Seroprevalence of Rickettsia Spp. and Orientia tsutsugamushi in Indigenous Populations from the Sierra Nevada de Santa Marta, Colombia.

Background: Rickettsia spp. are vector-borne zoonotic pathogens that cause febrile illness in humans. Rickettsioses is not included in the Colombian national surveillance system and is subsequently expected to be underreported. This cross-sectional study aimed to determine the seroprevalence of Rickettsia spp. and the closely related Orientia tsutsugamushi in two indigenous populations residing in the Sierra Nevada de Santa Marta, Colombia. Materials and Methods: Serum samples (n = 539) were collected from the Wiwa and Koguis people between 2021 and 2022. Serum samples were screened for spotted fever group (SFG) and typhus group (TG) Rickettsia spp. using the Fuller laboratories Rickettsia IgG IFA kit and for O. tsutsugamushi with the Scrub Typhus Detect™ IgG ELISA. Results: We observed an overall seroprevalence of 26.2% (95% confidence interval [CI] 22.5-30.1] for Rickettsia spp. of the SFG, 5.4% (95% CI 3.6-7.6) for Rickettsia spp. of the TG and 4.3% (95% CI 2.7-6.3) for O. tsutsugamushi. Common risk factors for zoonotic disease infections were assessed for 147 of the Wiwa participants. Increased odds of seropositivity for SFG Rickettsia spp. were observed for Wiwa participants who cared for livestock, including assisting with the birth of cattle (odds ratio [OR] = 8.85; 95% CI 1.54-50.90; p = 0.015) and goats (OR = 7.60; 95% CI 1.70-33.90; p = 0.008). Conclusions: These results highlight a notable exposure to Rickettsia spp., especially the SFG, in rural Colombia. Together with recent reports of high mortality for Rocky Mountain Spotted Fever in nearby regions of South America, more detailed investigations focusing on improving knowledge and awareness as well as "One Health" and "causes-of-fever" studies are needed. The characterization of Rickettsia spp. infections in humans, livestock, and tick vectors with their potential transmission routes could make a high impact on these easily treatable diseases.

Recovery of left ventricular systolic function in peripartum cardiomyopathy: an observational study from rural Tanzania.

BACKGROUND: The aim of this study was to evaluate the recovery rate of the left ventricular systolic function of women diagnosed with peripartum cardiomyopathy receiving specialized care in rural Tanzania. METHODS: In this observational study, women diagnosed with peripartum cardiomyopathy at a referral center in rural Tanzania between December 2015 and September 2021 were included. Women diagnosed between February and September 2021 were followed prospectively, those diagnosed between December 2015 and January 2021 were tracked back for a follow-up echocardiography. All participants received a clinical examination, a comprehensive echocardiogram, and a prescription of guideline-directed medical therapy. The primary outcome was recovery of the left ventricular systolic function (left ventricular ejection fraction > 50%). RESULTS: Median age of the 110 participants was 28.5 years (range 17-45). At enrolment, 49 (45%) participants were already on cardiac medication, 50 (45%) had severe eccentric hypertrophy of the left ventricle, and the median left ventricular ejection fraction was 30% (range 15-46). After a median follow-up of 8.98 months (IQR 5.72-29.37), 61 (55%) participants were still on cardiac medication. Full recovery of the left ventricular systolic function was diagnosed in 76 (69%, 95% CI 59.6-77.6%) participants. In the multivariate analysis, a higher left ventricular ejection fraction at baseline was positively associated with full recovery (each 5% increase; OR 1.7, 95% CI 1.10-2.62, p = 0.012), while higher age was inversely associated (each 10 years increase; OR 0.40, 95% CI 0.19-0.82, p = 0.012). CONCLUSION: Left ventricular systolic function recovered completely in 69% of study participants with peripartum cardiomyopathy from rural Tanzania under specialized care.

Status of zoonotic disease research in refugees, asylum seekers and internally displaced people, globally: A scoping review of forty clinically important zoonotic pathogens.

