Cell recovery in bronchoalveolar lavage fluid in smokers is dependent on cumulative smoking history

Background

Smoking is a risk factor for various lung diseases in which BAL may be used as a part of a clinical investigation. Interpretation of BAL fluid cellularity is however difficult due to high variability, in particular among smokers. In this study we aimed to evaluate the effect of smoking on BAL cellular components in asymptomatic smokers. The effects of smoking cessation, age and gender were also investigated in groups of smokers and exsmokers.

Methods

We performed a retrospective review of BAL findings, to our knowledge the largest single center investigation, in our department from 1999 to 2009. One hundred thirty two current smokers (48 males and 84 females) and 44 ex-smokers (16 males and 28 females) were included. A group of 295 (132 males and 163 females) never-smokers served as reference.

Result

The median [5–95 pctl] total number of cells and cell concentration in current smokers were 63.4 [28.6–132.1]×10⁶ and 382.1 [189.7–864.3]×10⁶/L respectively and correlated positively to the cumulative smoking history. Macrophages were the predominant cell type (96.7% [90.4–99.0]) followed by lymphocytes (2% [0.8–7.7]) and neutrophils (0.6% [0–2.9]). The concentration of all inflammatory cells was increased in smokers compared to never smokers and ex-smokers. BAL fluid recovery was negatively correlated with age (p<0.001). Smoking men had a lower BAL fluid recovery than smoking women.

Conclusion

Smoking has a profound effect on BAL fluid cellularity, which is dependent on smoking history. Our results performed on a large group of current smokers and ex-smokers in a well standardized way, can contribute to better interpretation of BAL fluid cellularity in clinical context.     

Gender difference of alanine aminotransferase elevation may be associated with higher hemoglobin levels among male adolescents

Background

To explore the gender difference of ALT elevation and its association with high hemoglobin levels.

Methods

A cross-sectional study of 3547 adolescents (2005 females, mean age of 16.5?.3 years) who were negative for hepatitis B surface antigen received health checkups in 2006. Body mass index (BMI), levels of hemoglobin, ALT and cholesterol were measured. ALT >42 U/L was defined as elevated ALT. Elevated ALT levels were detected in 112 of the 3547 participants (3.3%), more prevalent in males than in females (5.4% vs. 1.4%, p<0.001). Hemoglobin levels had a significant linear correlation with ALT levels in both genders. Abnormal ALT started to occur if hemoglobin >11 g/dl in females or >13.5 g/dl in males, but the cumulative cases of elevated ALT increased more quickly in males. Proportion of elevated ALT increased as either the BMI or hemoglobin level rise, more apparent in male adolescents. Logistic regression modeling showed odds ratio (95% confidence interval) were 24.7 (15.0–40.6) for BMI ≥27 kg/m²; 5.5 (2.9–10.4) for BMI 24–27 kg/m²; 2.7 (1.3–5.5) for Q5 (top 20th percentile) hemoglobin level; and 2.6 (1.6–4.1) for male gender. Further separately fitting the logistic models for two genders, the significance of Q5 hemoglobin level only appeared in the males.

Conclusions

High hemoglobin level is a significant risk factor of ALT elevation after control hepatitis B, obesity and gender. Males have greater risk of abnormal liver function which may be associated with higher hemoglobin levels.     

Risk of stillbirth in the relation to water disinfection by-products: a population-based case-control study in Taiwan

Background

Few epidemiological studies that have assessed the relation between water disinfection by-products (DBPs) and the risk of stillbirth provide inconsistent results. The objective was to assess the relation between exposure to water disinfection by-products and the risk of stillbirth.

Methods

We conducted a population-based case-control study of 3,289 cases of stillbirth and a random sample of 32,890 control subjects from 396,049 Taiwanese newborns in 2001–2003 using information from the Birth Registry and Waterworks Registry in Taiwan. We compared the risk of stillbirth in four disinfection by-product exposure categories based on the levels of total trihalomethanes (TTHMs) representing high (TTHMs 20+ µg/L), medium (TTHMs 10–19 µg/L), low exposure (TTHMs 5–9 µg/L), and 0–4 µg/L as the reference category. In addition, we conducted a meta-analysis of the results from the present and 5 previous studies focusing on stillbirth.

