Etiology of Severe Non-malaria Febrile Illness in Northern Tanzania: A Prospective Cohort Study.

The syndrome of fever is a commonly presenting complaint among persons seeking healthcare in low-resource areas, yet the public health community has not approached fever in a comprehensive manner. In many areas, malaria is over-diagnosed, and patients without malaria have poor outcomes. We prospectively studied a cohort of 870 pediatric and adult febrile admissions to two hospitals in northern Tanzania over the period of one year using conventional standard diagnostic tests to establish fever etiology. Malaria was the clinical diagnosis for 528 (60.7%), but was the actual cause of fever in only 14 (1.6%). By contrast, bacterial, mycobacterial, and fungal bloodstream infections accounted for 85 (9.8%), 14 (1.6%), and 25 (2.9%) febrile admissions, respectively. Acute bacterial zoonoses were identified among 118 (26.2%) of febrile admissions; 16 (13.6%) had brucellosis, 40 (33.9%) leptospirosis, 24 (20.3%) had Q fever, 36 (30.5%) had spotted fever group rickettsioses, and 2 (1.8%) had typhus group rickettsioses. In addition, 55 (7.9%) participants had a confirmed acute arbovirus infection, all due to chikungunya. No patient had a bacterial zoonosis or an arbovirus infection included in the admission differential diagnosis. Malaria was uncommon and over-diagnosed, whereas invasive infections were underappreciated. Bacterial zoonoses and arbovirus infections were highly prevalent yet overlooked. An integrated approach to the syndrome of fever in resource-limited areas is needed to improve patient outcomes and to rationally target disease control efforts

Invasive Salmonella infections in areas of high and low malaria transmission intensity in Tanzania.

BACKGROUND:  The epidemiology of Salmonella Typhi and invasive nontyphoidal Salmonella (NTS) differs, and prevalence of these pathogens among children in sub-Saharan Africa may vary in relation to malaria transmission intensity. METHODS:  We compared the prevalence of bacteremia among febrile pediatric inpatients aged 2 months to 13 years recruited at sites of high and low malaria endemicity in Tanzania. Enrollment at Teule Hospital, the high malaria transmission site, was from June 2006 through May 2007, and at Kilimanjaro Christian Medical Centre (KCMC), the low malaria transmission site, from September 2007 through August 2008. Automated blood culture, malaria microscopy with Giemsa-stained blood films, and human immunodeficiency virus testing were performed. RESULTS:  At Teule, 3639 children were enrolled compared to 467 at KCMC. Smear-positive malaria was detected in 2195 of 3639 (60.3%) children at Teule and 11 of 460 (2.4%) at KCMC (P < .001). Bacteremia was present in 336 of 3639 (9.2%) children at Teule and 20 of 463 (4.3%) at KCMC (P < .001). NTS was isolated in 162 of 3639 (4.5%) children at Teule and 1 of 463 (0.2%) at KCMC (P < .001). Salmonella Typhi was isolated from 11 (0.3%) children at Teule and 6 (1.3%) at KCMC (P = .008). With NTS excluded, the prevalence of bacteremia at Teule was 5.0% and at KCMC 4.1% (P = .391). CONCLUSIONS:  Where malaria transmission was intense, invasive NTS was common and Salmonella Typhi was uncommon, whereas the inverse was observed at a low malaria transmission site. The relationship between these pathogens, the environment, and the host is a compelling area for further research

Iron Depletion, Iron Deficiency, and Iron Deficiency Anaemia Among Children Under 5 Years Old in Kilimanjaro, Northern Tanzania: A Hospital-Based Cross-Sectional Study

