Post-exposure prophylaxis for HIV.
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Anti-HIV Agents↗
Biomedical subjects
V Gathiram
Publications and source records attributed to V Gathiram.
Invasive amoebiasis is associated with the development of anti-neutrophil cytoplasmic antibody.
Features of tissue damage in invasive amoebiasis, in particular polymorphonuclear neutrophil (PMN) degranulation and vasculitis, bear resemblance to that seen in Wegener's granulomatosis, the latter being associated with the presence of anti-neutrophil cytoplasmic antibodies (ANCA). We therefore tested sera from patients with confirmed amoebic liver abscess (ALA) for the presence of ANCA by means of an indirect fluorescent antibody test using pure neutrophils as substrate. ANCA was detected in 97.4% of amoebic sera; the pattern of staining was cytoplasmic, homogeneous, without central accentuation (C-ANCA). A proteinase 3 (PR3) ELISA demonstrated PR3 specificity in 75% of C-ANCA-positive ALA sera. Possible explanations are (i) a cross-reacting antibody to a component of Entamoeba histolytica, or (ii) an antibody to PMN components released, and possibly modified, by the action of E. histolytica on PMN. It is possible that this antibody contributes to the pathogenesis of invasive amoebiasis.
Adult↗
Control of an amoebiasis outbreak in the Philippi area near Cape Town.
Previous studies in Durban have shown that serological investigations, in combination with iso-enzyme electrophoresis, are invaluable for monitoring the endemicity of pathogenic strains of Entamoeba histolytica. We therefore proposed that antibody profiles could be used to detect epidemic situations. An outbreak of amoebiasis in the normally non-endemic Philippi area near Cape Town provided an opportunity for testing this hypothesis. Seven of 9 patients presenting at a district hospital with invasive amoebiasis originated from a single farm in Philippi. Iso-enzyme electrophoresis and serological investigations were used to monitor the endemicity of amoebiasis on 16 of the 49 farms in this district. In an attempt to contain disease transmission all inhabitants on farms from which patients came (including those where cyst-passers were identified) and all seropositive subjects were treated. The antibody profiles proved invaluable for confirming that the farm from which the hospitalised patients originated was the central focus of the outbreak, and also identified subjects infected with pathogenic zymodemes of E. histolytica on the adjacent 4 farms. On all 5 of these farms, 62.5-100% of seropositive subjects were strongly positive. In contrast weak to negative serological responses occurred on the remaining 11 farms. In addition the success of treatment was indicated by a notable drop in strong seropositive responses on the affected 5 farms to 11.5% within 9 months. The infection pathways implied that the pathogenic strain of E. histolytica was introduced into this non-endemic area by a foreigner from an endemic area; this suggests that the pathogenicity of E. histolytica is an immutable stable feature.
Animals↗
Secretory immunoglobulin A antibodies to the galactose-inhibitable adherence protein in the saliva of patients with amebic liver disease.
Monoclonal antibodies directed against the 260-kD galactose-inhibitable adherence protein (GIAP) of Entamoeba histolytica inhibit binding of amebic trophozoites to purified colonic mucins, suggesting that anti-GIAP secretory immunoglobulin A (sIgA) may have a role in host defense in invasive amebiasis. We determined by enzyme-linked immunosorbent assay (ELISA) whether a salivary anti-GIAP sIgA response was present in patients from the Republic of South Africa with invasive E. histolytica infection. In 13 patients with amebic liver abscess (ALA), salivary anti-GIAP sIgA was significantly higher (mean +/- SD optical density [OD] = 0.448 +/- 0.258) than that determined for seven South African adult patients hospitalized with nonamebic illness (0.084 +/- 0.072; P = 0.002), seven healthy South African Adults (0.194 +/- 0.119: P = 0.025), and seven healthy adults from Charlottesville, Virginia (0.036 +/- 0.023; P = 0.004). Of the patients with ALA, nine had acute disease, and four had been cured of amebiasis 2-8 months previously. There was no significant difference between these two groups in the anti-GIAP sIgA levels. All ALA patients had a high titer serum anti-amebic antibody response, and there was no direct correlation between the level of anti-GIAP salivary IgA and anti-GIAP serum antibodies (R = 0.187). These findings demonstrate that the E. histolytica GIAP is a mucosal antigen in naturally occurring invasive E. histolytica infection.
