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Friday, 27 March 2015

The malaria co-infection challenge: An investigation into the antimicrobial activity of selected Guinean medicinal plants

Journal of Ethnopharmacology
Available online 13 March 2015
In Press, Uncorrected Proof — Note to users

The malaria co-infection challenge: An investigation into the antimicrobial activity of selected Guinean medicinal plants



Abstract

Ethnopharmacological relevance

In sub-Saharan Africa, concomitant occurrence of malaria and invasive infections with micro-organisms such as Gram-positive Staphylococcus aureus, Gram-negative Escherichia coli and yeasts or fungi such as Candida albicans and Aspergillus fumigatus is common. Non-tuberculous mycobacteriosis caused by Mycobacterium chelonae has been recognized as a pulmonary pathogen with increasing frequency without effective therapy. Although less important, the high incidence of Trichophyton rubrum infections along with its ability to evade host defense mechanisms, accounts for the high prevalence of infections with this dermatophyte. Considering the treatment cost of both malaria and microbial infections, along with the level of poverty, most affected African countries are unable to cope with the burden of these diseases. In sub-Saharan Africa, many plant species are widely used in the treatment of these diseases which are traditionally diagnosed through the common symptom of fever. Therefore it is of interest to evaluate the antimicrobial activities of medicinal plants reported for their use against malaria/fever.

Materials and methods

Based on an ethnobotanical survey, 34 Guinean plant species widely used in the traditional treatment of fever and/or malaria have been collected and evaluated for their antimicrobial activities. Plants extracts were tested against Candida albicans, Trichophyton rubrum, Aspergillus fumigatus, Mycobacterium chelonae, Staphylococcus aureus and Escherichia coli.

Results

The most interesting activities against Candida albicans were obtained for the polar extracts of Pseudospondias microcarpa and Ximenia americana with IC50 values of 6.99 and 8.12 µg/ml, respectively. The most pronounced activity against Trichophyton rubrum was obtained for the ethanol extract of Terminalia macroptera (IC50 5.59 µg/ml). Only 7 of the 51 tested extracts were active against Staphylococcus aureus. From these, the methanolic extracts of the leaves and stem bark of Alchornea cordifolia were the most active with IC50 values of 2.81 and 7.47 µg/ml, respectively. Only Terminalia albida and Lawsonia inermis showed activity against Mycobacterium chelonae. None of the tested extracts was active against Escherichia coli.

Conclusion

A number of traditional Guinean plant species used against malaria/fever showed, in addition to their antiplasmodial properties and antimicrobial activity. The fact that some plant species are involved in the traditional treatment of malaria/fever without any antiplasmodial evidence may be justified by their antimicrobial activities.

