Impact of perinatal HIV exposure and infection on salivary properties among Nigerian children.

BACKGROUND: There is growing evidence that perinatal HIV infection and exposure affect salivary pH and flow rate in children in most parts of the world, but not against the background of caries and the African demographic. This study aimed to evaluate the impact of HIV infection as well as exposure on salivary properties and their influence upon the dental caries experience among school-aged children in Nigeria. METHOD: This cross-sectional study assessed the salivary flow rates and salivary pH of HIV infected and exposed school-aged (4-11) children receiving care at a Nigerian tertiary hospital. A total of 266 consenting participants which comprised of three groups as follows: (1) HIV Infected (HI) (n = 87), (2) HIV Exposed and Uninfected (HEU) (n = 82) and (3) HIV Unexposed and Uninfected (HUU) (n = 97) were recruited for the study. Questionnaires completed by parents/guardians were used for data collection. Three calibrated dentists performed oral examinations for dental caries. International Caries Detection and Assessment Scores (ICDAS) was used and presented as dmft/DMFT. Salivary pH was measured using MColourpHast™ pH indicator strips, while salivary flow rate was determined by collecting unstimulated whole saliva using the suction method. Data analysis relied on comparative statistics to determine the correlation between HIV exposure and infection on salivary pH and flow rates. RESULT: Across the groups, (HI, HEU, and HUU) mean pH of the HI was significantly less than that of HEU and HUU. Similarly, there was a statistically significant difference in the SFR across the three groups (p = 0.004). Other variables such as gender, age and oral hygiene status expressed by the gingival inflammatory scores had no significant influence on the pH and SFR of study participants. There was a rather unexpected positive correlation of DMFT of HI and HEU groups with increasing salivary flow rate; though, the relationship was weak and not significant. CONCLUSION: Perinatal HIV exposure and infection significantly impact salivary pH and flow rate among school-aged children in Nigeria. The findings of this study imply that HIV infection influenced the salivary pH, while HIV maternal exposure (without infection) impacted salivary flow rates when compared to the controls.

Prevalence and associated factors of enamel developmental defects among Nigerian children with perinatal HIV exposure.

To evaluate the prevalence and pattern of developmental defects of the enamel (DDE) and their risk factors among children born infected with Human Immunodeficiency Virus (HIV) and those born to HIV-infected mothers compared with their unexposed counterparts (i.e., children born to uninfected mothers). This was an analytic cross-sectional study evaluating the presence and pattern of distribution of DDE in three groups of school-aged children (age, 4-11 years) receiving care and treatment at a Nigerian tertiary hospital, comprising: (1) HIV-infected (HI) on antiretroviral therapy (ART) (n = 184), (2) HIV-exposed but uninfected (HEU) (n = 186) and (3) HIV-unexposed and uninfected (HUU) (n = 184). Data capture forms and questionnaires were used to record the children's medical and dental history based on clinical chart review and recall from their parents/guardians. Dental examinations were performed by calibrated dentists blinded to the study grouping. CD4+ (Cluster of Differentiation) T-cell counts were assayed for all participants. The diagnosis of DDE corresponded with the codes enumerated in the World Dental Federation's modified DDE Index. Analyses relied on comparative statistics to determine risk factors associated with DDE. A total of 103 participants distributed among the three groups presented with at least one form of DDE, which indicated a prevalence of 18.59%. The HI group had the highest frequency of DDE-affected teeth (4.36%), while that of the HEU and HUU groups were 2.73% and 2.05%, respectively. Overall, the most encountered DDE was code 1 (Demarcated Opacity), accounting for 30.93% of all codes. DDE codes 1, 4 and 6 showed significant associations with the HI and HEU groups in both dentitions (p < 0.05). We found no significant association DDE and either very low birth weight or preterm births. A marginal association with CD4+ lymphocyte count was observed in HI participants. DDE is prevalent in school-aged children, and HIV infection is a significant risk factor for hypoplasia, a common form of DDE. Our results were consistent with other research linking controlled HIV (with ART) to oral diseases and reinforce advocacies for public policies targeted at infants exposed/infected perinatally with HIV.

