Plasmodium ovale

Plasmodium ovale It is a species of unicellular protist that constitutes one of the best-known parasites in man, causing a disease that has always wreaked havoc on humanity, malaria.

It was the last of the malaria-causing parasites to be described. This was in the year 1922 by Stephens, who observed it years earlier in the blood of an East African patient. What caught his attention was the oval shape that erythrocytes take, which is why he decided to name it Plasmodium ovale.

The Plasmodium ovale is perhaps the least dangerous of the parasites of the genus Plasmodium. Even so, it is capable of generating the development of malaria in healthy individuals, although it is less virulent than the other species of Plasmodium.

Current Progress in the Pharmacogenetics of Infectious Disease Therapy

3.2 Primaquine

Primaquine is used in patients with Plasmodium ovale and Plasmodium vivax infections to clear the latent hepatic hypnozoite stage of the parasite and prevent relapse and transmissibility. It is primarily metabolized by CYP1A2 and CYP3A4. 155 Although ethnicity has been found to be significantly associated with plasma levels of primaquine, the genetic polymorphisms underpinning this variability, or their impact on efficacy or toxicity are yet to be characterized. 39,156,157

The first records of variability in response to antimalarials dates back to World War II when African–American soldiers were found to experience higher rates of acute hemolysis when they received primaquine compared to their Caucasian counterparts. 158 The basis of these observed differences was later attributed to glucose-6-phosphate dehydrogenase (G6PD) deficiency, an X-linked recessive disorder, 159 common in sub-Saharan Africans (∼10–25%). 160 The G6PD locus is highly polymorphic, so in clinical practice, prospective qualitative and quantitative tests are performed in patients requiring primaquine. 161

Plasmodium Ovale is not a very common type of malaria that has been identified in a soldier in Kerala who is believed to have contracted in Sudan during his posting, where Plasmodium Ovale is endemic.

What is Malaria?

It is a serious and sometimes fatal disease of the blood that is caused by the plasmodium parasite which is transmitted to people through the bite of an infected Anopheles mosquito. The disease is preventable and curable.

Through the bites of infected female anopheles mosquitoes known as ‘malaria vectors’ parasites spread to people. Parasite species that cause malaria in humans are of 5 types namely Plasmodium falciparum, Plasmodium vivax (the commonest ones), Plasmodium Malariae, Plasmodium Ovale, and Plasmodium Knowlesi. Malaria caused by Plasmodium falciparum is the most serious one and may even be fatal.

What happens when a female anopheles mosquito bites a person?

When a female anopheles mosquito bites a person, the parasite is released into the bloodstream of that person. Parasites travel to the liver when they are inside the body and there they mature. After a few days, parasites that are matured enter the bloodstream and begin to infect the Red Blood Cells. Now, they start multiplying inside the red blood cells within 48 to 72 hours which causes the infected cells to burst and open. The parasites continue to infect red blood cells, resulting in symptoms that occur in cycles.

Hence, we can say that if someone is contracted with the Plasmodium Ovale type of malaria means that the person has been infected by that particular parasite.

About Plasmodium Ovale

Plasmodium Ovale is termed as ovale because about 20% of the parasitised cells are oval in shape.

As per the scientists, P. ovale rarely causes severe illness.

An emeritus professor at the International Centre for Genetic Engineering and Biotechnology, New Delhi Dr. V S Chauhan said that P. Ovale is very similar to P vivax, which is not a killer form.

Symptoms

Fever for 48 hours,

Treatment

The treatment modality is also the same as it is for a person infected with P. vivax. Further, he said that P ovale is no more dangerous than getting a viral infection.

It is also said that the parasite can remain in the spleen or liver of the person’s body for a long time, even years, after the mosquito bite, and the person could become symptomatic later.

As per Dr. Chauhan, distinguishing between P vivax and P ovale may be tricky and can be differentiated through a good-quality lab.

Where is P ovale malaria-endemic?

It is endemic to tropical Western Africa. As per scientists at NIMR, P ovale is relatively unusual outside of Africa and, where found, comprises less than 1% of the isolates.

In the Philippines, Indonesia, and Papua New Guinea also it has been detected but still relatively rare in these areas.

Now, let us have a look at the cases in India

— As per the National Institute of Malaria Research (NIMR), the case of Kerala could be an isolated one, and cases of local transmission are not recorded so far.

— Previously, in Gujarat, Kolkata, Odisha, and Delhi isolated cases were reported but the local transmission was not recorded which means that these cases have been acquired.

