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Background: Plasma microbial cell-free DNA (mcfDNA) sequencing can establish the etiology of multiple infectious syndromes by identifying microbial DNA in plasma. However, data are needed to define the clinical scenarios where this tool offers the highest clinical benefit., Methods: We conducted a prospective multicenter observational study that evaluated the impact of plasma mcfDNA sequencing compared with usual care testing among adults with hematologic malignancies. This is a secondary analysis of an expanded cohort that evaluated the clinical utility of plasma mcfDNA sequencing across prespecified and adjudicated outcomes. We examined the percentage of participants for whom plasma mcfDNA sequencing identified a probable cause of pneumonia or clinically relevant nonpneumonia infection. We then assessed potential changes in antimicrobial therapy based on plasma mcfDNA sequencing results and the potential for early mcfDNA testing to avoid bronchoscopy and its associated adverse events., Results: Of 223 participants, at least 1 microbial detection by plasma mcfDNA sequencing was adjudicated as a probable cause of pneumonia in 57 (25.6%) and a clinically relevant nonpneumonia infection in 88 (39.5%). A probable cause of pneumonia was exclusively identified by plasma mcfDNA sequencing in 23 (10.3%) participants. Antimicrobial therapy would have changed for 41 (18.4%) participants had plasma mcfDNA results been available in real time. Among the 57 participants with a probable cause of pneumonia identified by plasma mcfDNA sequencing, bronchoscopy identified no additional probable cause of pneumonia in 52 (91.2%)., Conclusions: Plasma mcfDNA sequencing could improve management of both pneumonia and other concurrent infections in immunocompromised patients with suspected pneumonia., Competing Interests: Potential conflicts of interest. Deng B. Madut reports receiving consulting fees from Karius. Roy F. Chemaly reports being a scientific advisor or consultant for ADMA Biologics, Pulmotec, Janssen, Merck/MSD, Partner Therapeutics, Takeda, Shinoigi, Genentech, Astellas, Adagio Therapeutics, Oxford Immunotec, Qiagen, Karius, Moderna, and Ansun Pharmaceuticals and received research grants paid to his institution from NIH/NCI, Merck/MSD, Karius, AiCuris, Ansun Pharmaceuticals, Takeda, Genentech, Oxford Immunotec, Freestyle, and Eurofins-Viracor. Sanjeet Dadwal reports research grants paid to his institution from Karius, Merck, Gilead, Ansun Biopharma, Allovir. He has served on advisory boards for Merck, Takeda, Allovir, and Aseptiscope, Inc. He is on speakers’ bureaus of Merck, Astellas, and Takeda and holds stock options in Aseptiscope, Inc. Joshua A. Hill reports research grants paid to his institution from Karius and consulting for Karius. He reports no other relevant conflicts of interest. Yeon Joo Lee has served as an investigator for Astellas, Karius, AiCuris, and Scynexis and has received research grant support from Merck & Co. Inc. Ghady Haidar is a recipient of research grants from Allovir, Karius, and AstraZeneca and also serves on the scientific advisory boards of Karius and AstraZeneca. Alfred Luk reports no relevant conflicts of interest. Alexander Drelick reports no relevant conflicts of interest. Peter V. Chin-Hong reports no relevant conflicts of interest. Esther Benamu reports no relevant conflicts of interest. Fareed Khawaja reports an honorarium from Medscape and research support from Eurofins-Viracor. Deepa Nanayakkara reports no relevant conflicts of interest. Genovefa A. Papanicolaou reports research support from MSD and Takeda/Shire and consulting and other fees from AlloVir, Amplyx, SLC Behring, Cidara, MSD, Takeda, and Octapharma. Catherine Butkus Small reports research grant support from NIH, GlaxoSmithKline, ViiV, Abbott, Merck, Gilead, Chimerix, Shire/Takeda, Schering-Plough, Ablynx, Janssen, Ansun Biopharma, and Karyopharm Therapeutics. Monica Fung reports research grant support from NIH. Michelle A. Barron reports no relevant conflicts of interest. Thomas Davis reports no relevant conflicts of interest. Micah T. McClain reports being a consultant for UpToDate and a co-inventor of patents on Methods to Detect and Treat Acute Respiratory Infections. Eileen K. Maziarz reports no relevant conflicts of interest. Armando D. Bedoya reports no relevant conflicts of interest. Daniel L. Gilstrap reports no relevant conflicts of interest. Jamie L. Todd