Effectiveness of bubble continuous positive airway pressure for treatment of children aged 1-59 months with severe pneumonia and hypoxaemia in Ethiopia: a pragmatic cluster-randomised controlled trial.

BACKGROUND: The safety and efficacy of bubble continuous positive airway pressure (bCPAP) for treatment of childhood severe pneumonia outside tertiary care hospitals is uncertain. We did a cluster-randomised effectiveness trial of locally made bCPAP compared with WHO-recommended low-flow oxygen therapy in children with severe pneumonia and hypoxaemia in general hospitals in Ethiopia. METHODS: This open, cluster-randomised trial was done in 12 general (secondary) hospitals in Ethiopia. We randomly assigned six hospitals to bCPAP as first-line respiratory support for children aged 1-59 months who presented with severe pneumonia and hypoxaemia and six hospitals to standard low-flow oxygen therapy. Cluster (hospital) randomisation was stratified by availability of mechanical ventilation. All children received treatment in paediatric wards (in a dedicated corner in front of a nursing station) with a similar level of facilities (equipment for oxygen therapy and medications) and staffing (overall, one nurse per six patients and one general practitioner per 18 patients) in all hospitals. All children received additional care according to WHO guidelines, supervised by paediatricians and general practitioners. The primary outcome was treatment failure (defined as any of the following: peripheral oxygen saturation <85% at any time after at least 1 h of intervention plus signs of respiratory distress; indication for mechanical ventilation; death during hospital stay or within 72 h of leaving hospital against medical advice; or leaving hospital against medical advice during intervention). The analysis included all children enrolled in the trial. We performed both unadjusted and adjusted analyses of the primary outcome, with the latter adjusted for the stratification variable and for the design effect of cluster randomisation, as well as selected potentially confounding variables, including age. We calculated effectiveness as the relative risk (RR) of the outcomes in the bCPAP group versus low-flow oxygen group. This trial is registered with ClinicalTrial.gov, NCT03870243, and is completed. FINDINGS: From June 8, 2021, to July 27, 2022, 1240 children were enrolled (620 in hospitals allocated to bCPAP and 620 in hospitals allocated to low-flow oxygen). Cluster sizes ranged from 103 to 104 children. Five (0·8%) of 620 children in the bCPAP group had treatment failure compared with 21 (3·4%) of 620 children in the low-flow oxygen group (unadjusted RR 0·24, 95% CI 0·09-0·63, p=0·0015; adjusted RR 0·24, 0·07-0·87, p=0·030). Six children died during hospital stay, all of whom were in the low-flow oxygen group (p=0·031). No serious adverse events were attributable to bCPAP. INTERPRETATION: In Ethiopian general hospitals, introduction of locally made bCPAP, supervised by general practitioners and paediatricians, was associated with reduced risk of treatment failure and in-hospital mortality in children with severe pneumonia and hypoxaemia compared with use of standard low-flow oxygen therapy. Implementation research is required in higher mortality settings to consolidate our findings. FUNDING: SIDA Sweden and Grand Challenges Ethiopia.

Pneumococcal colonization and coinfecting respiratory viruses in children under 5 years in Addis Ababa, Ethiopia: a prospective case-control study.

