Síntomas gastrointestinales, disfunción respiratoria, hepática y renal, principales factores asociados a letalidad por rickettsiosis trasmitida por garrapatas en Mexicali, Baja California, México / Gastrointestinal symptoms, respiratory, hepatic and renal dysfunction, main factors associated with lethality due to tickborne rickettsiosis in Mexicali, Baja California, Mexico

INTRODUCCIÓN: La rickettsiosis, enfermedad potencialmente mortal, es trasmitida por vectores como Rhipicephalus sanguineus, Dermacentor variabilis y D. andersonii, reservorios de Rickettsia rickettsii. En Baja California, México, es endémica, multifactorial, tiene alta letalidad, sus manifestaciones clínicas inespecíficas y ataque multisistémico dificultan el diagnóstico y tratamiento oportuno. OBJETIVO: Identificar los factores de riesgo asociados a la letalidad por rickettsiosis trasmitida por garrapatas en Mexicali, Baja California. PACIENTES Y MÉTODOS : Estudio observacional, analítico, transversal, retrospectivo, de 40 registros de pacientes con diagnóstico confirmado de rickettsiosis, periodo 2014 a 2018. Variables analizadas: sociodemográficas, clínicas, laboratorio clínico, evolución y desenlace. Se reportan frecuencias y medidas de asociación. RESULTADOS: 24 defunciones y 16 vivos. Más de 90% tuvo contacto conocido con garrapatas. Afectó en su mayoría a < 45 años en ambos grupos. La evolución antes del ingreso fue similar y la estancia hospitalaria fue mayor en los pacientes vivos (3,2 ± 4.7 vs 10,62 ± 7,6 p = 0,0002). Fiebre, cefalea, mialgias fueron predominantes. Datos asociados con letalidad: disfunción respiratoria (OR 38,33 IC95% 4,06-361,3 p < 0,0001), creatinina elevada (OR 15,4 IC95% 3,08-76,77 p < 0,0003), retardo del llenado capilar (OR 13,0 IC95% 2,73-61,78 p = 0,0005), dolor abdominal (OR 8,33, IC95% 1,90-36,44 p = 0,0029), AST (OR 7,5, IC95% 1,69-33,27 p = 0,005). CONCLUSIÓN: Esta enfermedad requiere de identificación temprana de factores que se asocian con letalidad para un tratamiento oportuno y adecuado.

BACKGROUND: Rickettsiosis, a potentially fatal disease, is transmitted by vectors such as Rhipicephalus sanguineus, Dermacentor variabilis and D. andersonii, reservoirs of Rickettsia rickettsii. In Baja California, Mexico, it is endemic, multifactorial, has high lethality, its nonspecific clinical manifestations and multisystem attack make diagnosis and timely treatment difficult. AIM: Identify the risk factors associated with lethality due to tick-transmitted rickettsiosis in Mexicali, Baja California. METHODS: Observational, analytical, cross-sectional, retrospective study of 40 records of patients with a confirmed diagnosis of rickettsiosis, period 2014 to 2018. Analyzed variables: sociodemographic, clinical, clinical laboratory, evolution and outcome. Frequencies and association measures are reported. RESULTS: 24 patients died and 16 survived. More than 90% had reported contact with ticks. It mostly affected ≤ 45 years in both groups. The evolution before admission was similar, and the hospital stay was longer in patients who lived (3.2 ± 4.7 vs 10.62 ± 7.6 p = 0.0002). Fever, headache, and myalgia are predominant. Data associated with lethality: respiratory dysfunction (OR 38.33 95% CI 4.06-361.3 p < 0.0001), elevated creatinine (OR 15.4 95% CI 3.08-76.77 p < 0.0003), delayed capillary refill (OR 13.0, 95% CI 2.73-61.78 p = 0.0005), abdominal pain (OR 8.33, 95% CI 1.90-36.44 p = 0.0029), AST (OR 7.5, 95% CI 1.69-33.27 p = 0.005). CONCLUSION: This disease requires early identification of factors that are associated with lethality for timely and adequate treatment.

