Biology subjects

Franke, M. F.

Publications and source records attributed to Franke, M. F..

3 recordsLinked to original sources

bioRxiv2019

Lifetime changes in CD4 count, viral load suppression and adherence among adolescents living with HIV in urban Peru

IntroductionViral load suppression and adherence to combined antiretroviral therapy (cART) have been shown to be lower in adolescents than in other age groups; however, this relationship has not been documented longitudinally from childhood to adolescence and has rarely been examined outside of high-resource settings and sub-Saharan Africa. To address this knowledge gap, we quantified longitudinal changes in CD4 cell count, viral load suppression, and cART adherence in adolescents living with HIV in urban, Peru.\n\nMethodsWe conducted a retrospective chart review among adolescents ages 10-18 years on cART and receiving care at a large, public sector pediatric hospital as of December 2015. We abstracted clinical notes indicating nonadherence and viral load and CD4 counts from childhood to adolescence. We modeled the association between age and each outcome with restricted cubic splines accounting for multiple observations per person, and graphed study outcomes by age.\n\nResultsA median of 7.7 years (25th percentile=4.9, 75th percentile=10.2) of follow up were observed for 128 adolescents. Nearly 70% of patients had at least one nonadherence note and the proportion with nonadherence increased log-linearly with age (p<0.0001). The peak proportion with viral load suppression was 84% (95% CI: 79, 88) at age 13, which dropped to 67% (95% CI: 47, 83) by age 18. Mean CD4 count decreased at age 13, dropping from 723 cells/mm3 (95% CI: 666, 784) to 429 cells/mm3 (95% CI: 356, 517) by age 18.\n\nConclusionThis is the first report from Latin America to examine longitudinal changes in HIV outcomes from childhood into adolescence. Consistent with the limited evidence from other settings, decreases in viral load suppression and mean CD4 count occurred in early adolescence in tandem with increases in nonadherence. Adolescent-friendly cART adherence support interventions to target this critical period are urgently needed.

epidemiology↗

bioRxiv2019

Detection of Mycobacterium tuberculosis in pediatric stool samples using TruTip technology

BackgroundRapid and accurate diagnosis of childhood tuberculosis (TB) is challenging because children are often unable to produce the sputum sample required for conventional tests. Stool is an alternative sample type that is easy to collect from children, and studies investigating the use of stool for molecular detection of Mycobacterium tuberculosis (Mtb) have led to promising results. However, tests performed thus far are not able to examine multi-drug resistance. The TruTip workstation (Akonni Biosystems) is an automated lysis and extraction platform that can be integrated with a closed amplification system to detect both Mtb and resistance-associated mutations. Our objective here was to evaluate the use of TruTip extraction technology for Mtb detection in stool. MethodsWe tested stool samples of 259 children with TB symptoms, ages 0-14 years old, in Lima, Peru. We used the TruTip workstation for sample processing and extraction, followed by IS6110 real-time PCR to detect the presence of Mtb DNA. We calculated assay sensitivity in two groups: (1) children with culture confirmed TB (N=22); and (2) children with unconfirmed, clinically diagnosed TB (N=84). We calculated specificity among children in whom TB was ruled out (N=153). Among children with TB, we examined factors associated with a positive stool test. ResultsOverall assay sensitivity was 59% (95% confidence interval 39%-80%) and 1.2% (0.0%-6.5%) in children with culture-confirmed and clinically-diagnosed TB, respectively, and specificity was 97% (93%-99%). The assay detected Mtb in stool of 7/7 children with smear-positive TB [100% sensitivity; (59%-100%)], and in 6/15 [40% (16%-68%)] of children with smear-negative, culture-confirmed TB. Older age, smear positivity, culture positivity and cavitary disease were associated with a positive stool result. ConclusionFor molecular Mtb detection from stool, the TruTip workstation, in combination with IS6110 amplification, led to sensitivity and specificity estimates comparable to other tests such as Xpert. Future optimization is required to also diagnose TB disease in children who now received an unconfirmed diagnosis.

microbiology↗

bioRxiv2017

The Impact of Vitamin A and Carotenoids on the Risk of Tuberculosis Progression

BackgroundLow and deficient levels of vitamin A are common in low and middle income countries where tuberculosis burden is high. We assessed the impact of baseline levels of vitamins A and carotenoids on TB disease risk.\n\nMethods and FindingsWe conducted a case-control study nested within a longitudinal cohort of household contacts of pulmonary TB cases in Lima, Peru. We screened all contacts for TB disease at 2, 6, and 12 months after enrollment. We defined cases as HIV-negative household contacts with blood samples who developed TB disease at least 15 days after enrollment of the index patient. For each case, we randomly selected 4 controls from among contacts who did not develop TB disease, matching on gender and year of age. We used conditional logistic regression to estimate odds ratios (ORs) for incident TB disease by vitamin A and carotenoids levels, controlling for other nutritional and socioeconomic factors.\n\nAmong 6751 HIV-negative household contacts with baseline blood samples, 192 developed secondary TB disease during follow-up. We analyzed 180 cases with viable samples and 709 matched controls. After controlling for possible confounders, we found that baseline vitamin A deficiency was associated with a 10-fold increase in risk of TB disease among household contacts (aOR 10.42; 95% CI 4.01-27.05; p < 0.001). This association was dose-dependent with stepwise increases in TB disease risk with each decreasing quartile of vitamin A level. Carotenoid levels were also inversely associated with TB risk among adolescents.\n\nOur study is limited by the one year duration of follow up and by the relatively few blood samples available from household contacts under ten years of age.\n\nConclusionsVitamin A deficiency strongly predicted risk of incident TB disease among household contacts of TB patients. Vitamin A supplementation among individuals at high risk of TB may provide an effective means of preventing TB disease.

epidemiology↗