Pub Date : 2026-02-01Epub Date: 2025-09-24DOI: 10.1097/INF.0000000000004998
Margaret C Siu, Maria Selinopoulou, Susan Abarca Salazar, Jonathan P Sturgeon, Julie Huynh, Robin Basu Roy
Background: Diagnosing extrapulmonary tuberculosis (EPTB) in children is challenging due to nonspecific presentations and poor diagnostic yield from conventional microbiologic tests. Host gene expression signatures offer a non-sputum-based diagnostic alternative. This systematic review evaluates their diagnostic performance in pediatric EPTB.
Methods: We systematically reviewed host-based gene expression diagnostics for pediatric EPTB. PubMed, Embase and Cochrane Library (January 1965-May 2025) were searched for studies in children (0-18 years) with EPTB. Exclusions were adult-only studies, mixed data on pulmonary TB and EPTB without disaggregation, pulmonary TB-only studies, reviews and abstracts. Two reviewers screened data, resolving disagreements by discussion.
Results: Of 830 records, 2 studies met the inclusion criteria: Pan et al. (2017) and Olbrich et al. (2024), both in low and middle-income countries, enrolling a total of 891 children under 15 years. Olbrich et al.'s 3-gene MTB-HR prototype showed 59.8% sensitivity against a strict culture-confirmed reference standard and 50.0% in isolated EPTB with a low risk of bias. Using a microbiologic, clinical and radiologic composite standard, Pan et al.'s miRNA-29a assay achieved 67.2% sensitivity, 88.5% specificity in peripheral blood mononuclear cells; 81.1% sensitivity, 90.0% specificity in cerebrospinal fluid; 84.4% sensitivity, 95.4% specificity in combined peripheral blood mononuclear cell/cerebrospinal fluid with a high risk of bias.
Conclusions: Evidence for host gene expression diagnostics in pediatric EPTB is limited by few studies, small sample sizes, bias and lack of disaggregated data, with accuracy falling short of the World Health Organization targets.
{"title":"Diagnostic Performance of Host-based Gene Expression Diagnostics in Children With Extrapulmonary Tuberculosis: A Systematic Review.","authors":"Margaret C Siu, Maria Selinopoulou, Susan Abarca Salazar, Jonathan P Sturgeon, Julie Huynh, Robin Basu Roy","doi":"10.1097/INF.0000000000004998","DOIUrl":"10.1097/INF.0000000000004998","url":null,"abstract":"<p><strong>Background: </strong>Diagnosing extrapulmonary tuberculosis (EPTB) in children is challenging due to nonspecific presentations and poor diagnostic yield from conventional microbiologic tests. Host gene expression signatures offer a non-sputum-based diagnostic alternative. This systematic review evaluates their diagnostic performance in pediatric EPTB.</p><p><strong>Methods: </strong>We systematically reviewed host-based gene expression diagnostics for pediatric EPTB. PubMed, Embase and Cochrane Library (January 1965-May 2025) were searched for studies in children (0-18 years) with EPTB. Exclusions were adult-only studies, mixed data on pulmonary TB and EPTB without disaggregation, pulmonary TB-only studies, reviews and abstracts. Two reviewers screened data, resolving disagreements by discussion.</p><p><strong>Results: </strong>Of 830 records, 2 studies met the inclusion criteria: Pan et al. (2017) and Olbrich et al. (2024), both in low and middle-income countries, enrolling a total of 891 children under 15 years. Olbrich et al.'s 3-gene MTB-HR prototype showed 59.8% sensitivity against a strict culture-confirmed reference standard and 50.0% in isolated EPTB with a low risk of bias. Using a microbiologic, clinical and radiologic composite standard, Pan et al.'s miRNA-29a assay achieved 67.2% sensitivity, 88.5% specificity in peripheral blood mononuclear cells; 81.1% sensitivity, 90.0% specificity in cerebrospinal fluid; 84.4% sensitivity, 95.4% specificity in combined peripheral blood mononuclear cell/cerebrospinal fluid with a high risk of bias.</p><p><strong>Conclusions: </strong>Evidence for host gene expression diagnostics in pediatric EPTB is limited by few studies, small sample sizes, bias and lack of disaggregated data, with accuracy falling short of the World Health Organization targets.</p>","PeriodicalId":19858,"journal":{"name":"Pediatric Infectious Disease Journal","volume":" ","pages":"140-146"},"PeriodicalIF":2.2,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145131746","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-02-01Epub Date: 2025-09-24DOI: 10.1097/INF.0000000000005013
Yo Murata, Meiwa Shibata, Hanako Funakoshi, Kazue Kinoshita, Yuho Horikoshi
Background: Human bocavirus 1 (HBoV1) is a respiratory pathogen predominantly affecting children. However, its epidemiology and clinical impact remain poorly understood. This study aimed to investigate the seasonality, disease burden and clinical features of HBoV1 infection in hospitalized pediatric patients in Japan.
