CHAPTER 8
MEDICINAL FLORA AND RELATED TRADITIONAL KNOWLEDGE OF WESTERN GHATS: A POTENTIAL SOURCE FOR COMMUNITY-BASED MALARIA MANAGEMENT THROUGH ENDOGENOUS APPROACH
B. N. PRAKASH,1 P. M. UNNIKRISHNAN,2 and G. HARIRAMAMURTHI1
1Trans-Disciplinary University (TDU), School of Health Sciences, FRLHT, 74/2, Jarakabande Kaval, Attur post, Via Yelahanka, Bangalore – 560064, Karnataka, India. E-mail: vaidya_bnprakash@yahoo.co.in; unnipm@gmail.com; hariram_01@yahoo.com
2United Nations University – Institute for the Advanced Study of Sustainability, Tokyo, Japan
CONTENTS
8.2Epidemiology of Malaria in Areas of Western Ghats
8.3Botanical Listing of Traditional Anti-Malarials from Western Ghats
8.4Ethno-Pharmacology of Traditional Anti-Malarials
8.5An Example of a Remedy and Its Assessment: Ayurveda and Pharmacological Evidence
8.6Community-Based Participatory Study
ABSTRACT
The ecosystem specific plants have been used by local communities since many centuries to take care of their primary health care problems. In malaria endemic tropical regions, more than 1200 plant species have been reported to be used for management of malaria. There are several strategies followed to develop new drugs for prevention and treatment of malaria. This chapter outlines a strategy based on an endogenous development approach with trans-disciplinary research methods that can be used to identify new botanicals for management of malaria. It also describes low-cost activities that can be carried out at the community level, with the aim of translating research directly into improvements in the local management of malaria. It also highlights the specific use of 31 plant species for malaria treatment in Western Ghats region.
8.1INTRODUCTION
8.1.1OVERVIEW: MALARIA: A PUBLIC HEALTH PROBLEM
Globally, an estimated 3.3 billion people are at risk of being infected with malaria and developing disease, and 1.2 billion are at high risk. According to the latest estimates, 198 million cases of malaria occurred globally in 2013 and the disease led to 584,000 deaths (WHO, 2014). India contributes to over one fifth (22.6%) of clinical episodes of P. falciparum and 42% of episodes of P. vivax globally (Guerra et al., 2010; Hay et al., 2010) and around 200,000 persons die annually due to malaria (Dhingra et al., 2010). Although, there are several strategies to control and treat malaria infections, mortality and morbidity due to malaria infection have not declined. This is because of the evolution and spread of drug resistance to all important classes of anti-malarials and resistance to almost all types of insecticides. Moreover, many of the anti-malarials are expensive and inaccessible to the needy populations. There are several sincere efforts to develop malaria vaccine. This could play a role in transmission reduction in the future by preventing the infection of mosquitoes and by preventing vaccinated individuals from becoming infected by mosquitoes. Although a malaria vaccine is technically feasible, making a vaccine to protect people against a parasite has never been done. Thus, there is no licensed vaccine against malaria. Therefore, the population in malaria endemic areas depends on easily accessible traditional plant-based solutions for prevention and treatment of malaria.
8.1.2RELEVANCE OF TRADITIONAL MEDICINE
Medicinal plants have played a significant role in maintaining and improving the quality of human life for thousands of years. Herbal medicine is based on the principle that plants contain natural substances that can prevent disease, alleviate illness and promote health. The ecosystem specific plants continue to contribute to the health security of rural communities in India (Darshan and Unnikrishnan, 2004; Payyappallimana, 2010). Plant resources and the associated ethnobotanical knowledge of the communities are rich source of natural drug research and development (Albuquerque et al., 2014). In rural areas of developing countries, traditional medicines are often trusted, affordable and accessible, as they are made from locally available plants (Kitua and Malebo, 2004). A large proportion of the rural population continues to rely on traditional medical practitioners and local medicinal plants for primary health care, as a choice or when there is no access to other medicine (Phillipson, 2001).
