In spite of the a
In spite of the tremendous decline of malaria burden over the past decade, the disease still remains a major public health concern globally with sub-Saharan Africa bearing the greatest burden [1]. In 2018, approximately 219 million malaria cases and 446,000 deaths were reported worldwide. Of this 92% of cases and 93% of deaths were from sub-Saharan Africa, with children under five years of age and expectant mothers being affected the most [1]. There are 5 species of malaria parasites that infect humans: Plasmodium .falciparum, P. ovale, P. malaria, P. vivax and P. knowlesi with P. falciparum being the most life-threatening, and responsible for the majority of morbidity and mortality [1].
World Health Organization Global Malaria Programme (WHO/GMP) recommends three primary malaria interventions comprising of; 1) Prompt diagnosis & treatment with effective medicines; 2) Insecticide-treated nets (ITNs) distribution to achieve full coverage of populations at risk of malaria; and 3) Indoor Residual Spraying (IRS) as a major means to reduce and eliminate malaria transmission [2, 3]. Since the initiation of the Roll Back Malaria (RBM) Project, over a decade ago there has been increased Long Lasting Insecticide Treated Nets (LLINs) coverage and intense case management in most countries where malaria is endemic and success has been reported due to the decline in Malaria transmission [4].
Despite the success of the current tools there is a need for more stringent measures of monitoring their efficiency and implementation of novel strategies. Regrettably, although the malaria vaccine known by its scientific name Mosquirix has offered modest protection against malaria in children in various countries such as Malawi, Ghana, and Kenya, the vaccine may not be available in the next few years and no other highly effective vaccine is on the horizon [5]. This is calls for the integration of preventive chemotherapy and case treatment into main stream malaria interventions [6]. Early case detection and prompt treatment is the mainstay to minimize malaria-related morbidity and mortality with appropriate use of antimalarial drugs remaining the cornerstone of malaria control [1]. However, it’s being threatened by the parasite resistance to anti-malarial drugs that have been reported in Southeast Asia with potential spread to Africa.
In the early 1940s, chloroquine (CQ) was the drug of choice for the treatment of malaria in many countries having been confirmed as an anti-malarial drug with a quick metabolism, good curative effect including affordable cost [7-10]. The first case of P falciparum resistance to CQ was noted in the Thai-Cambodia border in Southeast Asia in 1957 and in 1959, the resistance observed in the Venezuela-Cambodia border in Northern South America and finally span to other countries around the world [11-12]. In Africa, resistance to chloroquine (CQ) led to its withdrawal as an antimalarial drug and replaced with sulfadoxine-pyrimethamine (SP) in the early 1980s [13]. Malawi was the first country in the continent to cease the administration of CQ in malaria chemotherapy in the year 1993 [14]. In Tanzania, CQ was used as a first-line malaria treatment drug since the 1970s but due to high levels of resistance, it was replaced with SP in the year 2001. This was short-lived, as resistance emerged soon after, thus necessitating the adoption of AL in 2006 [14].
In Cambodia ACTs was introduced in the year 2000 inform of artesunate with mefloquine (AM) [15]. Artemisinin resistance which is the cornerstone of ACTs was reported in western Cambodia and subsequently spreading several neighboring countries in the Greater Mekong sub region of Southeast Asia in recent years [16-20]. The World Health Organization recommends that malaria-endemic countries should monitor the efficacy of nationally recommended ACT to guide national treatment guidelines [11]. The Artemisinin-based combination reduces both malaria-associated morbidity and mortality as well as the transmission of P. falciparum by acting on gametocytes, decreasing the likelihood of drug resistance development [11, 21]. To date, approximately 40 countries in Africa and six in South America are using AL as their first or second-line treatments [2, 22].
The following artemisinin-based combinations are recommended; artemether-lumefantrine (AL), artesunate-amodiaquine (AS+AQ), artesunate-mefloquine (AS+MQ), artesunate-sulfadoxine/pyrimethamine (AS+SP), and dihydroartemisinin-piperaquine (DP) with AL being the most widely used combination and is currently the first-line antimalarial drug in most malaria endemic countries in the WHO African region [2, 19, 22]. AL which is a co-formulation Artemether and lumefantrine which, is an aryl related alcohol linked to quinine, mefloquine and halofantrine that is commercially accessible in fixed-dose combination. In this combination, artemether, existence as a first acting drug, rapidly lower the parasite biomass and reinstate the clinical symptoms, while long-acting lumefantrine counteracts recrudescent. This dual effect eventually reduces the selective pressure on the parasite to develop resistance [23].
