Impact of Malaria on Chronic Diseases

Dabuo B, Akantibila M, Oladipo OS, Osei EA, Odoi RNY and Abubakari A

Published on: 2023-12-28


Malaria, an infection caused by various Plasmodium strains, has implications for various health conditions, including chronic diseases. This review explores the impact of malaria on some selected chronic diseases. Malaria and kidney diseases often intersect, as research suggests a link between infection and the development of kidney complications. Additionally, in regions where both malaria and diabetes are prevalent, the coexistence of these conditions leads to higher rates of illness and death. The relationship between malaria and cancer is complex; while some studies suggest that certain immune responses triggered by malaria might offer protection against cancer, others indicate an increased risk of cancer development in areas with high transmission rates. Sickle cell disease is prevalent in regions affected by malaria; individuals with the sickle cell carrier have some protection against malaria and face increased vulnerability if they are homozygous for this trait. Evidence from studies also shows the relationship between cardiovascular diseases and malaria. Lastly, HIV and malaria commonly occur together in overlapping areas, which presents challenges for managing both diseases. Malaria can worsen the immunosuppression associated with HIV, leading to higher rates of illness and mortality. Hence, it is vital to grasp the interplay between malaria and these health conditions to develop healthcare strategies. The fact that malaria coexists with diseases such as diabetes, cancer, sickle cell disease, cardiovascular disease, and HIV emphasizes the importance of integrated approaches to healthcare. This involves combining malaria control measures with management and prevention strategies for these conditions.


Cancer; Plasmodium; Protozoan; Malaria; Public health


Malaria is a parasitic infection caused by the protozoan Plasmodium, which infects human erythrocytes. Malaria can be caused by five different species of Plasmodium: Plasmodium vivax, Plasmodium falciparum, Plasmodium ovale, Plasmodium malariae, and, less commonly, Plasmodium knowlesii [1]. The regions with the highest rates of malaria transmission are Oceania and Sub-Saharan Africa. In 2018, [2] approximately 50% of cases of malaria in endemic regions are asymptomatic [3]. In these regions, transmission is robust and consistent over time. Most adults living in these endemic areas have partial immunity to malaria as a result of these recurrent infections [4]. These kinds of asymptomatic malaria infections are a major barrier to the control of malaria because asymptomatic patients are unlikely to seek treatment. Instead, these individuals continue to infect others with the disease and act as a sustained reservoir for the malaria vector [5]. The risk of malaria is increased by the high prevalence of asymptomatic infection and increased human population movement, particularly in malaria-free zones [6]. Malaria is estimated to be endemic in 85 nations and territories. Malaria elimination programs have encountered numerous challenges, including the presence of asymptomatic carriers in endemic areas. These factors should be considered in malaria-control initiatives in endemic areas to effectively halt the disease's transmission [7]. There is a striking correlation between malaria, poverty, and slower rates of economic growth across the globe. Malaria impedes development in multiple ways, including effects on fertility, population growth, absenteeism, worker productivity, saving and investment, and medical costs [8]. Malaria organisms can affect several organ systems in the human body. According to [9], P. malaria and P. vivax exhibit the widest worldwide distribution. Coinfections are increasingly recognized as common risk factors that may contribute to the rise in morbidity observed worldwide. In endemic settings, P. falciparum infections often coexist with chronic illnesses; reports of this co-infection among the vulnerable, such as children and pregnant women, have increased from 0.7% to 1.7% in Ghana [10]. discussed the epidemiological ramifications of malaria-related chronic illness impairment in this review. This review acknowledges a substantial knowledge and research gap as the world struggles to address these important, co-infected global health priorities.

