Zoonotic febrile illnesses misdiagnosed as COVID-19: a review of reported clinical cases.

COVID-19 is a zoonotic coronavirus disease caused by SARS-CoV-2. Its fast spreading by aerosol transmission has made it a highly contagious disease, causing the most recent 2020 pandemic. Although it mainly affects the respiratory system, atypical forms of the disease have been described, including developing an undifferentiated febrile illness without respiratory symptoms, that can represent a diagnostic challenge, mainly in tropical areas where several zoonotic febrile diseases are circulating. Thus, despite the broad clinical spectrum of COVID-19, in the tropics, other zoonotic etiologies should always be considered as differential diagnoses. According to our case reports review, eight different zoonotic febrile diseases misdiagnosed as COVID-19 have been reported in the available scientific literature of four databases. These were only suspected due to the epidemiological history. Thus, making a complete and detailed clinical history of a febrile patient in the tropics is essential to suspect the etiology and request the necessary confirmatory tests. Therefore, COVID-19 must be included as a differential diagnosis of undifferentiated febrile illness in the tropics, but other zoonotic infectious diseases must not be ruled out.

Hepatotoxicity From Marijuana Gummies

Introduction: We report a case of drug-induced liver injury (DILI) induced by cannabis gummies containing Corydalis Rhizome. Case Description/Methods: A 37-year-old female presented to her primary care clinic with recurrent fevers, night sweats, and myalgias for 7 weeks accompanied by eye redness, brain fog, headache, nausea, and abdominal pain. She denied rashes, tick-bites, cough, dyspnea, chest pain, joint swelling, or genitourinary symptoms. Past medical history was notable for IBS, migraines, and anxiety. She reported edible marijuana use four times a week, rare alcohol use, and denied tobacco use. She denied a family history of liver disease. Physical exam was notable for tachycardia to 110 and scleral injection with the remainder of vitals and exam unremarkable. Initial labs were notable for AST 61, ALT 44 and CRP of 12. CBC, BMP, urinalysis, ESR, blood cultures, blood smear for parasite screen, tests for Lyme disease, Babesia, Tularemia, Anaplasma, Ehrlichia, Rickettsia, EBV, HIV, RPR, ANA, CMV, parvovirus B19, and chest x-ray were all negative. The patient was referred to infectious disease with further testing for West Nile, Leptospira, lymphocytic choriomeningitis virus, and COVID-19 returning negative. Repeat LFTs showed worsening transaminitis with ALT 979 and AST 712, alkaline phosphatase 88, total bilirubin 0.7, and albumin 4.9. Hepatitis workup including hepatitis A, B, and C, HSV, EBV, VZV serologies, AMA, ASMA, antiLKM Ab, acetaminophen level, INR, iron panel, CPK, TSH, and abdominal ultrasound were all normal. It was later discovered that her marijuana gummies contained Corydalis rhizome extract known to be hepatotoxic. Cessation of this drug was strongly advised. She was discharged with hepatology follow-up and underwent a liver biopsy showing patchy periportal and lobular inflammation with extension across the limiting plate, hepatocyte injury and apoptosis, and increased lipofuscin for age compatible with mild to moderate hepatitis. She had complete recovery after cessation of Corydalis-containing gummies. (Figure) Discussion: Our patient consumed '1906 Midnight', an American cannabis brand containing Corydalis rhizopus 100 mg, advertised to improve sleep, pain, and have a liver protective effect. A Korean systematic review on herbal-induced liver injury reported that Corydalis was the 3rd most frequent causative herb, with 36 cases. Although there are several personal accounts on social networking sites and other websites, there are no American-based publications reported on DILI from Corydalis. (Table Presented).

Reduced Cholesterol Levels during Acute Human Babesiosis.

