African region has been ravaging with many deadly diseases of malaria is one among these diseases. Malaria is life-threatening disease caused by deadliest parasites capable of transmitting the disease to people through anopheles mosquitoes. The common human parasite among the sporozoa is Plasmodium, the etiological agent of malaria [1]. The four species of Plasmodium that are capable of causing malaria include: P. falciparum, P. malaria, P. vivax, and P. ovale [2].  Therefore, the disease occurs wherever the mosquito which is the carrier disease vector is found and there are human hosts for the protozoan parasite Plasmodium [3]. In the year 2017, approximately 219 million cases of malaria were prevalent worldwide, in comparison with 239 million and 217 million cases in the year 2010 and year 2016 respectively. Also, about 20 million lesser malaria cases in the year 2017 which was much more than that of 2010 as it was captured through the data for the period 2015–2017 that no significant progress in reducing global malaria cases made in the timeframe. After which, fifteen countries in sub-Saharan Africa and India conveyed almost 80% of the worldwide malaria burden. So, five countries represented almost 50% of all malaria cases globally: Nigeria (25%), Democratic Republic of the Congo (11%), Mozambique (5%), India (4%) and Uganda (4%) [4].

The mortality cases are much higher in the Sub-Saharan African region. Although, the WHO areas of South-East Asia, Eastern Mediterranean, Western Pacific, and the Americas had similar cases and probably are at high danger of contracting malaria, and then develop serious illness, than others [5,39].

Mode of Transmission and the Parasite Favorable Factors in Africa

The spreads of malaria is through the vector mosquitoes which often becomes the carrier disease vector after biting an infected individual, and then bites a non-infected individual. The malaria parasites find its way into the individual's circulatory system and then transported to the liver of the victim. The parasites become mature and then leave the liver in order to infect red blood cells. When there is a favorable climatic condition in the region such as western part of Africa like Nigeria; the degree of transmission is consistently on the increase [5]. Thus, there is new proof of an increase advanced difference in country variance in malaria endemic rate in which 85 percent had been reported in Nigerians, West Africa where many people living in the region are capable of mesoendemic transmission and just 15% live under states of hyperholoendemic transmission [6-8]. Seasonally, malaria transmissions transform from one season to the next as indicated by the distinctive ecological strata of African region [9].

Life cycle of malaria is in stages through the repeatedly biting of infection of humans and female Anopheles mosquitoes. In the body of human beings, the parasites develop and multiply first and foremost in the liver cells and then gain entrance into the red cells of the blood. In the blood, development of the parasites occur and then grow within the red cells and destroy them thereby releasing merozoites (daughter parasites) that proceeds with the cycle through intrusion of other red cells. More also, the blood stage parasites are those that are capable of causing the side effects of malaria. When gametocyte which is also a form of blood stage parasites occur in male and female forms are ingested during blood taking by Anopheles mosquito, they go through mating in the gut of the mosquito and start a cycle of growth and then multiply in the mosquito. After ten to eighteen days, a type of the parasite known as sporozoite gain access into the salivary organs of the mosquito. When the Anopheles mosquito bites another human being, anticoagulant spit is infused along with the sporozoites, which delivery to the liver, in this way beginning another cycle. Thus the infected mosquito spread the disease from one human to another, while infected humans transmit the parasite to the mosquito. Nonetheless, the mosquito vector does not experience the ill effects of the presence of the parasites not at all like the human host [10-13].

Figure 1: The malaria parasite life cycle involves two hosts [11].

Pathophysiology of malaria shows that no malaria is without the infection of the red blood cells by the asexual forms of the malaria parasite and so the red cells involvement makes malaria a possibly multisystem illness because every organ of the body makes use of the blood [12-14]. Some patients with malaria may go through developmental process into severe malaria despites all types malaria have similar symptoms like fever.

Figure 2: Induction of Fever by Malaria Parasites [15].