Methods: We conducted a retrospective study at Tokyo Metropolitan Children's Medical Center from September 2023 to August 2024. Children ≤15 years old hospitalized with respiratory tract infections requiring oxygen therapy and/or noninvasive/invasive mechanical ventilation were included. HBoV1 DNA levels were quantified using real-time polymerase chain reaction (PCR), and acute HBoV1 infection was defined as ≥10 5 copies/mL. A quantitative PCR test was also performed for respiratory viruses simultaneously detected by a multiplex PCR, to distinguish between HBoV1 monoinfection and coinfection with other viruses.
Results: Among 327 eligible patients, acute HBoV1 infection was found in 13% (44/327), with peak incidence in June and July 2024. HBoV1 monoinfection was 41% (18/44). The patients with HBoV1 monoinfection had a median age of 25 months (interquartile range, 14-50), and 39% had underlying diseases. Fever and cough were common symptoms, and wheezing was observed in half of the patients. Intensive care unit admission was required in 33% of the patients with HBoV1 monoinfection, with 67% of them requiring mechanical ventilation. HBoV1 was the 3rd most common cause in patients admitted to the intensive care unit (19%).
Conclusions: HBoV1 was prevalent in the late spring and early summer during the 2023 to 2024 season in Tokyo, Japan. HBoV1 may contribute substantially to the burden of severe pediatric respiratory tract infections.
{"title":"Epidemiology and Diseases Burden of Human Bocavirus 1 Infection in a Children's Hospital in Japan.","authors":"Yo Murata, Meiwa Shibata, Hanako Funakoshi, Kazue Kinoshita, Yuho Horikoshi","doi":"10.1097/INF.0000000000005013","DOIUrl":"10.1097/INF.0000000000005013","url":null,"abstract":"<p><strong>Background: </strong>Human bocavirus 1 (HBoV1) is a respiratory pathogen predominantly affecting children. However, its epidemiology and clinical impact remain poorly understood. This study aimed to investigate the seasonality, disease burden and clinical features of HBoV1 infection in hospitalized pediatric patients in Japan.</p><p><strong>Methods: </strong>We conducted a retrospective study at Tokyo Metropolitan Children's Medical Center from September 2023 to August 2024. Children ≤15 years old hospitalized with respiratory tract infections requiring oxygen therapy and/or noninvasive/invasive mechanical ventilation were included. HBoV1 DNA levels were quantified using real-time polymerase chain reaction (PCR), and acute HBoV1 infection was defined as ≥10 5 copies/mL. A quantitative PCR test was also performed for respiratory viruses simultaneously detected by a multiplex PCR, to distinguish between HBoV1 monoinfection and coinfection with other viruses.</p><p><strong>Results: </strong>Among 327 eligible patients, acute HBoV1 infection was found in 13% (44/327), with peak incidence in June and July 2024. HBoV1 monoinfection was 41% (18/44). The patients with HBoV1 monoinfection had a median age of 25 months (interquartile range, 14-50), and 39% had underlying diseases. Fever and cough were common symptoms, and wheezing was observed in half of the patients. Intensive care unit admission was required in 33% of the patients with HBoV1 monoinfection, with 67% of them requiring mechanical ventilation. HBoV1 was the 3rd most common cause in patients admitted to the intensive care unit (19%).</p><p><strong>Conclusions: </strong>HBoV1 was prevalent in the late spring and early summer during the 2023 to 2024 season in Tokyo, Japan. HBoV1 may contribute substantially to the burden of severe pediatric respiratory tract infections.</p>","PeriodicalId":19858,"journal":{"name":"Pediatric Infectious Disease Journal","volume":" ","pages":"147-151"},"PeriodicalIF":2.2,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145131669","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-02-01Epub Date: 2025-09-26DOI: 10.1097/INF.0000000000005005
Hellen Moraa, Irene N Njuguna, Caren Mburu, Grace John-Stewart, Dalton C Wamalwa
We conducted verbal autopsies and abstracted medical records of deceased youth living with HIV to identify missed opportunities for intervention. Of 60 deceased youth, the median age was 20 years, 65% acquired HIV perinatally and 67% were female. Overall, 55% of deaths occurred in hospitals, and 74% had adherence challenges. Mental health challenges and viral failure were key contributors to mortality.