Findings

In logistic regression analysis adjusting for gender, maternal age, plurality, conception of season and population density of the municipality where the mother lived during pregnancy, the odds ratio (OR) for stillbirth was 1.10 (95% CI 1.00–1.21) for medium exposure and 1.06 (95% 0.96–1.17) for high exposure compared to reference category. In the meta-analysis, the summary odds ratio for stillbirth (1.11, 95% CI: 1.03, 1.19) was consistently elevated.

Conclusions

The present study is consistent with the hypothesis that the risk of stillbirth is related to prenatal exposure to disinfection by-products. This finding on stillbirth is consistent with previous epidemiologic studies, which strengthens the weight of evidence.     

Gender differences and effect of air pollution on asthma in children with and without allergic predisposition: northeast Chinese children health study

Background

Males and females exhibit different health responses to air pollution, but little is known about how exposure to air pollution affects juvenile respiratory health after analysis stratified by allergic predisposition. The aim of the present study was to assess the relationship between air pollutants and asthmatic symptoms in Chinese children selected from multiple sites in a heavily industrialized province of China, and investigate whether allergic predisposition modifies this relationship.

Methodology/Principal Findings

30139 Chinese children aged 3-to-12 years were selected from 25 districts of seven cities in northeast China in 2009. Information on respiratory health was obtained using a standard questionnaire from the American Thoracic Society. Routine air-pollution monitoring data was used for particles with an aerodynamic diameter ≤10 µm (PM₁₀), sulfur dioxide (SO₂), nitrogen dioxides (NO₂), ozone (O₃) and carbon monoxide (CO). A two-stage regression approach was applied in data analyses. The effect estimates were presented as odds ratios (ORs) per interquartile changes for PM₁₀, SO₂, NO₂, O₃, and CO. The results showed that children with allergic predisposition were more susceptible to air pollutants than children without allergic predisposition. Amongst children without an allergic predisposition, air pollution effects on asthma were stronger in males compared to females; Current asthma prevalence was related to PM₁₀ (ORs = 1.36 per 31 µg/m³; 95% CI, 1.08–1.72), SO₂ (ORs = 1.38 per 21 µg/m³; 95%CI, 1.12–1.69) only among males. However, among children with allergic predisposition, more positively associations between air pollutants and respiratory symptoms and diseases were detected in females; An increased prevalence of doctor-diagnosed asthma was significantly associated with SO₂ (ORs = 1.48 per 21 µg/m³; 95%CI, 1.21–1.80), NO₂ (ORs = 1.26 per 10 µg/m³; 95%CI, 1.01–1.56), and current asthma with O₃ (ORs = 1.55 per 23 µg/m³; 95%CI, 1.18–2.04) only among females.

Conclusion/Significance

Ambient air pollutions were more evident in males without an allergic predisposition and more associations were detected in females with allergic predisposition.     

Non-invasive cytology brush PCR diagnostic testing in mucosal leishmaniasis: superior performance to conventional biopsy with histopathology

Background

Traditional methods of diagnosing mucosal leishmaniasis (ML), such as biopsy with histopathology, are insensitive and require collection of an invasive diagnostic specimen.

Methods

We compared standard invasive procedures including biopsy histopathology, biopsy PCR, and leishmanin skin test (LST) to a novel, non-invasive, cytology-brush based PCR for the diagnosis of ML in Lima, Peru. Consensus reference standard was 2/4 tests positive, and outcome measures were sensitivity and specificity. Leishmania species identification was performed by PCR-based assays of positive specimens.

