Incidence and clinical and microbiological features of invasive and probable invasive streptococcal group A infections in children and adults in the Brussels-Capital Region, 2005-2020.

Assess the incidence, risk factors, clinical and microbiological features, and outcome of both probable invasive and invasive group A Streptococcus (GAS) infections in children and adults in the BrusselsCapital Region between 2005 and 2020. A retrospective, multicentric study was performed in three university hospitals in Brussels. Patients were identified through the centralized laboratory information system. Epidemiological and clinical data were collected from patients' hospital records. A total of 467 cases were identified. Incidence has increased from 2.1 to 10.9/100,000 inhabitants between 2009 and 2019 in non-homeless adults while it was above 100/100,000 on homeless in years with available denominators. Most of GAS were isolated from blood (43.6%), and the most common clinical presentation was skin and soft tissue infections (42.8%). A third of all the patients needed surgery, a quarter was admitted to the intensive care unit, and 10% of the adult patients died. Wounds and chickenpox disease were the main risk factors for children. Tobacco, alcohol abuse, wounds or chronic skin lesion, being homeless, and diabetes were identified as major predisposing factors for adults. The most common emm clusters were D4, E4, and AC3; 64% of the isolates were theoretically covered by the 30-valent M-protein vaccine. The burden of invasive and probable invasive GAS infections is on the rise in the studied adult population. We identified potential interventions that could contribute to decrease this burden: appropriate care of wounds, specifically among homeless and patients with risk factors such as diabetes and systematic chickenpox vaccination for children.

SARS-CoV-2 seroprevalence in children and their family members, July-October 2020, Brussels.

The aim of this study was to estimate the seroprevalence of SARS-CoV-2 antibodies in a pediatric population after the first pandemic wave in Belgium. All patients requiring a blood sample between 1 July 2020 and 31 October 2020 in our institution were invited to participate. Their parents and siblings could also participate to estimate familial transmission and the congruence between serological statuses. A questionnaire was completed for each participant to identify symptoms consistent with COVID-19 in the previous months. Blood samples were tested for SARS-CoV-2-specific immunoglobulin G using ELISA. The final population included 112 children, 24 siblings of these children, and 36 adults. The seroprevalence of cases was 6.9% before 8 September, a date that corresponds to 1 week after the beginning of the second wave in Belgium and 22.5% afterwards (OR = 3.89, 95% CI (1.20; 12.58), p-value = 0.03). Twenty-five percent of children were asymptomatic, and none experienced severe disease. The symptoms associated with SARS-CoV-2-positive antibodies were diarrhoea (OR = 9.9, 95% CI [2.88; 33.87.65] p-value < 0.01), fever (OR = 3.8, 95% CI [1.44; 10.22] p-value < 0.01), rhinitis (OR = 3.9, 95% CI [1.38; 10.90] p-value = 0.01), or anosmia (OR = 31.5, 95% CI [1.45; 682.7], p-value = 0.02). A child was the first symptomatic household member in 50% of the familial clusters.Conclusion: Seroprevalence in children was comparable to that of the general population. Children could represent the source of infection in the household. What is Known: • COVID-19 infection is generally mild or asymptomatic in children and adolescents. • Belgian strategy of testing was focused on symptoms. • Adults are believed to be responsible for most of familial clusters. What is New: • Serological testing gives a more accurate view of the rate of infected children. • Based on serological results, children have been infected as frequently as adults during the first and second wave in Belgium. • Seventy-five percent of SARS-CoV-2 IgG-positive children presented a mild symptomatology, and 25% were totally asymptomatic. • Children could represent the source of infection within household.

Paediatric enteric fever in Brussels: a case series over 16 years.

