scholarly journals Defective monocyte enzymatic function and an inhibitory immune phenotype in HIV-exposed uninfected African infants in the era of highly active anti-retroviral therapy

2021 ◽  
Author(s):  
Louise Afran ◽  
Kondwani C Jambo ◽  
Wilfred Nedi ◽  
David J.C Miles ◽  
Anmol Kiran ◽  
...  
Keyword(s):  
B Cell ◽  
Sub Saharan Africa ◽  
Haemophilus Influenzae Type ◽  
Cell Phenotype ◽  
Bacterial Disease ◽  
Enzymatic Function ◽  
Increased Risk ◽  
Hiv Exposure ◽  
Hiv Exposed ◽  
Exposed Uninfected

HIV-Exposed Uninfected (HEU) infants are a rapidly expanding population in Sub Saharan Africa and are highly particularly susceptible to disease caused by encapsulated bacteria in the first year of life. The mechanism of this increased risk is still poorly understood and we therefore, investigated if HIV exposure dysregulates HEU infant immunity and if this is amplified by human herpes infection (HHV). Here, we compared monocyte enzymatic function, innate and adaptive immune cell phenotype, and vaccine-induced antibody responses between HEU and HUU infants. We demonstrate altered monocyte phagosomal function and B cell subset homeostasis, and lower vaccine-induced anti-Haemophilus influenzae type b (Hib) and anti-Tetanus Toxoid (TT) IgG titers in HEU compared to HUU infants. There was no difference in the prevalence of HHV infection between HEU and HUU infants. Our findings suggest that even in the era of ART-mediated viral suppression, HIV exposure dysregulates monocyte and B cell function during a vulnerable period of immune maturation in infancy. This may contribute to the high rates of bacterial disease and pneumonia in HEU infants.

scholarly journals HIV-Exposed Uninfected Infants Show Robust Memory B-Cell Responses in Spite of a Delayed Accumulation of Memory B Cells: an Observational Study in the First 2 Years of Life

2016 ◽  
Vol 23 (7) ◽  
pp. 576-585 ◽  
Author(s):  
Eunice W. Nduati ◽  
Irene N. Nkumama ◽  
Faith K. Gambo ◽  
Daniel M. Muema ◽  
Miguel G. Knight ◽  
...  
Keyword(s):  
B Cells ◽  
B Cell ◽  
Lower Proportion ◽  
Memory B Cells ◽  
Hiv Care ◽  
Enzyme Linked Immunosorbent Assay ◽  
Hiv Exposure ◽  
Hiv Exposed ◽  
The Impact ◽  
Exposed Uninfected

Improved HIV care has led to an increase in the number of HIV-exposed uninfected (HEU) infants born to HIV-infected women. Although they are uninfected, these infants experience increased morbidity and mortality. One explanation may be that their developing immune system is altered by HIV exposure, predisposing them to increased postnatal infections. We explored the impact of HIV exposure on the B-cell compartment by determining the B-cell subset distribution, the frequency of common vaccine antigen-specific memory B cells (MBCs), and the levels of antibodies to the respective antigens in HEU and HIV-unexposed uninfected (HUU) infants born to uninfected mothers, using flow cytometry, a B-cell enzyme-linked immunosorbent spot assay, and an enzyme-linked immunosorbent assay, respectively, during the first 2 years of life. For the majority of the B-cell subsets, there were no differences between HEU and HUU infants. However, HIV exposure was associated with a lower proportion of B cells in general and MBCs in particular, largely due to a lower proportion of unswitched memory B cells. This reduction was maintained even after correcting for age. These phenotypic differences in the MBC compartment did not affect the ability of HEU infants to generate recall responses to previously encountered antigens or reduce the antigen-specific antibody levels at 18 months of life. Although HIV exposure was associated with a transient reduction in the proportion of MBCs, we found that the ability of HEU infants to mount robust MBC and serological responses was unaffected.

scholarly journals 364. Association of Maternal ARV Use with Microcephaly in HIV-Exposed Uninfected Children

2019 ◽  
Vol 6 (Supplement_2) ◽  
pp. S191-S191
Author(s):  
Paige L Williams ◽  
Cenk Yildirim ◽  
Ellen G Chadwick ◽  
Russell B Van Dyke ◽  
Renee Smith ◽  
...  
Keyword(s):  
Hiv Transmission ◽  
In Utero ◽  
Sensitivity Analyses ◽  
Relative Risks ◽  
Perinatal Hiv ◽  
Increased Risk ◽  
Hiv Exposed ◽  
Ongoing Surveillance ◽  
Combination Regimens ◽  
Exposed Uninfected

