Does Paging Clinicians about Tick-Borne Disease Serological Results Impact Clinical Care? A Retrospective Analysis of 70 Cases in North Carolina.

Delayed treatment of Rocky Mountain spotted fever is associated with increased morbidity and mortality. Because the diagnosis cannot be established from a single serological test, guidelines recommend empirical antibiotic initiation in suspect patients. We evaluated a policy used by UNC Health of paging clinicians when acute testing for Rickettsia returned with a titer ≥1:256. Our objective was to assess the potential effect of paging on routine treatment practices. Notably, we found that a high proportion of cases (N = 28, 40%) were not prescribed antibiotics until the results were available. The vast majority of these cases did not have evidence of compatible symptoms or disease progression. These findings suggest that paging may have prompted unnecessary treatment. Overall, the policy, which has now been discontinued, appears to have had limited benefit. Efforts are urgently needed to improve adherence to testing and treatment guidelines.

Evolution of Spatial Risk of Malaria Infection After a Pragmatic Chemoprevention Program in Response to Severe Flooding in Rural Western Uganda.

BACKGROUND: Malaria epidemics result from extreme precipitation and flooding, which are increasing with global climate change. Local adaptation and mitigation strategies will be essential to prevent excess morbidity and mortality. METHODS: We investigated the spatial risk of malaria infection at multiple timepoints after severe flooding in rural western Uganda employing longitudinal household surveys measuring parasite prevalence and leveraging remotely sensed information to inform spatial models of malaria risk in the 3 months after flooding. RESULTS: We identified clusters of malaria risk emerging in areas (1) that showed the greatest changes in Normalized Difference Vegetation Index from pre- to postflood and (2) where residents were displaced for longer periods of time and had lower access to long-lasting insecticidal nets, both of which were associated with a positive malaria rapid diagnostic test result. The disproportionate risk persisted despite a concurrent chemoprevention program that achieved high coverage. CONCLUSIONS: The findings enhance our understanding not only of the spatial evolution of malaria risk after flooding, but also in the context of an effective intervention. The results provide a "proof of concept" for programs aiming to prevent malaria outbreaks after flooding using a combination of interventions. Further study of mitigation strategies-and particularly studies of implementation-is urgently needed.

Impact of the COVID-19 pandemic on delays in diagnosis and treatment of tick-borne diseases endemic to southeastern USA.

BACKGROUND: The Coronavirus disease 2019 (COVID-19) pandemic was marked by an increase in diagnosis and treatment delays for a range of medical conditions. Yet the impact of the pandemic on the management of tick-borne diseases, which frequently manifest as an acute febrile illness similar to COVID-19, has not been well described. METHODS: In this retrospective cohort study of patients with suspected tick-borne disease attending the University of North Carolina Health facilities, we compared the timeliness of diagnosis and treatment in a "pre-COVID" period (March 2019 to February 2020) and a "post-COVID" period (March 2020 to February 2021). Participants included patients with an ICD-10 diagnosis code of spotted fever group rickettsiosis or ehrlichiosis and a positive Rickettsia rickettsii or Ehrlichia indirect immunofluorescence assay immunoglobulin G antibody test result. Of the 897 patients who had an eligible diagnosis, 240 (26.8%) met the inclusion criteria. The main outcome was time from initial presentation to definitive diagnosis and treatment. RESULTS: During the 2-year study period, 126 (52.5%) patients were grouped in the pre-COVID period and 114 (47.5%) were grouped in the post-COVID period; 120 (50.0%) were female; and 139 (57.9%) were aged > 50 years. Comparing the post-COVID to the pre-COVID period, the adjusted odds ratio (aOR) for delay in treatment > 0 days was 1.81 (95% confidence interval [CI] 1.07-3.07, P = 0.03), and for a treatment delay > 7 days, 1.65 (95% CI 0.94-2.90, P = 0.08). The odds of a delay in diagnosis were similar for patients in the post- and pre-COVID periods, with an aOR of 1.61 (95% CI 0.96-2.72, P = 0.07) for delays > 0 days, and aOR of 1.72 (95% CI 0.99-3.00, P = 0.05) for delays > 7 days. CONCLUSIONS: The odds of a delay in treatment > 0 days were significantly higher in the post-COVID period than in the pre-COVID period. However, the odds of a delay in treatment > 7 days, or a delay in diagnosis, were similar between these two periods. Shifts in care-seeking, alternative care delivery models and prioritization of COVID-19 may contribute to diminished timeliness of treatment for patients with tick-borne diseases.

"Leopards do not change their spots:" tick borne disease symptomology case report.

