Renal Involvement in Mediterranean Spotted Fever: Clinical and Histopathological Data.

OBJECTIVE: Mediterranean spotted fever (MSF) is a tick-borne rickettsial infection endemic to the Mediterranean coastline countries. As a result of growing tourism, imported cases have been registered in many nonendemic countries and regions. We present clinical laboratory parameters and histopathological data on renal impairment in patients with MSF. The study meets our goal of identifying kidney involvement and detecting renal damage in people with MSF. SUBJECTS AND METHODS: Three hundred fifty patients with MSF with a diagnosis confirmed by immunofluorescence analysis were tested for serum urea, creatinine, and albumin. Fifty-five patients with malignant form of MSF were divided into 2 groups: 19 fatalities and 36 survivors. The percentage of patients with acute renal failure (ARF) was compared in both groups. RESULTS: Subjects with elevated urea and creatinine levels increased from 5.21 to 3.47% in mild to 48.78 and 29.26% in severe MSF, respectively. Loss of serum albumin also increased from mild to severe MSF. Renal impairment comprised 60% of the cohort of 55 patients with malignant MSF: 89.4% in the group of deaths and almost twice less in the survivors. ARF developed in 84.2% of fatal cases and was >2 times less in survivors. Postmortem light microscopy of renal samples of 9 fatal cases revealed perivascular mononuclear inflammatory infiltrates, vasculitis with fibrinoid necrosis, acute tubular necrosis, interstitial edema, hemorrhage, and thrombosis. CONCLUSION: Renal pathology associated with MSF rickettsial infection consists of systemic small vessel vasculitis and vascular injury, leading to ARF in the most severe cases.

[Retrospective serological diagnostics of spotted fever group rickettsioses in high risk areas of Rickettsia conorii subsp. Caspia infection.]

723 blood sera from 537 patients of Regional Infectious Clinical Hospital, Astrakhan were obtained during high activity period of Rhipicephalus ticks (May-September 2015) and retrospectively studied for IgG/IgM to antigen of spotted fever group (SFG) Rickettsia. IgG and/or IgM to Rickettsia conorii were detected in 145 sera from 130 patients, and antibodies to R. sibirica (group-specific) were detected in 143 sera from 145. Antibodies to R. conorii were detected for 71,4% patients with Astrakhan spotted fever (ASF), for 28,4% patients with acute respiratory viral infection, for 19,1% patients with infection of unspecified etiology and for 40% patients having symptoms of a adenovirus infection. Acute rickettsiosis, provably ASF, is serologically validated for 71 patients. Dynamic of IgM/IgG to R. conorii in sera of patients having different preliminary diagnoses is discussed. IgM to R. conorii in sera of patients having adenovirus infection symptoms were detected at a later time as compared with others. For regions of high risk of R. conorii subsp. caspia infection the differentiation of diagnostic and anamnestic specific antibodies is very important. The absence of serological and molecular biological markers in third of patients with ASF symptoms is necessary to study. Preparations and algorithms for diagnosis of SFG rickettsioses are needed to improve.

[A Rickettsia case caused by Rickettsia conorii]. / Rickettsia conorii'nin neden oldugu riketsiyal enfeksiyon olgusu.

Rickettsia species are gram-negative intracellular, small pleomorphic coccobacilli in the Rickettsiaceae family. This genus is serologically and genotypically divided into four groups as spotted fever group, typhus group, Rickettsia belli and Rickettsia canadensis. Rickettsia conorii (R.conorii subsp. conorii) in the spotted fever group was reported to cause mediterranean spotted fever in Europe, especially in mediterranean countries including Turkey. The major vectors of Rickettsia species are ticks, and in some species fleas or mites. In this report a case with R.conorii infection was presented. A 46-year-old female patient, who had anorexia, fatigue, muscle aches, chills and high fever was admitted to a health institution. The patient was diagnosed as influenza. There was no regression in the patient's complaints with the recommended treatment. The patient was examined in our infectious diseases clinic and had several symptoms like severe muscle and joint pain with significant headache, and rashes at her body including hands and feet. The patient had a single eschar in the upper midline of the belly that matched tick biting and pink small maculopapular scars on the trunk, arms, legs, feet, and hands. Considering a Rickettsia pre-diagnosis, liquid electrolyte and doxycycline 2 x 100 mg oral treatment was started. On the third day of treatment, high fever, muscle and joint pain were decreased. On the fifth day, active skin lesions were started to fade. R.conorii IgM and IgG were negative in the first serum sample of the patient. In the biopsy sample taken from eschar tissue, Rickettsia spp. was detected as positive with rt-PCR. PCR was used by using the specific regions of the genetically specific gltA and ompA genes in the biopsy specimens and then the PCR products were determined by DNA sequence analysis. The DNA sequence results were compA red with Genbank data and determined that the gltA sequence was 99%, similar to R.conorii with accession number JN182786 and the ompA sequence was 99%, similar to R.conorii with accession number KR401144. When the phylogenetic tree was created, it was observed that the etiological agent was R.conorii. A week after the treatment, in the second serum sample R.conorii IFA IgM 1/192 titer and IgG 1/320 titer were detected as positive. In this case report, we have presented a Rickettsia case, clinically diagnosed as Rickettsia, serologically negative in the acute phase, PCR positive, with post-treatment seroconversion and etiologic agent determined as R.conorii.

