Successful treatment of a child with vascular pythiosis

<p>Abstract</p> <p>Background</p> <p>Human pythiosis is an emerging and life-threatening infectious disease caused by <it>Pythium insidiosum</it>. It occurs primarily in tropical, subtropical and temperate areas of the world, including Thailand. The aim of this report is to present the first pediatric case of typical vascular pythiosis.</p> <p>Case Presentation</p> <p>A 10-year-old boy with underlying β-thalassemia presented with gangrenous ulcers and claudication of the right leg which were unresponsive to antibiotic therapy for 6 weeks. Computerized tomography angiography indicated chronic arterial occlusion involving the right distal external iliac artery and its branches. High-above-knee amputation was urgently done to remove infected arteries and tissues, and to stop disease progression. Antibody to <it>P. insidiosum </it>was detected in a serum sample by the immunoblot and the immunochromatography tests. Fungal culture followed by nucleic sequence analysis was positive for <it>P. insidiosum </it>in the resected iliac arterial tissue. Immunotherapeutic vaccine and antifungal agents were administered. The patient remained well and was discharged after 2 months hospitalization without recurrence of the disease. At the time of this communication he has been symptom-free for 2 years.</p> <p>Conclusions</p> <p>The child presented with the classical manifestations of vascular pythiosis as seen in adult cases. However, because pediatricians were unfamiliar with the disease, diagnosis and surgical treatment were delayed. Both early diagnosis and appropriate surgical and medical treatments are crucial for good prognosis.</p

Immune reconstitution inflammatory syndrome from Penicillium marneffei in an HIV-infected child: a case report and review of literature

<p>Abstract</p> <p>Backgrounds</p> <p>Disseminated <it>Penicillium marneffei </it>infection is one of the most common HIV-related opportunistic infections in Southeast Asia. Immune reconstitution inflammatory syndrome (IRIS) is a complication related to antiretroviral therapy (ART)-induced immune restoration. The aim of this report is to present a case of HIV-infected child who developed an unmasking type of IRIS caused by disseminated <it>P. marneffei </it>infection after ART initiation.</p> <p>Case presentation</p> <p>A 14-year-old Thai HIV-infected girl presented with high-grade fever, multiple painful ulcerated oral lesions, generalized non-pruritic erythrematous skin papules and nodules with central umbilication, and multiple swollen, warm, and tender joints 8 weeks after ART initiation. At that time, her CD4⁺cell count was 7.2% or 39 cells/mm³. On admission, her repeated CD4⁺cell count was 11% or 51 cells/mm³and her plasma HIV-RNA level was < 50 copies/mL. Her skin biopsy showed necrotizing histiocytic granuloma formation with neutrophilic infiltration in the upper and reticular dermis. Tissue sections stained with hematoxylin and eosin (H&E), periodic acid-Schiff (PAS), and Grocott methenamine silver (GMS) stain revealed numerous intracellular and extracellular, round to oval, elongated, thin-walled yeast cells with central septation. The hemoculture, bone marrow culture, and skin culture revealed no growth of fungus or bacteria. Our patient responded well to intravenous amphotericin B followed by oral itraconazole. She fully recovered after 4-month antifungal treatment without evidence of recurrence of disease.</p> <p>Conclusions</p> <p>IRIS from <it>P. marneffei </it>in HIV-infected people is rare. Appropriate recognition and properly treatment is important for a good prognosis.</p

Global HIV mortality trends among children on antiretroviral treatment corrected for under-reported deaths: an updated analysis of the International epidemiology Databases to Evaluate AIDS collaboration.

