Case 2 

1. What test would help establish the diagnosis in this patient? 

• Stained smears of the peripheral blood will demonstrate malarial parasites. 
  • Thick and thin smears should be  obtained, stained with Wright or Giemsa stains, and examined for the presence of erythrocytic parasites. 
  • In thick  smears, erythrocytes are lysed with water prior to staining. This concentrates parasites and helps detection of  mild parasitemia. 
  • Thin smears allow for morphologic differentiation and species identification. 
• DNA probes and  antigen detection tests have be-In recently developed, but are not widely used. 
• Serologic testing is used for  epidemiologic investigations.  

Plasmodium falciparum infection is recognized by the presence of small rings, multiple rings within a red cell, and a high percentage of parasitization of erythrocytes. 

Trophozoites and schizonts are not seen in the peripheral  blood. The morphology of gametocytes is distinct from other species. 

Plasmodium vivax is characterized by  thicker, single rings. All stages of the parasite are seen in the peripheral circulation. 

2. What plasmodium species is Likely to be causing her infection? List the species and their geographical distribution. 

This patient has Plasmodium falciparum infection. 

• This is the most common plasmodium infection in Zaire.

• P. Falciparum infection in Zaire is chloroquine resistant. This patient has failed chloroquine, suggesting she might  have chloroquine- resistant P. falciparium infection. 

The plasmodium species that infect humans are P. falciparum, P. vivax. P. malariae and P. ovale. Their geographical distribution is - 

• P. Falciparum-   Central and South Africa, South America, South East Asia, Indian subcontinent

• P. vivax  -           Indian subcontinent, South east Asia, Central and South Africa

• P. ovale -            rare, found mainly in Africa

• P. malariae -      rare, worldwide 

3. Which species causes the most severe diseases, and what complications are seen with it? 

The most severe disease is produced by P. falciparum. This species can parasitize red cells in every state of  development, resulting in a higher percentage of parasitemia. 

Plasmodium, vivax will parasitize only the larger  reticulocytes, leading to a lower degree of parasitemia. 

The fever, anemia, circulatory changes and  immunopathologic phenomena are all the result of invasion of erythrocytes.

 Complications include: 

i. Cerebral malaria - altered mental states, confusion, coma, seizures. It is ametabolic encephalopathy produced when infected erythrocytes bind to cerebral vascular endothelium, resulting in increased glucose utilization, lactate production, and cerebral anoxia.

ii. Renal failure - results from microvascular disease (oxygen and glucose deprivation in the renal cortex), and hemolysis with circulating free hemoglobin and malarial pigment in the kidneys. Massive hemoglobinuria results in black urine ('Blackwater fever').

iii.  Pulmonary edema - sequestration of parasitized red cells, and effect of TNT.

iv. Gastroenteritis - seen in young children with P. falciparum. Results from adherence of red cells to vascular endothelium in the GI tract.   

v. Anemia - destruction of host red cells by the mature schizont as it liberates merozoites, TNF-alpha effect.   

4. What is the life cycle of the species you think is involved? 

• Sporogony, or the sexual cycle, begins when the female mosquito ingests circulating gametocytes. 

• After  fertilization, the zygote penetrates the gut walls and forms as oocyst. 

• Within the oocyst, sporozoites are formed,  released into the stomach, and migrate to salivary glands. 

• Sporozoites are injected into humans at the next blood  meal.  Schizogony, the asexual cycle, occurs when sporozotes are injected into capillaries. 

• They invade liver cells,  replicate, and produce merozoites. 

• Rupture of infected hepatocytes releases merozoites into the blood strewn.  

• Merozoites enter red blood cells and appear as ring-shaped trophozoites. 

• Nuclear division occurs, producing a  multinucleated schizont. 

• Cytoplasm condenses around each nucleus, forming merozoite daughter cells. 

• About 48  hours after invasion, infected erythrocytes rupture releasing merozoite, which invade new red cells. Some are  transformed into sexual forms or gametocytes. 

• Plasmodia falaparium is not dormant in the liver, hence late relapses do not occur. Mosquito Cycle (Sporogany)
  

5. Why had she failed treatment previously? How would you treat this patient?             

This patient had failed treatment because she was infected with a chloroquine- resistant strain of Plasmodium  falciparum. 

Chloroquine resistance is prevalent in Central and South Africa, South East Asia, the Indian  sub-continent, and Central America. 

The recommended regimens are 

• Quinine plus doxycycline

• Quinine plus  clindamycin

• Quinine plus pyrimethamine-sulfadoxine. 

Alternate regimens are Mefloquine, Halofantrine or  Artesunate. 

6. What control measures are available to prevent its transmission?  

•  Personal protection with screens, netting and mosquito repellants is necessary. 
•  Travelers should take malarial  prophylaxis, which is chloroquine for sensitive areas, and Mefloquine or doxycycline for resistant areas.
• Mosquito eradication has not been achieved as resistance to chemical agents has developed. 
• Vaccines against the various stages of the malarial parasite are being developed.