Abstract Background Perinatal HIV transmission has dramatically decreased with combination antiretroviral (ARV) regimens, but complications among HIV-exposed uninfected (HEU) children, such as microcephaly, warrant ongoing surveillance. Methods We evaluated HEU children enrolled in the Surveillance Monitoring for ART Toxicities (SMARTT) study, a prospective cohort study conducted by the PHACS network at 22 US sites. Microcephaly was defined using 2000 CDC Growth z-scores for head circumference (HC) measured at 6–36 months of age (z-score <−2) and using Nellhaus standards (<2nd percentile) after age 3 (“SMARTT” criteria), or using Nellhaus standards across all ages. Modified Poisson regression models were fit to obtain relative risks (RRs) for associations between in utero ARV exposure and microcephaly status, adjusted for potential confounders. Sensitivity analyses were conducted. Neurodevelopmental functioning was compared between HEU children with vs. without microcephaly. Results Among 3055 SMARTT participants enrolled as of April 2017 with a HC measurement over 5.1 years median follow-up (IQR = 3.0, 7.2), 159 (5.2%, 95% CI: 4.4–6.1%) had microcephaly identified by Nellhaus criteria and 70 (2.3%, 95% CI: 1.8–2.9%) by SMARTT criteria. In adjusted models, in utero exposure to efavirenz (4.7% exposed) was associated with increased risk of microcephaly by both Nellhaus standards (aRR=2.02, 95% CI: 1.16, 3.51) and SMARTT criteria (adjusted RR = 2.56, 95% CI: 1.22, 5.37). These associations were more pronounced among children exposed to combination regimens of efavirenz which included zidovudine+lamivudine than those including tenofovir+emtricitabine (Figure 1). Associations of microcephaly with efavirenz persisted in several sensitivity analyses (Figure 2). Protective associations were observed for darunavir exposure (aRR = 0.50; 95% CI: 0.24, 1.00). HEU children with microcephaly had lower mean scores on neurodevelopmental assessments at ages 1 and 5 years and higher prevalence of impairment than those without microcephaly. Conclusion Efavirenz exposure during pregnancy was associated with a higher risk of microcephaly in infancy and childhood. These findings may support identification of alternatives to efavirenz as part of first-line ARV therapy. Disclosures All authors: No reported disclosures.

Increased Risk of Serious Bacterial Infections Due to Maternal Immunosuppression in HIV-Exposed Uninfected Infants in a European Country

2014 ◽  
Vol 59 (9) ◽  
pp. 1332-1345 ◽  
Author(s):  
C. Taron-Brocard ◽  
J. Le Chenadec ◽  
A. Faye ◽  
C. Dollfus ◽  
T. Goetghebuer ◽  
...  
Keyword(s):  
European Country ◽  
Bacterial Infections ◽  
Increased Risk ◽  
Serious Bacterial Infections ◽  
Hiv Exposed ◽  
Exposed Uninfected

scholarly journals Evaluation of the Relationship between Clinical Outcome of Early Neonatal Sepsis and HIV Exposure in Homa bay County Referral Hospital, Western Kenya

2020 ◽  
Vol 3 (4) ◽  
pp. 139-145
Author(s):  
Mulongo Naulikha Jacqueline ◽  
◽  
O Adoka Samson ◽  
Obonyo Charles ◽  
◽  
...  
Keyword(s):  
Neonatal Sepsis ◽  
Referral Hospital ◽  
Sub Saharan Africa ◽  
Hiv Positive ◽  
Western Kenya ◽  
Maternal Hiv ◽  
Hiv Exposure ◽  
Early Neonatal Sepsis ◽  
Hiv Exposed ◽  
The Relationship

Background: Maternal HIV is the leading cause of both maternal and child morbidity in Sub-Saharan Africa and very little is known about the relationship of HIV exposure and early neonatal sepsis. Objective: To describe the association between maternal HIV and probable or confirmed early neonatal sepsis in Homa Bay County Referral Hospital, Western Kenya. Design: Hospital based cross- sectional study. Study Setting: Homa Bay County Referral Hospital. Subjects/Participants: One hundred and forty two (142) neonates aged 24 hours to 96 hours. Results: Data purposively collected included, characteristics of women and newborns at enrollment, by maternal HIV status and HIV- positive women and their newborns, prevalence of probable or confirmed sepsis, factors in association between maternal HIV infection and probable sepsis in newborns and associations between HIV exposure and probable or confirmed sepsis among newborns and HIV-exposed newborns, 0(0.00%) HIV-positive by 24-hours PCR, prevalence of positive culture 1.6% in HIV-exposed, 1.7% HIV-unexposed with a prevalence ratio: 1.11 (95% CI: 0.05, 8.00) p-value = 0.8615. There was no statistical relationship between clinical outcomes of early neonatal sepsis to HIV exposure. Conclusion: There was no association between maternal HIV and probable or confirmed early neonatal sepsis in Homa Bay County Referral Hospital, Western Kenya.