Enteric fever (EF) is a major public health problem and a witness of the global health disparities. It is caused by Salmonella enterica serovar Typhi (Salmonella ser. Typhi) and Salmonella enterica serovar Paratyphi A, B, C (Salmonella ser. Paratyphi) and is estimated to infect 12-26 million persons yearly. Paediatric data on enteric fever in Europe are scarce. A case series of EF was analysed to describe the clinical presentation, laboratory characteristics and diagnostic challenges identified in a paediatric population in Brussels. We performed a retrospective study of all lab-confirmed cases of enteric fever in children aged 0-15 years at two Brussels teaching hospitals, between January 2005 and December 2020. We reviewed age, gender, travel history, consultations before diagnosis, hospitalisation duration, clinical symptoms and laboratory findings. There were 34 positive isolates of S. typhi and S. paratyphi: 31 patients had positive blood culture, 1 patient had positive bone aspirate and 2 patients had positive stool culture (one was excluded for missing data). There were 20 girls (60%). Median age was 3.5 years (range 5 months to 14 years). Travel to EF endemic areas was present in 55% of patients. Diagnosis was delayed in 80% of children. Eosinopenia was present in 93% of the cohort. The patients had not received any preventive travel education or vaccination.  Conlusion: Enteric fever poses diagnostic challenges to clinicians. Eosinopenia in a febrile patient coming from the tropics should raise suspicion of EF. Travellers to endemic areas should be better educated about EF risks, and typhoid fever vaccination must be promoted. What is Known: • Enteric fever is a global public health problem and includes typhoid and paratyphoid fever. • Typhoid fever is vaccine preventable disease. Paratyphoid fever is not vaccine preventable. What is New: • Enteric fever diagnosis is very challenging in non-endemic settings, and a large proportion of patients may develop serious complications if they receive delayed management. Occurrence of small family clusters is possible and mandates education and monitoring of the families of enteric fever affected children. • We report that the widest majority of our enteric fever affected patients (69%) had aneosinophilia (zero eosinophil count), and almost all patients (93%) had eosinopaenia (less than 50 eosinophil count) during their bacteriaemic phase.

Long-term outcome of surgical excision for treatment of cervicofacial granulomatous lymphadenitis in children.

PURPOSE: Granulomatous inflammation is a common cause of subacute cervicofacial lymphadenitis in children. Nontuberculous mycobacterial (NTM) infections and cat-scratch disease (CSD) are the most frequent causes. Optimal treatment, which may include surgery, antibiotic treatment or wait-and-see approach, is debatable. The goal of this study was to compare the short- and long-term outcome of various surgical procedures. METHODS: Case series with a chart review of all children treated by surgical excision of granulomatous lymph nodes in the cervicofacial area from 2000 to 2016 at two tertiary care centers. RESULTS: Forty patients were included in this study. The median age at first symptoms was 3.7 years (13 months-14 years). Mean follow-up was 5.8 years (6 months-15.3 years). 25 patients fit with diagnosis of NTM infection, 6 with CSD while diagnosis remained uncertain in 9 patients. The primary surgical procedure consisted of total excision (n = 27), incision/drainage (n = 9) or incomplete excision (n = 4). None of the patients treated by primary complete excision needed further intervention contrary to the group of patients with incomplete surgical procedures where additional surgical management was required in 54%. At follow-up, all patients were healthy without evidence of recurrence. CONCLUSION: We advocate early surgical intervention with complete excision to reach quick resolution and reduce the need for additional surgery. The long-term outcome was favorable.

SARS-CoV-2 Infection in Children Less Than Forty Days Hospitalized in Belgium Between 2020 and 2022.

Our study aimed to assess the severity of severe acute respiratory syndrome coronavirus 2 infection in hospitalized infants under 40 days old, across 21 Belgian hospitals between 2020 and 2022. Of the 365 infants studied, 14.2% needed respiratory support. The median hospital stay was 3 days (interquartile range, 2-4), and there were no deaths. Infection severity was similar during the Omicron and Alpha/Delta periods.

Late renal sequelae in intravenously treated complicated urinary tract infection.

