Duration Of Parasitemia Research Articles

Yurt Dışı Kaynaklı Plasmodium falciparum Sıtmalı Olguların Değerlendirilmesi: Tanıda Polimeraz Zincir Reaksiyonunun Yeri

Malaria affecting almost half of the world population continues to be an important health problem. Although domestic malaria cases have been decreasing in Turkey recently, cases caused by Plasmodium falciparum have increased due to the frequent travelling to Africa. The aims of this study were to evaluate demographic characteristics, clinical and laboratory findings in cases with falciparum malaria who attended to our clinic in 2012-2013 period, and the impact of polymerase chain reaction (PCR) for diagnosis. Nine patients evaluated were all male with a mean age of 34.3 (age range: 18-48) years, with the history of travel to Africa. Six cases did not take prophylaxis against malaria and other three cases used insufficient time. Mean duration of symptoms after return was 18.4 (range: 1-75) days, and the patients were admitted to the clinic within a mean of 5.2 (range: 1-15) days. Two patients had leucopenia, two patients had anemia, and eight patients had thrombocytopenia on admission. Alanine aminotransferase (ALT) levels in four cases and total bilirubin levels of six cases were over upper normal limits. Definitive diagnosis of cases was performed with the detection of ring and/or gametocytes forms of the parasite in Giemsa-stained peripheral blood smears. Furthermore, samples from seven patients were studied by nested PCR by using genus (Plasmodium rPLU 1 and 5) and species (rFAL 1 and 2, rVIV 1 and 2, rMAL 1 and 2, rOVA 1 and 2) specific primers. All of these seven samples yielded positive results with primers specific for P.falciparum ssrRNA. In the treatment, arthemeter/lumefantrin and doxycycline combination was used in seven patients, while intravenous artesunate and doxycycline combination was given to two patients, resulting with complete cure. Mean duration for the resolving of fever was 3.3 days, and mean duration for clearing the parasitemia from peripheral blood was 4.9 days. Initial ALT values and the duration of fever resolution (-796; p= 0.010), as well as the duration of parasitemia and initial thrombocyte counts (-797; p= 0.010) were negatively- correlated. It was concluded that, providing sufficient information on malaria and prophylaxis to people travelling to the endemic areas are crutial for protection. Moreover, in endemic areas for Crimean-Congo hemorrhagic fever, patients with fever and thrombocytopenia should be questioned in detail about the travel history, and peripheral blood smears should be examined in terms of malaria, since their clinical features are similar. Plasmodium PCR should be considered as one of the alternative diagnostic method in malaria, especially in cases with inconclusive microscopy.

Quantitative analysis of parasite DNA in the blood of immunized and naïve mice after infection with Neospora caninum

Real-time PCR was used to study the duration and level of parasitaemia in mice immunized with immune-stimulating complexes (iscoms) containing recombinant NcSRS2, one of the immunodominant surface antigens of Neospora caninum. After challenge infection, blood was collected daily for 9 days. During this period the amounts of parasite DNA detected in immunized mice were significantly lower (P<0.001), and the duration of parasitaemia appeared to be shorter, than in non-immunized controls. Furthermore, the degree of parasitaemia seemed to correlate well with the amount of N. caninum DNA in the brain 3 weeks post-inoculation and with disease severity measured as changes in body weight. These results indicate that the protective immunity induced by the NcSRS2-iscoms was sufficient to reduce the level of parasitaemia, which probably reduced the number of parasites reaching the brain, and could be the reason for the reduction in brain parasite load and clinical symptoms. Furthermore, real-time PCR was found to be a sensitive means for rapid assessment of N. caninum in blood.

