|FACE TO FACE
|Year : 2018 | Volume
| Issue : 2 | Page : 127-131
An E-mail interview with Dr. Pradeep Das
|Date of Web Publication||27-Dec-2018|
|How to cite this article:|
. An E-mail interview with Dr. Pradeep Das. Trop Parasitol 2018;8:127-31
1. Being one of the leading parasitology researchers from India, could you please explain how would your research findings made an impact on National Leishmania Control Program?
| Answer|| |
There have been numerous clinical drug trials at the institute such as miltefosine phase III and IV, paromomycin phase III and IV, ambisome single dose (10 mg/kg), amphomul, and combination therapy (M + P) in collaboration with various international agencies, namely WHO/TDR, BMGF, DNDi, and DST. Miltefosine, paromomycin, combination therapy, and ambisome have been adopted in visceral leishmaniasis (VL) elimination program by the National Vector-Borne Disease Control Programme (NVBDCP), Government of India. Pharmacovigilance studies have been conducted by the institute in collaboration with WHO/TDR, World Bank, and NVBDCP, and these have also been incorporated in the national VL elimination program. Clinical drug trials for postkala-azar dermal leishmaniasis (PKDL) with miltefosine were conducted and were found to be highly effective and safe and hence were incorporated in the national program. PKDL short-course combination therapy is being tried out in collaboration with DNDi. VL–HIV clinical drug trial using ambisome and miltefosine combination is currently being conducted in collaboration with MSF. This will prove to be a cornerstone in the treatment of HIV–VL and it will be adopted in the program.
Earlier under national program only passive surveillance exists. Active case detection strategies (Camp, house-to-house, index and incentive-based approaches) were included under national program after researches conducted by the US. Strengthening of referral of Kala-azar (KA) cases through Accredited Social Health Activist (ASHA) toward early case detection and treatment has been demonstrated by RMRI through research and it has also been adopted by the national program. The concept of asymptomatic VL and HI-VL/tuberculosis (TB) and strengthening of PKDL surveillance has been provided to the national program by RMRI. Capacity building in terms of early detection, diagnosis, and management has also been carried out by us at the national level. Cost-effective tool (compression pump) for Indoor Residual Spray (IRS) and Insecticide Quantification Kit (IQK) (WHO approved) for checking the concentration of insecticide have also been incorporated in the national program. Similarly, the current insecticide (alpha-cypermethrin) used for IRS in place of dichlorodiphenyltrichloroethane (DDT) to control sandfly has also been inducted into the national program after various researches conducted by RMRI, Patna, program. In addition, RMRI had conducted several multicountry research studies in collaboration of various international and national agencies.
Details of the research studies may also be seen by visiting our website (http//www.rmrims.org.in)
2. What is the current scenario of vector-borne diseases in your region with special reference to malaria and leishmaniasis?
| Answer|| |
The leishmaniases are a group of diseases caused by protozoan parasites from >20. Leishmania species that are transmitted to humans by the bite of infected female phlebotomine sandflies. There are four main forms of the disease: VL, also known as kala-azar; PKDL; cutaneous leishmaniasis (CL); and mucocutaneous leishmaniasis. While CL is the most common form of the disease, VL or kala-azar is the most serious form and can be fatal if untreated. In 2012, global estimates of incidence of leishmaniasis from 102 countries were published with 58,227 reported VL cases per year with estimated annual VL incidence of 202, 200–389, and 100. VL or KA is a parasitic disease with anthroponotic (confined to human only, no animal reservoir) infection in the Asian continent. The disease is endemic in the Indian subcontinent in 119 districts in four countries, namely, Bangladesh, Bhutan, India, and Nepal. An estimated 147 million people in 119 districts in four countries, namely Bangladesh, Bhutan, India, and Nepal, are at risk with an estimated 100,000 new cases each year. India is one of the six countries which share 90% of global burden of VL: Brazil, Ethiopia, India, Somalia, South Sudan, and Sudan. Although KA is one of the most dangerous neglected tropical diseases (NTDs), it is amenable to elimination as a public health problem in Southeast Asia Region of the WHO. VL is targeted for elimination by 2020. The population at risk for KA is among the poorest in the community with limited access to health care due to various socioeconomic determinants. There are currently no accurate data on the burden of PKDL. VL–HIV coinfection has also emerged as a serious concern and is reported from 36 countries.