BACKGROUND: The treatment of complicated urinary tract infection in children is still a matter of debate. In our hospital, antimicrobial treatment is initiated intravenously, and the duration of this treatment is adapted according to the results of a Tc-99m dimercaptosuccinic acid (DMSA) scintigraphy. AIM: This study was conducted to evaluate retrospectively the frequency and the importance of late renal sequelae when treating intravenously for 7 days those patients with an abnormal acute DMSA. METHODS: A review was conducted of the medical charts of all patients consecutively admitted between 2005 and 2008 with positive urine culture and clinical and biological evidence of complicated urinary tract infection (UTI). RESULTS: There were 144 patients (59 %) with abnormal early DMSA scintigraphy and 98 (41 %) with normal scintigraphy. The median duration of intravenous treatment was 7.0 days in the children with DMSA lesions and 5.0 days in those without lesions. Obvious renal sequelae were observed on late DMSA scintigraphy in 4 (6 %) out of the 65 patients with an abnormal early DMSA who came back for control scintigraphy. CONCLUSION: Sequelae of acute DMSA lesions observed during complicated UTI treated 7 days intravenously were infrequent. Whether the mode and duration of antimicrobial treatment might explain the low rate of sequelae remains to be demonstrated.

Seroconversion and persistence of neutralizing antibody response after yellow fever vaccination in patients with perinatally acquired HIV infection.

OBJECTIVES: To describe the dynamics of neutralizing antibody (NAbs) response after yellow fever (YF) vaccine in young adults and adolescents with perinatally acquired HIV (pHIV). DESIGN: A retrospective cross-sectional study at three time points around YF vaccination and a matched case-control comparison of NAbs titers several years after YF vaccination. METHODS: We selected patients who had both documented YF vaccination and perinatally acquired HIV (n = 46). The NAbs titers were measured in plasma samples from the following three time points: during the two years before (TP0), within the year after (TP1) and >1 year after (TP2) administration of the YF vaccine. The impact of perinatal infection was assessed by comparing pHIV YF vaccinees with 44 controls infected with HIV during adulthood. RESULTS: The median time between the YF vaccine and TP1 and TP2 was 123 days and 7.3 years, respectively. After YF vaccination, 85% of vaccinees experienced seroconversion. The proportion of pHIV patients with NAbs above the protective threshold was stable between TP1 and TP2 (91% and 86%, respectively) but levels of NAbs decreased significantly between TP1 and TP2 (P = 0.0122). The case-control analysis found slightly higher geometrical mean titers (GMT) in pHIV than patients infected during adulthood. CONCLUSIONS: Patients with pHIV showed high seroconversion rate and NAbs persistence at levels above the protective threshold after first YF vaccination. However, a decline in antibody levels over time suggests that at least one revaccination may be necessary to maintain circulating antibodies, contrary to recommendations for the general population.

Retrospective comparison of respiratory syncytial virus and metapneumovirus clinical presentation in hospitalized children.

Respiratory syncytial virus (RSV) and Human metapneumovirus (hMPV), members of Pneumoviridae family are common causes of acute respiratory tract infections (ARTI) among children. Study material includes routine nasopharyngeal samples obtained during 8-year period for hMPV and one single season for RSV in children hospitalized for ARTI between 0 and 15 years at the Center Hospitalier Universitaire (CHU) Saint Pierre in Brussels. Positive samples for RSV or hMPV identified by viral culture, lateral flow chromatography test for RSV or direct fluorescent assay for hMPV were selected retrospectively. Characteristics of children hospitalized for RSV or hMPV infections were compared. Children hospitalized for RSV infection were significantly younger and requiring more respiratory support, longer hospital stay and transfers in Pediatric intensive Care Units than those hospitalized for hMPV infection. Pneumonia diagnostic and antibiotics therapies were more significantly associated with hMPV infections. In conclusion, despite their genetic similarities, RSV, and hMPV present epidemiological and clinical differences in pediatric infections. Our results should be confirmed prospectively.

Imported Malaria in Children: A Study Over an 11-Year Period in Brussels.

BACKGROUND: Malaria is a major global public health concern in endemic countries and imported childhood malaria is increasing in malaria non-endemic countries. METHODS: This was a retrospective case review of all laboratory-confirmed malaria cases in children 0-16 years admitted between 2009 and 2019 in 2 large university teaching Hospitals in Brussels. RESULTS: A total of 160 children with a median age of 6.8 years (range 5-191 months) were included. We identified 109 (68%) children living in Belgium who had acquired malaria during their visit to malaria-endemic countries to visiting friends and relatives (VFRs), 49 children (31%) visitors or newly installed migrants, and 2 Belgian tourists. Peak seasonal incidence occurred between August and September. Plasmodium falciparum was responsible for 89% of all malaria cases. Almost 80% of children living in Belgium visited a travel clinic for advice, but only one-third reported having taken the prophylaxis schedule according to the recommendations. Based on WHO criteria, 31 children (19.3%) developed severe malaria; most of the patients with severe malaria were VFR travelers and were significantly younger, had higher leukocytosis, had more thrombocytopenia, higher CRP, and lower natremia compared with patients with an uncomplicated course. All children recovered fully. CONCLUSIONS: Malaria is a significant cause of morbidity among returning travelers and newly arrived immigrants to Belgium. Most of the children had an uncomplicated disease course. Physicians should educate families about traveling to malaria-endemic areas to correct malaria preventive measures and prophylaxis.

