Disseminated Mycobacterial Infection With Reactive Polyarthritis (Poncet's Disease) During Immune-suppressive Treatment Including Ustekinumab for Pediatric Crohn's Disease.

BACKGROUND: The incidence of pediatric inflammatory bowel disease is increasing. tumor necrosis factor alpha inhibitors medicines improved the prognosis of affected subjects. Nonetheless, a proportion of patients do not respond or lose response to treatment. Newer biologics, like ustekinumab, have been approved for adults. The pediatric off-label use of these drugs is increasing, despite limited safety evidence. We report a case of disseminated mycobacterial infection (MI) presenting with reactive polyarthritis (Poncet's disease, PD) in a girl with Crohn's disease receiving various immunosuppressants, including ustekinumab. CASE REPORT: A 12-year-old girl with Crohn's disease was admitted for acute-onset migratory polyarthritis of large and small joints and opioid-resistant pain. She had recently received adalimumab and methotrexate and was currently under treatment with ustekinumab. She was vaccinated with Bacillus Calmette-Guérin and screened for tuberculosis before starting immunosuppressants. Interferon-gamma release assay, Mantoux test and chest computed tomography scan were negative. Disseminated MI with PD was diagnosed following positive cultures for Mycobacterium tuberculosis complex in blood and intestinal biopsies (with negative in synovial fluid and gastric aspirate). Whole-exome sequencing did not identify any genetic susceptibility to MI. Antituberculosis treatment eradicated MI. CONCLUSIONS: Children with inflammatory bowel disease receiving combination immunosuppressive treatments including tumor necrosis factor alpha inhibitors and anti-IL-12/23 agents are at higher risk for MI. Disseminated MI should be considered and ruled out in these patients when presenting with pulmonary, extrapulmonary or unusual clinical manifestations, like PD. The collection of multiple specimens (including intestinal biopsies) for mycobacterial culture is recommended when mycobacterial disease is suspected.

Clinical features of COVID-19 in Italian outpatient children and adolescents during Parental, Delta, and Omicron waves: a prospective, observational, cohort study.

Introduction: COVID-19 features changed with the Omicron variant of SARS-CoV-2 in adults. This study aims to describe COVID-19 symptoms in children and adolescents during the Parental, Delta, and Omicron eras. Methods: A single-centre, prospective observational study was conducted on individuals aged 0-20 years attending the University Hospital of Padua (Italy) from April 2020 to December 2022. COVID-19 cases were defined by positive SARS-CoV-2 molecular detection and/or serology; patient/family symptoms and virological positivity were considered to determine the infection onset. Variables were summarized and compared using appropriate tests of descriptive statistics. Results: A total of 509 cases [46% female, median age eight years (IQR: 4-12)] were studied. Three-hundred-eighty-seven (76%), 52 (10%), and 70 (14%) subjects experienced COVID-19 during the Parental, Delta, and Omicron waves, respectively. All subjects developed an asymptomatic/mild COVID-19. Overall, the most frequent symptoms were fever (47%) and rhinitis (21%), which showed a significant increasing incidence from the Parental to Omicron waves (p < 0.001). Conversely, diarrhea was most common during the pre-Omicron eras (p = 0.03). Stratifying symptoms according to the age group, fever, rhinitis, and skin rashes were observed more frequently among infants/toddlers; conversely, fatigue was more common in children older than five years. The duration of symptoms was similar across different SARS-CoV-2 variants of concern (VOCs); conversely, the number of symptoms varied according to the age group (p < 0.0001). Discussion: This study showed differences in COVID-19 clinical presentation among infants, children, and adolescents and confirmed Omicron infection is more likely to be associated with upper respiratory symptoms. However, further population-based studies are needed to support these findings. In addition, active surveillance will play a crucial role in assessing the disease severity of future VOCs.

Perceived Psychological Impact on Children and Parents of Experiencing COVID-19 Infection in One or More Family Members.

