Browsing by Author "Rubach, Matthew P"
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Item Open Access A prospective study of Escherichia coli bloodstream infection among adolescents and adults in northern Tanzania.(Transactions of the Royal Society of Tropical Medicine and Hygiene, 2020-05) Madut, Deng B; Rubach, Matthew P; Kalengo, Nathaniel; Carugati, Manuela; Maze, Michael J; Morrissey, Anne B; Mmbaga, Blandina T; Lwezaula, Bingileki F; Kilonzo, Kajiru G; Maro, Venance P; Crump, John ABackground
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.Item Embargo Antibacterial Utilization for Febrile Illnesses and Laboratory-confirmed Bloodstream Infections in Northern Tanzania(2023) Moorthy, Ganga S.Antibacterial management of febrile patients in low-resource settings is challenging and adherence to treatment guidelines is variable. We describe antibacterial use in febrile patients, use of effective therapy for laboratory-confirmed bloodstream infections, and adherence to published guidelines for common febrile illnesses among patients enrolled in prospective hospital-based fever surveillance studies in Moshi, Tanzania.
We compared data from two hospital-based prospective cohort studies, Cohort 1 (2011–2014) and Cohort 2 (2016–2019), that enrolled febrile infants, children, and adults. A study team member administered a standardized questionnaire, performed a physical examination, and collected blood cultures on all participants. Ceftriaxone, ciprofloxacin, amoxicillin-clavulanate, or azithromycin were categorized as broad-spectrum antibacterials based on published frameworks and local antimicrobial availability. Participants with laboratory-confirmed bloodstream infections were categorized as receiving effective or ineffective antibacterials based on culture and susceptibility data. Antimicrobials prescribed for preliminary or final diagnosis of pneumonia, urinary tract infection, or presumed sepsis were compared with syndrome-specific recommendations from the World Health Organization (WHO) and the Tanzania Standard Treatment Guidelines. We used descriptive statistics and logistic regression to describe factors associated with antibacterial use.
We analyzed data from 2175 participants. The median age of participants in Cohort 1 was 29 (IQR: 5-41) and 22 in Cohort 2 (IQR: 2-45). Among all participants, 50% were female. There were 430 (42.0%) and 501 (45.1%) participants who reported use of antibacterials prior to admission in Cohort 1 and Cohort 2, respectively. There were 989 (91.4%) participants who received antibacterials during admission for febrile illness in Cohort 1 versus 1060 (93.6%) in Cohort 2 (p < 0.001); 548 (52.5%) in Cohort 1 and 682 (60.2%) in Cohort 2 (p < 0.001) received broad-spectrum therapy. Inpatient use of ceftriaxone, metronidazole, and ampicillin increased between the two cohorts (ceftriaxone p = < 0.001; metronidazole p = 0.02; ampicillin p = < 0.001). Laboratory-confirmed bacteremia was found in 38 (3.6%) participants in Cohort 1 and 47 (4.2%) participants in Cohort 2. Complete data to determine appropriateness of antibacterial prescription were available for 81 (95.3%) of 85 participants and 52 (63.0%) participants were prescribed effective therapy. Guideline-consistent therapy for pneumonia, urinary tract infection, and sepsis increased over time.
Receipt of antibacterials prior to and after hospital admission were high and use of broad-spectrum medications was common. A large proportion of participants with culture-confirmed bloodstream infections were treated with ineffective antibacterials but consistency of antibacterial prescribing with WHO and Tanzanian treatment guidelines improved over time. Our results highlight the need for improved diagnostics for febrile illness, data on local antimicrobial resistance patterns, institution-specific clinical guidelines, and provider education to improve prescribing practices and rational use of antimicrobials in Tanzania.
