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Little is known about whether physical activity and fitness could enhance cognition in adolescents and young adults living with HIV. The purpose of this study was to examine this relationship in a group of 250 HIV+ (n = 88) and HIV negative (n = 162) participants from Botswana, aged 12–23 years (Mean = 17.87, SD = 2.24). Fitness was operationalized as muscular strength (push-ups) and aerobic endurance (PACER). PA was assessed using items from the Youth Risk Behavior Surveillance Survey. Cognition was measured using the Corsi Test, Berg Card Sorting Task (BCST), and Stroop Color Word Task (Stroop). Multiple regression analyses indicated that the HIV x push-ups interaction was a significant predictor of Corsi performance, and HIV status was a significant predictor of BCST performance (p

The objectives of this study were to examine differences in physical activity behaviors as a function of human immunodeficiency virus (HIV) status and sex, to test differences in physical activity self-efficacy (PASE), body weight satisfaction (BWS), and enjoyment of physical activity as a function of HIV status, and to determine if PASE, BWS, and enjoyment are associated with daily physical activity (daily PA), muscle strengthening activities, and sedentary behavior of youth with and without HIV. A total of 250 HIV positive (HIV+) and HIV negative (HIV-) youth from Botswana aged 12-23 years (Mean = 17.87, SD = 2.24) participated in the study. The HIV+ group (n = 88) was recruited from a previous 12-month antiretroviral therapy (ART) and nutrition intervention study. The HIV- group (n = 162) was randomly selected from public junior and senior (secondary) high schools in and around Gaborone. Participants' PASE, BWS, enjoyment of physical activity, daily PA, muscle strengthening, body mass index (BMI), and sedentary behavior were obtained using items from the Youth Risk Behavior Surveillance Survey. Multivariate analysis of variance (MANOVA) showed that the HIV- group (M = 1.20, SE = 0.06, CI = 1.08 to 1.32) had significantly higher daily PA than the HIV+ group (M = 0.99, SE = 0.08, CI = 0.82 to 1.15). The HIV- group (M = 0.91, SE = 0.06, CI = 0.79 to 1.03) also reported participating significantly more in muscle strengthening activities than the HIV+ group (M = 0.63, SD = 0.08, CI = 0.47 to 0.78). Multiple regression analyses showed that higher PASE (p < .001) and greater enjoyment of PA (p < .01) were predictive of higher daily PA. HIV- participants had higher PASE but lower BWS compared to HIV+ participants. Sex and age differences were observed in muscle strengthening activities and sedentary behavior. This study supports previous findings on the association of efficacy beliefs to daily PA and muscle strengthening activities. The findings have implications for PA interventions aimed at health promotion and mitigation of the effects of living with HIV/AIDS.

Loss to follow-up (LTFU) is a critical factor in determining clinical outcomes in HIV treatment programs. Identifying modifiable factors of LTFU is fundamental for designing effective patient-retention interventions. We analyzed factors contributing to children LTFU from a treatment program to identify those that can be modified. A case-control study involving 313 children was used to compare the sociodemographic and clinical characteristics of children LTFU (cases) with those remaining in care (controls) at a large pediatric HIV care setting in Botswana. We traced children through caregiver contacts and those we found, we conducted structured interviews with patients' caregivers. Children

