Biomedical subjects

V Kumaraswami

Publications and source records attributed to V Kumaraswami.

At least 37 records · Page 2Linked to original sources

PubMed2000

Apparent failure of ultrasonography to detect adult worms of Brugia malayi.

Adult worms of Wuchereria bancrofti, or rather their characteristic movements (the 'filarial dance'), can now be detected in the scrotal lymphatics of microfilaraemic males, using ultrasonography. This ability has been used to delineate the lymphatic pathology of bancroftian filariasis, guide the surgical removal of the adult worms and, most importantly, assess the macrofilaricidal effects of antifilarial drugs. In the present study, the first report of the use of ultrasonography in brugian filariasis, 22 men (aged 18-62 years) with 60-2972 (median = 370) Brugia malayi microfilariae/ml blood were subjected to ultrasonography using a linear, 7.5-MHz probe. In addition, four other men (aged 19-35 years), with W. bancrofti microfilaraemia [28-524 (median = 234) microfilariae/ml], were similarly examined. Adult worms were not detectable in any of the patients with B. malayi parasitaemia but were detected in the scrotal lymphatics of two of the four individuals with W. bancrofti infection. The reasons for the failure to detect adult B. malayi and the limitations of ultrasound as a screening tool are examined. The results highlight the differences between the two species that cause most lymphatic filariasis and the need for rapid development of tools that can be used for the control of brugian lymphatic filariasis.

Adolescent↗

PubMed2000

Two-year follow-up of the microfilaraemia of asymptomatic brugian filariasis, after treatment with two, annual, single doses of ivermectin, diethylcarbamazine and albendazole, in various combinations.

Repeated, single, oral doses of combinations of ivermectin, diethylcarbamazine (DEC) or albendazole are recognized as important tools for parasite control in lymphatic filariasis. In order to assess the effects of re-treatment using these combinations in Brugia malayi infections, 40 asymptomatic microfilaraemics were re-treated at the end of the first year, with an additional, single, dose of the combination they had previously received. They were then followed-up for another year. The subjects, of both sexes and aged 14-70 years, each received a two-drug combination: ivermectin (200 micrograms/kg) with DEC (6 mg/kg); ivermectin (200 micrograms/kg) with albendazole (400 mg); or DEC (6 mg/kg) with albendazole (400 mg). The kinetics of microfilarial clearance were similar to that seen during the first treatment, the members of the two groups given DEC having less intense microfilaraemias, 1 year after the re-treatment, than those given ivermectin with albendazole (P < 0.001 for each comparison). At this time, the two DEC groups also had a higher proportion of amicrofilaraemic individuals (22 of 26) than the ivermectin + albendazole group (three of nine). There were fewer adverse reactions in all the groups after re-treatment than seen after the first treatment. In countries such as India, where there is no co-endemicity of onchocerciasis or loiasis, the options for control programmes in areas where brugian filariasis is endemic are DEC alone or DEC in combination with ivermectin or albendazole. Where there is no access to ivermectin, transmission control must be based on DEC alone or in combination with albendazole.

Adolescent↗

PubMed2000

Perturbations in eosinophil homeostasis following treatment of lymphatic filariasis.

Treatment of patients with patent Wuchereria bancrofti infection results in an acute clinical reaction and peripheral eosinophilia. To investigate the dynamics of the eosinophil response, changes in eosinophil activation and degranulation and plasma levels of eosinophil-active chemokines and cytokines were studied in 15 microfilaremic individuals in south India by sequential blood sampling before and after administration of 300 mg of diethylcarbamazine (DEC). Clinical symptoms occurred within 24 h. Plasma interleukin-5 (IL-5) and RANTES levels peaked 1 to 2 days posttreatment, preceding a peak peripheral eosinophil count at day 4. Major basic protein secretion from eosinophils paralleled IL-5 secretion, while levels of eosinophil-derived neurotoxin peaked at day 13 after treatment. Expression of the activation markers HLA-DR and CD25 on eosinophils rose markedly immediately after treatment, while expression of VLA-4 and alpha4beta7 showed an early peak within 24 h and a second peak at day 13. Thus, the posttreatment reactions seen in filarial infections can be divided into an early phase with killing of microfilariae, clinical symptomatology, increases in plasma IL-5 and RANTES levels, and eosinophil activation and degranulation and a later phase with expression of surface integrins on eosinophils, recruitment of eosinophils from the bone marrow to tissues, and clearance of parasite antigen.