In spite of the great advances observed in modern medicine in recent decades, around 75% of the population still depends on traditional medicine for treatment of malaria particularly in Asian and African countries (Willcox et al., 2004). In fact, nature is, as ever, an extremely rich source of potential anti-malarial agents. The usual reason for exploration in traditional medicine stems from the recognition that two of the major anti-malarial drugs, quinine and artemisinin trace their origin to traditional medicine (Hirt and M’Pia, 2008; Kayser et al., 2003). Cinchona officinalis L. was traditionally used to treat intermittent fever or malaria by South American healers. Chinese traditional medicine explains the use of Artemisia annua L. for malarial fevers. Today, Artemisinin based combination therapy is the drug of choice for the management of malaria in many chloroquine resistant areas like in African countries. Apart from these two main plants, earlier study has reported that 1277 plant species have been used for the management of malaria (Willcox et al., 2004). Communities in malaria endemic area find several advantages in use of local plant species as they are cost effective, highly accessible, acceptable, strong belief, empirical evidence for cure, relatively good knowledge in the people and long-term usage of traditional medicine.
8.1.3ENDOGENOUS DEVELOPMENT METHODOLOGY AND TRANS-DISCIPLINARILY
In a situation where large-scale interventions and development approaches have either failed or are inaccessible to large percentage of the population, it is important to look at development strategies which are local resources based and are easily accessible to the communities. The approach proposed has its roots from the endogenous development practice which “is based on local communities’ own criteria for change and their vision for wellbeing based on the material, social and spiritual aspects of their livelihoods but in a constant and dynamic interface with external actors and the world around them. Endogenous development seeks to overcome a western bias by making peoples’ worldviews and livelihood strategies the starting point for development. Endogenous development moves beyond integrating traditional knowledge in mainstream development and seeks to build biocultural approaches that originate from local people’s worldviews and their relationship with the earth. Organizations can support and strengthen the endogenous development that is already present within the communities, promoting the interface between tradition and modernity. In doing so, endogenous development emphasizes the cultural aspects within the development process, in addition to the ecological, social and economic aspects.” (ETC, 2007). This is the guiding principle of the community outreach programs which mainly focuses on locally available resources, and related traditional knowledge of the communities. We believe that participatory, people-focused and local health knowledge driven knowledge and practices are relevant for primary health care interventions. This method is a judicious blending of locally available plant resources, knowledge, skills and expertise with appropriate elements of western scientific knowledge and modern technology to address specific health challenges (ETC, 2007). Most importantly this also requires a transdisciplinary and a multistakeholder approach.
As a methodology, trans-disciplinary research (TDR) refers to scientific inquiry that encompasses the various disciplines to address a ‘real-world’ problem. The basic concept of TDR is to transgress boundaries between scientific disciplines and between science and other societal fields and includes deliberation about facts, practices and values (Wiesmann et al., 2008). We adopt a participatory method which gives equal weightage to the strengths of every discipline and attempts to solve the problem holistically. While exploring traditional solutions for any health condition, this approach helps us in not only including the perspective of medicine related aspects (traditional medicine and modern bio-medicine), -but also other allied sciences as well as the social, economic and environmental dimensions in a community context.
The failure of national antimalarial programs over several decades, calls for developing such locally based solutions for the prevention as well as management of malaria. Following is such a methodology attempted by the Transdisciplinary University (at Jarakabande Kaval, Bangalore) for its malaria management interventions in communities of endemic regions. The method looks at the nature and patterns of the health condition, locally available plants and related traditional medical practice along with a strategic plan for local interventions. In the following section we elaborate the details of this methodology called DALHT (Documentation and Rapid Assessment of Local Health Traditions) with respect to management of malaria.
8.1.4DOCUMENTATION AND ASSESSMENT OF LOCAL HEALTH TRADITIONS
Many local health traditions are sound, some are incomplete and a few may be distorted. One of the major challenges in advocating local health practices is to have clear documentation on the efficacy and safety of these practices. Finding out effective practices through elaborate pharmacological and clinical trials is a colossal task. For example, to validate a single practice would involve 5–8 years of laboratory research with a huge amount of capital investment.
