This report describes patients with pulmonary melioidosis, detected through surveillance of ALRI. To our knowledge, this is the first report of pulmonary melioidosis cases that were followed several months after hospital discharge in Cambodia [12–14].
Fatality rates (~62%) in our cohort were high compared to that of Thailand (40.5% in 2006) [2, 16]. These high rates likely were related to multiple factors, including inadequate antibiotic therapy, low awareness of the disease and limited access to health care services rather than a severity of the disease that is peculiar to Cambodia.
Indeed, awareness of melioidosis among health professionals remains low. In the context of high TB endemicity and low microbiological capacity in public hospitals, misdiagnosis of melioidosis taken as TB may not be uncommon . All the more when six patients' chest X-rays were interpreted as TB-like infection by our clinical experts. In the surveillance study, many clinicians did not account for melioidosis in their first line antibiotic treatment when diagnosing severe pneumonia. Moreover, many patients were discharged before having received bacteriological results; it is recognized in Cambodia that many patients' families would rather go back home if they cannot afford to stay longer at the hospital or when patients are severely ill with little hope of cure.
The turning point in the treatment of bacteremic melioidosis was the use of ceftazidime reducing by half fatality [1, 17]. Parenteral co-amoxiclav would have been a cheaper alternative in our study hospital; unfortunately, both drugs are costly and not available in the National Essential Drugs list. With a potentially high burden of melioidosis in Cambodia (12 - 14), one should consider making ceftazidime available by using a generic form that is now manufactured in Thailand (http://www.drugs.com/international/cef-4.html). Notably, oral treatment can still rely on cotrimoxazole - a cheap and available drug - as susceptibility testing for this antibiotic using E-test method has demonstrated no resistance of B. pseudomallei isolates. This finding contrasts with that of Northern Thailand where susceptibility of isolates was lower at 87% .
The present study showed that melioidosis had a substantial financial impact on households in rural Cambodia. To pay for these costs, two-thirds of households had to borrow money and 25% had to sell assets or use their savings, a finding that is consistent with studies on cost-of-illness for other infectious diseases in Cambodia . To put in perspective, the average cost of melioidosis was similar to the Gross National Income per capita in Cambodia, i.e. US$600 in 2008 . These costs were overwhelming when compared to an average one-week expenditure on food of US$ 9.5 per household .
Previous series reported 37 to 60% of diabetes mellitus in patients with melioidosis . Only one study has documented a high prevalence of diabetes mellitus (~61%) in the sub-group of pulmonary melioidosis . Our results were consistent with that of studies which reported higher prevalence of diabetes mellitus in bacteremic patients [21–23]. However, the proportion of diabetes mellitus in our series appeared low. This is surprising as the prevalence of diabetes mellitus in Cambodia is thought to be high, accounting for 11% of the population in Kampong Cham province . Similarly, we observed that severe patients were less likely to have co-morbidities. Diabetes mellitus may have been under-reported among our patients. Since most of these patients died quickly after their admission, it is possible that clinicians were less demanding when interrogating the family on diabetes as an underlying condition.
Our study has additional limitations. Estimating the extent of melioidosis and its severity in ALRI is problematic due to the difficulties in obtaining microbiological diagnoses. Few of our patients were children in whom sputum was difficult to collect and therefore hardly available. However, it is very likely that fewer children suffer from pulmonary melioidosis [5, 12]. In Thailand, higher incidence rates were found in 40-60 year old adults . In addition, blood culture is rarely positive in children since they suffer from less severe forms of melioidosis . Of note, one patient was 2 months old at the time of diagnosis suggesting possible vertical transmission from mother to child or a neonatal infection . Unfortunately, we could not trace this child for the follow-up investigation. Two of the three children died and were co-infected by H3N2 influenza virus. It is difficult indeed to relate the severity of the disease to influenza infection, although reactivation of melioidosis following influenza infection has been described in adults .
Second, the surveillance study is limited to hospitalized cases of pulmonary infection and so does not include sub-acute forms and other presentations of the disease; the follow-up questionnaire revealed that one third of the patients actually had chronic melioidosis which resulted in overestimating the proportion of melioidosis in severe acute respiratory infections. Nevertheless, we believe that our series is reasonably representative of people in the provinces as our hospitals were the only reference hospitals for their respective provinces.