Uninfected Children Research Articles

Growth deficits in antiretroviral and HIV-exposed uninfected versus unexposed children in Malawi and Uganda persist through 60 months of age.

To compare childhood physical growth among antiretroviral drug and maternal HIV-exposed uninfected (AHEU) compared with HIV-unexposed uninfected (HUU) children. Longitudinal follow-up of PROMISE trial (NCT01061151) AHEU and age-matched and sex-matched HUU children, enrolled (September 2013 to October 2014) in Malawi and Uganda. We compared WHO population standardized z-scores [height-for-age (HAZ), weight-for-age (WAZ), weight-for-height (WHZ), head-circumference-for-age (HCAZ) at 12, 24, 36, 48, and 60 months of age]. We evaluated HUU versus AHEU [in-utero combination antiretroviral treatment (cART) versus Zidovudine (ZDV) alone]; stratified by country, using longitudinal linear and generalized linear mixed models. Of 466 Malawian and 477 Ugandan children, median maternal age at enrollment was 24.5 years (Malawi) and 27.8 years (Uganda); more than 90% were breastfed through 12 months except Uganda AHEU (64.0%). HAZ scores (adjusted for maternal age, breastfed, and socioeconomic status) were lower among AHEU versus HUU children at every time point, significant (P < 0.05) among Ugandan but not Malawian children. Similar patterns were seen for WAZ but not for WHZ or HCAZ scores. High stunting was observed in both countries, significantly higher in Malawi; and higher among AHEU versus HUU children through 48 months of age, significantly (P < 0.05) among Ugandan but not Malawian children. We found no differences in childhood growth trajectories with in-utero exposures to ZDV compared with cART. AHEU versus HUU children had lower median LAZ and WAZ scores persisting through 60 months of age. However, proportions of children with stunting or underweight decreased after 24 months of age.

T-Cell Homeostatic Imbalance in Placentas From Women With Human Immunodeficiency Virus in the Absence of Vertical Transmission.

Implementation of universal antiretroviral therapy (ART) has significantly lowered vertical transmission rates but has also increased numbers of human immunodeficiency virus (HIV)-exposed uninfected children, who remain vulnerable to morbid effects. In the current study, we investigated whether T-cell alterations in the placenta contribute to altered immune status in HIV-exposed uninfected. We analyzed T cells from term placenta decidua and villous tissue and paired cord blood from pregnant women living with HIV (PWH) who initiated ART late in pregnancy (n = 21) with pregnant women not living with HIV (PWNH) (n = 9). Placentas from PWH showed inverted CD4/CD8 ratios and higher proportions of tissue resident CD8+ T cells in villous tissue relative to control placentas. CD8+ T cells in the fetal capillaries, which were of fetal origin, were positively correlated with maternal plasma viremia before ART initiation, implying that imbalanced T cells persisted throughout pregnancy. In addition, the expanded memory differentiation of CD8+ T cells was confined to the fetal placental compartment and cord blood but was not observed in the maternal decidua. T-cell homeostatic imbalance in the blood circulation of PWH is reflected in the placenta. The placenta may be a causal link between HIV-induced maternal immune changes during gestation and altered immunity in newborn infants in the absence of vertical transmission.

Про роль уреамікоплазмового інфікування в розвитку бронхолегеневої дисплазії у дітей раннього віку

У статті описано літературні дані та власне спостереження уреамікоплазмового інфікування в розвитку бронхолегеневої дисплазії (БЛД) у дітей раннього віку. Бронхолегенева дисплазія як патологія, що виникає у новонароджених дітей після проведення їм реанімаційної допомоги, зокрема кисневої терапії чи штучної вентиляції легень, активно вивчається патоморфологами та клініцистами. Актуальними й недостатньо вивченими на сьогодні залишаються питання ролі інфекції у формуванні БЛД як у недоношених, так і у доношених дітей. Численними дослідженнями показано, що колонізація дихальних шляхів немовляти такими мікроорганізмами, як Chlamy­dia trachomatis, Ureaplasma urealyticum, Mycoplasma hominis, Cytomegalovirus, асоціюється з високим ризиком розвитку БЛД порівняно з неінфікованими дітьми. Ureaplasma urealyticum — найбільш поширені мікроби, які виявлені в зараженій амніотичній рідині, плаценті та респіраторному тракті новонароджених дітей, і їх здатність викликати запалення на цих ділянках беззаперечна. Бронхолегенева дисплазія, що виникає на фоні інфікування даними мікроорганізмами, не обов’язково пов’язана із самими бактеріями, а, швидше за все, розвивається через їх потенційне стимулювання прозапальних цитокінів (TNF, IL-1 і IL-8) або можливого блокування цитокінів (IL-6 і IL-10). Описаний нами клінічний випадок ілюструє роль даних мікроорганізмів у розвитку тяжкої пневмонії з формуванням БЛД у народженої в строк дитини. Особливістю даного випадку є те, що при правильній лікарській тактиці стосовно інфікованої вагітної і, можливо, ранній профілактиці розвитку уреамікоплазмового інфікування немовляти розвиток тяжких незворотних змін у його легенях можна було б уникнути.