Results

Twenty-eight patients were enrolled, 23 of whom fulfilled criteria for a diagnosis of ML. Sensitivity and specificity of biopsy with histopathology were 21.7% [95% CI 4.9–38.5%] and 100%; 69.6% [95% CI 50.8–88.4%] and 100% for LST; 95.7% [95% CI 87.4–100%] and 100% for biopsy PCR; and 95.7% [95% CI 87.4–100%] and 90% [95% CI 71.4–100%] for cytology brush PCR using both Cervisoft® and Histobrush® cervical cytology brushes. Represented species identified by PCR-RFLP included: L. (V). braziliensis (n = 4), and L. (V). peruviana (n = 3).

Conclusions

Use of commercial grade cytology brush PCR for diagnosis of ML is sensitive, rapid, well tolerated, and carries none of the risks of invasive diagnostic procedures such as biopsy. Further optimization is required for adequate species identification. Further evaluation of this method in field and other settings is warranted.     

TSH-CHECK-1 test: diagnostic accuracy and potential application to initiating treatment for hypothyroidism in patients on anti-tuberculosis drugs

Background

Thyroid-stimulating hormone (TSH) promotes expression of thyroid hormones which are essential for metabolism, growth, and development. Second-line drugs to treat tuberculosis (TB) can cause hypothyroidism by suppressing thyroid hormone synthesis. Therefore, TSH levels are routinely measured in TB patients receiving second-line drugs, and thyroxin treatment is initiated where indicated. However, standard TSH tests are technically demanding for many low-resource settings where TB is prevalent; a simple and inexpensive test is urgently needed.

Methods

As a proof of concept study TSH was measured in routinely collected sera at the University Medical Center Utrecht, Netherlands, using the TSH-CHECK-1 (VEDALAB, Alençon, France), a lateral-flow rapid immunochromatographic assay with a TSH cut-off value of 10 µIU/mL, the standard threshold for initiating treatment. These results were compared with TSH levels measured by a reference standard (UniCel DXi 800 imunoassay system, Beckman Coulter, USA). Sensitivity, specificity, and likelihood ratios were then calculated.

Results

A total of 215 serum samples were evaluated: 107 with TSH values <10 µIU/mL and 108 with values ≥10 µIU/mL. TSH-CHECK-1 test sensitivity was found to be 100.0% (95% CI: 96.6–100.0) and specificity was 76.6% (95% CI: 67.5–84.3). Predictive values (PV) were modelled for different levels of prevalence. For a prevalence of 10% and 50%, the positive PV was 32.2% (95% CI: 25.0–39.7%) and 81.1% (95% CI: 75.0–85.5%), respectively; the negative PV was 100% (95% CI: 98.9–100%) and 100% (95% CI: 91.3–100%) respectively.

Discussion/Conclusions

The TSH-CHECK-1 rapid test was practical and simple to perform but difficult to interpret on weak positive results. All sera with TSH≥10 µIU/mL were correctly identified, but the test lacked sufficient specificity. Given its excellent negative PV in this evaluation, the test shows promise for ruling out hypothyroidism. However, so far it appears that samples testing positive with TSH-CHECK-1 would require confirmation using another method.     

Bayesian latent class models in malaria diagnosis

Aims

The main focus of this study is to illustrate the importance of the statistical analysis in the evaluation of the accuracy of malaria diagnostic tests, without admitting a reference test, exploring a dataset (3317) collected in São Tomé and Príncipe.

Methods

Bayesian Latent Class Models (without and with constraints) are used to estimate the malaria infection prevalence, together with sensitivities, specificities, and predictive values of three diagnostic tests (RDT, Microscopy and PCR), in four subpopulations simultaneously based on a stratified analysis by age groups (, 5 years old) and fever status (febrile, afebrile).

Results

In the afebrile individuals with at least five years old, the posterior mean of the malaria infection prevalence is 3.2% with a highest posterior density interval of [2.3–4.1]. The other three subpopulations (febrile 5 years, afebrile or febrile children less than 5 years) present a higher prevalence around 10.3% [8.8–11.7]. In afebrile children under-five years old, the sensitivity of microscopy is 50.5% [37.7–63.2]. In children under-five, the estimated sensitivities/specificities of RDT are 95.4% [90.3–99.5]/93.8% [91.6–96.0] – afebrile – and 94.1% [87.5–99.4]/97.5% [95.5–99.3] – febrile. In individuals with at least five years old are 96.0% [91.5–99.7]/98.7% [98.1–99.2] – afebrile – and 97.9% [95.3–99.8]/97.7% [96.6–98.6] – febrile. The PCR yields the most reliable results in four subpopulations.