— According to the WMR 2019, India represents 3% of the global malaria burden. Despite being the highest malaria burden country in the SEA region, India showed a reduction in reported malaria cases of 49% and deaths of 50.5% compared with 2017.

— During recent years, India has made remarkable progress in reducing malaria incidence. In malaria incidence in India, World Malaria Report has also documented the remarkable decline. In 2017, the estimated malaria cases were reduced by 24% as compared to 2016 and in 2018, 28% as compared to 2017.

— According to the recent World Malaria Report 2020, cases in India dropped from about 20 million in 2000 to about 5.6 million in 2019.

Malaria is a contagious disease or not?

Malaria is not a contagious disease that is it does not spread from person to person like a cold or the flu. Also, it cannot be sexually transmitted. Here to note that a person cannot get malaria from casual contact with malaria-infected people like sitting next to someone who has malaria.

Some common symptoms of Malaria are:

For most people, symptoms begin 10 days to 4 weeks after infection but a person may feel ill as early as 7 days or late as 1 year later.

— High Fever
— Headache
— Nausea
— Vomiting
— Abdominal Pain
— Diarrhoea
— Anaemia
— Muscle Pain
— Profuse Sweating
— Shaking chills that can range from moderate to severe
— Convulsions
— Bloody stools
— Coma

Some of the life-threatening complications of malaria are:

— Blood vessels of the brain swell up or cerebral malaria.

— Organ failure of the kidneys, liver, or spleen.

— Low blood sugar

— Anaemia due to the destruction of red blood cells.

— Fluid accumulates in the lungs that cause breathing problems, or pulmonary edema.

Key facts of Malaria

According to WHO,

— 229 million cases of malaria were estimated in 2019 worldwide.

— In 2019, the estimated number of malaria deaths stood at 409000.

— The most vulnerable group affected by malaria are the children aged under 5 years; in 2019 they accounted for 67% (274000) of all malaria deaths worldwide.

— A disproportionately high share of the global malaria burden is carried by the WHO African Region. The region was home to 94% of malaria cases and deaths in 2019.

— In 2019, total funding for malaria control and elimination reached an estimated US$ 3 billion.

— The parasites of malaria requires two hosts- human and mosquitoes to complete its life cycle.

Ciclo de vida

A fase que ocorre dentro do mosquito é conhecida como esporogônica e a que ocorre dentro do ser humano, esquizogônica.

Dentro do ser humano

A mordida do ser humano pela fêmea do gênero Anopheles pode ser tomada como ponto de partida do ciclo de vida . No momento da picada, a forma do parasita conhecida como esporocoita é inoculada na corrente sanguínea do ser humano.

Essas formas são transportadas através da corrente sanguínea para o fígado, um órgão do corpo humano no qual a próxima etapa do ciclo se desenvolve.

No fígado, os esporocitos entram nos hepatócitos (células hepáticas). Dentro delas, passam por uma série de transformações, até atingir um grau de maturação em que são conhecidas como esquizontes.

Da mesma forma, dentro das células do fígado, cada esquizonte sofre reprodução assexuada , na qual é gerada uma forma do parasita chamado merozoito. Dentro de cada célula é gerada uma média entre dez mil e vinte e cinco mil merozoítos.

Eventualmente, devido ao enfraquecimento de suas máquinas celulares e de suas estruturas típicas, os hepatócitos sofrem lise celular, ou seja, são destruídos, liberando todos os merozoítos formados no sangue.

O objetivo principal dos merozoítos é entrar nos glóbulos vermelhos , infectá-los e colonizá-los. A razão pela qual essa forma do parasita tem predileção pelos eritrócitos pelo resto das células sanguíneas é que eles se alimentam de hemoglobina.

Essa proteína é encontrada exclusivamente nos glóbulos vermelhos e é responsável pelo transporte de oxigênio para todos os tecidos.

Ciclo de vida do plasma. Fonte: Por Crédito da foto: Provedor (es) de conteúdo: CDC / Alexander J. da Silva, PhD / Melanie Moser [Domínio público], via Wikimedia Commons

Dentro dos eritrócitos, o merozoito passa por um processo de maturação até se tornar trofozoíto. Com o tempo (cerca de 3 dias), a deterioração do eritrócito é total, rompendo suas membranas, liberando merozoítos no sangue juntamente com o conteúdo celular interno.

Duas coisas podem acontecer aqui: a primeira é que os merozoítos liberados são capazes de infectar outros glóbulos vermelhos, continuando com a produção de trofozoítos.

