Analysis of the origin and evolutionary history of HIV-1 CRF28_BF and CRF29_BF reveals a decreasing prevalence in the AIDS epidemic of Brazil

Background

HIV-1 subtype B and subtype F are prevalent in the AIDS epidemic of Brazil. Recombinations between these subtypes have generated at least four BF circulating recombinant forms (CRFs). CRF28_BF and CRF29_BF are among the first two BF recombinants being identified in Brazil and they contributed significantly to the epidemic. However, the evolution and demographic histories of the CRFs are unclear.

Methodology/Principal Findings

A collection of gag and pol sequences sampled within Brazil was screened for CRF28_BF-like and CRF29_BF-like recombination patterns. A Bayesian coalescent framework was employed to delineate the phylogenetic, divergence time and population dynamics of the virus having CRF28_BF-like and CRF29_BF-like genotype. These recombinants were phylogenetically related to each other and formed a well-supported monophyletic clade dated to 1988–1989. The effective number of infections by these recombinants grew exponentially over a five-year period after their emergence, but then decreased toward the present following a logistic model of population growth. The demographic pattern of both recombinants closely resembles those previously reported for CRF31_BC.

Conclusions

We revealed that HIV-1 recombinants of the CRF28_BF/CRF29_BF clade are still circulating in the Brazilian population. These recombinants did not exhibit a strong founder effect and showed a decreasing prevalence in the AIDS epidemic of Brazil. Our data suggested that multiple URFs may also play a role in shaping the epidemic of recombinant BF HIV-1 in the region.     

Impulsive SUI epidemic model for HIV/AIDS with chronological age and infection age

This paper develops an impulsive SUI model of human immunodeficiency virus/acquired immunodeficiency syndrome(HIV/AIDS) epidemic for the first time to study the dynamic behavior of this model. The SUI model is described by impulsive partial differential equations. First, the well-posedness of the model is attained by the method of characteristic lines and iterative method. Secondly, the basic reproduction number R₀(q,T) of the epidemic which depends on the impulsive HIV-finding period T and the HIV-finding proportion q is obtained by mathematical analysis. Our result shows that HIV/AIDS epidemic can be theoretically eradicated if we can have the suitable HIV-finding proportion q and the impulsive HIV-finding period T such that R₀(q,T)<1. We also conjecture that the infection-free periodic solution of the SUI model is unstable when R₀(q,T)>1.     

The priorities in realizing prophylactic programs in a region with a high level of HIV infection

The analysis of changes in the epidemic situation with HIV infection in Kaliningrad Province, the first territory in Russia involved into the epidemic, is presented. The experience in the realization of preventive programs is discussed with the analysis of both successes and problems arising in Kaliningrad, whose inhabitants constitute the absolute majority among HIV-infected persons in the region. The expediency of creating a new section--service of information, consultation and psychological assistance in the AIDS Centers is proposed for discussion.     

Qualitative analysis of the level of cross-protection between epidemic waves of the 1918-1919 influenza pandemic

The 1918-1919 influenza pandemic was composed of multiple waves within a period of nine months in several regions of the world. Increasing our understanding of the mechanisms responsible for this multi-wave profile has important public health implications. We model the transmission dynamics of two strains of influenza interacting via cross-immunity to simulate two temporal waves of influenza and explore the impact of the basic reproduction number, as a measure of transmissibility associated to each influenza strain, cross-immunity and the timing of the onset of the second influenza epidemic on the pandemic profile. We use time series of case notifications during the 1918 influenza pandemic in Geneva, Switzerland, for illustration. We calibrate our mathematical model to the initial wave of infection to estimate the basic reproduction number of the first wave and the corresponding timing of onset of the second influenza variant. We use this information to explore the impact of cross-immunity levels on the dynamics of the second wave of influenza. Our results for the 1918 pandemic in Geneva, Switzerland, indicate that a second wave can occur whenever R₀₁<1.5 or when cross-immunity levels are less than 0.58 for our estimated R₀₂ of 2.4. We also explore qualitatively profiles of two-wave pandemics and compare them with real temporal profiles of the 1918 influenza pandemic in other regions of the world including several Scandinavian cities, New York City, England and Wales, and Sydney, Australia. Pandemic profiles are classified into three broad categories namely “right-handed”, “left-handed”, and “M-shape”. Our results indicate that avoiding a second influenza epidemic is plausible given sufficient levels of cross-protection are attained via natural infection during an early (herald) wave of infection or vaccination campaigns prior to a second wave. Furthermore, interventions aimed at mitigating the first pandemic wave may be counterproductive by increasing the chances of a second wave of infection that could potentially be more virulent than the first.     