KA is presently endemic in 54 districts in the country, of which 33 districts of Bihar, 4 districts of Jharkhand, 11 districts of West Bengal, besides occurrence of cases in 6 districts of Eastern Uttar Pradesh. Sporadic cases are also reported from Assam, Himachal Pradesh, Kerala, Madhya Pradesh, Sikkim, and Uttarakhand. Imported cases have been reported from Delhi, Gujarat, and Punjab. The state of Bihar alone contributes >70% of total KA reported from the four states. There has been significant decline in disease burden so far.
Of the 38 districts of Bihar, 34 are affected. The population at risk is 34.65 million, in approximately 12,000 villages spread over 458 blocks. About 86% of these blocks have achieved level of elimination by end of 2016. In 10 districts, out of 33 affected, 500 or more cases detected annually and contribute to about 70% cases of the state. These are Araria, East Champaran, Madhepura, Muzaffarpur, Purnia, Saharsa, Samastipur, Saran, Sitamarhi, and Vaishali.
Out of 24 districts, 4 districts, namely Dumka, Godda, Pakur, and Sahibganj are endemic for KA. The population at risk is 5.7 million, in approximately 1507 villages spread over 33 blocks. Only 10% blocks have achieved elimination.
Out of 19 districts, 11 districts, namely, Malda, Murshidabad, Darjeeling, 24-Parganas (N), 24-Parganas (S), Nadia, Hooghly, Burdwan, Dinajpur (N), Dinajpur (S), and Birbhum are endemic for KA. The population at risk is 28.18 million, in approximately, 731 villages spread over 119 blocks. About 93% blocks have achieved level of elimination.
Out of 72 districts, 9 districts in the Eastern part of the State, namely Balia, Deoria, Gonda, Gazipur, Kushinagar, Jaunpur, Sant Ravidas Nagar, Sultanpur, and Varanasi, are reporting cases of KA. The number of cases reported during 2013 was 11 which increased to 131 in 2015 due to increased surveillance. In 2016, 22 blocks across 9 districts reported 107 cases. The population at risk in these blocks is 4.82 million. All the blocks have reached the level of elimination.
3. An eminent expert member of various organizations, please share your views on research progress in developing countries with respect to neglected tropical diseases?
| Answer|| |
The WHO integrated NTDs into global health and development. Five interventions recommended by the WHO to overcome NTDs, namely, preventive chemotherapy, innovative and intensified disease management, vector ecology and management, veterinary public health services, and the provision of safe water, sanitation, and hygiene. Preventive chemotherapy defines the strategy of treating infected individuals to reduce morbidity and preventing transmission by administering medicines in communities at risk. Innovative and intensified disease management uses different interventions ranging from medicine to surgery – to relieve the symptoms and consequences of those diseases for which effective tools are scarce or where the widespread use of existing tools is limited. Despite the restricted availability of effective responses to these complex diseases, the programs working within the framework of innovative and intensified disease management have achieved a great deal. Important reductions occurred in the numbers of new cases of human African trypanosomiasis (by 89%) during 2000–2015, of VL in Bangladesh, India, and Nepal (by 82%) since 2005 and of Buruli ulcer (by 60%) compared with 2008. A WHO-led international verification team and all Latin American countries achieved universal blood screening for Chagas disease among blood donors.
Vector ecology and management strategies, which focus on developing and promoting guidelines, are based on the principles and approaches of integrated vector management, including the judicious use of pesticides. Vector control remains an important component in preventing and controlling the transmission of vector-borne diseases. The implementation of a comprehensive approach to vector control will contribute to disease-specific national and global goals and help to attain the health-related sustainable development goals.
The strategies used in veterinary public health services and the one-health approach recognizes that the health of people is connected to the health of animals and the environment. This is particularly relevant to the neglected zoonotic diseases, a subset of NTDs that are naturally transmitted from vertebrate animals to humans and vice versa, such as rabies. The greatest burden of these neglected zoonotic diseases affects the 1 billion livestock keepers in Africa and Asia who live in close contact with their animals and depend on them for their livelihoods and nutrition. These same populations have the least access to services for human and animal health and to information.
