Publications by authors named "John A Crump"

216 Publications

Point-prevalence surveys of antimicrobial consumption and resistance at a paediatric and an adult tertiary referral hospital in Yangon, Myanmar.

Infect Prev Pract 2022 Mar 11;4(1):100197. Epub 2021 Dec 11.

Centre for International Health, University of Otago, Dunedin, New Zealand.

Background: Antimicrobial resistance is increasingly prevalent worldwide. The inappropriate use of antimicrobials, including in the hospital setting, is considered a major driver of antimicrobial resistance.

Aim: To inform improvements in antimicrobial stewardship, we undertook point prevalence surveys of antimicrobial prescribing at Yangon Children's Hospital and Yangon General Hospital in Yangon, Myanmar.

Methods: We conducted our surveys using the Global Point-Prevalence Survey of Antimicrobial Consumption and Resistance (Global-PPS) method. All inpatients who were prescribed an antimicrobial on the day of the survey were included in the analysis.

Findings: We evaluated a total of 1,980 patients admitted to two hospitals during December 2019. Of these, 1,255 (63.4%) patients were prescribed a total of 2,108 antimicrobials. Among antimicrobials prescribed, 722 (34.3%) were third-generation cephalosporins, the most commonly prescribed antimicrobial class. A total of 940 (44.6%) antimicrobials were prescribed for community-acquired infection, and 724 (34.3%) for surgical prophylaxis. Of 2,108 antimicrobials, 317 (15.0%) were prescribed for gastrointestinal tract prophylaxis, 305 (14.5%) for skin, soft tissue, bone and joint prophylaxis, and 303 (14.4%) for pneumonia treatment. A stop or review date was documented for 350 (16.6%) antimicrobial prescriptions, 673 (31.9%) antimicrobial prescriptions were guideline compliant, and 1,335 (63.3%) antimicrobials were administered via the parenteral route. Of 1,083 antimicrobials prescribed for a therapeutic use, 221 (20.4%) were targeted therapy.

Conclusion: Our findings underscore the need to update and expand evidence-based guidelines for antimicrobial use, promote the benefits of targeted antimicrobial therapy, and support the implementation of hospital-based antimicrobial stewardship programmes at the hospitals surveyed.
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http://dx.doi.org/10.1016/j.infpip.2021.100197DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8717234PMC
March 2022

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

Am J Trop Med Hyg 2021 Dec 20. Epub 2021 Dec 20.

Division of Infectious Diseases, Department of Medicine, Duke University, Durham, North Carolina.

Q fever and spotted fever group rickettsioses (SFGR) are common causes of severe febrile illness in northern Tanzania. Incidence estimates are needed to characterize the disease burden. Using hybrid surveillance-coupling case-finding at two referral hospitals and healthcare utilization data-we estimated the incidences of acute Q fever and SFGR in Moshi, Kilimanjaro, Tanzania, from 2007 to 2008 and from 2012 to 2014. Cases were defined as fever and a four-fold or greater increase in antibody titers of acute and convalescent paired sera according to the indirect immunofluorescence assay of Coxiella burnetii phase II antigen for acute Q fever and Rickettsia conorii (2007-2008) or Rickettsia africae (2012-2014) antigens for SFGR. Healthcare utilization data were used to adjust for underascertainment of cases by sentinel surveillance. For 2007 to 2008, among 589 febrile participants, 16 (4.7%) of 344 and 27 (8.8%) of 307 participants with paired serology had Q fever and SFGR, respectively. Adjusted annual incidence estimates of Q fever and SFGR were 80 (uncertainty range, 20-454) and 147 (uncertainty range, 52-645) per 100,000 persons, respectively. For 2012 to 2014, among 1,114 febrile participants, 52 (8.1%) and 57 (8.9%) of 641 participants with paired serology had Q fever and SFGR, respectively. Adjusted annual incidence estimates of Q fever and SFGR were 56 (uncertainty range, 24-163) and 75 (uncertainty range, 34-176) per 100,000 persons, respectively. We found substantial incidences of acute Q fever and SFGR in northern Tanzania during both study periods. To our knowledge, these are the first incidence estimates of either disease in sub-Saharan Africa. Our findings suggest that control measures for these infections warrant consideration.
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http://dx.doi.org/10.4269/ajtmh.20-1036DOI Listing
December 2021

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 Netw Open 2021 12 1;4(12):e2136398. Epub 2021 Dec 1.

Division of Infectious Diseases and International Health, Department of Medicine, Duke University Medical Center, Durham, North Carolina.

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.
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http://dx.doi.org/10.1001/jamanetworkopen.2021.36398DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8678687PMC
December 2021

Assessment of Rapid Diagnostic Tests for Typhoid Diagnosis and Assessment of Febrile Illness Outbreaks in Fiji.

Am J Trop Med Hyg 2021 Nov 29. Epub 2021 Nov 29.

School of Tropical Medicine and Global Health, University of Nagasaki, Nagasaki, Japan.

Typhoid is an endemic in Fiji with increases observed since the early 2000s and frequent outbreaks reported. We assessed the diagnostic accuracy of currently available typhoid rapid diagnostic tests (RDTs) (TUBEX, Typhidot Rapid, and Test-It assay) to establish their performance against blood culture in Fiji and to examine their suitability for rapid typhoid outbreak identification. The performance of RDTs was assessed in the public health reference laboratory in Suva, Fiji, according to the manufacturers' instructions. A simulation was used to examine the potential use of RDTs for attribution of a febrile illness outbreak to typhoid. For the diagnostic evaluation, 179 patients were included; 49 had blood culture-confirmed typhoid, 76 had fever as a result of non-typhoid etiologies, and 54 were age-matched community controls. The median (interquartile range) age was 29 (20-46) years. Of the participants, 92 (51.4%) were male and 131 (73.2%) were indigenous Fijians. The sensitivities of the tests were 77.6% for TUBEX, 75.5% for Typhidot Rapid, and 57.1% for Test-It assay. The Test-It assay had the highest specificity of 93.4%, followed by Typhidot Rapid 85.5% and TUBEX 60.5%. Typhidot Rapid had the best performance in the simulation for attribution of a febrile illness outbreak to typhoid. Typhoid RDTs performed suboptimally for individual patient diagnosis due to low sensitivity and variable specificity. We demonstrate that RDTs could be useful in the field for rapid attribution of febrile illness outbreaks to typhoid. Typhidot Rapid had the best combination of sensitivity, specificity, positive and negative predictive values, cost, and ease of use for this purpose.
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http://dx.doi.org/10.4269/ajtmh.21-0771DOI Listing
November 2021

": The Complex Narratives of Livestock Care in Northern Tanzania.