Mediterranean Spotted Fever in Children: Study of a Portuguese Endemic Region.

INTRODUCTION: Mediterranean spotted fever is an infectious disease included in the human rickettsiosis group, with its main distribution in the Mediterranean and South European countries. It is an endemic disease in Portugal, with dogs acting as the main domestic reservoir. Children are a particularly vulnerable group due to their close contact with household animals and by frequently playing outdoors. In this study, we aim to describe the local epidemiology and characterize the clinical features and treatment options in a Portuguese endemic region. MATERIALS AND METHODS: We performed a prospective descriptive study of the Mediterranean spotted fever cases admitted to the paediatrics emergency department of a of a group II hospital, between January 1st 2013 and December 31st 2015. All patients were examined by a physician, who was later asked to fill out a detailed questionnaire regarding clinical presentation, diagnostic attitudes and treatment of their patients. Parents were later interviewed and questioned about post-discharge disease evolution. RESULTS: We registered 32 cases (93.9% reported between July and October). After fever, the most frequent reported symptoms were myalgia (37.5%), abdominal pain (25%) and headache (25%). Exanthema was present in 84.4% of cases by the third day of fever:maculonodular (53.1%), papular (37.5%) and macular (9.4%). Eschars were found in 59% of patients, with regional lymphadenopathypresent in 46.9% of cases. Azithromycin (84.4%) and doxycycline (15.5%) were the selected treatments in our population, with no cases of therapeutic failure or side-effects reported. CONCLUSION: The incidence of Mediterranean spotted fever is higher in our population in comparison with the rest of the country. Fever, myalgia, abdominal pain and headache were the most common presenting symptoms, while exanthema was the predominant cutaneous finding. Azithromycin was the preferred treatment and it proved to be successful and safe in all cases.

Introdução: A febre escaro-nodular é uma doença infeciosa aguda incluída no grupo das rickettsioses humanas, que atinge sobretudo os países da bacia do Mediterrâneo e sul da Europa. É uma doença endémica em Portugal com o cão como principal reservatório doméstico. As crianças são um grupo particularmente vulnerável devido ao contato próximo com animais domésticos e a brincarem em campos e jardins. O principal objetivo deste estudo foi perceber e estudar a epidemiologia local, bem como caracterizar a clinica e a resposta terapêutica da nossa população. Material e Métodos: Foi realizado um estudo prospetivo descritivo de todas as crianças com febre escaro-nodular admitidas no serviço de urgência de um hospital grupo II, entre janeiro de 2013 e dezembro de 2015. Todos os doentes foram avaliados por médico, que respondeu a um questionário referente as manifestações clínicas apresentadas e atitudes de diagnóstico e terapêuticas instituídas. Os pais foram posteriormente contatados, por telefone, e questionados sobre a evolução da doença. Resultados: Foram registados 32 casos (93,9% de julho a outubro). Além da febre, as queixas mais frequentes foram mialgias (37,5%), dor abdominal e cefaleias (25%). O exantema estava presente no terceiro dia de febre em 84,4%: maculopapulonodular (53,1%); papular (37,5%) e macular (9,4%). Foi identificada escara em 59% e adenopatia satélite em 46,9%. Azitromicina (84,4%) ou doxiciclina (15,5%) foram os antibióticos de escolha, com sucesso em qualquer dos casos. Não foram relatadas complicações. Conclusão: A incidência de febre escaro-nodular na nossa população é alta, quando comparada com a incidência no restante país. Febre, mialgias e cefaleias foram os principais sintomas e sinais registados enquanto a presença de exantema foi o achado dermatológico predominante. Azitromicina, antibiótico de escolha na maioria dos casos, mostrou ser eficaz.

