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

Shenoy, R. K.; Kumaraswami, V.; Suma, Takeshi; Rajan, K.; Radhakuttyamma, G.

doi:10.1080/00034983.1999.11813433

Cited by 70 publications

(68 citation statements)

References 9 publications

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“…51 The improvement of lymphedema observed in this cohort during this 13-year period clearly coincided with results of the lymphedema management study during 1995-1998. Consistent with other literature is the significant decrease in ADL episodes 14,16,17,20 and the decrease in foot and ankle circumference observed during the lymphedema management program. 20 In addition, the improvement in quality of life associated with lymphedema management programs is consistent with previous findings.…”

Section: Discussionsupporting

confidence: 80%

“…12 Clinical and histopathologic studies suggest that lymphedema management can decrease the number of ADL episodes 9,[13][14][15][16][17][18][19] and halt or, in some cases, partially reverse disease progression. 14,[16][17][18]20 Although there are several studies demonstrating improvement in lymphedema in patients who adhere to a lymphedema management regimen, the literature exploring the effect of mass drug administration with DEC, either alone or in combination with albendazole, on filarial morbidity is inconclusive. Recent clinical research using ultrasonography and lymphoscintigraphy has documented the reversal of early lymph-vessel damage in Brugia malayi-infected children after MDA with DEC in India.…”

Section: Introductionmentioning

confidence: 99%

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A Longitudinal Analysis of the Effect of Mass Drug Administration on Acute Inflammatory Episodes and Disease Progression in Lymphedema Patients in Léogane, Haiti

Eddy

Blackstock

Williamson

et al. 2014

The American Society of Tropical Medicine and Hygiene

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Abstract. We conducted a longitudinal analysis of 117 lymphedema patients in a filariasis-endemic area of Haiti during [1995][1996][1997][1998][1999][2000][2001][2002][2003][2004][2005][2006][2007][2008]. No difference in lymphedema progression between those who received or did not receive mass drug administration (MDA) was found on measures of foot (P = 0.24), ankle (P = 0.87), or leg (P = 0.46) circumference; leg volume displacement (P = 0.09), lymphedema stage (P = 0.93), or frequency of adenolymphangitis (ADL) episodes (P = 0.57). Rates of ADL per year were greater after initiation of MDA among both groups (P 0.01). Nevertheless, patients who received MDA reported improvement in four areas of lymphedema-related quality of life (P 0.01). Decreases in foot and ankle circumference and ADL episodes were observed during the 1995-1998 lymphedema management study (P 0.01). This study represents the first longitudinal, quantitative, leg-specific analysis examining the clinical effect of diethylcarbamazine on lymphedema progression and ADL episodes.

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Section: Discussionsupporting

confidence: 80%

Section: Introductionmentioning

confidence: 99%

A Longitudinal Analysis of the Effect of Mass Drug Administration on Acute Inflammatory Episodes and Disease Progression in Lymphedema Patients in Léogane, Haiti

Eddy

Blackstock

Williamson

et al. 2014

The American Society of Tropical Medicine and Hygiene

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“…There is therefore ample opportunity for Wolbachia to interact with cells of the monocyte/macrophage cell lineage, an interaction that may well increase with chronicity and multiplicity of infection. Wolbachia-mediated negative regulation of macrophage inflammatory responses may have a direct effect on the susceptibility toward other microbial infections, an important implication in view of the evidence that recurrent secondary bacterial infections are a feature of chronic lymphoedema pathology (elephantiasis) (39). Because macrophages also serve as APCs, Wolbachia-mediated tolerance may also extend to a dysregulated APC-lymphocyte interface with concomitant effects on the generation of acquired immune responses.…”

Section: Discussionmentioning

confidence: 99%

Wolbachia Endosymbiotic Bacteria of Brugia malayi Mediate Macrophage Tolerance to TLR- and CD40-Specific Stimuli in a MyD88/TLR2-Dependent Manner