Background: Globally, the population of adolescents living with perinatally acquired HIV (APHs) continues to expand. In this study, we pooled data from observational pediatric HIV cohorts and cohort networks, allowing comparisons of adolescents with perinatally acquired HIV in “real-life” settings across multiple regions. We describe the geographic and temporal characteristics and mortality outcomes of APHs across multiple regions, including South America and the Caribbean, North America, Europe, sub-Saharan Africa, and South and Southeast Asia. Methods and findings: Through the Collaborative Initiative for Paediatric HIV Education and Research (CIPHER), individual retrospective longitudinal data from 12 cohort networks were pooled. All children infected with HIV who entered care before age 10 years, were not known to have horizontally acquired HIV, and were followed up beyond age 10 years were included in this analysis conducted from May 2016 to January 2017. Our primary analysis describes patient and treatment characteristics of APHs at key time points, including first HIV-associated clinic visit, antiretroviral therapy (ART) start, age 10 years, and last visit, and compares these characteristics by geographic region, country income group (CIG), and birth period. Our secondary analysis describes mortality, transfer out, and lost to follow-up (LTFU) as outcomes at age 15 years, using competing risk analysis. Among the 38,187 APHs included, 51% were female, 79% were from sub-Saharan Africa and 65% lived in low-income countries. APHs from 51 countries were included (Europe: 14 countries and 3,054 APHs; North America: 1 country and 1,032 APHs; South America and the Caribbean: 4 countries and 903 APHs; South and Southeast Asia: 7 countries and 2,902 APHs; sub-Saharan Africa, 25 countries and 30,296 APHs). Observation started as early as 1982 in Europe and 1996 in sub-Saharan Africa, and continued until at least 2014 in all regions. The median (interquartile range [IQR]) duration of adolescent follow-up was 3.1 (1.5–5.2) years for the total cohort and 6.4 (3.6–8.0) years in Europe, 3.7 (2.0–5.4) years in North America, 2.5 (1.2–4.4) years in South and Southeast Asia, 5.0 (2.7–7.5) years in South America and the Caribbean, and 2.1 (0.9–3.8) years in sub-Saharan Africa. Median (IQR) age at first visit differed substantially by region, ranging from 0.7 (0.3–2.1) years in North America to 7.1 (5.3–8.6) years in sub-Saharan Africa. The median age at ART start varied from 0.9 (0.4–2.6) years in North America to 7.9 (6.0–9.3) years in sub-Saharan Africa. The cumulative incidence estimates (95% confidence interval [CI]) at age 15 years for mortality, transfers out, and LTFU for all APHs were 2.6% (2.4%–2.8%), 15.6% (15.1%–16.0%), and 11.3% (10.9%–11.8%), respectively. Mortality was lowest in Europe (0.8% [0.5%–1.1%]) and highest in South America and the Caribbean (4.4% [3.1%–6.1%]). However, LTFU was lowest in South America and the Caribbean (4.8% [3.4%–6.7%]) and highest in sub-Saharan Africa (13.2% [12.6%–13.7%]). Study limitations include the high LTFU rate in sub-Saharan Africa, which could have affected the comparison of mortality across regions; inclusion of data only for APHs receiving ART from some countries; and unavailability of data from high-burden countries such as Nigeria. Conclusion: To our knowledge, our study represents the largest multiregional epidemiological analysis of APHs. Despite probable under-ascertained mortality, mortality in APHs remains substantially higher in sub-Saharan Africa, South and Southeast Asia, and South America and the Caribbean than in Europe. Collaborations such as CIPHER enable us to monitor current global temporal trends in outcomes over time to inform appropriate policy responses., 0, SCOPUS: ar.j, info:eu-repo/semantics/published

BACKGROUND Seizures are common among patients with HIV/AIDS in the developing world and are associated with significant morbidity and mortality. Early treatment with combination antiretroviral therapy (cART) may reduce this risk by decreasing rates of central nervous system infections and HIV encephalopathy. METHODS A case-control study of new-onset epilepsy among children aged 0-18 years with perinatally acquired HIV/AIDS followed in Gaborone, Botswana, during the period 2003-2009 was conducted. Children with epilepsy were identified and compared with age- and sex-matched controls without epilepsy with respect to timing of cART initiation. Early treatment was defined as treatment with cART before the age of 12 months, at a CD4% of greater than 25 in children aged 1-5 years, or at an absolute CD4 count of >350 cell per cubic millimeter in children aged 5 years and older. RESULTS We identified 29 cases of new-onset epilepsy and 58 age- and sex-matched controls. The most common identified etiologies for epilepsy were central nervous system infections and direct HIV neurotoxicity. Only 8 (28%) of the children who developed epilepsy received early treatment compared with 31 (53%) controls (odds ratio: 0.36, 95% confidence interval: 0.14 to 0.92, P = 0.03). This effect was primarily driven by differences in rates of epilepsy among children who initiated treatment with cART between the ages of 1 and 5 years (11% vs. 53%, odds ratio: 0.11, 95% confidence interval: 0.01 to 1.1, P = 0.06). CONCLUSIONS Earlier initiation of cART may be protective against epilepsy in children with HIV.

High mortality among adolescents with HIV reflects delays and failures in the care cascade. We sought to elucidate critical missed opportunities and barriers to care among adolescents hospitalized with HIV at Botswana's tertiary referral hospital. We enrolled all HIV-infected adolescents (aged 10-19 years) hospitalized with any diagnosis other than pregnancy from July 2015 to January 2016. Medical records were reviewed for clinical variables and past engagement in care. Semi-structured interviews of the adolescents (when feasible) and their caregivers explored delays and barriers to care. Twenty-one eligible adolescents were identified and 15 were enrolled. All but one were WHO Clinical Stage 3 or 4. Barriers to diagnosis included lack of awareness about perinatal HIV infection, illness or death of the mother, and fear of discrimination. Barriers to adherence to antiretroviral therapy included nondisclosure, isolation, and mental health concerns. The number of hospitalized HIV-infected adolescents was lower than expected. However, among those hospitalized, the lack of timely diagnosis and subsequent gaps in the care cascade elucidated opportunities to improve outcomes and quality of life for this vulnerable group.

