4-Jan-2023: Union Minister for Health & Family Welfare, Dr. Mansukh Mandaviya chairs a high-level meeting with State Governments to review elimination of Kala-Azar from the country by 2023

“India is committed to eliminating Kala Azar from the country by 2023. 632 (99.8%) endemic blocks have already achieved elimination status (<1 case/10,000). Only one block (Littipara) of Pakur district, Jharkhand is in the endemic category (1.23 case/10,000 population). We are working holistically with the state government and other stakeholders to achieve elimination in Jharkhand”. This was stated by Union Minister of Health and Family Welfare, Dr. Mansukh Mandaviya as he chaired a high level meeting to review the status of Kala-Azar disease in the four endemic states of Bihar, Uttar Pradesh, Jharkhand and West Bengal in the presence of Union Minister of State for Health and Family Welfare, Dr. Bharati Pravin Pawar. Shri Tejaswi Yadav, Deputy Chief Minister & Health Minister (Bihar), Shri Brajesh Pathak, Deputy Chief Minister & Health Minister (Uttar Pradesh) and Shri Banna Gupta, Health Minister (Jharkhand), and senior officers from West Bengal were present at the review meeting.

Dr. Mansukh Mandaviya appreciated the efforts of the State Governments towards meeting elimination target. He said that “under the visionary leadership of our Prime Minister, it remains our target to ensure health for all of our citizens.” Government has taken several steps towards elimination of Kala-Azar by 2023. From interventions like pucca houses through Pradhan Mantri Awas Yojana (PMAY), rural electrification, timely testing, treatment, periodic high-level review, to incentivizing through award distribution for states/districts/blocks, government along with its stakeholders are ensuring a robust ecosystem for early detection of the disease and its timely treatment.” Government of India is supporting the states in active case detection, surveillance, treatment, supply of diagnostic kits, medicines, sprays etc.

Dr. Mandaviya said that “While it is commendable that the endemic states are implementing targeted interventions, and some states have eliminated the disease in their districts, it is equally important to sustain the gain and work towards ensuring that the cases stay below 1 case/10,000 population”.   He urged the endemic states to ensure that there is a regular review and micro-stratification in high-risk blocks reporting incidence > 0.5 per 10000 populations. “Since Kala-azar impacts those among the lower socio-economic strata of society, early diagnosis & complete case management, integrated control and surveillance along with capacity building of human resource must be taken up on ground level”, he suggested. “For spreading public awareness, information regarding messages on prolonged fever, associated symptoms and free access to diagnosis and treatment and compensations/incentives, other government interventions are required to be widely disseminated through various mediums”, he further added.

Dr. Bharati Pravin Pawar, MoS (HFW) commended the states on their efforts and urged them to ensure that “Transmission through the notorious sandfly be prevented at any cost. Awareness campaigns regarding the symptoms, early detection and treatment available free of charge at Government health facilities are required to be strengthened for enabling early reporting by the affected persons”.

States informed about the status of disease in their respective states and shared their best practices too. The State Health Ministers expressed gratitude for the support provided by the Centre for detection, surveillance, treatment through various interventions. Health Ministers of states where elimination status is achieved assured to continue working in Mission mode to ensure that the stats is sustained.

  About 90% of global cases of kala Azar were reported from eight countries: Brazil, Eritrea, Ethiopia, India, Kenya, Somalia, South Sudan and Sudan in 2021, with India contributing 11.5% of total cases reported globally. Kala-azar is endemic in 633 blocks of 54 districts in four endemic states of Bihar, Jharkhand, Uttar Pradesh and West Bengal. It is a notifiable disease in these states. Currently more than 90% of the Kala-azar cases are contributed by Bihar and Jharkhand. Uttar Pradesh (2019) and West Bengal (2017) states have achieved their elimination targets at the block level.

Shri Rajesh Bhushan, Union Health Secretary, Shri. Rajiv Manjhi, JS and other senior officials of the Health Ministry were present. Senior government officials serving in the States/UTs, NGOs and development partners were also present virtually.

