Absence of Anti-Babesia microti antibody in commercial intravenous immunoglobulin (IVIG).

BACKGROUND: Babesiosis is a worldwide emerging protozoan infection that is associated with a spectrum of disease severity from asymptomatic infection to severe organ damage and death. While effective treatment strategies are available, some immunocompromised patients experience severe acute and prolonged/relapsing illness due in part to an impaired host antibody response. Intravenous immunoglobulin (IVIG) has been used as an adjunctive therapy in some immunocompromised babesiosis patients, but its therapeutic effect is uncertain. We evaluated the presence of Babesia microti antibodies in commercial samples of IVIG. METHODS/PRINCIPLE FINDINGS: The presence of B. microti antibodies in commercial samples of IVIG were tested using an immunofluorescence assay. A subset of samples was then tested for B. microti antibodies using an enzyme linked immunosorbent assay. Out of 57 commercial IVIG samples tested using IFA, and 52 samples tested using ELISA, none were positive for B. microti antibodies. CONCLUSIONS: Commercially available IVIG may not be of therapeutic benefit for babesiosis patients. Additional sampling of IVIG for B. microti antibody and a clinical trial of babesiosis patients given IVIG compared with controls would provide further insight into the use of IVIG for the treatment of babesiosis.

Immune Control in Repeated Babesia microti Infection in a Patient With B-Cell Deficiency.

The immunology of human babesiosis is poorly investigated. We present a comprehensive investigation of a 75-year-old man with B-cell deficiency who experienced 3 episodes of babesiosis over a 6-year period. Slowly evolving clinical immunity was observed, as evidenced by milder clinical symptoms and lower peak parasite burden after each subsequent babesiosis episode. The patient exhibited several striking immunologic findings. First, the patient had exceptionally high Babesia microti-specific antibodies despite very few circulating B cells, which predominantly coexpressed CD27 (memory marker) and CD95 (death receptor). Second, we demonstrated the presence of long-lasting NK cells and expansion of T memory stem cells. Third, levels of the IP-10 cytokine directly correlated with parasite burden. These results raise fundamental questions on the priming, maintenance, and location of a B-cell population that produces high antibody levels in the face of severe B-cell deficiency. Our results should invoke interest among researchers to study the immunology and pathogenesis of human babesiosis.

Transfusion-transmitted Babesia spp.: a changing landscape of epidemiology, regulation, and risk mitigation.

Babesia spp. are tick-borne parasites with a global distribution and diversity of vertebrate hosts. Over the next several decades, climate change is expected to impact humans, vectors, and vertebrate hosts and change the epidemiology of Babesia. Although humans are dead-end hosts for tick-transmitted Babesia, human-to-human transmission of Babesia spp. from transfusion of red blood cells and whole blood-derived platelet concentrates has been reported. In most patients, transfusion-transmitted Babesia (TTB) results in a moderate-to-severe illness. Currently, in North America, most cases of TTB have been described in the United States. TTB cases outside North America are rare, but case numbers may change over time with increased recognition of babesiosis and as the epidemiology of Babesia is impacted by climate change. Therefore, TTB is a concern of microbiologists working in blood operator settings, as well as in clinical settings where transfusion occurs. Microbiologists play an important role in deploying blood donor screening assays in Babesia endemic regions, identifying changing risks for Babesia in non-endemic areas, investigating recipients of blood products for TTB, and drafting TTB policies and guidelines. In this review, we provide an overview of the clinical presentation and epidemiology of TTB. We identify approaches and technologies to reduce the risk of collecting blood products from Babesia-infected donors and describe how investigations of TTB are undertaken. We also describe how microbiologists in Babesia non-endemic regions can assess for changing risks of TTB and decide when to focus on laboratory-test-based approaches or pathogen reduction to reduce TTB risk.

Neurologic Complications of Babesiosis, United States, 2011-2021.

