Medicinal plants traditionally used for management of malaria in rural communities of Uganda

Abstract

Background

Malaria remains a major cause of morbidity and mortality especially in sub-Saharan Africa. Whereas herbal medicines have long been used for disease remedy in many African communities, there is limited evidence on the extent of use, their safety, and efficacy. This study, sought to identify herbal medicinal plants used by communities in low and high malaria transmission settings in Uganda for managing of malaria.

Method

An Ethnobotanical survey was conducted across four geographical regions purposively selected to represent moderate-to-high (Apac, Arua and Tororo districts) and low (Kabale district) malaria transmission settings. One-hundred and two (102) traditional medicine practitioners (TMPs) in Ugandan local communities were included in the study. A checklist was used to collect data and covered the following areas; knowledge on malaria transmission, malaria symptoms, diagnosis, medicinal plants used, preparations, preservation methods and doses. Data was analyzed in MS Excel^®. Consensus factor, use value metrics and frequencies were calculated.

Results

Ninety-seven plant species distributed across 45 families were mentioned by TMPs in management of malaria in Ugandan communities. Plant family Asteraceae, 15.5% (15/97) had the highest distribution of plants reported by TMPs. Vernonia amygdalina Delile, Aloe vera Burm. F., Artemisia annua L., Vernonia grantii Oliv. and Justicia betonica L. were the most mentioned, with use values of 0.4, 0.3, 0.2, 0.15 and 0.14 respectively. Leaves 64% and root barks 18% were the most harvested plant parts while decoctions (54%) and infusions 26% were the most common methods of preparing herbal products for individuals with malaria. Medicines were stored as dry powders for extended periods although some were prepared as fresh plants. Nearly all medicinal preparations were administered orally with varying dosage (5 ml-500 ml*3times a day) recommendations. Treatment duration varied between 3 and 7 days among practitioners. TMPs mentioned that malaria is transmitted by mosquitoes while others, said poor hygiene, stagnant water and body contact.

Conclusion

A diverse number of plant species, use and preparation methods are documented in this study as a way of preserving traditional knowledge in Uganda. Vernonia amygdalina Del., Aloe vera (L) Burm. f, Vernonia grantii Oliv. and Justicia betonica L. were identified as important plant species that can be further studied to validate their safety, antiplasmodial and active bioactive phytochemicals that can provide novel lead compounds for malaria treatment. These plant species can also be conserved through cultivation for sustainable use.

Introduction

In Uganda, malaria is estimated to be responsible for 30–50% of out-patient visits, 15–20% of hospital admissions and up to 20% of in-patient deaths [1]. Malaria is thus one of the leading causes of morbidity and mortality in the country especially among children under five years [2]. Uganda is among the six African countries that account for approximately 55% of the global malaria burden [3]. The stagnation in malaria eradication efforts poses a challenge for the attainment of the sustainable development goals which target a reduction of 95% malaria incidence and mortality by 2030 [4].

Artemisinin-based combination therapies are the mainstay in malaria treatment however, recent studies in northern Uganda report prevalence of slow clearing parasites [5, 6]. Furthermore, the studies found increasing prevalence of K13 gene mutations, 469Y and 675 V associated with artemisinin resistance among P. falciparum parasites. With no known effective therapeutic alternatives to artemisinin-based agents, widespread emergence of artemisinin resistance threatens to worsen malaria disease outcomes especially in sub-Saharan Africa [7]. This calls for continuous search for effective alternative agents for malaria treatment especially from medicinal plants.

For millennia, majority of the modern medicines have been developed from natural products or their derivatives. Particularly, the history of antimalarial drug development and treatment is intimately linked with medicinal plants and quinine, the first drug that was used for treatment of malaria was isolated from the Cinchona tree in 1820 [8]. In 1945, Chloroquine, a 4-aminoquinoline was synthesized from quinine and it became the first line treatment of un complicated malaria replacing its congener quinine. However, in the early 1960s, there was a high spread and mortality of P. falciparum chloroquine resistance which inspired researchers to actively develop effective alternative antimalarials against chloroquine-resistant malaria. Accordingly, many antimalarials such mefloquine and halofantrine were synthesized and in 1973, a novel sesquiterpene lactone called qinghaosu and later renamed artemisinin, was isolated from the Chinese herb Artemisia annua L [9]. Artemisinin has a unique mechanism of action which involves the heme-mediated decomposition of the endoperoxide bridge to produce carbon-centered free radicals that are toxic to the parasite [10]. However, because of its poor bioavailability, more potent derivatives such as artesunate, arteether, artemether and dihydroartemisinin were synthesized [9]. In order to increase the sensitivity of P. falciparum to artemisinins and defer drug resistance development WHO recommends Artemisinin based combination therapy (ACTs) which involves combining an artemisinin derivative with another antimalarial drug like lumefantrine, mefloquine, amodiaquine, sulfadoxine/pyrimethamine, piperaquine and chlorproguanil/dapsone [11]. ACTs have thus remained the focal drugs for treatment of P. falciparum malaria. As such the role of plants in the development of novel antimalarial agents cannot be under estimated especially due to the diverse repository of compounds with potential antiplasmodial activity.

