Endemic African Kaposi's Sarcoma Research Articles

The spectrum of African Kaposi's sarcoma: is it consequential upon diverse immunological responses?

Kaposi's sarcoma (KS) is a complex, multicellular growth, the pathogenesis of which remains unclear. Endemic African Kaposi's Sarcoma (KS) is characterized by its epidemiological peculiarities, protean clinical manifestations and an unpredictable natural history. A wide spectrum of clinical manifestations occurs, although the reasons for the heterogeneity remain unclear. Clinical observations in the presentation of human immunodeficiency virus (HIV)-associated epidemic African KS show a considerable overlap with endemic African KS obscuring the conventional binomial concept of African KS which was developed in light of the HIV epidemic. It is probable that once the KS lesions are expressed clinically, the subsequent spectrum and behaviour of all forms of African KS are consequential upon a complex interplay between the nature of the host cell-mediated immune responses and the putative aetiological factor(s).

Variants of Kaposi's sarcoma in Southern Africa. A retrospective analysis (1980-1992).

All types of Kaposi's sarcoma (KS) are represented in the Southern African region. We present a retrospective analysis of patients with KS, treated and followed up at the Johannesburg General Hospital over a 12-year period (1980-1992). One hundred and nineteen patients with KS, divided into four groups according to their etiology (classical; endemic African; renal transplant recipients; epidemic AIDS-related) were analyzed. Choice of treatment (radiotherapy or chemotherapy) was individualized and based on clinical criteria, extent of disease and severity of symptoms. Kaposi's sarcoma showed a very high response rate to radiation therapy, regardless of variant, radiation modality or schedule. Chemotherapy was also effective in the more aggressive pattern of endemic African KS. Epidemic Kaposi's sarcoma showed the same poor outcome as demonstrated by its Western counterpart. We conclude that radiation therapy can provide excellent palliation with only minimal side-effects in all variants of KS seen in Southern Africa.

Recent Advances: Dermatology

Recent advances in dermatology and related fields have brought new answers to some old questions and new treatment options for some traditionally vexing diseases of the skin. This review focuses on several important reports of the past year, including progress in the understanding of pathogenesis, prevention, diagnosis, and treatment of some of the most difficult dermatologic maladies. Since the discovery of its association with human immunodeficiency virus infection, Kaposi's sarcoma (1) has remained one of the most puzzling entities in the cutaneous repertoire of patients infected with HIV. An exhausting array of potential aetiological agents has been proposed.1 Until recently, even the basic categorisation of the condition (malignancy, reactive process, infection) has remained uncertain. Reports of Kaposi's sarcoma in homosexual men negative for HIV,2 coupled with the observation that among patients positive for HIV Kaposi's sarcoma was more common in homosexual men than in injecting drug users,3 led to the suspicion that the condition was sexually transmitted, presumably by a virus distinct from but often transmitted with HIV. Fig 1 HIV associated (epidemic) Kaposi's sarcoma During the past year, several reports have emerged documenting the discovery of herpesvirus-like DNA sequences within Kaposi's sarcoma lesions.4 5 6 The DNA sequences (sometimes referred to as KS330(233) or KSHV) have been identified by polymerase chain reaction and by Southern blot hybridisation. These bits of DNA have been discovered in tissue from the lesions of patients with epidemic (HIV associated) Kaposi's sarcoma as well as classic Kaposi's sarcoma (on the legs of immunocompetent elderly men of Mediterranean descent) and African endemic Kaposi's sarcoma.5 The additional finding of similar sequences in tissue from some lymphomas in patients infected with HIV7 and in Kaposi's sarcoma from homosexual men negative for HIV6 lends support to the hypothesis that a novel group of …

Human herpesvirus-8: detection of novel herpesvirus-like DNA sequences in Kaposi's sarcoma and other lesions.

Kaposi's sarcoma (KS) is a malignancy suspected of having an infectious etiology. Unique viral DNA sequences were recognized in KS lesions, using a novel technique that identifies small differences between two complex genomes. The virus had homology with the herpesvirus family, especially Epstein Barr virus (EBV), yet it was distinct from the known herpesviridae, and was appropriately named human herpesvirus 8 (HHV-8) or Kaposi's sarcoma-associated herpesvirus (KSHV). HHV-8 DNA sequences were present in AIDS-associated KS, classic KS, African endemic KS, Mediterranean KS, iatrogenic KS, and KS in homosexual men without HIV infection. HHV-8 DNA sequences were also present in peripheral blood mononuclear cells (PBMC) of KS+ patients; body-cavity-based lymphomas in HIV positive patients without KS; and in tissue from a number of malignant and non-malignant lesions in patients without HIV infection. The role of HHV-8 in KS and other malignancies is not known. Viruses are notoriously trophic for lesional tissue. Therefore, in order to determine the role of HHV-8 in KS pathogenesis, HHV-8 needs to be isolated and shown to induce immortalization in a suitable system. Regardless of its role in KS, another human herpesvirus has been discovered, and the extent of its pathogenicity needs to be uncovered.