Front Vet Sci 2021 3;8:749561. Epub 2021 Nov 3.

School of Geography and Sustainable Development, University of St. Andrews, St. Andrews, United Kingdom.

Endemic zoonoses have important impacts for livestock-dependent households in East Africa. In these communities, people's health and livelihoods are severely affected by livestock disease losses. Understanding how livestock keepers undertake remedial actions for livestock illness has the potential for widespread benefits such as improving health interventions. Yet, studies about livestock and human health behaviours in the global south tend to focus on individual health choices. In reality, health behaviours are complex, and not solely about individualised health experiences. Rather, they are mediated by a range of "upstream" factors (such as unequal provision of services), which are beyond the control of the individual. This paper presents qualitative research conducted from 2014 to 2019 for a study focused on the Social, Economic, and Environmental Drivers of Zoonoses in Tanzania (SEEDZ). Qualitative data were collected via focus group discussions, community meetings, informal interviews, formal in-depth interviews, observations and surveys that addressed issues of health, disease, zoonotic disease risks, and routes for treatment across 21 villages. Thematic analysis was carried out on in-depth interviews and focus group discussions. Conceptual analyses and observations were made through application of social science theories of health. Livestock keepers undertake a range of health seeking strategies loosely categorised around self and formal treatment. Two key themes emerged that are central to why people make the decisions they do: access to resources and trust in health care providers. These two issues affect individual sense of agency which impacts their ability to act to improve livestock health outcomes. We suggest that individual choice and agency in veterinary health seeking decisions are only beneficial if health systems can offer adequate care and health equity is addressed. This study demonstrates the value of in-depth qualitative research which reveals the nuance and complexity of people's decisions around livestock health. Most importantly, it explains why "better" knowledge does not always translate into "better" practise. The paper suggests that acknowledging and addressing these aspects of veterinary health seeking will lead to more effective provision.
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http://dx.doi.org/10.3389/fvets.2021.749561DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8595325PMC
November 2021

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

Trop Med Int Health 2021 12 10;26(12):1668-1676. Epub 2021 Oct 10.

Division of Infectious Diseases and International Health, Duke University Medical Center, Durham, North Carolina, USA.

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.
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http://dx.doi.org/10.1111/tmi.13683DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8639662PMC
December 2021

Spread of Nontyphoidal Salmonella in the Beef Supply Chain in Northern Tanzania: Sensitivity in a Probabilistic Model Integrating Microbiological Data and Data from Stakeholder Interviews.

Risk Anal 2021 Sep 29. Epub 2021 Sep 29.

The New Zealand Food Safety Science and Research Centre, Massey University, Palmerston North, New Zealand.

East Africa is a hotspot for foodborne diseases, including infection by nontyphoidal Salmonella (NTS), a zoonotic pathogen that may originate from livestock. Urbanization and increased demand for animal protein drive intensification of livestock production and food processing, creating risks and opportunities for food safety. We built a probabilistic mathematical model, informed by prior beliefs and dedicated stakeholder interviews and microbiological research, to describe sources and prevalence of NTS along the beef supply chain in Moshi, Tanzania. The supply chain was conceptualized using a bow tie model, with terminal livestock markets as pinch point, and a forked pathway postmarket to compare traditional and emerging supply chains. NTS was detected in 36 (7.7%) of 467 samples throughout the supply chain. After combining prior belief and observational data, marginal estimates of true NTS prevalence were 4% in feces of cattle entering the beef supply and 20% in raw meat at butcheries. Based on our model and sensitivity analyses, true NTS prevalence was not significantly different between supply chains. Environmental contamination, associated with butchers and vendors, was estimated to be the most likely source of NTS in meat for human consumption. The model provides a framework for assessing the origin and propagation of NTS along meat supply chains. It can be used to inform decision making when economic factors cause changes in beef production and consumption, such as where to target interventions to reduce risks to consumers. Through sensitivity and value of information analyses, the model also helps to prioritize investment in additional research.
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http://dx.doi.org/10.1111/risa.13826DOI Listing
September 2021

Latent class evaluation of the performance of serological tests for exposure to Brucella spp. in cattle, sheep, and goats in Tanzania.

PLoS Negl Trop Dis 2021 08 24;15(8):e0009630. Epub 2021 Aug 24.

Institute of Biodiversity, Animal Health and Comparative Medicine, College of Medical Veterinary and Life Sciences, University of Glasgow, Glasgow, United Kingdom.

Background: Brucellosis is a neglected zoonosis endemic in many countries, including regions of sub-Saharan Africa. Evaluated diagnostic tools for the detection of exposure to Brucella spp. are important for disease surveillance and guiding prevention and control activities.

Methods And Findings: Bayesian latent class analysis was used to evaluate performance of the Rose Bengal plate test (RBT) and a competitive ELISA (cELISA) in detecting Brucella spp. exposure at the individual animal-level for cattle, sheep, and goats in Tanzania. Median posterior estimates of RBT sensitivity were: 0.779 (95% Bayesian credibility interval (BCI): 0.570-0.894), 0.893 (0.636-0.989), and 0.807 (0.575-0.966), and for cELISA were: 0.623 (0.443-0.790), 0.409 (0.241-0.644), and 0.561 (0.376-0.713), for cattle, sheep, and goats, respectively. Sensitivity BCIs were wide, with the widest for cELISA in sheep. RBT and cELISA median posterior estimates of specificity were high across species models: RBT ranged between 0.989 (0.980-0.998) and 0.995 (0.985-0.999), and cELISA between 0.984 (0.974-0.995) and 0.996 (0.988-1). Each species model generated seroprevalence estimates for two livestock subpopulations, pastoralist and non-pastoralist. Pastoralist seroprevalence estimates were: 0.063 (0.045-0.090), 0.033 (0.018-0.049), and 0.051 (0.034-0.076), for cattle, sheep, and goats, respectively. Non-pastoralist seroprevalence estimates were below 0.01 for all species models. Series and parallel diagnostic approaches were evaluated. Parallel outperformed a series approach. Median posterior estimates for parallel testing were ≥0.920 (0.760-0.986) for sensitivity and ≥0.973 (0.955-0.992) for specificity, for all species models.