In order to systematize and assess various malaria management practices in a rapid and cost effective way a participatory method called Documentation and Rapid Assessment of Local Health Traditions (RALHT) was applied (Figure 8.1). This method has been found very effective earlier in primary health care conditions in a number of locations in India. It is primarily community based and uses dialog and building consensus for assessing traditional health practices as their strategy. Community members who are knowledgeable in traditional practices, local healers, Ayurveda doctors, researchers, community members and other experts form the core group for dialog. To initiate the process in a community, nature and type of malaria, their incidences are documented along with comprehensive documentation of local knowledge on malaria management. Documentation is done in groups to facilitate maximum information sharing through cross referencing. Each group ideally consists of 5–7 community members, folk healers, Ayurveda doctor, a botanist and a documenter. Free, prior informed consent (FPIC) is taken before documentation. Detailed questionnaires have been prepared to document each of these aspects. Documentation includes details of the folk healer or community member sharing knowledge; details of the malarial fever as understood by the local healer or community member; preventive or curative methods for malaria management or vector control; and medicinal plants used for each practice identified by botanist. Following documentation voucher specimens of medicinal plants used in these practices are identified and inventoried. Detailed literature research is carried out from codified traditional knowledge systems, such as Ayurveda and Siddha along with also data on phytochemistry and pharmacology. Desk research consists of correlation of the health condition as per Ayurveda and modern science and compiling detailed data from secondary literature. This exhaustive data based on global data bases are compiled systematically into dossiers which are sent to experts for review. This is followed by an assessment workshop. During this community-based workshop these comprehensive dossiers are used as the reference material for commenting on the safety and efficacy of each prioritized malaria management practice. The unique feature of the assessment workshop is that it is a pluralistic platform for dialog between local experts and scientific experts on each practice. A typical workshop involves folk healers, Ayurvedic doctors, botanists, field data collectors, clinical pharmacologists or modern medical doctors and community members. These subject experts comment on a specific health practice based on the dossier information available with them from the respective knowledge streams. Each practice with their details is presented to the group. Community’s positive or negative experience about a practice and supporting evidence or precautions or additional information by any system of medicines is used for assessing a practice. Negative remarks from any system of knowledge are also documented and ambiguous practices are put aside for further detailed research. Positively assessed practices are then put through community based, participatory clinical studies especially for malaria prophylaxis. Once there is positive evidence from such clinical studies they are selected for wide promotion.
FIGURE 8.1Process of rapid assessment of local health traditions (Adopted from Nair, 2006).
8.2EPIDEMIOLOGY OF MALARIA IN AREAS OF WESTERN GHATS
Vector borne disease is a major health challenge in several districts of Western Ghats (Dhiman et al., 2011). Anopheles fluviatilis, Anopheles stephensi and Anopheles culicifacies are commonly seen vector species in Western Ghats which are responsible for transmission of malaria. The districts like Surat (Gujarath), Nandurbar (Maharashtra), Dakshina Kannada (Karnataka), Thrissur and Pathanamthitta (Kerala), Tirunelveli and Kanyakumari (Tamilnadu) are major malaria endemic districts in the region (http://www.malariasite.com/malaria-india/; http://www.nrhmtn.gov.in/vbdc.html; http://dhs.kerala.gov.in/). A recent study on projection of malaria by 2030, based on temperature and relative humidity at district level, indicates no major change in the transmission window, thus predicting the transmission of malaria to continue in similar trends in Western Ghats (Dhiman et al., 2011). As an illustration of current situation, Figure 8.2 shows the existing seasonal occurrence of malaria cases in a representative district of the Western Ghats, Dakshina Kannada (Karnataka).
FIGURE 8.2Incidence of malaria in Dakshina Kannada district, Karnataka.
8.3BOTANICAL LISTING OF TRADITIONAL ANTI-MALARIALS FROM WESTERN GHATS
In Western Ghats, there are around 4,500 plant species in which 35 percent of them are endemic. As malaria is widespread health condition in the region, population in these endemic areas have also reported to be using diverse local flora as a means to prevent and treat malaria infection. A brief literature survey showed 104 plant species which are used for malaria, fever and intermittent fevers. From this list, we shortlisted 31 plant species which are specifically used for malaria treatment in Western Ghats region based on existing literature both traditional as well as contemporary (FRLHT database, Ganeshaiah, 2013). Table 8.1 shows the important plants species reported to be used by the communities. The plant species used in single or in different combinations, belong to 23 families. Among 31 species, majority were herbs (13 species) and shrubs (10 species). Leaf was the most commonly used plant part (13 species). The principal mode of remedy preparations was decoction (Table 8.1).
