Disparities in access to Dolutegravir in West African children, adolescents and young adults aged 0-24 years living with HIV. A IeDEA Pediatric West African cohort analysis.

Introduction: We describe the 24-month incidence of Dolutegravir (DTG)-containing antiretroviral treatment (ART) initiation since its introduction in 2019 in the pediatric West African IeDEA cohorts. Methods: We included all patients aged 0-24 years on ART, from nine clinics in Côte d'Ivoire (n=4), Ghana, Nigeria, Mali, Benin, and Burkina Faso. Baseline varied by clinic and was defined as date of first DTG prescription; patients were followed-up until database closure/death/loss to follow-up (LTFU, no visit ≥ 7 months), whichever came first. We computed the cumulative incidence function for DTG initiation; associated factors were explored in a shared frailty model, accounting for clinic heterogeneity. Results: Since 2019, 3,350 patients were included; 49% were female;79% had been on ART ≥ 12 months. Median baseline age was 12.9 years (IQR: 9-17). Median follow-up was 14 months (IQR: 7-22). The overall cumulative incidence of DTG initiation reached 35.5% (95% CI: 33.7-37.2) and 56.4% (95% CI: 54.4-58.4) at 12 and 24 months, respectively. In univariate analyses, those aged <5 years and females were overall less likely to switch. Adjusted on ART line and available viral load (VL) at baseline, females >10 years were less likely to initiate DTG compared to males of the same age (aHR among 10-14 years: 0.62, 95% CI: 0.54-0.72; among ≥15 years: 0.43, 95% CI: 0.36-0.50), as were those with detectable VL (> 50 copies/mL) compared to those in viral suppression (aHR: 0.86, 95% CI: 0.77-0.97) and those on PIs compared to those on NNRTIs (aHR after 12 months of roll-out: 0.75, 95% CI: 0.65-0.86). Conclusion: Access to paediatric DTG was incomplete and unequitable in West African settings: children <5years, females ≥ 10 years and those with detectable viral load were least likely to access DTG. Maintained monitoring and support of treatment practices is required to better ensure universal and equal access. Key messages: What is already known on this topic?: Dolutegravir (DTG)-based ART regimens are recommended as the preferred first-line ART regimens recommended by the World Health Organisation in all people living with HIV since 2018, with a note of caution for pregnant women, then confirmed in all children with approved DTG dosing and adolescents since 2019.Deployment of universal DTG access in adults in West Africa has faced challenges such as infrastructure challenges, and healthcare system disparities, and was hindered by initial perinatal safety concerns affecting greatly women of childbearing age.Specific data on access to DTG in children, adolescents and young adults in West Africa is limited.What this study adds ?: This study describes the dynamic of the DTG roll-out over the first 24 months and its correlates since 2019 in a large West African multicentric cohort of children, adolescents and youth.We observed a rapid scale-up of DTG among children, adolescents and young adults living with HIV in West Africa, despite the COVID-19 pandemic.However, DTG access after 24 months was incomplete and unequitable, with adolescent girls and young women being less likely to initiate DTG compared to males, as were those with a detectable viral load (> 50 copies/mL) compared to those in success.Younger children < 5 years were also less likely to initiate DTG, explained by the later approval of paediatric formulations and their low availability.How this study might affect research, practice or policy?: Maintained monitoring, training and updating guidance for healthcare workers is essential to ensure universal access to DTG, especially for females, for whom inequity begins age 10 years.Efforts to improve access to universal DTG in West Africa require multifaceted interventions including healthcare infrastructure improvement and facilitation of paediatric antiretroviral forecasting and planification.

Hepatitis B Virus in West African Children: Systematic Review and Meta-Analysis of HIV and Other Factors Associated with Hepatitis B Infection.

