Circulating filarial antigen in cats infected with Brugia pahangi is indicative of the presence of adult worms

Using counterimmunoelectrophoresis with rabbit antisera raised against soluble extracts of adult females of Brugia pahangi parasite antigen was detected in the serum of all cats repeatedly infected with B. pahangi. Antigen was never detected in uninfected cats. The antigen was associated with the presence of adult worms. Antigen was detected consistently in a cat that was amicrofilaraemic but at autopsy harboured only two or three adult worms. Conversely, some cats showed slowly declining numbers of microfilariae and, in these, circulating antigen declined before the number of microfilariae. Eventually no antigen was detectable in circulation whereas microfilariae, although in diminishing numbers, were still present. At autopsy no adult worms were found in these cats. Antigen also appeared in several cats before they became microfilaraemic.     

Acute polymyositis associated with W. bancrofti

Two cases of acute polymyosotis associated with W. bancrofti , presented with generalised painful swelling and weakness of the muscles. These patients had elevated muscle enzymes, a myopathic EMG pattern, inflammatory myopathy on biopsy and W. bancrofti in the peripheral blood smear. The clinical, improvement of the disorder and total clearance of microfilariae was obtained with the combination therapy of steroid and diethyl-carbamazine in comparison with steroid alone.     

肥西县丝虫病流行特征及防治措施评析

目的　了解肥西县丝虫病的流行特征和防治工作采取措施的效果 ,为开展类似的工作提供借鉴作用。方法　对本县 1970～ 2 0 0 0年丝虫病的防治研究及相关调查资料进行整理、统计分析并进行评价。结果　 1970年调查人群微丝蚴率高达 18.2 5 % ,1973年平均微丝蚴率为 6 .31% ,80年代为 1.15 % ,全县各乡镇均有丝虫病的流行。 1991年调查人群平均微丝蚴率为 0 .6 1% ,主要流行区分布于县西北区域的 15个乡镇 ,以马来丝虫为主的马来、班氏两种丝虫病混合流行区。主要传播媒介为中华按蚊和嗜吸人血按蚊。经过 30年的积极防治 ,特别是 1991年 ,在现况调查的基础上 ,以行政村为单位 ,按不同的流行程度采用不同剂量的海群生药盐的防治 ,加快了基本消灭丝虫病的步伐 ,1993年经省厅考核 ,人群微丝蚴率为 0 .0 7% ,达到了基本消灭丝虫病的标准。 2 0 0 0年全县开展消灭丝虫病的监测 ,人群微丝蚴率和按蚊幼丝虫的自然感染率均为0 %。达到部颁消灭丝虫病的标准。结论　肥西县是以马来丝虫为主的马来和班氏两种丝虫病混合流行的地区 ,经过 30年的查治 ,传播已被阻断 ,达到部颁消灭丝虫病的标准     

Ivermectin for the chemotherapy of bancroftian filariasis: a meta-analysis of the effect of single treatment

Summary The efficacy and safety of ivermectin in the treatment of filariasis due to Wuchereria bancrofti was assessed by a meta-analysis of the results from 15 published clinical trials. Seven hundred and forty-eight microfilaraemic patients were enrolled in 7 dose-finding and 8 comparative studies. Administered as a single dose, ivermectin induced nearly complete clearance of microfilariae from the blood from the first day to 30 days post-treatment, followed by gradual recurrence of microfilaraemia and increase in its intensity. Higher doses of ivermectin showed greater clearance effects and maintained lower microfilaraemia levels for a longer time. The adverse reactions caused by the drug were flu-like, transient, generally mild and well tolerated by patients. The frequency and intensity of adverse reactions were strongly associated with pretreatment microfilaria counts in the blood, but independent of dose. The findings of the meta-analysis suggest that ivermectin given at a single annual dose of 200 μg/kg body weight or higher, whether or not in combination with DEC, has great potential for therapeutic strategies to control bancroftian filariasis.     