reports advisory board participation for Sanofi, Natera, Theravance, and Altavant Sciences (now Enzyvant Therapeutics), in addition to grants to the institution from Boehringer-Ingelheim, AstraZeneca, and CareDx. Christina E. Barkauskas reports no relevant conflicts of interest. Madeleine R. Heldman reports receiving consulting fees from Karius and Medacorp. Robert Bigelow reports stock holdings in Merck, Johnson & Johnson, COVIDien, Pfizer, Sanofi, McKesson, and Viatris and consulting fees from Elixir. Jeffrey D. Leimberger reports no relevant conflicts of interest. Ephraim L. Tsalik reports personal fees from Biomeme, stock options in Danaher, and being an employee of Danaher Corp. Olivia Wolf reports no relevant conflicts of interest. Mona Mughar reports being an employee of Karius Inc., Redwood City, California, and may own stock options. Constance Lau reports being an employee of Karius Inc., Redwood City, California, and may own stock options. Nicholas Noll reports being an employee of Karius Inc., Redwood City, California, and may own stock options. Desiree Hollemon reports being a former employee of Karius Inc., Redwood City, California. Radha Duttagupta reports being a former employee of Karius Inc., Redwood City, California. Daniel S. Lupu reports being an employee of Karius Inc., Redwood City, California, and may own stock options. Sivan Bercovici reports being an employee of Karius Inc., Redwood City, California, and may own stock options. Bradley A. Perkins reports being an employee of Karius Inc., Redwood City, California, and may own stock options. Timothy A. Blauwkamp reports being an employee of Karius Inc., Redwood City, California, and may own stock options. Vance G. Fowler Jr. reports personal fees from Novartis, Debiopharm, Genentech, Achaogen, Affinium, Medicines Co., MedImmune, Bayer, Basilea, Affinergy, Janssen, Contrafect, Regeneron, Destiny, Amphliphi Biosciences, Integrated Biotherapeutics, C3J, Armata, Valanbio, Akagera, Aridis, and Roche; grants from NIH, MedImmune, Allergan, Pfizer, Advanced Liquid Logics, Theravance, Novartis, Merck, Medical Biosurfaces, Locus, Affinergy, Contrafect, Karius, Genentech, Regeneron, Deep Blue, Basilea, and Janssen; royalties from UpToDate; stock options from Valanbio and ArcBio; honoraria from the Infectious Diseases Society of America for his service as Associate Editor of Clinical Infectious Diseases; and a pending patent on sepsis diagnostics. Thomas L. Holland reports being an advisor and consultant to Aridis, Basilea Pharmaceutica, Karius, and Lysovant and royalties from UpToDate. Stephen P. Bergin reports being a consultant to C3J Therapeutics., (© The Author(s) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Background: Pneumonia is a common cause of morbidity and mortality, yet a causative pathogen is identified in a minority of cases. Plasma microbial cell-free DNA sequencing may improve diagnostic yield in immunocompromised patients with pneumonia., Methods: In this prospective, multicenter, observational study of immunocompromised adults undergoing bronchoscopy to establish a pneumonia etiology, plasma microbial cell-free DNA sequencing was compared to standardized usual care testing. Pneumonia etiology was adjudicated by a blinded independent committee. The primary outcome, additive diagnostic value, was assessed in the Per Protocol population (patients with complete testing results and no major protocol deviations) and defined as the percent of patients with an etiology of pneumonia exclusively identified by plasma microbial cell-free DNA sequencing. Clinical additive diagnostic value was assessed in the Per Protocol subgroup with negative usual care testing., Results: Of 257 patients, 173 met Per Protocol criteria. A pneumonia etiology was identified by usual care in 52/173 (30.1%), plasma microbial cell-free DNA sequencing in 49/173 (28.3%) and the combination of both in 73/173 (42.2%) patients. Plasma microbial cell-free DNA sequencing exclusively identified an etiology of pneumonia in 21/173 patients (additive diagnostic value 12.1%, 95% confidence interval [CI], 7.7% to 18.0%, P < .001). In the Per Protocol subgroup with negative usual care testing, plasma microbial cell-free DNA sequencing identified a pneumonia etiology in 21/121 patients (clinical additive diagnostic value 17.4%, 95% CI, 11.1% to 25.3%)., Conclusions: Non-invasive plasma microbial cell-free DNA sequencing significantly increased diagnostic yield in immunocompromised