While Hepatitis B virus (HBV) and the human immunodeficiency virus (HIV) are endemic in West Africa, the prevalence of HBV/HIV coinfection and their associated risk factors in children remains unclear. In this review, we sought to assess HBsAg seroprevalence among 0- to 16-year-olds with and without HIV in West African countries and the risk factors associated with HBV infection in this population. Research articles between 2000 and 2021 that reported the prevalence of HBV and associated risk factors in children in West Africa were retrieved from the literature using the Africa Journals Online (AJOL), PubMed, Google Scholar, and Web of Science databases as search tools. StatsDirect, a statistical software, was used to perform a meta-analysis of the retained studies. HBV prevalence and heterogeneity were then assessed with a 95% confidence interval (CI). Publication bias was evaluated using funnel plot asymmetry and Egger's test. Twenty-seven articles conducted across seven West African countries were included in this review. HBV prevalence among persons aged 0 to 16 years was 5%, based on the random analysis, given the great heterogeneity of the studies. By country, the highest prevalence was observed in Benin (10%), followed by Nigeria (7%), and Ivory Coast (5%), with Togo (1%) having the lowest. HBV prevalence in an HIV-infected population of children was (9%). Vaccinated children had lower HBV prevalence (2%) than unvaccinated children (6%). HBV prevalence with a defined risk factor such as HIV co-infection, maternal HBsAg positivity, undergoing surgery, scarification, or being unvaccinated ranged from 3-9%. The study highlights the need to reinforce vaccination of newborns, screening for HBV, and HBV prophylaxis among pregnant women in Africa, particularly in West Africa, to achieve the WHO goal of HBV elimination, particularly in children.

Prevalence of HIV-1 Natural Polymorphisms and Integrase-Resistance-Associated Mutations in African Children.

Integrase inhibitors (INIs) are a potent option for HIV treatment. Limited data exist on INI resistance in West Africa, particularly in children living with HIV/AIDS. We determined the prevalence of integrase gene polymorphisms and the frequency of naturally occurring amino acid (aa) substitutions at positions associated with INI resistance. Dried blood spot (DBS) samples were obtained from one hundred and seven (107) HIV-1-infected children aged less than 15 years old in two West African countries, Benin and Mali. All children were naïve to INI treatment, 56 were naïve to anti-retroviral therapy (ART), and 51 had received ART. Genetic sequencing of HIV integrase was successful in 75 samples. The aa changes at integrase positions associated with INI resistance were examined according to the Stanford HIV Genotypic Resistance database. The median ages were 2.6 and 10 years for ART-naïve and -treated children, respectively. The most common subtypes observed were CRF02_AG (74.7%) followed by CRF06_cpx (20%). No major INI-resistance mutations at positions 66, 92, 121, 143, 147, 148, 155, and 263 were detected. The most prevalent INI accessory resistance mutations were: L74I/M (14/75, 18.6%) followed by E157Q (8/75, 10.6%), G163E/N/T/Q (5/75, 6.6%), Q95A/H/P (2/75, 2.6%), and T97A (4/75, 5.3%). Other substitutions observed were M50I/L/P, H51E/P/S/Q, I72V, T112V, V201I, and T206S. Polymorphisms at positions which may influence the genetic barrier and/or drive the selection of specific INI-resistance pathways were detected. However, no transmitted drug resistance (TDR) to INI was detected among samples of INI-naïve patients. These findings support the use of this treatment class for children with HIV-1, particularly in West Africa.

In-hospital mortality risk stratification in children aged under 5 years with pneumonia with or without pulse oximetry: A secondary analysis of the Pneumonia REsearch Partnership to Assess WHO REcommendations (PREPARE) dataset.

OBJECTIVES: We determined the pulse oximetry benefit in pediatric pneumonia mortality risk stratification and chest-indrawing pneumonia in-hospital mortality risk factors. METHODS: We report the characteristics and in-hospital pneumonia-related mortality of children aged 2-59 months who were included in the Pneumonia Research Partnership to Assess WHO Recommendations dataset. We developed multivariable logistic regression models of chest-indrawing pneumonia to identify mortality risk factors. RESULTS: Among 285,839 children, 164,244 (57.5%) from hospital-based studies were included. Pneumonia case fatality risk (CFR) without pulse oximetry measurement was higher than with measurement (5.8%, 95% confidence interval [CI] 5.6-5.9% vs 2.1%, 95% CI 1.9-2.4%). One in five children with chest-indrawing pneumonia was hypoxemic (19.7%, 95% CI 19.0-20.4%), and the hypoxemic CFR was 10.3% (95% CI 9.1-11.5%). Other mortality risk factors were younger age (either 2-5 months [adjusted odds ratio (aOR) 9.94, 95% CI 6.67-14.84] or 6-11 months [aOR 2.67, 95% CI 1.71-4.16]), moderate malnutrition (aOR 2.41, 95% CI 1.87-3.09), and female sex (aOR 1.82, 95% CI 1.43-2.32). CONCLUSION: Children with a pulse oximetry measurement had a lower CFR. Many children hospitalized with chest-indrawing pneumonia were hypoxemic and one in 10 died. Young age and moderate malnutrition were risk factors for in-hospital chest-indrawing pneumonia-related mortality. Pulse oximetry should be integrated in pneumonia hospital care for children under 5 years.