The Applicability of Commonly Used Severity of Illness Scores to Tropical Infections in Australia.

Many patients with leptospirosis, melioidosis, and rickettsial infection require intensive care unit (ICU) admission in tropical Australia every year. The multi-organ dysfunction associated with these infections results in significantly elevated severity of illness (SOI) scores. However, the accuracy of these SOI scores in predicting death from these tropical infections is incompletely defined. This retrospective study was performed at Cairns Hospital, a tertiary-referral hospital in tropical Australia. All patients admitted to ICU with laboratory-confirmed leptospirosis, melioidosis, and rickettsial disease between January 1, 1999 and June 30, 2020, were eligible for the study. The ability of Acute Physiology and Chronic Health Evaluation (APACHE) II, APACHE III, Simplified Acute Physiology Scores (SAPS) II, and Sequential Organ Failure Assessment (SOFA) scores to predict death before ICU discharge was evaluated. Overall, 18 (12.1%) of the 149 included patients died: 15/74 (20.3%) with melioidosis, 2/54 (3.7%) with leptospirosis and 1/21 (4.8%) with rickettsial disease. However, the APACHE II, APACHE III, SAPS II, and SOFA scores significantly overestimated the case-fatality rate of all the infections; the disparity between the predicted and observed mortality was most marked in the cases of leptospirosis and rickettsial disease. Commonly used SOI scores significantly overestimate the case-fatality rate of melioidosis, leptospirosis, and rickettsial infections in Australian ICU patients. This may be at least partly explained by the unique pathophysiology of these infections, particularly leptospirosis and rickettsial disease. However, SOI scores may still be useful in facilitating the comparison of disease severity in clinical trials that examine patients with these pathogens.

Rickettsia felis identified in two fatal cases of acute meningoencephalitis.

BACKGROUND: Rickettsia felis has recently emerged worldwide as a cause of human illness. Typically causing mild, undifferentiated fever, it has been implicated in several cases of non-fatal neurological disease in Mexico and Sweden. Its distribution and pathogenicity in Southeast Asia is poorly understood. METHODOLOGY/PRINCIPAL FINDINGS: We retroactively tested cerebrospinal fluid (CSF) or sera from 64 adult patients admitted to hospital in North Sulawesi, Indonesia with acute neurological disease. Rickettsia felis DNA was identified in the CSF of two fatal cases of meningoencephalitis using multi-locus sequence typing semi-nested PCR followed by Sanger sequencing. DNA from both cases had 100% sequence homologies to the R. felis reference strain URRWXCal2 for the 17-kDa and ompB genes, and 99.91% to gltA. CONCLUSION/SIGNIFICANCE: The identification of R. felis in the CSF of two fatal cases of meningoencephalitis in Indonesia suggests the distribution and pathogenicity of this emerging vector-borne bacteria might be greater than generally recognized. Typically Rickettsia are susceptible to the tetracyclines and greater knowledge of R. felis endemicity in Indonesia should lead to better management of some acute neurological cases.

Wolbachia spread dynamics in stochastic environments.

Dengue fever is a mosquito-borne viral disease with 100 million people infected annually. A novel strategy for dengue control uses the bacterium Wolbachia to invade dengue vector Aedes mosquitoes. As the impact of environmental heterogeneity on Wolbachia spread dynamics in natural areas has been rarely quantified, we develop a model of differential equations for which the environmental conditions switch randomly between two regimes. We find some striking phenomena that random regime transitions could drive Wolbachia to extinction from certain initial states confirmed Wolbachia fixation in homogeneous environments, and mosquito releasing facilitates Wolbachia invasion more effectively when the regimes transit frequently. By superimposing the phase spaces of the ODE systems defined in each regime, we identify the threshold curves below which Wolbachia invades the whole population, which extends the theory of threshold infection frequency to stochastic environments.

Effect of forest fragmentation on tick infestations of birds and tick infection rates by rickettsia in the Atlantic forest of Brazil.

