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Biomedical subjects

A Zumla

Publications and source records attributed to A Zumla.

At least 19 recordsLinked to original sources

HEp-2 cell-adherent Escherichia coli in patients with human immunodeficiency virus-associated diarrhea.

Diarrhea occurs commonly in African human immunodeficiency virus (HIV) infections. A case-control (HIV-positive vs. -negative) study of adults with diarrhea was done in Lusaka, Zambia, to determine the prevalence of intestinal infection by HEp-2 cell-adherent Escherichia coli. Adherent E. coli were more common in HIV-positive patients with acute diarrhea than among HIV-negative controls (60% vs. 33%) and were found significantly more often in HIV-positive patients with chronic diarrhea than among HIV-negative controls with chronic diarrhea (79% vs. 17%, P < .002). Adherent strains were found significantly more often among HIV-positive patients (69%) than in 22 asymptomatic subjects (36%, P < .02). The HEp-2 cell adherence of the E. coli strains did not show a common pattern. Adherent bacteria were also observed in colonic biopsies from 32% of Zambians with chronic diarrhea who underwent endoscopy. Adherent E. coli may be an important cause of HIV-associated diarrhea in Zambia.

Acute Disease

Intestinal parasites in HIV-seropositive Zambian children with diarrhoea.

We undertook a study over a period of 9 months to define the frequency of parasitic infections in hospitalized children with diarrhoea between the ages of 15 months and 5 years. Every alternate day, mothers of all children admitted with diarrhoea between 09.00 hours and 12.00 hours to one of the wards of the Department of Pediatrics and Child Health of the University Teaching Hospital (UTH) in Lusaka, Zambia, were interviewed for enrollment of their children into the study. A total of 178 children with diarrhoea were enrolled in the study. Of these 44 (25 per cent) were HIV seropositive and 134 (75 per cent) were seronegative for HIV. Out of 44 HIV-seropositive patients, 20 (45 per cent) had acute diarrhoea and 24 (55 per cent) had chronic diarrhoea. Of the 134 HIV-seronegative patients, 68 had acute diarrhoea (51 per cent) and 66 (49 per cent) had chronic diarrhoea. At least one intestinal parasite was found in 34 out of the 178 children enrolled. The commonest parasites identified were Ascaris and Cryptosporidia. No associations were identified between parasite isolation and the following: age, sex, or socio-economic status. Cryptosporidium spp. was isolated from 6 out of 44 (14 per cent) HIV-seropositive children, while 8 out of 134 (6 per cent) seronegative children had the parasite (P = 0.01). HIV-seropositive children with chronic diarrhoea had significantly higher cryptosporidium identification rates than those HIV-seropositive children with acute diarrhoea [5 out of 24 (21 per cent) patients with chronic diarrhoea compared to 1 out of 20 (5 per cent) patients with acute diarrhoea; (P > or = 0.01)].(ABSTRACT TRUNCATED AT 250 WORDS)

AIDS-Related Opportunistic Infections

Pattern of adult malignancies in Zambia (1980-1989) in light of the human immunodeficiency virus type 1 epidemic.

This study analysed histopathological and haematology records of 7836 neoplasms seen during the period 1980-1989 at the University Teaching Hospital, Lusaka, Zambia. The crude incidence rate of each malignancy per 100,000 adults per year was calculated and the patterns of malignancies were compared for the periods 1980-1983 and 1984-1989, the later coinciding with the advent of the human immunodeficiency virus (HIV) epidemic. The six most common tumours were carcinoma of the cervix (19.6%), Kaposi's sarcoma (7%), bladder carcinoma (6.3%), hepatoma (5.8%), lymphoma (4.6%) and carcinoma of the breast (4.4%). Significant increases in the crude incidence rates of Kaposi's sarcoma (KS) and carcinoma of the breast were observed during the last 6 years of the study period (P = 0.001). Nodal KS showed the most significant rise from a crude incidence rate of 0.25 per 100,000 adults per year in the 1980-1983 period to 1.11 during the 1984-1989 period. In contrast to findings from Europe and the USA, no significant increase in non-Hodgkin's lymphoma was detected in Zambia following the HIV epidemic.