Age-specific associations with dental caries in HIV-infected, exposed but uninfected and HIV-unexposed uninfected children in Nigeria.

BACKGROUND: HIV infection and its management confer a substantial health burden to affected individuals and have been associated with increased risk of oral and dental diseases. In this study, we sought to quantify HIV-associated differences in the prevalence and severity of dental caries in the primary and permanent dentition of 4-11-year-old Nigerian Children. METHODS: We used clinical, laboratory, demographic, and behavioral data obtained from an ongoing cohort study of age-matched HIV-infected (HI, n = 181), HIV-exposed-but-uninfected (HEU, n = 177), and HIV-unexposed-and-uninfected (HUU, n = 186) children. Measures of dental caries experience (i.e., prevalence and severity) were based on dmft/DMFT indices recorded by trained and calibrated clinical examiners. Differences in primary and permanent dentition caries experience between HI, HEU, and HUU were estimated using multivariable logistic and negative binomial regression modeling. RESULTS: HI children had significantly higher caries experience (33%) compared to HEU (15%) and HUU (22%) children. This difference persisted in fully adjusted analyses [odds ratio (OR) = 1.6; 95% confidence interval (CI) = 1.0-2.6], was most pronounced in the permanent dentition (OR = 3.4; 95% CI = 1.2-9.5), and mirrored differences in caries severity. While molars were predominantly affected in both primary and permanent dentitions, caries lesion patterns differed between dentitions. Caries severity was significantly associated with hypoplastic primary teeth, gingival inflammation, and lower CD4 counts. CONCLUSIONS: We found that the higher prevalence and severity of dental caries among HI children was driven by increased burden of permanent dentition caries compared to their uninfected counterparts. The dentition-specific associations identified in this study highlight the need to design and implement age-specific caries prevention strategies. These may include intensified oral hygiene regimens aimed at mitigating the cariogenic impact of hyposalivation among HI children. Similarly, the long-lasting impacts of developmental defects of the enamel in the primary and permanent dentitions must not be ignored.

Dental caries and its association with the oral microbiomes and HIV in young children-Nigeria (DOMHaIN): a cohort study.

BACKGROUND: This study seeks to understand better the mechanisms underlying the increased risk of caries in HIV-infected school-aged Nigerian children by examining the relationship between the plaque microbiome and perinatal HIV infection and exposure. We also seek to investigate how perinatal HIV infection and exposure impact tooth-specific microbiomes' role on caries disease progression. METHODS: The participants in this study were children aged 4 to 11 years recruited from the University of Benin Teaching Hospital (UBTH), Nigeria, between May to November 2019. Overall, 568 children were enrolled in three groups: 189 HIV-infected (HI), 189 HIV-exposed but uninfected (HEU) and 190 HIV-unexposed and uninfected (HUU) as controls at visit 1 with a 2.99% and 4.90% attrition rate at visit 2 and visit 3 respectively. Data were obtained with standardized questionnaires. Blood samples were collected for HIV, HBV and HCV screening; CD4, CD8 and full blood count analysis; and plasma samples stored for future investigations; oral samples including saliva, buccal swabs, oropharyngeal swab, tongue swab, dental plaque were collected aseptically from participants at different study visits. CONCLUSIONS: Results from the study will provide critical information on how HIV exposure, infection, and treatment, influence the oral microbiome and caries susceptibility in children. By determining the effect on community taxonomic structure and gene expression of dental microbiomes, we will elucidate mechanisms that potentially create a predisposition for developing dental caries. As future plans, the relationship between respiratory tract infections, immune and inflammatory markers with dental caries in perinatal HIV infection and exposure will be investigated.

Electrocardiographic findings in human immunodeficiency virus-infected children in Benin City, Nigeria.

