FILARIASIS

6044. Melrose WD. Lymphatic filariasis: new insights into an old disease. Int J Parasitol. 2002 Jul;32(8):947-60. Review.

Lymphatic filariasis has afflicted people in the tropical areas of the world for thousands of years but even up to comparatively recent times it has been poorly understood and its importance under recognised. In the last 2 decades or so there has been a flurry of activity in filariasis research, which has provided new insights into the global problem of filariasis, the pathogenesis of filarial disease, diagnosis and control.

6045. Sehri P, Krishnanand G, Gupta A, Mukherjee A. Breast filariasis. Indian J Path Microbiol. 200; 43(3): 363-4. No abstract.

Therapy:

6046. Etya'ale D. Eliminating onchocerciasis as a public health problem: the beginning of the end. Br J Ophthalmol. 2002 Aug;86(8):844-6.

Onchocerciasis is one of the diseases targeted by Vision 2020. It is the world's second leading infectious cause of blindness, responsible for at least one million blind or severely visually disabled people. The Onchocerciasis Control Programme (OCP) in sub-Saharan Africa will be closed down in 2002, after 27 years of operation. This is the clearest indication that the prospects of eliminating onchocerciasis as a public health problem may be achieved by the end of this decade. The programme's potential now is to serve as a model of global and multiple partnership, to address other poverty related, serious and intractable problems such as needless blindness in the world.

6047. Sharma DC. New goals set for filariasis elimination in India. Lancet Infect Dis. 2002 Jul;2(7):389. No abstract.

6048. Unnasch TR. River blindness. Lancet. 2002 Jul 20;360(9328):182-3. No abstract.

April 2003

6672. Arya SC.An enzyme-linked immunosorbent assay (ELISA) format to diagnose Wuchereria bancrofti specific immunoglobulin G4 class in urine samples.Am J Trop Med Hyg 2002 Oct;67(4):335. No abstract.

6673. Birley H, Duerden B, Hart CA, Curless E, Hay PE, Ison CA, Renton AM, Richens J, Wyatt GB.Sexually transmitted diseases: microbiology and management.J Med Microbiol 2002 Oct;51(10):793-807.No abstract.

6674. Bregani ER, Ghiringhelli C, Ceraldi T, Rovellini A. Identification of Mansonella perstans microfilariae in ascitic fluid.Trop Doct 2002 Oct;32(4):249-50 No abstract.

6675. Dash PK; Mishra GC; Pattanaik MR; Mohapatra N; Behera G. Clinical profile of tropical pulmonary eosinophilia with special reference to bronchoalveolar lavage Antiseptic. 2002 Sep; 99(9): 332-4

ABSTRACT: Tropical pulmonary eosinophilia (TPE) is a clinical entity characterized by cough, wheeze, breathlessness, more during night time and peripheral eosinophilia with an absolute count more than 3000 per micro liter of blood in the absence of micro-filaria with chest X-ray features of increased bronchovascular markings of mottling opacities in about 20 percent of cases (WHO, 1993). There is high rise of antibodies against microfilaria particularly Ige and rapid response to di-ethyl carbamazine citrate (DEC) in 3-7 days. This syndrome is prevalent in filaria endemic regions of the world especially Southeast Asia. Out of all cases of TPE about 90 percent occur in people of Indian origin. This disease is thought to be a manifestation of occult filariasis. Acute phase of the disease is caused by antibody mediated mechanism mechanism whereas chronicity is mediated by hypersensitivity reaction producing granuloma. Though the peripheral eosinophilia is the hallmark for the diagnosis of TPE, it is not directly related to the severity of the clinical feature. Recent investigations like bronchoalveolar lavage (BAL) has revealed that in TPE majority of inflammatory cells infiltrating the lungs are eosinophils. It has also been found that although the clinical response of TPE to DEC is rapid, as many as 50 percent of patients treated for three weeks with DEC maintain a persistent, low grade eosinophilia and alveolitis even 6-12 months after therapy. Thus morbidity due to TPE amounts to a lot of financial loss of the individual. Orissa is a state, endemic for filariasis. Hence this study was conducted to evaluate the clinical presentations of TPE and to find out if there is any correlation between clinical severity of the disease and peripheral eosinophilia and to study the cytological characteristics of BAL and correlate this with clinical severity of the disease and to correlate lung function tests with peripheral as well as pulmonary eosinophilia.

6676. Kipp W, Bamhuhiiga J. Onchodermal skin disease in a hyperendemic onchocerciasis focus in western Uganda. Am J Trop Med Hyg 2002 Nov;67(5):475-9

To assess the degree of skin disease in Simulium neavei s.s.-transmitted onchocerciasis, 72 patients infected with Onchocerca volvulus in the Kabarole district of Uganda were studied. They were clinically and parasitologically evaluated. Onchocercal skin lesions were determined using a modified Murdoch skin assessment, and skin scores were calculated. The chronic skin score (4.0) was associated with age, and the acute skin score (8.5) was significantly higher in males. The burden of onchocercal skin lesions was found to be high in most patients. The number of nodules (median number 1.9) and the microfilarial load (geometric mean of microfilaria 11.5) were not determinants for the burden of onchocercal skin disease in infected individuals. The study concludes that onchodermatitis is a serious medical condition in Kigoyera Parish and needs to be considered in all efforts to control onchocerciasis.

6677. Kundu AK, Giri A, Ghosh G, Saha SR.Microfilaria in a thyroid nodule which resolved on treatment. Trop Doct 2002 Oct;32(4):248. No abstract.

6678. R. Alli, B. Bhunia, GP Chhotray, MVR Reddy, BC Harinath. Microscopic haematuria as an occult filarial infection in Bhubaneshwar an endemic area for bancroftian filariasis. Indian J of Clin Biochem 2003, 18 (1): 61-64.No abstract.