TABLE 8.1Important Medicinal Plants Used for Malaria Management in Western Ghats
8.4ETHNO-PHARMACOLOGY OF TRADITIONAL ANTI-MALARIALS
The next step in a documentation and assessment methodology is to look at the existing scientific data on the local practices. In this section we outline the existing pharmacological data on the above selected plants.
Earlier studies have shown that there were great efforts to study the potential anti-malarial activity of Western Ghats plant species (Chenniappan and Kadarkarai, 2010; Samy and Kadarkari, 2011; Kaushik et al., 2015). The advantage in screening the plants which are widely used by traditional healers for treatment of malaria are significantly more active in vitro and/or in vivo against Plasmodium than plants which are not widely used, or not used at all, for the treatment of malaria (Leaman et al., 1995; Vigneron et al., 2005). Table 8.2 shows the list of plants which are studied for antiplasmodial and antipyretic activity using in vitro or in vivo models of Plasmodium species. However none of them have gone to stage of clinical trial and product development.
TABLE 8.2Cross-References in Published Literature on Antiplasmodial and Antipyretic Activities of Plants Used in the Western Ghats Region in India
8.5AN EXAMPLE OF A REMEDY AND ITS ASSESSMENT: AYURVEDA AND PHARMACOLOGICAL EVIDENCE
Before stepping into in vitro or in vivo activity of traditional anti-malarials, it is important to prioritize the plants on the basis of available Ayurvedic information and pharmacological information through RALHT approach. Here, we are showing an example of application of rapid assessment methodology on a single plant namely, Alstonia scholaris. Similar methodology can be adopted to prioritize other plants (Box-1 & 2).
8.6COMMUNITY-BASED PARTICIPATORY STUDY
In the process of rapid assessment, we can identify an effective traditional remedy which provides an appropriate solution for the local problem. In addition to this, a community based, participatory research can be organized to test the efficacy of the traditional remedy. We implemented such a research approach through organizing health interventions called Decoction (Kashaya camp) camp in Odisha, India to study the prophylactic efficacy of a traditional herbal malaria prophylactic remedy. The Kashaya camp is a unique approach where selected healthy human volunteers were administered a decoction (twice every week) made from the local plants traditionally used for prevention of malaria. The camps were spread over a three months period during the monsoon, e.g., malaria endemic season. The outcome of the study showed a significant reduction in the malaria incidence rate in the population who consumed decoction (Prakash and Unnikrishnan, 2011). This is also a prelude for the ‘reverse pharmacology’ approach where evidence for drug efficacy is generated first from field to laboratory instead of conventional approach, e.g., laboratory to field.
8.7CONCLUSION
Vector borne diseases continue to be a major health problem in the Western Ghats region today. Malaria epidemiological data shows there is high transmission rate in some of the districts in the Western Ghats region with a sudden increase in incidence rate in certain districts. Based on a study of 30 districts in the region it is predicted that the situation is expected to continue in a similar way for next 15 years.
Usage of large number of plants from the region show that the communities in the region have devised adaptation methods through local plant based innovations. Documenting these practices comprehensively and finding out most efficacious substances would be a pragmatic approach for malaria management. This has to follow a participatory, documentation and rapid assessment as a primary step to be followed by appropriate clinical studies to scientifically validate these practices.
When nation-wide interventions fail to tackle the problem or when conventional practices are not easily accessible for large section of the population such an endogenous, multi-stakeholder approach would be required for addressing such local development challenges.
ACKNOWLEDGEMENTS
We express sincere gratitude to the support extended by Dr. S.N. Venugopalan Nair, and Ms. Tabassum Ishrath Fathima, School of Conservation, TDU, Bangalore. Authors also thank Mrs. D. Tharini, School of Health Sciences, TDU for her support.