Shell-vial culture, coupled with real-time PCR, applied to Rickettsia conorii and Rickettsia massiliae-Bar29 detection, improving the diagnosis of the Mediterranean spotted fever.

Rickettsia conorii and Rickettsia massiliae-Bar29 are related to Mediterranean spotted fever (MSF). They are intracellular microorganisms. The Shell-vial culture assay (SV) improved Rickettsia culture but it still has some limitations: blood usually contains low amount of microorganisms and the samples that contain the highest amount of them are non-sterile. The objectives of this study were to optimize SV culture conditions and monitoring methods and to establish antibiotic concentrations useful for non-sterile samples. 12 SVs were inoculated with each microorganism, incubated at different temperatures and monitored by classical methods and real-time PCR. R. conorii was detected by all methods at all temperatures since 7th day of incubation. R. massiliae-Bar29 was firstly observed at 28°C. Real-time PCR allowed to detected it 2-7 days earlier (depend on temperature) than classical methods. Antibiotics concentration needed for the isolation of these Rickettsia species from non-sterile samples was determined inoculating SV with R. conorii, R. massiliae-Bar29, biopsy or tick, incubating them with different dilutions of antibiotics and monitoring them weekly. To sum up, if a MSF diagnosis is suspected, SV should be incubated at both 28°C and 32°C for 1-3 weeks and monitored by a sensitive real-time PCR. If the sample is non-sterile the panel of antibiotics tested can be added.

Skin lesions and inoculation eschars at the tick bite site in spotted fever group rickettsioses: experience from a patient series in eastern crete, Greece.

The main clinical signs and symptoms caused by a rickettsial infection typically begin 6-10 days after the bite and are accompanied by nonspecific findings such as fever, headache and muscle pain. The diagnosis is mainly based on serological tests, however antibody presentation may be delayed, at least at the early stages of the disease, while seroconversion is usually detected 10-15 days after disease onset. Culture is difficult, requires optimized facilities and often proves negative. Under this scope, the presence of a characteristic inoculation eschar at the bite site may prove a useful clinical tool towards the early suspicion and diagnosis/differential diagnosis of tick-borne rickettsioses, even before the onset of rash and fever or serological confirmation. We describe herein the presence of skin lesions and/or an inoculation eschar at the tick bite site in 17 patients diagnosed, by molecular means, as suffering from spotted fever group rickettsioses. The detection of the pathogen's DNA in biopsy samples proved to be a useful means for early rickettsiae detection and identification. Moreover, the presence of an infiltrated erythema always seemed to precede the appearance of an eschar by 2-5 days and the initiation of fever by 1-10 days; these two signs might also prove useful in the context of the final diagnosis.

Changes of Bcl-2, Bax and Caspase-3 expression in the dermal microvascular endothelial cells and the epidermal layers of the eschar (tache noire) in patients with Mediterranean spotted fever.

Mediterranean spotted fever (MSF) is widely prevalent in many endemic regions in Bulgaria. The disease is still not quite thoroughly studied as to some aspects of its pathogenesis and especially to issues that concern the crucial signals for apoptosis in the target microvascular endothelial cells. To study the expression of Bcl-2 family proteins and Caspase-3 in the dermal capillary endothelial cells from skin papules and in the eschar (tache noire) epidermal layers of patients with MSF so that we can establish apoptotic processes and the time of their occurrence and deployment. Immunohistochemical reactions for Bcl-2, Bax and Caspase-3 were obtained in slices of punch-biopsies taken from papules of the skin rash and from the eschars of eight patients with MSF. The average intensity of the reactions was compared with that in control punch-biopsy slices from four healthy subjects. MSF was etiologically confirmed in all patients by positive antibody response to a specific antigen, Rickettsia conorii, with indirect immunofluorescent assay performed by the Rickettsial Reference Laboratory. The immune reaction for Bcl-2 was found to be poorly expressed in the capillary endothelial cells of skin papules of patients without any differences from controls. The expression of Bax and Caspase-3 was strongly upregulated in comparison with the controls. The Bcl-2/Bax ratio was significantly decreased. Microvascular endothelial cells of the eschar showed similar changes. While the Bcl-2/Bax ratio decreased in the epidermal layers of the eschar "tache noire", there were no changes in the intensity of the immunoreactivity of Caspase-3 as compared with controls. The upregulation of Bax and Caspase-3 is an indication of ongoing apoptotic processes in the dermal microvascular endothelial cells of MSF patients. The epidermal layers of the eschar showed increased sensitivity to apoptosis, however, executive phase of apoptosis did not occur.

