Parasitemia and survival in mice infected with Plasmodium berghei; hybrids between Swiss (high parasitemia) and STR (low parasitemia) mice.
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Animals↗
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[Estimation of the parasitemia in Trypanosoma cruzi human infection: high parasitemias are associated with severe and fatal congenital Chagas disease].
The aim of this study was to validate the method of microhematocrit tube, as a rapid method to estimate the parasitemia in blood and to associate the parasites concentration with the morbidity and mortality of new born children with congenital Chagas diseases. Our results were determined experimentally and shown that the detection limit of the microhematocrit tube method is 40 parasites/ml when at least one of the four observed tubes is positive. Besides, it was also established that when the four examined tubes are positive the parasitemia in blood reaches more than 100 parasites/ml. It is important to highlight the modification made by our laboratory in the microscopic observation of the microhematocrit tubes with respect to the methodology used by previous investigators. A positive association exists between a high number of parasites in blood and the morbi-mortality of the newly born children with congenital chagas. The results of positive association between the parasitic load and the morbility and mortality could constitute an argument to understand the possible role of the parasite in the pathology of the disease.
Animals↗
Dose- and time-dependent relations between infective Anopheles inoculation and outcomes of Plasmodium falciparum parasitemia among children in western Kenya.
Blood-stage level Plasmodium falciparum infection (parasitemia density) is generally elevated prior to, or at the time of, clinical presentation of severe pediatric malaria episodes. Intensity of exposure to infective Anopheles mosquito bites is a suspected determinant of higher density parasitemia. Analyses of entomologic and parasitologic data collected in 1986-1987 were conducted to investigate whether the dose of infective bites predicted the incidence or degree of P. falciparum parasitemia in Kenyan children < 6 years old. At 21 consecutive 30-day intervals, a new cohort (n approximately 50 each) was enrolled, cured of malaria parasites, and monitored over 84 days for recurrent parasitemia. Outcomes included time to parasitemia, time to parasitemia > or = 5,000/microliter, and parasitemia density. Ecologic and individual-level analyses were conducted. The mean infective bite exposure experienced by each cohort was significantly associated with the incidence of parasitemia (age-adjusted r2 = 0.38, p = 0.022) and more strongly associated with the incidence of parasitemia > or = 5,000/microliter (age-adjusted r2 = 0.72, p < 0.001). The infective bite dose, analyzed as a time-dependent covariate, was associated with a 2.8 times higher rate of parasitemia > or = 5,000/microliter among children exposed to > or = 1 infective bite per day as compared with the referent (rate ratio (RR) = 2.82, 95% confidence interval (CI) 2.24-3.56). Cumulative infective bite exposure, exposure duration, and age were significant predictors of recurrent parasitemia density in multiple linear regression analyses. The results support the contention that reductions in P. falciparum transmission intensity, in the absence of complete elimination, will reduce higher level parasitemia among African children.
Animals↗
Plasmodium chabaudi chabaudi: effect of low parasitemias on immunity in CB6F1 mice.
We examined the effect that low parasitemias have on the immune response of CB6F1 mice infected with Plasmodium chabaudi chabaudi AS. Ascending parasitemias were stopped by chloroquine treatment when they were between 1.6 and 9.4%. Mice that suffered low parasitemias developed good immunity to homologous reinfection but, contrary to what happened in mice that suffered full parasitemias, they did not develop immunity to heterologous reinfection with Plasmodium yoelii 17XL. Total IgG antiparasite antibody responses were similar in mice that suffered low or full parasitemia, both in primary infection and after reinfection. At the level of isotypes, IgM, IgG1, IgG2b, and IgG3 responses were similar in mice that suffered low or full parasitemias, but after reinfection, mice that suffered low parasitemias responded with higher levels of IgG2a than mice that suffered full parasitemias. Mice that suffered low parasitemias did not have splenomegaly but their immunity to homologous reinfection was diminished after splenectomy in a manner similar to that of splenectomized mice that suffered full parasitemia. CB6F1 mice can develop homologous immunity even if exposed to low parasitemias but cannot develop heterologous immunity unless exposed to high parasite loads.
