The use of herbal medicine is on the increase globally (Asiimwe et al., 2014; Joshi and Joshi, 2000; Kamatenesi -Mugisha, 2005). In Africa, the situation is not different, over   80%  of  the  population  particularly  in  developing countries depend directly on plants for their primary healthcare requirements (Senthilkumar et al., 2013). In Ghana, where malaria is a major developmental and socioeconomic issue, many indigenes especially in rural communities rely on medicinal plants, solely and sometimes in combination with orthodox antimalarial drugs, for the treatment of the disease (Abbiw, 1990; Mshana et al., 2000). The Ghana government has specifically boosted the use of herbal medicines by integrating it into the main health care system by establishing herbal units in most of the government hospitals across the country. This has been necessitated by the consequences of limited access to modern health services in most developing countries including Ghana, high cost of modern medicine compared to the indigenous herbal medicines and wide socio-cultural acceptance of traditional medicine (Kamatenesi-Mugisha et al., 2005; Oreagba et al., 2011; Van Andel and Carvalheiro, 2013).

Malaria is the single most important cause of death, ill health and poverty in sub-Saharan Africa (Sachs and Malaney, 2002). Estimates suggest as many as 300 million acute cases of malaria occurring worldwide each year, resulting in 1 million deaths. Approximately 90% of these deaths occur in sub-Saharan Africa, and most of the victims are children younger than 5 years of age (Murphy and Breman, 2001). The disease is caused by members of the parasitic protozoa of the Plasmodium genus, which are transmitted by the female Anopheles mosquito to the human host. The five species of Plasmodium that infect humans include the deadly Plasmodium falciparum, which causes malignant malaria responsible for the severe symptoms and death in humans. It is also the most common in sub-Saharan Africa. Others are Plasmodium vivax, Plasmodium ovale, Plasmodium malariae and Plasmodium knowlesi which cause the milder, benign malaria (WHO, 2010).

Currently, the World Health Organization (WHO) has adopted an integrated approach in the control of the disease, and this involves case management and disease prevention. Together, they work against the transmission of the parasite from the mosquito vector to humans, and the development of illness and severe disease (WHO, 2012). Case management, which involves treatment with antimalarial drugs, continues to be the most extensive approach to malaria control. Preventive measures encompass intermittent preventive treatment (IPT) and malaria vector control. IPT involves the administration of a full course of an effective antimalarial treatment at specified times, and targets a defined population at risk of malaria, e.g. pregnant women, regardless of whether the recipients are parasitaemic or not, with the objective to reduce the malaria burden in the target population (WHO, 2012). Despite the gains made in malaria control, there are some key challenges in the fight against malaria. A growing concern is the emerging  parasites  (Plasmodium sp.), developing resistance to the most widely available, affordable, and safest first-line treatments such as Chloroquine and Sulfadoxine and pyrimethamine (Khalid et al., 1989; Sarker et al., 2000) ; resistance to a wide range of insecticides rendering mosquito control programmes unsuccessful ; the widespread production and marketing of “new” ineffective antimalarial drugs, such as Artesunate blister packs that contain no active ingredients (Newton et al., 2006); and the unavailability of needed infrastructure and resources to manage malaria in many African countries (Murphy and Breman, 2001) .

In light of the foregoing, the call for new chemical entities, probably with new mechanisms of action, for the treatment of malaria or alternative approaches to malaria treatment remains a priority. Indeed, some medicinal plants with antiplasmodial activity have shown enhanced activity against the parasite when formulated as nanoparticles (Murugan et al., 2016; Rajakumar et al., 2015). WHO, in fact, has put in place a strategy (Traditional Medicine Strategy, 2014-2023) to support the promotion of safe and effective use of traditional and complementary medicine (WHO, 2013).

The first step in conservation and sustainable usage of medicinal plants is to document material traditionally used to treat an ailment (Hamilton, 2004; Ssegawa and Kasenene, 2007). A larger number of medicinal plants and indigenous uses have not yet been documented. The rich history of African cultures and their innovative utilisation of plants as a source of remedies have been passed down through generations largely by oral tradition (Soelberg et al., 2015). This knowledge is gradually being lost (Tabuti et al., 2012) as the custodians die before passing on information to the younger generations. Besides the gradual loss of ethnobotanical knowledge due to lack of documentation, overharvesting of medicinal materials from their natural habitat and destruction of habitats have been two of the major threats to traditional medicine. In order to conserve wild plant species, there is need for reliable data on their distribution and level of use (Ahrends et al., 2011). The documentation of indigenous knowledge through ethnobotanical studies is therefore important in conservation and utilization of biological resources (Munthu et al., 2006).