Item Open Access Antibacterial Utilization for Febrile Illnesses and Laboratory-Confirmed Bloodstream Infections in Northern Tanzania.(Open forum infectious diseases, 2023-08) Moorthy, Ganga S; Madut, Deng B; Kilonzo, Kajiru G; Lwezaula, Bingileki F; Mbwasi, Ronald; Mmbaga, Blandina T; Ngocho, James S; Saganda, Wilbrod; Bonnewell, John P; Carugati, Manuela; Egger, Joseph R; Hertz, Julian T; Tillekeratne, L Gayani; Maze, Michael J; Maro, Venance P; Crump, John A; Rubach, Matthew PBackground
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.Item Open Access Bloodstream Infections and Frequency of Pretreatment Associated With Age and Hospitalization Status in Sub-Saharan Africa.(Clin Infect Dis, 2015-11-01) Nichols, Chelsea; Cruz Espinoza, Ligia Maria; von Kalckreuth, Vera; Aaby, Peter; Ahmed El Tayeb, Muna; Ali, Mohammad; Aseffa, Abraham; Bjerregaard-Andersen, Morten; Breiman, Robert F; Cosmas, Leonard; Crump, John A; Dekker, Denise Myriam; Gassama Sow, Amy; Gasmelseed, Nagla; Hertz, Julian T; Im, Justin; Kabore, Leon Parfait; Keddy, Karen H; Konings, Frank; Valborg Løfberg, Sandra; Meyer, Christian G; Montgomery, Joel M; Niang, Aissatou; Njariharinjakamampionona, Andriamampionona; Olack, Beatrice; Pak, Gi Deok; Panzner, Ursula; Park, Jin Kyung; Park, Se Eun; Rabezanahary, Henintsoa; Rakotondrainiarivelo, Jean Philibert; Rakotozandrindrainy, Raphaël; Raminosoa, Tiana Mirana; Rubach, Matthew P; Teferi, Mekonnen; Seo, Hye Jin; Sooka, Arvinda; Soura, Abdramane; Tall, Adama; Toy, Trevor; Yeshitela, Biruk; Clemens, John D; Wierzba, Thomas F; Baker, Stephen; Marks, FlorianBACKGROUND: The clinical diagnosis of bacterial bloodstream infections (BSIs) in sub-Saharan Africa is routinely confused with malaria due to overlapping symptoms. The Typhoid Surveillance in Africa Program (TSAP) recruited febrile inpatients and outpatients of all ages using identical study procedures and enrollment criteria, thus providing an opportunity to assess disease etiology and pretreatment patterns among children and adults. METHODS: Inpatients and outpatients of all ages with tympanic or axillary temperatures of ≥38.0 or ≥37.5°C, respectively, and inpatients only reporting fever within the previous 72 hours were eligible for recruitment. All recruited patients had one blood sample drawn and cultured for microorganisms. Data from 11 TSAP surveillance sites in nine different countries were used in the analysis. Bivariate analysis was used to compare frequencies of pretreatment and BSIs in febrile children (<15 years old) and adults (≥15 years old) in each country. Pooled Cochran Mantel-Haenszel odds ratios (ORs) were calculated for overall trends. RESULTS: There was no significant difference in the odds of a culture-proven BSI between children and adults among inpatients or outpatients. Among both inpatients and outpatients, children had significantly higher odds of having a contaminated blood culture compared with adults. Using country-pooled data, child outpatients had 66% higher odds of having Salmonella Typhi in their bloodstream than adults (OR, 1.66; 95% confidence interval [CI], 1.01-2.73). Overall, inpatient children had 59% higher odds of pretreatment with analgesics in comparison to inpatient adults (OR, 1.59; 95% CI, 1.28-1.97). CONCLUSIONS: The proportion of patients with culture-proven BSIs in children compared with adults was similar across the TSAP study population; however, outpatient children were more likely to have Salmonella Typhi infections than outpatient adults. This finding points to the importance of including outpatient facilities in surveillance efforts, particularly for the surveillance of typhoid fever. Strategies to reduce contamination among pediatric blood cultures are needed across the continent to prevent the misdiagnosis of BSI cases in children.Item Open Access Brucellosis in low-income and middle-income countries.(Curr Opin Infect Dis, 2013-10) Rubach, Matthew P; Halliday, Jo EB; Cleaveland, Sarah; Crump, John APURPOSE OF REVIEW: Human brucellosis is a neglected, underrecognized infection of widespread geographic distribution. It causes acute febrile illness and a potentially debilitating chronic infection in humans, and livestock infection has substantial socioeconomic impact. This review describes new information regarding the epidemiology of brucellosis in the developing world and advances in diagnosis and treatment. RECENT FINDINGS: The highest recorded incidence of human brucellosis occurs in the Middle East and Central Asia. Fever etiology studies demonstrate brucellosis as a cause of undifferentiated febrile illness