falciparum infection is the frequent causative agent of severe malaria which also does makes the disease complicated, although deaths have been reported due to non-falciparum malaria. The schizogony stage within the red cells was complete as each cycle lasted between 24-72 hours depending on the causative agent of the species. So, merozoites that are just newly developed gain freedom by the lysis of infected red blood cells (erythrocytes), and alongside them are both known and obscure waste substances like red cell membrane products; for example, hemozoincolour and other toxic factors like glycosylphosphatidylinositol (GPI) are likewise delivered into the blood as shown figure 2. They GPIspecifically initiate macrophages and endothelial cells to secrete cytokines and inflammatory mediators such as tumor necrosis factor, interferon-γ, interleukin-1, IL-6, IL-8, macrophage colony-stimulating factor, and lymph toxin, as well as superoxide and nitric oxide (NO). Many studies have implicated the GPI tail, common to several merozoite surface proteins such as MSP-1, MSP-2, and MSP-4, as a key parasite toxin [16-17]. Furthermore, fever, nausea and vomiting, looseness of the bowels (diarrhea), anorexia, sleepiness, throbbing joints and muscles and muscles, immunosuppression, thrombocytopenia, coagulopathy, and central nervous system manifestations have been largely attributed to the systemic manifestations of malaria in such that the various cytokines released to respond to the parasite and red cell membrane products [18]. Notwithstanding these factors, the plasmodia DNA is additionally exceptionally proinflammatory and can prompt cytokine mix and fever. The plasmodia DNA is introduced by hemozoin which is produced during the parasite developmental stage inside the red cell to have a connection through intracellular methods with the Toll-like receptor-9 and then lead to the free of proinflammatory cytokines that in later cause COX-2-upregulating prostaglandins thereby resulting into the induction of fever [15-19]. With respect to hemozoin, it has also been associated with the induction of apoptosis in developing elytroid cells' existence in the bone marrow leading to causes of anemia [20-21].

Pathogenesis of Severe Malaria

The impact of P. falciparum as the etiological agent of malaria which happened to be the deadliest parasite among other parasites in Africa cannot be overemphasized as the disease has a high prevalence in some parts of the region. This calls for a genuine prescription to decrease the rate of the disease in the region because drug resistance had been reported as a failure due to compromise in anti-malarial treatment [22]. In as much, the infection of the red cells by malaria parasites does bring progressive and structural, biochemical, and mechanical modifications to the red cells that can worsen the situation into a life-threatening illness. Although non-falciparum infections can likewise cause intricacy and even in the cases of severe illness can as well lead to deaths [23-30]. Therefore, the development of severe malaria fever is often the result of numerous pathophysiological factors such as the parasite biomass, malaria toxin(s), inflammatory response, cytoadherence, resetting and sequestration, altered deformability and fragility of parasitized erythrocytes endothelial enactment, dysfunction and injury and altered thrombocytosis [28-32].

Parasite Biomass

The parasite is such an interesting one, in the sense that P. falciparum is capable of invading red blood cells (RBCs) in every individual and then replicates its cycles inside the red cells; thereby leading to exponential growth in larger quantities as shown in figure 3 [33].

Figure 3: Schematic Representation of Pathogenesis of Severe Malaria [34].

Unlike P. falciparum, P. vivax has a preference for infection of only young RBCs and is consequently limited in reproductive capability and its resulting loads. But, the parasite load in P. falciparum infections can be very high, even exceeding 20 to 30 percent whereas in vivax malaria it rarely exceeds 2 percent, even in case of severe disease [28-31].

Quick diagnosis and treatment is the most effective and efficient measure to avoid a mild case of malaria from progressing into severe illness which could possibly be fatal. Malaria can be diagnosed by detection of P. falciparum through the use of Rapid Diagnostic Testing (RDT) and also by the used of microscope to diagnose the blood samples for malaria parasites; so thick and thin blood films are often prepared on a glass slide for parasite identification and speciation using Giemsa technique. The slides should be stained and viewed using 100× oil immersion objective lens of a compound microscope. At least 100 high power fields should examined before a thick smear which will shows either the result is positive or not. For positive slides, parasite species and stages will be assessed and parasite density (parasitaemia) should be determined by counting only the asexual stages against 300 white leucocytes (WBC) and then multiplying by 25, with the assumption that the mean total leucocytes count of individuals is 7500 cells/μL of blood35. So, slides should be blindly read by two independent level 1 microscopists. Positive/negative cases will be called only after confirmation by both microscopists. Microscopy-based estimates of parasite density will be calculated as the average of the values that will be within the margin of between-reader difference. Two readings will be considered discrepant if their difference is outside the 95% range of the limits of agreement of previous paired readings36.The level of parasitaemia that will be accounted for will be as low as (< 1000 parasites/μL of blood), moderate (1000–9999 parasites/μL of blood), and severe (≥ 10,000 parasites/μL of blood) [37-38].