Graphical abstract

Keywords

  • Antimicrobial;
  • Malaria;
  • Co-infection;
  • Guinea;
  • Plant extracts

1. Introduction

Areas of the world with high rates of malaria also carry a heavy burden of infectious diseases which are caused by pathogenic microorganisms, such as parasites, bacteria, viruses or fungi. Within the poorest and developing countries in Africa, malaria, acute respiratory infections, diarrhea, tuberculosis and recently Ebola figure among the major infectious killers. Although having serious consequences through a prolongation of illness along with an increasing mortality especially to the vulnerable pregnant women and children infected with Plasmodium falciparum, the magnitude and the impact of malaria co-infection with other pathogenic microorganisms are still largely unknown. Until now, it was suggested that the most important cause of death among children in Africa is malaria; however, the methodology of these studies has been questioned. More recent community-based studies of the incidence of invasive bacterial infections in rural Gambia and Kenya have all documented a significant contribution to childhood morbidity and mortality in developing countries. One of the risk factors to develop invasive bacterial infections in Africa is Plasmodium falciparum malaria (Anthony et al., 2009; Scott et al., 2011, Bassat et al., 2009, Bronzan et al., 2007 and Church and Maitland, 2014).
In sub-Saharan Africa, concomitant occurrence of malaria and invasive infections by micro-organisms is common. In children with severe Plasmodium falciparum malaria, evidence of invasive bacterial infections with Gram-positive Staphylococcus aureus, Gram-negative Escherichia coli, and other enteric Gram-negative bacteria has been reported in many countries including Tanzania, Kenya, Mozambique, Nigeria and Burkina Faso ( Berkley et al., 1999, Berkley et al., 2005, Brent et al., 2006, Chaturvedi et al., 2009, Church and Maitland, 2014, Crawley et al., 2010, Evans et al., 2004, Graham et al., 2000, Gwer et al., 2007, Keong and Sulaiman, 2006, Maltha et al., 2014, Uneke, 2008 and Walsh et al., 2000). Gram-negative bacteria like E. coli may cause amongst others urinary tract infections, pneumonia, neonatal meningitis, diarrhea and skin infections; while Gram-positive organisms like S. aureus may cause nosocomial infections, skin infections, respiratory diseases, meningitis, endocarditis, osteomyelitis and wound infections ( Gunaselvi et al., 2010).
The major yeasts and fungi implicated worldwide as a potential cause of invasive fungal infections include Candida and Aspergillus spp. These produce a wide variety of infections that are difficult to diagnose as most of the diagnostic tests are non-specific and the culture takes a long time. C. albicans can cause infections in specific physiological and pathological conditions such as infancy, pregnancy, diabetes, prolonged broad spectrum antibiotic administration, steroidal chemotherapy as well as AIDS ( Low and Rotstein, 2011). Aspergillosis is one of many opportunistic fungal infections that mainly affect the lungs ( Silva, 2010) and 90% of invasive aspergillosis is caused by the air-borne opportunistic fungal pathogen, Aspergillus fumigatus. The mortality rate of this disease is still very high (50–95%), partly because of diagnostic difficulties, limited antifungal treatment options, and the weak condition of patients at risk. But also in part because understanding of virulence factors involved in A. fumigatus pathogenicity and interactions of the pathogen with the host immune system is still poor ( Binder and Lass-Flörl, 2013 and McCormick et al., 2010).
Dermatophytic fungal infections are one of the most common infectious diseases and are among the most commonly diagnosed skin diseases in Africa (Nweze, 2010). Although the correlation between malaria and these fungal infections is not documented, they are present worldwide. Trichophyton rubrum is responsible for the vast majority of chronic dermatophytoses ( Scheers et al., 2013). Its high infectivity and its ubiquitous presence account for its high incidence. Together with the ability of T. rubrum to evade host defense mechanisms, this accounts for the high prevalence of infections with this fungus ( Dahl and Grando, 1994). Their co-infection with malaria must be common but is poorly documented particularly in malaria endemic areas.
Non-tuberculous mycobacteriosis with Mycobacterium chelonae is an opportunistic pathogen which has been recognized as a pulmonary pathogen with increasing frequency. It is an increasingly recognized cause of disease in immunocompromised patients. M. chelonae is characterized by a high degree of in vitro resistance to antituberculous drugs and has been associated with development of drug resistance and treatment failures. Attempts to eradicate the organism through chemotherapy have been largely unsuccessful. No effective therapy for M. chelonae lung infections has been established to date, and reported cases of pulmonary resection for the treatment of M. chelonae infections are extremely rare (Singh and Yu, 1992; Green et al., 2000, Goto et al., 2012 and Wallace et al., 2001).
Since routine antibiotics along with antimalarials are currently recommended for patients with severe malaria, the indiscriminate use of antibiotics would be both financially costly and could perpetuate the rise of antimicrobial resistance, which threatens the effective prevention and treatment of an ever-increasing range of infections caused by bacteria, parasites, viruses and fungi (World Health Organization, 2014). Considering the treatment cost of both malaria and microbial infections, along with the level of poverty, most affected African countries are unable to cope with the burden of these diseases. For many African people, particularly the rural populations, traditional medicines continue to be the first and most important source of medical solace when illness strikes health. Thus, many plant species are widely used in the treatment of various diseases as a recipe consisting of only one or more medicinal plants. Moreover, the same plant species or recipe could be frequently and indistinctly employed for the traditional symptomatic treatment of various diseases such as malaria, bacterial and viral infections. In Guinean rural areas where diagnosis based on blood cultures is usually unavailable and antibiotic choice is limited, traditional medicine is the unique way for the management of most of the diseases. Owing to the fact that it is very difficult for traditional healers to differentiate between malaria and other infectious diseases, their remedies mainly aim to treat the fever symptom.
From an ethnobotanical survey on malaria/fever conducted in Guinea, numerous plant species have been collected (Traoré et al., 2013), but only few of them exhibited an in vitro antimalarial potency with an IC50<64 μg/ml. To justify the “antimalarial” traditional use of the weakly active or inactive plant species against Plasmodium falciparum (IC50≥64 μg/ml), it was assumed that these could possibly act on symptoms of malaria such as febrile illnesses and/or enhance immunological responses ( Traore et al., 2014). Upon these considerations, it is of interest to clarify the biological importance and level of antimicrobial and/or antimalarial activity of the plant species cited by the Guinean traditional healers in the treatment of fever/malaria. Nowadays, a worldwide search for new classes of effective antimalarial and antibacterial drugs is in progress and natural products have been recognized as highly important candidates for such purpose ( Tobinaga et al., 2009). Therefore the present study was undertaken.