Adult↗
Immunological similarity between the 170 kD amoebic adherence glycoprotein and human beta 2 integrins.
Amoebiasis is an important cause of morbidity and mortality in developing countries. Virulence of Entamoeba histolytica depends on the trophozoite's being able to bind to colonic epithelium; binding is mediated by the 170 kD subunit of a 260 kD lectin. We found, by microcytofluorometry and western blotting studies, that this 170 kD subunit protein shares an epitope with human beta 2 integrins--a subfamily of cell-surface glycoproteins expressed exclusively on leucocytes and involved in many adhesive and signalling interactions. The immunological similarity between these proteins may explain the trophozoite's ability to bind to and invade colonic epithelium.
Amebiasis↗
Pancytopaenia associated with disseminated tuberculosis, reactive histiocytic haemophagocytic syndrome and tuberculous hypersplenism.
A 38-year-old black male is reported with a rare combination of disseminated tuberculosis together with a reactive histiocytic haemophagocytic syndrome and tuberculosis hypersplenism. Tuberculosis and histiocytic haemophagocytosis were diagnosed on bone marrow examination. The pancytopaenia and splenomegaly which were present on admission did not resolve despite adequate anti-tuberculosis chemotherapy. Prior to splenectomy the patient continued to have a marked thrombocytopenia which resulted in recurrent bouts of epistaxis; splenectomy together with tuberculostatic therapy was curative for the condition. The patient remains well with normal blood counts 1 year later.
Adult↗
Differentiation of pathogenic Entamoeba histolytica infections from nonpathogenic infections by detection of galactose-inhibitable adherence protein antigen in sera and feces.
We determined whether epitope-specific monoclonal antibodies to the galactose-inhibitable adherence protein (GIAP) of Entamoeba histolytica could be used in an enzyme-linked immunosorbent assay (ELISA) to detect antigen in serum and feces and differentiate between nonpathogenic zymodemes and the potentially invasive pathogenic organisms that require treatment. Overall, 57% of subjects from Cairo, Egypt, with symptomatic intestinal amebiasis and 42% with asymptomatic infection possessed GIAP antigen in their sera, whereas 4% of uninfected controls or subjects with other parasitic infections possessed GIAP antigen in their sera (P < 0.001). In subjects from Durban, South Africa, only 6% of uninfected controls or those with nonpathogenic E. histolytica infection were positive for GIAP in serum, whereas 3 of 4 with asymptomatic pathogenic intestinal infection and 75% with amebic liver abscess were positive for GIAP in serum. Fifteen stool samples from patients with intestinal amebiasis were available for study; all had a positive ELISA result for fecal GIAP antigen. Epitope-specific monoclonal antibodies identified 8 of 15 subjects with fecal antigen from pathogenic strains. Seven of those eight subjects had adherence protein antigen in their sera, whereas none of seven with apparent nonpathogenic E. histolytica infection had adherence protein antigen in their sera. In summary, we were able to detect E. histolytica adherence protein antigen directly in serum and fecal samples by ELISA. The presence of amebic antigen in serum demonstrated 94% specificity for pathogenic E. histolytica infection, and amebic antigen is present during asymptomatic intestinal infection. In conjunction with antibody detection, this method should be very useful in the diagnosis and management of intestinal amebiasis.
Animals↗
Morbidity from falciparum malaria in Natal/KwaZulu.