SARS-CoV-2 infection may impair behavior and mental health; we explored the psychological impact on parents and children who experienced COVID-19 within their families. A cross-sectional web-based survey was conducted on families attending the COVID-19 Follow-up Clinic at the Department for Women's and Children's Health, Padua (Italy). From April 2020 to August 2021, 75 surveys were collected from 66 families (97 parents and 129 children); almost 70% of participants had COVID-19, mostly asymptomatic/mildly symptomatic, and the median time from infection to survey compilation was 164.7 days (SD 56). Most parents (>87%) reported positive relationships with family members either before, during, or after COVID-19. More than one-third of children and adolescents were unable to adapt to isolation. Among 31 pre-school children with a median age of 3 (SD 1.7), a change of one or more functions was reported for 74.2% of cases irrespective of COVID-19 status, particularly a change in circadian rhythm (25%), in relationship with parents (42.8%), and poor emotional control (36%). Among 74 children with a median age of 10.9 years (SD 2.7), 8.1% had a score indicating a disease; however, significant impairment in attention was reported for 16.7%, along with anxiety/depression and problems with conduct in 5.6% and 6.5% of cases, respectively.

Long-term Immune Response to SARS-CoV-2 Infection Among Children and Adults After Mild Infection.

Importance: Understanding the long-term immune response against SARS-CoV-2 infection in children is crucial to optimize vaccination strategies. Although it is known that SARS-CoV-2 antibodies may persist in adults 12 months after infection, data are limited in the pediatric population. Objective: To examine long-term anti-SARS-CoV-2 spike receptor-binding domain (S-RBD) IgG kinetics in children after SARS-CoV-2 infection. Design, Setting, and Participants: In this single-center, prospective cohort study, patients were enrolled consecutively from April 1, 2020, to August 31, 2021, at the COVID-19 Family Cluster Follow-up Clinic, Department of Women's and Children's Health, University Hospital of Padua. A cohort of 252 COVID-19 family clusters underwent serologic follow-up at 1 to 4, 5 to 10, and more than 10 months after infection with quantification of anti-S-RBD IgG by chemiluminescent immunoassay. Exposures: SARS-CoV-2 infection. Results: Among 902 study participants, 697 had confirmed SARS-CoV-2 infection, including 351 children or older siblings (mean [SD] age, 8.6 [5.1] years) and 346 parents (mean [SD] age, 42.5 [7.1] years). Among 697 cases, 674 (96.7%) were asymptomatic or mild. Children had significantly higher S-RBD IgG titers than older patients across all follow-up time points, with an overall median S-RBD IgG titer in patients younger than 3 years 5-fold higher than adults (304.8 [IQR, 139.0-516.6] kBAU/L vs 55.6 [24.2-136.0] kBAU/L, P < .001). Longitudinal analysis of 56 study participants sampled at least twice during follow-up demonstrated the persistence of antibodies up to 10 months from infection in all age classes, despite a progressive decline over time. Conclusions and Relevance: In this cohort study of Italian children and adults following SARS-CoV-2 infection different kinetics of SARS-CoV-2 antibodies were found across several age classes of individuals with asymptomatic or mild COVID-19, which could help in optimizing COVID-19 vaccination strategies and prevention policies. This work provides further evidence of sustained immune response in children up to 1 year after primary SARS-CoV-2 infection.

Daptomycin for Treatment of S. Epidermidis Endocarditis in an Extremely Preterm Neonate-Outcome and Perspectives.

With a considerable morbidity and mortality burden, infective endocarditis still represents a challenge for clinicians. This is a case of persistent Staphylococcus epidermidis endocarditis in an extremely preterm newborn. The infection, initially treated with vancomycin, was successfully cured with daptomycin. Its use was safe and effective, ensuring a complete remission without adverse effects.

Treatment for Severe Malaria: Post-Artesunate Delayed Haemolysis and Neutropenia.

