**10. Gametocytes**

Most merozoites continue this explicative cycle but some merozoites differentiate into male or female sexual forms (gametocytes) (also in the blood), which are taken up by the female mosquito. This process of differentiation into gametocytes occur in the bone marrow. Five distinct morphological stages have recognized (stage I-V). Female gametocytes are produced about four times as commonly as male. In chonic infections in humans the gametocytes are often the only forms found in the blood. Incidentally the characteristic form of the female gametocytes in *Plasmodium falciparum* gave rise to this specie's name.

Gametocytes appear in the blood after a number of days post infection. In *P. falciprum* infections they appear after 7 to 15 days while on others they appear after 1 to 3 days. The ratio of asexual to sexual forms is between 10:1 and 156:1. The half life of the gametocytes has been estimated to be between 2 and 3 days but some are known to persist for up to four weeks.[18,19]

The five recognized morphological stages were first described by Field and Shute in 1956.

One constant feature of the gametocytes in all stages that distinguishes them from the asexual forms is the presence of a pellicular complex. This originates in small membranous vesicle observed beneath the gametocytes plasmalemma in late stage I. The structure itself consists of a subpellicular membrane vacuole. Deep to this is an array of longitudinally oriented microtubules. This structure is likely to be relatively inflexible and may help to explain the lack of amoeboid forms observed in asexual parasites.

Early stage one gametocytes are very difficult to distinguish from small round trophozoites. Later stages can be distinguished by the distribution of pigment granulues. Under the electron microscope the formation of the subpellicular membrane and a smooth plasma

escape. This is followed by an eversion of the entire erythrocyte membrane. An action that

Invasion of erythrocyte precursors has only recently been studied. The earliest stage susceptible to infection were the erythroblasts – the stage immediately preceding the reticulocyte stage which in turn is the immediate precursor to the mature erythrocyte. Invasion of the erythrocyte is inhibited by angiotensin 2. This is normally metabolized by erythrocytes to angiotensin (Ang) IV and Ang – (1-7). Parasite infection decreased the Ang – (1-7) levels and completely abolished Ang IV formation. Ang – (1-7), like its parent molecule, is capable of decreasing the level of infection. The mechanism of inhibition seems

More than a hundred late-stage trophozoites or early schizont infected erythrocytes of *P. falciparum* in a case of placental malaria of a Tanzanian woman were found to form a nidus in an intervillous space of placenta. While such a concentration of parasite in placental malaria is rare, placental malaria cannot give rise to persistent infection as pregnancy in humans normally lasts only 9 months. We have also found this kind of placental infection in

Most merozoites continue this explicative cycle but some merozoites differentiate into male or female sexual forms (gametocytes) (also in the blood), which are taken up by the female mosquito. This process of differentiation into gametocytes occur in the bone marrow. Five distinct morphological stages have recognized (stage I-V). Female gametocytes are produced about four times as commonly as male. In chonic infections in humans the gametocytes are often the only forms found in the blood. Incidentally the characteristic form of the female

Gametocytes appear in the blood after a number of days post infection. In *P. falciprum* infections they appear after 7 to 15 days while on others they appear after 1 to 3 days. The ratio of asexual to sexual forms is between 10:1 and 156:1. The half life of the gametocytes has been estimated to be between 2 and 3 days but some are known to persist for up to four

The five recognized morphological stages were first described by Field and Shute in 1956.

One constant feature of the gametocytes in all stages that distinguishes them from the asexual forms is the presence of a pellicular complex. This originates in small membranous vesicle observed beneath the gametocytes plasmalemma in late stage I. The structure itself consists of a subpellicular membrane vacuole. Deep to this is an array of longitudinally oriented microtubules. This structure is likely to be relatively inflexible and may help to

Early stage one gametocytes are very difficult to distinguish from small round trophozoites. Later stages can be distinguished by the distribution of pigment granulues. Under the electron microscope the formation of the subpellicular membrane and a smooth plasma

likely to be an inhibition of protein Kinase A activity within the erythrocyte.

gametocytes in *Plasmodium falciparum* gave rise to this specie's name.

explain the lack of amoeboid forms observed in asexual parasites.

propels the merozoites into the blood stream.

**9. Placental malaria** 

our own studies.[18]

**10. Gametocytes** 

weeks.[18,19]

membrane are recognizable. The nuclei are recognizably dimorphic into male and female. These forms may be found between 0 and 2 in *P falciprum* infections*.*

In stage two gametocytes becomes D shaped. The nucleus may occupy a terminal end of the cell or lie along its length. Early spindle formation may be visible. These forms are found between days 1 to day 4 in *P falciprum* infections.

In stage three the erythrocyte becomes distorted. A staining difference between the male and female gametocytes is apparent (male stain pink while female stain faint blue with the usual stains). The male nucleus is noticeably larger than the female and more lobulated. The female cytoplasm has more ribosomes, endoplasmic reticulum and mitochondria.

In stage four erythrocytes is clearly deformed and the gametocyte is elongated. The male gametocytes stain red while the female stain violet blue. In the male pigment granules are scattered while in the female they are denser. In the male the kinetochores of each chromosomes are located over a nuclear pore. Osmophilic bodies are found in both but are more numerous in the female. These forms are found between day 6 and day 10 in *P falciparum* infections.

In stage five the gametocytes are clearly recognizable on light microscopy with the typical banana shaped female gametocytes. The subpellicular microtubules depolymerise but the membrane itself remains. The male gametocyte exhibit a dramatic reduction in ribosomal density. Very few mitochondria are retained and the nucleus enlarges with a kinetochore complex attached to the nuclear envelope. In the female gametocytes there are numerous mitochondria, ribosome's and osmophillic bodies. The nucleus is small with a transcription factory.

Stages other than five are not normally found in the peripheral blood. For reasons not yet understood stage 1 to IV are sequestered preferentially in the bone marrow and spleen. Stage V gametocytes only become infections to mosquito's after a further two days of circulation.
