Helena Rabie

Universität Bern, Bern, BE, Switzerland

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Publications (67)174.35 Total impact

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    ABSTRACT: Malaria causes a quarter of all childhood deaths in SubSaharan Africa. Considerable gains in global malaria control have been achieved in the last decade but coverage of effective interventions remains low in areas of greatest malaria burden. Some countries have achieved reduced malaria related mortality through application of recent advances in malaria prevention and treatment of children. Artemisinin combination therapies (particularly artesunate) are highly efficacious and welltolerated in children, although several alternative treatments are available. However, the evolution of drug resistance (including emerging resistance to artemisinin derivatives) threatens the success of malaria treatment programmes. This special issue review is aimed at paediatric clinicians in resourcepoor settings and provides a summary of recent data from paediatric trials of malaria treatment and prevention interventions.
    Infectious disorders drug targets. 11/2013;
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    ABSTRACT: In antiretroviral treatment the role of therapeutic drug monitoring via measurement of serum levels remains unclear, especially in children. To quantify exposure to LPV and EFV in children receiving therapy in a routine clinical setting in order to identify risk factors associated with inadequate drug exposure. A prospective study was conducted in a routine clinical setting in Tygerberg Children?s Hospital, South Africa. A total of 53 random serum levels were analyzed. Serum concentrations were determined by an established high-performance liquid chromatography method. Of 53 HIV-infected children treated with lopinavir (n=29, median age 1.83 y) or efavirenz (n=24, median age 9.3 years), 12 showed serum levels outside the therapeutic range (efavirenz) or below Cmin (lopinavir). Low bodyweight, rifampicin co-treatment, and significant comorbidity were potential risk factors for inadequate drug exposure. These findings, together with previous studies, indicate that therapeutic drug monitoring can improve the management of antiretroviral therapy in children at risk.
    Paediatrics and international child health. 09/2013;
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    ABSTRACT: BACKGROUND:: Initiation criteria and pediatric antiretroviral treatment (ART) regimens have changed over the past few years in South Africa. We reported worse early virological outcomes associated with the use abacavir (ABC)-based regimens at one large site: here we expand this analysis to multiple sites in the IeDEA-Southern Africa collaboration. METHODS:: Data for 9543 ART-naive children <16 years at treatment initiation started on either stavudine/lamivudine (d4T/3TC) or ABC/3TC with efavirenz (EFV) or ritonavir-boosted lopinavir (LPV/r) treated at six clinics in Johannesburg and Cape Town, South Africa, were analysed with Chi-square tests and logistic regression to evaluate viral suppression at six and twelve months. RESULTS:: Prevalence of viral suppression at six months in 2174 children started on a d4T-based LPV/r regimen was greater (70%) than among 438 children started on an ABC-based LPV/r regimen (54%, p<0.0001). Among 3189 children started on a d4T-based EFV regimen a higher proportion (86%) achieved suppression at six months compared to 391 children started on ABC-containing EFV regimens (78%, p<0.0001). Relative benefit of d4T vs. ABC on six month suppression remained in multivariate analysis after adjustment for pre-treatment characteristics, cohort and year of program (LPV/r - OR 0.57 [CI: 0.46-0.72]; EFV - OR 0.46 [CI: 0.32-0.65]). CONCLUSION:: This expanded analysis is consistent with our previous report of worse virological outcomes after ABC was introduced as part of first-line ART in South Africa. Whether due to the drug itself or coincident with other changes over time, continued monitoring and analyses must clarify causes and prevent suboptimal long term outcomes.
    Pediatr Infect Dis J. 01/2013;
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    ABSTRACT: We describe an expansile necrotising pneumonia caused by Norcardia in a HIV-infected 3-week-old baby. The radiological images and treatment of Norcardia in immune deficient children are discussed.
    Case Reports 01/2013; 2013.