A comprehensive understanding of the dynamics of Streptococcus pneumoniae colonization in conjunction with respiratory virus infections is essential for enhancing our knowledge of the pathogenesis and advancing the development of effective preventive strategies. Therefore, a case-control study was carried out in Addis Ababa, Ethiopia to investigate the colonization rate of S. pneumoniae and its coinfection dynamics with respiratory viruses among children under the age of 5 years. Samples from the nasopharyngeal and/or oropharyngeal, along with socio-demographic and clinical information, were collected from 420 children under 5 years old (210 cases with lower respiratory tract infections and 210 controls with conditions other than respiratory infections.). A one-step Multiplex real-time PCR using the Allplex Respiratory Panel Assays 1-4 was performed to identify respiratory viruses and bacteria. Data analysis was conducted using STATA software version 17. The overall colonization rate of S. pneumoniae in children aged less than 5 years was 51.2% (215/420). The colonization rates in cases and controls were 54.8% (115/210) and 47.6% (100/210), respectively (p = 0.14). Colonization rates were observed to commence at an early age in children, with a colonization rate of 48.9% and 52.7% among infants younger than 6 months controls and cases, respectively. The prevalence of AdV (OR, 3.11; 95% CI [1.31-8.19]), RSV B (OR, 2.53; 95% CI [1.01-6.78]) and HRV (OR, 1.7; 95% CI [1.04-2.78]) tends to be higher in children who tested positive for S. pneumoniae compared to those who tested negative for S. pneumoniae. Further longitudinal research is needed to understand and determine interaction mechanisms between pneumococci and viral pathogens and the clinical implications of this coinfection dynamics.

Nasopharyngeal Staphylococcus aureus colonization among HIV-infected children in Addis Ababa, Ethiopia: antimicrobial susceptibility pattern and association with Streptococcus pneumoniae colonization.

Background: Staphylococcus aureus and Streptococcus pneumoniae are common inhabitants of the nasopharynx of children. HIV-infected children have higher risk of invasive diseases caused by these pathogens. With widespread use of pneumococcal conjugate vaccines and the emergence of methicillin-resistant S. aureus , the interaction between S. aureus and S. pneumoniae is of a particular significance. We sought to determine the magnitude of colonization by methicillin-sensitive and -resistant S. aureus and colonization by S. pneumoniae ; associated risk factors and antimicrobial susceptibility pattern among HIV-infected children in Addis Ababa, Ethiopia. Method: A prospective observational study was conducted among 183 HIV-infected children at ALERT hospital Addis Ababa, Ethiopia from September 2016 to August 2018. S. aureus and S. pneumoniae were identified using standard bacteriological techniques, antimicrobial susceptibility testing was performed on S. aureus and screening for methicillin resistance was carried out by amplifying the mecA gene. Risk factors were analysed by using binary logistic regression. Results: The prevalence of nasopharyngeal S. aureus , MRSA and S. pneumoniae colonization were 27.3, 2.7 and 43.2 %, respectively. Multivariable analysis indicated an inverse association between S. aureus and S. pneumoniae nasopharyngeal colonization [aOR, 0.49; CI, (0.24, 0.99); P=0.046]. The highest level of resistance in both methicillin-sensitive S. aureus (MSSA) and MRSA was observed against tetracycline. Conclusions: . We found an inverse association between S. aureus and S. pneumoniae colonization among HIV-infected children. Continued assessment of the impact of pneumococcal conjugate vaccines and antiretroviral therapy on nasopharyngeal bacterial ecology is warranted.

Viral etiologies of lower respiratory tract infections in children < 5 years of age in Addis Ababa, Ethiopia: a prospective case-control study.