{"title":"Missed Opportunities to Prevent Mortality Among Youth Living With HIV: Insights From Verbal Autopsies and Clinical Record Reviews.","authors":"Hellen Moraa, Irene N Njuguna, Caren Mburu, Grace John-Stewart, Dalton C Wamalwa","doi":"10.1097/INF.0000000000005005","DOIUrl":"10.1097/INF.0000000000005005","url":null,"abstract":"<p><p>We conducted verbal autopsies and abstracted medical records of deceased youth living with HIV to identify missed opportunities for intervention. Of 60 deceased youth, the median age was 20 years, 65% acquired HIV perinatally and 67% were female. Overall, 55% of deaths occurred in hospitals, and 74% had adherence challenges. Mental health challenges and viral failure were key contributors to mortality.</p>","PeriodicalId":19858,"journal":{"name":"Pediatric Infectious Disease Journal","volume":" ","pages":"170-172"},"PeriodicalIF":2.2,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145150242","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-02-01Epub Date: 2025-10-22DOI: 10.1097/INF.0000000000005016
Wasif Ullah Khan, Mehr Un Nisa, Aamir Khan
{"title":"In Reply: Impact of Respiratory Syncytial Virus Prevention in Infancy on Prevalence of Asthma Among Native American Children.","authors":"Wasif Ullah Khan, Mehr Un Nisa, Aamir Khan","doi":"10.1097/INF.0000000000005016","DOIUrl":"10.1097/INF.0000000000005016","url":null,"abstract":"","PeriodicalId":19858,"journal":{"name":"Pediatric Infectious Disease Journal","volume":" ","pages":"e69"},"PeriodicalIF":2.2,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145346507","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-02-01Epub Date: 2025-10-08DOI: 10.1097/INF.0000000000004984
İlknur Çağlar, Özlem Bağ, Miray Yilmaz Çelebi, Elif Kiymet, Elif Böncüoğlu, Şahika Şahinkaya, Ela Cem, Mustafa Gülderen, Pelin Kaçar, Deniz Ergün, İlker Devrim
Background: Postexposure prophylaxis (PEP) is critical in preventing HIV acquisition after risky exposures, particularly in pediatric sexual assault victims. Despite its importance, adherence and follow-up remain significant challenges.
Objectives: This study evaluates PEP and follow-up adherence and efficacy among pediatric sexual assault victims treated at a tertiary care hospital in Turkey.
Methods: A retrospective analysis was conducted on 119 pediatric patients 1 month to 18 years of age, treated between September 2017 and September 2022. Data were collected on demographics, PEP initiation and completion, follow-up rates and serologic testing for HIV. PEP compliance, follow-up adherence and outcomes were analyzed.
Results: PEP was initiated in 97% of the eligible 119 patients, with 70% completing the regimen. Compliance showed no significant differences by sex or age. Follow-up adherence decreased progressively, from 55% at the first month to 30% by the sixth month. Nausea and vomiting occurred in one case, indicating a low incidence of side effects. None of the patients seroconverted to HIV.
Conclusion: A structured care system involving multidisciplinary collaboration, pioneered by pediatric infectious diseases, can lead to high PEP initiation and completion rates in children. Single-pill PEP regimens may enhance adherence. However, the decline in follow-up rates underscores the need for improved follow-up mechanisms and future interventions.
