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Incidence and Control of malaria : A Situation in India


Abstract:

Malaria is a major public health problem in some States of India including the North East region. Recognizing the burden due to malaria on the health and economic development of the population living in ‘high-risk’ areas, the Government of India has given special attention to malaria control in these areas. In India malaria endemicity is characterized by diverse ecology and multiple disease vector species. India contributes about 70% of malaria in the South East Asian Region of WHO. Although annually India reports about two million cases and 1000 deaths attributable to malaria, there is an increasing trend in the proportion of Plasmodium falciparum as the agent. There exists heterogeneity and variability in the risk of malaria transmission between and within the states of the country as many ecotypes/paradigms of malaria have been recognized.

This paper reviews the incidence and control of malaria in India. This paper highlights the need for malaria elimination in India, malaria vectors, mortality rate, challenges in control, economic burden on government, drug resistance and strategies.

1. Introduction

Malaria is a major public health problem in India but is preventable and curable. Malaria interventions are highly cost-effective and demonstrate one of the highest returns on investment in public health. In countries where the disease is endemic, efforts to control and eliminate malaria are increasingly viewed as high-impact strategic investments that generate significant returns for public health, help to alleviate poverty, improve equity and contribute to overall development.

Each case of malaria has been shown to cost households at least US$ 2.67 (range US$ 0.34– 7.66) in direct out-of-pocket expenses. In adults, this leads to an average of 3.4 days (range 2–6 days) of lost productivity, at a minimum additional indirect cost of US$ 10.85. Mothers and other carers sacrifice a further 2–4 days each time a child or other family member contracts malaria, generating yet more indirect costs for households3 . Even though such estimates and studies are few and still evolving in India, the total economic burden from malaria could be around US$ 1940 million. Death rates are not a significant factor because 75% of the burden comes from lost earnings and 24% from treatment costs4 . A malaria burden analysis inferred that every Rupee invested in malaria control in India (1994) produces a direct return of Indian Rupees 19.70 5.

From the beginning of the 21st century, India has demonstrated significant achievements in malaria control with a progressive decline in total cases and deaths. Overall, malaria cases have consistently declined from 2 million in 2001 to 0.88 million in 2013, although an increase to 1.13 million cases occurred in 2014 due to focal outbreaks. The incidence of malaria in the country therefore was 0.08% in a population of nearly 1.25 billion. In 2015, 1.13 million cases (provisional) were also reported. It is worthwhile to note that confirmed deaths due to malaria have also declined from 1005 in 2001 to 562 in 2014. In 2015, the reported number of deaths has further declined to 287 (provisional). Overall, in the last 10 years, total malaria cases declined by 42%, from 1.92 million in 2004 to 1.1 million in 2014, combined with a 40.8% decline in malaria related deaths from 949 to 562.

India contributes 70% of malaria cases and 69% of malaria deaths in the South-East Asia Region. However, a WHO projection showed an impact in terms of a decrease of 50–75% in the number of malaria cases by 2015 in India (relative to 2000 baseline), which showed that the country has been on track to decrease case incidence 2000–2015 1 .

During 2000, 17 states and union territories (UTs) had an annual parasite incidence (API) of less than one case per thousand population at risk. Overall, in 2014 and 2015, in 26 and 27 states/ UTs respectively, the incidence of malaria was brought down to an API of less than one case per thousand. In 2000, 370 districts also had an API of less than one case per thousand population at risk. In 2014 and 2015, of a total of 677 districts (reporting units), 527 (78%) reported an API of less than one case per thousand population at risk.

Presently, 80% of malaria occurs among 20% of people classified as “high risk”, although approximately 82% of the country’s population lives in malaria transmission risk areas. These populations at high-risk for malaria are found in some 200 districts of Andhra Pradesh, Chhattisgarh, Gujarat, Jharkhand, Karnataka, Madhya Pradesh, Maharashtra, Odisha, West Bengal and seven north-eastern states.

Undoubtedly, such reduction of malaria morbidity and mortality reflects tangible success relative to the pre-independence era, before the launch of the National Malaria Control Programme (NMCP) in 1953, when malaria was a major public health problem with 75 million cases and 0.8 million deaths, causing enormous human suffering and loss to the nation, both in terms of manpower and money.

