The changes were done to adopt for the patients notified from PHCs as high-risk Areas. In the case of presumptive treatment, Chloroquine dose was increased and high expectations from drugs went to such extent that the policy even recommended weekly prophylaxis of chloroquine and Proguanil.

Next series of changes:

The review of drug policy in 2001 continued the 1995 recommendations, but the criteria for designation of chloroquine-resistant areas changed by more than 25% of treatment failure in at least 30 patients of one PHC reporting more than 25% cases. This change seems a net widening exercise as acceptance for accommodation of reported drug resistance.

The drug load increased in 2004 for the confirmed cases of vivax and falciparum from low-risk areas.

Till 2005, all areas labeled as sensitive (high risk or low risk) recommended higher drug loads while the areas labeled as resistant recommended AS+SP combination (AS = 4mg/kg daily for three days and SP=1500/75 mg/kg adult dose) because of SP monotherapy resistance and WHO recommendations. In 2007, the criteria to designate an area as resistant changed, and the new criteria were more than 10% treatment failure in at least 50 patients from Cluster of PHCs reporting more than 30% falciparum cases. The importance of clinical diagnosis and presumptive therapy abandoned under the influence of highly sensitive Rapid diagnostic Kit and high dose chloroquine (25mg/kg) recommended in case of unavailability of laboratory diagnosis in 24 hours. The Primaquine 14 days regimen again recommended because of proved poor Efficacy of 5 days regimen. Quinine plus Tetracycline or Doxycycline recommended in case of treatment failure from the highest available drug combination and use of primaquine recommended to stop in the case of AS+SP therapy.

In 2008, the criteria to designate an area as resistant again changed, and the new criteria were more than 10% treatment failure in at least 50 patients from Cluster of Blocks reporting more than 30% falciparum cases. The negative RDK cases also recommended providing a full treatment regimen.

In 2010, the primaquine (0.75mg/kg SD) was added into the AS+SP combination again, increasing the drug load. In 2013, Artemether Lumefantrine (80+480mg adult dose) recommended replacing combination in North East because of resistance to the SP.

Key findings of literature review:

The key findings of research review are as follows;

· Antimalarial drug list expanded extensively (Since 1982 to 2013 and till date) and the increasing drug dose is proportional to disease transmission in region/area; both the factors increasing drug load on the community and medicalizing them significantly.

· The criteria to designate chloroquine resistance has been changed significantly as net widening exercise allowing to accommodate increasing reported CQ resistance.

· Antimalarial drug policy undermines the immune and nutritional status of both individual and community.

· The conceptual understanding of malaria remains within biomedicine domain evidenced by the fact that much of importance (over-reliance) given to individual level technical interventions like drugs that too; without considering immunity and nutritional status of both individual and community.

· Indian Malaria experts/Planners seems confused (or ignoring) to differentiate between Malaria’s behavior at Individual level and community level. Thus, the Malaria planning lacks ethical consideration for resource allocation in Public Health Planning evidenced by the fact that large resources allocated to least effective intervention that serves the profit making purpose of private sector pharma industry largely.

· Sufferings of the most impoverished household of community remain unaddressed in Health planning, as drugs to ill individual are not the intervention for the household.

Indian context:

It is estimated that the maximum share of global Malaria morbidity (might be because of geographical and environmental conditions which facilitate high transmission) and mortality (might be because of the poorly developed healthcare system) is in Africa alone (approx. 90% of global burden).

The below-mentioned graphs (based on mortality and morbidity statistics from NVBDCP and National Malaria Control Program) could be used to understand the morbidity and mortality trend from 1961 to July 2018 also corroborates the fact that malaria is a significant Public Health problem in the subcontinent.

It has also been pointed out that we are dealing with the tip of the iceberg of malaria, and long term planning is required (Sharma, 2012). A country-level cross-sectional survey might prove useful in further demarking malaria and health-related mortalities and morbidities and can work as a baseline for planning. The accurate estimation data of mortality and morbidity is not available. However, it is quite clear that the Indian population suffers because of malaria, as India has the most considerable share in malaria-related morbidities and mortalities in the South East Asia Region of WHO. Thus, there is no doubt that malaria has relevance as a Public Health Problem in Subcontinent imposing high socioeconomic burden (Kumar, Valecha, Jain, and Dash, 2007; WHO, 2018).

It is important to note that both P. Falciparum and P. Vivax parasites prevail in India, and the possibility of mixed infections in an individual remains high. It can be predicted that considerable immunity must be present in a complex Indian setting.

