Evaluation of weight-based prescription of antiretroviral therapy in children.

OBJECTIVES: The aim of the study was to investigate the extent of and factors associated with incorrect dosing of antiretroviral therapy (ART) in HIV-infected children in Harare, Zimbabwe. METHODS: All children aged 0-10 years and children aged 11-17 years who weighed < 35 kg and taking ART were recruited from the paediatric HIV clinic at Harare Hospital. Their current doses of ART drugs were compared against doses recommended by the national guidelines. RESULTS: Among 309 children recruited [55% male; median age 7 years (interquartile range (IQR) 5-10 years)], the median CD4 count was 899 cells/µL and the median duration of their current ART regimen was 11.2 months (IQR 4.9-17.1 months). Overall, 110 (35.6%) children were prescribed incorrect doses of at least one drug component within their ART regimen; 64 (20.7%) under-dosed and 49 (15.9%) over-dosed on at least one drug. Children receiving a higher than recommended dose of at least one drug were younger compared with correctly dosed children (median 6 versus 7 years, respectively; P = 0.001), had been on their current ART regimen for a shorter time (median 7.2 versus 13 months, respectively; P = 0.003) and were less likely to be receiving a three-drug fixed-dose combination (FDC; 42.9 versus 63.3%, respectively; P = 0.009). Those who were under-dosed were also less likely to be on a three-drug FDC (25 versus 63.3%, respectively; P < 0.001). CONCLUSIONS: Over a third of children were prescribed incorrect doses of ART. Children taking triple-drug FDCs were likely to be correctly dosed. Our study highlights the importance of weight monitoring at each clinical contact, training of health care providers on paediatric drug dosing and the need for wider availability of FDCs for children.

Energy Cascade Rate Measured in a Collisionless Space Plasma with MMS Data and Compressible Hall Magnetohydrodynamic Turbulence Theory.

The first complete estimation of the compressible energy cascade rate |ϵ_{C}| at magnetohydrodynamic (MHD) and subion scales is obtained in Earth's magnetosheath using Magnetospheric MultiScale spacecraft data and an exact law derived recently for compressible Hall MHD turbulence. A multispacecraft technique is used to compute the velocity and magnetic gradients, and then all the correlation functions involved in the exact relation. It is shown that when the density fluctuations are relatively small, |ϵ_{C}| identifies well with its incompressible analog |ϵ_{I}| at MHD scales but becomes much larger than |ϵ_{I}| at subion scales. For larger density fluctuations, |ϵ_{C}| is larger than |ϵ_{I}| at every scale with a value significantly higher than for smaller density fluctuations. Our study reveals also that for both small and large density fluctuations, the nonflux terms remain always negligible with respect to the flux terms and that the major contribution to |ϵ_{C}| at subion scales comes from the compressible Hall flux.

TestMeEast: a campaign to increase HIV testing in hospitals and to reduce late diagnosis.

Late diagnosis occurs in almost half of those diagnosed in the UK (HIV Prevention England, 2013. Retrieved June 22, 2014, from HIV Prevention England: http://www.hivpreventionengland.org.uk/Campaigns-Current/National-HIV-Testing-Week ). Testing occurs mainly in sexual health and antenatal clinics despite recommendations to test more broadly [Ellis, S., & Curtis, H. (2012). HIV diagnoses and missed opportunities. Results of the British HIV association (BHIVA) National Audit 2010. Clinical Medicine, 12(5), 430-434]. We report the findings of an HIV-testing week campaign to offer testing to those who have blood tests as part of routine care within outpatient clinics and emergency departments of six London hospitals. The campaign target was to test 500 patients a day during the 2013 National HIV Testing Week (NHTW). Clinic staff and medical students were trained to offer routine HIV testing. Linkage to care was arranged for those who tested HIV-positive. During NHTW we tested 2402 of the planned 2500 test target. 2402/4317 (55.6% 95% CI 54.1-57.1%) of those who had routine blood tests were tested for HIV. There were eight HIV-positive tests; three were new diagnoses (all linked to care). The campaign hashtag #TestMeEast achieved a total Twitter "reach" of 238, 860 and the campaign had widespread news coverage. Our campaign showed that staff and students could be trained and mobilised to do thousands of routine HIV tests during a campaign.

