Zoonotic Diseases: A Comprehensive Review of Toxoplasmosis and its Impact on Public Health

Zoonotic diseases, also known as zoonoses, are infectious diseases that are transmitted between animals and humans. These diseases are caused by a variety of pathogens, including bacteria, viruses, parasites, and fungi, which can be transmitted directly or indirectly from animals to humans. Zoonoses represent a significant threat to global public health as they account for more than 60% of all human infectious diseases, with over 70% of emerging infectious diseases having an animal origin (1). Examples of zoonotic diseases include rabies, avian influenza, Ebola, and Toxoplasmosis. Zoonoses not only pose direct health risks but also contribute to economic burdens on health systems and agricultural sectors due to their impact on livestock and wildlife populations (2). Their transmission is influenced by environmental factors, human behavior, and the close interactions between humans and animals, particularly in urbanization, global trade, and climate change (3). Toxoplasmosis, caused by the protozoan Toxoplasma gondii, is one of the most common zoonotic infections worldwide, with significant public health implications. This disease is typically associated with domestic cats, which are the definitive hosts of the parasite, but humans and other animals can also serve as intermediate hosts. The significance of Toxoplasmosis lies in its ability to cause a wide spectrum of clinical manifestations, ranging from asymptomatic infections to severe outcomes such as encephalitis, ocular toxoplasmosis, and congenital toxoplasmosis, which can lead to neurological and developmental issues in newborns (4). It is a particularly serious concern for immunocompromised individuals, such as those with HIV/AIDS or organ transplant recipients, who are at increased risk for developing more severe forms of the disease (5). Furthermore, the potential for congenital transmission during pregnancy highlights the importance of early detection and management of the disease in pregnant women, as it can result in miscarriage, stillbirth, or lifelong disabilities in the child (6). Toxoplasmosis has a global distribution, with prevalence rates varying depending on geographic location, socio-economic conditions, and cultural practices. Studies suggest that approximately one-third of the global population has been exposed to Toxoplasma gondii at some point in their lives (7). The disease is more common in areas where foodborne transmission is prevalent, such as regions where undercooked meat is a part of the diet, or where there is poor sanitation and close contact with animals, particularly cats (8). For example, the prevalence of T. gondii antibodies is higher in countries in Latin America, Eastern Europe, and parts of Africa, while lower in parts of Asia and Scandinavia (9). In the United States, it is estimated that around 11% of the population is infected, but most cases are asymptomatic or mild (10). The distribution of the disease can be influenced by multiple factors, including the presence of domestic cats, agricultural practices, and food safety standards (11). Additionally, the disease has a substantial impact on public health due to its chronic nature and the associated healthcare costs related to treating severe cases, especially in immunocompromised individuals and pregnant women (12)

Figure 1: Transmission and Global Impact of Zoonotic Infections

Microorganism Overview: Description of Toxoplasma gondii, Its Taxonomy, Morphology, and Life Cycle

Toxoplasma gondii is an obligate intracellular protozoan parasite that belongs to the phylum Apicomplexa and the family Sarcosporidiidae. It is the causative agent of toxoplasmosis, a widespread zoonotic disease affecting a variety of warm-blooded animals, including humans. The organism was first described in 1908 by Nicolle and Manceaux in Tunisia, and its taxonomy has evolved since then, with T. gondii classified within the genus Toxoplasma. The parasite exists in several morphological forms during its life cycle, including oocysts, tachyzoites, bradyzoites, and sporozoites.

• Oocysts: The environmental form, shed in the feces of infected definitive hosts (e.g., domestic cats), which are highly resilient and can survive in the environment for extended periods.
• Tachyzoites: The rapidly dividing form, responsible for the acute phase of infection, that disseminates throughout the host’s body.
• Bradyzoites: The slowly replicating form that forms cysts in tissues, including the brain, muscles, and eyes, contributing to the chronic phase of infection.