6679. Stringfellow GJ, Francis IC, Coroneo MT, Walker J.Orbital dirofilariasis. Clin Experiment Ophthalmol 2002 Oct;30(5):378-80

Dirofilariasis is a parasitic disease of domestic and wild animals that occasionally may present as zoonotic infection in humans. The microfilariae are accidentally transmitted to humans by Culex and Aedes mosquitoes. Ophthalmic infections with Dirofilaria are well documented all over the world, including America, Europe and Australia. The infection may be periorbital, subconjunctival or intraocular. In this report a case is described of orbital dirofilariasis that presented as ptosis and lid swelling. Australian ophthalmologists should consider dirofilariasis as part of the differential diagnosis of orbital swelling and inflammation.

Pathogenesis:

6680. Bockarie MJ, Tisch DJ, Kastens W, Alexander ND, Dimber Z, Bockarie F, Ibam E, Alpers MP, Kazura JW. Mass treatment to eliminate filariasis in Papua New Guinea.N Engl J Med 2002 Dec 5;347(23):1841-8.

BACKGROUND: The global initiative to eradicate bancroftian filariasis currently relies on mass treatment with four to six annual doses of antifilarial drugs. The goal is to reduce the reservoir of microfilariae in the blood to a level that is insufficient to maintain transmission by the mosquito vector. METHODS: In nearly 2500 residents of Papua New Guinea, we prospectively assessed the effects of four annual treatments with a single dose of diethylcarbamazine plus ivermectin or diethylcarbamazine alone on the incidence of microfilariae-positive infections, the severity of lymphatic disease, and the rate of transmission of Wuchereria bancrofti by mosquitoes. Random assignment to treatment regimens was carried out according to the village of residence, and villages were categorized as having moderate or high rates of transmission. RESULTS: The four annual treatments with either drug regimen were taken by 77 to 86 percent of the members of the population who were at least five years old; treatments were well tolerated. The proportion with microfilariae-positive infections decreased by 86 to 98 percent, with a greater reduction in areas with a moderate rate of transmission than in those with a high rate. The respective aggregate frequencies of hydrocele and leg lymphedema were 15 percent and 5 percent before the trial began, and 5 percent (P<0.001) and 4 percent (P=0.04) after five years. Hydrocele and leg lymphedema were eliminated in 87 percent and 69 percent, respectively, of those who had these conditions at the outset. The rate of transmission by mosquitoes decreased substantially, and new microfilariae-positive infections in children were almost completely prevented over the five-year study period. CONCLUSIONS: Annual mass treatment with drugs such as diethylcarbamazine can virtually eliminate the reservoir of microfilariae and greatly reduce the frequency of clinical lymphatic abnormalities due to bancroftian filariasis. Eradication may be possible in areas with moderate rates of transmission, but longer periods of treatment or additional control measures may be necessary in areas with high rates of transmission. Copyright 2002 Massachusetts Medical Society

6681. Cooper PJ, Schwartz LB, Irani AM, Awadzi K, Guderian RH, Nutman TB. Association of transient dermal mastocytosis and elevated plasma tryptase levels with development of adverse reactions after treatment of onchocerciasis with ivermectin. J Infect Dis 2002 Nov 1;186(9):1307-13

To investigate the role of mast cells in treatment-associated adverse reactions in patients with onchocerciasis, changes in plasma tryptase levels and skin mast cell counts were examined in 2 groups of Onchocerca volvulus-infected subjects after ivermectin treatment. After treatment, an increase in tryptase levels was observed concurrent with the onset of blood eosinopenia and preceding the appearance of plasma eosinophil-derived neurotoxin (EDN) and interleukin-5. Tryptase levels were correlated with development of peripheral eosinopenia and markers of eosinophil activation and degranulation. Dermal mast cell numbers increased transiently at 24 h after treatment, preceding the onset of dermal eosinophil infiltration and the development of clinically apparent inflammation. Local reactions were strongly correlated with levels of plasma tryptase and EDN, and the severity of systemic reactions was correlated with levels of tryptase, EDN, and interleukin-5. The data indicate that mast cells play a role in initiation of tissue inflammatory reactions after ivermectin treatment of onchocerciasis.

6682. Doan NM, Keiser PB, Bates RA, Fedorko DP, Weina PJ, Lucey DR. A 33-year-old woman from Nigeria with eosinophilia. Clin Infect Dis 2002 Nov 15;35(10):1204, 1263-4. No abstract.

6683. Duke BO, Marty AM, Peett DL, Gardo J, Pion SD, Kamgno J, Boussinesq M. Neoplastic change in Onchocerca volvulus and its relation to ivermectin treatment. Parasitology 2002 Nov;125(Pt 5):431-44.

A pleomorphic neoplasm (PN) is described from sections of Onchocerca volvulus worms in nodules excised from Cameroonian patients. PN is confined to older, non-fecund, female worms, and those classed as moribund/dead. It is mainly composed of small, roundish, basophilic cells of diverse sizes, often forming a 'rosette' pattern around amorphous eosinophilic centres. The cells have a high nuclear/cytoplasmic ratio and up to 2-3 mitoses/high-power field; some become grossly enlarged, highly polymorphic and contain large, irregular blocks of chromatin. The eukaryotic PN cells first appear posteriorly in the pseudocoelom, probably from ovarian cells; they spread anteriorly, invading or compressing the uteri. Ivermectin treatment increased the prevalence PN from 3.7% of 1422 female worms in 637 patients before treatment to 17.5% of 1134 worms in 511 patients after 3 years treatment. Ivermectin at 400-800 microg/kg annually, or at 150 microg/kg or 400-800 microg/kg 3-monthly, over 3 years, did not increase the PN prevalence significantly, as compared with standard doses of 150 microg/kg annually. In other small series of African patients, PN prevalence increased in worms 2, 4, 6 and 10 months after ivermectin treatment; but there was no increase after treatment with amocarzine, albendazole or diethylcarbamazine and suramin. PN may partly account for the increased macrofilaricidal action of ivermectin on female O. volvulus in patients treated for 3 years at 3-monthly intervals.