patients with pneumonia undergoing bronchoscopy and extensive microbiologic and molecular testing., Clinical Trials Registration: NCT04047719., Competing Interests: Potential conflicts of interest. S. P. B. reports being a consultant to C3J Therapeutics. R. F. C. reports being a scientific advisor or consultant for ADMA Biologics, Pulmotec, Janssen, Merck/MSD, Partner Therapeutics, Takeda, Shinoigi, Genentech, Astellas, Adagio Therapeutics, Oxford Immunotec, Qiagen, Karius, and Ansun Pharmaceuticals and received research grants paid to his institution from National Institutes of Health (NIH)/National Cancer Institute (NCI), Merck/Merck, Sharp & Dohme (MSD), Karius, AiCuris, Ansun Pharmaceuticals, Takeda, Genentech, Oxford Immunotec, Freestyle, and Eurofins-Viracor, and reports payment or honoraria as a speaker for Qiagen and Viracor-Eurofins. S. D. reports research grants paid to his institution from Karius, Merck, Gilead, Ansun Biopharma, Allovir, Geovax. He has served on advisory boards of Merck, Takeda, Allovir, and Aseptiscope, Inc. He is on speaker's bureau of Merck, Astellas and Takeda, and reports payment or honoraria from Viracor for educational event at ID week 2022 and from MJH for cytomegalovirus (CMV) symposium at American Society of Hematology (ASH) 2022. He has stock options in Aseptiscope, Inc, Matinas Biopharma, and Cidara Therapeutics. He reports consulting fees from Merck and Allovir; support for attending meetings and/or travel from American Society of Transplantation and Cellular Therapy—Tandem 2022 and 2023 (registration credit), ID week 2022—Infectious Diseases Society of America (IDSA) (partial support—airfare), and Immunocompromised Host Society (ICHS) 2022 (air fare and hotel expenses); Patent # 9416395, Assigned to City of Hope. Inventors—Markus Kalkum, Karine Bagramyan, Diana Diaz-Arevalo, James I. Ito, Sanjeet S. Dadwal (assigned to City of Hope) and US Provisional Patent Application no. 63/067,855: Inventors—Markus Kalkum, Daniel Roeth, Sanjeet S. Dadwal (assigned to City of Hope); a role as Chair of Transplant Infectious Disease Special Interest Group of American Society of Transplant and Cellular Therapy (ASTCT). J. A. H. reports research grants paid to his institution from Karius and consulting for Karius and support for travel to advisory board meeting from Karius. Y. J. L. has served as an investigator for Astellas, Karius, AiCuris, and Scynexis and has received research grant support from Merck & Co Inc. G. H. is a recipient of research grants from Allovir, Karius, and AstraZeneca and also serves on the scientific advisory boards of and receives consulting fees from Karius and AstraZeneca, and reports grants or contracts from NIH; payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from MDOutlook, PeerView Medical Education, International AIDS Society. A. L. reports consulting fees from Karius. F. K. reports honorarium from Medscape and research support from Eurofins-Viracor. G. A. P. reports research support from MSD and Takeda/Shire and consulting and other fees from AlloVir, Amplyx, SLC Behring, Cidara, MSD, Takeda and Octapharma. C. B. S. reports research grant support from NIH, GlaxoSmithKline, ViiV, Abbott, Merck, Gilead, Chimerix, Shire/Takeda, Schering-Plough, Ablynx, Janssen, Ansun Biopharma, and Karyopharm Therapeutics; participation on Janssen Respiratory Viruses Advisory Board and Merck Scientific Input Engagement (SIE) Panel for Molnupirivir. M. F. reports research grant support from NIH, and research funding (UCSF PI Fung) from Scynexis and Vatic, Ltd. M. T. M. reports being a consultant for UpToDate and Karius and a co-inventor of patents on Methods to Detect and Treat Acute Respiratory Infections. E. K. M. reports consulting fees from Karius Inc as a Clinical Events Committee member/reviewer—received payments as clinical adjudicator for another Karius project. D. B. M. reports consulting fees from Karius Inc.. A. D. B . reports payment or honoraria from Novartis for lecture on Sepsis Watch, AI program developed at Duke. J. L. T. reports advisory board participation for Sanofi, Natera, Theravance and Altavant Sciences (now Enzyvant Therapeutics) in addition to grants to the institution from Boehringer-Ingelheim, AstraZeneca, Sanofi, NIH, Cystic Fibrosis Foundation and CareDx; and consulting fees from Sanofi. C. E. B. reports grants or contracts from American Lung Association and NIH (National Heart, Lung, and Blood Institute [NHLBI] and National Institute