Habitat loss and modifications affect biodiversity, potentially contributing to outbreaks of infectious diseases. We evaluated if the patch sizeinfragmented areas of Atlantic Forest in southeastern Brazil influences the diversity of forest birds and consequently the prevalence of ticks on birds and the rickettsial infection of these ticks. During 2 years, we collected ticks from birds in 12 sites: four small forest patches (80-140 ha), four large ones (480-1,850 ha), and four forest control areas within the much larger Morro do Diabo State Park (approximately 36,000 ha). A total of 1,725 birds were captured (81 species, 24 families), from which 223 birds were infested by 2,339 ticks of the genus Amblyomma, mostly by the species A. nodosum. Bird diversity and richness were higher in larger than smaller forest fragments. The prevalence of ticks on birds was inversely correlated with bird diversity and richness. Among 174 A. nodosum tested for rickettsial infection by polymerase chain reaction, 51 were found to be infected by Rickettsia bellii or Rickettsia parkeri. However, tick infection rates by Rickettsia spp. were not statistically different between forest patch sizes. The higher prevalence of ticks on birds in degraded patches might be caused by a dominance of a few generalist bird species in small patches, allowing an easier transmission of parasites among individuals. It could also be related to more favorable microclimatic conditions for the free-living stages of A. nodosum in smaller forest fragments.The higher burden of ticks on birds in smaller forest fragments is an important secondary effect of habitat fragmentation, possibly increasing the likelihood of Rickettsia contagion.

Host, pathogen and treatment-related prognostic factors in rickettsioses.

Diseases caused by rickettsiae, which are vector-borne bacteria, vary widely from mild and self-limiting, to severe and life-threatening. Factors influencing this diversity of outcome are related to the host, to the infectious agent and to the treatment used to treat the infection. A literature search was conducted on PubMed using the phrases "factors-related severity, outcome, host, pathogen, Rickettsia conorii, R. rickettsii, R. africae, R. felis, R. prowazekii, R. typhi, genomics". Among host factors, old age and the male gender have been associated with poor outcome in rickettsioses. Co-morbidities, ethnical factors and the genetic background of the host also seem to influence the outcome of rickettsial diseases. Moreover, although the degree of the host response is beneficial, it could also partly explain the severity observed in some patients. Among pathogen-related factors, traditional concepts of factors of virulence had been challenged and genomic reductive evolution with loss of regulatory genes is the main hypothesis to explain virulence observed in some species, such as Rickettsia prowazekii, the agent of epidemic typhus. R. prowazekii is the more pathogenic rickettsiae and harbours the smaller genome size (1.1 Mb) compared to less or non-virulent species, and is not intracellularly motile, a factor considered as a virulence factor for other intracellular bacteria. The antibiotic regimen used to treat rickettsioses also has an influence on prognosis. Usual concepts of severity and virulence in rickettsioses are challenging and are frequently paradoxical. In this mini-review, we will describe factors currently thought to influence the outcome of the main rickettsioses responsible for illness in humans.

Predictive values of clinical parameters for severe Japanese spotted fever.

Japanese spotted fever (JSF) is severe and can progress to disseminated intravascular coagulation (DIC) with a poor prognosis. We considered whether patient factors are related to serious complications. Between August 1999 and March 2009, all patients with JSF and retrievable clinical data (age, gender, length of hospital stay, medication, comorbidities), vital signs (blood pressure, heart rate, temperature), and laboratory test results [blood cell count, liver function, renal function, electrolytes, blood sugar, C-reactive protein (CRP), CRP normalization period, and aspartate aminotransferase normalization period] from the Integrated Intelligent Management System (IIMS) database, were retrospectively analyzed by logistic regression. There were 51 JSF patients (24 men, 27 women) with a mean age of 63.0 years. Six patients (11.8%) had DIC, but there were no in-hospital deaths. The time between fever onset and initiation of medication was approximately 5 days, but this delay was not associated with disease severity. We identified values correlating with disease severity (p < 0.1) by univariate analysis and then applied logistic regression. We found renal dysfunction [serum creatinine (Cr) ≥ 1.5 mg/dl] at the time of initial presentation to be predictive of DIC. Cr was also predictive of a prolonged disease course. In patients with JSF, renal function must be carefully monitored when determining clinical management.

