Endemic Scrub Typhus in South America Weitzel, Thomas; Dittrich, Sabine; López, Javier ...
New England journal of medicine/The New England journal of medicine,
09/2016, Volume:
375, Issue:
10
Journal Article
Peer reviewed
Open access
Scrub typhus, caused by
Orientia tsutsugamushi,
has been thought to be geographically restricted to the “tsutsugamushi triangle” in the Asia–Pacific region. In this report, a potential focus in ...southern Chile is identified.
Scrub typhus is a vector-borne zoonosis caused by
Orientia tsutsugamushi
. The infection is transmitted by “chiggers” (i.e., the larvae of trombiculid mites of the genus leptotrombidium). Although chiggers feed on various vertebrates, the main reservoir is the vector itself, which maintains orientia organisms through transstadial and transovarial transmission.
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After the bite of an infective chigger, a characteristic necrotic inoculation lesion, termed eschar, can develop, which typically contains high bacterial loads. The microorganism then spreads through the lymphatic fluid and blood, causing systemic manifestations that include fever, rash, and laboratory abnormalities such as elevated levels of C-reactive protein and liver . . .
Endemic scrub typhus was recently detected on Chiloé Island in southern Chile. We report a series of cases, acquired over a wide geographical range in continental Chile during 2016–2018, ...demonstrating that this emerging rickettsial infection is also found on the mainland of South America.
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Invasive pneumococcal disease (IPD) and pneumonia are a leading cause of morbidity and mortality throughout the world, and asthma is the most common chronic disease of childhood.
To evaluate the risk ...of IPD or pneumonia among children with asthma after the introduction of pneumococcal conjugate vaccines (PCVs).
Four electronic databases were searched.
We selected all cohorts or case-control studies of IPD and pneumonia in populations who already received PCV (largely 7-valent pneumococcal conjugate vaccine), but not 23-valent pneumococcal polysaccharide, in which authors reported data for children with asthma and in which healthy controls were included, without language restriction.
Two reviewers independently reviewed all studies. Primary outcomes were occurrence of IPD and pneumonia. Secondary outcomes included mortality, hospital admissions, hospital length of stay, ICU admission, respiratory support, costs, and additional medication use.
Five studies met inclusion criteria; of those, 3 retrospective cohorts (∼26 million person-years) and 1 case-control study (
= 3294 children) qualified for the meta-analysis. Children with asthma had 90% higher odds of IPD than healthy controls (odds ratio = 1.90; 95% confidence interval = 1.63-2.11; I
= 1.7%). Pneumonia was also more frequent among children with asthma than among controls, and 1 study reported that pneumonia-associated costs increased by asthma severity.
None of the identified studies had information of asthma therapy or compliance.
Despite PCV vaccination, children with asthma continue to have a higher risk of IPD than children without asthma. Further research is needed to assess the need for supplemental 23-valent pneumococcal polysaccharide vaccination in children with asthma, regardless of their use of oral steroids.
Scrub typhus is a potentially fatal rickettsiosis caused by Orientia species intracellular bacteria of the genus Orientia. Although considered to be restricted to the Asia Pacific region, scrub ...typhus has recently been discovered in southern Chile. We analyzed Orientia gene sequences of 16S rRNA (rrs) and 47-kDa (htrA) from 18 scrub typhus patients from Chile. Sequences were ≥99.7% identical among the samples for both amplified genes. Their diversity was 3.1%-3.5% for rrs and 11.2%-11.8% for htrA compared with O. tsusugamushi and 3.0% for rrs and 14.8% for htrA compared with Candidatus Orientia chuto. Phylogenetic analyses of both genes grouped the specimens from Chile in a different clade from other Orientia species. Our results indicate that Orientia isolates from Chile constitute a novel species, which, until they are cultivated and fully characterized, we propose to designate as Candidatus Orientia chiloensis, after the Chiloé Archipelago where the pathogen was identified.
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Monocytes and dendritic cells regulate adaptive and innate immunity. This study uncovers an association between mutations in the gene encoding interferon regulatory factor 8 and deficiency of ...dendritic cells and monocytes in the context of disseminated bacille Calmette–Guérin disease.
The discovery of human primary immunodeficiencies that affect the development of granulocytes, B cells, and T cells has been instrumental in defining the contribution of these cell types to protective immunity.
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Monocytes, macrophages, and dendritic cells — all mononuclear phagocytes — have essential functions in both innate and acquired immunity. These cells initially recognize and engulf invading microbes, produce proinflammatory cytokines (e.g., interleukin-12), and process antigens for presentation to naive T cells, which consequently secrete various lymphokines (e.g., interferon-γ).
