Available Online at http://www.recentscientific.com International Journal of Recent Scientific International Journal of Recent Scientific Research Research Vol. 5, Issue, 1, pp.312-317, January, 2014 ISSN: 0976-3031 RESEARCH ARTICLE FACTORS AFFECTING DISEASE TRANSMISSION AND INCIDENCE: A SPECIAL FOCUS ON VISAKHAPATNAM DISTRICT S.T.P.R.C. Pavan Kumar and N.N.R. Reddy

Department of Biochemistry & Bioinformatics, GITAM Institute of Science, GITAM University, Rushikonda Campus, ARTICLE INFO VisakhapatnamABSTRACT -530045, (AP), India

Article History: Malaria is a vector borne infectious disease wide spread in tropical and subtropical areas. Received 15th, December, 2013 Malaria situation in Visakhapatnam since 1961 is under closed surveillance of National Received in revised form 25th, December, 2013 Malaria Programmes. Malarial incidence reduced dramatically with the help of National Accepted 14th, January, 2014 Antimalarial Programmes, till the resurgence in 1970’s. Recent outbreaks in 1999 with the Published online 28th, January, 2014 gradual increase of malarial cases till date in Visakhapatnam demands a case study on factors affecting malaria disease transmission and incidence with special focus on Key words: Visakhapatnam district. Review provides new insights about the possible factors Climatic factors; Deforestation; Disease; contributing to malarial transmission and incidence. Interruption of Control Measures; Malaria; Urbanization © Copy Right, IJRSR, 2014, Academic Journals. All rights reserved.

INTRODUCTION Growth and division of each oocyst produces thousands of active haploid forms called sporozoites in 8-15 days. Upon release of Malaria is severe public health problem in developing countries, sporozoites they travel and invade the mosquito salivary glands which is a complex and fatal disease caused by four species of and the cycle of human infection re-starts when the mosquito parasites and transmitted by different number of takes a bloodmeal, injecting the sporozoites from its salivary vectors. Half of the world’s population i.e., 3.3 billion people live glands into the human bloodstream. in malaria transmission areas of 106 countries and territories at risk. An estimated 216 million positive cases and 655,000 deaths Factors Affecting Malaria Disease were reported in year 2010 due to malaria. According to WHO Transmission and Incidence report 86% of the malarial deaths were of children (Ahmad et al., Transmission of malaria depends on the factors affecting the 2013). Of this African region, South East Asian region, Eastern disease and varies from place to place. There are areas where the Mediterranean region reported 91%, 6%, 3% malaria deaths transmission and incidence of disease is high, low and in some respectively. Kumar et al.,( 2007) reported that India alone areas it is very brief that it lasts for several months or throughout contributes nearly 77% of the malaria cases in South East region. the year. Different climatic and non-climatic factors favor the Visakhapatnam, one of the major districts of Andhra Pradesh state transmission of the disease. Temperature, rainfall and relative contributes up to 2 % of the annual malaria incidence throughout humidity are the climatic variables that influence parasites life the country with an annual parasite index (API) of 8.46, 8.35 cycle in vector as well as in parasites (Gubler et al., 2001; during 1991-95, 1996-2000 respectively. Koenraadt et al., 2004). Non-climatic factors include parasites, Malaria Disease Transmission and Incidence vectors, human host factors, population movement or migration, urbanization and interruption of control and preventive measures. A female mosquito while feeding human injects sporozoites of malarial parasites into the bloodstream. The Climatic Factors sporozoites travel to the liver and invade liver cells. Sporozoites Climate change represents a potential environmental factor remain dormant or grow, divide, and produce haploid forms, affecting disease emergence. Shift in the geographic ranges of called merozoites over a period of 15-16 days. The merozoites hosts and vector, effect reproduction, development, and mortality exit the liver cells and re-enter the bloodstream, beginning a cycle rates on hosts, vectors, and pathogens. Effects of the increased of invasion of red blood cells. Parasite-infected cells in the host climate variability, floods and droughts all have the potential to bloodstream, lead to illness and complications of malaria. Some affect disease incidence and emergence either positively or of the merozoite-infected blood cells leave the cycle of asexual negatively. Divya et al., (2013) explained the associations multiplication and develop into sexual forms of the parasite, called between total, average rainfall and malaria outbreaks. Mosquitoes male and female gametocytes. When a mosquito bites an infected prefer water bodies and right amount of rainfall is most important human, it ingests the gametocytes and releases the gametocytes in factor for them to breed. So, changes in rainfall drive malaria the mosquito gut, which develop further into mature sex cells transmission to a higher state (Gao et al., 2012). Blanford et al., called gametes. Male and female gametes fuse to form diploid (2013) explained temperature as an important determinant of zygotes, which develop further into ookinetes and form oocysts.