Ethno-botanical data on plant species used for the treatment of malaria were collected during a two-week training course from 10th to 21st September 2018. This was achieved by interviewing 36 registered herbalists belonging to the Ghana Federation of Traditional and Alternative Medicine (GHAFTRAM). A well-structured questionnaire was used to obtain and document data during the training course organized by the Centre for Plant Medicine Research (CPMR), Mampong-Akuapem, Ghana. The purpose of the training was to educate the herbalists on best practices in cultivation of medicinal plants, sustainable harvesting or utilization of medicinal plants and best practices in the preparation of herbal medicines. Prior to conducting interviews, the objectives of the study  were explained to the herbalists to obtain their consent to participate. When asked, the herbalists associated malaria with a bite from a mosquito without knowledge of the specific species of mosquito that causes malaria. Symptoms of the disease they described included fevers, chills, and strong headaches. The questionnaires were pretested to 20 individuals randomly in the Mampong township and adjustments were made to validate it before detailed interviews were conducted. After being validated, the questionnaires were used to collect data on the socioeconomic status of the herbalists, common or vernacular names of plants, plant parts used, preparation methods, mode of administration, collection sites, and plant threats. The herbalists were interviewed individually by selected staff of CPMR who were trained purposely for this study. The herbalists were asked to present specimens of all plant species they reported from locations where they make collections for their malaria preparations. The reported local names of plants by the herbalists who mostly rely on sight as identification method, were confirmed using the Flora of West Tropical Africa (Hutchinson et al., 1963) and by comparison with herbarium vouchers at the herbarium of CPMR. The nomenclature of the species was confirmed using the International Plant Names Index (Croft et al., 1999) and Catalogue of Life (Bisby et al., 2009). Voucher specimens of all plant species reported were prepared and deposited in the CPMR’s herbarium.

Data analysis

The variation in the knowledge (mean ± standard error) of medicinal plants used for the treatment of malaria due to gender of the respondents was compared using Student’s t-test (p =0.3). A one-way analysis of variance (ANOVA) was used to compare differences within age groups, religious groups, educational background, and ethnic groups. The diversity of species used for the treatment of malaria was evaluated using the Shannon-Wiener index  ) where s is the total number of species and p is the relative abundance of species (Macías et al., 2008). The relative abundance of each species was estimated from the total citations from among the total number of interviews. Frequency of citation (FC) of the species of plants being used for the treatment of malaria was evaluated using the formula: (number of times a particular species was cited/total number of citations of all species in the study) × 100%. The percentages of threats to medicinal plants, plant parts used, habits and sources of plant materials were also calculated.

The treatment of malaria using plant materials was inquired into because in many parts of the world, including Ghana, the Plasmodium sp have developed resistance to frontline antimalarial drugs such as chloroquine, antifolates and recently artemisinin (Sebisubi and Tan, 2010). Resistance to these drugs has been reported to be as high as 40 to 60 percent in some African and Asian countries (Builders et al., 2011). There are also reported cases of debilitating adverse effects of the conventional antimalarial drugs (Builders et al., 2011).  This calls for an urgent need to discover new active agents that can overcome these pitfalls. Although hundreds of plants species are being used as a folkloric remedy for malaria and fever, the vast majority have not yet been adequately evaluated. The Ghana Health Service have recently endorsed  artesunate-amodiaquine combination drug for the treatment of malaria. However, amodiaquine (4-aminoquinoline) has been linked with hepatic toxicity, agranulocytosis, and other refutations (Asase and Asafo-Agyei, 2011). The combination drug is relatively high-priced, rendering the medication unobtainable to low income earners in endemic communities. The herbalists interviewed reported that most of the patients they treat, give account of how they use both the traditional medicines together with conventional medicine to treat themselves of malaria. This is similar to report of Vigneron et al. (2005). The probable complication of plant-drug interactions when conventional medicines are used together with traditional medicines may arise and ought to be researched into.

Sociodemographic impacts

Considering gender and the number of medicinal plants reported, there was no significant variation with a score of 13.06 ± 1.29 for males and 13.88 ± 2.29 for females. Most of the herbalists beyond 58 years (18.21 ± 1.73) reported on antimalarial uses of plants than within the age group 18 to 37 years (11.40 ± 2.77) and in the age group 38 to 57 years (11.36 ± 1.50) (Figure 1). The herbalists interviewed belonged to different religious groups and were considered knowledgeable in antimalarial uses of plants although the number of plant species mentioned differed. For Christians, 13.43 ± 1.28 plants were reported; for Muslims, 15.67 ± 2.03 plants were reported; for traditional spiritual believers, 12.75 ± 5.45 were reported (Figure 2).

