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Malaria: current strategies for control in India
Binny Dua, Anita S Acharya 
Department of Community Medicine, Lady Hardinge Medical College, New Delhi-110001, India.



Corresponding Author
: Dr Anita S Acharya
38,Engineer’s Enclave, Pitampura, New Delhi-110034, India. E-mail: anitaacharya29@gmail.com


History : Received - 27-Oct-2012 Accepted - 19-Dec-2012 Published Online -  30-Dec-2012
DOI : http://dx.doi.org/10.7713/ijms.2012.0089


Abstract

Malaria continues to be one of the important public health problems in India. India shares two thirds of malaria burden present in South East Asian Region. At present, malaria control strategies are being implemented under the National Vector Borne Diseases Control Programme (NVBDCP). The strategies for control of malaria depend largely on the vector bionomics as well as the disease burden present in a particular area. NVBDCP has established different strategies based on different ecotypes of malaria. With the decline in the annual positive cases over a period of time, much progress has been made in the field of malaria. However, major challenges remain in the form of chloroquine-resistance and increasing proportion of Plasmodium falciparum cases in recent years, which need to be addressed at the earliest. In addition, cases of fifth plasmodium species (P. knowlesi) reported from nearby countries, is another impending threat for India in the near future. As a result of these, major changes have been made in the strategic action plan for control of malaria. Future interventions in the form of malaria vaccine and development of genetically modified mosquito which is almost 100% immune to malaria will be a boon for effective malaria control. As of now, a number of challenges need to be resolved before India enters the pre-elimination phase.

Keywords : Chloroquine; India; malaria; malaria vaccines; Plasmodium; Plasmodium knowlesi.

Introduction

Malaria continues to be one of the important public health problems in India. As per World Health Organisation report 2011-2012, South East Asian Region bears the second largest burden of malaria (13%), only being next to African region (81%). Among South-east Asia region, India shares two-thirds of the burden (66%) followed by Myanmar (18%) and Indonesia (10%) [1]. The only country in South-east Asia region ‘free of malaria’ is Maldives while Srilanka and the Democratic People’s Republic of Korea are in the ‘pre-elimination phase’. India, Bangladesh, Bhutan, the Democratic Republic of Timor-Leste, Indonesia, Myanmar, Nepal and Thailand are in the ‘control phase’ [1].

Malaria distribution in India

Malaria is a vector borne disease usually caused by four species of Plasmodium. In India, the most common and deadliest species is P. falciparum contributing to 52% of the total malaria cases in 2010 which is closely followed by P. vivax. Other two species are P. malariae and P. ovale which contribute to < 10% of the burden with very few cases being due to ovale species. Recently a fifth plasmodium species, P. knowlesi which usually infects macaques has been identified and over the past few years hundreds of human cases have been reported in South and South East Asian countries especially Malaysia with increasing numbers in Europe as well [2]. The diagnosis of P. knowlesi in humans may have been missed by microscopy earlier owing to its morphologic similarity with P. malariae. Nested PCR technology and molecular characterisation remains the most reliable method for detecting P. knowlesi. However, research needs to be carried out on P. knowlesi affecting humans, to study whether the infections are acquired from macaque monkeys or whether a host switch to human beings has occurred as P. knowlesi can be a potential future threat due to its very short incubation period leading to high parasite density in a very short time (24 hours) leading to fatal infection in human beings [2]. Although till date, no case in India has been reported, but the risk of transmission remains especially for the four north-eastern states which share border with Myanmar, thus increasing the chances of import of cases [3].

Malaria distribution in India depends much upon vector bionomics. In India, 58 Anopheles species have been described, six of which have been implicated to be main malaria vectors, namely An. culicifacies, An. dirus, An. fluviatilis, An. minimus, An. sundaicus and An.stephensi. Besides, some are of local importance, viz. An. philippinensis-nivipes, An. varuna, An. annularis and An. jeyporiensis [4]. Vector bionomics of anopheles species are summarised in Table 1. The study of vector bionomics plays an important role in implementation of control strategies.



State-wise distribution of malaria cases is given in figure 1. As can be seen around 80% of malaria burden is confined to 20% of population residing in high risk areas like Odisha, Jharkhand, Chhattisgarh, Madhya Pradesh, north-eastern states except Sikkim, Maharashtra and Rajasthan.



