In this issue

Malaria News Guest Column Young Scientist Column Institutes Activities Annual Day Celebrated Symposia/Workshops/Trainings Organized Scientific and Research Advisory Committee Meetings Organized Awards Received Research Papers Published (JulyDecember 2008) Progress of NIMR (200408) 2 3 4 5 5 5 6 6 7 8

Fr om th e Dir ec tors De sk Fro the Direc ect Desk

Dear Readers, With great gratification I present this issue of Plasmodium. In the past six months, NIMR has achieved new heights in both quality and quantity of scientific accomplishment. During this period, NIMR has been identified as WHO collaborating centre for laboratory testing and evaluation of public health pesticides and the National referral centre for diagnosis of malaria by the National Vector Borne Disease Control Programme. The quality and quantity of scientific publications has been enhanced. Shifting to the new campus at Dwarka has been initiated and many activities have become functional in the new campus. NIMR is all set to start an integrated M.Sc.-Ph.D. course in Medical Entomology in affiliation with the Goa University, Goa. If I look back, NIMR has travelled far in almost every aspect during the last five years. Many pending assignments have been successfully completed and several new initiatives have been taken. We have gathered some of these activities and highlighted in this issue of Plasmodium. I wish you all a happy and prosperous new year. AP Dash

Editorial Board
Editor-in-Chief AP Dash Editors OP Singh, Aparup Das Anup Anvikar, Neelima Mishra Assistant Editor U Sreehari Production Jitender Kumar DS Sontiyal

National Institute of Malaria Research

(Indian Council of Medical Research), Sector 8, Dwarka, New Delhi110 077 Telephone: +91-11-25365774, 25365904; Fax: +91-11-25365904 E-mail: director@mrcindia.org; Website: www.mrcindia.org

Malaria News
Astronaut Food Approach to Medical Testing: Dehydrated, Wallet-sized Malaria Tests Promise Better Diagnoses in Developing World
Researchers at the University of Washington have developed a prototype malaria test printed on a disposable Mylar card that could easily slip into your wallet and still work when you take it out, even months later. Paul Yager, UW bioengineering professor, and colleagues described the prototype cards in the December issue of the journal Lab on a Chip. These tests are storable for long periods of time at ambient temperatures and do not involve wet reagents. In this test, malaria antibodies are dried in sugar matrices and were shown to retain 8096% of their activity even after 60 days of storage at elevated temperatures. To carry out the test, a clinician has to spot a drop of a patients blood onto a card and feed it into an instrument that gives a yes or no answer for a panel of infectious diseases in 20 min or less. Tests with the prototype malaria card can reach a result in less than nine minutes using an immunoassay, or antibody-based, approach. The malaria-test card is being developed as part of an automated diagnostic system informally called the DxBox, the Dx being medical shorthand for diagnosis. The DxBox consists of a portable, fully automatic reader being developed by Micronics that will process the card-based disposable tests. The UW prototype cards look for the presence of malarial proteins, but the team is also working on other kinds of protein tests as well as a second kind of test for each disease that looks for the pathogens DNA or RNA. The diagnostic tests in the DxBox system run much faster than conventional tests in part because the liquids involved behave differently, a key factor for clinicians who have limited time to spend with their patients. Source: ScienceDaily. Retrieved 28 January 2009 from h t t p : / / w w w. s c i e n c e d a i l y. c o m - / r e l e a s e s / 2 0 0 9 / 0 1 / 090121123049.htm to down-regulate, or switch off, saglin expression, which greatly diminished salivary gland invasion in the mosquito. Source: ScienceDaily. Retrieved 28 January 2009 from h t t p : / / w w w. s c i e n c e d a i l y. c o m - / r e l e a s e s / 2 0 0 9 / 0 1 / 090116073203.htm