Inflammatory cytokine responses in children with asymptomatic malaria infection living in rural, semi-urban and urban areas in south-eastern Gabon.

Cytokines are soluble mediators of the immune response, and their evolution influences the disease outcome. Gaining knowledge on cytokines has become important, as they can constitute biomarkers allowing the diagnosis of malaria and preventing severe forms of the disease. Here, we investigated 10cytokines and their circulating levels in asymptomatic Gabonese children with Plasmodium falciparum infection living in urban, semi-urban and rural areas. Blood samples were collected from 273 schoolchildren (153 uninfected and 120 infected) aged 6 to 192months. Hematological parameters were determined and P. falciparum diagnosis was performed using a rapid diagnosis test, microscopy and nested polymerase chain reaction (PCR). Plasma pro- [interferon (IFN)-γ, tumor necrosis factor (TNF)-α, interleukin (IL)-6, IL-12p70, IL-17A and IL-22] and anti-inflammatory [IL-10, IL-4, IL-13 and transforming growth factor (TGF)-β] cytokine levels were measured by enzyme-linked immunosorbent assay (ELISA) and compared between asymptomatic-infected and uninfected children. Results revealed that without distinction of area, IL-10 and IL-6 levels were higher in infected compared to uninfected children; however, the pro- and anti-inflammatory ratios (IL-6/IL-10 and TNF-α/IL-10) were similar. Furthermore, with area distinction significantly elevated levels of IL-10 in these asymptomatic children were always accompanied by either significantly low or high levels of a proinflammatory cytokine. Also, comparison between asymptomatic-infected children from the three areas showed significantly lower IL-17A, IL-22 and TGF-β levels in urban area compared to semi-urban and rural areas. These results suggest that asymptomatic malaria infections induce significantly high inflammatory cytokine levels without modifying the balanced between pro- and anti-inflammatory cytokines and underline the higher exposure to infections of children in rural areas.

Reproducible Breath Metabolite Changes in Children with SARS-CoV-2 Infection.

SARS-CoV-2 infection is diagnosed through detection of specific viral nucleic acid or antigens from respiratory samples. These techniques are relatively expensive, slow, and susceptible to false-negative results. A rapid noninvasive method to detect infection would be highly advantageous. Compelling evidence from canine biosensors and studies of adults with COVID-19 suggests that infection reproducibly alters human volatile organic compound (VOC) profiles. To determine whether pediatric infection is associated with VOC changes, we enrolled SARS-CoV-2 infected and uninfected children admitted to a major pediatric academic medical center. Breath samples were collected from children and analyzed through state-of-the-art GCxGC-ToFMS. Isolated features included 84 targeted VOCs. Candidate biomarkers that were correlated with infection status were subsequently validated in a second, independent cohort of children. We thus find that six volatile organic compounds are significantly and reproducibly increased in the breath of SARS-CoV-2 infected children. Three aldehydes (octanal, nonanal, and heptanal) drew special attention, as aldehydes are also elevated in the breath of adults with COVID-19. Together, these biomarkers demonstrate high accuracy for distinguishing pediatric SARS-CoV-2 infection and support the ongoing development of novel breath-based diagnostics.

Field evaluation of the gut microbiome composition of pre-school and school-aged children in Tha Song Yang, Thailand, following oral MDA for STH infections.

