Severe Rickettsia typhi Infections, Costa Rica.

Murine typhus is a febrile, fleaborne disease caused by infection with Rickettsia typhi bacteria. Cases can range from mild and nonspecific to fatal. We report 2 cases of murine typhus in Costa Rica, confirming the presence and circulation of R. typhi causing severe disease in the country.

Acute febrile illness among outpatients seeking health care in Bangladeshi hospitals prior to the COVID-19 pandemic.

Understanding the distribution of pathogens causing acute febrile illness (AFI) is important for clinical management of patients in resource-poor settings. We evaluated the proportion of AFI caused by specific pathogens among outpatients in Bangladesh. During May 2019-March 2020, physicians screened patients aged ≥2 years in outpatient departments of four tertiary level public hospitals. We randomly enrolled patients having measured fever (≥100.4°F) during assessment with onset within the past 14 days. Blood and urine samples were tested at icddr,b through rapid diagnostic tests, bacterial culture, and polymerase chain reaction (PCR). Acute and convalescent samples were sent to the Centers for Disease Control and Prevention (USA) for Rickettsia and Orientia (R/O) and Leptospira tests. Among 690 patients, 69 (10%) had enteric fever (Salmonella enterica serotype Typhi orSalmonella enterica serotype Paratyphi), 51 (7.4%) Escherichia coli, and 28 (4.1%) dengue detected. Of the 441 patients tested for R/O, 39 (8.8%) had rickettsioses. We found 7 (2%) Leptospira cases among the 403 AFI patients tested. Nine patients (1%) were hospitalized, and none died. The highest proportion of enteric fever (15%, 36/231) and rickettsioses (14%, 25/182) was in Rajshahi. Dhaka had the most dengue cases (68%, 19/28). R/O affected older children and young adults (IQR 8-23 years) and was detected more frequently in the 21-25 years age-group (17%, 12/70). R/O was more likely to be found in patients in Rajshahi region than in Sylhet (aOR 2.49, 95% CI 0.85-7.32) between July and December (aOR 2.01, 1.01-5.23), and who had a history of recent animal entry inside their house than not (aOR 2.0, 0.93-4.3). Gram-negative Enterobacteriaceae were the most common bacterial infections, and dengue was the most common viral infection among AFI patients in Bangladeshi hospitals, though there was geographic variability. These results can help guide empiric outpatient AFI management.

Genetic typing of isolates of Rickettsia typhi.

Murine typhus, which is caused by Rickettsia typhi, has a wide range of clinical manifestations. It has a low mortality rate but may result in meningoencephalitis and interstitial pneumonia in severe cases. Comparisons of complete genome sequences of R. typhi isolates from North Carolina, USA (Wilmington), Myanmar (B9991PP), and Thailand (TH1527) identified only 26 single nucleotide polymorphism (SNP) and 7 insertion-deletion (INDEL) sites in these highly syntenic genomes. Assays were developed to further define the distribution of these variant sites among 15 additional isolates of R. typhi with different histories from Asia, the USA, and Africa. Mismatch amplification mutation assays (MAMA) were validated for 22 SNP sites, while the 7 INDEL sites were analyzed directly on agarose gels. Six SNP types, 9 INDEL types, 11 total types were identified among these 18 isolates. Replicate DNA samples as well as comparisons of isolates with different passage and source histories gave consistent genetic typing profiles. Comparison of the SNP and INDEL markers to R. typhi's nearest neighbor Rickettsia prowazekii demonstrated that the majority of the SNPs represent intra-species variation that arose post divergence of these two species while several INDEL sites also exhibited intraspecies variability among the R. prowazekii genomes that have been completely sequenced. The assays for the presence of these SNP and INDEL sites, particularly the latter, comprise a low technology gel method for consistently distinguishing R. typhi and R. prowazekii as well as for differentiating genetic types of R. typhi.

Analytically sensitive Rickettsia species detection for laboratory diagnosis.