Earliest Evidence of Malaria Found in Ancient DNA of Egyptian Mummies

The ancient DNA of two Egyptian mummies who died more than 3,500 years ago has provided clear evidence for the earliest known cases of malaria. According to a report in Discovery News, Pathologist Andreas Nerlich and colleagues at the Academic Teaching Hospital Munchen-Bogenhausen in Munich, Germany, studied 91 bone tissue samples from ancient Egyptian mummies and skeletons dating from 3500 to 500 B.C. Using special techniques from molecular biology, such as DNA amplification and gene sequencing, the researchers identified ancient DNA for the malaria parasite Plasmodium falciparum in tissues from two mummies. In a previous study, Nerlich and colleagues discovered that most people buried at the site died between the ages of 20 and 30. The ancient scourge, which has shaped history by decimating invading armies and making villages in the grip of the fever hard to colonize, still plagues humanity. Nerlich and colleagues believe that their work in identifying one of the earliest forms of the disease may help develop new treatments.

New Target for Malaria Drugs Identified

A new study has identified one of the tricks malaria uses to hide from immune proteinsa finding that may help in future drug development. Once inside their human hosts the parasites first set up shop in liver cells, then move into red blood cells (RBCs) to replicate and wait for the next mosquito to help continue the cycle. After plasmodia infect a blood cell, they send out clusters of sticky proteins to the cell surface, enabling them to attach to blood vessels and escape destruction by the hosts spleen while they replicate. This tactic can be especially problematic during pregnancy as malariainfected RBCs congregate in the vessel-rich placenta (the source of food and oxygen for the growing fetus), creating health problems such as anemia, low birth-weight, fever and more. But targeting these sticky proteins with drugs is difficult, as plasmodia contain many different varieties, which they use to evade the human immune system. However, certain parts of the protein have to remain constant for proper function, and in this study, Matthew Higgins generated high-resolution 3-D structures of a malarial sticky protein that binds to placenta, PfEMP1, to detail how plasmodia protect these conserved areas. Higgins found that a variable region of PfEMP1 covers a section that is important for docking up with the placental wall. When the infected RBC gets close to chondroitin sulphate, a structural molecule on blood vessels, the variable region moves aside and ever so briefly exposes the binding region, just enough to allow anchoring to take place. Higgins noted that women in regions where malaria is endemic do gain some immunity to the build-up of RBCs at the placenta after multiple pregnancies by developing an (Source : medindia.com) immune response for PfEMP1.

Essential Proteins for Critical Stage of Malaria Discovered

Researchers at the Johns Hopkins Malaria Research Institute have identified the molecular components that enable the malaria-causing parasite Plasmodium to infect the salivary glands of the Anopheles mosquitoa critical stage for spreading malaria to humans. According to the researchers, saglin, a mosquito salivary protein, is a receptor for the Plasmodium protein Thrombospondin-Related Anonymous Protein (TRAP). The two proteins bind together to allow invasion of the salivary gland by Plasmodium sporozoites, which can be transmitted to a human when bitten by an infected mosquito. Through a series of experiments, Marcelo Jacobs-Lorena and his colleagues found that saglin bound with the artificial peptide SM1. The team then developed an antibody to find a protein similar to SM1 that existed naturally in the parasite, which they identified as TRAP. To further prove the interaction between saglin and TRAP, the team conducted experiments

2 Plasmodium

GuestColumn

The Plasmodium vivax Genome Project

Jane M. Carlton Associate Professor Department of Medical Parasitology New York University Langone Medical Center, New York, NY 10010, U.S.A.

