 6 Exogenous and Endogenous Phases of MalariaLife cycle of Malaria The life cycle of all human malaria species consists of two phases a sexual phase(sporogony), with development and multiplication in certain female anopheline mosquitoesand an asexual phase (schizogony) with multiplication in man. The asexual phase in man has two parts, schizogony in the cells of liver(preerythrocytic schizogony or tissue phase) and schizogony in the red cells (erythrocyticschizogony or erythrocytic phase). Bharangyadi Ghana Vati in Vishamajwara (malarial fever) 39
  51. 51. Asexual phase in human hostTissue phase Sporozoites are inoculated by infected mosquito into the host and disappear fromcirculation within half an hour. Some enter the parenchymal cells of liver where theyundergo development and multipication, known as pre-erythrocytic schozogony. The tissue schizont which develops from the sporozoite enlarges and the nucleus andcytoplasm divide to form many thousands of merozoites which after 6-16 days rupture theliver cells and invade the circulation, where they enter the red cells by a process ofinvagination. The prepatent period is the time from infection until the appearance ofparasites in the blood and varies with the species of parasite (P. vivax 6-8 days, P. malariae2-16 days, P. ovale 9 days. P. falciparum 51/2 –7 days).Exoerythrocytic schizogony In P. vivax and the P. ovale malaria some of exacoythrocytic trphozortes orginatingfrom sporozoites lie dormant and are known as hypnozoites. After a period of up to 250 daysthey they become active and mature, allowing merozoites to infect red cells and give rise toan erythrocytic phase. This is the mechanism responsible for delayed prepatent periods andrelapses in P. vivax and P. ovale malaria.Erythrocytic phase To enter the red cell the merozoite binds to glycophorin, the major erythrocyticglycoprotein, which is psecific for a particular species of parasite. The apex of merozoitereleases a substance which forms a deep pit in surface of red cells and, maintaining contactbya contact ring, the merozoites are enveloped by the red cell in a vacuole (parasitophorousvacuole) in which it is enclosed. In the red cell the merozoites develop into ringforms which Bharangyadi Ghana Vati in Vishamajwara (malarial fever) 40
  52. 52. grow in size to trophozoites absorbing haemoglogin leaving a pigment (haematin orhaemazoin) – a combination of haemoglobin with protein which can be seen as darkgranules. The trophozoite multiplies by schizogony dividing into a number of smallmerozoites varying with species to form mature schizont. The merozoites are released byrupture of red cell membrane and enter new red cells, particularlyyoung red cells. Theerythrocytic phase called schizogonic periodicity, which differs according to the species ofparasite, is responsible for the febrile paroxysms. In the early stages of infection there maybe several broods of parasites developing at different times so that there is no regularperiodicity, but with development of immunity the periodicity settle down and becomesregular.Gametogony After a period some merozoites give rise to two sexually differentiated forms ofgametocytes male (microgamete) and female (macrogamete) which differ in morphology inthe different species of parasite. These gametocytes are taken up by female anophelinemosquitoes and they undergo development.Sexual phase in anopheline mosquitoes In the stomach of mosquito the female gametocyte forms a macrogamete and themale a microgamete. The male gamete nucleus divides and forms a number of long slender,thread like structure or flagellae (exflagellation). These enter the female gamete and fuse toform a zygote, which becoming mobile as an olkinete and penetrating between the epithelialcells leaving the stomach, comes to rest on the outer surface of the stomach wall to form anoocyst, of which there may be several hundreds in one stomach. In the oocyst a largenumber of slender sporozoites form which burst out into the body cavity and enter the Bharangyadi Ghana Vati in Vishamajwara (malarial fever) 41