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    ABSTRACT: Since 2005, increasing numbers of children have started antiretroviral therapy (ART) in sub-Saharan Africa and, in recent years, WHO and country treatment guidelines have recommended ART initiation for all infants and very young children, and at higher CD4 thresholds for older children. We examined temporal changes in patient and regimen characteristics at ART start using data from 12 cohorts in 4 countries participating in the IeDEA-SA collaboration. Data from 30,300 ART-naïve children aged <16 years at ART initiation who started therapy between 2005 and 2010 were analysed. We examined changes in median values for continuous variables using the Cuzick's test for trend over time. We also examined changes in the proportions of patients with particular disease severity characteristics (expressed as a binary variable e.g. WHO Stage III/IV vs I/II) using logistic regression. Between 2005 and 2010 the number of children starting ART each year increased and median age declined from 63 months (2006) to 56 months (2010). Both the proportion of children <1 year and ≥10 years of age increased from 12 to 19% and 18 to 22% respectively. Children had less severe disease at ART initiation in later years with significant declines in the percentage with severe immunosuppression (81 to 63%), WHO Stage III/IV disease (75 to 62%), severe anemia (12 to 7%) and weight-for-age z-score<-3 (31 to 28%). Similar results were seen when restricting to infants with significant declines in the proportion with severe immunodeficiency (98 to 82%) and Stage III/IV disease (81 to 63%). First-line regimen use followed country guidelines. Between 2005 and 2010 increasing numbers of children have initiated ART with a decline in disease severity at start of therapy. However, even in 2010, a substantial number of infants and children started ART with advanced disease. These results highlight the importance of efforts to improve access to HIV diagnostic testing and ART in children.
    PLoS ONE 01/2013; 8(12):e81037. · 3.73 Impact Factor
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    ABSTRACT: BACKGROUND:: The prevalence of potentially stigmatizing lipoatrophy in children receiving antiretroviral therapy in Southern Africa is high, affecting around a third of children. Early diagnosis of lipoatrophy is essential for effective intervention to arrest progression. METHODS:: Pre-pubertal children receiving antiretroviral therapy were recruited from a hospital-based family HIV clinic in Cape Town and followed up prospectively. Lipoatrophy was identified and graded by consensus between two HIV pediatricians. A dietician performed anthropometric measurements of trunk and limb fat. Anthropometric measurements in children with and without lipoatrophy were compared using multivariable linear regression adjusting for age and gender. The most discerning anthropometric indicators of lipoatrophy underwent Receiver Operating Characteristic curve analysis. The precision of anthropometric measurements performed by an inexperienced healthcare worker was compared with that of a research dietician. RESULTS:: Of 100 recruits, 36 had lipoatrophy at baseline and a further 9 developed lipoatrophy by 15 month follow-up. Annual incidence of lipoatrophy was 12% (confidence interval [CI]: 5-20%) per person-year of follow-up. A biceps skin-fold thickness <5mm at baseline had a sensitivity of 89% (CI: 67-100%) and a specificity of 60% (CI: 46-75%) for predicting development of lipoatrophy by 15 month follow-up. Negative and positive predictive values were 97% (CI: 91-100%) and 32% (CI: 14-50%). CONCLUSION:: Biceps skin-fold thickness <5mm in pre-pubertal children exposed to thymidine analogue-based antiretroviral therapy may be a useful screening tool to identify children who are likely to develop lipoatrophy. The variation in precision of measurements performed by an inexperienced healthcare worker only marginally impacted performance.