of Allergy and Infectious Diseases [NIAID] funded projects—not related to this project); participation as member of a Data and Safety Monitoring Board (DSMB) for VASSPR—an ICU-based trial with no relationship to this project. R. B. reports stock holdings in Merck, Johnson & Johnson, COVIDien, Pfizer, Sanofi, McKesson, and Viatris and consulting fees from Elixir. E. L. T. reports personal fees from Biomeme and Predigen, stock options in Danaher, and being an employee of Danaher Corp. O, W. reports support for attending meetings and/or travel from Karius (as Clinical Events Classification [CEC] Project Leader initiated and attended meetings with Karius for the PICKUP study); a role as CEC Project Leader coordinated CEC committee meetings within Duke Clinical Research Institute (DCRI) for the PICKUP trial. M. M. reports being an employee of Karius Inc, Redwood City, California, and may own stock options. D. H. reports being a former employee of Karius Inc, Redwood City, California, and a patent issued for related work while at Karius as employee (WO-2020106987-A1—Detection and Prediction of Infectious Disease). R. D. reports being a former employee of Karius Inc, Redwood City, California, and is owner of Karius stock options. D. S. L. reports being an employee of Karius Inc, Redwood City, California, and may own stock options. S. B. reports being an employee of Karius Inc, Redwood City, California, and may own stock options, and reports support for attending meetings and/or travel and patents planned, issued, or pending with Karius Inc. B, A. P. reports being an employee of Karius Inc, Redwood City, California, patents planned, issued or pending with Karius Inc, and may own stock options. T. A. B. reports being an employee of and having a leadership or fiduciary role with Karius Inc, Redwood City, California, and may own stock options. V. G. F. reports personal fees from Novartis, Debiopharm, Genentech, Achaogen, Affinium, Medicines Co., MedImmune, Bayer, Basilea, Affinergy, Janssen, Contrafect, Regeneron, Destiny, Amphliphi Biosciences, Integrated Biotherapeutics; C3J, Armata, Valanbio; Akagera, Aridis, Roche, grants from NIH, MedImmune, Allergan, Pfizer, Advanced Liquid Logics, Theravance, Novartis, Merck; Medical Biosurfaces; Locus; Affinergy; Contrafect; Karius; Genentech, Regeneron, Deep Blue, Basilea, Janssen; royalties from UpToDate, stock options from Valanbio and ArcBio, honoraria from IDSA for his service as Associate Editor of Clinical Infectious Diseases, and a patent sepsis diagnostics pending. T. L. H. reports being an advisor and consultant to Aridis, Basilea Pharmaceutica, Karius, and Lysovant; royalties from UpToDate; reports grants or contracts with Karius (adjudication committee) and with NIH; reports consulting fees from Pfizer and Affinivax; participation on DSMB for platform trial for SNAP Trial; and on advisory board for Basilea. All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2023. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Community-based HIV testing offers an alternative approach to encourage HIV testing among men in sub-Saharan Africa. In this study, we evaluated a community-based HIV testing strategy targeting male bar patrons in northern Tanzania to assess factors predictive of prior HIV testing and factors predictive of accepting a real-time HIV test offer. Participants completed a detailed survey and were offered HIV testing upon survey completion. Poisson regression was used to identify prevalence ratios for the association between potential predictors and prior HIV testing or real-time testing uptake. Of 359 participants analyzed, the median age was 41 (range 19-82) years, 257 (71.6%) reported a previous HIV test, and 321 (89.4%) accepted the real-time testing offer. Factors associated with previous testing for HIV (adjusted prevalence ratio [aPR], 95% CI) were wealth scores in the upper-middle quartile (1.25, 1.03-1.52) or upper quartile (1.35, 1.12-1.62) and HIV knowledge (1.04, 1.01-1.07). Factors that predicted real-time testing uptake were lower scores on the Gender-Equitable Men scale (0.99, 0.98-0.99), never testing for HIV (1.16, 1.03-1.31), and testing for HIV > 12 months prior (1.18, 1.06-1.31). We show that individual-level factors that influence the testing-seeking behaviors of men are not likely to impact their acceptance of an HIV offer., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Madut et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