in the developing world. Brucellosis is a rare cause of fever among returning travelers, but is more common among travelers returning from the Middle East and North Africa. Sensitive and specific rapid diagnostic tests appropriate for resource-limited settings have been validated. Randomized controlled trials demonstrate that optimal treatment for human brucellosis consists of doxycycline and an aminoglycoside. Decreasing the burden of human brucellosis requires control of animal brucellosis, but evidence to inform the design of control programs in the developing world is needed. SUMMARY: Brucellosis causes substantial morbidity in human and animal populations. While improvements in diagnostic options for resource-limited settings and stronger evidence for optimal therapy should enhance identification and treatment of human brucellosis, prevention of human disease through control in animals remains paramount.Item Open Access Challenges of Maintaining Good Clinical Laboratory Practices in Low-Resource Settings: A Health Program Evaluation Framework Case Study From East Africa.(Am J Clin Pathol, 2016-08) Zhang, Helen L; Omondi, Michael W; Musyoka, Augustine M; Afwamba, Isaac A; Swai, Remigi P; Karia, Francis P; Muiruri, Charles; Reddy, Elizabeth A; Crump, John A; Rubach, Matthew POBJECTIVES: Using a clinical research laboratory as a case study, we sought to characterize barriers to maintaining Good Clinical Laboratory Practice (GCLP) services in a developing world setting. METHODS: Using a US Centers for Disease Control and Prevention framework for program evaluation in public health, we performed an evaluation of the Kilimanjaro Christian Medical Centre-Duke University Health Collaboration clinical research laboratory sections of the Kilimanjaro Clinical Research Institute in Moshi, Tanzania. Laboratory records from November 2012 through October 2014 were reviewed for this analysis. RESULTS: During the 2-year period of study, seven instrument malfunctions suspended testing required for open clinical trials. A median (range) of 9 (1-55) days elapsed between instrument malfunction and biomedical engineer service. Sixteen (76.1%) of 21 suppliers of reagents, controls, and consumables were based outside Tanzania. Test throughput among laboratory sections used a median (range) of 0.6% (0.2%-2.7%) of instrument capacity. Five (55.6%) of nine laboratory technologists left their posts over 2 years. CONCLUSIONS: These findings demonstrate that GCLP laboratory service provision in this setting is hampered by delays in biomedical engineer support, delays and extra costs in commodity procurement, low testing throughput, and high personnel turnover.Item Open Access Epidemiology of Coxiella burnetii infection in Africa: a OneHealth systematic review.(PLoS Negl Trop Dis, 2014-04) Vanderburg, Sky; Rubach, Matthew P; Halliday, Jo EB; Cleaveland, Sarah; Reddy, Elizabeth A; Crump, John ABACKGROUND: Q fever is a common cause of febrile illness and community-acquired pneumonia in resource-limited settings. Coxiella burnetii, the causative pathogen, is transmitted among varied host species, but the epidemiology of the organism in Africa is poorly understood. We conducted a systematic review of C. burnetii epidemiology in Africa from a "One Health" perspective to synthesize the published data and identify knowledge gaps. METHODS/PRINCIPAL FINDINGS: We searched nine databases to identify articles relevant to four key aspects of C. burnetii epidemiology in human and animal populations in Africa: infection prevalence; disease incidence; transmission risk factors; and infection control efforts. We identified 929 unique articles, 100 of which remained after full-text review. Of these, 41 articles describing 51 studies qualified for data extraction. Animal seroprevalence studies revealed infection by C. burnetii (≤13%) among cattle except for studies in Western and Middle Africa (18-55%). Small ruminant seroprevalence ranged from 11-33%. Human seroprevalence was <8% with the exception of studies among children and in Egypt (10-32%). Close contact with camels and rural residence were associated with increased seropositivity among humans. C. burnetii infection has been associated with livestock abortion. In human cohort studies, Q fever accounted for 2-9% of febrile illness hospitalizations and 1-3% of infective endocarditis cases. We found no studies of disease incidence estimates or disease control efforts. CONCLUSIONS/SIGNIFICANCE: C. burnetii infection is detected in humans and in a wide range of animal species across Africa, but seroprevalence varies widely by species and location. Risk factors underlying this variability are poorly understood as is the role of C. burnetii in livestock abortion. Q fever consistently accounts for a notable proportion of undifferentiated human febrile illness and infective endocarditis in cohort studies, but incidence estimates are lacking. C. burnetii presents a real yet underappreciated threat to human and animal health throughout Africa.Item Open Access Etiologies of illness among patients meeting integrated management of adolescent and adult illness district clinician manual criteria for severe infections in northern Tanzania: implications for empiric antimicrobial therapy.