BACKGROUND: At the end of 2022, there were over 108 million forcibly displaced people globally, including refugees, asylum seekers (AS) and internally displaced people (IDPs). Forced migration increases the risk of infectious disease transmission, and zoonotic pathogens account for 61% of emerging and re-emerging infectious diseases. Zoonoses create a high burden of disease and have the potential to cause large-scale outbreaks. This scoping review aimed to assess the state of research on a range of clinically relevant zoonotic pathogens in displaced populations in order to identify the gaps in literature and guide future research. METHODOLOGY / PRINCIPAL FINDINGS: Literature was systematically searched to identify original research related to 40 selected zoonotic pathogens of interest in refugees, AS and IDPs. We included only peer-reviewed original research in English, with no publication date restrictions. Demographic data, migration pathways, health factors, associated outbreaks, predictive factors and preventative measures were extracted and synthesized. We identified 4,295 articles, of which 347 were included; dates of publications ranged from 1937 to 2022. Refugees were the most common population investigated (75%). Migration pathways of displaced populations increased over time towards a more complex web, involving migration in dual directions. The most frequent pathogen investigated was Schistosoma spp. (n = 99 articles). Disease outbreaks were reported in 46 publications (13.3%), with viruses being the most commonly reported pathogen type. Limited access to hygiene/sanitation, crowding and refugee status were the most commonly discussed predictors of infection. Vaccination/prophylaxis drug administration, surveillance/screening and improved hygiene/sanitation were the most commonly discussed preventative measures. CONCLUSIONS / SIGNIFICANCE: The current research on zoonoses in displaced populations displays gaps in the spectrum of pathogens studied, as well as in the (sub)populations investigated. Future studies should be more inclusive of One Health approaches to adequately investigate the impact of zoonotic pathogens and identify transmission pathways as a basis for designing interventions for displaced populations.

Navigating challenges: a socioecological analysis of sexual and reproductive health barriers among Eritrean refugee women in Ethiopia, using a key informant approach.

OBJECTIVES: The study aimed to explore the experiences and perceptions of healthcare providers (HCPs) regarding the sexual and reproductive health (SRH) challenges of Eritrean refugee women in Ethiopia. DESIGN: A qualitative exploratory design with the key informant approach. SETTING AND PARTICIPANTS: The study was conducted in the Afar regional state, North East, Ethiopia. The study participants were HCP responsible for providing SRH care for refugee women. RESULTS: Eritrean refugee women have worse health outcomes than the host population. The SRH needs were found to be hindered at multiple layers of socioecological model (SEM). High turnover and shortage of HCP, restrictive laws, language issues, cultural inconsistencies and gender inequalities were among the main barriers reported. Complex multistructural factors are needed to improve SRH needs of Eritrean refugee women. CONCLUSIONS: A complex set of issues spanning individual needs, social norms, community resources, healthcare limitations and structural mismatches create significant barriers to fulfilling the SRH needs of Eritrean refugee women in Ethiopia. Factors like limited awareness, cultural taboos, lack of safe spaces, inadequate healthcare facilities and restrictive policies all contribute to the severe limitations on SRH services available in refugee settings. The overlap in findings underscores the importance of developing multilevel interventions that are culturally sensitive to the needs of refugee women across all SEM levels. A bilateral collaboration between Refugees and Returnees Service (RRS) structures and the Asayta district healthcare system is critically important.

Design of a targeted blood transcriptional panel for monitoring immunological changes accompanying pregnancy.

Background: Immunomodulatory processes exert steering functions throughout pregnancy. Detecting diversions from this physiologic immune clock may help identify pregnant women at risk for pregnancy-associated complications. We present results from a data-driven selection process to develop a targeted panel of mRNAs that may prove effective in detecting pregnancies diverting from the norm. Methods: Based on a de novo dataset from a resource-constrained setting and a dataset from a resource-rich area readily available in the public domain, whole blood gene expression profiles of uneventful pregnancies were captured at multiple time points during pregnancy. BloodGen3, a fixed blood transcriptional module repertoire, was employed to analyze and visualize gene expression patterns in the two datasets. Differentially expressed genes were identified by comparing their abundance to non-pregnant postpartum controls. The selection process for a targeted gene panel considered (i) transcript abundance in whole blood; (ii) degree of correlation with the BloodGen3 module; and (iii) pregnancy biology. Results: We identified 176 transcripts that were complemented with eight housekeeping genes. Changes in transcript abundance were seen in the early stages of pregnancy and similar patterns were observed in both datasets. Functional gene annotation suggested significant changes in the lymphoid, prostaglandin and inflammation-associated compartments, when compared to the postpartum controls. Conclusion: The gene panel presented here holds promise for the development of predictive, targeted, transcriptional profiling assays. Such assays might become useful for monitoring of pregnant women, specifically to detect potential adverse events early. Prospective validation of this targeted assay, in-depth investigation of functional annotations of differentially expressed genes, and assessment of common pregnancy-associated complications with the aim to identify these early in pregnancy to improve pregnancy outcomes are the next steps.