Derivation and validation of a novel risk assessment tool to identify children aged 2-59 months at risk of hospitalised pneumonia-related mortality in 20 countries.

INTRODUCTION: Existing risk assessment tools to identify children at risk of hospitalised pneumonia-related mortality have shown suboptimal discriminatory value during external validation. Our objective was to derive and validate a novel risk assessment tool to identify children aged 2-59 months at risk of hospitalised pneumonia-related mortality across various settings. METHODS: We used primary, baseline, patient-level data from 11 studies, including children evaluated for pneumonia in 20 low-income and middle-income countries. Patients with complete data were included in a logistic regression model to assess the association of candidate variables with the outcome hospitalised pneumonia-related mortality. Adjusted log coefficients were calculated for each candidate variable and assigned weighted points to derive the Pneumonia Research Partnership to Assess WHO Recommendations (PREPARE) risk assessment tool. We used bootstrapped selection with 200 repetitions to internally validate the PREPARE risk assessment tool. RESULTS: A total of 27 388 children were included in the analysis (mean age 14.0 months, pneumonia-related case fatality ratio 3.1%). The PREPARE risk assessment tool included patient age, sex, weight-for-age z-score, body temperature, respiratory rate, unconsciousness or decreased level of consciousness, convulsions, cyanosis and hypoxaemia at baseline. The PREPARE risk assessment tool had good discriminatory value when internally validated (area under the curve 0.83, 95% CI 0.81 to 0.84). CONCLUSIONS: The PREPARE risk assessment tool had good discriminatory ability for identifying children at risk of hospitalised pneumonia-related mortality in a large, geographically diverse dataset. After external validation, this tool may be implemented in various settings to identify children at risk of hospitalised pneumonia-related mortality.

Nasopharyngeal Viral and Bacterial Co-Detection among Children from Low- and Middle-Income Countries with and without Pneumonia.

The role of microbial coinfection in the pathogenesis of pneumonia in children is not well known. The aim of this work was to describe the prevalence of microorganism co-detection in nasopharyngeal samples (NPS) of pneumonia cases and control subjects and to study the potential association between nasopharyngeal microorganism co-detection and pneumonia. A case-control study was carried out from 2010 to 2014 in nine study sites located in low- or middle-income countries. The data from 888 children under 5 years of age with pneumonia (cases) and 870 children under 5 without pneumonia (controls) were analyzed. Nasopharyngeal samples were collected; reverse transcription polymerase chain reaction (RT-PCR) enabled the detection of five bacteria and 19 viruses. Multiple, mixed-effects logistic regression modeling was undertaken to evaluate the association between microorganism co-detection and pneumonia. A single Streptococcus pneumoniae colonization was observed in 15.2% of the controls and 10.1% of the cases (P = 0.001), whereas S. pneumoniae and a single virus co-detection was observed in 33.3% of the cases and in 14.6% of the controls (P < 0.001). Co-detections with rhinovirus, respiratory syncytial virus, parainfluenza virus, human metapneumovirus, and influenza virus were more frequent in the cases compared with the controls (P < 0.001) and were significantly associated with pneumonia in multiple regression analysis. The proportion of single virus detection without bacterial co-detection was not different between cases and controls (13.6% versus 11.3%, P = 0.13). This study suggests that coinfection of S. pneumoniae and certain viruses may play a role in the pathophysiology of pneumonia in children.

External validation of the RISC, RISC-Malawi, and PERCH clinical prediction rules to identify risk of death in children hospitalized with pneumonia.

