Scrub typhus, a disease caused by the mite-borne pathogen Orientia tsutsugamushi, is a major cause of acute undifferentiated fever (AUFI) in Asia (1). It was once believed to be limited to a conceptual area known as the 'tsutsugamushi triangle,' which encompasses the Indian subcontinent, Southeast Asia, China, Korea, Japan, and Northern Australia. However, recent cases have emerged in Peru and Kenya as well. Despite the considerable burden of this disease, scrub typhus is often overlooked, with a scarcity of high-quality research to support treatment decisions. A systematic review from India indicated that scrub typhus was responsible for one-quarter of AUFI cases in hospitalized patients (2). About 20% of those affected by scrub typhus exhibited severe symptoms that required intensive care. The median mortality rate for untreated patients is 6%, but this figure drops to 1.4% for those who receive proper treatment. Scrub typhus usually presents as an acute febrile illness, often accompanied by symptoms such as headache, cough, shortness of breath, and altered consciousness. A distinctive diagnostic sign is the eschar formed at the site of the mite bite. Severe illness can develop in about one-third of hospitalized patients, potentially leading to multiorgan dysfunction, shock, and death in approximately 25% of cases, even with treatment. In India, scrub typhus is re-emerging as a significant infectious disease and is the most common Rickettsial disease, found in various areas including the sub-Himalayan belt, Bihar, Karnataka, Tamil Nadu, and Kerala. Although chloramphenicol was previously used for treatment, its application has decreased due to its toxic effects (3). In a comprehensive review of treatment strategies, doxycycline and azithromycin were identified as the most commonly prescribed antibiotics for the management of scrub typhus [4]. The Indian Guidelines advocate for the use of either antibiotic for treatment, without establishing a clear preference [6]. Recent advancements in awareness and diagnostic capabilities have led to an increase in comparative studies regarding the management of scrub typhus. So this study was undertaken to compare the effectiveness of single dose of 500 mg azithromycin to a week-long course of 200 mg doxycycline in a patient with scrub typhus.

AIM AND OBJECTIVES:

To compare the effectiveness of single dose of 500 mg azithromycin to a week-long course of 200 mg doxycycline in a patient with scrub typhus. The time taken for fever resolution, length of hospital stay, and various clinical characteristics of cases in both groups were analysed. Additionally, the adverse reactions to the medication were assessed in both groups.

This investigation was conducted on 30 pediatric patients, all 14 years or younger, who experienced a fever for a minimum of one week and tested positive for Scrub typhus through IgM ELISA. The treatment regimen included either Azithromycin (10 mg/kg taken orally once daily for seven days) or Doxycycline (for children weighing 40 kg: 100 mg given twice daily for seven days). The study did not include children who had been treated with antibiotics prior to diagnosis or those who were noncompliant with their treatment. Fever Clearance Time was identified as the period from the initial antibiotic dose to the point at which the temperature decreased to 37.5 °C or below and stayed there for at least 24 hours. Furthermore, mortality rates during the treatment or follow-up stages for each group were documented, along with any noted adverse reactions to the medication.

Table 1: Mean Age of The Study Population

Graph 1: Mean Age of The Study Population

Table 2: Sex Distribution of The Study Population

Graph 2: Sex Distribution Of The Study Population

Table 3: Fever Clearance Time

Table 4: Duration Of Stay in Hospital

Table 5: Adverse Drug Reactions Among the Study Groups

Table 6: Mortality Rate In Between The Groups

Azithromycin is utilized in the treatment of scrub typhus through both oral and intravenous routes. The oral form is typically more convenient than the intravenous option, providing significant advantages as it can be administered in any outpatient or hospital context. As of now, there are four comparative research papers that assess the efficacy of azithromycin versus oral doxycycline for scrub typhus; one of these studies pertains to intravenous azithromycin, while the other three concentrate on the oral variant. Scrub typhus is named for its association with scrub vegetation, which can be found in sandy, semi-arid, and mountainous desert regions that may harbour the disease's vectors. Among the various stages of mites, it is the larval form, known as chiggers, that feeds on humans, which is why scrub typhus is also referred to as chiggerosis. The hallmark symptoms of scrub typhus include the formation of an eschar at the site of the bite, regional lymphadenopathy, and a maculopapular rash, observed in 40-50% of cases. Early non-specific symptoms may present as fever, headache, myalgia, cough, and gastrointestinal disturbances. In rare cases, complications such as encephalitis and intestinal pneumonia may occur during the later stages of the disease. A 2019 study by Bal et al. (11) in India focused on children diagnosed with scrub typhus, finding that doxycycline was the treatment of choice in most cases (85.5%), while azithromycin was used in a lesser number of instances (14.5%). The authors of the meta-analysis recommended azithromycin as a preferable alternative to doxycycline, particularly emphasizing its appropriateness for pregnant women and children younger than eight years (12). Azithromycin, a macrolide antibiotic, is noted for its effective intracellular penetration and a half-life exceeding 50 hours in children, allowing for once-daily administration and a shorter treatment duration. It has been shown to achieve high concentrations in neutrophils and macrophages, which are essential for the phagocytosis of pathogens. Studies conducted in vitro have confirmed the effectiveness of azithromycin against Orientia tsutsugamushi. The drug operates by reversibly binding to the 50S subunit of the bacterial ribosome, which results in the inhibition of protein synthesis in bacteria. The most commonly reported adverse effects are mild gastric disturbances and abdominal discomfort. The current research revealed no significant differences in gastrointestinal side effects between the azithromycin group and those treated with doxycycline or chloramphenicol. Nevertheless, the small sample size of the study is a limitation, indicating a need for further research to assess the effectiveness of azithromycin in pediatric scrub typhus cases. It is also important to mention that azithromycin is more expensive than doxycycline. Despite the higher cost, azithromycin shows comparable efficacy, is easier to administer with its once-daily dosing, and is generally better tolerated with fewer adverse effects, making it a recommended treatment option for pediatric patients with scrub typhus. Azithromycin is considered less effective for fever reduction when compared to other antimicrobial agents. Retrospective analyses have shown that the time required for fever resolution with azithromycin is longer than that associated with other antibiotics. However, findings from randomized controlled trials indicate that there is no significant difference in the time to fever clearance between patients treated with azithromycin and those receiving other therapeutic options.

Doxycycline has proven to be more effective in achieving fever reduction and in preventing negative drug reactions in individuals with Scrub typhus. Therefore, it is viewed as a safer and more well-tolerated treatment option for children suffering from this disease. It is suggested that further investigations involving a larger cohort be conducted to provide a higher degree of confidence in these results

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