Parenteral artesunate (AS) is the WHO first-line treatment recommended in adults and children for severe malaria. Post-artesunate delayed haemolysis (PADH) is an uncommon adverse reaction to AS with a mechanism that is not fully understood, occurring in adults and children. Neutropenia is another possible finding after AS treatment, albeit rare. We present the case of a child who experienced both effects after treatment with AS for imported severe Falciparum malaria with very high parasitaemia. In addition, thirty-five paediatric cases of PADH, five cases of delayed anaemia without known haemolysis, and fourteen cases of neutropenia after artesunate treatment were identified from the literature review. PADH seems to be a dose-independent reaction and is not strongly related to hyperparasitaemia, although it is more frequent in this case. To date, the benefits of AS outweigh its potential side effects. However, haematological follow-up is mandatory to avoid possible complications from anaemia and neutropenia, especially in children treated with other contemporary drugs.

Left ventricular longitudinal strain alterations in asymptomatic or mildly symptomatic paediatric patients with SARS-CoV-2 infection.

AIMS: Compared with adult patients, clinical manifestations of children's coronavirus disease-2019 (COVID-19) are generally perceived as less severe. The objective of this study was to evaluate cardiac involvement in previously healthy children with asymptomatic or mildly symptomatic severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection. METHODS AND RESULTS: We analysed a cohort of 53 paediatric patients (29 males, 55%), mean age 7.5 ± 4.7 years, who had a confirmed diagnosis of SARS-CoV-2 infection and were asymptomatic or only mildly symptomatic for COVID-19. Patients underwent standard transthoracic echocardiogram and speckle tracking echocardiographic study at least 3 months after diagnosis. Thirty-two age, sex, and body surface area comparable healthy subjects were used as control group. Left ventricular ejection fraction was within normal limits but significantly lower in the cases group compared to controls (62.4 ± 4.1% vs. 65.2 ± 5.5%; P = 0.012). Tricuspid annular plane systolic excursion (20.1 ± 3 mm vs. 19.8 ± 3.4 mm; P = 0.822) and left ventricular (LV) global longitudinal strain (-21.9 ± 2.4% vs. -22.6 ± 2.5%; P = 0.208) were comparable between the two groups. Regional LV strain analysis showed a significant reduction of the LV mid-wall segments strain among cases compared to controls. Furthermore, in the cases group, there were 14 subjects (26%) with a regional peak systolic strain below -16% (-2.5 Z score in our healthy cohort) in at least two segments. These subjects did not show any difference regarding symptoms or serological findings. CONCLUSION: SARS-CoV-2 infection may affect left ventricular deformation in 26% of children despite an asymptomatic or only mildly symptomatic acute illness. A follow-up is needed to verify the reversibility of these alterations and their impact on long-term outcomes.

Asymptomatic and Mild SARS-CoV-2 Infections Elicit Lower Immune Activation and Higher Specific Neutralizing Antibodies in Children Than in Adults.

Background: The immune response plays a pivotal role in dictating the clinical outcome in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-infected adults, but it is still poorly investigated in the pediatric population. Methods: Of 209 enrolled subjects, 155 patients were confirmed by PCR and/or serology as having coronavirus disease 2019 (COVID-19). Blood samples were obtained at a median of 2.8 (interquartile, 2.1-3.7) and 6.1 (5.3-7.2) months after baseline (symptom onset and/or first positive virus detection). The immune profiles of activation, senescence, exhaustion, and regulatory cells were analyzed by flow cytometry. Neutralizing antibodies (nAbs) were detected by a plaque reduction neutralization test. In available nasopharyngeal swabs at baseline, SARS-CoV-2 levels were quantified by digital droplet PCR (ddPCR). Results: Overall, COVID-19 patients had higher levels of immune activation, exhaustion, and regulatory cells compared to non-COVID-19 subjects. Within the COVID-19 group, activated and senescent cells were higher in adults than in children and inversely correlated with the nAbs levels. Conversely, Tregs and Bregs regulatory cells were higher in COVID-19 children compared to adults and positively correlated with nAbs. Higher immune activation still persisted in adults after 6 months of infection, while children maintained higher levels of regulatory cells. SARS-CoV-2 levels did not differ among age classes. Conclusions: Adults displayed higher immune activation and lower production of anti-SARS-CoV-2 nAbs than children. The different immune response was not related to different viral load. The higher expression of regulatory cells in children may contribute to reduce the immune activation, thus leading to a greater specific response against the virus.