The epidemic situation in relation to HIV infection in Ukraine (1987-1997)

The analysis of the dynamics of the epidemic process for 10 years made it possible to find out the presence of two separate epidemic waves of HIV infection. The first wave (1987-1994) was manifested as the slow type of the development of the epidemic, characterized mainly by sexual transmission. During this period 398 persons with HIV infection were detected, 24 persons were found to have AIDS; of these, 13 persons died. The second epidemic wave began in 1995 and was due to the spread of HIV among users of drugs introduced by injection. By the end of 1995 the number of HIV carriers was 34 times greater than that of 1994, reaching 1490 persons. In 1996-1997 this figure increased 8 times (annually). The number of AIDS patients rose to 420 persons. The most unfavorable regions with respect to HIV infection and AIDS morbidity were determined. The western regions of the Ukraine were noted to be in a more favorable situation in this respect with infection indices being lower more than 30 times. Up to 80% of all infected persons were found to be addicts introducing drugs intravenously. Growing morbidity in sexually transmitted disease, particularly in syphilis, contributed to the deterioration of the epidemiological situation. The conclusion was made on the necessity of introducing new prophylactic programs and expanding current ones. The signs of stabilization in Odessa and Nikolayev were observed; in these cities pilot programs aimed at the strategy of the "decrease of harm" have been introduced (in collaboration with UNAIDS) since 1996.     

Early detection surveillance for an emerging plant pathogen: a rule of thumb to predict prevalence at first discovery

Emerging plant pathogens are a significant problem for conservation and food security. Surveillance is often instigated in an attempt to detect an invading epidemic before it gets out of control. Yet in practice many epidemics are not discovered until already at a high prevalence, partly due to a lack of quantitative understanding of how surveillance effort and the dynamics of an invading epidemic relate. We test a simple rule of thumb to determine, for a surveillance programme taking a fixed number of samples at regular intervals, the distribution of the prevalence an epidemic will have reached on first discovery (discovery-prevalence) and its expectation E(q*). We show that E(q*) = r/(N/Δ), i.e. simply the rate of epidemic growth divided by the rate of sampling; where r is the epidemic growth rate, N is the sample size and Δ is the time between sampling rounds. We demonstrate the robustness of this rule of thumb using spatio-temporal epidemic models as well as data from real epidemics. Our work supports the view that, for the purposes of early detection surveillance, simple models can provide useful insights in apparently complex systems. The insight can inform decisions on surveillance resource allocation in plant health and has potential applicability to invasive species generally.     

On the dynamics of SEIRS epidemic model with transport-related infection

Transportation amongst cities is found as one of the main factors which affect the outbreak of diseases. To understand the effect of transport-related infection on disease spread, an SEIRS (Susceptible, Exposed, Infectious, Recovered) epidemic model for two cities is formulated and analyzed. The epidemiological threshold, known as the basic reproduction number, of the model is derived. If the basic reproduction number is below unity, the disease-free equilibrium is locally asymptotically stable. Thus, the disease can be eradicated from the community. There exists an endemic equilibrium which is locally asymptotically stable if the reproduction number is larger than unity. This means that the disease will persist within the community. The results show that transportation among regions will change the disease dynamics and break infection out even if infectious diseases will go to extinction in each isolated region without transport-related infection. In addition, the result shows that transport-related infection intensifies the disease spread if infectious diseases break out to cause an endemic situation in each region, in the sense of that both the absolute and relative size of patients increase. Further, the formulated model is applied to the real data of SARS outbreak in 2003 to study the transmission of disease during the movement between two regions. The results show that the transport-related infection is effected to the number of infected individuals and the duration of outbreak in such the way that the disease becomes more endemic due to the movement between two cities. This study can be helpful in providing the information to public health authorities and policy maker to reduce spreading disease when its occurs.     