BACKGROUND To compare steady-state (ss) pharmacokinetic targets of nevirapine extended-release (NVP-XR) tablets once-daily (QD) with immediate-release (NVP-IR) tablet or oral suspension twice-daily in HIV-1-infected children and adolescents. METHODS Phase I, open-label, multidose, cross-over study with optional extension phase, in 85 patients 3 to

SETTING Four public hospitals in Botswana, a high tuberculosis (TB) burden setting. OBJECTIVES To assess the feasibility and utility of sputum induction in the diagnosis of paediatric TB. DESIGN From 2008 to 2010, children aged ≤18 years referred for suspected pulmonary TB underwent sputum induction. Confirmed TB was defined as the presence of at least one of the signs and symptoms suggestive of TB and positive Mycobacterium tuberculosis culture. Information on TB-associated symptoms (cough, fatigue, night sweats, low appetite, chest pain, weight loss, haemoptysis and contact with a TB case) was collected for three risk groups: human immunodeficiency virus (HIV) positive children, HIV-negative children aged

A commentary is presented on the urgent need for a comprehensive effort to improve the practice of pediatric therapeutics in Africa. A call for action is addressed to a variety of practitioners internationally, many of whom possess skills that could be fruitfully applied to the improvement of health outcomes for African children. Successful engagement with the many challenges requires the complementary effort of researchers in basic and clinical pharmacology and toxicology, nurses, pharmacists, physicians, clinical pharmacologists, clinical pharmacists, and political leaders and civil servants. While a comprehensive or systematic review of the relevant literature has not been attempted, the authors have highlighted promising initiatives driven by international agencies and academic networks. Two African perspectives are presented to reinforce the prospect of child health gains that can be achieved through consistent pursuit of optimal therapy for conditions such as respiratory infection, diarrhea, malaria, and HIV/AIDS. There is an imperative for development of north-south and south-south partnerships that will amplify current research efforts and mobilize existing knowledge concerning pediatric drugs. The overall goal is a multidisciplinary commitment to making essential medicines available at the right time, the right place, and in the right formulation for African children from infancy to adolescence.

Antiretroviral treatment means many HIV infected children are surviving with a highly stigmatised condition. There is a paucity of data to inform policies for this growing cohort. Hence we carried out a study on the health, schooling, needs, aspirations, perspectives and knowledge of HIV infected and affected children in Botswana.A cross-sectional survey using interviews and focus group discussions among HIV infected children aged 6-18 years versus HIV aged matched HIV uninfected counterparts living in the same households between August 2010 and March 2011. Supplemental clinical data was abstracted from medical records for HIV infected participants.Nine hundred eighty-four HIV infected and 258 affected children completed the survey. Females predominated in the affected group (63.6 % versus 50.3 %, P 0.001). School attendance was high in both groups (98.9 % versus 97.3 %, P = 0.057). HIV infected children were mostly in primary school (grades 3-7) while affected children were mostly in upper primary or secondary grades. Sixty percent HIV infected children reported having missed school at least 1 day in the preceding month. Significantly more infected than affected children reported experiencing problems at school (78 % versus 62.3 %, P 0.001). Twenty-two percent of 15-18 year old HIV infected children were in standard seven and below compared to only 8 % of HIV affected children (p = 0.335). School related problems included poor grades, poor health/school attendance, stigma and inadequate scholastic materials. The wish-list for improving the school environment was similar for both groups and included extra learning support; better meals; protection from bullying/teasing; more scholastic materials, extracurricular activities, love and care; structural improvements; improved teacher attendance and teaching approaches. Significantly more HIV infected children reported feeling hungry all the time (50.6 % versus 41 %, P = 0.007) and more trouble hearing (26.8 % versus 12.5 %, P = 0.028). The mean age for HIV disclosure 10 years was high. Sexual activity (9.2 % versus 3 %, P = 0.001) and emotions of anger (71 % versus 55.3 %, P 0.001) were significantly higher among HIV affected children. Future perspectives were equally positive (93 % versus 96 %, P = 0.080), were predicated on children's school performance, self-belief/determination and/or ARVs and preference for medical or military careers was common.In Botswana almost all school-age HIV infected and affected children are attending school but many face daunting challenges that call for the creation of an empowering, empathetic, supportive, caring, and non-discriminating school environment.

Clinical mentoring by providers skilled in HIV management has been identified as a cornerstone of scaling-up antiretroviral treatment in Africa, particularly in settings where expertise is limited. However, little data exist on its effectiveness and impact on improving the quality-of-care and clinical outcomes, especially for HIV-infected children. Since 2008, the Botswana-Baylor Children’s Clinical Centre of Excellence (COE) has operated an outreach mentoring programme at clinical sites around Botswana. This study is a retrospective review of 374 paediatric charts at four outreach mentoring sites (Mochudi, Phutadikobo, Molepolole, Thamaga) evaluating the effectiveness of the programme as reflected in a number of clinically-relevant areas. Charts from one visit prior to initiation of mentoring and from one visit after approximately one year of mentoring were assessed for statistically-significant differences (p