scholarly journals Maternal Diarrhea and Antibiotic Use are Associated with Increased Risk of Diarrhea among HIV-Exposed, Uninfected Infants in Kenya

2020 ◽  
Vol 102 (5) ◽  
pp. 1001-1008
Author(s):  
Emily L. Deichsel ◽  
Patricia B. Pavlinac ◽  
Dorothy Mbori-Ngacha ◽  
Judd L. Walson ◽  
Elizabeth Maleche-Obimbo ◽  
...  
Keyword(s):  
Antibiotic Use ◽  
Increased Risk ◽  
Hiv Exposed ◽  
Exposed Uninfected

Infections in HIV-exposed Uninfected Children With Focus on Sub-Saharan Africa

2014 ◽  
Vol 33 (10) ◽  
pp. 1085-1086 ◽  
Author(s):  
Mark F. Cotton ◽  
Amy Slogrove ◽  
Helena Rabie
Keyword(s):  
Sub Saharan Africa ◽  
Sub Saharan ◽  
Hiv Exposed ◽  
Exposed Uninfected

scholarly journals Measles Immunity at 4.5 Years of Age Following Vaccination at 9 and 15–18 Months of Age Among Human Immunodeficiency Virus (HIV)–infected, HIV-exposed–uninfected, and HIV-unexposed Children

2018 ◽  
Vol 69 (4) ◽  
pp. 687-696 ◽  
Author(s):  
Eleonora A M L Mutsaerts ◽  
Marta C Nunes ◽  
Martijn N van Rijswijk ◽  
Kerstin Klipstein-Grobusch ◽  
Kennedy Otwombe ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Geometric Mean ◽  
Treatment Interruption ◽  
Enzyme Linked Immunosorbent Assay ◽  
Increased Risk ◽  
Immunodeficiency Virus ◽  
Antibody Titers ◽  
Measles Vaccination ◽  
Hiv Exposed ◽  
Exposed Uninfected

AbstractBackgroundHuman immunodeficiency virus (HIV)–infected and HIV-exposed–uninfected (HEU) children may be at increased risk of measles infection due to waning of immunity following vaccination. We evaluated persistence of antibodies to measles vaccination at 4.5 years of age in HIV-unexposed, HEU, and HIV-infected children with CD4+ ≥25% previously randomized to immediate antiretroviral therapy (ART) interrupted at 12 months (HIV/Immed-ART-12), 24 months (HIV/Immed-ART-24), or when clinically/immunologically indicated (HIV/Def-ART). The HIV/Def-ART group initiated ART by median 5.8 (interquartile range, 4.4–10.3) months of age.MethodsIn this study, HIV-unexposed (n = 95), HEU (n = 84), HIV/Immed-ART-12 (n = 70), HIV/Immed-ART-24 (n = 70), and HIV/Def-ART (n = 62) children were scheduled to receive measles vaccination at age 9 and 15–18 months. Antimeasles serum immunoglobulin G titers were quantified using enzyme-linked immunosorbent assay at 4.5 years.ResultsCompared with HIV-unexposed children (2860 mIU/mL), measles antibody geometric mean titers (GMTs) were significantly lower in both HIV/Immed-ART-12 (571; P < .001) and HIV/Immed-ART-24 (1136; P < .001) but similar in the HIV/Def-ART (2777) and HEU (3242) groups. Furthermore, compared with HIV-unexposed, antibody titers ≥330 mIU/mL (ie, presumed serocorrelate for protection; 99%) were also significantly lower in HIV/Immed-ART-12 (70%; P < .001) and HIV/Immed-ART-24 (83%; P < .001) but similar in the HIV/Def-ART (90%) and HEU (98%) groups.ConclusionsHIV-infected children in whom ART was interrupted at either 12 or 24 months had lower GMTs and lower proportions with seroprotective titers than HIV-unexposed children, indicating a potential downside of ART treatment interruption.Clinical Trials RegistrationNCT00099658 and NCT00102960.

scholarly journals The utility of a modified W.H.O. TB screening tool among children at a Botswana child welfare clinic

2021 ◽  
Vol 21 (1) ◽  
pp. 64-71
Author(s):  
Wame Dikobe ◽  
Mooketsi Molefi ◽  
Bornapate Nkomo ◽  
Botshelo Kgwaadira ◽  
Boingotlo Gasenelwe ◽  
...  
Keyword(s):  
Screening Tool ◽  
World Health ◽  
Resource Limited ◽  
Increased Risk ◽  
Child Welfare Clinic ◽  
Childhood Tb ◽  
History Of ◽  
Hiv Exposure ◽  
Hiv Exposed ◽  
Health Organization

