HIV coinfections with tuberculosis among HIV-1 infected individuals in old cross river state,Nigeria

ABSTRACT

Human immunodeficiency virus (HIV) and Tuberculosis (TB) are two main global public health threats that dent development in low and middle-income countries. This study evaluated the HIV/TB co-infection rate among HIV-1 infected individuals in old Cross River State, Nigeria. A total of 417 HIV-infected individuals participated in this study, 241 (57.8%) from Calabar, Cross River State, Nigeria and 176 (42.2%) from Uyo, Akwa-Ibom State, Nigeria. The age range of the 417 HIV-1 positive individuals who participated in the study was 4–72 years with an average age of 39.1 years. Plasma samples were analyzed for HIV and TB using fourth-generation Enzyme-Linked immunosorbent Assay. The CD4 count was enumerated using the Partec CyFlow® Counter. Plasma viral loads (PVL) were determined using the Abbott Real-Time HIV-1 assay. Results showed that 230 (55.2%) of the participants were in the 31–45 years age range. The majority (67.4%) of the HIV-1 infected individuals were females and 32.6% were males. An overall prevalence of HIV/TB coinfection in Old Cross River State, Nigeria was 1.4%, with Akwa Ibom State (0.6%) and Cross River State (1.2%). A higher prevalence of HIV/TB coinfection was observed among females (1.8%) than in males (0.7%). Higher prevalences of HIV/TB coinfections was observed in patients above 45 years of age (2.2%), married (2.3%), tertiary education (1.8%) followed by those with secondary education (1.4%), traders and civil servants (3.1%), patients with CD4 counts 200–349 and ≥500 cells/μl (1.9%), and those with viral load <40 copies/mL (2.7%). This study confirmed the presence of HIV/TB co-infection in old Cross River State, Nigeria. Although the prevalence rate of HIV/TB coinfection was low, its presence alone among HIV-1 infected individuals makes it a major source of concern. This finding highlights the need for a well-structured approach to the management of co-infection, and this includes both the social and medical aspects of the problem.     

Contribution of mitral valve leaflet length and septal wall thickness to outflow tract obstruction in patients with hypertrophic cardiomyopathy

We sought to examine whether elongation of the mitral valve leaflets in patients with hypertrophic cardiomyopathy (HCM) is synergistic to septal wall thickness (SWT) in the development of left ventricular outflow tract obstruction (LVOTO). HCM is a common genetic cardiac disease characterized by asymmetric septal hypertrophy and predisposition towards LVOTO. It has been reported that elongation of the mitral valve leaflets may be a primary phenotypic feature and contribute to LVOTO. However, the relative contribution of this finding versus SWT has not been studied. 152 patients (76 with HCM and 76 non-diseased age, race and BSA-matched controls) and 18 young, healthy volunteers were studied. SWT and the anterior mitral valve leaflet length (AMVLL) were measured using cine MRI. The combined contribution of these variables (SWT × AMVLL) was described as the Septal Anterior Leaflet Product (SALP). Peak LVOT pressure gradient was determined by Doppler interrogation and defined as “obstructive” if?≥?30 mmHg. Patients with HCM were confirmed to have increased AMVLL compared with controls and volunteers (p?<?0.01). Among HCM patients, both SWT and SALP were significantly higher in patients with LVOTO (N?=?17) versus without. SALP showed modest improvement in predictive accuracy for LVOTO (AUC?=?0.81) among the HCM population versus SWT alone (AUC?=?0.77). However, in isolated patients this variable identified patients with LVOTO despite modest SWT. Elongation of the AMVLL is a primary phenotypic feature of HCM. While incremental contributions to LVOTO appear modest at a population level, specific patients may have dominant contribution to LVOTO. The combined marker of SALP allows for maintained identification of such patients despite modest increases in SWT.     

Towards a better understanding of exclusive breastfeeding in the era of HIV/AIDS: a study of prevalence and factors associated with exclusive breastfeeding from birth, in Rakai,Uganda

Exclusive breastfeeding (EBF) is being promoted by WHO/UNICEF as the recommended mode of feeding for all infants from birth to around 6 months of age. It is also recommended for the initial few months, for infants born to HIV-positive mothers in the developing world where conditions may not be ideal for replacement feeding. A cross-sectional study was done to find the prevalence and factors associated with EBF from delivery, amongst mothers of infants 0-6 months of age in a rural Ugandan community with a high HIV/AIDS burden. A prevalence of EBF of 35.1 per cent was found. There was a very high use of prelacteal feeds. Factors positively associated with EBF from birth, after logistic regression, were: delivery from a health unit (OR 2.07; 95 per cent confidence interval, 1.2-3.6); and mother having a normal vaginal delivery (OR 10.54; 95 per cent CI, 3.0-36.6). Factors showing negative association were: male gender of child (OR 0.44; 95 per cent CI, 0.3-0.7); and age of child over 3 months (OR 0.48; 95 per cent CI, 0.3-0.7). Mothers knowledge of her HIV serostatus was not associated with EBF (p = 0.78). Breastfeeding is almost universal in this area but it is rarely exclusive from birth.     

