Can population differences explain the contrasting results of the Mwanza, Rakai, and Masaka HIV/sexually transmitted disease intervention trials?: A modeling study

OBJECTIVE: To determine whether population differences can explain the contrasting impacts on HIV observed in the Mwanza trial of sexually transmitted disease (STD) syndromic treatment (ST), the Rakai trial of STD mass treatment (MT), and the Masaka trial of information, education, and communication (IEC) with and without ST as well as to predict the effectiveness of each intervention strategy in each population. METHODS: Stochastic modeling of the transmission of HIV and 6 STDs was used with parameters fitted to demographic, sexual behavior, and epidemiological data from the trials and general review of STD/HIV biology. RESULTS: The baseline trial populations could be simulated by assuming higher risk behavior in Uganda compared with Mwanza in the 1980s, followed by reductions in risk behavior in Uganda preceding the trials. In line with trial observations, the projected HIV impacts were larger for the ST intervention in Mwanza than for the MT intervention in Rakai or the IEC and IEC + ST interventions in Masaka. All 4 simulated intervention strategies were more effective in reducing incidence of HIV infection in Mwanza than in either Rakai or Masaka. CONCLUSIONS: Population differences in sexual behavior, curable STD rates, and HIV epidemic stage can explain most of the contrast in HIV impact observed between the 3 trials. This study supports the hypothesis that STD management is an effective HIV prevention strategy in populations with a high prevalence of curable STDs, particularly in an early HIV epidemic.     

Follicular fluid renin concentration and IVF outcome

Total renin protein concentration (TRC) was measured in stored follicular fluid (FF) samples from 42 women. Samples were selected according to their origin from follicles either without recovered ova ('empty', n = 38) or fertilized but with failed implantation ('failed', n = 36) or successful deliveries ('deliveries', n = 71). Ratios of number of embryos transferred to number of infants delivered were 2:1, 3:1 or 4:2 but 1:1 was not available. Non-parametric testing was applied to FF-TRC, volume and outcome. TRC was significantly higher in the delivery than the failed (P = 0.001) or empty (P = 0.002) categories. Assuming that the range of renin in failed follicles can identify the sub-population of unsuccessful follicles in the delivery category, then elevated FF-TRC was clearly associated with successful outcome. For individual women, the odds of infant delivery increased 17-fold as a function of average FF-TRC between 10,000 and 25,000 microIU/ml. For failed and delivery but not empty follicles, higher renin levels occurred in the smaller follicles, consistent with a burst of renin synthesis associated with the presence of an oocyte. The results suggest that FF-TRC relates to ovum viability with ovarian hyperstimulation and may have predictive use in IVF programmes.     

HIV-1 RNA levels in an African population-based cohort and their relation to CD4 lymphocyte counts and World Health Organization clinical staging

Apart from a small number of reports from people who are based in hospitals, data on viral load in HIV-infected people in sub-Saharan Africa, where most infections occur, are lacking. We report serum HIV-1 RNA levels in a population-based cohort in rural Uganda using the nucleic acid sequence-based amplification procedure (NASBA) test kit and describe their relation to CD4 counts and World Health Organization (WHO) clinical staging. The median (interquartile range [IQR]) viral loads were 87,000 copies/ml (37,500-295,000 copies/ml) in 40 prevalent cases infected for >6 years, and 31,000 copies/ml (7800-174,000 copies/ml) in 65 incident cases with seroconversion dates within the previous 6 years. Although we found a correlation between viral load and absolute CD4 count (p < .0001), there was no evidence for an association with CD4 decline (p = .1). Overall, there was a significant trend of increasing viral load with worsening clinical stage from a median viral load of 15,000 for those in WHO stage 1 (asymptomatic) to 150,600 copies/ml for those in stage 4 (AIDS; p < .001). However, the association was seen only in incident cases. Thus, we found that the NASBA test on serum was a useful indicator of disease stage especially in persons known to be infected for <6 years. Such baseline data are important for vaccine research, and if antiretroviral drugs become available to more than a few people in Africa, it will be important that accurate viral load estimations are available at least in a proportion of people to monitor the effectiveness of treatment, and measure the compliance and emerging resistance to these drugs.     

A monoclonal blocking EIA for herpes simplex virus type 2 antibody: validation for seroepidemiological studies in Africa

A competitive type-specific enzyme-linked immunosorbent assay (ELISA) for herpes simplex virus type 2 (HSV-2) antibody was developed using an infected cell antigen and a monoclonal antibody to glycoprotein G-2. This assay has been validated for use for epidemiological studies using a large panel of sera collected in rural Uganda and a panel of 143 sera characterised previously by Western blotting, the 'gold standard' for HSV type-specific serology. This evaluation was found to have a sensitivity of 96% and a specificity of 91% in comparison with Western blot on 143 sera from clinic patients. The ELISA had a sensitivity of 93% and a specificity of 91% in comparison with Western blot on 495 sera collected in Uganda. The assay showed good reproducibility and a low percentage of sera gave equivocal results, indicating its suitability for epidemiological studies.     

