Pain Reactivity and Plasma β-Endorphin in Children and Adolescents with Autistic Disorder

Background

Reports of reduced pain sensitivity in autism have prompted opioid theories of autism and have practical care ramifications. Our objective was to examine behavioral and physiological pain responses, plasma β-endorphin levels and their relationship in a large group of individuals with autism.

Methodology/Principal Findings

The study was conducted on 73 children and adolescents with autism and 115 normal individuals matched for age, sex and pubertal stage. Behavioral pain reactivity of individuals with autism was assessed in three observational situations (parents at home, two caregivers at day-care, a nurse and child psychiatrist during blood drawing), and compared to controls during venepuncture. Plasma β-endorphin concentrations were measured by radioimmunoassay. A high proportion of individuals with autism displayed absent or reduced behavioral pain reactivity at home (68.6%), at day-care (34.2%) and during venepuncture (55.6%). Despite their high rate of absent behavioral pain reactivity during venepuncture (41.3 vs. 8.7% of controls, P<0.0001), individuals with autism displayed a significantly increased heart rate in response to venepuncture (P<0.05). Moreover, this response (Δ heart rate) was significantly greater than for controls (mean±SEM; 6.4±2.5 vs. 1.3±0.8 beats/min, P<0.05). Plasma β-endorphin levels were higher in the autistic group (P<0.001) and were positively associated with autism severity (P<0.001) and heart rate before or after venepuncture (P<0.05), but not with behavioral pain reactivity.

Conclusions/Significance

The greater heart rate response to venepuncture and the elevated plasma β-endorphin found in individuals with autism reflect enhanced physiological and biological stress responses that are dissociated from observable emotional and behavioral reactions. The results suggest strongly that prior reports of reduced pain sensitivity in autism are related to a different mode of pain expression rather than to an insensitivity or endogenous analgesia, and do not support opioid theories of autism. Clinical care practice and hypotheses regarding underlying mechanisms need to assume that children with autism are sensitive to pain.     

Occurrence of Natural Vertical Transmission of Dengue-2 and Dengue-3 Viruses in Aedes aegypti and Aedes albopictus in Fortaleza, Ceará, Brazil

Background

Aedes aegypti and Aedes albopictus perform an important role in the transmission of the dengue virus to human populations, particularly in the tropical and subtropical regions of the world. Despite a lack of understanding in relation to the maintenance of the dengue virus in nature during interepidemic periods, the vertical transmission of the dengue virus in populations of A. aegypti and A. albopictus appears to be of significance in relation to the urban scenario of Fortaleza.

Methods

From March 2007 to July 2009 collections of larvae and pupae of Aedes spp were carried out in 40 neighborhoods of Fortaleza. The collections yielded 3,417 (91%) A. aegypti mosquitoes and 336 (9%) A. albopictus mosquitoes. Only pools containing females, randomly chosen, were submitted to the following tests indirect immunofluorescence (virus isolation), RT-PCR/nested-PCR and nucleotide sequencing at the C-prM junction of the dengue virus genome.

Results

The tests on pool 34 (35 A. albopictus mosquitoes) revealed with presence of DENV-3, pool 35 (50 A. aegypti mosquitoes) was found to be infected with DENV-2, while pool 49 (41 A. albopictus mosquitoes) revealed the simultaneous presence of DENV-2 and DENV-3. Based on the results obtained, there was a minimum infection rate of 0.5 for A. aegypti and 9.4 for A. albopictus. The fragments of 192 bp and 152 bp related to DENV-3, obtained from pools 34 and 49, was registered in GenBank with the access codes {"type":"entrez-nucleotide","attrs":{"text":"HM130699","term_id":"297515956","term_text":"HM130699"}}HM130699 and {"type":"entrez-nucleotide","attrs":{"text":"JF261696","term_id":"340343903","term_text":"JF261696"}}JF261696, respectively.

Conclusions

This study recorded the first natural evidence of the vertical transmission of the dengue virus in populations of A. aegypti and A. albopictus collected in Fortaleza, Ceará State, Brazil, opening a discuss on the epidemiological significance of this mechanism of viral transmission in the local scenario, particularly with respect to the maintenance of these viruses in nature during interepidemic periods.     

