Visceral leishmaniasis, known in India as kala-azar or black fever, is a parasitic disease that kills an estimated 500,000 people a year, 90 percent of them in India, Nepal, Bangladesh, Brazil and Sudan.
In India, the disease is endemic in the northeastern Indian State of Bihar – the epicenter of kala-azar in the region – and in Jharkhand, Uttar Pradesh and West Bengal. It manifests with irregular bouts of fever, substantial weight loss, swelling of the spleen and liver, and anemia. Left untreated, kala-azar is almost always fatal, especially in children,
According to the World Health Organization (WHO), “Leishmaniasis is a poverty-related disease. It affects the poorest of the poor and is associated with malnutrition, displacement, poor housing, illiteracy, gender discrimination, weakness of the immune system and lack of resources. Leishmaniasis is also linked to environmental changes such as deforestation, building of dams, new irrigation schemes and urbanization, and the accompanying migration of non-immune people to endemic areas.”
Leishmania, the protozoan parasite that causes kala-azar, spreads to humans through the bite of infected female sandflies.
The sandfly bite causes tissue damage that, although minimal, promotes recruitment of neutrophils to the site of injury. Neutrophils are powerful phagocytic cells that participate in the primary immune defense mechanism of the host. However, neutrophils are also the primary target of leishmania — the parasite is not killed by the neutrophils — rather, the parasite survives within them until the neutrophils are engulfed by macrophages. Leishmania is not even killed during this step of the immune response — instead, it survives and multiplies inside the macrophages. There, it modulates the normal defense mechanisms, it increases the membrane fluidity of the macrophages and disrupts lipid rafts, thus impairing their ability to present the antigen. Thus, Leishmania starts a process that hijacks the entire immune system for its survival.
No vaccine has yet been licensed to prevent infection.
Drugs to treat the disease are toxic and expensive. In Bihar, where 90% of India’s large kala-hazar burden is located, the parasite has developed resistance to one of the main treatments, a group of drugs known as antimonial preparations. Indeed, the effectiveness of the antimonial preparations is now so low that these drugs are no longer recommended in the Indian subcontinent, whereas they remain an essential part of the treatment for visceral leishmaniasis in South America and sub-Saharan Africa.
Researchers at the Universities of Dundee and Aberdeen in the U.K. report, in an article published in the journal Proceedings of the National Academy of Sciences of the United States of America, that arsenic contamination of the water supply may have played a significant role in building the resistance of leishmania to the antimonial drugs.
In the article, the researchers state: “The Indian subcontinent is the only region where arsenic contamination of drinking water coexists with widespread resistance to antimonial drugs that are used to treat the parasitic disease visceral leishmaniasis.” The article (October 28, 2013) is titled “Chronic exposure to arsenic in drinking water can lead to resistance to antimonial drugs in a mouse model of visceral leishmaniasis”
Professor Alan Fairlamb, senior author of the article, said: ”The water supply in Bihar has been found to be affected by contamination from naturally occurring arsenic in the groundwater. What we have been able to show through experiments is that arsenic contamination of water can build resistance in Leishmania parasites to antimonial treatments.”
The researchers performed their experiments in animals. They serially passaged the leishmania parasites in mice. During the passages, mice received arsenic in drinking water at environmentally relevant levels. Results from these experiments show that after five monthly passages, the leishmania parasites become stably resistant to an antimonial preparation.
Meghan Perry, lead author of the study, said: “Arsenic contamination of the groundwater is a serious issue in Bihar. Many villagers continue to drink arsenic contaminated water as they have no alternative. Knowledge of the dangers of arsenic pollution is low and mitigation projects are not reaching all of those in need. Arsenic can lead to a myriad of health issues and our research adds to this long list. Community education and alternative drinking water sources are desperately needed.”
This new study points out an additional detrimental effect of arsenic in drinking water. Another example of adverse effect mediated by arsenic and recently demonstrated is the increase in respiratory diseases following fetal exposure.