Malaria is a life-threatening disease caused by plasmodium parasites that are transmitted to people through bites of the malaria vector-infected female mosquitoes. A vector is a living organism that transmits an infectious agent from an infected animal to a human or another animal. Vectors are usually arthropods such as mosquitoes, ticks, flies, fleas, and lice.
Malaria is the most lethal disease in Africa (CDC - Impact of Malaria 2015). In Benin and Zambia, up to 40 percent of all outpatient visits are due to malaria (Intensifying Fight Against Malaria, 2008). In 2015, the World Bank provided funding worth US$470 million to African countries to fight malaria. The World Health Organization (WHO) estimates that more than one million people in Africa die from malaria every year, including 3,000 children (Bank, 2002).
Most of the infected populations in endemic countries use antimalarial medicinal plants to treat malaria. However, very little scientific data exist to validate the antimalarial properties of most medicinal plants. Studies to establish the identity, purity, and quality of natural products include macroscopic and microscopic evaluations, physicochemical and chemical characteristics of crude plant extracts, and alkaloid contents (Vivekraj, 2015).
Alkaloids are a class of naturally occurring organic compounds that contain at least one nitrogen atom. This group also includes compounds with neutral or weakly acidic properties. Some synthetic compounds with similar structures can also be termed as alkaloids. Alkaloids in their pure form are usually colorless, odorless crystalline solids, but sometimes can be yellowish liquids. They often have bitter tastes. More than 3,000 alkaloids are known to be present in over 4,000 plants. They are all secondary compounds and are a collection of various elements and biomolecules derived from amino acids or transamination. There are three types of alkaloids: true alkaloids, protoalkaloids, and pseudoalkaloids. True alkaloids and protoalkaloids are produced from amino acids, whereas pseudoalkaloids are not derived from these compounds (Dey et al. 2020).
True Alkaloids
This alkaloid is obtained from amino acids and contains a nitrogen-containing heterocyclic ring. They are highly reactive and exhibit potent biological activity. They form water-soluble salts, many of which are crystalline. They then conjugate with acids to form salts. Almost all true alkaloids are bitter in taste and solid, except nicotine, which is a brown liquid (Aniszewski, 2007).
Their occurrence in plants occurs in three forms: (a) in the free state, (b) as N-oxides, or (c) as salts. Various amino acids, such as l-phenylalanine/l-tyrosine, l-ornithine, l-histidine, and l-lysine, are the main sources of alkaloids (Alamgir, 2017; Katavic & Peter, 2006). Cocaine, morphine, and quinine (Figs. 1, 2, and 3, respectively) are common alkaloids found in nature.
The Malaria Problem in Zambia
Zambia remains an endemic malaria country, with the entire population at risk of contracting malaria. The risk of contracting malaria is highest in the wetter, rural, and low-income provinces of Luapula, Northern, Muchinga, and North-Western, and lowest in Lusaka and Southern. The increase in malaria cases in Zambia has led to high demand for antimalarial drugs. In addition to the side effects, most modern medicines are too expensive for poor rural people. Some possible side effects of antimalarial drugs include dizziness, headache, sleep disturbances (insomnia and vivid dreams), and psychiatric reactions (anxiety, depression, panic attacks, and hallucinations). For many years, the local people have used herbs to treat malaria and other ailments. Despite recent efforts to study these herbal remedies, little is known about the medicinal contents of most herbs. Some studies have been conducted in Zambia on the treatment of malaria using herbal remedies, although there is very little available literature. This study is intended to add to the body of knowledge on a well-utilized antimalarial herbal remedy. This study aimed to determine the presence of alkaloids in selected plants from the Chikankata District, which are known to treat malaria and other malaria-related diseases in the local population for many generations.
The Malaria Disease
Malaria is a disease caused by Plasmodium parasites, which are transmitted to humans through the bites of infected female Anopheles mosquitoes (Hermans et al., 2004). In biology, a vector is a living organism that transmits an infectious agent from an infected animal to a human or another animal. Vectors are frequently arthropods such as mosquitoes, ticks, flies, fleas, and lice. The four parasitic species are known to cause malaria in humans. These are Plasmodium falciparum, plasmodium malariae, plasmodium ovale, and plasmodium vivax, but the two that present the great threat are the P. falciparum and P. vivax (Bruice, 2005).
Transmission of Malaria
Malaria is transmitted through the bites of female Anopheles mosquitoes (WHO 2020). There are more than 400 different species of Anopheles mosquitoes, of which only 30 are vectors of malaria of major importance. An important vector species bites between dusks and dawns (Ross 2001). The intensity of transmission depends on factors related to the parasite, namely the vector, human host, and environment (Kabula et al., 2012). Anopheles mosquitoes lay eggs in water, hatch into larvae, and eventually emerge as adult mosquitoes. Female mosquitoes seek blood to nurture eggs. During a blood meal, it sucks gametocytes, which develop into sporozoites in the female mosquitoes. The sporozoites were injected into another human at the next blood meal (US EPA, 2021).