Clinical and laboratory diagnosis of rickettsial diseases is challenging because of the undifferentiated symptoms (commonly fever, headache, and malaise) and low bacteremia (< 100 genomic copies [gc]/mL) during the early acute stage of illness. Early treatment with doxycycline is critical for a positive outcome, especially in Rickettsia rickettsii (Rocky Mountain spotted fever) infections where cases may be fatal within 5 to 10 days from symptom onset, emphasizing the need for more sensitive diagnostics. A real-time reverse transcriptase polymerase chain reaction (PCR) assay, RCKr, was developed and validated for Rickettsia spp. nucleic acid detection in human clinical samples. The limit of detection for RCKr was determined to be 20 gc/mL, compared with our 2013 (Kato et al.) laboratory developed test, PanR8 at 1,800 to 2,000 gc/mL. Inclusivity, exclusivity, accuracy, and precision results correlated as expected. From an evaluation of 49 banked clinical samples, RCKr detected 35 previously positive samples, as well as two specimens that were PanR8 real-time PCR negative yet clinically diagnosed as possible rickettsiosis. Ct values from RCKr clinical sample testing show a 100-fold increase relative to PanR8. Additional testing is needed to understand the clinical sensitivity of RCKr; however, this study demonstrates RCKr to have high analytical specificity and sensitivity for Rickettsia detection.

Development and validation of real-time PCR assays for the detection of Ehrlichia species and E. chaffeensis in clinical specimens.

Ehrlichiosis, caused by Gram-negative bacteria of the genus Ehrlichia, is considered an emerging infectious disease due to the increasing number of reported cases. Symptoms are non-specific and occur within 1 to 2 weeks following the bite of an infected tick. Confirmatory laboratory diagnostic methods vary in sensitivity and specimen requirements, which can lead to delayed diagnosis. PCR testing serves as an efficient approach to Ehrlichia confirmation in the acute stage of illness. Published assays have been effectively used to detect human ehrlichiosis at limit of detections ranging from 10 to 50 genomic copies (GC) of Ehrlichia DNA. With the discovery of new species capable of human infection, we wanted to develop assays that are sensitive and encompass a wide range of Ehrlichia. Here we developed and validated two sensitive and specific real-time PCR assays (PanE1 and PanE2) for the detection of Ehrlichia species, as well as two real-time PCR assays (ECh2 and ECh4) for the detection of Ehrlichia chaffeensis, specifically. The limit of detection was determined to be 10 GC per reaction with 100% confidence, and as little as 1 GC with lower efficiencies. Accuracy was assessed at 100% correlation. Specificity from exclusivity testing demonstrated that neither the Ehrlichia species assays (n = 60), nor the E. chaffeensis specific assays (n = 64) had cross reactivity with near neighbors or environmental bacteria. A positive predictive value of 100% and a negative predictive value of ≥93% was determined by evaluating banked clinical specimens from 62 patients with the assays. These real-time PCR assays are effective tools to detect human Ehrlichia species during the acute stage of illness. Early detection of Ehrlichia infection by these real-time PCR assays can facilitate diagnosis and treatment.

Expanding Recognition of Rickettsia parkeri Rickettsiosis in Southern Arizona, 2016-2017.