Q fever and Mediterranean spotted fever associated with hemophagocytic syndrome: case study and literature review.

BACKGROUND: Hemophagocytosis during Q fever (QF) and Mediterranean spotted fever (MSF) is rare and only a few cases have been reported. We aimed to investigate the characteristics, outcome, and treatment of QF/MSF-associated hemophagocytosis. METHODS: We retrospectively reviewed all patients with a diagnosis of QF or MSF and suspected hemophagocytic syndrome (HS), according to Henter's criteria, between 2002 and 2011, and compared the latter to patients without HS or with lymphoma-associated HS. RESULTS: Seventeen patients with HS (median age 42 years, range 5-68 years; five females (29%)) with QF (n=8) and MSF (n=9) were included in this study. When comparing patients with QF- and MSF-associated HS with patients without HS (n=11), HS-associated signs (splenomegaly, ferritinemia, hypertriglyceridemia, and cytopenia) were significantly more frequent in patients with histological HS (p<0.05), along with a greater number of Henter's criteria. Despite the presence of HS-associated signs, treatment was similar in these two subgroups, including the time to recovery and the outcome. When compared to lymphoma-associated HS (n=10), the outcome in QF/MSF-associated HS was significantly different, with mortality in 70% of lymphoma patients versus none in QF- and MSF-associated HS (p<0.05). CONCLUSION: Hemophagocytosis is a rare occurrence during the course of QF and MSF. The presence of profound cytopenia is quite unusual in QF and MSF and should bring to mind the presence of associated HS. Nevertheless, hemophagocytic syndrome is associated with a good outcome in this condition.

Mediterranean spotted fever--classification by disease course and criteria for determining the disease severity.

INTRODUCTION: Mediterranean spotted fever (MSF) in Bulgaria is caused by Ricketsia conorii conorii with a major vector the dog tick, Rhipicephalus sanguineus. The first cases of re-emerging MSF were reported in this country in the early 1990s after some 20 years of absence and then registered an annual increase until 2001-2003 after which the disease prevalence declined. MSF still poses a serious health problem in the country as severe, complicated cases with lethal outcome occur. The aim of this paper was to classify the forms of MSF according to the course of the disease process and to devise criteria for the disease severity in order to enable comparison of clinical manifestations of the disease at different stages of spreading, in different age groups, and between endemic and non-endemic regions in this country and abroad. PATIENTS AND METHODS: The study was carried out in a comparative aspect during the first phase of increase (1993-2003) with incidence of 11.88 per 100000 population and during the second phase of decline (2004-2011) with incidence of 9.56 per 100000 population. The disease was etiologically confirmed in 883 hospitalized patients by the positive antibody response to the specific antigen--Ricketsia conorii conorii by means of the immunofluorescence assay (IFA). The criteria we used for the classification of the forms of MSF included: 1. Typicality: forms having the most characteristic features of the MSF - eschar, fever, papular/maculopapular rash on the trunk and extremities, including hands and feet. 2. Manifestation: forms represented by all or some of the typical symptoms, giving sufficient grounds for preliminary diagnosis. 3. DURATION: fulminant, acute and protracted forms. The criteria for severity differentiate between mild, moderate, severe or malignant forms, and include clinical and laboratory parameters as shown in the present study. RESULTS: Classification of the forms according to MSF course defines them in order of severity, typicality, manifestation, duration of symptoms, complications and age characteristics. According to the accepted criteria for severity and with respect to the studied I and II phase of the disease the mild forms are 41.16%-35.62% (p > 0.05), moderate forms are 32.79%-43.11% (p < 0.01), severe forms are 16.03%-11.37% (p = 0.05), malignant forms are 6.56%-8.68% (p > 0.05), and mortality is 3.46%-1.19% (p < 0.05). The mean age was significantly higher for patients with severe forms of MSF (58.59 +/- 4.32 yrs) compared with those with moderate (46.10 +/- 3.71 yrs, p < 0.05) and mild forms (42.05 +/- 3.50 yrs, p < 0.01). For children up to 14 years old mild forms are more common than in adults over 65 (p < 0.0001). Among children up to 14 years old there were no lethal outcomes, while mortality rate in the patients older than 65 was as much as 10%. All this indicates that MSF runs a milder course in children and a severe, complicated course in the elderly. CONCLUSION: The criteria for MSF severity we have selected are based on our own experience and the experience of other authors. They are based on the reaction of human organism to the pathogenic agent and can be used during the different phases of emergence and development of rikettsial diseases, regardless of their geographic distribution. Unified use of these criteria would eliminate the differences in the data reported by different researchers regarding the disease development and severity.

