Sera from patients with poststreptococcal glomerulonephritis contain antibodies to glomerular heparan sulfate proteoglycan.

Antibodies, found in human sera from patients with poststreptococcal glomerulonephritis, against proteoglycans (PG) derived from bovine and human glomeruli were investigated. PG were isolated by 4 M guanidine-HCl extraction of whole glomeruli, followed by DEAE-Sepharose CL-6B ion exchange chromatography. The anionic fractions were further purified by chromatography on Sepharose CL-4B. Biochemical analysis of the two resulting peaks revealed the presence of high molecular weight anionic material containing protein, uronic acid, glucosamine, and galactosamine. Enzymatic and chemical susceptibilities indicated the presence of heparan sulfate PG and a galactosamine-containing PG. Immunologic studies revealed the presence of anti-PG antibodies to both PG peaks of the Sepharose CL-4B column in glomerulonephritis sera. Inhibition studies using an ELISA demonstrated that heparan sulfate was a major antigenic determinant. Cross-reactivity with both mammalian and streptococcal hyaluronate was noted. Inhibition studies also indicated the presence of a second antigenic site containing N-acetylgalactosamine, possibly representing chondroitin or dermatan sulfate PG.

Antibodies to basement membrane collagen and to laminin are present in sera from patients with poststreptococcal glomerulonephritis.

Sera from patients with poststreptococcal glomerulonephritis (PSGN) known to have antibodies to proteoglycans were studied for the presence of antibodies against other basement membrane (BM) components. BM collagen (type IV) was isolated in the native state by extracting bovine anterior lens capsule (ALC) with 0.5 M acetic acid. The 7-S (collagenous) domain and the NC-1 (noncollagenous) domain of type IV collagen were obtained after bacterial collagenase digestion of ALC followed by gel filtration. Laminin was isolated from the mouse EHS tumor and fibronectin from human plasma. Immunologic studies, using an ELISA and electroimmunoblot, revealed the presence of antibodies that reacted with intact, native type IV collagen and the 7-S collagenous domain of this molecule. Reaction with the NC-1 (noncollagenous) domain was minimal, and not higher than that obtained with control sera. Laminin reaction strongly with the patients' sera, but fibronectin did not. Unlike sera from patients with Goodpasture syndrome, which contain antibodies primarily against the NC-1 (noncollagenous) domain of type IV collagen, sera from patients with acute PSGN contain antibodies against all the major macromolecular components of BM. This difference in immunologic reactivity may account for the observed differences in the pathologic picture at the glomerular level.

Immunoglobulins and complement components in synovial fluid of patients with acute rheumatic fever.

Three components of complement and six other serum proteins were assayed in synovial fluid and serum samples from 25 patients with acute rheumatic fever in Trinidad. The resulting data indicate a relative decrease in both early and late components of complement within the synovial fluids which suggests local activation by immune complexes. Such activation of complement within the joint spaces may play a primary role in development of the inflammatory arthritis of acute rheumatic fever.

Changing types of nephritogenic streptococci in Trinidad.

The relation of seven different M types of streptococci to acute glomerulonephritis associated with skin lesions in South Trinidad has been studied by means of type-specific antibody assays as well as by isolation and identification of the strains. The data indicate that, one after another, five of these strains have prevailed among patients with acute glomerulonephritis during the past five years. At least three of the strains (M-types 55, 49, 57, and/or 60) were associated with epidemic increases in nephritis cases. The appearance of five consecutively predominant types of nephritogenic streptococci during a relatively short period of time is in contrast to the continuing prevalence of M-type 12 strains among nephritogenic streptococci primarily associated with respiratory infections in temperate zones. These observations suggest that the skin sores commonly found on children in tropical Trinidad, provide a particularly suitable environment for development of nephritogenic types. It remains to be seen whether these types will recur or whether new types will continue to emerge in Trinidad.

Presence of a non-HLA B cell antigen in rheumatic fever patients and their families as defined by a monoclonal antibody.

Numerous investigators have suspected that there is a genetic predisposition to rheumatic fever (RF). In this context we have recently produced a series of monoclonal antibodies directed against B cells obtained from RF patients one of which, labeled D8/17, identifies a B cell antigen present in 100% of all RF patients studied. While the highest percentage of positive cells were exhibited by RF probands (33.5% +/- SE), the percentage of cells in unaffected siblings and parents was 14.6 and 13%, respectively. The percentage of positive cells in APSGN probands, unaffected siblings, and parents was 2.96, 3.86, and 2.8%, respectively. A low level of B cells (5-7%) bearing the D8/17 marker was seen in control patients. The segregation pattern of the phenotypes defined by the percentage of D8/17 positive cells within HLA-typed RF families are consistent with an autosomal recessive mode of inheritance not associated with the human MHC system. We postulate that these phenotypes indicate the presence of at least one necessary genetic factor for susceptibility to RF.

Streptococcal serotypes newly associated with epidemic post-streptococcal acute glomerulonephritis.

The increasing incidence of reported scabies in Trinidad, from 24.2/100,000 population in 1984 to 59.5/100,000 in 1985, led to a careful monitoring in 1986 of all patients with post-streptococcal acute glomerulonephritis (PSAGN). There were 181 cases of PSAGN; 84 beta-haemolytic streptococcal isolates from 72 patients were sent to the Central Public Health Laboratory, Colindale, for grouping and serotyping. The PSAGN epidemic of 1986 was bimodal. Streptococci of M-type 73 appeared to be associated with the first phase (March-May) and comprised 20% of the isolates serotyped. New to Trinidad, streptococci of M-type 48 (4% of the isolates serotyped) preceded the first phase of the epidemic and were isolated from two patients with PSAGN. Provisional type (PT) 5757, also new to Trinidad, had been previously identified only among serotypes from the United Kingdom and the Federal Republic of Germany. This type was isolated from seven patients, in six from skin lesions and in one from the throat. PT 5757 occurred during the first wave of the epidemic and comprised 14% of the strains serotyped. Thus, the first wave of the bimodal epidemic involved serotypes M73, M48 and PT 5757. The more intense second phase (July-October) was associated with the previously documented nephritogenic M-type 55.