Previously, there were tremendous achievements made in bringing down the malaria burden with the overwhelming success of the NMCP leading to the launch of the National Malaria Eradication Programme (NMEP) in 1958. The NMEP was also initially a great success with malaria incidence dropping to 0.1 million cases with no deaths reported in 1965. However, the resurgence of malaria due to technical, operational and financial complexities resulted in an escalation of incidence to 6.4 million cases in 1976. With the Urban Malaria Scheme (UMS) implemented in 1971–1972 and a renewed focus and commitment, in 1977 the Modified Plan of Operation (MPO) and the Plasmodium falciparum containment programme (PfCP) were launched and malaria incidence was reduced to around two million cases per year by 1984 Amply demonstrating the success of the National Vector Borne Disease Control Programme (NVBDCP) is the fact that 75 million cases and 0.8 million deaths annually due to malaria in the pre-independence era fell to 1.1 million cases and 562 deaths in 2014.

As malaria is characterized by focal occurrences and achievements made with reduction in mortality and morbidity are fragile without constant attention to the existing malaria challenges, the sustaining of gains is critical as there is a risk of turning low endemic areas back into high risk areas

2. The Need for Malaria Elimination in India

Recent trends in malaria control efforts globally and in India demonstrate that achievements can be fragile, making sustained efforts vital. Scientific breakthroughs in recent years have provided better tools such as new drugs, diagnostics and vector control strategies. These tools need to be utilized and scaled up rapidly before they become ineffective in preventing or controlling malaria 11, 12 Additionally, there is also a growing threat of the spread of malaria multi-drug resistance including resistance to artemisinin-based combination therapies from the neighbouring Greater Mekong Subregion countries 13, coupled with the shortage of new and effective antimalarials 14, 15. All these reasons underscore the importance of shifting the country’s focus from malaria control to malaria elimination.

Malaria incidence has dropped to such low levels in some states/UTs in India that interruption of transmission has become a feasible objective in these states/UTs, and in another few years the interruption can be expected even in states/UTs with moderate transmission of malaria. In states/UTs with high transmission of malaria, a massive scale-up of preventive and curative interventions is expected to substantially reduce the transmission intensity and reservoir of infection.

There is also a need to ensure close coordination of malaria elimination activities with neighbouring countries, particularly where frequent movement takes place across international borders. With reports of artemisinin resistance emerging from bordering countries such as Myanmar 13, moving towards malaria elimination will be a step in the right direction, as is being done by countries in the Greater Mekong Subregion. Any further delay in addressing the problem of P. falciparum malaria could lead to the deterioration of the malaria situation and the emergence of multi-drug resistance, including resistance to artemisinin-based combination therapies.

Finally, there is now an increasing political commitment and participation of partners in the country’s march towards malaria elimination. This is shown by the participation of the Indian Prime Minister among the 18 leaders who endorsed the APLMA Malaria Elimination Roadmap released at the recently concluded East Asia Summit held in Kuala Lumpur, Malaysia, in November, 2015. 17

3. Malaria vectors

The transmission of malaria is governed by local and focal factors leading to vector abundance under favourable conditions. There are six primary vectors of malaria in India: An. culicifacies, An. stephensi, An. dirus, An. fluviatilis, An. minimus and An. epiroticus (previously: An. sundaicus). The secondary vectors are An. annularis, An. varuna, An. jeyporiensis and An. Philippinensis.

An. culicifacies is the main vector of rural and peri-urban areas and is widespread in peninsular India. It is found in a variety of natural and man-made breeding sites. It is highly zoophilic and therefore a high density of cattle limits its vectorial capacity. An. culicifacies is a complex of 5 sibling species designated as A, B, C, D and E. Species A has a relatively higher degree of anthropophagy as compared with species B. Species A is an established vector of P. vivax and P. falciparum, whereas species B is completely refractory to P. vivax and partially refractory to P. falciparum. It has been demonstrated that species B, however, may play a role as a vector of P. falciparum in areas where the cattle population is very low or absent.

An. stephensi is responsible for malaria in urban and industrial areas. An. stephensi is a complex of 3 variants, i.e. type form, intermediate form and mysorensis form. The type form is found in urban areas; intermediate form in urban and semi-urban localities and mysorensis form in rural areas. Both type form and intermediate form act as vectors whereas the mysorensis form is not a vector.