Use of a Handheld Ultrasonographic Device to Identify Heart Failure and Pulmonary Disease in Rural Africa.

Importance: Agreement in lung ultrasonography findings between clinicians using a handheld ultrasonographic device and expert sonographers using a high-end ultrasonographic machine has not been studied in sub-Saharan Africa. Objective: To determine the agreement in ultrasonographic findings and diagnoses between primary care clinicians trained in lung ultrasonography, board-certified expert sonographers, and senior physicians. Design, Setting, and Participants: This cross-sectional single-center study was conducted from February 1, 2022, to April 30, 2023 at a referral center in rural Tanzania. Individuals 5 years or older with respiratory symptoms and at least 2 distinct respiratory signs or symptoms were eligible. A total of 459 individuals were screened. Exposures: Participants provided their medical history and underwent a clinical examination and lung ultrasonography performed by a clinician, followed by a lung ultrasonography performed by an expert sonographer, and finally chest radiography and a final evaluation performed by a senior physician. Other tests, such as echocardiography and Mycobacterium tuberculosis testing, were conducted on the decision of the physician. Clinicians received 2 hours of instruction and three 2-hour sessions of clinical training in the use of a handheld lung ultrasonographic device; expert sonographers were board-certified. Main Outcomes and Measures: Percentage agreement and Cohen κ coefficient for sonographic findings and diagnoses compared between clinicians and expert sonographers, and between clinicians and senior physicians. Results: The median (IQR) age of 438 included participants was 54 (38-66) years, and 225 (51%) were male. The median (range) percentage agreement of ultrasonographic findings between clinicians and expert sonographers was 93% (71%-99%), with κ ranging from -0.003 to 0.83. Median (range) agreement of diagnoses between clinicians and expert sonographers was 90% (50%-99%), with κ ranging from -0.002 to 0.76. Between clinicians and senior physicians, median (range) agreement of diagnoses was 89% (55%-90%), with κ ranging from -0.008 to 0.76. Between clinicians and senior physicians, diagnosis agreements were 85% (κ, 0.69) for heart failure, 78% (κ, 0.57) for definite or probable tuberculosis, 50% (κ, 0.002) for viral pneumonia, and 56% (κ, 0.06) for bacterial pneumonia. Conclusions and Relevance: In this cross-sectional study, the agreement of ultrasonographic findings between clinicians and sonographers was mostly substantial. Between clinicians and senior physicians, agreement was substantial in the diagnosis of heart failure, moderate in the diagnosis of tuberculosis, but slight in the diagnosis of pneumonia. These findings suggest that handheld ultrasonographic devices used in addition to clinical examination may support clinicians in diagnosing cardiac and pulmonary diseases in rural sub-Saharan Africa.

Seroprevalence of Coxiella burnetii in an Indigenous Population from the Sierra Nevada De Santa Marta, Colombia.

Coxiella burnetii is an underreported zoonotic pathogen in many rural regions globally. We investigated C. burnetii exposure in a remote indigenous tribe residing in the Sierra Nevada de Santa Marta, Colombia. The high seroprevalence of 35% (95% CI, 27-43%) demonstrates the need for One Health studies to identify risk factors, clinical impact, and potential medical, veterinary, and environmental interventions.

Improving Primary Healthcare Access for Asylum Seekers and Refugees: A Qualitative Study From a Swiss Family Physician Perspective.

Since 2015 the need for evidence-based guidance in primary health care management of refugees, asylum seekers, and immigrants has dramatically increased. The aims of this study were to identify the challenges met by primary care physicians in Switzerland, by performing semi-structured interviews and to identify possible approaches and interventions. Between January 2019 and January 2020, 20 GPs in 3 Swiss cantons were interviewed. The interviews were transcribed, coded with MAXQDA 18, and analyzed using the framework methodology. Following relevant findings were highlighted; (i) problems relating to health insurance companies among (health-insured) asylum seekers and refugees were negligible; (ii) there is a high acceptance for vaccination by refugees, asylum seekers, and immigrants; (iii) limitations in time for consultations and adequate reimbursement for practitioners pose a serious challenge; (iv) the majority of consultations are complaint-oriented, preventive consultations are rare; and (v) the language barrier is a major challenge for psychosocial consultations, whereas this appears less relevant for somatic complaints. The following issues were identified as high priority needs by the study participants; (i) increased networking between GPs, that is, establishing bridging services with asylum centers, (ii) improved training opportunities for GPs in Migration Medicine with regular updates of current guidelines, and (iii) a standardisation of health documentation facilitating exchange of medical data, that is, digital/paper-based "health booklet" or "health pass."