    The Pediatric Infectious Disease Journal 12/2012; · 3.57 Impact Factor
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    ABSTRACT: BACKGROUND:: Accurate identification of Mycobacterium tuberculosis (M.tb) infection in young and HIV-infected children could guide delivery of preventive therapy, improve resource utilization, and help prevent tuberculosis. METHODS:: We assessed the performance of the tuberculin skin test (TST) and interferon-gamma release assays (IGRAs) for identifying M.tb infection in South African children presenting for out-patient care. Tuberculosis contact was quantified using a standardized measure of M.tb exposure. Logistic regression assessed the association between test positivity, age, nutritional and HIV status, while controlling for M.tb exposure, BCG vaccination and prior tuberculosis treatment. RESULTS:: Among 250 (130 HIV-infected) children (age 0.25-14.6 years, median 39 months), the proportion positive for each test varied: 34% (TST), 21% (T-SPOT.TB), 25% (QuantiFERON-TB Gold In-Tube, QFT-IT). IGRAs were more likely to be positive in HIV-uninfected compared with HIV-infected children; TST positivity did not differ between these groups. Agreement between tests was good-to-excellent in HIV-uninfected children and poor- to-good in HIV-infected children. In adjusted models, TST and T-Spot.TB were positively associated with age; this effect varied by HIV-status. The QFT-IT was negatively associated with chronic malnutrition; this effect varied by HIV-status. Since 93% of children had received BCG, we could not assess the contribution of BCG to false-positive TST results. CONCLUSIONS:: Our findings indicate that the TST and IGRAs perform similarly for the detection of M.tb infection in well-nourished HIV-uninfected children, but test performance is differentially affected by chronic malnutrition, HIV infection, and age. Similar to TST interpretation, clinicians and researchers should interpret IGRAs in children with caution taking age, nutritional, and HIV-status into consideration.
    The Pediatric Infectious Disease Journal 11/2012; · 3.57 Impact Factor
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    ABSTRACT: BACKGROUND:: We investigated 18-month incidence and determinants of death and loss-to-follow-up of children after antiretroviral therapy (ART) initiation in a multiregional collaboration in lower-income countries. METHODS:: HIV-infected children (positive PCR <18 months or positive serology ≥18 months) from IeDEA cohorts, <16 years, initiating ART were eligible. A competing risk regression model was used to analyze the independent risk of two failure types: death and loss-to-follow-up (>6 months). FINDINGS:: Data on 13611 children, from Asia (N=1454), East-Africa (N=3114), Southern-Africa (N=6212) and West-Africa (N=2881) contributed 20,417 person-years of follow-up. At 18 months, the adjusted risk of death was 4.3% in East-Africa, 5.4% in Asia, 5.7% in Southern-Africa and 7.4% in West-Africa (P=0.01). Age<24 months, WHO stage 4, CD4<10%, attending a private sector clinic, larger cohort size and living in West-Africa were independently associated with poorer survival. The adjusted risk of loss-to-follow-up was 4.1% in Asia, 9.0% in Southern-Africa, 14.0% in East-Africa, and 21.8% in West-Africa (P <0.01). Age<12 months, non NNRTI-based ART regimen, WHO stage 4 at ART start, ART initiation after 2005, attending a public sector or a non-urban clinic, having to pay for laboratory tests or antiretroviral drugs, larger cohort size, and living in East or West-Africa were significantly associated with higher loss-to-follow-up. CONCLUSION:: Findings differed substantially across regions but raise overall concerns about delayed ART start, low access to free HIV-services for children, and increased workload on program retention in lower-income countries. Universal free access to ART services and innovative approaches are urgently needed to improve pediatric outcomes at program level.
    JAIDS Journal of Acquired Immune Deficiency Syndromes 11/2012; · 4.65 Impact Factor
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    ABSTRACT: High prevalence of lipoatrophy in pre-pubertal South African children on antiretroviral therapy: a cross-sectional study
    BMC Pediatrics 11/2012; 12:183. · 1.98 Impact Factor
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    ABSTRACT: Rifampin-based tuberculosis (TB) treatment can cause sub-therapeutic concentrations of protease-inhibitors (PI) and virologic failure in children receiving antiretroviral therapy (ART). Among 217 children on ART, TB co-treatment (in 78) was associated with virologic failure. Ritonavir-based single PI ART regimen predicted virologic failure (adjusted odds ratio 3.7, 95% confidence interval 1.5-8.9, p=0.004) on multivariate analysis.