Sickle Cell Disease and Malaria

According to [11], both sickle cell disease and malaria are different hematological disorders. While malaria is caused by the parasitic organism Plasmodium, which gets its nourishment from blood cells, especially red blood cells, sickle cell disease is caused by a genetic abnormality affecting the hemoglobin gene [12]. A point mutation in the beta (β) globin, which is a component of adult normal hemoglobin A, causes sickle hemoglobin, an abnormal hemoglobin that is susceptible to hemolysis and sequestration, resulting in anemia and other crises. This genetic disorder is known as sickle cell disease (SCD) [13]. Each subunit of normal hemoglobin (Hb) is linked to a hemoglobin component that is capable of carrying oxygen [14]. Hb is composed of various units and subunits. One sickle hemoglobin (HbS) gene can be inherited in a healthy carrier state for sickle cell anemia, but two parents' HbS genes must be inherited for sickle cell anemia to manifest symptoms [15]. Owing to genetic modifications in sickle hemoglobin, deoxygenated sickle hemoglobin (deoxyHbS) is produced. This hydrophobic motif causes the β1 and β2 chains of the hemoglobin molecules in red blood cells to bind together, creating crystallization. The nucleus expands and takes up more space in the erythrocyte as a result of the polymerization that follows crystallization, changing the structure and pliability of red blood cells. The nucleus expands and takes up more space in the erythrocyte as a result of the polymerization that follows crystallization, changing the structure and pliability of red blood cells [16-18]. Clinical features of sickle cell anemia include hemolytic anemia, recurrent vascular occlusions, a systemic inflammatory state, severe multiorgan disease, decreased RBC lifespan, and significant pain [19]. However, the primary causes of morbidity and death in sickle cell disease—which account for 32–70% of deaths—are cardiopulmonary complications [20]. The life expectancies of males and females, respectively, around the world are 42 and 48 years old, due to the sickling of red blood cells (RBC) in SCA, which decreases cell flexibility and causes various complications like anemia, recurrent infections, and vaso-occlusive crisis (VOC) [21]. This area has one of the highest rates of sickle cell anemia prevalence in the region—up to 2% in some areas—making it one of the main genetic health issues in the area [21,22]. Thus, it is believed that India, the Middle East, the Mediterranean region, and sub-Saharan Africa are the origins of the HbS allele [23]. Even though these conditions don't seem to be the same, research has revealed a significant relationship between them (Locklear et al., 2022). The distribution of Plasmodium falciparum malaria in the past and present is strikingly consistent with epidemiology. It is now well established through multiple clinical field studies from various parts of Africa that heterozygotes for the sickle gene (AS) confer protection against the risk of dying from malaria at the malaria hotspot zones, an attribute that evolution once attributed to them. J. B. S. Haldane first hypothesized that, following Darwinian selection, individuals with hemoglobinopathies would be at a distinct risk of passing away when exposed to hemoparasites, even though the gene protection from the parasites would be detrimental. Scientists started undertaking ground-breaking research after a malaria outbreak at Laquintinie Hospital revealed that patients with sickle cell disease had a significantly lower death rate than those without the illness [24]. Furthermore, a thorough statistical analysis and numerous large sample population studies verified that AS red cells with parasites sickled more readily than AS red cells without parasites. After the parasite caused sickling, it would seem reasonable to assume—and it was later shown—that macrophages would destroy the sickled cells (Figure 1). The individuals' HbAS loss may be compensated for by the proliferation of normal functioning erythroid progenitor cells. In vitro studies of P. falciparum that demonstrate normal growth of P. falciparum in HbAS-red cells and HbAA-red cells have called into question the knowledge that HbAS inhibits P. falciparum growth and development.

Figure 1: Adopted from Haematology and Infectious Disease.

Based on empirical data, sickle cells are known to generate high concentrations of carbon dioxide (CO?). The malaria parasites are killed off by the increased levels of CO? in the blood, which hinders their ability to reproduce (Preprints & 2023). As a result, patients with sickle cell disease may exhibit milder malaria symptoms because the parasites cannot survive in their blood environment [24,25]. Remarkably, those who are heterozygous for sickle cell disease have a biological advantage over those who are not [26] against either sickle cell anemia or malaria. This is because only 50% of their cells show the typical sickling, meaning that 50% of the cells are normal and do not produce sickle cell anemia symptoms [26]. Concurrently, enough CO2 is produced by the other half of the cells, making the environment unfriendly for malaria parasites and providing protection from malaria.

