Distinguishing the Signals of Gingivitis and Periodontitis in Supragingival Plaque: a Cross-Sectional Cohort Study in Malawi.

UNLABELLED: Periodontal disease ranges from gingival inflammation (gingivitis) to the inflammation and loss of tooth-supporting tissues (periodontitis). Previous research has focused mainly on subgingival plaque, but supragingival plaque composition is also known to be associated with disease. Quantitative modeling of bacterial abundances across the natural range of periodontal severities can distinguish which features of disease are associated with particular changes in composition. We assessed a cross-sectional cohort of 962 Malawian women for periodontal disease and used 16S rRNA gene amplicon sequencing (V5 to V7 region) to characterize the bacterial compositions of supragingival plaque samples. Associations between bacterial relative abundances and gingivitis/periodontitis were investigated by using negative binomial models, adjusting for epidemiological factors. We also examined bacterial cooccurrence networks to assess community structure. The main differences in supragingival plaque compositions were associated more with gingivitis than periodontitis, including higher bacterial diversity and a greater abundance of particular species. However, even after controlling for gingivitis, the presence of subgingival periodontitis was associated with an altered supragingival plaque. A small number of species were associated with periodontitis but not gingivitis, including members of Prevotella, Treponema, and Selenomonas, supporting a more complex disease model than a linear progression following gingivitis. Cooccurrence networks of periodontitis-associated taxa clustered according to periodontitis across all gingivitis severities. Species including Filifactor alocis and Fusobacterium nucleatum were central to this network, which supports their role in the coaggregation of periodontal biofilms during disease progression. Our findings confirm that periodontitis cannot be considered simply an advanced stage of gingivitis even when only considering supragingival plaque. IMPORTANCE: Periodontal disease is a major public health problem associated with oral bacteria. While earlier studies focused on a small number of periodontal pathogens, it is now accepted that the whole bacterial community may be important. However, previous high-throughput marker gene sequencing studies of supragingival plaque have largely focused on high-income populations with good oral hygiene without including a range of periodontal disease severities. Our study includes a large number of low-income participants with poor oral hygiene and a wide range of severities, and we were therefore able to quantitatively model bacterial abundances as functions of both gingivitis and periodontitis. A signal associated with periodontitis remains after controlling for gingivitis severity, which supports the concept that, even when only considering supragingival plaque, periodontitis is not simply an advanced stage of gingivitis. This suggests the future possibility of diagnosing periodontitis based on bacterial occurrences in supragingival plaque.

Modelling CD4 T Cell Recovery in Hepatitis C and HIV Co-infected Children Receiving Antiretroviral Therapy.

BACKGROUND: The effect of hepatitis C virus (HCV) coinfection on CD4 T cell recovery in treated HIV-infected children is poorly understood. OBJECTIVE: To compare CD4 T cell recovery in HIV/HCV coinfected children with recovery in HIV monoinfected children. METHOD: We studied 355 HIV monoinfected and 46 HIV/HCV coinfected children receiving antiretroviral therapy (ART) during a median follow-up period of 4.2 years (interquartile range: 2.7-5.3 years). Our dataset came from the Ukraine pediatric HIV Cohort and the HIV/HCV coinfection study within the European Pregnancy and Paediatric HIV Cohort Collaboration. We fitted an asymptotic nonlinear mixed-effects model of CD4 T cell reconstitution to age-standardized CD4 counts in all 401 children and investigated factors predicting the speed and extent of recovery. RESULTS: We found no significant impact of HCV coinfection on either pre-ART or long-term age-adjusted CD4 counts (z scores). However, the rate of increase in CD4 z score was slower in HIV/HCV coinfected children when compared with their monoinfected counterparts (P < 0.001). Both monoinfected and coinfected children starting ART at younger ages had higher pre-ART (P < 0.001) and long-term (P < 0.001) CD4 z scores than those who started when they were older. CONCLUSIONS: HIV/HCV coinfected children receiving ART had slower CD4 T cell recovery than HIV monoinfected children. HIV/HCV coinfection had no impact on pre-ART or long-term CD4 z scores. Early treatment of HIV/HCV coinfected children with ART should be encouraged.