The patient was a 39-year-old Mozambican citizen who had been residing in Johannesburg. He reported multiple visits to Mozambique bi-annually, usually 3–4 weeks at a time. He had no known comorbidities and was previously well. He reported multiple previous episodes of malarial infection, the last of which was 2 years prior, treated with oral medication.

He had been in Mozambique for the last 3 weeks, where he developed fever and vomiting, which lasted 10 days, followed by non-bloody diarrhoea. He presented at a local clinic in Mozambique, where he was diagnosed with malaria and received outpatient treatment. He received four tablets twice a day for 3 days – which is in keeping with our presumption of artemether and lumefantrine (‘Coartem’). He returned to Johannesburg during his last day of treatment. On previous occasions, he would improve within days; however, after the completion of the treatment, he experienced worsening dyspnoea, fever, jaundice and macroscopic haematuria for 5 days. Thereafter, he presented to Helen Joseph Hospital Casualty.

On examination, the patient was pale, the blood pressure was 168/98 mmHg, the pulse rate was 121 beats per minute, the temperature was 37.8 °C and the respiratory rate was 36 breaths per minute using accessory muscles, indicating significant respiratory distress. This is in association with an oxygen saturation of 85% on ambient air, which did not improve on face mask oxygen at a fraction of inspired oxygen (FiO₂) of 60%. On systemic examination, the liver was enlarged (2 cm), with a smooth surface, and was non-pulsatile. On inspection of the urine sample, there was macroscopic haematuria confirmed as blood on the urine dipstick.

Laboratory investigations showed haemolysis evidenced by a haemoglobin decrease from 10 g/dL on admission to 4 g/dL (after 3 days), with a macrocytosis of 104 fL, aspartate aminotransferase (AST) of 2425 U/L (normal range 15–40), an unconjugated hyperbilirubinaemia (total bilirubin 35 µmol/L and conjugated bilirubin 17 µmol/L) and a lactate dehydrogenase (LDH) of > 3500 U/L (normal range 100–190) (see Table 1).

During the first 3 days of admission, the patient developed temperature spikes between 38.4 °C and 38.8 °C. The patient was in respiratory distress with a respiratory rate of 24–36 breaths per minute. There were no obvious respiratory signs on clinical examination or abnormalities on the chest X-ray, as seen in Figure 1. The patient was admitted to the high care unit and was initiated on intermittent haemodialysis.

The first arterial blood gas determination demonstrated a discrepancy between the reading of the pulse oximeter (85%) and the blood gas co-oximeter, which showed an oxygen saturation of 99.6%. The difference in the saturations can be explained by the methaemoglobin level of 12.4% demonstrating that this patient has methaemoglobinaemia, as seen in Table 2.

On day 2 of hospitalisation, an urgent blood smear was done, showing significant blister cells and Heinz bodies. In association with the haemolysis, glucose-6-phosphate dehydrogenase (G6PD) deficiency was suspected (see Figure 2 and Figure 3). The smear was negative for malaria and confirmed on a pan-malarial polymerase chain reaction.

A septic screen was done as part of the initial workup, including blood, urine and stool cultures. On day 6 of admission, the stool culture was positive for Salmonella typhi, as seen in Figure 4 (colonies are colourless and transparent with black centres as seen by black arrow), Figure 5 (colonies are red with black centres as seen by blue arrow) and Figure 6 (colonies are grey as seen by green arrow).

Supportive management, including intermittent haemodialysis, supplementary oxygen, fluids, blood products and targeted antibiotic (ceftriaxone), was the mainstay of treatment. Specific treatments for methaemoglobinaemia, such as methylene blue and high-dose ascorbic acid, were both relatively contraindicated because of the ongoing haemolysis and renal dysfunction in this clinical case. The patient subsequently improved and was discharged with full recovery. The patient was counselled on precautionary measures for G6PD deficiency, such as avoiding fava beans, mothballs and the use of aspirin. He was also counselled to let healthcare workers know if seeking medical advice that he has a G6PD deficiency.

The patient is a Mozambican citizen with a recent travel history to Mozambique. The prevalence of G6PD deficiency is greater in this region (up to 16%)¹ and is associated with protection against malarial infection. Typhoidal Salmonella is also endemic in this region. This patient has a G6PD deficiency and presented with an acute haemolytic episode secondary to acquiring typhoidal Salmonella while in Mozambique. The G6PD deficiency further caused the methaemoglobinaemia resulting in his respiratory distress, although the sepsis in itself, renal failure and anaemia were contributing factors. The renal dysfunction was caused by many factors stemming from the intravascular haemolysis, sepsis and methaemoglobinaemia. Other possible precipitants of the acute haemolysis from the G6PD deficiency could have been toxin or drug induced. However, the patient denied drug or toxin use besides the presumed artemether and lumefantrine (‘Coartem’) given by his local clinic.

Our patient had a higher risk compared to the general South African population of having a G6PD deficiency as he is native to Mozambique. His recent travel to Mozambique increased his risk of contracting typhoid because of its endemic nature in the area. Furthermore, the G6PD deficiency increased his risk of acquiring typhoid, and the typhoid increased his risk of having a haemolytic crisis and subsequent methaemoglobinaemia.

Glucose-6-phosphate dehydrogenase deficiency is rare in South Africa. This case report highlights the importance of always being vigilant for G6PD deficiency and ensuring that one looks at the specific presentation as displayed above.