Showing papers by "Karin Nielsen-Saines published in 2012"

Three Postpartum Antiretroviral Regimens to Prevent Intrapartum HIV Infection

Abstract: The Eunice Kennedy Shriver National Institute of Child Health and Human Development [NICHD] and others

Neuropsychological Function and Cerebral Metabolites in HIV-infected Youth

Abstract: The effects of HIV on brain metabolites and cognitive function are not well understood. Sixteen HIV+youths (15 vertical, 1 transfusion transmissions) receiving combination antiretroviral therapy and 14 age-matched HIV- youths (13-25 years of age) were evaluated with brain two-dimensional (2D) magnetic resonance spectroscopy (MRS) at 3 Tesla (T) and a neuropsychological battery that assessed three cognitive domains (attention/processing speed, psychomotor ability, and executive function). The relationship between brain metabolite ratios and cognitive performance was explored. Compared to HIV- controls, HIV+ subjects had higher sycllo-inositol (Scy)/total creatine (tCr) (+32%, p = 0.016) and higher Scy/total choline (tCho) (+31%, p = 0.018) on 2D-MRS in the right frontal lobe. HIV+ subjects also had higher glutamate (Glu)/tCr (+13%, p = 0.022) and higher Glu/tCho (+15%, p = 0.048) than controls. HIV+ subjects demonstrated poorer attention/processing speed (p = 0.011, d = 1.03) but similar psychomotor and executive function compared to HIV- controls. The attention/processing score also correlated negatively with the ratio of N-acetylaspartate (NAA) to tCr on 2D-MRS (r = -0.75, p = 0.0019) in the HIV- controls, but not in the HIV+ subjects (Fisher's r-z transformation, p < 0.05). Our results suggest that attention/processing speed is impacted by early HIV infection and is associated with right hemisphere NAA/tCr. Scy and Glu ratios are also potential markers of brain health in chronic, lifelong HIV infection in perinatally infected youths receiving antiretroviral therapy.

A mathematical framework for combining decisions of multiple experts toward accurate and remote diagnosis of malaria using tele-microscopy.

Abstract: We propose a methodology for digitally fusing diagnostic decisions made by multiple medical experts in order to improve accuracy of diagnosis. Toward this goal, we report an experimental study involving nine experts, where each one was given more than 8,000 digital microscopic images of individual human red blood cells and asked to identify malaria infected cells. The results of this experiment reveal that even highly trained medical experts are not always self-consistent in their diagnostic decisions and that there exists a fair level of disagreement among experts, even for binary decisions (i.e., infected vs. uninfected). To tackle this general medical diagnosis problem, we propose a probabilistic algorithm to fuse the decisions made by trained medical experts to robustly achieve higher levels of accuracy when compared to individual experts making such decisions. By modelling the decisions of experts as a three component mixture model and solving for the underlying parameters using the Expectation Maximisation algorithm, we demonstrate the efficacy of our approach which significantly improves the overall diagnostic accuracy of malaria infected cells. Additionally, we present a mathematical framework for performing ‘slide-level’ diagnosis by using individual ‘cell-level’ diagnosis data, shedding more light on the statistical rules that should govern the routine practice in examination of e.g., thin blood smear samples. This framework could be generalized for various other tele-pathology needs, and can be used by trained experts within an efficient tele-medicine platform.

Predicting Trends in HIV-1 Sexual Transmission in Sub-Saharan Africa Through the Drug Resource Enhancement Against AIDS and Malnutrition Model: Antiretrovirals for 5 Reduction of Population Infectivity, Incidence and Prevalence at the District Level

Abstract: Background. The use of antiretrovirals to reduce the incidence of human immunodeficiency virus (HIV) infection has been evaluated in mathematical models as potential strategies for curtailing the epidemic. Cohort data from the Drug Resource Enhancement Against AIDS and Malnutrition (DREAM) Program was used to generate a realistic model for the HIV epidemic in sub-Saharan Africa. Methods. Two combined stochastic models were developed: patient and epidemic models. Models were combined using virus load as a parameter of infectivity. DREAM data that assessed patient care in Mozambique and Malawi were used to generate measures of infectivity, survival, and adherence. The Markov chain prediction model was used for the analysis of disease progression in treated and untreated patients. A partnership model was used to assess the probability that an infected individual would transmit HIV. Results. Data from 26 565 patients followed up from January 2002 through July 2009 were analyzed with the model; 63% of patients were female, the median age was 35 years, and the median observation time was 25 months. In the model, a 5-fold reduction in infectivity (from 1.6% to 0.3%) occurred within 3 years when triple ART was used. The annual incidence of HIV infection declined from 7% to 2% in 2 years, and the prevalence was halved, from 12% to 6%, in 11 years. Mortality in HIV-infected individuals declined by 50% in 5 years. A cost analysis demonstrated economic efficiency after 4 years. Conclusions. Our model, based on patient data, supports the hypothesis that treatment of all infected individuals translates into a drastic reduction in incident HIV infections. A targeted implementation strategy with massive population coverage is feasible in sub-Saharan Africa.

