peak parasitaemia
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2021 ◽  
Vol 20 (1) ◽  
Author(s):  
Stephen D. Woolley ◽  
Louise Marquart ◽  
John Woodford ◽  
Stephan Chalon ◽  
Joerg J. Moehrle ◽  
...  

Abstract Background Malaria-associated anaemia, arising from symptomatic, asymptomatic and submicroscopic infections, is a significant cause of morbidity worldwide. Induced blood stage malaria volunteer infection studies (IBSM-VIS) provide a unique opportunity to evaluate the haematological response to early Plasmodium falciparum and Plasmodium vivax infection. Methods This study was an analysis of the haemoglobin, red cell counts, and parasitaemia data from 315 participants enrolled in IBSM-VIS between 2012 and 2019, including 269 participants inoculated with the 3D7 strain of P. falciparum (Pf3D7), 15 with an artemisinin-resistant P. falciparum strain (PfK13) and 46 with P. vivax. Factors associated with the fractional fall in haemoglobin (Hb-FF) were evaluated, and the malaria-attributable erythrocyte loss after accounting for phlebotomy-related losses was estimated. The relative contribution of parasitized erythrocytes to the malaria-attributable erythrocyte loss was also estimated. Results The median peak parasitaemia prior to treatment was 10,277 parasites/ml (IQR 3566–27,815), 71,427 parasites/ml [IQR 33,236–180,213], and 34,840 parasites/ml (IQR 13,302–77,064) in participants inoculated with Pf3D7, PfK13, and P. vivax, respectively. The median Hb-FF was 10.3% (IQR 7.8–13.3), 14.8% (IQR 11.8–15.9) and 11.7% (IQR 8.9–14.5) in those inoculated with Pf3D7, PfK13 and P. vivax, respectively, with the haemoglobin nadir occurring a median 12 (IQR 5–21), 15 (IQR 7–22), and 8 (IQR 7–15) days following inoculation. In participants inoculated with P. falciparum, recrudescence was associated with a greater Hb-FF, while in those with P. vivax, the Hb-FF was associated with a higher pre-treatment parasitaemia and later day of anti-malarial treatment. After accounting for phlebotomy-related blood losses, the estimated Hb-FF was 4.1% (IQR 3.1–5.3), 7.2% (IQR 5.8–7.8), and 4.9% (IQR 3.7–6.1) in participants inoculated with Pf3D7, PfK13, and P. vivax, respectively. Parasitized erythrocytes were estimated to account for 0.015% (IQR 0.006–0.06), 0.128% (IQR 0.068–0.616) and 0.022% (IQR 0.008–0.082) of the malaria-attributable erythrocyte loss in participants inoculated with Pf3D7, PfK13, and P. vivax, respectively. Conclusion Early experimental P. falciparum and P. vivax infection resulted in a small but significant fall in haemoglobin despite parasitaemia only just at the level of microscopic detection. Loss of parasitized erythrocytes accounted for < 0.2% of the total malaria-attributable haemoglobin loss.


Author(s):  
Christopher Kariuki ◽  
John M. Kagira ◽  
Victor Mwadime ◽  
Maina Ngotho

Background: A key objective in basic research on human African trypanosomiasis (HAT) is developing a cheap and reliable experimental model of the disease for use in pathogenesis and drug studies.Objective: With a view to improving current models, a study was undertaken to characterise the virulence and pathogenicity of three Trypanosoma brucei rhodesiense stabilates, labelled as International Livestock Research Institute (ILRI)-2918, ILRI-3953, and Institute of Primate Research (IPR)-001, infected into Swiss white mice.Methods: Swiss white mice were infected intraperitoneally with trypanosomes and observedfor parasitaemia using wet blood smears obtained by tail snipping. Induction of late-stagedisease was undertaken using diminazene aceturate (40 mg/kg, Berenil) with curativetreatment done using melarsoprol (3.6 mg/kg, Arsobal).Results: The prepatent period for the stabilates ranged from three to four days with mean peak parasitaemia ranging from Log10 6.40 to 8.36. First peak parasitaemia for all stabilates varied between six and seven days post infection (DPI) followed by secondary latency in ILRI-2918 (15–17 DPI) and IPR-001 (17–19 DPI). Survival times ranged from six DPI (ILRI-3953) to 86 DPI (IPR-001). Hindleg paresis was observed in both ILRI-3953 (at peak parasitaemia) and ILRI-2918 (after relapse parasitaemia). Mice infected with IPR-001 survived until 54 DPI when curative treatment was undertaken.Conclusions: This study demonstrated that the stabilates ILRI-2918 and ILRI-3953 were unsuitable for modelling late-stage HAT in mice. The stabilate IPR-001 demonstrated the potential to induce chronic trypanosomiasis in Swiss white mice for use in development of a late-stage model of HAT.