Transmission is more intense in places where the mosquito lifespan is longer, as this increases the chance of the parasite fully developing inside the mosquito. These mosquitoes prefer to bite humans than other animals. Approximately 90% of African malaria cases occur because of their long lifespan and human preferences (Rasmussen et al., 2022). Transmission also depends on climatic conditions, such as rainfall patterns, temperature, and humidity, which may affect the number of mosquitoes and their survival. Seasonal transmission peaks occur during and after the rainy season because of the many mosquito breeding sites (Bilia, 2006). Immunity is another factor that increases malaria transmission, especially in adults. Those with partial immunity, which develops over the years of exposure to the disease, provide partial protection (WHO, 2020).
Incubation of the Parasite
P. falciparum repeatedly replicates within erythrocytes over the course of 48 h, resulting in exponential growth and rapid disease progression. Following an infective bite by an Anopheles mosquito, its parasites grow and multiply first in liver cells and then in red blood cells. A period called the “incubation period” goes by before the first symptoms appear. The incubation period In most cases varies from seven to 30 days ( Centers for Disease Control and Prevention, 2010)). Each parasite has its own incubation period, that is; for plasmodium falciparum is nine-14 days, 12–17 days for Plasmodium vivax, and plasmodium malariae it is–18–40 days (Pelczar et al., 1998). Shorter periods were observed most frequently for P. falciparum and longer periods for P. malariae.
The Symptoms
The symptoms of malaria can develop as quickly as seven days after being bitten by an infected mosquito. Typically, the time between infection and symptom onset is 7–18 days, depending on the specific parasite that is infected. However, in some cases, symptoms can take up to a year to develop depending on the victim’s immunity (Blenkinsopp et al., 2008).
The initial symptoms of malaria are flu-like. These include a high temperature of 38°C or above, feeling hot and shivering, headaches, vomiting, muscle pain, diarrhea, and generally feeling unwell, just to mention a few. These symptoms are often mild and can sometimes be difficult to associate with malaria infection. In some types of malaria, symptoms occur in 48-hour cycles. During these cycles, one feels cold at first, with shivering, and then develops a high temperature, accompanied by severe sweating and fatigue. These symptoms usually last between 6 and 12 h ( Centers for Disease Control and Prevention, 2010). Without prompt treatment, this type can lead to the rapid development of severe and life-threatening complications such as breathing problems and organ failure. As the symptoms are similar to those of flu, malaria infection can only be confirmed using a malaria test.
The Fatality Rate
Malaria is among the leading causes of mortality and morbidity in Zambia (Nawa et al. 2019). Efforts to control, prevent, and eliminate it have intensified over the past two decades. These efforts have contributed to a reduction in the prevalence of malaria and fewer than five deaths (WHO 2015). However, the prevalence of malaria has increased by 21% between 2010 and 2015. According to the World Malaria Report, there were an estimated 241 million malaria cases and 627 000-malaria deaths worldwide in 2020. This represents approximately 14 million more cases in 2020 than in 2019 and 69,000 more deaths. Approximately two-thirds of these additional deaths (47 000) were linked to disruptions in malaria prevention, diagnosis, and treatment during the pandemic (WHO, 2021).
Since 2015, 24 countries have registered an increase in malaria deaths, the baseline year for the WHO’s global malaria strategy. In the 11 countries that carry the highest burden of malaria worldwide, cases increased from 150 million in 2015 to 163 million in 2020, and malaria deaths increased from 390,000 to 444,600 over the same period.
Alkaloids
Classes of Alkaloids
Alkaloids can be classified according to their biological system. The principal classes of alkaloids are pyrrolidines, pyridines, tropanes, pyrrolizidines, isoquinolines, indoles, quinolines, terpenoids, and steroids. (Kurek, 2019). Alkaloids are natural plant compounds with basic characteristics that contain at least one nitrogen atom in a heterocyclic ring and exhibit biological activities (Aniszewski, 2007). These compounds are mostly toxic and have strong physiological actions (Aniszewski, 2007). The bioactive properties of the class of plant secondary metabolites include antimalarial, anticancer, anti-inflammatory, antimicrobial, and analgesic properties (Nchabeleng et al., 2017). Uzor provides a very good review of the various types of alkaloids (Uzor, 2020)
Other Compounds that Treat Malaria
Owing to the resistance of P. falciparum to alkaloid treatment, many compounds that treat malaria have been discovered. Some of these compounds are phenols, carboxylic acid esters, carboxylic acids, flavonoids, etc. Polyunsaturated fatty acids such as hexadecanoic acid, methyl ester, 9,12-octadecadienoic acid methyl ester (linoleic acid), 9,12,15-octadecatrienoic acid, methyl ester (linoleic acid), 9-octadecenoic acid (Z)-2-hydroxyethyl ester, eicosanoic acid, and 2-(acetyloxy)-1-[(acetyloxy)methyl]ethyl ester have been found in active anti-plasmodial fractions (Mustofa et al., 2007; Okokon, Augustine, et al., 2017). Butanedioic acid, mono[(3R,5aS,6R,8aS,9R,10S,12R,12aR)-decahydro-3,6,9-trimethyl-3,12-epoxy-12Hpyrano[4,3-j]-1,2-benzodioxepin-10-yl] ester, common name Artesunate, and Artemether, with the chemical formula C16H26O5, are also used to treat malaria.