BACKGROUND: Babesiosis, an intra-erythrocytic protozoan disease, is an emerging zoonotic parasitic disease worldwide. Cholesterol levels are correlated with severe infections, such as sepsis and COVID-19, and anecdotal reports suggest that high-density lipoprotein (HDL) cholesterol declines during acute babesiosis. Our aim was to describe the cholesterol levels in patients with acute babesiosis diagnosed in an endemic area in New York, hypothesizing that HDL levels correlate with the severity of infection. METHODS: We reviewed the medical records of adult patients with babesiosis diagnosed by identification of Babesia parasites on a thin blood smear and confirmed by polymerase chain reaction from 2013 to 2018, who also had available a lipid profile drawn at the time of clinical presentation. Additional lipid profile levels were considered as "baseline" if they were drawn within 2 months before or after the infection as part of routine care. RESULTS: A total of 39 patients with babesiosis had a lipid profile drawn on presentation. The patients were divided into two groups for comparison based on the treating physician's clinical decision: 33 patients who were admitted to the hospital and 8 patients who were evaluated as outpatients. A history of hypertension was more common in admitted patients (37% vs. 17%, p = 0.02). The median levels of low-density lipoprotein (LDL) and HDL were significantly reduced in admitted patients compared to non-admitted patients (46 vs. 76 mg/dL, p = 0.04; and 9 vs. 28.5 mg/dL, p = 0.03, respectively). In addition, LDL and HDL levels returned to baseline values following resolution of acute babesiosis. CONCLUSION: LDL and HDL levels are significantly reduced during acute babesiosis, suggesting that cholesterol depletion may predict disease severity. Pathogen and host factors may contribute to a reduction in serum cholesterol levels during acute babesiosis.

Pathogenesis of Anemia in Canine Babesiosis: Possible Contribution of Pro-Inflammatory Cytokines and Chemokines-A Review.

Canine babesiosis is a tick-borne protozoan disease caused by intraerythrocytic parasites of the genus Babesia. The infection may lead to anemia in infected dogs. However, anemia is not directly caused by the pathogen. The parasite's developmental stages only have a marginal role in contributing to a decreased red blood cell (RBC) count. The main cause of anemia in affected dogs is the immune response to the infection. This response includes antibody production, erythrophagocytosis, oxidative damage of RBCs, complement activation, and antibody-dependent cellular cytotoxicity. Moreover, both infected and uninfected erythrocytes are retained in the spleen and sequestered in micro-vessels. All these actions are driven by pro-inflammatory cytokines and chemokines, especially IFN-γ, TNF-α, IL-6, and IL-8. Additionally, imbalance between the actions of pro- and anti-inflammatory cytokines plays a role in patho-mechanisms leading to anemia in canine babesiosis. This article is a review of the studies on the pathogenesis of anemia in canine babesiosis and related diseases, such as bovine or murine babesiosis and human or murine malaria, and the role of pro-inflammatory cytokines and chemokines in the mechanisms leading to anemia in infected dogs.

Babesiosis and Red Blood Cell Exchange Transfusion: Consider It Early

INTRODUCTION: Babesiosis, or Babesia microti in the blood, is a rare tickborne parasitic illness. It is endemic to the Northeast and upper Midwest regions of the United States, in warmer summer months, and is a reportable disease. Babesia is transmitted by the bite of an infected Ixodes scapularis nymph tick (black-legged or deer tick). Many people remain asymptomatic, while others experience life-threatening illness. even with low parasite index, such as the case described. Cases are rising in Pennsylvania overall since 2010, but since the start of COVID-19 pandemic, our small community hospital in rural Northeastern Pennsylvania (NEPA) has seen 12 cases. DESCRIPTION: A 63-year-old male presented with severe illness due to persistent Babesiosis parasitemia in a NEPA community hospital, with history of recent COVID-19 infection. He presented with fever, rigors, myalgias, diarrhea, and weakness. He reported history of tick bite two weeks prior to presentation. Initial exam was unremarkable. He was admitted to the hospital with hyponatremia, acute liver and kidney injury, anemia, thrombocytopenia, and elevated bilirubin. Babesia microti red blood cell (RBC) parasite index initially was 2%. He then became lethargic and hypotensive and parasite index escalated to 5% with worsening febrile illness, confusion, rapid atrial fibrillation, worsening acute kidney injury, and evidence of hemolysis and consumptive coagulopathy, despite standard-of-care antimicrobial regimen. He was fluid resuscitated and transferred to a higher level of care for urgent RBC exchange, which he obtained, and recovered after prolonged intensive care unit stay. DISCUSSION: Babesiosis can present indolently or acutely with flu-like and hemolytic illness. Those at higher risk of illness are elderly, and those with asplenia, baseline liver or kidney dysfunction, or immunocompromised status. Babesia cases are rising all over the country. Our single small hospital has seen 12 cases in the past 3 years. It is a possibility that the recent COVID-19 infection created a relative immunocompromised and pro-inflammatory state leading to susceptibility to the parasite. Illness can be life-threatening. Even with low parasitemia index, early RBC exchange should be considered if end organ dysfunction is present and clinical course is not improving.