Rural communities in Uganda and many parts of the world continue to use plant-sourced remedies against several ailments, including malaria. With the emerging reduction in efficacy of the current antimalarial agents and continued high burden of the disease, the need for efforts towards discovery and development of new effective therapies cannot be overstated. Previous studies [12–15] have documented the use of medicinal plants in treatment of malaria however such studies have mainly focused on the central and western regions of Uganda while high malaria settings like Apac and Arua have not been considered. A comprehensive assessment through ethnobotanical surveys of medicinal plants used in local communities in Uganda is key to preserve traditional knowledge, to conserve the important plant species and to provide baseline information about plant species needed in the drug development pipeline. This study, thus sought to document knowledge on herbal medicinal plants used for managing malaria by Ugandan communities in low, and high malaria transmission settings including Arua, Apac, Tororo and Kabale districts.

Methods

Study design

This was a cross sectional study. We used a descriptive exploratory approach to investigate communities’ knowledge on medicinal plants used for managing malaria. Aspects such as: (i) socio-demographic characteristics, (ii) knowledge on malaria symptoms and transmission, (iii) medicinal plants used for managing malaria, (iv) medicinal plant preparation, (v) source of the plant collection, (vi) drug administration and duration of treatment, and (vii) methods of preservation of the herbal preparations were investigated.

Study area

The study was conducted among in four rural districts of northern (Arua and Apac districts), eastern (Tororo district) and western Uganda (Kabale district) (Fig. 1) between October-December 2024. The districts were purposively selected based on malaria transmission intensities. Arua, Apac and Tororo districts are high transmission malaria areas while Kabale district is a low transmission area.

Fig. 1.

Map of Uganda showing location of study districts, sub counties and villages

Arua district is located in west Nile, covering a total of 3,236.4 km² between latitude 20º 30’N and 30º 50’N and longitude 30º 30’E and 31º 30’E with a population of 820,500 people. It is bordered by Maracha district in the North West; Yumbe in the North East; Democratic Republic of Congo in the West; Nebbi in the South; Zombo in the South East; and Amuru district in the East. The major economic activity in the district is crop farming.

Apac district is in northern Uganda, located between longitudes 32^o E and 34^o E and latitudes 2^o N and 3^o N. It occupies an area of 3,255.9 km2 of which 9% is under swamps and water while 15% is under forest. It has a population of approximately 349,000 people.

Tororo district is a predominantly rural district in the Eastern region of Uganda that is 241,551 square kilometres large and located between latitude: 0° 44’ 59.99” N and longitude: 34° 04’ 60.00” E. It has a population of approx. 517,000 people. Wetland rice growing is the major economic activity in Tororo District favoring mosquito breeding especially in rainy seasons that are characterized with flooding.

Kabale district is in the western region of Uganda between longitudes 29° 34’ E and 35° 0’ E latitude 1° 29’ S and 4° 12’ N, it harbors a population of approximately 248,700 distributed in 19 subcounties and 1,345 villages. The altitude of Kabale district ranges between 1,219 and 2,347 m above sea level and temperatures average 18ºC during day and 10ºC at night. The major economic activity is agriculture.

Study population

The study was done among adult TMPs and were purposively selected based on their reputation of using medicinal plants to manage malaria and willingness to participate in the study by providing written consent.

Sampling criteria and data collection

In each of the four districts (Arua, Apac, Tororo and Kabale), two sub counties were randomly selected i.e. Ayiva and Vurra from Arua District, West Budama and Tororo from Tororo District, Ibuje and Akokoro from Apac, Kabale North and Kabale south from Kabale Districts. From each of the sub counties, two villages were selected (Fig. 1). Within each village, TMPs were purposively selected. The interviews were conducted using a pretested key informant interview guide adopted from a previous study [16] with few modifications. The interview was conducted for an average of 30–45 min and written consent was sought and obtained from all TMPs that participated in the study. For each plant species that was mentioned in the study, a voucher specimen indexed as L 001- L 110 was prepared, identified by a taxonomist (Dr. Ssegawa Paul), and achieved at the Makerere University Museum. All plant species were named using Flora of Tropical East Africa (FTEA). Administrative clearance to conduct the study in the different Districts and villages was sought from the Resident District Commissioner and local councils respectively.

Data management and analysis

Numerical data were entered in MS Excel^© program where the relevant metrics were generated. Informant Consensus Factor (FIC) and Use Value (UV) metrics were computed. The FIC estimates homogeneity of information concerning use of medicinal plants for a particular ailment. It is calculated using the following formula [17].

where Nur = the number of use-reports in each category and nt = number of taxa used. On the other hand, the UV metric estimates the commonness of use of each plant species in each area and was determined using the following formula (20):

Where Nur is the number of use reports and Ni is total number of informants surveyed.

