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Empirical treatment with doxycycline may treat non-malarial fevers in Laos
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Excluding malaria, several treatable causes of fever — notably scrub typhus and leptospirosis — were identified in a recent study in northern and southern Laos.
These pathogens are likely to readily respond to doxycycline so empirical treatment with this inexpensive antibiotic may be prudent for those patients where tests are negative for malaria and dengue, according to the study findings.
Paul Newton, MRCP, and colleagues from the Lao Oxford Mahosot Hospital Wellcome Trust Research Unit studied 1,938 febrile patients from rural areas of Laos. Patients were recruited between May 2008 and December 2010 from two hospitals in southern and northern Laos to identify the causes of fever. Patients ranged in age from 5 to 49 years, with a median of 19 years.
The researchers reported that the causative agents of fever differed between the two sites, with leptospirosis, typhoid and Japanese encephalitis virus more common in the north, and dengue and malaria in the south.
“With use of evidence from Southeast Asia when possible, we estimated that azithromycin, doxycycline, ceftriaxone and ofloxacin would have had significant efficacy for 258 (13%), 240 (12%), 154 (8%), and 41 (2%) of patients, respectively,” the researchers concluded.
The investigators also said that treating febrile patients with doxycycline when malaria and dengue rapid tests were negative may be a good way to improve patient outcome for those who so often go untreated.
The researchers noted that their findings point to a need for rapid diagnostic tests for diverse other pathogens, such as leptospirosis and typhoid.
Paul Newton, MRCP, can be reached at paul@tropmedres.ac.
Disclosure: Newton reports no relevant financial disclosures.
Perspective
Back to TopChristopher W. Woods, MD, MPH
Former Speaker of the House Tip O’Neill coined the phrase “all politics is local,” emphasizing the importance of a politician’s understanding of his constituency. The same should be said for a physician’s need for understanding the local etiologies of febrile illness. Causes of fever vary by region, climate, demographics, season and HIV seroprevalence. Therefore, longitudinal fever surveillance, preferably taking place at multiple sentinel sites within a region, is important to provide data that help inform clinical decisions. However, establishing diagnoses for undifferentiated fever, despite the use of a combination of both classical and modern technologies, remains a difficult challenge.
Christopher W. Woods
In the referenced article, Mayxay and colleagues highlight the importance of doxycycline responsive pathogens among patients with undifferentiated fever including leptospirosis (8%), scrub typhus (7%) and other rickettsial infections, such as murine typhus and spotted fever group rickettsia. Each of these agents is difficult to cultivate and requires specialized reference laboratory techniques for diagnosis. The authors used extremely stringent interpretive criteria, likely underestimating the contribution of these pathogens. Several additional findings are worth noting. Malaria is uncommon in these areas of rural Laos, though differentially distributed among the sites. Arboviral infections such as dengue and Japanese encephalitis contributed another 14%, but require supportive care only. The contribution of arboviruses could also be much higher if they included serological case definitions. Blood cultures yielded only 2%.
Of particular interest is the high rate of influenza positive results among the small percentage tested. A major point of emphasis is that 59% of patients did not achieve a diagnosis, despite the extensive work-up. No obvious clinical algorithm was established to facilitate testing from the available data.
Longitudinal febrile illness surveillance is important to document the full range of pathogens causing febrile illness throughout the tropics, especially in regions where malaria is becoming less common. This study calls into question the value of substantial investments into developing classical microbiology laboratories for infrequently obtained pathogens, especially if antibacterial therapy can be limited to those with more severe illness.
However, the potential value of point-of-care diagnostics to allow more directed antibacterial therapy — or even antiviral therapy when warranted — should encourage additional research investment. Higher rates of empiric doxycycline could be an attractive treatment strategy but should be implemented with some caution, as the long-term population health implications are not known.
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