The Poor Man’s Disease

Perhaps the lesser known of the infectious disease of Southasia, and the most neglected, is Kala-azar. The name stands for "Black Sickness," because of the darkened colour assumed by the skin of some patients. Kala-azar is the Mogul period vernacular name of visceral Leishmaniasis, a disease fatal if not treated, that annually affects 500,000 people in 69 countries and has a population at risk of 350 million people. 90 percent of cases occur in Bangladesh, India, Nepal and Sudan.

Cause, symptoms, and distribution
The leishmaniasis are different illnesses caused by infection with a parasite called a protozoan, a single-celled organism considered to be the most simple in the animal kingdom. There are three forms of leishmaniasis – the cutaneous, the muco cutaneous and the third form that affects several organs and is called visceral leishmaniasis or Kala-azar. The last form of this disease is the one prevalent in India and Nepal.

The symptoms of Kala-azar include highly undulating fever, weight loss, fatigue, abdominal pain, cough and diarrhoea. Among the clinical signs are a dark colour of the skin, and enlargement of the spleen, liver and lymph nodes.

Kala-azar is normally present in areas of drought, famine and densely populated villages with poor or no sanitation and is not uniformly distributed in the affected areas. Among those most commonly affected are older children and young adults of both sexes with male preponderance. As a result of migration patterns, in recent years foci of Kala-azar are also present in cities where the poor live in densely populated ghettos in sub-standard conditions.

Early history
Kala-azar made its first documented attack on humans in Jessore District – now part of Bangladesh – in 1824, where it started in the village of Mohamedpur. The disease presented itself with typical signs and symptoms: darkened skin and wasted bodies with protruding abdominal veins. The weakened patients usually ended their lives amidst serious bouts of dysentery or pneumonia. In three years, it is estimated that this epidemic caused the death of 750,000 people.

Kala-azar had the characteristics of a communicable disease, and apparently spread through traffic routes. A few years after it was initially detected, the disease had expanded rapidly by roads and water through the entire Ganga plain, leaving death and destruction in its wake. A British civil surgeon working in India in the 1870s wrote of villages "in which not a healthy person was to be met with, while repeated relapses of fever, daily deaths, loss of their children, increasing depopulation of their villages and the absence of hope for better times, has so demoralised the population that they neglected to avail themselves of medical and other aid, unless brought actually to their homes".

The disease also appeared in Assam, carried by British steamers serving the Ganga and Brahmaputra rivers. Kala-azar ravaged the region, and for the next 25 years Kala-azar killed almost a fourth of the population in some parts. With what author Robert S Desowitz calls "remarkable epidemiological insight", the people of Assam called the new infection sarkari bemari, 'the government disease', since they associated it with the British presence and the changes they brought to the country. With the extension of the disease from Assam to Tamil Nadu, Kala-azar established permanent residency in the subcontinent.

As happens with many epidemics of infectious diseases, and for reasons not totally known, Kala-azar seems to have a specific cycle of activity, which is estimated to be between 15 to 20 years. With the beginning of the new century the epidemic in the Ganga plain waned, but did not completely disappear. Until 1900, the disease remained a mystery as to its causative agent or the mechanism of its transmission. It took 80 years since it was first documented to find the agent causing the disease.

A British soldier stationed in Calcutta in 1900 who contracted the disease was an invaluable link to the understanding of its origin. The soldier died in England, where his body was autopsied by William Boog Leishman, who had previously worked for the India Medical Service. For years, Leishman had been trying to find the causative organism of Kala-azar. He took a piece of the spleen from the soldier's body and stained the samples. To his surprise he found a new set of bodies which were later called 'Leishman bodies' and which he thought were the cause of the disease. The first person to confirm the finding was Charles Donovan in Madras.

In 1904, the organisms responsible for the disease were recognised as being protozoan in nature, were given the name 'Leishman-Donovan bodies' and received the taxonomic designation of Leishmania donovani. That it was an infectious disease was demonstrated by its spread from household to household, and from village to neighbouring villages. But the question as to how it was transmitted and which the responsible agents were, still remained. After several false starts, researchers were able to find some clues – geography, of all disciplines, proved useful.

Major John Sinton, a renowned specialist on malaria, became intrigued by Kala-azar. Working at the Central Research Institute's Medical Entomology Section at Kasauli, Himachal Pradesh, Sinton found an interesting trail. Sinton probably reasoned that epidemics happen over time, and so they have a history, but they also happen at particular places, so they must have a geographical spread pattern. On examination of the spread pattern he saw that the disease had a restricted distribution in the eastern half of India, from Madras to Assam. When he compared the distribution pattern of the blood-sucking insects with that of the Kala-azar, the map of one species of insects closely coincided with that of Kala-azar  -Phlebotomus argentipes, the silvery sandfly.

