Some Selected Abstracts: 

1.

2.

Dabir P, Dabir S, Reddy MVR. Cloning and expression of a 12 kDa serospecific epitope of Wuchereria bancrofti. Immunology and Cell Biology, 2005;83:520-524.

Department of Biochemistry and JB Tropical Disease Research Centre, Mahatma Gandhi Institute of Medical Sciences, Sevagram-442102, Wardha, India

Summary: The immunoscreening of a microfilarial cDNA library of Wuchereria bancrofti with microfilaraemic sera revealed many positive clones expressing filarial antigens. One immunoreactive clone, designated PMR1, was shown to encode a protein of 114 amino acid residues. The cDNA fragment was subcloned into an expression vector, Pinpoint XaT. The resulting recombinant (r)PMR1-biotin fusion protein was expressed in Escherichia coli (BL21 [DE3] pLys) and was affinity purified on avidin resin. Analysis of sera of different groups for filarial antibodies against rPMRI showed it to be highly reactive with microfilaraemic and clinical filarial sera compared to its reactivity with endemic and nonendemic controls. This indicates that the gene sequence of cDNA is expressing an immunodominant epitope, which could be useful in serodiagnosis of lymphatic filariasis.

3.

Molyneux DH. Vector-borne parasitic diseases--an overview of recent changes. Int J Parasitol. 1998 Jun;28(6):927-34.

Liverpool School of Tropical Medicine, U.K.

This paper summarises the impact of different changes (environmental, ecological, developmental) on the one hand, with the impact of control measures on the other. The former group of changes have tended to exacerbate the incidence and prevalence of vector-borne parasitic diseases while the reduced public funds available for the health sector have reduced disease surveillance systems. However, some vector control/eradication programmes have been successful. Vector control in onchocerciasis and Chagas' disease and immediate host control in Guinea worm have reduced the public health importance of these disease. This contrasts, with malaria, where the complexity of different ecological situations and the variable vector ecology have made control difficult and epidemics frequent and unpredictable. Advances in our knowledge of how to implement and sustain insecticide-impregnated bednets which reduce morbidity and mortality in under 5-year olds will be a key issue for the coming years. In African trypanosomiasis and leishmaniasis, where control is dependent on effective diagnosis and surveillance followed by high-cost drug treatment, the health services are faced with major challenges--lack of drug availability and diagnostics no vector control--the diseases in some areas assuming epidemic status yet health services are unable to respond. Human African trypanosomiasis and visceral leishmaniasis are fatal if untreated, and require an emergency response approach. Changing vector distribution of Glossina is related to the ability of riverine flies of Glossina palpalis group to adapt to new vegetation patterns. In leishmaniasis changes have occurred in the distribution of the disease associated with development impact, urbanisation, civil unrest and changed agroforestry practice.

4.

Nyame AK, Kawar ZS, Cummings RD. Antigenic glycans in parasitic infections: implications for vaccines and diagnostics. Arch Biochem Biophys. 2004 Jun 15;426(2):182-200

Department of Biochemistry and Molecular Biology, Oklahoma Center for Medical Glycobiology, University of Oklahoma Health Sciences Center, Biomedical Research Center, Room 417, 975 NE 10th Street, Oklahoma City, OK 73104, USA.

Infections by parasitic protozoans and helminths are a major world-wide health concern, but no vaccines exist to the major human parasitic diseases, such as malaria, African trypanosomiasis, amebiasis, leishmaniasis, schistosomiasis, and lymphatic filariasis. Recent studies on a number of parasites indicate that immune responses to parasites in infected animals and humans are directed to glycan determinants within cell surface and secreted glycoconjugates and that glycoconjugates are important in host-parasite interactions. Because of the tremendous success achieved recently in generating carbohydrate-protein conjugate vaccines toward microbial infections, such as Haemophilus influenzae type b, there is renewed interest in defining parasite-derived glycans in the prospect of developing conjugate vaccines and new diagnostics for parasitic infections. Parasite-derived glycans are compelling vaccine targets because they have structural features that distinguish them from mammalian glycans. There have been exciting new developments in techniques for glycan analysis and the methods for synthesizing oligosaccharides by chemical or combined chemo-enzymatic approaches that now make it feasible to generate parasite glycans to test as vaccine candidates. Here, we highlight recent progress made in elucidating the immunogenicity of glycans from some of the major human and animal parasites, the potential for developing conjugate vaccines for parasitic infections, and the possible utilization of these novel glycans in diagnostics.