Diabetes And Malaria

In Africa, hypoglycemia is a prevalent issue in pediatric emergency room admissions and is linked to numerous illnesses and conditions. According to [27], the percentage of pediatric patients with hypoglycemia at the time of admission varied from 3.2% to 7.3% in descriptive studies carried out in various African nations. The World Organization (WHO) has established the plasmatic glycemia threshold, defining hypoglycemia as <2.5 mmol/L (45 mg/dL) in a child who is adequately fed and <3 mmol/L (54 mg/dL) in a child who is severely malnourished [28]. However, intermediate levels of low glycemia have been linked to an increased risk of death [29], and the WHO advises correction when blood glucose levels are detected below 3.0 mmol/L. The majority of research on hypoglycemia in children identifies certain illnesses like malaria, diarrhea, or malnourishment, as well as other potentially fatal illnesses like meningitis and sepsis, as contributing factors to the occurrence and consequences of hypoglycemia. Malarial parasites are dependent on an external source of glucose because they are unable to store energy in the form of glycogen. The permeability of the infected erythrocyte to low-molecular-weight sugar is noticeably increased. According to an in vitro study, this parasite's ability to grow and proliferate is compromised at glucose concentrations below 5.5 mM [30]. Adults typically have blood glucose levels between 3.6 and 5.8 mM. The average blood glucose level in children under the age of six is 8.3 mM. It is also common for pregnant women to have elevated blood sugar. Malaria is more common in children and expectant mothers, and it has a strong correlation with blood glucose levels. Patients with type 2 diabetes had a 46% higher risk of contracting Plasmodium falciparum infection, according to a Ghanaian case-control study [31]. Due to both the underlying cancer and the ongoing immunosuppressive chemotherapy, people diagnosed with carcinoma have suppressed immune systems. The literature contains very little information about malaria infection in cancer patients [32].

HIV, AIDS, and Malaria

The two biggest health issues that kill over 4 million people each year in developing nations are HIV and malaria. Living in areas where both HIV and malaria are endemic increases the risk of co-infection [33-35]. Anemia is one of the main effects of malaria infection in terms of morbidity. HIV co-infection may make anemia worse by interfering with immune function or nutrition [36]. Determining whether a malaria infection has a direct or indirect effect on HIV can be difficult due to the complexity of both diseases [35]. Large populations of people in Africa coexist with HIV infections, so even a slight interaction between the two infections could have a significant impact on public health. Despite extensive research conducted in a range of contexts, no clear correlation has been found between HIV infection and malaria. Early research in Zaire and Uganda on the relationship between P. falciparum malaria infection and HIV infection in infants and early children revealed no higher rates of malaria infection in HIV-positive children when compared to HIV-negative control subjects [37]. However, effective reverse transcription and HIV genome incorporation into host DNA require immune cell activation [38]. According to in vivo research, patients with malaria initially have higher HIV-1 viral loads, which significantly decrease four weeks after anti-malaria medication is started. Additionally, there are numerous ways in which malaria increases the blood viral burden [33,34]. HIV infection was not linked to cerebral malaria in studies conducted in Burundi and Zambia [39]. HIV infection has been linked to more severe malaria disease in both adults and children during an epidemic of the disease in South Africa, where immunity to and transmission of the disease are low [40]. Due to its unique biology, P. vivax is difficult to eradicate. Different factors can lead to a P. vivax malaria episode, such as mosquito-borne infection, relapse from liver-stage hypnozoites, or recrudescence from blood-stage treatment failure. Clinical manifestations of P. vivax infection range from low parasitemia in asymptomatic individuals to severe illness and death 21. Malaria spreads more quickly when there is an increased risk of HIV infection, which also increases the severity of the infection. Malaria infection is also associated with strong CD4+ cell activation and an increase in proinflammatory cytokines. According to [33,34], these elements provide the ideal conditions for the virus to proliferate among CD4+ cells and for HIV-1 replication to happen quickly. According to [35], the concentrations of HIV-1 blood in individuals suffering from acute uncomplicated malaria in Malawi were seven times higher than those in HIV-1 blood donors who did not have malaria. Similar to other acute infections, the growing viral burden in malaria was eliminated by effective therapy. These findings are in line with an in vitro study in which malaria antigen-exposed peripheral blood mononuclear cells multiplied HIV-1 replication by ten to one hundred times. Tumor necrosis factor alpha (TNF-α) cytokine expression was upregulated, which facilitated this increase [41]. Additionally, studies have shown a correlation between acute malaria and an increase in the viral load and a decrease in the CD4+ cell count; nevertheless, after several weeks of successful malaria treatment, these parameters typically return to their pre-infection levels [33,34]. Though a prospective demonstration of this has not been established, it could potentially lead to increased HIV transmission or accelerated disease progression. According to a Cameroonian study, pregnant women with malaria may have an increased risk of HIV transmission to their foetuses [42]. An in vitro analysis of a potential mechanism for this found that binding of recombinant P. falciparum adhesin to chondroitin sulfate A, possibly through TNF-α stimulations, increased HIV-1 replication in human placental cells [33,34]. There aren't many reports of HIV-P. vivax co-infection in the literature, and even fewer that describe the clinical results. In a study conducted in the Brazilian Amazon, out of 21 patients hospitalized in a referral hospital with co-infection between HIV and P. vivax, 5 (23.8%) were diagnosed with severe malaria, and 1 patient (4.8%) passed away [43]. HIV-positive pregnant women have been shown to have increased malaria-related morbidity in several African locations [44], and they also have a higher incidence of placental malaria [45]. HIV-1-mediated immune deficiency is associated with higher parasite densities and a higher prevalence of clinical malaria, as evidenced by numerous epidemiologic populations of interest [44]. Higher viral loads in co-infected individuals compared to non-co-infected ones indicate that fewer studies have shown how co-infection with malaria can aid in the spread of HIV-1 [43].