Based on these findings, Sinton published a series of papers in 1924 and 1925 proposing the theory that the sandfly was the vector (the carrier) of the Kala-azar parasite, Leishmania donovani. Sinton thought that once infected in a person, the sandfly passes the infectious agent to other persons in whom the protozoan will set up residence and cause the disease.

Testing for proof
Further evidence to accept his hypothesis was needed, however. Robert Knowles and scientists at the Calcutta School of Tropical Medicine fed laboratory-bred sandflies to Kala azar patients. They then dissected the flies and searched for the presence of Leishmania donovani. They were able to find them in the gut, and later in the throat, of flies that had been fed on the patients earlier.

But crucial proof was necessary. Because the sandfly vector becomes infected when feeding on the blood of an infected individual or an animal reservoir host, an infected sandfly had to bite a person, and that person had to come down with Kala-azar to prove that it truly was carrying the infectious agent and that this agent was the cause of the disease.

An Indian physician, CS Swaminath, provided that final proof. Working with Henry Edward Shortt, a professor at the University of London's School of Hygiene and Tropical Medicine, they obtained the collaboration of six volunteers from the hill district of Assam and placed infected flies on them. Three of the volunteers contracted the disease. The finding confirmed that the disease is transmitted from person to person using the sandfly Phlebotomus argentipes as the vector of Leishmania donovani and that this infectious agent was responsible for Kala-azar. This was a significant moment in the history of the disease.

Search for a Cure
Parallel to the evolution of the disease was the search for a cure. Just as geography had helped in finding its vector, history (and cosmetics) helped in finding the first effective treatment for Kala-azar. That treatment, however, had some important secondary effects.

The women of ancient Egypt were known for their concern for looking beautiful and for taking good care of their bodies. They used a cosmetic paste that contained oxides and sulphides of the heavy metal antimony, which had accidentally proved effective in treating some skin disorders close to the eyes of women using that paste. Centuries later, the success in using arsenical and antimonial compounds against syphilis and African sleeping sickness called attention to the potential effectiveness of therapy with these heavy metals for treating Kala-azar patients.

The initial antimony compounds used were extremely toxic and not very effective. In 1935, a new antimony product, pentavalent antimonium (Pentostam) was developed, which was the first effective drug against this disease. This was not enough, however, to eliminate the threat posed by it, since the sandfly vector continued multiplying. What was necessary was a powerful, long lasting, and cheap insecticide that could eliminate the vector of the disease.

Effect of spraying with insecticide
It was discovered in the 1940s that using DDT (dichlorodiphenyl trichloroethylene) to combat malaria had another unsuspected effect. DDT was not only able to kill the anopheline mosquito that was a vector for the most common types of malaria but was also able to act against the sandfly vector for Kala-azar. Actually, because of the characteristics of the sandfly, the insecticide was more effective against them than against the anophelines vectors of malaria. The explanation for this difference is that sandflies (which actually do not fly but just hop from place to place) sit on the walls longer and at lower height than the anophelines, and can thus be more easily reached by the sprayed DDT.

The DDT used in India by the National Malaria Eradication Program in the 1940s ravaged the sandfly population and interrupted the transmission of Kala-azar. By the mid-1950s no new cases of Kala-azar were being recorded and in the mid-1960s Kala-azar had become an almost forgotten disease in the country. However, when the national anti-malaria campaign was interrupted in India, Kala-azar reappeared in 1970 in the village of Vaishali, in Bihar.

Vaishali, where the Buddha had his last enlightenment, now also had the dubious distinction of being the place where Kala-azar reclaimed its territory. In the late 1970s Kala-azar travelled downstream and appeared in Bangladesh, and shortly afterwards entered part of the Tarai, the agricultural plains of Nepal bordering India, where it became endemic. The Tarai covers 17 percent of the total land area of the country, where 48 percent of Nepal's total population presently lives.  Kala-azar is now present in 13 districts in Nepal, bordering Bihar in India.

The treatment of the disease cannot ignore that globalisation and trade, combined with increasing socio-economic disparities has led to increased international migration. India, Nepal, Bangladesh and Bhutan are an example of countries with porous borders and frequent migration of population. Migrants are particularly vulnerable populations, and their movement across borders entails risks for the propagation of communicable diseases and infections such as HIV/AIDS, tuberculosis, malaria and Kala-azar. This makes it even more imperative to find ways to control the spread of those diseases.

Asymptomatic or sub-clinical infections
An important finding from the point of view of preventing Kala-azar is that most infections remain asymptomatic or sub-clinical. It is estimated that asymptomatic infections outnumber those that are symptomatic by an estimated ratio of 10:1, or even higher. Due to the high number of persons who remain asymptomatic, but can still infect other people, effective control of the infection is very difficult.

Panduka Wijeyaratne, resident advisor for the Environmental Health Project in Nepal (funded by USAID) is an expert on Kala-azar. For the past several years, this project has carried out a series of actions aimed at reducing the threat of this disease. He has been working with leishmaniasis for the last 20 years and for 10 years had a network of several countries working on this problem.