2. Materials and methods

2.1. Ethnobotanical investigation

The selected plants were collected during an ethnobotanical survey conducted in the four main Guinean regions from May 2008 to September 2010. Botanical identification was first conducted in the field, and confirmed by Dr. S.M. Keita (CERE, University of Conakry), M.S. Barry and N. Camara (Centre de Recherche et de Valorisation des Plantes Médicinales – CRVPM, Dubreka). Voucher specimen registration numbers at the Herbarium of the CRVPM and local names are listed in Traoré et al., 2013. Traditional healers were interviewed in their homes, and herbalists in front of their stalls (on the roadside or on various market places). The questionnaire and oral interviews were based on the standardized model which was designed by CRVPM, Dubreka. The main questions focused on demographic data (age and sex), educational level, professional experience, knowledge about malaria: local names, cause, known signs and symptoms of malaria, plants used in the preparation of antimalarial remedies, plant parts employed, mode of preparation, and mode of administration.

2.2. Preparation of plant extracts

Plant extracts were prepared by macerating 10 g of powdered dried plant material with 50 ml solvent (hexane, chloroform, methanol, or ethanol 70%) for 24 h. With regard to the aqueous crude extract, a decoction of 10 g dried plant powder was prepared in 150 ml distilled water for 30 min, corresponding to the traditional preparation method. The extracts were then filtered and each filtrate was evaporated under reduced pressure to dryness; 5 mg were weighed and submitted for antimicrobial testing.

2.3. Biological evaluation

Antimicrobial evaluation was carried out as previously described by Cos et al., 2006a and Cos et al., 2006b. Extracts were tested on the following microorganisms: the enterobacteriaceae Gram-negative Escherichia coli ATCC 8739, the Gram-positive cocci Staphylococcus aureus ATCC 6538, the acid-fast bacteria Mycobacterium chelonae, the yeast Candida albicans ATCC 59630, the opportunistic filamentous fungi Aspergillus fumigatus ATCC 16404, and the dermatophyte Trichophyton rubrum ATCC 68183. The level of antimicrobial activity was arbitrarily ranked according to the following criteria: strong (IC50≤10 μg/ml); good (10 μg/ml<IC50≤20 μg/ml); moderate (20 μg/ml<IC50≤40 μg/ml); weak (40 μg/ml<IC50≤64 μg/ml); inactive (IC50≥64 μg/ml). Positive control substances included flucytosine for Candida albicans (IC50 0.34 µM), voriconazole for Trichophyton rubrum and Aspergillus fumigatus (IC50 0.18 µM and 0.75 µM, respectively), doxycycline for Staphylococcus aureus and Escherichia coli (IC50 0.83 µM and 0.82 µM, respectively) and rifampicin for Mycobacterium chelonae (IC50 0.1 µM).

