From the *Barwon Health and Deakin University Medical School, Geelong, Victoria, Australia; and †Menzies School of Health Research and Northern Territory Medical Program, Royal Darwin Hospital, Darwin, Northern Territory, Australia
The authors have no funding or conflicts of interest to disclose.
Address for correspondence: Christine Sanderson, FRACP, Child Health Research Unit, Barwon Health, Geelong, Victoria, Australia. E-mail: firstname.lastname@example.org.
Melioidosis is recognized as a pediatric disease in the endemic regions of tropical South East Asia and Northern Australia. Children with this potentially life-threatening infection, caused by Burkholderia pseudomallei, may also present in nonendemic areas, and thus awareness of the disease spectrum is important for all involved in pediatric acute care. This review discusses the epidemiology, range of clinical presentation and management of melioidosis in children. A comprehensive review of recent progress in the understanding of the pathogenesis and diagnostics of melioidosis is available elsewhere.1
In endemic regions, B. pseudomallei is found in the surface water and soil, and transmission of the bacteria to humans occurs through local inoculation, inhalation, aspiration and ingestion.2 Increased disease frequency is seen in the tropical wet season and after severe weather events.3 Although most data are from Thai and Australian studies, case reports are emerging from tropical regions, including the Americas and Africa, which confirm wider endemicity.4,5
Melioidosis has a broad spectrum of clinical disease in children, as in adults. Indeed many infections result in asymptomatic infection, reflected by the high seroprevalence in young children noted in Thailand.6 Melioidosis is characterized as a febrile illness and is an important cause of acute overwhelming septicemia, but less virulent forms, ranging from indolent chronic localized skin infection to abscess formation are also common. Nearly all tissues can be affected, with the lung, spleen and liver being most common.
Melioidosis is recognized as a leading cause of bacterial sepsis in children in regions of Thailand and potentially also Cambodia.7 There is a high mortality in both children and adults, which could be reduced with greater awareness, improved diagnostic investigations and early appropriate treatment.3 Many endemic areas of South East Asia are resource-poor and lack diagnostic and medical facilities.
THE FREQUENCY AND DIFFERENT SPECTRUM OF CLINICAL PRESENTATIONS IN CHILDREN
Children <16 years of age constitute 5–15% of melioidosis cases.7,8 Childhood melioidosis has lower mortality rates than in adults (35% compared with 50%6), is less likely to be associated with underlying immunosuppression and is more likely to involve localized disease.
In general, children present with fever, soft tissue abscess formation (at the site of presumed inoculation), pneumonia and organ abscesses (liver and spleen). However, there are regional differences in the spectrum of organ involvement. Parotid abscess and suppurative parotitis are very common in Thailand and Cambodia9 where up to 40% of children present with localized disease in the head and neck, especially parotid involvement—in contrast to Australian children where this is rare. The regionally specific occurrence of parotid infection and the higher rate of liver abscesses in the same locations may reflect exposure to B. pseudomallei in unchlorinated domestic water supplies and other water sources such as rivers, with ingestion or aspiration leading to infection.10 The proportion of pediatric melioidosis cases that can be attributed to inhalation remains unclear, although potential inhalation during severe weather events has been postulated to contribute to the higher rates of pneumonia and more severe disease seen during the monsoonal season in Northern Australia.1
Neurological presentations of melioidosis (brainstem encephalitis and/or peripheral motor weakness and flaccid paralysis from myelitis) are reported in both children and adults in Australian studies but very rarely elsewhere.8 Many of these cases have not identified host risk factor for melioidosis and recent animal studies have implicated potential direct inoculation of the brain through neural pathways from the nasopharynx.11
Immune suppression is recognized as a risk factor for clinical melioidosis and is present in up to 80% of adults—most commonly, diabetes, renal disease, hazardous alcohol use and immune suppression states. In contrast, only 25% of children have an associated underlying chronic disease (particularly thalassemia) or immune suppression. Recently cystic fibrosis has also been recognized as a particular risk for melioidosis in young travellers and residents of endemic regions.1
In nonendemic areas, melioidosis is reported in returned travellers, immigrants and refugees. Melioidosis should be suspected in young people with an underlying predisposing condition, who are unwell on return from an endemic area.
Despite children accounting for only 5–15% of the total cases overall, reports of melioidosis in the pediatric population have been the first recognition of newly defined endemic locations, with notable case clusters in children described in remote regions of Papua New Guinea and Brazil, and the recently described first case from Malawi.5 Local factors relating to domestic and play environments (such as swimming in contaminated waterways) may render children particularly susceptible to infection.
Transmission has occurred through human breast milk that is culture positive for B. pseudomallei when the lactating mother was asymptomatic and when mastitis was present.12 Vertical transmission is also rarely reported. Person to person contact is considered to be very rare but could potentially occur, through direct contact or inhalation, when an infected parent is in close contact with a child or infant.
THE ROLE OF HOST FACTORS IN PEDIATRIC MELIOIDOSIS
Serological studies in northeast Thailand indicate that exposure to B. pseudomallei occurs from the time that infants have exposure to water and soil and that 25% of children seroconvert each year for the first 4 years of life.6 Most of the population in this endemic area have antibodies, but importantly these are not protective. In general disease, results either from a failure of host defense because of disease or drugs or from an especially large inoculum, as may occur with immersion/drowning in infected water.
Similarly, the clinical manifestation and the severity of the illness are likely to be a function of the infecting dose, host risk factors, the virulence of the specific strain and the mode of infection. There are several additional factors that potentially make children more vulnerable, including a relatively immature innate immune system, coexistence of malnutrition and the lack of previous exposure. Interestingly, there is no evidence that HIV predisposes to infection with B. pseudomallei.1
TREATMENT GUIDELINES FOR CHILDREN
Apart from parotitis in endemic regions, there are no specific clinical features of melioidosis that lead readily to diagnosis; an awareness of the disease, the clinical spectrum and the possibility of environmental exposure are keys. The differential diagnoses vary with the specific presentation and may include tuberculosis.
In the life-threatening presentation of septicemic shock (usually associated with blood culture-positive infection), resuscitation should proceed according to guidelines for managing potential circulatory failure.13
An initial intensive phase of intravenous ceftazidime or meropenem/imipenem for a minimum of 10 days is followed by an eradication phase of at least 12 weeks with oral trimethoprim-sulfamethoxazole or amoxicillin/clavulanate. Both the use of ceftazidime or meropenem/imipenem and the adherence to the eradication phase have been shown to reduce mortality and the risk of relapse.
Note that the appropriate medications to treat severe melioidosis differ to the generally accepted first-line treatment for undifferentiated septicaemia/shock in children,13 which usually include a third generation cephalosporin (ceftriaxone, cefotaxime), with additional cover for Staphylococcus aureus and gentamicin if Gram negative etiology is supected. B. pseudomallei are resistant to gentamicin and although sensitive to ceftriaxone, outcomes are inferior when this agent is continued as therapy for confirmed melioidosis.
MILD LOCALIZED OR CUTANEOUS INFECTION
Trimethoprim-sulfamethoxazole taken orally for 3 months has been successful in limited cases with only localized disease, but exclusion of bacteremia and other foci of infection are important before considering an oral-only regimen.
Melioidosis causes an under-recognized disease burden to children in endemic areas. Awareness of this disease, improved surveillance and access to laboratory resources, appropriate antibiotics (especially ceftazidime) and quality clinical care together with further research will increase understanding of this complex infection and decrease the associated morbidity and mortality.
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