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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.)

Automated techniques for red cell [red blood cell (RBC)] exchange or depletion of malignant cells from the peripheral blood have allowed patients with life-threatening conditions to survive long enough to receive definitive treatment. Examples of such conditions include acute chest syndrome in sickle cell disease (SCD) or acute respiratory insufficiency due to leukostasis in acute leukemia. Conversely, other patients with SCD undergo RBC exchanges on a chronic basis to maintain a reasonable quality of life and prevent another stroke. In this review, we will discuss the techniques as well as indications for RBC exchange, leukocytapheresis, and thrombocytapheresis. To illustrate the uses of these therapeutic apheresis procedures, the authors included a summary of the most common diagnoses that comprise their use., (© 2014 Wiley Periodicals, Inc.)

The optimization of malaria control strategies is complicated by constraints posed by local health systems, infrastructure, limited resources, and the complex interactions between infection, disease, and treatment. The purpose of this paper is to describe the protocol of a randomized factorial study designed to address this research gap. This project will evaluate two malaria control interventions in Mvomero District, Tanzania: (1) a disease management strategy involving early detection and treatment by community health workers using rapid diagnostic technology; and (2) vector control through community-supported larviciding. Six study villages were assigned to each of four groups (control, early detection and treatment, larviciding, and early detection and treatment plus larviciding). The primary endpoint of interest was change in malaria infection prevalence across the intervention groups measured during annual longitudinal cross-sectional surveys. Recurring entomological surveying, household surveying, and focus group discussions will provide additional valuable insights. At baseline, 962 households across all 24 villages participated in a household survey; 2,884 members from 720 of these households participated in subsequent malariometric surveying. The study design will allow us to estimate the effect sizes of different intervention mixtures. Careful documentation of our study protocol may also serve other researchers designing field-based intervention trials.

Background: The research community relies heavily on measures of healthcare utilization from household surveys to understand health seeking choices and to evaluate interventions in developing countries. Such measures are known to suffer from recall problems but there is limited evidence of whether the method of data collection affects evaluation findings. We compared the results of a randomized trial of free healthcare using utilization data from two sources., Methods: Data are from a study in Ghana, in which 2,194 households containing 2,592 children under 5 y old were randomized into a prepayment scheme providing free primary and some referral care, or to a control group whose families paid user fees for healthcare. Data on morbidity and health seeking behaviour were collected using a standard household survey administered at endline and a pictorial diary given to households over a six month period, collected at monthly intervals., Results: Self-reported measures of morbidity and healthcare utilization were substantially lower in the household survey than the pictorial diary when the recall period was over a month. Introducing free healthcare had a positive effect on primary care visits based on the pictorial diary and a non-significant negative effect according to the household survey. Using any clinic visit in the past month as the outcome, the difference in the effect of free care between the two data collection methods was 3.6 percentage points (p = 0.078)., Conclusions: The findings raise methodological concerns about measures of healthcare utilization from household surveys, particularly in the evaluation of health financing interventions.

