What underpins the decline in syphilis in Southern and Eastern Africa? An exploratory ecological analysis.

BACKGROUND: AIDS mortality played an important role in the decline in syphilis prevalence in the USA, but its effect on the dramatic reduction in syphilis prevalence in Southern and Eastern Africa has not been explored. In this ecological study, we investigated the extent to which the relationship between syphilis and HIV prevalence at a population level varied between the early and late periods of the HIV epidemic. METHODS: We performed linear regression analysis to measure the association between the national prevalence of syphilis and the peak-HIV prevalence in the early and late phases of the HIV epidemic in 11 countries of Southern and Eastern Africa. RESULTS: Our analysis showed a strong positive association between peak-HIV prevalence and syphilis prevalence early in the HIV epidemic (R(2)=0.59; p=0.006). Although only of borderline statistical significance, this linear relationship between HIV prevalence and syphilis prevalence switched to a negative direction late in the HIV epidemic (R(2)=0.32; p=0.07). CONCLUSIONS: AIDS mortality may have played an important role in the decline in syphilis in this region. Consequently, with AIDS deaths declining in Sub-Saharan Africa, vigilant surveillance of syphilis prevalence will be necessary to detect a potential re-emergence, as has occurred in high-income countries, and to render a timely public health response

HIV prevalence correlates with high-risk sexual behavior in Ethiopia's regions

BACKGROUND: HIV prevalence varies between 0.9 and 6.5% in Ethiopia's eleven regions. Little has been published examining the reasons for this variation. METHODS: We evaluated the relationship between HIV prevalence by region and a range of risk factors in the 2005 and 2011 Ethiopian Demographic Health Surveys. Pearson's correlation was used to assess the relationship between HIV prevalence and each variable. RESULTS: There was a strong association between HIV prevalence and three markers of sexual risk: mean lifetime number of partners (men: r = 0.87; P < 0.001; women: r = 0.60; P = 0.05); reporting sex with a non-married, non-cohabiting partner (men: r = 0.92; P < 0.001, women r = 0.93; P < 0.001); and premarital sex. Condom usage and HIV testing were positively associated with HIV prevalence, while the prevalence of circumcision, polygamy, age at sexual debut and male migration were not associated with HIV prevalence. CONCLUSION: Variation in sexual behavior may contribute to the large variations in HIV prevalence by region in Ethiopia. Population-level interventions to reduce risky sexual behavior in high HIV incidence regions should be considered

It’s the network, stupid: a population’s sexual network connectivity determines its STI prevalence [version 2; referees: 2 approved]

There is little consensus as to why sexually transmitted infections (STIs), including HIV and bacterial vaginosis (BV) are more prevalent in some populations than others. Using a broad definition of sexual network connectivity that includes both structural and conductivity-related factors, we argue that the available evidence suggests that high prevalence of traditional STIs, HIV and BV can be parsimoniously explained by these populations having more connected sexual networks. Positive feedback, whereby BV and various STIs enhance the spread of other STIs, then further accentuates the spread of BV, HIV and other STIs. We review evidence that support this hypothesis and end by suggesting study designs that could further evaluate the hypothesis, as well as implications of this hypothesis for the prevention and management of STIs

Migration intensity has no effect on peak HIV prevalence: An ecological study

Background: Correctly identifying the determinants of generalized HIV epidemics is crucial to bringing down ongoing high HIV incidence in these countries. High rates of migration are believed to be an important determinant of HIV prevalence. This study has two aims. Firstly, it evaluates the ecological association between levels of internal and international migration and national peak HIV prevalence using thirteen variables from a variety of sources to capture various aspects of internal and international migration intensity. Secondly, it examines the relationship between circular migration and HIV at an individual and population-level in South Africa.Methods: Linear regression was used to analyze the association between the various measures of migration intensity and peak national HIV prevalence for 141 countries and HIV prevalence by province and ethnic group in South Africa.Results: No evidence of a positive ecological association between national migration intensity and HIV prevalence was found. This remained the case when the analyses were limited to the countries of sub-Saharan Africa. On the whole, countries with generalized HIV epidemics had lower rates of internal and external migration. Likewise, no association was found between migration and HIV positivity at an individual or group-level in South Africa.Conclusion: These results do not support the thesis that migration measured at the country level plays a significant role in determining peak HIV prevalence