BACKGROUND: Existing scores to identify children at risk of hospitalized pneumonia-related mortality lack broad external validation. Our objective was to externally validate three such risk scores. METHODS: We applied the Respiratory Index of Severity in Children (RISC) for HIV-negative children, the RISC-Malawi, and the Pneumonia Etiology Research for Child Health (PERCH) scores to hospitalized children in the Pneumonia REsearch Partnerships to Assess WHO REcommendations (PREPARE) data set. The PREPARE data set includes pooled data from 41 studies on pediatric pneumonia from across the world. We calculated test characteristics and the area under the curve (AUC) for each of these clinical prediction rules. RESULTS: The RISC score for HIV-negative children was applied to 3574 children 0-24 months and demonstrated poor discriminatory ability (AUC = 0.66, 95% confidence interval (CI) = 0.58-0.73) in the identification of children at risk of hospitalized pneumonia-related mortality. The RISC-Malawi score had fair discriminatory value (AUC = 0.75, 95% CI = 0.74-0.77) among 17 864 children 2-59 months. The PERCH score was applied to 732 children 1-59 months and also demonstrated poor discriminatory value (AUC = 0.55, 95% CI = 0.37-0.73). CONCLUSIONS: In a large external application of the RISC, RISC-Malawi, and PERCH scores, a substantial number of children were misclassified for their risk of hospitalized pneumonia-related mortality. Although pneumonia risk scores have performed well among the cohorts in which they were derived, their performance diminished when externally applied. A generalizable risk assessment tool with higher sensitivity and specificity to identify children at risk of hospitalized pneumonia-related mortality may be needed. Such a generalizable risk assessment tool would need context-specific validation prior to implementation in that setting.

Prevalence of cervical HPV infection, sexually transmitted infections and associated antimicrobial resistance in women attending cervical cancer screening in Mali.

OBJECTIVES: To assess the prevalence of sexually transmitted infections (STIs), antimicrobial resistance and cervical lesions among women from Sikasso, Mali. METHODS: Women infected with human immunodeficiency virus (HIV) (n=44) and HIV-negative women (n=96) attending cervical cancer screening were included. Screening for human papillomavirus (HPV), Chlamydia trachomatis (CT), Mycoplasma genitalium (MG), Neisseria gonorrhoeae (NG) and Trichomonas vaginalis (TV) was performed using polymerase chain reaction assays, and herpes simplex virus (HSV-1/2) serological status was assessed using enzyme-linked immunosorbent assays. Antibiotic resistance tests were performed for MG- and NG-positive cases. RESULTS: A high prevalence of high-risk HPV (hrHPV) infection (63%) was found. This was associated with cervical lesions in 7.5% of cases. An unusual distribution was found, with HPV31, HPV56 and HPV52 being the most prevalent. The hrHPV distribution differed by HIV status, with HIV-positive cases having HPV35/31/51-52-56 and HIV-negative cases having HPV31/56/52. The seroprevalence of HSV-2 was 49%, and the prevalence of other STIs was as follows: CT, 4%; MG, 9%; NG, 1%; and TV, 7%. Five of nine MG-positive specimens and the NG strains obtained were resistant to fluoroquinolone. CONCLUSIONS: These results showed high prevalence of hrHPV and fluoroquinolone resistance in several NG and MG strains. Further studies are required to confirm these data in Mali, and to improve prevention, screening and management of cervical cancer and other STIs in women.

Progressive Decline of the Glomerular Filtration Rate in HIV-infected Children Treated With Tenofovir Disoproxil Fumarate-based Regimens in West and Central Africa.

A cross-sectional study of 358 HIV-1-infected children and adolescents living in Sub-Saharan Africa treated with tenofovir disoproxil fumarate-based regimens for a median of 1.5 interquartile range [0.6-3.1 years] showed a loss of glomerular filtration rate estimated to be 0.41 mL/min/1.73 m per month of treatment. In contrast, there was no decrease depending on the duration of the previous antiretroviral treatment.

Characterization of drug resistance and the defective HIV reservoir in virally suppressed vertically infected children in Mali.