Plasmodium vivax is the most common species of malaria parasite outside Africa, and causes up to 40% of malaria cases per year world-wide. Despite this, vivax malaria is often referred to as neglected, primarily due to a concentration of resources and scientific effort on the greater threat to human lives, that of severe malaria caused by P. falciparum. In particular, the impracticality of continuous P. vivax in vitro culture has left the study of the biology and genetics of the species far behind that of P. falciparum, with consequent losses in the development of novel methods of control. Recently, however, the first genome sequence of P. vivax was completed, which has the potential to invigorate the field of basic vivax malaria research. In the mid-1990s, a groundswell of support among malaria researchers led to an international project to sequence the genome of P. falciparum. The project, coordinated among three genome sequencing centers in the United States (U.S.) and the United Kingdom (U.K.), used resources from several funding agencies as well as expertise from many malaria researchers, and was finally published in October 2002 [1]. Although there was some support for sequencing the genome of Plasmodium vivax during this time, the project did not start until the P. falciparum sequence was close to completion, perhaps reflecting the perception that P. vivax poses a less severe threat to human health. The P. vivax project used funds from the U.S. Department of Defense and the National Institute of Allergy and Infectious Disease/National Institute of Health (NIAID/NIH) remaining from the first Plasmodium sequencing project, and was sequenced in its entirety at The Institute for Genomic Research (TIGR) in Rockville, Maryland. The project to decode the P. vivax genome was fraught with problems from the outset. Since P. vivax cannot be grown in vitro and is present at low levels of parasitaemia in natural infections, an initial problem was obtaining sufficient DNA in

order to be able to generate genomic DNA libraries for highthroughput sequencing. The solution was to use a laboratory line from El Salvador (Salvador I) adapted to grow in Aotus and Saimiri monkeys in the 1970s and maintained at the Centers for Disease Control, Atlanta, Georgia, U.S. The Salvador I line is designated a reference strain because it has been passaged in human volunteers and through mosquitoes, and has been used for previous whole genome expression studies. With sufficient DNA generated from the successful infection of eight Saimiri saimiri monkeys, the material was shipped to TIGR where genomic libraries were constructed and highthroughput sequencing was undertaken. However, after completion of genomic sequencing and construction of the sequence data into an assembly, funds to close the gaps in the sequence and to annotate and analyze the genome were exhausted, and the project came to a halt in late 2003. An anxious period ensued during which many members of the vivax malaria community wrote supporting letters for several proposals to funding agencies in order to secure additional funds to complete the project. Finally, in late 2004, the Burroughs Wellcome Fund stepped up to the challenge and provided the additional funds for more monkey infections, thereby paving the way for NIAID/NIH to provide funding for closure, annotation, and analysis of the genome. At last, almost six years to the day that the P. falciparum genome was published, the paper describing the P. vivax sequence appeared as the front cover article in Nature [2]. What has analysis of the P. vivax genome told us? Briefly, we now know that the genome has very G+C-rich internal chromosome cores that contain genes involved in housekeeping activities, whereas the peripheral, subtelomeric regions of chromosomes are highly A+T-rich and contain multi-gene families in particular ~350 copies of the largest gene family
contd. on p. 4

Dr Jane M Carlton is Associate Professor of Parasitology at New York University Langone Medical Center. She received her doctorate in Genetics at the University of Edinburgh in 1995, and has spent the past 14 years as a member of several scientific institutions in the United States, including the University of Florida, the National Institutes of Health and The Institute for Genomic Research. Dr Carlton is passionate about genomics and the power that genomics technology has to revolutionize medicine. Her own research involves decoding the DNA of important human pathogens, in particular species of malaria, as well as parasites prevalent in the U.S. such as the common STD Trichomonas vaginalis. She has published more than 70 articles and book chapters, is the recipient of several multi-million dollar federal grants, and her work has been profiled by many media organizations including CNN, BBC, Reuters, The Economist and USA Today. Most recently, her work deciphering the genetic code of P. vivax, the most common malaria parasite in Asia and Latin America, was featured as the cover article in the journal Nature. Dr Carlton has a keen interest in training scientists to use genomic data, and has taught at several World Health Organization/World Bank workshops in Africa, Thailand and Brazil. Currently, she provides training and support for Indian students through a joint NYU Langone Medical Center-National Institute of Malaria Research grant with Drs Hema Joshi and A.P. Dash, with frequent exchange of scientists between New Delhi and New York.