IL-5 is essential for vaccine-induced protection and for resolution of primary infection in murine filariasis

The pathways conferring immunity to human filariases are not well known, in part because human-pathogenic filariae do not complete a full life cycle in laboratory mice. We have used the only fully permissive infection of mice with filariae, i.e., infection of BALB/c mice with the rodent filarial nematode Litomosoides sigmodontis. Our previous results showed that worm development is inversely correlated with Th2 cytokine production and eosinophilia. The scope of the present study was to directly elucidate the role of interleukin-5 (IL-5) and eosinophils in controlling the development of L. sigmodontis after vaccination and in primary infection. BALB/c mice immunized with irradiated third-stage larvae (L3) were confirmed to have elevated IL-5 levels as well as high subcutaneous eosinophilia and to attack and reduce incoming larvae within the first 2 days, resulting in 70% reduction of worm load. Treatment of vaccinated mice with anti-IL-5 antibody (TRFK-5) suppressed both blood and tissue eosinophilia and completely abolished protection. This demonstrates, for the first time in a fully permissive filarial infection, that IL-5 is essential for protection induced by irradiated L3 larvae. In contrast, in primary-infected mice, anti-IL-5 treatment did not modify filarial infection within the 1st month, most likely because during primary infection IL-5-dependent mechanisms such as subcutaneous eosinophilia are induced too late to disturb worm establishment. However, there is a role for IL-5 late in primary infection where neutrophil-dependent worm encapsulation is also under the control of IL-5. Received: 30 March 2000     

Naturally occurring human IgA autoantibodies against IgE-DES myeloma protein

The prevalence and specificity of naturally occurring human IgA anti-IgE autoantibodies (a-E Ab) were studied by ELISA with anti-IgA monoclonal antibodies (mAb) and a purified myeloma IgE as solid-phase protein, i.e., IgE-DES(κ). Such detected IgA a-E Ab were common among adults, and significantly increased geometric means (GM) were found in patients with atopy (P= 0.006; n= 41; GM = 79.3 arbitrary units (AU)/ml) and filariasis (P= 0.02; n= 41; GM = 75.9 AU/ml), as compared with nonatopic controls (n= 42; GM = 48.8 AU/ml). No such difference was observed between age-matched nonatopic (n= 22; GM = 36.7 AU/ml) and atopic (n= 22; GM = 38.6 AU/ml) children. Children had significantly (P= 0.001) lower IgA a-E Ab concentrations than adults, probably as a result of age, because IgA a-E Ab concentrations and age of children were significantly correlated (n= 44; P<0.05; r_s= 0.30). IgA a-E Ab concentrations were very low in cord serum (n= 32; median <0.1 AU/ml). Sex did not influence IgA a-E Ab concentrations in any study group. The specificity of IgA a-E Ab in nine sera was studied by ELISA inhibition assay using IgE-DES myeloma as solid-phase protein and inhibitory proteins of the IgG, IgM, IgD, and IgE classes, including five different IgE myeloma proteins, as well as three enzymatic fragments of IgE-DES. The inhibitions indicated that all IgA a-E Ab tested reacted in a low-affinity reaction with determinants restricted to IgE-DES, i.e., the solid-phase protein. These epitopes were heat-resistant (2 h; 56°C) and located in the Fab_?-DES fragment. No isotype-specific IgA a-E Ab were found because none of the four other IgE proteins were inhibitory. Subclass typing indicated that most IgA a-E Ab belonged to the IgA 1 subclass. It is unlikely, for reasons of restricted specificity, low affinity, and common prevalence, that such IgA 1 a-E Ab are connected with IgE-mediated disorders. The study also raises questions on the definition of anti-IgE antibodies.     

APC from mice harbouring the filarial nematode, Brugia malayi, prevent cellular proliferation but not cytokine production

Specific T cell hyporesponsiveness and depressed antibody productionis a key feature of human infection with the filarial nematodes,Brugia malayi and Wuchereria bancrofti Despite this immune suppression,responses indicative of T_h2 subset activation are present, includingunusually high levels of specific lgG4. We tested the possibilitythat infection with filarial nematodes causes a reduction inthe co-stimulatory or antigen-presenting capacity of macrophagesresulting in a failure to activate specific T cells. Adherentperitoneal exudate cells (PEC) from mice implanted with adultB. malayi were used to present antigen to the conalbumin-specificT cell clone, D10.G4. Proliferation of the D10 cells at evenbackground levels was completely blocked by the presence ofimplant-derived adherent PEC. However, cytokine production bythese cells in response to antigen was intact, and thus PECfrom implanted mice are capable of functionally processing andpresenting antigen. The elicitation of a suppressive cell populationwas specific for live adults as cells from mice implanted withdead adult parasites effectively stimulated D10 proliferation.The block in cellular proliferation is not due to the productionof factors typically associated with macrophage suppressionsuch as nitric oxide, prostaglandins or catalase. These observationsare consistent with the T cell hyporesponsiveness seen in humancases of patent Brugia infection and may provide a murine modelfor the immune suppression seen in lymphatic filariasis.     

