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.

Global distribution of Leptospira serovar isolations and detections from animal host species: A systematic review and online database.

OBJECTIVES: Leptospira, the spirochaete causing leptospirosis, can be classified into >250 antigenically distinct serovars. Although knowledge of the animal host species and geographic distribution of Leptospira serovars is critical to understand the human and animal epidemiology of leptospirosis, current data are fragmented. We aimed to systematically review, the literature on animal host species and geographic distribution of Leptospira serovars to examine associations between serovars with animal host species and regions and to identify geographic regions in need of study. METHODS: Nine library databases were searched from inception through 9 March 2023 using keywords including Leptospira, animal, and a list of serovars. We sought reports of detection of Leptospira, from any animal, characterised by cross agglutinin absorption test, monoclonal antibody typing, serum factor analysis, or pulsed-field gel electrophoresis to identify the serovar. RESULTS: We included 409 reports, published from 1927 through 2022, yielding data on 154 Leptospira serovars. The reports included data from 66 (26.5%) of 249 countries. Detections were from 144 animal host species including 135 (93.8%) from the class Mammalia, 5 (3.5%) from Amphibia, 3 (2.1%) from Reptilia, and 1 (0.7%) from Arachnida. Across the animal host species, Leptospira serovars that were detected in the largest number of animal species included Grippotyphosa (n = 39), Icterohaemorrhagiae (n = 29), Pomona (n = 28), Australis (n = 25), and Ballum (n = 25). Of serovars, 76 were detected in a single animal host species. We created an online database to identify animal host species for each serovar by country. CONCLUSIONS: We found that many countries have few or no Leptospira serovars detected from animal host species and that many serovars were detected from a single animal species. Our study highlights the importance of efforts to identify animal host species of leptospirosis, especially in places with a high incidence of human leptospirosis. We provide an updated resource for leptospirosis researchers.

Complete genome sequence of Brucella abortus isolated from a human blood culture sample in Tanzania.

Brucella abortus causes infections in humans and livestock. Bacterial isolates are challenging to obtain, and very little is known about the genomic epidemiology of this species in Africa. Here, we report the complete genome sequence of a Brucella abortus isolate cultured from a febrile human in northern Tanzania.

Host-response transcriptional biomarkers accurately discriminate bacterial and viral infections of global relevance.

Diagnostic limitations challenge management of clinically indistinguishable acute infectious illness globally. Gene expression classification models show great promise distinguishing causes of fever. We generated transcriptional data for a 294-participant (USA, Sri Lanka) discovery cohort with adjudicated viral or bacterial infections of diverse etiology or non-infectious disease mimics. We then derived and cross-validated gene expression classifiers including: 1) a single model to distinguish bacterial vs. viral (Global Fever-Bacterial/Viral [GF-B/V]) and 2) a two-model system to discriminate bacterial and viral in the context of noninfection (Global Fever-Bacterial/Viral/Non-infectious [GF-B/V/N]). We then translated to a multiplex RT-PCR assay and independent validation involved 101 participants (USA, Sri Lanka, Australia, Cambodia, Tanzania). The GF-B/V model discriminated bacterial from viral infection in the discovery cohort an area under the receiver operator curve (AUROC) of 0.93. Validation in an independent cohort demonstrated the GF-B/V model had an AUROC of 0.84 (95% CI 0.76-0.90) with overall accuracy of 81.6% (95% CI 72.7-88.5). Performance did not vary with age, demographics, or site. Host transcriptional response diagnostics distinguish bacterial and viral illness across global sites with diverse endemic pathogens.

Prevalence and risk factors for human leptospirosis at a hospital serving a pastoralist community, Endulen, Tanzania.

