Patient characteristics, treatment patterns, and outcomes of Rickettsial diseases among a commercially insured population in the United States, 2005-2017.

Rickettsial diseases (RDs) are transmitted to humans by ectoparasites, including ticks and fleas. Symptoms range from mild febrile illness, to severe disease or death. Doxycycline is the treatment of choice for patients of all ages; early treatment based on clinical diagnosis is critical to prevent severe outcomes. We conducted a descriptive analysis using insurance claims data captured by IBM MarketScan® research databases to describe demographics, treatment patterns, and outcomes of patients diagnosed with RDs in the United States during 2005-2017. Overall, 14,830 patients had a RD diagnosis during 2005-2017; 7,517 (50.7%) spotted fever rickettsiosis (SFR), 4,571 ( 30.8%) ehrlichiosis, 1,362 (9.2%) typhus group rickettsiosis (TGR), and 1,193 (8.0%) other rickettsial diseases. Among all patients diagnosed, 53.1% received doxycycline. Prescription rates varied by diagnosis and age; 24.1% of TGR and 61.1% of SFR patients received doxycycline; 23.9% of persons < 8 years received doxycycline, compared with 47.7% for 8-17 years, and 55.4% for ≥ 18 years. RDs are frequently diagnosed in the outpatient population; however, providers prescribed the recommended treatment to about half of patients. Continued education of treatment recommendations is critical to prevent severe outcomes.

Exploring Tropical Infections: A Focus on Cutaneous Larva Migrans.

GENERAL PURPOSE: To provide information about infection with cutaneous larva migrans (CLM). TARGET AUDIENCE: This continuing education activity is intended for physicians, physician assistants, NPs, and nurses with an interest in skin and wound care. LEARNING OBJECTIVES/OUTCOMES: After participating in this educational activity, the participant will:1. Distinguish the clinical features, diagnosis, and management of CLM.2. Explain the epidemiology of CLM. ABSTRACT: Cutaneous larva migrans is a hookworm infection and one of the most common skin diseases of tourists in tropical countries. Most commonly, the infection is transmitted by contact with feces of dogs and cats containing hookworm eggs. This case-based review explores the epidemiology, diagnosis, clinical features, and management of cutaneous larva migrans infection.

Cutaneous larva migrans is a hookworm infection and one of the most common skin diseases of tourists in tropical countries. Most commonly, the infection is transmitted by contact with feces of dogs and cats containing hookworm eggs. This case-based review explores the epidemiology, diagnosis, clinical features, and management of cutaneous larva migrans infection.

Probable African Tick Bite Fever in the United States.

African tick bite fever (ATBF) is a tick-borne rickettsial disease most often observed in North American and European tourists returning home from the southern portion of Africa. Ticks infected with Rickettsia africae transmit this parasitic bacterium to humans, who subsequently develop an influenza-like illness, one or more inoculation eschars, and in some cases, a cutaneous rash. Because ATBF often presents with non-specific symptoms that suggest other infectious diseases, establishing the diagnosis may be difficult. Confirmatory assays, including serology and nucleic acid amplification, may take weeks to return and cannot help with acute treatment decisions. We present a case of a previously healthy 60-year-old woman who developed an illness strongly suggestive of ATBF after a missionary trip to Zimbabwe and discuss the disease's diagnostic challenges. Our paper also reviews the epidemiology of this disease and the currently available diagnostic laboratory tests and recommended treatment options.

Rickettsial infections of the central nervous system.

As a result of migrations and globalization, people may face a possible increase in the incidence of central nervous system rickettsial infections (CNS R). These diseases, caused by Rickettsia species and transmitted to humans by arthropod bites, are putatively lethal. However, the diagnosis of CNS R is challenging and often delayed due to their nonspecific clinical presentation and the strict intracellular nature of rickettsiae. Furthermore, transfer of rickettsiae to the brain parenchyma is not yet understood. The aim of this review is to analyze and summarize the features and correlated findings of CNS R in order to focus attention on these intriguing but frequently neglected illnesses. We also incorporated data on CNS infections caused by Rickettsia-related microorganisms.

Rickettsioses: Cutaneous findings frequently lead to diagnosis - a review.