---

16-Aug-2021: Non-invasive, easy to administer, cost-effective bio-nanocarrier can enhance oral bioavailability and efficacy of Visceral Leishmaniasis therapy

Indian researchers have developed a non-invasive, easy to administer, cost-effective, and patient compliant potential therapeutic strategy against Visceral Leishmaniasis, a neglected tropical disease. Their strategy based on nano carrier-based oral drugs coated with Vitamin B12 enhanced oral bioavailability and efficacy of the therapy by more than 90%.

Visceral Leishmaniasis (VL) is a complex infectious disease transmitted by the bite of female Phlebotomine sandflies. It is a neglected tropical disease that affects millions annually, making it the second most common parasitic killer after malaria. The conventional treatment therapy of VL mainly involves painful intravenous administration, which imposes many treatment complications, including prolonged hospitalization, high cost, and high risk of infection. Oral drug delivery brings forth massive advantages that can help overcome these barriers. But with oral routes, there are other challenges as more than 90% of orally administered therapeutic drugs have less than 2% bioavailability and potentially high hepatic and renal toxic side effects.

A team led by Dr. Shyam Lal from the Institute of Nano Science and Technology (INST), an autonomous institute of the Department of Science and Technology (DST), GoI has developed a smart and intelligent nanocarrier utilizing the natural intrinsic Vitamin B12 pathway present in human body that can mitigate stability challenges and drug-associated toxicity. They have disguised the toxic but highly efficient drug of the disease within a biocompatible lipid nanocarrier shielding it from degradation in the hostile gastric environment, thus overcoming the gastrointestinal enzymatic barriers endured by any foreign synthetic drug molecule. This minimized its side effects, while the natural intrinsic Vitamin B12 pathway enhanced the oral bioavailability and antileishmanial therapeutic efficacy by more than 90%, as shown in the associated animal studies. The research was supported under the DST-SERB Early Career Research Award and published in Materials Science & Engineering C’.

The INST team critically evaluated the efficacy and properties of Vitamin B12 (VB12) coated solid lipid nanoparticles and their subsequent potential ramification in evading cytotoxicity and escalating stability.

They conceptualized an innate immune defence mechanism to enhance the physicochemical properties of orally administered nanoparticles, which can easily navigate through the gastrointestinal tract without being washed away by naturally present mucus barrier.

Anchoring Vitamin B12 on the surface of solid lipid nanoparticles augmented the stability and targeted delivery of the poorly soluble drugs and also enhanced the therapeutic efficiency with reduced risks of off-target actions. The research showed that Vitamin B12 being an essential lifesaving micronutrient, which plays a pivotal role in the body by modulating the toxic side effects associated with the most neglected tropical disease, also works as an innovative and beneficial supplement for its treatment and prevention. It not only reduces the risk of infection but also enhances the immunity of an individual. Moreover, it also improves the bioavailability and targeted delivery by utilizing the natural intrinsic Vitamin B12 pathway, which is present in the human body and hence developing resistance for infection spread.

---

30-Dec-2020: Dr. Harsh Vardhan reviews status of Kala Azar in Four States of Uttar Pradesh, Bihar, Jharkhand and West Bengal

Dr. Harsh Vardhan, Union Minister of Health and Family Welfare today chaired an event to review the status of the disease Kala-Azar in the four states of Uttar Pradesh, Bihar, Jharkhand and West Bengal.

Shri Mangal Pandey, Minister of Health, Bihar, Ms. Chandrima Bhattacharya, Minister of State for Health and Family Welfare, West Bengal, Shri Jai Pratap Singh, Minister of Medical and Health, Family Welfare, Mother and Child Welfare, Uttar Pradesh and Shri Banna Gupta, Health, Medical Education & Family Welfare, Jharkhand were also present in the event.

The Union Health Minister started by reminding the audience that the Government of India is strongly committed to the elimination of Kala Azar.  He stated “Kala Azar is the 2nd largest parasitic killer in the world after Malaria and results in a 95% fatality rate if the patients are not treated. Additionally, up to 20% of the patients who are correctly treated and cured, develop a skin condition called Post-Kala-Azar Dermal Leishmaniasis (PKDL) which surfaces within months to years after treatment. These patients can contain large amounts of parasites in their skin lesions, making them an important source of transmission.” He was apprised that there are 54 districts in four states namely Bihar, Jharkhand, Uttar Pradesh, and West Bengal that are currently affected by Kala-azar with sporadic cases in other states like Assam, HP, J&K, Kerala, Sikkim, and Uttarakhand.

