Melioidosis, caused by the gram-negative saprophyte Burkholderia pseudomallei, is a disease of public health importance in southeast Asia and northern Australia that is associated with high case-fatality rates in animals and humans. It has the potential for epidemic spread to areas where it is not endemic, and sporadic case reports elsewhere in the world suggest that as-yet-unrecognized foci of infection may exist. Environmental determinants of this infection, apart from a close association with rainfall, are yet to be elucidated. The sequencing of the genome of a strain of B. pseudomallei has recently been completed and will help in the further identification of virulence factors. The presence of specific risk factors for infection, such as diabetes, suggests that functional neutrophil defects are important in the pathogenesis of melioidosis; other studies have defined virulence factors (including a type III secretion system) that allow evasion of killing mechanisms by phagocytes. There is a possible role for cell-mediated immunity, but repeated environmental exposure does not elicit protective humoral or cellular immunity. A vaccine is under development, but economic constraints may make vaccination an unrealistic option for many regions of endemicity. Disease manifestations are protean, and no inexpensive, practical, and accurate rapid diagnostic tests are commercially available; diagnosis relies on culture of the organism. Despite the introduction of ceftazidime- and carbapenem-based intravenous treatments, melioidosis is still associated with a significant mortality attributable to severe sepsis and its complications. A long course of oral eradication therapy is required to prevent relapse. Studies exploring the role of preventative measures, earlier clinical identification, and better management of severe sepsis are required to reduce the burden of this disease.

https://ams.kku.ac.th/suchat/Mellioidosis/Melioidosis%20Epidemiology%20Pathophysiology,and%20Management.pdf

Melioidosis: Epidemiology, Pathophysiology, and Management

PROTRACED COUNTERINSURGENCY: CHINESE COIN STRATEGY IN XINJIANG by MAJ J. Scott LaRonde, USA, 95 pages. In 1949, following the conclusion of its revolutionary war against the Chinese Nationalist forces, the People’s Liberation Army (PLA) peacefully occupied China’s western most province of Xinjiang. For nearly sixty years, the PLA has conducted a counterinsurgency against several, mostly Uyghur-led, separatist movements. Despite periods of significant violence, particularly in the early 1950s and again in the 1990s, the separatist forces have not gained momentum and remained at a level one insurgency. Mao ZeDeng is revered as a master insurgent and the father of Fourth Generation Warfare. Strategists in armies worldwide study his writings on revolutionary and guerilla warfare. This monograph concludes that Mao, as well as the communist leaders who followed him, was also successful at waging protracted counterinsurgency. For nearly sixty years, separatist movements in Xinjiang, Tibet, and Taiwan have all failed. This monograph analyzes the conflict in Xinjiang and concludes that the Chinese continue to defeat the separatist movement in Xinjiang through a strategy that counters Mao’s seven fundamentals of revolutionary warfare.

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Approved for Public Release; Distribution is Unlimited

Background 
Over 20 years, from October 1989, the Darwin prospective melioidosis study has documented 540 cases from tropical Australia, providing new insights into epidemiology and the clinical spectrum.


Principal Findings 
The principal presentation was pneumonia in 278 (51%), genitourinary infection in 76 (14%), skin infection in 68 (13%), bacteremia without evident focus in 59 (11%), septic arthritis/osteomyelitis in 20 (4%) and neurological melioidosis in 14 (3%). 298 (55%) were bacteremic and 116 (21%) developed septic shock (58 fatal). Internal organ abscesses and secondary foci in lungs and/or joints were common. Prostatic abscesses occurred in 76 (20% of 372 males). 96 (18%) had occupational exposure to Burkholderia pseudomallei. 118 (22%) had a specific recreational or occupational incident considered the likely infecting event. 436 (81%) presented during the monsoonal wet season. The higher proportion with pneumonia in December to February supports the hypothesis of infection by inhalation during severe weather events. Recurrent melioidosis occurred in 29, mostly attributed to poor adherence to therapy. Mortality decreased from 30% in the first 5 years to 9% in the last five years (p<0.001). Risk factors for melioidosis included diabetes (39%), hazardous alcohol use (39%), chronic lung disease (26%) and chronic renal disease (12%). There was no identifiable risk factor in 20%. Of the 77 fatal cases (14%), 75 had at least one risk factor; the other 2 were elderly. On multivariate analysis of risk factors, age, location and season, the only independent predictors of mortality were the presence of at least one risk factor (OR 9.4; 95% CI 2.3–39) and age ≥50 years (OR 2.0; 95% CI 1.2–2.3).