Malaria control strategy in India

During the pre-independence era, malaria was considered as a major public health problem and the single largest cause of mortality in India. The highest incidence of malaria in India was reported in 1950s, with an estimated 75 million cases and 0.8 million deaths per year. With the advent of ‘National Malaria Control Programme’ in India in 1953, the situation drastically improved within five years of introduction that lead to change in its objective from ‘Control’ to ‘Eradication’. With initial success, an all-time lowest case incidence was reported in 1968. However, soon major setback was observed with a number of outbreaks occurring in different parts of the country due to various operational, administrative constraints. This led to the formulation of ‘Modified Plan of Operation’ in 1977, in which strategies differ in different regions according to the most commonly used parameter of annual parasite incidence (API). With the implementation of control strategy according to API, a decrease in overall number of cases was observed and total number of positive malaria cases being reported, have remained almost constant over the last few years to around 1.5 to 2 million cases per year. Scenario of malaria changed in 1990s as a result of number of factors that included emergence of DDT-resistance in vectors, emerging vectors with exophilic nature leading to failure of Indoor Residual Spray (IRS) method and above all increasing urbanisation leading to increased migration of populations thus changing the pattern of disease to a large extent (Figure 2).



Change in parasite occurrence with increasing proportion of falciparum from 10% in 1970s to around 50% in 2010 is also one of the growing concerns of today. Emerging chloroquine-resistance especially in case of P. falciparum is considered as one of the important contributing factors responsible for an increase in its occurrence. Further, it has been observed that in subsequent years resistant P. falciparum will be soon replacing the susceptible plasmodium population leading to further worsening of the situation. First case of chloroquine-resistance in P. falciparum in India was reported in 1973 and in 1974 in Karbi-Anglong and Nowgong districts of Assam, respectively. Gradually it spread towards the west and south, covering almost the entire country [6]. Mechanism of chloroquine-resistance is associated with the ability of P. falciparum to expel chloroquine at a much faster rate that does not allow chloroquine to reach the level required for inhibiting haem polymerase. Specific mutation leading to resistance to anti-folate drugs has also been recognised. It has also been observed that transmission of drug resistance may get enhanced by the combination of drug-resistant malarial parasite and particular vector species. For example in South-east Asia, Anopheles stephensi and An. dirus appear to be more susceptible to drug-resistant malaria than to drug-sensitive malaria [8]. Some cases of cross-resistance to chloroquine and amodiaquine have also been reported. Apart from the above mechanisms there are numerous factors which play an important role as far as intensification of drug resistance is concerned, for example, conditions decreasing the effectiveness of immune response of an individual to previous malarial infection lead to further enhancement of development of resistance.  

Keeping in view the malaria situation in 2002, a major breakthrough occurred when integrated accelerated action to control other vector-borne diseases as well was decided to be taken under one programme named as National Vector Borne Diseases Control Programme (NVBDCP).

Current strategies under the programme

The major strategies being pursued by the NVBDCP [9] for achievement of its objectives for control of malaria are: (i) disease management through early case detection and complete treatment, (ii) integrated vector management (IVM) to reduce the risk of vector-borne transmission; and (iii) supportive interventions which include communicating behaviour change, capacity building and monitoring and evaluation of programmes. Under the strategies, as far as diagnosis of the suspected case is concerned, Rapid Diagnostic Kits were introduced in inaccessible areas or in areas with high API /high P. falciparum to facilitate easy and immediate diagnosis. Involvement of ASHA, peripheral health worker for diagnosis is one of the newer initiatives introduced under National Rural Health Mission.

Earlier, any fever case was considered as malaria, until proven otherwise and presumptive treatment with chloroquine was initiated. Now, as per the drug policy 2011 [10], ‘presumptive treatment is no longer followed’. The treatment regimen currently followed under the programme is as follows [9]-

• Uncomplicated P. vivax- Chloroquine for 3 days (Day 1: 10 mg/kg + Day 2: 10 mg/kg + Day 3: 5 mg/kg) plus Primaquine 0.25 mg/kg daily for 14 days
• Uncomplicated P. falciparum- Artesunate (4 mg/kg body weight) daily for 3 days and sulfadoxine-pyrimethamine (25 mg/kg + 1.25 mg/kg body weight) on Day 0; plus Primaquine 0.75 mg/kg body weight single dose on day 2
• Mixed Infections (P. vivax + P. falciparum)- Full course of artemisinin-based combination therapy (ACT) + Primaquine 0.25 mg/kg daily for 14 days

During pregnancy-

First trimester- Quinine salt 10 mg/kg daily for 7 days
Second & third trimester- ACT to be given

According to the guidelines, initiation of alternative treatment regimen in the form of ACT (Artesunate plus Sulfadoxine-Pyrimethamine) at Treatment Failure Proportion = 10% (in a sample of minimum 30 P. falciparum cases) is recommended for treatment of P. falcipuram cases in chloroquine-resistant areas/block primary health centres [9]. Presently, ACT use is now implemented in 117 high endemic districts and 256 block primary health centres in 48 districts which have reported resistance to chloroquine [10].