KEYWORDS
•Endogenous Knowledge
•Herbal Anti-Malarial
•Malaria
•Traditional Medicine
•Western Ghats
REFERENCES
Al-Adhroey, A.H., Nor, Z.M., Al-Mekhlafi, H.M. & Mahmud, R. (2010). Median lethal dose, antimalarial activity, phytochemical screening and radical scavenging of methanolic Languas galanga rhizome extract. Mol. Basel Switz. 15, 8366–8376.
Albuquerque, U.P., Medeiros, P.M. de, Ramos, M.A., Júnior, W.S.F., Nascimento, A.L.B., Avilez, W.M.T. & Melo, J.G. de (2014). Are ethnopharmacological surveys useful for the discovery and development of drugs from medicinal plants? Rev. Bras. Farmacogn. 24, 110–115.
Bamunuarachchi, G.S., Ratnasooriya, W.D., Premakumara, S. & Udagama, P.V. (2013). Antimalarial properties of Artemisia vulgaris L. ethanolic leaf extract in a Plasmodium berghei murine malaria model. J. Vector Borne Dis. 50, 278–284.
Bhat, G.P. & Surolia, N. (2001). In vitro antimalarial activity of extracts of three plants used in the traditional medicine of India. Am. J. Trop. Med. Hyg. 65, 304–308.
Chenniappan, K. & Kadarkarai, M. (2010). In vitro antimalarial activity of traditionally used Western Ghats plants from India and their interactions with chloroquine against chloroquine-resistant Plasmodium falciparum. Parasitol. Res. 107, 1351–1364.
Darshan, S. & Unnikrishnan, P. (2004). Challenging the Indian medical heritage. Foundation books, New Delhi.
Dhiman, R., Chavan, L., Manoj, P. & Sharmila, P., (2011). National and regional impacts of climate change on malaria by 2030. Curr. Sci. 101, 372–383.
Dhingra, N., Jha, P., Sharma, V.P., Cohen, A.A., Jotkar, R.M., Rodriguez, P.S., Bassani, D.G., Suraweera, W., Laxminarayan, R. & Peto, R. (2010). Million Death Study Collaborators, Adult and child malaria mortality in India: a nationally representative mortality survey. Lancet 376, 1768–1774.
ETC-Compas (2007). Learning endogenous development, Practical action publishing, United Kingdom.
FRLHT database; http://www.frlth.org (Accessed on 24th June, 2015).
Ganeshaiah, K.N. (2013). Plants of Western Ghats, vol. 1 & 2, UAS, Bangalore.
Guerra, C.A., Howes, R.E., Patil, A.P., Gething, P.W., Van Boeckel, T.P., Temperley, W.H., Kabaria, C.W., Tatem, A.J., Manh, B.H., Elyazar, I.R.F., Baird, J.K., Snow, R.W. & Hay, S.I. (2010). The international limits and population at risk of Plasmodium vivax transmission in 2009. PLoS Negl. Trop. Dis. 4, e774.
Gupta, M., Mazumder, U.K., Kumar, R.S., Gomathi, P., Rajeshwar, Y., Kakoti, B.B. & Selven, V.T. (2005). Anti-inflammatory, analgesic and antipyretic effects of methanol extract from Bauhinia racemosa stem bark in animal models. J. Ethnopharmacol. 98, 267–273.
Hay, S.I., Okiro, E.A., Gething, P.W., Patil, A.P., Tatem, A.J., Guerra, C.A. & Snow, R.W. (2010). Estimating the global clinical burden of Plasmodium falciparum malaria in 2007. PLoS Med. 7, e1000290.
Herlina, T., Supratman, U., Soedjanaatmadja, M.S., Subarnas, A., Sutardjo, S., Abdullah, N.R. & Hayashi, H. (2010). Anti-malarial compound from the stem bark of Erythrina variegata. Indones. J. Chem. 9, 308–311.
Hilou, A., Nacoulma, O.G. & Guiguemde, T.R. (2006). In vivo antimalarial activities of extracts from Amaranthus spinosus L. and Boerhavia erecta L. in mice. J. Ethnopharmacol. 103, 236–240.