The number of patients who are often sick of malaria that were seen in public health facilities and tested with either a RDT or microscopy increase from 36% in year, 2010 to 84% in year, 2018 and in which 71% of moderate to high transmission nations in sub-Saharan Africa which shows that malaria treatment need urgent attention in the region. In addition, the level of suspected cases tried with any parasitological test was more noteworthy than 80% in 2018 and out 61 studies directed in 29 sub-Saharan Africa, the rate of juvenile that were infected with fever that received a diagnostic test before antimalarial treatment in the public health sector increased39. Hence, malaria treatment and prevention interventions by the choice of medications depending on the degree of malaria transmission; for instance, in areas of low transmission level, irregular preventive therapy for pregnant women [IPTp] may possibly not necessary40. Nonetheless, to close the treatment gap especially among children, World Health Organization suggestion was on use of integrated community case management (iCCM). This support incorporated administration of basic dangerous conditions in children malaria, pneumonia and diarrhea at health center and even at the community levels. Also, the suggested medication for acute malaria responsible by sensitive strains of Plasmodium includes Chloroquine. Chloroquine is capable of inhibiting the merozoites and then reducing the parasitemia, yet lacks the ability to have an effect on the hypnozoites of P. vivax and P. ovale in the liver. These are killed by primaqune, which must be used to prevent relapses. P. vivax and P. ovale can relapse due to hypnozoites that remain dormant in the liver of infected person. To eradicate the hypnozoites, patients should be given treatment with a 14-day course of primaquine phosphate. Chloroquine or hydroxychloroquine is still an effective and efficient medication to combat all P. vivax and P. ovale infections with exception of P. vivax infections acquired in Papua New Guinea [39-41].

Prevention

The utilization of Prevention Insecticide-treated nets (ITNs), Intermittent Preventive Treatment of malaria in pregnant women (IPTp), Intermittent Preventive Treatment of malaria in Infancy (IPTi) and Indoor Residual Spraying (IRS) are recommended techniques which are being implemented to prevent malaria. Periodically, other strategies which are as well put in place include larval control and other vector control mediations, mass drug administration and mass fever treatment. ITNs, IPTp, and IRS make up the fundamental package of malaria interventions channel towards diminishing of the rate of malaria related cases and deaths. Malaria has the largest disease burden in Africa and has been extremely difficult to control because of the presence of a productive mosquitoes that are capable of transmitting the infection, favorable climate and weak infrastructure which should be addressed on the disease in the region40.Thus, two forms of vector control which are very effective and efficient in a wide range of settings include the use Insecticide-Treated Mosquito Nets (ITNs) and Indoor Residual Spraying of insecticides (IRS). The Insecticide-treated nets (ITNs) are the main stay of malaria prevention efforts in sub-Saharan Africa [39-40].

Figure 4: Indicators of population-level coverage of ITNs, sub-Saharan Africa, and 2000–2019 [42].

IRS of insecticides is another powerful way to rapidly adopt in dropping the degree of transmission of malaria. The global trend shows that the numbers of the population being protected by IRS drop from 5% in year 2010 to 2% in year 2019 (Figure 4). So, the utilization of preventive anti-malarial drugs, either alone in synergy with other drugs, is another suggestion procedure to pregnant women, infants and children under 5 years of age brackets among the most susceptible groups in sub-Saharan Africa. Further measures were taken for protection of women folks in regions of moderate and high malaria transmission in Africa. WHO suggests IPTp with the anti-malarial drug sulfadoxine-pyrimethamine (SP). Therefore, Intermittent Preventive Treatment in pregnancy (IPTp) is executed to prevent malaria among pregnant women living in areas of  moderate to high malaria transmission in Africa [39-42], WHO recommendation include utilization of 3 or more doses of IPTp with the quality-assured medicine sulfadoxine-pyrimethamine (SP). In year 2019, just over one thirty - three percent (34%) of pregnant women in 33 African countries got the suggested at least 3 dosages of IPTp-SP. This addresses a significant expansion in coverage since 2010 but only a modest increase since 2018 (Figure 4).

ANC: antenatal care; CDC: Centers for Disease Control and Prevention; IPTp: intermittent preventive treatment in pregnancy; IPTp1: ?rst dose of IPTp; IPTp2: second dose of IPTp; IPTp3: third dose of IPTp; NMP: national malaria programme; US: United States; WHO: World Health Organization.

Figure 5: Percentage of Pregnant Women Attending an Anti-Clinic (ANC) At Least Receiving Iptp, By Dose in Sub-Saharan Africa [42].

Moreover, seasonal malaria chemoprevention (SMC) is recommended for children younger than the age of 5 in high-burden regions with highly seasonal malaria transmission areas. In 2019, a sum of 21.5 million children in 13 countries in Africa got preventive malaria therapy during the high-transmission rainy season [22-42].