  53. 53. salivary glands ready to be inoculated into a new host at the next blood meal. The durationof cycle in the mosquito is known as the extrinsic incubation period. It varies according tothe temperature being 8-10 days at 28°C, 16 days at 20°C and cannot be completed under15°C.Frequency: • Internationally: Malaria is a major health problem in Africa, Asia, Central America, Oceania, and South America. About 40% of the worlds population live in areas where malaria is common. Approximately 300-500 million cases of malaria occur every year, and 1-2 million deaths occur, most of them in young children. • In the US: Approximately 1000 cases are diagnosed every year, most of them acquired outside the country. Only about 1% of patients acquires the infection in the United States. Usually fewer than 10 deaths are reported in the United States annually.Mortality/Morbidity: • Cerebral malaria: Most of the mortality of malaria is due to this complication of Plasmodium falciparum malaria, an acute illness that is mostly observed in children aged 6 months to 3 years. Early diagnosis and prompt treatment with a drug to which the parasite is susceptible is important to save the life of the child. • Anaemia: Anaemia is so common in malaria that it is considered almost a part of the disease. The degree of anaemia is much greater than can be explained by destruction of parasitized erythrocytes. Malarial anaemia can be quite severe, sometimes causing death. Bharangyadi Ghana Vati in Vishamajwara (malarial fever) 42
  54. 54. • Repeated frequent seizures: Even without cerebral malaria, a child can experience prolonged, frequent convulsions, which can lead to prostration and death.Race: People of all races are affected, with some exceptions. People of West African originwho do not have the Duffy blood group are not susceptible to P vivax malaria.Sex: Malaria affects females and males equally.Age: Children of all ages living in non-malarious areas are equally susceptible to malaria. Inendemic areas, younger children are repeatedly have and often serious attacks of malaria.The survivors develop partial immunity. Thus, older children and adults often haveasymptomatic parasitemia, i.e., and presence of plasmodia in the bloodstream withoutclinical manifestations of malaria. Most deaths resulting from malaria occur in childrenyounger than 5 years 42.DIFFERENTIAL DIAGNOSIS There are many other conditions that may mimic malaria fever. A careful history andexamination with the aid of the laboratory, when necessary, will often resolve the difficulty.a. Malaria — This may be mistaken for typhoid in countries where both are endemic. Ahistory of previous attacks, the more rapid onset in malaria, the shivering and sweating, thehigh early pyrexia, the relative infrequency of abdominal symptoms and signs, and apositive blood slide all point to a diagnosis of malaria.b. Influenza — Influenza may also be confused with typhoid, but is usually of much morerapid onset with high temperature, severe sore throat, cough, and the absence of a palpablespleen and rose spots.c. Bacillary dysentery — This disease seldom causes much difficulty in diagnosis. Theonset is usually acute, with severe blood diarrhoea, although in mild cases the blood may be Bharangyadi Ghana Vati in Vishamajwara (malarial fever) 43
  55. 55. absent. Diarrhoea with blood is rare in early typhoid. The signs and symptoms in dysenteryare usually abdominal and remain so, the mental state and chest being clear.d. Typhus and other rickettsial infections — These conditions should be consideredimportant when considering the differential diagnosis. This is because both typhus andtyphoid can cause a febrile illness with delirium, chest signs, and abdominal discomfort. Intyphus, however, the onset is acute, and the temperature high at an early stage. Shiveringattacks are common at the onset, and prostration is rapid. The rash is quite different (brownish red in colour, and much more profuse). It doesnot fade on pressure, as does the rose spot in typhoid. There is a leucocytosis and the Weil-Felix test becomes significantly positive at about the tenth day.e. Pulmonary tuberculosis and atypical abdominal tuberculosis — These are probablythe most difficult diagnoses to differentiate from typhoid in economically poor countries.The pyrexia and vague symptoms and signs may be very similar. A chest X-ray, orlaboratory confirmation of typhoid, may be the only sure method of diagnosis.f. Brucellosis — This may cause difficulty, but the onset tends to be more insidious. Thepatient is also alert, and a painful joint is frequently present.g. Trypanosomiasis — This condition in endemic areas should also be considered in thedifferential diagnosis.h. There are numerous other diseases — Some other diseases could enter into thedifferential diagnosis category and some of these are illustrated. Suffice to say that there arefew conditions that cannot mimic, or be mimicked by, typhoid fever. Bharangyadi Ghana Vati in Vishamajwara (malarial fever) 44
