Zebras in the age of COVID

Malaria remains a significant global health problem. Malaria-free areas, including North America and Europe, report cases mostly in connection with recent travel to endemic areas. Although cyclical symptoms and chills are characteristic of the infection, a thorough social history, including previous travel, is essential for timely diagnosis, treatment initiation, and definitive prognosis of this potentially life-threatening condition.

introduction

Despite highly effective treatments, malaria remains a significant global health problem, accounting for a significant proportion of morbidity and mortality in developing countries [1]. Malaria is transmitted by the female Anopheles mosquito and is caused by one of five known species of the protozoan Plasmodium, including P. falciparum, S. vivax, P. ovale, P.malariaeand P.knowlesi. infection with P. falciparum is responsible for the most severe and deadliest forms and accounts for 90% of malaria mortality worldwide [2]. In particular, each species exhibits specific characteristics that affect its presentation and treatment considerations. For example, while the incubation period for any species can range from seven to 30 days, P. falciparum was observed to be present at the shorter end of the spectrum. Importantly, the incubation period may be longer in individuals with partial immunity or those using incompletely effective prophylaxis, creating a significant gap between exposure and presentation [3]. Alternatively both S. vivax and P. ovale may adopt a quiescent phase characterized by persistence of hypnozoites in hepatocytes, creating the possibility of late presentation or relapse [3, 4]. Treatment with agents such as primaquine is therefore used to eliminate any remaining hypnozoites. There P. falciparum has no exoerythrocytic phase, primaquine plays no role in achieving a cure and is therefore not generally administered. However, the World Health Organization has recommended the addition of primaquine to the treatment regimen for P. falciparum in certain areas to block the transmission [5]. Finally, despite no exoerythrocytic phase, P.malariae It has been reported to remain in the blood in a quiescent state at very low density, with the possibility of reappearance decades later [6].

North America and Europe are considered non-malarial areas, with cases predominantly attributable to travel within endemic areas [7]. Treatment for malaria depends on early detection and initiation of treatment. Here we present a case of uncomplicated falciparum malaria in Milwaukee, Wisconsin.

case presentation

A 64-year-old Caucasian male with a history of self-reported malaria in 2003 and latent tuberculosis s/p-isoniazid therapy presented one day after a sudden onset of fever, chills, chattering teeth, diaphoresis, and malaise. The patient reported that the symptoms appeared twice a day and lasted 1 hour. Between episodes, the patient advocated fatigue, nausea, headache, and loss of appetite. The patient also noted dizziness during flares, which corresponded to a drop in blood pressure to 80 systolic. The laboratory values ​​on admission are noted in the table 1.

laboratory Patiently reference range
sodium 132 mmol/L 136-145 mmol/L
bicarbonate 19 mmol/L 22-29 mmol/L
Blood Urea Nitrogen (BUN) 31mg/dl 6-23 mg/dl
creatinine 1.88mg/dL 0.9-1.0mg/dl*
Aspartate Transferase (AST) 73U/L 13-44U/L
total bilirubin 2.2mg/dL 0.2-1.2 mg/dl
hemoglobin 13.5 g/dl 13.7-17.5 g/dl
platelets 53×103/µL 150-450×103/µL
Prothrombin Time (PT) 15.5 sec 9.5-11.8 sec
Partial thromboplastin time (PTT) 34.1 sec 23-30 sec

The patient reported that the symptoms were similar to those of a previous episode of malaria in 2003. Medical history revealed that the patient had recently returned from Ghana, had not taken malaria prophylaxis, and recalled a mosquito bite on the first night of his trip (15 days before symptoms began). A peripheral blood smear showed intracellular organisms most closely matched to Plasmodium species, as confirmed by serological antigen testing. The antigen test was positive for both Plasmodium falciparum antigen and pan-malaria antigen. Peripheral parasitemia peaked at 3.6% of infected red blood cells (Figure 1). The patient was diagnosed with uncomplicated falciparum malaria and started on artemisinin-based combination therapy (ACT) administered twice daily for three days per infectious disease recommendations. Complete metabolic panel, blood count and parasite swab were repeated every 6 hours, with plans to start artesunate 2.4 mg/kg IV if the patient develops severe malaria.

