Mapping and characterising areas with high levels of HIV transmission in sub-Saharan Africa: A geospatial analysis of national survey data.

BACKGROUND: In the generalised epidemics of sub-Saharan Africa (SSA), human immunodeficiency virus (HIV) prevalence shows patterns of clustered micro-epidemics. We mapped and characterised these high-prevalence areas for young adults (15-29 years of age), as a proxy for areas with high levels of transmission, for 7 countries in Eastern and Southern Africa: Kenya, Malawi, Mozambique, Tanzania, Uganda, Zambia, and Zimbabwe. METHODS AND FINDINGS: We used geolocated survey data from the most recent United States Agency for International Development (USAID) demographic and health surveys (DHSs) and AIDS indicator surveys (AISs) (collected between 2008-2009 and 2015-2016), which included about 113,000 adults-of which there were about 53,000 young adults (27,000 women, 28,000 men)-from over 3,500 sample locations. First, ordinary kriging was applied to predict HIV prevalence at unmeasured locations. Second, we explored to what extent behavioural, socioeconomic, and environmental factors explain HIV prevalence at the individual- and sample-location level, by developing a series of multilevel multivariable logistic regression models and geospatially visualising unexplained model heterogeneity. National-level HIV prevalence for young adults ranged from 2.2% in Tanzania to 7.7% in Mozambique. However, at the subnational level, we found areas with prevalence among young adults as high as 11% or 15% alternating with areas with prevalence between 0% and 2%, suggesting the existence of areas with high levels of transmission Overall, 15.6% of heterogeneity could be explained by an interplay of known behavioural, socioeconomic, and environmental factors. Maps of the interpolated random effect estimates show that environmental variables, representing indicators of economic activity, were most powerful in explaining high-prevalence areas. Main study limitations were the inability to infer causality due to the cross-sectional nature of the surveys and the likely under-sampling of key populations in the surveys. CONCLUSIONS: We found that, among young adults, micro-epidemics of relatively high HIV prevalence alternate with areas of very low prevalence, clearly illustrating the existence of areas with high levels of transmission. These areas are partially characterised by high economic activity, relatively high socioeconomic status, and risky sexual behaviour. Localised HIV prevention interventions specifically tailored to the populations at risk will be essential to curb transmission. More fine-scale geospatial mapping of key populations,-such as sex workers and migrant populations-could help us further understand the drivers of these areas with high levels of transmission and help us determine how they fuel the generalised epidemics in SSA.

The rise and fall of HIV in high-prevalence countries: a challenge for mathematical modeling.

Several countries with generalized, high-prevalence HIV epidemics, mostly in sub-Saharan Africa, have experienced rapid declines in transmission. These HIV epidemics, often with rapid onsets, have generally been attributed to a combination of factors related to high-risk sexual behavior. The subsequent declines in these countries began prior to widespread therapy or implementation of any other major biomedical prevention. This change has been construed as evidence of behavior change, often on the basis of mathematical models, but direct evidence for behavior changes that would explain these declines is limited. Here, we look at the structure of current models and argue that the common "fixed risk per sexual contact" assumption favors the conclusion of substantial behavior changes. We argue that this assumption ignores reported non-linearities between exposure and risk. Taking this into account, we propose that some of the decline in HIV transmission may be part of the natural dynamics of the epidemic, and that several factors that have traditionally been ignored by modelers for lack of precise quantitative estimates may well hold the key to understanding epidemiologic trends.

High HIV risk in a cohort of male sex workers from Nairobi, Kenya.