Immunological mechanism of how malaria affects HIV transmission and progression

Falciparum infection may aid in the activation of viral transcription by macrophages and CD4+ cells. Elevated parasite density leads to a strong immune response, which boosts HIV-1 RNA turnover [33,34]. Additionally, fever is indicative of a cytokine response that could raise HIV-1 RNA concentrations [33,34]. According to several studies, people with higher blood levels of HIV-1 RNA are more likely to successfully transmit the virus during sexual encounters and develop clinical illness earlier [46]. An ideal environment for HIV replication is predicted to be created by the massive release of pro-inflammatory cytokines, such as TNF-α, in response to acute malaria infection, along with the activation of CD4+ cells [47]. This is due to TNF-α's ability to directly impact the HIV long-terminal repeat, which increases the rate of viral replication.

Renal Disease And Malaria

Multiple organ systems within the human body can be impacted by malaria organisms. Just two of the four malaria parasites—P. malaria and P. falciparum—are primarily linked to infections that cause clinically significant renal dysfunction, despite P. vivax and P. malaria having the greatest worldwide distribution. In tropical regions, malaria is the first parasitic infection that has been directly linked to nephrotic syndrome [48,49]. Although P. vivax infection has been linked to a small number of cases with aberrant renal function, P. malaria and P. falciparum are frequently linked to glomerular disease [50,51]. The two main renal disorders associated with malaria are thought to be MARF associated with falciparum malaria and chronic and progressive glomerulopathy in P. malaria (quartan malaria) [52]. Acute kidney injury (AKI) is a notable consequence of a severe P. falciparum infection in humans, distinguished by a sudden and rapid decline in renal function. Patient mortality rates have been continuously associated with this condition. Research has shown that acute kidney injury (AKI) is present in 40–60% of cases of severe malaria (SM) [53,54]. Patients who have malaria-associated acute kidney injury (MAKI) are more likely to experience unfavorable outcomes, such as increased mortality, renal failure progression, the development of chronic kidney disease, and other health complications [55]. It was previously thought that children were underrepresented in cases of malaria-associated acute kidney injury (MAKI), which primarily affected adult patients with severe malaria (SM). However, recent research shows that MAKI does occur in pediatric cases of SM and is a significant predictor of death, highlighting the significance of MAKI in pediatric malaria cases [56]. Acute kidney injury (AKI) is currently classified by KDIGO (Kidney Disease: Improving Global Outcomes) as follows: 1) a minimum 0.3 mg/dL increase in serum creatinine over 48 hours; 2) a minimum 1.5-fold increase in serum creatinine for the previous 7 days; or 3) a continuous 6-hour period of less than 0.5 mL/kg/h in urine output. This categorization offers a thorough framework for evaluating AKI according to particular standards [57].