Babesiosis is a globally distributed parasitic infection caused by intraerythrocytic protozoa. The full spectrum of neurologic symptoms, the underlying neuropathophysiology, and neurologic risk factors are poorly understood. Our study sought to describe the type and frequency of neurologic complications of babesiosis in a group of hospitalized patients and assess risk factors that might predispose patients to neurologic complications. We reviewed medical records of adult patients who were admitted to Yale-New Haven Hospital, New Haven, Connecticut, USA, during January 2011-October 2021 with laboratory-confirmed babesiosis. More than half of the 163 patients experienced >1 neurologic symptoms during their hospital admissions. The most frequent symptoms were headache, confusion/delirium, and impaired consciousness. Neurologic symptoms were associated with high-grade parasitemia, renal failure, and history of diabetes mellitus. Clinicians working in endemic areas should recognize the range of symptoms associated with babesiosis, including neurologic.

Human Borrelia miyamotoi Infection in North America.

Borrelia miyamotoi is an emerging pathogen that causes a febrile illness and is transmitted by the same hard-bodied (ixodid) ticks that transmit several other pathogens, including Borrelia species that cause Lyme disease. B. miyamotoi was discovered in 1994 in Ixodes persulcatus ticks in Japan. It was first reported in humans in 2011 in Russia. It has subsequently been reported in North America, Europe, and Asia. B. miyamotoi infection is widespread in Ixodes ticks in the northeastern, northern Midwestern, and far western United States and in Canada. In endemic areas, human B. miyamotoi seroprevalence averages from 1 to 3% of the population, compared with 15 to 20% for B. burgdorferi. The most common clinical manifestations of B. miyamotoi infection are fever, fatigue, headache, chills, myalgia, arthralgia, and nausea. Complications include relapsing fever and rarely, meningoencephalitis. Because clinical manifestations are nonspecific, diagnosis requires laboratory confirmation by PCR or blood smear examination. Antibiotics are effective in clearing infection and are the same as those used for Lyme disease, including doxycycline, tetracycline, erythromycin, penicillin, and ceftriaxone. Preventive measures include avoiding areas where B. miyamotoi-infected ticks are found, landscape management, and personal protective strategies such as protective clothing, use of acaricides, and tick checks with rapid removal of embedded ticks.

The impact of ABO and RhD blood types on Babesia microti infection.

BACKGROUND: Babesiosis is an emerging infectious disease caused by intraerythrocytic Babesia parasites that can cause severe disease and death. While blood type is known to affect the mortality of Plasmodium falciparum malaria patients, associations between red blood cell (RBC) antigens and Babesia microti infection and disease severity are lacking. METHODS: We evaluated RhD and ABO blood types of Babesia-infected (18S rRNA reactive) blood donors in 10 endemic states in the Northeastern and northern Midwestern United States. We also assessed possible associations between RhD and ABO blood types and disease severity among hospitalized babesiosis patients in Connecticut. RESULTS: A total of 768 Babesia-infected blood donors were analyzed, of which 750 (97.7%) had detectable B. microti-specific antibodies. B. microti-infected blood donors were more likely to be RhD- (OR of 1.22, p-value 0.024) than RhD+ donors. Hospitalized RhD- babesiosis patients were more likely than RhD+ patients to have high peak parasitemia (p-value 0.017), which is a marker for disease severity. No differences in RhD+ blood type were noted between residents of the Northeast (OR of 0.82, p-value 0.033) and the Midwest (OR of 0.74, p-value 0.23). Overall, ABO blood type was not associated with blood donor B. microti infection, however, B. microti-infected donors in Maine and New Jersey were more likely to be blood type B compared to non-type B (OR 2.49 [p = 0.008] and 2.07 [p = 0.009], respectively), while infected donors from Pennsylvania were less likely to be type B compared to non-type B (OR 0.32 [p = 0.02]). CONCLUSIONS: People expressing RhD antigen may have a decreased risk of B. microti infection and babesiosis severity. The association of B antigen with B. microti infection is less clear because the antigen appeared to be less prevalent in infected Pennsylvania blood donors but more prevalent in Maine and New Jersey infected donors. Future studies should quantify associations between B. microti genotypes, RBC antigens, and the frequency and severity of B. microti infection to increase our understanding of human Babesia pathogenesis and improve antibody, vaccine, and RBC exchange transfusion strategies.

Animal models of the immunology and pathogenesis of human babesiosis.

