Numerous protozoan parasites proliferate and expand inside the host cells. Leishmania and Toxoplasma, for example, are known to develop in macrophages, but Plasmodium is known to grow in hepatocytes first, then in red blood cells. A portion of the pathogen’s life cycle may be spent inside cells, where it is shielded from both intracellular digestion and the lethal response of lymphocytes and antibodies. For instance, it has been found that the extracellular sporozoite and merozoite stages of the life cycle of the protozoan parasite Plasmodium are susceptible to the antibody response. Other than this, it has been noted that Trypanosoma cruzi can break free from the phagocytic vacuole and enter the cytoplasm of the macrophage (Sibley, 2011; Graewe et al., 2012).

The pathogen encloses itself in the host’s contents during antigenic masking, allowing it to escape and be identified as foreign. For instance, the surface of several species of trypanosomes is attached to host immunoglobulins. These immunoglobulins block the parasite from being recognised by the host molecules’ immune systems because they are not linked to the variable region of the molecule, most likely through the Fc fragment (Chulanetra and Chaicumpa, 2021).

When antigen–antibody complexes in the serum of infected animals attach to the surface of the pathogen, they impede the pathogen’s ability to elicit a response from lymphocytes and cytotoxic antibodies, so precisely limiting the activity of lymphocytes directed towards the pathogenic organism (Chaplin, 2010). This kind of immunological escape mechanism has been proposed for parasite helminths and cancer cells. Figure 1 depicts the various immune evasion strategies employed by the pathogenic protozoa inside the human host.

In immunosuppression, the host’s immune activity is lowered either towards a pathogen specifically or in a generalised manner towards a foreign antigen. With context to protozoan infections, a number of mechanisms have been proposed that include: (i) The presence of the host components that non-specifically activate the proliferation of specific anti-parasitic B cells. (ii) Production of a particular immune suppressor component by the pathogen. (iii) The generation of regulatory cytokines by suppressor T-cells or macrophages, which impair the immune system (Dupont et al., 2012; Saleki et al., 2023).

Due to immunosuppression, a few microorganisms may be able to evade the immune system and develop a persistent infection. Because it allows for the undiscovered presence of a few parasites bearing novel surface antigens, this kind of mechanism may be useful for infections undergoing antigenic change (Finlay and McFadden, 2006). Experimentally induced immunosuppression by a number of external components has been observed to produce elevated parasitism, higher infection rates or both. Other than this, immunosuppression is taken to be pathogenic itself as it has been observed that a lowered response towards heterologous antigens could be advantageous for secondary infections and in turn these infections may often be involved in death as seen in the case of African trypanosomiasis (Evering and Weiss, 2006).

During an infection, some pathogenic protozoans change their surface antigens, a process known as antigenic variation, which helps them avoid being recognised by the host’s immune system. It has been determined that Babesia, Plasmodium, and Giardia are three significant groups of pathogenic protozoa that can change the antigenic characteristics of their surface coat (Dzikowski and Deitsch, 2006; Chulanetra and Chaicumpa, 2021). For example, African Trypanosomes can fully substitute the antigens on their surface glycocalyx every time the host exhibits a new humoral response. It has been documented that approximately one thousand genes encoding surface antigens can be found in African trypanosomes. For these genes to be active, they must be positioned in the telomeric region of the chromosome, even though they are located on various chromosomes. Furthermore, a multitude of separate gene families that encode outer surface proteins in Giardia have been identified and suggested to aid Giardia in evading the immune response of the host through the mechanism of antigenic diversity (Nash, 1997; Faubert, 2000; Lee et al., 2021). The apicomplexan parasites of the genus Plasmodium develop in erythrocytes in repeated cycles during malaria infection. In addition to variations in antigenic diversity within a strain, the species Plasmodium falciparum exhibits strains that differ in many polymorphic proteins. The Plasmodium falciparum-infected erythrocyte membrane protein 1 (PfEMP1) antigens, which are expressed on the surface of the infected erythrocytes, are the finest known example of genuine antigenic variation. Through altering the expression of PfEMP1, the parasite circumvents the immune reaction aimed at these immuno-dominant antigens. The PfEMP1 proteins also prevent dendritic cells from presenting antigens and enable infected red blood cells to adhere to the endothelium and extracellular matrix, preventing the spleen from eliminating the infected erythrocytes. PfEMP1 variable proteins have a molecular weight between 200 and 350 kDa. A range of endothelial receptors, including CD36, vascular cell adhesion molecule-1 (VCAM-1), E-selectin (ELAM-1), and intercellular cell adhesion molecule type 1 (ICAM-1), as well as the extracellular matrix protein thrombospondin, can be found in their extracellular region. These variable adhesive domains give the parasite-infected erythrocytes a specific binding specificity. The clinical signs of malaria are determined by the adhesive characteristics that cause infected erythrocytes to be sequestered in the liver, kidneys, brain, lungs, or other organs.