A segunda coisa que pode acontecer é que os merozoítos podem sofrer uma transformação nas células sexuais: microgametócitos (masculino) e macrogametócitos (feminino).

Estes constituem a forma infecciosa do Anopheles feminino , que é infectado quando morde uma pessoa infectada com malária.

Dentro do Anopheles feminino

No entanto, outra fase do ciclo de vida do Plasmodium ovale ocorre dentro da fêmea . Os gametócitos (feminino e masculino) são direcionados para o intestino do mosquito, no qual ocorre a fertilização. Como resultado disso, um zigoto é gerado, conhecido como ooquineto.

Isso passa por uma transformação em uma estrutura conhecida como oocisto. Daí se originam os esporocitos, que se deslocam em direção às glândulas salivares do mosquito, de onde são inoculados no ser humano, concluindo assim o ciclo de vida.

Plasmodium Ovale

Ring form — Of P. ovale is characterized by one or two large chromatin dots as well as a sturdy/thick cytoplasm. As they mature, the Schuffner’s dots may develop.

Trophozoites — Like in the ring forms, the cytoplasm of trophozoites is sturdy with a few chromatin dots. They are also irregular, while some may appear to be more compact.

Gametocytes — The gametocytes have a well defined shape (round or oval) and are large enough to fill the red cells. They are characterized by a brown pigment that tends to be more coarse when compared to that of P. vivax.

Schizonts — With 6 to 14 merozoites, the schizonts of P. ovale are characterized by a mass of dark-brown pigment that is surrounded by large nuclei.

Background: The Greater Mekong Subregion is aiming to achieve regional malaria elimination by 2030. Though a shift in malaria parasite species predominance by Plasmodium vivax has been recently documented, the transmission of the two minor Plasmodium species, Plasmodium malariae and Plasmodium ovale spp., is poorly characterized in the region. This study aims to determine the prevalence of these minor species in the China-Myanmar border area and their genetic diversity.

Methods: Epidemiology study was conducted during passive case detection in hospitals and clinics in Myanmar and four counties in China along the China-Myanmar border. Cross-sectional surveys were conducted in villages and camps for internally displaced persons to determine the prevalence of malaria infections. Malaria infections were diagnosed initially by microscopy and later in the laboratory using nested PCR for the SSU rRNA genes. Plasmodium malariae and P. ovale infections were confirmed by sequencing the PCR products. The P. ovale subtypes were determined by sequencing the Pocytb, Pocox1 and Pog3p genes. Parasite populations were evaluated by PCR amplification and sequencing of the MSP-1 genes. Antifolate sensitivity was assessed by sequencing the dhfr-ts and dhps genes from the P. malariae and P. ovale isolates.

Results: Analysis of 2701 blood samples collected from the China-Myanmar border by nested PCR targeting the parasite SSU rRNA genes identified 561 malaria cases, including 161 Plasmodium falciparum, 327 P. vivax, 66 P. falciparum/P. vivax mixed infections, 4 P. malariae and 3 P. ovale spp. P. vivax and P. falciparum accounted for >60 and

30% of all malaria cases, respectively. In comparison, the prevalence of P. malariae and P. ovale spp. was very low and only made up

1% of all PCR-positive cases. Nevertheless, these two species were often misidentified as P. vivax infections or completely missed by microscopy even among symptomatic patients. Phylogenetic analysis of the SSU rRNA, Pocytb, Pocox1 and Pog3p genes confirmed that the three P. ovale spp. isolates belonged to the subtype P. ovale curtisi. Low-level genetic diversity was detected in the MSP-1, dhfr and dhps genes of these minor parasite species, potentially stemming from the low prevalence of these parasites preventing their mixing. Whereas most of the dhfr and dhps positions equivalent to those conferring antifolate resistance in P. falciparum and P. vivax were wild type, a new mutation S113C corresponding to the S108 position in pfdhfr was identified in two P. ovale curtisi isolates.

Conclusions: The four human malaria parasite species all occurred sympatrically at the China-Myanmar border. While P. vivax has become the predominant species, the two minor parasite species also occurred at very low prevalence but were often misidentified or missed by conventional microscopy. These minor parasite species displayed low levels of polymorphisms in the msp-1, dhfr and dhps genes.

Keywords: Genetic diversity; Molecular identification; Plasmodium falciparum; Plasmodium malariae; Plasmodium ovale; Plasmodium vivax; Prevalence.