American trypanosomiasis, or Chagas disease, is caused by Trypanosoma cruzi, and a vaccine would greatly improve disease control. While some studies in mice suggest that a vaccine is feasible, limited efficacy has been observed in dogs. We evaluated here the safety and efficacy of a DNA vaccine encoding TSA-1 and Tc24 antigens in a dog model of acute T. cruzi infection. Mongrel dogs were immunized with two doses of 500 μg of DNA vaccine, two weeks apart, and infected with T. cruzi (SylvioX10/4 strain) two weeks after the second vaccine dose. Another group of dogs was infected first and treated with the vaccine. Disease progression was monitored for up to 70 days post-infection. The vaccine did not induce any critical change in blood parameters, nor exacerbation of disease in vaccinated animals. On the contrary, it prevented anemia and a decrease in lymphocyte counts following T. cruzi infection in vaccinated dogs. Both preventive and therapeutic vaccination significantly reduced parasitemia, cardiac inflammation and cardiac parasite burden, and tended to reduce the development of cardiac arrhythmias. These results indicate that a preventive or therapeutic DNA vaccine encoding TSA-1 and Tc24 antigens is safe and may reduce both parasite transmission and the clinical progression of Chagas disease in vaccinated dogs. This DNA vaccine may thus be an excellent veterinary vaccine candidate. These data also further strengthen the feasibility of a Chagas disease vaccine for humans., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Background: The role of exchange transfusion in the management of severe malaria is not well documented in Emergency Medicine literature., Objectives: The goal of this article is to review the importance of considering malaria in the differential diagnosis of the febrile returned traveler and to discuss the role of exchange transfusion in the management of severe Plasmodium falciparum malaria., Case Report: A 59-year-old woman presented to the Emergency Department (ED) with severe P. falciparum malaria. Her physical examination was remarkable for scleral icterus, dry mucous membranes, and tachycardia. Her complete blood count revealed a white blood cell count of 6.9 k/uL, with 71% segmented neutrophils, 19% bands, a hemoglobin level of 11.9 g/dL, hematocrit of 37.2%, and a platelet count of 9 k/uL. Hepatorenal impairment was present and malaria parasites with ring form were seen on malaria prep in 18% of red blood cells. The patient was treated with fluids, platelets, quinidine gluconate, doxycycline, and exchange transfusion with significant improvement in the patient's clinical condition., Conclusions: The high level of parasitemia presenting with acute kidney injury, hyperbilirubinemia, and thrombocytopenia supported the use of exchange transfusion as adjunct therapy. Exchange transfusion was a reasonable consideration in this case and was well tolerated by our patient. Institutions that are equipped with apheresis units should evaluate each case individually in concert with Centers for Disease Control experts and local consultants and weigh the risks and benefits of the use of exchange transfusion as an adjunct in the treatment of severe P. falciparum malaria., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Background: Severe falciparum malaria is associated with considerable rates of mortality, despite the administration of appropriate anti-malarial treatment. Since overall survival is associated with total parasite biomass, blood exchange transfusion has been proposed as a potential method to rapidly reduce peripheral parasitaemia. However, current evidence suggests that this treatment modality may not improve outcome. Automated red blood cell exchange (also referred to as "erythrocytapheresis") has been advocated as an alternative method to rapidly remove parasites from circulating blood without affecting patients' volume and electrolyte status. However, only limited evidence from case reports and case series is available for this adjunctive treatment. This retrospective cohort study describes the use of automated red blood cell exchange for the treatment of severe malaria at the Medical University of Vienna., Methods: Epidemiologic data for imported malaria cases in Austria are reported and data of patients treated for malaria at the General Hospital/Medical University of Vienna were extracted from electronic hospital records., Results: Between 2000 and 2010, 146 patients were hospitalized at the Medical University of Vienna due to malaria and 16 of those were classified as severe malaria cases. Eleven patients of this cohort were potentially eligible for an adjunctive treatment with automated red blood cell exchange. Five patients eventually underwent this procedure within a period of seven hours (range: 3-19 hours) after hospital admission. Six patients did not undergo this adjunctive treatment following the decision of the treating physician. The procedure was well tolerated in all cases and rapid reduction in parasite counts was achieved without occurrence of haemodynamic complications. One patient died within seven days, whereas four patients survived without any sequelae., Discussion and Conclusion: Automated red blood cell exchange was a safe and efficient procedure to rapidly clear peripheral parasitaemia. Whether the fast reduction in parasite biomass may ultimately improve patient survival remains however unclear. Randomized controlled trials are needed to conclusively appreciate the value of this adjunctive treatment.

Many questions remain about P. falciparum within-host dynamics, immunity, and transmission-issues that may affect public health campaign planning. These gaps in knowledge concern the distribution of durations of malaria infections, determination of peak parasitemia during acute infection, the relationships among gametocytes and immune responses and infectiousness to mosquitoes, and the effect of antigenic structure on reinfection outcomes. The present model of intra-host dynamics of P. falciparum implements detailed representations of parasite and immune dynamics, with structures based on minimal extrapolations from first-principles biology in its foundations. The model is designed to quickly and readily accommodate gains in mechanistic understanding and to evaluate effects of alternative biological hypothesis through in silico experiments. Simulations follow the parasite from the liver-stage through the detailed asexual cycle to clearance while tracking gametocyte populations. The modeled immune system includes innate inflammatory and specific antibody responses to a repertoire of antigens. The mechanistic focus provides clear explanations for the structure of the distribution of infection durations through the interaction of antigenic variation and innate and adaptive immunity. Infectiousness to mosquitoes appears to be determined not only by the density of gametocytes but also by the level of inflammatory cytokines, which harmonizes an extensive series of study results. Finally, pre-existing immunity can either decrease or increase the duration of infections upon reinfection, depending on the degree of overlap in antigenic repertoires and the strength of the pre-existing immunity.