It has been noticed that tropical strains have more risk of relapse and Epidemiological Picture of Malaria in Indian Context becomes complex because there are several factors contribute in it (Das et al., 2012), while different paradigm of malaria (such as tribal, rural, urban, industrial and border malaria has been defined in the Indian context) and each of these requires specific approaches (Pattanayak, Sharma, Kalra, Orlov, and Sharma, 1994).

The experience since the National Malaria Eradication Programme to Modern time has told that malaria transmission can't be ceased without comprehensive measures. Even if it breaks, success can’t be sustained in India where geographical and environmental conditions are favorable for Malaria transmission, the healthcare delivery system is inadequate and weakly developed or even absent in some areas, and larger share of the population is malnourished.

India has experienced the limitations of technologies and their harmful environmental effects. Many factors had played a significant role in Malaria transmissions such as migration and development projects such as green revolution, rail network, road network, and Dam constructions (Sharma, 1999). Faulty engineering in development projects had a significant role in Malaria transmission and Epidemics (Bose, 2004). Further, several characteristics disqualify malaria from being a suitable infectious disease for eradication (Dowdle, 1998).

The significance of anti-malarial drugs in public health program in Indian context:

The primary purpose of any policy for Pharmacotherapy should be relief in the suffering of community, prevention of mortalities, reducing morbidities, slowing down the resistance, and reducing drug load in community with effective, efficacious, and safe drugs. It should be reiterated that the mere inclusion of any single drug into policy does not necessarily mean that it has succeeded in achieving its desired objective. It will consume a large number of resources before to be added into drug policy as well as post implementing/post-marketing research regarding effectiveness, safety, and Efficacy (all are variable), which seems costly exercise for the resource constraint country like India. If not used before expiry, drugs further consume resources in manufacturing, storage, supply, and disposing of. Again, the well-developed health services system and accessibility to such a system needed to deliver the medicine to those who are in the most need in order to prevent mortalities and to relive morbidities. Moreover, the desired action of drugs, even in an individual, influenced by various factors such as the intrinsic property of the drug itself, degree of resistance shown by parasite, body size and weight of an individual and given nursing care, etc. Failure of one drug led to efforts and resources in search of the new drug, the cycle does not find an end, and obviously, it would have detrimental effects on overall health planning in resource-constrained settings.

A. Malaria Related Mortalities and Morbidities After Antimalarial Drug Policy:

It can be argued that antimalarial drugs have prevented mortalities and morbidities. However, the question would be obvious regarding the cost and claim would be questionable based on graph 1 and graph 2 (increasing Mortality trend and stationary morbidity for a long time after the introduction of the formal policy of Pharmacotherapy).

Graph 1: No. of Malaria Cases in India from the year 1961 to 2018 (up to July)

Graph 2: No. of Malaria Deaths in India from the year 1961 to 2018 (up to July)

It can be argued that indicators such as API, AFI, SPR, SFR, and ABER show improvement. The question is, does it work? Because these are program indicators only and reflect the trend, not the burden; in other words, if clinical and diagnostic services under the malaria program abandoned, immediately all these indicators will show the highest performance, and we can live in the euphoria of the documental tackle of Malaria as Public Health Problem.

Further, the extent of success in the prevention of mortalities and reduction in morbidities is unknown, and it is unknown who had benefitted? Furthermore, who had born the cost in complex Indian setting as it was not explicitly mentioned about directly associated factors of malaria-related morbidities and mortalities.

B. Drug load in community:

It is quite understandable and visible that the list of Antimalarial drugs has been expanded, consuming extensive resources and drug load on the community has been increased significantly. The community labeled as resistant or high risk and living in an area where healthcare services system weak/poor/absent has consumed and still consuming a larger proportion of this drug load irrespective of their individual immunity, nutritional status, and vulnerability.

C. Antimalarial drug resistance:

The argument in favor of slowing resistance is questionable because the criteria to designate an area as resistant have been changed continuously, and it seems like a net widening exercise. It may also be possible that parasite strains might have gone significant changes and resulted in developing resistance continuously towards antimalarial medications in the underdeveloped health system.

It suggests an unending fight between drug and parasite strain, which points out the limitations of antimalarial drugs, and again the introduction of new drugs would require considerable resources.

D. Relief in suffering of community by anti-malarial drugs:

It should be acknowledged that the least could be accomplished while investing a large number of resources following current allopathic Antimalarial pharmacotherapy because it has a limited or minimal role in the Public Health Program and the suffering of the most impoverished household remains unaddressed. It is often advisable not to take medicine too frequently because each medication has specific side effects beside desired effects, ranging from mild to severe. The role of drugs as medicine for the treatment of any illness starts after losing opportunities to prevent the infection or disease in the non-immune population. The current list of Antimalarials includes only Blood schizonticides and Tissues schizonticides, and these drugs are known to clear the only specific stage of the specific parasite. There is no single antimalarial available, which can clear all the stages of all parasites (WHO, 2015). Not a single antimalarial is proven totally safe as every drug has adverse effects and varying degree of tolerability while WHO recommends Pharmacovigilance for monitoring safety. Proven Efficacy of these antimalarial drugs ignores the role of host immunity, which prevents the failing drug from appearing effective (White, 2002). Radical treatment using primaquine has been proved to have little epidemiological and clinical significance in any case in the endemic area where transmission potential remains high (Yadav and Ghosh, 2002).