6684. McCarroll L, Hemingway J.Can insecticide resistance status affect parasite transmission in mosquitoes? Insect Biochem Mol Biol 2002 Oct;32(10):1345-51.No abstract

6685. Roberts L.Mosquitoes and disease. Science 2002 Oct 4;298(5591):82-3. No abstract.

6686. Shriram AN, Murhekar MV, Ramaiah KD, Sehgal SC. Prevalence of diurnally subperiodic bancroftian filariasis among the Nicobarese in Andaman and Nicobar Islands, India: effect of age and gender. Trop Med Int Health 2002 Nov;7(11):949-54.

We conducted a cross-sectional survey to assess the prevalence of disease and microfilaraemia caused by diurnally subperiodic strain of Wuchereria bancrofti transmitted by day biting Aedes niveus in Teressa Island, remotely located in the Nicobar district of Andaman and Nicobar Islands. Lymphatic filariasis is a considerable public health problem on this island with an overall endemicity rate of 16.2%. There was a gradual increase in microfilaraemia prevalence with age, reaching a plateau above 30 years. Both the microfilaraemia and disease rates were significantly higher in males (14.7% and 5.2%) than females (8.6% and 1.5%, P < 0.001). The age and gender specific distribution of chronic manifestations show a gradual increase with age, whereas acute disease started to occur from age 40 in males. Hydrocele (84.6%) was the commonest disease manifestation among males, whereas lymphoedema was the only manifestation encountered among females. As vector control measures are not practicable in this setting, chemotherapy using diethylcarbamazine (DEC) is the only potential option to control this disease.

Therapy:

6687. Onwujekwe O, Chima R, Shu E, Okonkwo P. Community-directed treatment with ivermectin in two Nigerian communities: an analysis of first year start-up processes, costs and consequences. Health Policy 2002 Oct;62(1):31-51

OBJECTIVES: To determine the start-up processes, costs and consequences of community-directed treatment with ivermectin (CDTI) in two onchocerciasis endemic rural towns of Southeast Nigeria; namely Achi and Nike. The other objectives were to discover the community-financing mechanisms, local ivermectin distribution strategies and communities' organisational capacity to handle the programme. METHODS: Structured questionnaires, informal interviews, observations, discussions with community members at general village assemblies and community outreach lectures were used at different stages of the study. RESULT: The towns had the organisational capacity to implement the programme. Coverage with ivermectin was between 31-73% in Achi (mean = 58.6%), and 36.6-72% in Nike (mean = 61.95%). The unit financial costs were $0.17 in Nike and $0.13 in Achi, but the unit aggregate cost was $0.37 in Nike and $0.39 in Achi. When research costs were removed, the unit aggregate cost was $0.22 in Achi and $0.20 in Nike. Provider's financial costs and communities' non-financial costs were the biggest contributors to the aggregate cost. The cost would decrease in subsequent years since the research cost and parts of the mobilisation and training costs would not be incurred after the first year. CONCLUSION: Governments and sponsors of CDTI should find means of continuously strengthening the programme and providing technical support to the communities. As both CDTI and communities are dynamic entities, continuous health education campaigns are needed to keep reminding the people of the benefit of long-term ivermectin distribution, together with the need for community ownership of the programme.

6688. Ottesen EA. Major progress toward eliminating lymphatic filariasis. N Engl J Med 2002 Dec 5;347(23):1885-6. No abstract.

6689. Rajendran R, Sunish IP, Mani TR, Munirathinam A, Satyanarayana K. Targeting of children in filariasis mass drug administration. Lancet 2002 Nov 2;360(9343):1430. No abstract.

July 2003

7198. Ali MM, Baraka OZ, AbdelRahman SI, Sulaiman SM, Williams JF, Homeida MM, Mackenzie CD. Immune responses directed against microfilariae correlate with severity of clinical onchodermatitis and treatment history. J Infect Dis 2003 Feb 15;187(4):714-7

The induction of pathological changes in Onchocerca volvulus infections is directly related to the presence of the microfilarial stage of this filarial nematode. Patients with either of the 2 major forms of the clinical disease (i.e., asymptomatic/mild [n=12] and severe [n=16] dermatopathology) were studied. The cellular immune responses (cell proliferation) of those with severe disease were stronger (stimulation index [SI], 12.3+/-1.9) than those with mild dermatopathological effects (SI, 2.9+/-0.6) or control patients (SI, 4.5+/-0.4). Cytoadherence antibody responses were greatest (grade 4) in the clinically severe group and only weak (grades < or = 1) in the mild group or the control patients. Ivermectin treatment was followed by an increase in immune responsiveness in those with initially poor responses. Thus, the degree of dermatopathological effect is related to the host's immune response against microfilariae, and ivermectin augments such responses.