Vector Control

In the vector control of malaria, new kinds of insect poison treated nets, spatial mosquito repellants, vector traps among others have been designed to draw and to also kill Anopheles mosquitoes. So, if these tools is not effective in controlling malaria, it very sure that WHO will have to plan new strategies or make an improvement on the existing ones in order to support their deployment in malaria-affected countries [43,44]. Although in the recent years, there have also been significant advances in gene-drive approaches aimed at suppressing mosquito populations and reducing their susceptibility to infection, as well as their capability to transmit the disease vectors. These advancements have prompted a discussion on the advantages and risks of genetically modified mosquitoes (GMMs). In October 2020, WHO published a new position statement clarifying its position on the assessment and utilization of GMMs for the control of vector-borne disease [42].

RTS, S Malaria Vaccine

In 2019, Ghana, Kenya and Malawi among other countries presented the RTS, S malaria vaccine in selected regions through a WHO-facilitated pilot programme. The vaccine has been shown through rigorous clinical trials to reduce 4 in 10 malaria cases in young children. Proof and experience from the programme will inform future policy decisions on the vaccine’s potential wider deployment. As of November 2020, almost a large portion of 1,000,000 children had gotten their first portion of the vaccine across three African nations (Ghana, Kenya, and Malawi) [45]. Despite the challenges posed by the COVID-19 pandemic, these countries have achieved good uptake of the vaccine in areas where children are at high risk of illness and death from malaria. Vaccination is continuing in all participating countries without major disruptions. Therefore, the RTS, S vaccine programme has been carried out in conjunction with Ministries of Health of the three nations, PATH, and GSK, the vaccine manufacturer. The programme is funded through contributions from Gavi, the Vaccine Alliance, and the Global Fund and Unit aid [46].

Regional Trends in Burden of Malaria Cases and Deaths Malaria Cases

In the year 2018, approximately 228 million cases of malaria are being diagnose all over the world, in comparison with 251 million cases diagnosed year in 2010 and 231 million cases diagnosed in year 2017. Most malaria cases diagnosed in year 2018 were in the World Health Organization (WHO) African Region (213 million or 93%), trailed by the WHO South-East Asia Region with 3.4% of the cases and the WHO Eastern Mediterranean Region with 2.1%. Nineteen nations in sub-Saharan Africa and India conveyed practically 85% of the global burden. Six nations represented the greater part of all malaria cases worldwide: Nigeria (25%), the Democratic Republic of the Congo (12%), Uganda (5%), and Côte d’Ivoire, Mozambique and Niger (4% each). The incidence rate of malaria declined globally between year 2010 and year 2018, from 71 to 57 cases per 1000 population at risk39. Of specific concern was the report's finding that, among the 10 most noteworthy weight African nations, there were 3.5 million additional cases in 2017 over the earlier year. In this manner, malaria fever keeps on negatively affecting pregnant women and children, especially in African region. When malaria in pregnancy is left untreated, maternal death, anemia and low birth weight, a major cause of a significant reason for baby mortality are inevitable. In year 2019, an estimated11.6 million pregnant women who live in 33African countries with moderate – to –high transmission were infected with malaria (that is, 35% of all pregnancies). As a result, an about 822,000 children in these 33 countries were brought into the world with a low birth weight [42].

Maternal, Infant and Child Health Consequences of Malaria

In the year 2018, around 11 million pregnancies in moderate and high transmission sub-Saharan African nations would have been presented to malaria infection. In 2018, prevalence of exposure to malaria infection in pregnancy was highest in the West African sub-region and Central Africa (each with 35%), followed by East and Southern Africa (20%). About 39% of these were in the Democratic Republic of the Congo and Nigeria. The 11 million pregnant women exposed to malaria infections in 2019 delivered about 872 000 children with low birth weight (16% of all children with low birth weight in these countries), with West Africa having the highest prevalence of low birth weight children due to malaria in pregnancy. Between 2015 and 2018 in 21 moderate to high malaria burden countries in the WHO African Region, the prevalence of anaemia in children under 5 years with a positive rapid diagnostic test (RDT) was double that of children with a negative RDT47.In the children who were positive for malaria, 9% had severe anaemia and 54% had moderate anaemia; in contrast, in the children without malaria, only 1% had severe anaemia and 31% had moderate anaemia. The countries with the highest percentage of severe anaemia among children aged less than 5 years who were positive for malaria were Senegal (26%), Mali (16%), Guinea (14%) and Mozambique (12%). For most other countries, severe anaemia ranged from 5% to 10%. Overall, about 24 million children were estimated to be infected with P. falciparum in year 2018 in sub-Saharan Africa, and an estimated 1.8 million of them were likely to have severe anaemia [39].