Gen Z and HIV-Strategies for Optimizing the Care of the Next Generation of Adolescents Living with HIV.

The management of adolescents living with HIV represents a particular challenge in the global response to HIV. The challenges specific to this age group include difficulties engaging and maintaining them in care, challenges with transition to adult care, and limited therapeutic options for treatment-experienced patients, all of which have been jeopardized by the COVID-19 pandemic. This paper summarizes some of the challenges in managing adolescents living with HIV, as well as some of the most recent and innovative therapeutic approaches in this population.

Genomic monitoring of SARS-CoV-2 variants using sentinel SARI hospital surveillance.

Background: To support the COVID-19 pandemic response, many countries, including Belgium, implemented baseline genomic surveillance (BGS) programs aiming to early detect and characterize new SARS-CoV-2 variants. In parallel, Belgium maintained a sentinel network of six hospitals that samples patients with severe acute respiratory infections (SARI) and integrated SARS-CoV-2 detection within a broader range of respiratory pathogens. We evaluate the ability of the SARI surveillance to monitor general trends and early signals of viral genetic evolution of SARS-CoV-2 and compare it with the BGS as a reference model. Methods: Nine-hundred twenty-five SARS-CoV-2 positive samples from patients fulfilling the Belgian SARI definition between January 2020 and December 2022 were sequenced using the ARTIC Network amplicon tiling approach on a MinION platform. Weekly variant of concern (VOC) proportions and types were compared to those that were circulating between 2021 and 2022, using 96,251 sequences of the BGS. Results: SARI surveillance allowed timely detection of the Omicron (BA.1, BA.2, BA.4, and BA.5) and Delta (B.1.617.2) VOCs, with no to 2 weeks delay according to the start of their epidemic growth in the Belgian population. First detection of VOCs B.1.351 and P.1 took longer, but these remained minor in Belgium. Omicron BA.3 was never detected in SARI surveillance. Timeliness could not be evaluated for B.1.1.7, being already major at the start of the study period. Conclusions: Genomic surveillance of SARS-CoV-2 using SARI sentinel surveillance has proven to accurately reflect VOCs detected in the population and provides a cost-effective solution for long-term genomic monitoring of circulating respiratory viruses.

PENTA 2009 guidelines for the use of antiretroviral therapy in paediatric HIV-1 infection.

PENTA Guidelines aim to provide practical recommendations for treating children with HIV infection in Europe. Changes to guidance since 2004 have been informed by new evidence and by expectations of better outcomes following the ongoing success of antiretroviral therapy (ART). Participation in PENTA trials of simplifying treatment is encouraged. The main changes are in the following sections: 'When to start ART': Treatment is recommended for all infants, and at higher CD4 cell counts and percentages in older children, in line with changes to adult guidelines. The number of age bands has been reduced to simplify and harmonize with other paediatric guidelines. Greater emphasis is placed on CD4 cell count in children over 5 years, and guidance is provided where CD4% and CD4 criteria differ. 'What to start with': A three-drug regimen of two nucleoside reverse transcriptase inhibitors (NRTIs) with either a nonnucleoside reverse transcriptase inhibitor (NNRTI) or a boosted protease inhibitor (PI) remains the first choice combination. Lamivudine and abacavir are the NRTI backbone of choice for most children, based on long-term follow-up in the PENTA 5 trial. Stavudine is no longer recommended. Whether to start with an NNRTI or PI remains unclear, but PENPACT 1 trial results in 2009 may help to inform this. All PIs should be ritonavir boosted. Recommendations on use of resistance testing, therapeutic drug monitoring and HLA testing draw from data in adults and from European paediatric cohort studies. Recently updated US and WHO paediatric guidelines provide more detailed review of the evidence base. Differences between guidelines are highlighted and explained.