Soil-transmitted helminths, such as roundworms (Ascaris lumbricoides), whipworms (Trichuris trichiura) and hookworms (Necator americanus and Ancylostoma spp.), are gastrointestinal parasites that occur predominantly in low- to middle-income countries worldwide and disproportionally impact children. Depending on the STH species, health status of the host and infection intensity, direct impacts of these parasites include malnutrition, anaemia, diarrhoea and physical and cognitive stunting. The indirect consequences of these infections are less well understood. Specifically, gastrointestinal infections may exert acute or chronic impacts on the natural gut microfauna, leading to increased risk of post-infectious gastrointestinal disorders, and reduced gut and overall health through immunomodulating mechanisms. To date a small number of preliminary studies have assessed the impact of helminths on the gut microbiome, but these studies are conflicting. Here, we assessed STH burden in 273 pre-school and school-aged children in Tha Song Yang district, Tak province, Thailand receiving annual oral mebendazole treatment. Ascaris lumbricoides (107/273) and Trichuris trichiura (100/273) were the most prevalent species and often occurred as co-infections (66/273). Ancylostoma ceylanicum was detected in a small number of children as well (n = 3). All of these infections were of low intensity (<4,999 or 999 eggs per gram for Ascaris and Trichuris respectively). Using this information, we characterised the baseline gut microbiome profile and investigated acute STH-induced alterations, comparing infected with uninfected children at the time of sampling. We found no difference between these groups in bacterial alpha-diversity, but did observe differences in beta-diversity and specific differentially abundant OTUs, including increased Akkermansia muciniphila and Bacteroides coprophilus, and reduced Bifidobacterium adolescentis, each of which have been previously implicated in STH-associated changes in the gut microfauna.

The Danish HIV Birth Cohort (DHBC) - a nationwide, prospective cohort

PurposeThe purpose of the Danish HIV Birth Cohort (DHBC) is to investigate the significance of HIV-1 infection in pregnancy and after delivery in women living with HIV (WLWH) in Denmark...

State of iodine supply in children with chronic gastroduodenitis

Objective — to study the state of iodine supply in children with chronic gastroduodenal pathology.&#x0D; Materials and methods. The study included 23 children with chronic gastroduodenitis: 13 girls (56 %) and 10 boys (43.5 %) aged 8 to 18 years. The control group consisted of 11 children matched in age and sex. All patients underwent endoscopic examination of the upper digestive tract. H. pylori infection was tested with a rapid urease breathing test «Helik‑test». All children underwent determination of iodine level in single portions of urine using the cerium‑arsenite method Sandell‑Koltoff modified by Dunn, with the following calculation of the median.&#x0D; Results. The frequency of iodine deficiency in children with chronic gastroduodenitis was 60.9 ± 10.2 %, which significantly exceeded this parameter in the control group (8.7 ± 8.6 %; p &lt; 0.01). A mild degree of iodine deficiency was noted in 43.5 ± 10.3 % of patients, which was also significantly higher than in the control group (9.09 ± 8.6 %; p &lt; 0.05). Moderate iodine deficiency was observed only in children of the main group (21.7 ± 8.5 %). Severe iodine deficiency in the study was not found among all children. The median ioduria in patients was 81.9 mg/l, which was significantly lower than in children in control group (183.7 mg/l; p &lt; 0.05). Analysis of ioduria level, taking into consideration the endoscopic picture of gastrointestinal tract lesions, showed that both in frequency (p &lt; 0.05) and median (p &lt; 0.05), children with a more severe inflammation of the gastric mucosa and duodenum had the worst indices of iodine supply. In children infected with H. pylori iodine deficiency was observed significantly more often (p &lt; 0.05), the median ioduria was significantly lower (p &lt; 0.05) than in uninfected children.&#x0D; Conclusions. In children with chronic gastroduodenal pathology, a significant frequency of iodine deficiency is revealed, which increases with the severity of inflammatory changes in the mucous membrane and the presence of H. pylori infection. Determination of the state of iodine supply in children with digestive tract pathology is advisable to prevent the development of concomitant diseases, primarily thyroid dysfunction.&#x0D;

Impact of in-utero antiretroviral drug exposure on expression of membrane-associated transporters in mouse placenta and fetal brain.