The life cycle of T. gondii involves both definitive and intermediate hosts, with domestic cats (and other Felidae) being the definitive hosts, where sexual reproduction of the parasite occurs. Intermediate hosts can include humans, other mammals, and birds, where the parasite undergoes asexual reproduction.

Table 1: Morphological Forms of Toxoplasma gondii and Their Characteristics

Infection Cycle: Explanation of the Biological Cycle (Definitive Host, Intermediate Hosts, Oocyst Formation)

The life cycle of T. gondii consists of sexual and asexual phases that occur in different hosts. The cycle begins when an infected cat sheds oocyst in its feces into the environment. These oocysts, which contain sporozoites, become infectious after 1–5 days in the environment. Intermediate hosts, including humans, become infected by ingesting oocysts from contaminated food, water, soil, or direct contact with infected cat feces. Upon ingestion, oocysts release sporozoites, which invade intestinal cells and differentiate into tachyzoites.

• Definitive Host (Cat): In the cat’s intestine, tachyzoites differentiate into gametocytes (male and female forms), which undergo fertilization, forming oocysts. These oocysts are then excreted in the cat's feces.
• Intermediate Hosts (Humans and Other Animals): In intermediate hosts, the tachyzoites rapidly proliferate and disseminate through the bloodstream, invading various tissues, including the brain, heart, and muscles. Over time, some tachyzoites convert into bradyzoites, forming tissue cysts that can persist for the lifetime of the host.

This cycle of infection and reproduction is central to the spread of T. gondii among both definitive and intermediate hosts. Transmission from intermediate hosts to definitive hosts occurs when a cat consumes infected prey, completing the cycle.

Genetic Variability: Variants of T. gondii and Their Impact on Virulence and Transmission

Toxoplasma gondii exhibits significant genetic diversity, with three primary clonal lineages identified: Types I, II, and III. These lineages are characterized by differences in virulence, transmission, and host adaptability.

• Type I: This lineage is associated with high virulence and is typically isolated from severe cases of toxoplasmosis, particularly in immunocompromised individuals. Type I strains replicate rapidly and are often associated with the acute phase of infection.
• Type II: This is the most common lineage found in human infections and is generally considered less virulent. However, it is the predominant strain in both animals and humans worldwide, contributing significantly to the chronic stages of the infection.
• Type III: Although less virulent than Type I, Type III strains are also frequently isolated from human and animal infections. These strains are often associated with asymptomatic infections.

The genetic variability of T. gondii affects its ability to invade host cells, replicate, and persist within host tissues, influencing disease progression and clinical outcomes. Additionally, the variation in virulence can affect the transmission dynamics of the parasite, influencing the incidence of congenital toxoplasmosis and the development of severe cases in immunocompromised individuals. The variability in these strains also affects the design of vaccines and treatment strategies, as different strains may exhibit varying levels of resistance to interventions.

Transmission of Toxoplasmosis

Toxoplasma gondii is transmitted through several routes, primarily involving animal reservoirs, human contact with infected animals, ingestion of contaminated food, and environmental exposure. The different modes of transmission highlight the complex lifecycle of the parasite and its wide-reaching effects on both animal and human health.

Animal Reservoirs: Role of Felines (Domestic Cats) as Definitive Hosts, and Other Animals as Intermediate Hosts

Felines, particularly domestic cats, are the definitive hosts of Toxoplasma gondii, meaning that sexual reproduction of the parasite occurs in their intestines. When cats ingest infected prey (such as rodents or birds), T. gondii undergoes sexual reproduction in the cat’s intestines, producing oocysts, which are then shed in the cat’s feces (13). These oocysts, once released into the environment, can remain viable for months and serve as a source of infection for intermediate hosts, including humans and other mammals (14). Intermediate hosts, which include a variety of animals like livestock (e.g., sheep, pigs) and rodents, acquire the parasite through ingestion of oocysts from contaminated food, water, or soil (15). In these animals, T. gondii forms cysts, predominantly in muscle and brain tissue. These cysts can later be transmitted to humans through the consumption of undercooked meat or by other means (16).