7199. Belizario VY, Amarillo ME, de Leon WU, de los Reyes AE, Bugayong MG, Macatangay BJ. A comparison of the efficacy of single doses of albendazole, ivermectin, and diethylcarbamazine alone or in combinations against Ascaris and Trichuris spp. Bull World Health Organ 2003;81(1):35-42

OBJECTIVE: To determine the efficacy of single doses of albendazole, ivermectin and diethylcarbamazine, and of the combinations albendazole + ivermectin and albendazole + diethylcarbamazine against common intestinal helminthiases caused by Ascaris and Trichuris spp. METHODS: In a randomized, placebo-controlled trial, infected children were randomly assigned to treatment with albendazole + placebo, ivermectin + placebo, diethylcarbamazine + placebo, albendazole + ivermectin, or albendazole + diethylcarbamazine. The Kato-Katz method was used for qualitative and quantitative parasitological diagnosis. The chi2 test was used to determine the significance of cure rates, repeated measures analysis of variance for the comparison of mean log egg counts, the Newman-Keuls procedure for multiple comparison tests, and logistic regression for the comparison of infection rates at days 180 and 360 after treatment. FINDINGS: Albendazole, ivermectin and the drug combinations gave significantly higher cure and egg reduction rates for ascariasis than diethylcarbamazine. For trichuriasis, albendazole + ivermectin gave significantly higher cure and egg reduction rates than the other treatments: the infection rates were lower 180 and 360 days after treatment. CONCLUSION: Because of the superiority of albendazole + ivermectin against both lymphatic filariasis and trichuriasis, this combination appears to be a suitable tool for the integrated or combined control of both public health problems.

7200. Bhunia B, Bhandari YP, Reddy MVR, Harinath BC. Analysis of IgG subclasses and IgE antibodies across the clinical spectrum of bancroftian filariasis in an endemic area. Indian J Patho Microbiol 2003; Vol 46(1):113-117.

Analysis of immune response in individuals with different clinical manifestations living in filaria endemic area will be of interest to understand the immunological events associated with the disease development in filarial infected endemic population. The levels of four IgG subclasses and IgE antibodies against Brugia malayi microfilarial excretory-secretory (Bm mf ES) antigen as well as circulating filarial antigen level were evaluated in 84 individuals belonging to different groups in an endemic area for bancroftian filariasis. Microfilaraemics showed significantly elevated levels of IgG4 and IgG3 antibodies compared to endemic normals (P<0.02). As many as 70% of this group were positive for IgG4 & IgG3 antibodies. While Acute filarial cases had pronounced IgG1 antibodies(P<0.001), the Grade I chronic cases showed higher levels of IgG3 and IgG4 antibodies (P<0.02), Occult filarial cases had higher levels of IgG4 and IgG3 (P<0.02) and also of IgG1 antibodies (P<0.001). IgE antibodies were found to be elevated in microfilaraemics and as well as other clinical filarial groups. Circulating filarial antigen was detected in 95% of microfilaraemics, 60% of acute cases, 75% to 90% of different grades of chronic filarial cases, 100% of occult cases and none of the endemic normals.

7201. Engelbrecht F, Oettl T, Herter U, Link C, Philipp D, Edeghere H, Kaliraj P, Enwezor F. Analysis of Wuchereria bancrofti infections in a village community in northern Nigeria: increased prevalence in individuals infected with Onchocerca volvulus. Parasitol Int 2003 Mar;52(1):13-20

Infections with Wuchereria bancrofti causing lymphatic filariasis still represent one of the major health problems in the tropics, with 120 million people infected and over 750 million exposed to this filarial parasite. We have studied lymphatic filariasis infections as part of a multi-parasite survey in a village community in the savannah of northern Nigeria. We analysed serum samples from 341 individuals aged 5-70 years, detecting a W. bancrofti circulating antigen using the commercially available ICT Filariasis card test. The prevalence of infections was 10% and clearly age-dependent, increasing from below 2% in children to over 20% in subjects older than 40 years. Measuring IgG4 antibodies against the recombinant W. bancrofti antigen SXP1 showed that 36% of all tested individuals had been at least exposed to the parasite. Antibody levels also increased very significantly with age. A further analysis measuring Onchocerca volvulus-specific IgG4 antibodies showed a very significant association between infections with O. volvulus and those with W. bancrofti. Our data show that infections with W. bancrofti in Nigeria are still a frequently occurring health problem, since they are more prevalent than previously reported, and that individuals with an O. volvulus infection are more often infected with W. bancrofti than expected statistically. Copyright 2002 Elsevier Science Ireland Ltd.

7202. Rahmah N, Lim BH, Azian H, Ramelah TS, Rohana AR. Short communication: use of a recombinant antigen-based ELISA to determine prevalence of brugian filariasis among Malaysian schoolchildren near Pasir Mas, Kelantan-Thailand border. Trop Med Int Health 2003 Feb;8(2):158-63

Brugian filariasis infects 13 million people in Asia. The routine prevalence survey method using night thick blood smear is not sensitive enough to reflect the actual infection prevalence. In 1997-2001, only three microfilaraemic cases (of 5601 individuals screened; 0.05%) were reported in Pasir Mas, a district in Kelantan (Malaysia), which shares a border with Thailand. We therefore investigated the infection prevalence in this district by employing a sensitive and specific serological assay (Brugia-Elisa). This test is based on detection of specific IgG4 antibody against a Brugia malayi recombinant antigen. A total of 5138 children, aged 7-12 years, from 16 primary schools, were tested. Eighteen pupils in eight schools, located in five subdistricts, tested positive, giving an overall prevalence rate of 0.35%. Infection in these children is significant as they represent more recent cases. These subdistricts should be included in the national filariasis elimination programme.

7203. Terhell AJ, Haarbrink M, van den Biggelaar A, Mangali A, Sartono E, Yazdanbakhsh M. Long-term follow-up of treatment with diethylcarbamazine on anti-filarial IgG4: dosage, compliance, and differential patterns in adults and children. Am J Trop Med Hyg 2003 Jan;68(1):33-9

We have followed a population in an area endemic for Brugia malayi for three years after intensive treatment with diethylcarbamazine (DEC). Microfilariae were cleared from the circulation within four months in all eligible study participants (n = 60). There appeared to be a strong correlation between the maximum reduction in specific IgG4 and the number of days drug was taken under supervision (p = 0.41, P < 0.001), indicating that high total dosage of DEC is necessary for optimal reduction of active infection. In individuals with good compliance (at least 180 mg/kg of body weight, n = 34), we observed variable IgG4 patterns. All pre-treatment IgG4+ children (9-14 years old) and 40% of the IgG4+ adult population (> or = 15 years old) showed a gradual decrease in anti-filarial IgG4; 53% of these showed complete clearance of worm burden by the end of the study. In contrast, another group of male IgG4+ adults showed IgG4 patterns that started to increase between nine months and two years after treatment, indicating either a partial efficacy of DEC that allowed recovery of resident adult worms or reinfection.

