Two Cases of Malaria-Associated Acute Respiratory Distress Syndrome and Severe Pulmonary Complications From Plasmodium falciparum in Tanzania

Introduction

Malaria is one of the most prevalent life-threatening parasitic infections worldwide and remains endemic in sub-Saharan Africa [1]. Plasmodium falciparum causes the most severe disease and is responsible for most malaria-related deaths [2,3]. A subset of patients with severe malaria develop pulmonary complications, including pulmonary edema, pleural effusion, and malaria-associated acute respiratory distress syndrome (MA-ARDS). Tanzania is among 11 countries with a high malaria burden, and approximately 4.4% of all malaria deaths annually occur in Tanzania [1–3]. Falciparum malaria alone accounts for more than 96% of all malaria cases in Tanzania [4,5]. The literature shows that more than 10% of patients with severe malaria will require intensive care unit (ICU) admission [5,6]. MA-ARDS is challenging to manage and is associated with high mortality, especially in settings where advanced respiratory support, such as extracorporeal membrane oxygenation (ECMO), is not available [7]. In such contexts, optimizing supportive care, including lung-protective ventilation, conservative fluid strategies, and prone positioning, is essential [8,9]. We present 2 cases of severe falciparum malaria complicated by life-threatening pulmonary manifestations managed in a resource-limited ICU.

Case Reports

CASE 1:

A 6-year-old boy of African descent presented to the outpatient department with a 4-day history of abdominal pain and vomiting. Vomitus was non-projectile and yellowish. He had been treated at a peripheral clinic for malaria and had received 2 doses of intramuscular artemether (34 mg per dose), without clinical improvement. He was unable to tolerate oral intake, and his parents noted facial swelling. Family and social histories were unremarkable.

On examination, he had fever (temperature 39.2°C) and jaundice and was moderately pale, with periorbital edema. His heart rate was 143 beats/min, and oxygen saturation was 94% on room air. Abdominal examination demonstrated right upper quadrant tenderness. He was admitted to the high-dependency unit with a working diagnosis of severe malaria. Laboratory results are summarized in Table 1.

Treatment was changed to intravenous artesunate (60 mg per weight-based dosing protocol), clindamycin 150 mg every 8 hours, and paracetamol as needed. A malaria blood film demonstrated a parasite density of 700 parasites per 200 white blood cells. Renal function tests showed elevated levels of creatinine (124 μmol/L) and urea (18 mmol/L). Given evidence of multiorgan involvement (acute kidney injury and acute liver injury), he was transferred to the ICU for close monitoring and supportive management.

On ICU day 3, the child developed worsening respiratory distress with tachypnea (respiratory rate 50 cycles/min), increased work of breathing with accessory muscle use, and oxygen desaturation to 78% while receiving 6 L/min oxygen via nasal cannula. Lung auscultation revealed bilateral crackles, and bilateral lower-limb swelling was noted. Continuous positive airway pressure was initiated, but oxygenation did not improve after 12 hours. Chest radiography demonstrated diffuse bilateral pulmonary infiltrates consistent with pulmonary edema (Figure 1).

The patient was intubated and mechanically ventilated using pressure-control ventilation, with a fraction of inspired oxygen (FiO₂) of 0.80, inspiratory pressure of 28 cmH₂O, respiratory rate of 40 cycles/min, positive end-expiratory pressure (PEEP) of 10 cmH₂O, and tidal volume of approximately 91 mL. Sedation was initiated with midazolam infusion (0.5 mg/h). On ICU day 5, midazolam was discontinued due to concern for hepatic dysfunction and was replaced with dexmedetomidine infusion (10 μg/h).

Given persistent severe hypoxemia and diffuse infiltrates, prolonged prone positioning was implemented for 18 hours/day, with return to the supine position for the remaining period, for 3 consecutive days. Neuromuscular blockade with atracurium infusion was used on ICU days 1 and 2 because of ventilator asynchrony and was discontinued on ICU day 3. Ventilator settings were gradually weaned as oxygenation improved; FiO2 was reduced from 0.80 to 0.35 by ICU day 4. The patient was successfully extubated on ICU day 6. A post-extubation chest radiograph showed marked improvement (Figure 2).

CASE 2:

A 39-year-old man of Asian descent presented to the emergency department with a 1-day history of progressive dyspnea. He was referred from peripheral health centers where he had been treated for severe malaria for 1 week. According to his next of kin, symptoms had not improved despite therapy. On arrival, he had fever (temperature 39.3°C) and jaundice. Oxygen saturation was 80% on room air, improving to 92% with 5 L/min oxygen via nasal cannula. His Glasgow Coma Scale score was 12/15 (E4, V2, M6), and he was agitated. Chest auscultation revealed crepitations, and bilateral lower-limb swelling was present.

A focused assessment with sonography for trauma (FAST) examination was performed to evaluate volume status; the inferior vena cava measured 1.2 cm in diameter. Laboratory investigations are summarized in Table 2. He was transferred to the ICU with a diagnosis of MA-ARDS, acute liver injury, and malaria-induced acute kidney injury.

Within 2 hours of ICU admission, his condition deteriorated with worsening hypoxemia, desaturating to 60% despite 10 L/min oxygen via non-rebreather mask. Rapid sequence intubation was performed, and mechanical ventilation was initiated using volume-control ventilation, with tidal volume of 380 mL, respiratory rate of 18 cycles/min, and FiO₂ of 0.80. Norepinephrine infusion (0.6 μg/kg/h) was started for persistent hypotension.