The host–parasite relationship in bovine neosporosis

Infection with the protozoan parasite Neospora caninum is thought to be a major cause of reproductive failure in cattle worldwide. Cattle infected with the parasite are three to seven times more likely to abort compared to uninfected cattle. The parasite may be transmitted to cattle through the ingestion of oocysts that are shed in the faeces of acutely infected dogs (definitive host of N. caninum) or by congenital infection from mother to foetus via the placenta. Interestingly, transplacental transmission can occur over consecutive pregnancies and congenitally infected heifers can transmit the parasite to their own offspring. This repeated vertical transmission observed in naturally infected cattle suggests that cattle do not easily develop effective immunity to the parasite, presenting a significant challenge to the development of a control strategy based on vaccination. Neosporosis is a disease of pregnancy and studying the bovine maternal and foetal immune responses during pregnancy will help us to understand the change in the balance between the parasite and the host that may result in disease of the foetus. Studies in non-pregnant cattle and in murine models of infection have shown the importance of T-helper 1-type immune responses involving pro-inflammatory cytokines, such as IFNγ and IL-12, in limiting intracellular multiplication of the parasite. During pregnancy, changes occur in the immune system allowing the mother to accept the foetal allograft. Research in other species has stressed the crucial role of T-helper 2-type cytokines at the materno–foetal interface in maintaining the pregnancy and regulating the potentially damaging effect of Th-1 responses. Studies in cattle have shown that cell proliferation and IFNγ responses may be significantly down-regulated around mid-gestation. This may mean that cattle are less able to cope with N. caninum infection at this time and are more likely to transmit the parasite to the foetus. Another important factor is the gestational age and hence immuno-competence of the foetus at the time of infection. Early in gestation, N. caninum infection of the placenta and subsequently the foetus usually proves fatal, whereas infection occurring in mid to late pregnancy may result in the birth of a congenitally infected but otherwise healthy calf. Studies of foetal immune responses have shown that at 14 weeks of gestation, lymphocytes only respond to mitogen, while by 24 weeks (mid-gestation), they respond to antigen by proliferating and releasing IFNγ. Clearly, there are several factors influencing the outcome of N. caninum infection in pregnancy: the timing, quantity and duration of parasitaemia, the effectiveness of the maternal immune response and the ability of the foetus to mount an immune response against the parasite. The challenge is to design a vaccine that will prevent foetal infection by N. caninum. This is likely to involve a fine balancing act with the immune system that will allow intervention in a manner that will tip the host–parasite balance in favour of the host without compromising the pregnancy.

Experimental Babesia gibsoni infection in coyotes (Canis latrans).

Four 5 mo old captive raised coyotes (Canis latrans) were experimentally inoculated with approximately 1 x 10(6) Babesia gibsoni organisms. Parasites were detected 1 wk post-inoculation in all coyotes with maximum parasitemia of 8-11% occurring at 34 wk. Parasitemias remained at or above 1% for at least 12 wk and were still detectable 20 wk post-inoculation. All experimentally infected coyotes developed pale mucous membranes, splenomegaly, and a positive heme reaction in urine while one coyote exhibited mild depression and inappetence. Infected coyotes also developed a regenerative anemia, thrombocytopenia, and neutropenia. The mild clinical signs coupled with the high level and long duration of parasitemia indicate that coyotes could serve as reservoirs for B. gibsoni. Entrance of this foreign parasite into the United States suggests the need for strict quarantines and thorough health and blood film examinations for imported animals.

The effect of l-thyroxine on the anaemia response in Trypanosoma congolense infected rabbits

The development of anaemia is a major pathological manifestation in chronic trypanosomosis. The anaemia in African trypanosomosis coincides with a marked decrease in plasma concentration of both thyroxine (T 4) and 3,5,3′ triidothyronine (T 3). To evaluate the effect of trypanosome-induced hypothyroidism on the development of anaemia, sexually mature white New Zealand rabbits were used. Three groups were set up, each of ten rabbits: one group was infected with Trypanosoma congolense; the second group was infected but given replacement doses of thyroxine (treated); the third group was not infected. Small volumes of blood were collected for the determination of parasitaemia and packed cell volume (PCV). The concentrations of T 3 and T 4 were measured in plasma by radioimmunoassay. The decrease in PCV correlated closely ( y= −0.38 x + 15.2; r=0.82, P=0.001) with the intensity and duration of parasitaemia. The critical PCV value was 0.15 11 −1 with a peak parasitaemia of approximately 5×10 6 trypanosomes ml −1 of blood. There was a significant correlation between the plasma T 3 and PCV ( y=0.049 x+0.57; r=0.66, P=0.020). There was also a good positive correlation between T 4 and PCV ( y=14.5+3.03; r=0.95, P<0.001) in the infected untreated group. The PCV levels were significantly different among the three groups of animals ( P<0.05). The infected-treated animals sustained longer periods of infection than the infected and untreated ones. The sustained physiological level of bioactive thyroid hormones T 3 and T 4 significantly arrested the decline in PCV as the disease progressed. The hormonal treatment thus enhanced the survival of the animals infected with Trypanosoma congolense.

Maintenance of the human malarial parasite, Plasmodium falciparum, in scid mice and transmission of gametocytes to mosquitoes.