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., Competing Interests: Potential conflicts of interest. All authors: No reported conflicts., (© The Author(s) 2023. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

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.

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., (Copyright © 2022. Published by Elsevier Ltd.)

Current care models are inadequate to address the dual epidemic of hypertension and HIV in sub-Saharan Africa. We developed a community health worker (CHW)-delivered educational intervention, integrated into existing HIV care to address hypertension in persons living with HIV. A detailed educational curriculum was created with five sessions: three in-person clinic sessions and two telephone sessions. The intervention was piloted among hypertensive adults at one HIV clinic in northern Tanzania over a 4-week period. Primary outcomes were feasibility, fidelity, and acceptability of the intervention. Secondary outcomes included hypertension care engagement and systolic and diastolic blood pressure (SBP and DBP). Among 16 eligible participants, 14 (64% women, median age of 54.5 years) were recruited into the study, and 13 (92.9%) completed all five intervention sessions. The intervention was delivered with 98.8% fidelity to the curriculum content. Hypertension care engagement improved following the intervention. At baseline, two (15.4%) participants had seen a doctor previously for hypertension, compared to 11 (84.6%) participants post-intervention (P = .0027). No participant was using antihypertensives at baseline, compared to 10 (76.9%) post-intervention (P = .0016). Pre-intervention median SBP was 164 (IQR 152-170) mmHg, compared to post-intervention SBP of 146 (IQR 134-154) mmHg (P = .0029). Pre-intervention median DBP was 102 (IQR 86-109) mmHg, compared to post-intervention DBP of 89 (IQR 86-98) mmHg (P = .0023). A CHW-delivered educational intervention, integrated into existing HIV care, is feasible and holds promise in improving hypertension care engagement and reducing blood pressure. Further research is needed to evaluate the efficacy and scale-up of our intervention., (© 2022 The Authors. The Journal of Clinical Hypertension published by Wiley Periodicals LLC.)

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., Competing Interests: The authors have declared that no competing interests exist.

Cite This Article: Preeti Manavalan et al. Hypertension among adults enrolled in HIV care in northern Tanzania: comorbidities, cardiovascular risk, and knowledge, attitudes and practices. Pan African Medical Journal. 2022;41(285). 10.11604/pamj.2022.41.285.26952., Introduction: the epidemiology of non-communicable diseases (NCDs) among people living with HIV (PLHIV) in sub-Saharan Africa is poorly described. In this observational study we examined a cohort of hypertensive PLHIV in northern Tanzania and described comorbidities, cardiovascular risk, and hypertension knowledge, attitudes and practices., Methods: consecutive patients attending an HIV clinic were screened for hypertension; those who met hypertension study criteria were enrolled. Participants completed a hypertension knowledge, attitudes and practices survey, and underwent height, weight, and waist circumference measurements and urine dipstick, fasting blood sugar, and lipid panel analyses. Kidney disease was defined as 1+ proteinuria, diabetes mellitus was defined as fasting glucose >126mg/dL, and 10-year atherosclerotic cardiovascular disease (ASCVD) risk was defined per the Pooled Cohorts Equations., Results: of 555 screened patients, 105 met hypertension criteria and 91 (86.7%) were enrolled. The prevalence of diabetes mellitus, kidney disease, and overweight or obesity was 8.8%, 28.6%, and 86.7%, respectively. Almost all participants (n=86, 94.5%) had two or more medical comorbidities. More than half (n=39, 52.7%) had intermediate or high 10-year risk for an ASCVD event. While only 3 (3.3%) participants were able to define hypertension correctly, most would seek care at a medical facility (n=89, 97.8%) and take medication chronically for hypertension (n=79, 87.8%)., Conclusion: we found a high burden of medical comorbidity and ASCVD risk among hypertensive PLHIV in northern Tanzania. Integration of routine NCD screening in the HIV clinical setting, in combination with large-scale educational campaigns, has the potential to impact clinical outcomes in this high-risk population., Competing Interests: The authors declare no competing interests., (Copyright: Preeti Manavalan et al.)

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.

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., (© 2021 John Wiley & Sons Ltd.)

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.

We investigated a novel community-based HIV testing and counseling (HTC) strategy by recruiting men from bars in northern Tanzania in order to identify new HIV infections. All bars in the town of Boma Ng'ombe were identified and male patrons were systematically invited to participate in a health study. HIV testing was offered to all enrolled participants. Outputs included HIV test yield, cost per diagnosis, and comparison of our observed test yield to that among male patients contemporaneously tested at five local facility-based HTC. We enrolled 366 participants and identified 17 new infections - providing a test yield of 5.3% (95% Confidence interval [CI] 3.3-8.4). The test yield among men contemporaneously tested at five local HTC centers was 2.1% (95% CI 1.6-2.8). The cost-per-diagnosis was $634. Our results suggest that recruiting male bar patrons for HIV testing is efficient for identifying new HIV infections. The scalability of this intervention warrants further evaluation.

