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Ethnopharmacological Relevance: Milk production, processing and consumption are integral part of traditional practices in Fulani tribe of Cameroon. It has been observed that Fulani are resistant to malaria. Dairy products traditionally processed by Fulani are intensively used in the ritual treatment of malarial, inflammations and behavioural disorders. Many studies have demonstrated that fermented milk is a rich source of probiotic bacteria. However, the antimalarial activity of probiotics isolated from this natural source has not been experimentally tested., Aim of the Study: Hence, this study was therefore aimed at evaluating the antimalarial activity of a probiotic bacterium Lactobacillus sakei isolated from traditionally fermented milk in mice infected with chloroquine sensitive Plasmodium berghei ANKA., Materials and Methods: The probiotic bacterium was isolated from the Cameroonian Mborro Fulani's traditionally fermented milk and identified using the 16S r RNA gene sequencing. The schizontocidal activity of Lactobacillus sakei on established malaria infection was evaluated. Eighty-four healthy young adult Balb/c mice infected with Plasmodium berghei parasite were randomly divided into two sets of seven group of six mice each, and were given three different doses of Lactobacillus sakei, chloroquine and sulfadoxine/pyrimethamine for seven and fourteen days respectively. The level of parasitaemia, body temperature, survival time and haematological parameters were evaluated., Results: The parasite growth inhibition was observed to increase with increasing dose of probiotic bacterium with maximum suppression being 100 % at dose 3 on day 20. Also, the probiotic bacterium significantly prevented body weight loss and was associated with body temperature reduction and prevented (p<0.05) a decrease in haematological parameters compared to that untreated malaria infected mice., Conclusion: The results obtained suggest that Lactobacillus sakei is a probiotic bacterium with antimalarial activity in mice infected with chloroquine sensitive Plasmodium berghei., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Human babesiosis is a parasitic disease prevalent in the Northeastern and Midwestern United States (US). Treatment with antibiotics is the standard of care but red cell exchange (RCE) has been used as an adjunctive treatment in more severe disease. Data for the efficacy of RCE in the treatment of babesiosis has been based on case reports and case series. An English language literature search was conducted for cases of babesiosis treated with RCE since 1980 and relevant laboratory and clinical outcome data were extracted. Similar data were obtained on severe cases of babesiosis referred for RCE in our hospitals in the time period 2000 to 2020. Fifty reports including forty-one individual case reports and nine case series were retrieved. There were 108 patients that underwent RCE with an overall mortality rate of 20%. Some patients had more than one RCE. The patients varied in the level of anemia and evidence of compromise of renal or pulmonary function. The pre-RCE level of parasitemia varied between 1.7% to 85% with the vast majority >10%. The post-RCE level of parasitemia varied between 1% to 10%. Since 2000, 32 patients were referred for RCE in our hospitals and RCE was performed on 23 of 32. There were more patients treated with RCE in the second decade as compared to the first decade, 19 versus 4 respectively. The overall mortality was 22% similar to the national data. Comparing the cohort treated with RCE to the 9 patients who were treated only with antibiotics, there were similar levels of parasitemia and laboratory parameters. The overall number of days needed to achieve a parasite count <1% was similar between the two cohorts and mortality for the antibiotics only cohort was 0%. More than 40 years after the first reported case of RCE in severe babesiosis it cannot be concluded that this adjunctive therapy favorably influences the clinical outcome. Since there is largely equipoise, a registry of severe patients treated with or without RCE could identify a benefit or otherwise., (Copyright © 2021. Published by Elsevier Inc.)