Vertical transmission of HIV in Belgium: a 1986-2002 retrospective analysis.

Prophylactic interventions have lead to the reduction of the mother-to-child transmission (MTCT) of human immunodeficiency virus type 1 (HIV-1) to less than 2% in industrialized countries. The aim of this study was to evaluate the changes over time in vertical transmission according to the standard care of prophylaxis in the practice of a single large reference center and to identify the risk factors for failure. The rate of MTCT decreased progressively from 10% in 1986-1993 to 4.7% in 1999-2002, reflecting the progressive implementation of newly available means of prevention. During the last period evaluated (1999-2002), where highly active antiretroviral therapy (HAART) prophylaxis was the standard of care, 17% of women had a viral load between 400 and 20,000 copies/ml around delivery and 5% had a viral load above 20,000 copies/ml. High viral load and low CD4 lymphocyte count were strongly associated with vertical transmission. The rate of MTCT in women who received HAART for more than one month during pregnancy was 1.7%, compared to 13.3% in women treated with HAART for less than one month. The risk of vertical transmission in the absence of therapy was four times higher than before the era of antiretroviral therapy (ART; p=0.05). In conclusion, since the prevention of MTCT of HIV with HAART is the standard of care, a short duration or absence of ART during pregnancy linked to late or absent prenatal care is associated with a high risk of transmission. The early detection of HIV-1 infection in pregnant women, and close follow up and support during pregnancy are crucial to the success of the prevention of transmission.

High rate of rubella seronegativity in perinatally-infected HIV women of childbearing age: A case-control study.

Rubella infection is a vaccine preventable disease. Maternal infection during pregnancy may lead to congenital infection and severe foetal malformations. Thanks to antiretroviral therapy, perinatally HIV-infected women have better prognosis and are now experiencing pregnancy. We evaluated the rate of rubella seronegativity in a cohort of HIV perinatally-infected women of childbearing age. A high rate of seronegativity was found in this group as compared to age-matched non-perinatally infected HIV-infected women (34.5% vs 6.90%, p < 0.01). MMR administration before rubella testing was identified in 75.8% of perinatally-infected women (22/29) with a mean of 2 doses (range: 1-3 doses). HIV perinatally-infected women of childbearing age should be screened repeatedly for rubella immunity.

Effectiveness of early initiation of protease inhibitor-sparing antiretroviral regimen in human immunodeficiency virus-1 vertically infected infants.

Each of the 17 vertically infected infants born to HIV-1-infected mothers in Belgian HIV reference centers since 1996 was treated with a combination of 3 reverse transcription inhibitors as soon as the diagnosis was established. Treatment was initiated in all patients before 66 days of life. Twelve patients, including 11/13 infants treated with the combination of zidovudine, lamivudine and nevirapine, experienced a complete viral suppression (<50 copies/mL) with their first drug regimen. At last follow-up, 12 patients were asymptomatic, 2 were CDC stage A and 3 were stage B; 15 had HIV-1 RNA levels of <50 copies/mL and 14 had >or=25% CD4 lymphocytes. These results suggest that early initiation of treatment with 3 reverse transcription inhibitors is highly effective to inhibit viral replication and to prevent clinical and immunologic progression of HIV infection in vertically infected infants.

Resistance testing in children changing human immunodeficiency virus type 1 protease inhibitor.

