A model of HIV-1 transmission for urban areas of Africa

A model of the transmission dynamics of HIV-1, appropriate to urban areas of Africa, is presented and its behaviour explored through numerical studies. The model is a two-sex model with age-dependent demographic and behavioural parameters. Adults are classified by age, sex, risk group, and epidemiologic status. HIV-1 is transmitted to adults heterosexually, and to infants and children vertically and parenterally. Numerical studies show that, while AIDS will slow population growth, growth rates do not become negative for reasonable parameter values. The sex and age patterns of infection are explored, as is the potential economic impact of changes in the sex and age composition of the population.     

Population homeostasis in sub-Saharan Africa

Global population growth remains one of the major challenges of the twenty-first century. This is particularly true for African countries which have been undergoing their demographic transitions. To investigate whether predicted increasing population density and urbanization can help to stabilize African population, we construct a database for 84 georeferenced Demographic and Health Survey (DHS) samples including 947,191 individuals in sub-Saharan Africa and match each location with gridded population density from NASA. We apply a proportional hazard model to evaluate the quantitative impact of local population density on the transitions from childlessness to motherhood, and from celibacy to marriage. Moving from the 5th to the 95th percentile of population density increases the median age at first birth by 2.2 years. This roughly decreases completed fertility by half a child. The same increase in population density increases the median age at first marriage by 3.3 years. These findings contribute to the understanding of why fertility has not dropped in Africa as fast as expected. One part of the answer is that population density remains low. Yet the total effect of increased density on fertility remains limited and counting on it to stabilize the population would be unrealistic.     

Schistosomiasis in infants and pre-school-aged children in sub-Saharan Africa: implication for control

Until recently, the epidemiology and control of schistosomiasis in sub-Saharan Africa have focused primarily on infections in school-aged children and to a lesser extent on adults. Now there is growing evidence and reports of infection in infants and pre-school-aged children (≤ 6 years old) in Ghana, Kenya, Mali, Niger, Nigeria and Uganda, with reported prevalence from 14% to 86%. In this review, we provide available information on the epidemiology, transmission and control of schistosomiasis in this age group, generally not considered or included in national schistosomiasis control programmes that are being implemented in several sub-Saharan African countries. Contrary to previous assumptions, we show that schistosomiasis infection starts from early childhood in many endemic communities and factors associated with exposure of infants and pre-school-aged children to infection are yet to be determined. The development of morbidity early in childhood may contribute to long-term clinical impact and severity of schistosomiasis before they receive treatment. Consistently, these issues are overlooked in most schistosomiasis control programmes. It is, therefore, necessary to review current policy of schistosomiasis control programmes in sub-Saharan Africa to consider the treatment of infant and pre-school-aged children and the health education to mothers.     

Design of a "microbicide" for prevention of sexually transmitted diseases using "inactive" pharmaceutical excipients.

The human immunodeficiency virus (HIV-1) pandemic has been driven primarily by the sexual transmission of the virus, and facilitated by prior infections with other sexually transmitted disease (STD) pathogens. Although treatment of these STDs has been proposed as a means to decrease the rate of HIV-1 sexual transmission, preventive measures effective against both HIV-1 and other STD pathogens are expected to have a larger impact. These measures include topically applied mechanical and chemical (i.e. microbicidal) barriers. Microbicides of preference should have a broad specificity against diverse STD pathogens and a well established safety record, considering their repeated use over decades. Here, we report that cellulose acetate phthalate (CAP), an "inactive" pharmaceutical excipient, commonly used in the production of enteric tablets and capsules: (1) has antiviral activity against HIV-1 and several herpesviruses (HSV); and (2) when appropriately formulated, in micronized form, inactivates HIV-1, HSV-1, HSV-2, cytomegalovirus, Neisseria gonorrhoeae, Trichomonas vaginalis, Haemophilus ducreyi and Chlamydia trachomatis but does not affect Lactobacilli, components of the natural vaginal flora contributing to resistance against STDs. Thus, the CAP formulations meet the criteria for preferred microbicides and warrant further evaluation in vivo in humans.     