Babesia spp. are tick-transmitted intra-erythrocytic protozoan parasites that infect humans and animals, causing a flu-like illness and hemolytic anemia. There is currently no human vaccine available. People most at risk of severe disease are the elderly, immunosuppressed, and asplenic individuals. B. microti and B. divergens are the predominant species affecting humans. Here, we present a whole-parasite Babesia vaccine. To establish proof-of-principle, we employed chemically attenuated B. microti parasitized red blood cells from infected mice. To aid clinical translation, we produced liposomes containing killed parasite material. Vaccination significantly reduces peak parasitemia following challenge. B cells and anti-parasite antibodies do not significantly contribute to vaccine efficacy. Protection is abrogated by the removal of CD4 + T cells or macrophages prior to challenge. Importantly, splenectomized mice are protected by vaccination. To further facilitate translation, we prepared a culture-based liposomal vaccine and demonstrate that this performs as a universal vaccine inducing immunity against different human Babesia species., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: The association between parasite burden and end-organ dysfunction in subjects with Babesia microti infection has not been extensively studied, nor has the optimal role of red blood cell exchange (RCE) transfusion in babesiosis treatment. This retrospective chart review evaluates the associations between parasitemia, end-organ dysfunction, and outcomes in babesiosis patients treated with antimicrobial agents and RCE compared to those treated with antimicrobial agents alone., Materials and Methods: We evaluated adults (≥18 years of age) with laboratory-confirmed babesiosis who were admitted between 2011 and 2017 to Yale New Haven Hospital, located in a Babesia-endemic region of the Northeastern United States. Patient demographics, parasitemia levels, clinical and laboratory indicators of end-organ dysfunction, and outcomes were examined., Results: Ninety-one subjects (mean age 65.1 years, 69.2% male) were studied. Subjects were stratified according to peak parasitemia: <1% (n = 34), 1-5% (n = 24), 5-10% (n = 15), and >10% (n = 18). Laboratory measures indicating degrees of hemolysis, coagulopathy, and pulmonary, renal and hepatic dysfunction differed significantly across peak parasitemia levels. Median length of hospital stay increased with each successive peak parasitemia level (P < .001). These results indicate a strong association between peak parasitemia level and disease severity. Nineteen subjects underwent RCE, all with peak parasitemia ≥9% and some degree of end-organ dysfunction., Conclusions: Babesia microti parasitemia is closely associated with disease severity, though not all subjects with end-organ dysfunction had high-grade parasitemia. Our data suggest that the use of parasitemia >10%, coupled with clinical status, is a reasonable indicator for RCE in babesiosis patients., (© 2020 Wiley Periodicals LLC.)

We report a case of severe babesiosis presenting with 43% parasitemia in a 73-year-old splenectomized woman on etanercept for rheumatoid arthritis. She initially was treated aggressively with clindamycin and quinine and exchange transfusion. Despite a post-exchange drop in parasitemia to 7.6%, it rebounded to 11.4% on hospital day 5 accompanied by new onset high fevers and hypoxia. She improved after a second exchange transfusion and ultimately resolved her infection after 12 weeks of antibabesial antibiotics. Although exchange transfusion is commonly used in immunocompromised hosts, there is a dearth of information about repeat exchange transfusion, including the risk for and outcome of repeat exchange. We performed a literature search for other cases of repeat exchange transfusion for severe Babesia microti infection and compared our case with those in other published reports., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Background: Infection with the protozoan parasite Babesia, the causative agent of babesiosis, can result in asymptomatic to life-threatening illness. Severe cases of babesiosis are characterized by high levels of parasitemia (>4%-10%) and commonly treated with adjunctive red blood cell exchange (RCE) in addition to antimicrobial therapy. The efficacy of RCE in this context is unknown., Study Design and Methods: Blood bank records were examined for requests for RCE during a 10-year period from 2007 to 2017. Relevant clinical and laboratory variables were extracted from medical records from presentation to 35 days after RCE and analyzed in univariate and multivariate models., Results: Nineteen cases of babesiosis were identified in which RCE was performed. The median age of patients was 77 years, 74% of whom were male. A total of 37% of patients were asplenic. RCE was performed on average 1.3 days after presentation, with procedural urgency driven mainly by the level of parasitemia. Mean pre- and post-RCE levels of parasitemia were 12.9 and 3.4%, respectively, resulting in a mean percent reduction in parasitemia of 75%. Preprocedural parasitemia (p = 0.047) and age (p = 0.028) were both significant predictors of postprocedural hospital length of stay (post-RCE LOS). Neither postprocedural parasitemia (p = 0.12) nor percent reduction in parasitemia (p = 0.72) correlated with post-RCE LOS. Four patients died, none of whom were asplenic. Mortality was not correlated with hematologic, parasitologic, or clinical variables analyzed., Conclusions: Reduction in the level of parasitemia is the only known benefit of RCE in severe babesiosis., (© 2019 AABB.)

Early trials of killed, whole-cell typhoid vaccine indicated a paradoxical, positive effect on malaria infections. British soldiers in India in 1898 reported > 90% decrease in malaria recurrences after receiving an investigational typhoid vaccine despite no intention or expectation to observe such an outcome. In the 1940s, multiple doses of intravenous typhoid vaccine appeared to control parasitemia and limit reinfection in three syphilis patients purposefully infected with Plasmodium vivax . Several modern vaccines (against human papillomavirus, hepatitis B virus, and malaria) use a detoxified lipid A derived from Salmonella as an immune adjuvant. Early typhoid vaccines could have plausibly functioned as an innate immune stimulus, leading to some protection against malaria.