Adult↗

PubMed1999

Bacteriological studies of blood, tissue fluid, lymph and lymph nodes in patients with acute dermatolymphangioadenitis (DLA) in course of 'filarial' lymphedema.

Filarial lymphedema is complicated by frequent episodes of dermatolymphangioadenitis (DLA). Severe systemic symptoms during attacks of DLA resemble those of septicemia. The question we asked was whether bacterial isolates can be found in the peripheral blood of patients during the episodes of DLA. Out of 100 patients referred to us with 'filarial' lymphedema 14 displayed acute and five subacute symptoms of DLA. All were on admission blood microfilariae negative but had a positive test in the past. Blood bacterial isolates were found in nine cases, four acute (21%) and five subacute (26%). In 10 acute cases blood cultures were found negative. Six blood isolates belonged to Bacilli, four to Cocci and one was Sarcina. To identify the sites of origin of bacterial dissemination, swabs taken from the calf skin biopsy wounds and tissue fluid, lymph and lymph node specimens were cultured. Swabs from the calf skin biopsy wound contained isolates in nine (47%) cases. They were Bacilli in nine, Cocci in three, Acinetobacter and Erwinia in two cases. Tissue fluid was collected from 10 patients and contained Bacilli in four (40%) and Staphylococci in three (30%). Lymph was drained in four patients and contained isolates in all samples (100%). They were Staphylococcus epidermis, xylosus and aureus, Acinetobacter, Bacillus subtilis and Sarcina. Three lymph nodes were biopsied and contained Staphylococcus chromogenes, xylosus, Enterococcus and Bacillus cereus. In six cases the same phenotypically defined species of bacteria were found in blood and limb tissues or fluids. In the 'control' group of patients with lymphedema without acute or subacute changes all blood cultures were negative. Interestingly, swabs from biopsy wound of these patients contained isolates in 80%, tissue fluid in 68%, lymph in 70% and lymph nodes in 58% of cases. In healthy controls, tissue fluid did not contain bacteria, and lymph isolates were found only in 12% of cases. This study demonstrates that patients with acute episodes of DLA reveal bacteremia in a high percentage of cases. Diversity of blood and tissue bacterial isolates in these patients points to a breakdown of the skin immune barrier in lymphedema and subsequently indiscriminate bacterial colonization of deep tissues and spread to an blood circulation.

Adolescent↗

PubMed1999

Treatment of the microfilaraemia of asymptomatic brugian filariasis with single doses of ivermectin, diethylcarbamazine or albendazole, in various combinations.

Several new chemotherapeutic tools are now available for the control of lymphatic filariasis. Combinations of single doses of antifilarial drugs are generally superior to single drugs. The efficacy and safety of albendazole in combination with diethylcarbamazine (DEC) or ivermectin, for the treatment of Brugia malayi infection, were investigated, for the first time, in an open, hospital-based study. Fifty-one asymptomatic microfilaraemics (with 108-4034 microfilariae/ml; median = 531) of both sexes and aged 14-70 years were randomly allocated to receive single-dose treatments of ivermectin (200 micrograms/kg) with diethylcarbamazine (DEC; 6 mg/kg), ivermectin (200 micrograms/kg) with albendazole (400 mg), DEC (6 mg/kg) with albendazole (400 mg), or albendazole (400 mg) alone. Albendazole alone had no effect on the microfilarial levels at the 1-year follow-up but both groups given DEC had significantly lower microfilaraemias (P < 0.015 and P < 0.02) than that given ivermectin with albendazole. Overall, 47%-64% of those given DEC but only 14% of those given ivermectin with albendazole appeared to be amicrofilaraemic 1 year post-treatment. The adverse reactions seen in the study were mild, transient and qualitatively similar to those seen earlier with ivermectin and DEC. The combination of DEC and albendazole, both well tested drugs, offers a new option for countries such as India where there is no onchocerciasis or loiasis and where ivermectin may not be immediately available. The direct and indirect effects of albendazole on intestinal helminths would be additional benefits.