High occurrence of Calodium hepaticum (syn. Capillaria hepatica) spurious infection in a village in the Atlantic Forest of southern Brazil

Calodium hepaticum (syn. Capillaria hepatica) is a nematode of the Capillariidae family that infects rodents and other mammals. In Brazil, human spurious infections of C. hepaticum have been detected in indigenous or rural communities from the Amazon Basin, but not in the southern states of the country. Here, we report the highest occurrence (13.5% of 37 residents) of C. hepaticum human spurious infection detected in Brazil and the first record in a southern region, Guaraqueçaba. The finding is explained by the area being located in the Atlantic Forest of the state of Paraná, surrounded by preserved forests and because the inhabitants consume the meat of wild mammals.     

Global behaviour of an age-infection-structured HIV model with impulsive drug-treatment strategy

In this paper, we develop an HIV model that considers the dependence of HIV/AIDS progress on infection age (duration since infection), chronological age and impulsive antiretroviral treatment. The analytical results show that there exists a globally asymptotically stable infection-free state when the impulsive period T and drug-treatment proportion p satisfy R₀(p,T)<1. The numerical simulation results indicate that there exist T and p such that R₀(p,T)<1. Due to pulses, it would be difficult to obtain the optimal pulse interval in the age distribution of population. However, our results demonstrate the effect of the impulsive drug-treatment strategy on the dynamics of HIV/AIDS.     

A Retrospective Study of Dermatophyte Infection in Newfoundland for the Period 1962-1968

The results of a survey of dermatophyte infection in New-foundland for the period 1962 to 1968 are presented. A steady annual rise in the number of specimen submissions is noted, with positive findings in an average of 21.7%. The contribution by source of specimens is recorded, and species distribution indicates that Microsporum canis has behaved in epidemic form whereas other species appear endemic. Trichophyton rubrum infection shows a steady annual increase. No cases of favus have been noted. The distribution of species by anatomical site is indicated.     

Hospitalizations for HIV/AIDS: Differences between sexes

Background: Women are especially vulnerable to HIV infection because of biological, social, cultural, and economic factors. In Brazil, AIDS was initially seen predominantly in homosexual men, but the epidemic gradually reached a gender balance as increasing numbers of women became infected with HIV.Objective: The aim of the present study was to identify the clinical and epidemiologic characteristics of hospitalized patients with HIV/AIDS of both sexes and compare the differences between them.Methods: This epidemiologic cross-sectional study evaluated gender differences in demographic, social, clinical, and epidemiologic characteristics of patients diagnosed with HIV/AIDS who were admitted for any reason to the Public Hospital of the Medical School of the Federal University of Triângulo Mineiro, Uberaba, Minas Gerais State, Brazil.Results: A total of 363 patients were included in the analysis, with a male/female ratio of 1.1:1.0. Forty-one percent of women were pregnant. Mean age at hospitalization and duration of hospitalization were significantly greater among men (P<0.05). Men and nonpregnant women were admitted because of infection significantly more often than were pregnant women (P<0.05). Significantly more single men who reported homosexual, bisexual, or heterosexual behavior associated with drug use were admitted compared with women (P<0.05). Women admitted for treatment were significantly more likely than men to be employed (P<0.05). Adherence to antiretroviral treatment and T CD4+ lymphocyte count indicated important differences between the sexes, with better parameters observed among nonpregnant and pregnant women compared with men.Conclusions: In the present study, women with HIV/AIDS who were admitted to the hospital for any reason were in better clinical condition compared with men. This observation may be partially explained by the proportion of pregnant women in the study population. These findings suggest that future studies should examine pregnant women with HIV/AIDS as a separate population group to avoid bias in analysis.     