An. fluviatilis is the main vector in hilly areas, forests and forest fringes in many states, especially in the east. An. fluviatilis is a complex of 4 sibling species designated as S, T, U and V, of which species S is highly anthropophagic and an efficient vector of malaria. An. minimus is the vector in the foothills of North-Eastern states. An. dirus is an important forest vector in the North-East, well known for its exophilic behaviour. An. epiroticus, a brackish-water breeder, in India is now restricted to the Andaman and Nicobar Islands. Resistance to DDT and malathion is common in An. culicifacies and An. stephensi in peninsular India. Insecticide resistance in other vectors is thought to be patchier, and information on this aspect is planned to be collected by a large number of studies in various parts of the country from 2009 to 2014. In addition to monitoring insecticide resistance, there is a need for field entomology in India to update knowledge on bionomics of species and subspecies as well as their vectorial status, taking into consideration climate and environmental changes and the long-term effects of various vector control methods.

The number of sibling species so far identified among the Indian anophelines is given in Table below:

Table 1. Species complexes among Indian anophelines

Source: NIMR, 2017

4. Incidence and Mortality rate due to Malaria in India

The countrywide malaria situation as reflected in surveillance data from 1995-2017 is given in the following Table: 1.

Table 1: Countrywide Epidemiological Situation (1995 - 2017*)

(Source: http://nvbdcp.gov.in/malaria3.html)

The case load, though steady around 2 million cases annually in the late nineties, has shown a declining trend since 2002. When interpreting API, it is important to evaluate the level of surveillance activity indicated by the annual blood examination rate. At low levels of surveillance, the Slide Positivity Rate (SPR) may be a better indicator. The SPR (not shown in table) has also shown gradual decline from 3.50 in 1995 to 0.87 in 2016. The reported Pf cases declined from 1.14 million in 1995 to 0.71 million cases in 2016. However, the Pf % has gradually increased from 39% in 1995 to 65.53% in 2016. Number of reported deaths has been levelling around 1000 per year. The mortality peak in 2006 was related to severe malaria epidemics affecting Assam caused by population movements.

5. Challenges in Malaria Control

The key challenges in malaria control can be summarized as follows:

a) Population movements, often uncontrolled across states/UTs, and sharing of large international borders with neighbouring malaria endemic countries

There are 36 states and union territories in India, most of which share large borders with each other. This often leads to the spread of malaria from one state to another due to movement of populations. With different administrative structures and variable functioning of health systems in each state, management of malaria in such mobile and migrant populations becomes difficult. Additionally, some of the high-endemic states including north-eastern states share their border with neighbouring countries such as Myanmar and Bangladesh where malaria is still prevalent and there is a persistent threat of influx of malaria cases from these countries. There is also a growing threat of the spread of malaria multi-drug resistance including ACT resistance as a result of sharing these international borders.

b) Shortage of skilled human resources

The programme is adversely affected by an insufficient number of sanctioned posts of health workers and other programme staff in different parts of the country. For instance, there are about 40 000 multipurpose health workers (MPWs) against approximately 80 000 sanctioned posts for nearly 150 000 sub-centres (SCs) across the country. Additionally, there is a shortage of qualified entomologists in the country leading to poor vector surveillance and a lack of robust data on entomological aspects of malaria.

There are existing vacancies of malaria workers and Entomologists in large numbers in many states leading to diminishing skilled manpower for vector control. The Entomologists working for vector control is a vanishing tribe which enjoys lower priority and prestige within the control programme playing second fiddle to the medical fraternity and often work primarily as data and/or file managers. This interferes with their primary responsibility in the field which is guiding and monitoring vector control operations, impact assessment of interventions, resistance studies and population dynamics of vectors for appropriate targeting. This situation needs correction and also vacancies of Entomologist need to be filled up on priority basis followed by ‘on job’ training and re-orientation to upgrade skills. Training programmes at the national and sub-national level for entomologists, epidemiologists and physicians handling complicated cases should be given top priority.