Maturation and Mip-1β Production of Cytomegalovirus-Specific T Cell Responses in Tanzanian Children,Adolescents and Adults: Impact by HIV and Mycobacterium tuberculosis Co-Infections

It is well accepted that aging and HIV infection are associated with quantitative and functional changes of CMV-specific T cell responses. We studied here the expression of Mip-1β and the T cell maturation marker CD27 within CMVpp65-specific CD4⁺ and CD8⁺ T cells in relation to age, HIV and active Tuberculosis (TB) co-infection in a cohort of Tanzanian volunteers (≤16 years of age, n = 108 and ≥18 years, n = 79). Independent of HIV co-infection, IFNγ⁺ CMVpp65-specific CD4⁺ T cell frequencies increased with age. In adults, HIV co-infection further increased the frequencies of these cells. A high capacity for Mip-1β production together with a CD27^low phenotype was characteristic for these cells in children and adults. Interestingly, in addition to HIV co-infection active TB disease was linked to further down regulation of CD27 and increased capacity of Mip-1β production in CMVpp65-specific CD4⁺ T cells. These phenotypic and functional changes of CMVpp65-specific CD4 T cells observed during HIV infection and active TB could be associated with increased CMV reactivation rates.     

Prevalence and Trends in Obesity among China’s Children and Adolescents, 1985–2010

Objectives

We examined the prevalence of and trends in obesity among children and adolescents in China (1985–2010).

Methods

We used data from the 1985, 1991, 1995, 2000, 2005, and 2010 Chinese National Surveys on Students’ Constitution and Health (CNSSCH). The CNSSCH is a national survey of physical fitness and health status in Chinese students that uses multistage stratified sampling of 31 provinces and municipalities. A subject was considered obese or overweight if weight-for-height exceeded the 20% or 10% of standard weight-for-height. The standard weight-for-height was the 80th percentile for sex- and age-specific growth charts.

Results

The age-adjusted prevalence of obesity and of overweight and obesity combined was 8.1% (95% CI, 8.0–8.3%) and 19.2% (95% CI, 19.1–19.4%) among children and adolescents 7–18 years in age. Obesity was more likely to be present among children or adolescents who were male (RR, 1.93; 95% CI, 1.90–1.97), urban (RR, 1.99; 95% CI, 1.95–2.02), or 10–12 years (RR, 1.43; 95% CI, 1.40–1.46). Trend analyses of the 25-year period revealed a significant increasing trend in males (RR, 1.59; 95% CI, 1.58–1.60) and in females (RR, 1.49; 95% CI, 1.48–1.50). The rate of increase in obese or overweight prevalence was highest in boys from rural areas (9% annual increase).

Conclusions

During 1985–2010, there was a significant and continuous increase in the prevalence of obesity in children and adolescents. Obesity is epidemic in China, but may be reduced with evidence-based interventions (e.g., school intervention programs).     

High Blood Pressure among Students in Public and Private Schools in Maceió, Brazil

The prevalence of hypertension in childhood is increasing, and investigation of its distribution is important for planning timely interventions. This study assessed the prevalence of high blood pressure (HBP) and associated factors in students between 9 and 11 years of age enrolled in public and private schools in Maceió, Brazil. A cross-sectional study was performed in a probabilistic sample of students (10.3 ± 0.5 years). The students were selected from a systematic sampling of 80 schools (40 public and 40 private). To maintain similar proportions of students existing in public and private schools in Maceió, 21 and 14 students were randomly selected from each public and private school, respectively. The prevalence ratio (PR) was estimated using Poisson regression. A total of 1,338 students were evaluated (800 from public schools and 538 from private schools). No differences were observed between school types in terms of student age and gender (p > 0.05). The prevalence of obesity (19.9% vs. 9.0%; PR = 2.2; 95% CI = 1.67–2.92) and hypertension (21.2% vs. 11.4%; PR = 1.86; 95% CI = 1.45–2.40) were higher in private schools. The association between high blood pressure and type of school (public or private) remained statistically significant even after adjustment for obesity (PR = 1.53; 95% CI = 1.19–1.97). In conclusion: (a) students from private schools have higher socioeconomic status, BMI, and HBP prevalence compared to those of public school; (b) among the evaluated students, the prevalence of obesity only partially explained the higher prevalence of high blood pressure among students from private schools. Other factors related to lifestyle of children from private schools may explain the higher prevalence of HBP. This results show the need to implement measures to promote healthy lifestyles in the school environment, since children with HBP are more likely to become hypertensive adults. Therefore, early detection and intervention in children with HBP is an important action for the prevention of hypertension in adulthood.     