Conclusions

The utility of this RDT in the field seems to be relevant. However, in all subpopulations, data provide enough evidence to suggest caution with the positive predictive values of the RDT. Microscopy has poor sensitivity compared to the other tests, particularly, in the afebrile children less than 5 years. This type of findings reveals the danger of statistical analysis based on microscopy as a reference test. Bayesian Latent Class Models provide a powerful tool to evaluate malaria diagnostic tests, taking into account different groups of interest.     

Attenuating effect of vigorous physical activity on the risk for inherited obesity: a study of 47,691 runners

Objective

Physical activity has been shown to attenuate the effect of the FTO polymorphism on body weight, and the heritability of body weight in twin and in family studies. The dose-response relationship between activity and the risk for inherited obesity is not well known, particularly for higher doses of vigorous exercise. Such information is needed to best prescribe an exercise dose for obesity prevention in those at risk due to their family history.

Design

We therefore analyzed self-reported usual running distance, body mass index (BMI), waist circumference, and mother''s and father''s adiposity (1 = lean, 2 = normal, 3 = overweight, and 4 = very overweight) from survey data collected on 33,480 male and 14,211 female runners. Age-, education-, and alcohol-adjusted regression analyses were used to estimate the contribution of parental adiposities to the BMI and waist circumferences in runners who ran an average of <3, 3–6, 6–9, ≥9 km/day.

Results

BMI and waist circumferences of runners who ran <3 km/day were significantly related to their parents adiposity (P<10⁻¹⁵ and P<10⁻¹¹, respectively). These relationships (i.e., kg/m² or cm per increment in parental adiposity) diminished significantly with increasing running distance for both BMI (inheritance×exercise interaction, males: P<10⁻¹⁰; females: P<10⁻⁵) and waist circumference (inheritance×exercise interaction, males: P<10⁻⁹; females: P = 0.004). Compared to <3 km/day, the parental contribution to runners who averaged ≥9 km/day was diminished by 48% for male BMI, 58% for female BMI, 55% for male waist circumference, and 58% for female waist circumference. These results could not be attributed to self-selection.

Conclusions

Exceeding the minimum exercise dose currently recommended for general health benefits (energy equivalent to running 2–3 km/day) may substantially diminish the risk for inherited obesity. The results are consistent with other research suggesting the physical activity dose required to prevent unhealthy weight gain is greater than that recommended for other health benefits.     

Is the Even Distribution of Insecticide-Treated Cattle Essential for Tsetse Control? Modelling the Impact of Baits in Heterogeneous Environments

Background

Eliminating Rhodesian sleeping sickness, the zoonotic form of Human African Trypanosomiasis, can be achieved only through interventions against the vectors, species of tsetse (Glossina). The use of insecticide-treated cattle is the most cost-effective method of controlling tsetse but its impact might be compromised by the patchy distribution of livestock. A deterministic simulation model was used to analyse the effects of spatial heterogeneities in habitat and baits (insecticide-treated cattle and targets) on the distribution and abundance of tsetse.

Methodology/Principal Findings

The simulated area comprised an operational block extending 32 km from an area of good habitat from which tsetse might invade. Within the operational block, habitat comprised good areas mixed with poor ones where survival probabilities and population densities were lower. In good habitat, the natural daily mortalities of adults averaged 6.14% for males and 3.07% for females; the population grew 8.4× in a year following a 90% reduction in densities of adults and pupae, but expired when the population density of males was reduced to <0.1/km²; daily movement of adults averaged 249 m for males and 367 m for females. Baits were placed throughout the operational area, or patchily to simulate uneven distributions of cattle and targets. Gaps of 2–3 km between baits were inconsequential provided the average imposed mortality per km² across the entire operational area was maintained. Leaving gaps 5–7 km wide inside an area where baits killed 10% per day delayed effective control by 4–11 years. Corrective measures that put a few baits within the gaps were more effective than deploying extra baits on the edges.