BACKGROUND: Lower respiratory tract infections (LRTIs) are a major cause of morbidity and mortality in children worldwide and disproportionally affect Sub-Saharan Africa. Despite the heaviest burden of LRIs in Ethiopia, to date, no published studies have reported a comprehensive viral etiology of LRTIs among children in Ethiopia. The objective of this study was to determine and estimate the etiological contribution of respiratory viruses to LRTIs in < 5 years children in Ethiopia. METHODS: A prospective case-control study was conducted from September 2019 to May 2022 in two major governmental hospitals, St. Paul Hospital Millennium Medical College and ALERT Hospital in Addis Ababa, Ethiopia. Nasopharyngeal/oropharyngeal samples and socio-demographic and clinical information were collected from children under 5 years. A one-step Multiplex real-time PCR (Allplex™ Respiratory Panel Assays 1-3) was done to detect respiratory viruses. STATA software version 17 was used for the data analysis. We computed the odds ratio (OR), the attributable fraction among exposed (AFE) and the population attributable fraction (PAF) to measure the association of the detected viruses with LRTIs. RESULTS: Overall, 210 LRTIs cases and 210 non-LRTI controls were included in the study. The likelihood of detecting one or more viruses from NP/OP was higher among cases than controls (83.8% vs. 50.3%, p = 0.004). The multivariate logistic regression showed a significantly higher detection rate for RSV A (OR: 14.6, 95% CI 4.1-52.3), RSV B (OR: 8.1, 95% CI 2.3-29.1), influenza A virus (OR: 5.8, 95% CI 1.5-22.9), and PIV 1 (OR: 4.3, 95% CI 1.1-16.4), among cases when compared with controls. The overall AFE and PAF for RSV A were (93.2% and 17.3%), RSV B (87.7% and 10.4%) and Influenza A virus (82.8% and 6.3%), respectively. The mean CT values were significantly lower for only RSV B detected in the case groups as compared with the mean CT values of RSV B detected in the control group (p = 0.01). CONCLUSIONS: RSV, Influenza A and PIV 1 viruses were significantly associated with LRTIs in < 5 years children in Addis Ababa, Ethiopia. Therefore, we underscore the importance of developing prevention strategies for these viruses in Ethiopia and support the importance of developing and introducing an effective vaccine against these viruses.

Perception and experience of clinicians and caregivers in treating childhood severe pneumonia and hypoxemia using bubble continuous positive airway pressure in Ethiopian tertiary and general hospitals.

BACKGROUND: In low and middle-income countries (LMICs), severe pneumonia with hypoxemia is the leading cause of child deaths, even with the provision of WHO-recommended antibiotic therapy, oxygen therapy and other supportive care. Previous studies found positive outcomes from the use of bubble continuous positive airway pressure (bCPAP) for treating these children compared to the standard oxygen therapy. Due to lack of data on the perceptions and experiences of hospital health care workers and caregivers of children on the feasibility and acceptability of bCPAP in treating children with severe pneumonia and hypoxemia in real-life settings, we examined these issues in tertiary and general hospitals in Ethiopia. METHODS: As part of a three-stages clinical trial, this qualitative study was conducted in two tertiary (stage I) and two general (stage II) hospitals from September 2019 to July 2020. During stages I and II, we have consecutively enrolled children with severe pneumonia and hypoxemia and put them on bCPAP to examine its feasibility and acceptability by clinicians and parents. A total of 89 children were enrolled (49 from two tertiary and 40 from two general hospitals). Then qualitative data were collected through 75 repeated in-depth interviews by social-science experts with purposively selected 30 hospital health workers and 15 parents of 12 children who received bCPAP oxygen therapy in the hospitals. Interview data were supplemented by 6 observations in the hospitals. Data were analyzed using a thematic approach. RESULTS: Identified structural and functional challenges for the introduction of bCPAP in treating childhood severe pneumonia and hypoxemia in the study hospitals include: inadequate number of pulse oximeters; unavailability of nasal prongs with age-specific size; inadequate and non-functioning oxygen flow meters, concentrator, and cylinders; disruption in power-supply; and inadequate number of staff. The opportunities in introducing bCPAP oxygen therapy included the availability of a dedicated corner for the study patients situated in front of nurse's station, required medicines and satisfactory level of clinicians' knowledge and skills for treating severe pneumonia patients. Additionally, the identified operational challenges were occasional lack of bubbling in the water-filled plastic bottle, lack of stand for holding the water-filled plastic bottle, and delayed shifting of oxygen source from an oxygen concentrator to a cylinder, particularly during electricity disruption. Participants (clinicians and parents) expressed their satisfaction as bCPAP oxygen therapy was found to be simple to handle, children had ease of breathing and recovered fast without major ill effects. CONCLUSION: Our study identified some important structural, functional, and operational challenges that need to be addressed before implementation of bCPAP oxygen therapy especially in frontline general hospitals with limited resources. In spite of these observed challenges, the clinicians and caregivers were highly satisfied with the overall performance of bCPAP oxygen therapy.

