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Integrated Human Practices

A Talk with Dr. Nahid Ali

Once we had created the basic framework of our project, it was time to understand the ground realities of the disease that we had taken on. We visited CSIR-IICB (Council of Scientific and Industrial Research – Indian Institute of Chemical Biology), and met Dr. Nahid Ali, a leading scientist of the country working in the field of Leishmaniasis.

After Dr. Ali had understood the details of our project, she briefed us about the situation of the disease across the globe. She told us that even though incidences of Leishmaniasis have decreased due to active government plans to combat the disease, the decrease can also be attributed to the cyclical nature of the disease, as previous statistics have shown that the disease prevalence shows a decadal increase-decrease cycle, so it cannot be said with certainty if the decrease is due to effective treatment or due to this cycle.

Another problem that has surfaced is the number of increasing Post Kala-Azar Dermal Leishmaniasis (PKDL) cases, a glaring problem which requires immediate attention. PKDL patients are individuals who have been successfully treated for Visceral Leishmaniasis, but the parasite resurfaces in the form of skin lesions. These do not respond to conventional treatment and are a potent reservoir of the parasite. For example, in African nations, almost 50% of patients previously infected with Leishmania develop PKDL! All these factors together can come together and lead to an outbreak of epidemic proportions. According to her, unless the incidence of the disease reduces to below 1 in 10,000 individuals, the disease should be considered an extant risk, and measures should be continually taken.

We then discussed with her the effectiveness of the treatments currently available in the market. She told us about Pentavalent Antimonials, which were the drugs of choice for decades in the Indian subcontinent. But not only did these show toxic side effects, the high usage led to a widespread resistance in the parasite against these solutions.

Amphotericin B, another compound used against Leishmaniasis is also toxic and requires close medical attention for a long period of time. In her words, “Amphotericin B somehow stimulates macrophages, activating the immune system, and makes it less susceptible to future infections (like PKDL). Another form of the same drug, Liposomal Amphotericin-B (AmBiSome®) , possesses higher efficacy and lower toxicity, but does not lead to the above ‘stimulation’ of the macrophage, leading to weaker activation of the immune system and thus reduced resistance of the macrophage against future infections.” The mechanism for this is not well understood. Increasing use of AmBisome® has led to an increase in cases of PKDL, which is a cause of concern, according to Dr. Ali. The drug Amphotericin-B and its liposomal counterpart are also very expensive. In India and a few other countries, the medicine has been subsidised due to government aid. However, other nations like those in Africa, may not have ready access to this medicine due to its high cost. And now, there are increasing reports of resistance to this drug as well.

Next, we asked her about the present diagnostic methods for Leishmaniasis, and their accuracies. According to her, the most accurate test for the disease is the highly invasive ‘splenic aspirate’ method, whereby a biopsy of the infected organ is taken and tested. Many other less invasive methods are being developed. A certain laboratory has been working on a dipstick test, which can identify certain pathogen-specific antibodies in the blood. She herself is working on a test device which can sense similar antibodies in the urine, making diagnosis totally non-invasive. But it’ll take time for these devices before it’s available for the general public. Nevertheless, these devices will also carry a substantial price tag with them. She was initially hesitant towards our approach to use bacteria in treating the disease. But when we broached the topic of studies on bacterial therapy, where bacteria are being used for efficient targeting of disease specific regions in cancer and how the same idea can be implemented in the case of anoxic Leishmania regions in spleen, she found the idea feasible but nevertheless emphasized that further studies need to be done to ensure that it is a safe treatment and the bacterial host chosen is not pathogenic while still being able to persist inside the body for some time to act against the Leishmania.

After these discussions, we got some conceptual and experimental doubts regarding our project clarified. We got to know that the change in nitric oxide concentration after infection with leishmaniasis is a global event i.e. it is a change that is not limited to the Parasitophorous Vacuoles (PV) but is present everywhere inside the macrophage, which was a crucial information for the viability of our project. We realised that different macrophages have different responses to Leishmania infection, and so we sought her help in choosing the correct macrophage cell lines for our project. She also confirmed that our bacteria should reach the PV where the Leishmania reside by fusion of the bacteria-containing endosome with the PV.

All these above points lead to the conclusion that Leishmaniasis is not a disease of the past, and cannot be ignored. The government and the medical community must be vigilant and work together to prevent any future outbreaks of the disease so that we can look forward to a Leishmaniasis-free future.