BACKGROUND: Human Monocytic Ehrlichiosis is caused by infection with the bacteria Ehrlichia chaffeensis through the bite of an infected lone star tick (Amblyomma americanum). Patients infected with Human Monocytic Ehrlichiosis often present with symptoms including fever, headache, myalgia, and occasionally a macular rash. The presence of other endemic tick-borne diseases with similar symptoms, such as Rocky Mountain Spotted Fever, complicate the diagnosis of Human Monocytic Ehrlichiosis. CASE PRESENTATION: A patient developed a fever, diffuse myalgia, headache, and a non-productive cough 5 days after a fishing trip in late May in central North Carolina. Over the course of the illness the patient's symptoms worsened, with arthralgia, bilateral lower extremity erythema and edema, and a developing bilateral rash on the palms. With testing that revealed elevated liver enzymes, a potential for recent tick exposure (e.g., fishing trip), presentation during tick season, and the development of a rash, Rocky Mountain Spotted Fever and Human Monocytic Ehrlichiosis were considered. The patient was prescribed a seven-day course of oral doxycycline and cefalexin, which would provide coverage from Rickettsia, Ehrlichia and gram-positive bacteria typically responsible for cellulitis. Many of the patient's symptoms resolved or improved, although the right shoulder remained painful to active movement. The patient was prescribed another seven-day course of doxycycline due to his perceived incomplete response to the first course. Approximately 5 weeks after symptom onset (D0 + 36), the patient followed up with a provider for convalescent testing and counseling. Convalescent Ehrlichia and Rickettsia serological tests were ordered. The acute Ehrlichia serology and acute Rickettsia serology were originally non-reactive with both titers measured at < 1:64. Convalescent serology, ordered 28 days after the acute sample collection, showed a greater than four-fold increase in the Ehrlichia IgG titer (1:256), satisfying clinical and laboratory case definitions for ehrlichiosis. In follow-up, 3 weeks later (D0 + 57), the patient reported that most of his pain had subsided, though he still occasionally got shooting nerve pain when exercising. CONCLUSION: This case of Human Monocytic Ehrlichiosis in North Carolina exemplifies the need for a knowledge of spatial epidemiological patterns and clinical manifestations in the diagnosis of tick-borne diseases.

Patterns Testing for Tick-Borne Diseases and Implications for Surveillance in the Southeastern US.

Importance: Tick-borne diseases (TBD), including spotted fever group rickettsiosis (SFGR), ehrlichiosis, and, increasingly, Lyme disease, represent a substantial public health concern throughout much of the southeastern United States. Yet, there is uncertainty about the epidemiology of these diseases because of pitfalls in existing diagnostic test methods. Objective: To examine patterns of diagnostic testing and incidence of TBD in a large, academic health care system. Design, Setting, and Participants: This cross-sectional study included diagnostic test results for TBD at UNC Health, a large academic health care system with inpatient and outpatient facilities, from January 1, 2017, to November 30, 2020. Participants included all individuals seeking routine care at UNC Health facilities who had testing for SFGR, ehrlichiosis, or Lyme disease performed during the study period. Main Outcomes and Measures: Rates of test positivity, testing completeness, and incidence of TBD. Results: During the 4-year study period, 11 367 individuals (6633 [58.4%] female; 10 793 [95%] non-Hispanic individuals and 8850 [77.9%] White individuals; median [IQR] age, 53 [37-66] years) were tested for TBD. Among the 20 528 diagnostic tests performed, 47 laboratory-confirmed, incident cases of SFGR, 27 cases of ehrlichiosis, and 76 cases of Lyme were confirmed, representing incidence rates of 4.7%, 7.1%, and 0.7%, respectively. However, 3984 of SFGR tests (79.3%) and 3606 of Ehrlichia tests (74.3%) lacked a paired convalescent sample. Of 20 528 tests, there were 11 977 tests (58.3%) for Lyme disease from 10 208 individuals, 5448 tests (26.5%) for SFGR from 4520 individuals, and 3103 tests (15.1%) for ehrlichiosis from 2507 individuals. Most striking, testing for ehrlichiosis was performed in only 55% of patients in whom SFGR was ordered, suggesting that ehrlichiosis remains underrecognized. An estimated 187 incident cases of SFGR and 309 of ehrlichiosis were potentially unidentified because of incomplete testing. Conclusions and Relevance: In this cross-sectional study, most of the patients suspected of having TBD did not have testing performed in accordance with established guidelines, which substantially limits understanding of TBD epidemiology. Furthermore, the data revealed a large discrepancy between the local burden of disease and the testing performed. These findings underscore the need to pursue more robust, active surveillance strategies to estimate the burden of TBD and distribution of causative pathogens.

Dihydroartemisinin-Piperaquine Chemoprevention and Malaria Incidence After Severe Flooding: Evaluation of a Pragmatic Intervention in Rural Uganda.

BACKGROUND: Malaria epidemics are a well-described phenomenon after extreme precipitation and flooding. Yet, few studies have examined mitigation measures to prevent post-flood malaria epidemics. METHODS: We evaluated a malaria chemoprevention program implemented in response to severe flooding in western Uganda. Children aged ≤12 years from 1 village were eligible to receive 3 monthly rounds of dihydroartemisinin-piperaquine (DP). Two neighboring villages served as controls. Malaria cases were defined as individuals with a positive rapid diagnostic test result as recorded in health center registers. We performed a difference-in-differences analysis to estimate changes in the incidence and test positivity of malaria between intervention and control villages. RESULTS: A total of 554 children received at least 1 round of chemoprevention, with 75% participating in at least 2 rounds. Compared with control villages, we estimated a 53.4% reduction (adjusted rate ratio [aRR], 0.47; 95% confidence interval [CI]: .34-.62; P < .01) in malaria incidence and a 30% decrease in the test positivity rate (aRR, 0.70; 95% CI: .50-.97; P = .03) in the intervention village in the 6 months post-intervention. The impact was greatest among children who received the intervention, but decreased incidence was also observed in older children and adults (aRR, 0.57; 95% CI: .38-.84; P < .01). CONCLUSIONS: Three rounds of chemoprevention with DP delivered under pragmatic conditions reduced the incidence of malaria after severe flooding in western Uganda. These findings provide a proof-of-concept for the use of malaria chemoprevention to reduce excess disease burden associated with severe flooding.