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Biomedical subjects

A Zumla

Publications and source records attributed to A Zumla.

At least 91 records · Page 5Linked to original sources

Sarcoidosis and leprosy--an epidemiological, clinical, pathological and immunological comparison.

Whilst the close relationship between sarcoidosis and tuberculosis has long been recognized, the similarity of sarcoidosis to leprosy has remained in the background. In most of the developing world sarcoidosis has been apparently eclipsed by the high prevalence of these two common mycobacterial diseases. The relevant epidemiological, clinical, immunological and pathological features of leprosy and sarcoidosis are compared and contrasted.

Developing Countries↗

DF-2 infection.

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Animals↗

Studies of a common idiotype PR4 in autoimmune rheumatic disease.

A new common idiotype, designated PR4, is described. This idiotype was originally identified on a human hybridoma-derived monoclonal antibody from a patient with leprosy, which binds the major Mycobacterium leprae-derived antigen, phenolic glycolipid-1, poly(ADP)-ribose, DNA, and poly(dT). The PR4 idiotype was found in patients with systemic lupus erythematosus (SLE) (70%), rheumatoid arthritis (40%), and Sjögren's syndrome (15%). It was not, however, found in the spouses of the SLE patients or (unlike other lupus idiotypes) in their healthy first-degree relatives. Although no correlation between PR4 idiotype levels and disease activity in SLE was found, a subset of rheumatoid arthritis patients with high levels of the idiotype was identified.

Antibodies, Anti-Idiotypic↗

Human monoclonal antibodies to phenolic glycolipid-1 from leprosy patients cross react with poly(ADP-ribose), polynucleotides and tissue bound antigens.

Antibodies which bind to poly(ADP-ribose) have been described in Systemic Lupus Erythematosus (SLE) and a variety of infectious diseases. Two IgM kappa human monoclonal antibodies (MAbs), TH3 and PR4, produced from the fusion of peripheral blood lymphocytes of leprosy patients with the GM4672 lymphoblastoid cell line, were found to bind to poly(ADP-ribose) in direct binding and inhibition ELISAs. Significant inhibition of binding of these MAbs to poly(ADP-ribose) occurred with phenolic glycolipid-1, the M. leprae specific glycolipid, ssDNA, dsDNA, poly(dT), as well as poly(ADP-ribose) itself. Up to 80% of binding of TH3, and 90% of binding of PR4, to poly(ADP-ribose) was inhibited by 10 mcg of ssDNA suggesting that there may be sharing of some conformational determinants. Although the serological binding profiles of TH3 and PR4 are similar, only PR4 was found to bind to basal keratinocytes of normal human interfollicular epidermis and astrocyte cytoplasm in normal brain tissue. These results support the concept that an antibody binding site may accommodate more than one epitope. Furthermore, small differences in antigen binding potential may distinguish relatively innocuous antibodies from those which may be more pathogenic.

Antibodies, Monoclonal↗

Dysgonic Fermenter-type 2: an emerging zoonosis. Report of two cases and review.

We report Dysgonic Fermenter-type 2 septicaemia presenting in two previously healthy individuals, and review 52 cases of infection with Dysgonic Fermenter-type 2 reported in the English language literature. This zoonosis is usually acquired through contact with dogs and cats. Infection often presents with little warning to patient or physician and carries a high mortality. The immunosuppressed patient, those without a spleen, alcoholics and those with chronic disease appear to be most susceptible, although the healthy individual is also prone to infection. The infection is probably underdiagnosed due to difficulties in isolating Dysgonic Fermenter-type 2 by conventional blood culture techniques. Clinical and microbiological awareness is of prime importance in the early diagnosis of this potentially lethal infection.

Animals↗

Human monoclonal antibodies to phenolic glycolipid-I derived from patients with leprosy, and production of specific anti-idiotypes.

Human monoclonal antibodies (mAb) were produced by hybridomas derived from fusion of the GM4672 lymphoblastoid cell line and peripheral blood mononuclear cells from leprosy patients. Hybridoma supernatants were screened for immunoglobulin (Ig) secretion, binding to Mycobacterium leprae, phenolic glycolipid-I (Phen GL-I), the unique M. leprae glycolipid and single-stranded(ss)DNA by ELISA. On the basis of direct-binding ELISAs, two IgMk mAb (PR4 and TH3) were selected for characterization. PR4 and TH3 bound to M. leprae, Phen GL-I and ssDNA; PR4 also bound to M. avium and M. kansasii and TH3 to M. kansasii. Inhibition assays demonstrated that these antibodies did not bind to the terminal disaccharide of Phen GL-I. In addition, both PR4 and TH3 bound to several autoantigens: ssDNA, double-stranded(ds)DNA and poly(ADP-ribose) but not RNA. PR4 and TH3 were used for preparation of rabbit anti-idiotype antisera. Inhibition studies demonstrated that the affinity purified rabbit anti-idiotype antisera were specific for their respective idiotype and that both Phen GL-I and ssDNA inhibited binding of idiotype to its anti-idiotype. PR4, but not TH3, was found to be similar but not identical to the 16/6 idiotype originally identified on a human monoclonal anti-DNA antibody derived from a patient with systemic lupus erythematosus (SLE).

Antibodies, Antinuclear↗

A serological study on primary hepatocellular carcinoma in Zambia.

The enzyme linked immunosorbent assay (ELISA) was used to measure alpha-foetoprotein (AFP) levels and to detect Hepatitis B surface antigen (HBsAg) and antibody to Hepatitis B surface antigen (anti-HBs) in patients with primary hepatocellular carcinoma and in controls free of the disease in Zambia. Virtually all the patients with primary hepatocellular carcinoma had grossly elevated AFP levels and about two thirds of them were positive for HBsAg. All the controls had much lower AFP levels and one sixth were positive for HBsAg.