Prediction models indicate that melioidosis may be common in parts of East Africa, but there are few empiric data. We evaluated the prevalence of melioidosis among patients presenting with fever to hospitals in Tanzania. Patients with fever were enrolled at two referral hospitals in Moshi, Tanzania, during 2007-2008, 2012-2014, and 2016-2019. Blood was collected from participants for aerobic culture. Bloodstream isolates were identified by conventional biochemical methods. Non-glucose-fermenting Gram-negative bacilli were further tested using a Burkholderia pseudomallei latex agglutination assay. Also, we performed B. pseudomallei indirect hemagglutination assay (IHA) serology on serum samples from participants enrolled from 2012 to 2014 and considered at high epidemiologic risk of melioidosis on the basis of admission within 30 days of rainfall. We defined confirmed melioidosis as isolation of B. pseudomallei from blood culture, probable melioidosis as a ≥ 4-fold rise in antibody titers between acute and convalescent sera, and seropositivity as a single antibody titer ≥ 40. We enrolled 3,716 participants and isolated non-enteric Gram-negative bacilli in five (2.5%) of 200 with bacteremia. As none of these five isolates was B. pseudomallei , there were no confirmed melioidosis cases. Of 323 participants tested by IHA, 142 (44.0%) were male, and the median (range) age was 27 (0-70) years. We identified two (0.6%) cases of probable melioidosis, and 57 (17.7%) were seropositive. The absence of confirmed melioidosis from 9 years of fever surveillance indicates melioidosis was not a major cause of illness.

Background: While factors that drive early mortality among people living with HIV (PLWH) initiating antiretroviral therapy (ART) in sub-Saharan Africa (SSA) have been described, less is known about the predictors of long-term mortality for those with ART experience., Methods: PLWH and on ART attending two HIV treatment clinics in Moshi, Tanzania were enrolled from 2008 through 2009 and followed for 3.5 years. Demographic, psychosocial, and clinical information were collected at enrollment. Plasma HIV RNA measurements were collected annually. Cause of death was adjudicated by two independent reviewers based on verbal autopsy information and medical records. Bivariable and multivariable analyses were conducted using Cox proportional hazard models to identify predictors of mortality., Results: The analysis included 403 participants. The median (IQR) age in years was 42 (36-48) and 277 (68.7%) participants were female. The proportion of participants virologically suppressed during the 4 collection time points was 88.5%, 94.7%, 91.5%, and 94.5%. During follow-up, 24 participants died; the overall mortality rate was 1.8 deaths per 100 person-years. Of the deaths, 14 (58.3%) were suspected to be HIV/AIDS related. Predictors of mortality (adjusted hazard ratio, 95% confidence interval) were male sex (2.63, 1.01-6.83), secondary or higher education (7.70, 3.02-19.60), receiving care at the regional referral hospital in comparison to the larger zonal referral hospital (6.33, 1.93-20.76), and moderate to severe depression symptoms (6.35, 1.69-23.87)., Conclusions: As ART coverage continues to expand in SSA, HIV programs should recognize the need for interventions to promote HIV care engagement for men and the integration of mental health screening and treatment with HIV care. Facility-level barriers may contribute to challenges faced by PLWH as they progress through the HIV care continuum, and further understanding of these barriers is needed. The association of higher educational attainment with mortality merits further investigation., Competing Interests: The authors have declared that no competing interests exist.

Failure to address hypertension among people living with HIV (PLWH) may undermine the significant progress made toward reducing mortality among this high-risk population in sub-Saharan Africa (SSA). Here, the authors report hypertension prevalence, diagnosis, and treatment among patients enrolled in HIV care in Tanzania. Patients attending an HIV clinic were consecutively screened for hypertension. Hypertension was defined as follows: a single blood pressure measurement ≥160 mm Hg systolic or ≥100 mm Hg diastolic, two measurements at separate visits ≥140 mm Hg systolic or ≥90 mm Hg diastolic, or self-reported hypertension diagnosis. The authors screened 555 patients, and 19.6% met hypertension criteria. Among a subset of 91 hypertensive participants, 44 (48.4%) reported previous blood pressure measurements, 32 (35.2%) were aware of diagnosis, 10 (11.0%) reported current antihypertensive use, and none had controlled blood pressure. Addressing barriers along the hypertension treatment cascade must be a top priority to improve cardiovascular outcomes among PLWH in SSA., (© 2020 Wiley Periodicals LLC.)