BACKGROUND: Leptospirosis is suspected to be a major cause of illness in rural Tanzania associated with close contact with livestock. We sought to determine leptospirosis prevalence, identify infecting Leptospira serogroups, and investigate risk factors for leptospirosis in a rural area of Tanzania where pastoralist animal husbandry practices and sustained livestock contact are common. METHODS: We enrolled participants at Endulen Hospital, Tanzania. Patients with a history of fever within 72 hours, or a tympanic temperature of ≥38.0°C were eligible. Serum samples were collected at presentation and 4-6 weeks later. Sera were tested using microscopic agglutination testing with 20 Leptospira serovars from 17 serogroups. Acute leptospirosis cases were defined by a ≥four-fold rise in antibody titre between acute and convalescent serum samples or a reciprocal titre ≥400 in either sample. Leptospira seropositivity was defined by a single reciprocal antibody titre ≥100 in either sample. We defined the predominant reactive serogroup as that with the highest titre. We explored risk factors for acute leptospirosis and Leptospira seropositivity using logistic regression modelling. RESULTS: Of 229 participants, 99 (43.2%) were male and the median (range) age was 27 (0, 78) years. Participation in at least one animal husbandry practice was reported by 160 (69.9%). We identified 18 (7.9%) cases of acute leptospirosis, with Djasiman 8 (44.4%) and Australis 7 (38.9%) the most common predominant reactive serogroups. Overall, 69 (30.1%) participants were Leptospira seropositive and the most common predominant reactive serogroups were Icterohaemorrhagiae (n = 20, 29.0%), Djasiman (n = 19, 27.5%), and Australis (n = 17, 24.6%). Milking cattle (OR 6.27, 95% CI 2.24-7.52) was a risk factor for acute leptospirosis, and milking goats (OR 2.35, 95% CI 1.07-5.16) was a risk factor for Leptospira seropositivity. CONCLUSIONS: We identified leptospirosis in approximately one in twelve patients attending hospital with fever from this rural community. Interventions that reduce risks associated with milking livestock may reduce human infections.

Global distribution of Leptospira serovar isolations and detections from animal host species: a systematic review and online database.

Objectives: Leptospira, the spirochaete causing leptospirosis, can be classified into >250 antigenically distinct serovars. Although knowledge of the animal host species and geographic distribution of Leptospira serovars is critical to understand the human and animal epidemiology of leptospirosis, currently data are fragmented. We aimed to systematically review the literature on animal host species and geographic distribution of Leptospira serovars to examine associations between serovars with animal host species and regions, and to identify geographic regions in need of study. Methods: Nine library databases were searched from inception through 9 March 2023 using keywords including Leptospira, animal, and a list of serovars. We sought reports of detection of Leptospira, from any animal, characterized by cross agglutinin absorption test, monoclonal antibody typing, serum factor analysis, or pulsed-field gel electrophoresis to identify the serovar. Results: We included 409 reports, published from 1927 through 2022, yielding data on 154 Leptospira serovars. The reports included data from 66 (26.5%) of 249 countries. Detections were from 144 animal host species including 135 (93.8%) from the class Mammalia, 5 (3.5%) from Amphibia, 3 (2.1%) from Reptilia, and 1 (0.7%) from Arachnida. Across the animal host species, Leptospira serovars that were detected in the largest number of animal species included Grippotyphosa (n=39), Icterohaemorrhagiae (n=29), Pomona (n=28), Australis (n=25), and Ballum (n=25). Of serovars, 76 were detected in a single animal host species. We created an online database to identify animal host species for each serovar by country. Conclusions: We found that many countries have few or no Leptospira serovars detected from animal host species and that many serovars were detected from a single animal species. Our study highlights the importance of efforts to identify animal host species of leptospirosis, especially in places with a high incidence of human leptospirosis. We provide an updated resource for leptospirosis researchers.

Antibacterial Utilization for Febrile Illnesses and Laboratory-Confirmed Bloodstream Infections in Northern Tanzania.