(Am J Trop Med Hyg, 2015-02) Rubach, Matthew P; Maro, Venance P; Bartlett, John A; Crump, John AWe describe the laboratory-confirmed etiologies of illness among participants in a hospital-based febrile illness cohort study in northern Tanzania who retrospectively met Integrated Management of Adolescent and Adult Illness District Clinician Manual (IMAI) criteria for septic shock, severe respiratory distress without shock, and severe pneumonia, and compare these etiologies against commonly used antimicrobials, including IMAI recommendations for emergency antibacterials (ceftriaxone or ampicillin plus gentamicin) and IMAI first-line recommendations for severe pneumonia (ceftriaxone and a macrolide). Among 423 participants hospitalized with febrile illness, there were 25 septic shock, 37 severe respiratory distress without shock, and 109 severe pneumonia cases. Ceftriaxone had the highest potential utility of all antimicrobials assessed, with responsive etiologies in 12 (48%) septic shock, 5 (14%) severe respiratory distress without shock, and 19 (17%) severe pneumonia illnesses. For each syndrome 17-27% of participants had etiologic diagnoses that would be non-responsive to ceftriaxone, but responsive to other available antimicrobial regimens including amphotericin for cryptococcosis and histoplasmosis; anti-tuberculosis therapy for bacteremic disseminated tuberculosis; or tetracycline therapy for rickettsioses and Q fever. We conclude that although empiric ceftriaxone is appropriate in our setting, etiologies not explicitly addressed in IMAI guidance for these syndromes, such as cryptococcosis, histoplasmosis, and tetracycline-responsive bacterial infections, were common.Item Open Access Evaluation of in-hospital management for febrile illness in Northern Tanzania before and after 2010 World Health Organization Guidelines for the treatment of malaria.(PLoS One, 2014) Moon, Andrew M; Biggs, Holly M; Rubach, Matthew P; Crump, John A; Maro, Venace P; Saganda, Wilbrod; Reddy, Elizabeth AOBJECTIVE: In 2010, the World Health Organization (WHO) published updated guidelines emphasizing and expanding recommendations for a parasitological confirmation of malaria before treating with antimalarials. This study aimed to assess differences in historic (2007-2008) (cohort 1) and recent (2011-2012) (cohort 2) hospital cohorts in the diagnosis and treatment of febrile illness in a low malaria prevalence area of northern Tanzania. MATERIALS AND METHODS: We analyzed data from two prospective cohort studies that enrolled febrile adolescents and adults aged ≥13 years. All patients received quality-controlled aerobic blood cultures and malaria smears. We compared patients' discharge diagnoses, treatments, and outcomes to assess changes in the treatment of malaria and bacterial infections. RESULTS: In total, 595 febrile inpatients were enrolled from two referral hospitals in Moshi, Tanzania. Laboratory-confirmed malaria was detected in 13 (3.2%) of 402 patients in cohort 1 and 1 (0.5%) of 193 patients in cohort 2 (p = 0.041). Antimalarials were prescribed to 201 (51.7%) of 389 smear-negative patients in cohort 1 and 97 (50.5%) of 192 smear-negative patients in cohort 2 (p = 0.794). Bacteremia was diagnosed from standard blood culture in 58 (14.5%) of 401 patients in cohort 1 compared to 18 (9.5%) of 190 patients in cohort 2 (p = 0.091). In cohort 1, 40 (69.0%) of 58 patients with a positive blood culture received antibacterials compared to 16 (88.9%) of 18 patients in cohort 2 (p = 0.094). In cohort 1, 43 (10.8%) of the 399 patients with known outcomes died during hospitalization compared with 12 (6.2%) deaths among 193 patients in cohort 2 (p = 0.073). DISCUSSION: In a setting of low malaria transmission, a high proportion of smear-negative patients were diagnosed with malaria and treated with antimalarials despite updated WHO guidelines on malaria treatment. Improved laboratory diagnostics for non-malaria febrile illness might help to curb this practice.Item Open Access Facility-based disease surveillance and Bayesian hierarchical modeling to estimate endemic typhoid fever incidence, Kilimanjaro Region, Tanzania, 2007-2018.