Conclusions/Significance

The uneven distribution of cattle within settled areas is unlikely to compromise the impact of insecticide-treated cattle on tsetse. However, where areas of >3 km wide are cattle-free then insecticide-treated targets should be deployed to compensate for the lack of cattle.     

Gender difference in 2-year mortality and immunological response to ART in an HIV-infected Chinese population, 2006-2008

Background

Since it was initiated in 2002, the China Free Antiretroviral Treatment (ART) Program has been progressing from an emergency response to a standardized treatment and care system. As of December 31, 2009, a total of 81,880 patients in 31 provinces, autonomous regions, and special municipalities received free ART. Gender differences, however, in mortality and immunological response to ART in this cohort have never been described.

Objective

To understand whether women and men who enrolled in the China National Free ART Program responded equally well to the treatment.

Methods

A retrospective analysis of the national free ART databases from June 2006–December 2008 was performed. HIV-infected subjects who were 18 years or older, ART naïve at baseline, and on a 3TC regimen enrolled in the program from June 1 to December 31, 2006, were included in this study, then followed up to 2 years.

Results

Among 3457 enrolled subjects who met the inclusion criteria, 59.2% were male and 40.8% female. The majority of the subjects were 19–44 years old (77%) and married (72%). Over the full 24 months of follow-up, the mortality rate was 19.0% in males and 11.4% in females (p = 0.0014). Males on therapy for 3–24 months were more likely to die than females (HR = 1.46, 95% CI: 1.04–2.06, p = 0.0307) after adjusting for baseline characteristics. Compared to men, women had higher CD4+ counts over time after initiating ART (p<0.0001).

Conclusions

Our study showed that women had an overall lower mortality and higher CD4+ counts than men in response to ART treatment, which may be attributed to adherence, biological factors, social, cultural and economic reasons. Further study is needed to explore these factors that might contribute to the gender differences in mortality and immunological response to ART.     

Increase in diarrheal disease associated with arsenic mitigation in Bangladesh

Background

Millions of households throughout Bangladesh have been exposed to high levels of arsenic (As) causing various deadly diseases by drinking groundwater from shallow tubewells for the past 30 years. Well testing has been the most effective form of mitigation because it has induced massive switching from tubewells that are high (>50 µg/L) in As to neighboring wells that are low in As. A recent study has shown, however, that shallow low-As wells are more likely to be contaminated with the fecal indicator E. coli than shallow high-As wells, suggesting that well switching might lead to an increase in diarrheal disease.

Methods

Approximately 60,000 episodes of childhood diarrhea were collected monthly by community health workers between 2000 and 2006 in 142 villages of Matlab, Bangladesh. In this cross-sectional study, associations between childhood diarrhea and As levels in tubewell water were evaluated using logistic regression models.

Results

Adjusting for wealth, population density, and flood control by multivariate logistic regression, the model indicates an 11% (95% confidence intervals (CIs) of 4–19%) increase in the likelihood of diarrhea in children drinking from shallow wells with 10–50 µg/L As compared to shallow wells with >50 µg/L As. The same model indicates a 26% (95%CI: 9–42%) increase in diarrhea for children drinking from shallow wells with ≤10 µg/L As compared to shallow wells with >50 µg/L As.

Conclusion

Children drinking water from shallow low As wells had a higher prevalence of diarrhea than children drinking water from high As wells. This suggests that the health benefits of reducing As exposure may to some extent be countered by an increase in childhood diarrhea.     

Evaluation of three sampling methods to monitor outcomes of antiretroviral treatment programmes in low- and middle-income countries

Background

Retention of patients on antiretroviral therapy (ART) over time is a proxy for quality of care and an outcome indicator to monitor ART programs. Using existing databases (Antiretroviral in Lower Income Countries of the International Databases to Evaluate AIDS and Médecins Sans Frontières), we evaluated three sampling approaches to simplify the generation of outcome indicators.