7204. Zhang X, Ye ZQ, Chen Z, Chen ZQ, Zhu QG, Xin M, Li LC. Comparison of open surgery versus retroperitoneoscopic approach to chyluria. J Urol 2003 Mar;169(3):991-3

PURPOSE: We compared the clinical effectiveness of renal pedicle lymphatic disconnection for chyluria performed by retroperitoneoscopy and by open surgery. MATERIALS AND METHODS: Three male and 4 female patients 33 to 68 years old (mean age 49) with chyluria underwent retroperitoneoscopic renal pedicle lymphatic disconnection. Chyluria was on the left side in 5 cases and on the right side in 2. Open renal pedicle lymphatic disconnection was performed in 4 men and 2 women 33 to 61 years old (mean age 45.8). Chyluria was on the left and right sides in 3 cases each. Mean operative time, intraoperative blood loss, postoperative intestinal function recovery time, intraoperative and postoperative complications, postoperative hospital delay and operative outcome were compared in these 2 groups. RESULTS: Compared with the open surgery group results in the retroperitoneoscopic group were superior in terms of operative time (42 to 90 minutes, mean +/- SD 65.0 +/- 18.8 versus 120 to 220, mean 156.7 +/- 38.8), intraoperative blood loss (20 to 50 ml., mean 29.3 +/- 10.2 versus 60 to 250, mean 171.7 +/- 76.5), postoperative intestinal function recovery time (24 to 48 hours, mean 36.0 +/- 6.9 versus 24 to 72, mean 54.0 +/- 21.1), intraoperative and postoperative complications, and postoperative hospital stay (3 to 6 days, mean 4.7 +/- 0.7 versus 7 to 9 days, mean 7.8 +/- 1.0). In the open surgery group primary anastomosis was performed in 1 case due to injury to a renal artery branch during the operation. Chyluria resolved the day after surgery in the 2 groups. No obvious complications developed postoperatively. The followup of 2 to 12 months (mean 6.7 +/- 4.0) showed no recurrence of chyluria. CONCLUSIONS: Retroperitoneoscopic renal pedicle lymphatic disconnection completely ligates the lymphatic vessels with minimal invasion, less blood loss, rapid recovery and a good short-term outcome.

Pathogenesis

7205. Chadee DD, Rawlins SC, Tiwari TS. Short communication: concomitant malaria and filariasis infections in Georgetown, Guyana. Trop Med Int Health. 2003 Feb;8(2):140-3.

Lymphatic filariasis and malaria are endemic in Guyana, South America. To determine the prevalence of concomitant infections, we conducted a 1-year survey of febrile patients attending the malaria (day) and filariasis (night) clinics in Georgetown. In all, 1278 thick blood smears were collected: 769 for filariasis, of which 103 were positive for Wuchereria bancrofti, and three for both W. bancrofti and malaria parasites; and 509 for malaria, 21 of which tested positive for malaria and 17 for both malaria and filariasis. The age groups and sex of the infected persons with malaria and W. bancrofti are described. These results suggest that the incidence of concomitant infections in Guyana may be quite low but efforts should be made to reduce the disease burden in Georgetown, Guyana.

7206. Guevara AG, Vieira JC, Lilley BG, Lopez A, Vieira N, Rumbea J, Collins R, Katholi CR, Unnasch TR. Entomological evaluation by pool screen polymerase chain reaction of Onchocerca volvulus transmission in Ecuador following mass Mectizan distribution. Am J Trop Med Hyg. 2003 Feb;68(2):222-7.

The prevalence of infected and infective black flies was estimated by pool screen polymerase chain reaction (PCR) amplification in the three river basins in Ecuador endemic for onchocerciasis. Mass distribution of ivermectin (Mectizan) resulted in dramatic declines in the prevalence of infected and infective flies. In the Rio Santiago river basin, no infections were detected, suggesting that transmission had ceased. The ratio of infected to infective flies in Simulium exiguum was 10-fold lower than the corresponding ratio for Simulium quadrivittatum, suggesting that S. exiguum is a more-competent vector for Onchocerca volvulus than S. quadrivittatum. However, the prevalence of infective flies in the two species was not different, suggesting that S. quadrivittatum may play an important vectorial role where it is the dominant human-biting species. The data demonstrate that pool screen PCR is an efficient way to monitor transmission in areas subject to control, and to certify an area as free of O. volvulus transmission.

7207. Hoerauf A, Buttner DW, Adjei O, Pearlman E. Onchocerciasis. BMJ. 2003 Jan 25;326(7382):207-10. No abstract available.

7208. Lobos E, Nutman TB, Hothersall JS, Moncada S. Elevated immunoglobulin E against recombinant Brugia malayi gamma-glutamyl transpeptidase in patients with bancroftian filariasis: association with tropical pulmonary eosinophilia or putative immunity. Infect Immun. 2003 Feb;71(2):747-53.