The study of human malaria has been hampered by the lack of small animal models for the human-infecting malarial parasites. To approach this problem, the erythrocytic stages of the human malarial parasite Plasmodium falciparum were adapted to in vitro growth in the presence of ascites fluid from mice homozygous for the severe-combined immunodeficiency (scid) mutation. Human red blood cells (hRBCs) infected with these adapted parasites were then injected i.p. into nonobese diabetic scid/scid (NOD/LtSz-scid) mice. With daily supplemental intraperitoneal boosts of uninfected hRBCs, parasites were detected in the peripheral circulation of these mice for an average of 7 d after injection. Splenectomy of NOD/LtSz-scid mice increased both the level and duration of parasitemia in the periphery, and it also promoted the circulation of mature sexual stage parasites (gametocytes). When Anopheline mosquitoes were allowed to feed on the splenectomized mice, the gametocytes were ingested by the mosquitoes and developed into oocysts in the mosquito midguts. To our knowledge, these results are the first demonstration of human malarial parasite propagation in mice and transmission of these parasites to the invertebrate vector.

A novel adjuvant for use with a blood-stage malaria vaccine

An effective vaccine delivery system has been developed for vaccination against a blood-stage malaria infection in mice. Subcutaneous vaccination with a semi-purified asexual blood-stage malaria antigen combined with an adjuvant formulation containing squalane, Tween 80 and pluronic L121 (AF) protected mice infected with a lethal P. yoelii infection against death and greatly reduced the severity and duration of parasitaemia. The adjuvant and the route of immunization are both clinically acceptable, thereby making this an attractive delivery system for a human malaria vaccine. Protective immunity appeared to be associated with an enhancement of both Th1 and Th2 subset cytokines.

The pathophysiology of ovine trypanosomosis: haemotological and blood biochemical changes

The course of Trypanosoma congolense infection in sheep was followed for 96 days. Infected animals developed fluctuating parasitaemia, macrocytic normochromic anaemia and leucocytosis which was principally a lymphocytosis. Following treatment with the trypanocidal drug, diminazene aceturate at 84 days after infection, the haematological values returbed to normal within 12 days. Infected sheep developed hypocholesterolaemia and hypophospholipidaemia leading to a reduction in total serum lipids. This study has shown that sheep infected with T. congolense develop anaemia, the onset of which follows the first wave of parasitaemia. The changes in blood lipids observed in infected sheep appeared to be related to the intensity and duration of parasitaemia.

Coagulation disorders in experimentally induced acute mouse malaria

The development of coagulation disorders was studied in murine malaria. Plasmodium vinckei was chosen following an initial experiment because onset and duration of parasitemia were more suitable for hemostasiological studies than in the short-lasting infection, caused by P. berghei. Evaluation of the time courses of hematocrit, platelets, antithrombin (AT) III activity, Factor V activity and parasitemia showed a significant decrease in platelets, hematocrit, Factor V and AT III activity during the course of infection. The obtained data strongly suggest the development of a disseminated intravascular coagulation in mice during the terminal phase of murine malaria.

Neither Heparin nor Acetylsalicylic Acid Influence the Clinical Course in Human Plasmodium Falciparum Malaria: a Prospective Randomized Study

Procoagulant alterations and thrombocytopenia in falciparum malaria correlate with parasitemia, serum levels of tumor necrosis factor alpha (TNF alpha), and clinical severity. Thus, heparin or acetylsalicylic acid (ASA), which are used frequently to prevent thrombosis and (in the case of ASA) to control fever, could be potentially beneficial. We randomized 97 patients with falciparum malaria into three groups: 33 patients received low-dose heparin subcutaneously, 31 received ASA intravenously, and 33 did not receive either drug. All patients received appropriate antiparasitic treatment. Eighteen of 97 patients (seven receiving heparin, five receiving ASA, and 6 in the control group) had complications upon admission. During therapy, elevated TNF alpha and lactate dehydrogenase levels and decreased platelet counts returned to normal values. Except for a minimal partial thromboplastin time prolongation with heparin, heparin or ASA did not affect any laboratory parameter, duration of parasitemia, fever clearance, or the length of hospitalization. Thus, it appears that ASA and heparin do not influence the course of falciparum malaria. Hence, in view of possible side effects, these substances should not be recommended for routine use in the treatment of human malaria.

