Respiratory cryptococcosis in HIV positive patients.

Although the lungs are the portal of entry of the infection, respiratory manifestations of AIDS related cryptococcosis have not been very well studied. The lack of typical findings in clinical and roentgenographic studies and the difficulties in the interpretation of the isolation of Cryptococcus neoformans from bronchial secretions, is probably the explanation for the lack of interest on this subject. The clinical and microbiological findings of 22 HIV positive patients, who presented C. neoformans in their respiratory tract clinical samples, are presented. Seventeen were males and 5 females, their age average was 30.8 years (21-50 years) and the following risk factors for HIV infection were detected: intravenous drug abuse 18, heterosexuals with several sexual partners two, one female prostitute and 1 homosexual man. All patients, except three, showed less than 100 CD4+ cells per microl. The following symptoms were observed: fever, cough, mucoid expectoration and chest ache. Roengenographic studies presented diffuse infiltrative patches in eleven cases, pulmonary cavities in three, pseudotumoral nodules in two, pneumonic infiltration in two and pleural effusion in four patients. C. neoformans was observed and/or isolated from sputum in nine patients, from bronchoalveolar lavage in seven, from lung biopsy in one and from pleural effusion in four cases. Blood cultures for C. neoformans were positive in 13 cases, urine cultures in 10 and in 11 patients C. neoformans was isolated from C.S.F. The latex agglutination tests for C. neoformans capsular polysaccharide rendered positive results in serum samples from 19 patients and from C.S.F. in 14 cases. Seven cases also presented active tuberculosis. According to these findings, it seems that the isolation of C. neoformans from bronchial secretion of HIV positive patients is a signal of disseminated cryptococcosis. It is important to isolate C. neoformans or detect its capsular antigen from other clinical samples in order to confirm the diagnosis of disseminated cryptococcosis. As observed in other studies, pleuropulmonary cryptococcosis does not present a typical clinical pattern.     

Insulin sensitivity and regional fat gain in response to overfeeding

Although insulin resistance and type 2 diabetes (T2DM) are associated with upper body fat distribution, it is unknown whether insulin resistance predisposes to upper body fat gain or whether upper body fat gain causes insulin resistance. Our objective was to determine whether insulin sensitivity predicts abdominal (subcutaneous and/or visceral) fat gain in normal weight adults. Twenty-eight (15 men) lean (BMI = 22.1 ± 2.5 kg/m(2)), healthy adults underwent ~8 weeks of overfeeding to gain ~4 kg fat. Body composition was assessed before and after overfeeding, using dual-energy X-ray absorptiometry (DXA) and abdominal computed tomography to measure total and regional (visceral, abdominal, and lower body subcutaneous) fat gain. We assessed insulin sensitivity with an intravenous glucose tolerance test (IVGTT) and the 24-h insulin area under the curve (AUC). We found a wide range of insulin sensitivity and a relatively narrow range of body fat distribution in this normal weight cohort. Participants gained 3.8 ± 1.7 kg of body fat (4.6 ± 2.2 kg body weight). The baseline 24-h AUC of insulin concentration was positively correlated with percent body fat (r = 0.43, P < 0.05). The contribution of leg fat gain to total fat gain ranged from 29 to 79%, whereas the contributions of abdominal subcutaneous fat and visceral fat gain to total fat gain ranged from 17 to 69% and -5 to 22%, respectively. Baseline insulin sensitivity, whether measured by an IVGTT (S(i)) or the 24-h AUC insulin, did not predict upper body subcutaneous or visceral fat gain in response to overfeeding. We conclude that reduced insulin sensitivity is not an obligate precursor to upper body fat gain.     