Conclusions: Our findings indicate that Brucella spp. surveillance in Tanzania using RBT and cELISA in parallel at the animal-level would give high test performance. There is a need to evaluate strategies for implementing parallel testing at the herd- and flock-level. Our findings can assist in generating robust Brucella spp. exposure estimates for livestock in Tanzania and wider sub-Saharan Africa. The adoption of locally evaluated robust diagnostic tests in setting-specific surveillance is an important step towards brucellosis prevention and control.
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http://dx.doi.org/10.1371/journal.pntd.0009630DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8384210PMC
August 2021

Salmonella Typhi Vi polysaccharide conjugate vaccine protects infants and children against typhoid fever.

Lancet 2021 08 9;398(10301):643-644. Epub 2021 Aug 9.

Department of Microbiology, University of Medicine 1, Yangon, Myanmar.

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http://dx.doi.org/10.1016/S0140-6736(21)01340-4DOI Listing
August 2021

The genomic epidemiology of multi-drug resistant invasive non-typhoidal in selected sub-Saharan African countries.

BMJ Glob Health 2021 08;6(8)

University of Antananarivo, Antananarivo, Madagascar.

Background: Invasive non-typhoidal (iNTS) is one of the leading causes of bacteraemia in sub-Saharan Africa. We aimed to provide a better understanding of the genetic characteristics and transmission patterns associated with multi-drug resistant (MDR) iNTS serovars across the continent.

Methods: A total of 166 iNTS isolates collected from a multi-centre surveillance in 10 African countries (2010-2014) and a fever study in Ghana (2007-2009) were genome sequenced to investigate the geographical distribution, antimicrobial genetic determinants and population structure of iNTS serotypes-genotypes. Phylogenetic analyses were conducted in the context of the existing genomic frameworks for various iNTS serovars. Population-based incidence of MDR-iNTS disease was estimated in each study site.

Results: Typhimurium sequence-type (ST) 313 and Enteritidis ST11 were predominant, and both exhibited high frequencies of MDR; Dublin ST10 was identified in West Africa only. Mutations in the gene (fluoroquinolone resistance) were identified in . Enteritidis and . Typhimurium in Ghana; an ST313 isolate carrying was found in Kenya. International transmission of MDR ST313 (lineage II) and MDR ST11 (West African clade) was observed between Ghana and neighbouring West African countries. The incidence of MDR-iNTS disease exceeded 100/100 000 person-years-of-observation in children aged <5 years in several West African countries.

Conclusions: We identified the circulation of multiple MDR iNTS serovar STs in the sampled sub-Saharan African countries. Investment in the development and deployment of iNTS vaccines coupled with intensified antimicrobial resistance surveillance are essential to limit the impact of these pathogens in Africa.
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http://dx.doi.org/10.1136/bmjgh-2021-005659DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8330565PMC
August 2021

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

J Am Heart Assoc 2021 08 29;10(15):e021004. Epub 2021 Jul 29.

Kilimanjaro Christian Medical Centre Moshi Tanzania.

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.
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http://dx.doi.org/10.1161/JAHA.121.021004DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8475708PMC
August 2021

Incidence of non-typhoidal Salmonella invasive disease: A systematic review and meta-analysis.

J Infect 2021 11 11;83(5):523-532. Epub 2021 Jul 11.

Centre for International Health, University of Otago, PO Box 56, Dunedin 9054, New Zealand. Electronic address:

Objectives: We sought to collate and summarize high-quality data on non-typhoidal Salmonella invasive disease (iNTS) incidence to provide contemporary incidence estimates by location and year.

Methods: We systematically searched the databases Embase + MEDLINE, Web of Science, and PubMed for articles published on the incidence of iNTS from inception of the database through 8 May 2020 with no language, country, date, or demographic restrictions applied. A meta-analysis was performed to report pooled iNTS incidence as a rate of cases per 100,000 per year.

Results: Among 13 studies eligible for analysis, there were 68 estimates of incidence. Overall pooled incidence (95% CI) was 44.8 (31.5-60.5) per 100,000 persons per year. When stratified by region, pooled incidence was significantly higher in Africa than Asia, 51.0 (36.3-68.0) compared to 1.0 (0.2-2.5), respectively. Incidence was consistently higher in children aged <5 years compared with older age groups. Incidence displayed considerable heterogeneity in both place and time, varying substantially between locations and over consecutive years in the same location.

Conclusions: iNTS incidence varies by region, location, age group, and over time. Concerted efforts are needed to address the limited high-quality data available on iNTS disease incidence.
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http://dx.doi.org/10.1016/j.jinf.2021.06.029DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8627500PMC
November 2021

On the robustness of latent class models for diagnostic testing with no gold standard.

Stat Med 2021 09 14;40(22):4751-4763. Epub 2021 May 14.

Department of Mathematics and Statistics, University of Otago, Dunedin, New Zealand.

It is difficult to estimate sensitivity and specificity of diagnostic tests when there is no gold standard. Latent class models have been proposed as a potential solution as they provide estimates without the need for a gold standard. Using a motivating example of the evaluation of point of care tests for leptospirosis in Tanzania, we show how a realistic violation of assumptions underpinning the latent class model can lead directly to substantial bias in the estimates of the parameters of interest. In particular, we consider the robustness of estimates of sensitivity, specificity, and prevalence, to the presence of additional latent states when fitting a two-state latent class model. The violation is minor in the sense that it cannot be routinely detected with goodness-of-fit procedures, but is major with regard to the resulting bias.
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http://dx.doi.org/10.1002/sim.8999DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8440412PMC
September 2021

Classification and characterisation of livestock production systems in northern Tanzania.