Evaluation of childhood acute leukemia incidence and underreporting in Brazil by capture–recapture methodology

Background: Population-based cancer registries (PBCR) are important in cancer epidemiology as they provide the basis for monitoring cancer incidence. Childhood acute lymphoblastic leukemia (ALL) is said to have lower incidence in developing countries, which has implications for its pathogenesis, but there are few studies concerning the completeness of cancer registries in developing countries. This study analyzes the number of cases and incidence of childhood acute lymphoblastic leukemia in three different cities in Brazil and estimates underreporting cases and possible PBCR failures. Methods: We evaluated the completeness of PBCR and the incidence rates of childhood ALL from three different Brazilian cities using the two-source capture–recapture method. The sources used were a population-based registry and databases from a diagnosis reference laboratory in 2001 and the Chapman's formula was used to calculate the estimates. Results: The estimated incidence was 5.76, 6.32 and 5.48 per 100,000 inhabitants for Salvador, Recife and Belo Horizonte, respectively. The estimated completeness of childhood ALL in PBCRs was 15.5%, 35.4% and 29.2%, respectively, for Salvador, Recife and Belo Horizonte. Conclusions: There was a high estimated underreporting of childhood leukemia cases in some Brazilian cities. The relationship between information systems and the capture–recapture method application improved epidemiological estimates. Childhood acute lymphoblastic leukemia incidence rates are similar to those of developed countries.     

A mechanistic and data-driven reconstruction of the time-varying reproduction number: Application to the COVID-19 epidemic

The effective reproduction number R_eff is a critical epidemiological parameter that characterizes the transmissibility of a pathogen. However, this parameter is difficult to estimate in the presence of silent transmission and/or significant temporal variation in case reporting. This variation can occur due to the lack of timely or appropriate testing, public health interventions and/or changes in human behavior during an epidemic. This is exactly the situation we are confronted with during this COVID-19 pandemic. In this work, we propose to estimate R_eff for the SARS-CoV-2 (the etiological agent of the COVID-19), based on a model of its propagation considering a time-varying transmission rate. This rate is modeled by a Brownian diffusion process embedded in a stochastic model. The model is then fitted by Bayesian inference (particle Markov Chain Monte Carlo method) using multiple well-documented hospital datasets from several regions in France and in Ireland. This mechanistic modeling framework enables us to reconstruct the temporal evolution of the transmission rate of the COVID-19 based only on the available data. Except for the specific model structure, it is non-specifically assumed that the transmission rate follows a basic stochastic process constrained by the observations. This approach allows us to follow both the course of the COVID-19 epidemic and the temporal evolution of its R_eff(t). Besides, it allows to assess and to interpret the evolution of transmission with respect to the mitigation strategies implemented to control the epidemic waves in France and in Ireland. We can thus estimate a reduction of more than 80% for the first wave in all the studied regions but a smaller reduction for the second wave when the epidemic was less active, around 45% in France but just 20% in Ireland. For the third wave in Ireland the reduction was again significant (>70%).     

Congenital transmission of Trypanosoma cruzi in central Brazil. A study of 1,211 individuals born to infected mothers

Transmission of Trypanosoma cruzi during pregnancy is estimated to occur in less than 20% of infected mothers; however, the etiopathogenesis is not completely understood. The Centre for Studies on Chagas Disease provides confirmation of T. cruzi infection for individuals living in central Brazil. In this retrospective hospital-based study, all requests for diagnosis of T. cruzi infection in individuals less than 21 years old from 1994-2014 were searched. We end with 1,211 individuals and their respective infected mothers. Congenital transmission of infection was confirmed in 24 individuals (2%) in central Brazil, an area where the main T. cruzi lineage circulating in humans is TcII. This low prevalence of congenital Chagas disease is discussed in relation to recent findings in the south region of Brazil, where TcV is the main lineage and congenital transmission has a higher prevalence (approximately 5%), similar to frequencies reported in Argentina, Paraguay and Bolivia. This is the first report to show geographical differences in the rates of congenital transmission of T. cruzi and the relationship between the prevalence of congenital transmission and the type of Tc prevalent in each region.     