Does gonorrhoea screening intensity play a role in the early selection of antimicrobial resistance in men who have sex with men (MSM)? A comparative study of Belgium and the United Kingdom [version 2; referees: 2 approved, 1 not approved]

Background: It is unclear why antimicrobial resistance in Neisseria gonorrhoeae in the United Kingdom (UK) and the United States has tended to first appear in men who have sex with men (MSM). We hypothesize that increased exposure to antimicrobials from intensive STI screening programmes plays a role. Methods: We assess if there is a difference in the distribution of azithromycin, cefixime and ceftriaxone minimum inhibitory concentrations (MICs) between MSM and women in the United Kingdom (UK) where 70% of MSM report STI screening in the past year vs. Belgium where 9% report STI screening in the past year. Our hypothesis is that MICs of the MSM should be higher than those of the women in the UK but not Belgium. Data for the MICs were taken from the Gonococcal Resistance to Antimicrobials Surveillance Programme (GRASP) in the UK in 2010/2011 and 2014 and a similar national surveillance programme in Belgium in 2013/2014 (the first most complete available data). We used the Mann–Whitney test to compare the MIC distributions between MSM and women within each country Results: In the UK the MICs for all three antimicrobials were significantly higher in MSM than women at both time points (P all <0.0005). In Belgium only the MIC distribution for azithromycin was higher in MSM (P<0.0005). Conclusion: The findings for cefixime and ceftriaxone, but not azithromycin are compatible with our hypothesis that screening-intensity could contribute to the emergence of AMR. Numerous other interpretations of our results are discussed

Strong association between higher-risk sex and HIV prevalence at the regional level: an ecological study of 27 sub-Saharan African countries [version 1; referees: 2 approved]

Background: It is unclear why HIV prevalence varies by nearly two orders of magnitude between regions within countries in sub-Saharan Africa. In this ecological study, we assess if HIV prevalence by region is associated with any of four markers of higher risk sexual behavior: lifetime number of partners, multiple partners in past year, higher risk sex (defined as sex with non-cohabiting, non-marital partners) and age at debut. Methods: We performed Pearson’s correlation between the 4 behavioral risk factors and HIV prevalence by region in 47 nationally representative surveys from 27 sub-Saharan African countries, separately by gender. In addition, principal components analysis was used to reduce the eight risk factors (four for each gender) to two principal components (PCs). Mixed effects linear regression was used to assess the relationship between the resulting two PCs and HIV prevalence after controlling for the prevalence of male circumcision. Results: HIV prevalence varied by a median 3.7 fold (IQR 2.9-7.9) between regions within countries. HIV prevalence was strongly associated with higher risk sex and, to a lesser extent, the other risk factors evaluated. Both PCs were strongly associated with HIV prevalence when assessed via linear regression. Conclusions: Differences in sexual behavior may underpin the large differences in HIV-prevalence between subpopulation within sub-Saharan African countries

The estimated burden of fungal disease in South Africa

Publication fees were paid via funding from a grant from Fonds.Peer reviewedPublisher PD

The value of blood culture audits at peripheral hospitals

Knowledge of local antibiotic sensitivities is crucial to creating appropriate empiric antibiotic guidelines. The new National Health Laboratory Service (NHLS) Data Warehouse allows clinicians to access collated spreadsheets of culture isolates and antimicrobial susceptibility patterns for their facilities. We used this service to study the trends in blood culture (BC) results at GF Jooste Hospital from 2005 to 2010. We investigated the BC contamination rate and changes in the antibiotic sensitivity profiles of selected organisms, and estimated the proportion of infections that were hospital-acquired. Over 3000 BCs were performed per year in this period. A very high contamination rate was observed (7 - 9%) in 2005 - 2007, with a gratifying reduction by 2010. Ceftriaxone resistance increased from 16% to 62% in Klebsiella pneumoniae (