January 2009

YoungScientistColumn

Genetic Basis of Innate Immune System in Malaria Vectors

It is a well known fact that immune system genes are responsible in development of immunity in organisms against foreign bodies. These genes also play very crucial roles in innate immune system of malaria vectors against the invasion of malaria parasite [1]. Many such immune gene families were identified in Anopheles gambiae (an African malaria vector) which is the only vector having entire genome sequence information [2]. In many recent studies, a total of 338 genes were found from 31 gene families in An. gambiae [3,4] that are involved in cellular and molecular interaction at different levels of malaria parasites life cycle in vectors [5]. Interestingly, functional characterization of immune genes in An. gambiae [6] yielded fruitful clues of direct involvement of specific immune genes in regulation of Plasmodium development in vectors. Despite the destruction of parasite, it was also found that many immune gene families facilitate transmission of parasite in malaria vectors such as C-type lectins that act as agonists and protecting parasite from innate immune response. In contrast, some immune gene families such as LRIM1 and TEP1 were also found that limit the parasite load in malaria vector (Fig 1) [7]. In depth understanding of diverse immune gene families [8] provides insight as to how the parasites invade the malaria vector and proliferate without any interruption. Understanding the detailed mechanisms could be helpful in designing transmission blocking vaccines and helping in controlling malaria.

References
1. Shin SW, et al. J Exp Biol 2003; 206: 383543. 2. Holt RA, et al. Science 2002; 298: 129149. 3. Waterhouse RM, et al. Science 2007; 316: 173843. 4. Christophides GK, et al. Science 2002; 298: 159165. 5. Alavi Y, et al. Int J Parasitol 2003; 33: 93343. 6. Dimopoulos G, et al. Proc Natl Acad Sci USA 2000; 97: 661924. 7. Osta MA, et al. J Exp Biol 2004; 207: 255163. 8. Cohuet A, et al. BMC Genomics 2008; 9: 113.
Hemlata Srivastava, SRF
Evolutionary Genomics and Bioinformatics Laboratory NIMR, Delhi

Fig.1: Schematic model of LRIM1 and CTL (CTL4 and CTLMA2) protein action during Plasmodium development in the mosquito midgut. During or soon after invasion of the midgut epithelium (four downward-oriented arrows), three out of four invading ookinetes are eliminated, partly through the antagonistic action of LRIM1 (upward oriented arrows). However, CTL4 and, to a lesser extent, CTLMA2 protect the remaining ookinetes from the melanization response (slanted black bars); melanization also requires LRIM1 activity (horizontal arrow) [7]

The Plasmodium vivax Genome Project contd.

in P. vivax, the vir family. We know that several gene families have expanded massively in P. vivax, such as those involved in red blood cell invasion and immune evasion. We also know that many of the genes are remarkably conserved between P. falciparum and P. vivax and that those that appear to be evolving quickly are likely to be involved in interactions with the hosts immune system. Finally, we have been able to compare the structure of P. falciparum proteins known to be involved in drug resistance with their P. vivax counterparts; should resistance arise in P. vivax, our comparison will help us predict what mutations might be involved. Perhaps more striking is what the genome sequence did not tell us. Unfortunately, although some putative candidates were suggested, it did not tell us the precise identity of genes involved in relapse, a characteristic feature of infection with P. vivax. Moreover, several thousand genes remain classified as hypothetical with no known equivalent in any other organism sequenced to date. Satisfyingly, however, the genome sequence has been used to elucidate the pattern of expression of all genes during the asexual blood stages [3], and other whole genome transcriptional studies are ongoing. Decoding the genome of the first P. vivax parasite has undoubtedly propelled our understanding of human Plasmodium biology, but there is much that remains to be done. For example, we need to understand how the parasite is evolving and in particular, how it will evolve in response to new drug regimes and potential vaccines. Since one genome sequence is not enough for such intra-species studies, we are now determining the sequence of six more P. vivax laboratory isolates adapted to growth in monkeys, including an isolate from India (for more details, see [4]). We also need to expand studies into uncovering the molecular mechanisms of drug resistance in P. vivax, so that genetic markers of resistance can be identified and used to monitor its spread. And finally, from a non-genomics point of view, we desperately need a continuous in vitro culture system so that researchers world-wide can have access to P. vivax biological material for their experiments, and thus truly take advantage of the genome sequence. The Plasmodium vivax genome article and associated papers can be viewed for free at http://www.nature.com/nature/focus/malaria/.

