Sunday, September 25, 2016

Case of the Week 415

This week's case is that of an elderly female with recent travel to a malaria-endemic area in South America. To evaluate the patient for malaria, venous blood was collected in tubes containing EDTA and thick and thin blood films were made immediately at the local hospital laboratory. These slides were stained and sent to my laboratory for examination, in addition to a tube of blood. Below are representative fields from those slides (images courtesy of Emily F.):

Two days later, we used the blood to make additional slides for teaching purposes. However, review of the new slides now revealed different forms than what was initially seen:
Thick film:
Thin Film:

What is the likely cause of these different forms?


Anonymous said...

Senescence of the Pf gametocytes

Kathy Murray Leisure, MD said...

Plasmodium falciparum "banana" gametocytes in fresh specimens. Possible coinfection with Plasmodium vivax with schizonts?

Maran said...

Banana shaped P. falciparum mature (stage IV-V) gametocytes are observed in the smears. Other forms seen in the smear could possibly be immature P. falciparum gametocytes (less likely as they are usually not seen in circulation). Likely explanation is co-infection with P. vivax which are seen as gametocytes or trophozoite forms.

Anonymous said...

Very interesting case of P. falciparum. In the first picture, the gametocyte on the left seems to have a Laveran's bib. Since the blood has been stored for 48 hours, could it be that the forms in the last pictures are macrogametes, the next stage of the sexual reproduction?

Florida Fan

Sheldon Campbell said...

I suspect maturation and 'hatching' of the falciparum gametocytes to exflagellating forms. When blood containing gametocytes is stored, the gametocytes, in response to lowered temperature and probably other cues say, 'Whoa, Dorothy, we're not in a Kansan anymore'; and begin to differentiate into the mosquito form. Exflagellated gametocytes normally look like (duh!) flagellated forms that'll eventually become sporozoites; I assume these are either doing so slowly due to refrigeration, or are perhaps not quite making it.

Bjorn Kafsack said...

Sheldon is almost spot on. The initial thin smears shows mature (Stage V) gametocytes. Immature stages (I-IV) sequester in the peripheral tissues and don't circulate. He was also correct that a drop in temperature (37C ->25C, Human -> Mosquito) signals transmission and triggers gametocyte activation. Activation for both males and females involves rounding up & exiting the RBC (its hard to see but the gametocytes in the first smear are still intracellular). For female gametocytes, egress and some swelling completes gamete formation.

However, Male gametocytes also undergo exflagellation, the incredibly rapid formation of 8 flagellated male gametes from a single male gametocyte. In about 15 min they undergo 3 rounds of genome replication, which remains the fastest known rate of replication for a eukaryote. S. cerevisae has a similar sized genome and would require 4.5h for 3 cycles.

Since one male gametocyte makes 8 gametes but one female gametocyte makes only one female gamete the P. falciparum male:female gametocyte ratio is about 1:3 to 1:6. So most of the activated shown in the smears 2 days later will be females.

However, I am surprised that there are no ring stage present in these smears. To yield a gametocytemia this high, parasitemia would have been quite high as well. Either the infection in this patient was incredibly synchronous and samples were collected on day 2 of the 48h cycle, or more likely this patient had already received treatment prior to sample collection. (Mature GCs are resistant to most antimalarials)

Jose Stoute said...

Obviously P. falciparum. I agree with the above comments that there could be exflagellation. The absence of rings is really puzzling. She must have been treated or been using prophylaxis but not fully compliant with it.