The malaria blood stage antigen PfCyRPA formulated with the TLR-4 agonist adjuvant GLA-SE elicits parasite growth inhibitory antibodies in experimental animals.

BACKGROUND: Plasmodium falciparum cysteine-rich protective antigen (PfCyRPA) is an invasion complex protein essential for erythrocyte invasion. In contrast to several previously clinically tested merozoite vaccine candidate antigens, PfCyRPA is not polymorphic, making it a promising candidate antigen for blood stage vaccine development. METHODS: Mice and rabbits were immunized with vaccine formulations of recombinantly expressed PfCyRPA adjuvanted either with the glucopyranosyl lipid A (GLA) containing adjuvants GLA-LSQ, GLA-SE, GLA-Alum or with Nanoalum. ELISA and indirect immunofluorescence assays (IFA) were used to analyse elicited IgG titers and the P. falciparum growth inhibitory activity was determined with a standardized in vitro [3H]-hypoxanthine incorporation assay. RESULTS: In the mouse experiments, the GLA adjuvanted formulations were superior to the Nanoalum formulation with respect to antibody titer development, IFA sero-conversion rates and in vitro parasite growth-inhibitory activity. In rabbits, the highest titers of parasite growth inhibitory antibodies were obtained with the GLA-SE formulation. Comparable mean ELISA IgG endpoint titers were reached in rabbits after three immunizations with GLA-SE adjuvanted PfCyRPA doses of 5, 25 and 100 µg, but with 100 µg of antigen, only two immunizations were required to reach this titer. CONCLUSION: PfCyRPA formulated with the human-compatible adjuvant GLA-SE represents an attractive vaccine candidate for early clinical testing in a controlled P. falciparum blood stage challenge trial.

Association of Hypertension, Diabetes, and Cardiovascular Disease with COVID-19 in Africa: Scoping Review Protocol.

BACKGROUND: COVID-19 caused devastating effects on global healthcare systems. The elderly and people with chronic comorbidities were at a particularly high risk of mortality and morbidity. However, the evidence on the association of COVID-19 severity with noncommunicable diseases (NCDs) in the African population is scarce. OBJECTIVE: The aim is to estimate COVID-19 severity among African patients with hypertension, diabetes, and cardiovascular diseases (CVDs) and its implications for case management. METHODS: We will adhere to the extension for Scoping Reviews of PRISMA (PRISMA-ScR). The following electronic databases will be searched: PubMed, Scopus, Web of Science, Embase, CINAHL, and Joanna Briggs Institute. The search will be conducted after the publication of this protocol. Two reviewers will extract data from articles published after March 2020 without language restrictions. A descriptive analysis of the important findings and a narrative synthesis of the results will serve as the basis for interpretation. Expected results and conclusions: This scoping review is expected to determine the odds of patients with chronic comorbidities to progress to severe stages of COVID-19. The review will generate an evidence-based and set foundation for recommendations toward the establishment of surveillance systems and referral guidelines for the management of NCDs in the face of COVID-19 and future pandemics.

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS): A preliminary survey among patients in Switzerland.

Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is a multi-factorial systemic chronic debilitating disease of poorly understood etiology and limited systematic evidence. The questionnaire and interview-based survey included 169 ME/CFS patients from the Swiss ME/CFS association. The majority of patients were females (72.2%), single (55.7%) and without children (62.5%). Only one third were working (full/part-time). The mean onset of ME/CFS was 31.6 years of age with 15% of patients being symptomatic before their 18th birthday. In this cohort, patients had documented ME/CFS for a mean 13.7 years, whereby half (50.3%) stated their condition was progressively worsening. Triggering events and times of disease onset were recalled by 90% of the participants. An infectious disease was associated with a singular or part of multiple events by 72.9% and 80.6%, respectively. Prior to disease onset, a third of the patients reported respiratory infections; followed by gastro-intestinal infections (15.4%) and tick-borne diseases (16.2%). Viral infections were recalled by 77.8% of the respondents, with Epstein Barr Virus being the most commonly reported agent. Patients self-reported an average number of 13 different symptoms, all described specific triggers of symptoms exacerbation and 82.2% suffered from co-morbidities. This study collated clinically relevant information on ME/CFS patients in Switzerland, highlighting the extent of disease severity, the associated factors negatively affecting daily life activities and work status as well as potential socio-economic impact.