References
1. 2. 3. 4. Gardner MJ et al. Nature 2002; 419: 498511. Carlton JM et al. Nature 2008; 455: 75763. Bozdech Z et al. Proc Natl Acad Sci U.S.A. 2008; 105: 162905. Carlton JM et al. Trends Parasitol 2008; 24: 54550.

4 Plasmodium

Institutes Activities

Annual Day Celebrated

The institute organized its annual day on 26 November 2008. Dr G.C. Mishra, Director, National Centre for Cell Science delivered the Annual Day lecture. Dr V.M. Katoch, Secretary, Department of Health Research, Ministry of Health and Family Welfare, and Director General, Indian Council of Medical Research presided over the function. Dr Katoch emphasized the need of translational research that would help to improve diagnosis and treatment of malaria in India. Prof. N.K. Ganguly, distinguished Biotechnology Fellow & Advisor, Translational Health Science & Technology Institute and Former DG, ICMR, Mr M. Rajamani, Senior Deputy Director General (Admin) and Mr Sanjeev Dutta, Financial Advisor, ICMR were the guests of honour. Prof. R.C. Mahajan, S.N. Bose INSA Research Professor and Emeritus Professor, PGIMER, Chandigarh introduced the speakers. On this occasion, employees completing 25 years of service were felicitated. Dr S. Pattanayak, Prof. M.K.K. Pillai, Dr V.P. Sharma, Dr Sarala K. Subbarao, Mr N.L. Kalra and other dignitaries were also present in the function.

Dr V.M. Katoch addressing the audience

Dr G.C. Mishra delivering the Annual Day lecture. On the dias, Mr Sanjeev Dutta, Prof. R.C. Mahajan, Dr V.M. Katoch, Prof. N.K. Ganguly, Prof. A.P. Dash and Mr M. Rajamani.

Dr V.M. Katoch felicitating Prof. A.P. Dash

Symposia/Workshops/Trainings Organized
A workshop was held for developing scientific skills among young researchers from 18 to 20 August 2008. It was facilitated by Drs Steven Sullivan and Jane Carlton, New York University School of Medicine. Training was organized on Treatment of malaria for resident doctors of Department of Community Medicine, B.J. Medical College, Ahmedabad in collaboration with Vector Borne Disease Control Programme in India from 23 to 29 July 2008 at the Institute. A workshop on P. vivax ex-vivo maturation was conducted from 25 August to 5 Sept. 2008. Faculty members were Dr Bruce Russell of the Singapore Immunology Network and A*STAR, Singapore apart from scientists of NIMR. NIMR organized a symposium on Malaria and dengue in collaboration with the Janakpuri Chapter of the Indian Medical Association and Municipal Corporation of Delhi, for clinicians on 27 September 2008. A seminar was organized on National Malaria Drug Policy for Post Graduate students of Community Medicine Department, NHL Medical College, Ahmedabad on 17 October 2008. A workshop on Malaria and other vector borne diseases was organized for medical officers of Municipal Corporation of Delhi on 3 December 2008.

January 2009

Institutes Activities

Scientific and Research Advisory Committee Meetings Organized

The Research Advisory Committee meeting of the Integrated Disease Vector Controlled Project was organized at NIMR Field Unit, Chennai on 17 December 2008 under the chairmanship of Dr S. Pattanayak. The Research Advisory Committee meeting of Epidemiology, Parasite Biology and Vector Biology and Control were held on 24 December 2008 under the chairmanship of Dr S. Pattanayak, Dr G.C. Mishra and Prof. M.K.K. Pillai respectively. The meeting of the 29th Scientific Advisory Committee was held at the NIMR campus on 25 December 2008 and was chaired by Prof. R.C. Mahajan. The members of the committees appreciated the progress made by NIMR in recent years.