One of the key components of a successful anti malaria campaign is the community participation which can be elicited by information, education and communication (IEC) and Behavioural Change Communication. For this, regular training/orientation of Mass Media Officers, Field Extension and Health Educators attached to the programme is necessary followed by their effective deployment in the field. Inadequate infrastructure and mobility are other key factors responsible for operational problems particularly in the remote and difficult areas.

c) Counterfeit drugs

Counterfeit antimalarials are a major threat to malaria control in the entire South East Asia including India threatening at the same time the lives of thousands of people and possibly leading to development of drug-resistant strains. Paul Newton and colleagues from Oxford University have reported that at least 12 different types of counterfeit antimalarials are in circulation in South East Asia (Newton et al 2006). It has been suggested that approx 30-50% of drugs are fakes.

6. Economic Burden on Government for Malaria Control

The purpose of malaria surveillance is to find out the trends and distribution of the disease for the purposes of planning, evaluation and early detection of epidemics. However, it is important to get a true estimate of malaria related morbidity and mortality in order to plan and project the resource requirements for its control.

The WHO has estimated that malaria was responsible for 10.6 million cases and 15,000 deaths in India in 2006.1 These estimates are based on extrapolations from surveillance data with assumptions made on underreporting. According to the World Malaria Report 2011, India contributed to 4.6 per cent of P. vivax cases, 1.1 per cent of P. falciparum cases and 1.7 per cent of world’s malaria burden in 2010.

Taking into consideration the highly focal distribution of malaria, the accurate estimation of national malaria mortality and morbidity burdens is inherently very difficult. Also, there are very few studies on estimation of the malaria morbidity, mortality and burden of malaria in pregnancy in the country. The NVBDCP intends to arrive at better estimates of severe malaria cases and mortality by establishment of a sentinel surveillance system in all high endemic areas. Non-governmental health care providers are also increasingly involved for reporting of malaria cases and deaths. Collaboration with research institutions is also enhanced for conducting studies to assess the true malaria burden in the country.

7. Drug Resistance

The National Programme has monitored antimalarial drug resistance over many decades with the help of NIMR. Although chloroquine-resistant P. falciparum was first reported near the India–Myanmar border in 1973, chloroquine-resistant P. vivax was unknown in India until 1995, when two cases of infection with resistance were detected in Mumbai. For many years, the Malaria Research Centre (now the NIMR) and other organizations supported a wide range of monitoring efforts in addition to the routine work of the regional teams. Between 1978 and 2007, at least 380 in vivo trials of chloroquine and/or sulfadoxine-pyrimethamine for the treatment of P. falciparum malaria were conducted in India, with involvement of almost 19,000 patients. Worryingly, the median percentage of cases failing to show an adequate response to sulfadoxine-pyrimethamine within 28 days of treatment increased from 7.7% in 1984–1996 to 25.9% in 1997–2007. Indian isolates of P. falciparum were also frequently found to carry mutations in the genes that code for the targets of sulfadoxine and pyrimethamine: dihydropteroate synthase (dhps) and dihydrofolate reductase (dhfr) respectively. In 2005, the combination of artesunate with sulfadoxine-pyrimethamine (AS+SP) replaced sulfadoxine-pyrimethamine as the nationally recommended first-line treatment for P. falciparum malaria in India. While the efficacy of AS+SP, again measured after 28 days of follow-up, was found to be high (96–100%) in nine studies conducted in India between 2005 and 2007, the numbers of cases investigated were quite small given the large size of the country. A major concern is that, since the efficacy and lifespan of ACTs depend largely on the partner drug, any pre-existing resistance to sulfadoxine-pyrimethamine could endanger the new combination.

For sulfadoxine-pyrimethamine, ≥10% treatment failure has been observed in Changlang and Lohit districts of Arunachal Pradesh; Karbi-Anglang, Darrang and Lakhimpur districts of Assam; West Garo Hills of Meghalaya and Purulia, Jalpaiguri and Bankura districts of West Bengal.

To address the continued problem of antimalarial drug resistance in India, a joint NVBDCP– NIMR surveillance system – the National Antimalarial Drug Resistance Monitoring System – was set up in 2008. This system has several innovations:

  • Only about 50% of the sites are monitored each year (so that each site is monitored every 2 years, and widespread coverage and information on long-term trends can be collected)
  • P. vivax studies are routinely conducted to track the emergence of chloroquine resistance in this species;
  • Blood smear examinations and data analysis undergo central quality control
  • Routine genotyping is performed to separate post-treatment reinfections from any recrudescent infections resulting from treatment failures
  • Molecular markers of drug resistance are genotyped simultaneously
  • In vivo trials of drug efficacy are integrated with supplementary studies, such as the evaluation of plasma drug concentrations and other pharmacokinetic parameters.