OBJECTIVES: Men who have sex with men (MSM) are at high risk of HIV-1 acquisition and transmission, yet there remains limited data in the African context, and for men who sell sex to men (MSM SW) in particular. METHODS: We enrolled 507 male sex workers in a Nairobi-based prospective cohort study during 2009-2012. All participants were offered HIV/STI screening, counselling and completed a baseline questionnaire. RESULTS: Baseline HIV prevalence was 40.0% (95% CI 35.8% to 44.3%). Prevalent HIV infection was associated with age, less postsecondary education, marijuana use, fewer female partners and lower rates of prior HIV testing. Most participants (73%) reported at least two of insertive anal, receptive anal and insertive vaginal sex in the past 3 months. Vaginal sex was reported by 37% of participants, and exclusive MSM status was associated with higher HIV rates. Condom use was infrequent, with approximately one-third reporting 100% condom use during anal sex. HIV incidence was 10.9 per 100 person-years (95% CI 7.4 to 15.6). Predictors of HIV risk included history of urethral discharge (aHR 0.29, 95% CI 0.08 to 0.98, p=0.046), condom use during receptive anal sex (aHR 0.05, 95% CI 0.01 to 0.41, p=0.006) and frequency of sex with male partners (aHR 1.33/sex act, 95% CI 1.01 to 1.75, p=0.04). CONCLUSIONS: HIV prevalence and incidence were extremely high in Nairobi MSM SW; a combination of interventions including increasing condom use, pre-exposure prophylaxis and access to effective treatment is urgently needed to decrease HIV transmission in this key population.

The individualistic fallacy, ecological studies and instrumental variables: a causal interpretation.

The validity of ecological studies in epidemiology for inferring causal relationships has been widely challenged as observed associations could be biased by the Ecological Fallacy. We reconsider the important design components of ecological studies, and discuss the conditions that may lead to spurious associations. Ecological associations are useful and valid when the ecological exposures can be interpreted as Instrumental Variables. A suitable example may be a time series analysis of environmental pollution (e.g. particulate matter with an aerodynamic diameter of <10 micrometres; PM10) and health outcomes (e.g. hospital admissions for acute myocardial infarction) as environmental pollution levels are a cause of individual exposure levels and not just an aggregate measurement. Ecological exposures may also be employed in situations (perhaps rare) where individual exposures are known but their associations with health outcomes are confounded by unknown or unquantifiable factors. Ecological associations have a notorious reputation in epidemiology and individualistic associations are considered superior to ecological associations because of the "ecological fallacy". We have argued that this is incorrect in situations in which ecological or aggregate exposures can serve as an instrumental variable and associations between individual exposure and outcome are likely to be confounded by unmeasured variables.

Prediction of the origin of French Legionella pneumophila strains using a mixed-genome microarray.

BACKGROUND: Legionella is a water and soil bacterium that can infect humans, causing a pneumonia known as Legionnaires' disease. The pneumonia is almost exclusively caused by the species L. pneumophila, of which serogroup 1 is responsible for 90% of patients. Within serogroup 1, large differences in prevalence in clinical isolates have been described. A recent study, using a Dutch Legionella strain collection, identified five virulence associated markers. In our study, we verify whether these five Dutch markers can predict the patient or environmental origin of a French Legionella strain collection. In addition, we identify new potential virulence markers and verify whether these can predict better. A total of 219 French patient isolates and environmental strains were compared using a mixed-genome micro-array. The micro-array data were analysed to identify predictive markers, using a Random Forest algorithm combined with a logistic regression model. The sequences of the identified markers were compared with eleven known Legionella genomes, using BlastN and BlastX; the functionality for each of the predictive markers was checked in the literature. RESULTS: The five Dutch markers insufficiently predicted the patient or environmental origin of the French Legionella strains. Subsequent analyses identified four predictive markers for the French collection that were used for the logistic regression model. This model showed a negative predictive value of 91%. Three of the French markers differed from the Dutch markers, one showed considerable overlap and was found in one of the Legionella genomes (Lorraine strain). This marker encodes for a structural toxin protein RtxA, described for L. pneumophila as a factor involved in virulence and entry in both human cells and amoebae. CONCLUSIONS: The combination of a mixed-genome micro-array and statistical analysis using a Random Forest algorithm has identified virulence markers in a consistent way. The Lorraine strain and related Dutch and French Legionella strains contain a marker that encodes a RtxA protein which probably is involved in the increased prevalence in clinical isolates. The current set of predictive markers is insufficient to justify its use as a reliable test in the public health field in France. Our results suggest that genetic differences in Legionella strains exist between geographically distinct entities. It may be necessary to develop region-specific mixed-genome microarrays that are constantly adapted and updated.