Prevalence of fever of unidentified aetiology in East African adolescents and adults: a systematic review and meta-analysis.

BACKGROUND: Primary health care settings and hospitals of low- and middle-income countries have few accessible diagnostic tools and limited laboratory and human resources capacity to identify multiple pathogens with high accuracy. In addition, there is a paucity of information on fever and its underlying aetiology in the adolescent and adult population in East Africa. The purpose of this study was to estimate the pooled prevalence of fever of unidentified aetiology among adolescent and adult febrile patients seeking health care in East Africa. METHODS: We pursued a systematic review using readily available electronic databases (i.e. PubMed, Cumulative Index to Nursing & Allied Health Literature, Scopus, Cochrane Library and Web of Science) without language restriction from inception date of the respective databases to October 31, 2022. We adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Identified studies were screened for relevance. Further analyses based on pre-set eligibility criteria were carried out for final inclusion. Two reviewers independently screened and extracted data. Risk of study bias was assessed. Meta-analysis of the prevalence of fever of unidentified aetiology was performed. RESULTS: We identified 14,029 articles of which 25 were eligible for inclusion, reporting data from 8538 participants. The pooled prevalence of febrile cases with unidentified aetiology was 64% [95% confidence interval (CI): 51-77%, I2 = 99.6%] among febrile adolescents and adults in East Africa. For the proportion of patients with identified aetiology, the studies documented bacterial pathogens (human bloodstream infections), bacterial zoonotic pathogens and arboviruses as the main non-malarial causative agents in East Africa. CONCLUSIONS: Our study provides evidence that almost two-thirds of adolescent and adult febrile patients attending health care facilities in East Africa might receive inappropriate treatments due to unidentified potential life-threatening fever aetiology. Hence, we call for a comprehensive fever syndromic surveillance to broaden a consequential differential diagnosis of syndromic fever and to considerably improve the course of patients' disease and treatment outcomes.

Correction: A time-course comparative clinical and immune response evaluation study between the human pathogenic Orientia tsutsugamushi strains: Karp and Gilliam in a rhesus macaque (Macaca mulatta) model.

[This corrects the article DOI: 10.1371/journal.pntd.0010611.].

A whole blood intracellular cytokine assay optimised for field site studies demonstrates polyfunctionality of CD4+ T cells in acute scrub typhus.

BACKGROUND: Assessment of cellular immune responses by combining intracellular cytokine staining and immunophenotyping using flow cytometry enables the simultaneous measurement of T cell phenotype and effector function in response to pathogens and vaccines. The use of whole blood samples rather than peripheral blood mononuclear cells avoids both the need for immediate processing and loss of functional antigen presenting cells due to processing and cryopreservation. Using whole blood provides the possibility to stimulate peripheral T cells in situ, and is more suitable for studies where sample volume is limited, such as those involving children, the elderly and critically ill patients. The aim of this study was to provide a robust tool for the assessment of antigen-specific T cell responses in a field site setting with limited resources. METHODOLOGY/PRINCIPLE FINDINGS: We optimised a flow cytometry-based whole blood intracellular cytokine assay (WBA) with respect to duration of antigen stimulation and intracellular protein retention time. We demonstrate the ability of the WBA to capture polyfunctional T cell responses in the context of acute scrub typhus infection, by measuring IFN-γ, TNF and IL-2 in CD4+ and CD8+ T cells in response to the causative agent O. tsutsugamushi (OT). Using an optimised OT antigen preparation, we demonstrate the presence of polyfunctional antigen-specific memory CD4+ T cells in the blood of scrub typhus patients. CONCLUSIONS/SIGNIFICANCE: In conclusion, this flow cytometry-based WBA is well-suited for use at field study sites, and enables the assessment of polyfunctional T cell responses to infectious agents and vaccines through delineation of antigen-specific cytokine secretion at the single cell level.