Parasitology ◽  
2015 ◽  
Vol 142 (6) ◽  
pp. 849-854 ◽  
Author(s):  
Y. F. FALAJIKI ◽  
O. AKINOLA ◽  
O. O. ABIODUN ◽  
C. T. HAPPI ◽  
A. SOWUNMI ◽  
...  

SUMMARYEmergence of malaria parasites resistant to artemisinin necessitates the need for development of new antimalarial therapies. Ciprofloxacin (CFX) a second generation quinolone antibiotic possesses some antimalarial activities. We investigated the in vivo antimalarial activities of CFX in combination with amodiaquine in mice infected with chloroquine-resistant Plasmodium berghei ANKA. Animals were treated orally with 80 or 160 mg kg−1 body weight of CFX alone given twice daily or in combination with amodiaquine (AQ) 10 mg kg−1 body weight. Parasitological activity and survival of the animals were assessed over 21 days. Peak parasitaemia in the untreated control group was 72·51%. Treatment with AQ alone resulted in clearance of parasitaemia by day 4 while treatment with CFX 80 and 160 mg kg−1 alone suppressed parasitaemia by 13·94–54·64% and 35·6–92·7%, respectively. However, the combination of CFX with AQ significantly enhanced response of infection in the animals to treatment (P < 0·05) resulting in complete resolution of parasitaemia throughout follow up period with CFX 160 mg kg−1, delayed recrudescence time with CFX 80 mg kg−1 and significant increase in survival rate of the animals. The results demonstrate beneficial interaction between AQ and CFX which may provide a clinically relevant antimalarial/antibiotic therapeutic option in the management of malaria.


2013 ◽  
Vol 2013 ◽  
pp. 1-10 ◽  
Author(s):  
Kalyan Kumar Kuthala ◽  
Sowjanya Meka ◽  
Sunita Kanikaram

To find out the efficacy and effect of artemisinin derivatives on haematological indices, C57BL/6J mice were challenged with Plasmodium falciparum and treated with therapeutic doses of AS, AE, and AL. Course of infection was studied in the infected and treated groups up to day 42. Peak level of parasitaemia (38%) was observed on day 11 in infected group. Haematological indices indicated significant (P<0.05) decrease in RBC, WBC, haemoglobin, packed cell volume, mean cell volume, and platelet counts in infected mice. But all the parameters were restored to normal values, and significant (P<0.05) changes were observed in all drug-treated groups. Insignificant changes were observed for MCHC (P>0.05) in all drug-treated groups. Percent of peak parasitaemia was much reduced in AL- (3.2% on day 3) treated group in comparison with AE- (2.4% on day 4) and AS- (4% on day 2) treated groups. Parasites were completely cleared on day 6 in AS group, day 5 in AE group, and day 4 in AL group. Hence, our results strongly support that combination therapy has high efficacy rates than monotherapy. No adverse effects were observed on haematological parameters when animals were treated with therapeutic dosages.


Author(s):  
A.A. Latif ◽  
M.A. Bakheit ◽  
Amna E. E. Mohamed ◽  
E. Zweygarth

A crossbred calf (3 months old) obtained from a farm where regular control of ticks was practised and found to be free of blood parasites was inoculated with 20 ml pooled blood collected from four field cattle which had very low Trypanosoma theileri parasitaemias (one parasite per 70 µl blood as determined by the haematocrit centrifugation technique). Trypanosoma theileri was present in the blood 6 days after injection and a peak parasitaemia of 42 parasites per 70 µl blood was recorded by day 12. Hyalomma anatolicum anatolicum nymphs were applied on the ears of the calf on day 8 and they dropped engorged by days 13 and 14. The resulting adult ticks were examined for the presence of T. theileri by severing a leg and making a smear of the clear haemolymph which exuded from the wound. The smear was fixed in methanol and stained with Giemsa stain. The infection rate with T. theileri in the ticks was 43.3 % (26 out of 60). The intensity of infection was very high and various developmental stages of the flagellates were observed (epimastigotes, sphaeromastigotes, trypomastigotes and other intermediate stages). The haemolymph from 12 ticks was also collected in tissue culture medium and the trypanosomes survived for 25 weeks before eventually dying. The results demonstrated unequivocally the high vectorial capacity of the tick H. a. anatolicum for T. theileri.


Parasitology ◽  
2004 ◽  
Vol 128 (3) ◽  
pp. 295-304 ◽  
Author(s):  
H. SATO ◽  
K. ISHITA ◽  
A. OSANAI ◽  
M. YAGISAWA ◽  
H. KAMIYA ◽  
...  