Plasmodium falciparum malaria is endemic in the northern KwaZulu areas of South Africa. The clinical morbidity produced by this parasite has not been studied since the institution of the present malaria control programme. Fifty-nine patients were prospectively studied at a peripheral clinic during the peak malaria season; symptoms and signs of the infection, parasite loads, haemoglobin values and leucocyte counts were recorded in all patients. Haemoglobin and leucocyte counts were also measured in 37 control subjects without malaria. The commonest symptoms were persistent headache (100%), rigors (98%) and myalgia (93%). None of the patients presented with coma, pulmonary oedema, hypoglycaemia or algid malaria. Splenomegaly was found in 49%, hepatomegaly in 20% and mental confusion in 5% of patients. Mean parasite load was 1.71% and 57% of patients had parasite loads of < 1%. Anaemia of < 10 g/dl was significantly more frequent (P < 0.0001) in the patient group than in the control group. Leucopenia (white cell count < 4.0 x 10(9)/l) was present in 12 of 50 patients in whom it was measured compared with 2 controls (P = 0.0175). The results show a wide range of morbidity, without severe complications as presenting manifestations. Symptomatic infection in the presence of low parasite loads suggests that there may be little or no immunity in this population.
Adolescent↗
The emergence of multi-antibiotic-resistant strains of Salmonella typhi in northern Natal-KwaZulu.
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Drug Resistance, Microbial↗
Use of a recombinant 170-kilodalton surface antigen of Entamoeba histolytica for serodiagnosis of amebiasis and identification of immunodominant domains of the native molecule.
We expressed the gene that encodes one of the major surface antigens of Entamoeba histolytica, the 170-kDa protein (1,270 amino acids), as a glutathione S-transferase fusion protein containing amino acids 1 to 1202 (lacking the putative transmembrane and cytoplasmic regions) and as separate fusion proteins containing each of three major domains of the 170-kDa molecule. Lysates from bacteria induced to express one of these proteins were used as the target antigens in a Western blot (immunoblot) analysis to determine whether a recombinant 170-kDa antigen could serve as the basis for a serologic test used to detect invasive amebiasis and whether there are differences in humoral immunogenicity among the three major domains of the 170-kDa antigen. Among patients with invasive amebiasis from three major areas where the disease is endemic and two sites in the United States, 54 (90%) of 60 had antibodies to the recombinant 170-kDa protein. Among 37 patients from regions where the disease is endemic and 20 patients from the United States without amebic disease, 1 (2%) of 57 had antibodies to the recombinant 170-kDa protein. We found significant differences in seroreactivity to each of three major domains of the molecule among patients seropositive for the complete construct, ranging from 100% seroreactivity with the fusion protein containing the domain designated cysteine rich and 89% seropositivity with the fusion protein incorporating a portion of the region designated cysteine poor to only 9% seropositivity for the fusion protein containing the pseudorepeat domain. Our study indicates that a serologic test based on the recombinant 170-kDA antigen could serve as a highly sensitive and specific test for acute invasive amebiasis.
Animals↗
Stability of the zymodemes of Entamoeba histolytica in culture.
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Animals↗
An outbreak of multiresistant Salmonella typhi in South Africa.
Typhoid fever caused by Salmonella typhi remains endemic to many parts of South Africa, including Natal and KwaZulu, Northern Transvaal and the Transkei. Until recently, the majority of S. typhi isolates from South Africa have remained susceptible to ampicillin/amoxycillin and chloramphenicol, and only three cases of typhoid due to multi-antibiotic resistant strains of S. typhi have been documented. Ampicillin/amoxycillin and chloramphenicol are, therefore, still recommended as first line therapy for patients with typhoid fever in this country. We describe a cluster of six cases of typhoid caused by S. typhi that was resistant to ampicillin, chloramphenicol and trimethoprim-sulphamethoxazole. All these patients presented over a 3-month period; the patients were from three adjacent districts in the Northern Natal area of South Africa. The high rate of intestinal perforation (two of six) was a direct consequence of inappropriate antibiotic treatment. Failure of surgical intervention, renal impairment as well as delay in starting appropriate antibiotic treatment were factors contributing to the high mortality (three of six). The good clinical outcome in the remaining three patients probably resulted from treatment with appropriate antibiotics; however, mild disease in two of these patients may have been a contributing factor. All isolates showed high minimal inhibitory concentrations (MIC) of greater than or equal to 256 micrograms/ml to ampicillin, chloramphenicol and trimethoprim-sulphamethoxazole. The isolates were all highly sensitive to the third generation cephalosporins (MIC less than or equal to 0.06 micrograms/ml) and quinolones (MIC less than or equal to 0.03 micrograms/ml). Conjugation studies suggest a genetic transfer of resistance, probably plasmid mediated. The presence of beta-lactamase and chloramphenicol acetyl transferase enzymes in all six isolates tested would account for the resistance to ampicillin and chloramphenicol respectively. The transfer of such plasmids to erstwhile sensitive strains could conceivably occur in this typhoid-endemic area, where sanitary conditions are poor and living conditions crowded, thus further exacerbating the problem. It is recommended that in areas where such multiresistant strains are encountered, the third generation cephalosporins or quinolones be used as empiric therapy for typhoid fever.