Low-Frequency Drug Resistance in HIV-Infected Ugandans on Antiretroviral Treatment Is Associated with Regimen Failure

Most patients failing antiretroviral treatment in Uganda continue to fail their treatment regimen even if a dominant drug-resistant HIV-1 genotype is not detected. In a recent retrospective study, we observed that approximately 30% of HIV-infected individuals in the Joint Clinical Research Centre (Kampala, Uganda) experienced virologic failure with a susceptible HIV-1 genotype based on standard Sanger sequencing. Selection of minority drug-resistant HIV-1 variants (not detectable by Sanger sequencing) under antiretroviral therapy pressure can lead to a shift in the viral quasispecies distribution, becoming dominant members of the virus population and eventually causing treatment failure. Here, we used a novel HIV-1 genotyping assay based on deep sequencing (DeepGen) to quantify low-level drug-resistant HIV-1 variants in 33 patients failing a first-line antiretroviral treatment regimen in the absence of drug-resistant mutations, as screened by standard population-based Sanger sequencing. Using this sensitive assay, we observed that 64% (21/33) of these individuals had low-frequency (or minority) drug-resistant variants in the intrapatient HIV-1 population, which correlated with treatment failure. Moreover, the presence of these minority HIV-1 variants was associated with higher intrapatient HIV-1 diversity, suggesting a dynamic selection or fading of drug-resistant HIV-1 variants from the viral quasispecies in the presence or absence of drug pressure, respectively. This study identified low-frequency HIV drug resistance mutations by deep sequencing in Ugandan patients failing antiretroviral treatment but lacking dominant drug resistance mutations as determined by Sanger sequencing methods. We showed that these low-abundance drug-resistant viruses could have significant consequences for clinical outcomes, especially if treatment is not modified based on a susceptible HIV-1 genotype by Sanger sequencing. Therefore, we propose to make clinical decisions using more sensitive methods to detect minority HIV-1 variants.     

Risk of Pregnancy-Related Hypertension Within 5 Years of Exposure to Drinking Water Contaminated With Escherichia coli O157:H7

J Clin Hypertens(Greenwich). 2010;12:613–620. © 2010 Wiley Periodicals, Inc. The authors evaluated the risk for pregnancy-related hypertension among previously healthy women who conceived within 5 years of exposure to drinking water contaminated with Escherichia coli O157.H7 in Walkerton, Canada (2000). Chronic hypertension was defined as systolic/diastolic blood pressure ≥140/90 mm Hg before 20 weeks gestation; gestational hypertension was defined as new onset systolic/diastolic blood pressure ≥140/90 mm Hg ≥20 weeks gestation. The incidence of hypertension was compared between women who were asymptomatic during the outbreak to those who experienced acute gastroenteritis. Blood pressure data were available for 135 of 148 eligible pregnancies. The adjusted relative risks for chronic and gestational hypertension were 1.5 (95% confidence interval [CI]: 0.3–7.7) and 1.0 (95% CI: 0.4–2.5), respectively. Mean arterial pressure before 20 weeks gestation was 2.7 mm Hg higher in women who had acute gastroenteritis (95% CI: 0.05–5.4). A trend toward higher chronic hypertension and mean arterial pressure in early pregnancy was observed among women who experienced gastroenteritis after exposure to bacterially-contaminated drinking water.     