A review of the role of infections in the aetiology of haemolysis in patients with sickle cell diseases: pathogenesis, management, and prevention

Background: Sickle cell disease (SCD) is associated with chronic haemolysis, immuno-suppression and susceptibility to infections, which may trigger infection-associated haemolysis (IAH). SCD patients are vulnerable to anaemic effect of IAH due to vicious interaction between pre-existing 'inherited' chronic haemolysis and 'acquired' IAH. IAH in SCD manifests as febrile haemolytic crisis with clinical and laboratory features of severe anaemia or pancytopenia. Clinico-pathological perspectives of IAH in SCD are fragmented. This review presents a comprehensive but concise overview of pathogenesis, management and prevention of IAH in SCD. Methodology and results: Online literature search using search terms such as 'sickle cell disease, viral, bacterial, parasitic, fungal, infections, hyperhaemolytic crisis, haemophagocytic syndrome, severe anaemia, pancytopenia' in various combinations was done on PubMed/Medline, Google, Google-Scholar and Bing. Overall, 112 relevant publications were retrieved, which included 109 peer reviewed journal articles, 2 World Health Organization (WHO) technical reports, and 1 edited text book. A range of bacterial (Bartonella spp, Mycoplasma spp., Mycobacterium avium complex), viral (Dengue, SARS-CoV-2, Parvovirus-B19, Cytomegalovirus, Epstein-Barr virus), parasitic (Plasmodium spp., Babesia spp.), and fungal (Histoplasma spp.) infections were associated with IAH in SCD. There are two broad types of IAH in patients with SCD;infection associated extra-medullary haemolysis (IAEMH) and infection associated intra-medullary haemolysis (IAIMH). While IAEMH is associated with severe anaemia due to intravascular haemolysis caused by red cell invasion, oxidative injury, auto-antibodies, and/or pathogen-haem interaction, IAIMH is associated with haemophagocytic tri-lineage destruction of haematopoietic precursors in the bone marrow. Conclusion(s): Various microbial pathogens have been associated with IAH in SCD. SCD patients with fever, severe anaemia or pancytopenia should be investigated for early diagnosis and prompt treatment of IAH, which is a life-threatening haematological emergency for which transfusion therapy alone may not suffice. Prompt and sustainable termination of IAH may require therapeutic combination of transfusion, anti-microbial chemotherapy, and immune modulation therapy. SCD patients should also receive counselling on hygiene, barrier protection against vectors, routine chemoprophylaxis for locally endemic diseases, and immunization for vaccine-preventable infections as a long-term preventive strategy against IAH. Copyright AJCEM 2022.