Rickettsia parkeri rickettsiosis is an emerging, tick-borne disease in the United States (US), transmitted by the bite of Amblyomma maculatum group ticks. Clinical manifestations include fever, headache, myalgia, maculopapular rash, and a characteristic eschar that forms at the site of the tick bite. Arizona's index case of R. parkeri rickettsiosis was reported in 2014. Seven additional confirmed and probable cases were identified during 2016-2017 through routine investigation of electronic laboratory reports and by self-reporting to public health authorities. Serum samples were evaluated for immunoglobulin G antibodies reactive with antigens of Rickettsia rickettsii (the agent of Rocky Mountain spotted fever [RMSF]) and R. parkeri using indirect immunofluorescence antibody tests. Eschar swab specimens were evaluated using Rickettsia genus-specific and R. parkeri-specific real-time PCR assays. Patients (six male, one female) ranged in age from 29 to 69 years (median of 41 years), and became ill between July 2016 and September 2017. Fever (6/7), myalgia (5/7), and arthralgia (5/7) were most commonly reported and 5/7 patients had a documented eschar. All patients reported a tick bite acquired in southern Arizona within 2-8 days before illness onset. Four patients worked as U.S. Border Patrol agents. Antibodies reactive to R. rickettsii, R. parkeri, or to both antigens were detected in all patients. Seroconversions between acute and convalescent-phase samples were identified for two patients and DNA of R. parkeri was identified in eschar swab samples from two patients. R. parkeri rickettsiosis is endemic to a region of the southwestern United States and presents an occupational risk that could be lessened by prevention messaging to Border Patrol agents. RMSF, a closely related and more severe spotted fever rickettsiosis, is also endemic to Arizona. Public health agencies can assist clinicians in distinguishing these two infections clinically through education and accessing species-specific diagnostic assays that can improve surveillance efforts for both diseases.

Seroprevalence of spotted fever group rickettsiae in canines along the United States-Mexico border.

Portions of northern Mexico are experiencing a re-emergence of Rocky Mountain spotted fever (RMSF), a tickborne disease caused by Rickettsia rickettsii, a member of the spotted fever group of rickettsiae (SFGR). Infection with R. rickettsii can result in serious and life-threatening illness in people and dogs. Canine seroprevalence has been used as a sentinel for human RMSF in previous studies. This study aims to quantify SFGR seroprevalence in canines in three northern Mexican states and identify risk factors associated with seropositivity. A total of 1,136 serum samples and 942 ticks were obtained from dogs participating in government sterilization campaigns and from animal control facilities in 14 Mexican cities in three states. SFGR antibodies were detected using indirect immunofluorescence antibody assays at titre values ≥1/64. Six per cent (69 dogs) showed antibodies to SFGR, with the highest seroprevalence reported in Baja California (12%), Coahuila (4%) and Sonora (4%). Dogs from Baja California had three times higher odds of having SFGR antibodies compared to dogs from Sonora (OR = 3.38, 95% CI, 1.81-6.37). Roughly one quarter (25%) of surveyed dogs were parasitized by ticks (Rhipicephalus sanguineus sensu lato) at the time of sample collection. A portion of collected ticks were tested for rickettsial DNA using polymerase chain reaction. Positive samples were then sequenced, showing evidence of SFGR including R. massiliae, R. parkeri and R. rickettsii. Dogs that spent the majority of time on the street, such as free-roaming or community-owned dogs, showed a greater risk of tick infestation, seropositivity, bearing seropositive ticks, and may play a pivotal role in the spread of SFGR among communities. Estimating the seroprevalence of SFGR in the canine population can help public health campaigns target high-risk communities for interventions to reduce human RMSF cases.

African Tick Bite Fever Treated Successfully With Rifampin in a Patient With Doxycycline Intolerance.

African tick bite fever is the most commonly encountered travel-associated rickettsiosis, occurring in as many as 5% of travelers returning from rural subequatorial Africa. This case report illustrates that rifampin represents an effective alternative to doxycycline for treatment of African tick bite fever in some selective situations.

Case report: Co-infection of Rickettsia rickettsii and Streptococcus pyogenes: is fatal Rocky Mountain spotted fever underdiagnosed?

Rocky Mountain spotted fever, a tick-borne disease caused by Rickettsia rickettsii, is challenging to diagnose and rapidly fatal if not treated. We describe a decedent who was co-infected with group A ß-hemolytic streptococcus and R. rickettsii. Fatal cases of Rocky Mountain spotted fever may be underreported because they present as difficult to diagnose co-infections.

Inadequacy of IgM antibody tests for diagnosis of Rocky Mountain Spotted Fever.

