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Compact or amoeboid forms may be seen in smears where there was a delay in processing the blood. Figure A: Trophozoites of P. Figure E: Trophozoites of P. Figure B: Trophozoite of P. Figure F: Trophozoites of P. Figure C: Trophozoite of P. Figure D: Trophozoite of P. In this figure, a gametocyte can also be seen in the upper half of the image.
Gametocytes of P. Gametocytes of Plasmodium falciparum are crescent- or sausage-shaped, and are usually about 1. The cytoplasm of the macrogametocytes female are usually a darker, deeper blue; the cytoplasm of the microgametocytes male is usually more pale. The red chromatin and pigment is more coarse and concentrated in the macrogametocytes than the microgametocytes.
Figure A: Gametocyte of P. Note also the presence of many ring-form trophozoites. Figure E: Gametocyte of P. Also seen in this image are ring-form trophozoites exhibiting Maurer's clefts.
Figure I: Gametocytes of P. The gametocyte in the upper right is undergoing exflagellation, a process that normally occurs in the mid-gut of the mosquito host. However, it may be observed in human blood specimens when there is a delay in processing the blood. Figure B: Gametocytes of P. Figure F: Gametocyte of P. In these specimens, Laveran's bibs can be seen. Figure C: Gametocytes of P. Figure G: Gametocytes of P. Figure D: Gametocyte of P.
Also seen in this image are ring-form trophozoites and an RBC exhibiting basophilic stippling upper left. Figure H: Gametocyte of P.
Schizonts of P. Schizonts are rarely seen in peripheral blood of Plasmodium falciparum infections, except in severe cases. When seen, schizonts contain anywhere from merozoites. Figure A: Schizont of P.
Figure B: Schizont of P. Figure C: Schizont of P. Trophozoites are also seen in this image. Plasmodium knowlesi Ring-form trophozoites of P. Early ring-form trophozoites rings of P. Red blood cells may also be multiply-infected.
When full-grown, non-amoeboid rings may occupy half or more of the host RBC. Note a multiply-infected RBC in this image. Figure B: Ring-form trophozoite of P. Older, developing trophozoites of P. In developing trophozoites of P. As the vacuole is lost during maturation of the trophozoite stage, the parasite becomes smaller and more compact. The pigment appears as dark grains and the red nucleus increases in size.
Figure A: Band-form trophozoite of P. Figure B: Band-form upper and ring-form lower trophozoites of P. Mature macrogametocytes of P. The cytoplasm stains blue and the eccentric nucleus stains red. Pigment is coarse and black, and is scattered irregularly in the cytoplasm. The microgametocyte is often, but not always, smaller than the macrogametocyte. The cytoplasm usually stains a pale pink, while the nucleus stains a darker red.
The nucleus may make up half the parasite. The coarse, black pigment is scattered irregularly thought the cytoplasm. Figure B: Gametocyte of P. Note also a ring-form trophozoite in the lower left of this image. The nucleus continues to divide until there are up to 16 average 10 merozoites.
As the schizont matures, it fills the host RBC and the pigment collects into one or a few masses. Figure A: Mature schizont in a Giemsa-stained thin blood smear from a patient that traveled to the Philippines. Figure B: Mature schizont in a Giemsa-stained thin blood smear from a patient that traveled to the Philippines. Note also a ring-form trophozoite to the right of the schizont in this figure.
Plasmodium malariae Ring-form trophozoites of P. Ring-form trophozoites have one rarely two chromatin dots and a cytoplasm ring that tends to be thicker than P. There is no enlargement of infected RBCs. Figure A: Ring-form lower right and developing upper left trophozoites of P.
Figure C: Ring-form trophozoite of P. Figure D: Ring-form trophozoite of P. Trophozoites of P. Pigment may be coarse and peripheral. Chromatin is usually in a single mass, less definite in outline. Pigment granules become larger and tend to have a more peripheral arrangement.
Figure A: Trophozoite of P. Band-form trophozoites of P. Figure E: Band-form trophozoite of P. Figure B: Band-form trophozoite of P. Figure C: Band-form trophozoite of P. Figure D: Band-form trophozoite of P.
Basket-form trophozoites of P. Figure A: Basket-form trophozoite of P. Figure B: Basket-form trophozoite of P. Figure C: Basket-form trophozoite of P.