Adolescent↗

PubMed1999

A double-blind, placebo-controlled study of the efficacy of oral penicillin, diethylcarbamazine or local treatment of the affected limb in preventing acute adenolymphangitis in lymphoedema caused by brugian filariasis.

Acute attacks of adenolymphangitis (ADL) contribute significantly to the morbidity seen in cases of filarial lymphoedema. Such cases are now being treated with multiple courses of the antifilarial drug diethylcarbamazine (DEC), either alone or in combination with antibiotics or anti-inflammatory drugs, based on anecdotal experience. In this, the first double-blind, placebo-controlled study, 150 patients with lymphoedema caused by brugian filariasis, each of whom recalled two or more ADL attacks in the previous year, were enrolled on a comprehensive foot-care programme. Each was also randomly allocated to one of the following five daily regimens (30 patients/regimen) for 1 year: 800 mg oral penicillin; 1 mg DEC/kg; 800 mg oral penicillin plus 1 mg DEC/kg; local antibiotics; or placebo. Each patient was followed up for another year. For each regimen group (including the placebo group), the number of ADL attacks in the treatment year was significantly less than that in the year prior to treatment (P < 0.001). Although, in all but the placebo group, there was a slight increase in the number of episodes in the follow-up year compared with the treatment year, the increase was only significant in the two groups given penicillin. Of all the treatments tested therefore, foot care seems to play the most important role in the prevention of ADL attacks. Additional benefit may accrue from local or systemic antibiotic use in those with high grades of oedema, but antifilarials have no place in the prevention of ADL attacks in an individual patient. These observations should help in the rational management and prevention of ADL attacks in filarial lymphoedema, so that the progression of the disease may be halted and morbidity reduced.

Acute Disease↗

PubMed1999

Long-term persistence of cellular hyporesponsiveness to filarial antigens after clearance of microfilaremia.

The persistence of parasite-specific cellular hyporesponsiveness after clearance of blood microfilariae (mf) was studied in 18 individuals who had been treated with a single dose of ivermectin, diethylcarbamazine, or a combination 2-3 years previously and who had initially cleared their parasitemia. At recruitment into the present study, 50% were again mf+ and 50% remained mf-. There were no significant differences between the mf+ and mf- groups in the amount of interferon-gamma (IFN-gamma) produced by peripheral blood mononuclear cells in response to adult or microfilarial antigens, although IFN-gamma production in response to purified protein derivative was greater in the mf+ group (geometric mean [gm] = 3,791 pg/ml; P = 0.02) than in the mf- group (gm = 600 pg/ml). These data suggest that although microfilaremic individuals may temporarily regain the ability to produce IFN-gamma to parasite antigens post-treatment, they subsequently revert to a state of hyporesponsiveness to mf-containing antigens that appears to be independent of the recurrence of microfilaremia and the response to nonparasite antigens.

Adult↗

PubMed1999

Bioavailability of rifampicin, isoniazid and pyrazinamide in a triple drug formulation: comparison of plasma and urine kinetics.

SETTING: The present study assesses bioavailability indices for rifampicin, isoniazid and pyrazinamide when administered to healthy volunteers separately or in a fixed triple-drug formulation, Rifater 125 SCT. OBJECTIVE: To compare the pharmacokinetics of rifampicin, isoniazid and pyrazinamide based on their blood concentrations up to 12 hours with the proportions of the doses of the drugs and their metabolites excreted in urine up to 12 hours, and to assess the bioavailability indices for the free and fixed triple drug formulations. DESIGN: An open cross-over study was conducted in 18 healthy volunteers with normal hepatic and renal functions to whom the drug combinations were administered in free and fixed dose formulations a week apart, to the same subject. RESULTS: Concentrations of the three drugs/metabolites were assessed in blood and urine. The results indicated the absence of negative pharmacokinetic interactions between the drugs when administered in both the free and the new fixed triple drug formulation. CONCLUSION: Human bioavailability studies provide direct straightforward information, particularly when studying compounds such as rifampicin and other major anti-tuberculosis drugs. The results of the present study indicate that the pharmacokinetic properties of rifampicin, isoniazid and pyrazinamide as assessed after individual and combined administration do not change when combined in a single pharmaceutical preparation. The bioavailability indices calculated based on plasma concentrations and urinary levels for all three drugs compared well.