Acquired Immunodeficiency Syndrome

Use of saliva as an alternative to serum for HIV screening in Africa.

Saliva has been recommended as a safe and effective alternative to serum for enzyme-linked immunosorbent assay (ELISA) for HIV antibodies in surveillance programmes in developing countries. We evaluated the use of saliva specimens for detection of HIV antibodies using three different commercially available ELISAs. Saliva specimens from 107 patients selected at random from HIV high-risk (38), medium-risk (27) and low-risk (42) areas of the hospital were screened with the Wellcozyme HIV1 + 2 GACELISA VK61 (recommended for use with saliva), Wellcozyme HIV1 + 2 VK54/55 and Wellcozyme HIV-1 recombinant VK56/57. Of the 107 patients, 50 were positive and 57 negative for antibodies to HIV on confirmatory Western blot testing. For detection of antibodies to HIV in saliva, the Wellcozyme HIV1 + 2 GACELISA VK61 had a sensitivity and a specificity of 98%, the Wellcozyme HIV-1 recombinant VK56/57 a sensitivity and specificity of 96%, and the Wellcozyme HIV1 + 2 VK54/55 a sensitivity of 94% and a specificity of 95%. For detection of antibodies to HIV in serum, the Wellcozyme HIV-1 recombinant VK56/57 had a sensitivity and a specificity of 100%, the Wellcozyme HIV1 + 2 GACELISA VK61 a sensitivity and a specificity of 98%, and the Wellcozyme HIV1 + 2 VK54/55 a sensitivity and a specificity of 96%. This study illustrates that saliva can be used as an alternative to serum for screening for anti-HIV antibodies in African patients.

Developing Countries

Human immunodeficiency virus type-1 infection in Zambian children with tuberculosis: changing seroprevalence and evaluation of a thioacetazone-free regimen.

SETTING: This study was conducted at the Department of Paediatrics and Child Health, University Teaching Hospital (UTH), in Lusaka, Zambia. OBJECTIVES: To monitor the seroprevalence of HIV type-1 in children with tuberculosis and to evaluate the response to anti-tuberculosis therapy using a thioacetazone-free treatment regimen. DESIGN: A prospective cross-sectional study of all consecutive newly diagnosed cases of TB in children from 1 month-15 years of age seen at the University Teaching Hospital (UTH) in Lusaka, Zambia between 1 October 1991 and 31 May 1992. RESULTS: 120 children with a clinical diagnosis of tuberculosis and 167 controls were enrolled in the study. The overall HIV type-1 seroprevalence rate in children with tuberculosis was 55.8% (67/120) compared to 9.6% (16/167) amongst the control group (P < 0.0001: odds ratio = 11.50; 95% CI = 5.99-22.7). Common clinical presentations among children with TB were bronchopneumonia (45/162), miliary TB (30/162) and tuberculous lymphadenopathy (21/33). There were no significant differences in clinical presentation of TB between the HIV-negative and HIV-positive groups. The follow-up of those patients with tuberculosis was poor, with only 65 patients (55%) returning to the clinic for scheduled appointments after discharge. All the 16 patients who died did so within 60 days of discharge from hospital; all of them were seropositive for HIV. There were no deaths among the HIV-negative group. Despite the exclusion of thioacetazone from the treatment regimen, cutaneous reactions occurring within 8 weeks of commencing treatment were observed in 7 of the 65 (11%) patients, 2 of whom developed fatal Stevens-Johnson syndrome. All 7 patients were seropositive for HIV-1. CONCLUSIONS: The seroprevalence rate of HIV type-1 among children with tuberculosis in Lusaka continues to rise; careful monitoring of anti-TB therapy (even in regimens excluding thioacetazone) for potentially lethal side effects should be carried out.

