India, home to more than 1 billion people, it is also home to the neglected tropical
disease Kalazhar. The disease has many names, Kalazhar, Kalajuar, Black Fever,
Dumb Dumb Fever and its medical name visceral lishminiasis or simply VL.
No matter what it's called, Kalazhar is very much a disease of the poor.
15-year-old Naina has Kalazhar. Naina lives in Bihar State, Northern India,
home to more than 100 million people and the epicenter of Kalazhar in India.
Half the world's cases of Kalazhar occur in India and 90% of those are in Bihar.
More than half of Bihar's population live below the poverty line and are among India's
poorest and most vulnerable. The importance of education is therefore well understood
in Bihar and this plays heavily on Naina's mind.
At the London School of Hygiene and Tropical Medicine, Dr. Saki Burza explains Kalazhar.
So Kalazhar is one of the most neglected tropical diseases. It exists in specific areas, specific
regions in the world, South America, East Africa and the Indian subcontinent. Essentially
it's a disease of parasites which is transmitted by a sand fly. The sand fly tends to reside
inside and around the domestic area of the house and especially prevalent in areas where
there's poor quality housing. As such, it tends to be a disease of the poorest that
affects the poorest and the most marginalized and vulnerable in society.
Dr. Temi Sunyoto works with Medicine Saint Frontiers in India.
The symptoms that may arise is first of all fever and the fever should be prolonged meaning
more than two weeks and then also the patients start to have a loss of appetite leading to
the weight loss and eventually a swelling of the internal organ like swelling of the
spleen and swelling of the liver. In the end, this Kalazhar will reduce the immunity of
the body so eventually the patient could die due to any other infection.
Dr. Pradeep Das works with RMRI, the Rajendra Memorial Research Institute of Medical Sciences
in Bihar's capital, Patna.
In India it is caused by Lishmanya Dhonavani, a protozoan parasite. But in the world there
are many species, about 20 species, which causes Lishmanya asses. But mainly are cutaneous,
but Kalajar causes visceral Lishmanya asses. And in India, practically in Bihar, it is
most common public health problem.
Kalazhar is almost always fatal if left untreated. Naina has come to the MSF-run Kalazhar ward
at Sadar Hospital in Hajipur in Vaishali district, Bihar.
There are many challenges working in an area like Bihar. Bihar is one of the poorest states
in India with some of the poorest health indicators and the poorest literacy rates.
An estimated 56% of the population lives below the poverty line and for the most part are
dependent on the public health system to receive quality treatment. But with a dysfunctional
public health system, the population is forced into the private health system, which is largely
non-allopathic, consisting of rural health practitioners without formal medical training.
So as a result, there's quite a lot of cost incurred to these patients. So these patients
who are already extremely poor, then incur sometimes catastrophic costs in order to achieve
inferior quality treatments and diagnoses.
Ganesh Paswan, who was treated more than four years ago, knows only too well the long and
costly road to diagnosis and inferior treatment.
Ganesh Paswan, who was treated more than four years ago, knows only too well the long and
costly road to diagnosis and inferior treatment.
Ganesh was soon misdiagnosed with malaria and received injections for several days,
injections that each cost the equivalent of a day's wages. The doctor then suggested
a blood test, another expense.
Ganesh was given a weak supply of pills and had to return every seven days for another
weak supply. He was also told to avoid strenuous work for a year.
Ganesh Paswan, who was treated more than four years ago, knows only too well the long and
costly road to diagnosis and inferior treatment.
Despite the seriousness of Kala Azar, it remains a neglected disease. Many believe this is
simply a matter of location. Not only does Kala Azar affect the poorest regions of India,
but it affects the poorest people within those states. It is, according to Dr. T.K.
Jha, one of the unjust characteristics of Kala Azar.
Take the history of Kala Azar. I say that this is one of the most undemocratic disease
because it affects the poorest of the poor.
Without a strong political voice, the marginalized and most vulnerable are left to compete with
what are considered more pressing health concerns, namely tuberculosis, malaria and HIV.
In a resource-poor setting like rural India, the ability to focus on a disease that affects
only a subset of society is impossible. As with so much of their lives, those with Kala
Azar simply become casualties of circumstance. There is also the financial issue, according
to Dr. Suman Rijal, from the Drugs for Neglected Diseases Initiative, DNDI.
There is no incentive for the current pharma industries to invest in making better tools
for treatment of Kala Azar. So, till about a decade ago, we were still using treatments
which was introduced in the 1940s and 50s, the sodium antimony gluconate. It's only
in the last 15 years when there has been a few champions who have come out and really
pushed the agenda.
One of those champions was MSF, an organization that has always had an interest in neglected
tropical diseases. For MSF, working in Bihar was a natural fit and by the early 2000s finding
a less toxic, less time consuming and an easily accessible treatment for Kala Azar, then what
was currently available became a priority. The move away from the toxic and increasingly
resistant sodium stebo-glutamate, SSG, had begun and other drugs and combination therapies
were being used, sodium antimony gluconate, pentamidine, miltephosine, paromomycin and
amphotericin B.