Hirt, H. & M’Pia, B. (2008). Natural medicine in the tropics. Winnenden: Anamed.
Hullatti, K. & Sharada, M. (2007). Antipyretic activity of Patha: An Ayurvedic drug. Pharmacogn. Mag. 3, 173–176.
Ijaz, F., Ahmad, N., Ahmad, I., ul Haq, A. & Wang, F. (2010). Two new anti-plasmodial flavonoid glycosides from Duranta repens. J. Enzyme Inhib. Med. Chem. 25, 773–778.
Inbaneson, S.J., Sundaram, R. & Suganthi, P. (2012). In vitro antiplasmodial effect of ethanolic extracts of traditional medicinal plant Ocimum species against Plasmodium falciparum. Asian Pac. J. Trop. Med. 5, 103–106.
Jagetia, G.C. & Baliga, M.S. (2005). The effect of seasonal variation on the antineoplastic activity of Alstonia scholaris R. Br. in HeLa cells. J. Ethnopharmacol. 96, 37–42.
Kaushik, N.K., Bagavan, A., Rahuman, A.A., Zahir, A.A., Kamaraj, C., Elango, G., Jayaseelan, C., Kirthi, A.V., Santhoshkumar, T., Marimuthu, S., Rajakumar, G., Tiwari, S.K. & Sahal, D. (2015). Evaluation of antiplasmodial activity of medicinal plants from North Indian Buchpora and South Indian Eastern Ghats. Malar. J. 14, 65. doi: 10.1186/ s12936-015-0564-z.
Kayser, O., Kiderlen, A.F. & Croft, S.L., (2003). Natural products as antiparasitic drugs. Parasitol. Res. 90 Suppl 2, S55–62.
Keawpradub, N., Kirby, G.C., Steele, J.C.P. & Houghton, P.J. (1999). Antiplasmodial activity of extracts and alkaloids of three Alstonia species from Thailand. Planta Medica. 65(8), 690–694.
Khan, M.A., Khan, H., Khan, S., Mahmood, T., Khan, P.M. & Jabar, A. (2009). Anti-inflammatory, analgesic and antipyretic activities of Physalis minima Linn. J. Enzyme Inhib. Med. Chem. 24, 632–637.
Kirtikar, K.R. & Basu, B.D. (1999). Indian Medicinal Plants. Dehradun: International Book Distributors, vol. II.
Kitua, A. & Malebo, H. (2004). Malaria control in Africa and the role of traditional medicine, in: Traditional Medicinal Plants and Malaria. CRC Press, London, pp. 3–18.
Leaman, D.J., Arnason, J.T., Yusuf, R., Sangat-Roemantyo, H., Soedjito, H., Angerhofer, C.K. & Pezzuto, J.M. (1995). Malaria remedies of the Kenyah of the Apo Kayan, East Kalimantan, Indonesian Borneo: A quantitative assessment of local consensus as an indicator of biological efficacy. J. Ethnopharmacol. 49, 1–16.
Mishra, P., Pal, N., Guru, P., Katiyar, J. & Tandon, J. (1991). Antimalarial activity of traditional plants against erythrocytic stages of Plasmodium berghei. Int. J. Pharmacogn. 29, 19–23.
Murthy, Srikantha (2004). Vataadi varga, Bhavaprakasha of Bhavamishra. Vo. 1, p 306, Chowkhamba krishnadas academy, Varanasi.
Nair, M.N.B. (2006). Documentation and assessment of ethnoveterinary practices from an Ayurvedic viewpoint. In: Balasubramanian, A.V., Nirmala, D. (eds.). Traditional knowledge system of India and Sri Lanka. Centre for Indian Knowledge Systems, Chennai, p. 83.
Natesh, S. (2015). Remarkable Trees on NII Campus, New Delhi. http://www.nii.res.in/others/remarkable-trees-nii-campus (accessed 20th July, 2015).
Nayak, P. (2010). Pharmacological evaluation of ethanolic extracts of the plant Alternanthera sessilis against temperature regulation. J. Pharm. Res. 3, 1381.
Payyappallimana, U. (2010). Role of traditional medicine in primary health care: An overview of perspectives and challenges. Yokohama J. Soc. Sci. 14, 57–77.
