STRATEGIES FOR SUSTAINABLE UTILIZATION OF PHYTOMEDICINES IN MANAGEMENT OF ACQUIRED IMMUNODEFICIENCY SYNDROME (AIDS) IN THE LAKE VICTORIA REGION OF KENYA

• STRATEGIES FOR SUSTAINABLE UTILIZATION OF PHYTOMEDICINES IN MANAGEMENT
  OF ACQUIRED IMMUNODEFICIENCY SYNDROME (AIDS) IN THE LAKE VICTORIA REGION
  OF KENYA
  
  
  By Professor Philip Aduma
  
  The author is a Viral Pharmacologist with interest and current work in
  use of phytomedicines in management of viral diseases and in
  conservation of medicinal plants. He is presently Head, department of
  Zoology, Biomedical Science and Technology at Maseno University, P.O.
  Private BAG, MASENO, Kenya
  His e-mail address is irmaseno@africaonline.co.ke.
  
  ABSTRACT
  
  The human immunodeficiency virus (HIV) is the aetiological agent of
  acquired immunodeficiency syndrome (AIDS). In the Lake Victoria region
  of Kenya, transmission of the virus occurs primarily by heterosexual
  intercourse, from mother to baby and to a lesser extent through
  transfusion of blood and through occupational risk factors. HIV-1 is the
  most common cause of AIDS in the region. The epidemic is continuing to
  explode and most hospitals in the region now have 50% bed occupancy with
  AIDS patients in the mid-terminal to terminal stages of the disease. The
  expansion of AIDS is thus posing great challenges and concerns on the
  very existence of the people of this region. As the disease ravages
  throughout the region, a general state of poor health has set in. This
  in turn has reduced life expectancy, slowed down productivity and
  inhibited growth. The rural poor who already do not have access to
  adequate health facilities are most severely affected. The required
  costs in diagnosing and treating the infection and its associated
  syndromes are well beyond the per capita expenditures on health. The
  production losses associated with the epidemic have caused a negative
  impact not only on the people’s health but also on the environment in
  which they live. The main problem experienced with current approaches to
  control is the limited ability to stop or reduce infection rates in the
  region, treat those who are already affected by the disease and resolve
  issues of nature conservation on one hand and poverty and food security
  on the other. This paper recognizes that antiretroviral drugs are beyond
  the reach of over 90% of HIV positive patients in the region. It further
  recognizes that the communities of the lake region have in the past
  employed local medicinal plants as sources of traditional medicines in
  the management of infections many of which are opportunistic in AIDS.
  Our own studies as well as studies elsewhere have shown that in deed the
  biological activities of some of these plants can be authenticated in in
  vitro and in vivo studies. To this effect the development of traditional
  medicines by value adding as phytomedicines should be encouraged and
  supported. By linking medicinal plants’ resource utilization to
  conservation, the recent loss of biodiversity of the lake region can be
  reversed and ecosystem stability restored. This would serve to support
  health care delivery and poverty alleviation in the lake region.
  
  
  
  
  1. BACKGROUND AND JUSTIFICATION
  The lake Victoria basin of Kenya covers several districts some of which
  like Migori, Homa bay, Suba, Rachuonyo, Nyando, Kisumu, Bondo, Siaya and
  Busia are contiguous to the lake while others like Kisii, Nyamira,
  Kuria, Kericho, Nandi, Vihiga and Teso form part of what is referred to
  as the catchment areas of the lake. The population of the basin by 1999
  census is about 7 million. The multiethnic communities of the lake
  region comprises severally the Luo, Suba, Teso, Kalenjin and
  Bantu-speaking peoples.
  
  A major problem facing the communities of the lake region is their poor
  economic status; rampant poverty, malnutrition and devastation caused by
  chronic and often debilitating diseases notably AIDS. Currently AIDS
  ranks as the most important infectious disease facing people of the lake
  region in the 21st century. This region is now part of the global
  epicenter and therefore the epidemic will continue to have upward trends
  in the region.
  