Fatal Mediterranean spotted fever in Greece.

Forty-five days after the first confirmed and fatal Crimean-Congo haemorrhagic fever (CCHF) case in Greece in 2008, a female patient with similar signs and symptoms (high fever, thrombocytopaenia) and resident of the same area, was admitted to the University General Hospital of Alexandroupolis. Before admission, she had visited a local hospital where a cephalosporin was prescribed. A rash manifested over subsequent days, which was misdiagnosed as an allergy to the drug. Upon admission to the University Hospital, she was given further antibiotics, including doxycycline; a few hours later, ribavirin was added because CCHF was suspected. After the patient's death, rickettsiosis caused by Rickettsia conorii conorii (Meditteranean spotted fever; MSF) was diagnosed. Extremely high values of interleukin (IL)-1ra, IL-6, interferon-gamma-inducible protein-10, monocyte chemoattractant protein-1 and an absence of tumour necrosis factor-alpha were observed. MSF is a potentially severe and even fatal disease resembling viral haemorrhagic fevers that has to be included in the differential diagnosis of febrile syndromes combined with thrombocytopaenia, even when a tick bite is not reported, and an eschar is absent. Physicians have to be aware of MSF in patients with severe disease who are returning from the Mediterranean area.

Prospective evaluation of rickettsioses in the Trakya (European) region of Turkey and atypic presentations of Rickettsia conorii.

In 2004 between the months of May-November, 11 patients with spotted fever group (SFG) rickettsioses were admitted to the Trakya University Hospital in Edirne, Turkey. SFG rickettsioses were diagnosed clinically. Before treatment, punch biopsy from skin lesions, especially from the eschar, was performed. Serum specimens were tested by IFA using a panel of nine rickettsial antigens, including SFG rickettsiae and R. typhi. Western blotting and standard PCR were also performed. The average age of the 11 patients (4 male and 7 female) was 51 years. All the patients had high fever; 10 (91%) had maculopapular rash; 8 (73%) had rash in the palms or on the soles. Five patients had a unique eschar; two had double eschars (64%). Two patients presented with multiple organ failure and one of them died. All the patients had significant antibody titers against SFG rickettsiae. PCR experiments of skin biopsies were positive in six (60%) of 10 skin biopsy samples and DNA sequencing of the positive PCR products gave 100% homology with Rickettsia conorii Malish 7 for opmA and gltA. Trakya Region in an endemic area for rickettsioses. In this series, three patients presented with life-threatening diseases and one of them died. This patient was the first fatal case (2.8%). Atypic and serous life-threatening presentations of rickettsioses must be kept in mind for the differential diagnosis of febrile disease in Turkey.

Characterisation of rickettsial diseases in a hospital-based population in Malta.

OBJECTIVE: The aim of the study was to characterise the causative agents of rickettsial disease in Malta. A secondary objective was to study the epidemiology of cases of rickettsial disease. METHODS: Cases admitted to St Luke's Hospital between June 2002 and May 2003 presenting with complaints of fever, headache, rash and/or an eschar were considered possible cases of rickettsial disease. A patient interview was conducted within 24h of admission. Paired sera were taken for serology and blood samples sent for rickettsial PCR and culture. Whenever an eschar was present, biopsies were taken for culture and immunohistochemical analysis. RESULTS: Thirty-three cases of possible rickettsial disease were identified. Although serological tests showed cross reactivities between different species of rickettsiae, one was diagnostic for Rickettsia conorii. None of the sera showed any cross-reactivity with Rickettsia typhi. There was one positive biopsy for R. conorii when tested by PCR and another was positive for spotted fever group Rickettsia by immunohistochemistry. CONCLUSION: Spotted fever rickettsiosis is endemic in Malta. Contrary to previous belief, none of the cases were due to murine typhus. The predominant causative agent of rickettsial disease in Malta is likely to be R. conorii, although the animal reservoir has still not been definitely identified.