While epidemic typhus caused by Rickettsia prowazekii posed a significant threat in Europe before and throughout World War II due to its high mortality, the condition fortunately no longer plays a significant role. Nevertheless, rickettsioses, such as African tick bite fever, have been increasingly diagnosed in travelers returning from sub-Saharan Africa. Caused by Rickettsia africae, African tick bite fever presents with characteristic cutaneous findings such as eschar (tache noir) and a rash. Similar findings are also observed in Mediterranean spotted fever caused by Rickettsia conorii. On the other hand, Rocky Mountain spotted fever - caused by Rickettsia rickettsii - is characterized by a rash without an eschar, in combination with distinctly more severe general symptoms. The objective of the present CME article is to familiarize dermatologists with the spectrum of the most common types of rickettsiosis in humans, including their epidemiology, clinical presentation, diagnostic workup, and treatment. Recognition of characteristic cutaneous manifestations and their correct interpretation facilitate early diagnosis. Prompt initiation of treatment usually results in recovery without sequelae.

[Knowledge of vector-borne diseases (dengue, rickettsiosis and Chagas disease) in physicians]. / Conocimiento de enfermedades transmitidas por vectores (dengue, rickettsiosis y enfermedad de Chagas) en médicos.

BACKGROUND: The ecological conditions of Yucatan made it a suitable region for the acquisition of vector-borne diseases such as dengue, rickettsiosis, and Chagas disease. As the epidemiological burden of these diseases shows an alarming increase of severe cases, the early establishment of diagnosis and therapeutics by first-contact physicians is a critical step that is not being fulfilled due to several reasons, including poor knowledge. OBJECTIVE: To determine the level of knowledge related to dengue, Chagas disease, and rickettsiosis among rural first-contact physicians of Yucatan. METHODS: A survey was applied to 90 first-contact physicians from rural clinics of Yucatan, which included 32 items related to the diagnosis, treatment, and prevention of dengue, rickettsiosis, and Chagas disease. Answers were analyzed by central tendency statistics. RESULTS: Differences were observed among every category, however; diagnosis and therapeutics showed the lower values. Globally, 62.5% of respondents showed moderate knowledge, 37.5% poor knowledge, and 0% adequate knowledge. DISCUSSION: Results suggest that a strong campaign for a continuous diffusion of knowledge regarding these diseases is needed. In regions with high prevalence of these kinds of diseases, like Yucatan, the impact of these results on the epidemiological burden of these diseases must be evaluated.

Anaplasma, Ehrlichia and Rickettsia species infections in cats: European guidelines from the ABCD on prevention and management

OVERVIEW: Anaplasma species, Ehrlichia species and Rickettsia species are vector-borne pathogens infecting a wide variety of mammals, but causing disease in very few of them. Infection in cats: Anaplasma phagocytophilum is the most important feline pathogen among these rickettsial organisms, and coinfections are possible. Little information is available on the pathogenesis of these agents in cats. Clinical signs are usually reported soon after tick infestation. They are mostly non-specific, consisting of fever, anorexia and lethargy. Joint pain may occur. Infection in humans: Some rickettsial species ( A phagocytophilum, Ehrlichia chaffeensis, Ehrlichia ewingii, Rickettsia conorii, Rickettsia rickettsii, Rickettsia felis, Rickettsia typhi and Candidatus Neoehrlichia mikurensis) are of zoonotic concern. Direct contact with cat saliva should be avoided because of potential contamination by R felis. Infected cats are 'sentinels' of the presence of rickettsial pathogens in ticks and fleas in a given geographical area, and they signal a risk for people exposed to vectors.

Molecular diagnosis of African tick bite fever using eschar swabs in a traveller returning from Tanzania.

African tick bite fever is an emerging infectious disease among travellers caused by the pathogen Rickettsia africae. Most travel-associated cases have been reported from countries in southern Africa. So far it has rarely been reported among travellers to eastern Africa and our patient is one of the first described cases imported from Tanzania. A woman presented with fever, chills, headache, myalgia and a rickettsial eschar on her ankle after returning from Tanzania. The diagnosis of African tick bite fever is often based on clinical grounds due to a lack of reliable diagnostic tests at commencement of symptoms. In this patient direct molecular detection of R. africae was performed by PCR from a sample obtained non-invasively with a swab from the rickettsial eschar. A positive PCR result was achieved although the patient had already started antibiotic treatment with doxycycline. In conclusion, this non-invasive method enables early diagnosis of African tick bite fever by direct molecular detection of R. africae and might improve the management of undifferentiated fever in travellers from Africa.