Results

Participant social demographics

A total of 102 TMPs from high 74.5% (76/102) and low 25.4% (26/102) malaria transmission settings participated in the study. Of these 65.7% (67/102) were males (Table 1). The mean age of the TMPs was 54 ± 2 years (range of 27–85). Majority, 71.5% (73/102) of the TMPs had completed the primary level of education while 19.6% (20/102) had no formal education. Most participants practiced herbal medicine as a secondary occupation and majority were primarily subsistence farmers.

Table 1.

Socio-demographic characteristics of traditional medicine practitioners interviewed across four districts in Uganda

Sociodemographic characteristics (n = 102)
Characteristics	Description	Frequency N (%)
Sex	Male	65.8
	Female	34.2
Education	Primary	71.8
	No formal education	29.2
Mean age ± SD	54 ± 2
Age categories (years)	18–29	2.9
	30–45	13.7
	46–55	33.3
	56–65	19.6
Marital Status	Married	85.3
	Single	3
	Separated	11.7
Occupation	Farmer	96
	Businessman	3
	Reverend	1
Malaria burden	High	74.5
	Low	25.5
Belonged to a professional association	No	74.5
	Yes	25.5

Knowledge on malaria cause, symptoms, transmission, and diagnosis

The common symptoms of malaria mentioned by traditional medicine practitioners included fever 94% (96/102), headache 67.6% (69/102), vomiting 62.7% (64/102) and convulsions 51.9% (53/102) (Fig. 2). Majority, 69.6% (71/102) of TMPs mentioned that malaria was spread through mosquito bites and over half, 64.7% (66/102) reported using symptoms in diagnosing malaria among individuals seeking care. A third 35.2% (36/102) of the TMPs mentioned managing individuals who already had malaria diagnosis from hospitals. TMPs neither had knowledge on the malaria causative parasite nor the conventional management of the disease as per the national malaria treatment guidelines. Participants also mentioned body contact, sharing utensils, drinking dirty water, stagnant waters, not sleeping under a mosquito net and a bushy environment as some of the other factors aiding malaria spread.

Fig. 2.

Shows symptoms of Malaria as mentioned by Traditional medicine practitioners and their frequency of mention

Malaria treatment practices and experiences among the study participants

TMPs were on average receiving 8±2 malaria patients per month in high transmission areas and 2–3 patients in low transmission areas. The duration of treatment for each malaria symptomatic patient varied among different TMPs ranging from 3 to 7 days. Traditional medicine practitioners mentioned that in most cases (96/102), their patients recovered, and this was assessed through self-reports. Those that did not recover were referred to health centers for further management. The cost of treatment varied widely amongst different TMPs. For some, treatment was free, and patients simply appreciated or gifted the practitioner after recovery. In high malaria transmission settings, treatment costs ranged between Uganda shillings 2000–10,000 (equivalent range 0.5-3 USD).

Plants used for management of malaria by the traditional medicine practitioners

A total of ninety seven (97) plant species were mentioned by study participants across the four districts for treatment of malaria (Table 2). Plant species were distributed across 45 families with Asteraceae 15.5% (15/97) having the highest frequency (Fig. 3). Vernonia amygdalina Del (41) and Aloe vera (L.) Burm. F. (32) were the most mentioned with use values of 0.4 and 0.3 respectively. These were followed by Artemisia annua L. (21), Vernonia grantii Oliv. (15), Justicia betonica L. (14), Senna hirsute (L.) H.S. Irwin and Barneby (10), Psidium guajava L. (8), Schkuhria pinnata (Lam.) O. Ktze (8), Tetradenia riparia (Hochst.) Codd (5) and Sarcocephalus latifolius (smith)Bruce (5) among others. Plant spp like Aloe vera and Justicia betonica L. were mentioned by practitioners in all the four regions surveyed. The Informant Consensus factor in this study was calculated as 0.82.

Table 2.

Shows plant species used in the treatment of malaria as reported by TMPs, local names, frequency of mention, parts used and use values

