Parasitic infections (also known as parasitism) are when one organism, through the expense of a host, survives and reproduces. Worldwide, millions of people suffer and die due to the complications caused by parasitic infections. In some instances, parasitic infections cause neurological symptoms, when the infection prolongs. There are new findings that show being positive for parasitic infections increases the chances of having adverse mental health conditions by four times.¹ 

Overview

Approximately 80% of people, in low-to-middle-income countries experience a mental health disorder within their lifetime. Mental health disorders can cause significant distress, impair daily functioning, and result in abnormal emotions, thoughts, and behaviours. Findings now link a higher prevalence of mental health disorders in regions of the world where parasitic infections are common, hinting at a likely link between the two.¹

Understanding parasitic infections

What are parasitic infections?

Three types of parasites can infect and lead to disease in humans. These are:

• Protozoa are unicellular (i.e., one-celled) organisms having relatively complex cellular functions. These free-living organisms are found worldwide and have over 50,000 species.² They are
  • Malaria caused by Plasmodium
  • Leishmaniasis caused by Leishmania 
  • Sleeping sickness and Chaga disease are caused by Trypanosoma and transmitted by vectors. Tsetse flies for sleeping sickness and triatomine bugs for Chagas disease
• Helminths are elongated, flat, or round-bodied worm-like organisms that are sub-categorized into flukes (trematodes), tapeworms (cestodes), and roundworms (nematodes).³ These organisms exist worldwide affecting over 1 billion people. Examples include:
  • Schistosomiasis caused by Schistosoma mansoni 
• Ectoparasites: commonly referred to as insects and arachnids (spiders/spider-like bugs). Ticks, lice, mites, and fleas are in this category. They inhabit the skin of the host and are more likely to be found near livestock and flourish in areas of warmer climates worldwide. Examples include:
  • Pediculosis (lice in head and body) caused by Pediculus humanus capitus (hair) and Pediculus humanus corporis (body)

How parasites affect the body and brain

The human body contains powerful defence mechanisms collectively termed the immune response. The immune response is a complex web of interactions that ultimately seeks to destroy any invading pathogen (organisms that cause disease). When parasites infect, they alter the body to suit their functions of survival and reproduction, resulting in adverse changes to the host body. The immune system is activated to remove these parasites. However, when infections are prolonged (chronic), this force for good persists too long, causing damage to the body and brain.⁴

Mechanisms through which parasitic infections affect the brain

Direct brain invasion

Diseases caused by protozoans and helminths, which carry high mortality and high morbidity, such as malaria and schistosomiasis, can lead to acute (short-term) or chronic (long-term) neurological complications. 

• Cerebral malaria is an example of a deadly complication resulting from the invasion of Plasmodium falciparum (a specific strain of malaria parasite) infection leading to coma, seizures, and, if not treated, death.⁵ People who survive cerebral malaria suffer from permanent neurological complications and cognitive problems

Immune system overactivation

When the immune system is overactive, acutely or chronically, chemicals that enhance inflammation under normal circumstances, prevent the disease from wreaking havoc. These chemicals, termed pro-inflammatory cytokines and chemokines, can lead to damage. Inflammation in the brain, referred to as neuroinflammation, can lead to psychiatric and cognitive issues. For example:

• The World Health Organisation describes Human African trypanosomiasis caused by the protozoa Trypanosoma brucei can, in its final stages, end with meningoencephalitis in human hosts
  • Meningoencephalitis is meningitis, inflammation of the membrane of the brain, and encephalitis,  inflammation of the brain
  • This parasitic infection causes psychiatric disturbances (such as hallucinations and fear-like behaviour), headaches, sleep disturbances, and in some cases, death

The long-term impact on mental health is not fully understood. However, studies have shown that by suppressing the immune system (for the parasite to survive in the host), certain parasites (including T. brucei) can alter the release of neuromodulators. These chemicals help balance mental states and, when disrupted, can lead to conditions such as depression and anxiety. ⁶ 

Cognitive impairments due to chronic parasitic infections

Neurotoxoplasmosis is caused by the protozoan parasite Toxoplasma gondii (T. gondii is a food-borne disease of the world), which can result in life-long persistence. T. gondi can remain in cells of the brain known as neurons (the functional cells of the brain) and interact with the brain's immune system.

Attention deficits

A recent study found a 2.8-fold increase in the odds of an individual having attention-deficit /hyperactivity disorder (ADHD) when also positive for T. gondii. This was the first study to suggest a link between parasitic infection and ADHD. Further studies are needed to explore this link and how to treat it. The reason is unclear, but a link to neuroinflammation is likely.⁸

Behavioural alterations

Survivors of severe malaria (cerebral malaria), and in some cases non-severe malaria, show signs of emotional reactiveness, and conduct disorders such as impulsive and aggressive behaviour, especially in child survivors. The theory is that following cerebral malaria, children become more predisposed to mental health disorders due to severe inflammation in the brain: affecting the development of the brain.⁹

Mental health consequences of chronic parasitic infections

Depression and anxiety

Depression and anxiety are complex neurological conditions with multiple aetiologies (causes), including genetics, environmental conditions, personal aspects, and more. 

