Global awareness of Leishmaniasis (LEESH-muh-NYE-uh-sis) remains limited, predominantly due to its concentration in poorer nations.¹ However, with one million new cases per year,² the disease persists and for many becomes a worrying threat. 

Cases are localised to tropical and subtropical regions,¹ attributed to the bite of an infected female sandfly that requires blood meals to complete its lifecycle and produce offspring. The bite serves almost like a transport network, enabling the parasite, leishmania (LEE-sh-MAY-nee-uh) to infect humans, persist, and engender disease.

Leishmaniasis presents itself in three forms: cutaneous (skin lesions), mucocutaneous (lesions within airways), and the most fatal, visceral (damages internal organs). Successful treatment relies heavily on early detection and diagnosis.³ However, it remains limited and far from satisfactory.² Further to this, over the last 20 years of drug resistance, leishmania has become a global threat.² 

What is leishmaniasis? 

Leishmaniasis is a result of infection by microscopic parasites due to leishmania species, so small you need a microscope to identify them. These organisms call the cells of your immune system home and use them as an almost delivery service to get essential nutrients, feed, and replicate.

There are currently 20 known species of leishmania known to cause disease, with 90 species of sandfly known to carry them.⁴ 

Cutaneous leishmania

Recognised as both the most common and less fatal form,² cutaneous leishmania causes skin sores. They are often painless and usually develop weeks or months after the initial bite.⁵ Usually, this form does not require medication, but the resulting scarring can be lifelong. 

Mucocutaneous leishmania 

Similar to cutaneous, this form results in skin sores but within the mucosal membrane (nose, mouth, and airways). It rarely improves on its own and can often be fatal if untreated.¹ Complications also include the destruction of nasal architecture, facial disfigurement, and airway compromise.⁶

Visceral leishmania 

Defined as the most fatal, visceral leishmania affects internal organs, symptoms manifest a few months to a year after initial infection ¹. However, unlike the others this form is caused by a small number of species.⁵ 

What are the symptoms?

Whilst the three forms share some similarities, they each exhibit symptoms that set them apart from one to another.

Cutaneous: Red sores that may change in appearance over time and can progress to ulcers. They are usually but not always painless.⁶

Mucocutaneous: Ulcers and inflammation within the mucous membrane of the nose, mouth, and throat.⁶

Visceral: Sudden and lasting fever, weight loss, swelling of the spleen and liver (seen in the abdomen), low iron levels, fatigue, and general weakness.^6,1 

Being aware of the typical signs and symptoms is the best approach for treatment. Early identification can help navigate treatment routes and improve outcomes, especially in patients known to have travelled to affected areas. 

Who is at risk?

Currently, leishmaniasis affects 90 known countries across South America, Central America, the Middle East, South Asia, and East Africa.^1,4 Estimates suggest that 12 million people are infected, with 90% of the global burden across India, Nepal, Bangladesh, and Brazil.²

The risk is highest in areas that increase sandfly breeding and as a result the likelihood of being bitten. These insects commonly favour more rural areas, where living conditions are typically poorer, lack proper sanitation and hygiene, and are crowded.⁵

In addition, the risk is determined by the individual. In cases of malnutrition, diets containing less protein, iron, vitamin A, and zinc increase both the likelihood and severity of disease.⁴ Since it weakens the immune system the body isn’t able to fight off the infection with the same power. The parasite uses this to its advantage, replicating more and causing more severe damage.

How is it diagnosed? 

Testing relies on the detection of the leishmania parasite, specifically fundamental for treatment due to varying clinical implications.⁷ Skin biopsies from ulcers are commonly used to detect cutaneous and mucocutaneous leishmaniasis.¹ For visceral leishmaniasis, best practice suggests the use of needle biopsies from either the spleen, lymph nodes, or bone marrow.¹ In all cases, visual identification through a microscope is required to confirm cases. 

Drug resistance leishmania 

The concept of drug resistant parasites is scary to grasp, at least at first. However, with correct and deeper understanding not only can the issue be addressed but future cases can benefit from understanding how to mitigate whilst approaching with better treatment.

For leishmania, this means the parasite no longer responds to treatments used to clear it and therefore persists within the host. However, the concern surrounding this issue is relatively recent and only became relevant within the last 20 years.² The first indication was from North Bihar, India where 30% of patients stopped responding to the most widely used treatment, pentavalent antimonials.² The issue also poses a significant health effect on communities, with a higher risk of disease spread, longer hospitalisations due to complications, and therefore associated costs.⁸

Drug resistance can occur for a variety of reasons. In the case of leishmania, treatment options have always been limited, with a focus on pentavalent antimonials for the past 60 years.² These drugs block the action of specific enzymes, causing essential body functions to be disrupted and eventual parasite clearance. However, this overreliance and misuse give the parasite more chances to adapt and counter. In many species of leishmania, resistance is developed through the upregulation of proteins.⁸ These either act to destroy or reduce the effect of pentavalent antimonials.⁸

Despite the challenges, patients are usually able to fully recover. It is important to recognise that drug resistance does not mean a lack of treatment but that the first line may not always work. Research has shown that there are other options, yet to be fully explored. 

New insights show:

• The development of simple, patient-friendly oral medication (LXE408) which offers an alternative to current complex injected therapies⁹
•  Several already in-use drugs have inhibitory effects on leishmania, including acebutolol (beta blocker), prilocaine (local anaesthetic), and phenylephrine (decongestant)¹⁰
•  Photodynamic therapy, which involves combining a light source and drug activated by light to kill infected cells is a new approach¹¹
• Resistance develops slower, where two drugs (combination therapy) are used to treat infections¹²

How to prevent infection

An often-overlooked way to manage leishmaniasis is to prevent the infection from happening in the first place. By minimising contact with sandflies, the risk is significantly reduced. It is these preventative measures that play a critical role in breaking the cycle of infection and are vital in fighting against emerging drug resistance. 

Preventative measures:

• Protective clothing, including long-sleeved shirts and trousers reduce areas of exposed skin¹
•  Applying insect repellents containing active ingredients, the most effective, usually contain DEET. These should be reapplied¹³
• Treating living and sleeping areas with insecticide with a focus on where sandflies may enter or rest such as windows or doors¹³
•  Ensure spaces are enclosed, either through keeping windows and doors shut or using a screen to prevent sandfly entry¹
•  Regularly cleaning living areas to prevent environments that favour sandfly breeding whilst improving overall living conditions¹

Summary 

Whilst drug-resistant leishmaniasis is still an emerging global threat, it is important to contextualise the risk. Drug resistance does not mean untreatable, and in fact, many patients recover without treatment. With the information contained within this article, we hope to empower patients and aid in finding the correct action plan quickly. Although resistance complicates treatment, it also pushes forward initiatives in research, explores new drugs, and strengthens our overall understanding. Although full eradication remains a long-term goal, staying informed and educating on risk can make a real difference. Remember, if someone you know is feeling overwhelmed or scared you aren’t alone, we at Klarity are here to help.