Majority of the herbalists were well informed about antimalarial uses of plants and had university education (36.5± 1.6) or only primary education (19.9± 3.6), whereas only a few have had secondary (17.2± 1.8), no formal education (14.0± 2.9) and college education (12.0± 3.8) indicating differences in familiarity of antimalarial plants due to differences in the level of education achieved (Figure 3).

Religious background and gender did not have any significant impact on the knowledge and usage of herbal preparations for malaria treatment by the herbalists, although educational background influenced their perception of alternatives. The knowledge on traditional uses of plants was possessed by the older generation (beyond fifty-eight years), indicating the lack of cultural and conservational importance of the medicinal species.

Plant species identified from the herbalists’ reports for the treatment of malaria

A total of 42 plant species belonging to 27 families were reported as being used for malaria treatment by Ghanaian herbalists (Table 1). Trees were the most dominant habit (47.6%) of plants used in the treatment of malaria. The  other  species  of  plants  identified included shrubs (28.6%), herbs (16.7%), grasses (4.8%) and climbers (2.4%) (Figure 4). The findings of this study indicate that, a considerable high number (42 species) of medicinal plants are being used for treatment of malaria by Ghanaian herbalists. The dominance of tree species used for the treatment of malaria was also reported in Dike et al. (2012).

About 93% of the herbalists interviewed collected plant materials from the wild, whereas the remaining 7% collected plant materials from their immediate surroundings, that is, within 100 m from their  homes. The frequency of collection was irregular, because plant parts were collected only when needed to treat malaria. According to the informants, farming activities pose a major (40%) threat to the survival of plant species although some informants also stated bush fires (33%), over-harvesting (14%), and drought (13%) as potential threats (Figure 5). Majority of the herbalists collected plant materials from the wild, similar to the results obtained by Boyom et al. (2011). Conservational strategies for sustainable utilization of medicinal plants are  therefore  needed  in  Ghana  to protect plant wealth.

Three (7.1%) species each belonged to the families Rutaceae, Meliaceae and Fabaceae. Two species each were identified for 9 families -Asteraceae, Cucurbitaceae, Euphorbiaceae, Lamiaceae, Rubiaceae, Zingiberaceae, Annonaceae, Longaniaceae and Poaceae. In contrast, 15 families-Caricaceae, Lauraceae, Meliaceae, Piperaceae, Malvaceae, Sterculiaceae, Bignoniaceae, Combretaceae, Moraceae, Myristicaceae, Sapindaceae, Myrtaceae, Mimosaceae, Amaranthaceae and Bromeliaceae-contributed with only one species to the total number of plant species reported (Table 1). The diversity of species used for malaria treatment by Ghanaian herbalists was high (Shannon-Wiener index = 3.5 ± 0.24). Most of the plants mentioned for the treatment of malaria, in this study, belonged to the families Rutaceae, Meliacea and Fabaceae. In contrast to this result, research from other parts of Africa showed that several species used for the treatment of malaria belonged to the family Rubiaceae (Asase et al., 2005; Iwu, 1994; Van Wyk et al., 2002). This shows that distinct groups of phytochemicals may account for the antimalarial properties possessed by plants being used traditionally for the treatment of malaria (Srisilam and Veersham, 2002). For instance, dissimilar phytochemical groups of compounds such as flavonoids (Citrus aurantifolia L.), phenols (Phyllanthus niruri L.) and terpenoids (Momordica charantia L.) (Berhow et al., 1994; Ishimaru et al., 1992; Chen et al., 2009) constituted different plant species belonging to different families such as Rutaceae, Euphorbiaceae and Cucurbitaceae respectively as reported by other works in Table 1. The most frequently cited plant was Azadirachta indica A. Juss  (FC   =   9.75).   Other   plant    species   commonly mentioned as being used for the treatment of malaria were Nauclea latifolia (FC=7.31) and Occimum grattissimum (FC = 6.09), whereas the least-cited plants were Acacia nilotica, Ananas comosus, Alchornea cordifolia , Anthocleista nobilis, Bidens Pilosa, Cassia alata, Cleistopholis patens, Gossypium barbadense, Khaya senegalensis, Mezoneuron benthamianum , Paullinia pinnata, Psidium guajava, Pycnanthus angolensis, Solanum torvum, Occimum basilicum, Persea americana , Piper guineense, Theobroma cacao, Spathodea campanulata, Zanthoxylum zanthoxyloides, Polyalthia longifolia, Alstonia boonei, Xylopia aethiopica, Terminalia ivorensis and Milicia excelsa  with a FC= 1.21 each. The most frequently cited plant species by the respondents (Azadirachta indica A. Juss (FC = 9.75) could provide a guide for antiplasmodial testing and phytochemical analyses as to their effectiveness in the search for plant materials for the treatment of malaria (Heinrich, 2009). A frequently cited plant, nonetheless, does not indicate the plant's effectiveness for malaria treatment, but its use and frequent citation may be due to its abundance or availability.