5436 例性病门诊患者流行病学调查及心理状况分析

目的:调查本地区5436例性病(STD)门诊患者流行病学特征,并对患者心理状况进行分析。方法:对2012年1月~2014年12月本地区3家医院性病门诊5436例患者(观察组)的5种生殖器疱疹(GH)、生殖道衣原体感染(GCI)、尖锐湿疣(CA)、淋病(GU)、梅毒(SYP)常见性传播疾病的基本情况、流行病学特征进行记录分析。采用自制心理测评量表对其中250例STD患者的心理状况进行评估,并与250例同期门诊治疗的一般感冒患者(对照组)进行比较。结果:2012~2014年门诊5种常见STD患者就诊人数呈上升趋势,以GU下降最为明显,GCI逐渐上升较为明显;STD患者发病主要集中于26~35岁,以司机、低学历及未婚人群居多。心理测评结果显示,STD患者的抑郁、焦虑、回避治疗、性欲障碍等因子分均高于对照组,差异有统计学意义(P0.05);交往障碍、社会攻击等因子分与对照组比较差异无统计学意义(P0.05)。结论:本地区STD患病以性活跃年龄人群、司机、学历低及未婚人群为主,临床上治疗性病的同时,应重视STD患者的心理健康。     

Decreasing HIV-1 seroprevalence in young adults in a rural Ugandan cohort.

OBJECTIVE--To assess the trend in HIV-1 seroprevalence in an adult population in Uganda. DESIGN--An observational cohort study with four year follow up. SETTING--A cluster of 15 villages in rural Uganda. SUBJECTS--All residents of the 15 villages--about 10,000 people. MAIN OUTCOME MEASURE--Prevalence of HIV-1 infection as assessed by enzyme immunoassay. RESULTS--During the five year period the overall standardised seroprevalence of HIV-1 showed little change; 8.2% in 1990, 7.6% in 1994. Among males aged 13-24 years the prevalence decreased from 3.4% to 1.0% (P for trend < 0.001); among females of the same age the corresponding values were 9.9% and 7.3%. The decrease was greatest in males aged 20-24 years and females aged 13-19 years. CONCLUSION--This is the first report of a decline in HIV-1 prevalence among young adults in a general population in sub-Saharan Africa with high overall HIV-1 prevalence. It is too early to conclude that the epidemic in this population is in decline, but the results of this study should be reason for some cautious optimism and encourage the vigorous pursuit of AIDS control measures.     

Mapping,Bayesian Geostatistical Analysis and Spatial Prediction of Lymphatic Filariasis Prevalence in Africa

There is increasing interest to control or eradicate the major neglected tropical diseases. Accurate modelling of the geographic distributions of parasitic infections will be crucial to this endeavour. We used 664 community level infection prevalence data collated from the published literature in conjunction with eight environmental variables, altitude and population density, and a multivariate Bayesian generalized linear spatial model that allows explicit accounting for spatial autocorrelation and incorporation of uncertainty in input data and model parameters, to construct the first spatially-explicit map describing LF prevalence distribution in Africa. We also ran the best-fit model against predictions made by the HADCM3 and CCCMA climate models for 2050 to predict the likely distributions of LF under future climate and population changes. We show that LF prevalence is strongly influenced by spatial autocorrelation between locations but is only weakly associated with environmental covariates. Infection prevalence, however, is found to be related to variations in population density. All associations with key environmental/demographic variables appear to be complex and non-linear. LF prevalence is predicted to be highly heterogenous across Africa, with high prevalences (>20%) estimated to occur primarily along coastal West and East Africa, and lowest prevalences predicted for the central part of the continent. Error maps, however, indicate a need for further surveys to overcome problems with data scarcity in the latter and other regions. Analysis of future changes in prevalence indicates that population growth rather than climate change per se will represent the dominant factor in the predicted increase/decrease and spread of LF on the continent. We indicate that these results could play an important role in aiding the development of strategies that are best able to achieve the goals of parasite elimination locally and globally in a manner that may also account for the effects of future climate change on parasitic infection.     

Age-dependent choice of sexual partners and the transmission dynamics of HIV in Sub-Saharan Africa.

