George Watt

Hepatic Penicilliosis in Patients Without Skin Lesions

Penicillium marneffei is a common cause of opportunistic fungal infection in patients with AIDS in Thailand. The diagnosis of penicilliosis is easily made when typical skin lesions appear but is frequently missed in their absence. We therefore attempted to identify noncutaneous indicators of P. marneffei infection in order to provide early curative treatment. We recognized a characteristic syndrome in six AIDS patients with penicilliosis involving primarily the liver but not the skin who presented with fever of short duration, hepatomegaly, and markedly elevated serum alkaline phosphatase levels. The diagnosis was confirmed by demonstrating the causative organism in the liver or in the blood. Increased awareness of hepatic penicilliosis and more-rapid diagnostic methods are needed to reduce the high mortality rate associated with this syndrome. P. marneffei is predominantly an Asian pathogen, but as a result of international travel, the need for increased awareness of penicilliosis is worldwide.

Doxycycline and rifampicin for mild scrub-typhus infections in northern Thailand: a randomised trial.

BACKGROUND Some strains of scrub typhus in northern Thailand are poorly responsive to standard antirickettsial drugs. We therefore did a masked, randomised trial to compare rifampicin with standard doxycycline therapy for patients with scrub typhus. METHODS Adult patients with strictly defined, mild scrub typhus were initially randomly assigned 1 week of daily oral treatment with 200 mg doxycycline (n=40), 600 mg rifampicin (n=38), or doxycycline with rifampicin (n=11). During the first year of treatment, the combined regimen was withdrawn because of lack of efficacy and the regimen was replaced with 900 mg rifampicin (n=37). Treatment outcome was assessed by fever clearance time (the time for oral temperature to fall below 37.3 degrees C). FINDINGS About 12,800 fever patients were screened during the 3-year study to recruit 126 patients with confirmed scrub typhus and no other infection, of whom 86 completed therapy. Eight individuals received the combined regimen that was discontinued after 1 year. The median duration of pyrexia was significantly shorter (p=0.01) in the 24 patients treated with 900 mg daily rifampicin (fever clearance time 22.5 h) and in the 26 patients who received 600 mg rifampicin (fever clearance time 27.5 h) than in the 28 patients given doxycycline monotherapy (fever clearance time 52 h). Fever resolved in a significantly higher proportion of patients within 48 h of starting rifampicin (900 mg=79% [19 of 24], 600 mg=77% [20 of 26]) than in patients treated with doxycycline (46% [13 of 28]; p=0.02). Severe gastrointestinal events warranted exclusion of two patients on doxycyline. There were two relapses after doxycycline therapy, but none after rifampicin therapy. INTERPRETATION Rifampicin is more effective than doxycycline against scrub-typhus infections acquired in northern Thailand, where strains with reduced susceptibility to antibiotics can occur.

HIV-1 suppression during acute scrub-typhus infection.

BACKGROUND In HIV-1-infected individuals, viral load has been reported to rise transiently if an acute infection with another organism occurs. Our study was prompted by the unexpected finding that HIV-1 copy number fell during an acute infection with Orientia tsutsugamushi, the causative agent of scrub typhus. METHODS Serial HIV-1 viral load determinations were made in ten Thai adults with scrub typhus, who were not receiving antiretroviral therapy, and in five HIV-1-infected patients who had other infections (four malaria, one leptospirosis), during and after acute infections. Sera from HIV-1-infected patients with scrub typhus and from mice immunised with O. tsutsugamushi were examined for HIV-1-suppressive activity. FINDINGS Median viral load 3 days after admission was significantly lower in the scrub-typhus group than in patients with other infections (193% vs 376% of day 28 values, p=0.03). In four O. tsutsugamushi-infected patients HIV-1 RNA copy number fell by three-fold or more compared with day 28 values, and HIV-1 copy numbers were below the assay threshold in two patients with scrub typhus. Five of seven HIV-1 isolates from non-typhus patients with CD4 lymphocytes less than 200 cells/microL were syncytia-inducing variants, whereas all ten isolates from O. tsutsugamushi-infected individuals matched by CD4-cell count were non-syncytia inducing (p=0.03). Sera from an HIV-1-negative patient with scrub typhus had potent HIV-1-suppressive activity in vitro. Sera from typhus-infected mice inhibited HIV-1 syncytia formation and bound by immunofluorescence to HIV-1-infected lymphocytes. INTERPRETATION HIV-1-suppressive factors are produced during some scrub-typhus infection and should be investigated further in the search for novel strategies for the treatment and prevention of AIDS.