Animals↗
Adverse perinatal outcomes of HIV-1-infected women in relation to malaria parasitemia in maternal and umbilical cord blood.
Malaria infection during pregnancy increases the risk of adverse birth outcomes among HIV-infected women. The role of umbilical cord parasitemia is not well characterized. We examined the risk of adverse perinatal outcomes in relation to maternal or umbilical cord Plasmodium falciparum parasitemia among 275 HIV-infected women from Tanzania, who participated in a randomized trial of zinc supplementation during pregnancy. Maternal parasitemia (> or = 1/microL) at the first antenatal visit was associated with increased risk of low birth weight < 2,500 g (adjusted relative risk [ARR] = 2.66; P = 0.01) and preterm delivery < 37 weeks (ARR = 1.87; P = 0.06). Maternal parasitemia at delivery was associated with preterm delivery (ARR = 2.27; P = 0.008), intrauterine growth retardation (ARR = 1.92; P = 0.03), and neonatal death (ARR = 3.22; P = 0.07). Cord parasitemia was associated with a large and significant increase in the risk of neonatal death (ARR = 8.75; P = 0.003). Maternal parasitemia at the first antenatal visit was strongly related to parasitemia at delivery, and the latter was associated with cord blood parasitemia. CD4 cell counts, parity, or assignment to the zinc arm (25 mg daily) were not associated with parasitemia in maternal or cord blood at delivery. Successful treatment of HIV-infected women who present to the first prenatal visit with malaria parasitemia and avoidance of reinfection are likely to decrease the risk of adverse outcomes during pregnancy and the early postpartum period. Cord blood parasitemia is a strong predictor of neonatal death. The potential effect of zinc supplementation on clinical malaria outcomes deserves future investigation.
Adult↗
Plasmodium chabaudi adami: use of the B-cell-deficient mouse to define possible mechanisms modulating parasitemia of chronic malaria.
Our previous observation that B-cell-deficient JH-/- mice utilize T cell-dependent immunity to suppress acute Plasmodium chabaudi adami-induced malaria but then develop chronic low-level parasitemia prompted this study of control mechanisms for chronic parasitemia. When we infected JH-/- mice with blood-stage parasites, chronic parasitemia exacerbated after the 6th month and persisted for up to 17 months. This exacerbation of parasitemia could not be attributed to host aging because the time-course of acute infection in naïve aged mice was nearly identical to that seen in young mice. Nor could exacerbated parasitemia be attributed to mutation in the parasite genome resulting in increased virulence; when subinoculated into naïve JH-/- mice, parasites from chronically infected JH-/- mice with exacerbated parasitemia produced acute stage parasitemia profiles in most recipients comparable to those seen in JH-/- mice upon infection with the original stabilate material. Of the pro-inflammatory cytokines measured, including IFNgamma, TNFalpha, IL-12p70, and MCP-1beta, none were significantly different in the sera of mice with exacerbated parasitemia compared to uninfected controls. Levels of IL-6 were significantly (P=0.002) less in the sera of mice with exacerbated parasitemia. Serum levels of the anti-inflammatory cytokine, TGFbeta, were significantly depressed in chronically infected JH-/- mice compared to uninfected controls. In contrast, IL-10 levels were markedly increased. These findings suggest that the cytokine balance may be disturbed during chronic malaria, thereby impacting on mechanisms that modulate levels of parasitemia.
Aging↗
Suppression of Plasmodium chabaudi parasitemia is independent of the action of reactive oxygen intermediates and/or nitric oxide.