BACKGROUND: Human immunodeficiency virus (HIV) infection is a global pandemic affecting mostly sub-Saharan Africa. It is a multisystem disease. Cardiovascular involvement detected by electrocardiogram (ECG) has been described mostly in adult populations with few studies on children. In this study, the ECG findings of HIV-infected as against HIV-uninfected children were evaluated. SUBJECTS AND METHODS: This comparative cross-sectional study was conducted in two public hospitals in Benin City. Using convenience sampling, 200 each of HIV-positive children attending the HIV clinics of both hospitals and age- and sex-matched HIV-negative children attending follow-up clinics in the same hospitals were recruited. Biodata/sociodemographic information was obtained, while each participant underwent 12-channel ECG evaluation. RESULTS: The prevalence of abnormal ECG findings in HIV-positive children was 34.5% compared to 4.5% in HIV-negative children (P < 0.0001). The mean PR, QRS and QT intervals in the participants were 0.13 ± 0.02 s, 0.11 ± 0.15 s and 0.41 ± 0.03, respectively. They were statistically significantly longer than controls, 0.12 ± 0.02 s, 0.08 ± 0.09 s and 0.40 ± 0.02 s, respectively, P < 0.05, in each case. The prevalence of prolonged PR, QRS and QTc was significantly higher in the patients, 5%, 3.5% and 3.5%, respectively, than controls, 05, 0% and 0%, respectively (P < 0.05 in each case). CONCLUSION: A third of the HIV-infected children in the study had abnormal ECG changes. It is recommended that ECG be included in their routine management of HIV-positive children so as to better supervise the affected children, retard the deterioration and improve their quality of health.

Impact of HIV on the Oral Microbiome of Children Living in Sub-Saharan Africa, Determined by Using an rpoC Gene Fragment Metataxonomic Approach.

Children living with HIV have a higher prevalence of oral diseases, including caries, but the mechanisms underlying this higher prevalence are not well understood. Here, we test the hypothesis that HIV infection is associated with a more cariogenic oral microbiome, characterized by an increase in bacteria involved in the pathogenesis of caries. We present data generated from supragingival plaques collected from 484 children representing three exposure groups: (i) children living with HIV (HI), (ii) children who were perinatally exposed but uninfected (HEU), and (iii) unexposed and therefore uninfected children (HUU). We found that the microbiome of HI children is distinct from those of HEU and HUU children and that this distinction is more pronounced in diseased teeth than healthy teeth, suggesting that the impact of HIV is more severe as caries progresses. Moreover, we report both an increase in bacterial diversity and a decrease in community similarity in our older HI cohort compared to our younger HI cohort, which may in part be a prolonged effect of HIV and/or its treatment. Finally, while Streptococcus mutans is often a dominant species in late-stage caries, it tended to be found at lower frequency in our HI cohort than in other groups. Our results highlight the taxonomic diversity of the supragingival plaque microbiome and suggest that broad and increasingly individualistic ecological shifts are responsible for the pathogenesis of caries in children living with HIV, coupled with a diverse and possibly severe impact on known cariogenic taxa that potentially exacerbates caries. IMPORTANCE Since its recognition as a global epidemic in the early 1980s, approximately 84.2 million people have been diagnosed with HIV and 40.1 million people have died from AIDS-related illnesses. The development and increased global availability of antiretroviral treatment (ART) regimens have dramatically reduced the mortality rate of HIV and AIDS, yet approximately 1.5 million new infections were reported in 2021, 51% of which are in sub-Saharan Africa. People living with HIV have a higher prevalence of caries and other chronic oral diseases, the mechanisms of which are not well understood. Here, we used a novel genetic approach to characterize the supragingival plaque microbiome of children living with HIV and compared it to the microbiomes of uninfected and perinatally exposed children to better understand the role of oral bacteria in the etiology of tooth decay in the context of HIV exposure and infection.

Supragingival mycobiome of HIV-exposed-but-uninfected children reflects a stronger correlation with caries-free-associated taxa compared to HIV-infected or uninfected children.