Malignant, non-hodgkin's lymphomas in trypanosoma cruzi-infected rabbits treated with nitroarenes

Use of 2-nitroimidazole, 5-nitrofuran and 5-nitroimidazole compounds in T. cruzi-infected rabbits resulted in a reduction in duration of parasitaemia in comparison with untreated, infected rabbits. The chronic myocarditis associated with Chagas' disease was not, however, prevented in nitroarene-treated rabbits; lymphocytic infiltrates associated with cardiac cell lysis, in the absence of parasites in situ, were present in both treated and untreated rabbits. The carcinogenic effect of each trypanocidal nitroarene used in this study was also assessed. Administration of nitroarenes to rabbits resulted in the appearance of solid tumours in 37.8 per cent of animals that received drug therapy. Untreated, control rabbits in this series did not show tumour growth. Furthermore, malignant, mixed-cell type, non-Hodgkin's lymphomas were seen in 32.4 per cent of the treated rabbits. It seems that a direct relationship could be present between the presence of the nitro group, the trypanocidal cytotoxicity and the prevalence of tumours. Benznidazole cleared up parasitaemias in the shortest time and was associated with 41.6 per cent of lymphoma growths, whereas MK-436 required twice as much time to clear blood parasites, and showed lymphomas in 25 per cent of experimental rabbits. The demonstration of a high prevalence of malignant tumours in addition to the chronic myocarditis of Chagas' disease in nitroarene-treated rabbits is important since indiscriminate use of such compounds currently used to treat T. cruzi infections in man could increase the risk of lymphoma.

Cryopreservation of Leucocytozoon caulleryi sporozoites.

Leucocytozoon caulleryi sporozoites that had been stored at -196 degrees C or -80 degrees C for 6 or 12 months in Eagle's minimum essential medium or Medium 199 supplemented with 5% glycerol and 10% chicken serum showed infectivity to chickens. Glycerol at a concentration of 10% and dimethyl sulfoxide at 10% and 5% were found to be ineffective cryoprotective agents for the low temperature preservation of sporozoites. Sporozoites isolated from the intact females of Culicoides arakawae, which had been stored at -80 degrees C for 6 or 12 months without cryoprotective agents, retained their infectivity. No differences were observed in the prepatent period, duration of parasitemia, and presence of serum-soluble antigens between chickens infected with frozen sporozoites and those infected with fresh sporozoites.

Antigenic variation duringTrypanosoma vivaxinfections of different host species

The sequence of appearance of specific lytic activity against more than 20 variable antigen types (VATs) of Trypanosoma vivax in the serum of 27 animals belonging to 5 species has been examined. For each host species there was a characteristic course of infection, with differences in height and duration of parasitaemia and in pathogenicity. The sequence of antigenic variation was similar in all host species, with some VATs consistently eliciting response more rapidly than others. The predominant group, comprising VATs which apparently developed within the first 3 weeks, varied in size according to the total number of trypanosomes in the bloodstream within that period, suggesting there is a spectrum, rather than discrete groupings, in the hierarchy of VAT expression. There was very little evidence for differences in appearance of VATs between host species; the only clear example was one VAT which apparently did not develop in one host species. The sequence of antigenic variation in T. vivax seems to be determined by the parasite rather than the host species.

Heterologous strain immunity in bovine babesiosis using a culture-derived soluble Babesia bovis immunogen.

The cross-protective capacity of culture-derived soluble immunogens against heterologous Babesia bovis strains from different geographical locations of Latin America was examined. Susceptible yearling cattle were either immunized with immunogens derived from Venezuelan or Mexican strains, or were administered a multi-component immunogen containing antigens of the Australian, Mexican and Venezuelan strains. Cattle were challenged with virulent B. bovis organisms of the Argentinian, Colombian, Ecuadorean, Mexican and Venezuelan strains. The major parameters used to evaluate cross-protection were the following: presence, level and duration of parasitemia; maximal PCV reduction; level and duration of fever; determination of fibrinogen and cryofibrinogen; homologous and heterologous antibody levels; and net gains in body weight. Results showed good protection with a Venezuelan B. bovis immunogen after homologous and heterologous challenge exposures. A low degree of cross-immunity was observed when cattle vaccinated with the Mexican immunogen were challenged with each of the heterologous strains.

Susceptibility of different breeds of goats in Kenya to experimental infection with Trypanosoma congolense.

To assess whether there was any evidence of genetic resistance to African trypanosomiasis, five breeds of goat (East African, Galla, and crossbreds between East African and Galla, Nubian or Toggenburg) were experimentally infected with Trypanosoma congolense either by needle inoculation or by tsetse-transmission. The goats had not been previously exposed to trypanosomiasis. With both methods of infection all breeds were found to be highly susceptible and suffered severe disease. Following tsetse-transmitted infection no significant differences were observed between breeds in the development, duration and size of the chancre reaction or in the degree and duration of parasitaemia. While Nubian goats developed anaemia more rapidly than the other breeds, all animals experienced a pronounced reduction in packed red cell volume. Similarly following needle inoculation no differences were found between breeds in the severity of anaemia or in the kinetics of parasitaemia. Immune responses against both metacyclic and bloodstream trypanosomes of the infecting serodeme were similar in all breeds as were the erythropoietic responses to the infection. No alterations in leucocyte parameters occurred.