Controlled human malaria infection (CHMI) by direct venous inoculation (DVI) with 3,200 cryopreserved Plasmodium falciparum sporozoites (PfSPZ) consistently leads to parasitemia and malaria symptoms in malaria-naive adults. We used CHMI by DVI to investigate infection rates, parasite kinetics, and malaria symptoms in lifelong malaria-exposed (semi-immune) Gabonese adults with and without sickle cell trait. Eleven semi-immune Gabonese with normal hemoglobin (IA), nine with sickle cell trait (IS), and five nonimmune European controls with normal hemoglobin (NI) received 3,200 PfSPZ by DVI and were followed 28 days for parasitemia by thick blood smear (TBS) and quantitative polymerase chain reaction (qPCR) and for malaria symptoms. End points were time to parasitemia and parasitemia plus symptoms. PfSPZ Challenge was well tolerated and safe. Five of the five (100%) NI, 7/11 (64%) IA, and 5/9 (56%) IS volunteers developed parasitemia by TBS, and 5/5 (100%) NI, 9/11 (82%) IA, and 7/9 (78%) IS by qPCR, respectively. The time to parasitemia by TBS was longer in IA (geometric mean 16.9 days) and IS (19.1 days) than in NA (12.6 days) volunteers ( P = 0.016, 0.021, respectively). Five of the five, 6/9, and 1/7 volunteers with parasitemia developed symptoms ( P = 0.003, NI versus IS). Naturally adaptive immunity (NAI) to malaria significantly prolonged the time to parasitemia. Sickle cell trait seemed to prolong it further. NAI plus sickle cell trait, but not NAI alone, significantly reduced symptom rate. Twenty percent (4/20) semi-immunes demonstrated sterile protective immunity. Standardized CHMI with PfSPZ Challenge is a powerful tool for dissecting the impact of innate and naturally acquired adaptive immunity on malaria.

Introduction: Acute kidney injury (AKI) is reported to occur in patients with falciparum malaria but not uncommon with vivax malaria. AKI, anemia, thrombocytopenia and jaundice is a recurrent finding in severe malaria and can mimic as thrombotic microangiopathy (TMA). Relationship of malaria with TMA is unclear till date however evidences suggest their association., Methods & Material: We reviewed our electronic database to evaluate relationship of malaria with TMA, of cases of malaria, jaundice and AKI., Results: 4 patients found to have P. vivax malaria and histopathologically confirmed TMA. All had fever, oliguria, jaundice at presentation. The time between onset of symptoms and admission ranged from 7 to 14 days. All had parasitemia at presentation so were treated with Artesuanate. Hemodialysis and Plasmapheresis was done in all patients. On follow-up all patients recovered and asymptomatic urinary abnormality persisting in one patient., Conclusion: High index of suspicion should be kept for TMA in a patient who has nonrecovering AKI with persistent anemia and thrombocytopenia even after clinical and laboratory evidences of recovery from malaria, as response to plasmapheresis seems excellent in this subset of malarial AKI. There could be a pathogenetic link between P.vivax and TMA though yet to be confirmed in larger studies.

Babesiosis is an increasingly recognized disease which may benefit from therapeutic apheresis (Category II/Grade 2C). Vulnerable populations include the splenectomized, those aged >50, those with malignancies, and the immunocompromised. In the setting of parasite levels > 10%, significant anemia, renal impairment, pulmonary compromise, or hepatic dysfunction, RBC exchange can rapidly reduce parasite burdens and decrease the bioavailability of proinflammatory cytokines. No previous report has shown such a rapid rebound in parasitemia despite adequate organism removal. Herein, we report a case of severe babesiosis in a splenectomized 56 year old male with a past medical history significant for benign multiple sclerosis. Following a week of flu-like symptoms, the patient presented to an outside hospital with anemia, elevated bilirubin, thrombocytopenia, and 15% of his RBCs containing Babesia forms on a peripheral smear. Despite initiation of appropriate antimicrobials, subsequent transfer to our facility revealed worsening parasitemia (25%), tachypnea, and hypoxia. An emergent two volume RBC exchange was performed, resulting in 15% post-exchange parasitemia. Twelve hours later, the parasitic burden had climbed to 30%. A second RBC exchange reduced the parasite burden to 1.5%. His post-procedural course was significant for diminishing periodic increases in parasitemia despite continued antimicrobial therapy. Rapid increases in parasitic burden following RBC exchanges can occur and post-procedural surveillance of parasitemia should be closely monitored to expedite additional exchanges., (© 2016 Wiley Periodicals, Inc.)

