Utilidad del diagnóstico molecular precoz de fiebre Q y rickettsiosis en pacientes con fiebre de duración intermedia / Usefulness of the early molecular diagnosis of Q fever and rickettsial diseases in patients with fever of intermediate duration

La mayor parte de los casos de fiebre de duración intermedia (FDI) en España corresponden a enfermedades infecciosas (principalmente fiebre Q y rickettsiosis). En la práctica clínica el diagnóstico causal de estas entidades se basa en el inmunodiagnóstico, con una escasa utilidad en fases precoces. Por ello, el objetivo de este trabajo fue la evaluación de la utilidad de técnicas moleculares en el diagnóstico precoz de fiebre Q y rickettsiosis en pacientes con FDI. Se estudió mediante PCR la presencia de material genético de Coxiella burnetii y Rickettsia spp. en muestras sanguíneas de 271 pacientes con FDI. La especificidad de ambas técnicas es elevada, permitiendo el diagnóstico en casos no diagnosticados mediante detección de anticuerpos específicos. Estos datos sugieren que el empleo de técnicas moleculares, con una adecuada selección de la muestra de estudio y el empleo de cebadores adecuados, es un elemento útil en el diagnóstico precoz de las principales causas de FDI, principalmente si la serología es negativa o no es concluyente (AU)

Most cases of fever of intermediate duration (FDI) in Spain are associated with infectious diseases (mainly Q fever and rickettsia infections). In clinical practice, the causal diagnosis of these entities is based on immunodiagnostic techniques, which are of little help in the early stages. Therefore, the aim of this study was to evaluate the usefulness of molecular techniques for the early diagnosis of Q fever and rickettsia diseases in patients with FDI. A PCR method was used to detect the presence of genetic material of Coxiella burnetii and Rickettsia spp. in blood specimens from 271 patients with FDI. The specificity of both techniques is high, allowing diagnosis in cases undiagnosed by specific antibodies detection. These data suggest that the use of molecular techniques, with proper selection of the study specimen, and using appropriate primers is a useful tool in the early diagnosis of the main causes of FDI, especially if serology is negative or inconclusive (AU)

Five-year analysis of rickettsial fevers in children in South India: Clinical manifestations and complications.

INTRODUCTION: Rickettsial infections are re-emerging in the Indian subcontinent, especially among children. Understanding geographical and clinical epidemiology will facilitate early diagnosis and management. METHODOLOGY: Children aged <18yrs hospitalized with clinically-diagnosed rickettsial fever were reviewed retrospectively. Frequency distributions and odds ratios were calculated from tabulated data. RESULTS: Among 262 children hospitalized between January 2008-December 2012, median age was five years, and 61% were male children. Hospitalized cases increased steadily every year, with the highest burden (74%) occurring between September and January each year. Mean duration of fever was 11.5 days. Rash was present in 54.2% (142/262) of children, with 37.0% involving palms and soles. Prevalence of malnutrition was high (45% of children were underweight and 28% had stunting). Retinal vasculitis was seen in 13.7% (36/262), and the risk appeared higher in females. Severe complications were seen in 29% (purpura fulminans, 7.6%; meningitis and meningoencephalitis, 28%; septic shock, 1.9%; acute respiratory distress syndrome, 1.1%). Complications were more likely to occur in anemic children. Positive Weil-Felix test results (titers ≥1:160) were seen in 70% of cases. Elevated OX-K titers suggestive of scrub typhus were seen in 80% (147/184). Patients were treated with chloramphenicol (32%) or doxycycline (68%). Overall mortality among hospitalised children was 1.9%. CONCLUSIONS: This five-year analysis from southern India shows a high burden and increasing trend of rickettsial infections among children. The occurrence of retinal vasculitis and a high rate of severe complications draw attention to the need for early diagnosis and management of these infections.