We describe a case of severe falciparum malaria with hyperparasitaemia. Treatment with automated erythrocytapheresis, in conjunction with parenteral artesunate, produced a rapid and sustained fall in parasite burden. Several poor prognostic features were present at admission. Despite the development of a severe headache with abnormal cerebrospinal fluid parameters and transient pulmonary oedema, a complete recovery was observed. Erythrocytapheresis can be considered in selected cases where facilities exist and has theoretical and practical advantages over traditional methods of red cell exchange transfusion. The paucity of systematic or trial evidence convincingly demonstrating a benefit in terms of morbidity or mortality has limited its application. However, the lack of robust trial data should not in itself invalidate considering this therapeutic option in the appropriate context., (© 2011 The Authors. Internal Medicine Journal © 2011 Royal Australasian College of Physicians.)

Background: Travelers returning to the United States from malaria-endemic areas are at increased risk of a potentially fatal infection from Plasmodium falciparum, which requires prompt and aggressive treatment., Study Design and Methods: Described is a case of a 7-year-old boy who was infected by P. falciparum while in Africa and developed features of severe infection, including hyperparasitemia, altered neurologic status, and malarial hepatitis., Results: A single automated erythrocytapheresis procedure reduced parasitemia from 14% to less than 1%. Along with intravenous quinidine, this reduced parasite level was maintained throughout the hospitalization and the patient recovered., Conclusion: Exchange transfusion (ET) is an effective adjunct therapy to reduce the parasite load in cases of severe P. falciparum malaria. When performed in certain defined settings, the benefits can outweigh the risks of the procedure. Discussed are the medical and technical considerations on the use of adjunctive ET for severe P. falciparum infection and a review of the literature of the use of adjunct ET in the treatment of severe P. falciparum malaria.

Background: Even in circumstances where optimal antimalarial and supportive treatment is available, severe Plasmodium falciparum malaria is still associated with a significant case fatality. Although exchange transfusion (ET) has been considered as a controversial adjunct therapy, we have not encountered any case fatality since ET was introduced as a standard adjunct therapy for patients with severe malaria., Study Design and Methods: In this retrospective cohort study of 25 patients with severe malaria, the efficacy and safety of ET as an adjunct to parenteral antimalarial treatment (which was implemented in our hospital starting in 1998) were evaluated and compared with 31 historical control patients who were treated with conventional parenteral antimalarial treatment in the period before ET was added to the standard of care for severe malaria (generally before 1997)., Results: The parasite clearance times (PCT)(25%), PCT(50%), PCT(75%) and PCT(90%) were all significantly shorter for patients treated with ET than for patients treated with parenteral quinine only. The shorter PCTs in the ET group were the result of a more rapid parasite clearance in the early phases after initiation of ET., Conclusion: No case fatalities were observed in the ET group. The complications that were observed with ET were more likely related either to the multiorgan dysfunction associated with severe malaria or to side effects of parenteral quinine rather than to the ET procedure. ET may be safely executed in a setting with intensive care facilities and availability of safe blood products and should be considered as a beneficial adjunct treatment to parenteral antimalarial therapy.

Phagocytic removal of apoptotic lymphocytes exacerbates replication of Trypanosoma cruzi in macrophages. We investigated the presence of Ab against apoptotic lymphocytes in T. cruzi infection and the role of these Ab in parasite replication. Both control and chagasic serum contained IgG Ab that opsonized apoptotic lymphocytes. Treatment of apoptotic lymphocytes with purified IgG from chagasic, but not control serum, reduced T. cruzi replication in macrophages. The protective effect of chagasic IgG depended on Fcgamma receptors, as demonstrated by the requirement for the intact Fc portion of IgG, and the effect could be abrogated by treating macrophages with an anti-CD16/CD32 Fab fragment. Chagasic IgG displayed increased reactivity against a subset of apoptotic cell Ag, as measured by flow cytometry and immunoblot analyses. Apoptotic lymphocytes treated with chagasic IgG, but not control IgG, increased production of TNF-alpha, while decreasing production of TGF-beta1 by infected macrophages. Increased control of parasite replication required TNF-alpha production. Previous immunization with apoptotic cells or injection of apoptotic cells opsonized with chagasic IgG reduced parasitemia in infected mice. These results indicate that Ab raised against apoptotic cells could play a protective role in control of T. cruzi replication by macrophages.