The focus of the present study was on the data collected, nationwide, during the first 2 years of the new surveillance system’s operation. These data were used to evaluate the efficacies of AS+SP against P. falciparum and of chloroquine against P. vivax, to determine the prevalence of several molecular markers of sulfadoxine-pyrimethamine resistance in P. falciparum (and so assess, independently, the probable efficacy of the “partner drug” in the ACT) and to determine the clinical, demographic and/or parasite-related risk factors for treatment failure.

Fig 2.6- Areas identified as Chloroquine resistant in India (1978-2008)

(Source: NVBDCP, NIMR and RMRC)

India’s National Antimalarial Drug Resistance Monitoring System completed therapeutic efficacy trials in 25 sites across India during its first 2 years. The results indicate that the firstline therapies for P. falciparum malaria and P. vivax malaria recommended by the national antimalarial drug policy (i.e. AS+SP and chloroquine, respectively) remain efficacious. The 28-day efficacy of AS+SP for treatment of P. falciparum infection was noted to be more than 98%. Although AS+SP treatment failures and parasitaemias showing prolonged clearance intervals after AS+SP treatment were rare, those identified were clustered in just a few sentinel sites. This clustering validates the design of the new monitoring system, which uses wide geographical coverage to increase the chances of detecting hotspots for resistance (as well as longitudinal studies to track emerging trends). There was no evidence of resistance to AS+SP in the sentinel sites in north-eastern India, though this is the region of the country where the highest frequencies of sulfadoxine-pyrimethamine treatment failure have been reported. The observation that four of the six patients who showed parasite clearance intervals of > 72 hours were confirmed to be treatment failures indicates the potential usefulness of measuring clearance intervals as a predictor of AS+SP treatment failure.

While the frequency of reinfection recorded is likely to be correlated with the length of the follow-up period, it also depends on the intensity of transmission in the study sites. The intensity of malarial transmission in India is generally lower than in many other parts of the world. Most (87.1%) of the isolates of P. falciparum that were successfully typed showed genotypic evidence of partial resistance to pyrimethamine, with either single (S108N) or double mutations (S108N/C59R) in the relevant dhfr codons. Such mutations have been found to increase the median inhibitory concentration (IC50) of pyrimethamine 10-fold. While seven isolates possessed the I164L mutation that has been associated with high-level resistance, the prevalence of triple or quadruple mutants among the genotyped isolates was low (3.2%). The prevalence of single or double dhps mutations among the isolates that were successfully genotyped was low (2.3%), although the possibility that dhps mutations caused non-amplification cannot be excluded. By monitoring trends in the prevalence of resistancerelated mutations in dhfr and dhps, the threat to treatment with the AS+SP combination posed by resistance to sulfadoxine-pyrimethamine in P. falciparum could be evaluated, independent of any observations of the clinical response. Treatment failure reflects a combination of drug resistance, host immunity and pharmacokinetics.

In the same study, younger age, fever at enrolment and a low level of parasitaemia at enrolment – all potential markers of relatively low immunity to parasite antigens – were associated with recrudescence following AS+SP treatment. Another association observed, the negative correlation between the dose of artesunate (in mg per kg body weight) and the probability of treatment failure, was not surprising. Although the recommended daily dose of artesunate is 4 mg per kg, 8.8% of the subjects of the present study who were given AS+SP received 3.0 to 3.5 mg of artesunate per kg, and 1.9% received < 3.0 mg per kg. The routine use of age, rather than body weight, as a guide for determining the dose of antimalarial drug needed by a patient is probably a cause of suboptimal dosing worldwide. The relationship between the administered dose and pharmacodynamic response is complex, however, and therapeutic levels may still be achieved when the dose is lower than recommended in standard guidelines.