As antimalarial medications undermine the role of individual immunity, current allopathic Antimalarial pharmacotherapy might work only in the areas where transmission is negligible, the more significant proportion of the population is non-immune, nutritional status of the community is considerably better. The healthcare services are fairly developed; still, the relapse/recrudescence can't be prevented for sure. However, where the larger proportion of the population possesses immunity because of repeated exposure, the transmission is possible, healthcare services are poor/weak/absent, and the nutritional status of the community is poor, the poorest had to suffer the most and resource allocation would not worth. Therefore, the limitations of these drugs/medicines should be explicitly acknowledged. It does not mean that medicines do not have an important role, but it can be emphasized that medicines have a limited role in relieving the suffering of the community's poorest households.

Application of individual Case management approach (largely focusing on antimalarial drugs) to the community by obscuring the differences between individuals and community and differences within the community would be an obstacle in tackling Malaria as Public Health Problem.

It is advised not to take any drug on an empty stomach because of severe side effects (WHO, 2015), and the safety of the poorest from adverse effects of drugs would be compromised under the fear of P. Falciparum mortality. Thus, it becomes vital to take note of immune and nutritional status. If the use of medicines can't be avoided in Public Health Program, there are simply two ways; first, if an area is labeled as resistant/sensitive, program should follow intervention for the area rather than Individuals of Area and; second, if the program is following case management approach, then each individual of community should be treated separately for their resistant or sensitive status considering immune and nutritional status at both individual and community level. It does not mean to say that we should leave it and let the people die, the response is of course needed, but critical planning in resource allocation would maximize the benefits. Otherwise, it would again prove false waves of optimism for Malaria eradication/control as Public Health Problem from India in existing healthcare delivery system ignoring the suffering of poorest, the role of immunity and nutritional status of both individual and community.

Thus, Policy for Pharmacotherapy is unable to serve its primary purpose of relieving suffering of community, prevention of mortalities, reducing morbidities, slowing down the resistance, and reducing drug load in community.

Suggested Remedial Measures:

Health planning is a comprehensive exercise that would need integration of all related disciplines (with addressing politics of knowledge), and the maximized role of Public sector Institutions in interdisciplinary research for Public Health would be crucial. Critical evaluation of the recommendations of any national or international organization would be needed to predict the implications in complex Indian context and limitations should be explicitly acknowledged. Every policy or program decision must be critically examined through the Public health ethics framework because accountability is greater on policymakers. Thus, they have the responsibility to accommodate the voice of dissent. Before embarking on the global saga of malaria eradication or control through the Public Health program, there is a need to learn from previous experiences (including NMEP and historical). A response strategy to malaria should consider the present stage of the country's social, political, economic development, and cultural context with an epidemiological lens to relieve the suffering of the most impoverished individual/household and to achieve sustainable success.

In the light of epidemiological complexity, it can be emphasized that overall socioeconomic development would be crucial as inequalities of health distribution and inequities of healthcare access (Qadeer, 1988) would reflect in morbidity and mortality distribution of Malaria in India. Thus, the context-specific concept of health, as suggested by Priya et al., 2019, should be considered in order to achieve health for all. The emphasis should be placed on start from the people and planning with public health ethical consideration for justified utilization of available resources to relieve the sufferings of the most impoverished household because human factors can't be tested in a laboratory. Instead, it needed to be experienced from the field and applied for action.

Issues and Reasons would be various. The solution is not the simple one without a strong political will for reforms to facilitate equitable and sustainable socioeconomic development, but what least could be done immediately to relieve suffering and for provision of Public Health:

· Planners and Implementers of Health Service system should be clear about the distinction between the behavior of malaria and strategies to tackle it at the Individual and community level.

· The starting can be done with the revival and strengthening of effective Public Health Engineering until ensuring water supply and sanitation for most impoverished household as an intervention and preventive measure to relieve their sufferings. It will eventually contribute to Health Provision and control the vector population without any harmful effect on any individual or environment.

· Strengthening and effective implementation of PDS (with improvement in the image of the existing Program in Community) would provide considerable relief to the poorest households and eventually lead to an improvement in the nutritional status of the community.