Animal models of human babesiosis have provided a basic understanding of the immunological mechanisms that clear, or occasionally exacerbate, Babesia infection and those pathological processes that cause disease complications. Human Babesia infection can cause asymptomatic infection, mild to moderate disease, or severe disease resulting in organ dysfunction and death. More than 100 Babesia species infect a wide array of wild and domestic animals, and many of the immunologic and pathologic responses to Babesia infection are similar in animals and humans. In this review, we summarize the knowledge gained from animal studies, their limitations, and how animal models or alternative approaches can be further leveraged to improve our understanding of human babesiosis.

Broad Antimicrobial Resistance in a Case of Relapsing Babesiosis Successfully Treated With Tafenoquine.

We describe a case of relapsing babesiosis in an immunocompromised patient. A point mutation in the Babesia microti 23S rRNA gene predicted resistance to azithromycin and clindamycin, whereas an amino acid change in the parasite cytochrome b predicted resistance to atovaquone. Following initiation of tafenoquine, symptoms and parasitemia resolved.

Cardiac Complications of Human Babesiosis.

BACKGROUND: Human babesiosis is a worldwide emerging tick-borne disease caused by intraerythrocytic protozoa. Most patients experience mild to moderate illness, but life-threatening complications can occur. Although cardiac complications are common, the full spectrum of cardiac disease and the frequency, risk factors, and outcomes in patients experiencing cardiac complications are unclear. Accordingly, we carried out a record review of cardiac complications among patients with babesiosis admitted to Yale-New Haven Hospital over the last decade to better characterize cardiac complications of babesiosis. METHODS: We reviewed the medical records of all adult patients with babesiosis admitted to Yale-New Haven Hospital from January 2011 to October 2021, confirmed by identification of Babesia parasites on thin blood smear and/or by polymerase chain reaction. The presence of Lyme disease and other tick-borne disease coinfections were recorded. RESULTS: Of 163 enrolled patients, 32 (19.6%) had ≥1 cardiac complication during hospitalization. The most common cardiac complications were atrial fibrillation (9.4%), heart failure (8.6%), corrected QT interval prolongation (8.0%), and cardiac ischemia (6.8%). Neither cardiovascular disease risk factors nor preexisting cardiac conditions were significantly associated with the development of cardiac complications. The cardiac complication group had a greater prevalence of high-grade parasitemia (>10%) (P < .001), longer median length of both hospital (P < .001) and intensive care unit stay (P < .001), and a higher mortality rate (P = .02) than the group without cardiac complications. CONCLUSIONS: Cardiac complications of acute babesiosis are common and occurred in approximately one-fifth of this inpatient sample. Further investigation is needed to elucidate the relationship between babesiosis severity and cardiac outcomes.

Comparing the Epidemiology and Health Burden of Lyme Disease and Babesiosis Hospitalizations in the United States.

Background: Lyme disease (LD) and babesiosis are increasing in the United States. We sought to characterize and compare their epidemiology and health burden using a nationally representative sample of hospitalizations. Methods: Data were extracted from the National Inpatient Sample (NIS) pertaining to LD and babesiosis for 2018 and 2019. The NIS is a comprehensive database of all-payer inpatient hospitalizations, representing a stratified systematic random sample of discharges from US hospitals. Patient demographics, clinical outcomes, and admission costs were evaluated, in addition to hospital-level variables (eg, location/teaching status and census division). Annual incidence of hospitalizations was calculated using US Census Bureau data. Results: The annual incidence of hospitalizations of LD-related and babesiosis-related hospitalizations were 6.98 and 2.03 per 1 000 000 persons/year. Of the 4585 LD hospitalizations in 2018-2019, 60.9% were among male patients, 85.3% were White, and 39.0% were ≥60 years. Of the 1330 babesiosis hospitalizations in 2018-2019, 72.2% were among male patients, 78.9% were White, and 74.1% were ≥60 years; 70.0% of LD and 91.7% of babesiosis hospitalizations occurred in Middle Atlantic or New England. Lower disease severity was noted in 81.8% of LD hospitalizations compared with 49.3% of babesiosis hospitalizations, whereas those suffering from high severity were 2.3% and 6.0%, respectively. The mean hospital charges for LD and babesiosis hospitalizations were $33 440.8 and $40 689.8, respectively. Conclusions: Despite overlap between the 2 diseases, LD has a broader geographic range and a greater number of hospital admissions, whereas babesiosis is more severe, incurring longer hospital stays, higher inpatient costs, and deaths.

