Diego F. Cuadros

Spatial epidemiology of hepatitis C virus infection in Egypt: analyses and implications.

Egypt has the highest hepatitis C virus (HCV) prevalence in the world (14.7%). The drivers of the HCV epidemic in Egypt are not well understood, but the mass parenteral antischistosomal therapy (PAT) campaigns in the second half of the 20th century are believed to be the determinant of the high prevalence. We studied HCV exposure in Egypt at a microscale through spatial mapping and epidemiological description of HCV clustering. The source of data was the 2008 Egypt Demographic and Health Survey. We identified clusters with high and low HCV prevalence and high and low PAT exposure using Kulldorff spatial scan statistics. Correlations across clusters were estimated, and each cluster age‐specific HCV prevalence was described. We identified six clusters of high HCV prevalence, three clusters of low HCV prevalence, five clusters of high PAT exposure, and four clusters of low PAT exposure. HCV prevalence and PAT exposure were not significantly associated across clusters (Pearson correlation coefficient [PCC] = 0.36; 95% confidence interval [CI] −0.12 to 0.71). Meanwhile, there was a strong association between HCV prevalence in individuals older than 30 years of age (who could have been exposed to PAT) and HCV prevalence in individuals 30 years of age or younger (who could not have been exposed to PAT) (PCC = 0.81; 95% CI 0.55‐0.93). Conclusion: The findings illustrate a spatial variation in HCV exposure in Egypt. The observed clustering was suggestive of an array of iatrogenic risk factors, besides past PAT exposure, and ongoing transmission. The role of PAT exposure in the HCV epidemic could have been overstated. Our findings support the rationale for spatially prioritized interventions. (Hepatology 2014;60:1150–1159)

Mapping HIV clustering: a strategy for identifying populations at high risk of HIV infection in sub-Saharan Africa

BackgroundThe geographical structure of an epidemic is ultimately a consequence of thedrivers of the epidemic and the population susceptible to the infection. The‘know your epidemic’ concept recognizes this geographicalfeature as a key element for identifying populations at higher risk of HIVinfection where prevention interventions should be targeted. In an effort toclarify specific drivers of HIV transmission and identify prioritypopulations for HIV prevention interventions, we conducted a comprehensivemapping of the spatial distribution of HIV infection across sub-SaharanAfrica (SSA).MethodsThe main source of data for our study was the Demographic and Health Surveyconducted in 20 countries from SSA. We identified and compared spatialclusters with high and low numbers of HIV infections in each country usingKulldorff spatial scan test. The test locates areas with higher and lowernumbers of HIV infections than expected under spatial randomness. For eachidentified cluster, a likelihood ratio test was computed. A P-valuewas determined through Monte Carlo simulations to evaluate the statisticalsignificance of each cluster.ResultsOur results suggest stark geographic variations in HIV transmission patternswithin and across countries of SSA. About 14% of the population in SSA islocated in areas of intense HIV epidemics. Meanwhile, another 16% of thepopulation is located in areas of low HIV prevalence, where some behavioralor biological protective factors appear to have slowed HIV transmission.ConclusionsOur study provides direct evidence for strong geographic clustering of HIVinfection across SSA. This striking pattern of heterogeneity at themicro-geographical scale might reflect the fact that most HIV epidemics inthe general population in SSA are not far from their epidemic threshold. Ourfindings identify priority geographic areas for HIV programming, and supportthe need for spatially targeted interventions in order to maximize theimpact on the epidemic in SSA.

Spatial variability in HIV prevalence declines in several countries in sub-Saharan Africa.

Evidence suggests substantial declines in HIV prevalence in parts of sub-Saharan Africa. However, the observed aggregate declines at the national level may obscure local variations in the temporal dynamics of the infection. Using spatial scan statistics, we identified marked spatial variability in the within-country declines in HIV prevalence in Tanzania, Malawi, Kenya, and Zimbabwe. Our study suggests that the declines in the national HIV prevalence in some of the SSA countries may not be representative of downward trends in prevalence in areas of high HIV prevalence, as much as the result of sharp declines in prevalence in areas of already low HIV prevalence. Our findings provide insights for resource allocation and HIV prevention interventions in these countries.

Variable effect of co-infection on the HIV infectivity: Within-host dynamics and epidemiological significance

