HYPERREACTIVE MALARIAL SPLENOMEGALY PDF

Elhassan,1 and Ibrahim M. This study was carried out in Khartoum, Sudan. Sudan is considered to be one of the countries where HMS is quite prevalent. The objective of the study was to determine the incidence of HMS in patients who reported to the Omdurman Tropical Diseases Hospital OMTDH in Sudan and to investigate the basic laboratory and immunological characteristics of this condition in these patients.

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Received Dec 29; Accepted Apr This article has been cited by other articles in PMC. Abstract Background The hyper-reactive malarial splenomegaly syndrome HMS is a leading cause of massive splenomegaly in malaria-endemic countries.

HMS is caused by a chronic antigenic stimulation derived from the malaria parasite. The syndrome is fatal if left untreated. The aim of this study is to systematically review the literature about HMS, particularly focussing on case definition, epidemiology and management.

Results Papers detected were , of which 89 were included. Splenomegaly was variably defined and the criterion of increased IgM was not always respected.

The most frequent anti-malarial treatments administered were weekly chloroquine or daily proguanil from a minimum of one month to lifelong. In non-endemic countries, a few authors opted for a single, short anti-malarial treatment. All treated patients with no further exposure improved. Conclusions For patients not re-exposed to endemic areas, a short course of treatment is sufficient, showing that eradicating the infection is sufficient to cure HMS.

Longer probably lifelong courses, or intermittent treatments, are required for those who remain exposed. Splenectomy, associated with high mortality, should be strictly limited to cases not responding to medical treatment. Keywords: Hyper-reactive, Malarial, Splenomegaly, Management, Treatment, Epidemiology, Review Background Hyper-reactive malarial splenomegaly HMS represents one of the leading causes of massive splenomegaly in malaria-endemic countries [ 1 ].

HMS is caused by an aberrant immune response to a chronic antigenic stimulation in subjects long exposed to malaria parasites [ 2 ]. Previously defined as tropical splenomegaly syndrome TSS , HMS has long been considered distinct from a splenomegaly directly resulting from malarial parasitaemia. The syndrome is characterized by macroglobulinaemia with overproduction of immunoglobulin, especially of the IgM class, which aggregate into high molecular immune complexes and cause persistent splenomegaly because of prolonged clearance from the reticuloendothelial tissue [ 3 ].

Cryoglobulins and autoantibodies, such as, for instance, rheumatoid factor, contribute to the macroglobulinaemia [ 4 ]. A direct correlation between the spleen size and the IgM titre has been described [ 5 - 8 ]. Genetic factors are likely to be involved in the development of HMS. Moreover a retrospective study carried out in Ghana evidenced that the relatives of patients with HMS were more likely to have splenomegaly than population controls [ 11 ]. Diagnostic criteria for HMS were proposed by Fakunle in [ 12 ].

Minor diagnostic criteria are: hepatic sinusoidal lymphocytosis, normal cellular and humoral immune responses to antigenic challenge, including phytohaemagglutinin stimulation PHA , hypersplenism, lymphocyte proliferation, occurrence within families or tribes.

Other laboratory findings are related to hypersplenism, such as variable degrees of pancytopaenia, especially anaemia. The underlying mechanism causing anaemia is the plasma volume expansion and the spleen sequestration along with an increased haemolysis. Reticulocytes and indirect bilirubin are often increased [ 14 , 15 ]. Acute episodes of haemolysis can also occur and seem to be associated with an autoimmune, cold-agglutinin-mediated response triggered by non-patent parasitaemia [ 16 ].

Sinusoidal lymphocytosis may be revealed by histologic examination of liver biopsy, but it is not specific. The peripheral blood smear in HMS subjects is most often negative.

However, using more sensitive diagnostic methods, such as polymerase chain reaction PCR , the proportion of positive cases increases [ 17 - 19 ].

The main, severe complications of HMS are acute infectious illnesses, haemolytic anaemia especially during pregnancy and splenic rupture. According to historical data, the syndrome is often fatal if left untreated [ 20 ]. Some authors have hypothesized that HMS could be considered as a pre-malignant state that could evolve to chronic lymphocytic or hairy cell leukaemia or splenic lymphoma with villous lymphocytes, as a result of a multi-step process with a single clone selection in a set of deregulated polyclonal expansion of lymphocytes [ 21 - 23 ].