Emirates Heart Health Project (EHHP): A protocol for a stepped-wedge family-cluster randomized-controlled trial of a health-coach guided diet and exercise intervention to reduce weight and cardiovascular risk in overweight and obese UAE nationals.

INTRODUCTION: Cardiovascular disease (CVD) is the most common cause of death both globally and in the United Arab Emirates. Despite public health measures and health education, the rates of death from CVD remain stable. Barriers previously identified to lifestyle changes include cultural reasons, boredom, and lack of family support. The Emirates Heart Health Project (EHHP) seeks to support healthy lifestyle changes through a family-based intervention using a health coach and fitness tracker. METHODS AND ANALYSIS: The EHHP is a stepped-wedge cluster-randomized trial with each cluster comprised of members of an extended family. Eligible participants will be ≥ 18 years of age, with BMI ≥ 25, have Emirati citizenship and be able to give informed consent for study participation. The cluster will have 16 weekly teaching sessions in the participants' family home by a health coach who will review individual weight, diet and exercise (monitored by a wearable fitness tracker). The clusters will have pre-intervention assessments of their weight and CVD risk profile and enter the intervention in randomized order. Each cluster will have a post-intervention assessment of the same measures. The primary outcome is weight reduction from baseline. Secondary outcomes will include change in CVD risk factors such as systolic and diastolic blood pressure, hemoglobin A1c, total cholesterol, LDL cholesterol, HDL cholesterol and triglycerides, waist circumference, and BMI. A mixed linear model will be used for analysis, where the parameters measured at the end of each 16-week episode will be the outcome values. These will be analyzed such that baseline values (measured just prior to the start of an episode) will be fixed covariables. Random effects are the family units. This trial has been registered with the NIH at clinicaltrials.gov (NCT04688684) and is being reported using the SPIRIT (Standard Protocol Items: Recommendations for Interventional Trials) and TIDieR (Template for intervention description and replication) framework. TRIAL REGISTRATION: Clinicaltrials.gov NCT04688684.

HIV-specific CD8+ T-cell proliferation is prospectively associated with delayed disease progression.

Human immunodeficiency virus (HIV)-specific CD8(+) T-cell proliferation is consistently correlated with enhanced host HIV immune control, but whether proliferative responses are a cause or consequence of immune protection is unclear. We measured Env-specific CD8(+) T-cell proliferation and interferon (IFN)-γ secretion in HIV-infected participants with CD4 counts >200, who then completed 121 person-years of prospective follow-up to monitor HIV disease progression. In all, 13 of 31 participants (42%) reached end point during longitudinal follow-up. Strong Env-specific CD8(+) T-cell proliferation (>10% of CD8(+) T cells) was observed in 14/31 participants at baseline, and this was associated with a longer time to HIV disease progression end point, stratified baseline CD4 count (P=0.016). No associations were observed for IFN-γ ELISPOT responses and progression (P>0.2). Strong proliferation remained significant in multivariate Cox regression analyses (P=0.044) as an independent predictor of delayed HIV disease progression, along with baseline CD4 count (P=0.04). Duration of HIV infection was associated with more rapid progression in univariate, but not multivariate, analysis (P=0.112). Age and baseline viral load were not predictive of progression. HIV-specific CD8(+) T-cell proliferation was a correlate of protective immunity in this prospective study; such responses may be important for HIV vaccine protection.

Determinants of carriage of resistant Staphylococcus aureus among S. aureus carriers in the Indonesian population inside and outside hospitals.