On ICU day 2, hemodialysis was initiated because of oliguric acute kidney injury (urine output approximately 200 mL over 48 hours) with persistently elevated creatinine. Chest computed tomography demonstrated diffuse parenchymal changes with marked bilateral pleural effusions, more pronounced on the left (Figures 3, 4). Prone positioning was initiated early as an adjunct to lung-protective ventilation, resulting in improved oxygenation and enabling gradual ventilator weaning. A summary of similar published cases and reported outcomes is provided in Table 3.

Discussion

PRESENTATION, DIAGNOSIS, AND CLINICAL COURSE:

Both of our patients presented with fever and evidence of hemolysis and hepatic dysfunction (jaundice), consistent with severe malaria. Diagnosis was supported by malaria blood film microscopy demonstrating P. falciparum parasitemia. The patient in case 1 developed delayed respiratory deterioration with diffuse infiltrates consistent with pulmonary edema/ARDS after initial admission, whereas the patient in case 2 presented with established respiratory failure and progressed rapidly to refractory hypoxemia requiring intubation within hours. Both cases required ICU-level supportive care and careful adjustment of ventilator settings, sedation, and hemodynamic support.

COMPARISON WITH PREVIOUSLY REPORTED CASES:

MA-ARDS is an uncommon but well-described complication of severe P. falciparum infection and has been reported in both endemic and imported malaria settings. Similar to our experience, published case reports describe the use of lung-protective ventilation and prone positioning as effective adjuncts when hypoxemia is severe and persistent. Mohanty and Nandeeshwara [6] reported successful prone ventilation in severe ARDS due to falciparum malaria, emphasizing early application in conjunction with definitive antimalarial therapy. Other reports and reviews of pulmonary manifestations of falciparum malaria similarly highlight that, in the absence of advanced rescue therapies (eg, ECMO), meticulous supportive care and prone positioning can be lifesaving. Our cases add to this literature by demonstrating feasibility of prolonged proning (18 hours/day) and successful outcomes in both a pediatric and an adult patient treated in a resource-limited setting.

SUPPORTIVE MANAGEMENT CONSIDERATIONS:

Intravenous artesunate remains the first-line therapy for severe malaria [10,11]. Quinine is also used as a second-line treatment, especially when artesunate has failed to achieve the required parasitaemia clearance [12]. In older adult patients and those with significant heart conditions, such as arrhythmia, the administration of quinine has been a challenge in resource-limited settings [13]; therefore, artemisinin-based combination is commonly used in these settings. However, no malaria-specific treatment for ARDS exists, and management follows general ARDS principles. Lung-protective ventilation with lower tidal volumes, limitation of plateau pressures, and individualized PEEP are recommended. Permissive hypercapnia is often avoided in severe malaria when cerebral involvement is suspected, as hypercapnia can increase cerebral blood flow and intracranial pressure. In both of our cases, prone positioning was used to improve ventilation-perfusion matching and recruit dependent lung regions, a strategy supported by broader ARDS evidence and increasingly applied in low-resource ICUs.

ADJUNCTIVE IMMUNOMODULATION:

The data reported on corticosteroid use in MA-ARDS are inconsistent. At least 1 randomized trial did not demonstrate benefit with pulse methylprednisolone and found its continued use was associated with a poor outcome [14]. A 2024 study by Oliveira et al found that use of non-steroidal anti-inflammatory drugs (aspirin) was associated with a large influx of inflammatory monocytes to the lung tissue [15]. Experimental and observational work has explored additional immunomodulators. In our cohort, the Janus kinase inhibitor tofacitinib was administered in the adult case early in the ICU course as an anti-inflammatory adjunct; however, evidence for this practice in MA-ARDS is limited and requires further study. No Janus kinase inhibitor was administered in the pediatric case, due to the absence of robust safety data in this context.

Studies have shown that ARDS caused by malaria is managed similarly to ARDS from other causes, without allowing permissive hypercapnia [16,17], since elevated carbon dioxide increases cerebral blood flow and, in turn, intracranial pressure, particularly in cases suspicious for cerebral malaria [17,18]. Lung protective ventilation should be used with lower tidal volumes (4–8 mL/kg), plateau pressures less than 30 cm of water, and PEEP, which can be adjusted depending on the patient’s oxygenation status [19]. Prone positioning is an effective technique used in the ICU to improve oxygenation for patients with ARDS [20]; however, its use depends on the clinician’s suspicion index. When applied in a timely manner, studies have shown that prone positioning can reduce ICU length of stay and improve outcomes [19,20]. In our resource-limited setting, where ECMO is unavailable, modified prone positioning was used in these 2 patients, both of whom were managed uneventfully until discharge.

LIMITATIONS:

Confirmation of P. falciparum infection is ideally supported by representative photomicrographs of peripheral blood films. However, these films were accidentally discarded and cannot be retrieved.

Conclusions

MA-ARDS can occur in children and adults with severe falciparum malaria and can progress rapidly to respiratory failure. In resource-limited settings, early recognition and prompt escalation to evidence-based supportive care—particularly lung-protective ventilation and prolonged prone positioning—may improve oxygenation and outcomes when advanced rescue therapies such as ECMO are not available.