γδ T Cells Are Involved in Acute HIV Infection and Associated with AIDS Progression

Background

Early diagnosis is vital to HIV control. γδ T cells play critical roles in viral infections, but their activation in acute HIV infected patients and follow up to 18 months has not been described.

Methods

Changes in γδ T cells, including subsets, function and activation, in treated and untreated acutely HIV-infected patients (n = 79) were compared by cytotoxicity assay and flow cytometry with healthy controls (n = 21) at month 0, 6, 12 and 18.

Results

In acutely HIV-infected patients, Vδ1 cell proportion was elevated (P = 0.027) with Vδ2 population reduced (P = 0.002). Effector and central memory γδ T cell factions were decreased (P = 0.006 and P = 0.001, respectively), while proportion of terminal γδ T cells increased (P = 0.002). γδ T cell cytotoxicity was compromised over time. Fraction of IL-17-producing cells increased (P = 0.008), and IFN-γ-producing cells were unaffected (P = 0.115). Elevation of a microbial translocation marker, sCD14, was associated with γδ T cell activation (P = 0.001), which increased in a time-dependent manner, correlating with CD4/CD8 T cell activation set-points and CD4 counts. Antiretroviral therapy did not affect these changes.

Conclusions

γδ T cell subpopulation and functions change significantly in acute HIV infection and over time. Early γδ T cell activation was associated with CD4/CD8 T cell activation set-points, which predict AIDS progression. Therefore, γδ T cell activation represents a potential surrogate marker of AIDS progression.     

Feasible,Efficient and Necessary,without Exception – Working with Sex Workers Interrupts HIV/STI Transmission and Brings Treatment to Many in Need

ConclusionDecades of empirical evidence, extended by analyses in this collection, argue that protecting sex work is, without exception, feasible and necessary for controlling HIV/STI epidemics. In addition, the disproportionate burden of HIV borne by sex workers calls for facilitated access to ART, care and support. The imperative for Africa is rapid scale-up of targeted prevention and treatment, facilitated by policies and action to improve conditions where sex work takes place. The opportunity is a wealth of accumulated experience working with sex workers in diverse settings, which can be tapped to make up for lost time. Elsewhere, even in countries with strong interventions and services for sex workers, an emerging challenge is to find ways to sustain them in the face of declining global resources.     

Cognition,Emotion and Behavior in Children with Tourette’s Syndrome and Children with ADHD-Combined Subtype—A Two-Year Follow-Up Study

Objective

This two-year follow-up study investigates the course of and association among measures of cognitive control, focused attention, decision-making and symptom severity (anxiety, depression and behavior) in children and adolescents with Tourette’s Syndrome (TS) or Attention-Deficit/Hyperactivity Disorder-Combined subtype (ADHD-C).

Method

19 children with TS, 33 with ADHD-C, and 50 typically developing children (TDC) were examined with a battery of psychometric measures and rating forms at baseline and two-years later.

Results

All three groups improved likewise in measures of cognitive control over time, whereas only the TDC improved in focused attention. The group of children with TS with comorbidities performed more similar to the children with ADHD-C in cognitive control at T1 and T2, whereas the children with TS without comorbidities performed more similar to the TDC in cognitive control at T1 and T2. In the decision-making task, the children with TS (with or without comorbidities) preferred a safer strategy in selecting advantageous choices than the children with ADHD-C and the TDC at T2. Children with TS and children with ADHD-C showed higher symptoms of anxiety and depression and more problems with emotional control compared with TDC at both time points. Finally, children with ADHD-C self-reported more depression symptoms than those with TS at both assessments. For the TS group, safer decision-making was related to better emotional control, and this relationship was stronger for the TS subgroup without comorbidities.