Usage and application

The commonest plant parts used for the treatment of malaria were the leaves (40.7%), followed by roots (24.1%), stem bark (24.1%), seeds (5.6%), fruits (3.7%) and whole plant (1.9%) (Figure 6). This corresponds with the findings of Caraballo et al. (2004) conducted in South-eastern  Venezuelan  Amazon,  where they proved that the leaves constituted 70% of the parts used. It is likely that leaves are more available and accessible to people and contain highly effective antimalarial substances. The constant use of leaves could also be due to the fact that they are the site of the synthesis of organic substances and, therefore, antimalarial substances. Bhattarai et al. (2010) and Njoroge and Bussmann (2005). In all cases of preparation, the plant parts were boiled alone or together with parts of other plants. Almost all species reported (95.2%) were used as combination  therapy   with   other   plant   species (Table 1). The mode of administration of the herbal preparations were all by drinking. Titanji et al. (2008) and Asase et al. (2005) by conducting similar studies have found forty-five preparation methods that combine more than one species of plants for the treatment of malaria with mode of preparation and administration being boiling and drinking the infusion respectively. Prescriptions were usually unspecific, and the intake of the herbal preparations continued until recovery. It became evident in this study that, the herbal preparations   used     by     the     herbalist’s   lack consistency and dosage instructions were indeterminate (Table 1). This means the quality of the herbal preparations may differ enormously amid prescriptions. This is not too different from observations reported elsewhere (Asase et al., 2005) and have been prominent also as a main drawback of traditional medicine (Evans-Anfom, 1986; Sofowora, 1993). The inclusion of certain plants, for instance Citrus sinensis fruits to herbal preparations might be to sweeten the decoction despite the fact that, C. sinensis has been mentioned  in  Bhat   and   Surolia   (2001)   as   a medicinal plant for the treatment of malaria itself. Again, C. sinensis may be used together with other plants as combination therapy because the antimalarial characteristics of medicines are contingent on synergy of the plant components. This renders identifying and characterizing the measure of bioactive compounds in herbal preparations very complex and poses immense challenges in coming up with quality control methods. However, WHO provides basic standards for quality of herbal preparations (WHO, 2007, 2011).

Antiplasmodial activity have been shown in some of the species used as sources of antimalarial preparations (Sendagire et al., 2005). For instance, in Ivory Coast, Alchornea cordifolia leaves are being used for the treatment of malaria, and an alcoholic concentrate of the leaves has clearly shown antiplasmodial activity at IC50 = 9.2 µg/ml (Okpekon et al., 2004). The leaves of Alstonia boonei are used for malaria treatment in Ghana and in Ivory Coast and Okpekon et al. (2004) accounted that the alkaloids extracted from this species possessed antiplasmodial activity at 8.4 µg/ml. In addition, methanol and  methylenechloride  extracts from root and stem bark of Morinda lucida indicated antiplasmodial activity that may be linked to anthraquinones (Tona et al., 1999). It is worth noting that, the extraction solvent, locality of collection and time of harvesting influence the presence of phytochemical expression levels and the efficacy of extracts from plants (Prance, 1994).

This study has emphasized the significance of plants in the treatment of malaria in Ghana. It has also contributed to the establishment of a complete database of traditional knowledge on medicinal plants used for the treatment of malaria in Ghana. In addition, this study provides useful information for new drug discovery, since it provides a list of plants amongst which an alternative phytochemical, that is more efficacious against the Plasmodium parasite could be discovered. More research should be conducted to find out the activities in the leaves of medicinal plants used for the treatment of malaria and other common diseases so that leaves can be used more than other plant parts such as roots and stem barks since harvesting of the roots and stem barks are more destructive and poses a greater threat to local plant populations, especially when whole plants are removed in some instances. The sourcing of plant materials from the wild by majority of the herbalists in this study, emphasizes the need to train them on sustainable cultivation and harvesting methods. Additional work can be done on the plants reported in this study to corroborate their antimalarial claim as well.

The authors have not declared any conflict of interests.