Sequestration and rosetting processes, pro- and anti-inflammatory cytokines, damaged components of erythrocyte membranes, the metabolic byproducts of malaria parasites after hemoglobin digestion, and the cytoadhesion of malaria parasites to the vascular endothelium are all part of the pathophysiology of severe malaria infection. This complex cascade illustrates the multifaceted dynamics of severe malaria infection. Although there aren't many thorough studies looking into the causes of acute kidney injury (AKI) linked to severe malaria in various settings, it's generally accepted that prerenal AKI predominates in pediatric cases of severe malaria in 2018 [58].

Extensive Intravascular Hemolysis and Heme-Mediated Toxicity

One of the unique characteristics of malaria infection is intravascular hemolysis, which primarily targets red blood cells (pRBCs) harboring Plasmodium infection. Cell-free heme and molecules from the parasite and host are released as a consequence of this process. These constituents potently trigger inflammatory reactions [59]. There are significant risks associated with both the presence of cell-free hemoglobin and the release of cell-free heme as a consequence of intravascular hemolysis, which are mainly related to oxidative stress. They also serve as Damage-Associated Molecular Patterns (DAMPs), which activate the immune system and cause inflammation to become more active [60]. Even though the body has natural scavenging mechanisms to get rid of cell-free heme and hemoglobin, these systems can be overpowered by severe hemolysis, as seen in severe malaria (SM) [61]. Significantly, when scavenging systems reach saturation levels, the kidneys—which are the main pathway for the clearance of these molecules—are especially vulnerable to the deleterious effects of cell-free heme and hemoglobin [61]. Acute kidney Injury (AKI) has been associated with both infectious and non-infectious factors that cause significant intravascular hemolysis. In patients with severe malaria (SM), increased levels of plasma and urine hemoglobin have concurrently shown a strong correlation with AKI [61].

Hypovolemia and Obstruction of Kidney Blood Flow

Acute Kidney Injury (AKI) is often caused by blood flow obstruction to the kidneys, which are extremely susceptible to ischemic events and hemodynamic fluctuations [62]. Significant hypovolemia brought on by severe malaria (SM) results in renal hypoperfusion, decreased GFR, the release of vasoactive mediators, and the start of inflammatory processes, all of which are factors in kidney damage [63]. Recent findings from a study using the P. Berghei ANKA malaria mouse model highlighted the role of inflammation related to hypovolemia in kidney damage associated with SM. In many AKI models, activation of the Angiotensin II (Ang II)/AT1 receptor pathway increased inflammatory reactions and immune cell infiltration into tissues. In the mouse model, blocking this pathway markedly reduced inflammation and lessened kidney damage [63].

In addition to hypovolemia, blood flow obstruction within the kidneys can also cause SM-induced kidney hypoperfusion. During SM, rosettes—clusters of red blood cells that are both infected and uninfected—accumulate in small blood vessels, obstructing blood flow, resulting in microvascular dysfunction, and causing tissue hypoxia. According to [64], this process leads to increased sequestration of parasites in tissues, which is correlated with worse outcomes for SM patients. The kidneys' extensive sequestration of parasites may cause a strong local inflammatory response, worsening the extent of kidney damage.

Immunological and Inflammatory Reactions in Malaria

The pathophysiology of severe malaria (SM) is largely dependent on the host immune response, which is typified by an inflated proinflammatory response directed against the parasite [59].

Pathogen-associated molecular patterns (PAMPs) and damage-associated molecular patterns (DAMPs) are released during intravascular hemolysis of both parasitized red blood cells (pRBCs) and non-infected RBCs [65].

These compounds engage in interactions with pattern recognition receptors (PRRs), such as NOD-like receptors (NLRs) and toll-like receptors (TLRs), which trigger transcriptional programs associated with the inflammatory and immune responses downstream. Proinflammatory cytokines, such as tumor necrosis factor (TNF) and cell adhesion molecules, are produced in response to PAMPs derived from parasitas, such as glycosylphosphatidylinositol (GPI) anchors and hemozoin. Cell-free hemoglobin and heme are two examples of host-derived DAMPs that are linked to this hyperinflammation. Elevated levels of proinflammatory cytokines, such as TNF, IL-1β, and IL-6, highlight the inflammatory upregulation in SM patients, which is a contributing factor to both malaria-associated acute kidney injury (AKI) and SM pathogenesis [63].