Scientific name (District*)	Local names	Family	Voucher No.	Preparation	Plant part	Frequency	Use value
Vernonia amygdalina Del	Muluswa/ Omubirizi	Asteraceae	L080	Decoction Infusion	L	41	0.40
Aloe Vera (L.) Burm.f.	Aloe Vera/ Nzoo/lukaka	Xanthorrhoeaceae	L081	Infusion Decoction	L	32	0.31
Artemisia annua L.	Artemisia	Asteraceae	L 069	Decoction Infusion	L	21	0.21
Vernonia grantii Oliv.	okello-kello Ecoro ego/ etwatwa	Asteraceae	L 042	Maceration	L	15	0.15
Justicia betonica L.	Quinine/ Nalongo	Acanthaceae	L 059	Decoction	FL, L, WS	14	0.14
Senna hirsute (L.) H.S. Irwin and Barneby	Oyed apar/ Gasia	Caesalpinioideae	L 038	Decoction	L	10	0.10
Psidium guajava L	Boke mapeera	Myrtaceae	L 052	Decoction	L, G	8	0.08
Schkuhria pinnata (Lam.) O. Ktze	Quinine, akweyo	Asteraceae	L 034	Decoction Infusion Maceration	L	8	0.08
Tetradenia riparia (Hochst.) Codd	Omuharavumba	Lamiaceae	L 082	Decoction	L	5	0.05
Sarcocephalus latifolius (smith)Bruce	Ibeleg, Ebeleng, Akeng	Rubiaceae	L 046	Decoction	RB/L	5	0.05
Persea americana Mill	Boke ovacado	Lauraceae	L 083	Decoction Infusion	L	4	0.04
Eucalyptus sp	Kalatunsi	Myrtaceae	L 083	Maceration Decoction	L	4	0.04
Annona senegalensis Pers.	Omukoonya	Annonaceae	L 084	Decoction	L	4	0.04
Schkuhria pinnata (Lam) O.Ktze.	Ekadwarit (Ateso)	Asteraceae	L 085	Decoction Infusion	L	3	0.03
Senna occidentalis (L.) Link	Yekeyeke	Fabacea	L 086	Maceration Infusion	L, RB	3	0.03
Markhamia lutea (Benth.) K.Schum	Emusoliat (Ateso), Musambya	Bignoniaceae	L 065	Decoction, Infusion	SB/L	3	0.03
Warbugia ugandesis Sprague	Abac	Canellaceae	L 087	Maceration	SB/L	3	0.03
Mangifera indica L.	Muyembe	Anacardiaceae	L 088	Maceration	SB	3	0.03
Senna didymobotrya Fresen.	Omugabagaba	Caesalpinioideae	L 072	Decoction	L	3	0.03
Maesa lanceolata Forssk	Omuhanga	Myrsinaceae	L 089	Decoction	L	3	0.03
Clerodendrum umbellatum Poir	Lolobi	Lamiaceae	L 027	Decoction	L	3	0.03
Bidens pilosa L	Sere (JAP)	Asteraceae	L 090	Infusion	R/L	2	0.02
Cissampelos mucronata A. Rich.	Kavamagombe/ agwaya-gwaya	Mennispermaceae	L 037	Infusion	SB/L	2	0.02
Tagetes minuta L.	mukazi mulofu	Asteraceae	L 073	Infusion	L	2	0.02
Gouania longispicata	omufulula	Rhamnaceae	L 091	Maceration Infusion	L	2	0.02
Momordica foetida schumach	kirerabaana / bombo	Cucubitaceae	L 068	Infusion	L	2	0.02
Tithonia diversifolia Gray	Okangali	Asteraceae	L 092	Decoction	L	2	0.02
Hyptis suaveolens Poir	Ajingurua	Lamiaceae	L 007	Decoction	WP	2	0.02
Harrisonia abyssinica Oliv.	Kawakawa	Samourabaceae	L 017	Powder	RB/SD	2	0.02
Aristolochia elegans mast	Emanimani, koolo	Aristolochiaceae	L 093, L027	Powder	F, L, SD	2	0.02
Moringa oleifera L.	Moringa	Moringaceae	L 033	Decoction	L/RB/SB/SD	1	0.01
Dicliptera laxata C.B.CL	Fula	Acanthaceae	L 064	Decoction	L	1	0.01
Hoslundia opposita (Vahl)	Kamunye	Asteraceae	L 066	Decoction	RB	1	0.01
Toddalia asiatica (L.) Lam.	Kawule/ Thwolikiluwi	Rutaceae	L 094	Decoction	RB	1	0.01
Conyza floribunda HB K	Emelliat	Asteraceae	L 061	Infusion	L	1	0.01
Azadirachta indica (A. Juss)	Neem/ Arubaine	Meliaceae	L 095	Infusion	L	1	0.01
Mondia whitei (Hook. f.) Skeels	Omulondo (Samia)	Apocynaceae	L 096	powder	L	1	0.01
Crassocephalum vitellinum Benth	Ensununu	Asteraceae	L 070	Decoction		1	0.01
Mukia maderaspatana (L) M.J Roem	Akabindizi	Cucubitaceae	L 069	Decoction	L	1	0.01
Hibiscus fuscus Garcke	omusinga	Malvaceae	L 074	Decoction	L	1	0.01
Ageratum conyzoides L.	omubuza	Asteraceae	L 075	Decoction	L	1	0.01
Ipomoea batatas (L.) Lam.	emikamba	Convolvulaceae	L 097	Infusion	L	1	0.01
Dicliptera laxata C. B. CL	nyarwehindura	Acanthaceae	L 098	Decoction	L	1	0.01
Ajuga remota Benth.	kitinwa	Lamiaceae	L 099	Decoction	L	1	0.01
Indigofera arrecta A. Rich	omushorooza	Papilionacaea	L 071	Decoction	L	1	0.01
Antidesma venosum E. Mey. ex Tul.	mulingwa/ embatabata	Phyllanthaceae	L 100	Decoction	L	1	0.01