Transmission potential of chikungunya virus and control measures: the case of Italy

During summer 2007 Italy has experienced an epidemic caused by Chikungunya virus - the first large outbreak documented in a temperate climate country - with approximately 161 laboratory confirmed cases concentrated in two bordering villages in North-Eastern Italy comprising 3,968 inhabitants. The seroprevalence was recently estimated to be 10.2%. In this work we provide estimates of the transmission potential of the virus and we assess the efficacy of the measures undertaken by public health authorities to control the epidemic spread. To such aim, we developed a model describing the temporal dynamics of the competent vector, known as Aedes albopictus, explicitly depending on climatic factors, coupled to an epidemic transmission model describing the spread of the epidemic in both humans and mosquitoes. The cumulative number of notified cases predicted by the model was 185 on average (95% CI 117-278), in good agreement with observed data. The probability of observing a major outbreak after the introduction of an infective human case was estimated to be in the range of 32%-76%. We found that the basic reproduction number was in the range of 1.8-6 but it could have been even larger, depending on the density of mosquitoes, which in turn depends on seasonal meteorological effects, besides other local abiotic factors. These results confirm the increasing risk of tropical vector-borne diseases in temperate climate countries, as a consequence of globalization. However, our results show that an epidemic can be controlled by performing a timely intervention, even if the transmission potential of Chikungunya virus is sensibly high.     

Modeling HIV Vaccines in Brazil: Assessing the Impact of a Future HIV Vaccine on Reducing New Infections,Mortality and Number of People Receiving ARV

Background

The AIDS epidemic in Brazil remains concentrated in populations with high vulnerability to HIV infection, and the development of an HIV vaccine could make an important contribution to prevention. This study modeled the HIV epidemic and estimated the potential impact of an HIV vaccine on the number of new infections, deaths due to AIDS and the number of people receiving ARV treatment, under various scenarios.

Methods and Findings

The historical HIV prevalence was modeled using Spectrum and projections were made from 2010 to 2050 to study the impact of an HIV vaccine with 40% to 70% efficacy, and 80% coverage of adult population, specific groups such as MSM, IDU, commercial sex workers and their partners, and 15 year olds. The possibility of disinhibition after vaccination, neglecting medium- and high-risk groups, and a disease-modifying vaccine were also considered. The number of new infections and deaths were reduced by 73% and 30%, respectively, by 2050, when 80% of adult population aged 15–49 was vaccinated with a 40% efficacy vaccine. Vaccinating medium- and high-risk groups reduced new infections by 52% and deaths by 21%. A vaccine with 70% efficacy produced a great decline in new infections and deaths. Neglecting medium- and high-risk population groups as well as disinhibition of vaccinated population reduced the impact or even increased the number of new infections. Disease-modifying vaccine also contributed to reducing AIDS deaths, the need for ART and new HIV infections.

Conclusions

Even in a country with a concentrated epidemic and high levels of ARV coverage, such as Brazil, moderate efficacy vaccines as part of a comprehensive package of treatment and prevention could have a major impact on preventing new HIV infections and AIDS deaths, as well as reducing the number of people on ARV. Targeted vaccination strategies may be highly effective and cost-beneficial.     

Spatial and temporal distribution of Alternaria spores in the Iberian Peninsula atmosphere, and meteorological relationships: 1993–2009

This paper provides an updated of airborne Alternaria spore spatial and temporal distribution patterns in the Iberian Peninsula, using a common non-viable volumetric sampling method. The highest mean annual spore counts were recorded in Sevilla (39,418 spores), Mérida (33,744) and Málaga (12,947), while other sampling stations never exceeded 5,000. The same cities also recorded the highest mean daily spore counts (Sevilla 109 spores m^?3; Mérida 53 spores m^?3 and Málaga 35 spores m^?3) and the highest number of days on which counts exceeded the threshold levels required to trigger allergy symptoms (Sevilla 38 % and Mérida 30 % of days). Analysis of annual spore distribution patterns revealed either one or two peaks, depending on the location and prevailing climate of sampling stations. For all stations, average temperature was the weather parameter displaying the strongest positive correlation with airborne spore counts, whilst negative correlations were found for rainfall and relative humidity.     