Diagnosis and Management of Tickborne Rickettsial Diseases: Rocky Mountain Spotted Fever and Other Spotted Fever Group Rickettsioses, Ehrlichioses, and Anaplasmosis - United States.

Tickborne rickettsial diseases continue to cause severe illness and death in otherwise healthy adults and children, despite the availability of low-cost, effective antibacterial therapy. Recognition early in the clinical course is critical because this is the period when antibacterial therapy is most effective. Early signs and symptoms of these illnesses are nonspecific or mimic other illnesses, which can make diagnosis challenging. Previously undescribed tickborne rickettsial diseases continue to be recognized, and since 2004, three additional agents have been described as causes of human disease in the United States: Rickettsia parkeri, Ehrlichia muris-like agent, and Rickettsia species 364D. This report updates the 2006 CDC recommendations on the diagnosis and management of tickborne rickettsial diseases in the United States and includes information on the practical aspects of epidemiology, clinical assessment, treatment, laboratory diagnosis, and prevention of tickborne rickettsial diseases. The CDC Rickettsial Zoonoses Branch, in consultation with external clinical and academic specialists and public health professionals, developed this report to assist health care providers and public health professionals to 1) recognize key epidemiologic features and clinical manifestations of tickborne rickettsial diseases, 2) recognize that doxycycline is the treatment of choice for suspected tickborne rickettsial diseases in adults and children, 3) understand that early empiric antibacterial therapy can prevent severe disease and death, 4) request the appropriate confirmatory diagnostic tests and understand their usefulness and limitations, and 5) report probable and confirmed cases of tickborne rickettsial diseases to public health authorities.

Delayed fatal diagnosis in atypical rickettsial infectious disease.

We report the case of an 84-year-old man admitted to ICU with symptoms/signs occurring after upper respiratory airways disease. The upper respiratory condition consisting in an uvula oedema required an empiric anti-inflammatory and antibiotic therapy which masked the clinical features usually seen in the case of rickettsial infections, especially cutaneous rash. Although the patient subsequently presented unexplained cardiac and neurological involvement, the starting treatment interfered with the diagnostic process, resulting in a delayed diagnosis. Rickettsia and other conditions related with a possible tick bite have to be considered in the list of differential diagnosis especially in the case of severe systemic or localised disease, particularly when the only suspicious sign is a clinical history indicative of a patient living in poor conditions of hygiene.

DHR-ICMR Guidelines for diagnosis & management of Rickettsial diseases in India.

Rickettsial diseases, caused by a variety of obligate intracellular, gram-negative bacteria from the genera Rickettsia, Orientia, Ehrlichia, Neorickettsia, Neoehrlichia, and Anaplasma, belonging to the Alphaproteobacteria, are considered some of the most covert emerging and re-emerging diseases and are being increasingly recognized. Among the major groups of rickettsioses, commonly reported diseases in India are scrub typhus, murine flea-borne typhus, Indian tick typhus and Q fever. Rickettsial infections are generally incapacitating and difficult to diagnose; untreated cases have case fatality rates as high as 30-45 per cent with multiple organ dysfunction, if not promptly diagnosed and appropriately treated. The vast variability and non-specific presentation of this infection have often made it difficult to diagnose clinically. Prompt antibiotic therapy shortens the course of the disease, lowers the risk of complications and in turn reduces morbidity and mortality due to rickettsial diseases. There is a distinct need for physicians and health care workers at all levels of care in India to be aware of the clinical features, available diagnostic tests and their interpretation, and the therapy of these infections. Therefore, a Task Force was constituted by the Indian Council of Medical Research (ICMR) to formulate guidelines for diagnosis and management of rickettsial diseases. These guidelines include presenting manifestations, case definition, laboratory criteria (specific and supportive investigations) and treatment.

[Exanthems and fever in travellers returning from the tropics]. / Exanthem und Fieber nach Tropenaufenthalt.