3. Results and discussion

Since the clinical features of malaria closely resemble those of other febrile illnesses, such as typhoid fever, septicemias, urinary tract infections, upper and lower respiratory tract infections, which are common in most of the tropical countries, antimalarial plant species with antimicrobial properties are of importance. The plants species were selected on the basis of their number of citations by traditional healers for their use against malaria which in fact include febrile illnesses. Of the 51 extracts from 34 plant species tested, only 17 (from 15 plant species) showed strong to weak antimicrobial activity (IC50<64 µg/ml). The 34 selected plant species are distributed into the following 24 families: Anacardiaceae (Pseudospondias microcarpa (A. Rich.) Engl.; Spondias mombin L.), Annonaceae (Cleistopholis patens Engl. & Diels), Apocynaceae (Strophanthus hispidus DC), Bignoniaceae (Newbouldia laevis (P. Beauv.) Seem.; Markhamia tomentosa (Benth.) K. Schum), Caesalpiniaceae (Cassia sieberiana DC; Mezoneuron benthamianum Baill.; Piliostigma thonningii (Schumach) Milne-Redhead), Caricaceae (Carica papayaL.), Combretaceae (Combretum glutinosum Perr., Guiera senegalensis J.F.Gmel., Terminalia albida Sc. Elliot, Terminalia macroptera Guill.); Dilleniaceae (Tetracera alnifolia Willd.), Ebenaceae (Diospyros mespiliformis Hochst.), Euphorbiaceae (Alchornea cordifolia (Schumach. & Thonn.) Müll.Arg., Bridelia micrantha (Hochst.) Baill), Fabaceae (Erythrina senegalensis DC), Hymenocardiaceae (Hymenocardia acida Tul.), Hypericaceae (Vismia guineensis (L.) Choisy), Icacinaceae (Rhaphiostylis beninensis (Hook f.) Planch.), Lythraceae (Lawsonia inermis L.), Meliaceae (Azadirachta indica A. Juss.; Trichilia emetica Vahl.), Mimosaceae (Albizia zygia (DC.) J. F. Macbr), Moraceae (Ficus sp; Ficus vallis-choudae Del.), Olacaceae (Ximenia americana L.), Rubiaceae (Morinda geminata DC), Rutaceae (Zanthoxylum zanthoxyloides (Lam.) Zepernick & Timber), Sapindaceae (Paullinia pinnata L.), Tiliaceae (Grewia villosa Willd.), Verbenaceae (Lantana camara L.)
A total of 51 extracts from 34 plant species were evaluated for their antibacterial and antifungal activity against C. albicans (34 extracts from 31 plant species), T. rubrum (26 extracts from 24 plant species), A. fumigatus (7 extracts from 7 plant species), S. aureus (51 extracts from 34 plant species), E. coli (47 extracts from 30 plant species) and M. chelonae (10 extracts from 9 plant species). The cytotoxicity of all the tested extracts has been established previously ( Traore et al., 2014).
A total of 26, 17, 6 and 2 plant extracts were prepared from leaves, stem bark, bark, and root bark, respectively. Among these, 42 were polar (23 methanol, 14 ethanol 70%, 5 aqueous extracts), and 9 were apolar (6 hexane, 3 chloroform). The maximum concentration tested for each sample was 64 µg/ml. Since for all anti-effective bioassays of extracts tested against Gram-negative bacteria, mycobacteria and fungi, IC50 values should be below 100 µg/ml to be considered as active (Cos et al., 2006), all tested samples with an IC50>64 µg/ml (S. aureus, M. chelonae, C. albicans, T. rubrum and A. fumigatus) could not be considered strictly speaking as inactive. But, based on arbitrarily defined criteria, any IC50 value above 64 µg/ml was considered as inactive in the present study.

3.1. Antifungal activity

3.1.1. Candida albicans

Except Ficus spp, H. acida and S. mombin, all the other 31 plant species were tested. This yeast was inhibited by only 6 plant extracts: P. microcarpa (IC50 6.99 µg/ml; methanol extract of stem bark) and X. americana (IC50 8.12 µg/ml; methanol extract of leaf), D. mespiliformis (IC50 21.69 µg/mL; ethanol extract of leaf), C. glutinosum (IC50 28.12 µg/mL; methanol extract of leaf), T. macroptera (IC50 21.93 µg/ml; ethanol extract of stem bark) and T. albida (IC50 34.55 µg/ml; methanol extract of root bark). The other 25 tested plant species were not active at a concentration ≤64 µg/ml.
C. albicans is known as a common cause of morbidity and mortality in immune-compromised individuals (( Lee et al., 2002). Previous investigations indicated a good activity against C. albicans for the chloroform extract of the leaf of X. americana, while the methanol and aqueous extracts were devoid of any activity ( Omer and Elnima, 2003). A weak activity was also described for the methanol and aqueous extracts of the stem bark ( Maikai et al., 2009). On the other hand, our results with P. microcarpa contrasted with the inactivity reported by Kisangau et al. (2007). All the active extracts against C. albicans are also active against T. rubrum, except C. glutinosum and M. geminata, which were only active against C. albicans and T. rubrum, respectively.
The antifungal properties of the tested plant species were in agreement with some previous results, such as the wide antifungal effect of the polar extracts of X. americana (leaf, stem-bark, or root) against C. albicans, A. niger, Sacchoromyces cerevisiae ( Omer and Elnima, 2003), the significant antifungal activity of D. mespiliformis against A. flavus, A. niger, Microsporum gypseum, T. rubrum and C. albicans ( Sadiq et al., 2013), the activity of A. cordifolia (leaf and stem-bark) against C. albicans ( Adeshina et al., 2012). The antifungal activities of Terminalia species are related to the presence of tannins and saponins ( Baba-Moussa et al., 1999). However, our results on the antifungal activity of T. macroptera contrasted with its inactivity described by Silva et al. (1997).