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On activation by cytokines secreted by T cells, mononuclear phagocytes destroy ingested microorganisms. There are no known genetic causes . . .
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the virus responsible of the current pandemic ongoing all around the world. Since its discovery in 2019, several circulating variants ...have emerged and some of them are associated with increased infections and death rate. Despite the genetic differences among these variants, vaccines approved for human use have shown a good immunogenic and protective response against them. In Chile, over 70% of the vaccinated population is immunized with CoronaVac, an inactivated SARS-CoV-2 vaccine. The immune response elicited by this vaccine has been described against the first SARS-CoV-2 strain isolated from Wuhan, China and the D614G strain (lineage B). To date, four SARS-CoV-2 variants of concern described have circulated worldwide. Here, we describe the neutralizing capacities of antibodies secreted by volunteers in the Chilean population immunized with CoronaVac against variants of concern Alpha (B.1.1.7), Beta (B.1.351) Gamma (P.1) and Delta (B.617.2).
Volunteers enrolled in a phase 3 clinical trial were vaccinated with two doses of CoronaVac in 0-14 or 0-28 immunization schedules. Sera samples were used to evaluate the capacity of antibodies induced by the vaccine to block the binding between Receptor Binding Domain (RBD) from variants of concern and the human ACE2 receptor by an in-house ELISA. Further, conventional microneutralization assays were used to test neutralization of SARS-CoV-2 infection. Moreover, interferon-γ-secreting T cells against Spike from variants of concern were evaluated in PBMCs from vaccinated subjects using ELISPOT.
CoronaVac promotes the secretion of antibodies able to block the RBD of all the SARS-CoV-2 variants studied. Seropositivity rates of neutralizing antibodies in the population evaluated were over 97% for the lineage B strain, over 80% for Alpha and Gamma variants, over 75% for Delta variant and over 60% for the Beta variant. Geometric means titers of blocking antibodies were reduced when tested against SARS-CoV-2 variants as compared to ancestral strain. We also observed that antibodies from vaccinated subjects were able to neutralize the infection of variants D614G, Alpha, Gamma and Delta in a conventional microneutralization assay. Importantly, after SARS-CoV-2 infection, we observed that the blocking capacity of antibodies from vaccinated volunteers increased up to ten times for all the variants tested. We compared the number of interferon-γ-secreting T cells specific for SARS-CoV-2 Spike WT and variants of concern from vaccinated subjects and we did not detect significant differences.
Immunization with CoronaVac in either immunization schedule promotes the secretion of antibodies able to block SARS-CoV-2 variants of concern and partially neutralizes SARS-CoV-2 infection. In addition, it stimulates cellular responses against all variants of concern.
Constant efforts to prevent infections by severe acute respiratory syndrome coronavirus 2 (SARS
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CoV
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2
)
are actively carried out around the world. Several vaccines are currently approved for ...emergency use in the population, while ongoing studies continue to provide information on their safety and effectiveness. CoronaVac is an inactivated SARS-CoV-2 vaccine with a good safety and immunogenicity profile as seen in phase 1, 2, and 3 clinical trials around the world, with an effectiveness of 65.9% for symptomatic cases. Although vaccination reduces the risk of disease, infections can still occur during or after completion of the vaccination schedule (breakthrough cases). This report describes the clinical and immunological profile of vaccine breakthrough cases reported in a clinical trial in progress in Chile that is evaluating the safety, immunogenicity, and efficacy of two vaccination schedules of CoronaVac (clinicaltrials.gov NCT04651790). Out of the 2,263 fully vaccinated subjects, at end of June 2021, 45 have reported symptomatic SARS-CoV-2 infection 14 or more days after the second dose (1.99% of fully vaccinated subjects). Of the 45 breakthrough cases, 96% developed mild disease; one case developed a moderate disease; and one developed a severe disease and required mechanical ventilation. Both cases that developed moderate and severe disease were adults over 60 years old and presented comorbidities. The immune response before and after SARS-CoV-2 infection was analyzed in nine vaccine breakthrough cases, revealing that six of them exhibited circulating anti-S1-RBD IgG antibodies with neutralizing capacities after immunization, which showed a significant increase 2 and 4 weeks after symptoms onset. Two cases exhibited low circulating anti-S1-RBD IgG and almost non-existing neutralizing capacity after either vaccination or infection, although they developed a mild disease. An increase in the number of interferon-γ-secreting T cells specific for SARS-CoV-2 was detected 2 weeks after the second dose in seven cases and after symptoms onset. In conclusion, breakthrough cases were mostly mild and did not necessarily correlate with a lack of vaccine-induced immunity, suggesting that other factors, to be defined in future studies, could lead to symptomatic infection after vaccination with CoronaVac.