BackgroundRecent studies have implicated viral characteristics in accounting for the variation in the HIV set-point viral load (spVL) observed among individuals. These studies have suggested that the spVL might be a heritable factor. The spVL, however, is not in an absolute equilibrium state; it is frequently perturbed by immune activations generated by co-infections, resulting in a significant amplification of the HIV viral load (VL). Here, we postulated that if the HIV replication capacity were an important determinant of the spVL, it would also determine the effect of co-infection on the VL. Then, we hypothesized that viral factors contribute to the variation of the effect of co-infection and introduce variation among individuals.MethodsWe developed a within-host deterministic differential equation model to describe the dynamics of HIV and malaria infections, and evaluated the effect of variations in the viral replicative capacity on the VL burden generated by co-infection. These variations were then evaluated at population level by implementing a between-host model in which the relationship between VL and the probability of HIV transmission per sexual contact was used as the within-host and between-host interface.ResultsOur within-host results indicated that the combination of parameters generating low spVL were unable to produce a substantial increase in the VL in response to co-infection. Conversely, larger spVL were associated with substantially larger increments in the VL. In accordance, the between-host model indicated that co-infection had a negligible impact in populations where the virus had low replicative capacity, reflected in low spVL. Similarly, the impact of co-infection increased as the spVL of the population increased.ConclusionOur results indicated that variations in the viral replicative capacity would influence the effect of co-infection on the VL. Therefore, viral factors could play an important role driving several virus-related processes such as the increment of the VL induced by co-infections. These results raise the possibility that biological differences could alter the effect of co-infection and underscore the importance of identifying these factors for the implementation of control interventions focused on co-infection.

Epidemiology of hepatitis C virus exposure in Egypt: Opportunities for prevention and evaluation.

AIM To critically evaluate the current epidemiology data on exposures, rather than infection, to hepatitis C virus (HCV) transmission and recommend epidemiologic strategies to fill gaps. METHODS Standard methods for identifying and evaluating relevant epidemiologic literature and available data were used. RESULTS There is a large body of literature on the epidemiology of HCV transmission in Egypt that collectively identifies ongoing iatrogenic exposures as the major driver for HCV transmission due to short comings in infection control and standard procedures. Additional epidemiologic studies on HCV transmission that requires the participation of human subject is unwarranted. Alternatively, very little literature was found on the epidemiology of exposure to HCV, infection control, and safe injection practices. The information that is available on patterns of HCV exposure shows high frequencies of inadequate infection control, problems in sterilization in health care facilities, low rates of hand washing, untrained personnel, lack of stated policies in facilities, HCV contamination of instruments and very large injection frequencies with low but very significant syringe and needle reuse. There is an important need to increase the number, size, and diversity of epidemiologic studies on HCV exposures, patterns of risk factors for infection, infection control, and safe injection practices. In addition to health care facilities evaluation, relevant knowledge attitude and practice studies are recommended. CONCLUSION Epidemiologic methods on HCV exposure can be used to characterize the magnitude of exposures to HCV infection, target interventions to reduce exposures, and provide the best method for evaluating interventions by demonstrating the reduction of exposure to HCV infection.

Are Geographical “Cold Spots” of Male Circumcision Driving Differential HIV Dynamics in Tanzania?

Background Growing evidence suggests significant geographic clustering of male circumcision (MC) in Tanzania. The impact of spatial heterogeneity of MC prevalence on HIV transmission dynamics in this country is not well documented. The aim of this study was to assess the spatial association between MC and HIV infection in Tanzania. Methods Data from three Demographic and Health Survey rounds conducted in Tanzania were analyzed to identify spatial associations between MC and HIV using bivariate local indicators of spatial association (LISA). Spatial clusters with low MC prevalence (MC cold spots) were identified using scan statistics. HIV incidence rates for males and females within and outside the MC cold spots were calculated. Results Local indicators of spatial association analysis indicated a significant association between MC and HIV in the northern and southwestern regions of Tanzania. Scan statistics identified two MC cold spots in the same locations. Males located outside the MC cold spots had the lowest HIV incidence rate at 0.28 per 100 person-years at risk (pyar). HIV incidence in females located outside the MC cold spots increased from 0.40/100 pyar during 2004–2008 to 0.68/100 pyar in 2008–2012. Conclusion Our study provides evidence for a geographic association between MC and HIV in Tanzania. MC could be one of the key factors driving the geographical distribution of the HIV epidemic in the country. Furthermore, in areas where most males are circumcised, the HIV infection burden could be concentrating in the female population. Therefore, along with the voluntary medical MC program, efforts targeting the female population should also be considered.

Geographical Patterns of HIV Sero-Discordancy in High HIV Prevalence Countries in Sub-Saharan Africa

Introduction: Variation in the proportion of individuals living in a stable HIV sero-discordant partnership (SDP), and the potential drivers of such variability across sub Saharan Africa (SSA), are still not well-understood. This study aimed to examine the spatial clustering of HIV sero-discordancy, and the impact of local variation in HIV prevalence on patterns of sero-discordancy in high HIV prevalence countries in SSA. Methods: We described the spatial patterns of sero-discordancy among stable couples by analyzing Demographic and Health Survey data from Cameroon, Kenya, Lesotho, Tanzania, Malawi, Zambia, and Zimbabwe. We identified spatial clusters of SDPs in each country through a Kulldorff spatial scan statistics analysis. After a geographical cluster was identified, epidemiologic measures of sero-discordancy were calculated and analyzed. Results: Spatial clusters with significantly high numbers of SDPs were identified and characterized in Kenya, Malawi, and Tanzania, and they largely overlapped with the clusters with high HIV prevalence. There was a positive correlation between HIV prevalence and the proportion of SDPs among all stable couples across within and outside clusters. Conversely, there was a negative, but weak and not significant, correlation between HIV prevalence and the proportion of SDPs among all stable couples with at least one HIV-infected individual in the partnership. Discussion: There does not appear to be distinct spatial patterns for HIV sero-discordancy that are independent of HIV prevalence patterns. The variation of the sero-discordancy measures with HIV prevalence across clusters and outside clusters demonstrated similar patterns to those observed at the national level. The spatial variable does not appear to be a fundamental nor independent determinant of the observed patterns of sero-discordancy in high HIV prevalence countries in SSA.

