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CASE REPORT
Year : 2022 | Volume
: 59
| Issue : 4 | Page : 375-379
The case report of a non-resident Indian with Plasmodium ovale curtisi from Kerala, India
Supriya Sharma1, V Meenakshy2, MS Sasi2, Naseem Ahmed1, Alex Eapen1, KK Shini2, Amit Sharma3, Bina Srivastava1
1 ICMR-National Institute of Malaria Research, New Delhi, India
2 National Vector Borne Disease Control Programme, Kerala, India
3 ICMR-National Institute of Malaria Research; Molecular Medicine, group, International Centre for Genetic Engineering and Biotechnology, New Delhi, India
Correspondence Address:
Bina Srivastava
STO, ICMR-National Institute of Malaria Research, Sector-8, Dwarka, New Delhi-110077
India
Source of Support: None, Conflict of Interest: None
CheckDOI: 10.4103/0972-9062.369243
India’s target of malaria elimination by 2030 may not be achieved solely by detecting Plasmodium falciparum and P. vivax, the two common Plasmodium species causing infections in humans. Sporadic reports have been documented on other Plasmodium species in the country, associated mostly with travel history. A febrile patient of Indian origin (Non-resident Indian (NRI)) was diagnosed with an infection of Plasmodium ovale curtisi malaria on his arrival from Sudan. A case report from Kerala was published in December 2020 and this is second report. Due to the inaccessibility of molecular techniques for routine diagnosis, this neglected non-falciparum malaria goes undetected. For an accurate diagnosis, suspected malaria cases should be tested using PCR and other advanced methods.
Supriya Sharma, V Meenakshy. Authors contributed equally
Background
Malaria, a public health hazard is caused by the parasite,Plasmodium species. There are six known species of Plasmodium infecting humans in South east Asia: Plasmodium falciparum, P. vivax, P. malariae, P. ovale, P. knowlesi and recently, P. cynomolgi[1]. Plasmodium ovale spp (P. ovale spp) including Plasmodium ovale curtisi (Poc) and Plasmodium ovale wallikeri (Pow) are differentiated by molecular methods[2]. Kerala remains a low endemic state for malaria in India, although a few cases are reported mainly imported from travellers returning from other endemic states or countries. Most infections are symptomatic of febrile nature due to the body’s reactions to any invading pathogens/microbes and hence quite non-specific to predict the exact causal factor. Also, many a times this may not result in significant severity of the disease. Diagnosis plays an important role in ruling out symptoms which may look like malaria. The ongoing COVID-19 pandemic has led to more confusions with similar fever presentation. However, malaria is generally diagnosed with the conventional method, microscopy being the gold standard, though bivalent RDT has also served the purpose of detection partially with a major limitation for identification of non-falciparum and non- vivax cases. In India, P. ovale cases are reported sporadic and mostly in northern and central India [Table 1].
An imported malaria case was diagnosed in December 2020. The Kerala state health minister quoted that one soldier returned from Sudan was found positive for P. ovale. The Malayala Manorama quoted this news on December 5, 2020[3]. Briefly, a 51-year-old male with intermittent fever, shivering and tiredness consulted the doctor in the outpatient department of District Hospital Kannur after two days of beginning of his symptoms. During the onset of symptoms, the patient was on quarantine at his native place after reaching from Delhi. The patient is an army personnel and as part of his job in United Nations (UN) Security had visited Sudan (Africa) and stayed there for about 8 months since June 14, 2019. While during his stay at Sudan he did not have any symptoms of malaria. He had also visited Uganda and had stayed there for one week. He had undergone COVID-19 test and was found negative. As he was having malaria-like symptoms and history of travel outside Kerala, malaria rapid diagnostic test (RDT) and peripheral blood smear examination were conducted. Malaria RDT turned out to be negative, but peripheral smear revealed Plasmodium ovale infection. The slides were immediately re-confirmed as P. ovale by WHO trained L2 technician (Malaria microscopy) from Calicut, India, and by another L1 technician at state headquarters. It was confirmed by the molecular analysis done at Vector Control Research Center (VCRC), Kottayam as Plasmodium ovale wallekeri.
