January 21, 2016
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Iatrogenic transmission fueled early spread of HIV pandemic in Africa

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The association of blood-borne viruses and previous IV procedures among aged residents of Kinshasa, Democratic Republic of the Congo, may suggest the rapid emergence of HIV in this region during the mid-20th century was driven by iatrogenic transmission, according to a recently published study.

“Evolutionary analyses of viral gene sequences show that HIV-1 flourished and diversified in the Belgian Congo’s capital, which was the major trading center of Central Africa,” Catherine Hogan, MD, MSc, of the University of Sherbrooke, Canada, and colleagues wrote. “Genetic estimates of the transmission history of HIV-1 group M in Central Africa indicate that the epidemic grew more slowly before 1950, then transitioned to much faster exponential growth sometime between 1952 and 1968. Factors that drove the emergence and spread of HIV-1 toward epidemic spread in Kinshasa remain unknown.”

Previous research has proposed iatrogenic transmissions as a major factor toward the emergence of HIV-1 in Kinshasa, the researchers wrote, but the disease’s high mortality has made it difficult to confirm this hypothesis. To circumvent this issue, Hogan and colleagues chose to analyze the prevalence of hepatitis C and human T-cell lymphotrophic virus type 1 (HTLV-1), two blood-borne viruses with greater survivability that could act as a proxy for HIV. From July to August 2012, they recruited a convenience sample of Kinshasa residents aged 70 years or older who had lived in the city for at least 30 years. Participants provided medical samples and completed questionnaires providing demographic and medical history, with a focus on previous tropical diseases and conditions requiring substantial IV injections. Collected samples underwent serological assays, amplification and sequencing, and phylogenetic reconstruction was performed to outline the genetic history of identified HCV.

The final analysis included 839 participants, aged 70 to 90 years (median age, 75 years). Participants reported living in Kinshasa for a median of 58 years (range, 30-92), and 74% recalled receipt of IV injections at least once in their lifetime.

The researchers wrote that 25.9% of participants tested positive for HCV, and 3.1% tested positive for HTLV-1. Of the 118 patients with HCV from which amplification products were obtained, subtypes 4r (n = 38) and 4k (n = 47) were most prevalent. Intramuscular TB therapy, IV injections before 1960, IV infections at a colonial-era venereology clinic and IV injections at a specific hospital were all identified as independent risk factors for subtype 4r, while antimalarial treatments and IV injections at another hospital were associated with subtype 4k. HTLV-1 subtype 1b was most commonly found among participants providing sequences, with notable risk factors of HTLV-1 infection consisting of transfusions and IV injections at two specific hospitals. In addition, viral sequence analysis showed a large increase in infections of both HCV subtypes beginning in the 1950s.

Despite some limitations and the loss of directly affected individuals, the researchers wrote that the associations found among participants with HCV directly align with those found among participants with HTLV-1, and vice versa. As such, these findings may be the first empirical evidence supporting the hypothesis of HIV-1 emergence through iatrogenic blood-borne virus transmission.

“The establishment of HIV-1 group M, uniquely among HIV strains, as a global pandemic undoubtedly resulted from multiple causal factors whose relative contributions may never be fully resolved,” the researchers wrote. “However, historical iatrogenic transmission in the hub of Central Africa appears to have been one such contributor.”

The findings of Hogan and colleagues fit well into the current understanding of HIV-1’s origins, which are largely based on evolution patterns gleaned from sequencing data, according to Simon D.W. Frost, DPhil, and Samuel K. Kwofie, PhD, both of the veterinary medicine department at the University of Cambridge. In a related editorial, they wrote that reductions in iatrogenic transmission should be pursued alongside efforts against sexual transmission, as this route continues to be a source of new infections across several countries and diseases.

“In an era of increasing population mobility, which drove the dissemination of HIV from Africa to the rest of the world, we have to take shared responsibility for development of health services and appropriate prevention strategies,” they wrote. “With current discussions of vaccination to protect against Ebola virus, iatrogenesis should remain a concern in the global health agenda.” – by Dave Muoio

Disclosure: The researchers report no relevant financial disclosures.