5.

Tisch DJ, Michael E, Kazura JW.Mass chemotherapy options to control lymphatic filariasis: a systematic review. Lancet Infect Dis. 2005 Aug;5(8):514-23.

Department of Epidemiology and Biostatistics and Center for Global Health and Diseases, Case Western Reserve University, Cleveland, Ohio 44106-7286, USA.

Understanding the efficacy of microfilaricidal drugs is important in guiding the global programme for the elimination of lymphatic filariasis as a public-health problem. We did a systematic review of the available literature to determine which currently available drug intervention most effectively decreases circulating Wuchereria bancrofti microfilaria in individuals and populations. 57 randomised studies of drug efficacy were identified. Data were combined and compared using weighted mean effect estimates taking into account the longitudinal nature of the data. Combined treatment with diethylcarbamazine plus ivermectin, diethylcarbamazine plus albendazole, and ivermectin plus albendazole resulted in average microfilarial intensity decreases that were 0.7%, 4.6%, and 12.7% of the pre-treatment values, respectively. Drug combinations containing diethylcarbamazine were the most effective against microfilarial prevalence and intensity relative to single drugs or other combinations. The relative efficacies of drug combinations have not been well documented from existing studies and therefore limit the application of evidenced-based recommendations for chemotherapy-based interventions to control lymphatic filariasis. These results provide valuable estimates of drug effect using existing data, but highlight the need for more comprehensive comparative drug studies.

6.

Simonsen PE, Magesa SM, Meyrowitsch DW, Malecela-Lazaro MN, Rwegoshora RT, Jaoko WG, Michael E.The effect of eight half-yearly single-dose treatments with DEC on Wuchereria bancrofti circulating antigenaemia. Trans R Soc Trop Med Hyg. 2005 Jul;99(7):541-7
 
DBL-Institute for Health Research and Development, Jaegersborg Alle 1D, 2920 Charlottenlund, Denmark. pesimonsen@dblnet.dk

The effect of eight half-yearly treatment rounds with diethylcarbamazine (DEC; 6mg/kg bodyweight) on Wuchereria bancrofti-specific circulating filarial antigen (CFA), a marker of adult worm infection, was followed in 79 individuals who were CFA-positive before start of treatment. Half of these were also microfilariae (mf)-positive. Microfilaraemia decreased rapidly after onset of treatment and became undetectable after four treatments. Circulating antigenaemia also decreased progressively, but at a much slower rate. After two, four and eight treatment rounds, the mean CFA intensity was reduced by 81, 94 and 98%, and the prevalence of CFA positivity was 85, 66 and 57%, compared with pre-treatment, respectively. CFA clearance rates were negatively related to pre-treatment CFA intensities, and were higher among pre-treatment mf-negative individuals than among pre-treatment mf-positive individuals. Even among patients who had pre-treatment CFA intensities above the upper measuring level (32000antigen units), and who continued to have intensities above this level after treatment, a decrease in post-treatment CFA intensities was obvious from a continuous decrease in ELISA optical density values. Repeated DEC therapy thus appears to have a slow but profound and persistent macrofilaricidal effect, which in the long run may be beneficial to populations undergoing DEC-based control interventions by reducing the probability of future morbidity development.

Diagnosis, Diagnostics, Immunodiagnosis & Immunodiagnostics:

13255.  Bhandari Y, Dabir P, Krithika KN, Kannayakanahalli MD, Shouche YS, Reddy MVR. Analysis of polymorphism of 18S rRNA gene in Wuchereria bancrofti microfilariae. Microbiol Immunol, 2005;49(10):909-914.

13256.  Boatin BA, Toe L, Alley ES, Dembele N, Weiss N, Dadzie KY. Diagnostics in onchocerciasis: future challenges. Ann Trop Med Parasitol. 1998 Apr;92 Suppl 1:S41-5. Review.

13257.    Boatin BA, Toe L, Alley ES, Nagelkerke NJ, Borsboom G, Habbema JD. Detection of Onchocerca volvulus infection in low prevalence areas: a comparison of three diagnostic methods. Parasitology. 2002 Dec;125(Pt 6):545-52.

13258.   Dabir P, Dabir S, Reddy MVR. Cloning and expression of a 12 kDa serospecific epitope of Wuchereria bancrofti. Immunology and Cell Biology, 2005;83:520-524.