    The Pediatric Infectious Disease Journal 10/2012; · 3.57 Impact Factor
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    ABSTRACT: Poor growth is an indication for antiretroviral therapy (ART) and a criterion for treatment failure. We examined variability in growth response to ART in 12 programs in Malawi, Zambia, Zimbabwe, Mozambique, and South Africa. Treatment naïve children aged <10 years were included. We calculated weight for age z scores (WAZs), height for age z scores (HAZs), and weight for height z scores (WHZs) up to 3 years after starting ART, by using the World Health Organization standards. Multilevel regression models were used. A total of 17 990 children (range, 238-8975) were followed for 36 181 person-years. At ART initiation, most children were underweight (50%) and stunted (66%). Lower baseline WAZ, HAZ, and WHZ were the most important determinants of faster catch-up growth on ART. WAZ and WHZ increased rapidly in the first year and stagnated or reversed thereafter, whereas HAZ increased continuously over time. Three years after starting ART, WAZ ranged from -2.80 (95% confidence interval [CI]: -3.66 to -2.02) to -1.98 (95% CI: -2.41 to -1.48) in children with a baseline z score < -3 and from -0.79 (95% CI: -1.62 to 0.02) to 0.05 (95% CI: -0.42 to 0.51) in children with a baseline WAZ ≥ -1. For HAZ, the corresponding range was -2.33 (95% CI: -2.62 to -2.02) to -1.27 (95% CI: -1.58 to -1.00) for baseline HAZ < -3 and -0.24 (95% CI: -0.56 to 0.15) to 0.84 (95% CI: 0.53 to 1.16) for HAZ ≥ -1. Despite a sustained growth response and catch-up growth in children with advanced HIV disease treated with ART, normal weights and heights are not achieved over 3 years of ART.
    PEDIATRICS 09/2012; 130(4):e966-77. · 4.47 Impact Factor
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    ABSTRACT: Objectives  To determine the improvement in positive predictive value of immunological failure criteria for identifying virological failure in HIV-infected children on antiretroviral therapy (ART) when a single targeted viral load measurement is performed in children identified as having immunological failure. Methods  Analysis of data from children (<16 years at ART initiation) at South African ART sites at which CD4 count/per cent and HIV-RNA monitoring are performed 6-monthly. Immunological failure was defined according to both WHO 2010 and United States Department of Health and Human Services (DHHS) 2008 criteria. Confirmed virological failure was defined as HIV-RNA >5000 copies/ml on two consecutive occasions <365 days apart in a child on ART for ≥18 months. Results  Among 2798 children on ART for ≥18 months [median (IQR) age 50 (21-84) months at ART initiation], the cumulative probability of confirmed virological failure by 42 months on ART was 6.3%. Using targeted viral load after meeting DHHS immunological failure criteria rather than DHHS immunological failure criteria alone increased positive predictive value from 28% to 82%. Targeted viral load improved the positive predictive value of WHO 2010 criteria for identifying confirmed virological failure from 49% to 82%. Conclusion  The addition of a single viral load measurement in children identified as failing immunologically will prevent most switches to second-line treatment in virologically suppressed children.
    Tropical Medicine & International Health 09/2012; · 2.94 Impact Factor
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    ABSTRACT: Tuberculosis-associated immune reconstitution inflammatory syndrome (TB-IRIS) is a potentially life-threatening complication in HIV infected children with tuberculosis (TB) of the central nervous system. HIV-associated TB-IRIS has not been previously described in children with neurotuberculosis. To describe the neurological and neuro-radiological features of 4 consecutive cases of TB-IRIS in children with neurotuberculosis and to discuss possible management strategies. Three patients treated for tuberculosis of the central nervous system experienced paradoxical worsening of neurological symptoms when combination antiretroviral therapy (cART) was initiated. Intracranial tuberculomas were unmasked in the 4th patient. All patients developed new neurological signs within 10 days of cART initiation. Neurological symptoms and signs included headache, seizures, meningeal irritation, decreased level of consciousness, ataxia and focal motor deficit. Interventions included the temporary discontinuation of cART and the use of corticosteroids in all patients. Three patients received thalidomide and 1 chloroquine and mycophenolate mofetil. One patient died and the others experienced prolonged hospitalization. TB-IRIS should be considered when new neurological signs develop shortly after initiation of cART in children. There is little data to guide the timing of initiation of cART and the management of complications in children.