Similar to Plasmodium, Babesia is an intraerythrocytic parasite that is spread by ticks rather than mosquitoes. Clonal antigenic variation of the bovine parasite Babesia bovis is the most reported variation, even though multiple multigene families have been described for different species of Babesia. The surface of infected red blood cells expresses a heterodimeric protein known as the variable erythrocyte surface antigen (VESA1) of Babesia bovis. These polymorphic proteins very quickly, which probably prolongs the parasite’s life through immune evasion and sequesters the infected red blood cells in peripheral organs, leading to chronic infection in cattle. With an estimated molecular weight of 128 kDa, the VESA1 proteins are expressed on the outermost tips of the membrane knobs in infected erythrocytes. The VESA1 proteins’ structural alterations and antigenic modifications determine their cytoadhesive behaviour (Barbour and Restrepo, 2000).

By altering its interaction with host phagocytic receptors as well as controlling downstream signaling cascades, Plasmodium species inhibits phagocytosis. For instance, Plasmodium yoelii primarily infects erythrocytes that express high levels of CD47 (marker responsible for preventing phagocytosis), thereby helping them avoid being phagocytosed by the splenic red pulp macrophages. Additionally, through modifications to complement regulatory proteins that insulate infected host cells from complement-mediated damage, parasites prevent phagocytosis. They deactivate C3b on the surface of infected erythrocytes, impeding complement-mediated phagocyte removal of the parasites (Cristina Vanrell and Silvia Romano, 2023).

In the case of Trypanosoma cruzi, reduction of ONOO synthesis in NO-exposed parasites, regulation of NO-exposed parasites, and protection from the direct lethal effects of O2/H2O2 on parasite mitochondria within the macrophage phagosome are few of the strategies that the parasite employs to resist the deleterious effects of oxidative responses from the host. T. cruzi possesses a plethora of detoxifying antioxidant defenses and redox metabolism for protection against host-derived oxidants. One of the most significant thiols utilized by the trypanosomatid-antioxidant system is trypanothiol (T[SH]2). Additionally, T. cruzi’s Fe-dependent superoxide dismutases (Fe-SODs) efficiently eliminate O2 and may aid in intracellular survival (Estrada et al., 2018). T. cruzi has also been reported to harbour TcAPxCcP, a type A hybrid peroxidase that uses cytochrome C and ascorbate as reducing substrates for H2O2 elimination. TcAPxCcP is a membrane-bound peroxidase that is present in the mitochondria and endoplasmic reticulum as well as plasma membrane during the parasite’s life cycle (Hugo et al., 2017). On the whole, T. cruzi’s antioxidant defense mechanism detoxifies reactive species in the phagosomal compartments, which contributes to its virulence.

In this case, the organelle harboring Toxoplasma gondii appears to be arrested and unable to merge with lysosomes, hence protecting host-defense system and successful survival of the parasite. Apart from this, T. gondii demonstrates ways by which intracellular pathogens employ certain components of the host pathway (for instance Rab-family GTPases) for nutrient transportation to promote the proliferation of the pathogen (Robibaro et al., 2001; Paone and Olivieri, 2022).