INTRODUCTION The Joint United Nations Programme on HIV/AIDS (UNAIDS) projections of paediatric HIV prevalence and deaths rely on the International epidemiology Databases to Evaluate AIDS (IeDEA) consortium for mortality estimates among children living with HIV (CHIV) receiving antiretroviral therapy (ART). Previous estimates, based on data through 2014, may no longer be accurate due to expanded paediatric HIV care and treatment eligibility, and the possibility of unreported deaths in CHIV considered lost to follow-up (LTFU). We therefore estimated all-cause mortality and its trends in CHIV (<15 years old) on ART using extended and new IeDEA data. METHODS We analysed (i) IeDEA observational data from CHIV in routine care globally, and (ii) novel data from an IeDEA tracing study that determined outcomes in a sample of CHIV after being LTFU in southern Africa. We included 45,711 CHIV on ART during 2004 to 2017 at 72 programmes in Africa, Asia-Pacific and Latin America. We used mixed effects Poisson regression to estimate mortality by age, sex, CD4 at ART start, time on ART, region and calendar year. For Africa, in an adjusted analysis that accounts for unreported deaths among those LTFU, we first modified the routine data by simulating mortality outcomes within six months after LTFU, based on a Gompertz survival model fitted to the tracing data (n = 221). RESULTS Observed mortality rates were 1.8 (95% CI: 1.7 to 1.9) and 9.4 (6.3 to 13.4) deaths per 100 person-years in the routine and tracing data, respectively. We found strong evidence of higher mortality at shorter ART durations, lower CD4 values, and in infancy. Averaging over covariate patterns, the adjusted mortality rate was 54% higher than the unadjusted rate. In unadjusted analyses, mortality reduced by an average 60% and 73% from 2005 to 2017, within and outside of Africa, respectively. In the adjusted analysis for Africa, this temporal reduction was 42%. CONCLUSIONS Mortality rates among CHIV have decreased substantially over time. However, when accounting for worse outcomes among those LTFU, mortality estimates increased and temporal improvements were slightly reduced, suggesting caution in interpreting analyses based only on programme data. The improved and updated IeDEA estimates on mortality among CHIV on ART support UNAIDS efforts to accurately model global HIV statistics

Characteristics, mortality and outcomes at transition for adolescents with perinatal HIV infection in Asia

Objectives: The aim of this study was to describe characteristics of perinatally HIV-infected adolescents (PHIVAs), factors associated with mortality, and outcomes at transition. Design: Ongoing observational database collating clinical data on HIV-infected children and adolescents in Asia. Methods: Data from 2001 to 2016 relating to adolescents (10-19 years) with perinatal HIV infection were analysed to describe characteristics at adolescent entry and transition and combination antiretroviral therapy (cART) regimens across adolescence. A competing risk regression analysis was used to determine characteristics at adolescent entry associated with mortality. Outcomes at transition were compared on the basis of age at cART initiation. Results: Of 3448 PHIVA, 644 had reached transition. Median age at HIV diagnosis was 5.5 years, cART initiation 7.2 years and transition 17.9 years. At adolescent entry, 35.0% hadCD4+ cell count less than 500 cells/ml and 51.1% had experience da WHO stage III/IV clinical event. At transition, 38.9% had CD4+ cell count less than 500copies/ml, and 53.4% had experienced a WHO stage III/IV clinical event. Mortality ratewas 0.71 per 100 person-years, with HIV RNA >1000copies/ml, CD4+ cell count less than 500cells/ml, height-for-ageorweight-for-agez-score less than - 2, historyofa WHO stage III/IV clinical event or hospitalization and at least second cART associated with mortality. For transitioning PHIVA, those who commenced cART age less than 5 years had better virologic and immunologic outcomes, though were more likely to be on at least second cART. Conclusion: Delayed HIV diagnosis and cART initiation resulted in considerable morbidity and poor immune status by adolescent entry. Durable first-line cART regimens to optimize disease control are key to minimizing mortality. Early cART initiation provides the best virologic and immunologic outcomes at transition

Use and outcomes of antiretroviral monotherapy and treatment interruption in adolescents with perinatal HIV infection in Asia