Kidney tissue involvement is indicated by macrophage infiltrates and elevated cytokine expression. TNF and IL-6 can activate endothelium, which can change endothelium permeability, encourage the expression of cell adhesion molecules, sequester proliferating blood cells, and infiltrate leukocytes, all of which can lead to AKI associated with malaria in 2021 [66].

Moreover, intravascular hemolysis is made worse by complement system activation, especially via the alternative pathway (16). The alternative complement pathway forms a feedback loop with neutrophil proinflammatory responses, which in turn contributes to tubular injury and the decline of kidney function [67].

This complex interplay demonstrates how complement activation, cytokines, and immune responses play a part in the complex pathophysiology of kidney damage caused by malaria.

Impact Of Malaria On The Heart

Tropical diseases like malaria are common in developing countries. Severe cases of malaria are caused by infection with the Plasmodium falciparum parasite, which can have potentially fatal consequences [68].

Due to underreporting or underdiagnosis, cardiac implications have not been well documented in the past. Heart failure, ischemia conditions, myocarditis, pericarditis, pericardial effusion, and electrocardiogram abnormalities are noteworthy cardiovascular complications in 2021, [6,69-71].

Although the malaria parasite can affect multiple body organs, its role in cardiovascular (CV) symptoms is generally considered an uncommon consequence. Despite the paucity of research on the cardiovascular consequences of this illness, it is crucial to remember that elevated rates of morbidity and death may be associated with cardiovascular involvement [72]. Due to a lack of comprehensive published research and restricted data availability in areas severely affected by the disease, the cardiovascular effects of malaria are still not fully understood [73].

Preliminary research indicates that P. falciparum is primarily responsible for a 14%–26% incidence rate for clinical cardiovascular problems, such as circulatory failure, heart failure, or pulmonary edema, in hospitalized cases of severe malaria. On the other hand, myocardial damage was infrequently (0.6%) seen in mild P. falciparum malaria cases without obvious cardiovascular symptoms in a retrospective study that included patients from both endemic and nonendemic malaria prevalence regions [6,69-71]. Many theories have been put forth to explain how malaria could affect the heart's ability to function. According to studies on malaria, cytoadhesion can cause infected red blood cells to stick to the walls of the heart's small blood vessels, potentially obstructing blood flow in these myocardial vessels mechanically in 2023 [74].

The cytoadhesive characteristics that cause this effect are attributed to the P. falciparum erythrocyte membrane protein (PfEMP-1) and are traits of adhesion to cells. These characteristics of P. vivax are linked to genes known as "variant genes," or Vir-genes [75]. An overly strong inflammatory response brought on by malaria infection is another mechanism. Inflammatory molecules can affect the body's availability of nitric oxides, such as tumor necrosis factor-alpha, which is present in malaria. The way that malaria impacts the cardiovascular system is influenced by this interaction [6,69-71,76]

Increased cytokine levels and decreased availability of nitric oxide can impair the endothelium, the blood vessel's inner lining. This disturbance might change the heart vessels' capacity to dilate, which could affect the subsequent delivery of oxygen. According to a study done on malaria patients, endothelium dysfunction may continue after the illness has passed its acute stage [77].

An experimental study revealed that glycosylphosphatidylinositol, which was isolated from P. falciparum's cell membrane, may be detrimental to the heart, suggesting that malaria may have an impact on the heart [78]. This material raised levels of tumor necrosis factor-alpha and caused heart muscle cells to undergo a process known as apoptosis. Potential side effects from malaria medications can also affect the heart; a prolonged QT interval is the most common problem. The heart can be affected by severe malarial complications such as anemia, low blood volume, and kidney failure.

According to current research, malaria exposure may have an impact on the levels of angiotensin II and the activity of the angiotensin-converting enzyme [79]. Consequently, this may increase the risk of hypertension, a disease associated with alterations in the structure of the heart and the emergence of heart failure (Frederick et al., 2023).


With the advent of several complications of malaria and the increasing prevalence of cancerous conditions, there is an increasing need to find existing linkages between the two to establish prospects for future remedies. Multiple research papers analyze the various aspects of malaria and cancer, discussing various facets of its parasitology and pathogenic considerations, but only a handful of research papers have capitalized on the impact of malaria on cancer in its different forms [80].