Although antiretroviral therapy (ART) during pregnancy is effective in limiting vertical HIV transmission, adverse outcomes persist amongst uninfected children exposed to antiretroviral drugs in utero. Membrane-associated drug transporters, metabolic enzymes, and tight junction proteins play important roles in adult antiretroviral drug disposition and toxicity; however, the fetal expression of these proteins in the context of ART, and their impact on in-utero antiretroviral drug distribution remain poorly understood. This study aimed to characterize the role of these proteins in modulating in-utero antiretroviral drug exposure. Pregnant mice were exposed to an ART regimen consisting of lamivudine, abacavir, atazanavir, and ritonavir, at clinically relevant doses. Fetal brain, liver, placenta amniotic fluid, and maternal plasma were collected on gestational day 18.5 and concentration of antiretroviral drugs in fetal tissues was measured by LC/MS/MS, whereas transporter expression was assessed by qPCR. Abacavir and lamivudine were detected in fetal brain and amniotic fluid, whereas atazanavir and ritonavir were detected in amniotic fluid only. Robust mRNA expression of key transporters was observed in adult and fetal tissues, and sex differences were identified in the expression of Abcc1 and Slc29a1 in the placenta. Antiretroviral drug exposure was associated with a reduction in relative placental Abcg2, Abcc1, and Slc29a1 expression. These findings identify a novel effect of fetal sex and antiretroviral drug treatment on the expression of placental transporters in a mouse model, and characterize the penetration of lamivudine and abacavir into fetal brain, uncovering a potential role of transporters in modulating fetal exposure to antiretroviral drugs.

Community-acquired bacteremia among HIV-infected and HIV-exposed uninfected children hospitalized with fever in Mozambique

Background:Bacteremia is a major cause of morbidity and mortality worldwide. Children infected with HIV present with patterns of bacteremia generally associated with poor prognosis. In Mozambique, data on bacteremia are sparce.Methods:We conducted an observational study of HIV-infected and HIV-exposed uninfected children, aged 0–59 months, hospitalized with fever between April 1, 2016 and February 28, 2019. A single bacterial culture was collected at admission. Descriptive statistics were used to summarize microorganisms detected and antibiotic susceptibility testing.Results:A total of 808 HIV-infected (90%) and HIV-exposed uninfected (10%) children were enrolled. Blood culture positivity was 12% (95% CI: 9.9%–14.4%). Five organisms accounted for most cases: Staphylococcus Aureus (37%), Klebsiella spp (11%), Salmonella spp (11%), Escherichia Coli (9%) and Micrococcus (7%). Antibiotic resistance was common. Nearly 70% of Staphylococcus Aureus were methicillin-resistant and roughly 50% of Klebsiella had ESBL production.Conclusion:Community-acquired bacteremia was common in HIV-infected and HIV-exposed uninfected children hospitalized in Mozambique with a febrile illness. High rates of MRSA and ESBL producing organisms has implications for empiric antibiotics utilized in Mozambique. Longitudinal data on the prevalence and antimicrobial resistance patterns of important pathogens are badly needed to guide policy for drug formulary expansion and antibiotic prescription guidelines.

Evaluation of the BioFire® FilmArray® Meningitis/Encephalitis panel in an adult and pediatric Ugandan population

BackgroundMeningitis causes significant mortality in sub-Saharan Africa and limited diagnostics exist. We evaluated the utility of the BioFire® FilmArray® Meningitis/Encephalitis multiplex PCR panel (BioFire ME) in HIV-infected adults and HIV-infected and uninfected children presenting with suspected meningitis in Uganda. MethodsWe tested cerebrospinal fluid (CSF) using a stepwise meningitis diagnostic algorithm including BioFire ME. We determined the diagnostic performance of BioFire ME for cryptococcal meningitis, using cryptococcal antigen (CrAg) and CSF culture as reference standards, and assessed other central nervous system (CNS) pathogens identified by the panel. ResultsWe evaluated 328 adult and 42 pediatric CSF specimens using BioFire ME. Of the adult CSF samples tested, 258 were obtained at baseline, and 70 were obtained from repeat lumbar punctures in cryptococcal meningitis. For Cryptococcus, sensitivity was 82%, specificity was 98%, PPV was 98%, and NPV was 79% in baseline specimens using CSF CrAg as the reference standard. Among follow-up specimens, a negative BioFire ME for Cryptococcus predicted CSF culture sterility with 84% NPV. Overall sensitivity was decreased at low fungal burdens: 29% for 0–99 Cryptococcus CFU/mL compared to 94% for ≥100 CFU/mL in baseline specimens. Other pathogens detected included E. Coli, H. influenzae, S. pneumoniae, CMV, enterovirus, HSV, HHV-6, and VZV. Two specimens tested positive for S. pneumoniae and one for Cryptococcus in the pediatric population. ConclusionsMultiplex PCR is a promising rapid diagnostic test for meningitis in adults and children in resource-limited settings. Cryptococcus at low fungal burdens in CSF may be missed by BioFire ME.