A person's genetic background increases the likelihood of developing depression and anxiety in certain environments. Interestingly, the same genes are associated with anxiety disorders (and depression): PSEN1 and GRIK3. These same genes are associated with immune activation; hence, when parasites invade the genes are turned on. Suppose an individual harbours a pathogenic gene, a genetic predisposition increases the susceptibility of an individual to a disease/disorder. In that case, parasitic infections can lead to the activation of these genes, which can cause symptoms of depression and anxiety. 

Sleep disorders

Human African trypanosomiasis, also known as sleeping sickness, has 10,000 new cases yearly. It is the best-characterised parasitic infection that affects sleep patterns. The disturbance this parasite causes to the circadian rhythm, the body clock, regulates wakefulness and sleep. It releases pro-inflammatory chemicals by the immune response to the parasite. It causes circadian rhythm changes and sickness. Unlike most other illnesses, sleeping sickness causes an increase in sleep but a lack of restfulness.¹⁰

Sleeping sickness due to an ectoparasite, the Tsetse fly, feeding on human blood. 

Global impact

Parasitic diseases that affect the brain and nervous system are a source of morbidity and mortality worldwide. Millions of children and adults are affected by the neurological, cognitive, and mental health problems that follow parasitic infections.  

Though difficult to accurately measure, according to the World Health Organisation (WHO), 23.2 million people are affected by food-borne parasitic infections (mostly protozoa) alone. Malaria has resulted in 45 million DALYs (disability-adjusted life years): a statistical measure quantifying the burden of disease on a population. DALYs calculate the years of life lost due to premature death or years lived with a disability.¹¹

Additionally, studies have found that among people with parasitic infections, 58.2% have a mental illness compared to 41.8% of uninfected people with mental illnesses.¹ A four-fold increase. 

Therefore, the burden of parasitic infections on human populations is truly horrendous, with many lives negatively affected. 

Diagnosis and treatment of cognitive and mental health effects

Parasitic infections of the brain are diagnosed through neuroimaging techniques. These include:

• Magnetic resonance imaging (MRI): detailed 3D image of the brain produced using strong magnets combined with radio waves
• Computed tomography (CT) scan: medical imaging using X-rays and computer programs to produce a detailed brain image

However, though these techniques enable a medical professional to identify a parasitic infection, the considerable overlap between different types of parasites means other specific diagnostic tools are required. Such as:

• Cerebrospinal fluid analysis helps to diagnose diseases of the brain and nervous system. The presence of parasites or their by-products of the infection can be detected to make accurate diagnoses
• Blood tests (serology) for antibodies or parasite antigens (pieces of parasite) give specific diagnoses 
• Fluid attenuation inversion recovery (FLAIR) is a form of MRI that reduces artefacts that interfere with the imaging by having a clear brain contrast for accurate diagnosis

Recovery and rehabilitation

Malaria

Malaria is treated by artemisinin-based combination therapy, this treatment technique uses two or more drugs that work against malaria in different ways. This technique is fast-acting and reduces the likelihood of drug-resistant development. 

Some neurological symptoms following cerebral malaria in children (and adults) subside following recovery, such as cortical blindness, aphasia (inability to understand and produce speech), and tremors. However, depending on the severity of the disease, seizures, language deficits, memory impairment, and behavioural alterations can persist.¹² Luckily, research shows that even these can recover, despite nine years following the episode of cerebral malaria.

Toxoplasmosis 

People who are healthy and have functional immune systems can recover from toxoplasmosis without the need for drug treatments. However, in those who are immune compromised, a combination of pyrimethamine and sulfadiazine is used as a treatment regime. ¹³ 

Human african trypanosomiasis 

There are multiple treatment options available depending on the location of the parasite and the parasite variant: 

• If trypanosomiasis has not spread to the brain, suramin for T. brucei rhodesiense, or fexinidazole (or pentamidine) for T. brucei gambiense
• If trypanosomiasis has affected the brain or cerebrospinal fluid, melarsoprol for T. brucei rhodesiense, or fexinidazole, eflornithine, nifurtimox or melarsoprol is used for T. brucei gambiense

Healthcare providers will continue to monitor affected individuals for 2 years to ensure complete parasite removal. If symptoms return, a re-test for Trypanosoma brucei is undertaken.⁶ 

Summary

Parasitic infections constitute a worldwide problem affecting millions of people. The long-lasting impact on mental health and cognitive function can result in psychological changes, behavioural changes, sleep disturbances, depressive mood disorder, and anxiety disorder. Research continues to unravel how parasitic infections contribute to long-term health even after treatment and potential remedies. However, existing medication, when taken rapidly following diagnosis, helps reduce symptoms and can increase the chances of a full recovery.