Neonatal malignant pertussis and exchange transfusion: A case report

Introduction

Whooping cough caused by Bordetella pertussis can progress to a severe form in infants, particularly those under 3 months of age ¹ necessitating management in an intensive care unit. ² Clinical and biological signs include leukocytosis with lymphocytosis, hyponatremia, severe neurological impairment, and acute respiratory distress syndrome (ARDS) accompanied by pulmonary arterial hypertension (PAH), which can compromise vital prognosis, with a mortality rate exceeding 70%. Exchange transfusion may be a beneficial therapeutic option to reduce leukocytosis contributing to PAH.

Pertussis is a vaccine-preventable disease, and the implementation of pertussis vaccination has significantly reduced the number of cases and deaths among children since the launch of the WHO Expanded Program on Immunization in 1974.^3,4

Case report

We report the case of a 26-day-old neonate, admitted to the neonatal intensive care unit (NICU) for malignant pertussis. The initial clinical examination revealed a persistent tachycardia between 160 and 180 beats per minute (bpm), a fever of 39°C, along with agitation. The lung examination revealed expiratory dyspnea along with crepitations. The blood count showed hyperleukocytosis at 90 G/L with hyperlymphocytosis at 45 G/L and thrombocytosis at 860 G/L. Chest X-ray revealed a right apical lesion (probably related to aspiration pneumonia) (Figure 1), pulmonary hyperinflation, and a normal cardio-mediastinal silhouette, associated with pulmonary hypertension on echocardiography (Figure 2).

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Figure 1.

Chest X-ray revealed right apical lesion, pulmonary hyperinflation, and a normal cardio-mediastinal silhouette.

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Figure 2.

Systolic pulmonary artery pressure (PASP) measured via Doppler echocardiography through tricuspid regurgitation (TR) is 42 mmHg, indicative of pulmonary arterial hypertension (PAH) with a PASP of 42 mmHg.

The diagnosis was confirmed by Polymerase Chain Reaction (PCR) testing on nasopharyngeal secretions; it was positive for Bordetella pertussis. Familial transmission was documented, with the mother reporting a persistent paroxysmal cough lasting over 21 days.

Treatment included josamycin, cefotaxime and gentamycin, hyperhydration at 3 L/m²/day, and high-flow nasal cannula ventilation, associated with treatment of coughing members. However, all these therapies proved ineffective against refractory hypoxemia. An exchange transfusion was performed on the 5th day, reducing hyperleukocytosis from 90 G/L to 29 G/L, followed by progressive clinical improvement. The exchange transfusion consisted of exchanging two blood volumes, totaling 140 mL/kg over a period of 2 h, in successive cycles of 5 mL/kg exchanges, using reconstituted whole blood with a hematocrit of 45%. This was done through an already established central venous line under close monitoring of calcium and blood glucose levels. The infant was discharged on day 42 of life after a 12-day hospital stay.

We report in this case the significant improvement observed following the exchange transfusion (Table 1).

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Table 1.

Summary of clinical, biological, and radiological variables before and after the exchange transfusion.

Variables	Before exchange transfusion	After exchange transfusion	Reference values
Heart rate (bpm)	180	150
Temperature (°C)	39	37
Respiratory rate (breaths/min)	80	52
Fraction of inspired oxygen (FIO2, %)	35	21
Cough frequency	3/h	1/5 h
Signs of respiratory distress	(+)	(−)
Oxygen saturation (SaO2, %)	84	91%
Leukocytes (G/L)	90	29	10,000–14,000
Hemoglobin (Hb, g/dL)	13.1	10.1	13–18
Neutrophils (G/L)	40	14	3000–5000
Lymphocytes (G/L)	45	12	5000–8000
Platelets (G/L)	864	155	200,000–350,000
Blood culture	Sterile
Serum sodium (mmol/L)	129	138	135–140
Echocardiography	Pulmonary hypertension	Normal

Discussion

Pertussis is one of the leading causes of bacterial infection-related mortality in pediatric intensive care units. ⁵ Severe pertussis encompasses two different groups of patients hospitalized in Pediatric Intensive Care Unit (PICU); those of the first group present recurrent apnea or apparent life-threatening events, and those of the second bronchopneumonia, some of whom will develop a critical course with refractory hypoxemia and pulmonary hypertension (PHT). ⁶