Providing safe water, sanitation, and hygiene (known as WASH) is a key component of the NTD strategy and is critical for preventing and providing care for most NTDs. Many of the pathogens that cause NTDs thrive where water and sanitation are inadequate. Reflecting the cross-sectional oral nature of the challenge posed by unsafe water and inadequate sanitation and hygiene, and the fact that the WASH component of the NTD strategy has tended to be neglected relative to its importance, in August 2015, the WHO launched a global strategy and action plan to integrate WASH with other public health interventions. Vector ecology and management is particularly important, being woefully underresourced despite its crucial importance, notably in response to outbreaks.
NTDs include a host of diseases such as VL, filariasis, HIV, TB, leprosy, and rabies. These have come up in a long way in developing countries as far as researches on these diseases are concern. Several NGO's and international organizations such as PHFI, DNDi, MSF, WHO/TDR, BMGF, DST, DBT, and CARE, are spending a lot of money on these NTDs.
4. Leishmaniasis has been linked to environmental changes such as deforestation, building of dams, irrigation schemes, and urbanization. How far it is true in Indian scenario?
| Answer|| |
The processes of deforestation and desertification, which are widespread, discrete when caused by human actions, and continuous when they occur naturally, are two of the major environmental concerns. The forests that occupy more than a quarter of the world's land area are of three broad types – tropical moist and dry, temperate, and degraded. The rapid loss of tropical forests, due to competing land uses and forms of exploitation that often prove to be unsustainable, is a major contemporary environmental issue. The main concern globally is with tropical forests that are disappearing at a rate that threatens the economic and ecological functions that they perform. Deforestation in developing countries is more recent, with tropical forests having declined by nearly one-fifth so far in this century. More recent statistics on deforestation suggest that, for tropical forests, the overall annual rate in the 1980s was 0.9%. Severe human pressures on forests in many tropical developing countries, especially those resulting from a need to provide for the welfare of numerous poor rural dwellers, will continue to threaten the existence of these resources. In parallel, forests continue to be lost in many developed countries owing to over-harvesting, inadequate regeneration, clearance for agriculture and urbanization, and air pollution. Deforestation might disturb the natural habitat of VL vector and hence lead to an epidemic of sylvatic VL disease among the flooded area following which VL vector may come in contact with village population and ultimately lead to the extension of VL endemic area. Deforestation may lead to flood situation ultimately lead to the active transmission of leishmaniasis. They are human population growth, agricultural expansion, plantations, atmospheric pollution, and resettlement. In addition to the above, the expansion of communication, the construction of large dams, and the failure to assist the poor and climatic anomalies of fire and drought only aggravate this problem further.
Indian villages have sandfly-genic environment because of close proximity with alluvial soil, particularly in the Indo-Gangetic belt. The people with VL belong to the poorest of the poor who live in dark muddy thatched houses which harbor animals and are a storehouse of sandflies. Transmission in Indian subcontinent generally occurs in rural areas with a heavy annual rainfall, with a mean humidity above 70%, a temperature range of 15°C–38°C, abundant vegetation, subsoil water, and alluvial soil. The disease is most common in agricultural villages where houses are frequently constructed with mud walls and earthen floors, and cattle and other livestock live close to humans. Hence, in the Indian subcontinent, environmental changes can lead to epidemics of VL.
5. Could you please elaborate on your work related to Vaishali model for leishmania and other works related to immunological models for this infection?
| Answer|| |
Vaishali is composed of 16 blocks, and out of that, 15 blocks were above the elimination level, when Vaishali was handed over to RMRI for VL elimination by the national program. We started piloting since 2015 and this pilot covered all 1569 villages. RMRIMS staff supervised the pilot which was composed of three elements:
Early case detection and management
The case referral system was strengthened through ASHA training which, reduce time-to-diagnosis. The trained ASHA worked exclusively on VL and PKDL case detections. This training program was repeated every year for two times.
Improved indoor residual spray
Mapping of hotspot villages through geographic information system
Village selection in Vaishali district used geographic information system-based mapping of endemic and nonendemic villages for VL trends and hotspot analysis to prepare the microaction plans (i.e., in addition to endemic villages of the last 3 years, periphery villages of hotspot villages within 500 m of the endemic village boundary, and which had had a case in the previous year would also be included). This algorithm provided a list of villages for the spray team.