Relation between chemokine receptor use, disease stage, and HIV-1 subtypes A and D: results from a rural Ugandan cohort

OBJECTIVES: To determine whether there are differences in coreceptor use in subjects infected with HIV-1 envelope subtypes A and D that could explain the differences in progression rates between these subtypes in a rural Ugandan cohort. METHODS: HIV-1 was subtyped in env by V3 sequencing or heteroduplex mobility assay. Coreceptor use was determined by the ability of the isolates to replicate in U87 CD4 cells expressing different coreceptors. The Fisher exact test was used to examine the relation between coreceptor use and subtype, clinical stage, and V3 charge. The Kruskall-Wallis nonparametric test was used to examine the association between median CD4 cell counts, coreceptor use, and subtype. Logistic regression was used to examine predicted coreceptor use at different CD4 groupings. RESULTS: Isolates from 66 participants were analyzed. Thirty-one were infected with subtype A, and 35 were infected with subtype D. Although this work was based on a small sample size, we found statistically significant differences. The probability of having an X4 virus was higher in subtype D infections than in subtype A infections among those with a non-AIDS clinical status (Fisher exact test, P = 0.040). Logistic regression analysis, in which we predicted X4 use by subtype and stratified by CD4 group, confirmed these findings among those with a CD4 count >200 cells/microL (likelihood ratio test, P = 0.003). R5 viruses were associated with higher median CD4 cell counts than X4 or X4/R5 (Kruskall-Wallis test, P = 0.0045). A V3 charge of +5 and greater was highly associated with X4 virus (Fisher exact test, P = 0.006). CONCLUSIONS: These subtype differences in coreceptor use may partially explain the faster progression rates we have previously reported in individuals infected with subtype D compared with subtype A. Our observations may have implications for the future use of coreceptor inhibitors in this population.     

Risk of Pregnancy‐Related Hypertension Within 5 Years of Exposure to Drinking Water Contaminated With Escherichia coli O157:H7

J Clin Hypertens(Greenwich). 2010;12:613–620. © 2010 Wiley Periodicals, Inc.The authors evaluated the risk for pregnancy‐related hypertension among previously healthy women who conceived within 5 years of exposure to drinking water contaminated with Escherichia coli O157.H7 in Walkerton, Canada (2000). Chronic hypertension was defined as systolic/diastolic blood pressure ≥140/90 mm Hg before 20 weeks gestation; gestational hypertension was defined as new onset systolic/diastolic blood pressure ≥140/90 mm Hg ≥20 weeks gestation. The incidence of hypertension was compared between women who were asymptomatic during the outbreak to those who experienced acute gastroenteritis. Blood pressure data were available for 135 of 148 eligible pregnancies. The adjusted relative risks for chronic and gestational hypertension were 1.5 (95% confidence interval [CI]: 0.3–7.7) and 1.0 (95% CI: 0.4–2.5), respectively. Mean arterial pressure before 20 weeks gestation was 2.7 mm Hg higher in women who had acute gastroenteritis (95% CI: 0.05–5.4). A trend toward higher chronic hypertension and mean arterial pressure in early pregnancy was observed among women who experienced gastroenteritis after exposure to bacterially‐contaminated drinking water.

In May of 2000, the municipal water supply in Walkerton, a small rural town in Ontario, Canada, became contaminated with bacteria, predominantly Escherichia coli O157:H7 and Campylobacter species. An unusually heavy rainfall and inadequate chlorination both contributed to the bacterial contamination of drinking water supplied by a shallow well. At the time of the outbreak, 5000 people lived in the town of Walkerton, of which 1000 (20%) were women aged 15 to 44 years. More than 2300 people became ill with symptoms of acute gastroenteritis; 27 cases of hemolytic uremic syndrome (HUS) were identified, and there were 7 deaths. ¹ The magnitude of this event attracted worldwide media attention and sparked public concern about the safety of public drinking water. ^{2 , 3} Following the outbreak, the Walkerton Health Study (WHS) was initiated to monitor the potential long‐term health sequelae of the water contamination.The Centers for Disease Control and Prevention estimate that E. coli O157:H7 infections cause between 50,000 and 120,000 gastroenteric illnesses annually in the United States, resulting in more than 2000 hospitalizations and 60 deaths. ^{4 , 5 , 6} However, apart from investigations into the long‐term sequelae of diarrhea‐associated HUS, ⁷ few studies have evaluated the long‐term health effects of exposure to this pathogen. In the developed world, it is rare for outbreaks of this magnitude to occur within a single community, ⁸ and this environmental catastrophe has allowed researchers to track long‐term health effects of E. coli O157:H7 exposure within a single cohort.Receptors for E. coli O157:H7 are found in the kidney, and exposure to this pathogen may result in substantial nephron loss and subsequent hyperfiltration without presenting as HUS. ^{9 , 10 , 11} An earlier analysis of the WHS reported an increased risk for hypertension and reduced kidney function 4 years after infection among adults who were ill with acute gastroenteritis, but not HUS. ¹ Hypertensive disorders during pregnancy complicate between 3% and 22% of pregnancies, and remain the leading cause of maternal and perinatal morbidity and mortality. ^{12 , 13} A subclinical renal injury from E. coli verotoxin may be unmasked by the physiologic demands of pregnancy and manifest as hypertension early in pregnancy. The present study of WHS participants evaluated the risk for pregnancy‐related hypertension (PRH) among previously healthy females who conceived within 5 years of drinking water contaminated with E. coli O157:H7. We compared the incidence of PRH, chronic, and gestational hypertension among participants who reported moderate to severe symptoms of gastroenteritis to participants who were asymptomatic at the time of the outbreak. Differences in mean arterial pressure (MAP) were also evaluated.     

