Exotic Infection Presentation of Plasmodium Ovale Malaria in Morgan County, Alabama

Int J Case Rep Images 2018;9:10.5348/100976Z01SR2018CR. Reddy et al. 1 www.ijcasereportsandimages.com

CASE REPORT PEER REVIEWED | OPEN ACCESS Exotic infection presentation of Plasmodium ovale malaria in Morgan County, Alabama

Sujana Reddy, Alexis Penot, Monita Soni

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Malaria is commonly associated with the virulent Reddy S, Penot A, Soni M. Exotic infection form of parasite species known as P. falciparum. presentation of Plasmodium ovale malaria in Another species that has the capability of causing Morgan County, Alabama. Int J Case Rep Images severe disease is Plasmodium vivax; however, 2018;9:100976Z01SR2018. in contrast to these two species, Plasmodium ovale, discovered in 1922, is much rarer and have been known to cause a benign version Article ID: 100976Z01SR2018 of malaria. The case of an exotic infection was presented in the non-malaria-endemic North Alabama area imported from Sub-Saharan ********* Africa. P. ovale was discovered in a 41-year-old doi: 10.5348/100976Z01SR2018CR woman complaining of fever and myalgia. First peripheral blood smear microscopic analysis was negative for malaria parasites. However, second blood smear confirmed the presence of INTRODUCTION P. ovale with a 1% parasitemia. Challenges in diagnosing this strain stem from the fact that A life-threatening, parasitic blood disease transmitted P. ovale is not endemic to the United States to humans via the bite of an infected female Anopheles and that the relapse phenomenon has not mosquito is known as malaria. Malaria can be caused been adequately researched. It remains for a by five parasite species of the genus Plasmodium: P. large part unexplained and warrant further falciparum, P, vivax, P. malariae, P. ovale(curtisi, investigation. wallikeri), and P. knowlesi [1–3].Travelers to areas that are malaria-endemic, pregnant women, children, and Keywords: Infectious disease, Malaria, Non- immunocompromised individuals are at greater risk [4]. endemic malaria, Plasmodium, P. ovale The main clinical manifestations of malaria, appear 10- 15 days after transmission, are alternating high fever, chills, anemia, jaundice, and flu-like symptoms [5]. The latest estimates by the World Health Organization approximate that 300-500 million people worldwide are currently infected with Plasmodium with nearly 1.5-2.7 Sujana Reddy1, Alexis Penot2, Monita Soni3 million people per year dying from this malicious blood parasite [6]. Research conducted by infectious disease Affiliations: 1Medical Student at Alabama College of Os- teopathic Medicine; 2Internal Medicine at Decatur-Morgan specialists have focused on the most virulent mode of Hospital; 3Medical Director & Clinical Pathology at Decatur- malaria, P. falciparum, which accounts for about 90% of Morgan Hospital & Prime Path PC. the cases predominately found in Sub-Saharan Africa [7– 8]. Clinical presentations of P. ovale and P.vivax overlap Corresponding Author: Sujana Reddy, Medical Student at Alabama College of Osteopathic Medicine, USA; Email: red- significantly, but P. ovale rarely causes severe parasitic [email protected] disease. This case report focuses on the P. ovale, as it is a rare form of malaria. The first stage of the complex malaria plasmodium Received: 28 September 2018 life cycle occurs when a healthy female Anopheles Accepted: 05 November 2018 mosquito feeds on a malaria infected person allowing Published: 30 November 2018 the mosquito’s eggs to be nourished and parasites to

