MALARIA ACTION RESEARCH PROJECT

Procedure report

1. The Background

2. Preliminary steps

3. Literature search to find out drugs used against malaria in Ayurveda and
herbal medicine.

4. Collecting information from local traditions in the treatment of malaria.

5. Search for collaborators for clinical trial and documentation

6. Preliminary clinical trial

7. Selection of medicine

8. Protocol for clinical trial

9. Ethical committee meeting

10. Perpetration of medicines.

11. Clinical trial and documentation.

1 . Second ethical committee meeting

13. Trial for preventive effect.

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1. The background

The initiative to take up a study of malaria to find suitable herbal alternative for malaria
came from Fr. Varghese Puthussery, S.J., the former Provincial of Dumka Raiganj Jesuit
Province. His interest in herbal alternative for malaria was because:

• Many people in remote villages die of malaria without having any access to
medical care
• The effectiveness of chloroquine seems to be very limited.
• At the same time people in the village do use several herbal medicines against
malaria.

Hence our purpose in this study is to find out the effectiveness of herbal medicine (at
least one formulation) both as curative and preventive against malaria, so that we can
promote it confidently among the people. Hence the objective of this study is to empower
people to manage malaria problems by themselves as far as possible with traditional
knowledge and skill.

2. Preliminary steps

As the first step, we wrote a project and send it to FASCI, a Jesuit organization to fund
small projects of social involvement, for financial help. It took time for the project to get
approved and money to come. Meanwhile I borrowed money from the Dumka province
and started the work.

Secondly I contacted experts in the field of Ayurveda amd Herbal medicine as well as
doctors involved in the field of malaria for advice and guidance. While in Secunderabad
itself I contacted Dr. C.M. Francis, Dr. Ravi Narayan and Dr. Thelma Narayan of
Community Health Cell (CHC), Bangalore. In Jan. 2003 I contacted Dr.Unnikrishnan, an
Ayurvedic doctor of FRLHT (Foundation for the Revitalization of Local Health
Traditions). I had been working with him in the same organization on a similar project.

I had several discussions with Dr. Prabir Chatterjee, UNICEF, Dr. P.P. Hembrom,
Maheshmunda, Dr. Isaac and Dr.Vijala Isaac, both of Prem Jyoti Hospital, Chandragoda,
to work out the modalities. Dr. Nandi, the director of Tropical Diseases, Calcutta was an
important guide in this study.

The outcome of these contacts was the advisory team consisting of Dr. P.P. Hembrom,Dr.
Prabir Chatterjee, Dr. Vijala Isaac, Dr.Isaac and. Dr. Nandi.

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3. Literature search

Literature search is to look for drugs used in Ayrvedic and herbal books against malaria.
The main Ayurvedic books I went trough are: Fundamentals of Ayurveda,
Sahasrayogam, and Astangahrudayam. The main herbal books studied are: Indian
Materia Medica by K.M.Natkarni, Dictionary of Indian Folk Lore and Ethno Botany, by
S.K. Jain, Chikitsakauthukam, by M.V. Kuttikrishna Menon, Aushuda Satsyangal by Fr.
Raphel Tharayil, Adivasi ausshad, by Dr. P.P.Hembrom

Outcome of the Literature Search: The term, Malaria doesn’t occur in Ayrveda. The
term that corresponds to Malaria here is “Vishamajwaram”. Ayurveda mentions several
plants and formulations against vishamajwaram. The main drugs are Neem, garlic,
chiretta, Nutmeg, Lemon grass Dry ginger, etc. A formulation called “Indukantaghitam”
mentioned in Sahasrayogam, if taken for about three months, gives certain immunity
against malaria.

The commonly used plants against malaria mentioned in herbal books are Acorus
calamus, Aerva lanata, Alstonia scholaris, Alteranthes sissilis, Andrographis paniculata,
Aristolochia indica, Azadirachta indica, Nyctanthes arbor-tristis, Ocimum sanctum,
Leucas aspera, Momordica charantia, Lantana camara, Bauhenia variegata, Caesalpinia
bonduc, Citrus lemon, Clerodendrum viscosum, Eucallyptus globulus, Hedyotis
corymbosa, Holorrhena antidysenterica, Hygrophylia spinosa, Pongamia
pinnata,Soymeda febrifuga, Swertia chireta, Tinespora cordifolia, Zingiber officinale,
Vitex peduncularis.