Dried Blood Specimens as an Alternative Specimen for Immune Response Monitoring During HIV Infection: A Proof of Concept and Simple Method in a Pediatric Cohort.

Programs to prevent mother-to-child HIV transmission do not reduce the number of infants exposed during pregnancy and breastfeeding. HIV-exposed but uninfected children (HEU) present higher risk of morbidity and mortality than HIV-unexposed and uninfected children (UU). In this line, the study of immune biomarkers in HIV could improve prediction of disease progression, allowing to diminish comorbidity risk. Dried blood specimens (DBS) are an alternative to serum for collecting and transporting samples in countries with limited infrastructure and especially interesting for groups such as pediatrics, where obtaining a high sample volume is challenging. This study explores the usefulness of DBS for immune profile monitoring in samples from 30 children under clinical follow-up in Kinshasa: 10 HIV-infected (HIV+), 10 HEU, and 10 UU. We have measured the gene expression levels of 12 immune and inflammatory markers (CD14, IL-6, TNFα, HVEM, B7.1, HIF-1α, Siglec-10, IRAK-M, CD163, B7H5, PD-L1, and Galectin-9) in DBS samples by reverse transcription of total RNA and RT-qPCR. Principal component analysis, Kruskal–Wallis test, and Mann–Whitney test were performed in order to study group differences. HIV+ children presented significantly higher levels of seven biomarkers (CD14, IL-6 HVEM, B7.1, Siglec-10, HIF-1α, and CD163) than the UU group. In HEU, we found seven biomarkers significantly elevated (CD14, IL-6, HVEM, B7.1, Siglec-10, HIF-1α, and IRAK-M) vs. UU. Six biomarkers (CD14, IL-6, HVEM, B7.1, Siglec-10, and HIF-1α) showed a significantly higher expression in both HIV+ and HEU vs. UU, with HVEM and CD14 being significantly overexpressed among HIV+ vs. HEU. Our data reveal the utility of DBS for immune response monitoring. Moreover, significant differences in specific biomarker expression across groups strongly suggest the effect of HIV infection and/or HIV exposure on these immune biomarkers' expressions.

School functioning of children with perinatal HIV-infection in high-income countries: A systematic review.

IntroductionSince the introduction of combination antiretroviral therapy, human immunodeficiency virus (HIV) infection is a manageable chronic disease. However, school-age children (4–18 years) living with HIV could still experience problems with functioning at school, due to the impact of the virus itself, medication, comorbidities and social stigma. School functioning covers academic achievement, school attendance, and social relationships and is of utmost importance to optimize normal participation.MethodsTo gain insight in school functioning problems of perinatally HIV-infected children, we performed a systematic review of the literature in multiple databases from January 1997 up to February 2019. Studies were included if they described outcomes of school functioning of school-age children perinatally infected with HIV, in high-income countries. Meta-analyses were performed for sufficiently comparable studies.Results and discussionResults from 32 studies show that HIV-infected children experience more problems in various areas of school functioning in comparison with national norms, matched healthy controls, siblings and HIV-exposed uninfected (HEU) children. The most pronounced differences concerned the usage of special educational services, general learning problems, and mathematics and reading performance scores. Comparisons with both national norms and siblings/HEU children show that the differences between HIV-infected children and siblings/HEU children were less pronounced. Moreover, siblings/HEU children also reported significantly worse outcomes compared to national norms. This suggests that problems in school functioning cannot be solely attributed to the HIV-infection, but that multiple socio-economic and cultural factors may play a role herein.ConclusionPerinatally HIV-infected children seem vulnerable to problems in various areas of school functioning. Therefore, monitoring of school functioning should be an important aspect in the care for these children. A family-focused approach with special attention to a child’s socio-environmental context and additional attention for siblings and HEU children, is therefore recommended.