Hemoglobin and ferritin (specific intracellular proteins) are the main cellular reserves of iron in mammals. Erythrocytes contain hemoglobin (Hb) which is a vital supply of iron and amino acids for pathogenic protozoa to flourish inside the infected host. For instance, in the case of Giardia lamblia (an intestinal protozoan parasite), the parasite is observed to exhibit lysosomes as peripheral vacuoles with hydrolase and acid phosphatase activity that might be pivotal in cell feeding and excystation. The ideal pH range for these proteinases to function against Hb is 3.5 to 7.0; hence, protease secretion directed against Hb influences host interactions. In addition to this, in the event of Trichomonas vaginalis, a certain percentage of the reason trichomonads are successful parasites of the vaginal epithelium is linked to their ability to take in vital nutrients like iron. Since, in addition to controlling cytoadherence, cytotoxicity, hemolysis, complement resistance, immunological evasion, and apoptosis in human cells, iron likewise impacts the virulence of T. vaginalis. As there is no free iron in the vaginal environment, T. vaginalis obtains iron from host proteins that either bind to iron or contain iron, including cytochromes, Lactoferrin, and Hb. When the amount of lactoferrin decreases during menstruation, hemoglobin (Hb) in erythrocytes serves as a significant source of iron. Hemolysis and erythrophagocytosis are the two main methods that T. vaginalis uses to obtain Hb iron in vivo, which serves to aid in the growth and differentiation of the parasite inside the host (Reyes-López et al., 2023).

Human African trypanosomiasis (sleeping Sickness) is a vector-borne parasitic disease. The disease is transmitted to humans by bites of Glossina (tsetse fly) which have acquired the disease-causing protozoa from infected animals or humans. Pathogenic protozoa take two forms depending on the parasite subspecies called as Trypanosoma brucei gambiense and Trypanosoma brucei rhodesiense. With a tiny kinetoplast and a well-developed undulating membrane, these two T. brucei subspecies are morphologically very similar. While in the blood or cerebral fluid, parasitic protozoa multiply. A feeding fly ingests trypanosomes, which then enter the salivary glands and reproduce rapidly as epimastigotes attach to the gland’s microvilli until they modify into metacyclic trypomastigotes found in the lumen. About 15 to 35 days after infection, the fly becomes contagious for humans. The disease is mainly transmitted through tsetse fly however there are other pivotal possible ways of disease transmission like: (i) Mother to child: Trypanosomes can cross the placental barrier and hence can infect the foetus. (ii) Infection in laboratories via pricks with contaminated needles. (iii) Transmission through sexual contact.

Trichomonas vaginalis is a pathogenic protozoan responsible for causing trichomoniasis, i.e., the most widespread, non-viral sexually transmitted infection (STI). T. vaginalis is a motile protozoan species that inhabits the lower genitourinary tract of females and prostate and urethral regions in males (Petrin et al., 1998; Menezes et al., 2016). The concerned disease is observed to elevate the risk of Human Immunodeficiency virus (HIV) transmission in both males and females. Other than this, the disease is also linked with detrimental outcomes during pregnancy. The pathogen possesses a pear-shaped body organization, a single anterior nucleus and a single posterior flagellum that constitutes the exterior border of an undulating membrane. The life cycle of Trichomonas is quite uncomplicated as it remains only as a single trophozoite form and since there is the absence of any resistant cyst-like stage the mode of transfer from host to host is simply direct. The various types of risk factors associated with the infection (Beri et al., 2019). It includes association with an infected partner, multiple sex partners, person associated with any history of Sexually Transmitted Infections (STIs), drug abuse, and avoiding usage of any barrier contraception.