Dengue fever with its subtle rash is today more common than malaria in travellers returning to Europe from the tropics (meta-analysis Geo Sentinel network). Up to 5 % of all safari tourists experience African tick bite fever during or soon after their journey; it is caused by rickettsiae and clinically presents with exanthems, focal necrotizing vasculitis (eschar, tache noir), lymphadenopathy and moderate fever. Typhoid fever is a severe infectious disease is which is difficult to diagnosis at first assessment. The presence of rose spots, which may be found in up to 33 % of patients with typhoid fever, can lead the way to diagnosis. Exanthems can be subtle and may occur weeks after infection without any other distinctive clinical sign. Particular importance in travel medicine has to be paid to acute HIV infection and secondary syphilis after exposition and infection in the tropics. Also the highly contagious infectious diseases of childhood as measles and rubeola have to be taken into account in adults with no or insufficient vaccination after a stay in tropical countries.

Rickettsiae, protozoa, and opisthokonta/metazoa.

Rhizobiales (formerly named Rickettsiales) cause in rare instances meningitis and meningovasculitis, respectively. In case of history of exposure, infection by Rhizobiales needs to be considered since both diagnosis and therapy may be extremely difficult and pathogen-specific. The same applies to protozoa; in this chapter, Babesia species, free-living amoebae and Entamoeba histolytica infection, including severe meningitis and brain abscess, infection by Trypanosoma species (South American and African trypanosomiasis) are discussed with respect to history, epidemiology, clinical signs, and symptoms as well as differential diagnosis and therapy. Parasitic flatworms and roundworms, potentially able to invade the central nervous system, trematodes (flukes), cestodes (in particular, Cysticercus cellulosae), but also nematodes (in particular, Strongyloides spp. in the immunocompromised) are of worldwide importance. In contrast, filarial worms, Toxocara spp., Trichinella spp., Gnathostoma and Angiostrongylus spp. are seen only in certain geographically confined areas. Even more regionally confined are infestations of the central nervous system by metazoa, in particular, tongue worms (=arthropods) or larvae of flies (=maggots). The aim of this chapter is (1) to alert the neurologist to these infections, and (2) to enable the attending emergency neurologist to take a knowledgeable history, with an emphasis on epidemiology, clinical signs, and symptoms as well as therapeutic management possibilities.

Doxicilina injetável e o cloranfenicol suspensão para terapêutica da febre maculosa brasileira e outras riquetsioses / Doxycycline and chloramphenicol suspension for therapy of Brazilian spot fever and other rickettsial

A febre maculosa brasileira (FMB) é uma doença infecciosa febril aguda, de transmissão vetorial exclusiva, de gravidade variável, cuja apresentação clínica pode variar desde formas leves e atípicas até formas graves, com elevada taxa de letalidade, sendo por isso considerada um problema de saúde pública e doença de notificação compulsória no Brasil. Tendo em vista a limitação das técnicas laboratoriais atuais em possibilitar o diagnóstico específico imediato e a rápida progressão para formas graves da doença, a recomendação formal é de que frente a casos suspeitos da doença, que apresentem os critérios clínicos e laboratoriais compatíveis com os critérios de definição vigentes, a terapêutica específica (doxiciclina ou cloranfenicol), seja em âmbito ambulatorial ou hospitalar, deve ser prontamente instituída. O sucesso do tratamento está relacionado à precocidade e à especificidade de sua instalação. Os únicos fármacos com comprovada ação e eficácia são as tetraciclinas e o cloranfenicol. A escolha entre a tetraciclina (doxiciclina) e o cloranfenicol relaciona-se à gravidade da doença, devendo-se priorizar a tetracilina em função de sua superioridade. Considerando o alto potencial de letalidade da FMB e frente às evidências científicas sob a eficácia do uso da doxiciclina e do cloranfenicol, o Ministério da Saúde, em seu material instrucional (Guia de Vigilância Epidemiológica) da Secretaria de Vigilância em Saúde, recomenda estes medicamentos para o tratamento de pacientes com sinais e sintomas clínicos da febre maculosa brasileira. No entanto, não estão disponíveis a doxiciclina injetável e o cloranfenicol solução, por desinteresse comercial de laboratórios produtores e indisponibilidade de registro dos medicamentos no Brasil, o que motiva a aquisição destas drogas via \r\nimportação e disponibilização como medicamentos do componente estratégico do Ministério da Saúde para o tratamento da FMB e outras riquetsioses. Conforme avaliação realizada pela área técnica de vigilância epidemiológica da FMB e outras riquetsioses e Departamento de Assistência Farmacêutica do MS, estes \r\nmedicamentos poderão ser adquiridos de forma centralizada pelo Ministério da Saúde com recurso próprio e destinados às áreas endêmicas do país. Nesta avaliação, considerando as opções terapêuticas existentes no Brasil (doxiciclina comprimidos e cloranfenicol injetável), será necessária para atender a demanda anual a aquisição do quantitativo de 24.000 mil ampolas de doxiciclina injetável (100 mg) e 4.000 frascos de cloranfenicol solução (125 mg), o que promoverá um impacto orçamentário anual na ordem de US$ 126.000,00 mil dólares, estimativa anual baseada nas notificações de casos da FMB, que deverão ser tratados com os \r\nrespectivos medicamentos. Diante do exposto, os membros da CONITEC, presentes na reunião ordinária do \r\ndia 1º de agosto de 2013, decidiram, por unanimidade, pela incorporação da doxiciclina injetável e cloranfenicol solução para terapêutica antimicrobiana em pacientes com febre maculosa brasileira e outras riquetsioses.