Epidemic scabies in four Caribbean islands, 1981-1988.

Scabies infestation has been reported to the PAHO/WHO Caribbean Epidemiology Centre (CAREC) from Trinidad and Tobago (T&T), Grenada, Dominica, the Turks and Caicos Islands (T&CI) and, more recently, St Lucia. Epidemic scabies was being reported from T&CI in 1981 (1200/100,000 population), but there were no reports from T&T until 1982 (8/100,000). The first phase of the bimodal epidemic in Grenada occurred between 1982 and 1984 (132/100,000) and the explosive second phase from 1985 to 1987 (474-699/100,000). In T&T there was a low incidence of scabies until 1985 (0-59/100,000) and in Dominica the rate fluctuated (67-14/100,000) during the same period. From 1986 to 1988, scabies infestation reached epidemic proportions in T&T (410-709/100,000) and fluctuated in Dominica (108-117/100,000). In Tobago alone, scabies was not reported until March 1986, and by December the incidence rate was 105/100,000; by 1988 it had increased to 1124/100,000 population. Although no secondary infections have been reported from Grenada, Dominica, T&CI or St Lucia, T&T has reported increased streptococcal skin infections and epidemic post-streptococcal acute glomerulonephritis (PSAGN). The observed trend of increasing scabies infestation, increasing streptococcal isolates from skin lesions, and increasing PSAGN in T&T is noteworthy.

Phagocytic, serological, and protective properties of streptococcal group A carbohydrate antibodies.

Group A streptococcal antibodies promote phagocytosis of several different strains of GR A streptococci. These antibodies passively protect against an in vivo mouse challenge model.

Ciguatera fish poisoning in industrial ship crewmembers: a retrospective study in a seaport general practice in Trinidad and Tobago.

The objective of this study was to outline the epidemiology of Ciguatera fish poisoning as seen in a general practice serving two industrial seaports in Trinidad and Tobago, in order to highlight the potential public health implications. A retrospective study was undertaken of all the cases of Ciguatera fish poisoning identified between November 1, 1992 and October 31, 1998 in a seaport general practice to identify signs, symptoms and treatment. An investigation of one outbreak was undertaken. Four outbreaks affecting 42 male ship crewmembers were identified. The suspect fish were caught in northern Caribbean waters en route to Trinidad and Tobago. The most common early symptoms were diarrhoea, vomiting, abdominal cramps, pruritus and tiredness. In the third outbreak, dysaesthesia was common. Progression to muscular weakness, ataxic gait, unsteadiness and other neurotoxic signs were seen in moderate to severe disease. Hypotension was an important prognostic sign in the initial case. Treatment was symptomatic and supportive and included vitamins B12 and BCO, folic acid, prostigmine, steroids and antihistamines as indicated. In the investigation of the second outbreak, the relative risk of 'eating fish meat' was 5 (95% CI 1.45, 17.27, p < 0.0001). Abdominal symptoms, pruritus, and muscle weakness with a history of consuming a fish-meal were diagnostic indicators of 'ciguatera fish poisoning.' All cases were industrial ship crewmembers. It is suggested that increased clinician awareness with early and appropriate treatment, and focussed public health intervention may help limit the potential public health impact of ciguatera poisoning in industrial ship crewmembers and other fish-consuming communities in the future.

Falciparum malaria treated with a chloroquine suspension administered rectally in Trinidad.

A new mode of administering malaria chemotherapy to patients unable to tolerate oral medication is described. A patient with Plasmodium falciparum malaria, severe hyponatremia and hypokalaemia who regurgitated oral treatment of chloroquine phosphate and pyrimethamine and sulfadoxine (Fansidar) is presented. But neither chloroquine nor quinine intravenous formulations were available locally. As the patient was deteriorating, a suspension of chloroquine phosphate was prepared and administered rectally, resulting in a decline in the level of parasitaemia from ++++ to ++ within 48 hours. The patient improved, and further clinical management was uncomplicated.

Leucocyte suppression in treatment of 72 patients with paraquat poisoning.

72 patients who had ingested more than 10 ml 20% or 24% liquid paraquat concentrate were treated for 2 weeks with high doses of dexamethasone and cyclophosphamide, forced diuresis with liberal potassium supplements, and, to eliminate paraquat from the gut, Fuller's earth suspension, activated charcoal, and magnesium sulphate. 52 patients (72%) survived. Serum paraquat concentrations were measured retrospectively in samples from 25 patients. 18 had levels of 2-76 mg/l; 6 survived and 12 died. The other survivors were a patient with a serum level of 0.5 mg/l at 24 h and 6 with positive urine tests but no measurable paraquat in serum collected 8-16 h after admission.

Spontaneous intraperitoneal rupture of a neurogenic bladder; the importance of ascitic fluid urea and electrolytes in diagnosis.

Spontaneous intraperitoneal bladder rupture in a 38 year old man with a spastic paraparesis since infancy is described. Delayed diagnosis resulted in peritoneal autodialysis so providing an opportunity for documentation of biochemical abnormalities. Surgery resulted in a successful outcome. The literature on this rare condition is outlined and difficulties in diagnosis are discussed. The diagnostic value of urea and electrolyte levels in ascitic fluid is emphasized.