Background Limited data are available on patterns of resistance mutations in pediatric patients in southern Africa, where HIV-1 subtype C (HIV-1C) predominates. Methods Retrospective chart review of pediatric patients. Nucleoside reverse transcriptase inhibitor (NRTI)- and nonnucleoside reverse transcriptase inhibitor (NNRTI)-associated resistance mutations quantified from population-based sequencing genotypic resistance assay results taken at time of first-line antiretroviral therapy (ART) failure (first-line ART = stavudine [d4T] or zidovudine [ZDV] + lamivudine [3TC] + nevirapine [NVP] or efavirenz [EFV]). Results Total number of patients with resistance assays analyzed is 45. Nucleoside reverse transcriptase inhibitor-associated mutation frequencies noted were M184V (n = 41; 91.1%); thymidine analogue mutations (TAMs; n = 20; 44.4%); >1 TAM (n = 9; 20%); TAM-2 pathway (n = 10; 22.2%); TAM-1 pathway (n = 7; 15.6%); TAM-1 and TAM-2 pathways (n = 3; 6.7%); K65R (n = 2; 4.4%); Q151M (n = 1; 2.2%); and L74V (n = 0; 0%). Nonnucleoside reverse transcriptase inhibitor-associated mutation frequencies noted were associated with notable resistance to either/both NVP and EFV (n = 40; 88.9%); K103N (n = 15; 33.3%); ≥1 mutations associated with etravirine (ETR) failure (K101E, Y181C, and G190A; n =20; 44.4%); and ≥2 notable NNRTI mutations (n = 12; 26.7%). Conclusions In this cohort, low-genetic barrier mutations were common, as were TAMs, including more than 1 TAM. Mutations compromising nonthymidine analogue backbones were rare, suggesting that it is likely that children who fail first-line NRTI backbones containing d4T or ZDV/3TC would still respond to abacavir (ABC), didanosine (ddI), and, for adolescents, tenofovir (TDF). Our data support the empiric continuation of 3TC in second-line regimens.

RationaleAccurate weight measurements are essential for both growth monitoring and drug dose calculations in children. Weight can be accurately measured using calibrated scales in resource-rich settings; however, reliable scales are often not available in resource-poor regions or emergency situations. Current age and/or length/height-based weight-prediction equations tend to overestimate weight because they were developed from Western children's measures.ObjectiveTo determine the accuracy of several proxy measures for children's weight among a predominately HIV-positive group of children aged 18 months to 12 years in Botswana.DesignWeight, length/height, ulna and tibia lengths, mid-upper arm circumference (MUAC) and triceps skinfold were measured on 775 children recruited from Gaborone, Botswana, between 6 July and 24 August 2011.ResultsMean (95% CI) age and weight were 7.8 years (7.5 to 8.4) and 21.7 kg (21.2 to 22.2), respectively. The majority of children were HIV-positive (n=625, 81%) and on antiretroviral treatment (n=594, 95%). The sample was randomly divided; a general linear model was used to develop weight-prediction equations for one half of the sample (n=387), which were then used to predict the weight of the other half (n=388). MUAC and length/height, MUAC and tibia length and MUAC and ulna length most accurately predicted weight, with an adjusted R2 of 0.96, 0.95 and 0.93, respectively. Using MUAC and length/height, MUAC and tibia length and MUAC and ulna length equations, ≥92% of predicted weight fell within 15% of actual weight, compared with ConclusionThe development of nomograms using these equations is warranted to allow for rapid and accurate weight prediction from these simple anthropometric measures in HIV-endemic, resource-constrained settings.

Psychosocial dysfunction is a risk factor for treatment non-adherence among children and adolescents. A previous study showed that high scores on the Pediatric Symptom Checklist (PSC) were associated with a history of HIV virologic failure. We assessed whether high scores on the PSC could predict virologic failure in HIV-infected youth. Caregivers of 234 adolescents between the ages of 10 and 16 years were asked to complete a PSC at baseline. Elevated PSC scores were associated with virologic failure in the subsequent 6 months. PSC scores may help guide resource utilization when viral load monitoring is limited.

The purpose of this study was to determine whether diary-driven adjustment of Medication Event Monitoring System (MEMS) data based on Supporting Information strengthens the relationship between measured antiretroviral medication adherence and plasma HIV viral load (VL).HIV+ adolescents on antiretroviral treatment were monitored with MEMS for 30 days preceding a VL measurement. The primary outcome was VL ≥ 400 copies/mL. Handwritten diaries were used to comprehensively record deviations from recommended use (bottle opened but dose not taken or bottle not opened and dose taken). Data were adjusted ("cleaned") based on diary events. Data were "capped" at the prescribed number of doses/day. Receiver operator characteristic analysis compared the relationships between (i) raw MEMS data, (ii) diary-cleaned, (iii) capped, or (iv) cleaned and capped MEMS data and VL.Over 30 days preceding VL measurements, 273 adolescents had 465 diary events. Capping resulted in fewer patients classified as 95% adherent (65.2%) compared with raw data (71.4%), p 0.001. Adherence was highly associated with VL (OR 1.05, p 0.001). The area under the receiver operating characteristic curve for continuous adherence compared with VL was 0.89 (95%CI: 0.82-0.95). Neither diary-cleaning, capping, nor cleaning and capping MEMS data significantly altered the association between adherence and VL (p = 0.14, 0.40, and 0.19, respectively).Medication Event Monitoring System data-cleaning based on diary entries did not affect the adherence-VL relationship.