The patient reported that cyclical flare-ups became less intense after starting treatment with Coartem. The level of parasitemia showed a sustained downward trend towards undetectable levels over the following two days. Notably, creatinine trended upwards to a peak of 2.38 mg/dL on day 2 of intake before subsequently trending downwards after continuous maintenance fluid (Ringer’s lactate 100 cc/hr). On Day 3 of admission, the patient noted a cough with inspiration and described it as originating from deep in his chest. Physical examination was significant for bibasilar crackles. Given the downward trend in creatinine, the fluids were discontinued, resulting in an improvement in the patient’s cough. The patient was discharged upon completion of Coartem dosing, with plans for outpatient laboratory testing and infectious disease surveillance.

discussion

Malaria can be categorized into either uncomplicated or severe presentations. The World Health Organization has established specific criteria for severe malaria [8]. These criteria utilize numerous factors, including metabolic chemistry, blood count, renal and pulmonary function, and degree of parasitemia, to name a few. Above all, P. falciparum is predominantly responsible for heavy presentations compared to alternative species [9]. Those who have not previously been exposed to malaria parasites, as well as those who have lost their immunity by leaving endemic areas for long periods of time, are at the highest risk of developing a severe presentation [10, 11]. Therefore, until proven otherwise, malaria should be among the leading differential diagnoses in any patient presenting with a febrile illness associated with a history of travel to malaria-endemic regions.

ACTs are currently considered the best treatment for uncomplicated falciparum malaria because of their rapid and reliable effectiveness [12]. In contrast, chloroquine, once widely used for both prophylaxis and treatment, is now rarely used unless the susceptibility of the dominant strain in the region is known. Chloroquine-resistant malaria has become widespread [13]and concerns about artemisinin resistance have increased [14]. In response to this issue, ACTs have been reported to remain the mainstay of therapy, but with a prolonged course. Instead of the standard 3-day course, using a 6-day course showed good efficacy with an associated cure rate of 97.7% [14].

Although our patient only met criteria for uncomplicated falciparum malaria, he was only slightly below diagnostic cut-offs for severe presentation, underscoring the urgency of the disease. Infected individuals can quickly progress to a serious condition that can manifest itself in a variety of ways. Here, our patient showed corresponding characteristics for hematological and pulmonary involvement. From a haematological point of view, malaria has been reported to cause coagulopathies. P. falciparum in particular, platelet consumption and prolonged coagulation studies may occur [15]which was previously summarized [16]. Interestingly, despite prolonged coagulation studies, malaria is associated with a hypercoagulable state. This change has been suggested to be involved in malaria pathogenesis [17]. In addition, it has also been reported that severe malaria manifests with noncardiogenic pulmonary edema [18], even several days after starting antimalarial therapy. Although the mechanism is unclear, it has been hypothesized to occur due to sequestration of parasitized red blood cells in pulmonary vessels or via cytokine-induced leakage [19]. Importantly, vigorous fluid resuscitation can make the problem worse. Our patient presented with poor oral intake and rising creatinine, requiring careful monitoring of pulmonary status during fluid infusion.

Conclusions

With only about 2,000 cases per year in the United States, malaria is an uncommon disease for most physicians. At a time when Covid is a likely possibility for flu-like presentations, this case underscores the critical nature of always seeking a thorough social history incorporating previous travel. Because patients can rapidly progress to severe disease, favorable outcomes require prompt diagnosis and treatment initiation, with frequent laboratory monitoring. Additionally, significant interprofessional collaboration is critical to maintaining quality care. Inpatient pharmacy teams and infectious diseases should be keenly aware of the patient’s condition, with plans to quickly change medications should the patient worsen. Importantly, ACT cannot be used in most facilities in the United States without authorization for both infectious disease and dispensary use. Discussions should include clear guidance on medication ordering and dosing to avoid treatment delays. Finally, it should be noted that the prevalence of ACT resistance in the United States is unknown, which will require further study.

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