Maternal systemic or cord blood inflammation is associated with birth anthropometry in a Tanzanian prospective cohort.

OBJECTIVES: HIV infection is associated with chronic systemic inflammation, with or without antiretroviral therapy. Consequences for foetal growth are not understood, particularly in settings where multiple maternal infections and malnutrition are common. The study was designed to examine maternal systemic circulating and umbilical cord blood cytokine concentrations in relation to birth anthropometry in a Tanzanian prospective cohort. METHODS: A 9-plex panel of maternal plasma cytokines in HIV-positive (n = 44) and HIV-negative (n = 70) mothers and the same cytokines in umbilical cord blood collected at delivery was assayed. Linear regression modelled associations between maternal or cord blood cytokines and birth anthropometry. RESULTS: Health indicators (haemoglobin, mid-upper-arm circumference, body mass index) in HIV-positive mothers without considerable immunosuppression did not differ from HIV-negative women. Despite this, HIV-exposed infants had lower birthweight and length. Subgroup analyses indicated that HIV management using HAART was associated with lower plasma TNF-α, as were longer durations of any antiretroviral therapy (≥2 months). Greater maternal plasma TNF-α was associated with earlier delivery (-1.7 weeks, P = 0.039) and lower birthweights (-287 g; P = 0.020), while greater umbilical cord TNF-α (-1.43 cm; P = 0.036) and IL-12p70 (-2.4 cm; P = 0.008) were associated with shorter birth length. Birthweight was inversely associated with cord IL-12p70 (-723 g; P = 0.001) and IFN-γ (-482 g, P = 0.007). Maternal cytokines during pregnancy did not correlate with umbilical cord cytokines at delivery. CONCLUSIONS: Systemic inflammation identified in maternal plasma or umbilical cord blood was associated with poorer birth anthropometrics in HIV-exposed and HIV-unexposed infants. Controlling maternal and/or foetal systemic inflammation may improve birth anthropometry.

Elevated hepcidin at HIV diagnosis is associated with incident tuberculosis in a retrospective cohort study.

Hepcidin inhibits ferroportin-mediated iron efflux, leading to intracellular macrophage iron retention, possibly favoring Mycobacterium tuberculosis iron acquisition and tuberculosis (TB) pathogenesis. Plasma hepcidin was measured at human immunodeficiency virus (HIV) diagnosis in a retrospective HIV-prevalent, antiretroviral-naïve African cohort to investigate the association with incident pulmonary and/or extra-pulmonary TB. One hundred ninety-six participants were followed between 5 August 1992 and 1 June 2002, with 32 incident TB cases identified. Greater hepcidin was associated with significantly increased likelihood of TB after a median time to TB of 6 months. Elucidation of iron-related causal mechanisms and time-sensitive biomarkers that identify individual changes in TB risk are needed.

Early childhood tuberculosis in northwestern Tanzania.

SETTING: Data on pediatric tuberculosis (TB) from TB-endemic, resource-constrained regions are limited, impacting awareness of disease burden and influencing diagnostic actions. OBJECTIVE: To obtain recorded incidence of childhood (age <5 years) TB in Mwanza Municipality, Tanzania, to estimate true incidence and to explore setting-specific reasons for differences. DESIGN: Recorded incidence of pediatric TB (2006-2010) was obtained from Mwanzan TB registries. Incident smear-positive pulmonary TB cases recruited from four TB clinics were used to estimate children exposed and the theoretical incidence of disease, assuming that either 10% or 23% of children would progress to disease following exposure. Reasons for underestimation were evaluated in the medical records of children who died at a secondary hospital. RESULTS: Between 2006 and 2010, 279 early childhood TB cases were recorded (TB incidence 63/100,000/year). Over a 3-month period in 2011, 44% of smear-positive TB patients being treated in Mwanza were living with a total of 139 children. From census data, we estimated that 1279 children were exposed in Mwanza in 2011. Using estimates of the likelihood of disease progression, the theoretical incidence of early childhood TB ranged from 134.2 to 308.5/100,000/year. CONCLUSIONS: The true burden of early childhood TB is likely much higher than recorded. Age-specific reporting, increasing clinical awareness and screening may reduce the magnitude of underdiagnosis in this vulnerable population.