Human herpesvirus-like nucleic acid in various forms of Kaposi's sarcoma

The association between a new human herpesvirus-like agent and various forms of Kaposi's sarcoma was examined by PCR. The DNA sequences of this agent were detected in 7 of 8 classic Kaposi's sarcoma specimens, 12 of 12 AIDS-associated specimens from the United States, and 7 of 10 specimens from African endemic Kaposi's sarcoma. Polymorphism of the herpesvirus-like DNA in the Kaposi's tissue from different populations was observed by both single-strand conformational polymorphism and direct sequencing. Furthermore, the presence and expression of the virus was detected in some Kaposi's tumours by Southern and northern blotting. This herpesvirus may be involved in the pathogenesis of different kinds of Kaposi's sarcoma seen among distinct and unrelated populations.

The appearance of kaposi sarcoma during corticosteroid therapy

Four epidemiologic types of Kaposi sarcoma (KS) are known: classic KS, endemic African KS, epidemic or acquired immunodeficiency syndrome-related KS, and KS associated with immunosuppressive therapy. In most of the latter patients, KS was reported to have developed after organ transplantation, particularly renal transplantation. Thirty-nine patients who have not had a transplant have been reported to have KS associated with corticosteroid therapy. The authors studied 10 patients with the appearance of KS during corticosteroid therapy (6 men, 4 women; age range, 42-79 years) who were treated with corticosteroids for autoimmune disorders (5 patients), lymphoproliferative disorders (2 patients), and diseases unrelated to the immune system (3 patients). Genetically programmed susceptibility to corticosteroid-related KS was suggested by the descent of the study patients as well as most of those reported previously. The prognosis was guarded in all the study patients. Corticosteroids should be withdrawn to achieve clinical remission.

An Ultrastructural Study of African Endemic Kaposi's Sarcoma.

An ultrastructural study of African endemic Kaposi's sarcoma (KS) of the skin and lymph nodes revealed an irregularity of blood vascular tissues and prominent diapiresis of erythrocytes in the early stage of the disease. In the advanced stage, incomplete blood capillary structures covered with primitive mesenchymal cells were observed. Erythrophagia was frequently seen. These results suggest that KS cells are derived from primitive mesenchymal cells which may differentiate to immature endothelial cells.

Non-AIDS-Associated Kaposi's Sarcoma (Classical and Endemic African Types): Treatment with Low Doses of Recombinant Interferon-Alpha

In the treatment of the classical and endemic African forms of Kaposi's sarcoma (KS), radiation therapy and chemotherapy have been widely used with varying degrees of success and morbidity. We here report our preliminary experiences with low doses of recombinant interferon alfa-2b (rIFN alpha-2b) in the treatment of these types of KS, non-linked to the acquired immunodeficiency syndrome (AIDS). Ten consecutive patients (eight patients with classical and two with endemic KS) with a median age of 62 years were treated long-term with 5 × 106 units of rIFN alpha-2b (Introna) given subcutaneously three times weekly for at least 6 months. Of the 10 patients, six presented with cutaneous disease only, and four had additional visceral involvement. After 6 months of treatment, seven of the 10 patients had a major response of the cutaneous lesions, and three patients showed stable skin diseases. Of the four patients with additional visceral disease, one patient showed a complete regression of an intramyocardial tumor involving the right atrium and ventricle, whereas in the three other patients stabilization of the visceral lesions with marked symptomatic improvement occurred. On the whole, the long-term results over a median duration of 12 months (range, 7 to 30) are also satisfactory: IFN-alpha continued to control KS in all patients. The treatment was generally well tolerated; no serious side effects were observed. Our preliminary data suggest that low-dose rIFN alpha-2b regimens are effective in classical and endemic African KS. However, further studies are needed to establish the exact role for IFN-alpha as alternative to radiation and chemotherapy.

Lack of association of cytomegalovirus with endemic African Kaposi's sarcoma.

