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Medical history

Tracking the origin, early spread, and ignition of pandemic #HIV-1 through new approaches to phylogenetic analysis

17 Nov, 14 | by Leslie Goode, Blogmaster

“Distribution of HIV-1 subtypes in a population”, state Mumtaz & Raddad (STI) in a study of the HIV pandemic in the Middle East, “tracks the spread and evolution of the epidemic”.  Various studies covered in our previous blogs have attempted to read the history of the progress of the HIV epidemic through the evidence of the distribution of HIV genetic sub-types: Tatem & Salemi (STI/blogs) have investigated its spread throughout Africa; Zhao & Roca (STI/blogs) pass beyond the human epidemic to consider the genetic evidence for repeated transmission from chimpanzees to humans.

Now Faria & Lemey (F&L), in a paper recently appearing in Science, offer an account of the critical early phase of limited spread within Central Africa and the ignition of pandemic HIV-1 around 1960, bringing statistical approaches to bear to HIV-1 sequence data.  F&L produce a time-scaled phylogenetic “tree” of HIV-1 group M lineages, matching these up in each case with the geographical location of their earliest manifestation.

This approach points to the very strong likelihood (PP = 0.99) of an origin of the HIV1 epidemic in Kinshasa around 1920. Study of lineage migration shows comparatively early spread from Kinshasa to Brazzaville (Republic of Congo (RC)), and Mbuji-Mayi and Lubumbashi (southern Democratic Republic of Congo (DRC)) along the railway network, and its arrival around a decade later in Bwamanda and Kisangani (northern DRC).  The crucial period around 1960 (1952-1968) sees, for group M HIV-1, an exponential growth in levels of M-group transmission, while growth in group O transmission remains at previous levels.

But the most interesting aspect of the study relates to conditions around the sudden surge in group M HIV-1 transmission, as indicated by the accelerated ramification of viral lineages during the crucial period.  The authors consider the hypothesis that associates this ramification with the geographic dispersal of the epidemic, with the lineages emerging in the more widely distributed populations now being infected.  They reject this hypothesis, however, on the grounds that, when the epidemic history of lineages maintaining ancestry within Kinshasa is constructed, these turn out to exhibit phylo-genetic characteristics that are comparable to those of lineages in central Africa.

They conclude that the crucial explosion of pandemic HIV-1 transmission probably occurred in Kinshasa as a result of a historic contingency affecting a particular population subgroup.  Prime contenders are iatrogenic transmission as a result of the administration of unsterilized injections at STI clinics, and/or post-independence changes in sexual behaviour e.g. among commercial sex-workers.  The authors find support for the iatrogenic hypothesis in a study of the hepatitis C virus in the DRC which shows that it exhibits an age cohort effect, and in reports of an epidemic of hepatitis B in Kinshasa around 1951-2.

The records of the US syphilis experiments in Guatemala: read them yourself!

2 May, 11 | by Leslie Goode, Blogmaster

Now open to public access: the documents at the heart of last October’s scandal over unethical experiments by US researchers in Guatemala.  In 1946-48, the US team, seeking an opportunity to study the effectiveness of penicillin against syphilis and gonorrhoea, conducted experiments involving the deliberate exposure to those diseases of 700 Guatemalan soldiers, mental health patients and prison inmates.

The scandal following last October’s discovery of papers relating to this experiment by a medical historian at Pittsburgh University occasioned a personal telephone call by President Obama to Guatemala’s president in order to apologize.  Representatives of Guatemala claimed their country had had no knowledge of the experiment prior to the call.  The documents now opened to public access belonged to the public health researcher Dr John C. Cutler, also known for his participation in the Tuskegee study, who died in 2003. Their publication (29.03.11) follows by only a couple of weeks the filing of a lawsuit (15.03.11) against the US government on behalf of victims and their heirs, seeking compensation for resulting health problems.

So what do these papers reveal?

For a start, a high degree of involvement on the part of the Guatemalans – though the US researchers were in control of the research.  The overall impression is of a genuine collaboration, with both Guatemalans and the American team expecting to derive benefit from participation in the research. The primary local collaborator was Dr. Juan Funes, chief of the VD control division of the Guatemalan Sanidad Publica.  Institutional partners included the Guatemalan Ministry of Health, the National Army of the Revolution, the National Mental Health Hospital, and the Ministry of Justice.  Contemporary Guatemalan attitudes to the US researchers appear to have been characterized by gratitude and appreciation.

How times have changed!

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