Among 13 suspected Rocky Mountain spotted fever (RMSF) cases identified through an enhanced surveillance program in Tennessee, antibodies to Rickettsia rickettsii were detected in 10 (77%) patients using a standard indirect immunofluorescent antibody (IFA) assay. Immunoglobulin M (IgM) antibodies were observed for 6 of 13 patients (46%) without a corresponding development of IgG, and for 3 of 10 patients (30%) at least 1 year post-onset. However, recent infection with a spotted fever group rickettsiae could not be confirmed for any patient, based on a lack of rising antibody titers in properly timed acute and convalescent serologic specimens, and negative findings by polymerase chain reaction testing. Case definitions used in national surveillance programs lack specificity and may capture cases that do not represent current rickettsial infections. Use of IgM antibodies should be reconsidered as a basis for diagnosis and public health reporting of RMSF and other spotted fever group rickettsiae in the United States.

Assessment of real-time PCR assay for detection of Rickettsia spp. and Rickettsia rickettsii in banked clinical samples.

Two novel real-time PCR assays were developed for the detection of Rickettsia spp. One assay detects all tested Rickettsia spp.; the other is specific for Rickettsia rickettsii. Evaluation using DNA from human blood and tissue samples showed both assays to be more sensitive than nested PCR assays currently in use at the CDC.

Treatment of accommodative dysfunction in children: results from a randomized clinical trial.

PURPOSE: To report the effectiveness of various forms of vision therapy/orthoptics in improving accommodative amplitude and facility in children with symptomatic convergence insufficiency (CI) and co-existing accommodative dysfunction. METHODS: In a randomized clinical trial, 221 children aged 9 to 17 years with symptomatic CI were assigned to one of four treatments. Of the enrolled children, 164 (74%) had accommodative dysfunction; 63 (29%) had a decreased amplitude of accommodation with respect to age, 43 (19%) had decreased accommodative facility, and 58 (26%) had both. Analysis of variance models were used to compare mean accommodative amplitude and accommodative facility for each treatment group after 4, 8, and 12 weeks of treatment. RESULTS: After 12 weeks of treatment, the increases in amplitude of accommodation [office-based vergence/accommodative therapy with home reinforcement group (OBVAT) 9.9 D, home-based computer vergence/accommodative therapy group (HBCVAT+) 6.7 D, and home-based pencil push-up therapy group (HBPP) 5.8 D] were significantly greater than in the office-based placebo therapy (OBPT) group (2.2 D) (p-values ≤0.010). Significant increases in accommodative facility were found in all groups (OBVAT: 9 cpm, HBCVAT+: 7 cpm, HBPP: 5 cpm, OBPT: 5.5 cpm); only the improvement in the OBVAT group was significantly greater than that found in the OBPT group (p = 0.016). One year after completion of therapy, reoccurrence of decreased accommodative amplitude was present in only 12.5% and accommodative facility in only 11%. CONCLUSIONS: Vision therapy/orthoptics is effective in improving accommodative amplitude and accommodative facility in school-aged children with symptomatic CI and accommodative dysfunction.

An analysis of vision screening data from New York City public schools.

OBJECTIVE: This study compares different vision screening batteries and documents the failure rates of different vision tests in children who receive periodic vision screenings. METHODS: Vision screenings were conducted on 1,992 preschool through fifth grade children attending schools in lower socioeconomic areas in New York City. The screening battery incorporated visual acuity, retinoscopy, cover test, stereopsis, near point of convergence, ocular motility, accommodation, color vision, and ocular health. RESULTS: Slightly less than one third (30%) of the children screened failed the State University of New York (SUNY) battery and were referred for a comprehensive examination, of which 249 (41%) children actually passed distance visual acuities. The referral rate for distance visual acuity alone was 19%. The referral rate for the Modified Clinical Technique (MCT) was 22%. A greater percentage (33%) of the children in grades kindergarten through fifth were referred compared with the preschoolers (20%). Only a small percentage (8%) of the children wore corrective lenses at the time of testing. There was a significant increase in the prevalence of binocular vision problems found in children from grades kindergarten through 5. CONCLUSIONS: Poor visual acuity and binocular vision problems exist in schoolchildren despite ongoing vision screenings. The results provide evidence for the necessity of periodic rescreening starting in kindergarten and the importance of screening for hyperopia and binocular vision problems in addition to distance visual acuities.