Evidence for a diffusible factor that induces susceptibility in the Colletotrichum-maize disease interaction.

Colletotrichum graminicola, the causal agent of maize anthracnose, is a hemibiotrophic fungus that initially infects living host cells via primary hyphae surrounded by a membrane. A nonpathogenic mutant disrupted in a gene encoding a component of the signal peptidase complex, and believed to be deficient in protein processing and secretion, regained pathogenicity when it was inoculated onto maize leaf sheaths close to the wild-type fungus. Evidence is presented suggesting that the wild-type produces a diffusible factor(s) that induces the localized susceptibility of host cells at the borders of expanding colonies, causing them to become receptive to biotrophic invasion. The induced susceptibility effect is limited to a distance of approximately eight cells from the edge of the wild-type colony, is dosage dependent and is specific to C. graminicola.

From Individuals to Populations: Immunological and Epidemiological Significance of Co-infection in the Dynamics of HIV

Immunological activation in response to an invading organism is essential in order to support an effective host response to an invading pathogen. Paradoxically, it also provides an optimal immunological environment for the viral replication in HIV-positive individuals. Indeed, the life cycle of HIV is closely related to the activation state of its host cells since it depends on host cell surface receptor expression for entry, and also on many cellular pathways and transcription machinery for viral gene expression. In this review, we focused on the overall impact of immune activations generated by co-infection in the viral life cycle at host level leading to increases in HIV replication. Moreover, we discussed the epidemiological implications of this increment on the HIV viral load generated by coinfection. Here, we described how the intimate relationship between HIV and the activation state of the host immune system supporting viral replication results in a synergistic interaction between HIV and concurrent infections such as herpes simplex virus type 2 and malaria. A common denominator of these co-infections is the systemic immune activation resulting in an enhancement of the HIV viral load that ultimately might facilitate the transmission of the virus. There is a need, however, for more population-based studies of concurrent infections, and microbe-microbe interaction at the host level to better understand the impact of co-infections on the natural history of HIV.

P3.208 Spatial Variability in the Decline of HIV Prevalence in Three Countries in Sub-Saharan Africa

Background HIV prevalence is decreasing in large parts of sub-Saharan Africa (SSA), but the impact of this decline on the geographical heterogeneity of HIV infectious burden is not well understood. We explored and described aspects of the spatial and temporal heterogeneity of the epidemic in three countries in SSA. Methods Data were obtained from Demographic and Health Surveys conducted at different times in Malawi, Tanzania, and Kenya. We identified and compared spatial clusters with high numbers of HIV infections at two different times from each country using Kulldorff spatial scan test. The test locates areas with higher numbers of HIV infections than expected under spatial randomness. For each identified cluster, a likelihood ratio test was computed. A P-value was then determined through Monte Carlo simulations to evaluate the statistical significance of each cluster. Results The table summarises the main results. We found no evidence of decline in HIV prevalence within clusters with high HIV prevalence despite the statistically significant decline in the national HIV prevalence in Malawi and Tanzania. National HIV prevalence decreased by 19% in Malawi, and 17% in Tanzania; meanwhile, HIV prevalence in areas outside of the clusters declined by 33% and 30%, respectively. There was no statistically significant decline in the national HIV prevalence in Kenya, but HIV prevalence within clusters increased by 27%. Conclusions We found marked spatial variability in the decline of HIV prevalence in the three studied SSA countries. Even in the presence of declining national HIV prevalence, HIV prevalence in the high HIV prevalence clusters either did not decline or even increased. Most of the gains in reducing HIV disease burden did not occur in the areas of most intense HIV transmission, but in areas outside of the clusters. Our findings provide insights for resource allocation and HIV prevention interventions in these countries. Abstract P3.208 Table 1 Country Survey 1 (2003–2004)HIV prevalence (%) Survey 2 (2009–2010)HIV prevalence (%) P value Malawi National 12.52 10.13 < 0.001 Within clusters 15.32 14.83 0.59 Outside clusters 10.35 6.97 < 0.001 Tanzania National 6.50 5.38 < 0.001 Within clusters 9.85 9.34 0.49 Outside clusters 5.13 3.61 < 0.001 Kenya National 6.59 6.30 0.62 Within clusters 10.77 13.72 0.01 Outside clusters 5.37 4.66 0.11