Malaria is a parasitic disease transmitted by Anopheles mosquito that causes acute life-threatening condition and poses a serious global health threat. The multistage developmental process of Plasmodium causes the infected host to have periodic fever bouts. With consideration to the life cycle of the pathogenic protozoan, Plasmodium undergoes two stages of development: an asexual stage in the human host and a sexual phase in the Anopheles mosquito, which serves as the carrier. Within the liver parenchymal cells, where they proliferate asexually, the sporozoites that are delivered during a blood meal quickly enter the bloodstream (a phase called as schizogony). The asexual reproduction of protozoa is known as schizogony, previously known as merogony. A schizont is made up of many cell nuclei; the daughter nuclei organize into single entities called merozoites when they are encircled by cytoplasm. Between 10,000 and over 30,000 merozoites can be produced by a single sporozoite. The enlarged liver cell bursts and discharges the mobile merozoites into the bloodstream when schizogony gets completed. These merozoites stick to the red blood cells through certain surface receptors (glycophorin A in the case of P. falciparum, or Duffy blood group antigen, Fya or Fyb, in the case of P. vivax). Following their entry into red blood cells, they develop into trophozoites. By the time the 48-to 72-h erythrocytic phase concludes, the red blood cells’ schizonts get developed. Vacuoles with parietal nuclei, often known as seal-ring forms, might develop during this period. Red blood cells that have degraded may release fresh merozoites that can infect more red blood cells. Within erythrocytes, a portion of the merozoites evolves into sexual phases, creating macro-and microgametocytes. The malaria pigment, an insoluble metabolite of hemoglobin, forms hemozoin in the intra-erythrocytic vacuoles. The Anopheles mosquito’s midgut produces a motile, flagellated zygote following the uptake of both male and female gametocytes during a blood meal. This zygote enters the gland that produces saliva. Finally, an oocyst forms, generating sporozoites that can spread to a new human host through the mosquito’s saliva (Arbeitskreis Blut, Untergruppe «Bewertung Blutassoziierter Krankheitserreger», 2009; Cox, 2010; Venugopal et al., 2020).

Symbiosis with its literal meaning as “living together” is defined as an organism that survives in a group and provides each other collective benefits. Hence, approach around symbiosis is suggested as a disease therapy model as it is assumed that protozoa that inhabit naturally in human tissues can be genetically altered for the production and transfer of curative proteins. One of the examples for such kind of therapy model is Leishmania that has been genetically modified for conditional auxotrophy and indicated no disease-causing signs in non-human primate and mouse model-based clinical examinations. Numerous protozoan species have been transfected with a plethora of genes and have been observed producing active foreign proteins quite efficiently hence contributing their positive attribute on the medicinal front (Vaccaro, 2000).

Wastewater treatment is considered a pivotal method in the context of the ever-increasing human population. Wastewater processing facilities are intended to manage higher activity and density measures of those microorganisms that actively participate in various purification methods. With context to this, protozoa are considered to be responsible for repairing the nature of the effluent as well as controlling the bacterial population by predation and hence are taken as one of the most pivotal parts in the man-made system environment and play a crucial role in wastewater purification. Investigations performed on ciliates considering acute toxicity of contaminants suggested protozoans as potential bio-indicators for measuring water toxicity contaminated by various metal doses (Madoni, 2011). One of the research investigations examined the bacterivorous behaviour of ciliates that were isolated from artificial wetlands using the root zone method of wastewater treatment. Examples of ciliates that were seen to graze on fluorescently labelled bacteria, most notably Escherichia coli include Paramecium spp. oxytrichids, Halteria and scuticociliates suggesting their positive role in wastewater treatment (Decamp and Warren, 1998). Additionally, it has been established that Uronema marinum is an indicator of eutrophication and situations that are both oxygen-poor and rich in organic matter, while algivorous ciliates like Tintinnopsis baltica and Favella ehrenbergii are indicators of low nutrient levels and bacterivorous/detritivorous environments (Ravindran et al., 2023).

One of the most important steps in the course of infection is thought to be binding on the host tissue, which appears to be facilitated by the identification of certain Extracellular Matrix components, such as basement membrane laminin, tenascin, types I and IV collagens, and fibrinogen. Disseminated infection most likely develops metastatic foci of infection throughout the body after attachment to the sub-endothelial extracellular matrix (ECM). In Candida albicans germinating cells, a variety of cell-surface receptors (68, 62, and 60 kDa) with various affinities for laminin, fibrinogen, and C3d were discovered. A 72-kDa cell-wall receptor and a 37-kDa laminin-binding receptor were identified in Aspergillus fumigatus. A glycoprotein of 120 kDa known as BAD1, is the most well-studied adhesin in Blastomyces dermatitidis. It can facilitate the adherence of yeast cells to host cells or extracellular matrix proteins. Thus, pathogenic fungal parasites can destabilize the molecules of their host to obtain entry that aids in their survival and development.