Speaking on the gains made in elimination of Kala Azar, he noted:

• As of 30th November 2020, only 12 blocks in Jharkhand and 4 blocks in Bihar have reported more than 1 case per 10,000 population.
• Bihar which has traditionally had a large burden of Kala-azar has achieved elimination target in almost all except 4 blocks located in districts of Siwan and Saran (out of 458 blocks).
• Jharkhand too has made significant progress both in reduction of Kala-azar and PKDL cases, as well as in number of blocks reporting more than 1 case per 10,000 population.
• Uttar Pradesh and West Bengal have achieved their elimination target and needs to be more vigilant and diligent to consolidate and sustain their gains; they will earn the Elimination Certificate at the end of 3 years.

Appealing to all the District Magistrates and their officers at the district and block/level that are still reporting more than 1 case  per 10,000 population to take some time out of their schedule for a regular review of Kala-azar and to help the district teams in overcoming the issues coming in the way of elimination target, Dr. Harsh Vardhan said, “A risk based stratified approach needs to be formulated with clear activities and responsibilities that come with measurable monitoring indicators. Kala Azar disproportionately impacts the people at lower socio-economic strata of society whose houses are not sprayed often. In addition, they are unable to apply for pucca houses since they don’t own land.”

In this respect, he underlined the importance of the following activities to target the elimination of the disease:

• Development of a plan for the “unreached poorest” or underprivileged sections in endemic areas.
• Leveraging of Kala-azar elimination programme within POSHAN Abhiyaan for maximum benefit at community level.
• Exploration of the opportunity of providing improved housing under the flagship program of the Prime Minister Awaas Yojana-Gramin (PMAY-G).  (The Minister added that Jharkhand has made good progress on this front).
• Exploration of the opportunity of providing improved housing under State Schemes, as has been done by Jharkhand under Birsa Munda Awaas Yojana and Bhimrao Ambedkar Awaas Yojana.
• Involvement of Rural Health Practitioners (RHPs) who are often used as the first point-of-care in referral, surveillance, and IEC.
• Co-ordination with the rural development department and engage with Panchayati Raj functionaries for awareness, community engagement, environment management and social empowerment.
• Focusing on IEC messages on prolonged fever, associated symptoms and free access to diagnosis and treatment, proper use of ITN/LLINs, and compensations/incentives.

Dr. Harsh Vardhan explored possible solutions in this regard like sensitization of the population, proper training of human resource, quick completion of Prime Minister’s dream of ‘Housing for All’ by 2022, strengthening adverse drug reaction reporting system, both for Kala-azar and PKDL with special focus on PKDL cases with eye complications, institutional management of Kala Azar/HIV cases at the district level, etc.

4-Nov-2020: CSIR-CDRI Scientist, Dr Susanta Kar, honoured with “Prof. A N Bhaduri Memorial Lecture Award-2020" by the Society of Biological Chemists (India)

To recognize the significant contributions towards defining the survival tactics of Leishmania donovani, Society of Biological Chemists (India) has chosen Dr Susanta Kar, Senior Scientist, Molecular Parasitology and Immunology, CSIR-CDRI, Lucknow for this year's Prof. A N Bhaduri Memorial Lecture Award.

Leishmania Donovani is a protozoan parasite that infects macrophages and is a causative agent of visceral leishmaniasis (Kala Azar), a lethal infectious disease affecting millions worldwide. DR. Susanta Kar’s  research group studied the interaction of Leishmania with immune cells like macrophages, dendritic cells and T cells and the fate of these interactions on modulation of various intracellular signaling cascades that ultimately affect immune response/infection progression.

Society of Biological Chemists (India) has instituted many awards, in order to recognize the meritorious and significant contributions made by the researchers/scientists on the development of biological sciences in the country, The Society of Biological Chemists (India) or SBC(I) was founded in 1930, with its Head Quarters at Indian Institute of Science, Bengaluru. This prestigious society was registered under the Societies Act in the then Princely State of Mysore.

The award is conferred in every two years. Recipient of the award should be below 50 years of age. The Award is given for Biological Chemistry and Allied sciences, preferably related to parasitic infections.