Malignant pertussis affects infants younger than 3 months and is characterized by acute respiratory distress, persistent tachycardia, and hyperleukocytosis exceeding 50 G/L, which can lead to multiple organ failure.^7,8 Despite resuscitative efforts and critical care, mortality occurs in up to 75% of cases.^6–12

A review study objectified a significant association between elevated white blood cell counts, pulmonary hypertension, and increased disease severity or mortality. ¹³

Pulmonary histopathological analysis^14–16 revealed extensive leukocyte aggregation within small pulmonary arteries, veins, and lymphatics. It is postulated that vascular infiltration and blood hyperviscosity due to elevated leukocyte counts contribute to the development of pulmonary hypertension and heart failure. Virulence factors, as key pathogenic determinants of Bordetella pertussis, mediate various stages of disease progression

In neonates and young infants, the pulmonary arteries retain a significant muscular component, rendering them more responsive to vasoconstrictive stimuli. ¹⁷ Hypoxemia and coexisting acidosis may precipitate pulmonary vasoconstriction, resulting in an acute rise in pulmonary vascular resistance. Therefore, critical hypoxemia and heart failure in severe pertussis likely arise from a multifactorial pathophysiology. Further studies are required to elucidate the precise mechanisms underlying refractory cardiopulmonary failure in malignant pertussis.

In our patient, the criteria for malignancy were present: Age, lack of vaccination, major hyperleukocytosis, pneumonia, and pulmonary hypertension (PHT) and was immediately hospitalized in Neonatal Intensive Care Unit (NICU).

The correlation between leukocyte counts and disease severity is well-documented; moreover, clinical interventions such as leukapheresis and exchange transfusion have been employed to mitigate elevated leukocyte levels; however standardized leukocyte cut-off values for initiating treatment remain absent. A systematic review of 18 publications documented the application of leukoreduction therapy in severe pertussis cases characterized by leukocyte counts ranging from 45 to 204.9 × 10^9/L. Notably, only one study articulated a specific leukodepletion strategy, recommending therapeutic interventions based on leukocyte thresholds of 50, 70, or 100 × 10^9/L, irrespective of the presence of cardiopulmonary dysfunction. This approach resulted in a significant reduction in mortality. ¹⁸

Exchange transfusion (ET), commonly performed in Intensive Care Units (PICU/NICU), is a procedure that can be carried out by most critical care staff and is rarely associated with significant complications. ¹⁹ In 2004, Romano et al. ²⁰ published the first documented case of ET in a patient with severe pertussis. Since then, ET has been described in several case series and reports involving patients with severe pertussis,^19,21 in which it was objectified that the survival rate of pertussis patients with hyperleukocytosis is significantly higher when ET is used.

In cases of profound leukocytosis, early initiation of exchange transfusion (ET) may mitigate the formation of leukocyte aggregates within the pulmonary microvasculature. This mechanism is thought to play a role in preventing the onset of pulmonary hypertension and subsequent hemodynamic instability, thereby enhancing patient survival outcomes. ²²

Our patient exhibited a significant improvement following the exchange transfusion. A remarkable and sustained decrease in white blood cell count was observed, accompanied by a rapid clinical recovery.

Alternative therapeutic approaches, such as Extracorporeal Membrane Oxygenation (ECMO), have been explored in patients with severe pertussis-associated respiratory failure; however, there is currently no consensus on its efficacy.^12,23 Some researchers propose that the early initiation of Extracorporeal Membrane Oxygenation (ECMO) may be crucial for achieving optimal therapeutic outcomes and enhancing patient survival. ¹³ Other studies are investigating additional potential therapies that are still in the experimental phase, including the application of immunosuppressants and anion channel modulators, such as pendrin, acetazolamide, and fingolimod. ²³

Conclusion

Therefore, although there are no randomized studies, exchange transfusion should be considered as a treatment option in cases of severe whooping cough with leukocytosis progressing to acute respiratory failure and pulmonary hypertension. This intervention should be implemented early due to the high mortality associated with this condition, even though prevention remains the most effective strategy, relying on improved vaccination coverage among both children and adults.