Adolescent

Intestinal secretory IgA immune response against human immunodeficiency virus among infected patients with acute and chronic diarrhea.

Diarrhea is common in patients infected with the human immunodeficiency virus (HIV) in Africa. There has been speculation that HIV itself may cause some of the enteropathy seen. The intestinal secretory IgA (sIgA) response was used to evaluate HIV intestinal infections in Zambian patients with acute and chronic diarrhea. sIgA was extracted from stool specimens and evaluated by an ELISA. Seven (58%) of 12 HIV-positive patients with acute diarrhea and 25 (69%) of 36 HIV-positive patients with chronic diarrhea showed an sIgA response to HIV p24, compared with 1 of 10 HIV-positive patients without diarrhea (P < .025 for acute and P < .001 for chronic diarrhea). The mean duration of diarrhea was significantly longer in patients showing an anti-p24 response. An sIgA response to HIV antigens occurs commonly in infected patients with diarrhea and may provide further evidence of an etiologic role of HIV in the diarrhea associated with AIDS.

Acute Disease

Association of rotavirus and human immunodeficiency virus infection in children hospitalized with acute diarrhea, Lusaka, Zambia.

In Lusaka, Zambia, rotavirus (RV) and human immunodeficiency virus (HIV) infection commonly coexist; 132 (25%) of 537 consecutively studied infants < 5 years old hospitalized with diarrhea were positive for both viral infections. Infants with RV infection were younger than those who were RV-negative (P > .05), and infants with both viruses more frequently experienced dehydration (P < .05). HIV-infected children more often exhibited respiratory symptoms on admission to the study (P < .0001) and were more frequently underweight (P < .0001) than were HIV-negative children, independent of RV infection. The mortality rate was highest in HIV-positive infants (P < .05), and coinfection with RV did not increase the risk of fatality. This study demonstrates that while RV and HIV infections commonly coexist in one region of Africa, RV infection is no more common nor is the illness more severe in HIV-positive infants.

Acute Disease

Gut parasites in HIV-seropositive Zambian adults with diarrhoea.

We undertook a nine month study to define the frequency of parasitic infections in adults with diarrhoea presenting at the medical filter clinic and the Dermatovenereology clinic of the University Teaching Hospital in Lusaka, Zambia. A total of 287 patients with diarrhoea were enrolled in the study; 130 from the adult medicine filter clinic recruitment consulting room and 157 patients from the Dermatovenereology clinic. Of 130 patients from the adult filter clinic, 85 (65%) were HIV-seropositive and 45 (35%) were seronegative for HIV. Out of 85 HIV-seropositive patients, 58 (68.2%) had acute diarrhoea and 27 (31.8%) had chronic diarrhoea. Of the 45 HIV-seronegative patients, 35 (77%) had acute diarrhoea and 10 (23%) had chronic diarrhoea. All of the 157 patients recruited from the Dermatovenereology clinic were HIV-seropositive. Of these, 97 (62%) had chronic diarrhoea; 7 (4%) had acute diarrhoea, and 53 (34%) patients had no diarrhoea. The common parasites detected were Ascaris lumbricoides, hookworm, Entamoeba coli, and Cryptosporidium spp. Isospora belli and Cryptosporidium spp were seen only in the HIV-seropositive group. In the Dermatovenereology clinic there was a statistically significant difference between parasite detection rate of Isospora belli and Cryptosporidium spp in HIV-seropositive patients with chronic diarrhoea compared to asymptomatic HIV-seropositive individuals P < 0.01 and p = 0.05, respectively). A significant difference in detection rates of Entamoeba coli was seen between the HIV-seropositive group in the Dermatovenereology clinic [17 (10.8%) out of 157] compared to 1 (1.5%) out of 85 in the adult medicine filter clinic.(ABSTRACT TRUNCATED AT 250 WORDS)

AIDS-Related Opportunistic Infections

Seroprevalence of human immunodeficiency virus type 1 infection in Zambian children with tuberculosis.