Spatio-Temporal Dynamics of Cholera during the First Year of the Epidemic in Haiti

Background

In October 2010, cholera importation in Haiti triggered an epidemic that rapidly proved to be the world''s largest epidemic of the seventh cholera pandemic. To establish effective control and elimination policies, strategies rely on the analysis of cholera dynamics. In this report, we describe the spatio-temporal dynamics of cholera and the associated environmental factors.

Methodology/Principal findings

Cholera-associated morbidity and mortality data were prospectively collected at the commune level according to the World Health Organization standard definition. Attack and mortality rates were estimated and mapped to assess epidemic clusters and trends. The relationships between environmental factors were assessed at the commune level using multivariate analysis. The global attack and mortality rates were 488.9 cases/10,000 inhabitants and 6.24 deaths/10,000 inhabitants, respectively. Attack rates displayed a significantly high level of spatial heterogeneity (varying from 64.7 to 3070.9 per 10,000 inhabitants), thereby suggesting disparate outbreak processes. The epidemic course exhibited two principal outbreaks. The first outbreak (October 16, 2010–January 30, 2011) displayed a centrifugal spread of a damping wave that suddenly emerged from Mirebalais. The second outbreak began at the end of May 2011, concomitant with the onset of the rainy season, and displayed a highly fragmented epidemic pattern. Environmental factors (river and rice fields: p<0.003) played a role in disease dynamics exclusively during the early phases of the epidemic.

Conclusion

Our findings demonstrate that the epidemic is still evolving, with a changing transmission pattern as time passes. Such an evolution could have hardly been anticipated, especially in a country struck by cholera for the first time. These results argue for the need for control measures involving intense efforts in rapid and exhaustive case tracking.     

Resurgence of HIV Infection among Men Who Have Sex with Men in Switzerland: Mathematical Modelling Study

Background

New HIV infections in men who have sex with men (MSM) have increased in Switzerland since 2000 despite combination antiretroviral therapy (cART). The objectives of this mathematical modelling study were: to describe the dynamics of the HIV epidemic in MSM in Switzerland using national data; to explore the effects of hypothetical prevention scenarios; and to conduct a multivariate sensitivity analysis.

Methodology/Principal Findings

The model describes HIV transmission, progression and the effects of cART using differential equations. The model was fitted to Swiss HIV and AIDS surveillance data and twelve unknown parameters were estimated. Predicted numbers of diagnosed HIV infections and AIDS cases fitted the observed data well. By the end of 2010, an estimated 13.5% (95% CI 12.5, 14.6%) of all HIV-infected MSM were undiagnosed and accounted for 81.8% (95% CI 81.1, 82.4%) of new HIV infections. The transmission rate was at its lowest from 1995–1999, with a nadir of 46 incident HIV infections in 1999, but increased from 2000. The estimated number of new infections continued to increase to more than 250 in 2010, although the reproduction number was still below the epidemic threshold. Prevention scenarios included temporary reductions in risk behaviour, annual test and treat, and reduction in risk behaviour to levels observed earlier in the epidemic. These led to predicted reductions in new infections from 2 to 26% by 2020. Parameters related to disease progression and relative infectiousness at different HIV stages had the greatest influence on estimates of the net transmission rate.

Conclusions/Significance

The model outputs suggest that the increase in HIV transmission amongst MSM in Switzerland is the result of continuing risky sexual behaviour, particularly by those unaware of their infection status. Long term reductions in the incidence of HIV infection in MSM in Switzerland will require increased and sustained uptake of effective interventions.