BABESIA MICROTI INFECTION WITH LOW-GRADE PARASITEMIA CAUSING ARDS IN AN IMMUNOCOMPETENT PATIENT

SESSION TITLE: Unusual Critical Care SESSION TYPE: Rapid Fire Case Reports PRESENTED ON: 10/18/2022 10:15 am - 11:10 am INTRODUCTION: Babesiosis can have a clinical spectrum ranging from mild illness in most cases to more severe manifestations in immunosuppressed individuals or in those with high-grade parasitemia. This patient had severe babesiosis resulting in ARDS and shock in spite of being immunocompetent and having low-grade parasitemia, making it a rare presentation. CASE PRESENTATION: A 49-year-old, previously healthy woman, was admitted with high-grade fevers. Physical exam findings were normal, except for fever (103 F). Initial lab results were significant for hemolytic anemia and thrombocytopenia. Chest radiography was normal. Other microbiology studies, including COVID-19, were negative. Empiric antibiotic therapy with piperacillin-tazobactam and doxycycline was started. Peripheral smear identified rare, minute intracellular ring forms, suspicious for babesia. IV azithromycin and oral atovaquone were started. PCR was done to confirm the diagnosis and Babesia microti DNA was detected. As peripheral smear showed parasitemia of only 1% (percentage of red blood cells infected), exchange transfusion was not considered as a treatment option. Two days after admission, worsening hemodynamic and respiratory status was noted with increasing oxygen requirements. CT chest now revealed diffuse interstitial infiltrates. ARDS ensued and the patient was intubated and started on mechanical ventilation with vasopressor support. Immunodeficiency workup was normal. In view of clinical deterioration, the antimicrobials were switched from atovaquone and azithromycin to IV clindamycin and quinidine for 14 days. After a protracted ICU stay, the patient showed gradual clinical improvement, parasitemia resolved, and she was eventually discharged to a rehabilitation facility. DISCUSSION: Babesiosis is a tick-borne infectious disease endemic to the North-East and Midwest United States. Majority of the infections are self-limited. However, in immunocompromised individuals and in those with high-grade parasitemia (>10%), it manifests as a severe illness with ARDS, severe hemolysis, or shock. Diagnosis is made by identifying parasites on thin peripheral blood smears with Giemsa/Wright stains. PCR can be used for species identification and for confirming the diagnosis in cases with low-grade parasitemia (<4%). IV azithromycin plus oral atovaquone is the preferred initial regimen and IV clindamycin plus quinidine is an alternative combination that can be used in severe infection. Red blood cell exchange transfusion can be considered in patients with high-grade parasitemia or organ failure. CONCLUSIONS: Babesiosis can very rarely cause ARDS and shock in immunocompetent patients with low-grade parasitemia. Prompt diagnosis and escalation of antimicrobial regimens to clindamycin and quinidine in such cases can lead to improved clinical outcomes. Exchange transfusion can serve as a treatment option in patients with high-grade parasitemia. Reference #1: Ord RL, Lobo CA. Human babesiosis: Pathogens, prevalence, diagnosis, and treatment. Current clinical microbiology reports. 2015 Dec;2(4):173-81. Reference #2: Ripoll JG, Rizvi MS, King RL, Daniels CE. Severe Babesia microti infection presenting as multiorgan failure in an immunocompetent host. Case Reports. 2018 May 30;2018:bcr-2018. Reference #3: Sanchez E, Vannier E, Wormser GP, Hu LT. Diagnosis, treatment, and prevention of Lyme disease, human granulocytic anaplasmosis, and babesiosis: a review. Jama. 2016 Apr 26;315(16):1767-77. DISCLOSURES: No relevant relationships by Shankar Chhetri No relevant relationships by Vasudev Malik Daliparty No relevant relationships by Preethi Dendi No relevant relationships by samer talib

High genetic diversity of Babesia canis (Piana & Galli-Valerio, 1895) in a recent local outbreak in Berlin/ Brandenburg, Germany.

Canine babesiosis caused by Babesia canis (Piana & Galli-Valerio, 1895) is emerging in new regions in Europe since its vector Dermacentor reticulatus (Fabricius, 1794) is expanding its geographic range. In the Berlin/Brandenburg area in northeast Germany, D. reticulatus is highly abundant but in the past only one autochthonous B. canis infection was reported. Since 2015, autochthonous cases were occasionally diagnosed but numbers increased since autumn 2019. The aim of the study was to genotype autochthonous canine Babesia spp. infections from Berlin/Brandenburg. Between 04/2015 and 01/2022, 46 dogs with acute babesiosis were presented to the small animal clinic (one dog was infected twice resulting in 47 samples). There were 32 dogs that had never left Berlin/Brandenburg and 14 others that had not left the region in the 6 weeks prior to disease onset. PCRs targeting the 18S rRNA and the Bc28.1 merozoite surface antigen were positive in 47 and 42 samples, respectively. Sequencing of cloned PCR products identified all samples as B. canis with 17 18S rRNA and 12 Bc28.1 haplotypes. Based on network analysis for 18S rRNA sequences and a previously described polymorphic dinucleotide, samples were assigned to two distinct clusters. One contained 31 and the other 16 samples. Using network analysis, the Bc28.1 haplotypes could also be separated into two clusters differing by at least five polymorphisms. Analyses of sequences from multiple clones indicated the presence of up to five 18S rRNA and eight Bc28.1 haplotypes and thus high parasite variability in an individual host. The genetic diversity could suggest that the parasites in the region have multiple origins, but diversity in individual dogs and dog populations from endemic regions is unknown. The suitability of both markers for genotyping is questionable due to potential intragenomic diversity for the rRNA and high intergenomic variability for the Bc28.1 marker.