Background: In high TB/HIV settings, the increased risk for TB amongst children exposed to HIV has been established through biomedical tests. Screening HIV exposed children for TB can improve early childhood TB detection and treatment. Objective: This study assessed the utility of a modified World Health Organization (WHO) tool by including HIV variables, to determine TB exposure amongst HIV exposed children presenting to a “Well Child” Clinic (CWC). Methods: Clinical data were obtained from medical records and/or from the caregivers of children presenting to CWC. Data was analyzed to explore factors associated with positive screening for TB, including being exposed to HIV and current HIV status. Results: Five percent (55/1100) screened reported a close TB contact and 21% (n=231) had positive TB symptom screen. History of close TB contact was a risk factor for positive screening for TB symptoms (OR 1.89 CI 1.05-3.4) while being HIV negative was protective (OR 0.3, Cl 0.19-0.62). HIV exposure was associated with increased risk of TB exposure (OR 2.9 CI 1.61-5.19). Conclusion: Integrating HIV variables in the existing WHO screening tool for childhood TB can be useful in early detec- tion and treatment of TB in HIV exposed children in resource limited settings. Keywords: Childhood TB screening; HIV Exposure screening; TB/HIV integration.

scholarly journals 2529. Child HIV Exposure and CMV Seroprevalence in Botswana: No Associations with 24-Month Growth and Neurodevelopment

2019 ◽  
Vol 6 (Supplement_2) ◽  
pp. S879-S879
Author(s):  
Natasha Onalenna Moraka ◽  
Sikhulile Moyo ◽  
Maryanne Ibrahim ◽  
Gloria Mayondi ◽  
Jean Leidner ◽  
...  
Keyword(s):  
Child Growth ◽  
World Health ◽  
Neurodevelopmental Outcomes ◽  
Women Living With Hiv ◽  
Increased Risk ◽  
Z Scores ◽  
Hiv Exposure ◽  
Hiv Exposed ◽  
Living With Hiv ◽  
Cmv Status

Abstract Background HIV-exposed but uninfected (HEU) children are at increased risk for poorer growth outcomes compared with HIV-unexposed/uninfected (HUU) children. Mechanisms underlying the poorer growth and delays in development of HEU children compared HUU children are not fully understood. We sought to define the relationship between child CMV status and HIV− exposure status and determine if a correlation existed between CMV status and growth (and neurodevelopmental) outcomes by 24 months of age in Botswana. Methods We used existing data and samples from the observational Botswana Tshipidi study, pregnant women living with HIV (WLHIV) and those without HIV, as well as their infants were enrolled and followed prospectively through 2 years postpartum. We tested 18-month child plasma samples from all available children for anti-HCMV IgG. We evaluated the association between positive (vs. negative) child CMV status at 18 months, and child growth, using the World Health Organization’s Growth Standard adjusted for age and sex and neurodevelopment at 24 months of age, using the Bayley Scales of Child Development (BSID) III. Results Of 317 children tested for CMV IgG at 18 months, 215 (67.8%) tested positive. Significantly higher proportions of HUU children had positive CMV serology (82.6%) compared with HEU children (47.4%, P < 0.01); 96.7% of HUU vs. 10.5% of HEU children breastfed. Child CMV infection was not associated with head circumference, weight-for-age, weight-for-height, nor height-for-age z-scores at 24 months. BSID III scores in receptive and expressive language, fine and gross motor, and cognitive domains at 24 months of age also did not differ by child CMV status. Conclusion We observed high rates of CMV seropositivity in 18-month-old children in Botswana with significantly higher CMV seropositivity among HUU children likely owing to breastfeeding. Positive CMV serostatus was not associated with child growth or neurodevelopmental outcomes at 24 months. Disclosures All authors: No reported disclosures.

Management of Contacts of Children in Day Care With Invasive Haemophilus influenzae Type b Disease

PEDIATRICS ◽  
1986 ◽  
Vol 78 (5) ◽  
pp. 939-941
Author(s):  
BARRY DASHEFSKY ◽  
ELLEN WALD ◽  
KARL LI
Keyword(s):  
Haemophilus Influenzae ◽  
Day Care ◽  
Care Setting ◽  
The United States ◽  
Haemophilus Influenzae Type ◽  
Bacterial Disease ◽  
Haemophilus Influenzae Type B ◽  
Type B ◽  
American Academy Of Pediatrics ◽  
Increased Risk

Haemophilus influenzae type b (HIB) is the most common cause of serious bacterial disease in children in the United States with 20,000 cases occurring annually. In 1979, it was convincingly reported that this pathogen could spread in households, resuiting in a significantly increased risk of subsequent disease in household contacts.1 Confusion resulting from changing recommendations of the Committee on Infectious Diseases of the American Academy of Pediatrics regarding rifampin prophylaxis for HIB disease2,3 and the recent advent of the HIB vaccine4 prompt this commentary on the management of contacts of children with invasive HIB disease with special emphasis on the day-care setting.

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