4. Collecting Information from Local Health Traditions in the treatment of

malaria

I contacted different people in several places to find out medicines used in different
places. The main people I contacted were Dr. P.P. Hembrum, Sr. Amulya, Sr. Graace,
People in Sokho, and people in Satia etc. In my search I came across the following herbs
used in local practice against malaria which are not mentioned in the standard herbal
books. These are: Calotropis gigantea, Cassia occidentalis, Celastrus paniculata (Kujur).
Vitex peduncularis (Charaigodwa) in decoction form is used as preventive of malaria.

5. Search for Collaborators for Clinical Trial

This activity was from July 2003 to April 2004. I Contacted 11 centers for collaboration
for clinical trial and documentation. These were: Satia, Kodma, Sohargati, Hathimara,
Badbanga, Sahibgunj, Dumka, Kundli, Mundli, Mariampahar, Premjyoti Hospital
Chandragoda.

Sr. Amulya, a well known herbalist, contributed much towards the preliminary trial.
Preliminary clinical trial was done in Kodma with a plant called Cassia occidentalis (Bara

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chakod). Satia centre could not be involved in the clinical trial because there was neither
laboratory facility nor lab technician.

In 2005 Sr. Anjana SCN from Sokho (Bhagalpur diocese) approached me for help to try
herbal medicine as preventive for their hostel children and their villages with the help of
her team of health workers. In March 2005 I gave an herbal training for the health team.
In one village called Karawateri, the health worker there did a very systematic work to
prevent malaria. The result was very successful.

In April 2006 the sisters of Holy Cross Hospital Belatarnh, Giridih Dt. showed interest in
using the herbal medicine for malaria treatment. I was looking for the help of such a
hospital for the clinical trial and documentation.

Finally, we got the following centers to collaaboratein the clinical trial and
documentation:

-Holy Cross Hospital, Sitapahaar.

-Prem Jyoti Community Hospital, Chabdragoda
-Hembrom clinic, Kundli.
-Holy Cross Hospital Belatarnh
-Nazaaraeth Health Centre, Sokho (trial for preventive effect)
-Healath Centre, Badbanga. (trial for preventive effect)

6. Preliminary Clinical Trial and Documentation to Select the Proper Medicine for
Study

This was a crucial activity in the whole process. From over 30 drugs we came across
from literature search and traditional practice, we have to select one drug/formulation that
is most effective, easily available and with out toxic effects for systematic clinical trial. If
drugs already mentioned in Ayurvedic texts are used, there is no need for toxicity test.
This task involved close observation of patients for about 10-15 days when a new drug is
administered. Proper dosage has to be decided by the one who administers the medicine.

People and Institutions Involved in this Activity:

-Holy Cross Hospital, Sitapahar (Here the programme coordinator himself monitored the
Process)
-Sr. Amulya, (Ursuline Hospital,Dumka and other centers)
-Dr. Bablu Benjamin Hembrom , Kundli.
- Sr. Catherine. St. Xaavier’s dispensary, Sahibgunj.
- Mr. Anthony, Health centre, Kodma.

All these people are experienced herbslists.

This activity extended for about 26 months. In Sept 2003, we started collecting different
drugs and trying out on patients in Holy Cross Hospital, Sitapahar.. It was over by July
2004. This was followed by the preparation of few select medicines to be supplied to

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different centers. From July 2004 to Oct.2005 was the time for preliminary clinical trial
and documentation in order to select the medicine.

The Procedure

From Mariampahar we supplied the medicines to different centers. They were instructed
how to administer the medicine and do the documentation. Medicine has to be given to a
patient who is found malaria positive by peripheral smear test. The patient should not
have taken any anti malarial drug before admission.

Those below ten years of age and above 60 years are to be excluded. Also to be excluded
are pregnant women and lactating mothers. Patients with other complications like kala
azar, typhoid, jaundice and very severe malaria cases also have to be excluded. The
response of the patient to the drug has to be closely observed and documented. The one
who administers the drug has also to determine the mode of administration. If a patient
does not respond to the drug within 3-5 days time, he/she should be given other (modern)
medicines.

Following are the drugs/formulations tried out.

1. Cassia occidentalis (single drug) We tried this drug only on 10 pwople

2. Pills of neem, karanj, tulsi, chiretta, and pepper – tried on 77 patients
3. Decoction of Nictanthes arbor tristis (parijat) with Vitex peduncularis
(chariagodwa) – 66 patients were treated with this preparation
4. Neem bark decoction with cinnamon powder – 24 patients treated
5. Samsamani preparation -147 patients were treated.

Samsamani preparation consists of Neem bark, Guduchi (Tinespora cordifolia) and little
cinnamon powder. This formulation can be prepared either as a confection, or powder or
capsules.

Results of the preliminary trial

1. Cassia occidentalis (chakod) : For PV (plasmodium Vivax), it showed 100% success

For PF however it was only 20% success.

