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Endemic Chediak-Higashi Syndrome occurs in a restricted geographic area (Pregonero, State of Táchira, Venezuela). Neutrophils from these patients were unable to digest Candida albicans in vitro, but showed normal or increased metabolic activities. This finding supports the view that the endemic syndrome is bona fide Chediak-Higashi Syndrome.

Serum samples from 850 individuals from Venezuela were tested for the presence of antibodies to HTLV-III/LAV virus, the probable etiological agent of acquired immune deficiency syndrome (AIDS). At the time of the study, none of the individuals tested had symptoms indicative of AIDS or related disorders. Viral antibodies were assayed by indirect immunofluorescence (IF) assay, using a chronically infected, HTLV-III/LAV producer cell line CEM/LAV-NIT established in our laboratory. Twenty individuals (2.5%), 8 of them (40%) female, were seropositive by IF and by confirmatory Western blotting and radioimmunoprecipitation assays. The seropositivity rate ranged from 2.4% (11 of 465) in the general healthy population, 4% (2 of 50) among patients with Chagas' disease, and up to 29.2% (7 of 24) among patients with acute malaria infection. The titers of HTLV-III/LAV antibodies ranged from 1:40 to 1:640. In addition, 2 of 36 patients with hemophilia A (5.5%) also had antibodies to HTLV-III/LAV. Two of 7 patients with acute malaria had specific antibodies both to HTLV-III/LAV and HTLV-I, as determined by IF and Western blotting. None of over 169 randomly chosen, healthy blood donors from seven major Venezuelan cities, as well as none of 99 patients with leukemia/lymphoma, had antibodies to HTLV-III/LAV. The presence of specific antibodies among various Venezuelan populations indicates that HTLV-III/LAV, or a closely related cross-reactive virus, is indigenous in Latin American subjects as was previously indicated for tropical populations of central Africa. Isolation and characterization of this virus will help to understand the origin and etiology of AIDS.

Four Venezuelan patients with the autosomal recessive Chediak-Higashi syndrome (CHS) were studied. The results confirm the severe reduction in natural killer (NK) cell activity, as previously described and showed also a decline in the activity of cells involved in antibody-dependent cellular cytotoxicity (ADCC). No defect was found in the production of immunoglobulins and of specific antibodies to measles, varicella, herpes simplex, and cytomegalo viruses. Two of the patients had extremely high antibody titers to the Epstein-Barr virus (EBV) specific viral capsid antigen (VCA), to the restricted (R) component of the EBV-induced early antigen complex, and to the EBV-associated nuclear antigen (EBNA). These two patients had enlarged livers, spleens, and lymph nodes indicative of the lymphoproliferative phase. The other two patients were initially negative for all EBV-associated antibodies but seroconverted subsequently and, in the course of a year, also developed high antibody titers to VCA and R. In one of these patients the primary infection was accompanied by moderate signs of infectious mononucleosis (IM) followed after more than 6 months by persistent hepatosplenomegaly. The other patient also developed signs of a lymphoproliferative syndrome with hepatosplenomegaly and jaundice and died 8 months later. Such high anti-R titers are seen frequently in Burkitt's lymphoma, but rarely in other conditions. It is likely that the high antibody titers reflect an increased production of VCA and R due to defective NK and ADCC cell activities so that productively infected B lymphocytes are no longer eliminated before they have synthesized maximal amounts of antigens. The high anti-EBNA titers suggest normal T lymphocyte function. The possibility that the accelerated, lymphoma-like phase of the CHS involves EBV-transformed cells is discussed.

The immunological profile of onchocercosis patients from an endemic region in Venezuela was studied. The sample was made up of patients suffering from onchocercosis and undergoing treatment, persons previously treated and apparently cured of the disease, and a group of apparently healthy individuals from the same area. The results obtained indicate that during the course of the disease the immunological apparatus suffers only slight modifications since no great variations were found in the immunoglobulin levels, the third component of the complement, the reactivity to DNCB, or the response of peripheral blood lymphocytes to mitogens. When under treatment, the levels of serum IgG and IgM are increased and there is a decrease in C3 levels. The slight modifications found can be attributed to the low severity of the disease as only one patient of those studied presented clinical manifestations ascribable to the disease (onchocercoma).