Molecular Epidemiology and Species Diversity of Tick-Borne Pathogens of Animals in Egypt: A Systematic Review and Meta-Analysis.

Ticks and tick-borne pathogens (TTBPs) are listed among the most serious concerns harming Egyptian livestock's productivity. Several reports on tick-borne pathogens (TBPs) from various geographical regions in the country were published. However, data on the molecular characterization of TBPs are the most beneficial for understanding the epidemiology of this important group of pathogens. In this study, we present the first meta-analysis on the molecular epidemiology and species diversity of TBPs infecting animals in Egypt. All published studies on TBPs were systematically collected from various databases (PubMed, Scopus, ScienceDirect, the Egyptian Knowledge Bank, and Google Scholar). Data from eligible papers were extracted and subjected to various analyses. Seventy-eight studies were found to be eligible for inclusion. Furthermore, ticks infesting animals that were molecularly screened for their associated pathogens were also included in this study to display high species diversity and underline the high infection risk to animals. Theileria annulata was used as parasite model of TBPs to study the genetic diversity and transmission dynamics across different governorates of Egypt. This study extends cross-comparisons between all published molecular data on TBPs in Egypt and provides resources from Egyptian data in order to better understand parasite epidemiology, species diversity, and disease outcome as well as the development and implementation of prevention and control methods for public health, veterinary care practitioners, and animal owners all over the country.

Quarterly report of investigations of suspected exotic diseases: July to September 2021

Exotic pest and disease investigations are managed and reported by the Ministry for Primary Industries' (MPI's) Diagnostic and Surveillance Directorate. This article presents a summary of investigations of suspect exotic and emerging pests and diseases in New Zealand during the period from July to September 2021.

An Alternative Culture Medium for Continuous In Vitro Propagation of the Human Pathogen Babesia duncani in Human Erythrocytes.

Continuous propagation of Babesia duncani in vitro in human erythrocytes and the availability of a mouse model of B. duncani lethal infection make this parasite an ideal model to study Babesia biology and pathogenesis. Two culture media, HL-1 and Claycomb, with proprietary formulations are the only culture media known to support the parasite growth in human erythrocytes; however, the HL-1 medium has been discontinued and the Claycomb medium is often unavailable leading to major interruptions in the study of this pathogen. To identify alternative media conditions, we evaluated the growth of B. duncani in various culture media with well-defined compositions. We report that the DMEM-F12 culture medium supports the continuous growth of the parasite in human erythrocytes to levels equal to those achieved in the HL-1 and Claycomb media. We generated new clones of B. duncani from the parental WA-1 clinical isolate after three consecutive subcloning events in this medium. All clones showed a multiplication rate in vitro similar to that of the WA-1 parental isolate and cause fatal infection in C3H/HeJ mice. The culture medium, which can be readily reconstituted from its individual components, and the tools and resources developed here will facilitate the study of B. duncani.

Fluorescence In Situ Hybridization (FISH) Tests for Identifying Protozoan and Bacterial Pathogens in Infectious Diseases.

Diagnosing and treating many infectious diseases depends on correctly identifying the causative pathogen. Characterization of pathogen-specific nucleic acid sequences by PCR is the most sensitive and specific method available for this purpose, although it is restricted to laboratories that have the necessary infrastructure and finance. Microscopy, rapid immunochromatographic tests for antigens, and immunoassays for detecting pathogen-specific antibodies are alternative and useful diagnostic methods with different advantages and disadvantages. Detection of ribosomal RNA molecules in the cytoplasm of bacterial and protozoan pathogens by fluorescence in-situ hybridization (FISH) using sequence-specific fluorescently labelled DNA probes, is cheaper than PCR and requires minimal equipment and infrastructure. A LED light source attached to most laboratory light microscopes can be used in place of a fluorescence microscope with a UV lamp for FISH. A FISH test hybridization can be completed in 30 min at 37 °C and the whole test in less than two hours. FISH tests can therefore be rapidly performed in both well-equipped and poorly-resourced laboratories. Highly sensitive and specific FISH tests for identifying many bacterial and protozoan pathogens that cause disease in humans, livestock and pets are reviewed, with particular reference to parasites causing malaria and babesiosis, and mycobacteria responsible for tuberculosis.