Health system support among patients with ME/CFS in Switzerland.

Objectives: Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a complex chronic and debilitating multifactorial disease. Adequate patient care is challenged by poor knowledge among health care professionals and the historical misconception that the disease is psychological in nature. This study assessed the health-related challenges faced by patients with ME/CFS in Switzerland and examined whether they receive adequate health care. Methods: Quantitative and qualitative data were collected through a self-administered questionnaire between June and September of 2021, among 169 patients with ME/CFS in Switzerland. Results: The mean age at diagnosis was 38.8 years. Only one-third of ME/CFS affected children and youth were correctly diagnosed before their 18th birthday. The mean time from disease onset to diagnosis was 6.7 years, and patients had an average of 11.1 different appointments and 2.6 misdiagnoses. A poor diagnosis rate and insufficient disease knowledge among health professionals in Switzerland led 13.5% of the patients to travel abroad to seek a diagnosis. Most patients (90.5%) were told at least once that their symptoms were psychosomatic. Swiss patients expressed high dissatisfaction with the health system and indicated that physicians lacked knowledge regarding ME/CFS. Therapies prescribed by physicians or tried by patients, as well as their perceived efficacy, were described. Graded Exercise Therapy (GET) was perceived as harmful by patients, whereas pacing, complementary/alternative medicine, and dietary supplements and medications to alleviate symptoms were reported to be helpful to varying degrees. Conclusion: This study highlights that poor disease knowledge among health care providers in Switzerland has led to high patient dissatisfaction, and delays in ME/CFS diagnoses and prescription of inappropriate therapies, thus adding to patient distress and disease burden.

Ultrasononography in Managing Extrapulmonary Tuberculosis: A Randomized, Controlled, Parallel, Superiority, Open-Label Trial.

BACKGROUND: Patients with suspected extrapulmonary tuberculosis are often treated empirically. We hypothesized that extended focused assessment with sonography for human immunodeficiency virus (HIV) and tuberculosis (eFASH), in combination with other tests, would increase the proportion of correctly managed patients with suspected extrapulmonary tuberculosis. METHODS: This trial in adults with suspected extrapulmonary tuberculosis was performed in a rural and an urban hospital in Tanzania. Participants were randomized 1:1 to intervention or routine care, stratified by site and HIV status. All participants underwent clinical evaluation, chest radiography, and testing with sputum Xpert MTB/RIF and urine Xpert MTB/RIF Ultra assays. The intervention was a management algorithm based on results of eFASH plus microbiology, adenosine deaminase (ADA), and chest radiography. The primary outcome was the proportion of correctly managed patients. The presence of positive microbiological or ADA results defined definite tuberculosis. An independent end-point review committee determined diagnoses of probable or no tuberculosis. We evaluated outcomes using logistic regression models, adjusted for randomization stratification factors. RESULTS: From September 2018 to October 2020, a total of 1036 patients were screened and 701 were randomized (350 to the intervention and 351 to the control group). Of participants in the intervention group, 251 (72%) had a positive eFASH outcome. In 258 (74%) of the intervention and 227 (65%) of the control participants antituberculosis was initiated treatment at baseline. More intervention participants had definite tuberculosis (n = 124 [35%]), compared with controls (n = 85 [24%]). There was no difference between groups for the primary outcome (intervention group, 266 of 286 [93%]; control group, 245 of 266 [92%]; odds ratio, 1.14 [95% confidence interval: .60-2.16]; P = .68). There were no procedure-associated adverse events. CONCLUSIONS: eFASH did not change the proportion of correctly managed patients but increased the proportion of those with definite tuberculosis. CLINICAL TRIALS REGISTRATION: Pan African Registry: PACTR201712002829221.

Orientia tsutsugamushi in Chiggers and Small Mammals in Laos.

