Tracing the HIV-1 subtype B mobility in Europe: a phylogeographic approach.

BACKGROUND: The prevalence and the origin of HIV-1 subtype B, the most prevalent circulating clade among the long-term residents in Europe, have been studied extensively. However the spatial diffusion of the epidemic from the perspective of the virus has not previously been traced. RESULTS: In the current study we inferred the migration history of HIV-1 subtype B by way of a phylogeography of viral sequences sampled from 16 European countries and Israel. Migration events were inferred from viral phylogenies by character reconstruction using parsimony. With regard to the spatial dispersal of the HIV subtype B sequences across viral phylogenies, in most of the countries in Europe the epidemic was introduced by multiple sources and subsequently spread within local networks. Poland provides an exception where most of the infections were the result of a single point introduction. According to the significant migratory pathways, we show that there are considerable differences across Europe. Specifically, Greece, Portugal, Serbia and Spain, provide sources shedding HIV-1; Austria, Belgium and Luxembourg, on the other hand, are migratory targets, while for Denmark, Germany, Italy, Israel, Norway, the Netherlands, Sweden, Switzerland and the UK we inferred significant bidirectional migration. For Poland no significant migratory pathways were inferred. CONCLUSION: Subtype B phylogeographies provide a new insight about the geographical distribution of viral lineages, as well as the significant pathways of virus dispersal across Europe, suggesting that intervention strategies should also address tourists, travellers and migrants.

Analysis of results from the Joint External Evaluation: examining its strength and assessing for trends among participating countries.

BACKGROUND: The Joint External Evaluation (JEE) is part of the World Health Organization's (WHO) new process to help countries assess their ability to prevent, detect and respond to public health threats such as infectious disease outbreaks, as specified by the International Health Regulations (IHR). How countries are faring on these evaluations is not well known and neither is there any previous assessment of the performance characteristics of the JEE process itself. METHODS: We obtained JEE data for 48 indicators collectively across 19 technical areas of preparedness for 55 countries. The indicators are scored on a 1 to 5 scale with 4 indicating demonstrated capacity. We created a standardized JEE index score representing cumulative performance across indicators using principal components analysis. We examined the state of performance across all indicators and then examined the relationship between this index score and select demographic and health variables to better understand potential drivers of performance. RESULTS: Among our study cohort, the median performance on 43 of the 48 (89.6%) indicators was less than 4, suggesting that countries were failing to meet demonstrated capacity on these measures. The two weakest indicators were related to antimicrobial resistance (median score = 1.0, interquartile range = 1.0-2.0) and biosecurity response (median score = 2.0, interquartile range = 2.0-3.0). JEE index scores correlated with various metrics of health outcomes (life expectancy, under-five year mortality rate, disability-adjusted life years lost to communicable diseases) and with standard measures of social and economic development that enable public health system performance in the total sample, but in stratified analyses, these relationships were much weaker in the AFRO region. CONCLUSIONS: We find large variations in JEE scores among countries and WHO regions with many nations still unprepared for the next disease outbreak with pandemic potential The strong correlations between JEE performance and metrics of both health outcomes and health systems' performance suggests that the JEE is likely accurately measuring the strength of IHR-specific, public health capabilities.

Two viral strains and a possible novel recombinant are responsible for the explosive injecting drug use-associated HIV type 1 epidemic in Estonia.

HIV-1 infection has been rare in Estonia. In 2000, an explosive epidemic among injecting drug users was detected in the Eastern border region, resulting in 3603 newly reported cases by the end of 2003. The molecular epidemiology of the outbreak was studied to establish whether the Estonian epidemic is linked to the epidemics in Eastern Europe. Over 200 newly infected individuals were prospectively sampled from June 2000 to March 2002 in a geographically representative way, with known dates of diagnosis and information of probable route of transmission. Viral regions coding for two viral gene regions were directly sequenced from plasma viral RNA and phylogenetically analyzed. In addition, a larger region coding for the entire env gene was sequenced from one sample and studied for indications of possible recombinant structure. The Estonian HIV outbreak was found to be caused by simultaneous introduction of two strains: a minor subtype A strain very similar to the Eastern European subtype A strain (approximately 8% of cases), and a second major strain (77%) found to be most closely related to the CRF06-cpx strain, previously described only from African countries. The variability in the two clusters was very low, suggesting point source introductions. Ten percent of cases seemed to be newly generated recombinants of the A and CRF06-cpx strains. Analysis of viral diversification over time revealed a rate of change within the V3 region of 0.83%/year for the CRF06-cpx strain, consistent with findings from other subtypes. Due to the relatively frequently found novel recombinant forms, the Estonian HIV-1 epidemic may allow studies of coinfection and intersubtype recombination in detail.

High plasma HIV load in the CRF01-AE outbreak among injecting drug users in Finland.

An explosive outbreak of HIV-1 caused by the recombinant subtype AE (CRF01-AE) was detected in 1998 among Finnish injecting drug users (IDUs). These IDUs were compared with IDUs from the Amsterdam Cohort Study (ACS) infected with subtype B, to detect possible differences between 2 western IDU cohorts infected with different subtypes. Markers for progression (viral load and CD4+lymphocyte count) were compared between 93 IDUs with CRF01-AE and 63 IDUs with subtype B. Only persons with a seroconversion interval =2 y were included. During 48 months of follow-up, both cohorts were similar in CD4+ cell decline, but the Finnish IDUs had 0.34-0.94 log10 copies/ml higher viral loads. The Amsterdam IDUs had a low viral load (<1000 copies/ml) significantly more often than the Finnish IDUs. The difference could not be explained by the use of antiretrovirals. The higher viral load may have contributed to the rapid spread of the recombinant virus in the Finnish outbreak.