HIV抗体阳性合并马尔尼菲青霉菌感染的临床特点

目的 对HIV阳性合并马尔尼菲青霉菌的临床特点进行分析,揭示免疫能力递减的程度,易感马尔尼菲青霉菌之间的关系,给临床诊断提供帮助。方法 以我院收治的3例HIV阳性合并马尔尼菲青霉菌感染患者为例,总结分析其生物学特点。结果 三位患者都为中年男性,以间断发热、呼吸困难、干咳为主要临床表现,肺部影像学提示双肺弥漫性病变,外院治疗无效后转入我院,确诊为HIV阳性,经血培养诊断为马尔尼菲青霉菌感染。患者血CD4+ T细胞计数后,CD4+ T细胞均＜2%（正常值31%~60%）。结论 HIV阳性时,不明原因发热,肺部感染,免疫功能受损到一定程度时,易合并马尔尼菲青霉菌感染,临床症状较重并有很高的死亡率。     

Pattern of neuropsychological performance among HIV positive patients in Uganda

Background  

Few studies have examined cognitive functioning of HIV positive patients in sub-Saharan Africa. It cannot be assumed that HIV positive patients in Africa exhibit the same declines as patients in high-resource settings, since there are differences that may influence cognitive functioning including nutrition, history of concomitant disease, and varying HIV strains, among other possibilities. Part of the difficulty of specifying abnormalities in neuropsychological functioning among African HIV positive patients is that there are no readily available African normative databases. The purpose of the current study was to evaluate the pattern of neuropsychological performance in a sample of HIV positive patients in comparison to HIV negative control subjects in Uganda.     

Creating a positive feedback loop in leadership to accelerate cultural change

Leadership skills are highly valued in institutional environments, but in the context of persons excluded because of ethnicity or race (PEERs) in science, support for developing those skills often is lacking. To increase leadership diversity, institutions and programs should practice and teach diverse leadership strategies.     

Short-term regional meal fat storage in nonobese humans is not a predictor of long-term regional fat gain

Although body fat distribution strongly predicts metabolic health outcomes related to excess weight, little is known about the factors an individual might exhibit that predict a particular fat distribution pattern. We utilized the meal fatty acid tracer-adipose biopsy technique to assess upper and lower body subcutaneous (UBSQ and LBSQ, respectively) meal fat storage in lean volunteers who then were overfed to gain weight. Meal fatty acid storage in UBSQ and LBSQ adipose tissue, as well as daytime substrate oxidation (indirect calorimetry), was measured in 28 nonobese volunteers [n = 15 men, body mass index = 22.1 ± 2.5 (SD)] before and after an ～8-wk period of supervised overfeeding (weight gain = 4.6 ± 2.2 kg, fat gain = 3.8 ± 1.7 kg). Meal fat storage (mg/g adipose tissue lipid) in UBSQ (visit 1: 0.78 ± 0.34 and 1.04 ± 0.71 for women and men, respectively, P = 0.22; visit 2: 0.71 ± 0.24 and 0.90 ± 0.37 for women and men, respectively, P = 0.08) and LBSQ (visit 1: 0.60 ± 0.23 and 0.48 ± 0.29 for women and men, respectively, P = 0.25; visit 2: 0.62 ± 0.24 and 0.65 ± 0.23 for women and men, respectively, P = 0.67) adipose tissue did not differ between men and women at either visit. Fractional meal fatty acid storage in UBSQ (0.31 ± 0.15) or LBSQ (0.19 ± 0.13) adipose tissue at visit 1 did not predict the percent change in regional body fat in response to overfeeding. These data indicate that meal fat uptake trafficking in the short term (24 h) is not predictive of body fat distribution patterns. In general, UBSQ adipose tissue appears to be a favored depot for meal fat deposition in both sexes, and redistribution of meal fatty acids likely takes place at later time periods.     

Serotypes of Candida albicans isolated from HIV positive patients.

Twenty-one HIV-positive patients in different stages of the disease were studied to evaluate candidosis in the oral cavity. All patients in clinical category C were infected with Candida. The most frequently observed clinical forms were pseudomembranous and hypertrophic, in contrast to reports by other authors. Candida albicans was the species isolated in these HIV-positive patients. Alterations of cell-mediated immunity were reflected in the negativity of intradermal test. The predominant serotype of C. albicans in these patients was A, in agreement with what has been found in non-immunosuppressed patients in Venezuela. There was no correlation between the serotype of C. albicans and the clinical forms of candidosis. Based in our results and those of other authors, no conclusions can be drawn concerning a particular serotype as an indicator of immunosuppression.     