Chemoprophylaxis

Short term (<6 weeks)- Doxycycline 100 mg daily in adults and 1.5 mg/kg bodyweight for children more than 8 years old. The drug should be started 2 days before travel and continued for 4 weeks after leaving the malaria-endemic area. It is contraindicated in pregnant and lactating women and children less than 8 years old.

Long term- Mefloquine 5 mg/kg body weight (up to 250 mg) weekly should be administered two weeks before, during and four weeks after leaving the area. This is given for a longer duration.

Under integrated vector management, vector control strategies vary according to the different ecotypes of malaria (Table 2).



As per the strategic action plan 2007-2012 [10], criteria for ‘indoor residual spray’ with synthetic pyrethroids that needs to be done on priority basis with suitable insecticide includes:

• all areas with = 5 API where ABER is 10% or more
• reporting = 5% SPR, if the ABER is below 10%
• Plasmodium falciparum proportion = 50%
• Drug resistant foci, project areas with population migration.

Another important recent strategy [11] used under ‘Integrated Vector Management’ includes the introduction of ‘long lasting insecticide bed nets’ (LLINs) and to replace the conventional bed nets giving priority to areas with consistently high API, high proportion of Plasmodium falciparum cases, and/or reported deaths. Inaccessible areas as well as areas operationally difficult for ‘indoor residual spray’ will also be given consideration. Presently, ‘long lasting insecticidal nets’ are given 2 per household considering 5 members in a family. ‘Long lasting insecticidal nets’ are treated by synthetic pyrethrum and can resist up to 20 washes. For its successful implementation, a strong and effective IEC (Information Education Communication) needs to be undertaken with special emphasis on safety of its users especially for pregnant women, children and infants and methods to maintain appropriate storage of nets [12]. The nets will be distributed free of cost through public health system or at community health camps. Involvement of various non-governmental organisations and Community Based Organisations is also encouraged for distribution of nets. The community should be made aware about its importance and its utility for prevention of malaria. The criteria for prioritisation of villages for bed net distribution are as follows: areas with consistently high API; high proportion of Plasmodium falciparum cases, and/or reported deaths; inaccessible areas like those cut off during high transmission, remote location; poor access to facilities for the treatment of severe & complicated cases and areas operationally difficult for ‘indoor residual spray’.

Newer initiatives taken for the control of malaria include establishment of sentinel hospitals to assess the magnitude and pattern of severe cases of malaria and to improve referral from primary health care facilities to sentinel surveillance hospitals. 

The above strategies are mostly implemented in the rural areas but malaria is very well present in the urban areas. In order to control malaria menace in urban area, urban malaria scheme was implemented in 1971. At present, the scheme is implemented in 131 towns in 19 states. Major vector control methods under the scheme include anti-larval measures which includes both chemical as well as biological control. Chemical control is done with the help of larvicides like abate while biological measure includes introduction of larvivorous fish e.g. gambusia & guppy in many states. Biocides from bacterium Bacillus thuringiensis are also being used under NVBDCP. Larvicides are being applied on a weekly basis in water bodies that are unsuitable for fish use. In addition, the implementation of urban bye-laws to prevent mosquito breeding in domestic and peri-domestic areas, and government buildings remains the major control measure in these areas [10].

Despite considerable success in control of malaria we lag far behind in the path to eliminate malaria in the near future. Number of challenges that need to be addressed along with suggested solutions are summarised in Table 3 [13].



Future interventions

Malaria vaccine continues to be a prospective future intervention needed to control malaria. Basis for development of malaria vaccine includes development of protective immunity by immunisation with irradiated sporozoites– T-cells against liver stage antigens considered as effector. Selective anti-malaria vaccines that are under different phases of trial are given in table 4 [14].



The development of vaccine and its inclusion in the programme is associated with a number of challenges which include difficulties in evaluation of efficacy of vaccine in endemic areas along with lack of understanding of immunosuppressive mechanism of the parasite.

Introduction of genetically modified mosquito which is almost 100% immune to malaria thus preventing the spread among the humans can be considered as yet another effective tool as far as control of malaria is concerned. The researchers at the University of Arizona have successfully bioengineered the world’s first malaria-proof mosquito [15]. Future prospects include replacement of wild- type mosquitoes with the new malaria-proof strains, thus effectively controlling the disease.
The success story of Maldives [1] in elimination of malaria is worth emulating. Malaria eradication in the Maldives was achieved through the elimination of two anopheline mosquito vectors; An. tessellatus and An. subpictus who were totally dependent on human blood due to lack of higher mammals in the area. They were made to be confined away from human habitation in addition to other control measures which finally lead to extinction of vector species. Since 1984, when the last case was reported, adequate measures in the form of entomological and parastiological surveillance are being carried out; along with full political commitment playing an equally important role in preventing the reintroduction of malaria.