Riquetsioses no Brasil e Portugal: ocorrência, distribuição e diagnóstico / Rickettsial diseases in Brazil and Portugal: occurrence, distribution and diagnosis

O presente artigo é uma atualização sobre a ocorrência e diagnóstico das riquetsioses existentes no Brasil e Portugal, com o objetivo de incentivar e incrementar a vigilância epidemiológica dessas doenças nos dois países. Realizou-se levantamento bibliográfico e foram apresentados dados não publicados de laboratórios e serviços de epidemiologia. Os resultados descreveram a ocorrência das riquetsioses no Brasil e Portugal, inclusive aquelas recém-descritas, advindas de riquétsias de potencial patogênico ainda incerto. Os métodos diagnósticos atualmente empregados foram discutidos. Como em outros países, as riquetsioses parecem assumir crescente importância em saúde pública. Relegadas a um plano secundário por muitas décadas, o interesse por essas infecções tem aumentado nos dois países, mas ainda carece de investigação para esclarecer seu real significado em saúde pública.

Rickettsial infections around the world, part 1: pathophysiology and the spotted fever group.

BACKGROUND: The rickettsial diseases are an important group of infectious agents that have dermatological manifestations. These diseases are important to consider in endemic areas, but in certain suspicious cases, possible acts of bioterrorism should warrant prompt notification of the appropriate authorities. OBJECTIVE: In this two part review article, we review these diverse diseases by examining established and up-to-date information about the pathophysiology, epidemiology, clinical manifestations, and treatment of the ricksettsiae. METHODS: Using PubMed to search for relevant articles, we browsed over 500 articles to compose a clinically based review article. RESULTS: Part one focuses on pathophysiology of the rickettsial diseases and the clinical aspects of the spotted fever group. CONCLUSIONS: At the completion of part one of this learning activity, participants should be able to discuss all of the clinical manifestations and treatments of the sported fever group. Participants should also be familiar with the pathophysiology of the rickettsial diseases.

Posterior segment manifestations of Rickettsia conorii infection.

PURPOSE: To characterize and analyze the posterior segment manifestations of Mediterranean spotted fever (MSF), an infectious disease caused by Rickettsia conorii. DESIGN: Prospective, noncomparative case series. PARTICIPANTS: Thirty patients (60 eyes) with serologically proven MSF at the acute stage. METHODS: Patients underwent complete ophthalmic examination, including dilated biomicroscopic fundus examination, fundus photography, and fluorescein angiography. Sequential follow-up examinations were performed in patients with evidence of posterior segment involvement. RESULTS: Of 30 patients, 25 (83.3%) had unilateral (n = 5) or bilateral (n = 20) posterior segment involvement related to MSF. Of those 25 patients, 16 (64%) had no ocular symptoms, and 9 (36%) had ocular complaints. Findings included mild vitreous inflammation (45 eyes [75%]), white retinal lesions (18 eyes [30%]), focal vascular sheathing (5 eyes [8.3%]), multiple arterial plaques (1 eye [1.7%]), intraretinal hemorrhages (14 eyes [23.3%]), white-centered retinal hemorrhages (2 eyes [3.3%]), subretinal hemorrhages (2 eyes [3.3%]), serous retinal detachment (3 eyes [5%]), macular star (2 eyes [3.3%]), cystoid macular edema (1 eye [1.7%]), optic disc edema (1 eye [1.7%]), branch retinal artery occlusion (1 eye [1.7%]), optic disc staining (30 eyes [50%]), retinal vascular leakage (27 eyes [45%]), delayed filling in a branch retinal vein (1 eye [1.7%]), and multiple hypofluorescent choroidal dots (10 eyes [16.7%]). One eye (1.7%) had retinal neovascularization at the 6-month follow-up examination. All posterior segment findings at the acute stage resolved in 3 to 10 weeks, and the final visual acuity was 20/20 in 42 of 45 affected eyes (93.3%). Retinal pigment epithelium changes developed in 9 eyes (15%), with resolved full-thickness white retinal lesions. No other abnormalities were noted in the eye with retinal neovascularization over a further follow-up of 6 months. CONCLUSION: Posterior segment involvement, frequently asymptomatic, is common in patients with acute MSF. Because the diagnosis can be easily overlooked, a careful dilated funduscopic examination, complemented by fluorescein angiography in selected cases, is recommended. Mild vitritis, retinal vasculitis, optic disc staining, white retinal lesions, retinal hemorrhages, and multiple hypofluorescent choroidal dots are the most common manifestations of MSF. Posterior segment changes in a patient with fever and/or skin rash living in or returning from a specific endemic area, especially during the spring or summer, strongly suggest R. conorii infection.