S.T.P.R.C. Pavan Kumar Department of Biochemistry & Bioinformatics, GITAM Institute of Science, GITAM University, Rushikonda Campus, Visakhapatnam - 530045,* Corresponding (AP), India author: International Journal of Recent Scientific Research, Vol. 5, Issue, 1, pp.312-317, January, 2014 malaria transmission. Maximum and minimum temperatures Urbanization affect the life cycle of malaria parasite. The maximum and Rapid urbanization in minimum temperatures for parasite development are 40°C and the world’s population has undergone unprecedented growth, it is estimated that by 2050 the people 18°C. Below 18°C, the life cycle of P. falciparum in the mosquito living in urban areas will increase up to 67% (Qi et al., 2012). body is limited. The minimum temperatures of P. vivax are Urbanization is associated with greater decline in malaria between 14 19°C, surviving at lower temperatures than P. – transmission (Tatem et al., 2013), but the presence of bushes, falciparum. Life cycle of the parasites in vectors can be shorter or stagnant water, rainfall, low altitude and high temperatures favor longer depending on temperature. A minimum of 10 to 19 days is the breeding of malaria vectors as well as parasite development required for the parasite to complete its life cycle in the gut of within them (Kimbi et al., 2013), thereby increasing malaria risk. mosquito. Sometimes life cycle decreases to less than 10 days as the temperature increases from 21°C to 27°C, with 27°C being the Population Movement optimum. Malaria transmission in areas colder than 18°C can Population movement has contributed to the spread of malaria occur because the Anopheles often live in houses, which tend to (Prothero, 1977). Malaria risk may increase in certain regions due be warmer than the outside temperature. Mosquito’s survival is to population movement by labor related to agriculture, mining, greatly influenced by relative humidity as they survive better and become active under conditions of high humidity greater than conflict and refugees, airport malaria, imported malaria (Marten’s and Hall, 2000). 60%, if it is below 60% the life cycle of mosquito is short or no malaria transmission. Therefore, rainfall, temperature and relative Deforestation humidity are the major climatic factors that guide malaria Forests have a density of mosquitos; deforestation generally transmission by showing their effect on Anopheles mosquitoes. reduces the density of mosquitos at the site of deforestation. Statistical methods like correlation (Kim and Jang, 2010), time Mosquitos rarely travel more than a few kilometers and therefore series analysis (Tian et al., 2008), regression methods (Robert, mosquitos reach to the nearest residential area thereby increasing 2012) were used to understand association between climate and in the availability of hosts to mosquitos. Thus, an increase in the malaria disease and also the effect of climate on malaria disease entomological inoculation rate to hosts is achieved, subsequently incidence and transmission. Most of the studies used either increasing the disease transmission and incidence when there is individualistic or combined effects of all the three climatic factors deforestation. on malaria incidence. Studies on climatic variability and its Human Host Factors influence on malaria disease in Mahaboobnagar district, Andhra Pradesh, India demonstrated that monthly temperature, rainfall, Human hosts factors like immunity, age, pregnancy, phenotypes, humidity and mosquito populations (Anopheles culicifacius, A. surface of the erythrocyte cells, ethnic differences, structural fluviatalis, A. subpictus and A. stephensi) showed positive variation of globin genes, regulatory variations in globin genes, correlation with monthly malaria disease incidence (Srinivasulu et oxidative stress, antibody response, proinflammatory response al., 2013). Correlation analysis between malaria cases and various and other serum factors provide resistance or susceptibility to meteorological variables (total rainfall, mean of maximum and malaria infection (Kwiatkowski, 2005) affecting the pattern of minimum, and relative humidity) showed positive correlation with malaria transmission and severity of the disease. An immune monthly incidence of malaria. Mathematical models were person has a better chance to eliminate the disease rather than