Effectiveness of Bubble Continuous Positive Airway Pressure (BCPAP) for Treatment of Children Aged 1-59 Months with Severe Pneumonia and Hypoxemia in Ethiopia: A Pragmatic Cluster Randomized Controlled Clinical Trial.

Despite the beneficial effect of bubble continuous positive airway pressure (BCPAP) oxygen therapy for children with severe pneumonia under the supervision of physicians that has been shown in different studies, effectiveness trials in developing country settings where low-flow oxygen therapy is the standard of care are still needed. Thus, the aim of this study is to assess the effectiveness of bubble CPAP oxygen therapy compared to the WHO standard low-flow oxygen therapy among children hospitalized with severe pneumonia and hypoxemia in Ethiopia. This is a cluster randomized controlled trial where six district hospitals are randomized to BCPAP and six to standard WHO low-flow oxygen therapy. The total sample size is 620 per arm. Currently, recruitment of the patients is still ongoing where the management and follow-up of the enrolled patients are performed by general physicians and nurses under the supervision of pediatricians. The primary outcome is treatment failure and main secondary outcome is death. We anticipate to complete enrollment by September 2022 and data analysis followed by manuscript writing by December 2022. Findings will also be disseminated in December 2022. Our study will provide data on the effectiveness of BCPAP in treating childhood severe pneumonia and hypoxemia in a real-world setting.

Prevalence of antimicrobial resistance and its clinical implications in Ethiopia: a systematic review.

BACKGROUND: Antimicrobial resistance is one of the major public health challenges in Ethiopia. However, there is no comprehensive summary of existing AMR data in the country. AIM: To determine the prevalence of antimicrobial resistance and its clinical implications in Ethiopia. METHODS: A systematic literature search was performed on the PubMed/Medline database. Original studies on antimicrobial resistance conducted in Ethiopia between 1st January 2009 and 31st July 2019 were included. The outcome measure was the number of isolates resistant to antimicrobial agents in terms of specific pathogens, and disease condition. Data was calculated as total number of resistant isolates relative to the total number of isolates per specific pathogen and medication. RESULTS: A total of 48,021 study participants enrolled from 131 original studies were included resulting in 15,845 isolates tested for antimicrobial resistance. The most common clinical sample sources were urine (28%), ear, nose, and throat discharge collectively (27%), and blood (21%). All the studies were cross-sectional and 83% were conducted in hospital settings. Among Gram-positive bacteria, the reported level of resistance to vancomycin ranged from 8% (Enterococcus species) to 20% (S. aureus). E. coli, K. pneumoniae and P. aeruginosa were the most common Gram-negative pathogens resistant to key antimicrobial agents described in the national standard treatment guideline and were associated with diverse clinical conditions: urinary tract infections, diarrhea, surgical site infections, pneumonia, ocular infections, and middle ear infections. CONCLUSION: Overall, there is a high prevalence of antimicrobial resistance in Ethiopia. Empirical treatment of bacterial infections needs to be guided by up-to-date national guidelines considering local antimicrobial susceptibility patterns. Equipping diagnostic laboratories with culture and drug susceptibility testing facilities, and establishing a strong antimicrobial stewardship program should be high priorities.

Variable Diagnostic Performance of Stool Xpert in Pediatric Tuberculosis: A Systematic Review and Meta-analysis.