BACKGROUND: In the perspective of ART-free HIV remission, vertically infected children treated with suppressive ART from early infancy represent an optimal population model to better understand the genetic complexity of the reservoir. OBJECTIVES: To evaluate the proportion of defective viral population and the genotypic resistance patterns in cell-associated HIV DNA. METHODS: In a cohort including 93 ART-treated vertically HIV-infected (VHIV) children in Mali with plasma HIV-1 RNA ≤50 copies/mL for at least 6 months, we studied total HIV DNA, percentage of defective genomes and resistance by reverse transcriptase and protease bulk sequencing from whole blood in dried blood spots. RESULTS: Children had a median age of 9.9 years at the time of inclusion (IQR = 7.6-13.4) and 3.3 years (IQR = 2-7) at ART initiation; median ART duration was 5.5 years (IQR = 3.7-7.3). The median level of total HIV DNA was 470 copies/106 cells with one patient presenting undetectable HIV DNA (<66 copies/106 cells). We observed the presence of at least one stop codon in viruses from 34 patients (37%). The presence of stop codons was not correlated with the level of HIV DNA or duration of ART. We showed a high prevalence of HIV-1 resistance in DNA with 26% of children harbouring virus resistant to at least one NRTI and 40% to at least one NNRTI. CONCLUSIONS: While these VHIV children were successfully treated for a long time, they showed high prevalence of resistance in HIV DNA and a moderate defective HIV reservoir.

Serotypes of Streptococcus pneumoniae in Children Aged <5 Years Hospitalized With or Without Pneumonia in Developing and Emerging Countries: A Descriptive, Multicenter Study.

BACKGROUND: Improving knowledge regarding Streptococcus pneumoniae distribution in pneumonia cases is important to better target preventive and curative measures. The objective was to describe S. pneumoniae serotypes in children with or without pneumonia. METHODS: It was a case-control study carried out in 8 developing and emerging countries between 2010 and 2014. Cases were children aged <5 years admitted to the hospital for pneumonia. Controls were children admitted for surgery or routine outpatient care. RESULTS: In nasopharyngeal samples, S. pneumoniae were detected in 68.2% of the cases and 47.5% of the controls (P < .001). Nasopharyngeal carriage was associated with a higher risk of being a case in 6/8 study sites (adjusted odds ratio ranged from 0.71 [95% confidence interval [CI], .39-1.29; P = .26] in India [Pune/Vadu] to 11.86 [95% CI, 5.77-24.41; P < .001] in Mongolia). The 13-valent pneumococcal conjugate vaccine (PCV13) serotypes were more frequently detected in cases with nasopharyngeal carriage (67.1%) than in controls with nasopharyngeal carriage (54.6%), P < .001. Streptococcus pneumoniae was detected in blood by polymerase chain reaction in 8.3% of the cases. Of 34 cases with an S. pneumoniae serotype detected in blood, 27 (79%) had the same serotype in the nasopharyngeal sample. CONCLUSIONS: The results confirm the assumption that the isolate carrying or causing disease in an individual is of the same serotype. Most serotypes independently associated with nasopharyngeal carriage or pneumonia are covered by PCV13, suggesting that increased PCV coverage would reduce the burden of S. pneumoniae-related pneumonia.

Stunting and growth velocity of adolescents with perinatally acquired HIV: differential evolution for males and females. A multiregional analysis from the IeDEA global paediatric collaboration.

INTRODUCTION: Stunting is a key issue for adolescents with perinatally acquired HIV (APH) that needs to be better understood. As part of the IeDEA multiregional consortium, we described growth evolution during adolescence for APH on antiretroviral therapy (ART). METHODS: We included data from sub-Saharan Africa, the Asia-Pacific, and the Caribbean, Central and South America regions collected between 2003 and 2016. Adolescents on ART, reporting perinatally acquired infection or entering HIV care before 10 years of age, with at least one height measurement between 10 and 16 years of age, and followed in care until at least 14 years of age were included. Characteristics at ART initiation and at 10 years of age were compared by sex. Correlates of growth defined by height-for-age z-scores (HAZ) between ages 10 and 19 years were studied separately for males and females, using linear mixed models. RESULTS: Overall, 8737 APH were included, with 46% from Southern Africa. Median age at ART initiation was 8.1 years (interquartile range (IQR) 6.1 to 9.6), 50% were females, and 41% were stunted (HAZ<-2 SD) at ART initiation. Males and females did not differ by age and stunting at ART initiation, CD4 count over time or retention in care. At 10 years of age, 34% of males were stunted versus 39% of females (p < 0.001). Females had better subsequent growth, resulting in a higher prevalence of stunting for males compared to females by age 15 (48% vs. 25%) and 18 years (31% vs. 15%). In linear mixed models, older age at ART initiation and low CD4 count were associated with poor growth over time (p < 0.001). Those stunted at 10 years of age or at ART initiation had the greatest growth improvement during adolescence. CONCLUSIONS: Prevalence of stunting is high among APH worldwide. Substantial sex-based differences in growth evolution during adolescence were observed in this global cohort, which were not explained by differences in age of access to HIV care, degree of immunosuppression or region. Other factors influencing growth differences in APH, such as differences in pubertal development, should be better documented, to guide further research and inform interventions to optimize growth and health outcomes among APH.