A new drug in the West that had been identified for the treatment of fungal infections in
cancer patients is something called liposomal amphotericin B which is in fact a slightly,
it's a different version of an old drug called amphotericin B which has a different formulation
which allows it to be given in a higher dose over a much shorter period and is far less
toxic. This is a drug that was recognized as an appropriate treatment for Kala Azar,
much safer and much more effective than the alternate treatments. As such MSF decided
to intervene in order to develop the evidence base that would allow policy makers to consider
liposomal amphotericin B as the most appropriate treatment for Kala Azar in the Indian subcontinent.
Dr. Nina Slima from MSF in Barcelona was involved in MSF's Kala Azar project in Bihar
from the beginning.
So what we really proposed in 2005 was to start a project treating the patients a large
cohort of patients with the best treatment available which has liposomal amphotericin
B. This was the best treatment option because it was the most effective treatment and the
safest so it could be used for all age groups and also for women in childbearing age.
However, there was reluctance to accept MSF's proposal. The use of liposomal amphotericin
B, what was to become known as ambizome, had not been proven at a large scale. The drug
was expensive and it required cold chain. The feasibility of using ambizome was not
looking promising.
I heard that there is a project submitted to Government of India and Government of Bihar
by MSF for treatment of Kala Azar cases but it was not been passed at 2005. In 2006 I presented
this project to Ministry of Health and Family Welfare. At that time the NBDCP people came
to Patna and they said that whether you really want to be a partner of this, we said okay,
we want to be a real partner of MSF and then we submitted again in 2006. They asked us to
some modification. Again I presented in the Health Ministry steering committee and this
project was then sanctioned in 2007 in partnership with MSF and RMRI.
Two years of negotiations followed but only when MSF could show that it could lower the
price and prove the effectiveness and safety of patients did they get the green light.
So we started to treat the first patient in 2007, the 16th of July. The first child was
treated in a hospital in Hajipur in Bishali district which was one of the highly endemic
districts of Bihar state and we could do it thanks to doing a partnership with a research
entity, Indian research entity. So RMRI was one of our major partnerships. They allowed
us to import the medication to set up properly the project and we were collaborating with
them so that we could possibly publish our data and try to establish the influence we
wanted to make in India to switch the protocols.
As the work continued and various combinations of Miltephocene, Paromomycin and Ambizone
were used, evidence began pointing towards single dose ambizone as the most effective
and beneficial first line treatment.
This is when MSF decides to do a study with DNDI to show it at a large scale so the different
combination modalities and the single dose ambizone which was really what MSF was supporting
because it's a single point of care so the patients can come and be treated with fatal
disease like Kalasar in one to two hours of hospitalization or at primary health care
level so either at hospital level, at community level which is really increasing the access
to these populations.
By December 2013 MSF could prove the effectiveness of single dose ambizone. They showed a 98%
cure rate of Kalasar, a reduced hospitalization cost alongside the reduced hospitalization
time and an increase in the access to health care.
Well the benefit of this new treatment would actually a lot will have impact to the patients
because the patient used to have to first undergo various different diagnostic before
finally diagnosed with Kalasar and in the end when they are diagnosed with Kalasar they
have to have treatment that are either having a very bad side effects or have to make them
hospitalized for quite a prolonged period so even a day of having to go to the hospital
and being hospitalized will mean a lot in terms of the loss of their income.
All those involved in Kalasar in India, Bangladesh and Nepal began pushing the WHO to recommend
single dose ambizone as the first line treatment to Kalasar. Success came when the treatment
protocols were changed in September 2014.
It's one long awaited change I would say in the treatment protocol and I think this
is going to be a crucial game changer in terms of finally controlling the disease in one
of the most high burdened center of Kalasar in the whole world.
Back in Sadar Hospital, nurses prepare single dose ambizone for Naina. The treatment is
given intravenously over a period of two to three hours.
Naina gets comfortable and her treatment begins.
Thankfully, 55-year-old farmer Jageshwar Rai was referred to the Sadar Hospital.
He says,
We woke up very early in the morning, really late.
When my mother was still alive, we got water in see-sheers.
I spoke to her in her net, and she was just listening.
My mother was pulling她 rope to a demon-eared woman.
I hope so.
It was very difficult, but I was able to overcome it.
Everything seemed to be fine.
At first, I felt a lot of pain.
Many people have been treated differently,
but I was the only one who was able to overcome it.
I didn't get any money.
My brother and sister-in-law went on a date.
At that time, I didn't have any medicines.
But medication is simply one part of the triangle that is Kalazar.
Former MSF doctor and now part of the Kalakor consortium,
Dr. Bernard Benka explains.
So it's a vector-borne disease.
So basically you have three important parts.
One is the patient or the host.
Then you have the parasite.
And then you have the vector, which is the sand fly, which carries the parasite.
So you have to intervene on each level.
And exactly that makes these vector-borne diseases really difficult to eliminate, let's say.
It depends also entirely on the host.
In India, we have the advantage that it's believed that human is the only host of the parasite.