21-Aug-2020: Oral nanomedicine may bring relief for Kala-Azar & other neglected diseases

Patients affected by Kala- Azar, scientifically called Visceral leishmaniasis (VL), one of the most neglected tropical diseases may soon find relief in an oral nanomedicine from India. The oral therapeutics could help in the control and elimination of VL, around 95 % of which is reported from Bangladesh, Brazil, China, Ethiopia, India, Kenya, Nepal, Somalia, South Sudan, and Sudan.

Scientists from the Institute of Nano Science & Technology (INST), Mohali, an autonomous institute of the Department of Science & Technology, Govt. of India, have developed an oral nanomedicine with the help of surface-modified solid lipid nanoparticles based combinational cargo system for combating visceral leishmaniasis. The findings of their study supported by the DST-SERB Early Career Research Award have been recently published in the journals ‘Scientific Reports’ and ‘Materials Science & Engineering C’.

According to the INST team, till-date there is no study reported where a combination of two anti-leishmanial drugs has been delivered through nanomodification as a potential therapeutic strategy against visceral leishmaniasis. This work suggests the superiority of as-prepared modified formulation (m-DDSLNs) surface modified with 2-hydroxypropyl-β-cyclodextrin (HPCD) as a promising approach towards the oral delivery of anti-leishmanial drugs.

In this study by INST team led by Dr. Shyam Lal M anti-leishmanial drugs Amphotericin B (AmB) & Paromomycin (PM) were encapsulated in solid lipid nanoparticles and further modified with 2-hydroxypropyl-β-cyclodextrin (HPCD). The scientists explored the oral therapeutic potential of the formulation in the treatment of visceral leishmaniasis. They employed an emulsion solvent evaporation method to prepare HPCD modified dual drug-loaded solid lipid nanoparticles (m-DDSLNs). The nanoparticle-based combinatorial drug delivery system developed by them enhanced the efficacy of the formulation in both in vitro and in vivo models by reducing intracellular amastigote growth in L. donovani-infected macrophages and hepatic parasite burden in L. donovani-infected BALB/c mice model, respectively without causing any significant toxic side effects.

According to the INST team, the solid lipid nanoparticles (SLNs) can help enhance the oral uptake of the therapeutic agent by retaining a solubilized state of the drug in the Gastrointestinal Tract and favors the formation of mixed micelles (a special case of solubilization) by inducing the secretion of bile salts and phospholipids. Further, 2-hydroxypropyl-β-cyclodextrin (HPCD) are cyclic oligosaccharides that are known to be molecular hosts which can selectively include water-insoluble guest molecules within their hydrophobic cavity through non-covalent interactions.

This study by INST team may lead to product and process patent enhancing the role of our country for developing innovative therapy against neglected diseases. The usage of lower therapeutic dose of the purified drugs through nanomodifications will be boon in reducing toxicity, which has been a major hindrance in the existing conventional treatment when administered orally.

24-Jun-2020: New biomolecules to fight drug resistance in Kala- azar

Leishmaniasis is a neglected tropical disease affecting almost 100 countries including India. It is caused by a parasite called Leishmania, which is transmitted through the bite of sand flies.

There are three main forms of leishmaniasis – visceral, which affects multiple organs and is the most serious form of the disease, cutaneous, which causes skin sores and is the most common form); and mucocutaneous, which causes skin and mucosal lesion).

Visceral leishmaniasis, which is commonly known as Kala-azar in India, is fatal in over 95% of the cases, if left untreated. The only drug available against leishmaniasis, miltefosine, is rapidly losing its effectiveness because of emerging resistance to this drug due to a decrease in its accumulation inside the parasite, which is necessary for the drug to kill the parasite.

Specific types of protein molecules, called transporter proteins, play a major role in carrying miltefosine into and out of the parasite’s body, which comprises a single cell. A protein called ‘P4ATPase-CDC50’, is responsible for intake of the drug by the parasite, and another protein, called ‘P-glycoprotein’, is responsible for throwing this drug out from within the parasite’s body.

A decrease in the activity of the former protein, and an increase in the activity of the latter results in less amounts of miltefosine being accumulated inside the parasite’s body, thus causing it to become resistant to the drug.