In Tanzania for example, AL was introduced as its first line for the treatment of uncomplicated malaria caused by P. falciparum in 2006 and it remained the drug of choice [24-25]. Several studies conducted in Uganda [26], Burundi [27], Rwanda [28] and other African countries have observed that AL including other artemisinin-based combinations, for example, ASAQ and DP which are first or second-line treatments in other African countries have extreme therapeutic efficacy [3]. However, among these studies, there are no reports of clinically significant artemisinin resistance in Africa, and the laboratory correlates of resistance in Southeast Asia including the delayed parasites clearance are rare in Africa [29-31].
In Kenya, CQ resistant P. falciparum was reported in 1977, whereby by 1998 resistant levels had reached 70% [7]. Like other sub-Saharan countries, Kenya replaced CQ with SP in 1999 as the official first-line in the treatment of uncomplicated malaria [14]. As a result of widespread increasing reports of SP efficacy being compromised in Kenya especially at the coast [32, 34], prompted another policy change in the treatment of malaria by introducing Coartem TM, an artemether-lumefantrine in government hospitals in the year 2006. A number of studies have observe that artemisinin-based combination therapy (ACT) is still efficacious for the treatment of uncomplicated falciparum malaria especially in Africa, and is the recommended antimalarial drug for the treatment of uncomplicated malaria caused by P. falciparum [10, 34-35]. However, as with other drugs, the curative effect of ACT has declined gradually along with its use within vivo P. falciparum susceptibility studies showing reduction over time [36]. Due to the threat of potential artemisinin drug resistance, the WHO recommends regular surveillance to monitor the performance of antimalarial drugs in malaria-endemic countries [2]. The study was carried out with the primary objective of assessing the clinical efficacy of AL with a six-dose regiment for the treatment of uncomplicated P. falciparum malaria using the WHO therapeutic efficacy protocols after its introduction in Kenya over a decade.
decline of malaria burden over the past decade, the disease still remains a major public health concern globally with sub-Saharan Africa bearing the greatest burden [
1]. In 2018, approximately 219 million malaria cases and 446,000 deaths were reported worldwide. Of this 92% of cases and 93% of deaths were from sub-Saharan Africa, with children under five years of age and expectant mothers being affected the most [
1]. There are 5 species of malaria parasites that infect humans:
Plasmodium .falciparum,
P. ovale, P. malaria, P. vivax and
P. knowlesi with
P. falciparum being the most life-threatening, and responsible for the majority of morbidity and mortality [
1].
World Health Organization Global Malaria Programme (WHO/GMP) recommends three primary malaria interventions comprising of; 1) Prompt diagnosis & treatment with effective medicines; 2) Insecticide-treated nets (ITNs) distribution to achieve full coverage of populations at risk of malaria; and 3) Indoor Residual Spraying (IRS) as a major means to reduce and eliminate malaria transmission [2, 3]. Since the initiation of the Roll Back Malaria (RBM) Project, over a decade ago there has been increased Long Lasting Insecticide Treated Nets (LLINs) coverage and intense case management in most countries where malaria is endemic and success has been reported due to the decline in Malaria transmission [4].
Despite the success of the current tools there is a need for more stringent measures of monitoring their efficiency and implementation of novel strategies. Regrettably, although the malaria vaccine known by its scientific name Mosquirix has offered modest protection against malaria in children in various countries such as Malawi, Ghana, and Kenya, the vaccine may not be available in the next few years and no other highly effective vaccine is on the horizon [5]. This is calls for the integration of preventive chemotherapy and case treatment into main stream malaria interventions [6]. Early case detection and prompt treatment is the mainstay to minimize malaria-related morbidity and mortality with appropriate use of antimalarial drugs remaining the cornerstone of malaria control [1]. However, it’s being threatened by the parasite resistance to anti-malarial drugs that have been reported in Southeast Asia with potential spread to Africa.