Background: Scrub typhus is a leading cause of febrile illness in Laos and accounts for a high burden of disease. There have been no previous studies on the causative agent, Orientia tsutsugamushi, in vector mites ("chiggers") or their small mammal hosts in Laos. Materials and Methods: Small mammals and free-living chiggers were trapped in districts of Vientiane Province and Capital. Tissues were tested for O. tsutsugamushi by PCR and serum for IgG to O. tsutsugamushi by immunofluorescence assays (IFAs). Chiggers removed from small mammals and collected in their free-living stage using black plates were identified and tested for O. tsutsugamushi by PCR. Results: Over an 18-month period, 131 small mammals of 14 species were collected in 5 districts. Seventy-eight of 131 small mammals were infested with chiggers, but all tissues were O. tsutsugamushi PCR negative. Eighteen species of chigger were identified and 1,609 were tested by PCR. A single pool of chiggers tested O. tsutsugamushi positive. Sera from 52 small mammals were tested by IFA, with 16 testing positive. Conclusions: These are the first molecular and serological data on O. tsutsugamushi in chiggers and small mammals in Laos. Further studies are needed to better understand the key vector species and ecology of scrub typhus in areas with high disease incidence in Laos.

The Chronic Diseases Clinic of Ifakara (CDCI)-Establishing a Model Clinic for Chronic Care Delivery in Rural Sub-Saharan Africa.

The rollout of antiretroviral drugs in sub-Saharan Africa to address the huge health impact of the HIV pandemic has been one of the largest projects undertaken in medical history and is an unprecedented medical success story. However, the path has been and still is characterized by many far reaching implementational challenges. Here, we report on the building and maintaining of a role model clinic in Ifakara, rural Southwestern Tanzania, within a collaborative project to support HIV services within the national program, training for staff and integrated research to better understand local needs and improve patients' outcomes.

A time-course comparative clinical and immune response evaluation study between the human pathogenic Orientia tsutsugamushi strains: Karp and Gilliam in a rhesus macaque (Macaca mulatta) model.

BACKGROUND: Scrub typhus is a vector-borne febrile illness caused by Orientia tsutsugamushi transmitted by the bite of Trombiculid mites. O. tsutsugamushi has a high genetic diversity and is increasingly recognized to have a wider global distribution than previously assumed. METHODOLOGY/PRINCIPLE FINDINGS: We evaluated the clinical outcomes and host immune responses of the two most relevant human pathogenic strains of O. tsutsugamushi; Karp (n = 4) and Gilliam (n = 4) in a time-course study over 80 days post infection (dpi) in a standardized scrub typhus non-human primate rhesus macaque model. We observed distinct features in clinical progression and immune response between the two strains; Gilliam-infected macaques developed more pronounced systemic infection characterized by an earlier onset of bacteremia, lymph node enlargement, eschar lesions and higher inflammatory markers during the acute phase of infection, when compared to the Karp strain. C-reactive protein (CRP) plasma levels, interferon gamma (IFN-γ, interleukin-1 receptor antagonist (IL-1ra), IL-15 serum concentrations, CRP/IL10- and IFN-γ/IL-10 ratios correlated positively with bacterial load in blood, implying activation of the innate immune response and preferential development of a T helper-type 1 immune response. The O. tsutsugamushi-specific immune memory responses in cells isolated from skin and lymph nodes at 80 dpi were more markedly elevated in the Gilliam-infected macaques than in the Karp-infected group. The comparative cytokine response dynamics of both strains revealed significant up-regulation of IFN-γ, tumor necrosis factor (TNF), IL-15, IL-6, IL-18, regulatory IL-1ra, IL-10, IL-8 and granulocyte-colony-stimulating factor (G-CSF). These data suggest that the clinical outcomes and host immune responses to scrub typhus could be associated with counter balancing effects of pro- and anti-inflammatory cytokine-mediated responses. Currently, no data on characterized time-course comparisons of O. tsutsugamushi strains regarding measures of disease severity and immune response is available. Our study provides evidence for the strain-specificity of host responses in scrub typhus, which supports our understanding of processes at the initial inoculation site (eschar), systemic disease progression, protective and/or pathogenic host immune mechanisms and cellular immune memory function. CONCLUSIONS/SIGNIFICANCE: This study characterised an improved intradermal rhesus macaque challenge model for scrub typhus, whereby the Gilliam strain infection associated with higher disease severity in the rhesus macaque model than the previous Karp strain infection. Difficulties associated with inoculum quantitation for obligate-intracellular bacteria were overcome by using functional inoculum titrations in outbred mice. The Gilliam-based rhesus macaque model provides improved endpoint measurements and contributes towards the identification of correlates of protection for future vaccine development.

Correction: Yuhana et al. Rickettsial Infections Are Neglected Causes of Acute Febrile Illness in Teluk Intan, Peninsular Malaysia. Trop. Med. Infect. Dis. 2022, 7, 77.

The authors wish to make the following correction to this paper [...].