A major allergen of the lymphatic filarial nematode Brugia malayi, a homologue of gamma-glutamyl transpeptidase (gamma-GT), is involved in the pathology of tropical pulmonary eosinophilia (TPE) through its potent allergenicity and the induction of antibodies against the host pulmonary epithelium. To investigate the immunoglobulin G (IgG) subclass and IgE responses to recombinant B. malayi gamma-GT, we analyzed the results obtained from 51 patients with differing clinical manifestations of bancroftian filariasis. gamma-GT-specific IgG1, rather than IgG4, was the predominant IgG subclass, particularly in patients with TPE (geomean, 6,321 ng/ml; range, 78 to 354,867 ng/ml) and was 75 times higher than in patients with elephantiasis (CP) (P < 0.003) and 185 times higher than in endemic normal individuals (ENL) (P < 0.010). IgG2 responses were low and IgG3 was almost absent, with no significant differences among the groups. gamma-GT-specific IgG4 responses were significantly elevated in those with subclinical microfilaremia (MF) compared to the CP and ENL groups and correlated with the presence of circulating filarial antigen (CAg). More significantly, gamma-GT-specific IgE antibody levels were strikingly elevated in patients with TPE (geomean, 681 ng/ml; range, 61 to 23,841 ng/ml) and in the ENL group (geomean, 106 ng/ml; range, 13 to 1,405 ng/ml) whereas the gamma-GT-specific IgE level was 44 and 61 times lower in those with MF and CP, respectively (P < 0.001). Elevated gamma-GT-specific IgE/IgG4 ratios were demonstrated in patients with TPE (ratio, 45) and ENL (ratio, 107). Because expression of gamma-GT in Brugia infective third-stage larvae (L3) was demonstrated by immunoblot analysis, the elevated gamma-GT-specific IgE antibodies appear to be associated not only with pulmonary pathology but also with possible resistance to infection in lymphatic filariasis.

7209. Palacio AM, Lichstein DM, Vaamonde CA, Tamariz L. Parasitic chyluria. South Med J. 2003 Jan;96(1):110-1. No abstract available.

7210. Rajendran R, Sunish IP, Mani TR. Mass treatment of filariasis in New Guinea. N Engl J Med. 2003 Mar 20;348(12):1179-81. No abstract available.

7211. Winter AD, Myllyharju J, Page AP. A hypodermally expressed prolyl 4-hydroxylase from the filarial nematode Brugia malayi is soluble and active in the absence of protein disulfide isomerase. J Biol Chem. 2003 Jan 24;278(4):2554-62.

The collagen prolyl 4-hydroxylase (P4H) class of enzymes catalyze the hydroxylation of prolines in the X-Pro-Gly repeats of collagen chains. This modification is central to the synthesis of all collagens. Most P4Hs are alpha(2)beta(2) tetramers with the catalytic activity residing in the alpha subunits. The beta subunits are identical to the enzyme protein disulfide isomerase. The nematode cuticle is a collagenous extracellular matrix required for maintenance of the worm body shape. Examination of the model nematode Caenorhabditis elegans has demonstrated that its unique P4Hs are essential for viability and body morphology. The filarial parasite Brugia malayi is a causative agent of lymphatic filariasis in humans. We report here on the cloning and characterization of a B. malayi P4H with unusual properties. The recombinant B. malayi alpha subunit, PHY-1, is a soluble and active P4H by itself, and it does not become associated with protein disulfide isomerase. The active enzyme form is a homotetramer with catalytic and inhibition properties similar to those of the C. elegans P4Hs. High levels of B. malayi phy-1 transcript expression were observed in all developmental stages examined, and its expression was localized to the cuticle-synthesizing hypodermal tissue in the heterologous host C. elegans. Although active by itself, the B. malayi PHY-1 was not able to replace enzyme function in a C. elegans P4H mutant.

Therapy:

7212. Addiss DG. Mass treatment of filariasis in New Guinea. N Engl J Med. 2003 Mar 20;348(12):1179-81. No abstract available.

7213. Babu BV, Satyanarayana K. Healthcare workers' knowledge of lymphatic filariasis and its control in an endemic area of Eastern India: implications on control programme. Trop Doct. 2003 Jan;33(1):41-2. No abstract available.

7214. Burnham G. The right word. Lancet. 2003 Feb 8;361(9356):456. No abstract available.

7215. Guevara AG, Vieira JC, Lilley BG, Lopez A, Vieira N, Rumbea J, Collins R, Katholi CR, Unnasch TR. Entomological evaluation by pool screen polymerase chain reaction of Onchocerca volvulus transmission in Ecuador following mass Mectizan distribution. Am J Trop Med Hyg. 2003 Feb;68(2):222-7.

7216. Hoerauf A, Buttner DW, Adjei O, Pearlman E. Onchocerciasis. BMJ. 2003 Jan 25;326(7382):207-10. No abstract available.

7217. Kerr C. Success for river blindness control campaign. Lancet Infect Dis. 2003 Feb;3(2):65. No abstract available.

7218. Nanda B, Krishnamoorthy K. Treatment seeking behaviour and costs due to acute and chronic forms of lymphatic filariasis in urban areas in south India. Trop Med Int Health. 2003 Jan;8(1):56-9.

Previous estimates on the economic burden of lymphatic filariasis (LF) in India and elsewhere were primarily based on studies in rural areas. We investigated the treatment costs due to acute and chronic forms of LF in urban areas, where nearly one-third of the affected people live. Almost 98% of the patients with acute episodes of adenolymphangitis (ADL) underwent treatment and 49% of chronic patients also received treatment. The average treatment cost per ADL episode (n = 108) was Rs 22.21 +/- 53.84 (US dollars 0.46 +/- 1.12). The overall (n = 200) treatment costs incurred by a chronic patient per visit were Rs 16.71 +/- 62.36 (US dollars 0.35 +/- 1.30); for those who paid (n = 98) they were Rs 34.10 +/- 85.90 (US dollars$ 0.71 +/- 1.79). These costs are considerably higher than in rural areas. Government health centres and private practitioners were important sources of treatment. Treatments received from private practitioners were considerably more expensive than those from government health facilities. The cost of medicine accounted for 44% and 50% of the total expenditure on treatment for acute and chronic disease patients, respectively. The medical personnel from these treatment sources need to be trained on the new morbidity management methods, which are likely to be more effective than the current methods of treatment.