(PLoS neglected tropical diseases, 2022-07-05) Cutting, Elena R; Simmons, Ryan A; Madut, Deng B; Maze, Michael J; Kalengo, Nathaniel H; Carugati, Manuela; Mbwasi, Ronald M; Kilonzo, Kajiru G; Lyamuya, Furaha; Marandu, Annette; Mosha, Calvin; Saganda, Wilbrod; Lwezaula, Bingileki F; Hertz, Julian T; Morrissey, Anne B; Turner, Elizabeth L; Mmbaga, Blandina T; Kinabo, Grace D; Maro, Venance P; Crump, John A; Rubach, Matthew PGrowing 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.Item Open Access Global distribution of Leptospira serovar isolations and detections from animal host species: a systematic review and online database.(medRxiv, 2023-10-03) Hagedoorn, Nienke N; Maze, Michael J; Carugati, Manuela; Cash-Goldwasser, Shama; Allan, Kathryn J; Chen, Kevin; Cossic, Brieuc; Demeter, Elena; Gallagher, Sarah; German, Richard; Galloway, Renee L; Habuš, Josipa; Rubach, Matthew P; Shiokawa, Kanae; Sulikhan, Nadezhda; Crump, John AOBJECTIVES: 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.Item Open Access Incidence Estimates of Acute Q Fever and Spotted Fever Group Rickettsioses, Kilimanjaro, Tanzania, from 2007 to 2008 and from 2012 to 2014.(The American journal of tropical medicine and hygiene, 2021-12) Pisharody, Sruti; Rubach, Matthew P; Carugati, Manuela; Nicholson, William L; Perniciaro, Jamie L; Biggs, Holly M; Maze, Michael J; Hertz, Julian T; Halliday, Jo EB; Allan, Kathryn J; Mmbaga, Blandina T; Saganda, Wilbrod; Lwezaula, Bingileki F; Kazwala, Rudovick R; Cleaveland, Sarah; Maro, Venance P; Crump, John AQ 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.Item Open Access Incidence of Acute Myocardial Infarction in Northern Tanzania: A Modeling Approach Within a Prospective Observational Study.(Journal of the American Heart Association, 2021-08) Hertz, Julian T; Madut, Deng B; Rubach, Matthew P; William, Gwamaka; Crump, John A; Galson, Sophie W; Maro, Venance P; Bloomfield, Gerald S; Limkakeng, Alexander T; Temu, Gloria; Thielman, Nathan M; Sakita, Francis MBackground 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.Item Open Access Incidence of human brucellosis in the Kilimanjaro Region of Tanzania in the periods 2007-2008 and 2012-2014.(Transactions of the Royal Society of Tropical Medicine and Hygiene, 2018-03) Carugati, Manuela; Biggs, Holly M; Maze, Michael J; Stoddard, Robyn A; Cash-Goldwasser, Shama; Hertz, Julian T; Halliday, Jo EB; Saganda, Wilbrod; Lwezaula, Bingileki F; Kazwala, Rudovick R; Cleaveland, Sarah; Maro, Venance P; Rubach, Matthew P; Crump, John ABackground
Brucellosis causes substantial morbidity among humans and their livestock. There are few robust estimates of the incidence of brucellosis in sub-Saharan Africa. Using cases identified through sentinel hospital surveillance and health care utilization data, we estimated the incidence of brucellosis in Moshi Urban and Moshi Rural Districts, Kilimanjaro Region, Tanzania, for the periods 2007-2008 and 2012-2014.Methods
Cases were identified among febrile patients at two sentinel hospitals and were defined as having either a 4-fold increase in Brucella microscopic agglutination test titres between acute and convalescent serum or a blood culture positive for Brucella spp. Findings from a health care utilization survey were used to estimate multipliers to account for cases not seen at sentinel hospitals.Results
Of 585 patients enrolled in the period 2007-2008, 13 (2.2%) had brucellosis. Among 1095 patients enrolled in the period 2012-2014, 32 (2.9%) had brucellosis. We estimated an incidence (range based on sensitivity analysis) of brucellosis of 35 (range 32-93) cases per 100 000 persons annually in the period 2007-2008 and 33 (range 30-89) cases per 100 000 persons annually in the period 2012-2014.Conclusions
We found a moderate incidence of brucellosis in northern Tanzania, suggesting that the disease is endemic and an important human health problem in this area.Item Open Access Investigation of Melioidosis Using Blood Culture and Indirect Hemagglutination Assay Serology among Patients with Fever, Northern Tanzania.(The American journal of tropical medicine and hygiene, 2020-12) Maze, Michael J; Elrod, Mindy Glass; Biggs, Holly M; Bonnewell, John; Carugati, Manuela; Hoffmaster, Alex R; Lwezaula, Bingileki F; Madut, Deng B; Maro, Venance P; Mmbaga, Blandina T; Morrissey, Anne B; Saganda, Wilbrod; Sakasaka, Philoteus; Rubach, Matthew P; Crump, John APrediction 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.Item Open Access 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.(JAMA network open, 2021-12) Bonnewell, John P; Rubach, Matthew P; Madut, Deng B; Carugati, Manuela; Maze, Michael J; Kilonzo, Kajiru G; Lyamuya, Furaha; Marandu, Annette; Kalengo, Nathaniel H; Lwezaula, Bingileki F; Mmbaga, Blandina T; Maro, Venance P; Crump, John AImportance