PLoS One 2020 30;15(12):e0229478. Epub 2020 Dec 30.

Institute of Biodiversity, Animal Health and Comparative Medicine, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, United Kingdom.

Livestock keepers in sub-Saharan Africa face a range of pressures, including climate change, land loss, restrictive policies, and population increase. Widespread adaptation in response can lead to the emergence of new, non-traditional typologies of livestock production. We sought to characterise livestock production systems in two administrative regions in northern Tanzania, an area undergoing rapid social, economic, and environmental change. Questionnaire and spatial data were collected from 404 livestock-keeping households in 21 villages in Arusha and Manyara Regions in 2016. Multiple factor analysis and hierarchical cluster analysis were used to classify households into livestock production systems based on household-level characteristics. Adversity-based indicators of vulnerability, including reports of hunger, illness, and livestock, land and crop losses were compared between production systems. Three distinct clusters emerged through this process. The ethnic, environmental and livestock management characteristics of households in each cluster broadly mapped onto traditional definitions of 'pastoral', 'agro-pastoral' and 'smallholder' livestock production in the study area, suggesting that this quantitative classification system is complementary to more qualitative classification methods. Our approach allowed us to demonstrate a diversity in typologies of livestock production at small spatial scales, with almost half of study villages comprising more than one production system. We also found indicators of change within livestock production systems, most notably the adoption of crop agriculture in the majority of pastoral households. System-level heterogeneities in vulnerability were evident, with agro-pastoral households most likely to report hunger and pastoral households most likely to report illness in people and livestock, and livestock losses. We demonstrate that livestock production systems can provide context for assessing household vulnerability in northern Tanzania. Policy initiatives to improve household and community well-being should recognise the continuing diversity of traditional livestock production systems in northern Tanzania, including the diversity that can exist at small spatial scales.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0229478PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7773236PMC
January 2021

Aetiology of acute febrile illness among children attending a tertiary hospital in southern Ethiopia.

BMC Infect Dis 2020 Nov 30;20(1):903. Epub 2020 Nov 30.

Kirby Institute, University of New South Wales, Sydney, Australia.

Background: The diagnosis of non-malarial aetiologies, which now represent the majority of febrile illnesses, has remained problematic in settings with limited laboratory capacity. We aimed to describe common aetiologies of acute febrile illness among children in a setting where malaria transmission has declined.

Methods: A prospective cross-sectional study was conducted among children aged at least 2 months and under 13 years presenting with fever (temperature of ≥37.5 °C or a history of fever in the past 48 h) to Hawassa Comprehensive Specialized Hospital, southern Ethiopia, from May 2018 through February 2019. Clinical and demographic data were gathered for consecutive participants, and malaria microscopy, HIV testing, and blood and urine cultures were performed regardless of clinical presentation. Additionally, stool analyses (culture and rotavirus/adenovirus RDT) and throat swab for group A Streptococcus (GAS) and urine Streptococcus pneumoniae were performed by RDTs for children with specific conditions. The antimicrobial susceptibility of bacterial isolates was determined using disc diffusion method.

Results: During the study period 433 children were recruited, median age 20 months (range, 2 months - 12 years) and 178 (41.1%) female. Malaria was diagnosed in 14 (3.2%) of 431 children, and 3 (0.7%) had HIV infection. Bacteraemia or fungaemia was detected in 27 (6.4%) of 421 blood cultures, with Staphylococcus aureus isolated in 16 (3.8%). Urinary tract infections (UTIs) were detected in 74 (18.4%) of 402, with Escherichia coli isolated in 37 (9.2%). Among 56 children whose stool specimens were tested, 14 (25%) were positive for rotavirus, 1 (1.8%) for Salmonella Paratyphi A, and 1 (1.8%) for Shigella dysenteriae. Among those with respiratory symptoms, a throat swab test for GAS and urine test for S. pneumoniae were positive in 28 (15.8%) of 177 and 31 (17.0%) of 182, respectively. No test was positive for a pathogen in 266 (61.4%) of 433 participants. Bacterial isolates were frequently resistant to ampicillin, trimethoprim-sulfamethoxazole, tetracycline, and amoxicillin and clavulanic acid.

Conclusion: Our results showed low proportions of malaria and bacteraemia among febrile children. In contrast, the frequent detection of UTI emphasize the need to support enhanced diagnostic capacity to ensure appropriate antimicrobial intervention.
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http://dx.doi.org/10.1186/s12879-020-05635-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7706267PMC
November 2020

Complications and mortality of typhoid fever: A global systematic review and meta-analysis.

J Infect 2020 12 2;81(6):902-910. Epub 2020 Nov 2.

Centre for International Health, University of Otago, PO Box 56, Dunedin 9016, New Zealand. Electronic address:

Objectives: Updated estimates of the prevalence of complications and case fatality ratio (CFR) among typhoid fever patients are needed to understand disease burden.

Methods: Articles published in PubMed and Web of Science from 1 January 1980 through 29 January 2020 were systematically reviewed for hospital or community-based non-surgical studies that used cultures of normally sterile sites, and hospital surgical studies of typhoid intestinal perforation (TIP) with intra- or post-operative findings suggestive of typhoid. Prevalence of 21 pre-selected recognized complications of typhoid fever, crude and median (interquartile range) CFR, and pooled CFR estimates using a random effects meta-analysis were calculated.

Results: Of 113 study sites, 106 (93.8%) were located in Asia and Africa, and 84 (74.3%) were non-surgical. Among non-surgical studies, 70 (83.3%) were hospital-based. Of 10,355 confirmed typhoid patients, 2,719 (26.3%) had complications. The pooled CFR estimate among non-surgical patients was 0.9% for the Asia region and 5.4% for the Africa region. Delay in care was significantly correlated with increased CFR in Asia (r = 0.84; p<0.01). Among surgical studies, the median CFR of TIP was 15.5% (6.7-24.1%) per study.