Background: Characterization of the epidemiology of Escherichia coli bloodstream infection (BSI) in sub-Saharan Africa is lacking. We studied patients with E. coli BSI in northern Tanzania to describe host risk factors for infection and to describe the antimicrobial susceptibility of isolates., Methods: Within 24 h of admission, patients presenting with a fever at two hospitals in Moshi, Tanzania, were screened and enrolled. Cases were patients with at least one blood culture yielding E. coli and controls were those without E. coli isolated from any blood culture. Logistic regression was used to identify host risk factors for E. coli BSI., Results: We analyzed data from 33 cases and 1615 controls enrolled from 2007 through 2018. The median (IQR) age of cases was 47 (34-57) y and 24 (72.7%) were female. E. coli BSI was associated with (adjusted OR [aOR], 95% CI) increasing years of age (1.03, 1.01 to 1.05), female gender (2.20, 1.01 to 4.80), abdominal tenderness (2.24, 1.06 to 4.72) and urinary tract infection as a discharge diagnosis (3.71, 1.61 to 8.52). Of 31 isolates with antimicrobial susceptibility results, the prevalence of resistance was ampicillin 29 (93.6%), ceftriaxone three (9.7%), ciprofloxacin five (16.1%), gentamicin seven (22.6%) and trimethoprim-sulfamethoxazole 31 (100.0%)., Conclusions: In Tanzania, host risk factors for E. coli BSI were similar to those reported in high-resource settings and resistance to key antimicrobials was common., (© The Author(s) 2019. Published by Oxford University Press on behalf of Royal Society of Tropical Medicine and Hygiene. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Introduction: Little is known about the burden of hypertension and diabetes on emergency department (ED) utilization and hospitalizations in sub-Saharan Africa., Methods: A retrospective review of adult ED patients in northern Tanzania was performed from September 2017 through March 2018. Hypertension was defined as documented diagnosis of hypertension or blood pressure ≥ 140/90 mm Hg. Diabetes was defined as documented diagnosis of diabetes mellitus or random glucose ≥ 200 mg/dL., Results: Of 3961 adult ED patients, 1359 (34.3%) had hypertension, 518 (13.1%) had diabetes, and 273 (6.9%) had both. Both hypertension (OR 1.42, 95% CI 1.23-1.63, P<.001) and diabetes (OR 2.05, 95% CI 1.66-2.54, P<.001) were associated with increased odds of admission. Of 2418 hospital admissions, 694 (28.7%) were for complications of hypertension or diabetes. Of 499 patients admitted for hypertensive complications, the most common admission diagnoses were: heart failure (163 patients, 32.7%); stroke (147 patients, 29.5%); and severe hypertension (139 patients, 27.9%). Of 278 patients admitted for diabetic complications, the most common admission diagnoses were: hyperglycemia (158 patients, 56.9%); infection (60 patients, 21.6%); and stroke (28 patients, 10.1%)., Conclusions: The burden of hypertension and diabetes in a Tanzanian ED is high, and the ED may serve as an opportune location for case identification and linkage-to-care interventions. Given the large proportion of Africans with undiagnosed hypertension and diabetes, an ED-based screening program would likely identify many new cases of these diseases. The high burden of hypertension- and diabetes-related hospitalizations highlights the urgent need for improvements in primary preventative care in Tanzania., Competing Interests: Competing Interests: None declared., (Copyright © 2019, Ethnicity & Disease, Inc.)