Scrub typhus (Orientia tsutsugamushi), spotted fever (Rickettsia australis) and dengue fever as possible causes of mysterious deaths in the Strickland Gorge area of Southern Highlands and West Sepik Provinces of Papua New Guinea.

A medical investigation was carried out in April 2001 into an outbreak of a mysterious haemorrhagic disease and deaths in the remote picturesque Strickland River area of Papua New Guinea (PNG). The area is in part of the Southern Highlands and West Sepik Provinces and situated downstream from the Porgera Joint Venture gold mine. 9 villages were visited and 140 persons, consisting of immediate blood relatives of the deceased (cases) and others in the village picked at random (controls), were physically examined. Specimens of blood, urine and faeces were collected from each person for laboratory tests in PNG and Australia. Positive sera for dengue (15%) and Japanese encephalitis (JE) (6%) were identified. Surprisingly, a number of the sera were positive for scrub typhus (Orientia tsutsugamushi) (28%) and spotted fever (Rickettsia australis) (11%). The last reported cases of scrub typhus in PNG were during World War Two among the allied troops. This is the first time spotted fever (R. australis) has been reported in PNG. These conditions may have been the cause of the deaths described by the villagers. However, there were significantly more dengue-positive results among relatives of the deceased than non-relatives though no such difference was found with rickettsial infections: haemorrhagic dengue fever is thus the most likely cause of this recurring outbreak. Mining did not appear to be a direct causal factor for the deaths in the area.

Brazilian spotted fever: a case series from an endemic area in southeastern Brazil: clinical aspects.

This case series study is based on a retrospective review of medical records and case notification files of patients admitted to The Hospital das Clínicas da UNICAMP from 1985 to 2003 with a confirmed diagnosis of BSF either by fourfold rise in indirect immunofluorescence assay (IFA) titers of IgG antibodies reactive with R. rickettsii or isolation of R. rickettsii from blood or skin specimens. A median lethality of 41.9 % was observed between 1985 and 2004. The case-fatality ratio of 30 % in our study, lower than the overall São Paulo state ratio, could be explained by a higher index of suspicion and a larger experience in our hospital, a regional referral center for BSF. The presence of the classical triad of fever, rash, and headache as described in RMSF was observed in fever than half (35.2%) of our patients.

Effect of blocking the CXCL9/10-CXCR3 chemokine system in the outcome of endothelial-target rickettsial infections.

Rickettsiae cause systemic infections such as Rocky Mountain spotted fever and boutonneuse fever. The main cellular target of these obligately intracellular bacteria is the endothelium. T lymphocytes are the most important effectors of immunity, and the CXCR3 ligands CXCL9 and CXCL10 may play an important role in the T cell-mediated clearance of rickettsiae from the infected vasculature as suggested by recent expression studies. Here we showed that antibody-mediated neutralization of CXCL9 and CXCL10, and CXCR3 gene knockout, had no effect on survival or bacterial loads of mice infected with rickettsiae. We also demonstrated that rickettsiae triggered the endothelial expression of intercellular adhesion molecule 1 and vascular cell adhesion molecule 1 in vivo. These findings suggested that antigenic presentation by endothelial cells together with an endothelial inflammatory phenotype induced by the rickettsial infection may be sufficient to arrest T cells and trigger their anti-rickettsial effector mechanisms without the need for chemokines.

Rickettsia felis in Ctenocephalides spp. fleas, Brazil.

In June 2000, suspected cases of Brazilian spotted fever (BSF) occurred in Coronel Fabriciano Municipality, Minas Gerais State, Brazil. Pooled fleas collected near two fatal cases contained rickettsial DNA. The nucleotide sequence alignment of the 391-bp segment of the 17-kDa protein gene showed that the products were identical to each other and to the R. felis 17-kDa gene, confirming circulation of R. felis in Brazil.