The killing of blood-stage malaria parasites in vivo has been attributed to reactive intermediates of oxygen (ROI) and of nitrogen (RNI). However, in the case of the latter, this contention is challenged by recent observations that parasitemia was not exacerbated in nitric oxide synthase (NOS) knockout (KO) (NOS2-/- or NOS3-/-) mice or in mice treated with NOS inhibitors. We now report that the time course shows that Plasmodium chabaudi parasitemia in NADPH oxidase KO (p47phox-/-) mice also was not exacerbated, suggesting a minimal role for ROI-mediated killing of blood-stage parasites. It is possible that the production of protective antibodies during malaria may mask the function of ROI and/or RNI. However, parasitemia in B-cell-deficient JH-/- x NOS2-/- or JH-/- x p47phox-/- mice was not exacerbated. In contrast, the magnitude of peak parasitemia was significantly enhanced in p47phox-/- mice treated with the xanthine oxidase inhibitor allopurinol, but the duration of patent parasitemia was not prolonged. Whereas the time course of parasitemia in NOS2-/- x p47phox-/- mice was nearly identical to that seen in normal control mice, allopurinol treatment of these double-KO mice also enhanced the magnitude of peak parasitemia. Thus, ROI generated via the xanthine oxidase pathway contribute to the control of ascending P. chabaudi parasitemia during acute malaria but alone are insufficient to suppress parasitemia to subpatent levels. Together, these results indicate that ROI or RNI can contribute to, but are not essential for, the suppression of parasitemia during blood-stage malaria.
Allopurinol↗
Prevalence of parasitemia and seroreactivity to Trypanosoma cruzi in a rural population of Northeast Brazil.
Age-specific prevalence rates of parasitemia and seroreactivity to Trypanosoma cruzi were determined in a rural area endemic for Chagas' disease in Northeast Brazil. Parasitemia was detected by blood cultures and xenodiagnosis, and serum antibodies to the parasite were measured by the complement fixation (CF) and indirect immunofluorescence (IFA) tests. Of the 116 persons examined, 39 (33.7%) had antibodies and 23 (19.8%) had parasitemia. Ninety-six percent of parasitemic individuals were seropositive and 56% of seropositive individuals were parasitemic. The percentage of seropositive individuals with detectable parasitemia declined with age; all seropositive children in the 1- to 4-year age group and two-thirds of seropositive persons 5-19 years old had parasitemia while only one-third of seropositive adults above 19 years had parasitemia. CF and IFA tests were equally sensitive in detecting persons with parasitemia. Xenodiagnosis was more sensitive than culture for detecting parasitemia, but the two methods together were more sensitive than either method alone. Using the age-dependent relationship of parasitemia to seropositivity determined in this study, the prevalence rate of T. cruzi parasitemia was estimated in a much larger adjacent population in which seropositivity rates and the demographic structure were already known.
Adolescent↗
Detection of parasitemia profiles by blood culture after treatment of human chronic Trypanosoma cruzi infection.
The change in parasitemia profile, measured by sequential blood cultures of 27 benznidazole (Bz) treated patients compared with 13 untreated patients, on the chronic phase of chagas disease, is described. All patients were adults (age limits: 23-88) with positive serology (three tests); 23 of them were females. All patients were submitted to six blood cultures, three before and three after Bz treatment. The parasitemia was classified as nondetected (with three negative blood cultures), medium (one positive culture in three), and high (two or three positive cultures). From the eight patients with nondetected parasitemia before Bz, seven still had the same profile and only one switched to medium; from eight with medium parasitemia, seven shifted to nondetected, and one to high parasitemia. From the 11 patients with high parasitemia before Bz, ten converted to nondetected and only one was positive after Bz. Nineteen of the 27 patients changed the parasitemia profile (70.4%), and the rate of therapeutic failure was 11.1% (3/27) during the first 24 months of follow-up after Bz. The shift to nondetected parasitemia profile was from 8/27 to 24/27 patients after Bz treatment for the first 2 years. Only 46.2% (6/13) of the nontreated individuals changed the parasitemia profile. We conclude that there is a strong trypanocide effect of Bz (88.8%) and a rate of therapeutic failure of 11.1% during the first 2 years after trypanocidal treatment.
Adult↗
Antigenic analysis by agglutination of Trypanosoma brucei brucei parasitemias initiated in mice with in vitro-produced metacyclics.