Background: We describe antibacterial use in light of microbiology data and treatment guidelines for common febrile syndromes in Moshi, Tanzania. Methods: We compared data from 2 hospital-based prospective cohort studies, cohort 1 (2011-2014) and cohort 2 (2016-2019), that enrolled febrile children and adults. A study team member administered a standardized questionnaire, performed a physical examination, and collected blood cultures. Participants with bloodstream infection (BSI) were categorized as receiving effective or ineffective therapy based upon antimicrobial susceptibility interpretations. Antibacterials prescribed for treatment of pneumonia, urinary tract infection (UTI), or presumed sepsis were compared with World Health Organization and Tanzania Standard Treatment Guidelines. We used descriptive statistics and logistic regression to describe antibacterial use. Results: Among participants, 430 of 1043 (41.2%) and 501 of 1132 (44.3%) reported antibacterial use prior to admission in cohorts 1 and 2, respectively. During admission, 930 of 1043 (89.2%) received antibacterials in cohort 1 and 1060 of 1132 (93.6%) in cohort 2. Inpatient use of ceftriaxone, metronidazole, and ampicillin increased between cohorts (P ≤ .002 for each). BSI was detected in 38 (3.6%) participants in cohort 1 and 47 (4.2%) in cohort 2. Of 85 participants with BSI, 81 (95.3%) had complete data and 52 (64.2%) were prescribed effective antibacterials. Guideline-consistent therapy in cohort 1 and cohort 2 was as follows: pneumonia, 87.4% and 56.8%; UTI, 87.6% and 69.0%; sepsis, 84.4% and 61.2% (P ≤ .001 for each). Conclusions: Receipt of antibacterials for febrile illness was common. While guideline-consistent prescribing increased over time, more than one-third of participants with BSI received ineffective antibacterials.

Etiologic Investigation of Patients Diagnosed with Bacteriologically Unconfirmed Tuberculosis in Tanzania.

Globally, half of patients with pulmonary tuberculosis (PTB) are diagnosed clinically without bacteriologic confirmation. In clinically diagnosed PTB patients, we assessed both the proportion in whom PTB could be bacteriologically confirmed by reference standard diagnostic tests and the prevalence of diseases that mimic PTB. We recruited adult patients beginning treatment of bacteriologically unconfirmed PTB in Moshi, Tanzania, in 2019. We performed mycobacterial smear, Xpert MTB/RIF Ultra, and mycobacterial culture, fungal culture, and bacterial culture on two induced sputum samples: fungal serology and computed tomography chest scans. We followed participants for 2 months after enrollment. We enrolled 36 (63%) of 57 patients with bacteriologically unconfirmed PTB. The median (interquartile range) age was 55 (44-67) years. Six (17%) were HIV infected. We bacteriologically confirmed PTB in 2 (6%). We identified pneumonia in 11 of 23 (48%), bronchiectasis in 8 of 23 (35%), interstitial lung disease in 5 of 23 (22%), pleural collections in 5 of 23 (22%), lung malignancy in 1 of 23 (4%), and chronic pulmonary aspergillosis in 1 of 35 (3%). After 2 months, 4 (11%) were dead, 21 (58%) had persistent symptoms, 6 (17%) had recovered, and 5 (14%) were uncontactable. PTB could be bacteriologically confirmed in few patients with clinically diagnosed PTB and clinical outcomes were poor, suggesting that many did not have the disease. We identified a high prevalence of diseases other than tuberculosis that might be responsible for symptoms.

Inter-epidemic Rift Valley fever virus infection incidence and risks for zoonotic spillover in northern Tanzania.