2. Pills of neem, karanj, tulsi chiretta and pepper: For PV it was 100% successful
For PF it was 55% successful
(When it was administered in larger dose
i.e.,4 pills together on first day, and
then 2 pills twice a day for 7 days, it
gave better results against PF)
3. Dcoction of parijat and charaigodwa: For PV - did not get any patients with PV
For PF: 95% successful

4. Neem bark decoction with cinnamon powder: did not get patients with PV

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 For PF – (95% successful)

5. Samsamani preparation: as syrup 2- 3 tsp twice a day

As capsules 3 – 4-pills twice a day: 100% success for PV
91% success for PF

NB: PV malaria is very rare in the centers we did the clinical trial

7. Selection of the Medicine for Study

Cassia occidentalis (Bara cahakod) is found to be very good for PV malaria. For PF,
however it is not found to be effective.

Pills of neem, karanj, tulsi, chiretta and pepper is seen very good for PV; but in the case
of PF, its effectiveness is not very satisfactory.

Decoction of parijat and charaigodwa is seen to be very good against PF. But
Charaigodwa is not easily available. It is found only in some forests. So it is not selected.

Neem bark decoction showed very positive result against PF malaria. So we selected this
drug with addition of Guduchi (Tinespora cordifolia), which is the samsamani
preparation.

Justification of selecting Samsamani preparation:

• In the preliminary study Samsamani preparation showed very positive result.

• The action of neem and giuduchi against malaria is mentioned in many classical
Ayervedic texts like Charaka samhita, Bhavaprakasa nighandu, and Astanga
Hrudaya. Chaaraka Samhitaa mentions the use of Guduchi against
Vishamajwara.

• In ancient palmera writings, we find a formulation of Samsamani vati against

vishamajwaram (Chikitsakautukam byV.M. Kuttikrishna Menon P.11&12)

• Dr. K.M. Natkarani in Indian Materia Medica mentions that Neem bark
decoction with the addition of little coriander powder and dry ginger powder or
little cinnamon powder or clove powder is effective for malaria where quinine
fails. (p.780)

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8. Protocol for Clinical Trial

1. Objective: To measure treatment efficacy of selected traditional remedy

compared to treatment of chloroquine

2. Studydesign: Randomized and double blind clinical trial

3. Place of trial: Premjyoti Community Hospital, Chandragoda, Holy Cross

Hospital, Sitapahar, Holy Cross Hospiital,Belatarnh, Hembrom Cliniic Kundly,
St. Xaavier’s dispensaaaary, Sahibgunj

4. Duration of the Study: One year (de facto it took 5yeears)

5. Inclusion criteria: Patients clinically suggestive of malaria and peripheral

smear positive for PlasmodiumVivax or Plasmodium Falciparaum

6. Exclusion Criteria:

6.1. Patients less than 10 years and more than 60 years old.
6.2. Pregnant and lactating women.
6.3. Severe malaria: Malaria with unconsciousness, convulsion, severe
anemia, respiratory diseases, bleeding from any site, auxiliary
temperature above105 F patients with any chronic diseases such as
diabetes, HIV AIDs. T.B., Kala azar
6.4. History of having taken Anti malarial drug within last 7 days prior to
enrollment.

7. Termination of the study : The study will be terminated on a subject , if:

7.1. He/she develops signs of severe malaria

7.2. No response till the end of 7 days of treatment.

8. Medicine to be tried out:

Medicines that are found to be effective in preliminary trial and approved by the
ethical committee will bee selected for trial. (Here we take samsamani preparation
which is a combination of neem, guduchi ( tinespora cordifolia) and cinnamon.

9. Procedure:

9.1. The centers will be provided with:

a. Form for informed consent.

b. Protocol for clinical trial
c. Documentation Performa
d. Randomized packets of herbal medicines and placebo

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 9.2. The Action research Project will meet the expenses of medicines and
the second smear test.

9.3.the patient who is found to be malaria positive by peripheral smear test

and who is within the inclusion criteria will be made to understand about
the herbal research study. If he iss willing to take the herbal medicine
along with chloroquine , he is included in the study.

9.3.1. He will then sign the informed consent form

9.3.2. He will be given chloroquin
9.3.3. He will be given the herbal packet.
9.3.4. he is asked to come on day 7 of the treatment; or earlier if, the
condition becomes worse.
9.3.5. He will be told that all the expenses for the treatment will be met
through the study programme i.e.,
Expenses for the second smear test.
The cost of chloroquin
Any other medicine given

10. Documentation: the documentation Performa will be duly filled up as wee

progress with the treatment of each patient.