Here, we highlight the case report of another non-indigenous P. ovale from Kerala and discuss its significance in the backdrop of an impending risk of malarial infections which may be a threat to the state if not attended promptly. A 55-year-old non-resident Indian, working in Sudan since 2013 returned to his native place in Kozhikode, Kerala, India on November 25, 2020. He had many episodes of mild intermittent fever and took self-medication during the pandemic period. After the first dose of Covid vaccination on May 27 2021 at Family Health Centre (FHC), Purameri, the patient reported high-grade fever probably due to vaccination. On administering the first dose of vaccination, as a general custom, the FHC provided antipyretic tablet paracetamol. Following the consumption of the antipyretic tablet, the fever subsided. However, fever with shivering was again reported on June 3, 2021 and the patient came to FHC, Purameri the following day. At FHC, RDT was conducted and was observed positive for Plasmodium vivax. Blood smear was also prepared at FHC Purameri and sent to Taluk Hospital, Kuttiady for examination. Subsequently, the blood smear was screened and declared positive for Plasmodium vivax at Taluk Hospital, Kuttiady. The patient was administered antimalarial treatment for P. vivax, chloroquine @ 25 mg/kg body weight for 3 days and primaquine @ 0.25 mg/kg body weight for 14 days as per National Vector Borne Disease Control Programme (NVBDCP) / ICMR-National Institute of Malaria Research (NIMR) treatment guidelines for malaria. On June 6, 2021, the blood smear was sent to Government general hospital at Kozhikode to cross-verify the blood smear by a L3 laboratory technician. Surprisingly, it was observed with blood stages (early and late trophozoites) of Plasmodium ovale. It was reconfirmed on June 7, 2021 by sending it to the state entomology laboratory at Thiruvananthapuram. On June 9, 2021, the blood smear was sent from Taluk hospital, Kuttiady to ICMR-National Institute of Malaria Research at New Delhi [Figure 1].
A stained thick and thin blood smear of suspected P. ovale was received by molecular diagnostic laboratory of ICMR-National Institute of Malaria Research, New Delhi, a collaborative centre of World Health Organization (WHO) for malaria diagnosis from 2020. The smear was handed over to two Level 1 microscopists certified by WHO for malaria parasite species confirmation. The blood smear was scraped for genomic DNA isolation. After scraping the thin smear with the help of an alcohol-wiped sharp surgical blade, the content was transferred to 1.5ml microcentrifuge tube. Lysis buffer was added and it was incubated overnight. The next day, genomic DNA was extracted following the manufacture’s instruction manual of Qiagen blood DNA isolation kit (Cat No. 51306). The PCR reaction was carried out following the published primers and cycling conditions as of Snounou et al., 1993[4] and the amplified product was send to Eurofin India Pvt Ltd for sequencing. The microscopic examination confirmed it as P. ovale infection with the presence of large oval shaped infected red blood cells. The genomic DNA on amplification showed the presence of P. ovale in gel electrophoresis with 1.5% agarose gel [Figure 2]A & [Figure 2]B. Once the PCR was positive for P. ovale, sequence analysis after sequencing also revealed the same result and interestingly it came out to be P. ovale curtisi [Figure 3]; gene bank accession number KJ871673.1 for P. ovale curtisi and KU315239.1 for P. ovale wallikeri.
Figure 2: (A) Microscopic image of thick and thin blood smear (B) Gel image of diagnostic PCR. Discussion The reported cases of non-falciparum and nonvivax malaria in India are mostly non-indigenous and commonly associated with non-resident Indians returning from various endemic countries. It is therefore important to diagnose such travelers to accurately identify the malaria parasite species at the point of care centre. P. ovale is another malaria parasite species in addition to P. vivax with a hypnozoite stage (dormant liver stage) that causes relapse. These cases highlight the importance of healthcare personnel including clinicians to consider malaria infections in febrile patients from travelers returning during the COVID-19 pandemic, the aetiology of which is not exclusively of viral origin at all times. In the present case it would have definitely caused many episodes of fever by its presence in the blood stream leading to clinical symptoms of malaria (relapsing malaria) even after many months of its first attack leading to infection. Such cases can remain undiagnosed due to oversight and lack of proper plan to screen the subjects returning from endemic countries or non-availability of species-specific diagnostic methods at the point of the care centre for detection. In such a scenario, it may spur malaria cases in a low-endemic states such as Kerala, which has high number of non-resident Indians in the country. Hence, it is pertinent to screen all subjects with a travel history from malaria endemic countries and follow up to avoid the spread of non-indigenous Plasmodium infections.
The significance of every non-indigenous case of malaria with non-falciparum malaria is now evident in view of the imported malaria reported in a low endemic state of Kerala. Prompt and accurate molecular diagnostic techniques will aid in the diagnosis of all species of human malaria infections even if it is of low density (submicroscopic). Intensified community-based surveillance to check the spread of malaria with other non-falciparum and non-vivax malaria infections will definitely help in tackling such situations in future as the focus is to eliminate malaria in India by 2030.
Ethical statement
The study is approved by Institutional Ethics Committee (IEC) of ICMR-NIMR, New Delhi, India on August 21, 2021.
Conflict of interest: None
AcknowledgementsThe authors acknowledge National Vector Borne Disease Control state programme (Kerala) for their support in tracking the case history and ICMR-NIMR institute for providing diagnosis support.
References
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