Human Babesiosis.

Babesiosis is caused by intraerythrocytic parasites that are transmitted primarily by ticks, infrequently through blood transfusion, and rarely through transplacental transmission or organ transplantation. Human babesiosis is found throughout the world, but the incidence is highest in the Northeast and upper Midwestern United States. Babesiosis has clinical features that resemble malaria and can be fatal in immunocompromised and older patients. Diagnosis is confirmed by identification of Babesia parasites on blood smear or Babesia DNA with polymerase chain reaction. Standard treatment consists of atovaquone and azithromycin or clindamycin and quinine for 7 to 10 days.

Correction: Kumar et al. The Global Emergence of Human Babesiosis. Pathogens 2021, 10, 1447.

In the original publication [...].

Borrelia miyamotoi Meningoencephalitis in an Immunocompetent Patient.

Borrelia miyamotoi is an underdiagnosed cause of tick-borne illness in endemic regions and, in rare cases, causes neurological disease in immunocompetent patients. Here, we present a case of serologically confirmed Borrelia miyamotoi meningoencephalitis in an otherwise healthy patient who rapidly improved following initiation of antibiotic therapy.

Correction: Kumar et al. The Global Emergence of Human Babesiosis. Pathogens 2021, 10, 1447.

There were two factual errors in the original publication of our manuscript [...].

The utility of a maximum entropy species distribution model for Ixodes scapularis in predicting the public health risk of Lyme disease in Ontario, Canada.

Lyme disease is an emerging public health threat in Ontario, Canada due to ongoing range expansion of the tick vector, Ixodes scapularis. Tick density is an important predictor of human Lyme disease risk and is typically measured using active tick surveillance via drag sampling, which is time and resource-intensive. New cost-effective tools are needed to augment current surveillance activities. Our objective was to evaluate the ability of a maximum entropy (Maxent) species distribution model to predict I. scapularis density in three regions of Ontario - Ottawa, Kingston, and southern Ontario - in order to determine its utility in predicting the public health risk of Lyme disease. Ticks were collected via drag sampling at 60 sites across the three regions. Model-predicted habitat suitability was calculated from a previously constructed Maxent model as the mean predicted habitat suitability within a 1-km radius of each site. Spearman's correlation coefficient was used to quantify the continuous relationship between model-predicted habitat suitability and tick density, and negative binomial regression was used to quantify the relationship between tick density and model-predicated habitat suitability. Spearman's correlation coefficients for the full study area, Kingston region, and Ottawa region were 0.517, 0.707, and 0.537, respectively, indicating a moderate positive relationship and ability of the model to predict tick density. Regression analysis further demonstrated a significant positive association between tick density and model-predicted habitat suitability (p< 0.001). Using a dichotomized measure of model-predicted habitat suitability, the incidence rate ratio - the ratio of ticks per m2 in sites predicted to have a 'suitable' habitat compared to those predicted to have 'not suitable' habitat - was 33.95, indicating that tick density was significantly higher at sites situated in areas with predicted suitable habitat. Given that tick density is an important component of Lyme disease risk, the ability to predict high tick density locations using the Maxent model may make it a cost-effective tool for identifying geographic areas that pose elevated public health risk of Lyme disease.

Frequency and Geographic Distribution of Borrelia miyamotoi, Borrelia burgdorferi, and Babesia microti Infections in New England Residents.

BACKGROUND: Borrelia miyamotoi is a relapsing fever spirochete that relatively recently has been reported to infect humans. It causes an acute undifferentiated febrile illness that can include meningoencephalitis and relapsing fever. Like Borrelia burgdorferi, it is transmitted by Ixodes scapularis ticks in the northeastern United States and by Ixodes pacificus ticks in the western United States. Despite reports of clinical cases from North America, Europe, and Asia, the prevalence, geographic range, and pattern of expansion of human B. miyamotoi infection are uncertain. To better understand these characteristics of B. miyamotoi in relation to other tickborne infections, we carried out a cross-sectional seroprevalence study across New England that surveyed B. miyamotoi, B. burgdorferi, and Babesia microti infections. METHODS: We measured specific antibodies against B. miyamotoi, B. burgdorferi, and B. microti among individuals living in 5 New England states in 2018. RESULTS: Analysis of 1153 serum samples collected at 11 catchment sites showed that the average seroprevalence for B. miyamotoi was 2.8% (range, 0.6%-5.2%), which was less than that of B. burgdorferi (11.0%; range, 6.8%-15.6%) and B. microti (10.0%; range, 6.5%-13.6%). Antibody screening within county residence in New England showed varying levels of seroprevalence for these pathogens but did not reveal a vectoral geographical pattern of distribution. CONCLUSIONS: Human infections caused by B. miyamotoi, B. burgdorferi, and B. microti are widespread with varying prevalence throughout New England.