Entering eukaryotic cells allows harmful fungi to take advantage of the generally unsuitable environment as a place to proliferate or hide from the host immune system. Candida albicans can cause endothelial cells to undergo phagocytosis by polymerizing their microfilaments and microtubules. The actin cytoskeleton can undergo disorganization due to the direct influence of fungal products released by Candida, such as actin-rearranging Candida-secreted factor (ARCSF), acting on actin or associated proteins. This disorganization is subsequently accompanied by rearrangement of cellular actin, a decrease in membrane ruffling, and a decline in cell motility. Wasylnka and Moore conducted an in vitro study exploring the uptake of two distinct strains of Aspergillus fumigatus in A549 lung epithelial cells, human umbilical vein endothelial cells (HUVEC), and J774 murine macrophages. The cytoskeleton of the host cell had to be rearranged for A549 to internalize the conidia. These results show that non-professional phagocytes can internalize a significant number of Aspergillus fumigatus conidia in vitro, and these cells may serve as repositories for immune cell evasion and host-disseminated immunity.

The investigation of signal transduction pathways in pathogenic fungi holds particular significance due to their potential involvement in the control of pathogenicity. A wide range of cellular functions are regulated by cAMP signaling cascades in both pathogenic and non-pathogenic fungi. Adenylyl cyclase-dependent signaling pathways govern the development of certain phenotypes necessary for virulence in Candida albicans and Candida fumigatus. Strains of Candida albicans (CaCDC35) containing a mutation in the adenylyl cyclase gene are unable to go through the morphological transition from budding yeast to polarised form, which is required for the organism to reach its maximal virulence. By extending their membranes and eluding macrophage defenses, invasive Candida albicans yeasts form germ tubes inside phagolysosomes and swiftly invade macrophage late endosome and lysosome compartments. These pathways may aid in the pathogen’s survival and pathogenicity. It appears that the uptake of Candida yeasts depends on protein kinase C (PKC) activity, needing intact actin filaments, and hence exhibiting phagocytosis-like features (Mendes-Giannini et al., 2005).

Aspergillus, a prevalent mold (a specific kind of fungus) that can flourish both indoors and outdoors is the major underlying cause of the disease aspergillosis. Aspergillus-related health issues are more likely to develop among individuals with compromised immune systems or respiratory disorders. Aspergillosis occurs in various forms, while some varieties are minor, others are extremely infectious (Barnes and Marr, 2006). About 8 different types of aspergillosis are described hereunder including:

Fungi is one of the most essential classes of microorganisms that could potentially be used in a variety of industries, including agriculture. Valuable fungi play a significant part in the long-term viability of agriculture (Watts et al., 2023). These fungi come in a variety of forms, including symbiotic and endophytic varieties. The potential of beneficial fungi could be used as an alternative to chemical pesticides for the management of plant pathogens, pests and weeds. Endophytic fungi, mushrooms, entomopathogenic fungi and dark septate fungi fall among the well-known groups of beneficial fungi. Certain beneficial fungi are also observed to be associated with the enhancement of plant growth. The beneficial effects of using fungi in agriculture encouraged the industries to use them to create biopesticides and biofertilizers which can further be used in place of synthetic chemicals and reduce the amount of chemical waste in the environment. Hence, fungi play a significant role in sustainable farming by gaining incorporation into integrated pest and disease management strategies (Lavado and Chiocchio, 2023).

There are various methods by which diagnosis of fungal pathogens can be established (Fang et al., 2023). Table 2 represents various strategies involved in the detection of infections caused by disease-causing fungi.

Antifungal drugs interfere with various aspects of fungal cell biological function, thus preventing further growth of the pathogen (Sanguinetti et al., 2015). Figure 3 describe the types of Antifungal Agents acting on different sections of the cell causing prevention of fungal infection these drugs can be classified into several categories described as:

The term “elastases” refers to the soluble serine proteases of Schistosoma mansoni cercariae. The transcripts of at least three of these serine proteases have been found in the precursor germ balls of the daughter sporocyst stage in the snail host, and they have been biochemically characterized from the secretions of the acetabular gland. The proteins of the stratum corneum and the epidermis, where the entering cercarial body forms a penetration tunnel, are most likely the substrate of the characterized serine proteases, and as the parasite penetrates the epidermis, its thick protective glycocalyx and cercarial tail are shed. Glycans are another component of cercarial secretions that is worthy of consideration as a virulence factor. The proteins found in soluble cercarial secretions have high levels of glycosylation. Mass spectrometry has discovered a large number of both N-and O-linked glycan structures, many of which are shared between the two stages of transmission, indicating a shared function by the stages entering and exiting the host. Therefore, as a component of the immune evasion system, glycans act as a covert barrier to divert antibodies from functional peptide epitopes that are susceptible to attack, drawing leucocytes away from the approaching larva to let them escape from the protective host machinery.