A clinical evaluation of proview pressure phosphene tonometry in children.

PURPOSE: The Proview tonometer measures intraocular pressure by inducing a pressure phosphene through the eyelid and, if reliable and valid, may offer a quick, nonthreatening and noninvasive alternative method of obtaining intraocular pressures (IOPs) without the use of eye drops. This study compares the IOP measurements obtained in children using Proview pressure phosphene tonometry (PPPT) and Goldmann tonometry (GT). METHODS: One hundred four 5- to 12-year-old patients of the University Optometric Center/SUNY College of Optometry participated in the study. Subjects were randomized to receive, by different investigators, either PPPT or GT first. Two measurements with each instrument were attempted on each eye of all subjects. A subgroup of 41 subjects was asked which of the two methods was preferred. RESULTS: Seven percent of the subjects did not report a pressure phosphene response compared with 12% of the subjects on whom the investigators were unable to perform GT. The remaining 85 subjects completed the subject protocol. Of the 41 subjects asked, 56% preferred PPPT, 24% had no preference, and 20% preferred GT. The coefficient of repeatability between the two readings was higher for PPPT (3-4 mm Hg) than for GT (1 mm Hg). Mean IOP was 4 mm Hg higher for PPPT than GT with the difference in readings between the two instruments increasing with higher IOPs (r >19%, p < 0.005). CONCLUSIONS: In our study of healthy young subjects, PPPT measurements of IOP appear to be repeatable within a few millimeters of mercury in most children, but for some children, variability in repeat measurements can be substantial. Our data showed a mean difference in readings of 4 mm Hg with a 95% confidence interval that the PPPT reading was between 12 mm Hg above GT and 4 mm Hg below GT. This wide range of values indicates that PPPT is not comparable to GT. However, because our study found that children can appreciate pressure phosphenes and most prefer PPPT over GT, the Proview monitor may have value as a noninvasive, portable screener in pediatric patients. To fully evaluate this potential, further studies are needed that include patients with high IOPs.

Ocular manifestations of chromosome 14 terminal deletion.

A boy with chromosome 14 terminal (14q32.3) deletion presented with typical facial dysmorphism, mental retardation, and hypotonia. Ocular examination revealed esotropia, jerk nystagmus, microcornea, and retinal-choroidal colobomas. We report the first case of microcorneas and colobomas in association with chromosome 14 terminal deletion to help further define this clinical syndrome.

An analysis of high myopia in a pediatric population less than 10 years of age.

PURPOSE: The purpose of this article is to document a comprehensive clinical profile-including the prevalence of amblyopia, strabismus, and anisometropia-of a pediatric population less than 10 years of age who manifested 6.00 diopters or more of myopia. METHOD: A retrospective record review was performed on all pediatric patients less than 10 years of age, examined at the State University of New York (SUNY) State College of Optometry between 1998 and 2001, and with a spherical equivalent of 6.00 diopters or more of myopia. RESULTS: One hundred seventy-eight patients met the criteria. Amblyopia or reduced corrected visual acuity was present in 75.8% of the patients. Strabismus was present in 31.5% of the patients, with essentially equal numbers of esotropes and exotropes. Anisometropia was present in 35.4% of the patients. One hundred forty-five patients had high myopia in the absence of significant ocular or systemic compromising conditions. In this sample of 145, strabismus or anisometropia was an etiology for amblyopia. There was a greater prevalence of bilateral high myopia (64.8%) than unilateral high myopia. Anisometropia was present in 10.6% of the bilateral high myopes, and 78.4% of the unilateral high myopes. CONCLUSION: Children less than 10 years of age with high myopia have a high risk of having amblyopia, strabismus, and anisometropia.