Mild SARS-CoV-2 Infections and Neutralizing Antibody Titers.

BACKGROUND: Recent evidence suggests that neutralizing antibodies (nAbs) to severe acute respiratory syndrome coronavirus 2 may persist over time; however, knowledge regarding pediatric subjects is limited. METHODS: A single-center, prospective observational study was conducted on 57 family clusters of coronavirus disease 2019, including children of neonatal and pediatric age attending the University Hospital of Padua (Italy). For each patient, blood samples were collected for both the quantification of nAbs through a plaque reduction neutralizing test and the detection of antinucleocapsid-spike protein immunoglobulin G and/or immunoglobulin M. RESULTS: We analyzed 283 blood samples collected from 152 confirmed coronavirus disease 2019 cases (82 parents and 70 children or older siblings of median age of 8 years, interquartile range: 4-13), presenting asymptomatic or with mildly symptomatic disease. Despite the decrease of immunoglobulin G over time, nAbs were found to persist up to 7 to 8 months in children, whereas adults recorded a modest declining trend. Interestingly, children aged <6 years, and, in particular, those aged <3 years, developed higher long-lasting levels of nAbs compared with older siblings and/or adults. CONCLUSIONS: Mild and asymptomatic severe acute respiratory syndrome coronavirus 2 infections in family clusters elicited higher nAbs among children.

Analytical and clinical performances of a SARS-CoV-2 S-RBD IgG assay: comparison with neutralization titers.

OBJECTIVES: SARS-CoV-2 serology presents an important role in several aspects of COVID-19 pandemic. Immunoassays performances have to be accurately evaluated and correlated with neutralizing antibodies. We investigated the analytical and clinical performances of a SARS-CoV-2 RBD IgG assay, automated on a high throughput platform, and the correlation of the antibodies (Ab) levels with the plaque reduction neutralization (PRNT50) Ab titers. METHODS: A series of 546 samples were evaluated by SARS-CoV-2 RBD IgG assay (Snibe diagnostics), including 171 negative and 168 positive SARS-CoV-2 subjects and a further group of 207 subjects of the COVID-19 family clusters follow-up cohort. RESULTS: Assay imprecision ranged from 3.98 to 12.18% being satisfactory at low and medium levels; linearity was excellent in all the measurement range. Considering specimens collected after 14 days post symptoms onset, overall sensitivity and specificity were 99.0 and 92.5%, respectively. A total of 281 leftover samples results of the PRNT50 test were available. An elevated correlation was obtained between the SARS-CoV-2 RBD IgG assay and the PRNT50 titer at univariate (ρ=0.689) and multivariate (ρ=0.712) analyses. CONCLUSIONS: SARS-CoV-2 S-RBD IgG assay shows satisfactory analytical and clinical performances, and a strong correlation with sera neutralizing activity.

SARS-CoV-2 infection in people living with HIV: a systematic review.

BACKGROUND AND SETTING: Little is known about SARS-CoV-2 impact on some vulnerable subgroups, such as people living with HIV/AIDS (PLWHA). In our study we reviewed the current knowledge on SARS-CoV-2 cases in PLWHA. METHODS: A systematic review was conducted by searching the MEDLINE, EMBASE and Google Scholar databases. Studies reporting data on PLWHA affected by SARS-CoV-2 were considered for inclusion. The aim of this study was the systematic characterization of cases of SARS-CoV-2 infection among PLWHA, particularly focusing on age, clinical findings at diagnosis, radiological features, therapeutic management and clinical outcomes. RESULTS: Twenty three relevant articles were identified, which reported 164 adults with both HIV and SARS-CoV-2 infection. Of those, the large majority were males (120/142, 84.5%), often with one or more comorbidities. Fifteen cases needed intensive care treatment and 16 died. For each group, respectively three patients had underlying comorbidities. There were no studies on children. The included studies were mostly retrospective or case series/reports (19 studies). The overall risk of bias was moderate, due to the study types and characteristics. CONCLUSION: It is still unclear if HIV infection may influence SARS-CoV-2 infection and disease course, however some PLWHA and particularly males affected by ARV-related complications may be at greater risk of severe Covid-19 course.