11. Lab investigation: Lab investigation to be carried out will include peripheral
smear for Malaria on day one of the treatment and any day between day 7 and 14 of
the treatment.

9. Ethical Committee Meeting

In Oct. 2005 the ethical committee was constituted with the following people.

• Dr. Vijala Isaac, Prem Jyoti Community Hospital, Chandragoda

• Dr. P.P.Hembrom, Founder Director, Indian Folk Medicine and Ethno-botany,
Maheshmunda, Giridih.
• Sr. Lucy Joseph, Advocate, Civil Court, Pakur.
• Mr Paulus Murmu, Vllage Headmen (Manjhiharam). Vill.Banjhi, Dt. Sahibgunj.
• Fr. Sevanand Melookunnel, S.J., Research Coordinator, Mariampahar.

We had the first Ethical committee meeting on Sunday, 30th Oct. 2005 at Maariampahar
mission. In the meeting we discussed in full detail the Protocol for clinical trial, the
Performa for documentation and the consent form. The programme coordinator explained
the medicine to be used for the trial. We also discussed the constituents of the
formulation –neem and guduchi. Question was raised about the dosage to be given. The
general dosage was explained by the PC. Dr. P.P. Hembrom explained that the dosage in
herbal medicine is to be determined by the “vaidya” understanding the condition of each

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patient. Question was raised about the need for toxicity test of the drugs used. Fr. Meloo
explained that since the drugs used in the formulation – Guduchi, Neem and Cinnamon –
are already in use in classical Ayurveda, no special toxicity test is need.

The Ethical committee approved the medicine to be studied, the protocol and the
documentation procedure.

10. Preparation of Medicine

Medicines were prepared at Maraimpahar mission. It was an on going work from

September 2005 to June 2008.

The people involved were a couple of daily laborers and a number of casual laborers to
procure raw materials from the jungles as per requirement. The medicines were prepared
under the supervision of the programme coordinator.

During the preliminary trial of 2004 and 2005 we prepared the pills of neem, karanj, tulsi,
chiretta and pepper, and the Samsamani preparations. Sr. Amulya prepared her own
medicines. The medicines for prevention at Sokho and Badbanga also were made at the
respective places. At this first stage we prepared medicines for over 350 people.

Preparation of Medicine for Clinical Trial

Samsamani formulation was the medicine for clinical trial. From May 2005 to Oct 2006
syrup form was used for the treatment. For about 400 people we used the syrup form.

Mode of preparation of the syrup: Boil equal quantities of neem bark and the stem of
guduchi in 4 times its weight of water and reduce it to 1/4th decoction. Strain the
decoction, add little cinnamon powder and enough jaggery and boil it down to the
consistency of confection (lehyam).

Dosage of the confection is 2-3 teaspoonfuls 2 or 3 times a day. The dosage has to be
determined according to the condition of the patient and the intensity of the disease.

Though the syrup form was very effective, we found it very difficult to handle. It used to
get easily spoiled through fungus formation. A good bit this medicine had to be thrown
away because of this problem. Later we prepared it in powder form.

Mode of preparation of powder/pills/capsules: Clean the outer portion of the neem

bark and dry it in the sun. Powder it and strain through a fine cloth. Mix little cinnamon
powder to the neem bark powder, and add guduchi stem juice to the powders and knead it
well. You can roll them into mutter size pills. After kneading well it can be dried in the
sun and preserved as powder form. The powder can be filled into capsules as well.

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11. Clinical Trial and Documentation

This is the most important task of the whole project. We followed the “Double blind
randomized clinical trial”.

We wanted to treat a total of 652 patients and document the results 326 patients will get
herbal medicine and another 326 will get placebo. When each centre is given the
medicine packets, each packet will have a number. Half of the number of packets will
contain herbal medicine and half will contain only placebo. Which numbers contain the
medicine and which numbers contain placebo will be noted down before supplying them
to the centers.

Most of the centres we selected for clinincal trial there were herbal parishioners or people
acquainted with herbal medicine.

In the hospital/health center the doctor or the sister in charge examines the patient. The
peripheral smear test and other necessary tests are done. If the patient is eligible for the
trial according to the protocol conditions, his/her consent is obtained and he is
recommended for the herbal medicine. Usually only the pharmacist or the nurse gives the
medicine packet. They know only the packets contain herbal medicine. But they do not
know that some of the packets contains placebo. So neither the doctor, nor the one who
gives the medicine nor the patient knows the content of the packet. This way it is
randomized and blinded. In some centres if the patient has high fever they routinely give
a dose of paracetamol to reduce fever.