So we think if we just find and treat every single patient,
we should be able to control the disease.
Finding patients can be as simple as going door-to-door.
This is where Ashas or accredited social health activists like Kishto Devi play a crucial role.
Ashas are community health workers employed by the Ministry of Health to actively identify and screen likely patients
and raise awareness about Kalazar.
We know a lot about the Ministry of Health. They are the only ones who have been trained.
We have been trained by the Ministry of Health to identify and screen likely patients.
There are hundreds of families who visit our homes and ask how they are doing.
They don't have any fever.
If they have a fever, they should go to the health centre and get a blood test done.
For example, if there is a Kalazar project, they should be taken away.
Kishto Devi has another way of spreading health messages about Kalazar.
She sings.
In addition to running the Kalazar ward at Southern Hospital,
MSF supports five primary health centres or PHCs throughout Vaishali district,
including on the River Island of Raghupur.
In this remote setting, MSF staff conduct an IEC session – Information, Education and Communication –
to inform villagers about Kalazar, how it is contracted, its symptoms and how to receive treatment.
In villages such as these, the unsanitary living conditions are obvious.
So too is the proximity of animals and animal waste to humans and the general use of fashed housing.
When combined with the abundance of water and high humidity, you have ideal conditions for sandflies to live and breed.
Ramchandra is the government nurse at the Raghupur Primary Health Centre.
The Kalazar ward is mostly covered in dirt and dust.
We have heard from the public about the Kalazar ward that it is important to go to the PSC.
If a person presents at a primary health centre or PHC with a fever, the doctor may suspect Kalazar.
The doctor will then recommend an RK39 test – a highly accurate, rapid diagnostic test for Kalazar.
We do RK39 tests. Then we check their aspirin. If we get the aspirin, if the RK39 test is positive, we will start treating it.
This single dose is very good. The patient is getting a good treatment and the patient is getting a good cure.
Apart from diagnosis and treatment, controlling the vector is equally important.
How is that done? Mostly by spraying. So in this IRS or indoor residual spraying, it's also a very important activity within Kalazar disease control, let's say.
It's not only treating the patients, there's like many other things in these kind of vector-borne diseases that you have to take care of to achieve actually elimination.
With continuing vector control, good IEC programmes and a highly successful first-line treatment, elimination of the disease is now firmly on the cards, but challenges and questions remain.
So the elimination of Kalazar would actually just mean that the Kalazar sees as a public health problem. It doesn't mean that we will have a zero case immediately, but let's say that the scope of the problem will not be as massive as it is now.
What we have to achieve is to bring down the incidence rate to one or less than one per 10,000 population at PSNR.
You have to understand and we understand that it will be probably like more difficult that once elimination is achieved, that actually everyone keeps up the good work and the effort to sustain this elimination and not like just lays back and relaxes and then like things turn bad again.
You have to maintain good quality of indoor residual spray, you have to maintain the surveillance, you have to maintain the treatment and although activities which are being done today, they have to continue it.
Once a patient is cured of Kalazar, they could also develop a skin complication called PKDL, the post-Kalazar dermalis minusis, which is also known to be quite an important reservoir for the parasite and then it potentially could prolong the transmission.
So apart from the Kalazar itself that are being treated by the single lusambisome, there are other subgroup populations with a patient that needs to be also addressed in order to achieve the elimination.
We have to also think about asymptomatic carriers because our study from this ensued first time showed that about 18% of the asymptomatic, they become the full blown cases within three months.
One of the things we realised after starting the project was that we were getting a lot of patients who were coming with relapses despite being treated with this very good drug, liposomalameteris and B. What we realised then is that a lot of these patients were presenting positive for HIV
and of whom half didn't even know that they had HIV so we were the first people to diagnose them with both Kalazar and with HIV.
HIV associated Kalazar, they are swarming with parasites, right from top to bottom you find the parasite is there. The parasitemia is more than 100 times than active case of Kalazar.
Co-infection itself is a real problem for both the patient and the public health provider because these patients tend to have very poor outcomes first of all. Secondly, they tend to relapse frequently.
And thirdly, when you've got a limited number of drugs to treat these patients, there's a much higher probability of these patients spreading the disease and developing resistant strains to the drugs that currently exist.
It is now the afternoon. Naina has received the ambizome and is feeling well. And just like that, it is time to go home.
I will go home and tell my brothers that this is how it is there. Kalazar is very good, the doctor is very good and the nurse is also very good.
I will tell my friends that if you go to Kalazar, you will be fine in the hospital.
The question of whether or not we're on the right track, I think, is the answer is yes. I think there's now, in my entire time of dealing in VL, I've never seen such a huge political commitment from across the spectrum,
both from the local governments, from the national, from the WHO, from the international stakeholders, from the international NGOs.
Over the last couple of years, there's been a real coming together of all the different partners to try and take these urgent steps to eliminate and control this disease.
To put it simply, if we don't manage to do it in the next couple of years with all the political, financial and stakeholder support that we have, then it's going to be hard to actually do it in the future.
Thank you very much.
Thank you.
