Protective immunity in human Bancroftian filariasis: inverse relationship between antibodies to microfilarial sheath and circulating filarial antigens

The existence and the nature of protective immunity in human filariasis continues to be a subject of intense debate. While there is no broad consensus on functional immunity against larval and adult stage parasites, anti-microfilarial immunity has been demonstrated to be mediated by antibodies to the microfilarial sheath. In the present study, circulating filarial antigens (CFA), a marker of active filarial infection in human Bancroftian filariasis, was found to be inversely associated with antibodies to microfilarial sheath in a cohort of 411 subjects representing all categories of filariasis across the clinical spectrum of the disease. Approximately 80% of humans of all age groups (5-65 years) were found to have either CFA or anti-sheath antibodies. The inverse relationship observed between these two parameters was found to be independent of the clinical manifestation; both symptomatic and asymptomatic cases were found to display similar inverse association between CFA and anti-sheath antibodies. The prevalence of anti-sheath antibodies in the paediatric group was found to be very high as compared to adults; 78% of children below the age of 10 years tested positive for anti-sheath antibodies although the mf rate and CFA rate were only 4.5% and 22.7%, respectively, in this age group, indicating that developing larvae or juvenile adult stage parasites could have been the source of antigenic stimulus for induction of antibodies to the microfilarial sheath.     

Antibodies to microfilarial sheath in bancroftian filariasis--prevalence and characterization

Antibodies directed towards the sheaths of microfilariae have been implicated in the elimination of circulating microfilariae, both in experimental and human filariasis. In the present study antisheath antibodies have been detected in human sera by indirect immunoperoxidase assay (IPA) using fixed Wuchereria bancrofti microfilariae as antigen. One hundred and eighteen sera collected from an area endemic for Bancroftian filariasis were tested. While 80% of sera from microfilariae carriers had no demonstrable antisheath antibodies, more than 80% of amicrofilaraemic samples (chronic filariasis cases and endemic normals) had antisheath antibodies. The antibody activity was found in IgG, IgM and also IgE isotypes. IgG subclass typing with monospecific antisera revealed significantly higher antisheath activity in IgG2 in comparison with other IgG subclasses. The determinants on sheathed microfilariae reacting with antisheath antibodies were found to be thermostable (100 degrees C for 30 minutes), resistant to protease treatment and significantly sensitive to sodium periodate treatment, indicating the possible role of carbohydrate moieties in eliciting protective antisheath antibodies in Bancroftian filariasis.     

Dermatologic disorders and the liver

Chronic liver disease is associated with several cutaneous manifestations. Although many of these changes are nonspecific, some are associated with distinct liver diseases and correlate with the severity of hepatic pathology. Often the first clue to a liver disease is manifested through skin. Although cirrhosis is associated with spider nevi and palmar erythema, disorders can result in noncirrhotic cutaneous manifestations. It is important for physicians to be familiar with the spectrum of these manifestations, to recognize, help detect, and treat the underlying hepatic disease. This article reviews the medical literature and discusses the spectrum of dermatologic manifestations of liver disorders and their pathogenesis, significance, and treatment.     

Concomitant parasitism: bancroftian filariasis and intestinal helminths and response to albendazole

Subjects in an disease-endemic area in Orissa, India concomitantly infected with filariasis and intestinal helminths had significantly lower intensity of filarial infection in comparison with those who were infected only with filariasis. Administration of albendazole resulted in a significant decrease in the prevalence of filarial antigenemia in subjects concomitantly infected with intestinal helminths, but produced little change in this infection measure in subjects infected only with Wuchereria bancrofti. These results indicate that intestinal helminths could play a role in the anti-filarial activity of albendazole, most probably by depressing filarial infection intensity in co-infected individuals. Confirmation of these findings in a larger cohort may yield important new insights regarding the role of using albendazole in the ongoing intervention programs for the control of lymphatic filariasis.     

Naturally occurring alpha-galactosyl antibodies in human sera display polyreactivity.