Conclusions: Our findings identify considerable typhoid-associated illness and death that could be averted with prevention measures, including typhoid conjugate vaccine introduction.
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http://dx.doi.org/10.1016/j.jinf.2020.10.030DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7754788PMC
December 2020

Investigation of Melioidosis Using Blood Culture and Indirect Hemagglutination Assay Serology among Patients with Fever, Northern Tanzania.

Am J Trop Med Hyg 2020 12 24;103(6):2510-2514. Epub 2020 Sep 24.

Division of Infectious Diseases and International Health, Department of Medicine, Duke University Health System, Durham, North Carolina.

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 latex agglutination assay. Also, we performed 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 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 , 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.
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http://dx.doi.org/10.4269/ajtmh.20-0160DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7695086PMC
December 2020

A Systematic Review on Antimicrobial Resistance among Typhi Worldwide.

Am J Trop Med Hyg 2020 12 24;103(6):2518-2527. Epub 2020 Sep 24.

Centre for International Health, University of Otago, Dunedin, New Zealand.

Understanding patterns and trends of antimicrobial resistance (AMR) in Typhi can guide empiric treatment recommendations and contribute to country decisions about typhoid conjugate vaccine (TCV) introduction. We systematically reviewed PubMed and Web of Science for articles reporting the proportion of Typhi isolates resistant to individual antimicrobials worldwide from any time period. Isolates resistant to chloramphenicol, ampicillin, and trimethoprim-sulfamethoxazole were classified as multidrug resistant (MDR), and isolates that were MDR plus resistant to a fluoroquinolone and a third-generation cephalosporin were extensively drug resistant (XDR). Among the 198 articles eligible for analysis, a total of 55,459 Typhi isolates were tested for AMR (median 80; range 2-5,191 per study). Of isolates from 2015 through 2018 in Asia, 1,638 (32.6%) of 5,032 were MDR, 167 (5.7%) of 2,914 were resistant to third-generation cephalosporins, and 148 (8.3%) of 1,777 were resistant to azithromycin. Two studies from Pakistan reported 14 (2.6%) of 546 isolates were XDR. In Africa, the median proportion of Typhi isolates that were MDR increased each consecutive decade from 1990 to 1999 through 2010 to 2018. Typhi has developed resistance to an increasing number of antimicrobial classes in Asia, where XDR Typhi is now a major threat, whereas MDR has expanded in Africa. We suggest continued and increased surveillance is warranted to inform empiric treatment decisions and that AMR data be incorporated into country decisions on TCV introduction.
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http://dx.doi.org/10.4269/ajtmh.20-0258DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7695120PMC
December 2020

Non-malarial febrile illness: a systematic review of published aetiological studies and case reports from Africa, 1980-2015.

BMC Med 2020 09 21;18(1):279. Epub 2020 Sep 21.

Infectious Diseases Data Observatory, University of Oxford, New Richards Building,Old Road Campus,Headington, Oxford, OX3 7LG, UK.

Background: The availability of reliable point-of-care tests for malaria has heralded a paradigm shift in the management of febrile illnesses away from presumptive antimalarial therapy. In the absence of a definitive diagnosis, health care providers are more likely to prescribe empirical antimicrobials to those who test negative for malaria. To improve management and guide further test development, better understanding is needed of the true causative agents and their geographic variability.

Methods: A systematic review of published literature was undertaken to characterise the spectrum of pathogens causing non-malaria febrile illness in Africa (1980-2015). Literature searches were conducted in English and French languages in six databases: MEDLINE, EMBASE, Global Health (CABI), WHO Global Health Library, PASCAL, and Bulletin de la Société Française de Parasitologie (BDSP). Selection criteria included reporting on an infection or infections with a confirmed diagnosis, defined as pathogens detected in or cultured from samples from normally sterile sites, or serological evidence of current or past infection. A number of published articles (rather than incidence or prevalence) reporting a given pathogen were presented.

Results: A total of 16,523 records from 48 African countries were screened, of which 1065 (6.4%) met selection criteria. Bacterial infections were reported in 564 (53.0%) records, viral infections in 374 (35.1%), parasitic infections in 47 (4.4%), fungal infections in nine (0.8%), and 71 (6.7%) publications reported more than one pathogen group. Age range of the study population was not specified in 233 (21.9%) publications. Staphylococcus aureus (18.2%), non-typhoidal Salmonella (17.3%), and Escherichia coli (15.4%) were the commonly reported bacterial infections whereas Rift Valley fever virus (7.4%), yellow fever virus (7.0%), and Ebola virus (6.7%) were the most commonly reported viral infections. Dengue virus infection, previously not thought to be widespread in Africa, was reported in 54 (5.1%) of articles.

Conclusions: This review summarises the published reports of non-malaria pathogens that may cause febrile illness in Africa. As the threat of antimicrobial resistance looms, knowledge of the distribution of infectious agents causing fever should facilitate priority setting in the development of new diagnostic tools and improved antimicrobial stewardship.

Trial Registration: PROSPERO, CRD42016049281.
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http://dx.doi.org/10.1186/s12916-020-01744-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7504660PMC
September 2020

Non-malarial febrile illness: a systematic review of published aetiological studies and case reports from Southern Asia and South-eastern Asia, 1980-2015.

BMC Med 2020 09 21;18(1):299. Epub 2020 Sep 21.

Infectious Diseases Data Observatory (IDDO), University of Oxford, NDMRB, Old Road Campus, Oxford, OX3 7FZ, UK.

Background: In the absence of definitive diagnosis, healthcare providers are likely to prescribe empirical antibacterials to those who test negative for malaria. This problem is of critical importance in Southern Asia (SA) and South-eastern Asia (SEA) where high levels of antimicrobial consumption and high prevalence of antimicrobial resistance have been reported. To improve management and guide further diagnostic test development, better understanding is needed of the true causative agents of fever and their geographical variability.

Methods: We conducted a systematic review of published literature (1980-2015) to characterise the spectrum of pathogens causing non-malarial febrile illness in SA and SEA. We searched six databases in English and French languages: MEDLINE, EMBASE, Global Health (CABI) database, WHO Global Health Library, PASCAL, and Bulletin de la Société Française de Parasitologie (BDSP). Selection criteria included reporting on an infection or infections with a confirmed diagnosis, defined as pathogens detected in or cultured from samples from normally sterile sites, or serological evidence of current or past infection.