12. Rao CR. Linear statistical inference and its applications. New York: Wiley, 1985:291-309 13. Esteban JI, Shih JW-K, Tai C-C, Bodner AJ, Kay JWD, Alter HJ. Importance of western blot analysis in predicting infectivity of anti-HTLV-III/LAV positive blood. Lancet 1985;2:1083-6 14. Curran JW, Morgan WM, Hardy AM, Jaffe HW, Darrow WW, Dowdle WR. The epidemiology of AIDS: current status and future prospects. Science 1985;229:1352-7 15. Kreiss JK, Koech D, Plummer FA, Holmes KK, Lightfoote M, Piot P, Ronald AR, Ndinya-Achola JO, D'Costa LJ, Roberts P, Ngugi EN, Quinn TC. AIDS virus infection of Nairobi prostitutes. Spread of the epidemic to East Africa. N Engl J Med 1986;314:414-8 16. Grant RM. Co-factors in seroconversion to the AIDSassociated retrovirus among homosexual men in San Francisco. Masters thesis, Berkeley, Calif: University of California, Berkeley, 1986 17. Levy JA, Kaminsky LS, Morrow WJW, Steimer K, Luciw P, Dina D, Hoxie J, Oshiro L. Infection by the retrovirus associated with the acquired immunodeficiency syndrome. Clinical, biological, and molecular features. Ann Intern Med 1985;103:694-9

HLA studies of endemic African Kaposi's sarcoma patients and matched controls: no association with HLA-DR5.

In the search for a genetic factor involved in the etiology of Kaposi's sarcoma, several studies have recently focused on a significantly increased HLA determinant, DR5, as well as a decreased DR3, among patients with both the classical and the AIDS-related form of Kaposi's sarcoma. To test the consistency of this phenomenon, we analysed the frequencies of HLA immunogenetic markers in 23 histologically confirmed Kaposi's sarcoma patients from Central Africa, where this tumor is endemic, and a local sex- and tribe-matched control group. No definite association was observed for any of the HLA antigens, including DR5 and DR3. We were not able to support the hypothesis that the same HLA-associated immune susceptibility factors are involved in all types of Kaposi's sarcoma.

Endemic African Kaposi's sarcoma is not associated with immunodeficiency.

Twenty-seven histologically confirmed Kaposi sarcoma (KS) patients resident in the Kivu Lake area of eastern Zaire were examined for immune competence. Only KS cases of the endemic African type have been observed in this high-incidence area. The median duration of the symptoms was 6 years and ranged from 1 to 38 years. Forty-one controls matched for age, sex and tribe and unrelated to the KS patients were selected from the community. Thirteen additional controls were first-degree relatives of the KS patients. No evidence of immune suppression among KS patients was found and there were no significant differences in the immune status between KS patients and controls. Total lymphocytes, B and T cells, and OKT4+ and OKT8+ cells varied within the normal range. Grouping of the KS patients in categories according to duration and disease extent did not reveal significant differences in their immune status. The number of KS patients reacting positively in a skin test to 5 recall antigens and I mitogen was similar to that of controls, except in the case of candidin, to which a higher number of KS patients were negative. The serum levels of immunoglobulins, complement factors and circulating immune complexes were comparable in KS patients and controls. Indicators of inflammatory processes [white blood cells (WBC), complement-reactive protein (CRP)] were positive in 27% of the KS patients. The prevalence and mean titer of antibody against cytomegalovirus (CMV), Epstein-Barr virus (EBV), hepatitis B virus (HBV) and syphilis were similar in KS patients and in controls.

ACQUIRED IMMUNODEFICIENCY SYNDROME IN RWANDA

To evaluate acquired immunodeficiency syndrome (AIDS) in central Africa a prospective study was done in Kigali, Rwanda, where Kaposi's sarcoma (KS) is endemic. During a 4 week period, 26 patients (17 males and 9 females) were diagnosed. 16 patients had opportunistic infections, associated with KS in only 2; 1 had multifocal KS alone; and 9 had clinical conditions consistent with prodromes of AIDS. All patients had severe T-cell defects characterised by cutaneous anergy, a striking decrease in the number of helper T cells, and a decreased OKT4:OKT8 ratio (mean 0·27). 21 of the 22 adult patients were living in urban centres and many of them were in the middle to upper income bracket. Most of the men were promiscuous heterosexuals and 43% of the females were prostitutes. No patient had a history of homosexuality, intravenous drug abuse, or transfusion in the previous 5 years. This study suggests that AIDS is present in central Africa as an entity probably unrelated to the well-known endemic African KS. An association of an urban environment, a relatively high income, and heterosexual promiscuity could be a risk factor for AIDS in Africa.