The authors describe clinical cases of two patients admitted to intensive care unit following severe Plasmodium falciparum malaria. Patients' sublingual microcirculation was monitored by on-line Sidestream dark-field imaging before and after treatment with erythrocytapheresis. Before treatment, microcirculatory flow alterations were obvious. Therapy produced a rapid decrease in infected red blood cells with a significant improvement in microcirculatory flows, capillary perfusion and patients' outcome. The present cases emphasize the relevance of microcirculation monitoring in patients with capillary perfusion alterations resulting from severe malaria. As far as we know, this is the first observations of an improvement of capillary perfusion after erythrocytapheresis.

We report four cases of clinically severe tick borne babesiosis treated with chemotherapy and adjunctive red cell exchange (RCE) at two Rhode Island hospitals from 2004 to 2007. All RCE procedures were performed using a Cobe Spectra device and were well tolerated without complications. The volume of allogeneic red cells used in the exchange was determined using the algorithm in the apheresis device with the input variables of preprocedure hematocrit, weight, height, an assumed allogeneic red cell hematocrit of 55 and a desired post procedure hematocrit of 27. The preprocedure level of parasitemia varied between 2.4% and 24% and the postprocedure level of parasitemia between 0.4 and 5.5% with an average overall percent reduction in parasitemia of 74%. Retrospectively, application of a new formula to calculate red cell mass appeared to correlate better with the percent reduction in parasitemia. Previous reports of RCE in babesiosis were reviewed. The reported reduction in parasitemia varied from 50% to >90%. Although a preprocedure level of parasitemia of 10% is sometimes used as a threshold for RCE in clinically severe babesiosis, this threshold does not have a firm empirical basis. No postprocedure desired level of parasitemia is indicated nor the mass of allogeneic red cells needed to achieve such a level. We conclude that current estimates of the dose of allogeneic red cells used in RCE are probably inaccurate, advocate a new formula to estimate this dose and suggest that a 90% reduction in parasitemia should be the minimally desired target of RCE in babesiosis.

Background and Objectives: Chagas disease is a transfusion-transmitted infection. This study evaluates the efficacy of a methylene blue (MB) and light system for reducing the viability of Trypanosoma cruzi in plasma. MATERIALS AND METHODS Trypanosoma cruzi strains were spiked in plasma pools. Treatment arms included combined filtration, MB, light and freezing. Post-treatment parasite viability was assayed through in vitro cultures and in vivo inoculation in inducible nitric oxide synthase- and interferon-gamma-receptor-deficient mice., Results: The filtration, MB and light combined treatment showed a log reduction of > 3.4 in in vitro cultures, and log reductions that ranged from > 4.9 to > 5.8 in deficient mice inoculated with different T. cruzi strains., Conclusion: The treatment of plasma units with the MB and light system reduces the T. cruzi burden and could be useful in preventing transfusion-transmitted Chagas disease.

While exchange transfusion has been advocated as an adjunctive treatment in severe falciparum malaria complicated by heavy parasitaemia, its role in severe life-threatening disease refractory to standard life support measures is less well recognised. We describe four children with severe falciparum malaria, multi-system involvement and heavy parasitaemia in whom we undertook exchange transfusion because of their deteriorating clinical condition despite antimalarials and supportive therapy. All patients received quinine (one also received artesunate). All patients improved dramatically following the procedure, with subsequent complete clinical recovery.