  56. 56. Nidana of Jwara: (Aetiology) The causative factor may be sarnikristha Nidana (immediate cause) and/orviprakristha Nidana (distant cause). So these two factors are responsible for vyadhijanaktvaas well as Vyadhi bodhakatva. On the basis of the above all the factors like Bahya (external)as jeevanu, mithya Ahara vihara etc. and the internal factor is vitiated Dosha and dushya.Gananath Sen described the external cause like abhighata (trauma). Jeevanu (parasite ormicrobes) and mithya Ahara-vihara (defective food and habits) are causes forVishamajwara.Role of Ahara and Vihara 43 Unsuitable food and drinks are provocative of Vata. Pitta and Kapha and ultimatelymay cause the development of Vishamajwara. According to Vagbhata if Shodhana is givenin Nava-Jwara cases when there is Indigestion State, aggravated Dosha becomes the causeof Vishamajwara. According to Yadvji Trikamji emaciated and weak patients if take ahitaAhara-vihara in course of time it produces Vishamajwara. So aetiology of Vishamajwara isdiscussed under following heads.Factors relating to Ahara - 1. Kasaya Dravya sevana 2. Ruksha Dravya sevana 3. Ushna drvya sevana 4. Shitambu pana 5. Santarpan Dravya sevana 6. Anupamansa bhakshana 7. Pinaka bhojana Bharangyadi Ghana Vati in Vishamajwara (malarial fever) 45
  57. 57. 8. Asatmya Dravya bhojana 9. Virudha Padartha bhojana (antagonist food) 10. Ahita Ahara sevanFactors relating to vihara 1. Visa ausadhi gandha sevan 2. Divaswapna (day sleeping) 3. Mithya vihar (the habits which is not good for health) 4. SorrowfulnessOthers – 1. Aupasargika Karana 2. Rutuparivartana 3. Kroda 4. Bhaya Flow chart -1 Classification of aetiology of Vishamajwara Nija (Internal) Agantuja (External) Abhichara Abhishanga Abhighata Abhishapa Ahara Vihara Dosha Bhutabhishanga Mahabhishanga Kala Prakruti Keetanu Drushya Adrushya (Macroscopic) (Microscopic) Bharangyadi Ghana Vati in Vishamajwara (malarial fever) 46
  58. 58. Role of bhuta (Keetanu) in Vishamajwara Susruta believed that Vishamajwara takes place due to agantuka Karana (externalcause). Agantuka is divided into 4 types i.e., abhighata, abhichara, abhishapa and abhisanga.Dalhana considered abhisanga as bhutavisanga. Chakrapani stated poisonous insects may beconsidered as bhuta. According Amarkosha it is keetanu. Therefore the keetanu introducedthe body by its corresponding portan entry and aggravates the doses. The time taken fromthe entry to manifestation of disease is known as sanchaya kala (incubation period). Aftersanchaya the doshas follow their normal pathway to travel for manifestation of diseases. Butin this instance which Dosha is principal may be considered on the type of keetanu and the 44strain of keetanu . Regarding the vectors, Charaka mentions countries which aboundmashaka (mosquitoes), mooshaka (rats) and makshika (flies) as unhealthy 45. In Charaka, itis stated that “unsanitary winds, unsanitary water, unsanitary countries and unsanitaryseasons are cause of catastrophes. Water is considered to be more important than wind, andcountry more important than water and season yet more important than country by virtue oftheir degree of indispensability 46. In this statement one can see the rudimentary concept ofgerm theory and epidemiology.Relation of Dosha in Vishamajwara Ayurvedic doctrine based on the Tridosha theory. The three Doshas are responsiblefor all diseases when they are deranged. The vitiated Dosha after localising in Dhatus of thebody are responsible to produce diseases. Through it is described in all classical texts thatVishamajwara is tridoshaja but Vata plays an important role. Charaka described thatVishamajwara is developed due to vitiation of Tridosha, but according to predominance ofDosha different features of its varieties may be noticed 47. Bharangyadi Ghana Vati in Vishamajwara (malarial fever) 47

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