In the optional extension of clinical trial 1100.1518 39/40, human immunodeficiency virus-infected patients (aged 3 to18 years) received ≥48 weeks of treatment with extended-release nevirapine. By last visit, all patients had undetectable viral loads and no new safety signals, demonstrating the safety and efficacy of a once-daily antiretroviral regimen.

Human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome (AIDS) is having a devastating impact on African men, women and children. Antiretroviral treatment of children has lagged behind that of adults in Africa and globally. Fortunately, several national and international initiatives are helping to catalyze access of HIV-infected children to treatment. In general, the principles of antiretroviral treatment are the same for resource-rich and resource-poor settings. However, the more rapid progression of HIV disease often observed among children in Africa and some other resource-poor settings may argue for a more aggressive approach to initiation of treatment. In addition, numerous barriers to treatment of HIV-infected children in Africa and other resource-poor settings exist and must be overcome, including the expense of antiretroviral medications, lack of pediatric drug formulations, and poor human capacity and infrastructure for treatment administration. The 2.2 million African children currently living with HIV/AIDS, and many more living in poor countries on other continents, are dependent on all of us to work creatively to overcome barriers to the large-scale implementation of programs for health-restoring, life-prolonging antiretroviral treatment.

This retrospective review evaluated records of cerebrospinal fluid samples between 2000 and 2008 at Princess Marina Hospital in Gaborone, Botswana. Of the 7501 cerebrospinal fluid samples reviewed, Streptococcus pneumoniae (n = 125) and Haemophilus influenzae (n = 60) were the most common bacteria cultured. There were also 1018 cryptococcal and 44 tuberculous meningitis cases. Antimicrobial susceptibilities are described. Public health interventions could decrease the burden of meningitis in Botswana.

Background: Children with HIV infection are often reported to be short. The aim of this study was to assess the prevalence of HIV-associated short stature in HIV endemic setting. Methods: Data were obtained by retrospective review of the electronic medical records. Patients were grouped into various clinical categories. For each category, the proportion of patients with height-for-age Z score of less than −2 standard deviation [SD] and of less than −3 SD was determined. Results: The prevalence of short stature (less than −2 SD) was 28.4%. Severe short stature (less than −3 SD) is more likely with percentage of CD4 400 copies/mL (OR 2.64, CI 1.27-5.38, P = .008) and poor adherence (Conclusion: In Botswana, short stature affects a quarter of HIV-infected children and severe short stature is associated with poor adherence to antiretroviral treatment, severe immunosuppression, and virologic failure.

We investigated the association between household food insecurity (HFI) and CD4% among 2-6-year old HIV+ outpatients (n = 78) at the Botswana-Baylor Children's Clinical Center of Excellence in Gaborone, Botswana. HFI was assessed by a validated survey. CD4% data were abstracted from the medical record. We used multiple linear regression with CD4% (dependent variable), HFI (independent variable), and controlled for sociodemographic and clinical covariates. Multiple linear regression showed a significant main effect for HFI [beta = -0.6, 95% confidence interval (CI): -1.0 to -0.1] and child gender (beta = 5.6, 95% CI: 1.3 to 9.8). Alleviating food insecurity may improve pediatric HIV outcomes in Botswana and similar Sub-Saharan settings.

Study Objectives Psychosocial factors such as outcome expectancy, perceived stigma, socio-emotional support, consideration of future consequences, and psychological reactance likely influence adolescent adherence to antiretroviral treatments. Culturally-adapted and validated tools for measuring these factors in African adolescents are lacking. We aimed to identify culturally-specific factors of importance to establishing local construct validity in Botswana. Methods Using in-depth interviews of 34 HIV+ adolescents, we explored how the psychosocial factors listed above are perceived in this cultural context. We evaluated six scales that have been validated in other contexts. We also probed for additional factors that the adolescents considered important to their HIV medication adherence. Analyses were conducted with an analytic framework approach using NVivo9 software. Results While the construct validity of some Western-derived assessment tools was confirmed, other tools were poorly representative of their constructs in this cultural context. Tools chosen to evaluate HIV-related outcome expectancy and perceived stigma were well-understood and relevant to the adolescents. Feedback from the adolescents suggested that tools to measure all other constructs need major modifications to obtain construct validity in Botswana. The scale regarding future consequences was poorly understood and contained several items that lacked relevance for the Batswana adolescents. They thought psychological reactance played an important role in adherence, but did not relate well to many components of the reactance scale. Measurement of socio-emotional support needs to focus on the adolescent-parent relationship, rather than peer-support in this cultural context. Denial of being HIV-infected was an unexpectedly common theme. Ambivalence about taking medicines was also expressed. Discussion In-depth interviews of Batswana adolescents confirmed the construct validity of some Western-developed psychosocial assessment tools, but demonstrated limitations in others. Previously underappreciated factors related to HIV medication adherence, such as denial and ambivalence, should be further explored.