A mathematical model of the transmission of HIV-1 within heterosexual populations in Sub-Saharan Africa is described and its properties analysed. The model incorporates epidemiological and demographic processes and extends previous work in this area via the inclusion of age and sex dependency in rates of sexual partner change, and sexual partner choice dependent on age. Parameter assignments are made on the basis of current data on the transmission dynamics of HIV-1 and the demography of human populations in Africa. Both age-dependent rates of sexual activity and the sexual contact of males with females younger than themselves act to enhance the predicted demographic impact. With realistic parameter values, the model suggests AIDS is able to reverse the sign of population growth rates from positive to negative values over a timescale of a few decades. The sensitivity of this prediction is examined in relation to changes in the pattern of sexual contact between different age classes of females and males, different patterns of change in the age-dependent rate of sexual partner change, different assumptions concerning the doubling time of the epidemic in its early stages, and the relative efficiencies of viral transmission between men and women, and vice versa. The impact AIDS is predicted to have on the number of young and elderly persons as a fraction of the number of productive adults (the dependancy ratio) is examined under various assumptions concerning the weighting to be applied to mirror the burden imposed by the care of those with AIDS. The paper includes an assessment of the influence of the timing of changes in sexual behaviour, or the promotion of the use of condoms, on the predicted course of the epidemic. The paper concludes with a discussion of data needs and the model refinements required to more accurately mirror current understanding of the epidemiology of HIV-1.     

The cumulative effects of management on the population dynamics of the Double‐crested Cormorant Phalacrocorax auritus in the Great Lakes

Wildlife species have been subject to control efforts throughout human history due to real or alleged human–wildlife conflicts. The Double‐crested Cormorant Phalacrocorax auritus in the interior of North America is no exception, with recent population growth leading to increased conflicts and consequently the development of many control programmes. These control programmes are usually conducted at local scales, often with little or no effort to assess their cumulative effects at the population level. We attempted the first comprehensive assessment of the cumulative effects of control at various spatio‐temporal scales, focusing on 199 colonies of Double‐crested Cormorant monitored during a 29‐year period. Linear models were used to assess the relationship between colony‐specific growth rates and a set of candidate factors using an information‐theoretic approach. Colony‐level density‐dependent effects and local control efforts had the greatest influences on population growth. We detected a cumulative effect of management, whereby (i) the reduction in population growth rate was generally stronger when different control activities such as culling or egg oiling were combined, and (ii) past control operations tended to have a pervasive impact on growth rates, especially egg oiling and nest destruction, which negatively affected local recruitment. However, our results also suggest that catastrophic events and the culling of breeding adults that occurred at least 2 years previously could fuel subsequent recruitment or natural immigration from nearby colonies, for instance if the breeding success of remaining pairs was increased through a diminution of density‐dependent regulatory processes. Density‐dependence at the metapopulation level constituted a third source of regulation, as local growth rates were reduced with increasing number or proximity of active neighbouring colonies. We also found evidence that the culling of Double‐crested Cormorants wintering in the southeastern USA could negatively impact the population growth of individual breeding colonies in the Great Lakes, although further research integrating models of migratory connectivity is needed to reach more definitive conclusions. Finally, despite previous studies emphasizing its importance, the net effect of management‐induced dispersal appeared small at large spatial scales. We show that this can be explained in part by control strategies (e.g. spatially clustered operations). The continuation of Cormorant management efforts will provide an opportunity to refine the present assessment of the relative importance of density‐dependence, breeding vs. non‐breeding season management and dispersal, particularly if population models are coupled with monitoring programmes within an adaptive management framework.     

What is the impact of acquired immunity on the transmission of schistosomiasis and the efficacy of current and planned mass drug administration programmes?

Schistosomiasis causes severe morbidity in many countries with endemic infection with the schistosome digenean parasites in Africa and Asia. To control and eliminate the disease resulting from infection, regular mass drug administration (MDA) is used, with a focus on school-aged children (SAC; 5–14 years of age). In some high transmission settings, the World Health Organization (WHO) also recommends the inclusion of at-risk adults in MDA treatment programmes. The question of whether ecology (age-dependant exposure) or immunity (resistance to reinfection), or some combination of both, determines the form of observed convex age-intensity profile is still unresolved, but there is a growing body of evidence that the human hosts acquire some partial level of immunity after a long period of repeated exposure to infection. In the majority of past research modelling schistosome transmission and the impact of MDA programmes, the effect of acquired immunity has not been taken into account. Past work has been based on the assumption that age-related contact rates generate convex horizontal age-intensity profiles. In this paper, we use an individual based stochastic model of transmission and MDA impact to explore the effect of acquired immunity in defined MDA programmes. Compared with scenarios with no immunity, we find that acquired immunity makes the MDA programme less effective with a slower decrease in the prevalence of infection. Therefore, the time to achieve morbidity control and elimination as a public health problem is longer than predicted by models with just age-related exposure and no build-up of immunity. The level of impact depends on the baseline prevalence prior to treatment (the magnitude of the basic reproductive number R₀) and the treatment frequency, among other factors. We find that immunity has a larger impact within moderate to high transmission settings such that it is very unlikely to achieve morbidity and transmission control employing current MDA programmes.     