7219. Rajendran R, Sunish IP, Mani TR. Mass treatment of filariasis in New Guinea. N Engl J Med. 2003 Mar 20;348(12):1179-81. No abstract avaialabe

October 2003

7938. De Silva NR, Pathmeswaran A, Fernando SD, Weerasinghe CR, Selvaratnam RR, Padmasiri EA, Montresor A. Impact of mass chemotherapy for the control of filariasis on geohelminth infections in Sri Lanka. Ann Trop Med Parasitol. 2003 Jun;97(4):421-5.

7939. Hoerauf A, Mand S, Volkmann L, Buttner M, Marfo-Debrekyei Y, Taylor M, Adjei O, Buttner DW. Doxycycline in the treatment of human onchocerciasis: Kinetics of Wolbachia endobacteria reduction and of inhibition of embryogenesis in female Onchocerca worms. Microbes Infect. 2003 Apr;5(4):261-73.

7940. Natarajan R. Another case of human subconjunctival infection by Macacanema formosana. Arch Ophthalmol. 2003 Apr;121(4):584-5. No abstract.

7941. Penzer R. Lymphoedema. Nurs Stand. 2003 May 14-20;17(35):45-51; quiz 52, 55. Lymphoedema is a symptom of a malfunctioning lymphatic system. It is characterised by chronic swelling caused by the accumulation of lymph. Rebecca Penzer examines the nursing management of lymphoedema and the ways in which non-specialist nurses can offer support and promote self-care in patients with this potentially debilitating condition.

7942. Yoshino N, Hisayoshi T, Sasaki T, Yamauchi S, Oaki Y, Hino M. Human pulmonary dirofilariasis in a patient whose clinical condition altered during follow-up. Jpn J Thorac Cardiovasc Surg. 2003 May;51(5):211-3.

Pathogenesis:

7943. Stanley P, Stein PE. BmSPN2, a serpin secreted by the filarial nematode Brugia malayi, does not inhibit human neutrophil proteinases but plays a noninhibitory role. Biochemistry. 2003 May 27;42(20):6241-8.

The filarial nematode, Brugia malayi, is a causative agent of lymphatic filariasis. Bm-spn-2, one of two serpin genes identified in B. malayi, is expressed only in humans where the encoded protein, BmSPN2, is secreted by blood-dwelling microfilariae. Previous work reported that BmSPN2 could inhibit the activities of elastase and cathepsin G from human neutrophils, despite an atypical amino acid sequence. This did not fit with accepted theories as to the sequence requirements of serpins for proteinase inhibition. We have cloned and expressed Bm-spn-2 in Escherichia coli and characterized the structural and functional properties of recombinant BmSPN2. Sequence alignment, circular dichroism spectroscopy, and susceptibility to cleavage by proteinases all suggest that BmSPN2 shares the tertiary structure typical of the serpin family including an accessible reactive center loop. However, we have found that BmSPN2 has no effect on the activity of neutrophil elastase or cathepsin G and does not form SDS-stable complexes with these proteinases. We provide evidence that BmSPN2 cannot undergo the characteristic stressed to relaxed transition required for proteinase inhibition by serpins. We conclude that BmSPN2 is not an atypical inhibitor but is a new noninhibitory serpin, in keeping with its sequence.

Therapy:

7944. Babu BV, Nayak AN. Footcare among lymphoedema patients attending a filariasis clinic in South India: a study of knowledge and practice. Ann Trop Med Parasitol. 2003 Apr;97(3):321-4. No abstract.

7945. Babu BV, Satyanarayana K. Factors responsible for coverage and compliance in mass drug administration during the programme to eliminate lymphatic filariasis in the East Godavari District, South India. Trop Doct. 2003 Apr;33(2):79-82.

The paper attempts to report the factors responsible for the coverage and compliance of mass diethylcarbamazine citrate (DEC) administration, during the programme to eliminate lymphatic filariasis in the East Godavari District of Andhra Pradesh, India. The evaluation survey indicates that single dose DEC was received by 77% and taken by 64% of eligible people. Reasons for non-reception and non-consumption of the drug at household level were identified. The factors that influenced the coverage and compliance of treatment are broadly categorized as health services related, community related and drug related factors. The study identified some key factors to be followed for the success of the programme.

7946. McLaughlin SI, Radday J, Michel MC, Addiss DG, Beach MJ, Lammie PJ, Lammie J, Rheingans R, Lafontant J. Frequency, severity, and costs of adverse reactions following mass treatment for lymphatic filariasis using diethylcarbamazine and albendazole in Leogane, Haiti, 2000. Am J Trop Med Hyg. 2003 May;68(5):568-73.

In October 2000, 71,187 persons were treated for lymphatic filariasis using albendazole and diethylcarbamazine (DEC) or DEC alone in Leogane, Haiti. We documented the frequency of adverse reactions, severity and cost of treatment. Adverse reactions were classified as minor, moderate, or severe. Overall, 24% (17,421) of the treated persons reported one or more adverse reactions. There were 15,916 (91%) minor and 1502 (9%) moderate adverse reaction reports. Men outnumbered women 2:1 in reporting moderate problems. Three patients, representing roughly one in 25,000 persons treated, were hospitalized with severe adverse reactions judged to be treatment-associated by physician review. The cost per person treated for adverse reactions was more than twice the cost per person treated for lymphatic filariasis (dollar 1.60 versus dollar 0.71). Severe adverse reactions to lymphatic filariasis treatment using DEC with or without albendazole are uncommon. Minor and moderate reactions are more commonly reported and their management represents a challenge to lymphatic filariasis elimination programs.