the developed nearly a century ago and are well established non-immune ones. Children’s less than five years of age and (Macdonald, 1957). A validated spatiotemporal modeling of pregnant women are at high risk because of theirs less immunity. malaria transmission, three climatic scenarios reported (Mabaso Interruption to control and preventive measures et al., 2006 ), the impact of climate change on malaria disease incidence and transmission (Parham and Michael, 2010). Several preventive and control methods were used worldwide to Development of valid and realistic models that capture climate eliminate malaria. These include immediate and proper change on malaria disease and vector populations remains medications to control parasites in humans (chemoprophylaxis), important research area and a crucial component towards prevention of mosquito bites to humans by mosquito repellents, improving the understanding on malaria transmission across a insecticide treated nets, bednets , indoor residual spraying to range of environmental changes. Reliability of such models is control mosquitos, destroying the breeding habitants in water estimated by forecasting methods and by comparing the past data bodies with insecticides and antilarval operations to control with the present data and predicting the future risks of the disease mosquitos. Sustained and long term implementation of preventive incidence rates. and control measures are necessary to significantly reduce or eliminate the problem from a country or in a specific region. If the Non-Climatic factors control measures are stopped or being interrupted malaria can Current scenario on malaria is clearly associated with the social revert back and cause infection to more number of people. Genus and demographic changes of the past 50 years. Factors that don’t Plasmodium includes 120 species or more each restricted to a come under the category climate are non-climatic factors. Social limited number of hosts. Malaria in humans is caused by four factors like urbanization, globalization, population movement, mainspecies - P. falciparum, P. vivax, P. ovale and P. malariae, deforestation, interruption to control measures; and biotic factors of which P. falciparum and P. vivax are predominant in India. like human host factors, parasites, vectors are the non-climatic Early Diagnosis and Prompt Treatment (EDPT) a part of factors that have they role in affecting disease incidence and NVBDCP is not only a curative programme, but also a means to severity. curtail the transmission process. As part of EDPT, the blood samples of patients are smeared on a glass slide and analyzed for presence of parasites.

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Figure 1 Map showing the total mandals in the Visakhapatnam district and surrounding border districts to the north Vizainagarm, Srikaklulam, east Bay of Bengal, west Orissa state and south Khammam district

Drugs like Artemether, Artesunate, Bulaquine, Chloroquine, Similarly high levels of sulfadoxine and pyrimethamine resistance Mefloquine, Mepacrine, Quinine and related agents, were observed in P. vivax in India (Ahmed et al., 2006; Ganguly Amodiaquine, Pyrimethamine, Proguanil, Sulfonamides, et al., 2014) Resistance to artesunate combination therapy was yet Mefloquine, Atovaquone, Primaquine, Artemisinin and reported in India. Emergence of drug resistance suggests the need derivatives, Halofantrine, Doxycycline, Clindamycin are used for for identifying novel drug targets and drugs for different stages of treatment of malarial parasite. Immediate antimalarial therapy is Plasmodium species by using various approaches. Insilco analysis followed up for 7 days in case of P. falciparum and 28 days in of genomes, proteomes, and metabolic pathways would provide a case of P. vivax. In addition to drugs a total of 52 vaccines have source or a pool of new drug targets. A comparative analysis of been developed and some vaccine candidates are being identified genomes between host and pathogen, virulent and avirulent and some of them are used against Plasmodium species for the strains, set of strains, set of species identify unique genes for the following stages of parasite - multistage (Tine et al., 1998, Rafi- organism. A comparative proteome analysis between host and Janajreh et al., 2002), pre-erythrocyte (Dolo et al., 1999, Bottius