In the early 1940s, chloroquine (CQ) was the drug of choice for the treatment of malaria in many countries having been confirmed as an anti-malarial drug with a quick metabolism, good curative effect including affordable cost [7–10]. The first case of P falciparum resistance to CQ was noted in the Thai-Cambodia border in Southeast Asia in 1957 and in 1959, the resistance observed in the Venezuela-Cambodia border in Northern South America and finally span to other countries around the world [11–12]. In Africa, resistance to chloroquine (CQ) led to its withdrawal as an antimalarial drug and replaced with sulfadoxine-pyrimethamine (SP) in the early 1980s [13]. Malawi was the first country in the continent to cease the administration of CQ in malaria chemotherapy in the year 1993 [14]. In Tanzania, CQ was used as a first-line malaria treatment drug since the 1970s but due to high levels of resistance, it was replaced with SP in the year 2001. This was short-lived, as resistance emerged soon after, thus necessitating the adoption of AL in 2006 [14].
In Cambodia ACTs was introduced in the year 2000 inform of artesunate with mefloquine (AM) [15]. Artemisinin resistance which is the cornerstone of ACTs was reported in western Cambodia and subsequently spreading several neighboring countries in the Greater Mekong sub region of Southeast Asia in recent years [16–20]. The World Health Organization recommends that malaria-endemic countries should monitor the efficacy of nationally recommended ACT to guide national treatment guidelines [11]. The Artemisinin-based combination reduces both malaria-associated morbidity and mortality as well as the transmission of P. falciparum by acting on gametocytes, decreasing the likelihood of drug resistance development [11, 21]. To date, approximately 40 countries in Africa and six in South America are using AL as their first or second-line treatments [2, 22].
The following artemisinin-based combinations are recommended; artemether-lumefantrine (AL), artesunate-amodiaquine (AS + AQ), artesunate-mefloquine (AS + MQ), artesunate-sulfadoxine/pyrimethamine (AS + SP), and dihydroartemisinin-piperaquine (DP) with AL being the most widely used combination and is currently the first-line antimalarial drug in most malaria endemic countries in the WHO African region [2, 19, 22]. AL which is a co-formulation Artemether and lumefantrine which, is an aryl related alcohol linked to quinine, mefloquine and halofantrine that is commercially accessible in fixed-dose combination. In this combination, artemether, existence as a first acting drug, rapidly lower the parasite biomass and reinstate the clinical symptoms, while long-acting lumefantrine counteracts recrudescent. This dual effect eventually reduces the selective pressure on the parasite to develop resistance [23].
In Tanzania for example, AL was introduced as its first line for the treatment of uncomplicated malaria caused by P. falciparum in 2006 and it remained the drug of choice [24–25]. Several studies conducted in Uganda [26], Burundi [27], Rwanda [28] and other African countries have observed that AL including other artemisinin-based combinations, for example, ASAQ and DP which are first or second-line treatments in other African countries have extreme therapeutic efficacy [3]. However, among these studies, there are no reports of clinically significant artemisinin resistance in Africa, and the laboratory correlates of resistance in Southeast Asia including the delayed parasites clearance are rare in Africa [29–31].
In Kenya, CQ resistant P. falciparum was reported in 1977, whereby by 1998 resistant levels had reached 70% [7]. Like other sub-Saharan countries, Kenya replaced CQ with SP in 1999 as the official first-line in the treatment of uncomplicated malaria [14]. As a result of widespread increasing reports of SP efficacy being compromised in Kenya especially at the coast [32, 34], prompted another policy change in the treatment of malaria by introducing Coartem TM, an artemether-lumefantrine in government hospitals in the year 2006. A number of studies have observe that artemisinin-based combination therapy (ACT) is still efficacious for the treatment of uncomplicated falciparum malaria especially in Africa, and is the recommended antimalarial drug for the treatment of uncomplicated malaria caused by P. falciparum [10, 34–35]. However, as with other drugs, the curative effect of ACT has declined gradually along with its use within vivo P. falciparum susceptibility studies showing reduction over time [36]. Due to the threat of potential artemisinin drug resistance, the WHO recommends regular surveillance to monitor the performance of antimalarial drugs in malaria-endemic countries [2]. The study was carried out with the primary objective of assessing the clinical efficacy of AL with a six-dose regiment for the treatment of uncomplicated P. falciparum malaria using the WHO therapeutic efficacy protocols after its introduction in Kenya over a decade.