Adult↗

PubMed1998

Treatment of microfilaraemia in asymptomatic brugian filariasis: the efficacy and safety of the combination of single doses of ivermectin and diethylcarbamazine.

Although combinations of ivermectin and diethylcarbamazine (DEC) have been shown to be superior to either drug alone in the suppression of bancroftian microfilariae, their efficacy against infections with Brugia malayi has never been investigated. The present, open trial is the first on the efficacy and safety of a combination of single doses of ivermectin and DEC when used against microfilaraemias of brugian filariasis. Twenty-one, asymptomatic but microfilaraemic (109-6934 microfilariae/ml blood, with a median of 841/ml) men, aged 18-48 years, each received oral doses of ivermectin (400 micrograms/kg) and DEC (6 mg/kg) as a single treatment. Twelve hours post-treatment, 96.5%-100% of the microfilariae in each subject had been cleared and 12 of the subjects were amicrofilaraemic. A further reduction in microfilarial counts was evident 1 month post-treatment (mean clearance = 99.0%) and the counts continued to fall at least until the last follow-up, at 1 year post-treatment, when the mean clearance was 99.9% and 13 (68.4%) of the 19 subjects then investigated were amicrofilaraemic. All subjects experienced adverse reactions of one form or another, lasting for up to 48 h post-treatment; these included fever, myalgia, headache, and lethargy. Postural hypotension was recorded in two subjects and dilated, inflamed lymphatic channels were seen in another two. The combination of ivermectin and DEC demonstrated a microfilaricidal effect superior to that of either drug used alone, both in the initial rapid clearance of microfilariae and in sustaining the effect for 1 year. This finding has important implications for the control of lymphatic filariasis.

Adolescent↗

PubMed1998

Prevention of acute adenolymphangitis in brugian filariasis: comparison of the efficacy of ivermectin and diethylcarbamazine, each combined with local treatment of the affected limb.

Acute attacks of adenolymphangitis (ADL) not only force patients with lymphatic filariasis to seek medical attention but also hasten the progression of filarial oedema. Patients with filariasis-associated ADL are currently treated with repeated courses of the antifilarial drug diethylcarbamazine (DEC), with or without antibiotics and anti-inflammatory agents. In this double-blind, placebo-controlled study, the efficacy of local treatment of the affected limb combined with repeated doses of ivermectin or DEC, in preventing the occurrence of ADL in Brugia malayi lymphatic filariasis, was examined. Overall, 120 patients who had each had at least two ADL attacks in the previous year were each admitted to the study at the time of an ongoing episode of ADL. The patients were randomly allocated to receive 12, monthly treatments of ivermectin (400 micrograms/kg), DEC (10 mg/kg) or placebo, in addition to local care of the affected limbs. There was a significant reduction in the frequency of ADL attacks in each of the three groups during the 2-year study period (P < 0.001 for each comparison). Most importantly, there were no significant differences in frequency of attacks between the three groups, either at the end of the treatment phase or at the end of the post-treatment phase (P > 0.15 for each comparison), suggesting that foot care combined with appropriate use of local antibiotics or antifungals is adequate to reduce the number of ADL attacks. The implications of these observations for planning morbidity control in lymphatic filariasis are discussed.

Acute Disease↗

PubMed1998

The efficacy, tolerability and safety of diethylcarbamazine-fortified salt in the treatment of the microfilaraemias of brugian filariasis: an open, hospital-based study.

