Melioidosis in Children, Brazil, 1989–2019

We studied 20 confirmed or suspected cases of melioidosis in children in Ceará, Brazil, during 1989–2019. We observed a high death rate, severe signs and symptoms, and substantial environmental exposure. These data suggest that childhood melioidosis might be more severe in Brazil than in other regions.

We investigated cases using data from patient records and, when possible, from interviews with the patients and their relatives. We analyzed data on age, sex, time of symptom onset, geographic location, occupational or recreational activity involving water or soil during the 2 weeks before symptom onset, underlying conditions, signs and symptoms, laboratory and radiographic fi ndings, clinical evolution, treatment, and clinical outcome. We used the Fisher exact test to assess the correlation between appropriate treatment using carbapenem or ceftazidime during the intensive phase of melioidosis (8) and survival. The study protocol was previously approved by the research ethics committees of the University of Fortaleza (Fortaleza, Brazil) (approval no. 3,094,492) and Albert Sabin Children's Hospital (Fortaleza) (approval no. 3,194,070).
We identifi ed 10 confi rmed (including 5 before 2005: 4 in 2003, and 1 identifi ed retrospectively in 1989) (3,6), and 10 suspected cases of melioidosis among children and adolescents. The 10 confi rmed cases in persons <18 years of age account for 23.2% of the 43 confi rmed cases of melioidosis in the state of Ceará as of May 2019. This proportion is substantially greater than the 5%-15% usually reported for children (9).
Most (9/20; 45%) patients were 10-17 years of age. The median age was 11 years for patients with confi rmed cases and 9 years for those with suspected cases. For comparison, childhood melioidosis is most prevalent in children <5 years of age in Malaysia (10) and in children >10 years of age in Australia (11).
As in previous studies (2,12), most (13/20; 65%) patients in this sample were male. Illnesses occurred most frequently during the rainy season (i.e. February-May), accounting for 65% (13/20) of all cases and 70% (7/10) of confi rmed cases. This trend resembles the results of a study in Australia (11)  We studied 20 confi rmed or suspected cases of melioidosis in children in Ceará, Brazil, during 1989-2019. We observed a high death rate, severe signs and symptoms, and substantial environmental exposure. These data suggest that childhood melioidosis might be more severe in Brazil than in other regions.
the association between heavy rainfalls and exposure to B. pseudomallei. Most (19/20; 95%) patients had environmental exposure during the 14 days before symptom onset (Table 2). Outdoor recreational behavior is common among children in Brazil, especially in the tropics. For example, when intense warm showers interrupt the extended droughts of northeastern Brazil, children often bathe and play in waterfalls, rivers, and dams. This might partially account for the high prevalence of melioidosis among children, especially older children and boys, in this region. The most frequent clinical manifestations were sepsis (18/20; 90%), pneumonia (18/20; 90%), and septic shock (17/20; 85%) ( Table 2). Among confirmed cases, 90% (9/10) of patients had sepsis and pneumonia and 80% (8/10) had septic shock. Among suspected cases, 90% (9/10) of patients had pneumonia, sepsis, and septic shock. Studies in Malaysia have reported similar figures (10); however, the main manifestations among children are skin lesions in Australia and infectious parotitis in Cambodia (13,14). Although the methods used by these studies differ, they suggest that children in Ceará might have more severe clinical manifestations of melioidosis.
Two patients had meningitis, accounting for 20% (2/10) of confirmed cases and 10% (2/20) of total cases; however, a study in Australia observed neuromelioidosis in 3% of pediatric patients (15). These findings might indicate either a greater proportion of neurologic involvement or substantial underreporting of less severe manifestations among children with melioidosis in Brazil.
In total, 45% (9/20) of patients died: 60% (6/10) of patients with confirmed cases and 30% (3/10) of those with suspected cases. Childhood melioidosis is associated with a death rate of 35% globally (9), although in Australia the rate is reported to be 7% (13). In Cambodia, 16.4% of patients die, including up to 71% of patients with bacteremia (14). Our findings, which include high prevalence of sepsis and septic shock, 2 cases of severe neurologic involvement, and high death rates, warrant further investigation.
We found that appropriate, timely treatment for melioidosis (8) was significantly associated with survival among 20 patients (p<0.01). Thus, physicians should consider empirical treatment for suspected melioidosis in patients in areas to which the disease is endemic, especially if the initial treatment was unsuccessful. We did not find a significant association between proper treatment and survival among patients with confirmed (p = 0.08) and suspected cases (p = 0.07) of melioidosis, possibly because of small sample size.

Conclusion
We describe a high prevalence, death rate, and severity of childhood melioidosis in Brazil. The high death rate and clinical severity might be partially explained by underreporting of mild cases, but the frequent environmental exposures of children in this region warrant further research. These findings emphasize the need for melioidosis awareness among healthcare providers and laboratory professionals. Physicians should consider melioidosis as a differential diagnosis; improved awareness might reduce underreporting and optimize the quality of epidemiologic data. Physicians also should consider empirical treatment in patients who have clinical manifestations compatible with the disease and whose prognosis is compromised by clinical severity.

About the Author
Dr. Lima is a professor at the University of Fortaleza Medical School in Fortaleza, Brazil. Her research interests include clinical pediatrics, neurodevelopment, and infectious disease.
Dr. Rolim is a professor at the University of Fortaleza Medical School in Fortaleza, Brazil. Her research0 interested include infectious disease, melioidosis, and epidemiology. All patients with suspected melioidosis must have epidemiologic exposure at any time, recent or not, associated with >1 of the following criteria: acute febrile illness and respiratory symptoms suggestive of community pneumonia that do not improve with conventional antimicrobial treatment (β-lactam antimicrobial drugs); febrile disease that progresses with systemic inflammatory response syndrome, severe sepsis, or septic shock; prolonged fever of unknown etiology or signs and symptoms similar to tuberculosis that do not respond to tuberculosis treatment; or soft tissue infection (e.g. cutaneous ulcers/abscesses, cellulite, or fasciitis) of chronic evolution (i.e. months) with no response to conventional antimicrobial treatment (e.g. oxacillin, ampicillin associated to sulbactam, or cefalexin).

Confirmed melioidosis
All patients with confirmed melioidosis must meet laboratory (bacteriologic confirmation by microbiological culture or positive PCR) or clinical-epidemiologic criteria (exposure to the same risk situation as patients with laboratoryconfirmed melioidosis). Patients with confirmed melioidosis must have signs and symptoms that are compatible with melioidosis and not attributable to a different cause. Severe disease Patients with severe melioidosis have clinical signs and symptoms and a high risk for death caused by pneumonia, sepsis, or septic shock. *These criteria were defined by references (5,7).