Lassa and Crimean-Congo Hemorrhagic Fever Viruses, Mali.

We report detection of Lassa virus and Crimean-Congo hemorrhagic fever virus infections in the area of Bamako, the capital of Mali. Our investigation found 2 cases of infection with each of these viruses. These results show the potential for both of these viruses to be endemic to Mali.

Evaluation of Two HIV Rapid Diagnostic Tests in a Context of Strains' Genetic Diversity in Mali.

The rapid diagnostic tests used in most resource-limited countries offer little specificity in the differentiation of HIV-1, HIV-2, and HIV-1 + 2. World Health Organization (WHO) does periodically evaluate rapid tests in use in the South Countries. Despite the prequalification from WHO, it is necessary at local level to conduct comparative studies between the available tests. To do this in Mali, we conducted a cross-sectional study at the University Teaching Hospital Gabriel Touré and the Research and Training Center (SEREFO) of Bamako on 172 samples from retrospective and prospective studies. The goal of this project was to compare the following rapid tests: "HIV TRI-DOT" and OnSite HIV1/2 Ab Plus Combo Rapid Test for screening HIV-1 and HIV-2 to "ImmunoComb II BiSpot" (gold standard). The sensibility and specificity of "HIV TRI-DOT" for HIV-1 detection were 100% each [95% confidence interval (CI): 87.13-100 and 95.31-100]. Its performance for HIV-2 detection was 95.24% (95% CI: 84.21-98.68) (sensibility) and 100% (95% CI: 72.25-100) (specificity). The positive and negative predictive values were, respectively, 100% (95% CI: 91.24-100) and 83.33% (95% CI: 55.20-95.30). The sensibility and specificity of OnSite HIV1/2 Ab Plus Combo Rapid Test assay performance were 100% (95% CI: 87.13-100 and 95.31-100). Overall, OnSite HIV ½ Ab Combo Rapid Test proved to be a good test for warm countries and does not require refrigeration in these settings. Blood and its products can be used to perform the test, unlike "ImmunoComb II BiSpot" and "HIV TRI-DOT," which must be kept cold and cannot be done with whole blood.

Efavirenz and Lopinavir Levels in HIV-Infected Women and Their Nursing Infants, in Mali.

Limited data are currently available on antiretroviral pharmacokinetics in breast milk (BM) and in breastfed infants' blood. To explore these parameters in patients in Mali, we measured plasma antiretroviral levels in human immunodeficiency virus (HIV)-infected mothers and their breastfed infants over 6 months. We specifically analyzed the concentrations of efavirenz (EFV) and lopinavir (LPV) in the plasma of mothers living with HIV and their breastfed infants. Blood samples were collected at delivery and at month 1, 3, and 6 postpartum. EFV and LPV concentrations were measured by liquid chromatography-tandem mass spectrometry. HIV-1 RNA load was measured by Abbott M2000RT RealTime System at delivery and 6 months postpartum for mothers, and at 3 and 6 months postbirth for infants. The median duration of antiretroviral therapy at study inclusion was 57 months [interquartile range (IQR), 0-168 months]. The median EFV ratios of infant plasma/maternal plasma (MP) were 0.057 at month 1, 0.072 at month 3, and 0.048 at month 6. During the study period, the median BM/MP ratio of EFV was 1.16 (IQR, 0.96-20.62), which corresponds to a relative infant dose of 2.46% of the recommended weight-adjusted pediatric EFV dose at month 6. The apparent infant clearance of EFV was 0.146 l/h per kilogram at month 6. The LPV concentrations in the plasma of all infants were undetectable. No drug-related adverse reaction or toxicity was observed in any of the infants. The two women who presented a viral load of >50 copies/ml at month 6 had undetectable plasma drug concentrations at the same period. This study showed that breastfed infants received a low level of EFV but not LPV from their treated mothers.