Descriptions in the medical literature of human immunodeficiency virus type 1 (HIV-1) in children with tuberculosis (TB) are scanty. This study determined the seroprevalence of HIV-1 in 237 hospitalized children between the ages of 1 month and 14 years with a clinical diagnosis of TB (125 males and 112 females) and in 242 control children (149 males and 93 females). The overall HIV-1 seroprevalence rate in patients with TB was 37% (88 of 237) compared with 10.7% (26 of 242) among the control group (P < 0.00001: odds ratio 5.37, 95% confidence interval = 3.21 < 5.37 < 9.47). HIV-1 seropositivity in children with TB ranged from 53% (31 of 58) in the 12- to 18-month age group to 14% (9 of 61) in the 10- to 14-year-olds. The risk of TB attributable to HIV infection was 29%. The predominant clinical presentation in both seronegative (84.6%) and seropositive (89.7%) groups was that of pulmonary TB and there were no significant differences in clinical presentation between the two groups of patients. Only 54.8% of the patients attended follow-up clinics regularly whereas 32% were lost to follow-up within 3 months. Bacillus Calmette-Guérin vaccination coverage was 87.3% among TB patients and 90.5% in the controls. No significant differences in B. Calmette-Guérin vaccination rates between the seronegative and seropositive children were seen. Coinfection with HIV and TB in children is now one of the major public health problems in Zambian children.

AIDS-Related Opportunistic Infections

Cutaneous hypersensitivity reactions due to thiacetazone in the treatment of tuberculosis in Zambian children infected with HIV-I.

Tuberculosis is one of the most common infections in Zambian adults and children infected with HIV. In Africa, cutaneous hypersensitivity reactions attributed to thiacetazone during treatment of tuberculosis in adults infected with HIV-I have been well documented. This study monitored adverse drug reactions during treatment for tuberculosis over an 18 month period (1 April 1990 to 31 October 1991) in 237 children with a clinical diagnosis of tuberculosis (125 boys and 112 girls; 88/237 (37%) infected with HIV-I) and 242 control children (149 boys and 93 girls; 26/242 (11%) infected with HIV-I). Twenty two (9%) of the 237 children with tuberculosis developed hypersensitivity skin reactions during the course of treatment. Adverse skin reactions were seen more often in children infected with HIV than in those who were not (odds ratio 11.65, 95% confidence interval 3.07 to 34.88). These represented 19 (21%) of 88 children infected with HIV and three (2%) of 149 children not infected with HIV. These skin reactions occurred after a period of treatment ranging between two and four weeks among 14 children receiving the HST (isoniazid, streptomycin, thiacetazone) regimen and eight children receiving the HSTR (isoniazid, streptomycin, thiacetazone, rifampicin) regimen. Twelve (55%) of the 22 children who reacted adversely to treatment developed the Stevens-Johnson syndrome. All 12 of these children with the Stevens-Johnson syndrome were infected with HIV. The mortality among these children who developed the Stevens-Johnson syndrome was 91% (11 of 12 died within three days of the onset of the reaction). No further reactions were observed in the 11 children who recovered from the cutaneous hypersensitivity reactions after thiacetazone was discontinued over a period of six months of further treatment of tuberculosis. The results of this study were in part responsible for the recommendations put forward by the World Health Organization to avoid the use of thiacetazone in the treatment of tuberculosis in children infected with HIV.

AIDS-Related Opportunistic Infections

Co-expression of human T cell receptor chains with mouse CD3 on the cell surface of a mouse T cell hybridoma.