  In the last 30 years there has been a shift of emphasis from traditional
  varieties of food crops to cash crops like sugar cane and rice which
  require heavy emphasis in terms of fertilizer and herbicide
  applications. This has resulted in alteration of structure and
  functioning of ecosystems. The consequences have been a 40-50% fall in
  production value of land. Overall people’s income has fallen drastically
  over the last 30 years. This has been compounded by a falling health
  services provision. In most parts of the lake region, there are few
  functional health centers especially in the rural areas.
  
  A recent survey of health provision in the lake communities revealed
  that the average distance people have to travel to a health center is
  10-30 km in Rachuonyo district,
  10-50 km in Homabay district and 10-80 km in Suba district. It was also
  observed that the health centers are inadequately equipped and some are
  inaccessible due to a devastated infrastructure largely attributed to
  the 1997 El-Ninho rains. Several cases of AIDS or AIDS-related syndromes
  were encountered both through interviews with traditional healers and in
  actual visits to hospitals. Many of those in rural areas had been
  unable to get proper treatment at local health centers or had been
  discharged to “ come and die at home”, to quote a term used by the local
  people. The survey was based on interviews with more than 50 traditional
  healers and custodians of indigenous knowledge. It revealed a total of
  48 diseases or clinical conditions treated or managed traditionally
  using medicinal plants. These included some of the most common
  opportunistic infections in patients infected by the HIV-1 namely; (1)
  -Oral thrush ( Candidiasis)
  -Tuberculosis and Pneumocystis carinii
  -Non-hemorrhagic chronic diarrhea (gastritis and gastroenteritis)
  -Pneumonia and chronic persistent coughs
  -Herpes zooster and Disseminated herpes simplex
  - Generalized wasting and weakness
  - Partial or complete loss of sight ( due to human cytomegalovirus
  retinitis)
  
  During the last part of 1999, the government of Kenya declared AIDS a
  national disaster when statistics revealed an average mortality of 500
  persons per day from AIDS. This figure is higher in the lake region
  where presently 50% of hospital bed occupancy is with AIDS patients in
  the mid-terminal to terminal stages of the disease. From a typical AIDS
  progression pattern one can deduce that many of these patients had
  contracted the virus in the early to mid-1990s.(2). Along the various
  landing beaches of lake Victoria where fish trade is high and in the
  peri-urban sugar cane growing zones (where population densities are
  higher than in rural areas), there is a very high infection rate largely
  attributed to a large number of migrant workers.
  
  1.1 The Health and Productivity of the lake people
  It is well established that a positive correlation exists between health
  of individuals and their income and between their health and
  productivity. This correlation is usually assumed to indicate a
  relationship that runs upwards from income to health but we know that
  health and productivity is also related in an upward trend. This is
  explained by the fact that because healthy people generally tend to be
  strong physically, mentally, spiritually and have a positive attitude to
  life, they therefore have a higher productivity.
  Poor health caused by the AIDS epidemic has therefore greatly reduced
  growth capacity in the lake region. Many people are chronically sick and
  are a burden to their families, friends and colleagues. Orphaned
  children have to be cared for by an already impoverized family or have
  to fend for themselves. With more than 80% of the AIDS cases occuring
  amongst the working age group of 25-49 years, the income and
  productivity losses due to the disease are alarming.
  
  1.2 Problems encountered in containing or controlling the spread of
  HIV/AIDS in the lake region
  Traditionally, intervention strategies in AIDS management have consisted
  largely of treating opportunistic infections and to a lesser extent use
  of antiretroviral drugs especially amongst the upper class members of
  the society.(3). AIDS awareness campaigns have been mounted with
  intensity yet all these approaches have failed to stem the spread of the
  disease. In the majority of opportunistic infections, treatment failure
  is attributed to;
  - Cases being presented when the conditions are advanced
  -Lack of proper diagnosis as most diagnostic centers are ill equipped
  -Lack of finances to buy expensive prophylactic and curative drugs. With
  regard to antiretroviral drugs, all of them are beyond the reach of over
  90% of HIV-positive patients .
  ? Frequency of appearance of viral mutants with altered sensitivity to
  drugs is high even with combination drugs, thus making treatment even
  more expensive.(4,5).
  ? Generalized energy, protein and micro-nutrient lack especially amongst
  the low class members of the society. This contributes to a low or
  deficient immune function
  
