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Warren, J. L.

Publications and source records attributed to Warren, J. L..

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Challenges in estimating the impact of vaccination with sparse data

BackgroundThe synthetic control (SC) model is a powerful tool to quantify the population-level impact of vaccines, because it can adjust for trends unrelated to vaccination using a composite of control diseases. Because vaccine impact studies are often conducted using smaller subnational datasets, we evaluated the performance of SC models with sparse time series data. To obtain more robust estimates of vaccine effects from noisy time series, we proposed a possible alternative approach, \"STL+PCA\" method (seasonal-trend decomposition plus principal component analysis), which first extracts smoothed trends from the control time series and uses them to adjust the outcome.\n\nMethodsUsing both the SC and STL+PCA models, we estimated the impact of 10-valent pneumococcal conjugate vaccine (PCV10) on pneumonia hospitalizations among cases <12 months and 80+ years of age during 2004-2014 at the subnational level in Brazil. The performance of these models was also compared using simulation analyses.\n\nResultsThe SC model was able to adjust for trends unrelated to PCV10 in larger states but not in smaller states. The simulation analysis confirmed that the SC model failed to select an appropriate set of control diseases when the time series were sparse and noisy, thereby generating biased estimates of the impact of vaccination when secular trends were present. The STL+PCA approach decreased bias in the estimates for smaller populations.\n\nConclusionsEstimates from the SC model might be biased when data are sparse. The STL+PCA model provides more accurate evaluations of vaccine impact in smaller populations.

epidemiology

Differences in Pneumococcal Serotype Replacement in Individuals with and without Underlying Medical Conditions

BackgroundPneumococcal conjugate vaccines (PCVs) have had a well-documented impact on the incidence of invasive pneumococcal disease (IPD) worldwide. However, declines in IPD due to vaccine-targeted serotypes have been partially offset by increases in IPD due to non-vaccine serotypes. The goal of this study was to quantify serotype-specific changes in the incidence of IPD that occurred in different age groups, with or without certain co-morbidities, following the introduction of PCV7 and PCV13 in the childhood vaccination program in Denmark.\n\nMethodsWe used nationwide surveillance data for IPD in Denmark and a hierarchical Bayesian regression framework to estimate changes in the incidence of IPD associated with the introduction of PCV7 (2007) and PCV13 (2010) while controlling for serotype-specific epidemic cycles and unrelated secular trends.\n\nResults and ConclusionsFollowing the introduction of PCV7 and 13 in children, the net impact of serotype replacement varied considerably by age group and the presence of comorbid conditions. Serotype replacement offset a greater fraction of the decline in vaccine-targeted serotypes following the introduction of PCV7 compared with the period following the introduction of PCV13. Differences in the magnitude of serotype replacement were due to variations in the incidence of non-vaccine serotypes in the different risk groups before the introduction of PCV7 and PCV13. The relative increases in the incidence of IPD caused by non-vaccine serotypes did not differ appreciably in the post-vaccination period. Serotype replacement offset a greater proportion of the benefit of PCVs in strata in which the non-vaccine serotypes comprised a larger proportion of cases prior to the introduction of the vaccines. These findings could help to predict the impact of next-generation conjugate vaccines in specific risk groups.

epidemiology

Trends in CRP, D-dimer and fibrinogen during therapy for HIV associated multidrug resistant tuberculosis

BackgroundHIV positive adults on treatment for multidrug-resistant tuberculosis (MDR-TB) experience high mortality. Biomarkers of HIV/MDR-TB treatment response may enable earlier treatment modifications that improve outcomes.\n\nMethodsTo determine whether trends in C-reactive protein (CRP), D-dimer and fibrinogen predict treatment outcome among those with HIV/MDR-TB co-infection we studied 20 HIV positive participants initiating therapy for MDR-TB. Serum CRP, fibrinogen, and D-dimer were measured at baseline and serially while on treatment. Results: At baseline, all biomarkers were elevated with median CRP 86.15 mg/L (IQR 29.25-149.32), D-dimer 0.85 g/mL (IQR 0.34-1.80) and fibrinogen 4.11 g/L (IQR 3.75-6.31). CRP decreased significantly within 10 days of treatment initiation and fibrinogen within 28 days; D-dimer did not change significantly. 5 (25%) participants died. Older age (median age of 38y among survivors and 54y among deceased, p=0.008) and higher baseline fibrinogen (3.86 g/L among survivors and 6.37 g/L among deceased, p=0.02) were significantly associated with death. Higher CRP concentrations at the beginning of each measurement interval were significantly associated with a higher risk of death during that interval.\n\nConclusionTrends in fibrinogen and CRP may be useful for evaluating early response to treatment among individuals with HIV/MDR-TB co-infection.

immunology

SUCCESSIVE BLOODMEALS ENHANCE VIRUS DISSEMINATION WITHIN MOSQUITOES AND INCREASE TRANSMISSION POTENTIAL

SUMMARY PARAGRAPHThe recent Zika virus (ZIKV) and chikungunya virus (CHIKV) epidemics highlight the explosive nature of arthropod-borne (arbo) viruses transmitted by Aedes aegypti mosquitoes1,2. Vector competence and the extrinsic incubation period (EIP) are two key entomological parameters used to assess the public health risk posed by arboviruses3. These are typically measured empirically by offering mosquitoes an infectious bloodmeal and temporally sampling mosquitoes to determine infection and transmission status. This approach has been used for the better part of a century; however, it does not accurately capture the biology and behavior of many mosquito vectors which refeed frequently (every 2-3 days)4. Here we demonstrate that administration of a second non-infectious bloodmeal significantly shortens the EIP of ZIKV-infected Ae. aegypti by enhancing virus escape from the mosquito midgut. Similarly, a second bloodmeal increased the competence of this species for dengue virus and CHIKV. This effect was also observed for ZIKV in Aedes albopictus, suggesting that this species might be a more important vector than once thought and that this phenomenon may be common among other virus-vector pairings. Modeling of these findings reveals that a shortened EIP would result in a significant increase in the basic reproductive number, R0. This increase helps explain how Ae.aegypti can sustain an explosive epidemic like ZIKV despite its relatively poor vector competence in single-feed laboratory trials. Together, these data demonstrate a direct and unrecognized link between mosquito feeding behavior, EIP, and vector competence.

microbiology