BACKGROUND: Difficult specimen collection and low bacillary load make microbiological confirmation of tuberculosis (TB) in children challenging. In this study, we conducted a systematic review and meta-analysis to assess the diagnostic accuracy of Xpert on stool for pediatric tuberculosis. METHODS: Our search included studies from 2011 through 2019, and specific search terms were used to retrieve articles from Pubmed, EMBASE, BIOSIS, ClinicalTrials.gov, and Google Scholar. Risk of bias was assessed using the QUADAS 2 tool. The protocol was registered in PROSPERO (CRD42018083637). Summary estimates of sensitivity and specificity were conducted using meta-disc Software assuming a random-effects model. RESULTS: We identified 12 eligible studies, which included data from 2177 children, of whom 295 (13.6%) had bacteriologically confirmed TB on respiratory specimens. The pooled sensitivity of Xpert MTB/RIF on stool specimens compared with bacteriologically confirmed tuberculosis with respiratory specimens was 0.50 (95% CI, 0.44-0.56) with an I 2 of 86%, which was statistically significant (P < .001). The pooled specificity was 0.99 (95% CI, 0.98-0.99; I 2 = 0.0%; P = .44). CONCLUSIONS: Despite the observed heterogeneity, stool may be considered an additional specimen to support diagnosis of pulmonary TB in children, especially in settings where it is impossible to get respiratory samples. Further studies should evaluate its optimization as a diagnostic tool.

Pneumococcal serotype 19A is the major cause of pediatric acute otitis media with ruptured tympanic membrane in Addis Ababa, Ethiopia, 5 years after the introduction of the ten-valent pneumococcal conjugate vaccine.

INTRODUCTION: In Ethiopia, there is a lack of data on pneumococcal serotypes causing acute otitis media (AOM) in children. We aimed to study the etiology, pneumococcal serotypes and antimicrobial resistance patterns of isolates from children with AOM with spontaneous perforation of the tympanic membrane (SPTM). METHODS: We carried out a prospective observational study in children with AOM with SPTM, aged 0-15 years in Addis Ababa, Ethiopia. Middle ear fluid was collected using sterile swabs, cultured and antibiotic susceptibility testing was performed. Serotypes of Streptococcus pneumoniae were determined by sequencing the cpsB gene and by the Quellung reaction. RESULTS: A total of 55 children were enrolled. Out of 55 samples that were cultured, 52 (94.5%) were culture positive for a total of 66 bacterial species, and 56.4% (31/55) samples were positive for 41 (62.1%) known pathogenic bacterial species. The most common pathogenic bacterial isolates were S. pneumoniae (36.6%), Staphylococcus aureus (19.5%), Streptococcus pyogenes (14.6%) and Haemophilus influenzae (12.2%). Serotype 19A (73.3%) was the predominant pneumococcal serotype. There was a high rate of non-susceptibility to penicillin (86.6%) and trimethoprim/sulfamethoxazole (80%) among pneumococcal isolates. Out of 21 different isolates tested for amoxicillin susceptibility, 15 (71.4%) were resistant. CONCLUSIONS: Pneumococcal serotype 19A was the predominant cause of AOM with SPTM in children in Addis Ababa, Ethiopia, 5 years after introduction of PCV10. There was a high rate of resistance to commonly prescribed antibiotics. The study highlights the need for wide scale surveillance of the etiology and antimicrobial susceptibility of AOM in Ethiopian children.

Pneumococcal Carriage, Serotype Distribution, and Risk Factors in Children With Community-Acquired Pneumonia, 5 Years After Introduction of the 10-Valent Pneumococcal Conjugate Vaccine in Ethiopia.