  Consequently a large percentage of patients have resorted to consulting
  traditional medical practitioners with varying degrees of success. The
  traditional healers use medicinal plants either singly or in
  combination. Thus their knowledge, accumulated over the years on what
  plants to use and how to use them is commendable. For example
  preliminary evaluation of some of the plants used; such as Chaemacrista
  nigricans in gastritis and gastroenteritis of bacterial origins or Aloe
  wallistoni in herpes virus infections show a sound pharmacological basis
  for use of the plants. Further more their knowledge of potential
  toxicity of the plants is equally sound.
  For example the plant Phytolacca dodecandra whose toxicity is well
  established in veterinary studies is used by the healers in milligram
  quantities to treat a number of conditions such as snakebites. (1).
  
  This region has a rich biological diversity in plant, animal and
  microbial life forms some of which are now threatened with extinction as
  most ecosystems and habitats are degraded or destroyed in order to
  create space for short-term development. This is being done at the
  expense of conservation-oriented strategies that would best serve the
  communities in the long run. (6).
  
  2. STATEMENT OF THE PROBLEM
  AIDS is the main health issue affecting the lake region, causing so much
  suffering and poverty. There is limited ability of current measures to;
  - Stop or reduce infection transmission rates
  - Treat those who are already affected by the disease
  - Resolve the issues of nature conservation on one hand and on the other
  hand food security and poverty alleviation.
  
  To address these problems, a workshop was held at Maseno University (
  which is situated in the lake region ) from 18 th to 21stApril 1999. The
  Participatory workshop on “Medicinal Plants and Biodiversity in the Luo
  and Suba communities of lake Victoria.” brought together a total of 90
  participants comprising of traditional healers, biomedical scientists,
  clinical workers, social scientists and other custodians of indigenous
  knowledge from the Luo - Suba communities of western Kenya and from
  Uganda. The main objective was to address issues relating to exchange of
  knowledge, conservation, preservation, awareness, acceptability of
  medicinal plants in AIDS treatment and reclamation of degraded areas for
  ecological restoration (7). The following presentation is based
  partially on recommendations of that workshop.
  
  3. PHYTOMEDICINES FOR MANAGEMENT OF HIV/AIDS
  In developing strategies for use of phytomedicines the following
  questions should be answered
  a) Are there medicinal plants in the lake region which have a curative
  or prophylactic effect in inhibiting the virus or treating opportunistic
  infections?
  i) Our own studies amongst the Luo and Suba communities show that
  several medicinal plants have effect in health management.of people with
  AIDS. Plants indicated for the medical condition is/are listed if at
  least three users similarly prescribe for the same condition. However
  their efficacy and therapeutic indices have yet to be established in
  controlled studies (1).
  ii) Studies elsewhere show that certain plants have molecules that are
  inhibitory to key metabolic pathways in the HIV-1 replication process
  (8).Examples are;
  -Ancistrocladus korupensis ( Michelamine B )
  - Castanospermum australe ( Castanospermine )
  Although these two plants are rare in this region, relatives who are
  likely to contain similar chemicals are likely to be present.
  iii) A plant with high content of Quercetins is currently used by a
  traditional healer in the region for treatment of other viral
  infections. Quercetins are known to inhibit viral RNA polymerase
  