SUMMARY OBJECTIVES: To identify determinants of carriage of resistant Staphylococcus aureus in both hospitalized patients and individuals from the community in two urban centres in Indonesia. METHODS: Staphylococcus aureus cultures and data on recent antibiotic use, demographic, socioeconomic, disease-related and healthcare-related variables were collected from 3995 community dwellers and hospitalized persons. Nasal S. aureus carriage was found in 362 persons (9.1%). Logistic regression analysis was performed to identify which variables were independently associated with carriage of resistant S. aureus. RESULTS: The penicillins were the most frequently used antibiotics both in the community and in hospitalized patients. In the community, admission to a hospital was associated with carriage of S. aureus resistant to any of the tested antibiotics [odds ratio (OR) 2.5, 95% confidence interval (95% CI) 1.3-4.9] and any tetracycline resistance (OR 2.4, 95% CI 1.1-5.1). Having no symptoms was associated with less carriage of S. aureus with resistance to any of the tested antibiotics (OR 0.5, 95% CI 0.3-0.9) and any tetracycline resistance (OR 0.5, 95% CI 0.3-0.9). Crowding (OR 4.5, 95% CI 1.2-4.9) and low income (OR 8.9, 95% CI 1.8-43.9) were associated with multidrug resistance. In hospitalized patients, the use of penicillins was associated with resistance to any of the tested antibiotics (OR 3.9, 95% CI 1.4-11.6) and any tetracycline resistance (OR 3.7, 95% CI 1.1-12.0). CONCLUSIONS: Antibiotic policies including proper diagnosis, treatment and drug delivery process should be made by healthcare providers in Indonesia to help limit the emergence of antibiotic resistance.

Detection of excess influenza severity: associating respiratory hospitalization and mortality data with reports of influenza-like illness by primary care physicians.

OBJECTIVES: We explored whether excesses in influenza severity can be detected by combining respiratory syndromic hospital and mortality data with data on influenza-like illness (ILI) cases obtained from general practitioners. METHODS: To identify excesses in the severity of influenza infections in the population of the Netherlands between 1999 and 2005, we looked for increases in influenza-associated hospitalizations and mortality that were disproportionate to the number of ILI cases reported by general practitioners. We used generalized estimating equation regression models to associate syndromic hospital and mortality data with ILI surveillance data obtained from general practitioners. Virus isolation and antigenic characterization data were used to interpret the results. RESULTS: Disproportionate increases in hospitalizations and mortality (relative to ILI cases reported by general practitioners) were identified in 2003/04 during the A/Fujian/411/02(H3N2) drift variant epidemic. CONCLUSIONS: Combined surveillance of respiratory hospitalizations and mortality and ILI data obtained from general practitioners can capture increases in severe influenza-associated illness that are disproportionate to influenza incidence rates. Therefore, this novel approach should complement traditional seasonal and pandemic influenza surveillance in efforts to detect increases in influenza case fatality rates and percentages of patients hospitalized.

A successful chronic care program in Al Ain-United Arab Emirates.

BACKGROUND: The cost effective provision of quality care for chronic diseases is a major challenge for health care systems. We describe a project to improve the care of patients with the highly prevalent disorders of diabetes and hypertension, conducted in one of the major cities of the United Arab Emirates. SETTINGS AND METHODS: The project, using the principles of quality assurance cycles, was conducted in 4 stages.The assessment stage consisted of a community survey and an audit of the health care system, with particular emphasis on chronic disease care. The information gleaned from this stage provided feedback to the staff of participating health centers. In the second stage, deficiencies in health care were identified and interventions were developed for improvements, including topics for continuing professional development.In the third stage, these strategies were piloted in a single health centre for one year and the outcomes evaluated. In the still ongoing fourth stage, the project was rolled out to all the health centers in the area, with continuing evaluation. The intervention consisted of changes to establish a structured care model based on the predicted needs of this group of patients utilizing dedicated chronic disease clinics inside the existing primary health care system. These clinics incorporated decision-making tools, including evidence-based guidelines, patient education and ongoing professional education. RESULTS: The intervention was successfully implemented in all the health centers. The health care quality indicators that showed the greatest improvement were the documentation of patient history (e.g. smoking status and physical activity); improvement in recording physical signs (e.g. body mass index (BMI)); and an improvement in the requesting of appropriate investigations, such as HbA1c and microalbuminurea. There was also improvement in those parameters reflecting outcomes of care, which included HbA1c, blood pressure and lipid profiles. Indicators related to lifestyle changes, such as smoking cessation and BMI, failed to improve. CONCLUSION: Chronic disease care is a joint commitment by health care providers and patients. This combined approach proved successful in most areas of the project, but the area of patient self management requires further improvement.