{"title":"Evaluation of Adherence to HIV Postexposure Prophylaxis and Follow-up in Pediatric Sexual Assault Victims in Turkey: A Tertiary Center Experience.","authors":"İlknur Çağlar, Özlem Bağ, Miray Yilmaz Çelebi, Elif Kiymet, Elif Böncüoğlu, Şahika Şahinkaya, Ela Cem, Mustafa Gülderen, Pelin Kaçar, Deniz Ergün, İlker Devrim","doi":"10.1097/INF.0000000000004984","DOIUrl":"10.1097/INF.0000000000004984","url":null,"abstract":"<p><strong>Background: </strong>Postexposure prophylaxis (PEP) is critical in preventing HIV acquisition after risky exposures, particularly in pediatric sexual assault victims. Despite its importance, adherence and follow-up remain significant challenges.</p><p><strong>Objectives: </strong>This study evaluates PEP and follow-up adherence and efficacy among pediatric sexual assault victims treated at a tertiary care hospital in Turkey.</p><p><strong>Methods: </strong>A retrospective analysis was conducted on 119 pediatric patients 1 month to 18 years of age, treated between September 2017 and September 2022. Data were collected on demographics, PEP initiation and completion, follow-up rates and serologic testing for HIV. PEP compliance, follow-up adherence and outcomes were analyzed.</p><p><strong>Results: </strong>PEP was initiated in 97% of the eligible 119 patients, with 70% completing the regimen. Compliance showed no significant differences by sex or age. Follow-up adherence decreased progressively, from 55% at the first month to 30% by the sixth month. Nausea and vomiting occurred in one case, indicating a low incidence of side effects. None of the patients seroconverted to HIV.</p><p><strong>Conclusion: </strong>A structured care system involving multidisciplinary collaboration, pioneered by pediatric infectious diseases, can lead to high PEP initiation and completion rates in children. Single-pill PEP regimens may enhance adherence. However, the decline in follow-up rates underscores the need for improved follow-up mechanisms and future interventions.</p>","PeriodicalId":19858,"journal":{"name":"Pediatric Infectious Disease Journal","volume":" ","pages":"165-169"},"PeriodicalIF":2.2,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145251963","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-02-01Epub Date: 2025-10-17DOI: 10.1097/INF.0000000000005015
Garyfallia Syridou, Sofia Karagiannidou, Maria Eleni Papakonstantinou, Myrto Manzana Peteinelli, Konstantinos Giannakopoulos, Vasiliki Papaevangelou
Background: Visceral Leishmaniasis is a systemic vector-borne infection with a poor prognosis if not treated. Classical antiparasitic therapy with liposomal amphotericin B (LAmB) is effective, but occasionally not well-tolerated.
Case presentation: An 11-month-old male infant was admitted to our hospital due to prolonged fever, following an RSV infection. The patient had pale skin and splenomegaly, but was hemodynamically stable. An infectious cause was investigated through serology for Leishmania species , Brucella melitensis , Toxoplasma gondii , EBV, CMV, PB19 and Salmonella species . After admission, the infant developed Hemophagocytic lymphohistiocytosis (HLH, with pancytopenia, triglycerides: 346 U/L, ferritin: 1071 ng/mL; γ-globulin was administered without clinical response). On the second hospitalization day, the Leishmania rapid test was positive, while blood polymerase chain reaction identified Leishmania Infantum as the cause of infection, and LAmB was initiated. After the 4th dose, the patient developed hypokalemia, bradycardia and premature supraventricular complexes. The arrhythmia persisted despite electrolyte replacement; amphotericin-induced cardiotoxicity was suspected, and LAmB was discontinued. Oral miltefosine was started after approval by the National Public Health Organization, since the medicine was given in Greece for the first time to a pediatric patient. Miltefosine therapy lasted 1 month, with remission. Hepatotoxicity occurred at the end of the treatment and gradually resolved over the following 4 months with complete normalization of hepatic markers. The child remained asymptomatic at the 1-year follow-up.
Conclusions: Leishmaniasis should always be investigated in pediatric patients with secondary HLH, especially in endemic countries. Cardiotoxicity of LAmB is extremely rare; in this case, however, miltefosine is an effective and safe alternative.