Conclusion

This study emphasizes the importance of addressing symptoms of anxiety and depression in children with TS or ADHD-C, identifying the effect of comorbidities in children with TS, and that children with TS or ADHD-C likely differ in their sensitivity to reinforcement contingencies.     

Symptoms of Emotional,Behavioral, and Social Difficulties in the Danish Population of Children and Adolescents with Type 1 Diabetes – Results of a National Survey

Objective

To assess the prevalence of psychological difficulties in Danish children and adolescents with type 1 diabetes using both child/adolescent and caregiver reports, and to investigate associations between these symptoms and metabolic control, adherence, and quality of life.

Research Design and Method:

A total of 786 children and adolescents (8–17 years) recruited through the Danish Registry of Childhood Diabetes completed subscales of the Beck''s Youth Inventories (BYI-Y), while 910 caregivers completed the Strength and Difficulties Questionnaire (SDQ). The participants also completed questionnaires assessing adherence and quality of life. BYI-Y and SDQ responses were compared with results from normative samples.

Results

Children with diabetes generally reported a lower level of symptoms of depression and anxiety, while older adolescents in most cases were comparable to the normative samples. However, the numbers of patients with elevated scores were similar to normative groups, especially regarding the proportion of participants with ‘Extremely elevated’ scores. Caregivers of children and adolescents with diabetes generally reported the prevalence of elevated scores on the SDQ to exceed the prevalence observed in the norm sample – particularly with regard to older boys. Both BYI-Y and SDQ responses were significantly correlated with HbA_1c, adherence, and quality of life.

Conclusions

This study finds Danish children and adolescents with diabetes to report lower or comparable levels of emotional difficulties compared to norms, while caregiver reports are less positive. The results therefore support the value of a multi-informant approach to the assessment of symptoms of psychological difficulty in girls and boys with diabetes.     

Trends in Prevalence of Overweight and Obesity in Danish Infants,Children and Adolescents – Are We Still on a Plateau?

Background

After the worldwide steep increase in child and adolescent overweight and obesity during the last decades, there is now evidence of a levelling off in the prevalence in many countries in the Western world.

Aim

To examine whether there still is a plateau in the prevalence of overweight and obesity in Danish children and adolescents, or whether the prevalence is decreasing or rising again.

Methods

The trends in the prevalence rates were based on three data sets providing comparable repeated estimates: 1) the Danish Health Visitors Child Health Database (DHVCHD) with measurements on infant and childhood height and weight from 2002 to 2011 (n up to 39,984), 2) the Danish National Birth Cohort (DNBC) with maternal reports of measured infant and childhood height and weight from 1998 to 2010 (n up to 56,826) and 3) the Danish part of the Health Behaviour in School-aged Children survey (HBSC) with self-reported information on adolescent height and weight from the years 2002 to 2010 (n = 16,557). Overweight and obesity were categorized according to WHO growth standards. Trends were assessed by repeated point estimates and linear regression analyses providing regression coefficients for changes in per cent per year with 95% confidence intervals (CI).

Results

The prevalence rates of overweight and obesity for infants, children and adolescents showed a mixed pattern of decline, stability and increase (ranging from -1.10 through 0.29 per cent per year with CI’s from -3.10 through 2.37). Overall, there were no consistent statistically significant trends upwards or downwards, although some significant downward trends in childhood and adolescence were observed.

Conclusion

This study, based on data from 1998 through 2011, showed that the prevalence rates of overweight and obesity among Danish infants, children and adolescents were largely still on a plateau with tendencies for a decline among children and adolescents.     

Factors Contributing to the Delay in Diagnosis and Continued Transmission of Leprosy in Brazil – An Explorative,Quantitative, Questionnaire Based Study

BackgroundLeprosy is a leading cause of preventable disability worldwide. Delay in diagnosis of patients augments the transmission of infection, and allows progression of disease and more severe disability. Delays in diagnosis greater than ten years have been reported in Brazil. To reduce this delay, it is important to identify factors that hinder patients from presenting to doctors, and those that delay doctors from diagnosing patients once they have presented. This study aimed to explore factors associated with the delayed diagnosis of leprosy in Brazil.

