Prevalence and risk factors for Q fever, spotted fever group rickettsioses, and typhus group rickettsioses in a pastoralist community of northern Tanzania, 2016-2017.

BACKGROUND: In northern Tanzania, Q fever, spotted fever group (SFG) rickettsioses, and typhus group (TG) rickettsioses are common causes of febrile illness. We sought to describe the prevalence and risk factors for these zoonoses in a pastoralist community. METHODS: Febrile patients ≥2 years old presenting to Endulen Hospital in the Ngorongoro Conservation Area were enrolled from August 2016 through October 2017. Acute and convalescent blood samples were collected, and a questionnaire was administered. Sera were tested by immunofluorescent antibody (IFA) IgG assays using Coxiella burnetii (Phase II), Rickettsia africae, and Rickettsia typhi antigens. Serologic evidence of exposure was defined by an IFA titre ≥1:64; probable cases by an acute IFA titre ≥1:128; and confirmed cases by a ≥4-fold rise in titre between samples. Risk factors for exposure and acute case status were evaluated. RESULTS: Of 228 participants, 99 (43.4%) were male and the median (interquartile range) age was 27 (16-41) years. Among these, 117 (51.3%) had C. burnetii exposure, 74 (32.5%) had probable Q fever, 176 (77.2%) had SFG Rickettsia exposure, 134 (58.8%) had probable SFG rickettsioses, 11 (4.8%) had TG Rickettsia exposure, and 4 (1.8%) had probable TG rickettsioses. Of 146 participants with paired sera, 1 (0.5%) had confirmed Q fever, 8 (5.5%) had confirmed SFG rickettsioses, and none had confirmed TG rickettsioses. Livestock slaughter was associated with acute Q fever (adjusted odds ratio [OR] 2.54, 95% confidence interval [CI] 1.38-4.76) and sheep slaughter with SFG rickettsioses case (OR 4.63, 95% CI 1.08-23.50). DISCUSSION: Acute Q fever and SFG rickettsioses were detected in participants with febrile illness. Exposures to C. burnetii and to SFG Rickettsia were highly prevalent, and interactions with livestock were associated with increased odds of illness with both pathogens. Further characterisation of the burden and risks for these diseases is warranted.

Investigating the etiology of acute febrile illness: a prospective clinic-based study in Uganda.

BACKGROUND: Historically, malaria has been the predominant cause of acute febrile illness (AFI) in sub-Saharan Africa. However, during the last two decades, malaria incidence has declined due to concerted public health control efforts, including the widespread use of rapid diagnostic tests leading to increased recognition of non-malarial AFI etiologies. Our understanding of non-malarial AFI is limited due to lack of laboratory diagnostic capacity. We aimed to determine the etiology of AFI in three distinct regions of Uganda. METHODS: A prospective clinic-based study that enrolled participants from April 2011 to January 2013 using standard diagnostic tests. Participant recruitment was from St. Paul's Health Centre (HC) IV, Ndejje HC IV, and Adumi HC IV in the western, central and northern regions, which differ by climate, environment, and population density. A Pearson's chi-square test was used to evaluate categorical variables, while a two-sample t-test and Krukalis-Wallis test were used for continuous variables. RESULTS: Of the 1281 participants, 450 (35.1%), 382 (29.8%), and 449 (35.1%) were recruited from the western, central, and northern regions, respectively. The median age (range) was 18 (2-93) years; 717 (56%) of the participants were female. At least one AFI pathogen was identified in 1054 (82.3%) participants; one or more non-malarial AFI pathogens were identified in 894 (69.8%) participants. The non-malarial AFI pathogens identified were chikungunya virus, 716 (55.9%); Spotted Fever Group rickettsia (SFGR), 336 (26.2%) and Typhus Group rickettsia (TGR), 97 (7.6%); typhoid fever (TF), 74 (5.8%); West Nile virus, 7 (0.5%); dengue virus, 10 (0.8%) and leptospirosis, 2 (0.2%) cases. No cases of brucellosis were identified. Malaria was diagnosed either concurrently or alone in 404 (31.5%) and 160 (12.5%) participants, respectively. In 227 (17.7%) participants, no cause of infection was identified. There were statistically significant differences in the occurrence and distribution of TF, TGR and SFGR, with TF and TGR observed more frequently in the western region (p = 0.001; p < 0.001) while SFGR in the northern region (p < 0.001). CONCLUSION: Malaria, arboviral infections, and rickettsioses are major causes of AFI in Uganda. Development of a Multiplexed Point-of-Care test would help identify the etiology of non-malarial AFI in regions with high AFI rates.