Rift Valley fever virus (RVFV) is a mosquito-borne pathogen that has caused epidemics involving people and animals across Africa and the Arabian Peninsula. A number of studies have found evidence for the circulation of RVFV among livestock between these epidemics but the population-level incidence of infection during this inter-epidemic period (IEP) is rarely reported. General force of infection (FOI) models were applied to age-adjusted cross-sectional serological data to reconstruct the annual FOI and population-level incidence of RVFV infection among cattle, goats, and sheep in northern Tanzania from 2009 through 2015, a period without reported Rift Valley fever (RVF) cases in people or animals. To evaluate the potential for zoonotic RVFV spillover during this period, the relationship between village-level livestock RVFV FOI and human RVFV seropositivity was quantified using multi-level logistic regression. The predicted average annual incidence was 72 (95% Credible Interval [CrI] 63, 81) RVFV infections per 10,000 animals and 96 (95% CrI 81, 113), 79 (95% CrI 62, 98), and 39 (95% CrI 28, 52) per 10,000 cattle, sheep, and goats, respectively. There was variation in transmission intensity between study villages, with the highest estimated village-level FOI 2.49% (95% CrI 1.89, 3.23) and the lowest 0.12% (95% CrI 0.02, 0.43). The human RVFV seroprevalence was 8.2% (95% Confidence Interval 6.2, 10.9). Human seropositivity was strongly associated with the village-level FOI in livestock, with the odds of seropositivity in an individual person increasing by around 1.2 times (95% CrI 1.1, 1.3) for each additional annual RVFV seroconversion per 1,000 animals. A history of raw milk consumption was also positively associated with human seropositivity. RVFV has circulated at apparently low levels among livestock in northern Tanzania in the period since the last reported epidemic. Although our data do not allow us to confirm human RVFV infections during the IEP, a strong association between human seropositivity and the FOI in cattle, goats, and sheep supports the hypothesis that RVFV circulation among livestock during the IEP poses a risk for undetected zoonotic spillover in northern Tanzania. We provide further evidence for the likely role of raw milk consumption in RVFV transmission from animals to people.

An outbreak of Rift Valley fever among peri-urban dairy cattle in northern Tanzania.

BACKGROUND: Human and animal cases of Rift Valley fever (RVF) are typically only reported during large outbreaks. The occurrence of RVF cases that go undetected by national surveillance systems in the period between these outbreaks is considered likely. The last reported cases of RVF in Tanzania occurred during a large outbreak in 2007-2008. METHODS: Samples collected between 2017 and 2019 from livestock suffering abortion across northern Tanzania were retrospectively tested for evidence of RVF virus infection using serology and reverse transcription quantitative polymerase chain reaction (RT-qPCR). RESULTS: A total of 14 RVF-associated cattle abortions were identified among dairy cattle in a peri-urban area surrounding the town of Moshi. RVF cases occurred from May to August 2018 and were considered to represent an undetected, small-scale RVF outbreak. Milk samples from 3 of 14 cases (21%) were found to be RT-qPCR positive. Genotyping revealed circulation of RVF viruses from two distinct lineages. CONCLUSIONS: RVF outbreaks can occur more often in endemic settings than would be expected on the basis of detection by national surveillance. The occurrence of RVF cases among peri-urban dairy cattle and evidence for viral shedding in milk, also highlights potentially emerging risks for RVF associated with increasing urban and peri-urban livestock populations.

Facility-based disease surveillance and Bayesian hierarchical modeling to estimate endemic typhoid fever incidence, Kilimanjaro Region, Tanzania, 2007-2018.