13259.   Molyneux DH. Vector-borne parasitic diseases--an overview of recent changes. Int J Parasitol. 1998 Jun;28(6):927-34. Review.

13260.   Nantulya VM. TrypTect CIATT--a card indirect agglutination trypanosomiasis test for diagnosis of Trypanosoma brucei gambiense and T. b. rhodesiense infections. Trans R Soc Trop Med Hyg. 1997 Sep-Oct;91(5):551-3.

13261. Nyame AK, Kawar ZS, Cummings RD. Antigenic glycans in parasitic infections: implications for vaccines and diagnostics. Arch Biochem Biophys. 2004 Jun 15;426(2):182-200. Review.

Pathogenesis:

13262.  Goodridge HS, Stepek G, Harnett W, Harnett MM. Signalling mechanisms underlying subversion of the immune response by the filarial nematode secreted product ES-62. Immunology. 2005 Jul;115(3):296-304. Review.

13263.  Kim YJ, Kumaraswami V, Choi E, Mu J, Follmann DA, Zimmerman P, Nutman TB.  Genetic polymorphisms of eosinophil-derived neurotoxin and eosinophil cationic protein in tropical pulmonary eosinophilia. Am J Trop Med Hyg. 2005 Jul;73(1):125-30.

13264.  Pion SD, Demanou M, Oudin B, Boussinesq M. Loiasis: the individual factors associated with the presence of microfilaraemia. Ann Trop Med Parasitol. 2005 Jul;99(5):491-500.

13265.  Tisch DJ, Michael E, Kazura JW. Mass chemotherapy options to control lymphatic filariasis: a systematic review. Lancet Infect Dis. 2005 Aug;5(8):514-23. Review.

Therapy:

13266.    Critchley J, Addiss D, Ejere H, Gamble C, Garner P, Gelband H; International Filariasis Review Group. Albendazole for the control and elimination of lymphatic filariasis: systematic review. Trop Med Int Health. 2005 Sep;10(9):818-25. Review.

13267.    Farid HA, Hammad RE, Hassan MM, Ramzy RM, El Setouhy M, Weil GJ. Effects of combined diethylcarbamazine and albendazole treatment of bancroftian filariasis on parasite uptake and development in Culex pipiens L. Am J Trop Med Hyg. 2005 Jul;73(1):108-14.

13268.  Fox LM, Furness BW, Haser JK, Desire D, Brissau JM, Milord MD, Lafontant J, Lammie PJ, Beach MJ. Tolerance and efficacy of combined diethylcarbamazine and albendazole for treatment of Wuchereria bancrofti and intestinal helminth infections in Haitian children. Am J Trop Med Hyg. 2005 Jul;73(1):115-21.

13269.  McCarthy J. Is anthelmintic resistance a threat to the program to eliminate lymphatic filariasis? Am J Trop Med Hyg. 2005 Aug;73(2):232-3.

13270.  Ramaiah KD, Ravi R, Das PK. Preventing confusion about side effects in a campaign to eliminate lymphatic filariasis. Trends Parasitol. 2005 Jul;21(7):307-8.

13271.  Schwab AE, Boakye DA, Kyelem D, Prichard RK. Detection of benzimidazole resistance-associated mutations in the filarial nematode Wuchereria bancrofti and evidence for selection by albendazole and ivermectin combination treatment. Am J Trop Med Hyg. 2005 Aug;73(2):234-8.

13272.  Shenoi SD, Kumar P, Khadilkar U, Johnston S. Crusted papule on forehead due to Dirofilaria repens. Trop Doct. 2005 Jul;35(3):181-2.

13273.  Simonsen PE, Magesa SM, Meyrowitsch DW, Malecela-Lazaro MN, Rwegoshora RT, Jaoko WG, Michael E. The effect of eight half-yearly single-dose treatments with DEC on Wuchereria bancrofti circulating antigenaemia. Trans R Soc Trop Med Hyg. 2005 Jul;99(7):541-7.

13274.  Yahathugoda TC, Wickramasinghe D, Weerasooriya MV, Samarawickrema WA.  Lymphoedema and its management in cases of lymphatic filariasis: the current situation in three suburbs of Matara, Sri Lanka, before the introduction of a morbidity-control programme. Ann Trop Med Parasitol. 2005 Jul;99(5):501-10.

Back 

Some Selected Abstracts: 

1.