Interaction of nutrition and infection: effect of zinc deficiency on resistance to Trypanosoma musculi

1. 1. Zinc deficiency was studied in mice infected with Trypanosoma musculi. 2. 2. In all dietary groups, the infected animals consumed more food and gained more wieght than the uninfected controls. 3. 3. In all studies, at the peak of parasitemia, the zinc-deficient animals showed three times the number of trypanosomes as that of the complete and pair-fed mice. 4. 4. The average coefficients of variation in body lengths of T. musculi cells indicated that the formation of the reproductive-inhibiting antibody (ablastin) occurred later in zinc-deficient animals compared to animals fed complete diets. The degree and duration of parasitemia in the zinc-deficient animals indicated a delay in the synthesis of the terminal lytic antibody. 5. 5. Irrespective of diets, severe depression in the primary and secondary antibody responses to in vivo immunization of sheep erythrocytes was observed in infected animals over non-infected controls.

Bovine trypanosomiasis: the red cell kinetics of ndama and Zebu cattle infected with Trypanosoma congolense.

The responses of susceptible Ndama and Zebu cattle to needle challenge with Trypanosoma congolense were followed using parasitological, haematological and radio-isotopic methods and compared with those of corresponding uninfected animals. In both breeds, infection became patent at the same time but peak parasitaemias were significantly lower, were attained later and were of short duration in the Ndama. All infected animals became anaemic, the severity of which correlated with the level and duration of parasitaemia. However, even when parasites could no longer be detected in the blood, packed cell volumes showed little tendency to recover. The anaemia was due to increased intravascular red cell destruction and was more pronounced in the Zebu. Haemodilution was not a feature. Increased red cell syntheisis occurred in infected animals of both breeds but particularly in the Zebu; this accounted for the capacity to maintain packed cell volume levels following the initial drop associated with parasitaemia. However, in most cases red cell synthesis was less than expected from the degree of anaemia, suggesting impairment of bone marrow function. Measurement of red cell iron utilization indicated that this was due to effective from re-utilization from degraded red cells arising from reticulo-endothelial blockade. It is concluded that the anaemia in this disease and its underlying processes are broadly in line with the number of parasites in the blood and that the superior resistance of the Ndama cattle lies in their ability to control parasitaemia rather than their capacity to mount a more efficient erythropoietic response.

Interaction of nutrition and infection: Effect of iron deficiency on resistance to Trypanosoma lewisi

1. 1. Iron deficiency was studied in rats infected with Trypanosoma lewisi. 2. 2. Iron-deficient and pair-fed control rats showed greater parasitemias than complete diet rats throughout the infection. 3. 3. The average coefficients of variation in body length of T. lewisi cells indicated that the formation of the reproduction-inhibiting antibody (ablastin) occurred 9 days later in iron-deficient hosts compared to hosts fed complete diets. The duration of parasitemia in the deficient animals also indicated a delayed production of the terminal lytic antibodies. 4. 4. Irrespective of diet, the infected animals consumed more food and gained more weight than un-infected controls.

Comparison of A 9-phenanthrene methanol (WR33063), a 4-quinoline methanol (wr30090), and quinine for falciparum malaria in Thailand

Quinine was compared with a 9-phenanthrene methanol (WR33063) and a 4-quinoline methanol (WR30090) for the treatment of 207 patients with falciparum malaria in Southeast Thailand. Quinine eradicated parasitaemia (average 70 hours) more rapidly than either WR30090 (72 hours) or WR33063 (77 hours). But WR33063 had a higher cure rate (92%) than WR30090 (86%) or quinine (85%). The mean duration of fever and of parasitaemia were combined with the failure rate to form an arbitrary efficacy index. Using this concept WR33063 was the most effective drug. The recrudescence rate correlated with the degree and duration of parasitaemia and with the duration of fever. WR33063 was the least toxic drug. Side effects associated with WR30090 appeared to be headache, backache and urticaria. Quinine was the most toxic drug. All 3 drugs were inconvenient in having to be administered every 8 hours for 6 days. One patient did not respond to oral quinine but did respond to an intravenous quinine infusion (IVQ). A “Medication Ward Round” was perfected during the study and comprised sequential history, drug administration, physical examination, dose notation and patient observation. Falciparum nephrosis was diagnosed in one patient.

Trypanosoma lewisi: cell populations and antibody formation in riboflavin deficient rats.

The influence of riboflavin deficiency on severity and duration of parasitemia was studied in Trypanosoma lewisi infected rats.