A Piscirickettsia salmonis-like bacterium associated with mortality of white seabass Atractoscion nobilis.

Mortality among hatchery-reared juvenile white seabass Atractoscion nobilis in southern California, USA, was associated with infections by a Piscirickettsia salmonis-like organism (WSPSLO). Infected fish had no consistent external signs other than pale gills, lethargy and impaired swimming behavior. Internally, the kidney and spleen were enlarged, and some fish had livers with multiple pale foci. Smears from infected kidney, liver, and spleen stained with Wright-Giemsa had intracytoplasmic coccoid organisms, often in pairs, that ranged in size from 0.5 to 1.0 microm. Microscopic lesions included multifocal hepatic, renal, and splenic necrosis, and intralesional macrophages often contained the WSPSLO. The bacterium was isolated from infected fish on cell lines of salmonid (CHSE-214) and white seabass (WSBK) origin. The WSPSLO induced plaque formation and destroyed the cell monolayers within 10 to 14 d incubation at temperatures of 15 and 20 degrees C. The bacterium retained infectivity for cell lines up to 14 d at 4 and 13 degrees C, up to 7 d at 20 degrees C, but it was inactivated at 37 and 56 degrees C within 24 and 1 h, respectively. Freezing at -20 degrees C reduced infectivity by 100-fold. Dehydration and resuspension in distilled water completely inactivated the bacterium. In contrast, the WSPSLO retained nearly all of its infectivity for CHSE-214 cells following a 72 h period in seawater at 20 degrees C. Polyclonal rabbit antibodies made to the WSPSLO reacted specifically in indirect fluorescent antibody tests (IFAT) with the bacterium in cell cultures and smears from infected fish tissues. Tissue smears from infected salmon or CHSE-214 cells with P. salmonis reacted weakly with the anti-WSPSLO serum. Conversely, polyclonal anti-P. salmonis serum produced a weakly positive reaction with the WSPSLO from infected CHSE-214 cells. The WSPSLO as propagated in CHSE-214 cells was highly virulent for juvenile coho salmon Oncorhynchus kisutch, inducing 80% mortality within 10 d of intraperitoneal injection of 10(2.5)-50% tissue culture infectious doses per fish. We conclude that the bacterium from white seabass possesses antigenic differences from P. salmonis yet possesses virulence for salmon equal to known strains of P. salmonis.

Rickettsial relative associated with male killing in the ladybird beetle (Adalia bipunctata).

A cytoplasmically inherited microorganism associated with male killing in the two-spot ladybird beetle, Adalia bipunctata, is shown to be closely related to bacteria in the genus Rickettsia. Sequencing of a PCR-amplified product of the 16S genes coding for rRNA (16S rDNA) shows the organism associated with male killing in ladybirds to share a common ancestry with the Rickettsias relative to other genera (e.g., Anaplasma, Ehrlichia, and Cowdria). The rickettsial 16S rDNA product is found in four strains of ladybird beetle showing male embryo lethality and is absent from two uninfected strains and an antibiotic-cured strain. In addition, a revertant strain that had naturally lost the male-killing trait failed to amplify the rickettsial 16S rDNA product. Use of PCR primers for a 17-kDa protein antigen which is found only in rickettsias also resulted in an amplified product from infected strains. Uninfected, cured, and revertant strains and insect species infected with related bacteria (cytoplasmic-incompatibility bacteria from Nasonia wasps) failed to amplify the product. Discovery of a close relative of rickettsias associated with sex ratio distortion in insects has implications for the evolution and population dynamics of this bacterial genus.

An apparent outbreak of rickettsial illness in Costa Rica, 1974.

A focal outbreak of highly fatal disease occurred in eastern Costa Rica in 1974. No rickettsial spotted fevers have previously been reported in Costa Rica. Nevertheless, the available evidence points to an unidentified rickettsial pathogen, probably of the spotted fever group, as the agent responsible for this outbreak.