Growing evidence suggests considerable variation in endemic typhoid fever incidence at some locations over time, yet few settings have multi-year incidence estimates to inform typhoid control measures. We sought to describe a decade of typhoid fever incidence in the Kilimanjaro Region of Tanzania. Cases of blood culture confirmed typhoid were identified among febrile patients at two sentinel hospitals during three study periods: 2007-08, 2011-14, and 2016-18. To account for under-ascertainment at sentinel facilities, we derived adjustment multipliers from healthcare utilization surveys done in the hospital catchment area. Incidence estimates and credible intervals (CrI) were derived using a Bayesian hierarchical incidence model that incorporated uncertainty of our observed typhoid fever prevalence, of healthcare seeking adjustment multipliers, and of blood culture diagnostic sensitivity. Among 3,556 total participants, 50 typhoid fever cases were identified. Of typhoid cases, 26 (52%) were male and the median (range) age was 22 (<1-60) years; 4 (8%) were aged <5 years and 10 (20%) were aged 5 to 14 years. Annual typhoid fever incidence was estimated as 61.5 (95% CrI 14.9-181.9), 6.5 (95% CrI 1.4-20.4), and 4.0 (95% CrI 0.6-13.9) per 100,000 persons in 2007-08, 2011-14, and 2016-18, respectively. There were no deaths among typhoid cases. We estimated moderate typhoid incidence (≥10 per 100 000) in 2007-08 and low (<10 per 100 000) incidence during later surveillance periods, but with overlapping credible intervals across study periods. Although consistent with falling typhoid incidence, we interpret this as showing substantial variation over the study periods. Given potential variation, multi-year surveillance may be warranted in locations making decisions about typhoid conjugate vaccine introduction and other control measures.

Clinical evaluation of the BioFire Global Fever Panel for the identification of malaria, leptospirosis, chikungunya, and dengue from whole blood: a prospective, multicentre, cross-sectional diagnostic accuracy study.

BACKGROUND: Acute febrile illness is a common presentation for patients at hospitals globally. Assays that can diagnose a variety of common pathogens in blood could help to establish a diagnosis for targeted disease management. We aimed to evaluate the performance of the BioFire Global Fever Panel (GF Panel), a multiplex nucleic acid amplification test performed on whole blood specimens run on the BioFire FilmArray System, in the diagnosis of several pathogens that cause acute febrile illness. METHODS: We did a prospective, multicentre, cross-sectional diagnostic accuracy study to evaluate the GF Panel. Consenting adults and children older than 6 months presenting with fever in the previous 2 days were enrolled consecutively in sub-Saharan Africa (Ghana, Kenya, Tanzania, Uganda), southeast Asia (Cambodia, Thailand), central and South America (Honduras, Peru), and the USA (Washington, DC; St Louis, MO). We assessed the performance of six analytes (chikungunya virus, dengue virus [serotypes 1-4], Leptospira spp, Plasmodium spp, Plasmodium falciparum, and Plasmodium vivax or Plasmodium ovale) on the GF Panel. The performance of the GF Panel was assessed using comparator PCR assays with different primers followed by bidirectional sequencing on nucleic acid extracts from the same specimen. We calculated the positive percent agreement and negative percent agreement of the GF Panel with respect to the comparator assays. This study is registered with ClinicalTrials.gov, NCT02968355. FINDINGS: From March 26, 2018, to Sept 30, 2019, 1965 participants were enrolled at ten sites worldwide. Of the 1875 participants with analysable results, 980 (52·3%) were female and the median age was 22 years (range 0-100). At least one analyte was detected in 657 (35·0%) of 1875 specimens. The GF Panel had a positive percent agreement for the six analytes evaluated as follows: chikungunya virus 100% (95% CI 86·3-100), dengue virus 94·0% (90·6-96·5), Leptospira spp 93·8% (69·8-99·8), Plasmodium spp 98·3% (96·3-99·4), P falciparum 92·7% (88·8-95·6), and P vivax or P ovale 92·7% (86·7-96·6). The GF Panel had a negative percent agreement equal to or greater than 99·2% (98·6-99·6) for all analytes. INTERPRETATION: This 1 h sample-to-answer, molecular device can detect common causative agents of acute febrile illness with excellent positive percent agreement and negative percent agreement directly in whole blood. The targets of the assay are prevalent in tropical and subtropical regions globally, and the assay could help to provide both public health surveillance and individual diagnoses. FUNDING: BioFire Defense, Joint Project Manager for Medical Countermeasure Systems and US Army Medical Materiel Development Activity, and National Institute of Allergy and Infectious Diseases.

Prevalence and predictors of uncontrolled hypertension, diabetes, and obesity among adults with HIV in northern Tanzania.