Hearing impairment and deafness among HIV infected children and adolescents in Harare, Zimbabwe.

Background: Among HIV-infected children ear infections are recurrent and chronic, which may lead to hearing loss. Objective: To determine the prevalence, cause and severity of hearing impairment among HIV-infected children aged 5-17 years attending for HIV care in Harare. Design and Setting: An analytical cross-sectional survey conducted at Newlands Clinic, an opportunistic infections clinic in Harare. Materials and Methods: Participants underwent a standardised otoscopic examination of the ear and Pure Tone Audiometry (PTA). Factors associated with hearing impairment were investigated using multivariate logistic regression. Results: Three hundred and eighty (380) participants (55% female and mean age 11 years (SD: 3.3 years)) were consecutively recruited. The vast majority of participants (n=338; 89% were taking antiretroviral therapy (ART) for a median of 3 (IQR: 2-5) years at recruitment, and the most recent median CD4 Count (i.e. CD4 count measured within 6 months of the study recruitment) was 725 (IQR: 497-1000) cells/µL, with no difference by ART status. 61% (n= 231) of participants had an abnormal ear examination. Of the 359 participants who underwent audiometry, the prevalence of hearing impairment was 32.3% (95%CI: 27.5%-37.4%) based on a PTA threshold ≥26Db. Hearing impairment was associated with a recent CD4 count <350cell/µL (OR 2.1, P<0.037). Conclusion: There is a high prevalence of hearing impairment among HIV-infected children and adolescents. Low CD4 count remains a risk factor even among those who are on ART. We recommend that HIV infected children and adolescents, particularly those with low CD4 counts, should have routine evaluation of hearing as part of HIV care.

Acquired epidermodysplasia verruciformis due to multiple and unusual HPV infection among vertically-infected, HIV-positive adolescents in Zimbabwe.

BACKGROUND: We have previously described the presentation of epidermodysplasia verruciformis (EV)-like eruptions in almost a quarter of hospitalized adolescents with vertically-acquired human immunodeficiency virus (HIV) infection in Harare, Zimbabwe, a region with a high prevalence of HIV infection. METHODS: We performed a clinical case note review and skin biopsy from affected sites in 4 HIV-infected adolescents with EV-like lesions in Harare. Biopsies were processed for histology and for human papillomavirus (HPV) typing. RESULTS: All patients had long-standing skin lesions that pre-dated the diagnosis of HIV by several years. The histology of skin biopsies from all patients was consistent with EV. In each biopsy, EV-associated ß-HPV type 5 was identified (additionally, type 19 was found in 1 biopsy). Cutaneous wart-associated HPV types 1 and 2 were detected in all biopsies, together with genital lesion-associated HPV types 6, 16, and 52, (as well as ≥3 other genital lesion-associated HPV types). Despite immune reconstitution with combination antiretroviral therapy (cART), there was no improvement in EV-like lesions in any patient. CONCLUSIONS: EV is a disfiguring and potentially stigmatizing condition among this patient group and is difficult to treat; cART appears to have no impact on the progression of skin disease. Among adolescents with longstanding HIV-induced immunosuppression and with high levels of sun exposure, close dermatological surveillance for potential skin malignancy is required.

Local energy transfer and dissipation in incompressible Hall magnetohydrodynamic turbulence: The coarse-graining approach.

We derive the coarse-graining (CG) equations of incompressible Hall magnetohydrodynamic (HMHD) turbulence to investigate the local (in space) energy transfer rate as a function of the filtering scale ℓ. First, the CG equations are space averaged to obtain the analytical expression of the mean cascade rate. Its application to three-dimensional simulations of (weakly compressible) HMHD shows a cascade rate consistent with the value of the mean dissipation rate in the simulations and with the classical estimates based on the "third-order" law. Furthermore, we developed an anisotropic version of CG that allows us to study the magnitude of the cascade rate along different directions with respect to the mean magnetic field. Its implementation on the numerical data with moderate background magnetic field shows a weaker cascade along the magnetic field than in the perpendicular plane, while an isotropic cascade is recovered in the absence of a background field. The strength of the CG approach is further revealed when considering the local-in-space energy transfer, which is shown theoretically and numerically to match at a given position x, when locally averaged over a neighboring region, the (quasi-)local dissipation. Prospects of exploiting this model to investigate local dissipation in spacecraft data are discussed.