3.1.2. Aspergillus fumigatus

At the highest tested concentration (64 µg/ml), none of the seven tested extracts from Bridelia micrantha, Combretum glutinosum, Lantana camara, Pseudospondias microcarpa, Raphiostylis beninensis, Ximenia americana and Zanthoxylum zanthoxyloides were active. Nevertheless, for related species such as Bridelia atroviridis and Zanthoxylum gilletii, antifungal activity against Aspergillus niger has been reported ( Agyare et al., 2006). According to Saadabi (2006), the CHCl3 leaf extract of Grewia villosa was strongly active against Aspergillus flavus, Candida albicans and slightly active against A. fumigatus and A. niger. These opportunistic filamentous fungi were considered for years to be weak pathogens. With an increasing number of immunosuppressed patients, however, there has been a dramatic increase in severe and usually fatal invasive aspergillosis, which now is the most common mold infection worldwide ( Latgé, 1999).

3.1.3. Trichophyton rubrum

Only the ethanol extract of bark of T. macroptera (IC50 5.59 µg/ml), the ethanol extract of the root of M. geminata (IC50 19.5 µg/ml), the ethanol extract of leaf of D. mespiliformis (IC50 24.44 µg/ml), the methanol extract of leaf of X. americana (IC50 26.06 µg/ml) and the methanol extract of bark of P. microcarpa (IC50 28.15 µg/ml) showed a significant activity. The other 19 tested plant species were devoid of any activity at the highest concentration of 64 µg/ml (A. zygia, A. indica, B. micrantha, C. sieberiana, C. patens, C. glutinosum, E. senegalensis, F. vallis-choudae, G. villosa, G. senegalensis, L. camara, M. tomentosa, P. pinnata, P. thonningii, R. beninensis, S. hispidus, T. emetic, V. guineensis, and Z. zanthoxyloides).

3.2. Antibacterial activities

3.2.1. Esherichia coli

The Gram-negative E. coli was the least susceptible among the 3 tested micro-organisms; none of the 47 tested extracts were active at the highest tested concentration (64 µg/ml). However, previous activities against E. coli have been described for A. cordifolia, Bridelia micrantha, S. mombin, T. albida, L. inermis, L. camara, and R. beninensis ( Adeyemi et al., 2008, Corthout et al., 1994 and Gull et al., 2013; Ayodole et al., 2010; Ganjewala et al., 2009, Barreto et al., 2010 and Lasisi et al., 2011).