Results: A total of 29,558 records from 19 countries in SA and SEA were screened, of which 2410 (8.1%) met the selection criteria. Bacterial aetiologies were reported in 1235 (51.2%) articles, viral in 846 (35.1%), parasitic in 132 (5.5%), and fungal in 54 (2.2%), and 143 (6.0%) articles reported more than one pathogen group. In descending order of frequency, Salmonella Typhi, Escherichia coli, Staphylococcus aureus, Klebsiella pneumoniae, and coagulase negative Staphylococcus were the commonly reported bacteria, while dengue virus, chikungunya virus, Japanese encephalitis virus, hepatitis B virus, and hepatitis C virus were common viral pathogens reported. Reports of rarely reported or emerging pathogens included a case report of Borrelia burgdorferi (Lyme disease) in India in 2010 and reports of Nipah virus in Singapore and India.

Conclusions: This review summarises the reported non-malaria pathogens that may cause febrile illness in SA and SEA. The findings emphasise the need of standardising the reporting of aetiological studies to develop effective, evidence-based fever management and improved surveillance. Research and development of diagnostic tools would benefit from up-to-date epidemiological reporting of the regional diversities of non-malaria fever aetiologies.

Trial Registration: PROSPERO registration, CRD42016049281.
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http://dx.doi.org/10.1186/s12916-020-01745-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7504862PMC
September 2020

Investigating the Meat Pathway as a Source of Human Nontyphoidal Salmonella Bloodstream Infections and Diarrhea in East Africa.

Clin Infect Dis 2021 10;73(7):e1570-e1578

Institute of Biodiversity, Animal Health, and Comparative Medicine, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, Scotland, United Kingdom.

Background: Salmonella Enteritidis and Salmonella Typhimurium are major causes of bloodstream infection and diarrheal disease in East Africa. Sources of human infection, including the role of the meat pathway, are poorly understood.

Methods: We collected cattle, goat, and poultry meat pathway samples from December 2015 through August 2017 in Tanzania and isolated Salmonella using standard methods. Meat pathway isolates were compared with nontyphoidal serovars of Salmonella enterica (NTS) isolated from persons with bloodstream infections and diarrheal disease from 2007 through 2017 from Kenya by core genome multi-locus sequence typing (cgMLST). Isolates were characterized for antimicrobial resistance, virulence genes, and diversity.

Results: We isolated NTS from 164 meat pathway samples. Of 172 human NTS isolates, 90 (52.3%) from stool and 82 (47.7%) from blood, 53 (30.8%) were Salmonella Enteritidis sequence type (ST) 11 and 62 (36.0%) were Salmonella Typhimurium ST313. We identified cgMLST clusters within Salmonella Enteritidis ST11, Salmonella Heidelberg ST15, Salmonella Typhimurium ST19, and Salmonella II 42:r:- ST1208 that included both human and meat pathway isolates. Salmonella Typhimurium ST313 was isolated exclusively from human samples. Human and poultry isolates bore more antimicrobial resistance and virulence genes and were less diverse than isolates from other sources.

Conclusions: Our findings suggest that the meat pathway may be an important source of human infection with some clades of Salmonella Enteritidis ST11 in East Africa, but not of human infection by Salmonella Typhimurium ST313. Research is needed to systematically examine the contributions of other types of meat, animal products, produce, water, and the environment to nontyphoidal Salmonella disease in East Africa.
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http://dx.doi.org/10.1093/cid/ciaa1153DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8492120PMC
October 2021

An In-Depth Examination of Reasons for Autopsy Acceptance and Refusal in Northern Tanzania.

Am J Trop Med Hyg 2020 10;103(4):1670-1680

Duke Global Health Institute, Duke University, Durham, North Carolina.

Uncertainty about the causes of death (COD) in low- and middle-income countries (LMICs) has been recognized as a constraint to global health and development. Although complete diagnostic autopsy (CDA) is the best way to assess COD, it is uncommon in LMICs because of low investment priority and assumptions about poor acceptability. Social science research was conducted from May 2016 through July 2017 to examine issues related to acceptability of CDAs in northern Tanzania where autopsy was being offered in two referral hospitals to assess COD associated with febrile illness. Initial formative research entailed 29 key informant interviews, seven observations of burial practices, and four group discussions. In-depth interviews were conducted with families of deceased, including nine families that accepted and 11 families that refused CDA. The formative research identified concepts related to death, understandings of CDA, and cultural practices and psychosocial considerations associated with death that informed the authorization process. Most families who accepted CDA cited the desire to get clarity regarding the COD as a primary reason for acceptance. An unexpected finding was that CDA is perceived as a means to determine witchcraft involvement, a common explanation for COD and a common reason for postmortem acceptance. Death resulting from chronic illness or conditions presumed to have a clinical diagnosis were reasons for CDA to be viewed as unnecessary. The timing, way families were approached, and content of information shared during authorization influenced acceptance and refusal of CDA. Findings show that CDAs can be acceptable in settings where traditional disease models prevail.
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http://dx.doi.org/10.4269/ajtmh.20-0029DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7543794PMC
October 2020

Molecular Detection and Typing of Pathogenic in Febrile Patients and Phylogenetic Comparison with Detected among Animals in Tanzania.

Am J Trop Med Hyg 2020 10;103(4):1427-1434

Duke Global Health Institute, Duke University, Durham, North Carolina.

