WilliamA. Blattner

Infective dermatitis of Jamaican children: a marker for HTLV-I infection

In Jamaican children infective dermatitis is a chronic eczema associated with refractory nonvirulent Staphylococcus aureus or beta-haemolytic streptococcus infection of the skin and nasal vestibule. 14 children between the ages of 2 and 17 years with typical infective dermatitis, attending the dermatology clinic at the University Hospital of the West Indies in Jamaica, were tested for antibody to human T-lymphotropic virus type 1 (HTLV-1). All were seropositive, whereas 11 children of similar age with atopic eczema were all negative. In 2 of 2 cases of infective dermatitis, the biological mother was HTLV-1 seropositive. None of the 14 patients showed signs of adult T-cell leukaemia/lymphoma, though experience with previous cases of infective dermatitis indicates the possibility of such progression.

DETERMINANTS OF RETROVIRUS (HTLV-III) ANTIBODY AND IMMUNODEFICIENCY CONDITIONS IN HOMOSEXUAL MEN

A cohort of homosexual men at high risk of the acquired immunodeficiency syndrome (AIDS) was monitored to examine the relation between lifestyle, clinical conditions, T-lymphocyte subsets, and antibody to the AIDS-associated human retrovirus, human T-cell leukaemia virus III (HTLV-III). HTLV-III antibodies were present in 35 (53%) of the 66 subjects tested in June, 1982. 4 of the seronegative subjects had HTLV-III antibodies when re-tested one year later, a seroconversion rate of 1.2% per month. In the HTLV-III seropositive subjects, AIDS developed at a rate of 6.9% per year (minimum incidence of AIDS = 4.6% per year) and other clinical signs of immunodeficiency (lesser AIDS) at 13.1% per year. All 6 of the AIDS cases and at least 8 of the 10 lesser AIDS cases had detectable HTLV-III antibodies 1 week to 21 months before diagnosis. Of 24 other subjects with stable lymphadenopathy, 19 (79%) had or acquired HTLV-III antibodies. Lower helper T-cell counts were very closely related to HTLV-III seropositivity (r = -0.53, p = 0.0001), even in the 26 healthy subjects with no clinical abnormalities (r = -0.37, p = 0.07). In both univariate and multivariate analyses, the lifestyle risk factors for HTLV-III seropositivity were large number of homosexual partners (p less than or equal to 0.03) and receptive anal intercourse (p less than or equal to 0.03), with an apparent synergistic interaction between these two activities (chi 2 = 8.71, p = 0.003). These data suggest that frequent receptive anal intercourse with many homosexual partners predisposes to HTLV-III infection with the consequent emergence of lymphadenopathy and the various manifestations of lesser and fully fledged AIDS.

MOTHER-TO-INFANT TRANSMISSION OF HUMAN IMMUNODEFICIENCY VIRUS TYPE 1: ASSOCIATION WITH PREMATURITY OR LOW ANTI-gp120

In a prospective study of pregnant women infected with human immunodeficiency virus type 1 (HIV-1) in Brooklyn, New York, USA, 16 (29%) of 55 evaluable infants were infected with HIV-1. 9 infants had paediatric acquired immunodeficiency syndrome, 6 had less severe clinical manifestations of HIV-1 infection, and 1 was symptom-free but was seropositive for HIV-1 beyond 15 months of age. The 10 infants born at 37 weeks of gestation or earlier were at higher risk of HIV-1 infection than infants born at 38 weeks of gestation or later (60% vs 22%) but the median age at appearance of disease was approximately 5 months in both groups. The HIV-1 transmission rate was not associated with predelivery levels of maternal T cells, anti-p24, or neutralising antibodies but it was higher, among full-term infants, for those with mothers in the lowest third of the distribution of anti-gp120 levels (53%). On immunoblot, transmitting mothers lacked a gp120 band but not other bands. Protection was not associated with antibody to recombinant peptides from the hypervariable region of the major neutralising gp120 epitope, and the anti-gp120 endpoint dilution titre was similar in transmitting and non-transmitting mothers. Mothers of uninfected full-term infants appear to confer immunological protection against HIV-1 infection of their offspring by way of a high-affinity antibody to a gp120 epitope, whose specificity has importance for vaccine development and possibly perinatal immunotherapy.

AMYL NITRITE MAY ALTER T LYMPHOCYTES IN HOMOSEXUAL MEN

To evaluate the recent outbreak of Kaposis sarcoma (KS) and opportunistic infections in homosexual men, clinical, virological, and immunological data on two homosexual men with KS and on fifteen healthy homosexual volunteers were collected. Both KS patients had regularly used amyl or butyl nitrite (AN); they had low helper/suppressor (H/S) T-lymphocyte ratios before chemotherapy and high titres of antibody against cytomegalovirus (CMV). Eight of the fifteen volunteers were regular AN users; seven of the eight had low H/S ratios due to larger than normal numbers of OKT8-positive suppressor cells and smaller numbers of OKT4-positive helper cells. In all eight AN users the fluorescence profile obtained with monoclonal antibody 9.6 (which detects the sheep E-rosette receptor) was bimodal, indicating a subpopulation of T cells with increased receptor density. A similar pattern was observed when OKT8, the antibody which detects cytotoxic suppressor cells, was used. Two of the seven men who did not use AN had abnormal fluorescence with reagent 9.6, and one of these also had a low H/S ratio. CMV-antibody titres were persistently high in fourteen of the fifteen healthy men, but the titres were not related to AN use of T-cell abnormalities. The data suggest that nitrites may be immunosuppressive in the setting of repeated viral antigenic stimulation and may contribute to the high frequency of DS and opportunistic infections in homosexual men.