High Burden to High Effect Approach

There were about 155 million malaria diagnosed cases in the 11 high burdens to high impact (HBHI) countries in year 2018, compared with 177 million in 2010. The Popularity based Republic of the Congo and Nigeria represented 84 million (54%) of complete diagnosed cases. Of the 10 highest burden countries in Africa, Ghana and Nigeria reported the highest absolute increases in cases of malaria in year 2018 in comparison with that of year 2017. The burden in 2018 was similar to that of 2017 in all other countries, apart from in Uganda and India, where the malaria cases prevalence drop from 1.5 and 2.6 million respectively, in 2018 compared with 201747. Malaria deaths decreased from about 400 000 in 2010 to about 260 000 in 2018, the largest reduction being in Nigeria, from almost 153 000 deaths in 2010 to about 95 000 deaths in 2018. By 2018, in all of the 11 HBHI countries, at least 40% of the populations at risk were sleeping under long-lasting insecticidal nets (LLINs), the highest percentage being in Uganda (80%) and the lowest in Nigeria (40%). Only Burkina Faso and the United Republic of Tanzania were estimated as having more than half of pregnant women who are receiving three doses of intermittent preventive treatment in pregnancy (IPTp3) in 2018. In Cameroon, Nigeria and Uganda, the assessed inclusion was about 30% or less. Six countries in Africa’s Sahel sub-region implemented seasonal malaria chemoprevention (SMC) in 2018; a mean total of 17 million children, out of the 26 million targeted, were treated per SMC cycle. The percentage of children aged less than 5 years with fever seeking treatment varied from 58% in Mali to 82% in Uganda. In the Democratic Republic of the Congo and Mali, more than 40% of children were not brought for care at all. Testing was likewise worryingly low in children who were brought for care, with 30% or less being tried in Cameroon, the Popularity based Republic of the Congo and Nigeria [39-47].

Recent Public Health Interventions on Plasmodium falciparum in Africa

In 2018, an expected US$ 2.7 billion was put resources into malaria control and elimination efforts globally by governments of malaria endemic countries and international partners making a reduction from the US$ 3.2 billion that was invested in 2017. The amount invested in year 2018 fell short of the US$ 5.0 billion estimated to be required globally to stay on track towards the GTS milestones. So, in year 2018, 47% of all out subsidizing for malaria was put resources into low-income countries, 43% in lower middle-income countries and 11% in upper-middle-income countries [39-40]. However, the global COVID-19 pandemic that emerged in December 2019 also had serious additional challenge to malaria challenge not only in African region but worldwide. Since the early days of the pandemic, WHO and partners have raised concerns that lockdowns and other COVID-19 restrictions could lead to major disruptions in essential services for the prevention, detection and treatment of malaria. After which there was heeding the call, many malaria-endemic countries mounted impressive responses to the pandemic, adapting the way they deliver malaria services to the COVID-19 restrictions imposed by governments. Thus, most malaria prevention campaigns moved forward in 2020 without significant postponements in Africa's Sahel sub-region, as most of the countries with planned SMC campaigns are on track to complete by the end of 2020. All 31 countries (25 in Africa) that had planned ITN campaigns in 2020 are aiming to complete them by the end of the year. As of 23 November 2020,105 million of the expected 222 million LLINs had been distributed [39-42, 47].

The malaria parasite leading other parasites as the deadliest parasites in the Africa is no longer new in the public health. It exhibits endemic effect in West Africa. The disease remains a major public health problem as it specifically affect young children less than 5 years and pregnant women are more affected in the population. Notwithstanding, malaria is preventable, treatable, and even curable; yet, Africa still bears a larger proportion of the global malaria burden. Plasmodium falciparum the culprit parasite which is the etiological agent of the disease causes the highest number of malaria-related death all over the world of which Africa is not excluded. Consequently, practically 50% of the world's populations are at risk of malaria in Africa. Apart from young children and pregnant women who are at higher risk of being infected with malaria, non-immune travelers who are from malaria-free region are another set of individuals that are susceptible to the disease when they become infected. Nonetheless, to complement the recent public health interventions on plasmodium falciparum in African region; advance measures on traditional way of controlling mosquitoes breeding and given treatment for plasmodium in the blood stream of carriers of the parasite is recommended to put an end to the situation whereby an individual carrier serves as a reservoir of infecting others in a particular environment or region. Hence, eliminating malaria in African region especially in those countries with a high disease burden is not an individual role but it should be a public concern. Although, likely require tools may not be available today; yet, there should be substantial progress against the threat pose by malaria which should further be put in place as seen over the decades. Thus, COVID-19 should not distract public health attentions. Hence, the whole world should not forget to also focus on research and development of new tools to curb the effect of malaria not only in African region but also in other part of the world where the of the disease ravage.

The authors gratefully acknowledge World Health Organization (WHO) and all the authors whose works were cited in this article.

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