Old zoonotic agents and novel variants of tick-borne microorganisms from Benguela (Angola), July 2017.

BACKGROUND: Ticks and tick-borne diseases constitute a real threat for the livestock industry, which is increasing in Angola. In addition, ticks are vectors of zoonoses of public health concern, and scarce information is available from this country. In an effort to contribute to the prevention of zoonotic infectious diseases affecting humans and animals, the molecular screening of certain tick-related microorganisms collected on cattle in Angola was performed under a 'One Health' scope. METHODS: Ticks collected from cattle in Cubal (Benguela Province, Angola) in July 2017 were analysed in pools using specific PCR assays for bacteria (Rickettsia, Anaplasmataceae, Borrelia, Coxiella and Spiroplasma) and protozoa (Theileria and Babesia) detection. RESULTS: A total of 124 tick specimens were grouped in 25 pools (two Amblyomma variegatum, three Hyalomma truncatum, 16 Rhipicephalus decoloratus, two Rhipicephalus duttoni, one Rhipicephalus evertsi mimeticus and one Rhipicephalus sp.). The amplified microorganisms were (pools): Rickettsia africae (two A. variegatum and one R. decoloratus), Rickettsia aeschlimannii (three H. truncatum), Ehrlichia spp. (six R. decoloratus), Coxiella spp. (all but H. truncatum), Francisella sp. (one H. truncatum), Spiroplasma sp. closely related to Spiroplasma ixodetis (three R. decoloratus), Babesia bigemina (two R. decoloratus) and Babesia spp. (two A. variegatum). The obtained nucleotide sequences from Ehrlichia spp., two Coxiella genotypes (from R. duttoni and Rhipicephalus sp.), Francisella sp. and Babesia spp. (from A. variegatum) reached low identities with known genetically characterized species. CONCLUSIONS: This study demonstrates the circulation in Angola of the pathogen R. aeschlimannii and potential novel tick-related microorganisms belonging to Ehrlichia, Coxiella, Francisella, Spiroplasma and Babesia spp. and corroborates the presence of R. africae and B. bigemina. Our results should be considered in developing protocols for the management of fever of unknown origin and for veterinary practices. Further studies are required to evaluate the risk of tick-borne diseases in Angola.

Detection of Anaplasma phagocytophilum, Babesia odocoilei, Babesia sp., Borrelia burgdorferi Sensu Lato, and Hepatozoon canis in Ixodes scapularis Ticks Collected in Eastern Canada.

Tick-borne pathogens cause infectious diseases that inflict much societal and financial hardship worldwide. Blacklegged ticks, Ixodes scapularis, are primary vectors of several epizootic and zoonotic pathogens. The aim was to find varius pathogens of I. scapularis and to determine their prevalence. In Ontario and Quebec, 113 I. scapularis ticks were collected from songbirds, mammals, including humans, and by flagging. PCR and DNA sequencing detected five different microorganisms: Anaplasma phagocytophilum, 1 (0.9%); Babesia odocoilei, 17 (15.3%); Babesia microti-like sp., 1 (0.9%); Borrelia burgdorferi sensu lato (Bbsl), 29 (26.1%); and Hepatozoon canis, 1 (0.9%). Five coinfections of Bbsl and Babesia odocoilei occurred. Notably, H. canis was documented for the first time in Canada and, at the same time, demonstrates the first transstadial passage of H. canis in I. scapularis. Transstadial passage of Bbsl and B. odocoilei was also witnessed. A novel undescribed piroplasm (Babesia microti-like) was detected. An established population of I. scapularis ticks was detected at Ste-Anne-de-Bellevue, Quebec. Because songbirds widely disperse I. scapularis larvae and nymphs, exposure in an endemic area is not required to contract tick-borne zoonoses. Based on the diversity of zoonotic pathogens in I. scapularis ticks, clinicians need to be aware that people who are bitten by I. scapularis ticks may require select antimicrobial regimens.