Methods and Findings

We used individual patient data from 27 ART sites and included 27,201 ART-naive adults (≥15 years) who initiated ART in 2005. For each site, we generated two outcome indicators at 12 months, retention on ART and proportion of patients lost to follow-up (LFU), first using all patient data and then within a smaller group of patients selected using three sampling methods (random, systematic and consecutive sampling). For each method and each site, 500 samples were generated, and the average result was compared with the unsampled value. The 95% sampling distribution (SD) was expressed as the 2.5^th and 97.5^th percentile values from the 500 samples. Overall, retention on ART was 76.5% (range 58.9–88.6) and the proportion of patients LFU, 13.5% (range 0.8–31.9). Estimates of retention from sampling (n = 5696) were 76.5% (SD 75.4–77.7) for random, 76.5% (75.3–77.5) for systematic and 76.0% (74.1–78.2) for the consecutive method. Estimates for the proportion of patients LFU were 13.5% (12.6–14.5), 13.5% (12.6–14.3) and 14.0% (12.5–15.5), respectively. With consecutive sampling, 50% of sites had SD within ±5% of the unsampled site value.

Conclusions

Our results suggest that random, systematic or consecutive sampling methods are feasible for monitoring ART indicators at national level. However, sampling may not produce precise estimates in some sites.     

Association between serum interleukin-6 concentrations and mortality in older adults: the Rancho Bernardo study

Background

Interleukin-6 (IL-6) may have a protective role in acute liver disease but a detrimental effect in chronic liver disease. It is unknown whether IL-6 is associated with risk of liver-related mortality in humans.

Aims

To determine if IL-6 is associated with an increased risk of all-cause, cardiovascular disease (CVD), cancer, and liver-related mortality.

Methods

A prospective cohort study included 1843 participants who attended a research visit in 1984–87. Multiple covariates were ascertained including serum IL-6. Multivariable-adjusted Cox proportional hazards regression analyses were used to examine the association between serum IL-6 as a continuous (log transformed) variable with all-cause, CVD, cancer, and liver-related mortality. Patients with prevalent CVD, cancer and liver disease were excluded for cause-specific mortality.

Results

The mean (± standard deviation) age and body-mass-index (BMI) of participants was 68 (±10.6) years and 25 (±3.7) Kg/m², respectively. During the 25,802 person-years of follow-up, the cumulative all-cause, CVD, cancer, and liver-related mortality were 53.1% (N = 978), 25.5%, 11.3%, and 1.3%, respectively. The median (±IQR) length of follow-up was 15.3±10.6 years. In multivariable analyses, adjusted for age, sex, alcohol, BMI, diabetes, hypertension, total cholesterol, HDL, and smoking, one-SD increment in log-transformed serum IL-6 was associated with increased risk of all-cause, CVD, cancer, and liver-related mortality, with hazard ratios of 1.48 (95% CI, 1.33–1.64), 1.38 (95% CI, 1.16–1.65), 1.35 (95% CI, 1.02–1.79), and 1.88 (95% CI, 0.97–3.67), respectively. CRP adjustment attenuated the effects but the association between IL-6 and all-cause and CVD mortality remained statistically significant, independent of CRP levels.

Conclusions

In community-dwelling older adults, serum IL-6 is associated with all-cause, CVD, cancer, and liver-related mortality.     

Evidence of latitudinal migration in tri-colored bats, Perimyotis subflavus

Background

Annual movements of tri-colored bats (Perimyotis subflavus) are poorly understood. While this species has been considered a regional migrant, some evidence suggests that it may undertake annual latitudinal migrations, similar to other long distance North American migratory bat species.