Phillipson, J.D. (2001). Phytochemistry and medicinal plants. Phytochemistry 56, 237–243.
Prakash, B. & Unnikrishnan, P. (2011). Documentation and validation of traditional practices for management of malaria. In: Balasubramanian, A., Vijayalakshmi, K., Shylaja, R., Abarna, R. (Eds.), Testing and Validation of Indigenous Knowledge. Centre for Indian Knowledge Systems, Chennai.
Pravin, B., Nandkishor, J. & Shilpa., A. (2015). Evaluation of in vitro Antimalarial activity of Hedyotis herbacea by Schizont maturation inhibition assay. Int. J. Pharm. Phytopharm. Res.
Pratyush, K., Chandra, S.M., James, J., Lipin, D., Arun Kumar, T.V. & Thankamani, V. (2011). Ethnobotanical and Pharmacological Study of Alstonia (Apocynaceae) – A Review. J. Pharm. Sci., Res 3, 1394–1403.
Samy, K. & Kadarkari, M. (2011). Antimalarial activity of traditionally used Western Ghats plants from India and their interactions with chloroquine against chloroquine-tolerant Plasmodium berghei. Vector Borne Zoonotic Dis. Larchmt. N 11, 259–268. doi: 10.1089/ vbz.2009.0208.
Santhosh, B., Bhanudas, S. & Sagar, B. (2015). Antipyretic Activity of β-Sitosterol Isolated from leaves of Oxalis corniculata Linn. Am. J. Pharmtech Res. 5, 214–222.
Simoes-Pires, C., Hostettmann, K., Haouala, A., Cuendet, M., Falquet, J., Graz, B. & Christen, P. (2014). Reverse pharmacology for developing an anti-malarial phytomedicine. The example of Argemone mexicana. Int. J. Parasitol. Drugs Drug Resist., Includes articles from two meetings: “Anthelmintics: From Discovery to Resistance,” pp. 218–315, and “Global Challenges for New Drug Discovery Against Tropical Parasitic Diseases,” pp. 316–357, 338–346.
Simonsen, H.T., Nordskjold, J.B., Smitt, U.W., Nyman, U., Palpu, P., Joshi, P. & Varughese, G. (2001). In vitro screening of Indian medicinal plants for antiplasmodial activity. J. Ethnopharmacol. 74, 195–204.
Sireeratawong, S., Itharat, A., Lerdvuthisopon, N., Piyabhan, P., Khonsung, P., Boonraeng, S. & Jaijoy, K. (2012). Anti-Inflammatory, Analgesic, and Antipyretic activities of the ethanol extract of Piper interruptum Opiz. and Piper chaba Linn. Int. Sch. Res. Not. e480265.
Ukwe, V., Epueke, E., Ekwunife, O., Okoye, T., Akudor, G. & Ubaka, C. (2010). Antimalarial activity of aqueous extract and fractions of leaves of Ageratum conyzoides in mice infected with Plasmodium berghei. Int. J. Pharm. Sci. 2, 33–38.
Vigneron, M., Deparis, X., Deharo, E. & Bourdy, G. (2005). Antimalarial remedies in French Guiana: a knowledge attitudes and practices study. J. Ethnopharmacol. 98, 351–360. doi: 10.1016/j.jep.2005.01.049.
WHO (2014). World Malaria Report, 2014. World Health Organization, Geneva. Wiesmann, U., Biber-Klemm, S., Grossenbacher-Mansuy, W., Hadorn, G.H., Hoffmann-Riem, H., Joye, D., Pohl, C. & Zemp, E. (2008). Enhancing transdisciplinary research: A synthesis in fifteen propositions, In: Hadorn, G.H., Hoffmann-Riem, H., Biber-Klemm, S., Grossenbacher-Mansuy, W., Joye, D., Pohl, C., Wiesmann, U. & Zemp, E. (Eds.), Handbook of Transdisciplinary Research. Springer: Netherlands, pp. 433–441.
Willcox, M., Bodeker, G. & Rasoanaivo, P. (2004). Traditional Medicinal Plants and Malaria. CRC Press, London.