Actually, HMS and lymphoproliferative disorders are often clinically indistinguishable. In the latter condition, too, a markedly raised anti-malarial antibody and IgM level have been observed [ 24 ]. Spleen reduction after a prolonged anti-malarial treatment is one of the main criteria used to diagnose HMS. Failure to respond makes an alternative diagnosis more likely [ 25 ].

Despite a comparatively large amount of literature on malaria, only a few papers deal with this particular complication. Moreover, diagnostic criteria are not uniform, epidemiological data are scarce and the clinical management has been variable. This aim of this review was to retrieve the relevant literature on HMS, focusing in particular on three key aspects: diagnostic criteria for the case definition, epidemiology prevalence and mortality and management.

Methods Searching The search strategy was based on the following database sources: Pubmed, EmBase, Scopus, with no limitation as for the year of publication. The oldest paper retrieved was published in Our searching strategy was based on these keywords using of course the specific language of each database : asymptomatic malaria, chronic malaria, malarious splenomegaly, splenomegaly syndrome, splenomegalic syndrome, tropical splenomegaly, malarial splenomegaly.

Additional search terms used were: epidemiology, prevalence, incidence, pathogenesis, diagnosis, case definition, prognosis, mortality, fatality, management, treatment.

The search was carried out in March Reference lists of all the articles identified were also examined and relevant cited references were reviewed similarly.

Reviews were excluded from the analysis. Inclusion criteria Articles had to deal with hyperactive malaria splenomegaly or its synonymous, such as tropical splenomegaly or chronic malaria, as a main subject. All papers identified were assessed by two reviewers SL and DB who independently screened the titles and abstracts, using the criteria mentioned above. Then they read the full text of those retained after the first screening. In case of differences, a final consensus was reached after discussion that included a third reviewer ZB.

Data were extracted from all finally retained papers and specific fields of an Excel spreadsheet were populated. With available data the analysis was focused first on epidemiology, such as gender and age of patients, country where the study was conducted and country of origin of the patients, prevalence of the syndrome in a given area, mortality rate, etc. Finally data were extracted considering the type and duration of the treatment and when available, also data on outcome at follow-up.

Finally, the reported treatment outcome of studies with more than 10 recruited subjects was summarized. The studies were obviously heterogeneous but, because of the extreme poverty of papers dealing with HMS, it was aimed to provide the most comprehensive picture of the main reported aspects of the syndrome since the first publication until now.

Sixty-eight duplicates were discarded. After an evaluation of language, titles and abstracts, a total of papers were detected that may relate to this review. Thirteen were not retrieved. On the basis of the full text, 51 papers were discarded since they did not deal with HMS.

The remaining 89 papers were included.

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Hyperreactive Malarial Splenomegaly Syndrome—Can the Diagnostic Criteria Be Improved?

Abstract Background The hyper-reactive malarial splenomegaly syndrome HMS is a leading cause of massive splenomegaly in malaria-endemic countries. HMS is caused by a chronic antigenic stimulation derived from the malaria parasite. The syndrome is fatal if left untreated. The aim of this study is to systematically review the literature about HMS, particularly focussing on case definition, epidemiology and management. Results Papers detected were , of which 89 were included. Splenomegaly was variably defined and the criterion of increased IgM was not always respected.

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Immunological Characteristics of Hyperreactive Malarial Splenomegaly Syndrome in Sudanese Patients

Abstract Background The hyperreactive malarial splenomegaly HMS represents a chronic, potentially fatal complication of malaria. Case definition includes: gross splenomegaly, high level of anti-malarial antibody and IgM, response to long-term anti-malarial prophylaxis. In this study, a large series of patients not fully meeting the case definition was tentatively classified as early hyperreactive malarial splenomegaly e-HMS. And if so, what are the main factors influencing this evolution? Methods Retrospective, longitudinal study. The patient database was searched to retrieve all potentially eligible patients. The clinical outcome at following visits was analysed in relation to re-exposure to malaria, and to treatment only part of the patients with e-HMS were treated with a single anti-malarial treatment and advised to follow an effective anti-malarial prophylaxis, if re-exposed.

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The hyper-reactive malarial splenomegaly: a systematic review of the literature

Cutoff was mean of the negative controls plus 0. We examined fields in a thick film. Cases Case 1. A year-old pregnant woman from Sierra Leone was admitted to hospital with shortness of breath and fatigue.

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Tropical splenomegaly syndrome

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