Bhandary YP, Krithika KN, Kulkarni S, Reddy MVR & Harinath BC. Detection of dehydrogenases and        proteases in Brugia malayi parasites, Indian Journal of clinical Biochemistry, 2006; 21 (1): 36-42.

Department of Biochemistry and J B Tropical Disease Research Centre, Mahatma Gandhi Institute of Medical Sciences, Sevagram 442 102, Wardha, Maharashtra, India.

Lymphatic filariasis caused mainly by infection from W. bancrofti and B. malayi remains a major cause of clinical morbidity in tropical and subtropical countries. Analysis of B.malayi mf. infective larval and adult worm lysates for the activity of enzymes led to the demonstration of activities of three key enzymes of carbohydrate metabolism viz. Malate dehydrogenase (MDH), Malic enzyme (ME) and Glucose -6- phosphate dehydrogenase (G6PDH) in all the three stages of the parasite. The specific activity of all the three dehydrogenases was significantly high in mf lysate compared to their activity in lysates of the two stages (P<0.001). Analysis by native polyacrylamide gel electrophoresis ( PAGE) using 7.5% non-gradient gel showed the presence of two isoforms of each of the three enzymes ( MDH, ME & G6PDH) in mf lysate, while only one form of each enzyme was present in L3 larval and adult worm lysates. Further proteolytic enzyme activity was demonstrated both in microfilarial and infective larval lysates of B.malayi. while both mf and L3 larval lysates showed optimal protease activity at alkaline pH 9.0 . the mf lysate showed increased activity also at pH 3.0. The infective larval lysate was markedly inhibited by Tosylamide –L-Phenylalanine chromethyl ketone (TPCK), a thiol protease inhibitor, while the protease activity in mf lysate was significantly inhibited by both TPCK and a serine protease inhibitor Phenyl Methyl Sulphonyl Flouride (PMSF). In sodium do-decyl sulphate polyacrylamide gel electrophoresis (SDS-PAGE), using gelatin copolymerized gel, the microfilarial lysate showed 3 protease molecules of 40 kDa, 180 kDa and 200 kDa and L₃ larval lysate had 6 protease molecules of 18,25, 37, 49, 70 and 200 kDa size.

2.

Dabir P, Dabir S, Siva Prasad BV, Reddy MVR.  Isolation and analysis of partial cDNA sequence coding for superoxide dismutase in Wuchereria bancrofti.  Infection. Genetics and Evolution 2005. (PMID: 16199210).

Department of Biochemistry and J B Tropical Disease Research Centre, Mahatma Gandhi Institute of Medical Sciences, Sevagram 442 102, Wardha, Maharashtra, India.

Molecular characterization of Wuchereria bancrofti is essential to develop suitable anti-filarial drugs and vaccines. We describe here isolation, sequence analysis and cloning of a partial cDNA of an enzyme superoxide dismutase from this parasite. The immunoscreening of a lambda zap W. bancrofti microfilarial (Mf) cDNA library with microfilaremic sera had resulted in the isolation of several seroreactive clones including, WbSOD. This clone contained a 309bp insert and showed significant nucleotide and deduced amino acid sequence homologies to the superoxide dismutases of other nematode parasites. The antioxidant property of this enzyme may have important contribution in the defense mechanism of the parasite against host immune response

3.

Hoerauf A, Satoguina J, Saeftel M, Specht S. Immunomodulation by filarial nematodes. Parasite Immunol. 2005 Oct-Nov;27(10-11):417-29. Review. 

Institute for Medical Parasitology, University Clinic Bonn, Sigmund Freud Strasse 25, 53105 Bonn, Germanyhoerauf@parasit.meb.uni-bonn.de  In order to chronically infect their hosts, filarial nematodes have generated a range of strategies to evade and down-modulate the host's immune system. The recent concept of suppression of immune responses by regulatory T cells has in part benefited from examinations in human and murine filariasis. Its further development in basic immunology animal models has in turn helped to better understand down-regulatory immune mechanisms in filariasis. Thus, filarial nematodes orchestrate down-regulation by inducing regulatory T cells and alternatively activated macrophages, which are able to suppress both Th1 and Th2 responses. Regulatory T cells can also induce the secretion of IgG4 from B cells as another arm of modulation. Dendritic cells are down-regulated upon first encounter with infective L3 larvae. Failure to respond to down-regulatory induction is based on genetic traits in hosts and leads to reduced parasite loads, albeit at the expense of pathology and disease. Since down- regulation in chronically and heavily infected hosts extends to third-party antigens, it is essential to analyse the impact of filarial infection for vaccination, allergy and important coinfections such as malaria, in order to foresee and avert potentially disastrous consequences of filariasis control programmes.

