191 research outputs found
Towards a Strategic Plan for Research to Support the Global Program to EIiminate Lymphatic FiIariasis: Summary of Immediate Needs and Opportunities for Research on Lymphatic Filariasis. 2.2 Essential tools – Drugs and Clinical Drug Trials
A series of advances during the past decade transformed
LF from a neglected disease of poor countries into a disease
now recognized as potentially eradicable. Principal among the
reasons for these advances were the identification of ivermectin
and albendazole as new, effective anti-filarial agents and
the discovery of new virtues for an old anti-filarial drug, DEC
(i.e., its single-dose efficacy and macrofilaricidal action).
These discoveries were essential for the subsequent creation
of the Global Program to Eliminate LF,1 whose very basis is
the large-scale use of DEC, ivermectin (Mectizan�; Merck
and Co., Inc., Rahway, NJ) and albendazole. Indeed, in many
endemic countries literally millions of tablets of these drugs
are distributed over a few short days each year (often on a
single day), making GPELF the largest chemotherapy program
ever undertaken.
Currently it is just these three drugs that are available for
use in single-dose, annual MDA programs. Albendazole is
co-administered with ivermectin in areas of Africa and Yemen
where LF and onchocerciasis are co-endemic. For all
other LF-endemic regions, albendazole is co-administered
with DEC. At the recommended dose levels, none of the
drugs is completely macrofilaricidal, although all appear to
inflict some lasting damage to adult worms. Both DEC and
ivermectin kill mf efficiently; albendazole, on the other hand,
has no direct effect on mf, but rather appears to suppress
embryogenesis in the adult female worm. An alternative
treatment strategy involving the use of DEC as a fortificant in
table/cooking salt for a period of 1−2 years is currently used
in just one country, but was a mainstay of the earlier, successful
LF elimination program in China
Eosinophils and the lung in tropical pulmonary eosinophilia
Tropical pulmonary eosinophilia (TPE) is commonly
seen in areas endemic for filariasis. It must be
remembered that the respiratory manifestations are
part of a systemic disease characterised by marked
increase in the blood eosinophil counts, malaise,
fever and weight loss in addition to the respiratory
symptoms. The clinical and laboratory features of
the disorder have been extensively reviewed
Immunology of occupational lung diseases caused by dust: an overview
The lungs are exposed to numerous injurious substances.Such injury may be the result of immunological or non-immunological mechanisms. The lung clears itself of inhaled particles by means of ciliated cells lining the airways and the macrophages.The latter play an important role in the immune process as well.Inorganic particles are ingested by macrophages and if found inert are transported for eventual expulsion.Particles such as silica are poorly handled by macrophages, they not only damage the macrophages but also impair their function. Others, such as asbestos, may stimulate fibrosis. Endogenous factors such as the presence of auto-antibodies (rheumatoid factor or anti-nuclear factor) alter the response of the host to inhaled particles.The pathological changes caused by handling inorganic dusts include intestitial fibrosis, nodular fibrosis or macule formation leading to emphysema.Occupational asthma a occurs when individuals are exposed to dusts during the course of their work. The lung responds differently to organic dust. T cells and complement are important elements in handling organic dust.The role of inhaled steroids which have no significant systemic effects in the prevention of certain occupational asthmas is worth evaluating, apart from control measures which minimise the exposure
Skin changes in chronic lymphatic filariasis
Seventeen men and 31 women with unilateral lower limb lymphoedema attributed to chronic lymphatic filariasis were examined in the filarial out-patient clinic of the Government General Hospital, Madras, India. Skin changes such as skin fold thickening, hyperkeratosis, hypo-or hypertrichosis, pachydermia, pigmentary changes, chronic ulceration, epidermal and sub-epidermal nodules, and clinical intertrigo were observed and compared between the different lymphoedema grades. These lesions are not specific to chronic lymphatic filariasis, and have been described in other conditions displaying lymphostasis. They are thought to be favoured by secondary infections, which should be dealt with appropriately to prevent the progression of the disease and the onset of elephantiasi
Transcriptional Control of Impaired Th1 Responses in Patent Lymphatic Filariasis by T-Box Expressed in T Cells and Suppressor of Cytokine Signaling Genes
T-bet (T-box expressed in T cells) and GATA-3 are transcription factors that play a critical role in the
development of Th1 and Th2 cells, as do genes of the SOCS (suppressor of cytokine signaling) family, albeit
indirectly. Another transcription factor, Foxp3, is a master regulator of natural regulatory T cells (Tregs). To
identify the role of these factors in impaired Th1 responses of patent filarial infection, analysis of cytokine,
SOCS, and transcription factor mRNA expression was performed on purified T cells of filaria-infected
individuals (n � 6) and uninfected controls (n � 6). As expected (and in contrast to cells of uninfected
individuals), there was a significant depression of gamma interferon (IFN-�) and a concomitant increase in
interleukin-4 (IL-4), IL-5, and IL-10 mRNA expression following stimulation with parasite antigen (BmA) but
not with a polyclonal T-cell (anti-CD3) stimulus. T-bet (but not GATA-3) was expressed at significantly lower
levels in cells of filaria-infected individuals in response to BmA compared with those from the uninfected
group, accounting, at least partially, for the diminished IFN-� expression. Second, we found no significant
differences in expression of Foxp3 between the two groups, although induction of Foxp3 expression correlated
with induced expression levels of IL-10, implicating Tregs in the IL-10 expression seen. Finally, parasitespecific
T-cell expression of SOCS-1, SOCS-5, and SOCS-7 was significantly diminished among infected
patients; in contrast, expression of SOCS-3 increased. Our data therefore indicate that the impaired Th1
responses observed in patent lymphatic filariasis are associated with decreased expression of T-bet, SOCS-1,
SOCS-5, and SOCS-7 and increased expression of SOCS-3 in T cells
Parasite specific energy in human filariasis; insights after analysis of parasite antigen-driven lymphokine production
The antigen-specific immune unresponsiveness seen in bancroftian
filariasis was studied by examining lymphokine production
in peripheral blood mononuclear cells (PBMC) or PBMC subpopulations
from 10 patients with asymptomatic microfilaremia,
13 patients with elephantiasis and 6 normal North Americans.