A syncytial layer of cytoplasm connects the schistosome interface with the circulation, often known as the tegument, to cell bodies located beneath the muscle. Evasion of the host immune response primarily takes place on the surface of the tegument. The ability of a few exposed enzymes on the outer leaflet of the tegument plasma membrane to alter the parasite’s immediate environment within the blood vessel has led to their being considered as possible virulence factors. The discovery that ATP-diphosphohydrolase functioned externally on the tegument raised the possibility that the enzyme may control the number of purine nucleotides surrounding the parasites, allowing them to evade the host’s hemostasis by blocking ADP-induced platelet activation. It has also been observed that the external surface GPI-anchored ADP-ribosyl cyclase enzyme may catabolize extracellular NAD+ to stop host enzymes from using it to promote immunological responses. Additionally, tegumental alkaline phosphatase’s production of adenosine from adenosine monophosphate has been proposed to have a localized immunosuppressive effect (Wilson, 2012).

Fasciolosis is an extremely infectious parasitic disease that infects humans as well as livestock and is caused by flat worms that belong to the genus Fasciola. Fasciola hepatica belongs to class trematoda and the infection caused by it is responsible for causing serious mortality and morbidity and is associated to elevated sensitivity to co-infections and decreased yield and potency. Consuming infected plants and vegetables is the primary way that humans acquire liver fluke infection. F. hepatica uses snails as intermediary hosts in its life cycle. When the pathogen finds appropriate environmental conditions, the meracid undergoes the asexual phase of its life cycle after infecting the snail host. Eventually, it transforms into cercariae (Lalor et al., 2021).

All ecosystems benefit from the contribution of the soil biota to soil production and long-term viability. Earthworms (EWs) make up a significant amount of the biomass of macrofauna and are a major component of soil fauna communities in most habitats. Their activity is advantageous because it can improve the nutrient cycle of soil by quickly incorporating detritus into mineral soils. Apart from the effect of mixing, the creation of mucus resulting from water excretion in the stomachs of earthworms also amplifies the activity of other advantageous soil microbes. Furthermore, earthworms appear to quicken the process of soil organic matter turnover and mineralization. Through their direct and indirect effects on the microbial population, earthworms are also known to boost nitrogen mineralization. The potential for earthworms to aid in the stabilization and accumulation of soil organic matter in agricultural systems is shown by the increased transfer of organic carbon and nitrogen into soil aggregates (Bhadauria and Saxena, 2010). Some of the examples of earthworms that aid in the improvement and maintenance of soil fertility include Hyperiodrilus africanus and Eudrilus eugeniae (Tian and Badejo, 2001).

Earthworms and other microorganisms break down and stabilize organic waste through a process called vermicomposting. The organic waste substrates are broken up by the earthworms, which also significantly boosts microbial activity and accelerates mineralization rates. Since vermicompost is a stable, fine-granular organic matter, adding it to clay soil enhances airflow and loosens the soil. The mucus connected to the hydrophobic cast enhances water-holding capacity by absorbing water and preventing water logging. The plant can absorb the nutrients because of the organic carbon in vermicompost, which distributes the nutrients into the system gradually. Additional nutrients that are absent from artificial fertilizers are added to the soil when it is treated with vermicompost. Vermicomposting provides a way to recycle and utilize the tonnes of organic agricultural waste that farmers are burning to support our agricultural development in a more economical, ecologically friendly, and efficient way. Earthworms play a well-established function in the management of organic solid waste, and waste products can be processed using adapted technology to create vermicompost, an effective bioproduct. Vermicomposting is done with epigeic earthworms such as Perionyx excavatus, Eisenia fetida, Lumbricus rubellus, and Eudrilus eugeniae; however, native species, such as Perionyx excavatus, have shown to be effective composting earthworms in tropical or sub-tropical environments (Garg et al., 2006; Ali et al., 2015).