Epidemiological and molecular evidence of intrafamilial transmission through sexual and vertical routes in Bahia, the state with the highest prevalence of HTLV-1 in Brazil

Introduction Familial clustering of HTLV-1 and related diseases has been reported in Brazil. However, intrafamilial transmission of HTLV-1 based on molecular analysis has been studied only in few communities of Japanese immigrants and African-Brazilians. Objective To investigate the familial clustering of HTLV-1 infection and to determine the likely routes of transmission through epidemiological and genetic analyzes. Methods Medical records of 1,759 HTLV-1+ patients from de the Center for HTLV in Salvador, Brazil, were evaluated to identify first-degree relatives previously tested for HTLV-1. Familial clustering was assumed if more than one member of the same family was HTLV-1+. LTR regions of HTLV-1 sequences were analyzed for the presence of intrafamilial polymorphisms. Family pedigrees were constructed and analyzed to infer the likely transmission routes of HTLV-1. Results In 154 patients at least one other family member had tested positive for HTLV-1 (a total of 182 first-degree relatives). Of the 91 couples (182 individuals), 51.6% were breastfed, and 67.4% reported never using a condom. Of the 42 mother-child pairs, 23.8% had a child aged 13 years or younger; all mothers reported breastfeeding their babies. Pedigrees of families with 4 or more members suggests that vertical transmission is a likely mode of transmission in three families. Three families may have had both vertical and sexual transmission routes for HTLV-1. The genetic signatures of the LTR region of 8 families revealed 3 families with evidence of vertical transmission, another 3 families (spouses) with sexual transmission, and one family with both transmission routes. HTLV-1 sequences belonged to Cosmopolitan subtype HTLV-1a Transcontinental subgroup A. Conclusion: Sexual and vertical transmission routes contribute to the intrafamilial spread of HTLV-1 in the state of Bahia. AUTHOR SUMMARY Human T-lymphotropic virus type 1 (HTLV-1) was the first human retrovirus isolated in the early 1980s. It is estimated that approximately 10 million people worldwide are currently infected with HTLV-1, and most people living with HTLV (PLwHTLV) live in developing countries. The virus is associated with a wide range of diseases, including neoplasms such as adult T-cell leukemia/lymphoma and progressive and disabling myelopathy, but most PLwHTLV are unaware of their serologic status. HTLV-1 is transmitted through contact with contaminated blood and derivatives, sexually, and from mother to child, especially through breastfeeding. Only recently has WHO recognized HTLV-1 as a as threatening pathogen to human, but in many parts of the world HTLV screening is not performed in blood banks or in pregnant women. This may promote silent intrafamilial transmission of the virus across generations and promote familial clustering of the virus and associated diseases. In this study, we investigated the familial clustering of HTLV-1 infection in the state of Bahia, an endemic area for this virus in Brazil. We found that both sexual and vertical pathways contribute to the transmission and persistence of the virus in families across multiple generations. Therefore, in addition to expanding screening for pregnant women and providing infant formula to infected mothers, it is of utmost importance to combat sexual transmission through effective measures that can help address this serious and neglected public health problem. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement This work was supported by the Coordination of Superior Level Staff Improvement-Brazil (CAPES) - Finance Code 001 and National Foundation for the Development of Private Higher Education (FUNADESP), grants 9600140 and 9600141. Maria Fernanda R. Grassi and Bernardo Galvão-Castro are research fellows of CNPq (process no. 308167/2021-0 and 473667/2012-6, respectively). ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: The studies involving human participants were reviewed and approved by the Comitê de Ética em Pesquisa em Seres Humanos da Bahiana (CAAE: 60554416.8.0000.5544). Written informed consent from the patients/participants or their legal guardian/next of kin was not required to participate in this study in accordance with the national legislation and the institutional requirements. 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