Background: Data on the use of ritonavir-boosted darunavir (DRV/r) and/or raltegravir (RAL) in resource-limited settings are rare and there is currently no published data regarding their use among African children. Botswana has recently made DRV/r and RAL available for patients failing second-line antiretroviral therapy (ART). Methods: Retrospective chart review of 4 multidrug-resistant pediatric patients on DRV/r- and/or RAL-based regimens. Viral load, CD4 count, adherence by pill count, and World Health Organization (WHO) clinical stage prior to and after switch to DRV/r- and/or RAL-based regimen were assessed. Antiretroviral therapy history, duration of virologic failure, and time to viral suppression were also noted. Genotypic resistance assays reviewed for mutations present prior to switch. Results: All patients achieved viral suppression, showed improved/stable CD4 counts, and obtained or maintained WHO clinical treatment stage I, even after long-standing virologic/immunologic failure. Conclusions: Well tolerated by and effective in our patients, DRV/r and RAL provide potentially lifesaving ART options for children and adolescents in resource-limited settings failing ART due to ritonavir-boosted lopinavir (LPV/r) resistance.

This review was conducted to examine the current status of paediatric medicines initiatives across the globe.The authors made a non-systematic descriptive review of current world situation.Two regions, the United States (US) and the European Union (EU), and the World Health Organization (WHO) have introduced strong paediatric initiatives to improve children's health through improving access to better paediatric medicines. The experience from the US initiative indicates that it is possible to stimulate development and study of paediatric medicines and provide important new information for improvement of paediatric therapy. The early results from the EU initiative are similarly encouraging. In Canada, Japan, Australia and other developed countries, specific paediatric medicines initiatives have been less extensive and weaker, with modest results. Disappointingly, current evidence suggests that results from clinical trials outside the US often do not benefit children in the country in which the trials were largely conducted. Pharmaceutical companies that have derived a financial benefit commensurate with the cost of doing the paediatric trials in one country do not seem to be making the results of these trials available to all countries if there is no financial incentive to the company. The WHO campaign 'make medicines child size' has produced substantive accomplishments in building improved foundations to improve mechanisms that will enhance children's access to critical medicines in resource-limited settings. However, practically all of this work has been performed using an amalgamation of short-term funding from a variety of sources as opposed to a sustained, programmatic commitment.Although much still needs to be done, it's clear that with concerted efforts and appropriate resources, change is possible but slow. Retaining and fostering public and political interest in paediatric medicines is challenging, but pivotal for success.

It is estimated that more than 2.1 million adolescents (10–19 years of age) live with human immunodeficiency virus (HIV) in low-income and middle-income countries.1 When compared with both adults and younger children, HIV-infected adolescents have higher rates of nonadherence, virologic failure, and death.2,3 As they age, adolescents generally increase their health care–related autonomy. Adolescents may attend a clinic with or without an adult caregiver (parent). The relationship between parental attendance at clinic visits and adolescent chronic disease outcomes is unknown. We hypothesized that routine clinic attendance without a parent would be associated with the risk of HIV treatment failure, particularly in younger adolescents.

There is little published literature on the effects of skin contactants during early infancy on eventual development of atopic dermatitis (AD). The purpose of this study was to determine whether or not a relationship exists between the use of skin care products in early infancy and the subsequent development of AD. We studied a group of 54 Kenyan children with AD and 63 age and sex matched controls. Emollients had been used to lubricate the skin during early infancy in a similar proportion of children in both groups (odds ratio = 0.33; 95% CI = 0.14, 0.80). Similarly, no association was found between the use of toilet soaps or laundry detergents in early infancy and development of AD. These findings suggest that baby soaps and vaseline petroleum jelly can safely be used in the skin care of AD susceptible individuals.

Background Malaria is a major cause of pediatric mortality in sub-Saharan Africa. Worldwide estimates of mortality among children with Plasmodium falciparum malaria range from 1 to 2 million deaths per year. Management of malaria is increasingly difficult because of the global spread of drug-resistant strains of P. falciparum. There is an urgent need for safe and effective new therapies to treat multidrug-resistant malaria. Methods This open label, randomized trial compared atovaquone and proguanil hydrochloride with halofantrine for treatment of acute, uncomplicated P. falciparum malaria in children age 3 to 12 years (84 patients per group). Study drug dosages were adjusted by weight (approximately 20 and 8 mg/kg daily for three doses for atovaquone and proguanil hydrochloride and 8 mg/kg every 6 h for three doses for halofantrine). Patients were monitored by serial clinical and laboratory assessments for 28 days after starting treatment. Results Both regimens were effective (cure rate, 93.8% for atovaquone and proguanil hydrochloride and 90.4% for halofantrine) and produced prompt defervescence. Mean parasite clearance times were 50.2 h for halofantrine and 64.9 h for atovaquone and proguanil hydrochloride. More adverse experiences were reported in children treated with halofantrine (119) than with atovaquone and proguanil hydrochloride (73). Conclusions In Kenyan children the combination of atovaquone and proguanil hydrochloride has efficacy comparable with that of halofantrine for treatment of acute uncomplicated multidrug-resistant falciparum malaria and is associated with a lower rate of adverse events.