Dracaena fragrans (L.) Ker Gawl.	ndugaho/ omugolora	Asparagaceae	L 101	Decoction	RB	1	0.01
Chenopodium opulifolium Schrad. ex W.D.J.Koch & Ziz	Omwetango, Atiko	Chenopodiaceae	L102, L055	Decoction	L	4	0.01
Agrocharis incognita (Norman) Hey &Jury	akatankolora/akatampuhi	Apiaceae	L 103	Decoction	L	1	0.01
Spathodea campanulata Buch. -Harm. ex DC.	Omwatashare	Bignoniaceae	L 104	Decoction	SB	1	0.01
Cactus spp	Lubamba	Cactaceae	L 105	Decoction	L	1	0.01
Sida rhombifolia L.	Omunyiganyenje/ muzimba ndegeya	Malvaceae	L 106	Decoction	L	1	0.01
Plectranthus cyaneus (Forssk.) Schweinf. Ex. Sprenger	Kibwankula	Lamiaceae	L 107	Decoction	L	1	0.01
Physalis peruviana L.	Entuntunu	Solanaceae	L 108	Decoction	L	1	0.01
Markhamia lutea (Benth.) K. Schum.	Musambya	Bignoniaceae	L 109	Decoction	RB/L	1	0.01
Allium Sativum L.	Garlic	Amaryllidaceae	L 110	Decoction	B	1	0.01
Vernonia spp	Ecolo	Asteraceae	L 010	maceration	L	1	0.01
Oxalis corniculata	Ewaandre	Oxalidaceae	L 005	Decoction	WP	1	0.01
Lactuca capensis thumb.	Embereko	Asteraceae	L 026	Decoction	WP	1	0.01
Citrus lemon Burm. F	lemon	Myrtaceae	L 043	Maceration	fruit	1	0.01
Senna occidentalis (L.) Link	Boyo boyo	Caesalpinioideae	L 035	Decoction	L/ WP	1	0.01
Solanum nigrum Linn	Ocuga	Solanaceae	L 044	Infusion	L	1	0.01
Clematis hirsuta per.&guill	Adwe	Ranunculaceae	L 046	Infusion	WR	1	0.01
Dyschoriste nagchana (Nees) Bennet	pilopilo	Acanthaceae	L 30	Decoction Infusion	L/SB/RB	1	0.01
Maerua triphylla A. Rich	Okwenyo/Ayebi	Capparaceae	L 047	Infusion	RB/L	1	0.01
Euclea racemosa Murray subsp. Schimperi	Jewee	Ebenaceae	L051	Power	L	1	0.01
Solanum incanum L.	Ocokocok	Solanaceae	L049	Decoction	L	1	0.01
Crotalaria ochroleuca G. Don	Alayo	Papilionacaea	L 039	Maceration Powder	RB	1	0.01
Leonotis nepetifolia(L.) Ait. F.	Ating ating	Lamiaceae	L 053	Decoction	L	1	0.01
Periploca Linearifolia Quart. Dill. & A, Rich	Agaba	Apocynaceae	L 052	Decoction	L	1	0.01
Indigofera spicata Forssk.	Icac	Papilionacaea	L 062	Decoction	RB	1	0.01
Zanthoxylum chalybeum Engl.	Iucu	Rutaceae	L 050	Decoction	WR	1	0.01
Rhamnus prinoides L. Herit	Kirikolo	Rhamnaceae	L 011	Decoction	L	1	0.01
Cyperus rigidifolius Steudel	enkumbo/ omulemampango	Cyperaceae	L079	Deccoction	L	1	0.01
Guoania longispicata Hemsl.	Omufurura	Rhamnaceae	L 078	Infusion	L	1	0.01
Euphorbia splendens Hook.	Labi	Euphorbiacea	L 029	Maceration	L/SB	1	0.01
Lepidotrichilia volkensii (Guerke) Leroy	Okaa	Meliaceae	L 008	Swallowed fresh	SD	1	0.01
Canavalia afriacana Dunn	Osnosu	Papilionacaea	L 006	Powder	SD	1	0.01
Chenopodium Procerum Moq.	Omujumbajumba	Chenopodiaceae	L 411	Infusion	L	1	0.01
Crassocephalum gracile (Hook.f.) Milne-Redh.	Unknown	Asteraceae	L 002	Maceration	L	1	0.01
Phyllanthus amarus Schumach	Unknown	Euphorbiaceae	L 005	Decoction	L	1	0.01
Caesalpinia decapetala (Roth) Alston	Unknown	Apiaceae	L 412	Infusion	L	1	0.01
Ekebergia capensis Sparrm.	Unknown	Meliaceae	L014	Infusion	L	1	0.01
Ricinodendron heudelotii (Baill) Heckel	Unknown	Euphorbiaceae	L016	Infusion	L	1	0.01
Senna alata (L.) Roxb.	Unknown	Caesalpinioideae	L 020	Maceration	L	1	0.01
Allamanda cathartica L.	Unknown	Aponynaceae	L019	Maceration	L	1	0.01
Lippia woodii Mold.	Unknown	Verbanaceae	L009	Decoction	L	1	0.01
Burnatia enneandra Micheli	Unknown	Alismataceae	L025	Decoction	L	1	0.01
Solanum macrocarpon L.	Olianziri	Solanaceae	L015	Infusion	L	1	0.01
Sclerocarya birrea (A.Rich.) Hochst. subsp. Birrea	Unknown	Anacardiaceae	L 032	Decoction	L	1	0.01
Chenopodium ambrosioides L.	Anjigun	Chenopodiaceae	L 030	Infusion	L	1	0.01
Gomphrena celosioides Mast.	Unknown	Amarantahceae	L 041	Decoction	L	1	0.01
Carissa spinarum L.	Acuga	Apocynaceae	L 036	Infusion	L	1	0.01
Senna obtusifolia L.	Unknown	Caesalpinioideae	L 026	Decoction	L	1	0.01