· Strengthening and Effective implementation of Employment Schemes (such as MGNREGA) and Pension Schemes would be crucial for improving living standards and eventually reducing malaria-related morbidities and mortalities.

CONFLICT OF INTEREST:

No any

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Received on 07.01.2022 Modified on 09.05.2022

Asian J. Pharm. Ana. 2022; 12(4):233-242.

DOI: 10.52711/2231-5675.2022.00038

Step of Review	Particulars	Details
1.	Specific Objective	“Understanding Basics of Malaria and Antimalarial Drugs”
1.	Source of Information	· Medical Textbooks on Malaria
2.	Specific Objective	“Identification of Historical Roots of Antimalarial Drugs”
2.	Source of Information	· Book Title:- Maladies, preventives, and curatives: Debates in public health in India” Edited By A. K. Bagchi and K. Soman, Chapter on Cinchona Policy in British India by V.R. Muraleedharan 2005
3.	Specific Objective	“Understanding the Context before the emergence of a formal policy for Antimalarial drugs”
3.	Source of Information	· The report of the consultative committee of experts, 1974 · RACMR (Regional Advisory Committee on Medical Research) WHO document of 1976 · The document of the decision taken in Annual Malaria conference of Malaria and Filaria workers at Chandigarh, 1981
4.	Specific Objective	“Understanding the formal policy 1981 and significant policy changes since introduction of first formal policy document”
4.	Source of Information	· Anvikar et. al, (2014). Antimalarial drug policy in India: Past, present and future. The Indian Journal of Medical Research, 139(2), 205–215
5.	Specific Objective	“Writing The Argument and Discussion following Brief explanation of formal policy, Analyzing the changes, and identification of issues”
5.	Source of Information	· Research papers/documents searched on Internet (using key words “Antimalarial Drugs, Malaria, and Malaria Epidemiology in India etc. on PubMed) · NVBDCP Data on Malaria related mortalities and morbidities in India · Relevant Documents from NICD (National Institute of Communicable Diseases, New Delhi) Library and Documentation Cell of CSMCH (Centre of Social Medicine and Community Health, Jawaharlal Nehru University, New Delhi)

Till Late 1950s
Presumptive Treatment	Treatment after confirmation		Special Groups
Presumptive Treatment	P. Falciparum Malaria	P. Vivax Malaria	Severe Malaria	Malaria in Pregnancy	Chemoprophylaxis or MDA
CQ or AQ (10mg/kg SD)	PQ (0.25mg/kg for 5 days)		---	-----	MDA: Presumptive + PYR (adult SD 50 mg)

Criteria for Designating Chloroquine Resistance:
*Presumptive Treatment*	Treatment after confirmation		Special Groups
*Presumptive Treatment*	*P. Falciparum Malaria*	P. Vivax Malaria	Severe Malaria	Malaria in Pregnancy	Chemoprophylaxis or MDA
CQ (10 mg/ kg SD) in ACD, DDCs, and FTDs	CQ (10 mg/kg SD) + PQ (0.75mg/kg SD)	CQ (10 mg/kg SD) + PQ (0.25 mg/kg for 5 days)	Parenteral CQ or Quinine	Contraindications: PQ	MDA in migrants: CQ (10 mg/kg) + PQ (0.75 mg/kg)
AQ (10 mg/ kg SD) in ACD, DDCs, FTDs and SLP (adult SD 1000/50mg) in PCD	SLP (adult SD 1000/50 mg) + PQ (0.75mg/kg SD)
First Formal Policy 1982 Source: Anvikar et. al. 2014

Major Changes in Antimalarial Drug Policy 1995
*Presumptive Treatment*	Treatment after confirmation		Special Groups
*Presumptive Treatment*	*P. Falciparum Malaria*	P. Vivax Malaria	Severe Malaria	Malaria in Pregnancy	Chemoprophylaxis or MDA
CQ (10 mg/ kg SD)	CQ (10mg/kg SD) + PQ (0.75mg/kg SD)	CQ (10mg/kg SD) + PQ (0.25mg/kg for 5 days)	Parenteral CQ or quinine	Contraindications: PQ	MDA in migrants: CQ (10 mg/kg) + PQ (0.75 mg/kg)
CQ (25 mg/ kg over 3 days)+PQ (0.75mg/kg SD)	CQ Sensitive: No further Treatment CQ Resistant: SP (Adult dose 1500/75mg) with PQ (0.75 mg/kg SD)	+ PQ (0.25mg/kg for 5 days)	Parenteral Artemisini derivatives or quinine	___“”____	CQ Sensitive: CQ (10 mg/kg LD then 5 mg/kg weekly) CQ Resistant: CQ (5 mg/kg weekly) + proguanil (100 mg daily)