Purpose: Antiretroviral monotherapy and treatment interruption are potential strategies for perinatally HIV-infected adolescents (PHIVA) who face challenges maintaining effective combination antiretroviral therapy (ART). We assessed the use and outcomes for adolescents receiving monotherapy or undergoing treatment interruption in a regional Asian cohort. Methods: Regional Asian data (2001-2016) were analyzed to describe PHIVA who experienced >= 2 weeks of lamivudine or emtricitabine monotherapy or treatment interruption and trends in CD4 count and HIV viral load during and after episodes. Survival analyses were used for World Health Organization (WHO) stage III/IV clinical and immunologic event-free survival during monotherapy or treatment interruption, and a Poisson regression to determine factors associated with monotherapy or treatment interruption. Results: Of 3,448 PHIVA, 84 (2.4%) experienced 94 monotherapy episodes, and 147 (4.3%) experienced 174 treatment interruptions. Monotherapy was associated with older age, HIV RNA >400 copies/mL, younger age at ART initiation, and exposure to >= 2 combination ART regimens. Treatment interruption was associated with CD4 count = 1,000 copies/mL, ART adverse event, and commencing ART age >= 10 years compared with age <3 years. WHO clinical stage III/IV 1-year event-free survival was 96% and 85% for monotherapy and treatment interruption cohorts, respectively. WHO immunologic stage III/IV 1-year event-free survival was 52% for both cohorts. Those who experienced monotherapy or treatment interruption for more than 6 months had worse immunologic and virologic outcomes. Conclusions: Until challenges of treatment adherence, engagement in care, and combination ART durability/tolerability are met, monotherapy and treatment interruption will lead to poor long-term outcomes

Early and late virologic failure after virologic suppression in HIV-infected Asian children and adolescents

Background: Virologic failure is a major threat to maintaining effective combination antiretroviral therapy, especially for children in need of lifelong treatment. With efforts to expand access to HIV viral load testing, our understanding of pediatric virologic failure is evolving. Setting: An Asian cohort in 16 pediatric HIV services across 6 countries. Methods: From 2005 to 2014, patients younger than 20 years who achieved virologic suppression and had subsequent viral load testing were included. Early virologic failure was defined as a HIV RNA >= 1000 copies per milliliter within 12 months of virologic suppression, and late virologic as a HIV RNA >= 1000 copies per milliliter after 12 months following virologic suppression. Characteristics at combination antiretroviral therapy initiation and virologic suppression were described, and a competing risk time-to-event analysis was used to determine cumulative incidence of virologic failure and factors at virologic suppression associated with early and late virologic failure. Results: Of 1105 included in the analysis, 182 (17.9%) experienced virologic failure. The median age at virologic suppression was 6.9 years, and the median time to virologic failure was 24.6 months after virologic suppression. The incidence rate for a first virologic failure event was 3.3 per 100 person-years. Factors at virologic suppression associated with late virologic failure included older age, mostly rural clinic setting, tuberculosis, protease inhibitor-based regimens, and early virologic failure. No risk factors were identified for early virologic failure. Conclusions: Around 1 in 5 experienced virologic failure in our cohort after achieving virologic suppression. Targeted interventions to manage complex treatment scenarios, including adolescents, tuberculosis coinfection, and those with poor virologic control are required

Dual analysis of loss to follow-up for perinatally HIV-infected adolescents receiving combination antiretroviral therapy in Asia

Background: Perinatally HIV-infected adolescents (PHIVA) are an expanding population vulnerable to loss to follow-up (LTFU). Understanding the epidemiology and factors for LTFU is complicated by varying LTFU definitions. Setting: Asian regional cohort incorporating 16 pediatric HIV services across 6 countries. Methods: Data from PHIVA (aged 10-19 years) who received combination antiretroviral therapy 2007-2016 were used to analyze LTFU through (1) an International epidemiology Databases to Evaluate AIDS (IeDEA) method that determined LTFU as >90 days late for an estimated next scheduled appointment without returning to care and (2) the absence of patient-level data for >365 days before the last data transfer from clinic sites. Descriptive analyses and competing-risk survival and regression analyses were used to evaluate LTFU epidemiology and associated factors when analyzed using each method. Results: Of 3509 included PHIVA, 275 (7.8%) met IeDEA and 149 (4.3%) met 365-day absence LTFU criteria. Cumulative incidence of LTFU was 19.9% and 11.8% using IeDEA and 365-day absence criteria, respectively. Risk factors for LTFU across both criteria included the following: age at combination antiretroviral therapy initiation = 5 years, rural clinic settings compared with urban clinic settings, and high viral loads compared with undetectable viral loads. Age 10-14 years compared with age 15-19 years was another risk factor identified using 365-day absence criteria but not IeDEA LTFU criteria. Conclusions: Between 12% and 20% of PHIVA were determined LTFU with treatment fatigue and rural treatment settings consistent risk factors. Better tracking of adolescents is required to provide a definitive understanding of LTFU and optimize evidence-based models of care