BACKGROUND: Little is known about the prevalence of atopic eczema outside Northern Europe. OBJECTIVES: We sought to describe the magnitude and variation in the prevalence of atopic eczema symptoms throughout the world. METHODS: A cross-sectional questionnaire survey was conducted on random samples of schoolchildren aged 6 to 7 years and 13 to 14 years from centers in 56 countries throughout the world. Those children with a positive response to being questioned about the presence of an itchy relapsing skin rash in the last 12 months that had affected their skin creases were considered to have atopic eczema. Children whose atopic eczema symptoms resulted in sleep disturbance for 1 or more nights per week were considered to have severe atopic eczema. RESULTS: Complete data was available for 256,410 children aged 6 to 7 years in 90 centers and 458,623 children aged 13 to 14 years in 153 centers. The prevalence range for symptoms of atopic eczema was from less than 2% in Iran to over 16% in Japan and Sweden in the 6 to 7 year age range and less than 1% in Albania to over 17% in Nigeria for the 13 to 14 year age range. Higher prevalences of atopic eczema symptoms were reported in Australasia and Northern Europe, and lower prevalences were reported in Eastern and Central Europe and Asia. Similar patterns were seen for symptoms of severe atopic eczema. CONCLUSIONS: Atopic eczema is a common health problem for children and adolescents throughout the world. Symptoms of atopic eczema exhibit wide variations in prevalence both within and between countries inhabited by similar ethnic groups, suggesting that environmental factors may be critical in determining disease expression. Studies that include objective skin examinations are required to confirm these findings.

Background: As part of the International Study of Asthma and Allergies in Childhood (ISAAC), prevalence surveys were conducted among representative samples of school children from locations in Europe, Asia, Africa, Australasia, North and South America. Subjects: 257,800 children aged 6-7 years from 91 centres in 38 countries, and 463,801 children aged 13-14 years from 155 centres in 56 countries. Methods: Written symptom questionnaires were translated from English into the local language for self-completion by the 13-14-year-olds and completion by the parents of the 6-7-year-olds. Rhinitis was described as a problem with sneezing, or a runny, or blocked nose when you (your child) DID NOT have a cold or the flu. Additional questions were asked about rhinitis associated with itchy-watery eyes, interference with activities and a history of hay fever ever. Results: The prevalence of rhinitis with itchy-watery eyes (“rhinoconjunctivitis”) in the past year varied across centres from 0.8%(to 14.9% in the 6-7-year-olds and from 1.4% to 39.7% in the 13-14-year-olds. Within each age group, the global pattem was broadly consistent across each of the symptom categories. In centres of higher prevalence there was great variability in the proportion of rhinoconjunctivitis labelled as hay fever. The lowest prevalences of rhinoconjunctivitis were found in parts of eastern Europe. south and central Asia. High prevalences were reported from centres in several regions. Conclusion: These results suggest substantial worldwide variations in the prevalence and labelling of symptoms of allergic rhinoconjunctivitis which require further study. These differences, if real, may offer important clues to environmental influences on allergy.

Worldwide, the nonnucleoside reverse transcriptase inhibitors (NNRTIs) efavirenz and nevirapine are commonly used in first-line antiretroviral regimens in both adults and children with human immunodeficiency virus (HIV) infection. Data on the comparative effectiveness of these medications in children are limited.To investigate whether virological failure is more likely among children who initiated 1 or the other NNRTI-based HIV treatment.Retrospective cohort study of children (aged 3-16 years) who initiated efavirenz-based (n = 421) or nevirapine-based (n = 383) treatment between April 2002 and January 2011 at a large pediatric HIV care setting in Botswana.The primary outcome was time from initiation of therapy to virological failure. Virological failure was defined as lack of plasma HIV RNA suppression to less than 400 copies/mL by 6 months or confirmed HIV RNA of 400 copies/mL or greater after suppression. Cox proportional hazards regression analysis compared time to virological failure by regimen. Multivariable Cox regression controlled for age, sex, baseline immunologic category, baseline clinical category, baseline viral load, nutritional status, NRTIs used, receipt of single-dose nevirapine, and treatment for tuberculosis.With a median follow-up time of 69 months (range, 6-112 months; interquartile range, 23-87 months), 57 children (13.5%; 95% CI, 10.4%-17.2%) initiating treatment with efavirenz and 101 children (26.4%; 95% CI, 22.0%-31.1%) initiating treatment with nevirapine had virological failure. There were 11 children (2.6%; 95% CI, 1.3%-4.6%) receiving efavirenz and 20 children (5.2%; 95% CI, 3.2%-7.9%) receiving nevirapine who never achieved virological suppression. The Cox proportional hazard ratio for the combined virological failure end point was 2.0 (95% CI, 1.4-2.7; log rank P.001, favoring efavirenz). None of the measured covariates affected the estimated hazard ratio in the multivariable analyses.Among children aged 3 to 16 years infected with HIV and treated at a clinic in Botswana, the use of efavirenz compared with nevirapine as initial antiretroviral treatment was associated with less virological failure. These findings may warrant additional research evaluating the use of efavirenz and nevirapine for pediatric patients.