Background:&nbsp;Iron depletion results from reduced iron stores, and it is an early stage of disease progression before iron deficiency, which leads to iron deficiency anaemia (IDA). IDA is associated with delayed infant growth and development, diminished cognitive function, poor academic performance, decreased exercise tolerance, and impaired immune function. &nbsp; This study aimed to determine the prevalence of iron depletion and IDA and factors associated with low ferritin levels among children under 5-years-old receiving care at Kilimanjaro Christian Medical Centre (KCMC) in Moshi, Tanzania. &nbsp; Methods:&nbsp;Under-5 children presenting at KCMC were successively enrolled and screened for iron depletion and IDA using complete blood count and serum ferritin levels. The generally accepted World Health Organization cut‑off levels for normal haemoglobin (Hb) and ferritin level were used. Iron depletion, iron deficiency, and IDA prevalences were estimated in relation to the combination measures of haemoglobin, mean corpuscular volume, and ferritin levels. Dietary and sociodemographic characteristic of the children were recorded after parents or caretakers provided informed consent. Data analysis was conducted using SPSS version 21.0. &nbsp; Results:&nbsp;A total of 303 children aged 2 to 59 months were enrolled in the study. Anaemia was detected in169 (55.8%) children. Children aged 2 to 12 months had a higher prevalence of anaemia (n=101, 60.1%). The overall prevalences of iron depletion, iron deficiency with no anaemia, and IDA were 2.6% (n=8), 9.6% (n=29), and 28.1% (n=84), respectively. Low ferritin levels were detected in 124 (40.9%) children. Drinking more than 500 ml of cow's milk per day was associated with an increased risk of anaemia (adjusted odds ratio [AOR] 5.6; 95% confidence interval [CI], 2.6 to 12.1) relative to those not drinking cow's milk. Children whose families had meals that included beef more than 3 times per week were less likely to have low ferritin (AOR 0.6; 95% CI, 0.3 to 1.3), though the difference was not significant. &nbsp; Conclusion:&nbsp;The IDA prevalence among children in the Kilimanjaro area was high, with more than 50% of infants being anaemic. Drinking cow's milk was associated with an increased risk of IDA. Future community-based research is recommended to elucidate more details about iron deficiency in the general population

Brucellosis among Hospitalized Febrile Patients in Northern Tanzania

Acute and convalescent serum samples were collected from febrile inpatients identified at two hospitals in Moshi, Tanzania. Confirmed brucellosis was defined as a positive blood culture or a &#8805; 4-fold increase in microagglutination test titer, and probable brucellosis was defined as a single reciprocal titer &#8805; 160. Among 870 participants enrolled in the study, 455 (52.3%) had paired sera available. Of these, 16 (3.5%) met criteria for confirmed brucellosis. Of 830 participants with &#8805; 1 serum sample, 4 (0.5%) met criteria for probable brucellosis. Brucellosis was associated with increased median age (P = 0.024), leukopenia (odds ratio [OR] 7.8, P = 0.005), thrombocytopenia (OR 3.9, P = 0.018), and evidence of other zoonoses (OR 3.2, P = 0.026). Brucellosis was never diagnosed clinically, and although all participants with brucellosis received antibacterials or antimalarials in the hospital, no participant received standard brucellosis treatment. Brucellosis is an underdiagnosed and untreated cause of febrile disease among hospitalized adult and pediatric patients in northern Tanzania. Disclaimer: The findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the Centers for Disease Control and Prevention. Use of trade names and commercial sources is for identification only and does not imply endorsement by the U.S. Department of Health and Human Services or the Centers for Disease Control and Prevention

Study flow diagram.

<p>KCMC: Kilimanjaro Christian Medical Centre; MRH: Mawenzi Regional Hospital; MAT: microagglutination test; IFA: immunoflouresence assay; NAAT: nucleic acid amplification test.</p

Laboratory confirmed causes of febrile illness among infants and children (panel A) and adolescents and adults (panel B) hospitalized in northern Tanzania, 2007–8*.

<p>*In instances that diagnostic test results were not available for all participants, the proportion positive from <a href="http://www.plosntds.org/article/info:doi/10.1371/journal.pntd.0002324#pntd-0002324-t001" target="_blank">Table 1</a> was applied to the whole study population. Pie graphs do not account for concurrent infections. A complete listing of specific bacterial, mycobacterial, and fungal bloodstream infections is available elsewhere <a href="http://www.plosntds.org/article/info:doi/10.1371/journal.pntd.0002324#pntd.0002324-Crump1" target="_blank">[7]</a>, <a href="http://www.plosntds.org/article/info:doi/10.1371/journal.pntd.0002324#pntd.0002324-Crump2" target="_blank">[8]</a>.</p

Calculation of the proportion of hospitalized infants and children, and adolescents and adults, with specific etiologies of febrile illness, northern Tanzania, 2007–8.

<p>Due to changing denominators for individual diagnostic tests, the proportion with no diagnosis is calculated as the proportion without a positive result from any test. Bloodstream infections are those diagnosed predominantly by blood culture, including organisms such as <i>Salmonella enterica</i>, <i>Streptococcus pneumoniae</i>, <i>Cryptococcus neoformans</i>, and <i>Mycobacterium tuberculosis</i>. Bacterial zoonoses, including brucellosis, leptospirosis, Q fever, and rickettsioses were diagnosed predominantly by serology, based on a 4-fold or greater rise in antibody titer between an acute and convalescent sample.</p

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

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