Anti-gal is a dominant autoantibody constituting nearly 1% of total circulating IgG in humans and old world primates. Raised levels of anti-gal have been demonstrated in parasitic diseases such as malaria, leishmaniasis and Chagas disease and in a variety of autoimmune diseases. It has also been implicated as a primary cause of rejection of xenogeneic cells and organs transplanted in old world primates since Gal-alpha 1,3 Gal is thought to be the major antigenic epitope to which xenoreactive natural antibodies bind. Since polyreactive antibodies have also been widely implicated in xenotransplantation and anti-gal is yet to be demonstrated to be polyreactive, we have attempted to study this property of anti-gal antibodies. Anti-gal levels were assayed in 72 human sera and compared with DNA-binding antibodies. A significant positive correlation was found between anti-gal and DNA-binding antibodies. Absorption of sera with fresh rabbit erythrocytes (which express abundant alpha-galactose on their surface) resulted in significant removal of both anti-gal and DNA-binding antibodies. Affinity purified anti-gal were found to be reactive to DNA, actin, myosin and tubulin indicating the polyreactive nature of naturally occurring anti-gal antibodies in human sera. The observed polyreactivity was not an exclusive feature of sera collected from tropical countries-anti-gal affinity purified from sera of North Americans were also found to react with DNA. The demonstration of polyreactivity of anti-gal indicates a much wider biological role for this autoantibody in humans and old world primates.     

Affected parents' and other stakeholders' perception of a fire disaster management in India: a situational analysis.

BACKGROUND: Fires that result in a large number of deaths and injuries are quite common in India, presenting many complex emergency management challenges. While significant improvement in disaster management has been noted in recent years, full integration of government emergency management initiatives at the provincial level is still in its infancy. This article presents the findings of a study of a school fire in India that resulted in the deaths of 93 children. The effective provincial level management of this fire, in the absence of a well-defined disaster management plan, was quite encouraging and provides guidance for other disaster managers in the country. METHODS: The purpose of the study was to analyze the factors leading to the tragedy, the response of the stakeholders, the relief and rehabilitation support provided to the affected families, and the perceptions of the affected parents regarding their level of satisfaction with the management of this disaster. Extensive visits were made to the damaged school, schools where the rescued and evacuated children were relocated, affected households, injured children, various stakeholders and institutions playing a significant role in managing the incident, and nongovernment organizations working in the field. The study methodology included structured interviews to determine the parents' level of satisfaction with the different elements of the response, participant observations, intensive interaction with the members of the affected families, and focused group discussion with different relevant government officials. RESULTS: The findings indicate a high level of parent and stakeholder satisfaction in the majority of response and relief efforts associated with the disaster. Also reinforced were the importance of adherence to school safety regulations; the role of effective relief and rehabilitation; public-private partnership in disaster management; and the importance of media management, humanitarian assistance during crisis management and response, gender sensitivity in relief and rehabilitation, and services provided to reduce mental health risks for the injured children and families who lost their children in the incident. CONCLUSIONS: While the participants in the study perceived the management of the disaster as highly satisfactory, several disaster management elements, particularly disaster mental health services, require further attention at all levels.     

Presence of Mycobacterium leprae in epidermal cells of lepromatous skin and its significance

A 49-year-old man with lepromatous leprosy treated with dapsone monotherapy for 12 years (1967 to 1979) reported in the hospital in 2003, with relapsed disease. A slit skin smear showed a bacteriological index of 4+. Biopsies from skin lesions before and after anti-leprosy therapy showed features of lepromatous leprosy. Both biopsies showed unusual features of bacillary clumps in epidermal cells demonstrating clearly that dissemination of M. leprae can take place even through unbroken skin. The presence of lepra bacilli in clumps in the epidermis is an indicator that the skin is a potential route of transmission of the disease.     

High Tregs and systemic IL-10 expressions linked to the absence of sheath antibodies in lymphatic filariasis: implications on the persistence of residual infection

The persistence of residual infection is one of the major factors in failure of the Global Programme to Eliminate Lymphatic Filariasis (GPELF). The present study aims to explore the status of sheath antibody and regulatory T cells (Tregs) known to play key roles in clearance of parasite and patent filarial infection, in individuals with residual infection after MDA. A total of 61 microfilaremic (Mf) individuals were followed up after at least 6 rounds of MDA. Infection status of subjects was assessed through the detection of Mf and circulating filarial antigen (CFA). Antibodies to Mf sheath were determined by immuno-peroxidase assay (IPA). The expression of Tregs was measured by a flow cytometer. IL-10 and IFN-γ were evaluated using the commercially available ELISA kit. The sheath antibody was present in subjects who have cleared both Mf and CFA and absent in individuals who were found to be Mf /CFA positive. Further individuals carrying infection have significantly high levels of Tregs and IL-10. A positive correlation was observed between Tregs, IL-10, and CFA in infected individuals. In contrast, a negative correlation was observed between IFN-γ and IL-10 in both infected and uninfected subjects. Our study reveals that the absence of a sheath antibody and a high level of Tregs and IL-10 are the hallmarks of the persistence of residual filarial infection.