Research Advisory Comittee meeting of Vector Biology held on 24 December 2008 at Delhi

Research Advisory Comittee meeting of Parasite Biology held on 24 December 2008 at Delhi

Scientific Advisory Committee (SAC) of NIMR held on 25 December 2008 at New Delhi

Research Advisory committee of Integrated Disease Vector Control Project held on 17 December 2008 at Chennai

Awards Received
Dr V.K. Dua was felicitated with Dr V.P. Sharma Oration Award at the Symposium on Recent advances in vector biology & control at DAV College, Dehradun, Uttarakhand held from 34 December 2008. Ms. Gauri Awasthi visited Ludwig Maximilian University, Munich, Germany for three months to study the selective forces operating in and around pfcrt in P. falciparum. She was awarded prestigious travel fellowships from the Journal of Cell Sciences, UK and Boehringer Ingelheim Fonds, Germany. She was also awarded Geprufte wissenschafliche Hilfskraft fellowship from LMU, Munich. Ms.Prerana Sethi and Mr. Gaurav Verma were awarded Young Scientist awards for Oral and Poster presentations respectively at the Symposium on Recent advances in vector biology & control at DAV College, Dehradun, Uttarakhand held from 34 December 2008. Ms. Prerana Sethi and Ms. Kumkum Mishra were awarded Young Scientist Awards for their best Posters in Chemistry and Environment Science respectively in 3rd Uttarankhand Science Congress held at IIT, Roorkee.

6 Plasmodium

Institutes Activities

Research Papers Published (JulyDecember 2008)