Lymphoedema management: An international intersect between developed and developing countries. Similarities,differences and challenges

Abstract

Lymphoedema is a chronic swelling condition that contributes to disability, dysfunction and lost quality of life. Significant disparities exist worldwide regarding the availability of resources necessary to identify, treat and manage lymphoedema. This disparity transcends socio-economic status and is a common problem in both developed and developing countries. The overall impact of lymphoedema as a public health problem, however, is underestimated, principally due to the lack of epidemiologic data. These problems pose barriers to optimal identification and management of this disabling, lifelong condition.

In 1997, the World Health Organization (50.29) resolved that lymphatic filariasis should be eliminated as a public health problem. A component of this strategy focuses on disability management for those suffering from lymphatic filariasis-related morbidity. This initiative has enhanced lymphoedema awareness in developing countries. However, significant deficits persist in health care providers' knowledge, educational initiatives and basic disease identification and treatment.

In developed countries, lymphoedema continues to be an underrecognised condition and assumed to be only cancer-related. Health care resources allocated to treat and manage the disease are insufficient for basic and ongoing care, resulting in disease progression and disability. The International Lymphoedema Framework project, established in 2002, seeks to establish a consensus for best practices in the management of lymphoedema worldwide to reduce this disability burden.

A basic global construct for lymphoedema management is needed to decrease morbidity and promote optimal disease management across all cultural and socio-economic boundaries. Many countries are unaware of the importance of lymphoedema management and have not defined a national strategy with respect to this problem. The objective of this article is to define similarities and differences in strategies for lymphoedema management between developed and developing countries and advocate for a cohesive and concerted approach to disease management.     

Inflammatory and regulatory CCL and CXCL chemokine and cytokine cellular responses in patients with patent Mansonella perstans filariasis

Mansonella perstans (Mp) filariasis is present in large populations in sub-Saharan Africa, and to what extent patent Mp infection modulates the expression of immunity in patients, notably their cellular cytokine and chemokine response profile, remains not well known. We studied the spontaneous and inducible cellular production of chemokines (C-X-C motif) ligand 9 (CXCL9) [monokine induced by interferon (IFN)-γ (MIG)], CXCL-10 [inducible protein (IP)-10], chemokine (C-C motif) ligand 24 (CCL24) (eotaxin-2), CCL22 [macrophage-derived chemokine (MDC)], CCL13 [monocyte chemotactic protein-4 (MCP-4)], CCL18 [pulmonary and activation-regulated chemokine (PARC)], CCL17 [thymus- and activation-regulated chemokine (TARC)] and interleukin (IL)-27 in mansonelliasis patients (Mp-PAT) and mansonelliasis-free controls (CTRL). Freshly isolated peripheral mononuclear blood cells (PBMC) were stimulated with helminth, protozoan and bacterial antigens and mitogen [phytohaemagglutinin (PHA)]. PBMC from Mp-PAT produced spontaneously (without antigen stimulation) significantly higher levels of eotaxin-2, IL-27, IL-8, MCP-4 and MDC than cells from CTRL, while IFN-γ-IP-10 was lower in Mp-PAT. Helminth antigens activated IL-27 and MCP-4 only in CTRL, while Ascaris antigen, Onchocerca antigen, Schistosoma antigen, Entamoeba antigen, Streptococcus antigen, Mycobacteria antigen and PHA stimulated MIG release in CTRL and Mp-PAT. Notably, Entamoeba antigen and PHA strongly depressed (P < 0·0001) eotaxin-2 (CCL24) production in both study groups. Multiple regression analyses disclosed in Mp-PAT and CTRL dissimilar cellular chemokine and cytokine production levels being higher in Mp-PAT for CCL24, IL-27, IL-8, MCP-4, MDC and PARC (for all P < 0·0001), at baseline (P < 0·0001), in response to Entamoeba histolytica strain HM1 antigen (EhAg) (P < 0·0001), Onchocerca volvulus adult worm-derived antigen (OvAg) (P = 0·005), PHA (P < 0·0001) and purified protein derivative (PPD) (P < 0·0001) stimulation. In Mp-PAT with hookworm co-infection, the cellular chemokine production of CXCL10 (IP-10) was diminished. In summary, the chemokine and cytokine responses in Mp-PAT were in general not depressed, PBMC from Mp-PAT produced spontaneously and selectively inducible inflammatory and regulatory chemokines and cytokines at higher levels than CTRL and such diverse and distinctive reactivity supports that patent M. perstans infection will not polarize innate and adaptive cellular immune responsiveness in patients.