Trypanosomes from 14 first-peak parasitemias initiated in mice by injection of in vitro-produced metacyclics were stabilated. Strains derived from these stabilates were analyzed for their antigenic composition by cross-agglutination with immune sera produced in rabbits against 12 of the stabilates. The antigenic composition of the 14 stabilates was compared also with two first-peak parasitemias from mice inoculated with fly-derived metacyclics, the variant-specific antigen of the strain used to initiate the cultures that ultimately became infective, and the antigenic variant that was used to infect the flies. One variant-specific, presumably basic, antigen was found, either as the predominant (nine parasitemias) or as a minor (seven parasitemias) antigen, in all first peak-parasitemia strain initiated with culture- or fly-derived metacyclics; it was absent, however, from the strains (not first-peak parasitemias) used to start the cultures or to infect the flies. Only one of the first-peak parasitemias appeared to have the basic antigen alone. The remaining parasitemia populations seemed to have from about two to six antigens, some of which were common to culture- and fly-derived infections. There was very little, if any, antigenic relationship between the foregoing populations and the strains employed for initiation of cultures or for infection of flies. It is evident from the results that much antigenic similarity exists between the culture- and tsetse fly-derived first-peak parasitemias.
Adsorption↗
Genetic control of responses to Trypanosoma cruzi in mice: multiple genes influencing parasitemia and survival.
Inbred strains of mice can be divided into two groups based on the level of parasitemia which develops after injection with 10(3) trypomastigotes of Trypanosoma cruzi (Peru). Strains which developed parasitemias of greater than 10(7) trypomastigotes per ml by day 17, including C3H/HeJ, BALB/c, and CBA/N mice, were termed high parasitemia strains. Low parasitemia strains, including C57BL/6J and DBA/2J mice, developed parasitemias of less than 5 x 10(6) trypomastigotes per ml by day 17 of infection. Congenic mice from C57BL/10J, C57BL/6J, and BALB/c backgrounds which differed at the H-2 region were injected with 10(3) trypomastigotes to determine the effect of the H-2 locus on response to infection. The H-2 locus had no effect on the level of parasitemia attained during infection. However, one strain, B10.S (H-2s), was unusual in that most of the mice survived infection. The results of infection of F1 hybrid progeny with T. cruzi (Peru) suggest that the low parasitemia response in inherited in a dominant manner and that survival may be influenced by several other genes. The response to T. cruzi infection in inbred mice, as measured by parasitemia and survival time, was influenced by several genes. One or more genes, located outside the H-2 region, were involved in regulating the level of parasitemia reached during infection. Another H-2-linked gene(s) was involved in survival of the infection and appeared to be unique to the H-2s haplotype.
Animals↗
Effect of Plasmodium falciparum parasitemia density on hemoglobin concentrations among full-term, normal birth weight children in western Kenya, IV. The Asembo Bay Cohort Project.
The relative importance of acute high-density versus persistent low-density Plasmodium falciparum parasitemia in contributing to the public health problem of malarial anemia remains unclear. The Asembo Bay Cohort Project in western Kenya collected monthly hemoglobin (Hb) and parasitologic measurements and biweekly assessments of antimalarial drug use among 942 singleton live births between 1992 and 1996. A mixed-model analysis appropriate for repeated measures data was used to study how time-varying parasitemia and antimalarial drug exposures influenced mean Hb profiles. Incidence of World Health Organization-defined severe malarial anemia was 28.1 per 1,000 person-years. Among children aged less than 24 months, concurrent parasitemia was significantly associated with lower mean Hb, especially when compared to children with no concurrent parasitemia. Increased densities of the 90-day history of parasitemia preceding Hb measurement was more strongly associated with mean Hb levels than concurrent parasitemia density. While the highest quartile of 90-day parasitemia history was associated with lowest mean Hb levels, children in the lowest 90-day exposure quartile still experienced significantly lower Hb levels when compared to children who remained parasitemia-free for the same 90-day period. The results highlight the importance of collecting and analyzing longitudinal Hb and parasitologic data when studying the natural history of malarial anemia.
Anemia↗
Malaria parasitemia during delivery.