Adult↗
Serodiagnosis of invasive amebiasis using a recombinant Entamoeba histolytica protein.
One hundred eight serum samples from 106 patients were examined by Western blot analysis for the presence of antibodies to a recombinant fusion protein containing the sequence of the newly described serine-rich Entamoeba histolytica protein (SREHP). Among patients with invasive amebiasis from Durban, Republic of South Africa; San Diego, Calif; Mexico City, Mexico; and St Louis, Mo, 53 (82%) of 65 had antibodies to SREHP. In contrast, only one patient (2%) of 43 without acute invasive amebiasis had antibodies to SREHP. The predictive value of a positive test for anti-SREHP antibodies in the detection of acute invasive amebiasis was most marked when analyzed in the patients from Durban, where 11 (92%) of 12 patients who were seropositive for SREHP had acute invasive amebiasis vs 17 (65%) of 26 patients who had a positive serologic diagnosis as determined by agar gel diffusion. The use of a serologic test based on the recombinant SREHP fusion protein may be a useful adjunct to the diagnosis of acute invasive amebiasis in endemic regions.
Amebiasis↗
A comparative assessment of commonly employed staining procedures for the diagnosis of cryptosporidiosis.
Following an increase in the number of reports of Cryptosporidium infections and the problems encountered in detecting these organisms in faecal smears, a comparative assessment of a modification of the Sheather's flotation technique and other commonly employed staining procedures proved the modified Sheather's technique to be most useful in identifying Cryptosporidium oocysts in diarrhoeal stools. This technique not only detected the parasite in the highest number of stools but also proved to be cost-effective and the least time-consuming. Other staining techniques assessed were the modified Ziehl-Neelsen, safranin-methylene blue and auramine-phenol fluorescence. Both the modified Ziehl-Neelsen and the auramine-phenol fluorescence procedures produced nonspecific staining, while the safranin-methylene blue method was found to be the least sensitive technique.
Animals↗
Cryptosporidium infections in children in Durban. Seasonal variation, age distribution and disease status.
One hundred and eleven of 1,229 children (9%) aged less than 10 years admitted to King Edward VIII Hospital, Durban, with gastro-enteritis over a period of 1 year were found to harbour Cryptosporidium. Of these, 96 (89.7%) were less than 2 years of age. Cryptosporidium was the only potential pathogen identified in 80 of these patients (6.5%). The prevalence in paediatric patients without gastro-enteritis was 2.4% (3/124). During the study period Cryptosporidium infections were significantly more prevalent during the high rainfall season (P = 0.03).
Age Factors↗
Monoclonal antibodies directed against the galactose-binding lectin of Entamoeba histolytica enhance adherence.