BACKGROUND: There is a scarcity of data on pneumococcal serotypes carried by children in Ethiopia. We studied pneumococcal nasopharyngeal carriage rate, serotypes, and risk factors among children with community acquired pneumonia (CAP). METHODS: A prospective observational cohort study was performed in children with CAP, aged 0-15 years, in 2 pediatric emergency departments in Addis Ababa, Ethiopia. Nasopharyngeal swabs were cultured, and serotypes of Streptococcus pneumoniae were determined by sequencing the cpsB gene and by the Quellung reaction. Risk factors were analyzed by using binary logistic regression. RESULTS: Nasopharyngeal swabs were collected from 362 children with CAP. Pneumococcal carriage rate was 21.5% (78 of 362). The most common serotypes were 19A (27%), 16F (8.5%), and 6A (4.9%). In addition, 8.5% of the pneumococcal isolates were nontypeable. In bivariate analysis, children with a parent that smokes were more likely to carry pneumococci (crude odds ratio, 3.9; 95% confidence interval [CI], 1.2-12.3; P = .023) than those with parents that do not smoke. In multivariable analysis, living in a house with ≥2 rooms (adjusted odds ratio [AOR], 0.48; 95% CI, 0.28-0.82; P = .007) and vaccination with ≥2 doses of 10-valent pneumococcal conjugate vaccine (PCV10) (AOR, 0.37; 95% CI, 0.15-0.92; P = .033) were protective of pneumococcal carriage. CONCLUSIONS: Five years after introduction of PCV10 in Ethiopia, the vaccine-related serotype 19A was predominant in the nasopharynx of children with CAP. Continued evaluation of the direct and indirect impact of PCV10 on pneumococcal serotype distribution in Ethiopia is warranted.

Homing defects of B cells in HIV-1 infected children impair vaccination responses.

BACKGROUND: Successful vaccinations rely on antibody responses. Chemokine receptors play an important role in B cell homing to differentiation niches. We assessed CXCR4, CXCR5 and CCR6 expression on B cells during HIV-1 infection and relate it to antibody responses against a HBV vaccine. METHODS: Blood was obtained from 54 healthy controls and 38 ART-treated HIV-1 infected children, aviremic (n = 25) or viremic (n = 13). Frequency of naïve and memory B cell subsets was studied by immunostaining. Homing capacity of blood B cells to lymphoid and inflamed tissues was evaluated through CXCR4, CXCR5 and CCR6 expression. Plasma CXCL12 and CXCL13 levels and antibody titers to HBV antigen were determined by ELISA. RESULTS: The frequency of naïve and resting memory (RM) B cells in ART treated children was comparable to control subjects. Profound defects in the homing phenotypes of naïve and memory B cells were identified, with lower CXCR4 and CXCR5 expression. Increased CXCL13 levels were observed in infected children, inversely correlating to CXCR5 expressing B cell subpopulations. Antibody titers to HBV vaccine correlated with frequency of resting and switched memory B cells in HIV-1 infected children. CONCLUSIONS: Homing defects of B cells to germinal center may underlie impaired vaccine responses during HIV-1 infection.

T follicular helper cells and antibody response to Hepatitis B virus vaccine in HIV-1 infected children receiving ART.

HBV vaccine has 95% efficacy in children to prevent HBV infection and related cancer. We conducted a prospective study in HIV-1 infected children receiving ART (n = 49) and controls (n = 63) to assess humoral and cellular responses to HBV vaccine provided with three doses under an accelerated schedule of 4 weeks apart. At 1 month post-vaccination all children, except 4 HIV-1 infected, displayed protective antibody (ab) titers to HBV vaccine; ab titers were lower in infected children (P < 0.0001). Ab titers decreased (P < 0.0001) in both HIV-1 infected and control children at 6 months. The frequency of circulating Tfh (cTFh) cells was 20.3% for controls and 20.8% for infected children prior to vaccination and remained comparable post-vaccination. Cytokine expression by cTfh cells upon activation with HBV antigen was comparable in the two groups at baseline and 1 month post-vaccination. Higher plasma levels (P < 0.0001) of CXCL13 were found in infected children which correlated with cTfh cell frequency at baseline. In conclusion, a lower ab response to HBV vaccine was measured in HIV-1 infected children. The frequency and activation profile of cTfh cells was comparable in infected children and controls suggesting that cells other than Tfh cells are responsible for impaired ab response to HBV vaccine.

Anthropometric Improvement among HIV Infected Pre-School Children Following Initiation of First Line Anti-Retroviral Therapy: Implications for Follow Up.