An examination of factors influencing black fertility decline in the Mississippi Delta, 1880-1930

Although the fertility decline in the black population in the Mississippi Delta between the late 1870's and early 1930's closely paralleled that of the national black population, it rose much more dramatically in the 1940's and 1950's to almost 1880 levels. Given the especially rural and oppressed conditions of blacks there, the initial decline seems puzzling. Low fertility rates in the 1930's reflected a large proportion of childless females. Investigations of changing contraceptive usage and mate exposure suggest both were minor components at most. Several physiological impairments were investigated including dietary deficiences, malaria, tuberculosis, and sexually transmitted diseases (STD). Evidence suggests STD played the major role, facilitated by nutritional and other health problems. Models relying heavily on those developed by McFalls and McFalls (1984) suggest 50-80 percent of the decline could have been due to the spread of STD. Age-specific birth rates for different periods and post-World-War-II fertility increases seem consistent with this finding.     

The molecular population genetics of HIV-1 group O

HIV-1 group O originated through cross-species transmission of SIV from chimpanzees to humans and has established a relatively low prevalence in Central Africa. Here, we infer the population genetics and epidemic history of HIV-1 group O from viral gene sequence data and evaluate the effect of variable evolutionary rates and recombination on our estimates. First, model selection tools were used to specify suitable evolutionary and coalescent models for HIV group O. Second, divergence times and population genetic parameters were estimated in a Bayesian framework using Markov chain Monte Carlo sampling, under both strict and relaxed molecular clock methods. Our results date the origin of the group O radiation to around 1920 (1890-1940), a time frame similar to that estimated for HIV-1 group M. However, group O infections, which remain almost wholly restricted to Cameroon, show a slower rate of exponential growth during the twentieth century, explaining their lower current prevalence. To explore the effect of recombination, the Bayesian framework is extended to incorporate multiple unlinked loci. Although recombination can bias estimates of the time to the most recent common ancestor, this effect does not appear to be important for HIV-1 group O. In addition, we show that evolutionary rate estimates for different HIV genes accurately reflect differential selective constraints along the HIV genome.     

An examination of factors influencing black fertility decline in the Mississippi Delta, 1880–1930

Abstract

Although the fertility decline in the black population in the Mississippi Delta between the late 1870's and early 1930's closely paralleled that of the national black population, it rose much more dramatically in the 1940's and 1950's to almost 1880 levels. Given the especially rural and oppressed conditions of blacks there, the initial decline seems puzzling. Low fertility rates in the 1930's reflected a large proportion of childless females. Investigations of changing contraceptive usage and mate exposure suggest both were minor components at most. Several physiological impairments were investigated including dietary deficiences, malaria, tuberculosis, and sexually transmitted diseases (STD). Evidence suggests STD played the major role, facilitated by nutritional and other health problems. Models relying heavily on those developed by McFalls and McFalls (1984) suggest 50–80 percent of the decline could have been due to the spread of STD. Age‐specific birth rates for different periods and post‐World‐War‐II fertility increases seem consistent with this finding.     