Mitochondrial DNA Instability Is Common in HIV-Exposed Uninfected Newborns.

Worldwide, one million HIV-exposed uninfected (HEU) children are born yearly, and chronic health impairments have been reported in these children. Mitochondrial DNA (mtDNA) instability and altered mtDNA content have been evidenced in these children, but an exhaustive characterization of altered mitochondrial genomes has never been reported. We applied deep mtDNA sequencing coupled to the deletion identification algorithm eKLIPse to the blood of HEU neonates (n = 32), which was compared with healthy controls (n = 15). Dried blood spots (DBS) from African HEU children were collected seven days after birth between November 2009 and May 2012. DBS from French healthy controls were collected at birth (or <3 days of life) in 2012 and in 2019. In contrast to the absence of mtDNA instability observed at the nucleotide level, we identified significant amounts of heteroplasmic mtDNA deletions in 75% of HEU children and in none of controls. The heteroplasmy rate of the 62 mtDNA deletions identified varied from 0.01% to up to 50%, the highest rates being broadly compatible with bioenergetic defect and clinical expression. mtDNA integrity is commonly affected in HEU neonates. The nature of the deletions suggests a mechanism related to aging or tumor-associated mtDNA instability. This child population may be at risk of additional mtDNA genetic alterations considering that they will be exposed to other mitotoxic drugs including antiretroviral or anti-tuberculosis treatment.

Association of nasopharyngeal viruses and pathogenic bacteria in children and their parents with and without HIV

BackgroundBacteria and respiratory viruses co-occur in the nasopharynx, and their interactions may impact pathogenesis of invasive disease. Associations of viruses and bacteria in the nasopharynx may be affected by HIV.MethodsWe conducted a nested case-control study from a larger cohort study of banked nasopharyngeal swabs from families with and without HIV in West Bengal India, to look at the association of viruses and bacteria in the nasopharynx of parents and children when they are asymptomatic. Quantitative polymerase chain reaction for 4 bacteria and 21 respiratory viruses was run on 92 random nasopharyngeal swabs from children--49 from children living with HIV (CLH) and 43 from HIV uninfected children (HUC)-- and 77 swabs from their parents (44 parents of CLH and 33 parents of HUC).ResultsBacteria was found in 67% of children, viruses in 45%, and both in 27% of child samples. Staphylococcus aureus (53%) was the most common bacteria, followed by Streptococcus pneumoniae (pneumococcus) (37%) in children and parents (53, 20%). Regardless of HIV status, viruses were detected in higher numbers (44%) in children than their parents (30%) (p = 0.049), particularly rhinovirus (p = 0.02). Human rhinovirus was the most frequently found virus in both CLH and HUC. Children with adenovirus were at six times increased risk of also having pneumococcus (Odds ratio OR 6, 95% CI 1.12–31.9) regardless of HIV status. In addition, the presence of rhinovirus in children was associated with increased pneumococcal density (Regression coeff 4.5, 1.14–7.9). In CLH the presence of rhinovirus increased the risk of pneumococcal colonization by nearly sixteen times (OR 15.6, 1.66–146.4), and, pneumococcus and S. aureus dual colonization by nearly nine times (OR 8.7).ConclusionsChildren more frequently carried viruses regardless of HIV status. In CLH the presence of rhinovirus, the most frequently detected virus, significantly increased co-colonization with pneumococcus and S. aureus.