1. Alam MT, Bora H, Singh N, Sharma YD. High immunogenecity and erythrocyte-binding activity in the tryptophan-rich domain (TRD) of the 74-kDa Plasmodium vivax alanine-tryptophan-rich antigen (PvATRAg74). Vaccine 2008; 26: 378794. Anvikar AR, Dolla CK, Dutta S, Gadge V, Shukla GP, Rao S, Karforma C, Rao VG. Diarrheagenic Escherichia coli and acute diarrhea in tribal preschool children of central India. Pediatr Perinatal Epidemiol 2008; 22: 406. Anvikar AR, Rao VG, Savargaonkar DD, et al. Seroprevalence of sexually transmitted viruses among tribal population of central India. International J Infect Dis 2008; June 21 [Epub ahead of print]. Awasthi G, Singh S, Dash AP, Das A. Genetic characterization and evolutionary inference of TNF- with computational analyses. Braz J Infect Dis 2008; 12: 3749. Bharti PK, Silawat N, Singh PP, Singh MP, Shukla MM, Gyanchand, Dash AP, Singh Neeru. The usefulness of a new rapid diagnostic test, First Response Combo Malaria Ag (pLDH/HRP2) card test for malaria diagnosis in forested belt of central India. Malar J 2008; 7: 126. Bhatt RM, Srivastava HC, Rajnikant, Yadav RS. Dynamics of Anopheles culicifacies transmitted malaria in the absence of effective zooprophylaxis in a riverine settlement in Gujarat, India. Curr Sci 2008; 95: 8287. Dash AP, Yadav RS. Insecticide treated nets - technological and operational challenges. Indian J Med Res 2008; 128: 2312, Dash AP, Valecha N, Anvikar AR, Kumar A. Malaria in India: challenges and opportunities. J Biosci 2008; 33 (4): 58392. Dev V, Doley GC, Dash AP. Rolling back malaria is possible. Indian J Med Res 2008; 128: 823. Dhamodharan R, Das MK, Hoti SL, Das PK, Dash AP. Genetic variability of diurnally sub-periodic Wuchereria bancrofti in Nicobarese tribe of Nicobar group of Islands, Andaman and Nicobar Islands, India. Parasitol Res 2008; 103: 5966. Dixit RK, Sharma A, Shouche YS. Identification and characterization of a novel salivary cecropin cDNA from malaria vector Anopheles stephensi. I CFAI J Biotechnol 2008; 2: 712. Dua VK, Alam MF, Pandey AC, Rai S, Chopra AK, Kaul VK, Dash AP. Insecticidal activity of Valeriana jatamansi (Valerianaceae) against mosquitoes. J Am Mosq Control Assoc 2008; 24: 3158. Dua VK, Verma G, Dash AP. In vitro antiprotozoal activity of some xanthones isolated from the roots of Andrographis paniculata. Phytother Res 2008; Aug 6 [Epub ahead of print]. Ghosh SK, Tiwari SN, Ragahavendra K, Sathyanarayan TS, Dash AP. Observation of sporozoites in naturally infected sibling species of Anopheles culicifacies complex and variance of An. stephensi in Karnataka, India. J Biosci 2008; 33 (3): 3336. Jain V, Nagpal AC, Joel PK, Shukla M, Singh MP, Gupta RB, Dash AP, Mishra SK, Udhayakumar V, Stiles JK, Singh N. Burden of cerebral malaria in central India (2004-2007). Am J Trop Med Hyg 2008; 79: 63642. Kiwanuka GN, Joshi H, Isharaza WK, Eschrich K. Dynamics of Plasmodium falciparum alleles in children with normal haemoglobin and with sickle-cell trait in western Uganda. Trans R Soc Trop Med Hyg 2008; 103: 879. Lalitha PV, Biswas S, Pillai CR, Saxena RK. Immunogenicity of a recombinant malaria vaccine candidate, domain I+II of AMA-1 ectodomain, from Indian P. falciparum alleles. Vaccine 2008; 26 (35): 452635. Lucchi NW, Tongren JE, Jain V, Nagpal AC, Kauth CW, Woehlbier U, Bujard H, Dash AP, Singh N, Stiles JK, Udhayakumar V. Antibody responses to the merozoite surface protein-1 complex in cerebral malaria patients in India. Malar J 2008; 7: 121. 19. Mohanty SS, Raghavendra K, Dash AP. Induction of chymoelastase (Pr1) of Metarhizium anisopliae and its role in causing mortality to mosquito larvae. World J Microbiol Biotechnol 2008; 24: 22838. 20. Mohanty SS, Raghavendra K, Mittal PK, Dash AP. Efficacy of culture filtrates of Metarhizium anisopliae against larvae of Anopheles stephensi and Culex quinquefasciatus. J Ind Microbiol Biotechnol 2008; 35: 1199202. 21. Neafsey DE, Schaffner SF, Volkman SK, Park D, Montgomery P, Milner DA Jr, Lukens A, Rosen D, Daniels R, Houde N, Cortese JF, Tyndall E, Gates C, Stange-Thomann N, Sarr O, Ndiaye D, Ndir O, Mboup S, Ferreira MU, do Lago Moraes S, Dash AP, Chitnis CE, Wiegand RC, Hartl DL, Birren BW, Lander ES, Sabeti PC, Wirth DF. Genome-wide SNP genotyping highlights the role of natural selection in Plasmodium falciparum population divergence. Genome Biol 2008; 9: R171. 22. Nishant Khare, Dhananjaya Sharma, Uday Somashekar, Advait Prakash, S. Prakash, MJ Mendki, Anup Anvikar: Detection of bacterial DNA in cholesterol gall stones. International J Surgery 2008; 16 (2). 23. Prakash A, Sharma D, Saxena A, Somashekar U, Khare N, Mishra A, Anvikar A. Effect of Candida infection on outcome in patients with perforation peritonitis. Indian J Gastroenterol. 2008; 27(3):1079. 24. Raghavendra K, Sharma P, Dash AP. Biological control of mosquito populations through frogs: opportunities and constrains. Indian J Med Res 2008; 128: 225. 25. Rao VG, Gopi PG, Yadav R, Sadacharam K, Bhat J, Subramani R, Anvikar AR, et al. Tuberculous infection in Saharia, a primitive tribal community of central India. Trans R Soc Trop Med Hyg 2008; 102(9):898904. 26. Rao VG, Gopi PG, Yadav R, Subramani R, Bhat J, Anvikar AR, Sadacharam K, Tiwari BK, Gadge V, Bhondeley MK, Shukla GP, Ukey M, Jain S, Wares DF. Annual risk of tuberculosis infection among tribal population of central India. Trop Med Int Health 2008; 13(11):13727. 27. Sharma MK, Rao VK, Agarwal GS, Rai GP, Gopalan N, Prakash S, Sharma SK, Vijayaraghavan R. Highly sensitive amperometric immunosensor for detection of Plasmodium falciparum histidinerich protein 2 in serum of humans with malaria: comparison with a commercial kit. J Clin Microbiol 2008; 46:375965. 28. Sharma SK, Tyagi PK, Upadhyay AK, Haque MA, Adak T, Dash AP. Building small dams can decrease malaria: a comparative study from Sundargarh District, Orissa, India. Acta Trop 2008; 107: 1748. 29. Sharma SK, Upadhyay AK, Haque MA, Raghavendra K, Dash AP. Field evaluation of a previously untested strain of biolarvicide (Bacillus thuringiensis israelensis H14) for mosquito control in an urban area of Orissa, India. J Am Mosq Control Assoc 2008; 24: 4104.