Methodology/ Principal Findings

This is an exploratory study using a self-constructed questionnaire delivered to patients attending three leprosy referral clinics across three states in Brazil. Data were analysed to determine associations between variables and the time taken for participants to present to the health-service, and between variables and the time taken for doctors to diagnose participants once they had presented. Participants who suspected they had leprosy but feared community isolation were 10 times more likely to wait longer before consulting a doctor for their symptoms (OR 10.37, 95% CI 2.18–49.45, p = 0.003). Participants who thought their symptoms were not serious had a threefold greater chance of waiting longer before consulting than those who did (OR 3.114, 95% CI 1.235–7.856, p = 0.016). Forty-two point six per cent of participants reported initially receiving a diagnosis besides leprosy. These had a three times greater chance of receiving a later diagnosis of leprosy compared to those not misdiagnosed or not given a diagnosis (OR 2.867, 95% CI 1.288–6.384, p = 0.010).

Conclusions/ Significance

This study implies a need for patient education regarding leprosy symptoms and the reduction of stigma to encourage patients to present. The high rate of misdiagnosis reported suggests a need to increase clinician suspicion of leprosy. Further education regarding disease symptoms in medical school curriculums may be advisable.     

Gag-Specific CD4 and CD8 T-Cell Proliferation in Adolescents and Young Adults with Perinatally Acquired HIV-1 Infection Is Associated with Ethnicity — The ANRS-EP38-IMMIP Study

The ANRS-EP38-IMMIP study aimed to provide a detailed assessment of the immune status of perinatally infected youths living in France. We studied Gag-specific CD4 and CD8 T-cell proliferation and the association between the proliferation of these cells, demographic factors and HIV disease history. We included 93 youths aged between 15 and 24 years who had been perinatally infected with HIV. Sixty-nine had undergone valid CFSE-based T-cell proliferation assays. Gag-specific proliferation of CD4 and CD8 T cells was detected in 12 (16%) and 30 (38%) patients, respectively. The Gag-specific proliferation of CD4 and CD8 T cells was more frequently observed in black patients than in patients from other ethnic groups (CD4: 32% vs. 4%, P = 0.001; CD8: 55% vs. 26%, P = 0.02). Among aviremic patients, the duration of viral suppression was shorter in CD8 responders than in CD8 nonresponders (medians: 54 vs. 20 months, P = 0.04). Among viremic patients, CD8 responders had significantly lower plasma HIV RNA levels than CD8 nonresponders (2.7 vs. 3.7 log₁₀ HIV-RNA copies/ml, P = 0.02). In multivariate analyses including sex and HIV-1 subtype as covariables, Gag-specific CD4 T-cell proliferation was associated only with ethnicity, whereas Gag-specific CD8 T-cell proliferation was associated with both ethnicity and the duration of viral suppression. Both CD4 and CD8 responders reached their nadir CD4 T-cell percentages at younger ages than their nonresponder counterparts (6 vs. 8 years, P = 0.04 for both CD4 and CD8 T-cell proliferation). However, these associations were not significant in multivariate analysis. In conclusion, after at least 15 years of HIV infection, Gag-specific T-cell proliferation was found to be more frequent in black youths than in patients of other ethnic groups, despite all the patients being born in the same country, with similar access to care.     

HIV/AIDS,Food Supplementation and Livelihood Programs in Uganda: A Way Forward?

Background

Over the last decade, health, nutrition and policy experts have become increasingly aware of the many ways in which food insecurity and HIV infection negatively impact and reinforce one another. In response, many organizations providing HIV care began supplying food aid to clients in need. Food supplementation, however, was quickly recognized as an unsustainable and incomplete intervention. Many HIV care organizations therefore developed integrated HIV and livelihood programs (IHLPs) to target the root causes of food insecurity.