Conclusion

To conclude, malaria still continues to be a public health problem in India. For adequate control strong inter-sectoral coordination with a good political commitment is needed for effective implementation followed by appropriate monitoring and evaluation of programme. Multicentric studies need to be planned to fill the information gaps. In addition, we need to do a situational analysis and find out appropriate solutions to various challenges and practical issues that are present before /during the implementation process. In the end, we hope India soon enters the pre-elimination phase but as we all know it is still a long way to go and a lot needs to be done.

Key Points

• India contributes to two-third of malaria burden in South-east Asia region.
• A fifth plasmodium species (P. knowlesi) reported from nearby countries, is another impending threat for India in the near future.
• Major challenges facing India are chloroquine-resistance and increasing burden of P. falciparum in recent years.
• Malaria vaccine and genetically modified mosquito are likely to be the future interventions for malaria control.

References

1. World Health Organization. World Malaria report 2011. Available at www.who.int/malaria/world_malaria_report_2011/. Accessed on 15th October 2012.
2. Singh B, Kim Sung L, Matusop A, Radhakrishnan A, Shamsul SS, Cox-Singh J, et al. A large focus of naturally acquired Plasmodium knowlesi infections in human beings. Lancet 2004;363:1017-24. [PUBMED]
3. Subbarao SK. Plasmodium knowlesi: from macaque monkeys to humans in South-east Asia and the risk of its spread in India. J Parasit Dis 2011;35:87–93. [PUBMED]
4. Dash AP, Adak T, Raghavendra K, Singh OP. The biology and control of malaria-vectors in India. Current Science 2007;92:1571-8.
5. NVBDCP. Available at http://nvbdcp.gov.in Accessed on 15th October 2012.
6. Sehgal PN, Sharma MID, Sharma SL, Gopal S. Resistance to chloroquine in falciparum malaria in Assam state, Indian J Comm Dis 1973;5:175–80.
7. Farooq U, Mahajan RC. Drug resistance in malaria. J Vect Borne Dis 2004;41:45-53.
8. Bloland BP. Drug resistance in malaria. Department of Communicable Disease Surveillance and Response. World Health Organization 2001. http://www.who.int/csr/resources/publications/drugresist/malaria.pdf Accessed on October 16, 2012.
9. National Institute of Malaria Research, National Vector Borne Disease Control Programme. Guidelines for diagnosis and treatment of Malaria 2011. 2nd edition, Delhi: NIMR; 2011. Available at www.mrcindia.org/Guidelines%20for%20Diagnosis2011.pdf Accessed on October 16, 2012.
10. Strategic Action Plan for Malaria Control in India 2007-2012. Directorate of National Vector Borne Disease Control Programme. Directorate General of Health Services, Ministry of Health and Family Welfare, Delhi. Available at http://nvbdcp.gov.in/Round-9/Annexure-2%20%20Strategic%20action%20plan.pdf Accessed on October 16, 2012.
11. Operational manual for implementation of malaria programme 2009. Directorate of National Vector Borne Disease Control Programme. Directorate General of Health Services, Ministry of Health and Family Welfare. Available at http://nvbdcp.gov.in/Doc/malaria-operational-manual-2009.pdf Accessed on October 16, 2012.
12. Action plan for scaling up long lasting insecticidal nets for malaria control in India. Directorate of National Vector Borne Disease Control Programme. Directorate General of Health Services, Ministry of Health and Family Welfare. Available at http://nvbdcp.gov.in/Doc/LLIN-Action-Plan-2009.pdf Accessed on October 16, 2012.
13. Dash AP, Valecha N, Anvikar AR, Kumar A. Malaria in India: challenges and opportunities. J Biosci 2008;33:583–92.
14. Valecha N. Malaria vaccine. Available at www.hisindia.org/data/malaria-vaccine.pdf Accessed on October 26, 2012.
15. Corby-Harris V, Drexler A, Watkins de Jong L, Antonova Y, Pakpour N, Ziegler R, et al. Activation of Akt signaling reduces the prevalence and intensity of malaria parasite infection and lifespan in Anopheles stephensi Mosquitoes. PLoS Pathog 2010;6:e1001003.[PUBMED]

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