OBJECTIVE: The aim of this study is to investigate the impact of plasmodium falciparum infection in parturient women in Central Sudan where malaria transmission is mesoendemic. The purpose of this paper is to find out the prevalence of malaria parasitemia and the risk of anemia among parturient women and to suggest appropriate strategies to lower their prevalence rates. METHODS: This prospective study was conducted at Medani Teaching Hospital, Sudan, a tertiary regional referral center, during the period January 1997 through to December 1997. All cases were admitted during labor to the delivery room and were clinically suspected to have malaria. History, examination and investigations were carried out on all patients. RESULTS: The total number of patients enrolled in this study was 550, amounting to 14.9% of all women (N=3,687) who delivered during the study period. The prevalence of malaria parasitemia was 58.9% (N=550) while prevalence of anemia (defined as hemoglobulin <9.0 g/dl) was 24.1%. The mean hemoglobulin levels in patients with positive and negative malaria parasitemia was 9.72 1.62 and 9.85 1.60 g/dl. Statistically the difference in the mean hemoglobulin level was not significant, t=0.879, (P>0.05). A significant negative correlation between parasite count in maternal blood and hemoglobulin level of the mother, was observed, where r=-0.121 (P=0.032). Out of 17 (3.3%) patients who had used chloroquine tablets for prophylaxis, 11 patients still had positive parasitemia. Although there was a higher parasite count in those 11 patients, statistically the difference was not significance where P> 0.05. CONCLUSION: The study documents a high prevalence of malaria parasitemia and anemia among the parturient women in Central Sudan. There were 533 pregnant women (97%) who did not use chloroquine tablets as chemoprophylaxis and 17 (3%) had prophylaxis. Eleven of the later (N=17) had positive parasitemia. In view of the high prevalence of parasitemia and anemia, and although the sample of patients who used chloroquine tablets for prophylaxis and had positive parasitemia is small (17 out of 550), a wide scale prophylaxis placebo-controlled trial is recommended to test the impact of prophylactic drugs in pregnancy and to measure the effect on the mother, and the neonate. The drug that proves to be effective as a prophylactic, should be an integral part of ante-natal care along with iron and folic acid as anti-anemic therapy. Moreover, prompt treatment of malaria infection with the appropriate anti-malarial drug, spray of insecticides and the use of insecticide-impregnated bed-nets and curtains for preventing malaria are recommended.
Adolescent↗
[Parasitemia in chronic chagasic patients evaluated using the index of infected Triatoma in xenodiagnosis].
As part of a pre-treatment study of chronic Chagas infections, the parasitemia of 206 patients (85 men and 121 women, aged 7 to 80 y) from Virgem da Lapa, Minas Gerais State Brazil, was evaluated by three xenodiagnoses per patient during a one year period. Each time, 40 3rd or 4th instar nymphs of Triatoma infestans were applied. The parasitemia was arbitrarily classified as: not detected (when all nymphs were negative), low (when the number of infected nymphs was less than 2%), medium (when it was higher than 2% and up to 7%) and high (when higher than 7%). The parasitemia was not detected in 105 (51%) of the patients, and was considered low in 55 (26.7%), medium in 27 (13.1%) and high in 19 (9.2%). There was no significant differences in levels of parasitemia in relation to sex or age, but the high parasitemia was more frequent among the patients with chagasic cardiomyopathy. Persistent parasitemia (all three xenodiagnoses positive) was observed in 100% of the patients with high parasitemia, in 22.2% with medium and in none with low parasitemia.
Adolescent↗
Behaviour of a Trypanosoma brucei brucei stock (STIB 348C) in mice. 4. Different course of primary parasitemia in trypanosome variants of different virulence.