OBJECTIVE: To assess genotypic and phenotypic resistance testing in HIV-1-infected children failing a first protease inhibitor (PI) therapy. METHODS: In a multicenter observational study 21 children, ages 3 to 16 years, were given two reverse transcriptase inhibitors and one PI (mainly ritonavir, n = 18). They were subsequently treated with single or dual PI-based therapy (predominantly nelfinavir, n = 10, or ritonavir-saquinavir, n = 7). Resistance testing was performed at the time of therapy switch via direct sequencing and a recombinant virus susceptibility assay. RESULTS: A total of 21 genotypic and 15 phenotypic resistance profiles were obtained. Most viruses displayed several reverse transcriptase mutations; however, 7 isolates maintained a wild-type protease. Ritonavir targeted the well-known pathway containing 82, 54, 46 and other secondary (nonactive site) mutations including T74A. No in vitro cross-resistance, i.e. > or = 8-fold resistance to saquinavir or amprenavir, was encountered. Secondary mutations enhanced the prediction of ritonavir resistance (i.e. L10I) and in vitro nelfinavir cross-resistance (i.e. K20R/I) conferred by primary (active site) resistance mutations. Either the 82, 54, 46 mutational genotype or the phenotype showing > or = 8-fold nelfinavir cross-resistance predicted a poorer virologic response to nelfinavir salvage therapy. CONCLUSION: In a small cohort of heavily pretreated pediatric patients, resistance testing appears to predict the response to nelfinavir as salvage for a ritonavir-based therapy. This is further supported by the correlation between ritonavir-selected mutations and in vitro nelfinavir cross-resistance. Prospective studies should assess clinical outcome in children undergoing regimen changes based on resistance testing.

Age-related immune reconstitution during highly active antiretroviral therapy in human immunodeficiency virus type 1-infected children.

OBJECTIVES: To evaluate the immune reconstitution in HIV-1-infected children in whom highly active antiretroviral therapy (HAART) controlled viral replication and to assess the existence of a relation between the magnitude of this restoration and age. METHODS: All HIV-1-infected children in whom a new HAART decreased plasma viral load below 400 copies/ml after 3 months of therapy were prospectively enrolled in a study of their immune reconstitution. Viral load, lymphocyte phenotyping, determination of CD4+ and CD8+ T cell receptor repertoires and proliferative responses to mitogens and recall antigens were assessed every 3 months during 1 year. RESULTS: Nineteen children were evaluated. Naive and memory CD4+ percentages were already significantly increased after 3 months of HAART. In contrast to memory CD4+ percentages, naive CD4+ percentages continued to rise until 12 months. Age at baseline was inversely correlated with the magnitude of the rise in naive CD4+ cells after 3, 6 and 9 months of therapy but not after 12 months. Although memory and activated CD8+ cells were already decreasing after 3 months, abnormalities of the CD8 T cell receptor repertoire and activation of CD8+ cells persisted at 1 year. HAART increased the response to mitogens as early as 3 months after starting therapy. CONCLUSIONS: In children the recovery of naive CD4+ cells occurs more rapidly if treatment is started at a younger age, but after 1 year of viral replication control, patients of all ages have achieved the same level of restoration. Markers of chronic activation in CD8+ cells persist after 1 year of HAART.

High incidence of invasive group B streptococcal infections in HIV-exposed uninfected infants.

OBJECTIVES: The occurrence of an unusual number of group B streptococcal (GBS) infections in HIV-exposed uninfected (HEU) infants who were followed in our center prompted this study. The objective of this study was to describe and compare the incidence and clinical presentation of GBS infections in infants who were born to HIV-infected and -uninfected mothers. METHODS: All cases of invasive GBS infections in infants who were born between 2001 and 2008 were identified from the database of HEU infants and from the microbiology laboratory records. The medical charts of all infants with GBS infection were reviewed. RESULTS: GBS invasive infections were described for 5 (1.55%) infants who were born to 322 HIV-infected mothers who delivered in our center. The incidence of GBS infections during the same period was 16 (0.08%) of 20 158 infants who were born to HIV-uninfected mothers. One HEU infant presented a recurrent infection 28 days after completion of treatment for the first episode. Late-onset infection was more frequent in HEU infants (5 of 6 vs 2 of 16 episodes in the control population). The diseases were also more severe in HEU infants with 5 of 6 sepsis or sepsis shock in HEU infants versus 10 of 16 in control subjects, and most HEU infants had leukopenia at onset of infection. CONCLUSIONS: The incidence of GBS infection was significantly higher in HEU infants than in infants who were born to HIV-uninfected mothers. These episodes of GBS sepsis in HEU infants were mostly of late onset and more severe than in the control population, suggesting an increased susceptibility of HEU infants to GBS infection.