Burden of Influenza in Less Than 5-Year-Old Children Admitted to Hospital with Pneumonia in Developing and Emerging Countries: A Descriptive, Multicenter Study.

This descriptive 4-year study reports the proportion of detection of influenza viruses in less than 5-year-old children hospitalized for pneumonia in eight developing and emerging countries and describes clinical and microbiological characteristics of influenza-related pneumonia cases. Hospitalized children presenting radiologically confirmed pneumonia aged 2-60 months were prospectively enrolled in this observational standardized study. Mean proportion of isolated influenza virus was 9.7% (95% confidence interval: 7.9-11.8%) among 888 pneumonia children analyzed, with moderate heterogeneity between countries-ranging from 6.2% in Cambodia to 18.8% in Haiti. The clinical characteristics of children with influenza-related pneumonia were not substantially different from those of other pneumonia cases. Influenza A H1N1-related pneumonia cases appeared as more severe than pneumonia cases related to other strains of influenza. Streptococcus pneumoniae was detected more often in blood samples from influenza-related cases than in those without detected influenza viruses (19.7% versus 9.5%, P = 0.018). Influenza-related pneumonia is frequent among children less than 5 years old with pneumonia, living in developing and emerging countries. Influenza might be a frequent etiologic agent responsible for pneumonia or a predisposing status factor for pneumococcal-related pneumonia in this population.

Treatment of retinoblastoma in Sub-Saharan Africa: Experience of the paediatric oncology unit at Gabriel Toure Teaching Hospital and the Institute of African Tropical Ophthalmology, Bamako, Mali.

BACKGROUND: Retinoblastoma (Rb) is the most common intraocular primary malignancy in children. In industrialised countries, the cure rate is about 95%. We present the results of a prospective study on the management of Rb in the paediatric oncology unit of Gabriel Touré Teaching Hospital and African Institute of Tropical Ophthalmology, from November 1, 2011 to December 31, 2015. PROCEDURE: The aims of this prospective study were to evaluate the treatment of localised Rb, ocular prosthesis after enucleation, conservative management for bilateral Rb as well as survival rates in all patients. Patients with early stage Rb at diagnosis were included. The treatment was performed according to the retinoblastoma treatment guidelines of the French-African Paediatric Oncology Group. RESULTS: Eighty-eight patients were included in the study. Sex ratio was 1:1 (M = 44, F = 44). Median age at diagnosis was 3 years (range: 2 months-5 years). Unilateral intraocular Rb was predominant (n = 50; 56.8%). Conservative treatments were performed on nine eyes in nine patients. Overall survival and event-free survival of the entire cohort at the end of 4 years were 73% (95% CI 60.8-81.2%) and 59% (95% CI 47.9-69.5%), respectively, with a median follow-up of 3.7 years (0.1-5.6 years). In conclusion, early enucleation in early stage of Rb can improve outcomes in resource-limited countries. Delayed enucleation and refusal of adherence to treatment are still major concerns and remain a barrier to improving overall patient survival.

Evaluation of a Nutritional Support Intervention in Malnourished HIV-Infected Children in Bamako, Mali.