International Journal of Case Reports and Images, Vol. 9, 2018. ISSN: 0976-3198 Int J Case Rep Images 2018;9:10.5348/100976Z01SR2018CR. Reddy et al. 2 www.ijcasereportsandimages.com reproduce [9]. Once the infected mosquito bites, mainly country, South Africa. The patient reported that her at dusk and dawn, it will transmit the parasite haploid previous residence in South Africa had many insects form, known as sporozoites, from its saliva into the such as mosquitoes. No intravenous drug use, surgical human blood stream [10–12]. These organisms then intervention, blood transfusion, or other risk factors for travel to the liver to complete the hepatocellular phase. transmission of malaria were reported. Inside the liver, the parasites multiply and mature until Upon physical examination, the patient did not appear they are released back into the bloodstream as merozoites. to be chronically ill and no hepatosplenomegaly was [1, 8, 13]. Merozoites invade red blood cells where they noted.Hematology lab results indicated a low hemoglobin further divide and grow with schizonts. Two to three days level of 8.2 g/dL, low hematocrit of 26.1%, low MCV or later, the merozoite cells burst, infecting unparasitized mean corpuscular volume of 80.6 FL, low MCH or mean red blood cells which ultimately become trophozoites corpuscular hemoglobin of 25.3 PG, low MCHC or mean [9]. Merozoites can also asexually reproduce in the corpuscular hemoglobin concentration of 31.4 g/dL, low erythrocytic cycle to form male/female gametocytes to lymphocyte number of 1.09 x109 per liter, high level of be taken up by healthy mosquitoes [9, 14]. If hypnozoites monocytes of 0.67 x109 per liter, high basophils of 1%, remain dormant in the liver, unique to P. ovale and P. normal WBC 5.76x109 per liter, and normal platelet level vivax, then a recrudescence or relapse can occur weeks to of 164x109 per liter. Pathology review was requested, months after initial transmission [15]. and a Wright-Giemsa stained peripheral blood film was The diagnosis of malaria is fairly complex and examined. First thick and thin blood smear noted no challenging due to the broad nature and delayed detection of parasites. Second sampling and examination manifestation of the symptoms. Gathering a detailed of blood smears showed 1% parasitemia (Figure 1). patient history, including travel to foreign countries, Upon examination of the peripheral blood smear, red performing a thorough physical examination, and blood cells appeared normocytic and normochromic with conducting a blood analysis are critical factors in mild anisocytosis. Total leukocyte count was elevated properly diagnosing malaria. The standard diagnostic with neutrophils while no basophils and myeloblasts tool for detection is blood smear microscopy analysis, were seen. Leucocytes and monocytes were seen with Giemsa Stain, which detects the presence of parasites minimal reactivity. Platelets appeared normal in number, in the blood within a few hours [16–17]. If available, distribution, and morphology. Surprisingly, a non- diagnosis can be made by Rapid Detection Test, RDT. falciparum type malaria, Plasmodium ovale, was noted This immunochromgenic test can be conducted with a dipstick or cassette format, and results are available 2-15 minutes later [10]. A positive detection to plasmodium can be followed up with a PCR to confirm the species prior to treatment [18]. PCR analysis is often not used due to time constraints and patient sensitivity. Although there are prevention efforts for malaria treatment and control, no vaccine exists. Consequences of not providing prompt treatment include hemolysis, capillary clogging, vital organ function loss, and even death. Antimalarial medications are specific to the type of plasmodium transmitted, the severity of the disease, and the region where the infection was acquired [9]. According to the Center for Disease Control, strict guidelines for treating P. vivax and P. ovale include a combination therapy of primaquine phosphate with either chloroquine phosphate or hydroxychloroquine. Primaquine is essential because it is anti-hypnozoitocidal treatment and prevents relapse [19] The combination primaquine with either chloroquine phosphate or hydroxychloroquine allows for the treatment of the liver hypnozoites and the blood parasites [20].

CASE REPORT Figure 1: Ring-form trophozoite with prominent chromatin dot A 41-year-old female was seen in Morgan County, of P. ovale in Giemsa-stained thin blood smear from a human Alabama due to a constant, alternating fever of 40°C patient. Trophozoites also seen outside the red blood cells. (104°F). She had no medical history, but a travel Infected RBCs are slightly larger, exhibit a jagged fimbriated history indicated an occupation to a malaria-endemic edge, and are classically oval in shape.

