Characterization and Investigation of Risk Factors for Late-Relapsing Hepatitis After Yellow Fever.

BACKGROUND: Late-relapsing hepatitis after yellow fever (LHep-YF) during the convalescent phase of the disease has been described during recent yellow fever (YF) outbreaks in Brazil. LHep-YF is marked by a rebound in liver enzymes and nonspecific clinical manifestations around 46-60 days after YF symptom onset. METHODS: Here we have characterized the clinical course and risk factors for LHep-YF using data from a representative cohort of patients who survived YF in Brazil, 2017-2018. A total of 221 YF-positive patients were discharged from the infectious disease reference hospital in Minas Gerais and were followed up at 30, 45, and 60 days post-symptom onset. RESULTS: From 46 to 60 days post-symptom onset, 16% of YF patients (n = 36/221) exhibited a rebound of aminotransferases (aspartate aminotransferase or alanine aminotransferase >500 IU/L), alkaline phosphatase, and total bilirubin levels. Other etiologies of liver inflammation such as infectious hepatitis, autoimmune hepatitis, and metabolic liver disease were ruled out. Jaundice, fatigue, headache, and low platelet levels were associated with LHep-YF. Demographic factors, clinical manifestations, laboratory tests, ultrasound findings, and viral load during the acute phase of YF were not associated with the occurrence of LHep-YF. CONCLUSIONS: These findings provide new data on the clinical course of Late-relapsing hepatitis during the convalescent phase of YF and highlight the need for extended patient follow-up after acute YF.

Presence of Antibodies Against Haemophilus influenzae Serotype a in Alaska Before and After the Emergence of Invasive Infections.

BACKGROUND: Haemophilus influenzae bacteria can cause asymptomatic carriage and invasive disease. Haemophilus influenzae serotype a (Hia) is an emerging cause of invasive disease in Alaska, with greatest burden occurring among rural Alaska Native (AN) children. The first case of invasive Hia (iHia) in Alaska was reported in 2002; however, it is unclear how long the pathogen has been in Alaska. METHODS: We quantified immunoglobulin G antibodies against Hia (anti-Hia) in 839 banked serum samples from Alaska residents, comparing antibody concentrations in samples drawn in the decades before (1980s and 1990s) and after (2000s) the emergence of iHia. We also assessed serum antibody concentration by age group, region of residence, and race. RESULTS: The anti-Hia was >0.1 µg/mL in 88.1% (348 of 395) and 91.0% (404 of 444) of samples from the decades prior and after the emergence of Hia, respectively (P = .17). No significant differences in antibody levels were detected between people from rural and urban regions (1.55 vs 2.08 µg/mL, P = .91 for age ≥5) or between AN and non-AN people (2.50 vs 2.60 µg/mL, P = .26). CONCLUSIONS: Our results are consistent with widespread Hia exposure in Alaska predating the first iHia case. No difference in Hia antibody prevalence was detected between populations with differing levels of invasive disease.

Ixodes scapularis (Acari: Ixodidae) Nymphal Survival and Host-Finding Success in the Eastern United States.

The blacklegged tick (Ixodes scapularis Say) is the primary vector of Borrelia burgdorferi sensu stricto (Spirochaetales: Spirochaetaceae), the Lyme disease agent in North America. The basic reproduction number (R0) for B. burgdorferi in I. scapularis in the Northeast is highly sensitive to the probability that engorged larvae survive the winter, molt into nymphs, and find a host. These processes are dependent on local environmental variables, including climate, host population size and movement, and tick behavior. A simple model is presented for estimating host-finding success from the ratio of tick abundance in two subsequent years, accounting for overwinter survival and possible differences in host associations between nymphs and larvae. This model was parameterized using data from two sites in mainland Connecticut and two on Block Island, RI. Host abundance and tick burdens were estimated via mark-recapture trapping of the primary host, Peromyscus leucopus Rafinesque. Overwintering survival was estimated using engorged larvae placed in field enclosures at each site. Only nymphs were recovered alive, and no significant differences in model parameters were observed between Connecticut and Block Island. Host-finding success was predicted to be high across a wide range of host association patterns at three of four sites. Assuming equivalent host association between larvae and nymphs, R0 was also estimated to be greater than one at three of four sites, suggesting these conditions allow for the persistence of B. burgdorferi. The model output was highly sensitive to differences between nymphal and larval host associations.

Incorporating Health Outcomes into Land-Use Planning.

The global trend toward increased agricultural production puts pressure on undeveloped areas, raising the question of how to optimally allocate land. Land-use change has recently been linked to a number of human health outcomes, but these are not routinely considered in land-use decision making. We review examples of planners' currently used strategies to evaluate land use and present a conceptual model of optimal land use that incorporates health outcomes. We then present a framework for evaluating the health outcomes of land-use scenarios that can be used by decision makers in an integrated approach to land-use planning.

Climate impacts on blacklegged tick host-seeking behavior.

The nymph of the blacklegged tick (Ixodes scapularis), the primary North American vector of the causative agent of Lyme disease, must attach to a host by the end of its questing season in order to feed and subsequently molt into an adult. The proper timing of this behavior is critical both for the tick's survival and for perpetuating the transmission of tick-borne pathogens. Questing also depletes limited nymphal lipid reserves and increases desiccation risk. Given this tradeoff, questing behavior and its environmental influences can be expressed in a dynamic state variable model. We develop what we believe to be the first such model for a tick, and investigate the influence of climate on nymph fitness predictions. We apply these results to the hypothesized inland migration of I. scapularis from island refugia, evaluating fitness under suboptimal questing strategies and uncertain environmental conditions.

Reconciling the Entomological Hazard and Disease Risk in the Lyme Disease System.

Lyme disease (LD) is a commonly cited model for the link between habitat loss and/or fragmentation and disease emergence, based in part on studies showing that forest patch size is negatively related to LD entomological risk. An equivalent relationship has not, however, been shown between patch size and LD incidence (LDI). Because entomological risk is measured at the patch scale, while LDI is generally assessed in relation to aggregate landscape statistics such as forest cover, we posit that the contribution of individual patches to human LD risk has not yet been directly evaluated. We design a model that directly links theoretical entomological risk at the patch scale to larger-scale epidemiological data. We evaluate its predictions for relative LD risk in artificial landscapes with varying composition and configuration, and test its ability to predict countywide LDI in a 12-county region of New York. On simulated landscapes, we find that the model predicts a unimodal relationship between LD incidence and forest cover, mean patch size, and mean minimum distance (a measure of isolation), and a protective effect for percolation probability (a measure of connectivity). In New York, risk indices generated by this model are significantly related to countywide LDI. The results suggest that the lack of concordance between entomological risk and LDI may be partially resolved by this style of model.