BACKGROUND: We assessed a nutritional support intervention in malnourished HIV-infected children in a HIV-care program of the University Hospital Gabriel Touré, Bamako, Mali. METHODS: All HIV-infected children younger than 15 years were diagnosed for malnutrition between 07 and 12, 2014. Malnutrition was defined according to the WHO growth standards with Z-scores. Two types were studied: acute malnutrition (AM) and chronic malnutrition (CM). All participants were enrolled in a 6-month prospective interventional cohort, receiving Ready-To-Use Therapeutic Food, according to type of malnutrition. The nutritional intervention was offered until child growth reached -1.5 SD threshold. Six-month probability to catch up growth (>-2 SD) was assessed for AM using Kaplan-Meier curves and Cox model. RESULTS: Among the 348 children screened, 198 (57%) were malnourished of whom 158 (80%) children were included: 97 (61%) for AM (35 with associated CM) and 61 (39%) with CM. Fifty-nine percent were boys, 97% were on antiretroviral therapy, median age was 9.5 years (Interquartile Range: 6.7-12.3). Among children with AM, 74% catch-up their growth at 6-month; probability to catch-up growth was greater for those without associated CM (adjusted Hazard Ratio = 1.97, CI 95%: 1.13 to 3.44). Anemia decreased significantly from 40% to 12% at the end of intervention (P < 0.001). CONCLUSIONS: This macronutrient intervention showed 6-month benefits for weight gain and reduced anemia among these children mainly on antiretroviral therapy for years and aged greater than 5 years at inclusion. Associated CM slows down AM recovery and needs longer support. Integration of nutritional screening and care in the pediatric HIV-care package is needed to optimize growth and prevent metabolic disorders.

High Rates of Baseline Drug Resistance and Virologic Failure Among ART-naive HIV-infected Children in Mali.

BACKGROUND: Limited data exist on drug resistance and antiretroviral treatment (ART) outcomes in HIV-1-infected children in West Africa. We determined the prevalence of baseline resistance and correlates of virologic failure (VF) in a cohort of ART-naive HIV-1-infected children <10 years of age initiating ART in Mali. METHODS: Reverse transcriptase and protease genes were sequenced at baseline (before ART) and at 6 months. Resistance was defined according to the Stanford HIV Genotypic Resistance database. VF was defined as viral load ≥1000 copies/mL after 6 months of ART. Logistic regression was used to evaluate factors associated with VF or death >1 month after enrollment. Post hoc, antiretroviral concentrations were assayed on baseline samples of participants with baseline resistance. RESULTS: One-hundred twenty children with a median age 2.6 years (interquartile range: 1.6-5.0) were included. Eighty-eight percent reported no prevention of mother-to-child transmission exposure. At baseline, 27 (23%), 4 (3%) and none had non-nucleoside reverse transcriptase inhibitor (NNRTI), nucleoside reverse transcriptase inhibitor or protease inhibitor resistance, respectively. Thirty-nine (33%) developed VF and 4 died >1 month post-ART initiation. In multivariable analyses, poor adherence [odds ratio (OR): 6.1, P = 0.001], baseline NNRTI resistance among children receiving NNRTI-based ART (OR: 22.9, P < 0.001) and protease inhibitor-based ART initiation among children without baseline NNRTI resistance (OR: 5.8, P = 0.018) were significantly associated with VF/death. Ten (38%) with baseline resistance had detectable levels of nevirapine or efavirenz at baseline; 7 were currently breastfeeding, but only 2 reported maternal antiretroviral use. CONCLUSIONS: Baseline NNRTI resistance was common in children without reported NNRTI exposure and was associated with increased risk of treatment failure. Detectable NNRTI concentrations were present despite few reports of maternal/infant antiretroviral use.

Qualitative and quantitative HIV antibodies and viral reservoir size characterization in vertically infected children with virological suppression.

Background: Absence of detectable viraemia after treatment cessation in some vertically HIV-infected (VHIV) children suggests that early initiation of HAART could lead to functional cure. Objectives: We described the factors associated with HIV antibody levels and the viral reservoir size in HAART-treated VHIV children. Methods: Study included 97 VHIV children with virological suppression, in Bamako, Mali. The anti-gp41 antibody activities and HIV serostatus were assessed. The viral reservoir size was measured by quantifying total cell-associated HIV DNA. Results: Among the children studied, the median total HIV DNA level was 445 copies/10 6 cells (IQR = 187-914) and the median anti-gp41 antibody activity was 0.29 OD (IQR = 0.18-0.75). Low activity of anti-gp41 antibodies was associated with a younger age of HAART initiation ( P = 0.01). Overall, eight HIV-1 seroreversions were identified. Conclusions: Study identified potential candidates with low viral reservoir and low antibody levels or activities for future trials aiming to reduce HIV-1 reservoir to limit HAART duration.