Turner

Langley

Johnston

et al. 2006

The Journal of Immunology

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Lymphatic filarial nematodes are able to down-regulate parasite-specific and nonspecific responses of lymphocytes and APC. Lymphatic filariae are reliant on Wolbachia endosymbiotic bacteria for development and survival. We tested the hypothesis that repeated exposure to Wolbachia endosymbionts would drive macrophage tolerance in vitro and in vivo. We pre-exposed murine peritoneal-elicited macrophages to soluble extracts of Brugia malayi female worms (BMFE) before restimulating with BMFE or TLR agonists. BMFE tolerized macrophages (in terms of IFN-β, IL-1β, IL-6, IL-12p40, and TNF-α inflammatory cytokine production) in a dose-dependent manner toward self, LPS, MyD88-dependent TLR2 or TLR9 ligands (peptidoglycan, triacyl lipopeptide, CpG DNA) and the MyD88-independent/TRIF-dependent TLR3 ligand, polyinosinic-polycytidylic acid. This was accompanied with down-regulation in surface expression of TLR4 and up-regulation of CD14, CD40, and TLR2. BMFE tolerance extended to CD40 activation in vitro and systemic inflammation following lethal challenge in an in vivo model of endotoxin shock. The mechanism of BMFE-mediated macrophage tolerance was dependent on MyD88 and TLR2 but not TLR4. Evidence that desensitization was driven by Wolbachia-specific ligands was determined by use of extracts from Wolbachia-depleted B. malayi, aposymbiotic filarial species, and a cell line stably infected with Wolbachia pipientis. Our data promote a role for Wolbachia in contributing toward the dysregulated and tolerized immunological phenotype that accompanies the majority of human filarial infections.

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“…These episodes are responsible for worsening the lymphatic damage and future development of swelling in the limbs (Shenoy et al 1999). In children having asymptomatic LF infection, the underlying sub-clinical lymphatic damage predisposes them to acute attacks following minor injuries or bacterial skin infections.…”

Section: Discussionmentioning

confidence: 99%

“…The dilatation of the lymphatics, which is the early and basic sub-clinical pathology induced by the adult worms, once established is reported to be irreversible even with treatment (Freedman et al 1995). In the affected limbs this persistent lymphatic damage predisposes to later development of lymph stasis, secondary bacterial infections precipitating ADLA attacks, consequent development of lymphoedema and its progression (Shenoy et al 1999). Therefore detection of LF infection in the early asymptomatic stage itself and prompt treatment are important in preventing future chronic disability.…”

Section: Diagnosis Of Lf Infection and Disease In Childrenmentioning

confidence: 99%

Lymphatic filariasis in children: Clinical features, infection burdens and future prospects for elimination

Shenoy

Bockarie

2011

Parasitology

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S U M M A R YLymphatic filariasis (LF), a common parasitic infection in tropical countries, causes lymphoedema of limbs, hydrocele and acute attacks of dermato-lymphangio-adenitis. Recent advances in diagnosis have helped to recognize that LF infection is often acquired in childhood. Newly available diagnostic techniques like sensitive antigen and antibody assays, Doppler ultrasonography and lymphoscintigraphy have helped to understand the subclinical pathology caused by this infection, which was hitherto generally believed to be irreversible. Recent studies indicate that drugs used in the mass drug administration (MDA) programme under GPELF are capable of reversing the sub-clinical lymphatic damage in children and provide benefits other than interruption of transmission. Albendazole and ivermectin used in MDA are effective against soil-transmitted helminthic infections common in children in LF endemic areas. Thus MDA had other 'beyond LF' benefits in treated children including increased appetite, weight gain, greater learning ability and concentration, better school attendance and prevention of anaemia. MDA should no longer be viewed as a measure for interrupting transmission alone. Recent findings of reversibility of early lymphatic pathology in treated children indicate that both MDA and 'foothygiene' measures are effective strategies in preventing and managing morbidity. Programme managers should effectively utilize this information to strengthen their advocacy efforts to achieve high and sustainable coverage in MDA.

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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

Cited by 70 publications

References 9 publications

A Longitudinal Analysis of the Effect of Mass Drug Administration on Acute Inflammatory Episodes and Disease Progression in Lymphedema Patients in Léogane, Haiti

A Longitudinal Analysis of the Effect of Mass Drug Administration on Acute Inflammatory Episodes and Disease Progression in Lymphedema Patients in Léogane, Haiti

Wolbachia Endosymbiotic Bacteria of Brugia malayi Mediate Macrophage Tolerance to TLR- and CD40-Specific Stimuli in a MyD88/TLR2-Dependent Manner

Lymphatic filariasis in children: Clinical features, infection burdens and future prospects for elimination

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