Tropical Splenomegaly Syndrome Research Articles

Chronic malarial infection in Balb/c mice. Effect on the immune response to sheep erythrocytes and histological changes in the liver and spleen

Chronic malarial infection was established in Balb/c mice by following Plasmodium berghei yoelii with P. b. berghei infection. It was found that the IgG plaque-forming cell response to sheep erythrocytes was depressed for at least six months. A preliminary investigation of the histological changes in the spleen and liver is described. The possibility that chronically infected mice could serve as a model for the tropical splenomegaly syndrome is discussed.

Characteristics of African blood.

Genetic markers in people of African ancestry and tables comparing Africans and Europeans are compiled to illustrate the blood differences. The existence of the African genetic characters, R0 (cDe), D-u and Ee (e-s, ce-s) in an Rh-Hr system are discussed. The high incidence of R0 (81.9%) in Africans is evident. Studies of ABO and the sickle cell trait in East Africa reveal the African tribes responsible for the original populating of Africa. The pygmoids of Uganda and Zaire, the Nilotes of West Nile, and the Bantu of Uganda are possibly responsible. Subgroups of A antigen in Africans and Europeans are compared, and their differences are outlined. These antigens appear to be different in the two races, and a reliable method for grouping A1 and A2 in Africans is described. For convenience, A2, Aint., Abantu, and other subgroups of A in Africans are renamed "non-A1." Attention to these subgroups on African paternity studies is emphasized. African problems in MNSs, Duffy, P, Lewis, and Sutter are presented. Immunoglobulines, Rh(D) immunization, enzyme autoantibodies, and a technique to detect them are discussed and described in detail. Studies on tropical splenomegaly syndrome show that it is an immune complex disease. Fluctuation titers of ABO iso-antibodies are observed to vary more strikingly in Africans than in Europeans. This is offered as a possible explanation of the high incidence of ABO hemolytic disease of the newborn in Africans.

Relapses after withdrawal of proguanil treatment in tropical splenomegaly syndrome.

After the remission of symptoms and reduction in spleen size while on proguanil therapy four patients with the tropical splenomegaly syndrome defaulted from treatment. The withdrawal of proguanil caused a recrudescence of original symptoms, splenomegaly, and a return of the initially raised serum IgM. Complete return to normal values was again effected with proguanil therapy.The role of the spleen in the tropical splenomegaly syndrome in the production of the raised serum IgM is discussed. These patients should be educated as to the nature of their disease and the importance of continued medical treatment.

The rǒle of plasma proteins in chronic expansion of plasma volume in tropical splenomegaly syndrome I. Metabolism of 131I-labelled albumin

Metabolic studies using 131I-labelled human serum albumin have been performed in 19 adult inhabitants of the Upper Watut Valley of New Guinea, all of whom were suffering from tropical splenomegaly syndrome with at least Grade III splenomegaly. Albumin synthesis was generally increased, the mean synthesis rate being 1·45 times the Caucasian mean. This resulted in an increase in total body albumin, most of which was retained in the intravascular space. There was a tendency for highest synthesis rates to occur in subjects with the greatest expansion in plasma volume, though the correlation coefficient was not statistically significant.

The role of plasma proteins in chronic expansion of plasma volume in tropical splenomegally syndrome II. The metabolism of 131I-Labelled IgG

Metabolic studies using 181I-labelled outologous IgG have been performed in 14 adult New Guineans suffering from tropical splenomegaly syndrome, each of whom had at least Grade III splenomegaly. Synthesis rates were elevated in all subjects and despite shortened half-lives, marked increases in both intravascular and extravascular IgG pools were observed in most subjects. There was a significant positive correlation between synthesis rate and plasma volume, indicating that in this disease overproduction of IgG is in part responsible for the expansion of plasma volume which is commonly seen.

Ultrastructure of the hepatic sinusoids in the tropical splenomegaly syndrome.

Abstract In Ugandan cases of TSS electron microscopy shows that the hepatic sinusoids are filled by Kupffer cells and lymphocytes. The Kupffer cells are both hyperplastic and hypertrophied, much of the latter being due to extensive proliferation of their surface membranes similar to that of antigen trapping dendritic macrophages from germinal centres. The membrane extensions are apparently functioning as a trapping zone which accumulates an electron-dense deposit on the cell surface. There is no evidence that this deposit is taken up into the cell. A group of cells described here as M cells, though basically similar to Kupffer cells, lack many of the Kupffer cell characteristics and in particular the extensive plasma membrane development. Such cells show considerable evidence of uptake of material via large coated vesicles and have fewer mitochondria and less endoplasmic reticulum than the Kupffer cells. They probably represent a different functional development from the Kupffer cells or possibly from a common stem cell. Many of the lymphocytes show, by their ribosome content, expanded perinuclear space, and increased numbers of endoplasmic reticulum elements and mitochondria, that they are not small lymphocytes but are of the activated lymphocyte series. The general appearance is consistent with a complex immunological reaction occurring in the liver sinusoids.

Humoral immune responses in the tropical-splenomegaly syndrome in New Guinea.