Multivariate approach for longitudinal analysis of brain metabolite levels from ages 5-11 years in children with perinatal HIV infection

Treatment guidelines recommend that children with perinatal HIV infection (PHIV) initiate antiretroviral therapy (ART) early in life and remain on it lifelong. As part of a longitudinal study examining the long-term consequences of PHIV and early ART on the developing brain, 89 PHIV children and a control group of 85 HIV uninfected children (HIV-) received neuroimaging at ages 5, 7, 9 and 11 years, including single voxel magnetic resonance spectroscopy (MRS) in three brain regions, namely the basal ganglia (BG), midfrontal gray matter (MFGM) and peritrigonal white matter (PWM). We analysed age-related changes in absolute metabolite concentrations using a multivariate approach traditionally applied to ecological data, the Correlated Response Model (CRM) and compared these to results obtained from a multilevel mixed effect modelling (MMEM) approach. Both approaches produce similar outcomes in relation to HIV status and age effects on longitudinal trajectories. Both methods found similar age-related increases in both PHIV and HIV- children in almost all metabolites across regions. We found significantly elevated GPC+PCh across regions (95% CI=[0.033; 0.105] in BG; 95% CI=[0.021; 0.099] in PWM; 95% CI=[0.059; 0.137] in MFGM) and elevated mI in MFGM (95% CI=[0.131; 0.407]) among children living with PHIV compared to HIV- children; additionally the CRM model also indicated elevated mI in BG (95% CI=[0.008; 0.248]). These findings suggest persistent inflammation across the brain in young children living with HIV despite early ART initiation.

Association Between Dyslipidemia and Helicobacter Pylori Infection

Introduction: The association between Helicobacter pylori infection and elevated plasma levels of LDL cholesterol and decreased HDL cholesterol has been reported. Objective: To determine the frequency of altered plasma levels of LDL cholesterol, HDL cholesterol and triglycerides in pediatric patients with Helicobacter pylori infection. Materials and Methods: Prospective, observational and analytical study. Pediatric patients with Helicobacter pylori infection, July 2019 - June 2020 period. Exclusion criteria: Obesity, diabetes mellitus, hypothyroidism, hepatopathy, nephropathy, collagen disease, corticotherapy, use of proton pump inhibitors and H2 antihistamines. Antibodies against Helicobacter pylori and plasma levels of total cholesterol, LDL cholesterol, HDL cholesterol and triglycerides were studied. Two groups of patients: Those with Helicobacter pylori infection and the other of uninfected children. Results: Patients attended: 39; studied: 22; excluded: 17. Group of non-infected: 25.Triglyceride levels (mg/dL) were 117 + -21 in patients with Helicobacter pylori and 98 + -19 in those not infected (p = 0.01); HDL cholesterol levels (mg/dL), 39 + -14 in those infected and 47 + -13 in patients without Helicobacter pylori infection (p = 0.03). Conclusions:Patients with Helicobacter pylori infection had a higher frequency of dyslipidemia, compared to the group of uninfected children.

Cytokine Levels and Micronutrient Status in Ascaris lumbricoides - Infected Nigerian School Children after Albendazole Treatment

Background Intestinal helminth infection is associated with altered immune responses and deranged micronutrient status in infected children. There is no information on the status of serum cytokine levels and micronutrient status in Ascaris lumbricoides infected Nigerian school children at pre- and post- albendazole anti-helminthic treatment. Aim To provide data on serum levels of cytokines and micronutrients in Ascaris lumbricoides infected Nigerian children at pre- and post- albendazole anti-helminthic treatment. Method This case-control prospective study assessed serum levels of micronutrients (zinc, iron, selenium, vitamin A, vitamin C), transferrin and cytokines (TNF–α, IFN–γ, IL-6, IL-8, IL-4 and IL-10) in 46 Ascaris lumbricoides infected and 40 uninfected Nigerian school children before and after anthelminthic treatment using Atomic Absorption Spectrophotometry, high performance liquid chromatography (HPLC) and Enzyme Linked Immunosorbent Assay (ELISA) as appropriate. Data were analysed using Mann-Whitney U test, Wilcoxon Signed Ranks Test and Kruskal Wallis Test, with levels of significance set at α0.05. Results More males than females were infected with helminthes and most helminth infected schoolchildren were within 5-9yrs of age. Ascaris lumbricoides has the highest prevalence. Most (77%) children were infected with Ascaris lumbricoides and 2% of the children had co-infection of Ascaris lumbricoides with hookworms and Trichuris trichiuria. Pre-albendazole anti-helminth treatment, serum zinc and vitamin A levels were significantly lower (p=0.044 and p=0.002 respectively) while transferrin, selenium, IL-8, IL-6, IFN–γ and IL-4 levels were significantly higher (p=0.001, p=0.032, p=0.014, p=0.001, p=0.014 and p=0.010 respectively) in Ascaris lumbricoides-infected group compared with controls. Serum vitamin A levels were significantly higher at one month (p=0.001) and two months (p=0.001) post-albendazole treatment while IL-8 (p=0.031) was significantly lower at one month compared with pre-treatment values. Conclusion Inflammation, zinc and vitamin A deficiencies associated with A. lumbricoides infection in Nigerian children were reversed from one month of albendazole. Recommendation Periodic anthelminthic drug treatment coupled with taking diet containing zinc and vitamin A by school children is recommended. Keywords: Albendazole, Ascaris lumbricoides, Cytokines, Zinc, Vitamin A, School children.