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.Item Open Access Performance of Xpert Ultra nasopharyngeal swab for identification of tuberculosis deaths in northern Tanzania.(Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases, 2022-08) Costales, Cristina; Crump, John A; Mremi, Alex R; Amsi, Patrick T; Kalengo, Nathaniel H; Kilonzo, Kajiru G; Kinabo, Grace; Lwezaula, Bingileki F; Lyamuya, Furaha; Marandu, Annette; Mbwasi, Ronald; Mmbaga, Blandina T; Mosha, Calvin; Carugati, Manuela; Madut, Deng B; Nelson, Ann M; Maze, Michael J; Matkovic, Eduard; Zaki, Sherif R; Maro, Venance P; Rubach, Matthew PObjective
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.Item Open Access Prevalence and risk factors for human leptospirosis at a hospital serving a pastoralist community, Endulen, Tanzania.(PLoS neglected tropical diseases, 2023-12) Maze, Michael J; Shirima, Gabriel M; Lukambagire, Abdul-Hamid S; Bodenham, Rebecca F; Rubach, Matthew P; Cash-Goldwasser, Shama; Carugati, Manuela; Thomas, Kate M; Sakasaka, Philoteus; Mkenda, Nestory; Allan, Kathryn J; Kazwala, Rudovick R; Mmbaga, Blandina T; Buza, Joram J; Maro, Venance P; Galloway, Renee L; Haydon, Daniel T; Crump, John A; Halliday, Jo EBBackground
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 (31.1%) participants were Leptospira seropositive and the most common predominant reactive serogroups were Icterohaemorrhagiae (n = 21, 30.0%), Djasiman (n = 19, 27.1%), and Australis (n = 17, 24.3%). 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.Item Open Access Sepsis in sub-Saharan Africa: a prospective observational study of clinical characteristics, management, and outcomes for adolescents and adults with sepsis in northern Tanzania(2020) Bonnewell, JohnBackground: Sepsis is a leading cause of death and disability globally. Despite a high burden of sepsis in sub-Saharan Africa, clinical data for sepsis in that setting are limited. We sought to describe the clinical characteristics, management, and outcomes in a cohort of adults and adolescents with sepsis in northern Tanzania. We also assessed for associations between clinical factors and in-hospital mortality.
Methods: We carried out a prospective observational cohort study at Kilimanjaro Christian Medical Centre in Moshi, Tanzania. We collected data on demographics, baseline clinical characteristics, and management, with an emphasis on hours 0-6 after arrival to the Emergency Department. Log risk regression was carried out to assess for associations between demographic and clinical factors and our primary outcome of in-hospital death. Separate multivariable regression analyses were conducted for both antimicrobial administration by hour 6 and administration of intravenous (IV) fluids >1L by hour 6 and the outcome of in-hospital mortality.
Results: Fifty-eight participants were included in our analysis. Seventeen (29.3%) participants died in-hospital. Baseline characteristics associated with inpatient mortality included inability to drink unassisted, respiratory rate >30 breaths per minute, hypoxia, and altered mentation. Less than half of participants received any antimicrobial by hour 6, and most participants received <1L of IV fluids. HIV antibody testing was performed for only one participant in the first 6 hours. On multivariable analysis, neither antimicrobial administration nor IV fluids >1L by hour 6 was associated with inpatient mortality.
Conclusion: Sepsis in northern Tanzania carries a high risk of in-hospital mortality. Further research is urgently needed to establish the highest-yield interventions suited to the unique characteristics of sepsis in sSA.
Item Open Access Trends in fever case management for febrile inpatients in a low malaria incidence setting of Tanzania.(Tropical medicine & international health : TM & IH, 2021-12) Madut, Deng B; Rubach, Matthew P; Bonnewell, John P; Cutting, Elena R; Carugati, Manuela; Kalengo, Nathaniel; Maze, Michael J; Morrissey, Anne B; Mmbaga, Blandina T; Lwezaula, Bingileki F; Kinabo, Grace; Mbwasi, Ronald; Kilonzo, Kajiru G; Maro, Venance P; Crump, John AObjectives
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.