Human Transmission

Humans can become infected with T. gondii through several pathways:

• Consumption of Undercooked Meat (e.g., Pork, Lamb): One of the most common routes of transmission to humans is through the consumption of undercooked or raw meat from infected animals, particularly pork, lamb, and venison. Toxoplasma gondii forms tissue cysts in these animals, and inadequate cooking of the meat can lead to the ingestion of viable cysts (17). This is a significant concern in areas where eating raw or undercooked meat is part of traditional dietary practices (18).
• Contamination via Oocysts in Cat Feces: Humans can also become infected by handling contaminated soil, water, or surfaces that have been exposed to cat feces containing oocysts. Activities such as gardening, cleaning a cat’s litter box, or consuming unwashed produce grown in contaminated soil can lead to infection. Cats shed oocysts in their feces, which can contaminate the environment for up to several months (19). Direct contact with infected feces is a well-documented source of infection for humans, especially for pregnant women, who are at risk of congenital toxoplasmosis (20).
• Congenital Transmission (Mother-to-Child): Pregnant women who become infected with T. gondii for the first-time during pregnancy may transmit the infection to their unborn child. The parasite can cross the placenta, leading to congenital toxoplasmosis. This can result in severe outcomes such as miscarriage, stillbirth, or neurological damage, including hydrocephalus and retinochoroiditis in newborns (21). Congenital infection is particularly concerning because it can cause long-term health issues in children if not diagnosed and treated early (22).
• Organ Transplantation and Blood Transfusion: Transmission of Toxoplasma gondii can also occur through organ transplantation or blood transfusions. In immunocompromised individuals, particularly those who have received a solid organ transplant, the parasite can cause severe illness, including toxoplasmic encephalitis (23). This route of transmission is relatively rare but significant in certain high-risk populations, such as transplant recipients or patients with HIV/AIDS.

Environmental Factors: Role of Contaminated Water and Soil in Transmission

Environmental factors, including contaminated water and soil, play a key role in the transmission of Toxoplasma gondii. Oocysts excreted by infected cats can contaminate water sources, agricultural soil, and even recreational water bodies. When these oocysts are ingested by humans through contaminated drinking water or during activities like swimming in polluted water, they can cause infection (26). Additionally, oocysts can contaminate soil, where they persist for long periods. Individuals who handle contaminated soil (such as gardeners) or consume contaminated, unwashed fruits and vegetables are at increased risk. In particular, waterborne outbreaks of toxoplasmosis have been reported in various parts of the world, including cases linked to agricultural irrigation water and contaminated public water supplies.

Clinical Manifestations and Symptoms

Asymptomatic Infections

A majority of individuals infected with Toxoplasma gondii experiences asymptomatic infections. In fact, it is estimated that up to 80% of infected individuals show no obvious symptoms (24). These individuals carry the parasite in a latent form, which can persist in the body for long periods, typically within tissues such as the brain and muscles. In healthy individuals with an intact immune system, the parasite remains dormant and does not cause overt clinical illness. However, even in the absence of symptoms, the infection can still be detected through serological tests that identify specific antibodies, reflecting past exposure to the parasite (25).

Acute Symptoms

In cases where the infection progresses to an acute phase, symptoms are often mild and non-specific, resembling a flu-like illness. The most common manifestations include fever, headache, muscle aches, and fatigue. Lymphadenopathy, or the swelling of lymph nodes, is another characteristic feature of acute toxoplasmosis. These symptoms are usually self-limiting and may resolve within weeks without medical intervention (26). The acute phase of the infection is typically more apparent in immunocompetent individuals who are experiencing their first infection, as the immune system mounts a response to the parasite. In contrast, individuals who have been previously exposed to Toxoplasma may not exhibit noticeable symptoms during reactivation (27).

