Infant Pertussis: Early White Blood Cell Counts Crucial

Yael Waknine

January 16, 2013

Early serial monitoring of white blood cell (WBC) counts is crucial for determining the prognosis of infants with pertussis, according to a retrospective study published online January 10 in the Journal of the Pediatric Infectious Diseases Society.

Erin L. Murray, PhD, from the California Department of Public Health, Richmond, and colleagues found that infants 90 days old or younger with severe Bordatella pertussis infection leading to pulmonary hypertension or death had high and rapidly rising WBC counts compared with their less-ill counterparts, all reaching or exceeding 30,000/μL within a mean of 5.1 days from cough onset.

Among infants with severe pertussis, WBC counts tended to double or more within 24 hours of cough onset compared with those with less severe disease (57% vs 0%; P = .03), and to reach significantly higher peaks (mean, 74,200/μL vs 26,900/μL; median, 74,100/μL vs 24,200/μL; P < .001 for both).

The higher WBC counts were accompanied by significantly higher levels of tachycardia and hyperventilation that developed much more quickly after cough onset, a 100% likelihood of developing pneumonia (vs 43% of those with milder disease) requiring higher fraction of inspired oxygen on intubation, and increased risks for seizures, hypotension/shock, and renal failure.

"Because very young infants have not yet been vaccinated and are at the highest risk for severe disease, we need to better manage and treat it," commented Dr. Murray in a news release. "This study shows the importance of aggressive pediatric intensive care and provides us additional metrics as we treat these very young patients."

"Our data suggest that a predictor of more severe B pertussis disease in young infants is an elevated and rapidly rising WBC count, making early and serial WBC count determinations critical to the evaluation of all infants with suspected or proven pertussis," the authors write, noting that close monitoring of heart and respiratory rates is likewise imperative because of the correlation with severe disease progression.

"The findings of this study underscore the importance of aggressive PICU care as well as early consideration of exchange transfusion in the management of infants at high risk for severe pertussis," they conclude.

Early Identification Crucial

Although leukocytosis with lymphocytosis is a well-described finding in young infants with pertussis infection, its link with hypertension and death remains unclear, the authors write, noting that the presence of mixed leukocyte aggregates in small pulmonary vessels may be a factor.

Successful leukodepletion therapy with double volume exchange transfusion or leukofiltration has supported this theory in some cases, but disappointing results have also occurred, the authors add, suggesting that early identification of cases may be the key.

"It is likely that 4 infants in our study [who died] did not receive exchange transfusions early enough for the procedure to be beneficial," the authors write, adding that early determination of WBC count and close monitoring is essential even for infants with initially mild disease.

For the study, researchers reviewed the medical records for 31 infants who were hospitalized for pertussis in 5 southern Californian pediatric intensive care units from September 1, 2009, to June 30, 2011. Mean age at cough onset was 39.2 days. Eight patients had more severe pertussis infection, 6 had pulmonary hypertension, and 4 infants died. Two of the infants who died had pulmonary hypertension.

Results showed that the magnitude of WBC count and rate of increase corresponded directly with hypertension and death; all infants with severe pertussis developed WBC counts of 30,000 or more compared with only 36% of those with less critical illness (P < .01), reaching that mark in a shorter time interval from cough onset (mean, 5.1 days vs 22.2 days; P = .002), with a doubling or more of WBC count within 24 hours (mean, 57% vs 0%; P = .03).

As a result, exchange transfusions were more likely to be performed sooner in the course of the disease (median WBC count, 75,000; range, 61,700 - 102,000; mean, 7.8 days from cough onset; median, 7.5 days: range, 3 - 14 days). All 4 severely ill infants who died were in shock during the transfusion; the 2 survivors were not.

Severe pertussis was also linked to a significantly earlier onset of tachycardia (rate, ≥170 beats/minute: mean, 6.1 vs 10.9 days from cough onset; P = .01) and to higher mean and median peak heart rates (210.8 vs 188.5 beats/minute and 209.5 bpm vs 193.0 beats/minute; P = .002 for both), a pattern that held true for respiration rates as well (≥70/minute after cough onset; mean, 6.9 days vs 21.0 days; mean peak, 104.5/minute vs 70.5/minute; median peak, 97.5/minute vs 67.0/minute; P < .001 for all).

Infants with severe pertussis all developed pneumonia, and did so sooner after cough onset than their less-ill counterparts (100% vs 43%; P = .01; 6.5 days vs 21.1 days; P < .001), more often requiring intubation and use of a higher mean fraction of inspired oxygen (75% vs 9% [P < .001]; 0.88 vs 0.55 [P = .01], respectively).

Other morbidities associated with severe pertussis included seizures (38% vs 4%; P = .04), hypotension/shock (50% vs 0%; P = .002), and renal failure (38% vs 0%; P = .01).

The authors caution that the study is limited by its small sample size and that a larger study would be "beneficial" to confirm their findings.

The study was funded by the California Department of Public Health; the Children's Hospital of Orange County; Rady Children's Hospital in San Diego, California; Children's Hospital in Los Angeles, California; Cedars-Sinai Medical Center; and Mattel Children's Hospital at the University of California in Los Angeles. The authors have disclosed no relevant financial relationships.

J Ped Infect Dis. Published online January 10, 2013. Abstract