International Journal of Case Reports and Images, Vol. 9, 2018. ISSN: 0976-3198 Int J Case Rep Images 2018;9:10.5348/100976Z01SR2018CR. Reddy et al. 3 www.ijcasereportsandimages.com on the infected erythrocytes with a parasitemia index for P. ovale remain undetermined. This uncertainty can of 1%. Patient was treated with chloroquine phosphate be attributed to diagnostic difficulties related to the low 1000mg immediately followed by 500mg every 6, 24, and parasitemia levels and drawbacks to the use of thick 48 hours. In addition, 30 mg of primaquine phosphate as well as thin blood films [3, 5, 24]. These challenges for 14 days was given. are particularly alarming because P. ovale often gets diagnosed as P. vivax, also a much milder form of malaria. Severe cases of P. ovale are often missed by not identifying DISCUSSION the correct plasmodium species. These misdiagnoses contribute to the ongoing public perception that malaria Malaria is a commonly contracted disease from the is not a debilitating disease needing immediate attention. bite of a mosquito infected with P. falciparum. While the Over 10 published cases, however, have shown P. ovale disease has been most commonly associated with Africa, exhibiting severe symptoms including acute respiratory cases have been reported worldwide for over a century. distress syndrome, metabolic acidosis, acute renal P. ovale is a more difficult strain of malaria to diagnose failure, hypertension, and splenic rupture [10, 12, 14]. because of its rarity, the broad nature of its symptoms, With the number of P. ovale cases being underreported, and the difficulty in microscopically diagnosing due to low these symptoms represent only a known summary of the parasite density and the parasitic morphology resembling possible symptoms related to P. ovale. that of P.vivax [21]. P. ovale was initially discovered in One of the major factors contributing to the a patient from East Africa by Stephens in 1922. While misdiagnosis of P. ovale relates to the acquisition of a malaria has been a commonly diagnosed disease for well thorough patient history, a proper initial assessment, and over a century, with over 700,000 deaths in 2016 alone, physical examination. A patient’s travel history, timeline observations of the relapse of symptoms deriving from P. of symptoms, and previous medical history are essential ovale have only been cited in less than 20 cases since 1922 in properly diagnosing malaria. The rarity of this disease [14]. along with the vagueness of the symptoms contribute Though mortality and morbidity are not typically to this difficulty. Better diagnostic measures need to be associated with P. ovale, this disease can be fatal as implemented to more accurately identify the plasmodium evidenced by a few cases [7, 10, 22].The recurrence infecting the individual. Traditionally, thick and thin of parasites dormant in the liver further complicates blood smears are utilized for determining if malaria the difficulty of diagnosing this disease [19, 20]. is present and parasitemia levels, respectively. This In 2010, two sub-species of P.ovale, Plasmodium includes performing a repeat blood smear, which helped ovalecurtisi and Plasmodium ovalewallikeri, were in our case, based on the fluid life cycle of the parasites. discovered, and discrepancies between the two is still Other tests that could aid in the proper diagnosis include being researched [17]. These factors validate the need PCR or rapid antigen testing. Therefore, performing for further research into this parasite strain. From 2007 thick and thin blood smear is preferable in order to to 2012, the number of P. ovale cases has increased ensure correct diagnosis. Treatment options for malaria by 80% in travelers [18]. This correlates with this case are vast and specific to the type of infected plasmodium. report of an individual traveling from a malaria endemic Early treatment allows for a better long-term prognosis. country to the USA. Despite this increase, the rarity and The gold standard for P. ovale includes a combination complicated nature of diagnosing this strain presented therapy, chloroquine and primaquine, that targets the significant challenges. different blood-stages [25]. However, it has been noted While malaria was never endemic to America, it did by other studies that anti-hypnozoite treatment is not experience a spike in reported cases following World War 100% effective in preventing release. Recrudesce in the II, around 1947-1950 [10, 16]. Swift government action liver cells has been researched on and shown to only be in the 1950s significantly reduced transmission, and dormant for a limited time. Furthermore, non-human small outbreaks that continued were controlled. In fact, studies have shown that dormancies can also occur in according to the CDC, there have been only 63 cases of the epidermis, brain, kidneys, and lungs [26]. These malaria being transmitted in the U.S. from 1957-2015 [17, discoveries warrant the need for further research into 23]. In particular, the Tennessee Valley Authority (TVA) targeting the hypnozoites in an accurate mechanism of implemented measures to confront the malaria issue by action. In conclusion, this case presents a number of building reservoirs on the Tennessee River and addressing challenges to the proper diagnosis and treatment of P. the issue of stagnant water. Government records indicate ovale and exhibits the need for further research into this these efforts successfully suppressed this disease. This strain of malaria. case illustrates the rarity of this disease being diagnosed in Alabama: according to the CDC’s 2013 records 0.34% of reported cases came from Alabama [23]. CONCLUSION Over the last century, primary research has focused on P. falciparum with P. ovale largely being neglected and Unique to P. ovale and P. vivax, hypnozoites remain underdiagnosed. Risk factors and the pathophysiology dormant in the liver which can cause relapse occurring

International Journal of Case Reports and Images, Vol. 9, 2018. ISSN: 0976-3198 Int J Case Rep Images 2018;9:10.5348/100976Z01SR2018CR. Reddy et al. 4 www.ijcasereportsandimages.com weeks to months after initial transmission. Thick and thin 18. https://www.sciencedirect.com/topics/immunology- blood smears are utilized to detect malaria presence and and-microbiology/plasmodium-ovale parasitemia levels, respectively. People at risk for malaria 19. Groger M, Fischer HS, Veletzky L, Lalremruata A, include travelers to areas that are malaria-endemic, Ramharter M. A systematic review of the clinical presentation, treatment and relapse characteristics of pregnant women, children, and immunocompromised human Plasmodium ovale malaria. Malar J 2017 Mar individuals. Symptoms of malaria appear 10-15 days after 11;16(1):112. transmission are alternating high fever, chills, anemia, 20. D’Abramo A, Gebremeskel Tekle S, Iannetta M, et jaundice, and flu-like symptoms. al. 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