An integrative bioinformatic approach for studying escape mutations in human immunodeficiency virus type 1 gag in the Pumwani Sex Worker Cohort.

Human immunodeficiency virus type 1 (HIV-1) is able to evade the host cytotoxic T-lymphocyte (CTL) response through a variety of escape avenues. Epitopes that are presented to CTLs are first processed in the presenting cell in several steps, including proteasomal cleavage, transport to the endoplasmic reticulum, binding by the HLA molecule, and finally presentation to the T-cell receptor. An understanding of the potential of the virus to escape CTL responses can aid in designing an effective vaccine. To investigate such a potential, we analyzed HIV-1 gag from 468 HIV-1-positive Kenyan women by using several bioinformatic approaches that allowed the identification of positively selected amino acids in the HIV-1 gag region and study of the effects that these mutations could have on the various stages of antigen processing. Correlations between positively selected residues and mean CD4 counts also allowed study of the effect of mutation on HIV disease progression. A number of mutations that could create or destroy proteasomal cleavage sites or reduce binding affinity of the transport antigen processing protein, effectively hindering epitope presentation, were identified. Many mutations correlated with the presence of specific HLA alleles and with lower or higher CD4 counts. For instance, the mutation V190I in subtype A1-infected individuals is associated with HLA-B*5802 (P = 4.73 x 10(-4)), a rapid-progression allele according to other studies, and also to a decreased mean CD4 count (P = 0.019). Thus, V190I is a possible HLA escape mutant. This method classifies many positively selected mutations across the entire gag region according to their potential for immune escape and their effect on disease progression.

Associations of cardiovascular risk factors in Al Ain, United Arab Emirates.

BACKGROUND: Over the last 30 years the citizens of the United Arab Emirates have experienced major changes in life-style secondary to increased affluence. Currently, 1 in 5 adults have diabetes mellitus, but the associations (clustering) among risk factors, as well as the relevance of the concept of the metabolic syndrome, in this population is unknown. AIM: To investigate the prevalence and associations among cardiovascular risk factors in this population, and explore to what extent associations can be explained by the metabolic syndrome according to ATP-III criteria. METHOD: A community based survey, of conventional risk factors for cardiovascular disease was conducted among 817 national residents of Al Ain city, UAE. These factors were fasting blood sugar, blood pressure, lipid profile, BMI, waist circumference, smoking, or CHD family history. Odds ratios between risks factors, both unadjusted and adjusted for age and sex as well as adjusted for age, sex, and metabolic syndrome were calculated. RESULTS: Various risk factors were positively associated in this population; associations that are mostly unexplained by confounding by age and sex. For example, hypertension and diabetes were still strongly related (OR 2.5; 95% CI 1.7-3.7) after adjustment. An increased waist circumference showed similar relationship with hypertension (OR 2.3; 95% CI 1.5-3.5). Diabetes was related to an increased BMI (OR 1.5; 96% CI 1.0-2.3). Smoking was also associated with diabetes (OR 1.9, 95% CI 1.0-3.3).Further adjustment for metabolic syndrome reduced some associations but several remained. CONCLUSION: In this population risk-factors cluster, but associations do not appear to be explained by the presence/absence of the ATP-III metabolic syndrome. Associations provide valuable information in planning interventions for screening and management.

Validation of syndromic surveillance for respiratory pathogen activity.

Syndromic surveillance is increasingly used to signal unusual illness events. To validate data-source selection, we retrospectively investigated the extent to which 6 respiratory syndromes (based on different medical registries) reflected respiratory pathogen activity. These syndromes showed higher levels in winter, which corresponded with higher laboratory counts of Streptococcus pneumoniae, respiratory syncytial virus, and influenza virus. Multiple linear regression models indicated that most syndrome variations (up to 86%) can be explained by counts of respiratory pathogens. Absenteeism and pharmacy syndromes might reflect nonrespiratory conditions as well. We also observed systematic syndrome elevations in the fall, which were unexplained by pathogen counts but likely reflected rhinovirus activity. Earliest syndrome elevations were observed in absenteeism data, followed by hospital data (+1 week), pharmacy/general practitioner consultations (+2 weeks), and deaths/laboratory submissions (test requests) (+3 weeks). We conclude that these syndromes can be used for respiratory syndromic surveillance, since they reflect patterns in respiratory pathogen activity.