Decrease in human immunodeficiency virus type 1 load during acute dengue fever.

Rather than the expected increase in human immunodeficiency virus type 1 (HIV-1) load, there was transient suppression of HIV-1 replication during acute dengue infection in a 29-year-old Thai woman. Acute-phase (but not convalescent-phase) serum samples obtained from an HIV-1-uninfected patient with dengue fever reduced HIV-1 infectivity, as determined by a peripheral blood mononuclear cell assay, suggesting the possibility that HIV-1 replication is suppressed during acute dengue fever, as occurs during some cases of scrub typhus infection and measles.

Performance of a Dot Blot Immunoassay for the Rapid Diagnosis of Scrub Typhus in a Longitudinal Case Series

A rapid dipstick test for scrub typhus was prospectively evaluated in Chiangrai, northern Thailand. Sera from 162 patients with fever of unclear etiology were tested by a dot blot immunoassay using two different antigen concentrations. Dipsticks coated with lower concentration of antigen lacked sensitivity compared with the indirect immunoperoxidase test. Dipsticks with higher antigen concentration had increased sensitivity that was equivalent to that of the immunoperoxidase test. By increasing the antigen concentration on the dipstick, sensitivity increased from 67% to 100%, positive predictive value increased from 90% to 93%, and negative predictive value rose from 92% to 100%. The specificity of both antigen concentrations was 98%. This study establishes that scrub typhus can be confirmed serologically by use of a dipstick assay and that serodiagnosis can be effectively tailored to a target population.

Human Immunodeficiency Virus Type 1 Test Results in Patients with Malaria and Dengue Infections

Six rapid enzyme immunoassays for the detection of HIV antibody were performed on paired sera from 66 patients with malaria and 9 patients with dengue. Kit specificities ranged from 77% to 100%, demonstrating that more data are needed on cross-reactivity with endemic diseases as the use of rapid HIV tests increases.

Infective Endocarditis in Northeastern Thailand

Despite rigorous diagnostic testing, the cause of infective endocarditis was identified for just 60 (45.5%) of 132 patients admitted to hospitals in Khon Kaen, Thailand, during January 2010–July 2012. Most pathogens identified were Viridans streptococci and zoonotic bacteria species, as found in other resource-limited countries where underlying rheumatic heart disease is common.

The first reported case of Bartonella endocarditis in Thailand.

Bartonella species have been shown to cause acute, undifferentiated fever in Thailand. A study to identify causes of endocarditis that were blood culture-negative using routine methods led to the first reported case in Thailand of Bartonella endocarditis A 57 year-old male with underlying rheumatic heart disease presented with severe congestive heart failure and suspected infective endocarditis. The patient underwent aortic and mitral valve replacement. Routine hospital blood cultures were negative but B. henselae was identified by serology, PCR, immunohistochemistry and specific culture techniques.

Blood Culture-Negative Endocarditis

Despite progress in blood culture media and automated growth detection systems, blood culture-negative endocarditis (BCNE) still represents 5–69.7 % of all endocarditis cases. Under the BCNE acronym are grouped diverse clinical entities: (i) the most common are cases of bacterial endocarditis caused by usual pathogens in which the negativity of blood cultures is explained by the early antibiotic treatment started prior to blood sampling; (ii) endocarditis caused by fastidious microorganisms that require prolonged incubation and/or specific media, including Brucella sp., defective streptococci (Abiotrophia sp., Gemella sp.), HACEK bacteria, Propionibacterium acnes, fungi; (iii) endocarditis caused by strictly (Coxiella burnetii, Tropheryma whipplei) or facultative (Bartonella sp.) intracellular bacteria; and (iv) endocarditis that complicate cancers (marantic endocarditis), auto-immune diseases (lupus, Behcet, rheumatoid arthritis) or allergy to pork. Various diagnostic strategies, combining systematic serological, molecular, biochemical and/or histological assays, have improved the diagnostic yield of BCNE but this condition remains challenging.

The first reported cases of Q fever endocarditis in Thailand

We describe the first two reported cases of Q fever endocarditis in Thailand. Both patients were male, had pre-existing heart valve damage and had contact with cattle. Heightened awareness of Q fever could improve diagnosis and case management and stimulate efforts to identify risk factors and preventive measures.