Interrupting malaria transmission: quantifying the impact of interventions in regions of low to moderate transmission

Malaria has been eliminated from over 40 countries with an additional 39 currently planning for, or committed to, elimination. Information on the likely impact of available interventions, and the required time, is urgently needed to help plan resource allocation. Mathematical modelling has been used to investigate the impact of various interventions; the strength of the conclusions is boosted when several models with differing formulation produce similar data. Here we predict by using an individual-based stochastic simulation model of seasonal Plasmodium falciparum transmission that transmission can be interrupted and parasite reintroductions controlled in villages of 1,000 individuals where the entomological inoculation rate is <7 infectious bites per person per year using chemotherapy and bed net strategies. Above this transmission intensity bed nets and symptomatic treatment alone were not sufficient to interrupt transmission and control the importation of malaria for at least 150 days. Our model results suggest that 1) stochastic events impact the likelihood of successfully interrupting transmission with large variability in the times required, 2) the relative reduction in morbidity caused by the interventions were age-group specific, changing over time, and 3) the post-intervention changes in morbidity were larger than the corresponding impact on transmission. These results generally agree with the conclusions from previously published models. However the model also predicted changes in parasite population structure as a result of improved treatment of symptomatic individuals; the survival probability of introduced parasites reduced leading to an increase in the prevalence of sub-patent infections in semi-immune individuals. This novel finding requires further investigation in the field because, if confirmed, such a change would have a negative impact on attempts to eliminate the disease from areas of moderate transmission.     

Monogamous networks and the spread of sexually transmitted diseases

Patterns of sexual mixing and heterogeneity in the number of sexual partners can have a huge effect on the spread of a sexually transmitted disease (STD). The sexual mixing network identifies all partnerships within a population over a given period and is a powerful tool in the study of such infections. Previous models assumed all links within the network to be concurrent active partnerships. We present a novel modelling approach in which we adapt the notion of a sexual contact network to a monogamous population by allowing the nature of the links to change. We use the underlying network to represent potential sexual partnerships, only some of which are active at any one time. Thus serial monogamy can be modelled while maintaining the patterns of mixing displayed by the population.     

Unequal evolutionary rates in the human immunodeficiency virus type 1 (HIV-1) pandemic: the evolutionary rate of HIV-1 slows down when the epidemic rate increases

HIV-1 sequences in intravenous drug user (IDU) networks are highly homogenous even after several years, while this is not observed in most sexual epidemics. To address this disparity, we examined the human immunodeficiency virus type 1 (HIV-1) evolutionary rate on the population level for IDU and heterosexual transmissions. All available HIV-1 env V3 sequences from IDU outbreaks and heterosexual epidemics with known sampling dates were collected from the Los Alamos HIV sequence database. Evolutionary rates were calculated using phylogenetic trees with a t test root optimization of dated samples. The evolutionary rate of HIV-1 subtype A1 was found to be 8.4 times lower in fast spread among IDUs in the former Soviet Union (FSU) than in slow spread among heterosexual individuals in Africa. Mixed epidemics (IDU and heterosexual) showed intermediate evolutionary rates, indicating a combination of fast- and slow-spread patterns. Hence, if transmissions occur repeatedly during the initial stage of host infection, before selective pressures of the immune system have much impact, the rate of HIV-1 evolution on the population level will decrease. Conversely, in slow spread, where HIV-1 evolves under the pressure of the immune system before a donor infects a recipient, the virus evolution at the population level will increase. Epidemiological modeling confirmed that the evolutionary rate of HIV-1 depends on the rate of spread and predicted that the HIV-1 evolutionary rate in a fast-spreading epidemic, e.g., for IDUs in the FSU, will increase as the population becomes saturated with infections and the virus starts to spread to other risk groups.     

Regional differences in prevalence of HIV-1 discordance in Africa and enrollment of HIV-1 discordant couples into an HIV-1 prevention trial

Background

Most HIV-1 transmission in Africa occurs among HIV-1-discordant couples (one partner HIV-1 infected and one uninfected) who are unaware of their discordant HIV-1 serostatus. Given the high HIV-1 incidence among HIV-1 discordant couples and to assess efficacy of interventions for reducing HIV-1 transmission, HIV-1 discordant couples represent a critical target population for HIV-1 prevention interventions and prevention trials. Substantial regional differences exist in HIV-1 prevalence in Africa, but regional differences in HIV-1 discordance among African couples, has not previously been reported.