Change in insecticide
Initial survey was carried out; Information – education and communication (IEC) and behaviour change communication were carried out at the 16 Primary Health Centers of Vaishali district. Most important activities achieved that villagers were not supported DDT due to different reasons such as white patches over the sprayed surface and bad smell after its spray. Most importantly, it was found that the vector species had been developed hard resistance against DDT. On the evidence-based decision, the Government of India replaced DDT with alpha-cypermethrin which was highly effective and also acceptable to the villagers.
Entomological activities to monitor indoor residual spray qualities
Before IRS operations, sandfly density were monitored at the period of every 15 days, 2 weeks, 4 weeks, and 3 months in accordance with prescribed the WHO guidelines, and significant drop-off in sandfly population was monitored following alpha-cypermethrin IRS. Comparative evaluation of serological test was carried out at population of DDT-sprayed areas and alpha-cypermethrin-sprayed areas to evaluate the biting activities of sandflies.
Evaluation of Insecticide
IQKs were used to take 3000 samples from four interior walls of one sleeping room of a household at three different heights (1·8 m, 1·1 m, and 0·3 m) from eight districts during the first round of 2015. Previous research has shown the performance of IQK as comparable to high-performance liquid chromatography – the gold standard. Now, we are in the process of developing IQK for alpha-cypermethrin also.
For early case detection and treatment, IRS was conducted using audio broadcasts from autorickshaws. It was conducted outside 1196 places including marketplaces, private hospitals, and block- and panchayat-level health centers; rural child care centers (anganwadis); schools; state and central government offices; and households covered down to the ward level. Supporting literature over the course of the study covered banners (block level n = 44; village n = 495), hoardings (marketplaces and government offices n = 52), posters (n = 47,840), leaflets (n = 95,680), and stickers (n = 47,840). These activities were repeated at every spray round.
Using an interrupted time–series analysis, we compared monthly surveillance data of KA in Vaishali. A spatiotemporal model estimated cases averted by the pilot. Strengthening control strategies may have led to a faster decline in VL case numbers in Vaishali and suggests this approach should be piloted in other highly endemic districts, which could be benefited from a similar approach
Immunological model for visceral leishmaniasis [Figure 1]
Using an immunological analysis, early case detection for VL in endemic area can be made by screening the population based on rK-39 and direct agglutination test (DAT) positivity, later the detection based on real-time polymerase chain reaction positive among rK-39 pos and DAT positivity. Such asymptomatic hotspots may be examined for adenosine deaminase level and interferon-gamma/IL-10 ratio and in change during follow-up till the VL development (active VL Case).
6. It has been a major concern that, in recent decade or so Plasmodium vivax malaria is turning out to be severe like Plasmodium falciparum, what is your take on this issue?
| Answer|| |
Bihar is not endemic for malaria and we do not have any research publications. In the recent past, P. vivax malaria is also leading to malignant malaria or black water fever similar to that of P. falciparum malaria as has been reported from Orissa, Jharkhand, Chhattisgarh, Rajasthan, and Northeast.
7. What you would like to suggest the young aspirants who would like to take up parasitology as a research interest?
| Answer|| |
Research in NTDs is growing up as a challenging and interesting aspect. Hence, I would request young aspirants to take up parasitology as a research interest. Several NGO's and international organizations such as PHFI, DNDi, MSF, WHO/TDR, BMGF, DST, DBT, and CARE, are spending a lot of money on these NTDs.
8. You have been working all over the world, what is your opinion on research approach in developing countries when compared to developed nations?
| Answer|| |
Developed nations are mainly working on noncommunicable diseases such as cardiovascular, cerebravascular, collagen diseases, cancer and inborn errors of metabolism, diabetes, and inherited diseases. Developing countries, on the other hand, are mainly dealing with communicable tropical diseases.
9. Different novel strategies are being publicized globally for leishmania control, which of these do you consider would be practically feasible?
| Answer|| |
There are a few strategies which could be practically feasible for leishmania control. These include, active cases detection toward early diagnosis and treatment, strengthening of existing surveillance, integrated vector management, single dose treatment with ambisome, treatment of PKDL and HIV–VL, good housing, clean environment, safe drinking water, use of alpha-cypermethrin, deltamethrin for vector control, and use of long-lasting impregnated bed nets. These can be used as models for vector control.
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