Incidence Estimates of Acute Q Fever and Spotted Fever Group Rickettsioses, Kilimanjaro, Tanzania, from 2007 to 2008 and from 2012 to 2014.

Q fever and spotted fever group rickettsioses (SFGR) are common causes of severe febrile illness in northern Tanzania. Incidence estimates are needed to characterize the disease burden. Using hybrid surveillance-coupling case-finding at two referral hospitals and healthcare utilization data-we estimated the incidences of acute Q fever and SFGR in Moshi, Kilimanjaro, Tanzania, from 2007 to 2008 and from 2012 to 2014. Cases were defined as fever and a four-fold or greater increase in antibody titers of acute and convalescent paired sera according to the indirect immunofluorescence assay of Coxiella burnetii phase II antigen for acute Q fever and Rickettsia conorii (2007-2008) or Rickettsia africae (2012-2014) antigens for SFGR. Healthcare utilization data were used to adjust for underascertainment of cases by sentinel surveillance. For 2007 to 2008, among 589 febrile participants, 16 (4.7%) of 344 and 27 (8.8%) of 307 participants with paired serology had Q fever and SFGR, respectively. Adjusted annual incidence estimates of Q fever and SFGR were 80 (uncertainty range, 20-454) and 147 (uncertainty range, 52-645) per 100,000 persons, respectively. For 2012 to 2014, among 1,114 febrile participants, 52 (8.1%) and 57 (8.9%) of 641 participants with paired serology had Q fever and SFGR, respectively. Adjusted annual incidence estimates of Q fever and SFGR were 56 (uncertainty range, 24-163) and 75 (uncertainty range, 34-176) per 100,000 persons, respectively. We found substantial incidences of acute Q fever and SFGR in northern Tanzania during both study periods. To our knowledge, these are the first incidence estimates of either disease in sub-Saharan Africa. Our findings suggest that control measures for these infections warrant consideration.

Sensitivity of C-reactive protein for the identification of patients with laboratory-confirmed bacterial infections in northern Tanzania.

OBJECTIVE: Identifying febrile patients requiring antibacterial treatment is challenging, particularly in low-resource settings. In South-East Asia, C-reactive protein (CRP) has been demonstrated to be highly sensitive and moderately specific in detecting bacterial infections and to safely reduce unnecessary antibacterial prescriptions in primary care. As evidence is scant in sub-Saharan Africa, we assessed the sensitivity of CRP in identifying serious bacterial infections in Tanzania. METHODS: Samples were obtained from inpatients and outpatients in a prospective febrile illness study at two hospitals in Moshi, Tanzania, 2011-2014. Bacterial bloodstream infections (BSI) were established by blood culture, and bacterial zoonotic infections were defined by ≥4 fold rise in antibody titre between acute and convalescent sera. The sensitivity of CRP in identifying bacterial infections was estimated using thresholds of 10, 20 and 40 mg/l. Specificity was not assessed because determining false-positive CRP results was limited by the lack of diagnostic testing to confirm non-bacterial aetiologies and because ascertaining true-negative cases was limited by the imperfect sensitivity of the diagnostic tests used to identify bacterial infections. RESULTS: Among 235 febrile outpatients and 569 febrile inpatients evaluated, 31 (3.9%) had a bacterial BSI and 61 (7.6%) had a bacterial zoonosis. Median (interquartile range) CRP values were 173 (80-315) mg/l in bacterial BSI, and 108 (31-208) mg/l in bacterial zoonoses. The sensitivity (95% confidence intervals) of CRP was 97% (83%-99%), 94% (79%-98%) and 90% (74%-97%) for identifying bacterial BSI, and 87% (76%-93%), 82% (71%-90%) and 72% (60%-82%) for bacterial zoonoses, using thresholds of 10, 20 and 40 mg/l, respectively. CONCLUSION: C-reactive protein was moderately sensitive for bacterial zoonoses and highly sensitive for identifying BSIs. Based on these results, operational studies are warranted to assess the safety and clinical utility of CRP for the management of non-malaria febrile illness at first-level health facilities in sub-Saharan Africa.