Babesiosis is caused by a haemotropic protozoal parasite of the genus Babesia, member of the phylum Apicomplexa and transmitted by the bite of an infected tick. There are many Babesia species affecting livestock, dogs, horses and rodents which are of economic significance. Infections can occur without producing symptoms, but babesiosis may also be severe and sometimes fatal caused by the intraerythrocytic parasite development. The disease can cause fever, fatigue and haemolytic anemia lasting from several days to several months. There are a number of effective babesiacides, but imidocarb dipropionate (which consistently clears the parasitaemia; often the only available drug on the market) and diminazene aceturate are the most widely used. Some Babesia spp. can infect humans, particularly Babesia microti and Babesia divergens, and human babesiosis is a significant emerging tick-borne zoonotic disease. Clinical manifestations differ markedly between European and North American diseases. In clinical cases, a combination of clindamycin and quinine is administered as the standard treatment, but also administration of atovaquone-azithromycin is successful. Supportive therapy such as intravenous fluids and blood transfusions are employed when necessary. More specific fast-acting new treatments for babesiosis have now to be developed. This should be facilitated by the knowledge of the Babesia spp. genome and increased interest for this malaria-like parasite.

Reported efficacies from vaccine trials may depend heavily on the clinical case definition used in the trial. The dependence may be particularly striking for diseases such as malaria, in which no single case definition is appropriate. We used logistic regression modeling of the relationship between parasitemia and fever in data sets from Ghanaian children to determine the fraction of fevers attributable to malaria and to model how the choice of a threshold parasitemia in the clinical case definition affects the measured efficacy of malaria vaccines. Calculated clinical attack rates varied 10-fold as a function of the threshold parasitemia. Strikingly, measured vaccine efficacies in reducing clinical malaria depended heavily on the threshold parasitemia, varying between 20% and 80% as the threshold varied between 1 and 5000 parasites/ microL. We suggest that clinical case definitions of malaria that incorporate a threshold parasitemia are arbitrary and do not yield stable estimates of vaccine trial end points.

Malaria continues to be a wide-spread infection in tropical areas. According to World Health Organization, malaria is present in over 100 countries, populated by over 3 bln people. Malaria morbidity in these areas is difficult to estimate. Tropical malaria caused by Plasmodium falciparum is responsible for more than 95% of fatal cases. Other Plasmodium species able to infect humans are P. vivax, P. ovale and P. malariae, typically responsible for more prolonged course of the disease, with possibility of late relapse, but rarely resulting in fatal outcome. We present a case of tropical malaria, illustrating wide spectrum of complications associated with P. falciparum infection, especially in cases of massive parasitemia.

Background: Within the last few years there is more and more evidence for nonspecific ocular symptoms caused by "exotic" pathogens. We herewith report another case of such an infection to underline the increasing importance and diagnostic relevance even of rare diseases., Patient: A 35-year-old female German patient presented with recurrent left retrobulbar "feeling of pressure" after a 6-month-stay in Central Africa 5 years ago. In addition, she reported on repeated swelling of the skin and joints of her hands and arms. Multiple ophthalmologic and rheumatologic investigations had been carried out without diagnostic results. Her ophthalmologist referred her with the presumed diagnosis of a subconjunctival worm., Results: Slit-lamp biomicroscopy confirmed the original suspicion, and after topical anesthesia a female Loa-Loa worm was easily removed with forceps through a conjunctival incision. The general examination showed symptoms of systemic infection (calabar swelling, eosinophilia). Classification and initiation of treatment with diethylcarbamazine and mebendazole were carried out by the University Institute of Parasitology., Conclusion: Loa-Loa is a parasitic infection endemic in the tropical rain forests of Western, Central, and Eastern Africa. It is transmitted by the Chrysops fly. An increasing number of oculosystemic infections in non-African patients with Loa-Loa are being published. Therefore, any patient with an unclassifiable eye affection should also be investigated for those rare pathogens.

Transfusion-acquired malaria in a neonate is uncommon and factors such as drug resistance and concomitant G6PD deficiency can cause treatment difficulties. We report a 26-day-old premature infant with chloroquine-resistant malaria who underwent exchange transfusion. The aim was to correct anaemia, decrease parasitaemia and remove G6PD-deficient cells to allow successful use of quinine.