Infant outcomes after maternal antiretroviral exposure in resource-limited settings.

Abstract: BACKGROUND AND OBJECTIVE: The impact of maternal antiretrovirals (ARVs) during pregnancy, labor, and postpartum on infant outcomes is unclear. METHODS: Infants born to HIV-infected mothers in ARV studies were followed for 18 months. RESULTS: Between June 2006 and December 2008, 236 infants enrolled from Africa ( n = 36), India ( n = 47), Thailand ( n = 152), and Brazil ( n = 1). Exposure to ARVs in pregnancy included ≥3 ARVs (10%), zidovudine/intrapartum ARV (81%), and intrapartum ARV (9%). There were 4 infant infections (1 in utero, 3 late postpartum) and 4 deaths with 1.8% mortality (95% confidence interval [CI], 0.1%–3.5%) and 96.4% HIV-1–free survival (95% CI, 94.0%–98.9%). Birth weight was ≥2.5 kg in 86%. In the first 6 months, Indian infants (nonbreastfed) had lowest median weights and lengths and smallest increases in growth. After 6 months, African infants had the lowest median weight and weight-for-age z scores. Infants exposed to highest maternal viral load had the lowest height and height-for-age z scores. Serious adverse events occurred in 38% of infants, did not differ by country, and correlated with less maternal ARV exposure. Clinical diagnoses were seen in 84% of Thai, 31% of African, and 9% of Indian infants. Congenital defects/inborn errors of metabolism were seen in 18 (7.6%) infants, of which 17 were Thai (11%: 95% CI, 6.7%–17.0%); none had first trimester ARV exposure. CONCLUSIONS: Infant follow-up in large international cohorts is feasible and provides important safety and HIV transmission data following maternal ARV exposure. Increased surveillance increases identification of congenital/inborn errors. * Abbreviations: ARV — : antiretroviral CD4 — : cluster of differentiation 4 (T4 helper cell) CI — : confidence interval HAZ — : height-for-age z score NIH — : National Institutes of Health NVP — : nevirapine PCR — : polymerase chain reaction PMTCT — : prevention of mother-to-child transmission SAE — : significant adverse event WAZ — : weight-for-age z score ZDV — : zidovudine

Prolonged leptospira urinary shedding in a 10-year-old girl.

Abstract: We present a case of leptospirosis in a previously healthy girl following a trip to Costa Rica. While she was clinically asymptomatic, she had spirochetes cultured from her urine six weeks following her trip. Prolonged urinary shedding following infection with Leptospira is possible in humans and often has subtle manifestations in children.

Nutritional Rehabilitation of HIV-Exposed Infants in Malawi: Results from the Drug Resources Enhancement Against AIDS and Malnutrition Program

Abstract: Infant malnutrition in sub-Saharan Africa is a public health priority and a challenge in high HIV prevalence areas. The Drug Resources Enhancement Against AIDS and Malnutrition program, with multiple medical centers in Sub-Saharan Africa, developed an innovative intervention for the surveillance and control of malnutrition. In a pilot initiative, 36 HIV-exposed children were evaluated at baseline upon presentation for malnutrition and at six months post- treatment. Parameters included HIV-free survival, nutritional status and change in diet. Food diary data was entered and processed using the Nutrisurvey (WHO) software. At 6 months post-intervention, a significant improvement in anthropometric parameters was noted. Slowing of linear growth was observed in patients with malaria with a mean gain in centimetres of 4.4 ± 1.7 as compared to 5.6 ± 1.7 in children with no malaria, p < 0.048 (CL 95%: −2.32, −0.01). Dietary diversity scores increased from 5.3 ± 1.9 to 6.5 ± 1.3, p < 0.01 at 6 months. A significant increase (+25%, p < 0.02) in the number of children eating fish meals was noted. Our pilot data describes positive outcomes from a rehabilitative nutritional approach based on use of local foods, peer education, anthropometric and clinical monitoring in areas of high food insecurity. The relationship between malaria and linear growth retardation requires further investigation.