There is no enlargement of the infected RBC and sometimes there is a reduction in size. The cytoplasm stains blue and the chromatin pink to red. Abundant dark pigment may be scattered throughout the cytoplasm. In contrast, data from malaria-therapy studies indicate that in non-immune adults blood-stage infections can persist for 60—70 days, and possibly even longer at sub-microscopic densities [ 4 , 14 ]. Based on these observations, it is hypothesized that a primary P.
This concurs with other data from malaria-therapy studies demonstrating a reduction in parasite density between primary P. Further evidence can be obtained from observations of Plasmodium cynomolgi : a simian malaria parasite that is genetically closely related to P. In controlled infections in rhesus macaques, untreated blood-stage infections due to P. Addressing the knowledge gap on the duration of blood-stage P. If blood-stage P. In contrast, if the majority of P.
Another substantial limitation concerns the use of single-locus genotype markers. A single infectious mosquito bite may inoculate batches of parasites with different genotypes that may be unrelated or meiotic siblings that differ at the locus of interest [ 35 , 37 ].
It is also possible that a relapse may have a different genotype to its primary infection, but still be a half-sibling. To overcome these challenges, multiple-locus genotype markers are being developed, which should provide an even richer pattern of P. In particular, the utilization of multi-locus genotype markers may resolve the issue of identifiability faced here by allowing a relapse to be distinguished from a primary blood-stage infection in cases where they are meiotic siblings.
There are a number of other limitations to the analytic methods applied here. Firstly, the role of heterogeneity and seasonality in exposure to mosquito bites are not accounted for, which is likely to increase the prevalence of co-infection with multiple P. However, application of the methods to simulated data assuming heterogeneity or seasonality in exposure suggested that population-level parameters can still be estimated. Secondly, it is assumed that during co-infection, infections of different genotypes both within and between species are independent of one another.
However it is likely that they interact due to induced innate immune responses and density-dependent regulation [ 42 ]. Thirdly, it is assumed relapses have a tropical phenotype [ 7 , 8 ] and occur at a constant rate following primary infection, thus the authors do not account for the variation in relapse rate that may arise due to variation in the number of hypnozoites in the liver [ 29 ].
In particular, it is assumed that time to next relapse is exponentially distributed when the data may be better described by a more flexible distribution such as a Weibull distribution [ 17 ].
The predicted results may also depend on the frequency of sampling. To investigate this, alternate samples from individuals in the PNG cohort were excluded, and after repeating the analysis found only limited differences in the estimated population-level parameters see Additional file 4 : Fig.
The results may also depend on genotype detectability. Prior information from a series of experiments was relied upon where two blood samples were taken 24 h apart and the presence of genotypes compared between the two samples [ 43 ]. Higher parasite densities were found to increase genotype detectability, and increased multiplicity of infection MOI was found to reduce detectability.
In addition, data from malaria-therapy studies has demonstrated a reduction in parasite density between primary P. Therefore, the assumption of constant genotype detectability may be a limitation of the method, leading to underestimation of the proportion of P.
Imperfect specificity and density-dependent sensitivity will be investigated in future work. Despite increasingly detailed observations of hypnozoites in vivo [ 44 ], the biological processes regulating hypnozoite activation remain unknown [ 9 ].
The combination of longitudinal data collection, genotyping of samples, and statistical modelling presented here provides a new approach for investigation of P. Whilst recurrences cannot be definitively classified into re-infections, recrudescences or relapses, the probability of each can be estimated, allowing a probabilistic relapse phenotype to be assigned to a P.
The association between anti-malarial treatment and the incidence of P. Similar findings have been reported by Tarning et al. It is hypothesized that this is due to the suppression by treatment prophylaxis of blood-stage parasites originating from relapses, with parasite densities rebounding after drug concentrations have waned. The statistical model presented here provides a useful tool for detailed analysis of P. There are potentially important contributions to be made in the study of P.
The dynamics of P. A mathematical model where the times of infection and clearance of blood-stage parasites allows for the infection dynamics of P. However, such a model was not able to reliably estimate the parameters describing the infection dynamics of P. It is anticipated that further development of these methods and application to more informative genotyping markers will allow for a deeper understanding of P.
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Amanda Ross is thanked for helpful comments. For the Thai study informed consent and assent for children aged 7—13 years was obtained from all participants in the study, and ethics approval was obtained from the Ethics Committee at the Faculty of Tropical Medicine, Mahidol University MUTM The study was clearly explained to all volunteers.
The authors declare that they have no competing interests. Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
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