Methodology/Principal Findings

We investigated migration in P. subflavus by conducting stable hydrogen isotope analyses of 184 museum specimen fur samples and comparing these results (δD_fur) to published interpolated δD values of collection site growing season precipitation (δD_precip). Results suggest that the male molt period occurred between June 23 and October 16 and 33% of males collected during the presumed non-molt period were south of their location of fur growth. For the same time period, 16% of females were south of their location of fur growth and in general, had not travelled as far as migratory males. There were strong correlations between δD_fur from the presumed molt period and both growing season δD_precip (males – r ² = 0.86; p<0.01; females – r ² = 0.75; p<0.01), and latitude of collection (males – r ² = 0.85; p<0.01; females – r ² = 0.73; p<0.01). Most migrants were collected at the northern (>40°N; males and females) and southern (<35°N; males only) extents of the species'' range.

Conclusions/Significance

These results indicate a different pattern of migration for this species than previously documented, suggesting that some P. subflavus engage in annual latitudinal migrations and that migratory tendency varies with latitude and between sexes. We suggest that this species'' hibernation ecology makes it particularly susceptible to long winters, making migration from the northern extent of the species'' range to more southern hibernacula preferable for some individuals. Fur δD values for some of the northern individuals may indicate an increase in the currently accepted northern range of this species. Sex-biased differences in migration may be the result of differences in reproductive pressures.     

Gender differences in immune reconstitution: a multicentric cohort analysis in sub-Saharan Africa

Background

In sub-Saharan Africa, men living with HIV often start ART at more advanced stages of disease and have higher early mortality than women. We investigated gender difference in long-term immune reconstitution.

Methods/Principal Findings

Antiretroviral-naïve adults who received ART for at least 9 months in four HIV programs in sub-Saharan Africa were included. Multivariate mixed linear models were used to examine gender differences in immune reconstitution on first line ART.A total of 21,708 patients (68% women) contributed to 61,912 person-years of follow-up. At ART start,. Median CD4 at ART were 149 [IQR 85–206] for women and 125 cells/µL [IQR 63–187] for men. After the first year on ART, immune recovery was higher in women than in men, and gender-based differences increased by 20 CD4 cells/µL per year on average (95% CI 16–23; P<0.001). Up to 6 years after ART start, patients with low initial CD4 levels experienced similar gains compared to patients with high initial levels, including those with CD4>250cells/µL (difference between patients with <50 cells/µL and those with >250 was 284 cells/µL; 95% CI 272–296; LR test for interaction with time p = 0.63). Among patients with initial CD4 count of 150–200 cells/µL, women reached 500 CD4 cells after 2.4 years on ART (95% CI 2.4–2.5) and men after 4.5 years (95% CI 4.1–4.8) of ART use.

Conclusion

Women achieved better long-term immune response to ART, reaching CD4 level associated with lower risks of AIDS related morbidity and mortality quicker than men.     

Evaluation of portable point-of-care CD4 counter with high sensitivity for detecting patients eligible for antiretroviral therapy

Background

Accurate, inexpensive point-of-care CD4+ T cell testing technologies are needed that can deliver CD4+ T cell results at lower level health centers or community outreach voluntary counseling and testing. We sought to evaluate a point-of-care CD4+ T cell counter, the Pima CD4 Test System, a portable, battery-operated bench-top instrument that is designed to use finger stick blood samples suitable for field use in conjunction with rapid HIV testing.

Methods

Duplicate measurements were performed on both capillary and venous samples using Pima CD4 analyzers, compared to the BD FACSCalibur (reference method). The mean bias was estimated by paired Student''s t-test. Bland Altman plots were used to assess agreement.

Results

206 participants were enrolled with a median CD4 count of 396 (range; 18–1500). The finger stick PIMA had a mean bias of −66.3 cells/µL (95%CI −83.4−49.2, P<0.001) compared to the FACSCalibur; the bias was smaller at lower CD4 counts (0–250 cells/µL) with a mean bias of −10.8 (95%CI −27.3−+5.6, P = 0.198), and much greater at higher CD4 cell counts (>500 cells/µL) with a mean bias of −120.6 (95%CI −162.8, −78.4, P<0.001). The sensitivity (95%CI) of the Pima CD4 analyzer was 96.3% (79.1–99.8%) for a <250 cells/ul cut-off with a negative predictive value of 99.2% (95.1–99.9%).