Adaptation and coping: a look at a sickle cell patient population over age 30--an integral phase of the life long developmental process

Individuals with sickle cell disease experience a variety of psychosocial issues, some of which lead to maladjustments. To gather baseline data on coping and adjustment by a group of individuals over 30 years of age, a pilot study was conducted with 30 patients followed routinely at the Duke University Comprehensive Sickle Cell Center. The purpose of the study was to characterize such psychosocial parameters as coping behaviors, education, employment, group affiliation, health beliefs, marital status, parenting and perceptions regarding the disease. Using Erickson's stage of development as a point of reference, the middle adulthood stage was used as a theoretical framework for explaining and interpreting the results of this study. Study results reflect that, on the whole, the participants employed a wide variety of life skills to promote positive psychological and physical well being. These data suggest that this population of sickle cell disease patients have attained a reasonable level of psychosocial adjustment and many are leading productive lives. However, the minority of patients, who use the health care facilities more frequently, might lead one to speculate otherwise.     

Genetic mapping of modifier loci affecting malignant hypertension in TGRmRen2 rats.

BACKGROUND: Genetic background has a major influence on the manifestation of multifactorial diseases such as hypertension in which severe complications may be caused through an interaction with additional factors, which may be genetically determined. We have previously described a genetic model of malignant hypertension (MH) in rats carrying the mouse Ren2 gene (TGRmRen2-27), in which the phenotype is dependent on the genetic background. METHODS: Using a single homozygous TGRmRen2-27 male as transgene donor, we produced two F1 populations with (a) 100% penetrance of MH in progeny heterozygous for the Fischer F344 genetic background and (b) 58.5% penetrance in progeny heterozygous for the Lewis genetic background. To identify the modifier loci affecting the phenotype, a cohort of 252 males was produced by breeding the same single male with Fischer-Lewis F1 females. The progeny were phenotyped for clinical and pathological features of MH. RESULTS: Genome-wide screening and quantitative trait loci (QTL) analysis identified two loci, on chromosome 10 (LOD 4.4) and on chromosome 17 (LOD 3.9) close to the Ace and At1 genes, respectively, which contribute to the lethal MH phenotype. Their influence on mortality was consistent with a multiplicative effect of the two loci. In addition, we found higher plasma angiotensin-converting enzyme activity in progeny receiving the Fischer allele than in progeny receiving the Lewis allele (123.5 +/- 9.5 vs. 91.8 +/- 4.9 U/liter, P < 0.01), suggesting the association of angiotensin-converting enzyme and MH. CONCLUSIONS: Our study demonstrates the application of a transgene as a "major gene" to facilitate the identification of modifier loci, which can affect the phenotype of MH, and reveals Ace and At1 as candidate genes involved in the manifestation of the MH phenotype.     

Use of methotrexate in juvenile idiopathic arthritis.

Methotrexate (MTX) has transformed the outlook for children with juvenile idiopathic arthritis (JIA). Most of the evidence from uncontrolled clinical trials suggests that MTX is an effective agent for treating active JIA. Data from controlled clinical trials suggests that MTX has statistically significant effects on patient centred disability measures in JIA patients with active arthritis. Although we would like a much larger study directed evidence base for our use of the drug, the studies that have been done are sound and have been followed by a change in clinical expectations and advice that speak of qualitative evidence from clinical practice, confirming the scientifically acquired data. Randomised controlled multicentre trials using sufficient numbers of patients, including functional assessment and quality of life measures, are needed to confirm the long term efficacy and safety of MTX in JIA.     

Sonographic measurements of fetal parts to predict pulmonary maturity among twins and singletons

To determine if sonographic examination of fetus can be readily utilized to predict a mature lecithin/sphingomyelin (L/S) ratio among twins and singletons. Twins (n = 36) undergoing amniocentesis for assessment of pulmonary maturity were matched with singleton (1:2) for maternal demographics, gestational age (GA), and indications for procedure. At the time of amniocentesis, twins and singletons with mature L/S ratios differed significantly in mean GA (33.2 +/- 2.7 vs 34.5 +/- 4.6 wks, p = 0.01), biparietal diameter (BPD), abdominal circumference (AC), femur length (FL) and estimate of birth weight (EFW). Based on ten receiver operating characteristics curves constructed, the following diagnostic thresholds predicted a mature L/S ratio with a true positive rate of 100% among twins and singletons, respectively: 1) BPD $84 and $92 mm; 2) head circumference $315 and $320 mm; 3) AC $295 and $350 mm; or 4) FL $64 and $72 mm; or 5) EFW $2400 and $3200 g. Using any one of these five criteria correctly identified pulmonary maturity among 59% of twins and 28% of singletons (p = 0.001). Sonographic measurement of fetal parts or EFW may be a noninvasive method to predict a mature L/S ration among twins as well as singletons.     

Do Multiple Measurements Employing Different Ultrasonic Techniques Improve the Accuracy of Amniotic Fluid Volume Assessment?

Summary: This investigation was undertaken to determine if the accuracy of the ultrasound assessment of abnormal amniotic fluid volume (oligohydramnios or poly-hydramnios) is improved by employing multiple sonographic amniotic fluid measurements. Four ultrasound techniques consisting of the subjective assessment (ultrasonic visualization without measurement), largest vertical pocket, amniotic fluid index and 2-diameter pocket technique were performed followed by amniocentesis and dye-dilution confirmation of amniotic fluid volume in 66 singleton pregnancies. The ultrasound accuracy to detect abnormal amniotic fluid volume ranged from 61% with the largest vertical pocket to 70% with the 2-diameter pocket procedure used separately. Receiver operator characteristic curves demonstrated that combining the 4 ultrasonic measurements did not improve the accuracy of identifying amniotic fluid volumes.