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Research Article

High GUD Incidence in the Early 20th Century Created a Particularly Permissive Time Window for the Origin and Initial Spread of Epidemic HIV Strains

  • João Dinis de Sousa mail,

    joao.sousa@rega.kuleuven.be

    Affiliation: Laboratory for Clinical and Evolutionary Virology, Rega Institute for Medical Research, Katholieke Universiteit Leuven, Leuven, Belgium

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  • Viktor Müller,

    Affiliation: Institute of Biology, Eötvös Loránd University, Budapest, Hungary

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  • Philippe Lemey,

    Affiliation: Laboratory for Clinical and Evolutionary Virology, Rega Institute for Medical Research, Katholieke Universiteit Leuven, Leuven, Belgium

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  • Anne-Mieke Vandamme

    Affiliations: Laboratory for Clinical and Evolutionary Virology, Rega Institute for Medical Research, Katholieke Universiteit Leuven, Leuven, Belgium, Centro de Malária e Outras Doenças Tropicais, Instituto de Higiene e Medicina Tropical, Universidade Nova de Lisboa, Lisboa, Portugal

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  • Published: April 01, 2010
  • DOI: 10.1371/journal.pone.0009936

Reader Comments (6)

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What is the basis of this?

Posted by jmoore on 14 Apr 2010 at 17:47 GMT

the recognized early epicenter
http://plosone.org/article/info:doi/10.1371/journal.pone.0009936#article1.body1.sec2.sec4.p2

HIV has been found in early samples from Kinshasa, but unless there's been comparable search effort in samples of comparable number and quality elsewhere, it is premature to e.g. distinguish Kinshasa from Brazzaville with respect to the disease's origin.

No competing interests declared.

Why is Kinshasa the most likely early epicenter

jdsousa replied to jmoore on 14 Apr 2010 at 21:01 GMT

Thank you for raising this question, Jim. It is very pertinent.

We are not the first to suggest that the early epicenter of HIV-1-M was Kinshasa. Keele et al (2006) consider Kinshasa the "most likely" early epicenter. In previous papers from the same team, it is argued that Kinshasa shows evidence of being the earlier epicenter because it, not only contains all group M subtypes, but also shows them with relatively even proportions (unlike other cities of Central Africa). Putting it shortly, samples from Kinshasa in both 1985 (Kalish et al 2004), 1997 (Vidal et al 2000) and 2002 (Vidal et al 2005) show about 40% subtype A, and the rest evenly distributed by all or almost all subtypes. This evenness of distribution is not seen in other cities (Vidal et al 2000, 2005). This has been considered evidence of Kinshasa being the epicenter (Paul Sharp, 13th Conf Retr Oport Inf, 2006).

A very old diversification of HIV-1 group M in Kinshasa is also supported by the recent finding of a second strain from 1960 (Worobey et al 2008). This strain is a basal subtype A, and the ZR59 one is a basal subtype D. So by 1959-60, Kinshasa had a wide diversity of group M strains.

Now, moving to epidemiology, Hooper (2000) shows a table of early AIDS cases connected with Central Africa and there are many from the DRC (of which many from Kinshasa), and the non-DRC ones (from Zambia, Rwanda, Burundi) start to appear only in the late 1970s (that is immediately before AIDS recognition in the USA). Before 1978, virtually all cases are from the DRC. None is from Congo Brazzaville, Gabon, Cameroon, or CAR. There is the case of the Norwegian sailor, acquired in Cameroon, but this is a HIV-1 group O infection (Hooper 2000).

Early serology. There are several early samples showing evidence of HIV-1 in the DRC: The ZR59 and DRC60 samples already referred (Nahmias et al 1986; Worobey et al 2008); prevalences of 0.25% in 1970 and 3% in 1980 in Kinshasa (Desmyter et al, Int Conf on AIDS, 1985); of 1.7% in adult women in Yambuku (Nzilambi et al 1988). There is a 8% prevalence in Bujumbura, Burundi, 1980 (Morvan et al 1989); Burundi is to the east of DRC.

Several samples exist from Gabon, Cameroon, and Congo Brazzaville from before 1980 and they do not show evidence of HIV (reviewed in Rémy 1993). This later paper is a great review of serological studies of Central Africa from the 1980s and before.

Therefore, I think the case can be made that Kinshasa is the best candidate for having been the earlier epicenter. Brazzaville and Bangui received the virus late, perhaps in the 1970s, when the DRC was already exporting it to many countries, including Haiti and the West.

It is possible that the virus used other town or city (e.g. Brazzaville) as a "stepping stone" before landing in Kinshasa, and we recognize this in our Discussion. However, if it happened, the virus seems to have disappeared from these earlier "stepping stones" in the long term.

References (the remaining references cited here are listed in the paper itself):

Kalish et al (2004) Emerg Inf Dis 10: 1227-34
Nzilambi et al (1988) New Engl J Med 318: 276-79
Morvan et al (1989) Bull Soc Path Exot Fil 82: 130-40

No competing interests declared.

RE: Why is Kinshasa the most likely early epicenter

jmoore replied to jdsousa on 15 Apr 2010 at 16:18 GMT

Thanks much, Joao.
It isn't surprising that Kinshasa would become the major focal point for *diversification* of the virus, but when looking for factors critical to the *origin* I think we need to look closely at the possible stepping stones (Brazzaville and perhaps Ouesso being candidates for HIV-1, assuming an origin in SE Cameroon & travel downriver).

I looked for Remy 1993 online, could find only the abstract, which seems to lump Kinshasa and Brazaville:
GEOGRAPHICAL-DISTRIBUTION OF HIV-1 INFECTION IN CENTRAL-AFRICA - REMARKABLE DISCONTINUITIES
Author(s): REMY G
Source: ANNALES DE LA SOCIETE BELGE DE MEDECINE TROPICALE Volume: 73 Issue: 2 Pages: 127-142 Published: JUN 1993
Abstract: The (confirmed) serological data, collected since 1985 and spread in space and in time, allow to draw a geographical image - distribution, dissemination - of HIV1 infection. These data raise some questions and hypotheses on the nature and the dynamics of the epidemiological factors involved.

The geographical distribution of the infection in the global population is heterogenous. Ever since the first surveys, the virus is widely spread at low level, in the rural as well as in the urban areas, covering a large territory, from Chad to Gabon; later it tends to focus on the large metropolitan and secondary towns. The endemicity is more pronounced in a double urban conglomerate (Kinshasa, Brazzaville) and in two regional foci, the southwest of the Congo and the south of Shaba; in the two towns the prevalence rate does not progress between 1985-86 and 1991-92. The Central African Republic has suffered an active epidemic outbreak, affecting the capital and the whole network of secondary towns.

If the *origin* of HIV-1 lies in social/cultural factors, it might be quite relevant which side of the river it started on. We certainly agree that because of its larger size and larger economy, Kinshasa would have been most important as secondary incubator, the question is whether it was primary also.

No competing interests declared.

RE: RE: Why is Kinshasa the most likely early epicenter

jdsousa replied to jmoore on 05 May 2010 at 14:20 GMT

The reason why Rémy (1993) lumps Kinshasa and Brazzaville together as having similar HIV-1 prevalences in its abstract, is because he is referring mostly to the epidemiological situation of the late 1980s. If we focus on older serological collections, another picture emerges, singling out the Democratic Republic of Congo as a far more important (and possibly exclusive) epicenter in the decades preceding the "pandemic big bang" of the mid 1970s.

We develop this evidence in a new comment: "The existing pre-1981 serological evidence singles out the Democratic Republic of Congo".

No competing interests declared.