  b) Why phytomedicines and not medicinal plants or pure active molecules
  from plants?
  i) Phytomedicines are medicinal preparations that have been extracted
  with solvents
  from plants. Solvents used are as close as possible in polarity to
  solvents used by traditional healers. They should provide immediate
  remedy to patients with AIDS.
  ii) High molecular weight compounds such as tannins are removed and
  extract tested to ensure biological activity is still present
  iii) They are processed by several concentration and other procedures
  such as freeze-drying or dried in a rotavapour, then reconstituted in an
  appropriate vehicle, usually for oral or topical administration.
  iv) Safety, efficacy, standardization, processing and quality assurance
  are maintained on a batch to batch preparation
  v) The extracts are sold directly to the consumers and without doctor’s
  prescription.
  vi) There are less regulatory requirements in marketing of
  phytomedicines
  vii).They are less expensive to produce than pure active molecules and
  are more acceptable by doctors and consumers than plants or plant parts.
  Cash from sale of phytomedicines is then used in activity-guided
  purification active molecules.
  
  c) What are the research issues essential for developing medicinal
  plants into phytomedicines?
  i) Inventory and population biology of plants used for particular
  conditions followed by data base development. We have done this
  partially for the southern districts of Nyanza province of the lake
  region; duration 6 months
  ii) Enlisting the support and cooperation of traditional healers and
  custodians of indigenous knowledge, through seminars and training
  workshops; the 1999 Maseno University workshop is an example.
  iii) Initiation and support of community-based cultivation and
  conservation of the plants. This will be done in collaboration with
  University–based researchers to assist in agronomic practices. This also
  ensures supply of raw materials. We are now exploring the possibility of
  growing selected plants for AIDS management. The main beneficiaries here
  will be women who form over 60% of healers in this region, who will be
  involved directly in plant growing.
  
  iv) Standadisation of extracts to include;
  -Botanical definition, including plant parts ie reference material;
  duration 3-6 months
  -Toxicological assessment to include acute and chronic toxicity in
  laboratory animals, using route of administration and dosage as used by
  healers and 5x and 10x dosage ; establish
  LD 50 duration 6 months
  - Tests for carcinogenicity and mutagenicity; duration 6 months
  -Chemical reference or a type of fingerprinting to ensure consistency in
  preparation; duration 3 months
  -Pharmacological investigations; specifically cell culture assays to
  establish IC 50, ED 50 MTC and TI; for HIV-1 eg. Lymphoid cell line
  protection assays (XTT, RT, p24 antigen, inhibition of syncytium
  formation);
  for HSV and HCMV monolayer cell culture assays (plaque reduction
  and virus yield reduction assays),; duration 12 months
  -Microbiological screening to determine spectrum of activity against
  common opportunistic bacteria and fungi associated with AIDS and also to
  establish level of microbial contaminants (common sensitivity tests on
  agars); duration 3 months
  v) Pharamaceutical preparations, quality assurance, heavy metal
  determination, preservation and good manufacturing practice must be
  maintained
  vi) Clinical prospective or cohort studies; randomization and comparison
  with standard drugs such as Zidovudine or Nevirapine. Must have baseline
  data on all patients before onset of trials ( eg. p24 levels, CD4
  counts, ) Cooperation with clinicians must be ensured.; duration 12
  months
  
  Total duration from stadardization to completion of cohort studies is
  approximately
  24 months because some procedures overlap one another. This is five
  times sorter than it would take to develop and test pure molecules.
  
  d) How to create awareness and acceptability in the use of proven and
  standardized phytomedicines?
  i) Lake Victoria Regional Initiative on Phytomedicines for Management of
  HIV/AIDS (RIPHA); a kind of a regional server as was proposed in the
  Maseno workshop. A similar proposal on “networking on medicinal plants
  and traditional medicine in Africa” was discussed at the recent Abidjan
  workshop. RIPHA is to be dedicated to work on catastrophic diseases ;
  notably AIDS and Cancer.
  ii) Local chapters or affliates to the RIPHA; or a kind of local area
  network comprising; traditional healers, custodians of indigenous
  knowledge, clinical workers and biomedical scientists
  iii) Popularisation through radio, TV, barazas, seminars, agricultural
  shows
  iv) Training of traditional healers
  v) Therapeutic strategies with an industrial partner
  