HIV is associated with increased risk of cardiovascular disease, but there has been less study of cardiovascular comorbidities among people with HIV in sub-Saharan Africa. In a cross-sectional observational study, Tanzanian adults presenting for outpatient HIV care completed a questionnaire and underwent weight, height, blood pressure, and blood glucose measurement. Hypertension was defined by blood pressure ≥140/90 mmHg or self-reported hypertension. Uncontrolled hypertension was defined as measured blood pressure ≥140/90 mmHg. Diabetes was defined by fasting glucose ≥126 mg/dl, random glucose ≥200 mg/dl, or self-reported diabetes. Obesity was defined by body mass index ≥30 kg/m2. Multivariate logistic regression was performed to identify predictors of uncontrolled hypertension. Among 500 participants, 173 (34.6%) had hypertension, 21 (4.2%) had diabetes, and 99 (19.8%) were obese. Of those with hypertension, 116 (67.1%) were unaware of their hypertension, and 155 (89.6%) had uncontrolled hypertension. In multivariate analysis, uncontrolled hypertension was associated with older age (OR 1.07, 95% CI: 1.05-1.10, p < 0.001) and higher body mass index (OR 1.17, 95% CI: 1.11-1.22, p < 0.001). Interventions are needed to improve screening and treatment for hypertension, diabetes, and obesity among Tanzanians with HIV.

Performance of Xpert Ultra nasopharyngeal swab for identification of tuberculosis deaths in northern Tanzania.

OBJECTIVE: Numerous tuberculosis (TB) deaths remain undetected in low-resource endemic settings. With autopsy-confirmed tuberculosis as our standard, we assessed the diagnostic performance of Xpert MTB/RIF Ultra (Ultra; Cepheid) on nasopharyngeal specimens collected postmortem. METHODS: From October 2016 through May 2019, we enrolled pediatric and adult medical deaths to a prospective autopsy study at two referral hospitals in northern Tanzania with next-of-kin authorization. We swabbed the posterior nasopharynx prior to autopsy and tested the samples later by Ultra. At autopsy we collected lung, liver, and, when possible, cerebrospinal fluid for mycobacterial culture and histopathology. Confirmed tuberculosis was defined as Mycobacterium tuberculosis complex recovery by culture with consistent tissue histopathology findings; decedents with only histopathology findings, including acid-fast staining or immunohistochemistry, were defined as probable tuberculosis. RESULTS: Of 205 decedents, 78 (38.0%) were female and median (range) age was 45 (0,96) years. Twenty-seven (13.2%) were found to have tuberculosis at autopsy, 22 (81.5%) confirmed and 5 (18.5%) probable. Ultra detected M. tuberculosis complex from the nasopharynx in 21 (77.8%) of 27 TB cases (sensitivity 70.4% [95% confidence interval {CI} 49.8-86.2%], specificity 98.9% [95% CI 96.0-99.9%]). Among confirmed TB, the sensitivity increased to 81.8% (95% CI 59.7-94.8%). Tuberculosis was not included as a death certificate diagnosis in 14 (66.7%) of the 21 MTBc detections by Ultra. DISCUSSION: Nasopharyngeal Ultra was highly specific for identifying in-hospital tuberculosis deaths, including unsuspected tuberculosis deaths. This approach may improve tuberculosis death enumeration in high-burden countries.

Performance Assessment of the Universal Vital Assessment Score vs Other Illness Severity Scores for Predicting Risk of In-Hospital Death Among Adult Febrile Inpatients in Northern Tanzania, 2016-2019.