Antibiotic Prescribing Patterns in Paediatric Primary Care in Italy: Findings from 2012-2018.

Comprehensive data are needed to monitor antibiotic prescribing and inform stewardship. We aimed to evaluate the current antibiotic prescribing patterns, including treatment switching and prolongation, in the paediatric primary care setting in Italy. This database study assessed antibiotic prescriptions retrieved from Pedianet, a paediatric primary care database, from 1 January 2012 to 31 December 2018. Descriptive analyses were stratified by diagnosis class, calendar year, and children's age. Generalized linear Poisson regression was used to assess variation in the prescriptions. In total, 505,927 antibiotic prescriptions were included. From 2012 to 2018, the number of antibiotics per child decreased significantly by 4% yearly from 0.79 in 2012 to 0.62 in 2018. Amoxicillin prescriptions decreased with increasing children's age, while macrolides and third-generation cephalosporins had the opposite trend. Prescriptions were associated with a diagnosis of upper respiratory infection in 23% of cases, followed by pharyngitis (21%), bronchitis and bronchiolitis (12%), and acute otitis media (12%). Eight percent of treatment episodes were prolonged or switched class, mostly represented by co-amoxiclav, macrolides, and third-generation cephalosporins. Our findings report an overall decrease in antibiotic prescriptions, but pre-schoolers are still receiving more than one antibiotic yearly, and broad-spectrum antibiotics prescription rates remain the highest.

Antibiotic Prescriptions for Children With Community-acquired Pneumonia: Findings From Italy.

INTRODUCTION AND OBJECTIVE: Community-acquired pneumonia (CAP) is one of the most common reasons of prescribing antibiotics for children, often with overuse of broad-spectrum antibiotics. The aim of this study is to describe the antibiotic prescriptions for Italian children with CAP, at the primary care level. STUDY DESIGN: Retrospective cohort study conducted among children 3 months-14 years of age with CAP, enrolled in Pedianet (http://www.pedianet.it) from January 1, 2009 to December 31, 2018. Antibiotic treatment was defined as narrow-spectrum (NS-ABT) if amoxicillin and broad-spectrum (BS-ABT) if amoxicillin/clavulanic acid, cephalosporins or any combination. Crude and adjusted logistic regressions for the odds of receiving NS-ABT were conducted (all episodes of CAP and per patient). A P value <0.05 was considered statistically significant. RESULTS: Among 9691 CAP, 7260 episodes from 6409 children followed by 147 pediatricians were analyzed. The 16.7% of CAP [1216/7260, 95% confidence interval (CI): 15.9%-17.6%] received an NS-ABT while 53.3% (3863/7260, 95% CI: 52%-54.4%) received BS-ABTs and 30% (2181/7260, 95% CI: 28.9%-31.1%) macrolides. Within 10 years, a slight but increasing trend of NS-ABT prescription was observed (P < 0.001). Factors independently associated with reduced odds of receiving an NS-ABT compared with BS-ABT including macrolides were being older than 5 years [odds ratio (OR) 0.45, 95% CI: 0.39-0.52], living in Central/Southern Italy (OR 0.13, 95% CI: 0.10-0.16) and being exposed to ABT 3 months before (OR 0.61, 95% CI: 0.53-0.70). These findings were confirmed comparing NS-ABT versus BS-ABT excluding macrolides (n = 5079) and when the analysis was limited to index CAP. CONCLUSION: Our findings report a very limited prescription of narrow-spectrum antibiotics for Italian children with CAP.

Children's Hospital Management in the COVID-19 Era: The Reorganization of a Tertiary Care Pediatric Emergency Department in Northern Italy.