Needle lost in the haystack: multiple reaction monitoring fails to detect Treponema pallidum candidate protein biomarkers in plasma and urine samples from individuals with syphilis [version 2; referees: 2 approved]

Background: Current syphilis diagnostic strategies are lacking a sensitive manner of directly detecting Treponema pallidum antigens. A diagnostic test that could directly detect T. pallidum antigens in individuals with syphilis would be of considerable clinical utility, especially for the diagnosis of reinfections and for post-treatment serological follow-up. Methods: In this study, 11 candidate T. pallidum biomarker proteins were chosen according to their physiochemical characteristics, T. pallidum specificity and predicted abundance. Thirty isotopically labelled proteotypic surrogate peptides (hPTPs) were synthesized and incorporated into a scheduled multiple reaction monitoring assay. Protein extracts from undepleted/unenriched plasma (N = 18) and urine (N = 4) samples from 18 individuals with syphilis in various clinical stages were tryptically digested, spiked with the hPTP mixture and analysed with a triple quadruple mass spectrometer. Results: No endogenous PTPs corresponding to the eleven candidate biomarkers were detected in any samples analysed. To estimate the Limit of Detection (LOD) of a comparably sensitive mass spectrometer (LTQ-Orbitrap), two dilution series of rabbit cultured purified T. pallidum were prepared in PBS. Polyclonal anti-T. pallidum antibodies coupled to magnetic Dynabeads were used to enrich one sample series; no LOD improvement was found compared to the unenriched series. The estimated LOD of MS instruments is 300 T. pallidum/ml in PBS. Conclusions: Biomarker protein detection likely failed due to the low (femtomoles/liter) predicted concentration of T. pallidum proteins. Alternative sample preparation strategies may improve the detectability of T. pallidum proteins in biofluids

Transcription controls growth, cell kinetics and cholesterol supply to sustain ACTH responses

Chronic ACTH exposure is associated with adrenal hypertrophy and steroidogenesis. The underlying molecular processes in mice have been analysed by microarray, histological and immunohistochemical techniques. Synacthen infused for 2 weeks markedly increased adrenal mass and plasma corticosterone levels. Microarray analysis found greater than 2-fold changes in expression of 928 genes (P < 0.001; 397 up, 531 down). These clustered in pathways involved in signalling, sterol/lipid metabolism, cell proliferation/hypertrophy and apoptosis. Signalling genes included some implicated in adrenal adenomas but also upregulated genes associated with cyclic AMP and downregulated genes associated with aldosterone synthesis. Sterol metabolism genes were those promoting cholesterol supply (Scarb1, Sqle, Apoa1) and disposal (Cyp27a1, Cyp7b1). Oil red O staining showed lipid depletion consistent with reduced expression of genes involved in lipid synthesis. Genes involved in steroidogenesis (Star, Cyp11a1, Cyp11b1) were modestly affected (P < 0.05; <1.3-fold). Increased Ki67, Ccna2, Ccnb2 and Tk1 expression complemented immunohistochemical evidence of a 3-fold change in cell proliferation. Growth arrest genes, Cdkn1a and Cdkn1c, which are known to be active in hypertrophied cells, were increased >4-fold and cross-sectional area of fasciculata cells was 2-fold greater. In contrast, genes associated with apoptosis (eg Casp12, Clu,) were downregulated and apoptotic cells (Tunel staining) were fewer (P < 0.001) and more widely distributed throughout the cortex. In summary, long-term steroidogenesis with ACTH excess is sustained by genes controlling cholesterol supply and adrenal mass. ACTH effects on adrenal morphology and genes controlling cell hypertrophy, proliferation and apoptosis suggest the involvement of different cell types and separate molecular pathways