BACKGROUND: Antiretroviral therapy (ART) is a lifesaving intervention for HIV infected children. There is a scarcity of data on immunological recovery and its relation with growth indicators among HIV infected young children. The current study aims to assess the pattern of anthropometric Z-score improvement following initiation of first-line ART among under-five children and the relationship between anthropometric Z-score improvement and immunologic recovery. METHODS: We included under-five children who were on first-line ART at five major hospitals in Addis Ababa, Ethiopia. We measured anthropometry and collected clinical and laboratory data at follow up, and we retrieved clinical and anthropometric data at ART initiation from records. Z-scores for each of the anthropometric indices were calculated based on WHO growth standards using ENA for SMART 2011 software. Linear regression was used to assess the relationship between time on ART and anthropometric Z-score improvement; and the relationship between anthropometric Z-score improvement and immunologic recovery. Multiple linear regression was used to assess the independent predictors of anthropometric Z-score change. RESULTS: The median age of the participants was 4.1 (Interquartile range (IQR): 3.3-4.9) years. More than half (52.48%) were female. The median duration of follow up was 1.69 (IQR: 1.08-2.63) years. There was a significant improvement in all anthropometric indices at any follow up after initiation of first-line ART (underweight; 39.5% vs16.5%, stunting; 71.3% vs 62.9% and wasting; 16.3% vs 1.0%; p-value< 0.0001). There was an inverse relationship between improvement in weight for age Z-score (WAZ) and duration of ART (R2 = 0.04; F (1, 158); p = 0.013). Height for age Z-score (HAZ) both at the time of ART initiation and follow up has a positive linear relationship with CD4 percentage at follow up (Coef. = 1.92; R2 = 0.05; p-value = 0.002). Duration on ART (Std. Err. = 0.206, t = -1.99, p-value = 0.049) and level of maternal education (Std. Err. = 0.290, t = 2.64, p-value = 0.009) were the only independent predictors of the change in WAZ and change in HAZ at any follow up visit respectively. CONCLUSION: There was a significant improvement in all anthropometric indices at any follow-up after initiation of first-line ART among under-five children. HAZ was linearly related with immunologic recovery following ART initiation. The findings indicate that anthropometric indices could be taken as proxy indicators of immunologic recovery for under-five children.

Impaired Phenotype and Function of T Follicular Helper Cells in HIV-1-Infected Children Receiving ART.

T follicular helper (Tfh) cells are important components in development of specific humoral immune responses; whether the number and biology of Tfh cells is impaired in HIV-1-infected children is not yet studied.The frequency, phenotype, and function of Tfh cells and B cells were determined in blood of HIV-1-infected children receiving antiretroviral therapy (ART) and age-matched controls. Flow cytometry was used to characterize the frequency of Tfh cells and B cell subsets. Cytokine expression was measured after in vitro activation of Tfh cells.A reduced frequency of memory Tfh cells (P < 0.001) was identified in HIV-1-infected children and, on these cells, a reduced expression of programmed death-1 (PD-1) and inducible T cell costimulator (ICOS) (P < 0.001 and P < 0.01). Upon activation, the capacity of Tfh cells to express IL-4, an important cytokine for B cell function, was impaired in HIV-1-infected children.B cell subpopulations in HIV-1-infected children displayed significant differences from the control group: the frequency of resting memory (RM) B cells was reduced (P < 0.01) whereas the frequency of exhausted memory B cells increased (P < 0.001). Interestingly, the decline of RM cells correlated with the reduction of memory Tfh cells (P = 0.02).Our study shows that function and phenotype of Tfh cells, pivotal cells for establishment of adaptive B cell responses, are impaired during HIV-1 infection in children. A consistent reduction of memory Tfh cells is associated with declined frequencies of RM B cells, creating a novel link between dysfunctional features of these cell types, major players in establishment of humoral immunity.