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Papers in pipeline
1. 2. 3. 4. 5. 6. Plasmodium falciparum and P. vivax: So similar yet very different (Lancet Infectious Diseases) An open label randomised study of Dihydroartemisininpiperaquine for uncomplicated malaria in India, Laos & Thailand (PLoS Med) Arterolane, a New Synthetic Trioxolane for Treatment of Uncomplicated P. falciparum Malaria (Lancet) Extent of genetic diversity at non coding DNA of Indian P. vivax (Journal of Infectious Diseases) Reconstruction of Phylogenetic status of indian malaria vectors using multilocus DNA fragments (Systematic Biology) Evolutionary genetics of P. falciparum functional genes (PLoS Computational Biology)

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January 2009

Institutes Activities

Progress of NIMR (200408)

NIMR progressed in all fronts in the last five years. Here are some glimpses of the same. Malaria Research Centre was renamed as National Institute of Malaria Research. The Liquid Nitrogen Plant was procured and installed. Extramural funding increased substantially. The long pending Standing Finance Committee approval of the Integrated Disease Vector Control (IDVC) Project was obtained. IDVC project has been included as an intramural activity in 11th Plan of ICMR. IDVC field units were reorganised and two new field units were opened at Raipur (Chhattisgarh) and Ranchi (Jharkhand). IDVC field units were strengthened in terms of manpower and infrastructure. Field units at Bengaluru, Chennai, Sonapur and Jabalpur were shifted to new campuses. NIMR carried out a number of clinical trials with new drugs/ combinations and insecticide, LLINs, larvicides, etc. NIMR was a part of the IPCC document (2007) which got the Nobel Prize. Linkages of NIMR were strengthened. NIMR carried out collaborative research projects with a number of research organizations, universities, medical colleges, hospitals, industries, etc. A number of research outputs of NIMR have gone into the national programme. own campus is now over. Agreement has been signed for construction of animal house, auditorium and other buildings. State-of-the-art laboratories have been established with modern equipments.

Ph.D. Programme
NIMR is affiliated for Ph.D. programme to I.P. University, Delhi, Goa University, Goa, Jiwaji University, Gwalior, and Rani Durgavati University, Jabalpur. NIMR scientists have also been recognized as independent guides by these Universities. The number of Ph.D. students increased. Currently 40 candidates are persuing Ph.D.

Infrastructure development
NIMR was functioning from four different campuses till date. The construction of research block of NIMR in its
Research papers published in indexed journals

Printed and published by Prof. A.P. Dash, Director on behalf of National Institute of Malaria Research (ICMR), and Printed at M/s Royal Offset Printers, A-89/1, Naraina Industrial Area, Phase-I, New Delhi-110 028 and published at National Insitute of Malaria Research (ICMR), Sector 8, Dwarka, New Delhi-110 077. Editor-in-Chief: Prof. A.P. Dash

8 Plasmodium