Process evaluation of an intervention to improve HIV treatment outcomes among children and adolescents.

SETTING: Children and adolescents with HIV encounter challenges in initiation and adherence to antiretroviral therapy (ART). A community-based support intervention of structured home visits, aimed at improving initiation, adherence and treatment, was delivered by community health workers (CHWs) to children and adolescents newly diagnosed with HIV. OBJECTIVES: To 1) describe intervention delivery, 2) explore CHW, caregiver and adolescents' perceptions of the intervention, 3) identify barriers and facilitators to implementation, and 4) ascertain treatment outcomes at 12 months' post-HIV diagnosis. DESIGN: We drew upon: 1) semi-structured interviews (n = 22) with 5 adolescents, 11 caregivers and 6 CHWs, 2) 28 CHW field manuals, and 3) quantitative data for study participants (demographic information and HIV clinical outcomes). RESULTS: Forty-one children received at least a part of the intervention. Of those whose viral load was tested, 26 (n = 32, 81.3%) were virally suppressed. Interviewees felt that the intervention supported ART adherence and strengthened mental health. Facilitators to intervention delivery were convenience and rapport between CHWs and families. Stigma, challenges in locating participants and inadequate resources for CHWs were barriers. CONCLUSION: This intervention was helpful in supporting HIV treatment adherence among adolescents and children. Facilitators and barriers may be useful in developing future interventions.

CONTEXTE: Les enfants et les adolescents séropositifs rencontrent des difficultés dans l'initiation et l'adhésion à la thérapie antirétrovirale (TAR). Des agents de santé communautaires (CHW) ont mis en place une intervention de soutien communautaire sous forme de visites structurées à domicile visant à améliorer l'initiation, l'adhésion et le traitement, auprès d'enfants et d'adolescents nouvellement diagnostiqués séropositifs. OBJECTIFS: 1) Décrire la mise en œuvre de l'intervention, 2) explorer les perceptions de l'intervention par les CHW, les soignants et les adolescents, 3) identifier les obstacles et les facilitateurs de la mise en œuvre, et 4) vérifier les résultats du traitement 12 mois après le diagnostic du VIH. METHODES: Nous nous sommes appuyés sur 1) des entretiens semi-structurés (n = 22) avec 5 adolescents, 11 soignants et 6 CHW, 2) 28 manuels de terrain des CHW, et 3) des données quantitatives sur les participants à l'étude (informations démographiques et résultats cliniques du VIH). RÉSULTATS: Quarante et un enfants ont reçu au moins une partie de l'intervention. Parmi ceux dont la charge virale a été testée, 26 (n = 32 ; 81,3%) étaient sous suppression virale. Les personnes interrogées ont estimé que l'intervention soutenait l'adhésion au TAR et renforçait la santé mentale. Les facilitateurs de la mise en œuvre de l'intervention étaient la commodité et les rapports entre les CHW et les familles. La stigmatisation, les difficultés à trouver des participants et les ressources inadéquates pour les CHW étaient des obstacles. CONCLUSION: Cette intervention a été utile pour soutenir l'adhésion au traitement du VIH chez les adolescents et les enfants. Les facilitateurs et les obstacles peuvent être utiles pour développer de futures interventions.

Chest radiography patterns in 75 adolescents with vertically-acquired human immunodeficiency virus (HIV) infection.

AIM: To evaluate lung disease on chest radiography (CR), the relative frequency of CR abnormalities, and their clinical correlates in adolescents with vertically-acquired human immunodeficiency virus (HIV) infection. MATERIALS AND METHODS: CRs of 75 patients [59 inpatients (33 males; mean age 13.7±2.3 years) and 16 outpatients (eight males; mean age 14.1±2.1 years)] were retrospectively reviewed by three independent observers. The overall extent of disease (to the nearest 5%), its distribution, and the proportional extents (totalling 100%) of different radiographic patterns (including ring/tramline opacities and consolidation) were quantified. CR features and clinical data were compared. RESULTS: CRs were abnormal in 51/75 (68%) with "extensive" disease in 38/51 (74%). Ring/tramline opacities and consolidation predominated (i.e., proportional extent >50%) in 26 and 21 patients, respectively. Consolidation was significantly more common in patients hospitalized primarily for a respiratory illness than patients hospitalized for a non-respiratory illness or in outpatients (p<0.005, χ(2) for trend); by contrast, ring/tramline opacities did not differ in prevalence across the groups. On stepwise logistic regression, predominant consolidation was associated with progressive dyspnoea [odds ratio (OR) 5.60; 95% confidence intervals (CI): 1.60, 20.1; p<0.01] and was associated with a primary respiratory cause for hospital admission (OR: 22.0; CI: 2.7, 181.1; p<0.005). Ring/tramline opacities were equally prevalent in patients with and without chronic symptoms and in those admitted to hospital with respiratory and non-respiratory illness. CONCLUSION: In HIV-infected adolescents, evaluated in secondary practice, CR abnormalities are prevalent. The presence of ring/tramline opacities, believed to reflect chronic airway disease, is not linked chronic respiratory symptoms.