Two mathematical models to predict the level of parasitaemia after exchange transfusion in severe malaria have been described. One formula, described by Wilkinson and colleagues, calculates the level from the total volume of blood exchanged whereas the other, derived by Van den Ende and colleagues, is recursive and gives estimates of the reduction in parasitaemia after each aliquot of exchange. The accuracies of predictions based on these two formulae were compared using data collected from 20 patients undergoing partial exchange transfusion (40 ml blood/kg body weight). The transfusions led to significant changes in the mean (S.D.) haemoglobin concentrations, which rose from 8.9 (2.4) to 10.1 (1.5) g/dl, and in the median levels of parasitaemia, which fell from 16.5% (interquartile range = 12.8%-28.8%) to 4.5% (interquartile range = 1.2%-9.3%). The median level of post-transfusion parasitaemia predicted by the Van den Ende formula (6.6%, with an interquartile range of 4.5%-10.2%) was similar to that observed, whereas that predicted by the Wilkinson formula (7.2%, with an interquartile range of 5.6%-12.4%) was significantly higher (P = 0.018). However, the median difference between the predictions based on the two formulae was represented by a parasitaemia of only 1.0% (interquartile range = 0.6%-1.85%). Thus, although the Van den Ende formula is more accurate than the Wilkinson, the difference is unlikely to be clinically significant.

Anti-malaria vaccines and drugs could be greatly improved if we knew which phases of Plasmodium falciparum development in red blood cells are major inducers and which are major targets of natural immune responses. This information should focus attention on relevant immunogens and prove useful in developing immune-based therapies. Here we explore the hypothesis that innate immune responses mediate synchronization between the replication cycles of parasites in different red blood cells which is reflected in periodic fevers. Based on a recently developed, rather general mathematical model, we find that periodicity is highly sensitive to the position of both the inducing phase interval and the target phase interval in the parasite replication cycle. In addition, the degree of variability in the length of the replication cycle also strongly affects periodicity. To produce synchronization, the inducing and the target phase intervals must be developmentally distant from each other. We developed a computer program which prompts for information based on measurements of the numbers of erythrocytes in two replication cycle intervals chosen by the researcher, tests our model, and predicts the two phase intervals most critical to the synchronizing immune response. The program can be obtained from the authors.

The roles of antibodies (Ab) and Fc receptors (FcR) in clearance of Brugia malayi microfilariae (Mf) in vivo have not been previously elucidated. Different background strainsof mice clear Mf at different rates and we established that there were no major differences in Ab production between three particular strains. However, genetic immunodeficiencies in B cell and Ab production on each of these background strains significantly enhanced Mf survival. B cell-deficient microMT (C57BL/6) mice injected with B. malayi Mf i.v. retained significant numbers of live Mf in comparison to wild-type mice. Treatment of microMT mice with hyperimmune whole sera in the first week of infection significantly reduced the number of Mf surviving in the cardiac blood at 135 days p.i. Mf survival in FcRgamma-deficient (Sv129xC57BL/6) mice was also dramatically increased in the cardiac blood compared to wild-type mice, indicating that Ab itself is involved in Mf clearance most likely via a mechanism involving ADCC. These data indicate that Ab plays an important role in vivo in Mf killing in mice and this role is mediated via the FcR.

Passive immunisations with a monoclonal antibody termed 1-5H showed a partial but significant inhibition of parasitaemia against Babesia microti challenge infection. By immunoscreening with 1-5H, a clone (termed p58 gene) was obtained from a cDNA expression library of B. microti and the complete nucleotide sequence was determined. A protein homology search showed significant amino acid identities to the eta subunit of the chaperonin containing T-complex protein 1 (CCT) of human (59%), mouse (58%) and Plasmodium falciparum (62%). Genomic analyses indicated that the p58 gene is present as a single copy gene and contains a total of approximately 400-bp introns in the genome of B. microti. The mAb 1-5H recognised a 58-kDa protein of B. microti and was found to cross-react with a 60-kDa protein of Babesia rodhaini. These results suggest the possibility that the p58 protein is the CCT eta subunit of B. microti and functions as a chaperonin.

In malaria due to Plasmodium falciparum, life-threatening complications are in part related to the degree of parasitemia. Whole blood exchange and red blood cell exchange (RCE) have been used for the rapid removal of parasites from the circulation of patients with a high parasite load complicated by cerebral, pulmonary, and renal dysfunction. We have treated three 5-45-year-old patients with hyperparasitemia and end-organ dysfunction with red cell exchange by automated apheresis as an adjunct to specific anti-malarial chemotherapy. Parasitemia dropped more than 80% in all three patients immediately after the exchange, and all patients had an uneventful and full recovery. In combination with effective anti-malarial chemotherapy, apheresis RCE is a safe and rapid approach to treat complicated malaria due to P. falciparum.