Epidemiology of Hospitalized Patients with Babesiosis, United States, 2010-2016.

Babesia spp. are tickborne parasites that cause the clinical infection babesiosis, which has an increasing incidence in the United States. We performed an analysis of hospitalizations in the United States during 2010-2016 in which babesiosis was listed as a diagnosis. We used the National Inpatient Sample database to characterize the epidemiology of Babesia-associated admissions, reflecting severe Babesia-related disease. Over a 7-year period, a total of 7,818 hospitalizations listed babesiosis as a primary or secondary admitting diagnosis. Hospitalizations were seasonal (71.2% occurred during June-August) and situated overwhelmingly in the Northeast and Midwest. The patients were predominantly male and of advanced age, which is consistent with the expected epidemiology. Despite a higher severity of illness in more than (58.5%), the mortality rate was low (1.6%). Comparison with state reporting data suggests that the number of hospitalized persons with babesiosis increased modestly during the observation period.

The Global Emergence of Human Babesiosis.

Babesiosis is an emerging tick-borne disease caused by intraerythrocytic protozoa that are primarily transmitted by hard-bodied (ixodid) ticks and rarely through blood transfusion, perinatally, and organ transplantation. More than 100 Babesia species infect a wide spectrum of wild and domestic animals worldwide and six have been identified as human pathogens. Babesia microti is the predominant species that infects humans, is found throughout the world, and causes endemic disease in the United States and China. Babesia venatorum and Babesia crassa-like agent also cause endemic disease in China. Babesia divergens is the predominant species in Europe where fulminant cases have been reported sporadically. The number of B. microti infections has been increasing globally in recent decades. In the United States, more than 2000 cases are reported each year, although the actual number is thought to be much higher. In this review of the epidemiology of human babesiosis, we discuss epidemiologic tools used to monitor disease location and frequency; demographics and modes of transmission; the location of human babesiosis; the causative Babesia species in the Americas, Europe, Asia, Africa, and Australia; the primary clinical characteristics associated with each of these infections; and the increasing global health burden of this disease.

Babesia microti: Pathogen Genomics, Genetic Variability, Immunodominant Antigens, and Pathogenesis.

More than 100 Babesia spp. tick-borne parasites are known to infect mammalian and avian hosts. Babesia belong to Order Piroplasmid ranked in the Phylum Apicomplexa. Recent phylogenetic studies have revealed that of the three genera that constitute Piroplasmida, Babesia and Theileria are polyphyletic while Cytauxzoon is nested within a clade of Theileria. Several Babesia spp. and sub-types have been found to cause human disease. Babesia microti, the most common species that infects humans, is endemic in the Northeastern and upper Midwestern United States and is sporadically reported elsewhere in the world. Most infections are transmitted by Ixodid (hard-bodied) ticks, although they occasionally can be spread through blood transfusion and rarely via perinatal transmission and organ transplantation. Babesiosis most often presents as a mild to moderate disease, however infection severity ranges from asymptomatic to lethal. Diagnosis is usually confirmed by blood smear or polymerase chain reaction (PCR). Treatment consists of atovaquone and azithromycin or clindamycin and quinine and usually is effective but may be problematic in immunocompromised hosts. There is no human Babesia vaccine. B. microti genomics studies have only recently been initiated, however they already have yielded important new insights regarding the pathogen, population structure, and pathogenesis. Continued genomic research holds great promise for improving the diagnosis, management, and prevention of human babesiosis, and in particular, the identification of lineage-specific families of cell-surface proteins with potential roles in cytoadherence, immune evasion and pathogenesis.