In this study we demonstrate that human T cell receptor (TcR) chains can be co-expressed with murine CD3 on the cell surface of a murine T cell hybridoma. Human TcR alpha and beta genes from the Jurkat leukaemic cell line were transfected into a TcR-negative mouse T cell hybridoma, TG40. The Jurkat TcR was successfully co-expressed at the cell surface with mouse CD3 components. Brightly staining transfectants were selected by fluorescence-activated cell sorting, and levels of expression comparable to a normal T cell line were achieved suggesting that the human TcR dimer assembled efficiently with the mouse CD3 complex. Northern blot analysis demonstrated similar levels of TcR messenger RNA to those found in the parental Jurkat line. Although we have not formally demonstrated surface expression of the Jurkat TcR alpha chain, the residual alpha gene transcript which is present in murine TG40 line is non-expressible. In order to test the signalling capacity of this human/mouse complex, the transfectants were stimulated with an anti-V beta 8 monoclonal antibody. This stimulus led to interleukin-2 production by the transfectants, demonstrating the delivery of a transmembrane signal. In addition, B10.A mice were immunised with the transfectants, and the antisera from these mice stained the transfectant and the Jurkat cell line, but not the parental T cell hybridoma. This interspecies transfection approach should now permit us to explore the requirements for T cell activation, the constraints on TcR alpha beta chain pairing, and creates ideal reagents for inducing a mouse anti-human TcR-specific response with a view to producing panels of anti-human TcR monoclonal antibodies.

Animals

Use of a murine T-cell hybridoma expressing human T-cell receptor alpha- and beta-gene products as a tool for the production of human T-cell receptor-specific monoclonal antibodies.

We describe the production of mouse monoclonal antibodies specific for the human TcR using as the immunogen transfected murine T-cell hybridoma cells coexpressing mouse CD3 with human Jurkat TcR alpha and beta chains. The shortage of monoclonal antibodies (mAbs) specific for the human TcR-V alpha and V beta families reflects the difficulties in their production by conventional methods using whole human T cells or purified soluble receptors as immunogens. As an alternative strategy to circumvent these difficulties, we have generated a transfected mouse T-cell line expressing a human (Jurkat) TcR alpha beta dimer in a complex with mouse CD3. The parental mouse T-cell line, TG40, is a cell surface TcR-negative, cytoplasmic CD3-positive variant of the mouse T-cell hybridoma 2B4. The human-TcR alpha beta expressing mouse transfectant was used to immunize mice with the same genetic background as the parent mouse T-cell line, and a human TcR-specific response was successfully achieved. MAb-producing hybridomas were generated by fusing spleen cells from the immunized mice with the mouse myeloma cell line NSO. Of 124 hybridoma supernatants screens, 72 showed reactivity to the human T-cell line Jurkat. Twenty-four of the hybridomas producing human (Jurkat) TcR-specific antibodies were cloned and screened for reactivity to Jurkat TcR. Several IgG2b and IgM mAbs specific for the Jurkat T cell line were selected on the basis of their ability to modulate surface CD3 expression on Jurkat cells. Most of the antibodies do not stain other TcR-expressing human T cell leukemia cell lines, implying specificity for the variable domains of the Jurkat TcR.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

Chemotherapy and immunity in opportunistic parasitic infections in AIDS.

Parasitic diseases are endemic in parts of the tropics, but there is no convincing evidence that their prevalence or incidence is increasing due to the HIV epidemic. Available scientific data on parasitic infections in patients with the Acquired Immunodeficiency Syndrome (AIDS) suggests a predominance of Pneumocystis carinii, Toxoplasma gondii and Cryptosporidium spp. For reasons which are unclear, parasitic infections such as Plasmodium falciparum, Strongyloides stercoralis and Entamoeba histolytica, where cell-mediated immune responses are also thought to be significant, do not appear to be opportunists of importance. It is being increasingly recognized that chemotherapy for parasitic diseases has a host-dependent component, although scientific data on this subject remain scanty. The management of opportunistic parasitic infections in patients infected with HIV is dogged by failures and relapses, aptly illustrating the notion of the relationship between chemotherapy and the immune response. This review discusses the immunity and chemotherapy of opportunistic parasite infections in patients infected with the Human Immunodeficiency Virus (HIV).

AIDS-Related Opportunistic Infections