Importance: Severity scores are used to improve triage of hospitalized patients in high-income settings, but the scores may not translate well to low- and middle-income settings such as sub-Saharan Africa. Objective: To assess the performance of the Universal Vital Assessment (UVA) score, derived in 2017, compared with other illness severity scores for predicting in-hospital mortality among adults with febrile illness in northern Tanzania. Design, Setting, and Participants: This prognostic study used clinical data collected for the duration of hospitalization among patients with febrile illness admitted to Kilimanjaro Christian Medical Centre or Mawenzi Regional Referral Hospital in Moshi, Tanzania, from September 2016 through May 2019. All adult and pediatric patients with a history of fever within 72 hours or a tympanic temperature of 38.0 °C or higher at screening were eligible for enrollment. Of 3761 eligible participants, 1132 (30.1%) were enrolled in the parent study; of those, 597 adults 18 years or older were included in this analysis. Data were analyzed from December 2019 to September 2021. Exposures: Modified Early Warning Score (MEWS), National Early Warning Score (NEWS), quick Sequential Organ Failure Assessment (qSOFA), Systemic Inflammatory Response Syndrome (SIRS) assessment, and UVA. Main Outcomes and Measures: The main outcome was in-hospital mortality during the same hospitalization as the participant's enrollment. Crude risk ratios and 95% CIs for in-hospital death were calculated using log-binomial risk regression for proposed score cutoffs for each of the illness severity scores. The area under the receiver operating characteristic curve (AUROC) for estimating the risk of in-hospital death was calculated for each score. Results: Among 597 participants, the median age was 43 years (IQR, 31-56 years); 300 participants (50.3%) were female, 198 (33.2%) were HIV-infected, and in-hospital death occurred in 55 (9.2%). By higher risk score strata for each score, compared with lower risk strata, risk ratios for in-hospital death were 3.7 (95% CI, 2.2-6.2) for a MEWS of 5 or higher; 2.7 (95% CI, 0.9-7.8) for a NEWS of 5 or 6; 9.6 (95% CI, 4.2-22.2) for a NEWS of 7 or higher; 4.8 (95% CI, 1.2-20.2) for a qSOFA score of 1; 15.4 (95% CI, 3.8-63.1) for a qSOFA score of 2 or higher; 2.5 (95% CI, 1.2-5.2) for a SIRS score of 2 or higher; 9.1 (95% CI, 2.7-30.3) for a UVA score of 2 to 4; and 30.6 (95% CI, 9.6-97.8) for a UVA score of 5 or higher. The AUROCs, using all ordinal values, were 0.85 (95% CI, 0.80-0.90) for the UVA score, 0.81 (95% CI, 0.75-0.87) for the NEWS, 0.75 (95% CI, 0.69-0.82) for the MEWS, 0.73 (95% CI, 0.67-0.79) for the qSOFA score, and 0.63 (95% CI, 0.56-0.71) for the SIRS score. The AUROC for the UVA score was significantly greater than that for all other scores (P < .05 for all comparisons) except for NEWS (P = .08). Conclusions and Relevance: This prognostic study found that the NEWS and the UVA score performed favorably compared with other illness severity scores in predicting in-hospital mortality among a hospitalized cohort of adults with febrile illness in northern Tanzania. Given its reliance on readily available clinical data, the UVA score may have utility in the triage and prognostication of patients admitted to the hospital with febrile illness in low- to middle-income settings such as sub-Saharan Africa.

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.

Trends in fever case management for febrile inpatients in a low malaria incidence setting of Tanzania.