Conclusions 
Melioidosis should be seen as an opportunistic infection that is unlikely to kill a healthy person, provided infection is diagnosed early and resources are available to provide appropriate antibiotics and critical care.

/pdf/the-epidemiology-and-clinical-spectrum-of-melioidosis-540-5fgsohf4ik.pdf

The epidemiology and clinical spectrum of melioidosis: 540 cases from the 20 year Darwin prospective study.

Melioidosis is a serious community-acquired infectious disease caused by the Gram-negative environmental bacterium Burkholderia pseudomallei. A prospective cohort study identified 2,243 patients admitted to Sappasithiprasong Hospital in northeast Thailand with culture-confirmed melioidosis between 1997 and 2006. These data were used to calculate an average incidence rate for the province of 12.7 cases of melioidosis per 100,000 people per year. Incidence increased incrementally from 8.0 (95% confidence interval [CI] = 7.2–10.0) in 2000 to 21.3 (95% CI = 19.2–23.6) in 2006 (P < 0.001; χ2 test for trend). Male sex, age ≥ 45 years, and either known or undiagnosed diabetes were independent risk factors for melioidosis. The average mortality rate from melioidosis over the study period was 42.6%. The minimum estimated population mortality rate from melioidosis in 2006 was 8.63 per 100,000 people (95% CI = 7.33–10.11), the third most common cause of death from infectious diseases in northeast Thailand after human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome (AIDS) and tuberculosis.

/pdf/increasing-incidence-of-human-melioidosis-in-northeast-1b16dqx3so.pdf

Increasing Incidence of Human Melioidosis in Northeast Thailand

In a 12-year prospective study of 318 culture-confirmed cases of melioidosis from the Top End of the Northern Territory of Australia, rainfall data for individual patient locations were correlated with patient risk factors, clinical parameters, and outcomes. Median rainfall in the 14 days before admission was highest (211 mm) for those dying with melioidosis, in comparison to 110 mm for those surviving (p=0.0002). Median 14-day rainfall was also significantly higher for those with pneumonia. On univariate analysis, a prior 14-day rainfall of 125 mm was significantly correlated with pneumonia (odds ratio [OR] 1.70 [confidence interval [CI] 1.09 to 2.65]), bacteremia (OR 1.93 [CI 1.24 to 3.02]), septic shock (OR 1.94 [CI 1.14 to 3.29]), and death (OR 2.50 [CI 1.36 to 4.57]). On multivariate analysis, rainfall in the 14 days before admission was an independent risk factor for pneumonia (p=0.023), bacteremic pneumonia (p=0.001), septic shock (p=0.005), and death (p<0.0001). Heavy monsoonal rains and winds may cause a shift towards inhalation of Burkholderia pseudomallei.

/pdf/intensity-of-rainfall-and-severity-of-melioidosis-australia-4w1c54nthi.pdf

Intensity of rainfall and severity of Melioidosis, Australia

In a prospective study of melioidosis in northern Australia, 252 cases were found over 10 years. Of these, 46% were bacteremic, and 49 (19%) patients died. Despite administration of ceftazidime or carbapenems, mortality was 86% (43 of 50 patients) among those with septic shock. Pneumonia accounted for 127 presentations (50%) and genitourinary infections for 37 (15%), with 35 men (18%) having prostatic abscesses. Other presentations included skin abscesses (32 patients; 13%), osteomyelitis and/or septic arthritis (9; 4%), soft tissue abscesses (10; 4%), and encephalomyelitis (10; 4%). Risk factors included diabetes (37%), excessive alcohol intake (39%), chronic lung disease (27%), chronic renal disease (10%), and consumption of kava (8%). Only 1 death occurred among the 51 patients (20%) with no risk factors (relative risk, 0.08; 95% confidence interval, 0.01-0.58). Intensive therapy with ceftazidime or carbapenems, followed by at least 3 months of eradication therapy with trimethoprim-sulfamethoxazole, was associated with decreased mortality. Strategies are needed to decrease the high mortality with melioidosis septic shock. Preliminary data on granulocyte colony-stimulating factor therapy are very encouraging.

Diane P. Stephens

Papers

Endemic Melioidosis in Tropical Northern Australia: A 10-Year Prospective Study and Review of the Literature