A team of researchers at the Department of Biotechnology’s National Centre for Cell Science (DBT-NCCS) in Pune led by Dr. Shailza Singh has been exploring ways to tackle miltefosine resistance. The researchers worked with one of the species of Leishmania that causes infection, called Leishmania major. They tried to manipulate these transporter proteins in the species in a manner that would result in increased uptake of the drug and decrease in its being thrown out of the parasite’s body.

Scientists need to be extremely careful while seeking to manipulate the transport proteins.  They exist across a diverse range of organisms from bacteria to mammals, including humans and any mishandling could cause more harm than be of use. Consequently, though various researchers have been working over the past two decades to combat drug resistance, their activities were limited to laboratory studies.

Dr. Singh’s research group used computational methods to design small molecules, called peptides, that could very specifically interact with the transporter proteins of L. major alone, and not interfere with human proteins in any way. The peptides were designed to modulate the transporter proteins “allosterically”, i.e. by interacting with the protein molecule at a location other than the specific location where miltefosine binds to it.

This group is the first to have shown allosteric modulation of transporter proteins of Leishmania using computationally-designed synthetic peptides, and their findings were reported in the ‘Biochemical Journal’. These promising research outcomes indicate that this approach could prove useful in the long run to develop novel therapeutics against drug-resistant Leishmania parasites.

---

23-Jul-2019: Kala azar patients can infect others even after treatment

A study has highlighted the need to keep track of patients even after they are treated successfully to see whether they develop a skin condition called post-kala azar dermal leishmaniasis over the period.

Public health programmes normally ignore the condition since it merely develops as skin lesions in the form of rashes and nodules. Even though the lesions were found to contain the parasite causing kala azar, it was not fatal like kala azar. It also appears in only some patients and not all.

The new study has found that it, however, is not that benign. The research showed that the patients with the condition can be a source of infection for others in their community.

As part of the trial, 47 patients were asked to plunge their hands into a cage containing laboratory-reared sandflies. Sandflies are carriers of the parasite and the laboratory reared ones were free from the infection. The patients kept their hands inside the cage for 15 minutes each. The sandflies were then analysed. The results showed that nearly 60% of the patients in the study passed on the parasites to sandflies.

Until now, information on the role of post-kala azar dermal leishmaniasis was scarce and scattered across decades of different research initiatives. The new study unequivocally show that it is of pivotal importance for maintaining transmission of the disease in-between epidemics.

Because post-kala azar dermal leishmaniasis is not fatal it has largely been ignored by public health efforts, and many scientific questions around its role have remained unaddressed. While these new findings don’t answer all our questions, they do show that early treatment of patients showing the condition will be a critical element of any leishmaniasis elimination strategy.

Great strides have been made in the control of kala-azar in South Asia, but this study shows that now we must engage in active post-kala azar dermal leishmaniasis case detection and provide prompt treatment as an integral part of kala-azar control and elimination. The condition must be addressed in order to sustain elimination or we risk jeopardizing our earlier successes.

---

11-Jan-2018: India misses 2017 deadline for Kala Azar elimination

India has missed the 2017 deadline that Finance Minister Arun Jaitley had announced for elimination of Kala Azar (black fever) in his Budget speech last year. In spite of decreasing, endemic blocks have increased from 61 to 68 in 17 districts of Bihar and Jharkhand.

Officials said, the delay in construction of concrete houses pending since 2001-02, was the primary reason behind the failure to control the disease. Further, a little-known skin condition called Post Kala Azar Dermal Leishmaniasis (PKDL) — a red flag for transmission of KA — has been growing steadily over the past few years.

Elimination is defined as reducing the annual incidence of Kala Azar (KA) to less than 1 case per 10,000 people at the sub-district level.

Active case findings rather than an actual increase in the disease is the reason why the number of endemic blocks have increased.

KA vector needs to be eliminated to eliminate Kala Azar. As the endemic blocks have majority of houses made from wood, it is very difficult to eliminate the vector as it dwells in the wooden structure and escapes various measures to kill it. Hence, to stop the infection transmission, pucca houses need to be built. Secondly even after treatment of Kala Azar patients, it is the PKDL cases which become a source for future KA cases.

The meeting resolved to take up the issue of building concrete houses in KA endemic blocks with the rural development ministry on priority, and recommended that one-time incentive for PKDL patients should be doubled from Rs 2,000 to Rs 4,000.