Increased risk of HIV-infection among school-attending orphans in rural Zimbabwe.

In Zimbabwe around 1.1 million children have been orphaned due to AIDS. We conducted a survey among school-attending youth in rural south-eastern Zimbabwe in 2003, and examined the association between orphaning and risk of HIV. We enrolled 30 communities in three provinces. All students attending Year 2 of secondary school were eligible. Each completed a questionnaire and provided a finger-prick blood specimen for testing for HIV-1 and HSV-2 antibodies. Female participants were tested for pregnancy. Six thousand seven hundred and ninety-one participants were recruited (87% of eligible); 35% had lost one or both parents (20% of participants had lost their father; 6% their mother; and 9% both parents). Orphans were not poorer than non-orphans based on reported access to income, household structure and ownership of assets. There was strong evidence that orphans, and particularly those who had lost both parents, were at increased sexual risk, being more likely to have experienced early sexual debut; to have been forced to have sex; and less likely to have used condoms. Fifty-one students were HIV positive (0.75%). Orphans were three times more likely to be HIV infected than non-orphans (adjusted odds ratio = 3.4; 95% confidence interval: 1.8-6.6). Over 60% of those HIV positive were orphaned. Among school-going youth, the rates of orphaning were very high; there was a strong association between orphaning and increased risk of HIV, and evidence of greater sexual risk taking among orphans. It is essential that we understand the mechanisms by which orphaned children are at increased risk of HIV in order to target prevention and support appropriately.

A comparison of HIV outpatient care in primary and secondary healthcare-level settings in Zimbabwe.

SETTING: Decentralisation of HIV care to nurse-led primary care services is being implemented across low- and middle-income countries in sub-Saharan Africa. OBJECTIVE: To compare services offered to clients attending for HIV care at a physician-led and a nurse-led service in Harare, Zimbabwe. DESIGN: A cross-sectional study was performed at Harare Central Hospital (HCH) and Budiriro Primary Care Clinic (PCC) from June to August 2018. An interviewer-administered questionnaire was used to collect sociodemographics, HIV treatment and clinical history from clients attending for routine HIV care. The Mann-Whitney U-test was used to evaluate for differences between groups for continuous variables. For categorical variables, the χ2 test was used. RESULTS: The median age of the 404 participants recruited was 38 years (IQR 28-47); 69% were female. Viral suppression was comparable between sites (HCH, 70% vs. PCC, 80%; P = 0.07); however, screening for comorbidities such as cervical cancer screening (HCH, 61% vs. PCC, 41%; P = 0.001) and provision of referral services (HCH, 23% vs. PCC, 13%; P = 0.01) differed between sites. CONCLUSION: Efforts to improve service provision in primary care settings are needed to ensure equity for users of health services.

Auditing use of antibiotics in Zimbabwean neonates.