Green‐wave surfing increases fat gain in a migratory ungulate

Each spring, migratory herbivores around the world track or ‘surf’ green waves of newly emergent vegetation to distant summer or wet‐season ranges. This foraging tactic may help explain the great abundance of migratory herbivores on many seasonal landscapes. However, the underlying fitness benefits of this life‐history strategy remain poorly understood. A fundamental prediction of the green‐wave hypothesis is that migratory herbivores obtain fitness benefits from surfing waves of newly emergent vegetation more closely than their resident counterparts. Here we evaluate whether this behavior increases body‐fat levels – a critically important correlate of reproduction and survival for most ungulates – in elk Cervus elaphus of the Greater Yellowstone Ecosystem. Using satellite imagery and GPS tracking data, we found evidence that migrants (n = 23) indeed surfed the green wave, occupying sites 12.7 days closer to peak green‐up than residents (n = 16). Importantly, individual variation in surfing may help account for up to 6 kg of variation in autumn body‐fat levels. Our findings point to a pathway for anthropogenic changes to the green wave (e.g. climate change) or migrants’ ability to surf it (e.g. development) to impact migratory populations. To explore this possibility, we evaluated potential population‐level consequences of constrained surfing with a heuristic model. If green‐wave surfing deteriorates by 5–15 days from observed, our model predicts up to a 20% decrease in pregnancy rates, a 2.5% decrease in population growth, and a 30% decrease in abundance over 50 years. By linking green‐wave surfing to fitness and illustrating potential effects on population growth, our study provides new insights into the evolution of migratory behavior and the prospects for the persistence of migratory ungulate populations in a changing world.     

Investigation of the results obtained following repeated boosters with Di-Te vaccine in HIV positive children

The paper is an attempt to study the effect of repeated boosters with Di-Te vaccine in positive children. The efficacy of their administration (vaccinal coverage degree, level of secreted antitoxins, the persistency of the immune response) and their influence upon the subsequent evolution of HIV infection are investigated.     

Lymphatic filariasis: a method to identify subclinical lower limb change in PNG adolescents

Lymphedema related to lymphatic filariasis (LF) is a disabling condition that commonly manifests in adolescence. Fifty-three adolescents, 25 LF infected and 28 LF non-infected, in age and sex-matched groups, using the Binax ICT rapid card test for filarial antigen were recruited to the study. None of the participants had overt signs of lymphedema. Lymphedema assessment measures were used to assess lower limb tissue compressibility (tonometry), limb circumference (tape measure), intra- and extra-cellular fluid distribution (bioimpedance) and joint range of motion (goniometry). The mean tonometric measurements from the left, right, and dominant posterior thighs were significantly larger in participants with LF compared to participants who had tested negative for LF (p = 0.005, p = 0.004, and p = 0.003, respectively) indicating increased tissue compressibility in those adolescents with LF. ROC curve analysis to define optimal cut-off of the tonometry measurements indicated that at 3.5, sensitivity of this potential screening test is 100% (95%-CI = 86.3%, 100%) and specificity is 21.4% (95%-CI = 8.3%, 41.0%). It is proposed that this cut-off can be used to indicate tissue change characteristic of LF in an at-risk population of PNG adolescents. Further longitudinal research is required to establish if all those with tissue change subsequently develop lymphedema. However, thigh tonometry to identify early tissue change in LF positive adolescents may enable early intervention to minimize progression of lymphedema and prioritization of limited resources to those at greatest risk of developing lifetime morbidity.     