Cooking salt fortified with diethylcarbamazine (DEC) has been successfully used to control lymphatic filariasis in several parts of the world. The kinetics and efficacy of DEC-fortified salt in clearing microfilaraemias of Brugia malayi and the salt's tolerability and safety are examined in this study. Twenty individuals with B. malayi microfilaraemias (pre-treatment levels of 108-6358 microfilariae/ml; median = 309/ml) consumed DEC-fortified salt (0.2%, w/w) with their food for 1 year, initially in hospital (for 1 week) and later at home. The mean daily intake of DEC was 21.4 mg (range = 9.0-39.4 mg). Even on the first day of consuming the salt, there was a decrease in the microfilarial levels of 14 patients and a sharp increase in six patients. Microfilarial levels tended to fluctuate thereafter but there was a progressive, general decline. At the end of the study year, eight patients were amicrofilaraemic and microfilarial clearance was > 95% in 58% of the patients. Eight patients did not develop any adverse reactions. Lymph-node tenderness and enlargement were seen in eight patients (40%), and dilated, inflamed lymphatic channels standing out as cords ('string sign') were seen in another five patients. These reactions were transient and did not require any specific treatment. The DEC-fortified salt was well accepted by the study population. The DEC content of fortified salt and the duration of its use for the control of brugian filariasis need to be re-examined. Health education should include messages that mild, self-limiting, adverse reactions are likely to occur even with the use of such salt.

Adolescent↗

PubMed1997

Elevated IL-10 mRNA expression and downregulation of Th1-type cytokines in microfilaraemic individuals with Wuchereria bancrofti infection.

To understand the molecular basis of parasite-specific anergy in human lymphatic filariasis caused by the nematode Wuchereria bancrofti, parasite antigen-dependent cellular proliferation and cytokine gene expression were investigated. By reverse transcriptase polymerase chain reaction (RT-PCR), the levels of cytokine mRNA were determined in the peripheral blood mononuclear cells (PBMCs) of different clinical groups of filariasis patients. This includes individuals with circulating microfilariae (MF), patients with chronic lymphatic obstruction (CP), and exposed but uninfected individuals (EN). Those with CP exhibited both a Th2 and a Th1 parasite antigen-driven response. In PBMCs from those with MF, there was a marked downregulation of cellular response to parasite antigens, with lowered expression of Th1-specific cytokines (IFN-gamma and IL-2) and this was paralleled by increased IL-10 expression. The EN individuals had a purely Th1-type pattern with absence of IL-4 and IL-5 expression. Further, the mRNA expression of the costimulatory surface marker, CD80 (B7-1), was not associated with either disease status or IL-10 expression. There was a significant negative correlation between IL-10 mRNA expression and PBMC proliferation in the MF individuals, thus indicating the possible role of IL-10 in antigen-specific hyporesponsiveness.

Animals↗

PubMed1997

Regulation of parasite antigen-driven immune responses by interleukin-10 (IL-10) and IL-12 in lymphatic filariasis.

We investigated the mechanisms by which interleukin-10 (IL-10) regulates antigen-specific hyporesponsiveness in asymptomatic microfilaremic (MF) individuals. Peripheral blood mononuclear cells from MF individuals (n = 11) were stimulated in vitro with Brugia malayi antigen (BMA) or mycobacterial purified protein derivative (PPD) in the presence of neutralizing anti-IL-10 or isotype control monoclonal antibodies. As expected, BMA stimulated little or no gamma interferon (IFN-gamma) secretion in MF individuals, whereas PPD stimulated IFN-gamma in all but one. Neutralization of endogenous BMA-driven IL-10 secretion led to augmentation of IFN-gamma in seven of nine MF individuals (1.5- to 10-fold) and did so in a BMA-specific manner (PPD-driven IFN-gamma was augmented in only two of eight MF individuals and only 1.5- to 2-fold), indicating that IL-10 downregulates type 1 responses in these individuals. Type 2 responses (IL-5 secretion) were unaffected by the IL-10 blockade. To assess whether IL-12 could reverse the type 1 downregulation observed, the effect of recombinant human IL-12 (rhIL-12) on BMA-driven IL-5 and IFN-gamma production was also evaluated. rhIL-12 augmented both BMA- and PPD-driven IFN-gamma production 5- to 10-fold in six of nine MF individuals. These data demonstrate that IL-10 downregulates BMA-driven type 1 responses and that IL-12 can overcome downregulation of Th1 responses associated with MF but does so in a non-antigen-specific manner.