1. Humoral immune capacity was measured in New Guineans with tropical splenomegaly or who had been splenectomized for this disease, to assess relationships between tropical splenomegaly and immunological function; the test antigens were flagellin and monovalent influenza vaccine. 2. Controls included age- and sex-matched healthy and hospitalized Caucasians, and comparative data on responses to flagellin were available for New Guinean school children. 3. For flagellin, geometric mean titres in the primary immune response in New Guineans with tropical splenomegaly were significantly lower than those of other groups, whereas pre-immunization titres and those obtained during the secondary response were comparable. 4. For influenza vaccine, both pre-inoculation and peak mean post-inoculation titres of antibody were significantly lower in New Guineans, attributable possibly to lack of previous exposure to this antigen. 5. The low primary antibody responses in New Guineans with tropical splenomegaly could result from pre-emption of antibody-producing tissues arising from abnormal demands for antimalarial antibody; this may determine the increased susceptibility to, and high mortality from, bacterial infection in tropical splenomegaly.

Tropical splenomegaly syndrome in a Rwandan kindred in Uganda.

Twenty members of an immigrant Rwandan kindred were all found to have tropical splenomegaly syndrome compared with 29 out of 50 matched neighbour controls. Splenomegaly among the controls tended to cluster within families. IgM levels were significantly raised in the kindred compared with the control subjects without splenomegaly but were similar to those of neighbours with splenic enlargement. We advance a hypothesis that tropical splenomegaly syndrome results from the production of circulating immune complexes in individuals genetically predisposed to produce an IgM antibody response.

Tropical splenomegaly syndrome in New Guinea. II. Long term results of splenectomy.

Between 1965 and 1967 splenectomy was performed on 21 Watuts and 5 other New Guineans to relieve persistent incapacitating symptoms of tropical splenomegaly syndrome. There were 3 operative deaths. Post-operatively abolition of the splenic red cell pool, correction of the shortened red cell survival time and reduction in plasma volume occurred, leading to a mean rise in haemoglobin concentration of 3·7 g./100 ml. Neutropenia and thrombocytopenia were also corrected. There was a rapid post-operative fall in serum IgG and IgM concentrations, and a prolonged reduction in intravascular pools of both immunoglobulin fractions. The 18 Watuts discharged from hospital and followed for from 41 to 74 months have had significant symptomatic relief, although 7 have died following short illnesses; this mortality rate (36%) is substantially less than that of a comparable group of Watuts not subjected to splenectomy.

Tropical splenomegaly syndrome in New Guinea. I. Natural history.

Abstract The course of the tropical splenomegaly syndrome has been observed for periods of up to 6 1 2 years in 75 adults living in the Upper Watut Valley of New Guinea. During this time there were 27 deaths, 2 from septicaemia and another 8 from similar fulminating febrile illnesses. The mortality rate in those with Grade V splenomegaly was 57%, almost 3 times that of the remainder. Serial hospital assessment of 26 subjects demonstrated progression of the disease, characterized by further enlargement of the spleen and a fall in haemoglobin concentration in 9; increases in splenic red cell pool, in plasma volume and in serum IgM concentration were sometimes, but not invariably, associated. In none of the total group of 75 subjects was a decrease in spleen size observed. Thus the natural history of the tropical splenomegaly syndrome is that of a progressive disease with a high mortality in the fully developed case. Periodic fluctuations in the clinical severity of the disorder are frequently seen and are largely related to the occurrence of episodes of acute haemolysis; however, spontaneous remission has not been observed.

Familial cases of endomyocardial fibrosis in Uganda.

This report describes nine cases of endomyocardial fibrosis occurring in four families. All patients came from Rwanda or South-western Uganda, and five had tropical splenomegaly syndrome as well. It seems likely that genetic as well as environmental factors are operative in the aetiology of endomyocardial fibrosis.

Tropical splenomegaly syndrome in Zambia: further observations and effects of cycloguanil and proguanil.

Nineteen Zambian patients with the tropical splenomegaly syndrome and sinusoidal lymphocytosis on liver biopsy were studied. The association of macrobulinaemia with the tropical splenomegaly syndrome has again been confirmed. Sixteen patients were treated with antimalarials-12 with cycloguanil pamoate alone, 3 with cycloguanil and proguanil, and 1 with proguanil alone. Twelve patients were observed for periods of sufficient length for the drug effect to be assessed, and in 11 there was a good response in terms of decrease in spleen size.Cycloguanil pamoate may be of value both for prophylaxis and treatment in areas where tropical splenomegaly syndrome is endemic.

Tropical splenomegaly syndrome.

Tropical splenomegaly syndrome.