Effects of TNF-α and IL-10-819 T>C single nucleotide polymorphisms on urogenital schistosomiasis in preschool children in Zimbabwe.

BackgroundKnowledge gaps exist between host genetic factors and susceptibility to schistosomiasis.ObjectiveThis study determined cytokine levels and single nucleotide polymorphisms of tumour necrosis factor (TNF)-α (rs1800629) and interleukin (IL)-10 (rs1800871) and their possible impact on susceptibility to schistosomiasis in preschool-age children in the Madziva area of Shamva district, Mashonaland Central province, Zimbabwe.MethodsUrogenital schistosomiasis was diagnosed using the urine filtration method, while a sandwich enzyme-linked immunosorbent assay was used for cytokine level determination. The survey was done in August 2015 and reinfection levels post treatment were assessed at 3, 6 and 12 months. Amplification refractory mutation system polymerase chain reaction with visualisation on 2% agarose gel electrophoresis was used for genotyping.ResultsSchistosomiasis prevalence was found to be 10.5% (59/563). Reinfections were detected in only six children at 3 months and only one was reinfected at 12 months. There were no significant differences in TNF-α-308 G/A allele or genotype frequencies between the Schistosoma haematobium infected participants (p = 0.360) and uninfected participants (p = 0.279). However, no children with the IL-10-819 TT genotype had schistosomiasis. The TNF-α GG genotype corresponded with significantly lower TNF-α levels when compared with the GA or AA genotypes (p < 0.001), and TNF-α levels were significantly lower in infected children compared to uninfected children (p < 0.001).ConclusionHigher TNF-α levels and lower IL-10 levels are potentially protective against schistosomiasis infection. The IL-10-819 TT genotype is potentially protective against infection through its association with lower IL-10 levels.

Bordetella pertussis in School-Age Children, Adolescents, and Adults: A Systematic Review of Epidemiology, Burden, and Mortality in Africa.

The Global Pertussis Initiative recommends diphtheria–tetanus–pertussis (DTP3) vaccination of infants aged < 1 year for all African countries, and recommends the vaccination of pregnant women as a primary prevention strategy. However, the role of older children and adults in the transmission of pertussis in Africa is not clear. A systematic search of MEDLINE, EMBASE, and BIOSIS was undertaken to identify studies published between 1 January 1990 and 17 June 2019, with information on pertussis epidemiology, burden of illness, and mortality in school-aged children, adolescents, and adults in Africa. Studies identified for inclusion were reviewed narratively because a statistical comparison was not possible because of the mix of methodologies used.Studies from North Africa (Morocco, Tunisia, and Algeria) reported that although DTP4 vaccine coverage is high, severe pertussis-related complications persist in young children, vaccine-acquired immunity wanes in adolescents, and household contacts are important transmitters of infection. A serosurvey in Gambia showed that 6% of the general population had pertussis antibody levels suggesting recent infection, and studies from Senegal showed that pertussis infection was endemic despite high DTP3 coverage. During a pertussis outbreak in Ethiopia, the case fatality rate was 3.7% overall, and 6.3% among children aged 5–9 years. In a case-surveillance study in South Africa, the incidence of pertussis among hospitalized children was 526/100,000, and infection rates were higher in HIV-exposed and -infected children compared with uninfected children. In conclusion, the highest burden of pertussis in Africa is among infants, and surveillance is lacking in many African countries meaning that the burden of pertussis among infants and infection rates among older children and adults are not well reported, and likely underestimated.Electronic supplementary materialThe online version of this article (doi:10.1007/s40121-021-00442-6) contains supplementary material, which is available to authorized users.