Severe Cases

Severe cases of toxoplasmosis occur primarily in immunocompromised individuals, such as those with HIV/AIDS or transplant recipients. In these individuals, the immune system’s ability to control the parasite is compromised, leading to toxoplasmic encephalitis (TE), a life-threatening condition that involves inflammation of the brain (28). Toxoplasmic encephalitis is characterized by symptoms such as seizures, confusion, motor weakness, and altered mental status. It is one of the most common causes of focal brain lesions in patients with HIV/AIDS (29). Another severe complication is ocular toxoplasmosis, which affects the eyes and can lead to vision loss if left untreated. This form of toxoplasmosis presents as retinochoroiditis, causing pain, blurred vision, and eye redness (30). Ocular involvement can occur in both immunocompetent and immunocompromised individuals but is more frequent in those with compromised immune systems (31).

Congenital Toxoplasmosis

Congenital toxoplasmosis occurs when a pregnant woman acquires the infection for the first-time during pregnancy and transmits it to her unborn child through the placenta. The clinical outcomes of congenital toxoplasmosis can range from asymptomatic to severe, with newborns presenting with a variety of symptoms. In severe cases, congenital toxoplasmosis can lead to miscarriage, stillbirth, or neurological disorders such as hydrocephalus, microcephaly, and chorioretinitis (32). Newborns infected with the parasite at birth may show signs such as jaundice, fever and seizures, and long-term complications, including developmental delays and vision problems, may manifest later in life (33). Early diagnosis and treatment are crucial in preventing or mitigating these outcomes, as untreated congenital toxoplasmosis can lead to significant morbidity and mortality in affected infants (34).

Table 2: Clinical Forms and Key Features of Toxoplasmosis

Diagnosis of Toxoplasmosis

Serological Tests: Use of IgM and IgG Antibodies to Detect Acute and Chronic Infections

Serological testing remains the cornerstone for the diagnosis of toxoplasmosis. The detection of specific IgM and IgG antibodies in the patient's blood can help differentiate between acute and chronic infections. The presence of IgM antibodies indicates a recent or acute infection, while IgG antibodies suggest past exposure or chronic infection (35). In individuals with a primary infection, IgM antibodies appear first, typically within one to two weeks after exposure, and can remain detectable for several months. IgG antibodies, on the other hand, appear later but persist for life, indicating prior exposure and immunity (36). These serological markers are useful not only for diagnosing active infections but also for determining whether an individual is at risk of congenital transmission, especially in pregnant women (37).

PCR and Molecular Diagnostics: Molecular Techniques for Detecting T. gondii DNA

Polymerase chain reaction (PCR) is an advanced diagnostic tool used to detect Toxoplasma gondii DNA directly from blood, cerebrospinal fluid (CSF), or tissue biopsies (38). PCR is particularly valuable in diagnosing severe cases, such as toxoplasmic encephalitis, and in immunocompromised patients who may not produce a strong antibody response. This molecular technique offers high sensitivity and specificity, enabling the detection of low quantities of the parasite's DNA, even during the latent or reactivated phases of infection. Additionally, PCR has been employed in diagnosing congenital toxoplasmosis in neonates by detecting the presence of parasite DNA in amniotic fluid or cord blood (39).

Other Diagnostic Methods: Imaging (e.g., CT, MRI) in Severe Cases, Histopathological Examination

For patients with severe manifestations, such as toxoplasmic encephalitis, imaging techniques like CT (computed tomography) or MRI (magnetic resonance imaging) are often used. These imaging modalities help identify characteristic brain lesions caused by the infection, including ring-enhancing lesions, which are indicative of toxoplasmic encephalitis (40). Histopathological examination of biopsy samples from affected tissues can also confirm the presence of the parasite. In cases of ocular toxoplasmosis, fundoscopic examination of the retina may reveal characteristic lesions, such as retinochoroiditis, providing further diagnostic insight (41).

Table 3: Diagnostic Methods for Detection of Toxoplasma gondii Infection