3.2.2. Staphylococcus aureus

All the extracts were tested against the Gram-positive S. aureus and 11/51 (21.56%) showed activity with an IC50 less than 64 µg/ml. The best antibacterial activity was observed for the methanolic extracts of the leaves and stem barks of Alchornea cordifolia (IC50 values 2.18 and 7.47 µg/ml, respectively), the methanol and hexane extracts of the leaves of S. mombin (IC50 11.81, and 19.97 µg/ml, respectively), and the methanol extract of the leaves of L. camara (IC50 14.35 µg/ml). The hexane extract of the root bark of V. guineensis, the methanol extract of the leaves of T. alnifolia and the stem-bark of Ficus sp. exhibited a moderate effect against S. aureus (IC50 24.41, 26.91 and 29.23 µg/ml, respectively), while the extracts of Guiera senegalensis (ethanol leaf), Hymenocardia acida (aqueous stem bark) and Morinda geminata (ethanol root bark) were weakly active (IC50 46.59, 58.69 and 61.17 µg/ml, respectively).
The antibacterial activity of some of these plant species has extensively been studied. Among these, A. cordifolia (leaf and stem-bark) showed a wide and significant inhibition of many pathogenic microorganisms such as S. aureus and Pseudomonas aeruginosa ( Okeke et al., 1999 and Igbeneghu et al., 2007), Bacillus subtilis and Klebsiella pneumonia ( Ajali, 2000). Some A. cordifolia fractions from the most active leaf extract, notably those containing phenolics and terpenoids, exhibited significant activity against P. aeruginosa, B. subtilis and E. coli ( Ganjewala et al., 2009). S. mombin showed a moderate activity against, S. aureus, K. pneumoniae, Salmonella typhosa, Serratia marcescens, Proteus mirabilis and Enterobacter cloacae ( Abo et al., 1999, Corthout et al., 1994, Umeh et al., 2009 and Da Silva et al., 2012). T. albida and L. inermis exhibited an antimicrobial activity against S. aureus, Klebsiella pneumoniae, E. coli, Streptococcus pyogenes, P. aeruginosa and P. mirabilis ( Gull et al., 2013; Ayodole et al., 2010). The leaf extract of Lantana camara was found to be effective against B. subtilis, P. aeruginosa, S. aureus, P. vulgaris and V. cholerae ( Ganjewala et al., 2009 and Barreto et al., 2010).