Risk-Taking Behavior for HIV Acquisition during Pregnancy in Porto Alegre, Brazil

Abstract: Recent studies suggest that acquisition of HIV-1 infection during pregnancy and breastfeeding is associated with a high risk of HIV mother-to-child transmission. This study evaluates risk factors associated with HIV acquisition during pregnancy in women delivering at a large metropolitan medical facility located in the south of Brazil. From February to August 2009, our group conducted a cross-sectional study assessing women's risk for HIV acquisition by administering an oral survey to peripartum women. Of 2465 participants, 42% (n = 1046) knew that partner had been tested for HIV. During pregnancy, 82% (n = 2022) of participants never used condoms; yet 97% (n = 2399) practiced vaginal sex. Multivariate logistic regression analysis showed that patients with more years of education, in a relationship for more than 1 year, and who knew their own HIV status were more likely to know their partners' HIV status (P < 0.05). Those who were in relationship for more than 1 year and were married/living together were more likely to be comfortable discussing HIV testing with partners (P < 0.05). In conclusion, women in Brazil are at risk of HIV-infection during pregnancy as they remain sexually active, often do not know their sexual partner's HIV status, and have minimal condom use.

Evaluation of different deoxyribonucleic acid (DNA) extraction methods using dried blood spot for early infant diagnosis of HIV1 in Sub-Saharan Africa

Abstract: Mother-to-child transmission leads to death of 50% of infected children in the first 2 years of life. Early diagnosis is essential for timely treatment. Dried blood spots (DBS) collected on filter paper provide a simple approach for sample collection especially in resource limited settings, because storage and shipment are very easy. The aim of the study was to standardize reproducible, affordable and not expensive deoxyribonucleic acid (DNA) extraction procedures. 146 samples were collected in the context of DREAM Program activity (Drug Resources Enhancement against AIDS and Malnutrition), a large public health programme in Africa to treat AIDS, and nine experimental methods were compared with the HIV-DNA extraction from whole blood using Amplicor HIV-1 DNA Roche Molecular Systems. The results obtained demonstrates that it is possible to extract DNA form DBS using a Chelex resin based method with comparable efficiency to that of a commercial standardized kit, as Qiagen, decreasing test costs by about 50% and with an excellent correlation with whole blood extraction.

Quantitative Computerized Tomography (QCT) versus Dual X-Ray Absorptiometry (DXA) in the Assessment of Bone Mineral Density of HIV-1 Infected Children

Abstract: Bone studies of HIV-infected children using dual X-ray absorptiometry (DXA) suggest bone mineral density (BMD) abnormalities. Pediatric studies are often performed using DXA instead of computed tomography (CT), which accounts for 3-dimensional differences in bone size of growing children. We evaluated whether CT would match DXA measurements in this population. For this purpose, the BMD of 16 perinatally HIV-infected patients, ages 6 to 22 was assessed. Subjects were matched by age, gender, and race to controls. BMD was assessed via DXA and QCT. Clinical anthropometric data, body mass index, immunologic and virologic parameters and laboratory markers for osteoblastic and osteoclastic activity were performed. No statistically significant differences in age and anthropometric parameters between subjects and controls were found. Individual CT and DXA z-scores were significantly different when subjects were evaluated as a group (p = 0.0002) or when males and females were analyzed independently (p = 0.001 and 0.03). DXA z-scores were below 1 SD, while CT z-scores were above the mean. 31% of subjects were identified as having poor bone mineralization by DXA while none had osteopenia/osteoporosis by CT. There was no correlation between immunologic/virologic parameters and BMD by either method. Increased osteoclastic activity was noted in 10 patients receiving tenofovir. In summary, decreased BMD diagnosed by DXA in pediatric HIV-infected subjects was not confirmed by CT. Increased bone turnover in patients on tenofovir was suggested by laboratory markers. Prospective studies using CT as the imaging standard are needed for evaluation of bone mineral changes in HIV-infected children.