Background: Little is known about community knowledge of myocardial infarction symptoms and perceptions of self-risk in sub-Saharan Africa., Methods: A community survey was conducted in northern Tanzania, where the prevalence of cardiovascular risk factors is high. Households were selected randomly in a population-weighted fashion and surveys were administered to self-identified household healthcare decision-makers. Respondents were asked to list all symptoms of a heart attack and asked whether they thought they had a chance of suffering a heart attack. Associations between participant sociodemographic features and responses to these questions were assessed with Pearson's chi-squared and the Student t test., Results: There were 718 survey participants, with median (IQR) age 48 (32, 62) years. Of these, 115 (16.0%) were able to identify any conventional symptom of a heart attack, including 24 (3.3%) respondents who cited chest pain as a possible symptom. There was no association between ability to identify a conventional symptom and gender, level of education, socioeconomic status, urban residence, or age. Of respondents, 198 (27.6%) thought they had a chance of suffering a heart attack. Older respondents were more likely to perceive themselves to be at risk (P < .001), but there was no association between perception of self-risk and gender, level of education, socioeconomic status, or urban residence., Conclusions: In northern Tanzania, knowledge of myocardial infarction symptoms is poor among all segments of the population and only a minority of residents perceive themselves to be at risk of this disease. Educational interventions regarding ischemic heart disease are urgently needed., (Copyright © 2019 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: Self-treatment with antimicrobials is common in sub-Saharan Africa. Little is known about the prevalence of this practice where malaria transmission intensity is low, and little is known about the prevalence of self-treatment with other medications such as antihypertensives and antihyperglycemics., Methods: A two-stage randomized population-based cluster survey with selection proportional to population size was performed in northern Tanzania. Self-identified healthcare decision-makers from randomly selected households were asked to report instances of self-medication without a prescription in the preceding year. Associations between self-treatment and sociodemographic characteristics were assessed with Pearson's chi-squared and the Student's t-test., Results: A total of 718 participants completed the survey, and 344 (47.9%) reported any household member obtaining medication without a prescription. Of these, 85 (11.8%) obtained an antimicrobial and four (0.6%) obtained an antihypertensive or antihyperglycemic. Of respondents reporting self-treatment, 306 (89.0%) selected the medication themselves. Self-treatment with antimicrobials was associated with post-primary education (OR 1.95, 95% CI 1.22-3.16, p=0.005), younger age (43.1 vs 48.7 years, p=0.007) and higher socioeconomic status score (0.42 vs 0.34, p=0.023)., Conclusions: Self-treatment with antimicrobials in an area of low malaria transmission intensity was uncommon and self-treatment with antihypertensives and antihyperglycemics was rare., (© The Author(s) 2018. Published by Oxford University Press on behalf of Royal Society of Tropical Medicine and Hygiene.)

Background: Little is known about community perceptions of chest pain and healthcare seeking behavior for chest pain in sub-Saharan Africa., Methods: A two-stage randomized population-based cluster survey with selection proportional to population size was performed in northern Tanzania. Self-identified household healthcare decision-makers from randomly selected households were asked to list all possible causes of chest pain in an adult and asked where they would go if an adult household member had chest pain., Results: Of 718 respondents, 485 (67.5%) were females. The most commonly cited causes of chest pain were weather and exercise, identified by 342 (47.6%) and 318 (44.3%) respondents. Two (0.3%) respondents identified 'heart attack' as a possible cause of chest pain. A hospital was selected as the preferred healthcare facility for an adult with chest pain by 277 (38.6%) respondents. Females were less likely to prefer a hospital than males (OR 0.65, 95% CI 0.47-0.90, p = 0.008)., Conclusions: There is little community awareness of cardiac causes of chest pain in northern Tanzania, and most adults reported that they would not present to a hospital for this symptom. There is an urgent need for educational interventions to address this knowledge deficit and guide appropriate care-seeking behavior., Competing Interests: The authors have declared that no competing interests exist.

Background: Little is known about knowledge of stroke symptoms, perceptions of self-risk, and health-care-seeking behavior for stroke in East Africa., Methods: A 2-stage randomized population-based cluster survey with selection proportional to population size was performed in northern Tanzania. Self-identified household health-care decision makers were asked to list all symptoms of a stroke. They were further asked if they thought they had a chance of having a stroke and where they would present for care for stroke-like symptoms. A socioeconomic status score was derived via principal component analysis from 9 variables related to wealth., Results: Of 670 respondents, 184 (27.4%) knew a conventional stroke symptom and 51 (7.6%) thought they had a chance of having a stroke. Females were less likely to perceive themselves to be at risk than males (OR 0.49, 95% CI 0.28-0.89, p = 0.014). Of respondents, 558 (88.3%) stated they would present to a hospital for stroke-like symptoms. Preference for a hospital was not associated with knowledge of stroke symptoms or perception of self-risk but was associated with a higher socioeconomic status score (p < 0.001)., Conclusions: Knowledge of stroke symptoms and perception of self-risk are low in northern Tanzania, but most residents would present to a hospital for stroke-like symptoms., (© 2019 The Author(s) Published by S. Karger AG, Basel.)