The relationship between cancer and mosquito-borne pathogens is discussed in the abstract of Ward and [81], along with the relationship between simian and avian malaria and cancer. It was necessary to conduct more focused research to gain a deeper understanding of how different Plasmodium species directly affect humans. According to [82], a genetic component mutation increases the risk of cancer in particular populations. This study goes into further detail about how malaria affects the liver and causes liver cancer. The function of the DARC gene was explicitly described as preventing the expression of cancer by preventing tumor angiogenesis and stowing away chemokines needed for metastasis. According to [83], the negative association of DARC 1 with triple-negative breast cancer in black women is linked to the low Hp 2-2 genotype's association with a lower risk of breast cancer in Nigerian women. Prospective studies have also been conducted to investigate immune checkpoint gene variants as potential treatments for a variety of diseases. [82] assert that knowledge from malaria can be applied to the fight against cancer and vice versa. It is noteworthy to mention that a direct correlation has been established between Plasmodium falciparum infection and endemic Burkitt's lymphoma, a type of cancer. According to [84], Plasmodium falciparum is a class 2A carcinogen for the illness, which is demonstrated by antibody markers for the parasite infection. There is a connection between endemic infection and cancer, even though the specifics are still unknown. In addition, a tabular representation of different tumors and cancers connected to the percentage prevalence of Plasmodium falciparum is provided in the publication by [84]. In addition, aside from vector implications, haptoglobin protein and genotypes have been linked to a correlation between Plasmodium falciparum infection and breast cancer [83]. Burkitt's lymphoma risk is correlated with cancer susceptibility, as evidenced by studies conducted in multiple African nations [83]. There have been additional links to other lymphoproliferative disorders [85]. After mentioning the study's limitations and potential confounding variables, it was underlined that chronic inflammation and the selection pressure of malaria may be responsible for genetic variation in the Nigerian population with breast cancer [83]. According to what is currently known about the potential pro- and anti-cancer roles of malaria, unlike other eukaryotic parasites that affect humans, Plasmodium-related cancers are primarily lymphoproliferative disorders that can be caused by virus reactivation, while malaria's anti-tumor effects are primarily linked to carcinomas and certain sarcomas [86]. A few studies have pointed out a correlation between an increase in brain tumors and a rise in malaria cases in the 2000s. Furthermore, it has been demonstrated that Anopheles mosquitoes, along with other mosquito species, can transmit tumor cells through their analysis of the relationship between vectors of different arthropod-borne diseases and cancer [80].


This thorough examination of the relationship between malaria and renal diseases, diabetes, cancer, sickle cell disease, cardiovascular diseases, and HIV highlights the complex interplay between these conditions and the need for advanced, integrated healthcare solutions. The diverse and ever-changing character of these interactions is emphasized by the epidemiological patterns seen in each association. The complex relationship between malaria and renal diseases necessitates targeted research to close knowledge gaps. There is evidence of increased susceptibility and complications, but to optimize prevention and intervention strategies, it is imperative to define the underlying mechanisms. The burden on impacted populations is increased when diabetes and malaria coexist. Although integrated care approaches are becoming more widely acknowledged as valuable instruments for managing this illness, there is still information lacking about how they specifically interact with diabetes. There is a dichotomy in the relationship between malaria and cancer that needs to be carefully considered. Different study results highlight the need for continued investigation to address disparities and determine the best preventative and intervention measures. One area of strength that will serve as the basis for further research on this complex relationship is the understanding of the immune responses triggered by malaria. Nonetheless, one of sickle cell disease's well-known advantages—that it protects against severe malaria—needs further investigation from a wider angle. However, there are persistent gaps in knowledge regarding immunosuppression synergy that need to be addressed through focused research for better management plans. By focusing on specific knowledge gaps through intensive research projects, we could learn more about the complex relationships between different health issues and malaria. Based on current strengths, it is important to develop integrated management strategies for malaria and kidney diseases, diabetes, cancer, sickle-cell anemia, cardiovascular diseases, and HIV. Bridging these gaps will enable healthcare strategies that are comprehensive for malaria management in populations with prevalent genetic conditions. However, integrated healthcare approaches can take care of both problems at once, thereby reducing the cost and time involved in treatment.


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