背景:内脏利什曼病是一种全身性媒介传播感染,如果不及时治疗,预后很差。经典的两性霉素B (LAmB)脂质体抗寄生虫治疗是有效的,但有时耐受性不佳。病例介绍:一名11个月大的男婴因呼吸道合胞病毒感染后持续发热入院。患者皮肤苍白,脾肿大,但血流动力学稳定。通过血清学调查利什曼原虫、梅利氏布鲁氏菌、刚地弓形虫、EBV、CMV、PB19和沙门氏菌的感染原因。入院后患儿出现噬血细胞性淋巴组织细胞增多症(HLH,伴全血细胞减少,甘油三酯:346 U/L,铁蛋白:1071 ng/mL;给予γ-球蛋白,无临床反应)。住院第2天,利什曼原虫快速检测阳性,血液聚合酶链反应确定感染原因为婴儿利什曼原虫,启动兰姆治疗。第4次给药后,患者出现低钾血症、心动过缓和过早室上复合体。尽管补充了电解质,心律失常仍然存在;怀疑是两性霉素引起的心脏毒性,停用兰姆。口服米替福辛是在国家公共卫生组织(National Public Health Organization)批准后开始使用的,因为这种药物首次在希腊被用于儿科患者。米替福辛治疗持续1个月,缓解。肝毒性在治疗结束时出现,并在随后的4个月内逐渐消退,肝脏标志物完全正常化。在1年的随访中,儿童仍无症状。结论:在继发性HLH患儿中应始终调查利什曼病,特别是在流行国家。羊肉的心脏毒性极为罕见;然而,在这种情况下,米替福辛是一种有效和安全的替代品。
{"title":"Liposomal Amphotericin B-induced Cardiac Arrhythmias in Infantile Visceral Leishmaniasis: A Case Report.","authors":"Garyfallia Syridou, Sofia Karagiannidou, Maria Eleni Papakonstantinou, Myrto Manzana Peteinelli, Konstantinos Giannakopoulos, Vasiliki Papaevangelou","doi":"10.1097/INF.0000000000005015","DOIUrl":"10.1097/INF.0000000000005015","url":null,"abstract":"<p><strong>Background: </strong>Visceral Leishmaniasis is a systemic vector-borne infection with a poor prognosis if not treated. Classical antiparasitic therapy with liposomal amphotericin B (LAmB) is effective, but occasionally not well-tolerated.</p><p><strong>Case presentation: </strong>An 11-month-old male infant was admitted to our hospital due to prolonged fever, following an RSV infection. The patient had pale skin and splenomegaly, but was hemodynamically stable. An infectious cause was investigated through serology for Leishmania species , Brucella melitensis , Toxoplasma gondii , EBV, CMV, PB19 and Salmonella species . After admission, the infant developed Hemophagocytic lymphohistiocytosis (HLH, with pancytopenia, triglycerides: 346 U/L, ferritin: 1071 ng/mL; γ-globulin was administered without clinical response). On the second hospitalization day, the Leishmania rapid test was positive, while blood polymerase chain reaction identified Leishmania Infantum as the cause of infection, and LAmB was initiated. After the 4th dose, the patient developed hypokalemia, bradycardia and premature supraventricular complexes. The arrhythmia persisted despite electrolyte replacement; amphotericin-induced cardiotoxicity was suspected, and LAmB was discontinued. Oral miltefosine was started after approval by the National Public Health Organization, since the medicine was given in Greece for the first time to a pediatric patient. Miltefosine therapy lasted 1 month, with remission. Hepatotoxicity occurred at the end of the treatment and gradually resolved over the following 4 months with complete normalization of hepatic markers. The child remained asymptomatic at the 1-year follow-up.</p><p><strong>Conclusions: </strong>Leishmaniasis should always be investigated in pediatric patients with secondary HLH, especially in endemic countries. Cardiotoxicity of LAmB is extremely rare; in this case, however, miltefosine is an effective and safe alternative.</p>","PeriodicalId":19858,"journal":{"name":"Pediatric Infectious Disease Journal","volume":" ","pages":"e43-e46"},"PeriodicalIF":2.2,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145308550","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}