The efficacy and safety of a single daily dose of sodium stibogluconate, 20 mg/kg body weight, given by deep intramuscular injection was compared with the conventional dose of 10 mg Sb/kg body weight in a randomised trial in Kenyan children and adults with visceral leishmaniasis. Splenic aspiration proved a safe and simple method for assessing parasitological response to treatment. In children the higher dose was associated with a faster clinical and parasitological response, and 100% were cured within 4 weeks, compared with 60% receiving the lower dosage. This difference is statistically significant by life-table analysis (x2 = 4.41, p less than 0.05). The superiority of the higher dose was not, however, seen in adults. In both children and adults the higher dose given daily for 2--4 weeks and in one patient for up to 7 weeks was found to be safe and well tolerated. It is likely, but not proven, that the use of sodium stibogluconate in a dose of 20 mg/kg bw daily for 4 weeks will reduce the relapse-rate in Kenyan children with visceral leishmaniasis.

Ten Kenyan patients with visceral leishmaniasis unresponsive to sodium stibogluconate, at a dose of 16 to 20 mg Sb/kg body-weight/day given for 30 to 98 days, were treated with 20 mg Sb/kg bw given every eight hours. This regimen was modified or abandoned in six patients because of suspected toxicity, although toxicity was difficult to assess because of intercurrent illness. Toxic effects included lethargy, anorexia, vomiting, electrocardiographic changes, fall in haemoglobin and rise in liver enzymes. One patient died, probably from a cardiac arrhythmia. Two patients were cured, four responded partially and four showed no response. Pentamidine, at a dose of 4 mg/kg body-weight given one to 3 times per week for 5 to 39 weeks, was given as initial treatment in one patient and after failure of sodium stibogluconate in seven. Toxic effects included nephritis, hepatitis, transient diabetes and subcutaneous abscesses. Two patients were cured, two responded partially, three showed no response and one, after apparent cure, relapsed and was unresponsive to additional pentamidine treatment. Low-frequency, long-duration pentamidine was often useful in maintaining any improvement made during treatment with the less well tolerated high-dose, high frequency sodium stibogluconate. We observed the step-wise development of resistance to both sodium stibogluconate and pentamidine. The problems of managing patients with visceral leishmaniasis which is unresponsive to conventional doses of pentavalant antimonials are discussed and some tentative suggestions put forward.

A community survey was conducted to determine the prevalence of rheumatic heart disease in Kenyan children in all primary schools in 2 sublocations in Western Kenya. In total, 3631 children (97% school attendance) aged from 5 to 15 years were examined by one experienced physician and 2 cardiologists between September and December 1985. Six children were found to have evidence of rheumatic heart disease, giving a prevalence rate of 1.7/1000. As all cases occurred in the age group between 10 and 15 years, the rate was calculated for this group as 2.4/1000. None of these patients had previously been diagnosed as having rheumatic fever. There were 3 males and 3 females. Four patients had mitral regurgitation, one had aortic regurgitation and one had mitral stenosis. Three had electrocardiographic evidence of left atrial abnormality and one showed findings of left ventricular hypertrophy but two patients had normal tracings. Half were symptomatic with dyspnoea on exertion and two gave a history of fleeting polyarthritis. The socio-economic status (peasant), family size (mean = 6 siblings) and the number of children sleeping per room were the same in both the cases with rheumatic heart disease and their controls. The health workers achieved low scores (mean 26%) with regard to the clinical diagnosis, treatment and prevention of rheumatic fever at the level of primary health care. Rheumatic heart disease, nonetheless, was relatively insignificant in the overall picture of health care of school children in Western Kenya.

Five patients with long-standing visceral leishmaniasis who were unresponsive to sodium stibogluconate, 20 mg antimony/kg body-weight once or twice daily, were treated for 14 to 54 days with a combination of sodium stibogluconate at the same dose plus allopurinol at a dose of 20 mg/kg body-weight per day in three divided doses. This combination was safe and effective. Negative splenic aspirate smears were obtained from all patients within 19 days, and none has relapsed in at least 12 months of follow-up.