Carcinoma, Hepatocellular↗

Four-year study of abdominal ultrasound in 900 Central African adults with AIDS referred for diagnostic imaging.

BACKGROUND: In the majority of sub-Saharan African countries, the absence of computed tomography facilities makes abdominal ultrasound (US) an alternative diagnostic tool in the clinical investigation of infectious and noninfectious complications of human immunodeficiency virus (HIV)-infected individuals. We studied the abdominal US findings in Central African adult AIDS patients to determine whether the findings were consistent between different population groups and neighboring countries. We performed a longitudinal study of AIDS patients and age- and sex-matched HIV-negative adults referred for abdominal US at two tertiary referral city hospitals: the Gecamines Sendwe Hospital (GSH), Lubumbashi, Congo, and the University Teaching Hospital (UTH), Lusaka, Zambia. METHODS: Between 1992 and 1996, abdominal US findings in 900 adults (300 Congolese adults from GSH and 600 Zambian adults from UTH; age range = 15-55 years) with a diagnosis of AIDS referred for diagnostic imaging from the inpatient medical wards were recorded; 900 abdominal ultrasound findings from age and sex-matched HIV-negative adults were studied for comparative purposes. RESULTS: Abdominal US for diagnostic purposes in AIDS patients is requested by clinicians for a range of primary clinical indications: abdominal pain, fever of unknown origin, hepatosplenomegaly, lymphadenopathy, and abnormal liver function tests. Compared with the HIV-individuals, the AIDS group of patients had a significantly higher proportion of splenomegaly (35% vs. 24%; p < or = 0.001), hepatomegaly (35% vs. 22%; p = 0.001), lymphadenopathy (31% vs. 11%; p < or = 0.001), biliary tract abnormalities (25% vs. 12%; p < or = 0.001), gut wall thickening (15% vs. 5%; p < or = 0.001), and ascites (22% vs. 9%; p < or = 0.001). There were no differences in renal tract and pancreatic abnormalities between the AIDS and HIV-groups. There were significantly fewer gallstones in the AIDS group (23% vs. 75%; p < or = 0.001). These patterns of abdominal US abnormalities were consistent across both hospitals. CONCLUSIONS: Diagnostic imaging by abdominal US is commonly used in the management of a variety of clinical indications in Central Africa. The changes seen on abdominal US in AIDS patients appear uniform across the two countries in Central Africa. These findings may have implications for the radiologist, especially in developing countries, where accurate microbiological or pathologic diagnosis of infectious and noninfectious diseases afflicting the HIV-infected patient is often not possible and US is sometimes relied upon as a "diagnostic" investigation by many physicians. Further studies are required to define patterns of clinical findings, plain films, and pathologic and laboratory correlates with US to develop and refine diagnostic algorithms for clinical use in resource-poor countries.

Abdomen↗

Autoantibodies and tropical infections.

Autoantibodies against diverse autoantigens have long been known to exist in the sera of several tropical infections. The introduction of monoclonal antibody technology has allowed immortalization of autoantibody secreting B-lymphocytes and subsequent analysis of these autoantibodies. This paper discusses the current literature on the induction, origins, significance and analysis of autoantibodies.

Autoantibodies↗

Toxoplasma serology in Zambian and Ugandan patients infected with the human immunodeficiency virus.

In the USA and Europe, toxoplasmosis is well recognized as an important cause of morbidity and mortality among immunocompromised individuals. Toxoplasma gondii has been shown to be a common opportunistic infection in patients infected with the human immunodeficiency virus (HIV) in the USA and Europe with published estimates ranging from 20% to 80%. The importance of Toxoplasma infection in East Africa has not yet been defined. The seroprevalence rates of toxoplasmosis in Zambian and Ugandan patients were determined using the dye test (DT) and the latex agglutination test (LAT). The geographical variation in seroprevalence rates noted in western countries was also found in these African countries, with Zambia showing significantly lower rates than Uganda. 34% of Ugandan (64/186) and 4% of Zambian (8/187) patients infected with HIV, compared with 27% of Ugandan (26/93) and 11% of Zambian (20/189) HIV-negative persons, had anti-Toxoplasma immunoglobulin G antibodies. With the LAT, 13% of the Ugandan and 7% of the Zambian sera gave a false positive result. The relevance of Toxoplasma serology in Africa is discussed.

Antibodies, Protozoan↗

The tuberculosis pandemic: implications for health in the tropics.

Among infectious diseases, tuberculosis is the leading cause of death, killing around 3 million people each year. Most cases occur in young adults but it is also a major cause of illness and death in children. The problem has been exacerbated in recent years by the HIV pandemic and by the emergence of multidrug resistance. Co-infection with HIV greatly enhances the risk of overt tuberculosis and in 1999 it is expected that tuberculosis will account for 30% of the predicted 2.5 million AIDS-related deaths. By inducing clinically and radiologically atypical forms of tuberculosis, and by increasing pressure on diagnostic facilities by sheer numbers, serious diagnostic difficulties are increasingly occurring in both adults and children in the tropics. At the present time, 2% of all cases of tuberculosis are multidrug resistant but, as the treatment of such cases is often grossly inadequate in many tropical countries, their frequency will doubtless grow. There are no simple solutions to the global emergency of tuberculosis: clearly there is a need for better use of available control measures but there is also a need to reach a much clearer understanding of the underlying immune phenomena in this disease so as to develop more effective vaccines and therapeutic agents. Finally, it cannot be ignored that tuberculosis is a disease of poverty--95% of cases and 98% of deaths due to it occur in the developing nations--and thus a major control measure is a resolution of the gross inequities in health care provision both between and within nations.

Acquired Immunodeficiency Syndrome↗