Adolescent↗

PubMed1997

Bacteriologic studies of skin, tissue fluid, lymph, and lymph nodes in patients with filarial lymphedema.

Filarial lymphedema is complicated by frequent episodes of dermatolymphangioadenitis (DLA). It is not certain whether DLA is of filarial or bacterial etiology. The frequency of episodic DLA does not depend on the presence or absence of microfilariae. Antibiotic therapy is effective in prevention and treatment of DLA. These observations point to the bacterial rather than filarial etiology of DLA. Skin and lymph node biopsies, tissue fluid, lymph, and blood from patients with chronic filarial lymphedema, and during acute episodes of DLA, were cultured for detection of bacteria. A high prevalence of bacterial isolates from the tissue fluid (64%), lymph (75%), and inguinal lymph nodes (66%) of limbs with filarial lymphedema was found. Bacillus cereus, Staphylococcus epidermidis, S. hominis, S. capitis, S. xylosus, and Micrococcus spp. were the most common isolates. Bacteria were also isolated from the blood of patients with recent episodes of DLA, with strains of the same phenotype and antibiotic sensitivity in all specimens from patients with DLA. Bacterial strains of the same phenotype and antibiotic sensitivity were documented on the toe web surface and in tissue fluid (25%), lymph (26%), or lymph nodes (41%). Increasing prevalence of bacterial isolates in tissue fluid, lymph, and lymph nodes was observed in advanced stages of lymphedema. Bacilli and cocci were sensitive to gentamicin, tetracyline, rifampicin, vancomycin, kanamycin and cotrimoxazole, and least sensitive to penicillin. Blood cultures of patients in the periods between DLA attacks were negative. In healthy controls without edema and episodes of DLA, tissue fluid did not contain bacteria. In lymph, only single colonies of Micrococcus and Acinetobacter were cultured in 12% of the cases. Impaired lymph drainage and lack of elimination of penetrating bacteria may be responsible for progression of lymphedema and recurrent attacks of DLA.

Adolescent↗

PubMed1997

Ultrasonographic diagnosis of subclinical filariasis.

Asymptomatic persons with lymphatic filariasis may harbor microfiliariae in the circulation, and despite the lack of symptoms, these patients may have occult pathologic lesions and renal abnormalities. Earlier investigators have shown that it is possible to detect live adult filarial worms and dilation of lymphatic channels with ultrasonography. It is also possible to assess response to therapy. Using sonography, we detected twirling motions in dilated lymph channels and characteristic sonographic findings associated with presence of adult filariae. On follow-up examination we also found evidence of loss of worm activity after chemotherapy.

Animals↗

PubMed1997

Inherited resistance to HIV-1 conferred by an inactivating mutation in CC chemokine receptor 5: studies in populations with contrasting clinical phenotypes, defined racial background, and quantified risk.