IMPORTANCE: Globally, caries is among the most frequent chronic childhood disease, and the fungal component of the microbial community responsible is poorly studied despite evidence that fungi contribute to increased acid production exacerbating enamel demineralization. HIV infection is another global health crisis. Perinatal HIV exposure with infection are caries risk factors; however, the caries experience in the context of perinatal HIV exposure without infection is less clear. Using high-throughput amplicon sequencing, we find taxonomic differences that become pronounced during late-stage caries. Notably, we show a stronger correlation with health-associated taxa for HIV-exposed-but-uninfected children when compared to unexposed and uninfected children. This aligns with a lower incidence of caries in primary teeth at age 6 or less for exposed yet uninfected children. Ultimately, these findings could contribute to improved risk assessment, intervention, and prevention strategies such as biofilm disruption and the informed design of pro-, pre-, and synbiotic oral therapies.

Dynamics of the infant gut microbiota in the first 18 months of life: the impact of maternal HIV infection and breastfeeding.

BACKGROUND: Access to antiretroviral therapy (ART) during pregnancy and breastfeeding for mothers with HIV has resulted in fewer children acquiring HIV peri- and postnatally, resulting in an increase in the number of children who are exposed to the virus but are not infected (HEU). HEU infants have an increased likelihood of childhood infections and adverse growth outcomes, as well as increased mortality compared to their HIV-unexposed (HUU) peers. We explored potential differences in the gut microbiota in a cohort of 272 Nigerian infants born to HIV-positive and negative mothers in this study during the first 18 months of life. RESULTS: The taxonomic composition of the maternal vaginal and gut microbiota showed no significant differences based on HIV status, and the composition of the infant gut microbiota at birth was similar between HUU and HEU. Longitudinal taxonomic composition of the infant gut microbiota and weight-for-age z-scores (WAZ) differed depending on access to breast milk. HEU infants displayed overall lower WAZ than HUU infants at all time points. We observed a significantly lower relative abundance of Bifidobacterium in HEU infants at 6 months postpartum. Breast milk composition also differed by time point and HIV infection status. The antiretroviral therapy drugs, lamivudine and nevirapine, as well as kynurenine, were significantly more abundant in the breast milk of mothers with HIV. Levels of tiglyl carnitine (C5) were significantly lower in the breast milk of mothers without HIV. ART drugs in the breast milk of mothers with HIV were associated with a lower relative abundance of Bifidobacterium longum. CONCLUSIONS: Maternal HIV infection was associated with adverse growth outcomes of HEU infants in this study, and these differences persist from birth through at least 18 months, which is a critical window for the development of the immune and central nervous systems. We observed that the relative abundance of Bifidobacterium spp. was significantly lower in the gut microbiota of all HEU infants over the first 6 months postpartum, even if HEU infants were receiving breast milk. Breastfeeding was of benefit in our HEU infant cohort in the first weeks postpartum; however, ART drug metabolites in breast milk were associated with a lower abundance of Bifidobacterium. Video abstract.

Prevalence of congenital malaria in newborns of mothers co-infected with HIV and malaria in Benin city.

BACKGROUND: HIV and Plasmodium falciparum malaria co-infection annually complicates about one million pregnancies in sub-Saharan Africa. Congenital malaria (CM) has deleterious effects on newborns. Little is known about the effect of co-infections on the prevalence of CM in infants born by these women. This study was carried out to determine the prevalence of CM in newborns of mothers co-infected with HIV and malaria compared to HIV-negative mothers with malaria in Benin-City. METHODS: Subjects were 162 newborns of mothers co-infected with HIV and malaria. Controls were 162 newborns of HIV negative malaria infected mothers. Blood film for malaria parasites was done on cord blood and peripheral blood on days 1, 3 and 7 in the newborns. Maternal peripheral blood film for malaria parasite was done at delivery and placental tissue was obtained for confirmation of placental malaria by histology. Diagnosis of malaria in blood films was by light microscopy. RESULTS: The prevalence of CM in subjects was significantly higher than in controls (34.6% and 22.2%, p=.014). Profound immunodepression (maternal CD4 cell count <200 cell/mm3) was significantly associated with CM (p=.006). The major predictors of CM in subjects were maternal CD4 cell count <200 cell/mm3 and placental malaria while in controls placental malaria was the only predictor. CONCLUSIONS: Babies born to mothers co-infected with HIV and malaria are at increased risk for CM. All babies born by HIV positive mothers should be screened for CM.