A neglected disease

 

 

 

On 23 September 2005, the Dutch secretary of Defence reports to Parliament:
Early this September the skin disease ‘cutaneous leishmaniasis’ was diagnosed at the Amsterdam Medical Centre among four soldiers of the battalion that was stationed in Mazar-e-Sharif in Afghanistan. In the past two weeks, about ninety Dutch soldiers who were involved in the establishment of the compound or who provided support for Parliament elections in Afghanistan, as well as several journalists that visited Mazar-e-Sharif, have been diagnosed with this disease.

This Global Medicine’s Neglected Disease is leishmaniasis (also known as Orient boil, kala-azar or sandfly disease). It is a tropical disease, caused by intracellular protozoan parasites and transmitted by the sandfly, often resulting in horrible disfigurements or even death.

Leishmaniasis typology

There are three types of leishmaniasis. The first and the most common type is cutaneous leishmaniasis that creates an open sore and subsequent skin lesion at the site of the sandfly bite. Patients recover spontaneously from the lesion. However, an unsightly scar remains at the site of infection and people often suffer from psychologically destructive stigma. Mucocutaneous leishmaniasis is characterized by partial or complete destructive, irreversible lesions of the mouth, nose, and throat cavities. Although the disease is serious, less than 5% of cases are fatal. The third type is visceral leishmaniasis or kala-azar (black fever). This is the most serious type, in which internal organs are infected and over time fever, diarrhoea, lower immune status, severe bleeding, inflamed and enlarged liver and spleen or anaemia occur. In the medical field, visceral leishmaniasis is one of the notorious causes of markedly enlarged spleen, which may become larger even than the liver. Untreated visceral leishmaniasis results in death within two years after initial infection. There are more than 20 species of Leishmania parasites that infect humans. Different species are endemic in different regions of the world. Also, the species determines which symptoms a patient will present with. Immunity for that species is often acquired after infection with a species of Leishmania.

Transmission

The Leishmania parasite is transmitted by the bite of a tiny insect (so small it can fly right through malaria preventing bed nets): the sandfly. If a female feeds on an infected host, the parasite is ingested with the blood. The parasite enters a human or other mammalian host through the consecutive bite of the sandfly. Inside the host, the parasite invades the host’s macrophages, multiplies and eventually kills the host cells. Leishmaniasis symptoms manifest from this cell loss as epidermal skin damage, damaged red blood cells leading to anaemia, and destroyed T-cells resulting in lowered immune status. There are only a few Leishmania species for which humans can function as a reservoir. Pet dogs are the most common and problematic reservoir in developing countries.

Epidemiology

Poverty, famine and mass population movement have led to a tremendous increase in leishmaniasis incidences in the last decennia. The majority of new cases are unreported or undiagnosed and thus the magnitude of leishmaniasis is greatly underestimated. Official data only report 600.000 annual infections. However, the World Health Organization (WHO) estimates 2 million new cases annually, which adds to the world wide prevalence of 12 million cases. Leishmaniasis has been reported in 88 countries worldwide. 

Diagnosis

In the case of cutaneous and mucocutaneous leishmaniasis, diagnosis is usually based on the appearance of the lesion(s). Microscopy of the parasite in Giemsa stain may reveal the parasites in up to 70% of patients. Culture is also an option, but problematic due to the scantness of organisms. Diagnosis for visceral leishmaniasis is made by observing the parasites in a Giemsa stain or growing culture of bone marrow, splenic, hepatic, or lymph node aspirates. Other diagnostic tools such as PCR, ELISA or immunoblotting can be used, but are usually unavailable in most endemic areas. Finally, a leishmaniasis skin test (Montenegro test) comparable to the Mantoux test for tuberculosis, is available. It becomes positive three months after initial infection and remains positive for life.

Treatment

Reasonably effective cures are obtainable in the treatment of leishmaniasis. Cutaneous leishmaniasis is often self-limiting. Treatment is indicated to prevent scarring and progression to mucocutaneous infection. When risk for mucosal spread is low, topical treatment (antimony compounds or paromomycin) can be used. With more invasive lesions or mucosal involvement, as well as for visceral leishmaniasis, systemic therapy is indicated. Two recently developed drugs, miltefosine and paromomycin, show promising results. As an appurtenant benefit they are both relatively inexpensive.

Risk factors and prevention

Several factors contribute to the current spread of leishmaniasis. Here below, the most important ones are mentioned as well as concomitant possibilities for prevention.

Poverty

Lack of money for appropriate diagnosis or treatment contributes greatly in developing countries to the burden of disease. Poverty also relates to all other risk factors mentioned below, therefore it is a large contributor to the causes of the disease.

 

Impaired host health

Malnutrition is a well-known risk factor for leishmaniasis and it thrives in cases of famine, emergency and mass population movement. Co-infection with HIV is also common.

 

Education

Knowledge to identify symptoms and prevent transmission is lacking, especially in illiterate populations. Educational interventions prevent leishmaniasis infections by informing the host about disease symptoms and about how to avoid transmission. Something as simple as sleeping in beds at least one meter above the ground is a promising strategy to reduce night-time sandfly bites.

 

Environment

Rural areas with lack of proper sanitation and with widespread deforestation provide the sandfly with an ideal breeding ground. Nowadays however, urban outbreaks of leishmaniasis are also common. Large numbers of individuals are at risk of infection because they live in densely populated urban areas and are in close contact with rural migrants carrying the causative parasite. Environmental interventions include the elimination of random garbage and animal burrows which greatly reduce the sandfly population. Also, sandflies feed on plants. The paper flower damages the Leishmania protozoa in the sandfly’s gut. This permanently impairs the transmission of leishmaniasis from sandfly to human or other hosts. Immediately after taking a blood meal, sandflies cannot fly away and rest on house walls. Insecticides sprayed on the interior and exterior walls of houses reduce the number of sandflies and subsequent infection rates. In addition, even though the sandfly flies right through malaria preventing mosquito nets, insecticide-impregnated bed nets may reduce transmission.

 

Animal reservoirs

As dogs are the most common and most problematic reservoir, animals with apparent leishmaniasis infection should be culled. Dogs that do not show any visible signs of infection might be fitted with an insecticide-impregnated dog collar to deter future sandfly bites.

Conclusions

Leishmaniasis symptoms range from self-limiting single cutaneous laesions to potentially horrible disfigurements and possible death. Treatment and accurate diagnosis is possible, but often not available. Many factors, almost all related to underdevelopment, contribute to the heavy burden of disease of leishmaniasis.

About the authors

All authors are enrolled in the Master of Science programme on International Public Health at the Vrije Universiteit Amsterdam. 

Further reading

• WHO (2007). Leishmaniasis: Burden of disease, magnitude of the problem.
• WHO (2007). Parasitic and Neglected Diseases: The PAHO Regional Program.
• Emedicine: Leishmaniasis, by Renee Y Hsia, MD, MSc. Last Updated: Mar 31, 2008.

References

1. Shyam S, Jha TK, Chandreshwar PT, Prabhat KS, Bhattacharya SK. Injectable Paromomycin for Visceral Leishmaniasis in India. NEJM 2007(356): 2571-2581.
2. Sundar, S., Jha TK, Thakur CP, Bhattacharya SK, Rai M. Oral miltefosine for the treatment of Indian visceral leishmaniasis.Trans R Soc Trop Med Hyg 2006;100(suppl 1): S26-33.