    European journal of paediatric neurology: EJPN: official journal of the European Paediatric Neurology Society 05/2012; 16(6):676-82. · 2.01 Impact Factor
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    ABSTRACT: Because of serious adverse effects, the Food and Drug Administration warns against using lopinavir in infants younger than 42 weeks postconception. However, there is an imperative for early treatment. We report on our use of LPV in 8 premature HIV-infected infants. The median age at initiation was 27 days. Trough values guided dosing. Five infants needed doses above 300 mg/m. Although no adverse events were noted, lopinavir usage requires caution and careful monitoring.
    The Pediatric Infectious Disease Journal 03/2012; 31(6):602-4. · 3.57 Impact Factor
  • Mark F Cotton, Helena Rabie
    The Lancet 02/2012; 379(9815):502-3. · 39.06 Impact Factor
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    ABSTRACT: After witnessing an episode of poor injection safety in large numbers of children in a rural under-resourced hospital in Uganda, we briefly review our own experience and that of others in investigating HIV infection in children considered unlikely to be through commonly identified routes such as vertical transmission, sexual abuse or blood transfusion. In the majority of cases, parents are HIV uninfected. The cumulative experience suggests that the problem is real, but with relatively low frequency. Vertical transmission is the major route for HIV to children. However, factors such as poor injection safety, undocumented surrogate breast feeding, an HIV-infected adult feeding premasticated food to a weaning toddler, poor hygienic practice in the home and using unsterilised equipment for minor surgical or traditional procedures are of cumulative concern.
    Journal of the International AIDS Society 01/2012; 15(2):17377. · 3.94 Impact Factor
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    ABSTRACT: The historic use of full-dose ritonavir as part of an unboosted protease inhibitor (PI)-based antiretroviral therapy regimen in some South African children contributes to the frequent accumulation of major PI resistance mutations. In order to describe the prevalence of major PI resistance in children failing antiretroviral therapy and to investigate the clinical, immunological and virological outcomes in children with PI resistance, we conducted a cross-sectional study, with a nested case series, following up those children with major PI resistance. The setting was public health sector antiretroviral clinics in the Western Cape province of South Africa, and the subjects were children failing antiretroviral therapy. The following outcome measures were investigated: CD4 count, viral load and resistance mutations. Fourteen (17%) of 82 patients, referred from tertiary hospitals, had major PI resistance. All these patients were exposed to regimens that included ritonavir as a single PI. Immune reconstitution and clinical benefit were achieved when using a lopinavir/ritonavir-based treatment regimen in these children with prior PI resistance. At first HIV-1 viral load follow up after initial resistance testing (n = 11), only one patient had a viral load of less than 400 copies/ml; at a subsequent follow up (n = 9), the viral loads of five patients were less than 400 copies/ml. Patients retained on LPV/r had lower viral loads than those switched to a non-nucleoside reverse transcriptase inhibitor (NNRTI). However, two of three patients with follow-up resistance tests accumulated additional PI resistance. In children with pre-existing PI resistance, although initially effective, the long-term durability of a lopinavir/ritonavir-based treatment regimen can be compromised by the accumulation of resistance mutations. Furthermore, a second-line NNRTI regimen is often not durable in these patients. As genotypic resistance testing and third-line treatment regimens are costly and limited in availability, we propose eligibility criteria to identify patients with high risk for resistance and guidance on drug selection for children who would benefit from third-line therapy.
    Journal of the International AIDS Society 11/2011; 14:55. · 3.94 Impact Factor
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    ABSTRACT: Two centres in Soweto and Cape Town, South Africa. To assess the effects of timing of initiation of antiretroviral treatment (ART) and other factors on the risk of bacille Calmette-Guérin (BCG) related regional adenitis due to immune reconstitution inflammatory syndrome (BCG-IRIS) in human immunodeficiency virus (HIV) infected infants. HIV-infected infants aged 6-12 weeks with CD4 count ≥25% enrolled in the Children with HIV Early Antiretroviral Therapy (CHER) Trial received early (before 12 weeks) or deferred (after immunological or clinical progression) ART; infants with CD4 count <25% all received early ART. All received BCG vaccination after birth. Reactogenicity to BCG was assessed prospectively during routine study follow-up. Of 369 infants, 32 (8.7%) developed BCG-IRIS within 6 months of starting ART, 28 (88%) within 2 months after ART initiation. Of the 32 cases, 30 (93.8%) had HIV-1 RNA > 750 000 copies/ml at initiation. Incidence of BCG-IRIS was 10.9 and 54.3 per 100 person-years (py) among infants with CD4 count ≥25% at enrolment receiving early (at median age 7.4 weeks) vs. deferred (23.2 weeks) ART, respectively (HR 0.24, 95%CI 0.11-0.53, P < 0.001). Infants with CD4 count <25% receiving early ART had intermediate incidence (41.7/100 py). Low CD4 counts and high HIV-1 RNA at initiation were the strongest independent risk factors for BCG-IRIS. Early ART initiation before immunological and/or clinical progression substantially reduces the risk of BCG-IRIS regional adenitis.