Espectro de las enfermedades transmitidas por garrapatas / Spectrum of thick-borne diseases

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Rickettsiosis, un caso de TIBOLA / Rickettsia, a case of TIBOLA

Las rickettsiosis están cobrando especial protagonismo a raíz de nuevas especies descritas en los últimos años. La más frecuente en nuestro medio es la infección por Rickettsia conorii, que produce la fiebre botonosa mediterránea. Recientemente se incluye con más frecuencia en el diagnóstico diferencial la denominada TIBOLA (tick-borne lymphadenopathy) o DEBONEL (dermacentor-borne necrosis eritema lymphadenopathy), cuya primera confirmación serológica data de 1997 en Francia y que es transmitida por la garrapata Dermacentor marginatus, producida por R. slovaca, entre otras, y con similares características clínicas a las de la fiebre botonosa mediterránea. Se presenta el caso de una niña de ocho años de edad que acude al Servicio de Urgencias con la presencia de fiebre y una lesión costrosa, de aspecto necrótico, en el cuero cabelludo, así como adenopatías de localización cérvico-occipital y retroauricular, refiriendo la picadura de una garrapata hace 15 días. El diagnóstico se confirma mediante la presentación clínica y serologías cruzadas con Rickettsia conorii. Tras pauta de eritromicina a dosis de 40 mg/kg/día durante ocho días se evidencia la desaparición progresiva de las lesiones a lo largo de un mes (AU)

Rickettsia are gaining special importance following new species discovered in recent years. The most common in our environment is Rickettsia conorii infection, which produces the so-called Mediterranean fever boutonneuse. Recently are included more often in the differential diagnosis the called TIBOLA (tick-borne lymphadenopathy) or also known as DEBONEL (dermacentor-borne necrosis lymphadenopathy erythema), whose first serologic confirmation dates back to 1997 in France and is transmitted by the tick Dermacentor marginatus, produced by R. slovaca among others and has similar clinical features as the Mediterranean spotted fever. The case of an 8 year-old who came to the Emergency Services with the presence of fever and scabby lesion, necrotic scalp and cervical lymphadenopathy of occipital and retroauricular location is presented, referring tick bite 15 days ago. The diagnosis is confirmed by clinical and serological tests Rickettsia conorii cross-presentation. After erythromycin dose regimen of 40 mg/kg/day for 8 days, progressive disappearance of lesions was evident after a month (AU)

Rickettsiosis Variceliforme o Viruela Rickettsiósica / Varicelliform Rickettsiosis or Rickettsial pox

El género de las Rickettsias tiene como característica ser bacterias gramnegativas intracelulares que precisan de un vector para su transmisión. Las fiebres exantemáticas producidas por Rickettsias son endémicas en nuestra región (Albacete), sobre todo en áreas rurales. Se presenta el caso de un paciente con una variedad inusual de enfermedad producida por Rickettsias, caracterizada por lesiones papulovesiculosas (AU)

Rickettsia is a genus of intracellular, gram-negative bacteria that requires a vector for transmission. Spotted fever caused by Rickettsia is endemic in our region (Albacete), especially in rural areas. We present a patient with an unusual variety of Rickettsial disease, characterised by papulovesicular lesions (AU)

Transforming growth factor-beta expression by host cells is elicited locally by the filarial nematode Onchocerca volvulus in hyporeactive patients independently from Wolbachia.

Transforming growth factor-beta (TGF-beta) is a key cytokine in immune regulation, cell differentiation, development, wound healing, and tissue remodelling. It mediates immunosuppression in filarial infections facilitating parasite persistence, while attenuating immunopathology, which is induced by migrating microfilariae. Immunosuppression rises with parasite burden, but it remains unknown whether filariae elicit local release of immunosuppressive cytokines. Therefore, using immunohistology, we investigated the expression of stable, released latent TGF-beta1 in subcutaneous nodules from highly infected, hyporeactive onchocerciasis patients, harbouring adult Onchocerca volvulus. Since many cell types produce TGF-beta, we elucidated the cellular source, distribution and dependency on the worms' sex, productivity and vitality. We found TGF-beta1 to be abundantly expressed by T cells, plasma/B cells, macrophages, mast cells, fibrocytes, and vascular endothelial cells, particularly in onchocercomas with productive or previously productive females, damaged, dead and resorbed adult worms or microfilariae. We conclude TGF-beta to be antigen induced by the filariae since expression was scarce around subcutaneous arthropods or cholesterol crystals in onchocercomas. Enhanced expression after ivermectin or endobacteria-depleting doxycycline treatment indicates induction to depend on filariae and not on Wolbachia endobacteria. TGF-beta(+) cells were reduced in HIV co-infection. This finding of local and sustained TGF-beta induction by vital and dead filariae, untreated and after treatment, adds new aspects to immunomodulation by helminths.