OBJECTIF: Identifier les patients fébriles nécessitant un traitement antibactérien est un défi, en particulier dans les milieux à faibles ressources. En Asie du Sud-Est, il a été démontré que la protéine C-réactive (CRP) est très sensible et modérément spécifique dans la détection des infections bactériennes et qu'elle réduit en toute sécurité les prescriptions antibactériennes inutiles dans les soins primaires. Comme les données sont rares en Afrique subsaharienne (ASS), nous avons évalué la sensibilité de la CRP dans l'identification des infections bactériennes sévères en Tanzanie. MÉTHODES: Des échantillons ont été obtenus auprès de patients hospitalisés et ambulatoires dans une étude prospective sur les maladies fébriles dans deux hôpitaux à Moshi, en Tanzanie de 2011 à 2014. Les infections bactériennes du sang (IBS) ont été identifiées par la culture du sang et les infections bactériennes zoonotiques ont été définies par une élevation ≥ 4 fois le titre des anticorps entre les sérums en aiguë et en convalescence. La sensibilité de la CRP dans l'identification des infections bactériennes a été estimée en utilisant des seuils de 10, 20 et 40 mg/L. La spécificité n'a pas été évaluée parce que la détermination des résultats faux positifs de la CRP était limitée par le manque de tests de diagnostic pour confirmer les étiologies non bactériennes et parce que la confirmation des vrais cas négatifs était limitée par la sensibilité imparfaite des tests de diagnostic utilisés pour identifier les infections bactériennes. RÉSULTATS: Sur 235 patients ambulatoires fébriles et 569 patients hospitalisés fébriles évalués, 31 (3.9%) avaient une IBS et 61 (7.6%) avaient une zoonose bactérienne. Les valeurs médianes (intervalle interquartile) de la CRP étaient de 173 (80-315) mg/L dans les IBS et de 108 (31-208) mg/L dans les zoonoses bactériennes. La sensibilité (intervalles de confiance à 95%) de la CRP était de 97% (83-99%), 94% (79-98%), 90% (74-97%) pour identifier les IBS et 87% (76-93% ), 82% (71-90%), 72% (60-82%) pour les zoonoses bactériennes, en utilisant des seuils de 10, 20 et 40 mg/L respectivement. CONCLUSION: La CRP était modérément sensible pour les zoonoses bactériennes et hautement sensible pour l'identification des IBS. Sur la base de ces résultats, des études opérationnelles sont justifiées pour évaluer la sécurité et l'utilité clinique de la CRP pour la prise en charge des maladies fébriles non paludiques dans les établissements de santé de premier niveau en ASS.

Ebola Virus Disease Diagnostics, Sierra Leone: Analysis of Real-time Reverse Transcription-Polymerase Chain Reaction Values for Clinical Blood and Oral Swab Specimens.

During the Ebola virus outbreak of 2013-2016, the Viral Special Pathogens Branch field laboratory in Sierra Leone tested approximately 26 000 specimens between August 2014 and October 2015. Analysis of the B2M endogenous control Ct values showed its utility in monitoring specimen quality, comparing results with different specimen types, and interpretation of results. For live patients, blood is the most sensitive specimen type and oral swabs have little diagnostic utility. However, swabs are highly sensitive for diagnostic testing of corpses.

Incident Tick-Borne Infections in a Cohort of North Carolina Outdoor Workers.

Tick-borne diseases cause substantial morbidity throughout the United States, and North Carolina has a high incidence of spotted fever rickettsioses and ehrlichiosis, with sporadic cases of Lyme disease. The occupational risk of tick-borne infections among outdoor workers is high, particularly those working on publicly managed lands. This study identified incident tick-borne infections and examined seroconversion risk factors among a cohort of North Carolina outdoor workers. Workers from the North Carolina State Divisions of Forestry, Parks and Recreation, and Wildlife (n = 159) were followed for 2 years in a randomized controlled trial evaluating the effectiveness of long-lasting permethrin-impregnated clothing. Antibody titers against Rickettsia parkeri, Rickettsia rickettsii, "Rickettsia amblyommii," and Ehrlichia chaffeensis were measured at baseline (n = 130), after 1 year (n = 82), and after 2 years (n = 73). Titers against Borrelia burgdorferi were measured at baseline and after 2 years (n = 90). Baseline seroprevalence, defined as indirect immunofluorescence antibody titers of 1/128 or greater, was R. parkeri (24%), R. rickettsii (19%), "R. amblyommii" (12%), and E. chaffeensis (4%). Incident infection was defined as a fourfold increase in titer over a 1-year period. There were 40 total seroconversions to at least one pathogen, including R. parkeri (n = 19), "R. amblyommii" (n = 14), R. rickettsii (n = 9), and E. chaffeensis (n = 8). There were no subjects whose sera were reactive to B. burgdorferi C6 antigen. Thirty-eight of the 40 incident infections were subclinical. The overall risk of infection by any pathogen during the study period was 0.26, and the risk among the NC Division of Forest Resources workers was 1.73 times that of workers in other divisions (95% confidence interval [CI]: 1.02, 2.92). The risk of infection was lower in subjects wearing permethrin-impregnated clothing, but not significantly (risk ratio = 0.81; 95% CI: 0.47, 1.39). In summary, outdoor workers in North Carolina are at high risk of incident tick-borne infections, most of which appear to be asymptomatic.