ELISA HTLV retrovirus antibody reactivity associated with malaria and immune complexes in healthy africans

A serological survey of 250 outpatients in rural Zaire showed that the prevalence of antibody against HTLV-I, HTLV-II, and HTLV-III, as detected by enzyme-linked immunosorbent assay, correlated strongly with level of antibodies against Plasmodium falciparum. The age curve for the prevalence of antibody against these retroviruses and high titres of antibodies against P falciparum were similar. Tests with control sera obtained from HTLV-III seropositive homosexual men and American subjects repeatedly infected with malaria who had high antibody titres against P falciparum indicated that there was no cross-reactivity between P falciparum and these retroviruses. Immune-complex levels, but not IgG, IgM, or IgE levels, also correlated strongly with seropositivity in the ELISA HTLV-I and HTLV-III assay, although immune-complex-positive control samples were negative. Possible explanations include coincidental distribution paralleling malaria; similar mode of transmission; virus activation and/or enhanced antibody production due to the effect of malaria on the immune system; and false-positive reactivity in the ELISA assay due to cross-reactive antibodies or other unknown factors.

Evidence for heterosexual transmission and clinical manifestations of human immunodeficiency virus infection and related conditions in Lusaka, Zambia.

In a hospital-based survey in Lusaka, Zambia, 189 (17.5%) of 1078 subjects had antibodies against the human immunodeficiency virus (HIV). The prevalence of antibodies was low in subjects aged less than 20 or greater than 60 years; in men the peak prevalence (32.9%) occurred in those aged 30-35 years, and in women (24.4%) it occurred in the 20-25 year age-group. There was no significant difference in prevalence by sex after adjusting for age. High educational level was independently associated with HIV seropositivity; the antibody against HIV was found in 18.4% of blood donors and in 19.0% of hospital workers. Among patients the antibody prevalence ranged from 8.7% in antenatal women and 9.3% in orthopaedic patients to 29.2% in those attending sexually transmitted disease (STD) clinics (the prevalence being 37.3% in previous attenders and 22.8% in first-time attenders). Seropositivity rates were higher in patients with an infectious problem (23.4%) than in those without (11.4%, p = 0.0002). Herpes zoster, oral thrush, diarrhoea, tuberculosis, and weight loss were independently correlated with seropositivity. The data strongly suggest that HIV infection is prevalent in Africa and is transmitted heterosexually. The restricted distribution of seropositivity to the sexually active age-groups indicates that the epidemic, at least in this part of Africa, is newly introduced; this has substantial implications for prevention.

HUMAN T-CELL LEUKAEMIA/LYMPHOMA VIRUS-ASSOCIATED LYMPHORETICULAR NEOPLASIA IN JAMAICA

19 (34%) of 56 Jamaicans with lympho-proliferative neoplasia had antibody to the human T-cell leukaemia/lymphoma virus (HTLV) in their sera. 17 of those positive had either non-Hodgkins lymphoma (NHL) or chronic lymphocytic leukaemia. Of 16 consecutive patients presenting with NHL, 11 (69%) were HTLV seropositive. Virus-positive patients with NHL, among whom females were over-represented, had the clinical features and poor survival typical of adult T-cell leukaemia/lymphoma. HTLV-associated leukaemia/lymphoma is a distinct clinicopathological entity, and the high incidence in this series suggests that HTLV is an important cause of lymphoreticular neoplasia in Jamaica.

TRANSMISSION OF IN-VITRO RADIORESISTANCE IN A CANCER-PRONE FAMILY

Neoplasms of possible radiogenic origin developed in two members of a family prone to a diversity of cancers, including bone and soft-tissue sarcoma, brain and breast cancers, and leukaemia. Gamma-irradiation survival studies in these two patients and three other relatives, but not their spouses, over three generations demonstrated resistance to cell killing. The D10 value (radiation dose required to reduce survival to 10%) was significantly higher for the five radioresistant strains (491 +/- 30 rad) than for control cultures (405 +/- 18 rad). There was a significant correlation between individual D10 values and D0 survival-curve parameters, indicating that changes in the exponential slope of the survival curves accounted for much of the increase in D10 values. This novel radiation phenotype could be a manifestation of a basic cellular defect, predisposing to a variety of tumours in family members. Thus in-vitro radioresistance, like radiosensitivity, may be a phenotype of a mechanism that increases cancer risk in man.

Spontaneous lymphocyte proliferation in HTLV-II infection

We measured lymphocyte proliferation in the absence of antigenic stimulation in 45 HTLV-II infected, 9 HTLV-I infected, and 19 HTLV-I seronegative intravenous drug users (IVDU). Lymphocyte proliferation was higher in IVDUs infected with HTLV-II than in seronegative IVDUs but lower than among those infected with HTLV-I. Higher rates of proliferation were also associated with needle sharing, CD4+ and IL2R+ lymphocyte counts, and HTLV-I antibody titres.

Type-specific antigens for serological discrimination of HTLV-I and HTLV-II infection.

55 HTLV-I (human T-cell lymphotropic virus) and 45 HTLV-II carriers, confirmed by HTLV-type specific polymerase chain reaction (PCR), were distinguished by western blot assays with recombinant HTLV I or II envelope glycoproteins. Recombinant protein (RP) B1 contains aminoacids 166-201 from HTLV-I exterior glycoprotein gp46 and was reactive with HTLV-I samples only. RP-IIB, which contains aminoacids 96-235 from HTLV-II exterior glycoprotein gp52, was reactive with all HTLV-II samples. 39 patients (86.6%) had high reactivity by densitometry. Of 55 HTLV-I samples, 35 (65.5%) had antibody reactivity to RP-IIB, but only 1 (1.8%) had high reactivity by densitometry. RP B1 and IIB western blot assays may replace the PCR test in diagnosis of HTLV infection.