Scrub typhus is an emerging vector-borne zoonosis, caused by Orientia spp. and transmitted by larvae of trombiculid mites, called chiggers. It mainly occurs within a region of the Asia-Pacific called ...the tsutsugamushi triangle, where rodents are known as the most relevant hosts for the trombiculid vector. However, the reservoir(s) and vector(s) of the scrub typhus outside Asia-Pacific are unknown. The disease has recently been discovered on and is considered endemic for Chiloé Island in southern Chile. The aim of the present work was to detect and determine the prevalence of chiggers on different rodent species captured in probable sites for the transmission of orientiae responsible for scrub typhus on Chiloé Island in southern Chile and to molecularly examine collected chiggers for the presence of Orientia DNA.
During the austral summer 2018, rodents were live-trapped in six sites and examined for chigger infestation. All study sites were rural areas on Chiloé Island, previously identified as probable localities where human cases acquired the scrub typhus. During a total of 4,713 trap-nights, 244 rodents of seven species were captured: the most abundant was Abrothrix olivacea. Chiggers were detected on all seven rodent species with a 55% prevalence rate. Chiggers showed low host specificity and varied according to site specific host abundance. Three genera of trombiculids were identified. Herpetacarus was the most abundant genus (93%), prevalent in five of the six sites. Infestation rates showed site specific differences, which were statistically significant using a GLM model with binomial errors. Molecular analyses proved that 21 of 133 (15.8%) mite pools were positive for Orientia species, all of them belonged to the genus Herpetacarus.
This study firstly reports the presence of different rodent-associated chigger mites positive for Orientia sp., in a region endemic for scrub typhus in southern Chile. Herpetacarus and two other genera of mites were found with high infestation rates of rodents in sites previously identified as probable exposure of scrub typhus cases. A substantial percentage of mite pools were positive for Orientia DNA, suggesting that chigger mites serve as vectors and reservoirs of this emerging zoonosis in South America.
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Scrub typhus is a potentially severe infection caused by bacteria of the genus Orientia, endemic in Asia-Pacific and recently discovered in southern Chile. The presented study aimed to determine the ...prevalence and species richness of rodent-associated trombiculid mites and their infection with Orientia spp. in different areas of two regions in southern Chile.
During summer 2020, trombiculid mites were collected from rodents captured in three areas in southern Chile known to be endemic for scrub typhus (Cochamó and Chiloé Island in the Los Lagos Region and Tortel in the Aysén Region). A total of 132 rodents belonging to five species were captured using Sherman-like traps; 89.4% were infested with trombiculids. Mite specimens were morphologically identified and subsequently tested by Orientia-specific qPCR. Six mite species were identified. Among chigger-infested rodents, 33.9% carried Orientia-positive mites; this rate was higher in Tortel (63.8%) than in Cochamó (45.0%) and Chiloé Island (2.0%). The analysis of individual mites (n = 901) revealed that 31.2% of Herpetacarus antarctica samples (n = 202) were positive for Orientia DNA; the prevalence was 7.0% in Paratrombicula neuquenensis (n = 213), 6.9% in Herpetacarus eloisae (n = 144), 3.6% in Argentinacarus expansus (n = 55), and 0% in Paratrombicula goffi (n = 110) and Quadraseta chiloensis (n = 177). The southernmost site (Tortel) showed the highest rates of trombiculid infestation, trombiculid load, and Orientia infection in the captured rodents.
Our study provides new insights into the trombiculid fauna and prevalence of Orientia in mites collected from wild rodents in southern Chile. Orientia DNA was detected in four of the six mite species. Rates of infestation, mite loads, and Orientia prevalences differed geographically and were highest in the Aysén Region. Our data improve our knowledge on possible vectors of scrub typhus and their distribution in Chile.
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We report a case of scrub typhus in a 54-year-old man who was bitten by several terrestrial leeches during a trip to Chiloé Island in southern Chile in 2006. A molecular sample, identified as related ...to Orientia tsutsugamushi based on the sequence of the16S rRNA gene, was obtained from a biopsy specimen of the eschar on the patient's leg. Serologic analysis showed immunoglobulin G conversion against O. tsutsugamushi whole cell antigen. This case and its associated molecular analyses suggest that an Orientia-like agent is present in the Western Hemisphere that can produce scrub typhus-like illness. The molecular analysis suggests that the infectious agent is closely related, although not identical, to members of the Orientia sp. from Asia.
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