3.2.3. Mycobacterium chelonae

The methanol extract of the root bark of Terminalia albida and the leaf of Lawsonia inermis were the only samples active against M. chelonae with interesting IC50 values of 11.81 and 16 µg/ml, respectively. This result could be interesting as compared with some recent in vitro susceptibility studies demonstrating activity of newly developed antimicrobials such as linezolid which inhibited M. chelonae with a MIC 50% at 8 µg/ml or MIC 90% at 16 µg/ml ( Wallace et al., 2001). The antimycobacterial activity of the leaf extract of L. inermis (IC50 16 µg/ml) against non-tuberculous mycobacteriosis caused by M. chelonae overlapped with previous reported activity against M. tuberculosis H37Rv which was inhibited by 6 µg/ml of L. inermis extract. Moreover, in in vivo studies on guinea pigs and mice at a dose of 5 mg/kg body weight, the herb showed significant resolution of experimental tuberculosis following infection with M. tuberculosis H37Rv ( Sharma, 1990). Such activities could be related at least in part to the presence of lawsone, i.e. 2-hydroxynaphthoquinone, one of the major bioactive constituents of L. inermis ( Lall et al., 2003) and lawsonicin, which showed an IC50 value of 6.25 µg/ml against M. tubeculosis H37Rv ( Bhatti et al., 2013). Moreover, our current findings on the antimycobacterial properties of T. albida (IC50 11.81 µg/ml) are in line with earlier reports on Terminalia species particularly T. avicennioides, which inhibited significantly the growth of M. tuberculosis and Bacillus Calmette-Guerin (BCG) at 78 and 200 μg/ml, respectively ( Mann et al., 2008). Like other oleanane triterpenoids, friedelin isolated from T. avicennioides exhibited an in vitro antimycobacterial activity against BCG with a MIC value of 4.9 μg/ml ( Abdullahi et al., 2011). On the other hand, the bark and root are used as an antibiotic in Nigeria ( Ayodele et al., 2010). Noteworthy, the two Terminalia species viz. T. albida and T. macroptera figure among the most frequently cited antimalarial plant species by Guinean traditional healers and herbalists ( Traoré et al., 2013). Although inactive against M. chelonae at the highest tested concentration (64 µg/ml), the leaf and root bark of Tetracera alnifolia were active against M. tuberculosis ( Lawal et al., 2011). Neem seed oil and essential oils from leaves and bark have been shown to inhibit the growth of various genera of pathogenic microorganisms, such as Mycobacterium and Plasmodium ( Habluetzel et al., 2009).
Based on our previous in vitro antiplasmodial study of Guinean plant species ( Traore et al., 2014), the relationship between the in vitro antimicrobial and antimalarial activities of the tested plant species is heterogeneous:
4/34 (12%) were devoid of any antimicrobial or antiplasmodial activity against P. falciparum-K1 at the highest tested concentration (IC50 >64 µg/ml), i.e. Bridelia sp., Raphiostylis beninensis, Strophantus hispidus and Zanthoxylum zanthoxyloides;
3/34 (9%) were only antimicrobially active, viz. Pseudospondias microcarpa (C. albicans: IC50 6.99 µg/ml), Tetracera alnifolia (S. aureus IC50 26.91 µg/ml) and Ximenia americana (T. rubrum IC50 8.12 µg/ml);
14/34 (41%) were only antiplasmodially active (Traore et al., 2014). The relative absence of antimicrobial activity of these plant species could favor of their nearly exclusive antimalarial use. The most important antiplasmodial effects against P. falciparum-K1 were observed for Mezoneuron benthamianum (IC50 5.8 µg/ml), Newbouldia laevis (IC50 9.1 µg/ml), Albizia zygia (IC50 18.1 µg/ml), Carica papaya (IC50 11.4 µg/ml), Ficus vallis-choudae (IC50 16.3 µg/ml), Paullinia pinnata (IC50 17.3 µg/ml) and Azadirachta indica (IC50 5.8 µg/ml) ( Traore et al., 2014);
13/34 (38%) of the tested plant species showed antimicrobial as well as antiplasmodial (Traore et al., 2014) activities. Among these, strong to moderate inhibition was observed for the polar extracts of A. cordifolia (S. aureus: IC50 2.81–7.47 µg/ml; P. falciparum: IC50 9.3–11 µg/ml), the methanol extract of S. mombin (S. aureus: IC50=11.81 µg/ml; P. falciparum: IC50 2.8 µg/ml), the chloroform extract of V. guineensis (S. aureus: IC50 24.41 µg/ml; P. falciparum: IC50 1.9 µg/ml), the methanol extract of T. albida (C. albicans and M. chelonae: IC50 34.55 and 11.81 µg/ml, respectively; P. falciparum: IC50 0.6 µg/ml), the aqueous ethanolic extract of T. macroptera (C. albicans and T. rubrum: IC50 21.93 and 5.59 µg/ml, respectively; P. falciparum: IC50 6.8 µg/ml), the methanol extract of L. inermis (M. chelonae: IC50 16 µg/ml; P. falciparum: IC50 23.4 µg/ml) and the methanol extract of L. camara (S. aureus: IC50 14.35 µg/ml; P. falciparum IC50 24.4 µg/ml).
Failure to treat concurrent bacterial infections in children with malaria may lead to severe morbidity and mortality. Taking into account that severely ill patients with complicated P. falciparum malaria are also profoundly immunosuppressed and susceptible to opportunistic fungal infections ( Soesan et al., 1993 and Däbritz et al., 2011), and that there is evidence of altered immune function in children with malaria ( Okwara et al., 2004), the antimalarial plant species with an evidence of antimicrobial properties are of interest. On the other hand, the fact that some plant species are involved in the treatment of diseases with febrile symptoms without any antiplasmodial evidence could be justified by their antimicrobial activities.
Patients with complicated P. falciparum malaria are also profoundly immunosuppressed and susceptible to opportunistic infections. The frequent presence of complicating pathologies in relatively non-immune young children with malaria contributes to a high morbidity and mortality. In addition the diagnosis of malaria in traditional medicine is tentative and mainly based on fever symptoms, which is common to many other microbial infections as well.
Although the present antimicrobial investigation was not exhaustive, these preliminary results may justify at least partly the traditional use of some “antimalarial” plant species without any in vitro or in vivo antiplasmodial evidence. To the best of our knowledge, this is the first report on the antimycobacterial activity of T. albida and L. inermis against M. chelonae. This finding could be of interest since L. inermis and Terminalia spp. have been reported to be active against M. tuberculosis. Moreover, the antiplasmodial activity previously described for T. albida (0.6 µg/ml) ( Traore et al., 2014) may be of therapeutic importance in the treatment of malaria associated with cough in view of its favorable Selectivity Index (SI>100). Further studies are required to validate and rationalize such considerations. Future perspectives include a wide antimicrobial testing of all other antimalarial plant species, the identification of active antimalarial and/or antimicrobial constituents, the evaluation of the toxicity of the most interesting plant species along with a clinical trial to evaluate the efficacity and tolerability of standardized plant extracts.

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