Wijeyaratne told this writer that, "What we have already seen is only the tip of the iceberg, because below are all these asymptomatic cases, some of which will become symptomatic, particularly among the poor". Wijeyaratne adds, "Kala-azar is a controllable, treatable disease that affects those most neglected and dispossessed".

In Nepal, most cases of Kala-azar had been diagnosed based on the clinical picture and relatively non-specific tests such as the total white blood cell count or by a test called the aldehyde test. The most specific one is demonstration of parasites, usually carried out by taking an aspirate from the spleen or bone marrow and examining the smear under a microscope.

A new test recently developed is called k39. The test requires only one drop of finger-prick blood and replaces the traditional diagnosis by biopsy of the liver or spleen or by puncture of the bone marrow or a lymph gland.  Nepal at present has the diagnostic Kit-39 for Kala-azar. This new test offers interesting possibilities for eventually eliminating the disease, since it will be much easier to diagnose those affected — even if asymptomatic — and start the treatment of the disease earlier.

Control of the disease
Both effective treatment and prevention are the cornerstones of control of this disease, but there have been three serious complicating circumstances. Firstly, was the finding that co-infection with HIV was becoming more frequent, making treatment even more difficult. Secondly, there was the increasing resistance to pentavalent antimonium (Pentostam), which had been the best weapon against the disease for more than half a century. Finally, there was the matter of population movements across borders.

A significant recent development has been the identification of the drug miltefosine as the first oral agent against the disease. Presently, clinical trials of this drug are being conducted in Nepal, and if miltefosine proves its effectiveness it will be a tremendous step forward in the fight against the disease, since it will replace the painful and highly inconvenient treatments presently used.

Another recent development has been the agreement between Nepal and India's National Vector Borne Disease Control Programme. Through this agreement, both India and Nepal will share information and resources as part of cross-border collaboration efforts, which will increase dramatically the effectiveness and efficiency of efforts for controlling the disease.

Impact of the disease
Although the number of cases of Kala-azar in Nepal is estimated at approximately 2,000 per year, this number does not take into account the number of asymptomatic cases, nor gives an indication of how serious an epidemic of this disease can become if the risk factors are allowed to increase. In addition, the disease has a tremendous economic impact on the affected families, particularly since a sick person in the family means that sooner or later other members are also going to be affected, including those responsible for the family's economic support.

This writer visited the village of Juri, a heavily endemic area in the Janakpur District and met a man in his early forties (he ignores his real age), Ram Sewak, from the Danuwar, a low socio-economic caste. Ram Sewak revealed that of the 35 persons in his extended family, 17 had had Kala-azar. His own wife had died of the disease; he had had to sell his plot of land to pay for her care and had been left destitute. Unable to take of his children, a boy of 10 and a girl of eight, he had sent them to live with a maternal uncle. He now does not have a home and does whatever work he can find. There were several similarly tragic stories in Janakpur, the result of the predations of Kala-azar.

Kala-azar is a good example of a bad situation, a disease that affects those of low socio-economic level in households where hygiene and sanitation are poor, circumstances that favour the spreading and multiplication of the sandfly vector of the disease. What can be done to improve the situation?

Perhaps the best approach is to try to diminish the risk factors/situations associated with the disease. The Sandfly is attracted to livestock, breeds in animal waste, and is present in wall cracks, and damp floors in the homes. Children should avoid sleeping on the ground floor, and wall cracks should be repaired. Bed nets and spraying houses with insecticide have proven to be effective measures to avoid the disease. At the same time, there should be a campaign at the community level to reduce sandfly breeding sites using local materials, and education both at the community level and with health staff at all levels aimed at improving case recognition, surveillance and reporting.

Can Kala-azar be controlled?
An important element in the fight against this disease is to have the political will to carry out the necessary actions, something that frequent political changes make difficult. Another person, Vijay Kumar Singh, senior physician at Janakpur Zonal Hospital, was eager to communicate his experience in dealing with Kala-azar for over 20 years and seeing over a thousand patients. He said that one of the reasons not enough attention was paid to the disease, was the fact that it affected the lower socio-economic classes, the voiceless ones. Ishwor Prasad Upadhyaya, at the Primary Health Care Centre at Gaushala, Mahottari District, had no doubts, "Kala-azar is a poor man's disease".

On being asked if Kala-azar could be controlled and eventually eliminated, Vijay Kumar Singh said: "Yes, it can… But we need at least 10 years of sustained effort. What is necessary is a complementary set of activities including early detection at community level, prompt treatment, regular follow up and completion of treatment, as well as close synchronisation of activities between India and Nepal, and continuing political will". As things stand now, all the elements are in place to effectively control this dreadful disease.

~ Dr. César Chelala is an international public health consultant.

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Himal Southasian