A randomized trial of doxycycline for Mansonella perstans infection.

BACKGROUND: Mansonella perstans infection is common in areas of Africa where Wuchereria bancrofti, a causative agent of lymphatic filariasis, is endemic. M. perstans is refractory to standard antifilarial therapies. The recent discovery of bacterial endosymbionts (e.g., wolbachia) in most filarial species, including M. perstans, provides new therapeutic options for reducing microfilaremia. METHODS: In an open-label, randomized trial, we recruited subjects with M. perstans microfilaremia, with or without concomitant W. bancrofti infection, from four villages in Mali and randomly assigned them to receive doxycycline, at a dose of 200 mg daily for 6 weeks (106 subjects), or no treatment (110). At 6 months, subjects who were coinfected with W. bancrofti underwent a second random assignment, to treatment with a single dose of albendazole (400 mg) and ivermectin (150 microg per kilogram of body weight) or no treatment. Subjects were monitored daily during the first 6-week study period for adverse events. M. perstans and W. bancrofti microfilarial levels were assessed at 6, 12, and 36 months. RESULTS: At 12 months, 67 of 69 subjects who had received treatment with doxycycline only (97%) had no detectable M. perstans microfilariae per 60 microl of blood, as compared with 10 of 63 subjects who had received no treatment (16%) (relative risk, 6.18; 95% confidence interval, 3.63 to 11.89; P<0.001). At 36 months, M. perstans microfilaremia remained suppressed in 48 of 64 subjects who had received treatment with doxycycline only (75%), a finding that was consistent with a macrofilaricidal effect of doxycycline. Vomiting was more frequent in the doxycycline-treated group than in the untreated group (17% vs. 4%). CONCLUSIONS: These results are consistent with previous findings that M. perstans harbors the intracellular endosymbiont, wolbachia, and suggest that doxycycline is an effective therapy for M. perstans infection. (ClinicalTrials.gov number, NCT00340691.)

Brote de fiebre exantemática mediterránea por picaduras de garrapatas en una plaza pública / Outbreak of mediterranean exanthematic fever due to tick bites in a public square

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Hepatitis in association with rickettsialpox.

Rickettsialpox is an acute, self-limited, febrile illness caused by Rickettsia akari and transmitted by Liponyssoides sanguineus, a mite that infests the common house mouse, Mus musculus. Liver involvement in rickettsialpox has received little attention, although hepatitis has been reported in several other rickettsial infections. In this report, we describe two patients with rickettsialpox who had acute hepatitis that resolved completely. In the appropriate clinical setting, rickettsialpox should be considered in the differential diagnosis of hepatitis.

A propósito de un caso de fiebre por picadura de garrapata africana / A case report of African tick bite fever

Durante muchos años, la única rickettsiosis conocida en España del grupo de las fiebres manchadas ha sido la fiebre botonosa mediterránea. Sin embargo, la existencia de viajes a países cada vez más lejanos por turismo y el continuo incremento de la inmigración ha dado lugar a un aumento de los casos de las rickettsiosis adquiridas de otros países. Presentamos el caso clínico de un paciente con fiebre por picadura de la garrapata africana (Rickettsia africae)

For many years, the only rickettsiosis known in Spain from the spotted fever group was Mediterranean boutonneuse fever. However, the existence of tourist trips to increasingly far away countries and the continuous increase of immigration have given rise to an increase in the cases of rickettsiosis acquired from other countries. We present the clinical case of a patient with African tick bite fever (Rickettsia africae)

[Ocular manifestations of rickettsial diseases].