Potential benefits of controlling coronary heart disease risk factors in the United Arab Emirates.

BACKGROUND: Cardiovascular risk factors including obesity, diabetes, hypertension, and dyslipidemia, are highly prevalent in the United Arab Emirates. In spite of significant awareness initiatives, little is known about the potential benefits of controlling these risk factors. AIMS: To assess the prevalence of preventable risk factors for coronary heart disease (CHD), and the likely benefits of controlling these risk factors. METHODS: In a health survey stratified by self-reported hypertension, we enrolled 349 hypertensive and 641 normotensive subjects of diverse ethnicity in Al-Ain city, and measured CHD risk factors. We used the Framingham risk score to estimate the proportion of CHD potentially preventable by controlling hypertension, dyslipidemia, diabetes mellitus (DM), and smoking. RESULTS: Smoking was similar in the two groups (hypertensives 13.2% vs. normotensives 14.2%). The prevalence of diabetes, dyslipidemia [mean (SD) triglycerides, high-density lipoprotein-cholesterol (HDL-C)], overweight/obesity, and thus the 10-year Framingham risk were all significantly (p < 0.001) higher among hypertensive than normotensives. CONCLUSION: Prevention of type 2 DM, aggressive control of hypertension and dyslipidemia, and smoking cessation could potentially reduce the 10-year incidence of CHD. Barriers include lack of awareness of this problem among the general population and health care providers.

High prevalence of the cardiovascular risk factors in Al-Ain, United Arab Emirates. An emerging health care priority.

OBJECTIVE: In the United Arab Emirates (UAE) cardiovascular mortality is a leading cause of death. Yet, there is a dearth of data on its risk factors. METHODS: A cross-sectional community based study on established cardiovascular risk factors carried out between February 2004 - February 2005 in Al-Ain City, UAE. Subjects were interviewed, blood pressure, weight, height, fasting blood sugar, and lipid profile measured. Framingham risk scores were used for risk assessment. RESULTS: Eight hundred seventeen subjects (403 males and 414 females) completed the survey, of these 28.4% had a Framingham risk assessment score of more than 20%, 23.3% had diabetes mellitus, 20.8% hypertension, 37.3% obesity, 22.7% metabolic syndrome, and 19.6% of male smoked. Coronary heart disease was reported in 2.4%. Lipid profiles were abnormal in 64% of the males, and in 53.9% of the females, mostly due to low high-density lipoproteins or high triglycerides levels. CONCLUSION: The overall cardiovascular risk assessment of the population screened calls for targeted interventions.

Modelling the public health impact of male circumcision for HIV prevention in high prevalence areas in Africa.

BACKGROUND: Recent clinical trials in Africa, in combination with several observational epidemiological studies, have provided evidence that male circumcision can reduce HIV female-to-male transmission risk by 60% or more. However, the public health impact of large-scale male circumcision programs for HIV prevention is unclear. METHODS: Two mathematical models were examined to explore this issue: a random mixing model and a compartmental model that distinguishes risk groups associated with sex work. In the compartmental model, two scenarios were developed, one calculating HIV transmission and prevalence in a context similar to the country of Botswana, and one similar to Nyanza Province, in western Kenya. RESULTS: In both models, male circumcision programs resulted in large and sustained declines in HIV prevalence over time among both men and women. Men benefited somewhat more than women, but prevalence among women was also reduced substantially. With 80% male circumcision uptake, the reductions in prevalence ranged from 45% to 67% in the two "countries", and with 50% uptake, from 25% to 41%. It would take over a decade for the intervention to reach its full effect. CONCLUSION: Large-scale uptake of male circumcision services in African countries with high HIV prevalence, and where male circumcision is not now routinely practised, could lead to substantial reductions in HIV transmission and prevalence over time among both men and women.

Modulation of mammary tumor development in Tg.NK (MMTV/c-neu) mice by dietary fatty acids and life stage-specific exposure to phytoestrogens.