  e) How to ensure sustainable supply of raw plant materials?
  i) Initiation and support of community-based conservation plots and
  gardens. Current sites have been identified on basis of soil types,
  rainfall availability and most needed and endangered species. These are,
  Kabwoch in Homabay district, Kaswanga in Suba district, Kapwonja in
  Kisumu district and the sacred sites of Got Ramogi in Bondo district and
  Ndere island in lake Victoria
  ii) Plant tissue culture for plants, culture media and cells as sources
  of extracts
  iii) germ plasm bank and genetic resources preservation ;seeds, tubers,
  cuttings, tissues and single cells
  f) How local people, TH, CIK Scientists and IP will share in commercial
  benefits arising from such enterprises .
  i) University-based researchers as brokers in forming a bridge between
  local communities and industrial partners
  ii) Contracts and agreements only for a specified time
  iii) Payments to traditional healers and custodians of indigenous
  knowledge to include all expenses in collection and handling
  iv) Research and screening should maximally be done in home institution
  to enhance capacity building
  v) 7.5% of royalties to local communities from which plant was derived
  to support development activities such as rural health, schools,
  conservation plots. 2.5% to individual TH or CIK
  vi) Co-authorship and patent rights to scientists, participating home
  institution and industrial partners to be determined on basis of
  contributions and value added to final product. These patents may cover
  production processes, chemical structure, use, applications and
  modifications on the structure to make synthetic or semi-synthetic
  derivatives. The source of the original material must be acknowledged
  vii) Where an industrial partner uses knowledge obtained from the
  supplied extracts to derive synthetic or semi-synthetic analogs,
  recognition should also be given by payment of royalties to TH, CIK,
  Scientists and participating home institution.
  4. CONCLUSION
  AIDS has become a tragedy of immense proportions in this region. We
  recognize that in this region, like most African countries, medicinal
  plants continue to serve as man’s weapon against the disease As most
  affected people can not access western drugs it is our request that this
  conference supports the Regional Initiative On Phytomedicines For
  Management Of HIV/AIDS. This paper has proposed linkage between
  ethnobotany, health care and biodiversity conservation as a way forward
  in combating AIDS and alleviating poverty.
  
  5. REFERENCES
  1. Aduma P.J. (1998). Medicinal Plants and Biodiversity in the Luo and
  Suba communities of lake Victoria. IDRC technical report 1
  2. Aduma P.J. (2000). Acquired Immunodeficiency syndrome in Africa:
  Perspectives and Challenges in control. IRPS reprint series No 6. Maseno
  University
  3. Aduma P.J. (1995). Steps in the viral replication process:Potential
  targets for antiviral drug development. Discovery and Innovation
  7(2).125-137
  4. Aduma P.J., N. Bischofbergerand A. Fridland . Development of
  resistance and cross-resistance to anti-HIV compounds. Unpublished
  5. Hammer S.M.. (1996). Advances in antiretroviral therapy and virus
  load monitoring. AIDS 1 :SI-SII
  6. Aduma P.J. .(1998). Biological Diversity of the lake Victoria region
  with emphasis on ecosytems that contain plants and microorganisms of
  industrial concerns. Kenya National Academy of Sciences Public lecture
  on :Environment and Development”. Jan 29 1998
  7. Aduma P.J (1999). Participatory workshop on Medicinal plants and
  Biodiversity in the Luo and Suba communities of lake Victoria; April
  18-21, 1999, Maseno University.IDRC publication report 2
  8. Yarchoan R, H. Mitsuya and S. Broder (1993).Challenges in the therapy
  of HIV infection. TIPS Vol 14;196-202.
  9. Aduma P.J., Connelly M., Bischofberger N, and A. Fridland. (1994).
  Comparison of anti-HSV activity and metabolism of acyclic nucleotide
  phosphonate analogs. Antiviral. Res. 23 (suppl 1) p 41 .7th
  International conference on antiviral research, Charleston S.C february
  27-march 4, 1994 USA.

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