pathogen would provide information about important unique et al., 1996), erythrocytic (Chen 2007, Peek et al., 2006,), asexual molecules or enzymes for organism. Metabolic pathway analysis, blood stage (Graves et al., 1998), sexual stage (Malkin et al., chokepoints detection and flux balance analysis of metablomes 2005). Drug resistance in parasites is an important factor which provides information on metabolically important molecules. Some interrupts control measures. Plasmodium species causing malaria invivo and invitro strategies like haploinsufficiency profiling, in humans have developed drug resistance to available drugs. chemogenomics, chemical proteomics, signature tag mutagenesis, Resistance to chloroquine was observed in almost all the areas expression profiling and geneknockout technologies are the wet affected with malaria (Bloland, 2001). Chloroquine resistance was lab technques that can be used to identify potential drug targets for first identified in 1973 in Assam (Sehgal et al., 1973), wide spread Plasmodium species. Later these drug targets can be validation (Vathsala et al., 2004) and observed in P. falciparum in India and either by growth bioassays and geneknockout methodologies. P. vivax. But chloroquine remains affective against P. vivax in India (Nandy et al., 2003; Valecha et al., 2006).

50000 40000 30000 20000 10000 Total No.of Totalcases 0 1984 1986 1988 1990 1992 1994 1996 1998 2000 2002 2004 2006 2008 2010 Year Figure 2 Yearly data of malarial cases reported by District Malarial Office in district of Visakhapatnam

314 International Journal of Recent Scientific Research, Vol. 5, Issue, 1, pp.312-317, January, 2014 These drug targets can be used to analyze the target structures for method and observed association between rainfall and malarial possible binding/ active sites, generate lead candidate molecules, disease incidence. In this context, a case study in the district of check for their drug likeness, dock these molecules with the target, Visakhapatnam to map malarial disease incidence cases; to rank them according to their binding affinities, further optimize evaluate relationship between climatic factors, mosquito the molecules to improve binding characteristics and identify a populations and malarial disease incidence using statistical new drug candidate for Plasmodium species. Not all the anopheles methods; models and predictions of climatic factors, mosquito mosquitoes can carry the malarial parasites; only female populations and malarial disease incidence helps us in identifying anopheles mosquitoes can transmit malaria. There are about 3,500 malaria transmission patterns to understand Malaria Transmission mosquito species and those that transmit malaria all belong to a Mechanism (MTM). Previously National Institute of Malaria sub-set called the Anopheles. Approximately 40 Anopheles Research (NIMR), National Antimalaria Programme (NAMP), species were able to transmit malaria and are well enough to cause National Malaria Eradication Programme (NMEP), National significant human illness and death. Anopheles culicifacies, A. Malaria Control Programme (NMCP) addressed the rising fluviatilis, A. minimus, A. Sundaicus and A. Stephensi are malarial disease incidence. Currently malarial control dominant malaria vectors in India (Dev and Sharma, 2013). programmes fall under the ambit of National Vector Borne Successful eradication or control of malaria in different places of Disease Control Programme (NVBDCP), Primary Health Centres the world was achieved by controlling the mosquito vector (PHC), District Malaria Office (DMO), Indian Council of Medical population with different chemical insecticides (Harrison, 1979). Research (ICMR) and State Government. These organizations in Two types of methods were generally used for vector control first coordination carry out investigations of malarial epidemics. one is indoor residual spraying (IRS) and second option is long Epidemiological investigations in Paderu division of lasting insecticide treated nets (LN’s) for controlling malaria Visakhapatnam district, Andhra Pradesh found chloroquine transmission (Enayati et al., 2009). In India pyrethrum (Persian resistant using the slide positivity rate insect powder), mercuric chloride, paris green, phenols, cresols, (SPR). Further, it was found that A. culicifacies and A. fluviatilis