^{Key: L=Leaves, SB=stem bark, WS=whole stem, RB=rootbark, WP=whole plant, SD=seeds, FL=Flower, B=bulb}

Fig. 3.

Number of plant spp distributed among different families.

Medicinal plant preparation, packaging and administration in management of malaria

Leaves were most frequently used (69%) in herbal medicine preparations followed by root bark (20%) and stem bark (7%) (Fig. 4). Most medicines were prepared in combination using methods such as by decoctions (54%) followed by infusions (26%), maceration (12%), and powder (7%) (Fig. 5). Medicinal products were stored as powders if the place of collection was far from the TMP however, most medicines were prepared and used fresh as and when needed. The oral route was principally used for treatment administration. The dose recommendations varied widely amongst the different TMPs and ranged from ½ teaspoon (~ 5mls) 2 or 3 times daily to 1 cup (~ 500 ml) taken 2 or 3 times daily. Plastic bottles, polythene bags and papers were used as storage material. In Kabale district, most TMPs cultivated their own medicinal plants as compared to other districts where plants were picked from nearby gardens, forests, or hills where they are abundant.

Fig. 4.

Plant parts used by TMPs for preparation of antimalarial herbal medicine in different parts of Uganda

Fig. 5.

Preparation methods used by traditional medicinal practitioners as reported in different parts of Uganda

Discussion

Uganda ranks third among countries with the highest burden of Malaria in the world [2]. Malaria affects communities in rural settings in endemic areas with favorable climatic conditions for mosquito vector breeding [73]. Such conditions include ample rainfall (average 200 mm), optimal temperatures (26–47ºC), swamps, water bodies and forest cover. The high malaria transmission intensity in the three study districts of Apac, Arua and Tororo range from 390 to 1586 infective bites per person per year. Worse still, in such impoverished communities, the cost of antimalarial treatment coupled with long distances to health facilities fuels the use of alternative medicines such as medicinal plants for malaria treatment.

The results of this study show that communities in Arua, Apac, Tororo and Kabale districts use a diverse number of plant species for management of malaria. Plant species like Vernonia amygdalina Del, Aloe Vera (L.) Burm.f., Artemisia annua L., Vernonia grantii Oliv. and Justicia betonica L. were the most used across the four surveyed local communities and they contribute to the high informant consensus factor. The use of Vernonia amygdalina, Artemisinin annua, Aloe vera and Justicia betonica L. for treatment of malaria is well documented across Uganda in previous studies [66, 74, 75]. The wide use of the plant species by different communities across Uganda poses a challenge of sustainability and plant conservation strategies should be encouraged.

Artemisinin annua, from family Asteraceae has strong antimalarial activity and is the source of current antimalarial drugs including dihydroartemisinin, artemether and artesunate. However, recently, there is increasing artemisinin drug resistance reported especially in northern Uganda, calling for more efforts to search for novel compounds [76]. Vernonia amygdalina, a renowned antimalarial plant in communities, yielded two alkaloids namelyvernodalin and vernolide with median inhibitory concentrations of 0.52 µg/ml and 1.87 µg/ml against a chloroquine sensitive strain of P. falciparum (D10) [19] (Table 3). Similarly, fagamine a secondary carboxamide, isolated from Zanthoxyllum Chalybeum had an MIC value of 2.85 µg/ml [77]. The three phytochemicals can be used as leads for development of new antimalarial drugs.

Table 3.