Molecular data are required to improve our understanding of the epidemiology of leptospirosis in Africa and to identify sources of human infection. We applied molecular methods to identify the infecting species and genotypes among patients hospitalized with fever in Tanzania and compared these with genotypes detected among animals in Tanzania to infer potential sources of human infection. We performed real-time PCR to detect the presence of pathogenic in acute-phase plasma, serum, and urine samples obtained from study participants with serologically confirmed leptospirosis and participants who had died with febrile illness. blood culture was also performed. In positive specimens, we performed species-specific PCR and compared participant sequences with reference sequences and sequences previously obtained from animals in Tanzania. We detected DNA in four (3.6%) of 111 participant blood samples. We detected (one participant, 25.0%), (one participant, 25.0%), and (one participant, 25.0%) (one [25%] undetermined). Phylogenetic comparison of sequence from the and genotypes detected from participants was closely related to but distinct from genotypes detected among local livestock species. Our results indicate that a diverse range of species is causing human infection. Although our analysis suggests a close relationship between genotypes found in people and livestock, continued efforts are needed to obtain more genetic material from human leptospirosis cases to help prioritize species and genotypes for control.
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http://dx.doi.org/10.4269/ajtmh.19-0703DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7543812PMC
October 2020

Tenacious Endemic Typhoid Fever in Samoa.

Clin Infect Dis 2020 07;71(Suppl 2):S120-S126

Center for Vaccine Development and Global Health, University of Maryland School of Medicine, Baltimore, Maryland, USA.

Background: Typhoid fever has been endemic on the island nation of Samoa (2016 population, 195 979) since the 1960s and has persisted through 2019, despite economic development and improvements in water supply and sanitation.

Methods: Salmonella enterica serovar Typhi isolates from the 2 hospitals with blood culture capability and matched patient demographic and clinical data from January 2008 through December 2019 were analyzed. Denominators to calculate incidence by island, region, and district came from 2011 and 2016 censuses and from 2017-2019 projections from Samoa's Bureau of Statistics. Data were analyzed to describe typhoid case burden and incidence from 2008 to 2019 by time, place, and person.

Results: In sum, 53-193 blood culture-confirmed typhoid cases occurred annually from 2008 to 2019, without apparent seasonality. Typhoid incidence was low among children age < 48 months (17.6-27.8/105), rose progressively in ages 5-9 years (54.0/105), 10-19 years (60.7-63.4/105), and 20-34 years (61.0-79.3/105), and then tapered off; 93.6% of cases occurred among Samoans < 50 years of age. Most typhoid cases and the highest incidence occurred in Northwest Upolu, but Apia Urban Area (served by treated water supplies) also exhibited moderate incidence. The proportion of cases from short-cycle versus long-cycle transmission is unknown. Samoan S. Typhi are pansusceptible to traditional first-line antibiotics. Nevertheless, enhanced surveillance in 2019 detected 4 (2.9%) deaths among 140 cases.

Conclusions: Typhoid has been endemic in Samoa in the period 2008-2019. Interventions, including mass vaccination with a Vi-conjugate vaccine coadministered with measles vaccine are planned.
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http://dx.doi.org/10.1093/cid/ciaa314DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7388710PMC
July 2020

Assessing the Feasibility of Typhoid Elimination.

Clin Infect Dis 2020 07;71(Suppl 2):S179-S184

Centre for International Health, University of Otago, Dunedin, New Zealand.

In 1993, the International Task Force on Disease Eradication classified the political will for typhoid eradication as "none." Here we revisit the Task Force's assessment in light of developments in typhoid vaccines and increasing antimicrobial resistance in Salmonella Typhi that have served to increase interest in typhoid elimination. Considering the requisite biological and technical factors for elimination, effective interventions exist for typhoid, and humans are the organism's only known reservoir. Improvements in water supply, sanitation, hygiene, and food safety are critical for robust long-term typhoid control, and the recent Strategic Advisory Group of Experts on Immunization recommendation and World Health Organization prequalification should make typhoid conjugate vaccine more accessible and affordable in low-income countries, which will allow the vaccine to offer a critical bridge to quickly reduce burden. While these developments are encouraging, all current typhoid diagnostics are inadequate, having either poor performance characteristics, limited scalability, or both. No clear solution exists, and this should be viewed as a critical challenge to any elimination effort. Moreover, asymptomatic carriers and limited data and surveillance remain major challenges, and countries considering elimination campaigns will need to develop strategies to identify high-risk populations and to monitor progress over time. Finally, policymakers must be realistic in planning, learn from the planning failures of previous elimination and eradication efforts, and expect unforeseeable shocks and setbacks. In the end, if we assume neither unanticipated breakthroughs in typhoid control nor any chaotic shocks, history suggests that we should expect typhoid elimination to take decades.
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http://dx.doi.org/10.1093/cid/ciaa585DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7388713PMC
July 2020

Febrile Illness Evaluation in a Broad Range of Endemicities (FIEBRE): protocol for a multisite prospective observational study of the causes of fever in Africa and Asia.

BMJ Open 2020 07 21;10(7):e035632. Epub 2020 Jul 21.

Faculty of Infectious and Tropical Diseases, London School of Hygiene & Tropical Medicine, London, UK.

Introduction: Fever commonly leads to healthcare seeking and hospital admission in sub-Saharan Africa and Asia. There is only limited guidance for clinicians managing non-malarial fevers, which often results in inappropriate treatment for patients. Furthermore, there is little evidence for estimates of disease burden, or to guide empirical therapy, control measures, resource allocation, prioritisation of clinical diagnostics or antimicrobial stewardship. The Febrile Illness Evaluation in a Broad Range of Endemicities (FIEBRE) study seeks to address these information gaps.

Methods And Analysis: FIEBRE investigates febrile illness in paediatric and adult outpatients and inpatients using standardised clinical, laboratory and social science protocols over a minimum 12-month period at five sites in sub-Saharan Africa and Southeastern and Southern Asia. Patients presenting with fever are enrolled and provide clinical data, pharyngeal swabs and a venous blood sample; selected participants also provide a urine sample. Laboratory assessments target infections that are treatable and/or preventable. Selected point-of-care tests, as well as blood and urine cultures and antimicrobial susceptibility testing, are performed on site. On day 28, patients provide a second venous blood sample for serology and information on clinical outcome. Further diagnostic assays are performed at international reference laboratories. Blood and pharyngeal samples from matched community controls enable calculation of AFs, and surveys of treatment seeking allow estimation of the incidence of common infections. Additional assays detect markers that may differentiate bacterial from non-bacterial causes of illness and/or prognosticate illness severity. Social science research on antimicrobial use will inform future recommendations for fever case management. Residual samples from participants are stored for future use.