In the Veneto Region, an exponential spread of patients affected by 2019 novel Coronavirus disease (COVID-19) has been observed after February 21st. Since then, we have been evaluating children suspected or confirmed for SARS-CoV-2 infection. A protocol for pediatric hospital reorganization and children management has been developed, since the beginning of the epidemic. A pre-triage area has been created at the immediate entrance of the pediatric emergency room, for all uncritical pediatric patients. According to the epidemiologic and clinical risk factors, all children/adolescents have been addressing to one of the four different pathways created. The strict application of this protocol has been leading to quickly identification, isolation, and management of all positive children, preventing SARS-CoV-2 intrahospital spread.

COVID-19 Pandemic: Perspective of an Italian Tertiary Care Pediatric Center.

Since February 2020, Italy has been faced with the dramatic spread of novel Coronavirus SARS-CoV-2. This impetuous pandemic infection forced many hospitals to reorganize their healthcare systems. Predicting a rapid spread of the SARS-CoV-2 virus within our region, the Department for Women's and Children's Health promptly decided (i) to revise the distribution of the clinical areas in order to create both designated COVID-19 and COVID-19-free areas with their own access, (ii) to reinforce infection prevention control (IPC) measures for all healthcare workers and administrative staff and (iii) to adopt the new "double-gate approach": a phone call pre-triage and nasopharyngeal swab for SARS-CoV-2 detection before the admission of all patients and caregivers. Between 21 February 2020 till 04 May 2020, only seven physicians, two nurses and two of the administrative staff resulted positive, all during the first week of March. No other cases of intra-department infection were documented among the healthcare workers since all the preventive procedures described above were implemented. It is predicted that similar situations can happen again in the future, and thus, it is necessary to be more prepared to deal with them than we were at the beginning of this COVID-19 pandemic.

Optimizing Antibiotic Treatment Strategies for Neonates and Children: Does Implementing Extended or Prolonged Infusion Provide any Advantage?

Optimizing the use of antibiotics has become mandatory, particularly for the pediatric population where limited options are currently available. Selecting the dosing strategy may improve overall outcomes and limit the further development of antimicrobial resistance. Time-dependent antibiotics optimize their free concentration above the minimal inhibitory concentration (MIC) when administered by continuous infusion, however evidences from literature are still insufficient to recommend its widespread adoption. The aim of this review is to assess the state-of-the-art of intermittent versus prolonged intravenous administration of antibiotics in children and neonates with bacterial infections. We identified and reviewed relevant literature by searching PubMed, from 1 January 1 2000 to 15 April 2020. We included studies comparing intermittent versus prolonged/continuous antibiotic infusion, among the pediatric population. Nine relevant articles were selected, including RCTs, prospective and retrospective studies focusing on different infusion strategies of vancomycin, piperacillin/tazobactam, ceftazidime, cefepime and meropenem in the pediatric population. Prolonged and continuous infusions of antibiotics showed a greater probability of target attainment as compared to intermittent infusion regimens, with generally good clinical outcomes and safety profiles, however its impact in terms on efficacy, feasibility and toxicity is still open, with few studies led on children and adult data not being fully extendable.

Fecal-Oral Transmission of SARS-CoV-2 In Children: is it Time to Change Our Approach?

Starting from 2 pediatric cases of COVID-19, with confirmation at nasopharyngeal and rectal swabs, we considered the lesson learnt from previous Coronavirus epidemics and reviewed evidence on the current outbreak. Surveillance with rectal swabs might be extended to infants and children, for the implications for household contacts and isolation timing.

Implementation and Operational Research: Implementation of the WHO 2011 Recommendations for Isoniazid Preventive Therapy (IPT) in Children Living With HIV/AIDS: A Ugandan Experience.