Serum samples of 769 healthy Venezuelan donors were assayed for natural antibodies to HTLV-I by the ELISA technique. Specific HTLV-I antibody prevalence was 6.8% but varied from 1% in Caracas to 13.7% in the Amazonas region and the State of Zulia. Adults infected with Trypanosoma cruzi had the highest HTLV-I antibody prevalence of 15%. Areas of high antibody prevalence were correlated most strongly with the presence of arthropod-borne diseases and to a lesser extent with socio-economic factors. Genetic factors were not correlated with antibody prevalence. Antibodies were seen in children as young as 3 years of age in the most endemic areas. Antibody titers increased with age, suggesting continuous exposure to the virus. The data provide clues for elucidation of the geographic variation in HTLV-I antibody prevalence seen Venezuela and other HTLV-I endemic areas. In addition, they further confirm the Caribbean region as being endemic for HTLV-I and extend this region to inland areas of South America.

Serum samples from 224 aboriginal Amazonian Indians were tested for antibodies to HTLV-III/LAV by an indirect immunofluorescence (IF) assay. 9 individuals (4%), 5 of them female, were seropositive by IF and by confirmatory western blotting and radioimmunoprecipitation tests. 3 of the positive sera were collected in 1968. HTLV-III/LAV seropositivity rates varied among the ethnic groups and ranged from 13.3% among the Pemon Indians to 3.3% among the Yanoama tribe. The titres of HTLV-III/LAV antibodies ranged from 1/40 to 1/320. All individuals tested were apparently healthy at the time of the study. None of 211 randomly chosen, healthy blood donors from Venezuelan cities had antibodies to HTLV-III/LAV. The prevalence of specific antibodies among Amazonian Indians suggests the HTLV-III/LAV or a closely related cross-reactive virus may be endemic in this area. The findings also indicate that this virus is indigenous in non-negroid Latin American and negroid tropical populations.

Fourteen cases of the Chediak-Higashi syndrome found in twelve non-related families living in a defined geographical area not larger than 200 km2 of the Tachira State, Venezuela (population of around 72,000 inhabitants) were diagnosed between 1967 and 1974. The patients were pre-school or nursing age children except one eleven year old female. Six of the patients were male. All showed the same typical somatic characteristics of this syndrome. Four cases were 2 pairs of brothers. Consanguinity of the parents was seen in only two families, even though the majority of them come from the same restricted geographic zone (Pregonero). Since this anomaly is supposedly produced by a rare recessive autosomal gene, the existence of its high frequency in a small Venezuelan region may be explained through the "founder effect" in a population with a high inbreeding coefficient.

The presence of serum antibodies to human T-cell leukemia/lymphoma Virus-I (HTLV-I) and to Epstein-Barr Virus (EBV) was studied in homosexuals and hemophilia patients from the State of Zulia (Venezuela), a highly endemic area for HTLV-I infection. No serum antibodies to HTLV-I were detected despite the presence of alterations in peripheral blood lymphocyte subsets. Anti-EBV antibodies in homosexuals were indicative of persistent infection with this virus. Our results suggest that HTLV-I does not play a role in the immunological alterations in homosexuals or hemophiliacs in an area of high prevalence for this virus.

One case of Chédiak-Higashi syndrome (CHS) in a black male child, born to a consanguineous couple from a rural village in the State of Falcón, is described. At birth the child had marked skin depigmentation and ash-gray hair. A few months later he developed an almost normal black skin color. The diagnosis of CHS was established by the presence of large peroxidase-positive granules in his leukocytes. Neutrophils showed decreased chemotaxis and lack of digestive capacity against Candida albicans. Unusual features included extreme rarity of CHS in blacks, progressive repigmentation of the skin, and an early benign evolution. A high consanguinity index in the village from which this patient originated raised the possibility of the presence of a new cluster of this disease in Venezuela.