Detection of toxoplasmic encephalitis in HIV positive patients in urine with hydrogel nanoparticles

BackgroundDiagnosis of toxoplasmic encephalitis (TE) is challenging under the best clinical circumstances. The poor clinical sensitivity of quantitative polymerase chain reaction (qPCR) for Toxoplasma in blood and CSF and the limited availability of molecular diagnostics and imaging technology leaves clinicians in resource-limited settings with few options other than empiric treatment.Methology/principle findingsHere we describe proof of concept for a novel urine diagnostics for TE using Poly-N-Isopropylacrylamide nanoparticles dyed with Reactive Blue-221 to concentrate antigens, substantially increasing the limit of detection. After nanoparticle-concentration, a standard western blotting technique with a monoclonal antibody was used for antigen detection. Limit of detection was 7.8pg/ml and 31.3pg/ml of T. gondii antigens GRA1 and SAG1, respectively. To characterize this diagnostic approach, 164 hospitalized HIV-infected patients with neurological symptoms compatible with TE were tested for 1) T. gondii serology (121/147, positive samples/total samples tested), 2) qPCR in cerebrospinal fluid (11/41), 3) qPCR in blood (10/112), and 4) urinary GRA1 (30/164) and SAG1 (12/164). GRA1 appears to be superior to SAG1 for detection of TE antigens in urine. Fifty-one HIV-infected, T. gondii seropositive but asymptomatic persons all tested negative by nanoparticle western blot and blood qPCR, suggesting the test has good specificity for TE for both GRA1 and SAG1. In a subgroup of 44 patients, urine samples were assayed with mass spectrometry parallel-reaction-monitoring (PRM) for the presence of T. gondii antigens. PRM identified antigens in 8 samples, 6 of which were concordant with the urine diagnostic.Conclusion/significancesOur results demonstrate nanoparticle technology’s potential for a noninvasive diagnostic test for TE. Moving forward, GRA1 is a promising target for antigen based diagnostics for TE.     

Predictors of excessive and inadequate gestational weight gain in Hispanic women

Factors influencing gestational weight gain are incompletely understood, particularly among Hispanic women. We assessed medical, sociodemographic, behavioral, and psychosocial predictors of overall gestational weight gain, as well as gains below, within, or above the range recommended by the Institute of Medicine (IOM) within a prospective study of 770 Hispanic (predominantly Puerto Rican) prenatal care patients at a large tertiary care facility in Western Massachusetts. One third of women gained within the recommended range, 22% gained below, and 45% gained above the range. In multivariate analysis, women in the highest category of BMI (P(trend)<0.001) and parity (P(trend)<0.001) gained on average 9 lbs less than those in the lowest category. Increasing time in residence in the continental United States (P(trend)<0.01) as well as a number of prenatal care visits (P(trend)=0.03) were positively associated with weight gain. Overweight women (odds ratio (OR)=2.2, 95% confidence interval (CI) 1.3, 3.8) and those over age 30 years (OR=2.5, 95% CI 1.2, 5.0) were more likely to gain above the IOM range as compared to normal-weight women and those aged 20-24, respectively. Women with <10 years of residence in the United States were 50% less likely to gain above the IOM range as compared to third-generation women (95% CI 0.3, 0.9). Findings identify determinants of gestational weight gain which can form the basis of targeted interventions in this rapidly growing ethnic group.     

Determinants of two-year mortality among HIV positive patients with Cryptococcal meningitis initiating standard antifungal treatment with or without adjunctive dexamethasone in Uganda

