Fevers Along the Thai-Myanmar Border

Abstract & Commentary

By Lin H. Chen, MD

Assistant Clinical Professor, Harvard Medical School, Director, Travel Resource Center, Mount Auburn Hospital, Cambridge, MA

Dr. Chen reports no financial relationship relevant to this field of study.

Synopsis: Malaria, leptospirosis, and rickettsiosis are the most commonly identified etiologies of fever in adult patients near the Thai-Myanmar border, and dual infections occur frequently. Travelers planning rural stays in this region should be advised regarding the risks and prevention.

Source: Ellis RD, et al. Causes of Fever in Adults on the Thai-Myanmar Border. Am J Trop Med Hyg. 2006;74:108-113.

Collaborators from the Armed Forces Research Institute for Medical Sciences (AFRIMS) and the Kwai River Christian Hospital assessed the causes of febrile illness in the adult population in Sangkhlaburi, Thailand, near the border with Myanmar. Six hundred thirteen inpatients and outpatients were included in a study from June 1999 to March 2002, with an age range from 20-87 years. The patients were tested at fever presentations for complete blood count, malaria smears, biochemistry panel including alanine transferase (ALT), glutamyl transferase (GGT), blood urea nitrogen (BUN), and creatinine. Leptospirosis, dengue, and Japanese encephalitis serologies were tested. Subjects were selected for serology or PCR testing for rickettsioses, typhoid, melioidosis, Q fever (Coxiella burnetii), and other tests based on both clinical criteria and judgment. Testing was repeated 2-4 weeks after enrollment.

About half of the subjects had specific etiologies identified. Malaria was the most common etiology, diagnosed in 25% of subjects, with 61% being Plasmodium falciparum. Leptospirosis was the second most frequent etiology, diagnosed in 17.5% of subjects. Rickettsiosis was diagnosed in 6%, followed by dengue (1.5%), pulmonary tuberculosis (1.1%), typhoid fever (0.8%), and Japanese encephalitis (0.2%).

Among the subjects who had clinical diagnoses (but no etiologic diagnoses), fever not specified was the most common category (25%), followed by respiratory infections, gastroenteritis, and urinary tract infections. There were 8 deaths, ultimately attributed to typhoid (2), leptospirosis (1), clinical end-stage AIDS (2), fever not specified (2), and hepatitis of unidentified etiology (1).

Dual diagnoses were common among the subjects involving 17% of smear-positive malaria cases, 26% of leptospirosis cases, 11% of rickettsial cases, and 22% of dengue cases. Comparison of age, sex, admission status, symptoms at presentation, and laboratory abnormalities showed association for malaria with outpatient status, documented fever, and thrombocytopenia. Leptospirosis was associated with elevated ALT. Rickettsial disease was associated with older age, elevated GGT, and rash, although the latter was a criteria for serologic testing.

Commentary

The landscape around Sangkhlaburi near the Thai-Myanmar border is rural, with rice fields, farms, lakes, streams, and forests. There is frequent flooding, and the area is endemic for malaria. This study confirms that Plasmodium falciparum is the most commonly identified etiology for fever in adults residing in the area, which is consistent with other data that have shown P. falciparum to cause 56% of malaria cases in Thailand.1 Travelers visiting border areas of Thailand should take precautions to reduce the risk of acquiring malaria in this region.

The study highlights the prevalence of leptospirosis and rickettsiosis as causes of fever in rural Thailand. Leptospirosis is the second most frequent etiologic diagnosis identified, caused by a zoonotic spirochete usually infecting rodents and domestic animals. Leptospires are shed in animal urine, which can contaminate fresh water. Humans are exposed through contact with fresh water, soil, or direct contact with infected animals, and the organisms enter through abraded skin. After the infection, there is an incubation period of 7-12 days (range, 3-30 days) before onset of symptoms, which include fever, myalgia, headaches, rash, conjunctival suffusion, nausea, and vomiting.2 Severe symptoms, including aseptic meningitis, pulmonary hemorrhage, liver dysfunction, and renal failure can occur.2 Residents in this region with much exposure to fresh water in the environment are understandably at significant risk of acquiring leptospirosis.

Similarly, the local population has significant exposure to rickettsioses through their outdoor occupations in farming or forestry. In addition, many houses are open wood and thatch constructions, some with walls made of scrap materials only. Many village homes in the area have domestic animals all around them. There is likely an abundance of ticks, mites, and fleas, vectors of spotted fever group (SFG) rickettsiosis, scrub typhus, and murine typhus, respectively. Spotted fever group (SFG) rickettsioses are zoonoses caused by obligate intracellular gram-negative coccobacilli within the genus Rickettsia. The etiologic agent of scrub typhus is Orientia tsutsugamushi, known to be endemic in Asia, and the agent of murine typhus is Rickettsia typhi, with worldwide distribution.

Infections with SFG rickettsiosis, scrub typhus, and murine typhus generally have incubation periods of 1-2 weeks (4-7 days for SFG and up to 20 days for scrub typhus).3-5 The diseases are associated with fever, myalgias, headache, eschar, rash, abdominal pain, nausea, vomiting, and sometimes cough, renal failure, confusion, seizures and arrhythmias.3-5 Skin manifestations include eschars, maculopapular, or vesicular rash.3-5

Ellis and colleagues found dengue and Japanese encephalitis to be less common causes of fever in this study on adults, due to the fact that these infections occur more frequently in childhood. Adults in rural Thailand may be immune against Japanese encephalitis from childhood immunization. The majority of dengue cases in Thailand occur in children, and adults are often immune to dengue from prior exposures.

Leptospirosis is an emerging disease, and outbreaks have occurred in travelers participating in water sports or competitions.6 Because of leptospirosis’ worldwide distribution, travelers with possible exposure to fresh water should be advised of the risk of acquiring leptospirosis.

SFG rickettsiosis has previously been reported in travelers, most frequently in travelers to Africa,7-9 but this study in Thailand illustrates the presence of the disease and its significance as a cause of febrile illnesses. This is probably the tip of the iceberg, and rickettsiosis should be considered an emerging disease. Travelers with rural destinations, especially with outdoors activities, should be advised of the risk.

Unfortunately, cultures could not be performed in this study to ascertain the true prevalence of typhoid fever and melioidosis, as well as endocarditis and bacteremia of various causes. However, typhoid fever was identified by PCR, and its association with deaths and bowel perforation supports its significance as a cause of fever in rural areas of Thailand. Melioidosis is prevalent in other parts of Thailand, and confirmation of presence of the infection in this region is important for therapeutic considerations. Tuberculosis is probably a more common cause of fever, but the study only classified cavitary lesions and/or acid-fast bacilli on sputum smear to be pulmonary tuberculosis.

Finally, coinfections appear to be common. It is important to keep in mind the possibility of coinfection in assessing patients returning from the tropics with multiple possible exposures. If a febrile traveler is not responding to treatment for an identified pathogen, a second etiology must be sought. Because of its efficacy against leptospirosis and rickettsiosis, and because of mefloquine-resistant P. falciparum in the region, doxycycline appears to be an optimal malaria chemoprophylaxis for travelers visiting the Thai-Myanmar border. This study provides additional emphasis on preventing arthropod bites and fresh water exposure for travelers visiting rural Thailand and Myanmar, and likely most SE Asian countries.

References

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