BACKGROUND: CC chemokine receptor 5 (CCR5) is a cell entry cofactor for macrophage-tropic isolates of human immunodeficiency virus-1 (HIV-1). Recently, an inactive CCR5 allele (designated here as CCR5-2) was identified that confers resistance to HIV-1 infection in homozygotes and slows the rate of progression to AIDS in heterozygotes. The reports conflict on the effect of heterozygous CCR5-2 on HIV-1 susceptibility, and race and risk levels have not yet been fully analyzed. Here we report our independent identification of CCR5-2 and test its effects on HIV-1 pathogenesis in individuals with contrasting clinical outcomes, defined race, and quantified risk. MATERIALS AND METHODS: Mutant CCR5 alleles were sought by directed heteroduplex analysis of genomic DNA from random blood donors. Genotypic frequencies were then determined in (1) random blood donors from North America, Asia, and Africa; (2) HIV-1+ individuals; and (3) highly exposed-seronegative homosexuals with quantified risk. RESULTS: CCR5-2 was the only mutant allele found. It was common in Caucasians, less common in other North American racial groups, and not detected in West Africans or Tamil Indians. Homozygous CCR5-2 frequencies differed reciprocally in highly exposed-seronegative (4.5%, n = 111) and HIV-1-seropositive (0%, n = 614) Caucasians relative to Caucasian random blood donors (0.8%, n = 387). This difference was highly significant (p < 0.0001). By contrast, heterozygous CCR5-2 frequencies did not differ significantly in the same three groups (21.6, 22.6, and 21.7%, respectively). A 55% increase in the frequency of heterozygous CCR5-2 was observed in both of two cohorts of Caucasian homosexual male, long-term nonprogressors compared with other HIV-1+ Caucasian homosexuals (p = 0.006) and compared with Caucasian random blood donors. Moreover, Kaplan-Meier estimates indicated that CCR5-2 heterozygous seroconvertors had a 52.6% lower risk of developing AIDS than homozygous wild-type seroconvertors. CONCLUSIONS: The data suggest that homozygous CCR5-2 is an HIV-1 resistance factor in Caucasians with complete penetrance, and that heterozygous CCR5-2 slows the rate of disease progression in infected Caucasian homosexuals. Since the majority (approximately 96%) of highly exposed-seronegative individuals tested are not homozygous for CCR5-2, other resistance factors must exist. Since CCR5-2 homozygotes have no obvious clinical problems, CCR5 may be a good target for the development of novel antiretroviral therapy.

Adult↗

PubMed1997

Estimation of ASO titer as an indicator of streptococcal infection precipitating acute adenolymphangitis in brugian lymphatic filariasis.

Recurrent episodes of acute adenolymphangitis (ADL) are important clinical manifestations of lymphatic filariasis which contribute significantly to the progression of lymphedema. It is increasingly being recognized that secondary bacterial infections play an important role in the etiology of ADL. We examined the role of streptococcal infection as a precipitating factor of ADL in brugian filariasis, by determining the anti-streptolysin O (ASO) titers and by isolating the causative organism wherever possible. The study population consisted of 30 patients with filariasis related ADL (Group A), 30 patients with chronic filarial edema (Group B) and 60 age and sex matched healthy adults (Group C). ASO titer was estimated by the latex agglutination method at the time of entry into the study, at the 15th day and at 3, 6 and 12 months. ASO titers were persistently elevated in 90% of patients in Group A and a portal of entry for bacterial infection was detected in all of these patients. In Group B only six patients had persistently elevated ASO titers. These patients had grade III lymphedema and three of them had monilial infections in the affected limb. In the control group none had persistently elevated ASO titers. The elevated ASO titers and the detection of a site of entry for bacteria in patients with ADL supports a streptococcal etiology for this condition.

Acute Disease↗

PubMed1996

Stage-specific induction of cytokines regulates the immune response in lymphatic filariasis.

Parasite stage-specific T cell responses were studied in Indians with lymphatic filariasis manifesting as elephantiasis (CP, n = 11) and asymptomatic microfilaremia (MF, n = 8), using antigens derived from the microfilarial, adult male only, and mixed adult male and female worms. Proliferative responses to microfilarial and mixed (male-female adult worm) antigens in MF individuals were markedly impaired compared to corresponding responses in individuals with CP. In contrast, T cell proliferative responses to adult male-derived antigens were not statistically different between the two groups. Analysis of antigen-driven cytokine secretion by peripheral blood mononuclear cells from MF and CP individuals revealed significantly lower IL-2 and IFN-gamma production by MF in response to microfilarial and mixed antigens (but not to adult male antigen) compared to CP individuals. No differences were observed between MF and CP in parasite antigen-driven IL-4 or IL-5 production. Spontaneous and parasite-specific IL-10 secretion was also measured to determine if cytokine cross-regulation of Th1 responses may be a mechanism underlying the observed Th1 suppression. Spontaneous and microfilarial antigen-driven IL-10 was found to be significantly higher in MF than in CP individuals. These data indicate that MF individuals exhibit preferentially impaired Th1-type responses to microfilarial antigens and that microfilarial-induced IL-10 may be critical in the downregulation of specific Th1 responses.

Adolescent↗