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Low HTLV-I/II Seroprevalence in Pregnant Women in Congo and a Geographic Cluster of an HTLV-Like Indeterminate Western Blot Pattern

1996; Lippincott Williams & Wilkins; Volume: 11; Issue: 1 Linguagem: Inglês

10.1097/00042560-199601010-00014

2331-6993

Philippe Tuppin, Maria Makuwa, Teguest Guerma, Marie M. Bazabana, Jean-Claude Loukaka, Dominique Jeannel, Pierre MʼPelé, Guy de Thé,

Vector-Borne Animal Diseases

Human T-lymphotropic virus type I (HTLV-I) is the etiological agent of adult T-cell leukemia/lymphoma and tropical spastic paraparesis/HTLV-I-associated myelopathy (1,2). In Central Africa, only scarce data are available for the Congo, which borders areas of high HTLV-I endemicity such as the Haut-Ogooué region in Southern Gabon and Equateur region in Western Zaire (3,4). The National AIDS Control Program (NACP) of Congo carries out a national sentinel survey on HIV seroprevalence among pregnant women living in seven cities covering the different areas of the country: Brazzaville, the capital located on the shore of the Congo river, facing Kinshasa, the capital of Zaire; Pointe-Noire, the main commercial city of the Congo with a harbor on the Atlantic coast; Sibiti and Nkayi, industrialized cities located between Brazzaville and Pointe-Noire on the main road; and Owendo and Ouesso, located in the north of the country and more isolated than the other cities. Blood samples were taken anonymously for the first 300 pregnant women attending the selected antenatal clinics in each city. Sera collected were assigned a code number, age and parity, and tested at the National Laboratory of Public Health. We used this network to study HTLV-I/II seroprevalence rates among 2,070 pregnant women during the second half of 1992. Serum samples were screened for anti-HTLV-I/II antibodies using an HTLV enzyme-linked immunosorbent assay (EIA; Diagnostic Biotechnology, Singapore). All EIA reactive specimens were tested by HTLV-I/II Western blotting (WB 2.3; Diagnostic Biotechnology, Singapore). This WB contains not only disrupted HTLV-I virions and a recombinant env p21e but also type-specific gp46 env peptides MTA-I (HTLV-I) and K-55 (HTLV-II). Sera were considered HTLV-I positive with stringent criteria for WB positivity (5): clear reactivity against the major gag antigens (p19 and p24), and env antigens (p21e and MTA-I). A serum was considered HTLV-II positive if it reacted with p24, p21e and the K-55 peptide. χ2 and trend tests were used for statistical analysis, and observed prevalences in the cities were compared with the overall prevalence. The overall HTLV-I seroprevalence observed was surprisingly low (0.7%) compared to that in southern Gabon where 6.8% of women of reproductive age (4) were positive or to that of Equateur region of Zaire where 2.4% and 14.8% of pregnant women were positive in Gemena and Basankusu respectively (3). This confirmed the distinctive and low prevalence of HTLV-I in Central Africa with however separate foci of high endemicity. No women exhibited an HTLV-II WB-specific profile.Fig. 1. Besides the above, an indeterminate Western blot pattern characterized by the presence of strong gag reactivities (p19, p26, p28, p53) but with lack of reactivities against p24, p21e and MTA-1 emerged with an overall prevalence of this specific pattern of 1.5% but with evidence of a geographical cluster (p < 0.01) in Mouyondzi (3.3%, 10/300). The prevalence of this pattern was also high in the city of Nkayi (2.0%, 6/300) separated from Mouyondzi by 100 km. In Mouyondzi, it increased with age: 1.6% (1/64) before 20, 2.2% (2/91) for 20-24, 4.3% (3/69) for 25-29, 7.1% (3/42) for 30-34, and 2.9% (1/34) after 34, but not significantly. Other different indeterminate Western blot patterns were observed with limited and faint reactivity against gag proteins (p19 or p24) and/or against recombinant p21e but at a very low overall prevalence of 1.5%. Our study extends the observation of Goubau et al. (3), who described in blood donors a cluster of the same HTLV-like indeterminate pattern in Central Africa (3%, 3/100) in the region of Bas-Zaire bordering south Congo. Epidemiological results such as the clustering and the increasing prevalence with age, similarly to HTLV-I, could argue for a viral reactivity. Several biological hypotheses can be put forward to explain indeterminate patterns: (a) There may be a restricted immune response to HTLV-I infection that may be dependent upon genetic factors. As we could not obtain peripheral blood mononuclear cells (PBMC), we were not able to search for HTLV-I-related proviral sequences. However, this distinctive pattern has been also reported in Zaire and Cameroon (6,7) and Melanesia (8-10). Moreover, several studies failed to detect HTLV-I proviral sequences by polymerase chain reaction using a battery of highly conserved HTLV-I/II primers on fresh or cultured PBMCs of individuals presenting such distinctive WB pattern (6-9). It was not possible to associate our indeterminate reactions with any particular ethnic group. (b) A recent seroconversion may exist. Repeated testing of subjects exhibiting such indeterminate pattern has failed to show any progression to full positivity with time (6). (c) There may be an immune response to endogenous or exogenous viruses closely related to HTLV. A protein of an endogenous sequence (HRES-1) has similarities to the p24 protein, but the indeterminate pattern had a lack of reactivity against p24 (11). In the absence of PBMC, we could not investigate this further. (d) Cross-reactivity between bacterial antigens of the expression system and recombinant such as recombinant p21e may exist, but the indeterminate WB profile exhibits a lack of reactivity for rgp21 and MTA-I but not for gag antigens such as p19, p26, p28 and p53. Cross-reactions were described between nonviral antigens and HTLV-I gag antigens such as the p19 in individuals with a heavy parasitic burden as in malaria (12,13). Mouyondzi was not an hyperendemic area for malaria, compared to the other cities of Congo. However, the geographic cluster could be due to a cluster of peculiar individuals with a heavy parasitic burden, but the eventuality of this event should be rare. The only possible distinguishing feature was a high endemicity of filariasis (Loa loa). We tested 15 people infected with filariasis by HTLV-I Western blot, without finding any indeterminate profiles as previously described in regions where filiariasis is endemic (12). Tb1 Finally, the presence of geographical clusters of the indeterminate pattern suggests a link with as yet unidentified environmental or genetic factors. Further epidemiological studies are required to determine if there is a vertical and/or horizontal transmission of the pattern, which would provide evidence in favor of an infectious agent. Acknowledgment: We thank Dr. Antoine Gessain for reviewing the Western blots and the manuscript. This study was supported by grants from the Agence Nationale de Recherche sur le Sida et du Ministère de la Coopération, Paris, France, and from the Université des Résaux d'Expression Française (UREF), Montréal, Canada. P.T. was the recipient of a CANAM/Institut Pasteur fellowship. *Philippe Tuppin; †Maria Makuwa; ‡Teguest Guerma; ‡Marie M. Bazabana; ‡Jean-Claude Loukaka; *Dominique Jeannel; ‡Pierre M'Pelé; *Guy de Thé *Unité d'Epidemiologie des Virus Oncogenes; Institut Pasteur; Paris, France †Laboratoire National de Santé Publique ‡Programme National de Lutte contre le SIDA; Brazzaville, CongoFIG. 1: . Recombinant Western blot patterns of selected sera using the WB HTLV-I/II 2.3 from Diagnostic Biotechnology. Lane 1, HTLV-I positive control; lane 2, HTLV-II positive control; lanes 3-10, representative western blot of sera exhibiting the indeterminate profile (strong HTLV-I gag pattern lacking reactivity against p24, p21e, and MTA-1 peptide).