Literature on antiplasmodial activity and isolated compounds from some of the mentioned plant species

No	Plant species	Plant part	Extract (IC50)	Invitro activity(µg/ml) / Plasmodium strain	Isolated compound (IC50 µg/ml)	Citation
1.	Vernonia amygdalina	Leaves	methanol/ ethyl acetate	2.7 mg/ml	Vernodalin (0.52) Vernolide (1.87)	[18, 19]
2.	Aloe Vera	Leaves			Aloin (67 µg/ml) Aloe-emodin (22 µg/ml)	[20]
3.	Artemisia annua L.	Leaves	Dichloromethane Methanol	3.79 3.00	Arteether (3.88nM) Artemether (3.71nM) Artelinate (3.46nM)	[21, 22]
4.	Justicia betonica L	Leaves	Methanol	13.36	Justiciosides A–D, Jusbetonin	[23–25]
5.	Psidium guajava	Leaves	Dichloromethane	3.3–4.6/ Dd2, D10	Ellagic acid Gallic acid Guavin B Gualjaverine Quacetrine	[26, 27]
6.	Tetradenia riparia	Root		13.2/NF54	Abietane and Royleanone	[28]
7.	Sarcocephalus latifolius	Leaves	Methanol	14.7/Field isolates	Quinovic acid Strictosamide	[29, 30]
8.	Annona senegalensis Pers.	Leaves	Ethanol	17–19/ 3D7 & Dd2		[31]
9.	Senna occidentalis (L.) Link	Roots	Methanol	1.7/3D7		[32]
10.	Warbugia ugandesis Sprague	Stem bark	Ethanol	15.6–8.92/ 3D7&Dd2	Polygodial 1a Warburganal 2a Muzigadial 2b	[33, 34]
11.	Senna didymobotrya Fresen.	Leaf	Dichloromethane	23–24/ D6& W2	Bianthraquinones	[35, 36]
12.	Maesa lanceolata Forssk	Twig, Leaf	Dichloromethane: Methanol	P. falciparum, D10		[37]
13.	Bidens pilosa L	Leaf	Water	5–11/D10		[38]
14.	Cissampelos mucronata A. Rich.	RB	Ethanol	8.0-9.2/ W2, D6	Stigmasterol Hentriacontane Simiarenol Nonacosene	[39, 40]
15.	Momordica foetida schumach	Leaves	Ethyl acetate	29.3/K1	Phenolic glycosides Sitosterylglucoside 5,25-stigmastadien-3β-ylglucoside	[41, 42]
16.	Tithonia diversifolia Gray	Leaves	Water	18–19/D7, W2	Sesquiterpene lactones Tephrostachin Quercetin	[35, 43]
17.	Harrisonia abyssinica Oliv.	Stem bark	Methanol	4.7–10/ Dd2, 3D7	2-hydroxymethylalloptaeroxylin.	[44]
18.	Moringa oleifera L	Leaves	Methanol, Hexane	3.3–3.4/ D7	Kaempferol Myricetin Quercetin Gallic acid Luteolin	[45, 46]
19.	Aristolochia elegans mast	Seeds	Methanol	> 50/ 3D7	β-caryophyllene	[47, 48]
20.	Hoslundia opposita (Vahl)	Leaf	Water	4–12/ P. falciparum	1,4- Citric acid Tetracontane-1,40-diol	[49, 50]
21.	Toddalia asiatica (L.) Lam.	Leaf	Methanol	6.8–13.9/ D6, W2	Toddanolic acid Toddalic acid	[51, 52]
22.	Azadirachta indica (A. Juss)	Leaf	Methanol	1.7–5.8/D7, DD5	Dodecanoic acid Oleic acid 13-octadecyl 15-tetracosanoic acid methyl ester	[44, 53]
23.	Ageratum conyzoides L.	Whole plant	Dichloromethane	2.15–3.44/ W2, D6	Precocene II β-caryophyllene Eugenol	[54, 55]
24.	Chenopodium opulifolium Schrad.	leaves	Dichloromethane	0.1/ 3D7	Allantoin Decan-2-one	[56]
25.	Spathodea campanulata Buch.	Fruit	Ethyl acetate	28.1/3D7	5,7-Dihydroxy-4-Metilcoumarin Quercetin Kaempferol	[57, 58]
26.	Sida rhombifolia L.	Whole plant	Ethyl acetate Fraction	3.56/ Dd2	Rhombifoliamide	[59]
27.	Physalis peruviana L. (KB)	Leaf	Dichloromethane	8-14.7/ D6, W2	Kaempferol Quercetin Luteolin Apigenin	[60, 61]
28.	Citrus lemon Burm. F	Leaf	10% Methanol: water	12/ P. falciparum	Hesperidin eriocitrin, diosmin Citric acid	[62, 63]
29.	Leonotis nepetifolia(L.) Ait. F.	Whole plant	Dichloromethane: Methanol	15/ d10	Cirsiliol Catechin P-coumaric acid Rosmarinic acid	[64, 65]
30.	Zanthoxylum chalybeum Engl. Var. Molle	Husk	Ethyl acetate	3.7–9.3/ INDO, 3D7	Fagaramide (2.85)	[66]
31.	Phyllanthus amarus Schumach	leaves	Water	23.1/ P. falciparum	Niranthin Phyllanthin Nirtetralin	[67, 68]
32.	Ekebergia capensis Sparrm.	Husks, Stem bark	Methanol	> 5/ K1		[69]
33.	Ricinodendron heudeloti (Baill) Heckel	Leaf	Methanol	28/D6		[70]
34.	Carissa spinarum L.	Husks, Root bark	Methanol	< 3-14.5/ 3D7, NIDO, D6	Scopoletin Evomonoside	[71, 72]