Immunoglobulin levels in the Kaiapit and upper Watut areas of New Guinea: with special reference to the tropical splenomegaly syndrome

Serum concentrations of IgA, IgG and IgM were estimated for 2,000 inhabitants of 2 malarious areas of New Guinea—Kaiapit, where spleen rates are high in children but splenomegaly occurs infrequently in adults and is never gross, and the Upper Watut Valley, where the tropical splenomegaly syndrome is particularly common, and 80% of adults and children have palpable spleens. Kaiapit adults had significantly higher IgM levels than children: IgM levels tended to increase throughout life, were higher in women than in men and in adults with splenomegaly. IgG and IgA levels showed no significant relation to increasing age above 10 years, to sex or to the presence or absence of splenomegaly. The youngest Watut children had higher IgM levels than Kaiapit subjects. IgM concentrations rose more rapidly with age, particularly in the first 20 years of life, so that the mean Watut adult level was more than twice that of Kaiapit adults. In Watut children splenomegaly was associated with significantly higher levels of all 3 immunoglobulin fractions, whereas adults with splenomegaly showed markedly higher levels of IgM, but significantly lower IgA concentrations than did subjects with impalpable spleens. The change in the pattern of immunoglobulin levels in association with splenomegaly occurred between the ages of 6 and 20 years, indicating that the transition from simple malarious splenomegaly to tropical splenomegaly syndrome probably occurs at this age. Subjects living near the valley floor had higher spleen rates than those living in high villages; IgM concentrations were also affected by altitude. The reason for this remains obscure, but it is suggested that both observations may be related to differences in intensity of operation of the factors responsible for the development of the tropical splenomegaly syndrome.

Malaria and the tropical splenomegaly syndrome in New Guinea.

The pattern of malarial parasitaemia and the incidence and degree of splenomegaly have been studied in the population of the Upper Watut Valley in New Guinea. Malaria is the only apparent cause of splenomegaly found in this area, and all cases of gross splenomegaly in adults conform to the descriptions of the tropical splenomegaly syndrome. Malaria is meso-endemic and moderately stable. The incidence of parasitaemia is similar in villages at 3300 feet and 5200 feet above sea level, although the incidence of splenomegaly in adults is lower at the higher altitude. Peak parasitaemia is recorded at 3 years of age and then declines slowly, and parasite rates are significantly lower in adult subjects with splenomegaly than in those without palpable spleens. No difference in distribution of species of plasmodia was found between individuals with different grades of splenomegaly or in different age groups or at different altitudes. P. vivax was the predominant species in all groups.

Tropical splenomegaly syndrome.

Tropical splenomegaly syndrome.

Tropical splenomegaly syndrome.

Tropical splenomegaly syndrome.

Tropical splenomegaly syndrome: long-term proguanil therapy correlated with spleen size, serum IgM, and lymphocyte transformation.

Forty-three patients with an initial diagnosis of tropical splenomegaly syndrome were placed on long-term proguanil therapy. All patients who failed to respond to proguanil and who were adequately followed up developed identifiable disease, usually malignant lymphoma or chronic lymphatic leukaemia. In patients who responded to proguanil IgM values were always very high and phytohaemagglutinin (P.H.A.)-lymphocyte-transformation scores were always normal before treatment was started. In patients who failed to respond IgM values were within the normal range or below, while P.H.A.-lymphocyte-transformation scores were abnormally low. During proguanil treatment IgM values fell gradually, closely paralleling the decrease in spleen size.

Tropical splenomegaly syndrome in a caucasian in Africa.

Tropical splenomegaly syndrome in a caucasian in Africa.

Immunological studies in tropical splenomegaly syndrome

Serum protein levels, serum immunoglobulin levels and the incidences of positive serological tests were measured in 169 natives with tropical splenomegaly syndrome and compared with results in 30 Caucasians and 62 normal natives. Serum levels of total protein, globulin, gamma-globulin, IgA and IgM; and positive tests for rheumatoid factor, thyroglobulin antibodies, euglobulin and cryoprotein were all higher in all groups of natives than in Caucasians. The highest levels occurred in natives with marked splenomegaly, especially the serum level of IgM. The mean serum IgM in natives with splenomegaly was 11 times that in Caucasians. The polyclonal nature of this hyperimmunoglobulinaemia was confirmed by serum electrophoresis and immunoelectrophoresis. Analytical ultracentrifugation also confirmed the presence of macroglobulinaemia; New Guinea natives resembling Africans with ‘Ie syndrôme splénomégalie-macroglobulinémie’. Tropical splenomegaly syndrome is thought to represent an unusual immunological response to repeated infection with malarial parasites of varying antigenicity. It is suggested that some of the IgG malarial antibody molecules become attached to unparasitized red cells with minimal alterations in both the IgG molecule and the red cell. The changes in the IgG molecule are then postulated as the initial stimulus to the rheumatoid factor detected in 36·1% of natives with splenomegaly with the S.S.C.A.T. The alterations in the red cell are postulated as the initial stimulus to the production of cold haemagglutinins detected with Cynomolgus monkey cells in 90% of natives with splenomegaly. Such changes could also account for the presence of antibodies against tanned red cells but there is no obvious explanation for the presence of thyroglobulin antibodies in 35·5% of natives with splenomegaly. The clarification of these postulates will involve confirmation of the malarial aetiology of tropical splenomegaly syndrome and demonstration of the attachment of IgG malarial antibody molecules to unparasitized red cells.