BACKGROUND: Intensified tuberculosis (TB) case finding and isoniazid preventive therapy (IPT) are strongly recommended for children who are HIV infected. Data are needed to assess the feasibility of the WHO 2011 intensified tuberculosis case finding/IPT clinical algorithm. METHODS: Children who are HIV infected and attending Nsambya Home Care at Nsambya Hospital, Uganda, were screened for TB following WHO recommendations. IPT was given for 6 months after excluding TB. Factors associated with time to IPT initiation were investigated by multivariate Cox proportional hazard regression. Health care workers were interviewed on reasons for delay in IPT initiation. RESULTS: Among the 899 (49% male) children with HIV, 529 (58.8%) were screened for TB from January 2011 to February 2013. Children with active TB were 36/529 (6.8%), 24 (4.5%) were lost to follow-ups and 280 (52.9%) started IPT, 86/280 (30.7%) within 3 months of TB screening and 194/280 (69.3%) thereafter. Among the 529 children screened for TB, longer time to IPT initiation was independently associated with cough at TB screening (hazard ratio 0.62, P = 0.02, 95% confidence interval: 0.41 to 0.94). Four children (1% of those starting treatments) interrupted IPT because of a 5-fold increase in liver function measurements. In the survey, Health care workers reported poor adherence to antiretroviral therapy, poor attendance to periodic HIV follow-ups, and pill burden as the 3 main reasons to delay IPT. CONCLUSION: In resource-constrained settings, considerable delays in IPT initiation may occur, particularly in children with HIV who are presenting with cough at TB screening. The good safety profile of isoniazid in antiretroviral-therapy-experienced children provides further support to IPT implementation in this population.

Predictors of Treatment Failure in HIV-Positive Children Receiving Combination Antiretroviral Therapy: Cohort Data From Mozambique and Uganda.

BACKGROUND: Delays detecting treatment failure and switching to second-line combination antiretroviral therapy (cART) are often observed in human immunodeficiency virus (HIV)-infected children of low-middle-income countries (LMIC). METHODS: An observational study included HIV-infected children attending the Beira Central Hospital (Mozambique) and the Nsambya Hospital, Home Care Department (Uganda) evaluated clinical and immunological failure according to World Health Organization (WHO) 2006 guidelines. Baseline predictors for cART failure and for drug substitution were explored in unadjusted and adjusted Cox proportional hazard models. RESULTS: Two hundred eighteen of 740 children with at least 24 weeks follow-up experienced treatment failure (29%; 95% confidence interval [CI] 26-33), with crude incidence of 20.0 events per 100 person-years (95% CI 17.5-22.9). Having tuberculosis co-infection or WHO stage 4, or starting a nontriple cART significantly increased risk of failure. Two hundred two of 769 (26.3%) children receiving cART substituted drug(s), with crude incidence of 15.4 events per 100 person-years (95% CI 13.4-17.7). Drug toxicity (18.3%), drug availability (17.3%), and tuberculosis drugs interaction (52, 25.7%) were main reported reasons, while only 9 (4%) patients switched cART for clinical or immunological failure. Children starting lamivudine-zidovudine-nevirapine or lamivudine-stavudine-efavirenz or lamivudine-zidovudine-efavirenz were more likely to have substitute drugs. Increased substitution was found in children with mild immunosuppression and tuberculosis co-infection at cART initiation as well as poor adherence before drug substitution. CONCLUSIONS: Considerable delay in switching to second-line cART may occur despite an observed high rate of failure. Factors including WHO clinical stage and tuberculosis co-infection should be evaluated before starting cART. Toxicity and drug adherence should be monitored to minimize drug substitution in LMIC.

Viral load detection using dried blood spots in a cohort of HIV-1-infected children in Uganda: correlations with clinical and immunological criteria for treatment failure.

Correlations between clinical/immunological treatment failure and viral load (VL) detected by dried blood spot (DBS) sampling were explored in HIV-1-infected children in Uganda. Of 104 children on combined antiretroviral treatment (cART), 12.5% experienced clinical and/or immunological failure, while 28.8%, 44.2%, and 26.9% had VLs of <1,000, 1,000 to 5,000, and >5,000 copies/ml, respectively. Clinical/immunological failure poorly predicted virological failure.