4

Nuchprayoon S, Junpee A, Poovorawan Y, Scott AL. Detection and differentiation of filarial parasites by universal primers and polymerase chain reaction-restriction fragment length polymorphism analysis. Am J Trop Med Hyg. 2005 Nov;73(5):895-900.

Lymphatic Filariasis Research Unit, Department of Parasitology and Department of Pediatrics, Chula Medical Research Center, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand. fmedstt@md2.md.chula.ac.th

Filarial nematode parasites are a serious cause of morbidity in humans and animals. Identification of filarial infection using traditional morphologic criteria can be difficult and lead to misdiagnosis. We report on a polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP)-based method to detect and differentiate a broad range of filarial species in a single PCR. The first internal transcribed spacer 1 (ITS1) along with the flanking 18S and 5.8S ribosomal DNA (rDNA) were isolated and cloned from Wuchereria bancrofti, Brugia malayi, and Brugia pahangi. Sequence analysis identified conserved sites in the 18S and 5.8S rDNA sequence that could be used as universal priming sites to generate ITS1- distinctive PCR products that were useful for distinguishing filariae at the genus level. The addition of a digestion of the ITS1 PCR product with the restriction endonuclease Ase I generated a fragment profile that allowed differentiation down to the species level for W. bancrofti, B. malayi, B. pahangi, Dirofilaria immitis, and D. repens. The PCR-RFLP of ITS1 rDNA will be useful in diagnosing and differentiating filarial parasites in human, animal reservoir hosts, and mosquito vectors in disease-endemic areas.

Some selected abstracts: 

1.

Summary: Wuchereria bancrofti-mediated lymphatic filariasis is widely prevalent. Diversity in immune response presumably may lead to myriad clinical presentations, such as overt chronic filariasis, occult filariasis with atypical systemic manifestation and asymptomatic microfilariae carrier state. Anticipated oxidative stress during inflammatory response to infective conditions might complicate the immune response and thus might alter the disease outcome. The present study was carried out to assess the status of oxidative stress in different clinical presentations of bancroftian filariasis. Twenty-five microfilariae carriers and 30 cases each of chronic filariasis and occult filariasis were compared to 30 endemic normal individuals. Serum malondialdehyde level and superoxide dismutase enzyme activity were measured by spectrophotometric methods and levels of filarial antigen were measured by ELISA. In the filarial cases, the levels of these parameters were assayed again after treatment with diethylcarbamazine citrate (DEC). Results showed significant (P < 0.05) association of oxidative stress with chronic and occult filariasis but not with microfilarial carriers. DEC therapy in both clinical cases and carriers resulted in a significant reduction of oxidative stress associated with decreased antigen level (P<0.01). These findings suggest the possible involvement of oxidative stress in filarial disease pathology. © 2005 Royal Society of Tropical Medicine and Hygiene. Published by Elsevier Ltd. All rights reserved.

October 2006

Diagnosis, Diagnostics, Immunodiagnosis & Immunodiagnostics:

14709.  Rao RU, Atkinson LJ, Ramzy RM, Helmy H, Farid HA, Bockarie MJ, Susapu M, Laney SJ, Williams SA, Weil GJ. A real-time PCR-based assay for detection of Wuchereria bancrofti DNA in blood and mosquitoes. Am J Trop Med Hyg. 2006 May;74(5):826-32. 

Vaccines:

14710.  Mitre E, Nutman TB. IgE memory: persistence of antigen-specific IgE responses years after treatment of human filarial infections. J Allergy Clin Immunol. 2006 Apr;117(4):939-45.

 Therapy:

14711.  De Kraker ME, Stolk WA, van Oortmarssen GJ, Habbema JD. Model-based analysis of trial data: microfilaria and worm-productivity loss after diethylcarbamazine-albendazole or ivermectin-albendazole combination therapy against Wuchereria bancrofti. Trop Med Int Health. 2006 May;11(5):718-28. Review. 

14712.  Michael E, Malecela-Lazaro MN, Kabali C, Snow LC, Kazura JW.   Mathematical models and lymphatic filariasis control: endpoints and optimal interventions. Trends Parasitol. 2006 May;22(5):226-33.