27-Dec-2022: Transfer of technology ‘Inactivated low pathogenic avian influenza (H9N2) vaccine for chickens’ developed by ICAR-NIHSAD, Bhopal

‘Inactivated low pathogenic avian influenza (H9N2) vaccine for chickens’, developed by the scientists of ICAR-NIHSAD, Bhopal was transferred to M/s Globion India Pvt. Ltd., Secunderabad, M/s Venkateshwara Hatcheries Pvt. Ltd., Pune, M/s Indovax Pvt. Ltd., Gurgaon and M/s Hester Biosciences Ltd., Ahmedabad today, facilitated by M/s. Agrinnovate India Ltd. (AgIn) at NASC, New Delhi. The event was graced by Dr. Himanshu Pathak, Secretary (DARE) & Director General (ICAR) and Chairman, AgIn, Dr. B.N. Tripathi, DDG (Animal Science), Dr. Praveen Malik, CEO, Agrinnovate India Ltd., Dr. Aniket Sanyal, Director ICAR-NIHSAD, representatives of commercial firms, other officials from ICAR and AgIn.

Dr. Himanshu Pathak appreciated the sincere efforts of the ICAR-NIHSAD scientists in development of the first indigenous vaccine for H9N2 virus and commended the Agrinnovate India limited (AgIn) for the efforts in the transfer of the technology to industry. DDG (AS) asserted that the vaccine will meet the standard of the market both in India and abroad. The vaccine will contribute significantly to increasing the income of poultry farmers by reducing the economic loss due to the disease.

13-Jan-2020: H9N2 virus infected an Indian child

Indian scientists have detected the country’s first case of infection with a rare variant of the virus that causes avian influenza, or bird flu. Scientists of the National Institute of Virology (NIV), Pune, have reported avian influenza A(H9N2) virus infection in a 17-month-old boy in Maharashtra.

H9N2 is a subtype of the influenza A virus, which causes human influenza as well as bird flu. The H9N2 subtype was isolated for the first time in Wisconsin, US in 1966 from turkey flocks. According to the US National Centre for Biotechnology Information (NCBI), H9N2 viruses are found worldwide in wild birds and are endemic in poultry in many areas. However, they are somewhat neglected. H9N2 viruses could potentially play a major role in the emergence of the next influenza pandemic. According to the World Health Organization (WHO), with avian influenza viruses circulating in poultry, there is a risk for sporadic infection and small clusters of human cases due to exposure to infected poultry or contaminated environments. Therefore, sporadic human cases are not unexpected.

H9N2 virus infections in humans are rare, but likely under-reported due to typically mild symptoms of the infections. Cases of human infection have been observed in Hong Kong, China, Bangladesh, Pakistan, and Egypt. One case was detected in Oman recently. The first case globally was reported from Hong Kong in 1998. A total of 28 cases in China have been reported since December 2015. Cases continue to be reported mainly from mainland China and Hong Kong.

The virus has, however, spread extensively among poultry populations. Surveillance for influenza viruses in poultry in Bangladesh during 2008-2011 found H9N2 virus to be the predominant subtype. The virus was also identified in poultry populations in surveillance studies in Myanmar during 2014-16 and Burkina Faso in 2017.

The virus was picked up in February 2019 during a community-based surveillance study in 93 villages of Korku tribes in Melghat district of Maharashtra. NIV scientists were looking to determine the incidence of deaths associated with respiratory syncytial virus (RSV) among children under age two. In the process, they identified A(H9N2) virus infection in one boy. The child had fever, cough, breathlessness, and difficulty in feeding for two days after illness onset on January 31, 2019, and was fully immunised with treatment. After a series of confirmatory tests, the findings were reported last month.

The child was not exposed to poultry. A week before showing the symptoms, he had travelled with his parents to a religious gathering. The father showed similar symptoms but could not undergo serologic testing.

NIV scientists said H9N2 viruses have been observed in poultry in India several times. Now, identification of the first clinical human case of H9N2 virus infection highlights the importance of systemic surveillance in humans and animals to monitor this threat to human health.

The same concerns were expressed after the first reported case in Oman. Despite the low pathogenicity of this subtype, the continuing emergence of the virus in unpredicted region and now rise in number of human cases pose a pandemic threat and the need to adopt a multi sector One Health approach.