BACKGROUND: Neonatal sepsis is a major cause of morbidity and mortality in low-income settings. As signs of sepsis are non-specific and deterioration precipitous, antibiotics are often used profusely in these settings where diagnostics may not be readily available. Harare Central Hospital, Zimbabwe, delivers 12000 babies per annum admitting ∼4800 to the neonatal unit. Overcrowding, understaffing and rapid staff turnover are consistent problems. Suspected sepsis is highly prevalent, and antibiotics widely used. We audited the impact of training and benchmarking intervention on rationalizing antibiotic prescription using local, World Health Organization-derived, guidelines as the standard. METHODS: An initial audit of admission diagnosis and antibiotic use was performed between 8th May - 6th June 2018 as per the audit cycle. An intern training programme, focusing on antimicrobial stewardship and differentiating between babies 'at risk of' versus 'with' clinically-suspected sepsis was instituted post-primary audit. Re-audit was conducted after 5 months. RESULTS: Sepsis was the most common admitting diagnosis by interns at both time points but reduced at repeat audit (81% versus 59%, P<0.0001). Re-audit after 5 months demonstrated a decrease in antibiotic prescribing at admission and discharge. Babies prescribed antibiotics at admission decreased from 449 (98%) to 96 (51%), P<0.0001. Inpatient days of therapy (DOT) reduced from 1243 to 1110/1000 patient-days. Oral amoxicillin prescription at discharge reduced from 349/354 (99%) to 1% 1/161 (P<0.0001). CONCLUSION: A substantial decrease in antibiotic use was achieved by performance feedback, training and leadership, although ongoing performance review will be key to ensuring safety and sustainability.

Vertically acquired HIV diagnosed in adolescence and early adulthood in the United Kingdom and Ireland: findings from national surveillance.

OBJECTIVE: The aim of the study was to describe the characteristics of young people with vertically acquired HIV diagnosed aged > or =13 years. METHODS: A retrospective review of HIV diagnoses reported to well-established national paediatric and adult HIV surveillance systems in the United Kingdom/Ireland was conducted. RESULTS: Forty-two young people with vertically acquired HIV diagnosed aged > or =13 years were identified; 23 (55%) were female, 40 (95%) were black African and 36 (86%) were born in sub-Saharan Africa. The median age at HIV diagnosis was 14 years (range, 13-20 years). Half of the patients presented with symptoms; the remainder were screened for HIV following diagnosis of a relative. The median CD4 count at diagnosis was 210 cells/microL (range, 0-689 cells/microL), 12 patients (29%) were diagnosed with AIDS at HIV diagnosis or subsequently, and 34 (81%) started combination antiretroviral therapy (ART), most (31 of 34) within a year of diagnosis. CONCLUSION: A small number of young people with vertically acquired HIV survive childhood without ART and are diagnosed at age > or =13 years in the United Kingdom/Ireland. Half of the patients were asymptomatic, highlighting the importance of considering HIV testing for all offspring of HIV-infected women, regardless of age or symptoms. Increased awareness among clinicians and parents is required to reduce delayed presentation with advanced disease and to avoid onward transmission as these young people become sexually active.

Monte Carlo modelling of the treatment line of the Proton Therapy Center in Orsay.

This paper presents the main results of a Monte Carlo simulation describing the Orsay Proton Therapy Center (CPO) beam line. The project aimed to obtain a prediction of the dose distribution in a water phantom within 2% accuracy in the dose value and a 2 mm of range. The simulation tool used was MCNPX, version 2.5.0, and included all the elements of the CPO beam line. A new algorithm of multiple Coulomb scattering has been incorporated in MCNPX, resulting in a better prediction of the spatial dose distribution and absolute values of the deposited energy. The simulations of 3D dose profiles in water show a very good agreement with measured data to within 2%. We first performed a comparative analysis of the dosimetry in heterogeneous phantoms between the pencil beam algorithm and MCNPX. The simulations give a better agreement with experimental data compared to the pencil beam approach. In a second phase, we simulated the patient-dependent fields along with the spatial dose distributions in a water phantom. The simulated response of a Pixel chamber located 2 m upstream of the water phantom revealed a good agreement with the measured data to within 1%. The results presented herein support the applicability of Monte Carlo models for absolute dosimetry and for design purposes regarding existing and new beam lines at CPO. This work completes a series of publications reporting the progress in the development of a Monte Carlo simulation tool for the CPO beam line dedicated for the treatment of head and neck tumours.

Recurrence of cryptococcal meningitis in HIV-infected patients following immune reconstitution.

Two HIV-infected patients had recurrent cryptococcal meningitis (CM) despite treatment with fluconazole and immune reconstitution with combination antiretroviral therapy (CART). Following treatment of CM with fluconazole, lumbar puncture should be performed either after completion of induction treatment for CM or before starting CART, in order to confirm cerebrospinal fluid sterility.