Details of the patient profile, the signs and symptoms, report of the lab test, the number
on the packet will be noted down the documentation sheet The patient is asked to come
again within five to seven days. He will undergo a second blood test and the result of the
test will the entered along with his previous record. If no improvement is seen at the 2nd
test, he will be give modern medicine or other medicines.

From time to time I collected the reports. Good number of people who got ok with the
medicine did not turn up for the second time. Some of those people when they came for
some other ailments, the nurse inquired why they did not come second time after taking
malaria medicine, their response invariably was, “After getting all right, why should I
come for second time for the same sickness”.

In 2006 Jan. Dr. Nandi, the director of tropical diseases in Calcutta came to
Mariampahar. While discussing about our study, he suggested that unless we give the
herbal medicine alone we cannot access the effectiveness of the herbal drug. I asked him
whether it is all right for an allopathic centre giving herbal drug, he suggested the
possibility of getting herbal parishioners to give the herbal drug. So from 2006 onwards I
started giving herbal medicine without chloroquine, after consulting some of the ethical
committee members.

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People and Institutions Involved in this Task
• Prem Jyoti Community Hospital, chandragoda
• Holy Cross Hospital Sitapahar
• Dr.Benjamin Babulu Hembrom, Kundli
• Holy Cross Hospital, Belatarnh (Bhagalpur diocese)
• Sr. Catherine, St. Xavier’s dispensary, Sahibgunj

12. Second Ethical committee meeting

The second ethical committee meeting of Malaria Action research programme was held
at Catholic Church, Mariampahar on afeb. 24 2010,at 4.00 P.M.

The following people were present for the meeting.

Dr. Isaac, Prem Jyoti Community hospital, Chandragoda

Sr. Lucy LLB, Advocate, Civil court, Pakur
Mr. Paulus Murmu, Manjhi Haram, Bara Banjhi,

(Dr. P.P. Hembrom, being sick could not be present.)

Fr. Meloo, the programme coordinator, presented the whole process of the study in detail.
The study was started as a comparison between the curative effect of chloroquin along
with herbal medicine and that of chloroquin along with placebo. More than 400 people
were treated and only less than half the number came for the second blood test. Later on
as suggested by,Dr.Nandi, an expert in malaria control programme, we were giving
herbal medicine alone without chloroquine.

Thus we have three groups in this study. Group A= Herbal medicine with chloroquine;
group B= Chloroquine with placebo and group C=Herbal medicine alone.

Under group A, we have the 2nd blood test of 124 people; under group B we have the 2nd
blood test of over 278 people and under group C we have the 2nd blood test of177
people.

Medicine used is a combination preparation of Neem bark with guduchi TTinespora

Coradifolia with little of cinnamon powder. The preparation of the medicine was done
under the supervision of Fr. Meloo.

All the centers followed the protocol carefully. All those who did not get all right with
the packet medicines were treated with modern medicines like E mal injection, Cipro as
antibiotic, vitamin B complex, Paracetamol and liver tonic as per requirement. The

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expenses incurred for the continued treatment was borne by the project. There were no
serious complications under this process. First of all as per the protocol, there was
screening of serious cases of malaria as well as complications like kala azar, typhoid,
jaundice, T.B. etc.

In the ethical committee meeting, the group inquired mainly about the follow up
treatment of those who did not get well.

13. Trial for Prevention of Malaria.

In two centers – Badbanga and Sokho – a combination preparation of neem, karanj, tulsi,
chiretta and pepper were given as preventive. It was prepared in pills form. The mode of
administration was as follows: For first month, take one pills per day. In the second
month, take three pills a week in alternate days. In the third month, take two pills per
week. From fourth month onwards, take one pill every week, if you are staying in a
malaria prone area.

According to Sr. Savita, the health centre in charge at Badbanga, the malaria incident in
their hostel came down by 60% from 2005 to 2007.

Sr. Anjana in Sokho also used the same preparation both for the hostel students and for
the village community of Karwateri. She also claims that the malaria incident came down
among very much among hostel children in one year time.

Karwateri village in Khaira block near Sokho mission, (Bhagalpur diocese) was a highly
malaria prone area. Sr. Anjana with the help of Mr. Christopher began to give the Malaria
preventive medicine very systematically to the people. Within one year there was a very
remarkable decrease in the incidence of malaria in that village. In 2007 when I visited the
place second time they told me that there is hardly any malaria case in the village.

Both in the boys and girls’ hostel also malaria incident came down by 60% in 2006,
according to the health centre register of Sokho.

T R T C, Chaibasa. . Fr. Sevanand Melookunnel, S.J.

April 13, 2010 Programme Coordinator.

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