Methods and Findings

We conducted a qualitative study using in-depth interviews with 21 key informants who worked at seven organizations providing HIV care, food aid, or IHLPs in Kampala, Uganda in 2007-2008 to better understand the impact of IHLPs on the well-being of people living with HIV and AIDS (PLWHAs) and the challenges in transitioning clients from food aid to IHLPs. There was strong consensus among those interviewed that IHLPs are an important intervention in addressing food insecurity and its adverse health consequences among PLWHAs. Key informants identified three main challenges in transitioning PLWHAs from food supplementation programs to IHLPs: (1) lack of resources (2) timing of the transition and (3) logistical considerations including geography and weather. Factors seen as contributing to the success of programs included: (1) close involvement of community leaders (2) close ties with local and national government (3) diversification of IHLP activities and (4) close integration with food supplementation programs, all linked through a central program of HIV care.

Conclusion

Health, policy and development experts should continue to strengthen IHLPs for participants in need. Further research is needed to determine when and how participants should be transitioned from food supplementation to IHLPs, and to determine how to better correlate measures of food insecurity with objective clinical outcomes so as to better evaluate program results.     

HIV Status Disclosure to Sexual Partners,among People Living with HIV and AIDS on Antiretroviral Therapy at Sokodé Regional Hospital,Togo

BackgroundMany studies have reported factors associated with HIV status disclosure among People Living With HIV and AIDS (PLWHA) but very few were conducted among PLWHA receiving ART. In Togo, no study on HIV status disclosure to sexual partners has been conducted among PLWHA on ART yet. We sought to document factors associated with HIV status disclosure among PLWHA receiving ART at Sokodé regional hospital in Togo.MethodThis was a cross-sectional study conducted from May to July 2013 at the regional hospital of Sokodé among 291 PLWHA who had been on ART for at least three months.ResultsA total of 291 PLWHA on ART were enrolled in this study. Their mean age (±SD) was 37.3±9.3 years and the sex ratio (Male/Female) was 0.4. Among them, 215 (74.6%) completed the questionnaire on HIV sero-status disclosure. We found that 131 PLWHA (60.9%) had disclosed their HIV sero-status to their sexual partners; 130 (60.5%) were aware of the HIV status of their sexual partners. In the multivariate analysis, the factors associated with HIV status disclosure to sexual partners were: adherence to ART (aOR = 4.89; 95%CI = [1.52; 15.78]), sexual partner awareness of HIV sero-status (aOR = 52.73; 95%CI = [14.76; 188.36]) and marital status of PLWHA (aOR = 6.10; 95%CI = [1.74; 21.37]).ConclusionThis study allowed us to note that the disclosure of HIV status to sexual partners is relatively low and to document the associated factors such as adherence to ART, sexual partner awareness of HIV sero-status and marital status.     

Treatment Adherence and Health Outcomes in MSM with HIV/AIDS: Patients Enrolled in “One-Stop” and Standard Care Clinics in Wuhan China

Background

Conducted in Wuhan China, this study examined follow-up and health markers in HIV patients receiving care in two treatment settings. Participants, all men who have sex with men, were followed for18–24 months.

Method

Patients in a “one-stop” service (ACC; N = 89) vs those in standard care clinics (CDC; N = 243) were compared on HIV treatment and retention in care outcomes.

Results

Among patients with CD4 cell count ≦350 cells/µL, the proportion receiving cART did not differ across clinic groups. The ACC was favored across five other indicators: proportion receiving tests for CD4 cell count at the six-month interval (98.2% vs. 79.4%, 95% CI 13.3–24.3, p = 0.000), proportion with HIV suppression for patients receiving cART for 6 months (86.5% vs. 57.1%, 95% CI 14.1–44.7, p = 0.000), proportion with CD4 cell recovery for patients receiving cART for 12 months (55.8% vs. 22.2%, 95% CI 18.5–48.6, p = 0.000), median time from HIV confirmation to first test for CD4 cell count (7 days, 95% CI 4–8 vs. 10 days, 95% CI 9–12, log-rank p = 0.000) and median time from first CD4 cell count ≦350 cells/µL to cART initiation (26 days, 95% CI 16–37 vs. 41.5 days, 95% CI 35–46, log-rank p = 0.031). Clinic groups did not differ on any biomedical indicator at baseline, and no baseline biomedical or demographic variables remained significant in the multivariate analysis. Nonetheless, post-hoc analyses suggest the possibility of self-selection bias.

Conclusions

Study findings lend preliminary support to a one-stop patient-centered care model that may be useful across various HIV care settings.     