Mongolian jirds,Meriones unguiculatus, are susceptible to infection withTrypanosoma grosi, which naturally parasitizesApodemusspp. The present study investigated T cell dependence of elimination ofT. grosifrom the bloodstream of jirds byin vivoT cell depletion using a monoclonal antibody (HUSM-M.g.15). In T cell-depleted jirds, elimination ofT. grosi, particularly the dividing forms, from the bloodstream was significantly delayed, occurring at around week 3 p.i. The kinetics of serum levels of IgM and IgG specific to trypanosomes in T cell-depleted and control immunocompetent jirds were different; peak levels of IgM were noted on days 6–8 p.i. around the time of peak parasitaemia (day 6 p.i.) in immunocompetent jirds, whereas the serum levels began to increase abruptly after day 10 p.i., peaking at around day 18 p.i. in T cell-depleted jirds. Similarly, serum IgG increased after day 6 p.i. in immunocompetent jirds, in contrast to after day 12 p.i. in T cell-depleted jirds, and the level increased steadily even after disappearance of parasitaemia. Our findings indicate that T cells play a major role at least in the ‘first crisis’ during elimination of dividingT. grosifrom the bloodstream.


1997 ◽  
Vol 129 (1) ◽  
pp. 83-89 ◽  
Author(s):  
D. L. ROMNEY ◽  
A. N'JIE ◽  
D. CLIFFORD ◽  
P. H. HOLMES ◽  
D. RICHARD ◽  
...  

Thirty-two N'Dama heifers were offered ad libitum Andropogon hay plus 10·2 g/kg liveweight (LW) groundnut hay (GNH) (L) or 10·2 g/kg LW GNH and 3·9 g/kg LW groundnut cake (GNC) (H). After 4 weeks on the diets, half of each group were infected intradermally with Trypanosoma congolense clone (ITC 50) (LI and HI). Peak parasitaemia occurred 6–8 days after infection and started to decrease c. 56 days later. No differences in parasitaemia were observed between LI and HI animals. Packed cell volume (PCV) fell in all treatments (by 5·4, 13·8, 3·7 and 9·4 units after 49–63 days post-infection (p.i.) for the L, LI, H and HI groups respectively) and significant effects of infection and diet were observed. GNH and GNC intakes were maintained during the trial; however, infected animals had a decreased intake of Andropogon hay. LI animals lost significantly more weight during the experimental period than the non-infected controls (−71·4 v. −13·7 g/day). Meanwhile, HI animals gained less weight compared with the H group (52·2 v. 167·6 g/day). Weight losses appeared to be due to decreased food intake. In the period 54–68 days p.i., plasma concentrations of albumin were lower and plasma protein was higher in infected animals. Plasma cholesterol concentrations were also lower in infected animals 54–68 days p.i. Plasma urea concentrations were higher in supplemented animals but were not affected by infection. The results showed that animals on a higher plane of nutrition showed less severe clinical signs of infection. However, for all the parameters considered, the magnitude of the difference between groups on different diets was similar for both infected and control animals, suggesting that mechanisms of resistance were not affected by the planes of nutrition considered.


Parasitology ◽  
1993 ◽  
Vol 107 (2) ◽  
pp. 183-192 ◽  
Author(s):  
C. J. Barnard ◽  
J. M. Behnke ◽  
J. Sewell

SUMMARYUnrelated and initially unfamiliar male CFLP mice, maintained for different periods in groups of 6, differed in both their rate of clearance of Babesia microti and the time taken to reach peak parasitaemia in relation to their aggressive behaviour within groups prior to infection. Males maintained in groups for shorter periods and showing more aggression within their group were slower to clear infection and males showing more marked external evidence of aggressive interaction reached a peak of parasitaemia sooner. Serum IgG and corticosterone analyses were consistent with increased aggression causing stress-induced immunodepression but relationships with aggression and social status were not simple. Males showing more aggression tended to enter their groups with higher levels of corticosterone and, to a lesser extent, reduced levels of IgG compared with other mice. The results thus suggest that increased susceptibility to disease may be a cost to males aggressively maintaining high social status.


Parasitology ◽  
1989 ◽  
Vol 99 (2) ◽  
pp. 157-163 ◽  
Author(s):  
W. Jarra ◽  
K. N. Brown

SummaryDuring the early stages of the primary Plasmodium chabaudi chabaudi AS parasitaemia in CBA/Ca mice this parasite invaded normocytes, but as the parasitaemia developed increasing numbers of parasites were seen within reticulocytes. During and just after peak parasitaemia, as further parasite replication was controlled, the ‘crisis’ phase ensued, mice became increasingly anaemic and reticulocyte numbers were markedly increased. As the parasitaemia was resolved during crisis in excess of 25% of parasites had invaded reticulocytes. In phenylhydrazine-pretreated mice with artificially high reticulocyte levels and infected with P. c. chabaudi AS, normocyte/reticulocyte invasion occurred with equal frequency. No reduction in the infectivity of parasite populations developing in reticulocytes was observed.


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