People with sickle cell disease have weakened immune systems and are at increased risk for developing infection, especially in the lungs, kidneys, bones, and central nervous system. Repeated crises damage the spleen, which over time, causes it to stop functioning.

The development of cerebral malaria, possibly the worst and lethal complication of falciparum malaria infection is related to sequestration of infected red cells in the vasculature of the brain. It is now clear that the ability of PfEMP1 to mediate adhesion also depends on its interaction with other exported parasite proteins that are located inside infected red cells and that interact specifically with the red cell membrane skeleton. For example, if the cytoplasmic domain of surface-expressed PfEMP1 does not bind to the histidine-rich parasite-produced protein KAHRP, that clusters PfEMP1 at knobs on the red cell surface, then the infected red cells are incapable of binding to the vascular endothelium under normal circulatory flow.

A recent ultra structural study revealed fewer and smaller knobs at the membrane skeleton of P. falciparum-infected HbCC red cells and Hb AS red cells which may affect the amount or distribution of PfEMP1 or other antigens expressed on the red cell surface which could affect their ability to cytoadhere. This is a very interesting hypothesis and could offer a possible additional mechanism for protection against severe disease in HbCC and sickle cell disease

The effects of homozygous state Sickle Cell Anemia includes:

1. Pains that can last days or weeks.

2. Damage or impared Spleenic functions .

3. Periodic crisis associated with the pathology of this case.

4. Vision imparement as some stages, due to obstructed flow of red cells to supply the retina with required metabolites for optimized functions.

5. Low capacity for Hemoglogon to carry and effectively distibute oxygen to tissues to support tissue respiration, leading to potentials for periodic or even frequent fatigue.

Heterozygotes for the sickle cell gene (AS) are relatively protected against increasing heights of pathology and danger of dying when infected by malaria parasites. Several published studies have pointed in this line- through a number of clinical field studies from different parts of Africa where Plasmodium falciparum as good footing.

However, patients who are homozygous for the sickle cell gene (SS) who therefore suffer from sickle cell anaemia (SCA) are very susceptible to the lethal effects of malaria. Several Journal- published data and studies also indicate this.

As such,  malaria can potentially make the anaemia of SCA pateints more severe;, recalling that in homozygous Sickle cell condition, there is often hyposplenism with derailed Spleenic functions, which reduces capacity for normally immune linked clearance of parasites, like that of. Plasmodium malaria paraaite. Several studies have indicated this to be the scenario.

So, if Sickle cell anaemia in its homozygous state is poorly managed, the pooled negative effects of co-morbidity will worsen matters for such sickler and encourage progression of malaria pathology. Let's recall that the ugly sides of Plasmodium faliciparum malaria pathology includes- fever, chills, nausea, pains, joint specific pains, weakness, loss of consciousness in badly managed ones, cracked lips, loss of appetite, neuropathies steming from increased progression that involve parasite migration to reach the brain/CNS.(especially in children where it is associated with the lethal cerebral malaria), among others.

Some typical study revealed that:

The sickle gene confers an increased susceptibility to infection, especially to certain bacterial pathogens, and at the same time infection provokes a cascade of SCD-specific pathophysiological changes. Historically, infection is a major cause of mortality in SCD, particularly in children, and it was implicated in 20–50% of deaths in prospective cohort studies over the last 20 years (.Booth at al 2010 ), corroborated by a finding that within the SCD population, those admitted with malaria are twice more likely to die  (Eleonore at Al, 2020 ) among other findings

from literature /research repositories..

The picture does not support good outcome for pateint when homozygous state Sickle cell patient is not clinically well managed due to lack of health facility or inaccessible health facility, or due to lack of funds to present self for proper management in health centres, then suffers malaria infection. Malfunctioning spleen from poor state of health in sickle cell Anemia will likely compound management of malaria infection, and if treatment options are not optimized, the risk of mortality can be higher.

It is advisable for homozygous state Sickle cell patients to be on malaria prophykxis, to narrow down the corridors made available for severity of malaria and effects of co-morbidity.

Computer Algorithm enhanced studies based on pre-clinical data and clinical data, coupled to genomic characterizations will be good prospects for xraying and defining other features that can provide clearer understanding of other features and enhance management and controls

Malaria and sickle cell anaemia are still major challenges to infectious disease medicine and to haematology respectively, and both are also major public health problems. One might have hoped that what we have learnt about the of advantage of AS heterozygotes with respect to malaria would enable us to protect from malaria mortality other people as well. That this has not yet happened is disappointing but perhaps not surprising, because the key is sickling of red cells, and this is a unique phenomenon. It cannot be a straightforward task to mimic sickling by a pharmacological approach in subjects who do not have Hb S, and in a way that would act selectively only on parasitized red cells. We can still hope that human imagination will evolve novel approaches that can match the power of mutation and selection in biological evolution. In the meantime SCA remains a source of great suffering to patients, especially in those developing countries where the numbers are staggering . It is urgent that more is done in order to offer to these patients a better way of life: this ought to include optimal management of pain, often hydroxyurea and, especially in Africa,34 protection against the potentially fatal threat of P falciparum malaria. If, as doctors, we have a professional obligation towards all of our patients, for those with SCA we have an added human obligation, if we consider that they carry the genetic burden that has helped human populations to survive in malaria-endemic regions of the world.

Yes, the coinfection severe malaria and sickle cell are possible.

Years ago it was not taught that sickle cell patient are malaria free, but recently evidence shows that the coinfection is possible.

Paul Marie Bello Mr. Bello, you are talking about coinfection. Maybe you wish to realize that sickle cell anemia and sickle cell trait are not infectious diseases, but genetic disorders.

Christian G Meyer Sickle and the erythrocytic cycle of Plasmodium are not mutually exclusive. Cases of severe malaria are found in patients with sickle cell disease.