Ethics And Dissemination: Ethics approval was obtained from all relevant institutional and national committees; written informed consent is obtained from all participants or parents/guardians. Final results will be shared with participating communities, and in open-access journals and other scientific fora. Study documents are available online (https://doi.org/10.17037/PUBS.04652739).
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http://dx.doi.org/10.1136/bmjopen-2019-035632DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7375419PMC
July 2020

Meat Safety in Northern Tanzania: Inspectors' and Slaughter Workers' Risk Perceptions and Management.

Front Vet Sci 2020 18;7:309. Epub 2020 Jun 18.

Institute of Biodiversity, Animal Health and Comparative Medicine, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, United Kingdom.

Through a social scientific lens, this paper considers the risk perceptions and "risk-based decision-making" of two key groups in a northern Tanzanian context: (1) frontline government meat inspectors and health officers charged with ensuring that red meat sold commercially is safe for people to consume, and (2) the workers who slaughter and process cattle and red meat prior to its sale in rural butcheries. In contrast to techno-scientific understandings of disease risk and "rational" approaches to its management, this paper foregrounds the role of social, economic and institutional context in shaping the perceptions and practices around meat safety of these actors whose daily, close proximity to meat means they play a significant role in mitigating potential meat-borne disease. We show how limited resources, and a combination of scientific and local knowledge and norms result in "situated expertise" and particular forms of risk perception and practice which both enhance and compromise meat safety in different ways. Actors' shared concerns with what is visible, ensures that visibly unsafe or abnormal meat is excluded from sale, and that infrastructure and meat is kept "clean" and free of certain visible contaminants such as soil or, on occasion, feces. While such contaminants serve as a good proxy for pathogen presence, meat inspectors and especially slaughter workers were much less aware of or concerned with invisible pathogens that may compromise meat safety. The role of process and meat handling did not figure very strongly in their concerns. Microorganisms such as and , which can easily be transferred onto meat and persist in slaughter and meat sale environments, went unacknowledged. Although health officers expressed more concern with hygiene and meat handling, their influence over slaughter process and butchery operations was unclear. Ultimately, recognizing the perceptions and practices of frontline actors who engage with meat, and the ways in which social, material and institutional realities shape these, is important for understanding how decisions about risk and meat safety are made in the complexity and context of everyday life, and thus for finding effective ways to support them to further enhance their work.
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http://dx.doi.org/10.3389/fvets.2020.00309DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7314929PMC
June 2020

Child undernutrition in households with microbiologically safer drinking water and 'improved water' in Tanna, Vanuatu.

J Water Health 2020 Jun;18(3):416-429

Department of Preventive and Social Medicine, University of Otago, Dunedin, New Zealand E-mail: Public Health Unit, Southern District Health Board, Dunedin, New Zealand.

The Sustainable Development Goal drinking water indicators include microbiological safety measures, whereas the Millennium Development Goal indicator 'improved water' may be microbiologically unsafe. In rural Vanuatu, we undertook household surveys, child anthropometry, and tested stored drinking water, to investigate relationships between water and undernutrition. Using Escherichia coli most probable number, we categorized results according to Compartment Bag Test drinking water cutoffs: <1/100 mL (safe), 1-10/100 mL (intermediate risk), >10-100/100 mL (high risk), and >100/100 mL (very high risk). Of 201 households, 191 (95%) had microbiologically unsafe drinking water, regardless of 'improved' status. We investigated cross-sectional associations between households with microbiologically safer drinking water (≤10 E. coli/100 mL) versus 'improved water' and undernutrition among children. Of children under 5, 145 (48.8%, 95% CI: 42.8, 54.8) were stunted and 59 (19.1%, 95% CI: 14.4, 23.8) were underweight. Among households with 'improved water', the adjusted prevalence ratio (95% CI) of stunting was 0.61 (0.46, 0.80) and underweight was 0.46 (0.29, 0.73) compared with 'unimproved water'. However, we found no association between having drinking water with ≤10 E. coli/100 mL at one point in time and undernutrition. Longer-term variations in water quality and unmeasured conditions beyond water may have contributed to these associations.
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http://dx.doi.org/10.2166/wh.2020.262DOI Listing
June 2020

Estimating acute human leptospirosis incidence in northern Tanzania using sentinel site and community behavioural surveillance.

Zoonoses Public Health 2020 08 6;67(5):496-505. Epub 2020 May 6.

Centre for International Health, University of Otago, Dunedin, New Zealand.

Many infectious diseases lack robust estimates of incidence from endemic areas, and extrapolating incidence when there are few locations with data remains a major challenge in burden of disease estimation. We sought to combine sentinel surveillance with community behavioural surveillance to estimate leptospirosis incidence. We administered a questionnaire gathering responses on established locally relevant leptospirosis risk factors and recent fever to livestock-owning community members across six districts in northern Tanzania and applied a logistic regression model predicting leptospirosis risk on the basis of behavioural factors that had been previously developed among patients with fever in Moshi Municipal and Moshi Rural Districts. We aggregated probability of leptospirosis by district and estimated incidence in each district by standardizing probabilities to those previously estimated for Moshi Districts. We recruited 286 community participants: Hai District (n = 11), Longido District (59), Monduli District (56), Moshi Municipal District (103), Moshi Rural District (44) and Rombo District (13). The mean predicted probability of leptospirosis by district was Hai 0.029 (0.005, 0.095), Longido 0.071 (0.009, 0.235), Monduli 0.055 (0.009, 0.206), Moshi Rural 0.014 (0.002, 0.049), Moshi Municipal 0.015 (0.004, 0.048) and Rombo 0.031 (0.006, 0.121). We estimated the annual incidence (upper and lower bounds of estimate) per 100,000 people of human leptospirosis among livestock owners by district as Hai 35 (6, 114), Longido 85 (11, 282), Monduli 66 (11, 247), Moshi Rural 17 (2, 59), Moshi Municipal 18 (5, 58) and Rombo 47 (7, 145). Use of community behavioural surveillance may be a useful tool for extrapolating disease incidence beyond sentinel surveillance sites.
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http://dx.doi.org/10.1111/zph.12712DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7497209PMC
August 2020
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