In spite of sporadic case reports of chloroquine-resistant P. vivax in India, all of the P. vivaxinfected patients investigated in the study appeared to be cured by chloroquine treatment. Although many of the patients in sentinel sites in southern and western India who were given were migrant workers from elsewhere in India, more trials to investigate the therapeutic efficacy of chloroquine against P. vivax infections are needed in the north and east of India. Primaquine treatment to prevent relapses forms a critical component in the effective treatment of P. vivax infections. Unfortunately, no standard protocols for evaluating the therapeutic efficacy of primaquine, alone or in combination with chloroquine, exist. Another remaining challenge is the treatment of mixed infections. No data on the efficacy of AS+SP against P. vivax malaria are available, although, according to India’s national drug policy, AS+SP is the recommended treatment for a patient found to be co-infected with P. falciparum and P. vivax. Recent reports across south-eastern Asia have described a high incidence of P. vivax malaria following the treatment of P. falciparum infection, presumably the result of the reactivation of the liver stages of P. vivax.

8. Malaria Control Strategies

a) Early case Detection and Prompt Treatment (EDPT)

  • EDPT is the main strategy of malaria control - radical treatment is necessary for all the cases of malaria to prevent transmission of malaria.
  • Chloroquine is the main anti-malaria drug for uncomplicated malaria.
  • Drug Distribution Centres (DDCs) and Fever Treatment Depots (FTDs) have been established in the rural areas for providing easy access to anti-malarial drugs to the community.
  • Alternative drugs for chloroquine resistant malaria are recommended as per the drug policy of malaria.

b) Vector Control

(i) Chemical Control

  • Use of Indoor Residual Spray (IRS) with insecticides recommended under the programnme
  • Use of chemical larvicides like Abate in potable water
  • Aerosol space spray during day time

Malathion fogging during outbreaks

(ii) Biological Control

  • Use of larvivorous fish in ornamental tanks, fountains etc.
  • Use of biocides.

(iii) Personal Prophylatic Measures that individuals/communities can take up

  • Use of mosquito repellent creams, liquids, coils, mats etc.
  • Screening of the houses with wire mesh
  • Use of bednets treated with insecticide
  • Wearing clothes that cover maximum surface area of the body

c) Environmental Management & Source Reduction Methods

  • Source reduction i.e. filling of the breeding places
  • Proper covering of stored water
  • Channelization of breeding source

d) Community Participation

  • Sensitizing and involving the community for detection of Anopheles breeding places and their elimination
  • NGO schemes involving them in programme strategies
  • Collaboration with CII/ASSOCHAM/FICCI

e) Monitoring and Evaluation of the programme

  • Monthly Computerized Management Information System(CMIS)
  • Field visits by state by State National Programme Officers
  • Field visits by Malaria Research Centres and other ICMR Institutes
  • Feedback to states on field observations for correction actions.

9. Conclusion

Malaria is the third most common of these diseases in India after diarrhoea and typhoid. India is also one of the three countries that accounts for 97% of the malaria cases in South East Asia. During the past decade, there has been significant progress in development of molecular techniques in identification of sibling species of the dominant mosquito vector taxa, understanding their bionomical characteristics and role in malaria transmission in India. Among these, for An. culicifacies and An. fluviatilis which account for nearly 80% of malaria cases, vector control strategy has been formulated for judicious application of insecticide and saving operational costs. In the changing ecological context, An. culicifacies that is fast invading new territories is reportedly developing resistance to multiple insecticides including pyrethroids and inter-alia rising proportions and spread of multi-drug resistant P. falciparum malaria are some of the major concerns which call for continued research efforts for newer interventions that are evidence-based, community oriented and sustainable. Future priority area of research in vector control should include developing malaria-risk maps for focused interventions, monitoring insecticide resistance, cross-border initiative with neighboring countries for data sharing and coordinated control efforts for achieving substantial transmission reduction, and help check spread of drug-resistant malaria.

With the availability of new interventions for malaria control and the intensive implementation of the programme, the future looks optimistic for malaria control in India. The scaling up of these simple interventions in the east and north-east is likely to lead to the massive reductions in malaria burden. In urban areas, strategies for urban vector control are gradually crystallizing and it is intended to maintain this momentum. In urban areas as well as rural areas with low malaria transmission, found mainly in the rest of the country, targeted application of locally suitable interventions would be able to achieve better larval, and therefore vector borne disease control.

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