In each group of patients, the kinetics of the lymphokine response
and the response to mitogens and nonparasite antigens
did not differ significantly. In marked contrast, when antigeninduced
lymphokine production was examined, most patients with
microfilaremia were unable to produce either interleukin 2 (IL-
2) or y-interferon (i.e., were nonresponders), and the few who
could (hyporesponders, generally with quite low microfilaremia
levels) did so at levels significantly less than those of patients
with elephantiasis, all of whom showed strong responses to parasite
antigen. Removal of neither adherent cells or T8+ cells
affected the parasite-specific anergy seen in those with microfilaremia,
suggesting a state of T cell tolerance to the parasite in
patients with this most common clinical manifestation of bancroftian
filariasis
A Qualitative Study on the Feasibility and Benefits of Foot Hygiene Measures Practiced by Patients with Brugian Filariasis
Disability alleviation is an important component of Global
Programme for Elimination of Lymphatic Filariasis'. In Brugia malayi
infection the disability is largely due to acute attacks of
adenolymphangitis (ADL), which frequently prevent patients from
attending their normal activities, causing much suffering and
economic loss. The foot care programme has been shown to reduce
the frequency and severity of these episodes. In the present study
we used semi-structured interviews to evaluate the impact of the
foot care in 127 patients with brugian filariasis. They were previously
trained in this procedure and were advised to practice it regularly,
unsupervised. All except one could recollect the various components
of foot hygiene and were practicing it regularly. They were aware of
the factors causing ADL attacks and were able to avoid them. Majority
(95.2%) expressed their happiness with the relief provided by foot
care, which prevented or reduced the ADL episodes. The motivation
was such that they transmitted this knowledge to others suffering in
the community and even physically helped them to carry out foot
care. This study fully endorses the advocacy of foot care programme
as an easy to carry out, effective, sustainable and economically
feasible ,procedure to prevent acute ADL attacks
Urticaria - some observations
Urticaria has been known from antiquity. The disorder was
known to the Arabs as essera and it has found a place in the
writings of Cesius (circa 30 BC–45 AD). Although the condition
was recognised as an entity, its cause was a mystery to the
physicians of those times. It was initially thought to be a
manifestation of idiosyncrasy and later believed to be a form
of neuroses. However, now the pathophysiological basis of
urticaria is well understood. The development of antihistamine
group of drugs, paved the way for the management of urticaria
Ivermectin in the treatment of Bancroftian filariasis infection in Orissa, India
Ivermectin treatment has evaluated for its efficacy and side reactions in sixty patients of
Orissa with Bancroftian filarial infection and microfilaremia. Ivermectin was administered as a single oral
dose at four dosage levels (20, 50. 100 and 200 μg/kg), and both microfilarial clearance and associated
side reactions were monitored in a double blind fashion. Blood microfilariae were cleared in all patients at
all dosages within 1 to 14 days. In most patients microfilariae reappeared by third month. The microfilaria
appearance by third and sixth month averaged 12.2 to 44 percent of pretreatment values in the fourstudy
groups. Side reactions were encountered in almost all patients, the commonest being fever. headache,
weakness, myalgia and cough which occured most prominently 12 to 72 hours after treatment. Side reactions
were more frequent and severe in patients with high microfilaria counts. Clinical reaction scores for
each group were independent of the dose administered. The 200 μg dose group showed significantly
more rapid microfilariae clearance and its delayed reappearance as compared with the other dosage
groups and without inducing significantly greater clinical reaction scores
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
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