Childhood rickettsiosis.

Rickesttsial diseases are a group of diseases caused by obligate intracellular gram negative bacilli and transmitted to man by arthropod vectors (except Q fever). It is increasingly realised that rickesttsial diseases are underdiagnosed. It is now well documented that rickettsial disease is prevalent all over India, in pockets. The hallmark of rickettsial infection is microvasculitis, causing microinfarcts in various organs. Usually the patients present with classical triad of Fever, Headache & Rash. Apart from this, pain in legs, oedema, Gastro-intestinal symptoms, hepato-splenomegaly, anaemia, necrotic rash, gangrene of digits, toes, earlobes, scrotum, painless eschar and lymphadenopathy are other manifestations. Complications include encephalitis, ARDS, pneumonia, Myocarditis, Renal failure and Vascular collapse. Endocarditis is seen in Q fever. Gold standard test for confirmation of diagnosis is I.F.A. Weil felix test is widely available but unacceptable for accurate diagnosis. Weil Felix test can be used in developing countries where other tests are not available. ELISA Should be preferred and is now available in India. The drug of choice for all age group is doxycycline. Rickettsia are potentially dangerous pathogens and unfortunately, specific serological tests are available in only a few specialized laboratories. Hence, it is imperative to have a high index of suspicion for Rickettsial diseases and make a clinical diagnosis based on prudent history taking and appropriate physical findings. A therapeutic trial with a specific agent in these patients is justified because a delay in initiating treatment may prove fatal. A rapid and favorable response is suggestive of a correct diagnosis.

Rickettsial and ehrlichial infections.

Rickettsial diseases represent a clinically homogeneous group of infections characterized by fever, headache myalgias, variable presence of a rash, and a broad spectrum of neurological manifestations. Epidemiological information including time of year, geography, history of arthropod exposure, and animal contact gives important clues to the diagnosis, and should be actively elicited. Abnormalities in hematological indices of liver function tests should also increase suspicion for illness. Delay in initiation of doxycycline therapy while awaiting laboratory confirmation of infection has been associated with progressive neurological impairment and death. Clinicians should maintain a low threshold to initiate empiric therapy for rickettsial diseases in any patient with neurological findings and compatible exposures, signs, or laboratories, as these syndromes represent readily treatable causes of neurological dysfunction.

Fever in returned travellers presenting in the United Kingdom: recommendations for investigation and initial management.

International travel is increasing. Most physicians and general practitioners will encounter returned travellers with fever and the majority of travel-related infection is associated with travel to the tropics. In those returning from the tropics malaria must always be excluded, and HIV considered, from all settings. Common causes of non-malarial fever include from Africa rickettsial diseases, amoebic liver abscess and Katayama syndrome; from South and South East Asia, enteric fever and arboviral infection; from the Middle East, brucellosis and from the Horn of Africa visceral leishmaniasis. Other rare but important diseases from particular geographical areas include leptospirosis, trypanosomiasis and viral haemorrhagic fever. North and South America, Europe and Australia also have infections which are geographically concentrated. Empirical treatment may have to be started based on epidemiological probability of infection whilst waiting for results to return. The evidence base for much of the management of tropical infections is limited. These recommendations provide a pragmatic approach to the initial diagnosis and management of fever in returned travellers, based on evidence where it is available and on consensus of expert opinion where it is not. With early diagnosis and treatment the majority of patients with a potentially fatal infection related to travel will make a rapid and full recovery.