The Entamoeba histolytica galactose-binding lectin is a surface glycoprotein composed of 170- and 35-kDa subunits. Inhibition of this lectin with galactose or anti-170 kDa subunit polyclonal antibody blocks amebic adherence to target cells and colonic mucin glycoproteins. We describe the properties of 10 mAb with specificity for the 170-kDa subunit. Based on competitive binding studies, six nonoverlapping antigenic determinants on the lectin were identified. The effect of the mAb on adherence of amebic trophozoites to both Chinese hamster ovary (CHO) cells and human colonic mucins was measured. Antilectin antibodies directed against epitopes 1 and 2 enhanced adherence, with the number of amebae having at least three adherent CHO cells increasing with the addition of epitope 1 mAb from 26 +/- 9 to 88 +/- 2% and the binding of colonic mucins increasing from 34 +/- 1 to 164 +/- 3 pg/10(5) amebae. Antibody-enhanced adherence remained 90 to 100% galactose inhibitable, occurred at 4 degrees C and was not Fc mediated. Univalent Fab fragments of epitope 1 mAb augmented mucin binding by 238% and CHO cell adherence by 338%. The binding of purified lectin to CHO cells was increased from 1.1 +/- 0.1 to 2.4 +/- 0.3 ng/10(3) CHO cells by mAb directed to epitope 1, demonstrating that enhanced adherence was due to direct activation of the lectin. mAb to epitope 3 bound to the lectin only upon its solubilization from the membrane and had no effect on adherence. Adherence to CHO cells and mucins was inhibited from 50 to 75% by mAb to epitopes 4 and 5; epitope 6 mAb inhibited amebic adherence to CHO cells but not mucins. The pooled sera from 10 patients with amebic liver abscess blocked the binding to the 170-kDa subunit of mAb directed to all six epitopes. Striking individual variations in the effects of immune sera on adherence were observed. Although the sera of all 44 South African patients with amebic liver abscess had high titer anti-lectin antibodies, 16 patients' sera significantly (more than 3 SEM) enhanced adherence whereas 25 patients' sera significantly inhibited adherence. Antilectin antibodies exert profound functional effects on the interaction of E. histolytica with target cells and human colonic mucins. Exploration of the clinical consequences of adherence-enhancing and inhibitory antibody responses may give insight into the role of antilectin antibodies in immunity to invasive amebiasis.
Amebiasis↗
Clinical diagnosis of cardiac beriberi.
The clinical features of 28 patients with biochemically proven cardiac beriberi were prospectively studied. Patients recruited over a 2-year-period fell into two groups: (i) those with signs of hyperdynamic circulation; and (ii) those presenting with heart failure and circulatory shock with or without metabolic acidosis. All patients showed a dramatic response to intravenous thiamine; in group 1 the hyperdynamic state resolved within hours and in group 2 there was an immediate rise in the blood pressure with gradual resolution of the acidosis in 6-8 hours. Two patients in whom the diagnosis was missed died soon after admission to hospital. A notable finding was that even in the presence of peripheral circulatory shock, patients with beriberi had preservation of the femoral pulses often with 'pistol shots' and femoral bruit; this finding has clinical value in the diagnosis of acute cardiovascular beriberi (shoshin beriberi).
Acidosis, Respiratory↗
Association of serum antibodies to adherence lectin with invasive amebiasis and asymptomatic infection with pathogenic Entamoeba histolytica.
The recognition of the Entamoeba histolytica galactose-inhibitable adherence lectin by antibodies was studied using sera obtained from subjects in South Africa with an amebic liver abscess or asymptomatically pathogenic or nonpathogenic E. histolytica infection and from uninfected regional controls. In addition, sera from healthy American controls or Americans known to be infected with other parasites were studied. Of the 95 sera containing antibodies to total parasite protein, 95% demonstrated antibodies to the 170-kDa heavy subunit but not to the 35-kDa light lectin subunit. All sera (n = 253) were tested by ELISA for antibodies to lectin: 99% from liver abscess patients and all 4 from individuals asymptomatically infected with pathogenic E. histolytica were positive; all from the 40 healthy American controls and the 29 infected with other parasites were negative (P less than .01). The prevalence of serum anti-lectin antibodies was identical (25%) in asymptomatic South Africans with either a nonpathogenic infection or a negative stool culture for E. histolytica. Thus, the presence of serum antibodies to lectin seems to indicate current or prior invasive amebiasis or asymptomatic intestinal infection with pathogenic E. histolytica.
Amebiasis↗