Chronic knee stiffness and swelling in a Zimbabwean adolescent.

A 12-year-old Zimbabwean girl presented with tuberculous monoarthritis. She was moderately wasted, stunted and sexually immature. These clinical findings lead to the diagnosis of underlying HIV infection, which was thought to have been acquired from mother-to-child transmission.

[An original contention system for hadron therapy]. / Un système de contention original applicable à l'hadronthérapie.

In hadron therapy centers that have only fixed horizontal beams (i.e. most carbon ions centers and protons centers of first generation), the angulations of the beam remain technically limited, especially for the treatment of children under general anaesthesia with posterior-oblique (40 degrees or so) beams in supine position. We have been developing recently an original positioning system allowing for treatment with posterior-oblique beams, either from right or left directions, by keeping the child in the adequate position.

Tackling STI epidemics through the HIV clinic: is sex high enough on the agenda?

Sexually transmitted infection (STI) rates among men having sex with men continue to increase. HIV services may operate independently to genitourinary medicine clinics and the sexual health of HIV-positive patients may be of low priority in the context of medical problems related to HIV. A prospective study of HIV-positive gay men was conducted in a London outpatient clinic over a three-month period. Data were available for 90 men. Forty-five percent had STI screens in the preceding six months. These revealed a high rate of infections; 26 infections diagnosed in 14 men in the study period. Fifty-seven percent of the 90 men in the study had more than one partner in the past three months and approximately one-third had unprotected sexual activity. A significant proportion of men were unaware of recent outbreaks of hepatitis C and lymphogranuloma venereum and of HIV postexposure prophylaxis. We therefore recommend that sexual history-taking, STI screens and health promotion should become a routine feature of HIV outpatient consultations in this group.

Cholangiocarcinoma presenting in an adolescent with vertically acquired HIV infection.

An adolescent with long-standing HIV infection who was severely immunosuppressed during HIV diagnosis developed cholangiocarcinoma 1.5 years after starting antiretroviral therapy.

Extensive cerebrovascular disease and stroke with prolonged prodromal symptoms as first presentation of perinatally-acquired human immunodeficiency virus infection in a young adult.

A 26-year-old black African woman presented with an acute onset of hemiparesis and visual symptoms. This had been preceded several months by symptoms which were apparently psychiatric in nature. She had no apparent risk for cerebrovascular disease. Neurological evaluation revealed a striking burden of cerebrovascular disease for her age, including the rare stroke syndrome of basilar artery occlusion. Human immunodeficiency virus (HIV) infection was identified during clinical assessment. This was judged to be perinatally acquired, as there was no history of sexual debut or blood transfusion; her mother was taking antiretroviral therapy and she had facial planar warts and underlying bronchiectasis. Therefore, it has been concluded that presentation of stroke should prompt HIV testing in young people and perinatally-acquired infection can present in adulthood.

Impact of scaling up Xpert® MTB/RIF testing for the detection of rifampicin-resistant TB cases in Karachi, Pakistan.

SETTING: Pakistan ranks fourth among the countries with a high burden of multidrug-resistant tuberculosis (MDR-TB), with only 19.2% of the 15 000 estimated incident cases being notified. Increasing treatment coverage for MDR-TB is a key priority for Pakistan's National Tuberculosis Programme. The World Health Organization recommends the use of the Xpert® MTB/RIF assay as the first-line diagnostic test for individuals with presumed TB. OBJECTIVE: To describe a multifaceted case-finding intervention targeting public and private sector health care facilities that used the Xpert assay as a frontline diagnostic test for individuals with presumptive TB, in Karachi, Pakistan, and its impact on case notifications of MDR-TB. DESIGN: Cross-sectional study. RESULTS: A total of 51 168 individuals were tested using Xpert, of whom respectively 7581 and 1534 people were diagnosed with TB in the public sector (reverse public-private mix) and private sector (social business model) arms; 574 (6.3% of all TB cases) were identified as having rifampicin (RMP) resistance. A total of 517 (90.1%) people with RMP-resistant TB (RR-TB) identified through the project were initiated on second-line treatment. The intervention resulted in 194 additional cases of RR-TB, an increase of 43% over the baseline. CONCLUSION: This project, one of the largest Xpert testing programmes conducted at city level, resulted in significantly increased detection and treatment of MDR-TB.