Vitamin D? Supplementation in Batswana Children and Adults with HIV: A Pilot Double Blind Randomized Controlled Trial

ObjectivesSince vitamin D insufficiency is common worldwide in people with HIV, we explored safety and efficacy of high dose cholecalciferol (D₃) in Botswana, and evaluated potential modifiers of serum 25 hydroxy vitamin D change (Δ25D).DesignProspective randomized double-blind 12-week pilot trial of subjects ages 5.0–50.9 years.MethodsSixty subjects randomized within five age groups to either 4000 or 7000IU per day of D₃ and evaluated for vitamin D, parathyroid hormone, HIV, safety and growth status. Efficacy was defined as serum 25 hydroxy vitamin D (25D) ≥32ng/mL, and safety as no simultaneous elevation of serum calcium and 25D. Also assessed were HIV plasma viral RNA viral load (VL), CD4%, anti-retroviral therapy (ART) regime, and height-adjusted (HAZ), weight-adjusted (WAZ) and Body Mass Index (BMIZ) Z scores.ResultsSubjects were 50% male, age (mean±SD) 19.5±11.8 years, CD4% 31.8±10.4, with baseline VL log₁₀ range of <1.4 to 3.8 and VL detectable (>1.4) in 22%. From baseline to 12 weeks, 25D increased from 36±9ng/ml to 56±18ng/ml (p<0.0001) and 68% and 90% had 25D ≥32ng/ml, respectively (p = 0.02). Δ25D was similar by dose. No subjects had simultaneously increased serum calcium and 25D. WAZ and BMIZ improved by 12 weeks (p<0.04). HAZ and CD4% increased and VL decreased in the 7000IU/d group (p<0.04). Younger (5–13y) and older (30–50y) subjects had greater Δ25D than those 14–29y (26±17 and 28±12 vs. 11±11ng/ml, respectively, p≤0.001). Δ25D was higher with efavirenz or nevirapine compared to protease inhibitor based treatment (22±12, 27±17, vs. 13±10, respectively, p≤0.03).ConclusionsIn a pilot study in Botswana, 12-week high dose D₃ supplementation was safe and improved vitamin D, growth and HIV status; age and ART regimen were significant effect modifiers.

Trial Registration

ClinicalTrials.gov {"type":"clinical-trial","attrs":{"text":"NCT02189902","term_id":"NCT02189902"}}NCT02189902     

The Dynamics of Transmission and Spatial Distribution of Malaria in Riverside Areas of Porto Velho,Rond?nia,in the Amazon Region of Brazil

The study area in Rondônia was the site of extensive malaria epidemic outbreaks in the 19^th and 20^th centuries related to environmental impacts, with large immigration flows. The present work analyzes the transmission dynamics of malaria in these areas to propose measures for avoiding epidemic outbreaks due to the construction of two Hydroelectric Power Plants. A population based baseline demographic census and a malaria prevalence follow up were performed in two river side localities in the suburbs of Porto Velho city and in its rural vicinity. The quantification and nature of malaria parasites in clinical patients and asymptomatic parasite carriers were performed using microscopic and Real Time PCR methodologies. Anopheles densities and their seasonal variation were done by monthly captures for defining HBR (hourly biting rate) values. Main results: (i) malaria among residents show the riverside profile, with population at risk represented by children and young adults; (ii) asymptomatic vivax and falciparum malaria parasite carriers correspond to around 15% of adults living in the area; (iii) vivax malaria relapses were responsible for 30% of clinical cases; (iv) malaria risk for the residents was evaluated as 20–25% for vivax and 5–7% for falciparum malaria; (v) anopheline densities shown outdoors HBR values 5 to 10 fold higher than indoors and reach 10.000 bites/person/year; (vi) very high incidence observed in one of the surveyed localities was explained by a micro epidemic outbreak affecting visitors and temporary residents. Temporary residents living in tents or shacks are accessible to outdoors transmission. Seasonal fishermen were the main group at risk in the study and were responsible for a 2.6 fold increase in the malaria incidence in the locality. This situation illustrates the danger of extensive epidemic outbreaks when thousands of workers and secondary immigrant population will arrive attracted by opportunities opened by the Hydroelectric Power Plants constructions.