napthelene, Bordeaux mixture, rosin-fish oil soap, calcium were resistant and susceptible to DDT and Malathion, arsenate and nicotine sulphate were used as insecticides in 18th Deltamethrin respectively (Dhiman et al., 1999). (Srinvasulu et and 19th century (ICMR Bulletin, 2002). Similar to drug resistance al., 2013) identified dominant cerebral malarial cases in tribal in parasites, insecticide resistance in vectors is also one of the populations of Visakhapatnam. (Dantu et al., 2013) further major problem for spread of malaria in endemic areas. A. observed that drugs used for malarial treatment induced hemolytic culicifacies has developed a wide spread resistance to DDT anemia and variants of enzyme glucose -6-phosphatase (organochlorine) due to continuous usage in indoor residual dehydrogenase are responsible for hemolysis. The growing spraying (Sharma et al., 1986, Sharma et al., 1999). problem of malaria in Visakhapatnam demands a case study on A Special Focus on Visakhapatnam District efficacy of drugs that are used to control malaria. The same EDPT principle can be applied to the district of Visakhapatnam to Visakhapatnam district stands in 44th place in the country and 5th understand the efficacy of drug. Studies on climatic variability, in Andhra Pradesh state in terms of populations and a vector population, drug efficacy on malarial disease incidence geographical area of 11.24 lakhs hectares with long sea coast line may provide new insights on the disease patterns in (Figure 1). Visakhapatnam the north coastal district of Andhra Visakhapatnam district. Pradesh is located between 17° 15' and 18° 32' North latitude and 18° 54' and 83° 30' east longitude. It is bounded in the north partly CONCLUSION by Orissa and Vizianagaram district, in the south by East Godavari district, in the west by Orissa and in the east by the Bay Malaria disease transmission and incidence is affected by a of Bengal. According to the 2011 India census, population of number of factors. Different factors favoring the transmission of Visakhapatnam is 37, 89, 820 with an area covering of 11,161 the disease are climatic and non-climatic factors. Temperature, square kilometres. Visakhapatnam is the first district receiving rainfall and relative humidity are the climatic variables. Parasites, high annual malaria incidence in the state with 43 mandals and 86 vectors, human host factors, population movement or migration, primary health centres (Figure 1). The coastal regions are deforestation, urbanization and interruption of control and pleasantly humid and comfortable, further inland the air gets preventive measures are the non-climatic factors. Studies on warmer while in the hill areas it is noticeably cooler on account of climatic variability, vector population, drug efficacy on malarial elevation and vegetation with little variation in temperature disease incidence in the district of Visakhapatnam may provide through the year. May is the hottest month with average new insights on the disease patterns in Visakhapatnam temperatures around 32°C (90°F), while January is the coolest district. Though resistance to artesunate combination therapy was month with average temperatures near 23°C (73°F). The humidity not yet reported in India, emergence of drug resistance to others remains high throughout the year. The total annual rainfall is drugs/current treated drugs in the near future suggests the need for around 945mm (38inches), the bulk of which is received during identifying novel drug targets and drugs for different stages of the south-west monsoon. October is the wettest month with Plasmodium species. around 204mm (8 inches) of rainfall. Acknowledgements According to the available data on malarial disease incidence NNRR and STRPCPK are thankful to the GITAM University, from the year 1984 to 2009, highest number of cases were Visakhapatnam, India for providing the facility and support. The reported in 1999 (i.e.41,977), followed by a gradual decrease in assess the association of rainfall, spatial patterns of malaria malaria positive cases till the year 2009 in 2005 (Figure 2) and disease authors also thankful to Prof. I. Bhaskar Reddy and Dr Plasmodium falciparum and P. vivax infections were predominant Malla Rama Rao for constant support throughout the research in Visakhapatnam. 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