Breast cancer is a major public health problem among women worldwide. Phytoestrogens and dietary fat composition are being investigated to elucidate the role of nutrition in breast cancer risk. Both epidemiological and rodent studies suggest that the chemopreventive effect of phytoestrogens depends on timing of exposure. We investigated spontaneous mammary tumor development in female heterozygous MMTV/c-neu (Tg.NK) mice upon isoflavone exposure on background diets rich in either n-6 or n-3 polyunsaturated fatty acids (PUFAs). Three different exposure protocols were used, either from conception to weaning, or from weaning onwards, or lifelong. Mice fed diets high in n-3 PUFAs developed mammary tumors 15 weeks later than mice fed n-6 PUFA diets. In the latter mice, isoflavone exposure from weaning onwards resulted in a significant decrease in tumor incidence and a delay in tumor onset. Therefore, the effects of phytoestrogen exposure on tumor formation appear to depend on the composition of the background diet and on the timing of exposure within the life cycle.

Impact of Ramadan fasting on glucose levels in women with gestational diabetes mellitus treated with diet alone or diet plus metformin: a continuous glucose monitoring study.

OBJECTIVE: Women with gestational diabetes mellitus (GDM) are categorized as at high risk for adverse events during Ramadan fasting. However, this is largely based on clinical opinion. In this study, we shed some light on what happens to glucose levels during Ramadan fasting. METHODS: This is a prospective observational study. A total of 32 patients with GDM were recruited; 10 patients, treated with diet only (group 1), to observe their glucose levels before fasting and 22 patients who insisted on fasting the month of Ramadan, 13 treated with diet only (group 2) and nine treated with diet plus metformin 500 mg twice daily (group 3), to evaluate their glucose levels during fasting. Interstitial glucose was monitored in all by using the iPro2 Professional continuous glucose monitoring (CGM) system. RESULTS: Mean glucose level was 116±21 mg/dL (6.16±1.16 mmol/L), 106±9 mg/dL (5.88±0.49 mmol/L) and 99±7 mg/dL (5.49±0.34 mmol/L) in groups 1, 2 and 3, respectively. Patients in group 1 had the lowest rate of hypoglycemia (50%), followed by patients in group 2 (60%), whereas patients in group 3 had the highest rate of hypoglycemia (78%). CONCLUSIONS: CGM data indicates that Ramadan fasting in women with GDM treated with diet alone or with diet plus metformin was associated with lower mean glucose levels and higher rates of hypoglycemia when compared with non-fasting glucose levels. Women with GDM should be advised against fasting during Ramadan until further data is available.

Clinical and Mucosal Immune Correlates of HIV-1 Semen Levels in Antiretroviral-Naive Men.

BACKGROUND: This study was done to characterize parameters associated with semen human immunodeficiency virus (HIV)-1 ribonucleic acid (RNA) viral load (VL) variability in HIV-infected, therapy-naive men. METHODS: Paired blood and semen samples were collected from 30 HIV-infected, therapy-naive men who have sex with men, and 13 participants were observed longitudinally for up to 1 year. Human immunodeficiency virus RNA, bacterial load by 16S RNA, herpesvirus (Epstein-Barr virus and cytomegalovirus [CMV]) shedding, and semen cytokines/chemokines were quantified, and semen T-cell subsets were assessed by multiparameter flow cytometry. RESULTS: Semen HIV RNA was detected at 93% of visits, with >50% of men shedding high levels of virus (defined as >5000 copies/mL). In the baseline cross-sectional analysis, an increased semen HIV VL correlated with local CMV reactivation, the semen bacterial load, and semen inflammatory cytokines, particularly interleukin (IL)-8. T cells in semen were more activated than blood, and there was an increased frequency of Th17 cells and γδ-T-cells. Subsequent prospective analysis demonstrated striking interindividual variability in HIV and CMV shedding patterns, and only semen IL-8 levels and the blood VL were independently associated with semen HIV levels. CONCLUSIONS: Several clinical and immune parameters were associated with increased HIV semen levels in antiretroviral therapy-naive men, with induction of local proinflammatory cytokines potentially acting as a common pathway.