Optimal Method of Coronary Revascularization in Patients Receiving Dialysis: Systematic Review

Background and objectives: Patients receiving dialysis have a high burden of cardiovascular disease. Some receive coronary artery revascularization but the optimal method is controversial.Design, setting, participants, & measurements: The authors reviewed any randomized controlled trial or cohort study of 10 or more patients receiving maintenance dialysis which compared coronary artery bypass graft (CABG) to percutaneous intervention (PCI) for revascularization of the coronary arteries. The primary outcomes were short-term (30 d or in-hospital) and long-term (at least 1 year) mortality.Results: Seventeen studies were found. There were no randomized trials: all were retrospective cohort studies from years 1977 to 2002. There were some baseline differences between the groups receiving CABG compared with those receiving PCI, and most studies did not consider results adjusted for such characteristics. Given the variability among studies and their methodological limitations, few definitive conclusions about the optimal method of revascularization could be drawn. In an exploratory meta-analysis, short-term mortality was higher after CABG compared to PCI. A substantial number of patients died over a subsequent 1 to 5 yr, with no difference in mortality after CABG compared to PCI.Conclusions: Although decisions about the optimal method of coronary artery revascularization in dialysis patients are undertaken routinely, it was surprising to see how few data has been published in this regard. Additional research will help inform physician and patient decisions about coronary artery revascularization.Cardiovascular disease accounts for almost half of all deaths in patients with end-stage renal disease (1). More than two thirds of patients receiving dialysis have prevalent coronary artery disease, among whom three fourths are symptomatic and have multivessel disease (2). Coronary revascularization is often pursued in select patients who are sufficiently fit for the procedures or are symptomatic despite maximal medical therapy. The most appropriate method of revascularization is a matter of debate (3).Percutaneous coronary intervention (PCI) is an increasingly attractive treatment option for patients with stable multivessel coronary artery disease. With advances in technology, the risk of complications has declined, and success has improved (4). New advances in coronary artery bypass graft (CABG) surgery have also reduced rates of operative morbidity and mortality (5).In the general population, a recent trial suggested that survival and major cardiovascular events were no different in patients with atherosclerosis of the proximal left anterior descending artery randomized to receive either PCI or CABG surgery (4). However, the need for repeat revascularization was higher in patients receiving PCI (6). It has been highlighted that no quantitative review on this topic has been published regarding patients with kidney failure (7). Thus we undertook a systematic review to compile existing evidence on the following question: in patients receiving dialysis, what are the short and long-term risks of death for those undergoing CABG compared with those undergoing PCI? We also considered the effects of these procedures on cardiovascular outcomes of myocardial infarction and need for repeat revascularization.     

HIV diversity, recombination and disease progression: how does fitness "fit" into the puzzle?

HIV appears to have diverged into several lineages upon multiple zoonotic introductions from the nonhuman primates. The HIV-2 and HIV-1 groups M, N, and O likely represent different cross-species transmission events. The radial evolution of group M in multiple clades or subtypes is likely due to adaptation and expansions in the human hosts. It is not well understood why HIV strains such as HIV-1 subtype C in particular or group M in general have spread disproportionately as compared to other subtypes, groups, or types, which often remained geographically constrained to local epidemics. Host genetic effects, transmission bottlenecks, social/behavioral and environmental limitations, founder effect and other viral factors could have contributed to variable spread through the human population. Even after transmission, viruses evolve at different rates during disease progression. Recent studies have explored phenotypic differences between HIV types, groups, and subtypes in attempts to explain or understand this radial evolution and expansion. This review explores some of the important aspects relating to fitness during disease progression, during global distribution of different HIV subtypes, and related to circulation of recombinant forms in the epidemic.