7947. Penzer R. Lymphoedema. Nurs Stand. 2003 May 14-20;17(35):45-51; quiz 52, 55.

Lymphoedema is a symptom of a malfunctioning lymphatic system. It is characterised by chronic swelling caused by the accumulation of lymph. Rebecca Penzer examines the nursing management of lymphoedema and the ways in which non-specialist nurses can offer support and promote self-care in patients with this potentially debilitating condition.

7948. Post RJ, Flook PK, Millest AL, Cheke RA, McCall PJ, Wilson MD, Mustapha M, Somiari S, Davies JB, Mank RA, Geenen P, Enyong P, Sima A, Mas J. Cytotaxonomy, morphology and molecular systematics of the Bioko form of Simulium yahense (Diptera: Simuliidae). Bull Entomol Res. 2003 Apr;93(2):145-57.

Cytotaxonomic analysis of the polytene chromosomes from larvae of the Simulium damnosum Theobald complex from the island of Bioko in Equatorial Guinea is reported, and a new endemic cytoform is described. Chromosomally this cytoform is close to both S. squamosum (Enderlein) and S. yahense Vajime & Dunbar, but is not identical to either. However, it is morphologically and enzymatically identical to S. yahense. The Bioko form was also found to differ from other cytoforms of the S. damnosum complex in West Africa in the copy number or RFLP pattern of several different repetitive DNA sequences. It is clear that the Bioko form is genetically distinct from other populations of the S. damnosum complex, and whilst it is closest to S. yahense, it shows features that suggest a high degree of geographical and genetic isolation. Such isolation is an important consideration in the assessment of the potential for onchocerciasis vector eradication on Bioko.

7949. Sunish IP, Rajendran R, Mani TR, Gajanana A, Reuben R, Satyanarayana K. Long-term population migration: an important aspect to be considered during mass drug administration for elimination of lymphatic filariasis. Trop Med Int Health. 2003 Apr;8(4):316-21.

Annual 2-drug, single-dose mass drug administration (MDA) to 80-90% of the eligible population for 4-6 years are pre-requisites for the successful elimination of lymphatic filariasis (LF) from endemic communities by interruption of transmission and eventual elimination of new infections. In an experimental intervention project on the control of LF in Villupuram district of Tamil Nadu state, India, migration patterns of the villagers were investigated to determine the appropriate timing to implement MDA in order to attain high coverage in a village-level study. Between January and December 1997, 16 observations took place at 3-week intervals, following MDA with two drugs viz., diethylcarbamazine and ivermectin, in July-August 1996. The migrants from the village constituted 17-27% at different points of time and both short-term and long-term migrating patterns were observed. More villagers were available during the agricultural season (September-January), peaking around mid-January [83%; significantly higher (P < 0.05)] than during most of the remaining months, including a substantial portion of the migrant population. There is an urgent need to reschedule the yearly MDA in this area to take place in January and to plan mopping up operations by involving local self-help groups to include migrants (both short-term and long-term) in the LF elimination efforts.

7950. Taylor MJ. Wolbachia in the Inflammatory Pathogenesis of Human Filariasis. Ann N Y Acad Sci. 2003 Jun;990:444-449.

Filarial nematodes cause some of the most debilitating diseases in tropical medicine. Recent studies, however, have implicated the parasites' endosymbiotic Wolbachia bacteria, rather than the nematode, as the cause of inflammatory-mediated filarial disease. Soluble extracts of a variety of filarial species stimulate innate inflammatory responses, which are absent or reduced when using extracts derived from species either devoid of bacteria, or those cleared of bacteria by antibiotics. Characterization of the molecular nature of the bacterial derived inflammatory stimulus points toward an endotoxin-like activity that is dependent on the pattern recognition receptors CD14 and TLR4 and can be inhibited by lipid A antagonists. TLR4 dependent inflammation has been shown to occur in the systemic inflammatory adverse reaction to Brugia malayi following anti-filarial chemotherapy and in the development of neutrophil-mediated ocular inflammation in a mouse model of river blindness. The development of acute and severe inflammatory responses in people infected with Brugia malayi and Onchocerca volvulus is associated with the release of Wolbachia into the blood following death or damage of the worms after anti-filarial chemotherapy. Together these studies suggest that Wolbachia are the principal cause of acute inflammatory filarial disease. Accumulated exposure to acute episodes of inflammation may also underlie the development of chronic filarial pathology. The use of antibiotic therapy to target Wolbachia of filarial parasites may therefore provide a means to prevent the development of filarial pathology.

7951. Volkmann L, Fischer K, Taylor M, Hoerauf A. Antibiotic therapy in murine filariasis (Litomosoides sigmodontis): comparative effects of doxycycline and rifampicin on Wolbachia and filarial viability.Trop Med Int Health. 2003 May;8(5):392-401.

The symbiosis of filarial nematodes and rickettsial Wolbachia endobacteria has been exploited as a target for antibiotic therapy of filariasis. Depletion of Wolbachia after tetracycline treatment results in filarial sterility because of interruption of embryogenesis and inhibits larval development and adult worm viability. The aim of this study was to investigate if antibiotic intervention of BALB/c mice infected with the rodent filaria Litomosoides sigmodontis with rifampicin or the combination of rifampicin and doxycycline can be used to shorten the treatment period. Both regimens, when given over a period of 14 days initiated with infection, were sufficient to deplete Wolbachia as evidenced by immunohistology and semiquantitative PCR. Worm development and filarial load were significantly reduced in experiments followed up until 63 days p.i. The therapy inhibited embryogenesis and led to filarial sterility. In contrast, treatment with doxycycline alone for 21 days led only to a modest reduction of Wolbachia, filarial growth retardation, worm viability and fertility. In conclusion, the combination of antirickettsial drugs could be used as a suitable tool to explore the minimum duration of therapy required for the depletion of Wolbachia in parasitized hosts subsequent to the onset of patency in human and animal filariasis and the prevention of adverse reactions in human infections.

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