OBJECTIVES: In 2010, WHO published guidelines emphasising parasitological confirmation of malaria before treatment. We present data on changes in fever case management in a low malaria transmission setting of northern Tanzania after 2010. METHODS: We compared diagnoses, treatments and outcomes from two hospital-based prospective cohort studies, Cohort 1 (2011-2014) and Cohort 2 (2016-2019), that enrolled febrile children and adults. All participants underwent quality-assured malaria blood smear-microscopy. Participants who were malaria smear-microscopy negative but received a diagnosis of malaria or received an antimalarial were categorised as malaria over-diagnosis and over-treatment, respectively. RESULTS: We analysed data from 2098 participants. The median (IQR) age was 27 (3-43) years and 1047 (50.0%) were female. Malaria was detected in 23 (2.3%) participants in Cohort 1 and 42 (3.8%) in Cohort 2 (p = 0.059). Malaria over-diagnosis occurred in 334 (35.0%) participants in Cohort 1 and 190 (17.7%) in Cohort 2 (p < 0.001). Malaria over-treatment occurred in 528 (55.1%) participants in Cohort 1 and 196 (18.3%) in Cohort 2 (p < 0.001). There were 30 (3.1%) deaths in Cohort 1 and 60 (5.4%) in Cohort 2 (p = 0.007). All deaths occurred among smear-negative participants. CONCLUSION: We observed a substantial decline in malaria over-diagnosis and over-treatment among febrile inpatients in northern Tanzania between two time periods after 2010. Despite changes, some smear-negative participants were still diagnosed and treated for malaria. Our results highlight the need for continued monitoring of fever case management across different malaria epidemiological settings in sub-Saharan Africa.

Degradation of endothelial glycocalyx in Tanzanian children with falciparum malaria.

A layer of glycocalyx covers the vascular endothelium serving important protective and homeostatic functions. The objective of this study was to determine if breakdown of the endothelial glycocalyx (eGC) occurs during malaria infection in children. Measures of eGC integrity, endothelial activation, and microvascular reactivity were prospectively evaluated in 146 children: 44 with moderately severe malaria (MSM), 42 with severe malaria (SM), and 60 healthy controls (HC). Biochemical measures of eGC integrity included plasma syndecan-1 and total urinary glycosaminoglycans (GAG). Side-stream dark field imaging was used to quantitatively assess integrity of eGC. Plasma angiopoietin-2 (Ang-2) was measured as a marker of endothelial activation and also as a possible mediator of eGC breakdown. Our results show that urinary GAG, syndecan-1, and Ang-2 were elevated in patients with MSM and SM compared with HC. Syndecan-1 and GAG levels correlated significantly with each other and with plasma Ang-2. The eGC breakdown products also inversely correlated significantly with hemoglobin and platelet count. In the MSM group, imaging results provided further evidence for eGC degradation. Although not correlated with markers of eGC degradation, vascular function (assessed by non-invasive near infrared spectroscopy [NIRS]) demonstrated reduced microvascular reactivity, particularly affecting the SM group. Our findings provide further evidence for breakdown of eGC in falciparum malaria that may contribute to endothelial activation and adhesion of parasitized red blood cells, with reduced nitric oxide formation, and vascular dysfunction.

Incidence of Acute Myocardial Infarction in Northern Tanzania: A Modeling Approach Within a Prospective Observational Study.

Background Rigorous incidence data for acute myocardial infarction (AMI) in sub-Saharan Africa are lacking. Consequently, modeling studies based on limited data have suggested that the burden of AMI and AMI-associated mortality in sub-Saharan Africa is lower than in other world regions. Methods and Results We estimated the incidence of AMI in northern Tanzania in 2019 by integrating data from a prospective surveillance study (681 participants) and a community survey of healthcare-seeking behavior (718 participants). In the surveillance study, adults presenting to an emergency department with chest pain or shortness of breath were screened for AMI with ECG and troponin testing. AMI was defined by the Fourth Universal Definition of AMI criteria. Mortality was assessed 30 days following enrollment via in-person or telephone interviews. In the cluster-based community survey, adults in northern Tanzania were asked where they would present for chest pain or shortness of breath. Multipliers were applied to account for AMI cases that would have been missed by our surveillance methods. The estimated annual incidence of AMI was 172 (207 among men and 139 among women) cases per 100 000 people. The age-standardized annual incidence was 211 (263 among men and 170 among women) per 100 000 people. The estimated annual incidence of AMI-associated mortality was 87 deaths per 100 000 people, and the age-standardized annual incidence was 102 deaths per 100 000 people. Conclusions The incidence of AMI and AMI-associated mortality in northern Tanzania is much higher than previously estimated and similar to that observed in high-income countries.