In three types of trypanosomes with low virulence, trypanosome numbers increased by a factor of 18-21 per day on average during prepatency and by a factor of 70-219 on average from the first to second day of patency. By contrast, a very virulent trypanosome variant showed an average increase of trypanosome numbers per day by 32 and 28 during prepatency and early patency, respectively. --In detailed studies, trypanosomes of low virulence exhibited a rapidly rising parasitemia in early patency which lasted for 20-30 hours and was followed by a plateau of slowly rising and falling parasitemia. Trypanosomes of high virulence showed a constant logarithmic increase of their numbers, slowing down at concentrations above antilog 5.5 per microliters of blood. In mild trypanosomes with peak parasitemias of antilog 5-5.7 per microliters of blood, after low dose infections the primary parasitemia was abruptly terminated after 70-100 hours of patency, obviously by the action of antibody. After massive infections, the parasitemia was terminated at 109-122 hours after infection. --In trypanosomes with higher peak parasitemias, primary parasitemias were seen to last longer, in some cases for 7 to 12 days. --Mice infected with low doses of highly virulent trypanosomes died with high parasitemias after some 60-90 hours of patency, before antibodies could normally become effective. After massive infections they died at 40-60 hours after infection. There is clearly no need to invoke non-immunogenicity of these trypanosomes or immunosuppression by these trypanosomes to explain this course of the infection.
Animals↗
MalariaCount: an image analysis-based program for the accurate determination of parasitemia.
Malaria is a serious global health problem and rapid, precise determination of parasitemia is necessary for malaria research and in clinical settings. Manual counting by light microscopy is the most widely used technique for parasitemia determination but it is a time-consuming and laborious process. The aim of our study was to develop an automated image analysis-based system for the rapid and accurate determination of parasitemia. We have developed, for the first time, a software, MalariaCount, that automatically generates parasitemias from images of Giemsa-stained blood smears. The potential application and robustness of MalariaCount was tested in normal and drug-treated in vitro cultures of Plasmodium falciparum. The results showed a tight correlation between MalariaCount and manual count parasitemia values. These findings suggest that MalariaCount can potentially be used as a tool to provide rapid and accurate determination of parasitemia in research laboratories where frequent, large-scale, efficient determination of parasitemia is required.
Animals↗
TNF as a malaria candidate gene: polymorphism-screening and family-based association analysis of mild malaria attack and parasitemia in Burkina Faso.
We have previously obtained strong evidence for linkage of mild malaria attack to the MHC region, with a peak close to the tumor necrosis factor (TNF) gene. We screened, for polymorphisms, the entire TNF gene in the same sample of 34 families comprising 197 individuals living in a Plasmodium falciparum endemic area and we found 17 polymorphisms. In a longitudinal study, we investigated whether the 11 most frequent and informative polymorphisms were associated with mild malaria attack and maximum parasitemia, which was the highest parasitemia in each individual over 2 years. Mild malaria attack and maximum parasitemia were positively correlated. Transmission disequilibrium tests showed nominal evidence for association between TNF-1031, TNF-308, TNF851 and TNF1304 polymorphisms, and mild malaria attack on the one hand, and between TNF-238, TNF851 and TNF1304 polymorphisms, and maximum parasitemia on the other hand. After accounting for multiple tests, we confirmed the association of TNF-238 with maximum parasitemia and the association of TNF1304 and TNF851 with maximum parasitemia and mild malaria attack. The association tests with mild malaria attack suggest a moderate effect of TNF-308 polymorphism. In conclusion, our study suggests that several TNF variants may be part of the genetic determinants for maximum parasitemia and/or mild malaria attack.
Alleles↗
Trypanosoma cruzi parasitemia in chronic Chagas disease: comparison between human immunodeficiency virus (HIV)-positive and HIV-negative patients.
This study evaluated Trypanosoma cruzi parasitemia in persons with chronic Chagas disease, compared the parasitemia in human immunodeficiency virus (HIV)-positive and -negative subjects, and, for HIV-positive subjects, analyzed the association between parasitemia and occurrence of acquired immunodeficiency syndrome-defining illnesses, CD4 cell counts, HIV loads, and antiretroviral therapy. In total, 110 adults with chronic Chagas disease (29 HIV positive, 81 HIV negative) were studied. T. cruzi parasitemia was evaluated by xenodiagnosis, blood culture, and direct microscopic examination of blood. T. cruzi parasitemia was detected significantly more frequently in HIV-positive than in HIV-negative subjects (odds ratio, 12.3; 95% confidence interval, 3.7-41.2). HIV-positive patients also had higher levels of parasitemia. No statistically significant association was seen between parasitemia and the variables of interest among the HIV-positive subjects.
AIDS-Related Opportunistic Infections↗