Rickettsial infection may cause severe systemic disease. The ocular manifestations of rickettsial infection may include sub-conjunctival hemorrhages, corneal abscesses, uveitis, optic nerve head edema, retinal vasculitis hemorrhages and infiltrates and endophthalmitis. Ocular complications may result in significant visual loss. Ocular manifestations may precede other systemic signs and symptoms and assist in clinical diagnosis. This report describes two cases with ocular involvement of rickettsial disease.

Distrés respiratorio secundario a rickettsiosis / Respiratory distress secondary to Rickettsiosis

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Antibiotic therapy in murine filariasis (Litomosoides sigmodontis): comparative effects of doxycycline and rifampicin on Wolbachia and filarial viability.

The symbiosis of filarial nematodes and rickettsial Wolbachia endobacteria has been exploited as a target for antibiotic therapy of filariasis. Depletion of Wolbachia after tetracycline treatment results in filarial sterility because of interruption of embryogenesis and inhibits larval development and adult worm viability. The aim of this study was to investigate if antibiotic intervention of BALB/c mice infected with the rodent filaria Litomosoides sigmodontis with rifampicin or the combination of rifampicin and doxycycline can be used to shorten the treatment period. Both regimens, when given over a period of 14 days initiated with infection, were sufficient to deplete Wolbachia as evidenced by immunohistology and semiquantitative PCR. Worm development and filarial load were significantly reduced in experiments followed up until 63 days p.i. The therapy inhibited embryogenesis and led to filarial sterility. In contrast, treatment with doxycycline alone for 21 days led only to a modest reduction of Wolbachia, filarial growth retardation, worm viability and fertility. In conclusion, the combination of antirickettsial drugs could be used as a suitable tool to explore the minimum duration of therapy required for the depletion of Wolbachia in parasitized hosts subsequent to the onset of patency in human and animal filariasis and the prevention of adverse reactions in human infections.

Rickettsialpox in a patient with HIV infection.

We describe the first case of rickettsialpox in a patient infected with HIV. Immunohistochemical staining of biopsied lesions showed a relatively large number of rickettsiae within the papulovesicular rash. Rickettsialpox is easily treated and may resemble more serious cutaneous eruptions in patients infected with HIV. This diagnosis should be considered in immunocompromised city-dwellers, with fever and a papulovesicular rash.

Clinical manifestations and complications of rickettsiosis in southern Taiwan.

BACKGROUND AND PURPOSE: Taiwan is an endemic area for scrub typhus. Recent increases have been noted in two other infectious diseases caused by obligate intracellular organisms, Q fever and murine typhus. These diseases usually present as an acute febrile illness with non-specific symptoms and are difficult to distinguish. This study describes the clinical manifestations and complications of cases of rickettsial infections treated at a medical center in southern Taiwan. METHODS: Serum samples from patients with acute febrile illness with or without shock, but without a clinical diagnosis of localized bacterial infection after a preliminary work-up, were collected for serologic study. Medical records of cases with serologic evidence of infection were reviewed and their clinical manifestations were analyzed. RESULTS: From October 1992 to July 2000, 51 serologically diagnosed cases of rickettsiosis were studied. Q fever predominated (28 cases). All cases of acute Q fever presented with hepatitis during the course of the illness and more than half (54%) reported an animal contact history. Most patients with Q fever (96%) and murine typhus (86%) were male, Serious complications, especially pneumonitis, occurred more frequently with scrub typhus than with acute Q fever. Spontaneous remission frequently occurred with acute Q fever. Administration of tetracycline or its analogues usually resulted in defervescence by the third day of treatment of scrub typhus. CONCLUSIONS: In our study, serious complications including pneumonitis, meningitis/meningoencephalitis, shock, acute renal failure, and disseminated intravascular coagulation were not uncommon in patients with scrub typhus. Physicians should include scrub typhus in the differential diagnosis of suspected cases of community-acquired febrile illness with multiple organ dysfunction in this endemic area. As Q fever is an emerging infectious disease in southern Taiwan, further large-scale epidemiologic surveillance and clinical data are needed.