35% (34/96) of the plant species in this study have been evaluated for their in-vitro antiplasmodial activity (Table 3). This verifies and confirms their local use in the Ugandan communities for treatment of malaria. From previous studies, plant species such as; Psidium guajava, Senna occidentalis, Harrisonia abyssinica, Moringa oleifera, Hoslunda opposita, Azadiracha indica, Ageratum conyzoides, Chemopodium opulifolium, sida rhombifolia and Carissa spinarum were very active with minimum inhibitory concentrations < 5 µg/ml [26, 32, 44, 45, 49, 54, 56, 71]. With the high antiplasmodial activity, these plants can be potential sources for new antimalarial drugs. On the other hand, medicinal plants such as Vernonia granti Oliv. with a high use value is yet to be investigated for its anti-plasmodial activity.

Most of the active and mentioned plant species belong to family Asteraceae which is one of the largest families in the plant kingdom with over 2500 species distributed widely all over the world. The family is knowned for its diverse pharmacological activities owed to presence of numerous phytochemicals including phenolic compounds like quercetin (a) that has shown significant antimalarial activity invitro [78–80].

Most herbal medicines were prepared as decoctions or infusions. An infusion is prepared by soaking fresh plant parts for a short period of time with cold or boiling water while a decoction is prepared by boiling two or more plant spp at minimum heat for a given period of time [81]. Decoction is a common method of medicine preparation among local communities; for instance, one of the TMPs in this study mentioned that Zanthoxylum chalybeum and Sarcocephalus latifolius are dried, pounded and boiled together in water and then 150 ml are taken three times a day. Another TMP mentioned that Vernonia grantii, Crotalaria ochroleuca, aloe vera and Justicia betonica are boiled together and 200mls are taken once per day. The combination of different medicinal herbs ensures use of less plant materials thus potentially minimizing toxic effects while maximizing efficacy through additive or synergistic effects. Also, some plant species in the decoction play different roles for example, Azadirachta indica (A. Juss) in a preparation can act as an antipyretic to control high temperatures [82]. On the other hand, Euclea racemosa contains phytosterols that possess anti-inflammatory and anti-pain activity; it was noted that in this study, TMPs rub the plant powder on joints to control joint pain [83]. Eucalyptus is also added in herbal medicines as a preservative to prolong the shelf life of the herbal products [84].

This study showed that TMPs in the surveyed communities had knowledge about malaria disease and its mode of transmission. This was evident by the symptoms most frequently mentioned which were consistent with the well-known clinical symptoms of malaria. On the contrary, practitioners demonstrated limited knowledge about the malaria causative agent and lacked sufficient knowledge on conventional treatment of malaria. Furthermore, the variable nature of dosing among different practitioners, even within the same village was concerning as it shows a lack of dose standardization. Dose standardization presents a challenge that has long been experienced among TMPs mainly due to the numerous and diverse bioactive phytochemicals contained in plant based medicines, numerous range of indigenous healing practices, lack of training for the TMPs, lack of a basic knowledge of the possible side effects and efficacy of the plant remedies. Since TMPs play an important role in rural health care, this calls for training and education on such pertinent issues especially in poverty-stricken regions where the malaria transmission and disease burden remain high.

Conclusion

A diverse number of plant species, plant use and preparation methods are documented in this study as a way of preserving traditional knowledge in Uganda. Vernonia amygdalina Del., Aloe vera (L) Burm. f, Vernonia grantii Oliv. and Justicia betonica L. were identified as important plant species that can be further studied to validate their safety, antiplasmodial and active bioactive phytochemicals that can provide novel lead compounds for malaria treatment. These plant species can also be conserved through cultivation for sustainable use.

Author contributions

LB conceived the research idea, collected field data, analyzed and interpreted the data as well as prepared the first draft of the manuscript. MO, FWO, SN, COO, GO and AL conceived the research idea and collected field data. All authors revised and efficiently contributed to improvement of drafts and approved the final manuscript.

Funding

The research study was funded by the government of Uganda under the office of the president Science and Technology innovation (OP-STI) research grant. The funding agent was not involved in the study design and implementation.

Data availability

The study tools used in acquiring the data presented in this manuscript are available as raw data in questionnaire documents. This can be acquired from the corresponding author when needed.

Declarations

Ethics approval and consent to participate

The study protocol was reviewed and received ethics approval from Makerere University School of Biomedical Sciences’ Research and Ethics Committee (#SBS-2022-213). Clearance to conduct the study in Uganda was granted by the Uganda National Council of Science and Technology (#NS431ES). A written informed consent was obtained from each traditional medicine practitioner prior to the interview. The study adhered to ethical principles in the Declaration of Helsinki (2013).

Consent of publication

Not applicable.

Competing interests

The authors declare no competing interests.