    The international journal of tuberculosis and lung disease: the official journal of the International Union against Tuberculosis and Lung Disease 09/2011; 15(9):1194-200, i. · 2.61 Impact Factor
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    ABSTRACT: To determine the diagnostic accuracy of World Health Organization (WHO) 2010 and 2006 as well as United States Department of Health and Human Services (DHHS) 2008 definitions of immunological failure for identifying virological failure (VF) in children on antiretroviral therapy (ART). Analysis of data from children (<16 years at ART initiation) at South African ART sites at which CD4 count/per cent and HIV-RNA monitoring are performed 6-monthly. Incomplete virological suppression (IVS) was defined as failure to achieve ≥1 HIV-RNA ≤400 copies/ml between 6 and 15 months on ART and viral rebound (VR) as confirmed HIV-RNA ≥5000 copies/ml in a child on ART for ≥18 months who had achieved suppression during the first year on treatment. Among 3115 children [median (interquartile range) age 48 (20-84) months at ART initiation] on treatment for ≥1 year, sensitivity of immunological criteria for IVS was 10%, 6% and 26% for WHO 2006, WHO 2010 and DHHS 2008 criteria, respectively. The corresponding positive predictive values (PPV) were 31%, 20% and 20%. Diagnostic accuracy for VR was determined in 2513 children with ≥18 months of follow-up and virological suppression during the first year on ART with sensitivity of 5% (WHO 2006/2010) and 27% (DHHS 2008). PPV results were 42% (WHO 2010), 43% (WHO 2006) and 20% (DHHS 2008). Current immunological criteria are unable to correctly identify children failing ART virologically. Improved access to viral load testing is needed to reliably identify VF in children.
    Tropical Medicine & International Health 08/2011; 16(11):1367-71. · 2.94 Impact Factor
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    ABSTRACT: HIV-infected children experience a high burden of tuberculosis. With recent advances in international pediatric HIV treatment guidelines significant numbers of infants and children will require simultaneous treatment for both TB and HIV. This article attempts to concisely outline strategies for effective co-treatment of both infections. Rifamycins, an essential component of short course TB chemotherapy, alter the metabolism of a number of antiretroviral drugs. These interactions and their consequences are considered. Options for antiretroviral therapy and the optimal timing of its initiation in the presence of antituberculosis therapy are discussed.
    Current Pediatric Reviews 07/2011; 7(3):173-179.

Publication Stats

471 Citations
174.35 Total Impact Points

Institutions

  • 2012
    • Universität Bern
      • Institute of Social and Preventive Medicine
      Bern, BE, Switzerland
  • 2004–2012
    • Stellenbosch University
      • Department of Paediatrics and Child Health
      Stellenbosch, Province of the Western Cape, South Africa
  • 2011
    • University of the Western Cape
      • School of Pharmacy
      Cape Town, Province of the Western Cape, South Africa
  • 2009
    • University of Cape Town
      • Institute of Infectious Disease & Molecular Medicine (IIDMM)
      Cape Town, Province of the Western Cape, South Africa
  • 2008
    • Royal College Of Paediatrics and Child Health
      Londinium, England, United Kingdom
  • 2006
    • University of Amsterdam
      Amsterdamo, North Holland, Netherlands
  • 2001–2006
    • Tygerberg Hospital
      Kaapstad, Western Cape, South Africa