Chagas disease, caused by Trypanosoma cruzi, results in an acute febrile illness that progresses to chronic chagasic cardiomyopathy in 30% of patients. Current treatments have significant side effects and poor efficacy during the chronic phase; therefore, there is an urgent need for new treatment modalities. A robust TH1-mediated immune response correlates with favorable clinical outcomes. A therapeutic vaccine administered to infected individuals could bolster the immune response, thereby slowing or stopping the progression of chagasic cardiomyopathy. Prior work in mice has identified an efficacious T. cruzi DNA vaccine encoding Tc24. To elicit a similar protective cell-mediated immune response to a Tc24 recombinant protein, we utilized a poly(lactic-co-glycolic acid) nanoparticle delivery system in conjunction with CpG motif-containing oligodeoxynucleotides as an immunomodulatory adjuvant. In a BALB/c mouse model, the vaccine produced a TH1-biased immune response, as demonstrated by a significant increase in antigen-specific IFNγ-producing splenocytes, IgG2a titers, and proliferative capacity of CD8(+) T cells. When tested for therapeutic efficacy, significantly reduced systemic parasitemia was seen during peak parasitemia. Additionally, there was a significant reduction in cardiac parasite burden and inflammatory cell infiltrate. This is the first study demonstrating immunogenicity and efficacy of a therapeutic Chagas vaccine using a nanoparticle delivery system.

During their lifespan, circulating RBC are frequently checked for their deformability. This mechanical quality control operates essentially in the human spleen. RBC unable to squeeze though narrow splenic slits are retained and cleared from the blood circulation. Under physiological conditions this prevents microvessels from being clogged by senescent, rigid RBC. Retention of poorly deformable RBC is an important determinant of pathogenesis in malaria and may also impact the clinical benefit of transfusion. Modulating the splenic retention of RBC has already been proposed to support therapeutic approaches in these research fields. To this aim, the development of microplates for high throughput filtration of RBC through microsphere layers (microplate-based microsphiltration) has been undertaken. This review focuses on potential therapeutic applications provided by this technology in malaria chemotherapy and transfusion., (Copyright © 2015 Elsevier Masson SAS. All rights reserved.)

We present a case of a 66-year-old woman with decompensated alcoholic liver cirrhosis and poorly controlled non-insulin-dependent diabetes mellitus who was admitted with a 1 day history of altered mental status, high-grade fevers, worsening jaundice and generalised malaise with subsequent development of hypotension requiring intensive care. She was diagnosed with severe babesiosis with high-grade parasitaemia. She was also found to have Lyme disease coinfection. Despite aggressive therapeutic measures including appropriate antibiotics and multiple exchange blood transfusions, she developed septic shock and fulminant multiple organ failure with eventual demise. In this article, we highlight multiple tick-borne illnesses in a vulnerable host, in this case an elderly patient with liver cirrhosis, as risk factors for severe morbidity and potentially fatal outcomes., (2015 BMJ Publishing Group Ltd.)

Chagas disease is caused by the protozoan parasite Trypanosoma cruzi, and activation of CD8(+) T cells is crucial for a protective immune response. Therefore, the identification of antigens with major histocompatibility complex class I epitopes is a crucial step for vaccine development against T. cruzi. Our aim was to identify novel antigens and epitopes by immunoinformatics analysis of the parasite proteome (12 969 proteins) and to validate their immunotherapeutic potential in infected mice. We identified 172 predicted epitopes, using NetMHC and RANKPEP. The corresponding protein sequences were reanalyzed to generate a consensus prediction, and 26 epitopes were selected for in vivo validation. The interferon γ (IFN-γ) recall response of splenocytes from T. cruzi-infected mice confirmed that 10 of 26 epitopes (38%) induced IFN-γ production. The immunotherapeutic potential of a mixture of all 10 peptides was evaluated in infected mice. The therapeutic vaccine was able to control T. cruzi infection, as evidenced by reduced parasitemia, cardiac tissue inflammation, and parasite burden and increased survival. These findings illustrate the benefits of this approach for the rapid development of a vaccine against pathogens with large genomes. The identified peptides and the proteins from which they are derived are excellent candidates for the development of a vaccine against T. cruzi., (© The Author 2014. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.)