Globally, early initiation of antiretroviral therapy for HIV led to a reduction in the estimated mortality from cryptococcal meningitis (CCM) from 624,700 in 2009 to 181,100 in 2014. However, CCM remains one of the leading causes of mortality among HIV infected patients especially in sub-Saharan Africa where 75% of the deaths occur. Most of the studies evaluating mortality have reported short-term mortality (at or before 10 weeks of therapy). We determined mortality and associated factors among patients treated for CCM in the CryptoDex trial (ISRCTN59144167) in Uganda, and the effect of dexamethasone adjunctive therapy on mortality at two years. We conducted a retrospective cohort study between May 2017 and July 2017 to determine the long term survival (up to 2 years post-randomization) of all patients who had been enrolled into the CryptoDex trial in Uganda. The CryptoDex trial recruited between April 2013 and February 2015. We estimated mortality rates and determined factors affecting mortality at two years using Cox regression. The study followed up 211 participants, 127 (60.2%) of whom were male. Sixteen participants (7.58%) were diagnosed with HIV at the same admission when CCM was diagnosed. By two years following randomization 127 (60%) participants had died, a mortality rate of 67 deaths per 100 person-years. Mortality was associated with Glasgow coma score (GCS) below 15 (adjusted Hazard ratio (aHR) 1.77, 95% CI: 1.02–2.44), p = 0.040; weight (aHR 0.97, per 1 Kg increase; 95% CI: 0.94–0.99), p = 0.003; and presence of convulsions (aHR 2.31, 95% CI: 1.32–4.04), p = 0.004, while dexamethasone use and fungal burden had no effect. Long-term mortality in CCM patients remains high even among patients receiving recommended therapy. Strategies to improve long-term survival in CCM patients are urgently needed, especially targeting those with reduced GCS, low weight, and convulsions.     

Predictors of multidrug- and extensively drug-resistant tuberculosis in a high HIV prevalence community

Background

Multidrug-resistant (MDR) and extensively drug-resistant (XDR) tuberculosis (TB) have emerged in high-HIV-prevalence settings, which generally lack laboratory infrastructure for diagnosing TB drug resistance. Even where available, inherent delays with current drug-susceptibility testing (DST) methods result in clinical deterioration and ongoing transmission of MDR and XDR-TB. Identifying clinical predictors of drug resistance may aid in risk stratification for earlier treatment and infection control.

Methods

We performed a retrospective case-control study of patients with MDR (cases), XDR (cases) and drug-susceptible (controls) TB in a high-HIV-prevalence setting in South Africa to identify clinical and demographic risk factors for drug-resistant TB. Controls were selected in a 1∶1∶1 ratio and were not matched. We calculated odds ratios (OR) and performed multivariate logistic regression to identify independent predictors.

Results

We enrolled 116, 123 and 139 patients with drug-susceptible, MDR, and XDR-TB. More than 85% in all three patient groups were HIV-infected. In multivariate analysis, MDR and XDR-TB were each strongly associated with history of TB treatment failure (adjusted OR 51.7 [CI 6.6-403.7] and 51.5 [CI 6.4–414.0], respectively) and hospitalization more than 14 days (aOR 3.8 [CI 1.1–13.3] and 6.1 [CI 1.8–21.0], respectively). Prior default from TB treatment was not a risk factor for MDR or XDR-TB. HIV was a risk factor for XDR (aOR 8.2, CI 1.3–52.6), but not MDR-TB. Comparing XDR with MDR-TB patients, the only significant risk factor for XDR-TB was HIV infection (aOR 5.3, CI 1.0–27.6).

Discussion

In this high-HIV-prevalence and drug-resistant TB setting, a history of prolonged hospitalization and previous TB treatment failure were strong risk factors for both MDR and XDR-TB. Given high mortality observed among patients with HIV and drug-resistant TB co-infection, previously treated and hospitalized patients should be considered for empiric second-line TB therapy while awaiting confirmatory DST results in settings with a high-burden of MDR/XDR-TB.     

Upper gastrointestinal Kaposi's sarcoma in patients positive for HIV antibody without cutaneous disease

Six patients with antibodies to the human immunodeficiency virus (HIV) and with persistent gastrointestinal symptoms of HIV infection but without cutaneous lesions of Kaposi''s sarcoma underwent endoscopy. Four also underwent barium meal examination. In all six cases small lesions were seen in the stomach at endoscopy, and histological examination of biopsy specimens taken from the lesions confirmed the diagnosis of Kaposi''s sarcoma. The barium meal examinations were reported as normal in three patients and showed oesophageal candidiasis in the fourth.These findings suggest that Kaposi''s sarcoma of the upper gastrointestinal tract is common in patients positive for HIV antibody, even those without cutaneous lesions. Endoscopy, with biopsy of suspicious lesions, is necessary to make the diagnosis and is recommended in all HIV antibody positive patients with persistent upper gastrointestinal symptoms.