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

https://web.iitd.ac.in/~arunku/files/CEL795_2011/Microbial%20contamination%20of%20drinking%20water%20and%20disease%20outcomes%20in%20developing%20regions_Ashbolt.pdf

Microbial contamination of drinking water and disease outcomes in developing regions.

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.

/pdf/approved-for-public-release-distribution-is-unlimited-2qs7y34q3g.pdf

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.

Burkholderia pseudomalleiinfection can present with such a diverse array of clinical symptoms thatB. pseudomallei is known as the 'great mimicker'. Here, current knowledge of B. pseudomallei–host interactions is reviewed, and key topics for future research are highlighted. Burkholderia pseudomallei is a potential bioterror agent and the causative agent of melioidosis, a severe disease that is endemic in areas of Southeast Asia and Northern Australia. Infection is often associated with bacterial dissemination to distant sites, and there are many possible disease manifestations, with melioidosis septic shock being the most severe. Eradication of the organism following infection is difficult, with a slow fever-clearance time, the need for prolonged antibiotic therapy and a high rate of relapse if therapy is not completed. Mortality from melioidosis septic shock remains high despite appropriate antimicrobial therapy. Prevention of disease and a reduction in mortality and the rate of relapse are priority areas for future research efforts. Studying how the disease is acquired and the host–pathogen interactions involved will underpin these efforts; this review presents an overview of current knowledge in these areas, highlighting key topics for evaluation.

/pdf/melioidosis-insights-into-the-pathogenicity-of-burkholderia-5elmf3a9dl.pdf

Melioidosis: insights into the pathogenicity of Burkholderia pseudomallei

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.

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

The epidemiology of melioidosis in Australia and Papua New Guinea.

Background. A method is presented for estimating the confidence limits (CLs), or accuracy, of the arteriovenous fistula flow rate measured at haemodialysis by the ‘on-line’ thermodilution technique. Methods. This was by derivation of an expression to estimate what variance a set of repeated measures of flow would yield, using values pertaining to a single measure of flow. (Laws of variance were applied to the formula used to calculate flow, to account for its variables’ values and measurement errors.) This enabled CLs of a single measure to be estimated. Results. The variance estimated from a single measure was compared with that actually observed upon immediately taking a second measurement; differences in 189 pairs were not significantly different from zero (Ps0.56). Applying the results demonstrated that measured flow values of 430‐570 mlumin typically had associated 95% CLs that included 500 mlumin; therefore, true flow could not be said to be either side of 500 mlumin. The same was the case for 500‐700 mlumin with regard to 600 mlumin. CLs widened considerably with the magnitude of flow rate, limiting the accurate measurement of higher flows and the detection of falls in flow. Conclusion. A method to estimate CLs of flow rate measured by the thermodilution technique is presented and validated. Application demonstrates an accurate measurement of low flow, but limitations at higher flow and in detecting falls in flow. Appreciating the magnitude of such is critical to informed clinical decision making when using flow rate in an access surveillance programme.

/pdf/confidence-limits-of-arteriovenous-fistula-flow-rate-1bgq5ebxyp.pdf

Confidence limits of arteriovenous fistula flow rate measured by the ‘on‐line’ thermodilution technique

SUMMARY: A team approach to fistula surgery, with a weekly ward round and elective fistula list, was introduced at the Royal Darwin Hospital in April 1999. This study has evaluated the impact of this team approach and assessed factors influencing fistula patency. Data was prospectively recorded on all patients who underwent fistula surgery between 1993 and August 2000. Three hundred and forty-seven operations were performed in 161 patients, with 142 (41%) for revision of an established fistula. One hundred and nine operations (m 79 patients) were performed after the onset of the team approach. A 30-day fistula patency rate was significantly greater for new operations than revision operations, at 86 and 77% (P= 0.047). Primary and secondary patency rates were 56 and 75%, respectively, at 1 year, and 38 and 42% at 3 years. Factors associated with reduced duration of fistula patency following any operation included operations before the team approach (P=0.0002), operations out-of-hours (P=0.020), use of an interposition graft (P=0.035), and persons NOT of aboriginal race (P=0.007). Diabetes was suggestive of reduced patency (P=0.065). the only factor associated with reduced secondary patency was the use of an interposition graft (P= 0.020). Factors not shown to influence primary or secondary patency included the artery or vein used, peripheral vascular disease, hypertension, cerebrovascular disease, and the particular surgeon who performed the operation. Out-of-hours surgery was reduced, from 37 to 28% by the dedicated theatre list We conclude that the team approach to fistula surgery, with a dedicated theatre list, prolongs fistula patency, plus allows the surgeon to steep at night. an interposition graft should be avoided whenever possible.

Impact of a multidisciplinary team approach upon patency rates of arteriovenous fistulae

SUMMARY:

Background: Measurement of blood flow within native arteriovenous fistula during haemodialysis is recommended to detect incipient fistula failure. In the present study the value of such flow measurements was assessed in a group of patients on maintenance haemodialysis, with access via native arteriovenous fistulas.



Methods:  Flow was measured using the ‘on-line’ thermodilution technique, on three separate occasions, and correlated with subsequent fistula failure within 6 months.



Results:  Of the 53 patients studied, there were six failures (three thromboses and three inadequate dialysis filtration rates). Flow rates in patients who progressed to fistula failure were significantly less than flow rates in patients whose fistulas did not fail (U = 13.0, P < 0.0003). Failure was no more common in one type of fistula than another (type fistula: F = 0.29, P = 0.88; flow predicting failure: F = 7.22, P = 0.010). Receiver operating characteristic (ROC) curve analyses confirmed flow measurement to be a useful predictor of fistula failure (area under ROC curve 0.91). The optimal threshold of 576 mL/min flow gave a sensitivity of 89% and a specificity of 81%. Measurement of access resistance was less useful in predicting failure (area under ROC curve 0.87). Measurement of fall in flow from the previous measurement was of no use (area under ROC curve 0.535).



Conclusion:  On-line thermodilution measurement of flow within established native arteriovenous fistula is useful in surveillance and early prediction of fistula failure. Fistula flow <576 mL/min may indicate incipient native fistula failure, and should prompt further investigation.

Paul Snelling

Papers

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

The epidemiology of melioidosis in Australia and Papua New Guinea.

Confidence limits of arteriovenous fistula flow rate measured by the ‘on‐line’ thermodilution technique

Impact of a multidisciplinary team approach upon patency rates of arteriovenous fistulae

Prediction of failure of native arteriovenous fistulas using 'on-line' fistula flow measurements