Conclusions

The Pima CD4 finger stick test is an easy-to-use, portable, relatively fast device to test CD4+ T cell counts in the field. Issues of negatively-biased CD4 cell counts especially at higher absolute numbers will limit its utility for longitudinal immunologic response to ART. The high sensitivity and negative predictive value of the test makes it an attractive option for field use to identify patients eligible for ART, thus potentially reducing delays in linkage to care and ART initiation.     

A large change in temperature between neighbouring days increases the risk of mortality

Background

Previous studies have found high temperatures increase the risk of mortality in summer. However, little is known about whether a sharp decrease or increase in temperature between neighbouring days has any effect on mortality.

Method

Poisson regression models were used to estimate the association between temperature change and mortality in summer in Brisbane, Australia during 1996–2004 and Los Angeles, United States during 1987–2000. The temperature change was calculated as the current day''s mean temperature minus the previous day''s mean.

Results

In Brisbane, a drop of more than 3°C in temperature between days was associated with relative risks (RRs) of 1.157 (95% confidence interval (CI): 1.024, 1.307) for total non-external mortality (NEM), 1.186 (95%CI: 1.002, 1.405) for NEM in females, and 1.442 (95%CI: 1.099, 1.892) for people aged 65–74 years. An increase of more than 3°C was associated with RRs of 1.353 (95%CI: 1.033, 1.772) for cardiovascular mortality and 1.667 (95%CI: 1.146, 2.425) for people aged <65 years. In Los Angeles, only a drop of more than 3°C was significantly associated with RRs of 1.133 (95%CI: 1.053, 1.219) for total NEM, 1.252 (95%CI: 1.131, 1.386) for cardiovascular mortality, and 1.254 (95%CI: 1.135, 1.385) for people aged ≥75 years. In both cities, there were joint effects of temperature change and mean temperature on NEM.

Conclusion

A significant change in temperature of more than 3°C, whether positive or negative, has an adverse impact on mortality even after controlling for the current temperature.     

Persistence of Mycoplasma genitalium following azithromycin therapy

Background

To determine clinical outcomes and cure rates for M.genitalium genital infection in men and women following azithromycin 1 g.

Methodology

Patients attending Melbourne Sexual Health Centre between March 2005 and November 2007 with urethritis/epididymitis, cervicitis/pelvic inflammatory disease and sexual contacts of M.genitalium were tested for M.genitalium by polymerase chain reaction (PCR). M.genitalium-infection was treated with 1 g of azithromycin and a test-of-cure (toc) was performed one month post-azithromycin. Response to azithromycin, and response to moxifloxacin (400 mg daily for 10 days) in individuals with persistent infection post-azithromycin, was determined.

Principal Findings

Of 1538 males and 313 females tested, 161 males (11%) and 30 females (10%) were infected with M.genitalium. A toc was available on 131 (69%) infected individuals (median = 36 days [range 12-373]). Of 120 individuals prescribed azithromycin only pre-toc, M.genitalium was eradicated in 101 (84%, 95% confidence intervals [CI]: 77–90%) and persisted in 19 (16%, 95% CI: 10–23%). Eleven individuals with persistent infection (9%, 95% CI: 5–15%) had no risk of reinfection from untreated-partners, while eight (7%, 95% CI: 3–12%) may have been at risk of reinfection from doxycycline-treated or untreated-partners. Moxifloxacin was effective in eradicating persistent infection in all cases not responding to azithromycin. Patients with persistent-M.genitalium were more likely to experience persistent symptoms (91%), compared to patients in whom M.genitalium was eradicated (17%), p<0.0001.

Conclusion

Use of azithromycin 1 g in M.genitalium-infected patients was associated with unacceptable rates of persistent infection, which was eradicated with moxifloxacin. These findings highlight the importance of follow-up in M.genitalium-infected patients prescribed azithromycin, and the need to monitor for the development of resistance. Research to determine optimal first and second-line therapeutic agents for M.genitalium is needed.