Plasmodium Cynomolgi Transmission

What is plasmodium cynomolgi?

Have you ever wondered if a small parasitic vector is causing illness and mortality to the people in various countries? Malaria is one of the most prevalent vector-borne illnesses in the world. The four most pervasive Plasmodium species, Plasmodium falciparum, Plasmodium malaria, Plasmodium ovale and Plasmodium vivax, are responsible for infections in human illnesses. The four zoonotic species, are Plasmodium brasilianum, Plasmodium cynomolgi, (Pcy) Plasmodium knowlesi, and Plasmodium inui.

Zoonotic infections are the ones that get transmitted from animals to humans. Plasmodium cynomolgi is a malarial infection that spreads from an animal species and is termed a Zoonotic parasite.^1,2

Epidemiology of plasmodium cynomolgi 

The Pcy parasite naturally infects monkeys of the Macaca and Presbytis genera. In nature, Pcy can cause mono-infections or combination infections with other simian malaria parasites. Several reports on incidental and experimental human Pcy infections demonstrate the possibility of detecting natural human infections with this simian malaria parasite, which is an emerging zoonotic infection. In 2014, a 39-year-old lady in the Hulu Terengganu district on Peninsular Malaysia's east coast reported the first spontaneous human infection.³

The life cycle of plasmodium species

It is important to know about the life cycle of Plasmodium species so that the transmission can be well understood. Plasmodium species life cycle includes two hosts. During blood feeding, a female Anopheles mosquito infected with Plasmodium introduced sporozoites into the bloodstream of the host. Sporozoites reach the liver and mature into schizonts, undergo rounds of schizogony (asexual reproduction) within the hepatic cells, producing merozoites, and burst while releasing merozoites into the bloodstream. Merozoites infect red blood cells (RBCs) and develop into ring-stage trophozoites, which mature into schizonts and multiply several times; schizonts break and release merozoites into the bloodstream. These cyclic cycles, which result in the release of merozoites, produce high fever and severe anaemia when red blood cells are destroyed. In this way, the infection develops and causes problems for the human.²

Symptoms of plasmodium cynomolgi

This infection in humans has two groups, some people were symptomatic and others were asymptomatic. The symptoms include:

• Cyclical fevers, 
• Myalgia,(Muscle pain,weakness)
• General malaise,(general discomfort, illness)
• Cephalgia, (Pain in the head, neck, and face)
• Abdominal pain

Challenges in the diagnosis of plasmodium cynomolgi

The true incidence rates of P. cynomolgi are probably much greater than what is currently thought to be because of the disease's limited severity and morphological similarities to P. vivax, which make proper microscopic speciation challenging. Blood samples were obtained and examined using molecular diagnostic techniques as well as microscopy to diagnose the symptomatic patients. Amoeboid trophozoites, which are spherical, mature microgametocytes that resemble P. vivax at a similar embryonic stage, were among the morphological characteristics of P. vivax that were seen in the blood films. The differentiation among these species was identified using Polymerase Chain Reaction or PCR testing. Hence in the diagnosis of Plasmodium cynomolgi, it is important to have PCR testing.⁴

Diagnosis and treatment of plasmodium cynomolgi

It is important to confirm malaria and find the specific Plasmodium species, hence there are various methods to diagnose Plasmodium infections.

The different diagnosis methods include:

• Microscopic method
• Serodiagnostic assay
• Molecular methods

Microscopic method

The "gold standard" method for diagnosing malaria in laboratories is still the microscopic examination of thick and thin blood smears. A blood sample from the patient is obtained by venepuncture or finger pricking, and it is processed on two slides to create a thick and thin blood smear. A droplet of blood is applied to the slide to create a thick smear, while a smaller droplet dispersed across the slide's transparent region creates a thin smear. Methanol can only be used to cure thin smears, and both must be stained, 4% Giemsa dye is usually used for this. After that, they are observed under a light microscope. Since thick smears preserve more blood and may have lower densities of plasmodium parasites, they are most suited for the early diagnosis of malaria. Due to the lack of fixation, blood cells in these smears hemolyze, revealing only leukocytes and parasites. Since it is simpler to identify individual Plasmodium parasites in this preparation, thin smears are frequently utilised for species identification and parasitemia estimation. This method is traditional and is used for the initial diagnosis of malaria.

Serodiagnostic assay

Antibodies or antigens specific to Plasmodium that are circulating in a patient's blood are identified using serodiagnostic techniques. The immune-fluorescence antibody test (IFAT) finds IgG and IgM antibodies specific to Plasmodium species that are produced by the body's defence against the parasites' asexual blood stage. These antibodies are created about two weeks after infection and remain in the body for three to six months after the parasites have been eradicated. Species-specific antigens are placed on a slide and used in the test itself to bind complementary antibodies found in the serum sample. These are bound by a secondary antibody that has a fluorescent tag, creating a complex that can be seen under fluorescence microscopy. The drawback is that this test is not useful in case of acute infections as the antibodies can be detected only after two weeks.

Molecular methods

Plasmodium nucleic acid identification and amplification have been the focus of more recent advancements in malaria diagnostics. Similar to antigen detection, this enables the direct detection of Plasmodium species; however, these techniques are frequently significantly more sensitive and capable of detecting parasites at much lower densities because nucleic acids may be amplified from a very small quantity of DNA. To minimise the number of false-positive results, an assay's high sensitivity needs to be combined with acceptable specificity. Additional information regarding the identification of Plasmodium species can be obtained through the use of 

• Polymerase chain reaction (PCR), 
• Loop-mediated isothermal amplification (LAMP),
• Sequencing techniques, also enhance the characterization of DNA sequences.²

Treatment

Lowering peripheral asexual parasitemia, eliminating dormant stages to minimise relapses, and eventually preventing disease transmission to other members of the community are the goals of managing malaria. There isn't a single drug available that could eradicate P. vivax or P. cynomolgi at every point of their life cycles. Consequently, combined therapy is advised. In addition to the selected primary anti-malarial medication, combination therapy includes the use of primaquine in individuals without a deficit in glucose-6-phosphate dehydrogenase. Because P. cynomolgi is a rare illness, it should be highlighted that there have not been any clinical trials addressing the treatment of the infection in naturally infected persons. To effectively treat future P. cynomolgi infections in humans, it is recommended to follow the treatment options for its sister taxon, P. vivax.⁴

Summary

Plasmodium cynomolgi is a zoonotic malaria parasite that normally infects monkeys of the Macaca and Presbytis genera but can also infect humans. First identified in a 39-year-old woman in Malaysia in 2014, it can cause symptomatic or asymptomatic infections in humans, presenting with cyclic fevers, myalgia, malaise, cephalgia, and abdominal pain. Diagnosis is challenging due to its similarity to Plasmodium vivax, often requiring PCR testing for accurate identification. Treatment strategies mirror those for P. vivax, focusing on reducing parasitemia and preventing relapses, though specific clinical trials for P. cynomolgi are lacking.