Methodology/Principal Findings

The Partners in Prevention HSV-2/HIV-1 Transmission Trial (“Partners HSV-2 Study”), the first large HIV-1 prevention trial in Africa involving HIV-1 discordant couples, completed enrollment in May 2007. Partners HSV-2 Study recruitment data from 12 sites from East and Southern Africa were used to assess HIV-1 discordance among couples accessing couples HIV-1 counseling and testing, and to correlate with enrollment of HIV-1 discordant couples. HIV-1 discordance at Partners HSV-2 Study sites ranged from 8–31% of couples tested from the community. Across all study sites and, among all couples with one HIV-1 infected partner, almost half (49%) of couples were HIV-1 discordant. Site-specific monthly enrollment of HIV-1 discordant couples into the clinical trial was not directly associated with prevalence of HIV-1 discordance, but was modestly correlated with national HIV-1 counseling and testing rates and access to palliative care/basic health care (r = 0.74, p = 0.09).

Conclusions/Significance

HIV-1 discordant couples are a critical target for HIV-1 prevention in Africa. In addition to community prevalence of HIV-1 discordance, national infrastructure for HIV-1 testing and healthcare delivery and effective community outreach strategies impact recruitment of HIV-1 discordant couples into HIV-1 prevention trials.     

The Characteristics of Heterosexual STD Clinic Attendees Who Practice Oral Sex in Zhejiang Province,China

Background

The characteristics of heterosexual attendees who visit sexually transmitted disease (STD) clinics and practice oral sex have not been revealed in China. This information is important for the development of targeted STD prevention programmes for this population.

Study Design

A self-administered questionnaire survey with a cross-sectional design was administered to consecutive attendees at four STD clinics in Zhejiang Province, China, between October and December in 2007. Demographic, psychosocial, and behavioural factors associated with oral sex over a lifetime were identified using univariate and multivariate analyses.

Results

Of the 872 attendees, 6.9% engaged in oral sex over their lifetimes. Of the oral-sex group, 96.6% also engaged in vaginal sex. The correlates for oral sex over a lifetime as determined by the multivariate analysis were high income (odds ratio [OR] = 2.53, 95% confidence interval [CI] 1.39–4.59), high human immunodeficiency virus (HIV)-related knowledge (OR = 2.71, 95% CI 1.26–5.81), early sex initiation (OR = 2.42, 95% CI 1.37–4.27), multiple sexual partners (OR = 3.09, 95% CI 1.58–6.06), and sexually active in the previous 6 months (OR = 7.73, 95% CI 1.04–57.39).

Conclusions

Though the prevalence of oral sex is low, the heterosexual STD clinic attendees practicing oral sex was found to have higher risks associated with STD/HIV transmission than those not. Behavioural and medical interventions conducted by clinicians in Chinese STD clinics should take into account the characteristics and related risks of those who practice oral sex.     

Affordable ART services in Africa: synthesis and adaptation of laboratory services

¹ Correspondence address. E-mail: carin.huyser{at}up.ac.za The aim of this paper is to provide information, opinions andsuggestions on affordable laboratory-orientated fertility screeningand treatment. Resource management to provide such servicesin developing countries, basic and advanced assisted reproductiveservices and assisted reproduction treatment (ART) of patientswith sexually transmitted infections are addressed. Alternativeviewpoints and parallel thinking should be encouraged to synthesizeand adapt first-world ART guidelines and recommendations intosafe and workable directives for developing regions. AffordableAfrican ART programmes, devoid of commercialism, can provideessential sexual health screening services en route to safefertility services for human immunodeficiency virus type-1 (HIV-1)serodiscordant couples (male HIV-positive), who wish to havetheir own biological child.     

The impact of disease on the survival and population growth rate of the Tasmanian devil

1. We investigated the impact of a recently emerged disease, Devil Facial Tumour Disease (DFTD), on the survival and population growth rate of a population of Tasmanian devils, Sarcophilus harrisii, on the Freycinet Peninsula in eastern Tasmania. 2. Cormack-Jolly-Seber and multistate mark-recapture models were employed to investigate the impact of DFTD on age- and sex-specific apparent survival and transition rates. Disease impact on population growth rate was investigated using reverse-time mark-recapture models. 3. The arrival of DFTD triggered an immediate and steady decline in apparent survival rates of adults and subadults, the rate of which was predicted well by the increase in disease prevalence in the population over time. 4. Transitions from healthy to diseased state increased with disease prevalence suggesting that the force of infection in the population is increasing and that the epidemic is not subsiding. 5. The arrival of DFTD coincided with a marked, ongoing decline in the population growth rate of the previously stable population, which to date has not been offset by population compensatory responses.