Scrub Typhus

(1) Background: Scrub typhus (ST) is endemic to Nepal. It is often underdiagnosed and misdiagnosed due to non-specific clinical presentation coupled with limited microbiological facilities, leading to adverse clinical outcomes. This study aimed to assess the seroprevalence of scrub typhus in febrile patients attending Sukraraj Tropical and Infectious Disease Hospital (STIDH), Nepal, from August 2018 to April 2019. (2) Materials and Method: Blood/serum samples and clinical and demographic data of adult febrile patients (≥19 years) who attended or were referred to the hospital were collected after obtaining written informed consent from the participants excluding immunocompromised individuals. Collected blood/serum samples were subjected to hematological, biochemical, and serological tests. A serological test for scrub typhus was performed using the ImmuneMed scrub typhus rapid diagnostic test kit. Data generated were analyzed using SPSS software version 24.0. (3) Results: Amongst the 2070 febrile patients, 462 (22.3%) were seropositive to at least one etiological agent of febrile illnesses (scrub typhus: 253 cases, dengue: 101 cases, leptospirosis: 9, brucellosis: 52, malaria: 9 and kala-azar: 20 cases). Scrub typhus accounted for 12.2% (n = 253) of total febrile illnesses followed by dengue (4.9%, n = 101). Mixed seropositivity of scrub typhus with dengue, brucellosis, and typhoid was found in 12 (0.6%), 9 (0.4%), and 5 (0.2%) cases, respectively. Among 253 scrub typhus patients, 53.4% were female. Among the 154 patients, the most common symptoms were fever (100%), headache (79.2%), sweating (70.1%), breathing difficulty (51.3%), redness of the eye (43.5%), and pathognomonic eschar was observed in 9.1% patients. Fifty percent of scrub typhus patients had low platelet count and >30% of patients had an elevated level of liver enzymes (such as serum glutamic oxaloacetic transaminase (SGPT) and serum glutamic pyruvic transaminase (SGOT). (4) Conclusion: Scrub typhus is a considerable cause of febrile illness in Nepal. Females apparently have a higher chance of acquiring scrub typhus. ST presents nonspecific clinical presentation. The diagnostic dilemma of typhus patients can be minimized by the early monitoring of ST-associated symptoms. The country’s health system needs to be strengthened for early outbreak detection, and immediate response actions against scrub typhus to control the future outbreak of ST.

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. 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. 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. 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.

We developed an intradermal (ID) challenge cynomolgus macaque (Macaca fascicularis) model of scrub typhus, the leading cause of treatable undifferentiated febrile illness in tropical Asia, caused by the obligate intracellular bacterium, Orientia tsutsugamushi. A well-characterized animal model is required for the development of clinically relevant diagnostic assays and evaluation of therapeutic agents and candidate vaccines. We investigated scrub typhus disease pathophysiology and evaluated two O. tsutsugamushi 47-kDa, Ag-based candidate vaccines, a DNA plasmid vaccine (pKarp47), and a virus-vectored vaccine (Kp47/47-Venezuelan equine encephalitis virus replicon particle) for safety, immunogenicity, and efficacy against homologous ID challenge with O. tsutsugamushi Karp. Control cynomolgus macaques developed fever, classic eschars, lymphadenopathy, bacteremia, altered liver function, increased WBC counts, pathogen-specific Ab (IgM and IgG), and cell-mediated immune responses. Vaccin...

Scrub typhus (ST), hitherto absent from many parts of India, is now recently being recognized as a significant cause of morbidity and mortality throughout the country. Its diverse clinical presentations, low of the index of suspicion by the treating physician, and lack of diagnostic testing in many parts of the country result in delayed treatment, leading to a host of complications. We here report such a complication, where ST manifested with a large intracerebral hemorrhage, of which, to the best of our knowledge, only nine cases have been reported in the English language worldwide. Family physicians, who are the often first point of contact for treatment of febrile illness, as ST typically manifests, need to be aware of this entity to prevent such catastrophic consequences.