Falciparum malaria is frequently associated with significant morbidity and mortality. The use of exchange transfusion as a therapeutic modality for severe cases of malaria has been described previously. We describe a case of a 49 year-old African American gentleman with a history of hemoglobin-SC disease who presented with a severe case of Plasmodium falciparum malaria 3 weeks after having received an infected blood transfusion. His peripheral smear showed the presence of numerous intraerythrocytic ring forms and "banana-shaped" gametocytes with a high-grade parasitemia, estimated at 18%. He was treated with antimalarial chemotherapy and also underwent a 12-unit red blood cell exchange transfusion, decreasing his parasite load to < 1%, as determined on repeat smear. It is prudent to be aware of the efficacy of this adjunctive treatment, especially with ever-increasing travel and a resultant increase in the prevalence of tropical diseases in the United States.

In severe falciparum malaria with high parasitaemia, removal of parasitized erythrocytes is generally considered to be of value as adjunctive therapy in addition to standard chemotherapy. Such removal is commonly achieved by exchange transfusion but this procedure is time-consuming and may be associated with haemodynamic disturbance. Current-generation automated cell-separator hardware and software allows prompt red cell exchange, erythrocytapheresis, in a single continuous-flow isovolaemic procedure. We describe the application of this procedure to 5 cases of severe falciparum malaria in travellers returning to the UK from the tropics. All patients also received quinine and conventional supportive therapy. In all cases, dramatic reduction in parasitaemia was achieved within 2 h with subsequent complete clinical recovery. Erythrocytapheresis has significant advantages over exchange transfusion in terms of speed, efficiency, haemodynamic stability and retention of plasma components such as clotting factors and may thus represent an improvement in adjunctive therapy for severe malaria.

Background: Cerebral malaria is a life-threatening complication of Plasmodium falciparum infection. RBC exchange transfusion can reduce the level of parasitemia in this setting. Experience with automated RBC exchange for cerebral malaria may be limited, as most cases occur when the necessary equipment and blood components are not readily available., Case Reports: Three patients were admitted with cerebral malaria. Parasites were found in more than 30 percent of RBCs in two cases and in more than 60 percent of RBCs in the third case. Many RBCs contained multiple organisms. In each case, antimalarial therapy was begun, and an automated RBC exchange was performed emergently with a cell separator. Exchange transfusion was repeated within 24 hours for two patients. Parasitemia levels were less than 1 percent in all patients 24 hours after the last exchange. The neurologic status of these patients returned to baseline, and they were discharged 7 to 18 days after admission., Conclusion: Automated RBC exchange transfusion can rapidly reduce the level of parasitemia and restore neurologic functioning in patients with cerebral malaria.

Removal of parasitized erythrocytes is generally considered to be of value as adjunctive therapy in severe falciparum malaria with high parasitaemia. This is commonly achieved by exchange transfusion. We describe three cases of severe falciparum malaria treated by automated erythrocytapheresis (red cell exchange) in addition to quinine and conventional supportive therapy. Erythrocytapheresis consists of removal of the red-cell fraction by apheresis. Plasma, leukocyte and platelet fractions are returned to the patient. In all cases, dramatic reduction in parasitaemia was achieved within 2 h with subsequent complete clinical recovery. Erythrocytapheresis has significant advantages over exchange transfusion in terms of speed, efficiency, haemodynamic stability and retention of plasma components such as clotting factors and may thus represent an improvement in adjunctive therapy for severe malaria.

We report a case of traveller to Kenya who contracted severe plasmodium falciparum malaria complicated by disseminated intravascular coagulation and acute renal failure. She had taken no antimalarial prophylaxis in view of concerns in the media regarding the adverse effects of mefloquine. There was a protracted delay before the diagnosis of malaria was made. Clinical recovery occurred following treatment with intravenous quinine, haemofiltration and manual/automated red-cell exchange transfusions. Automated red-cell exchange transfusion resulted in a marked decrease in the parasitaemia, before a response to quinine therapy would have been anticipated, leading to a successful outcome thereafter. In conjunction with other groups we therefore feel that exchange transfusions should be considered in seriously ill patients with falciparum malaria, multiorgan complications and parasitaemias greater than 10%.