Metagenomic Detection of Bacterial Zoonotic Pathogens among Febrile Patients, Tanzania, 2007-20091.

Bacterial zoonoses are established causes of severe febrile illness in East Africa. Within a fever etiology study, we applied a high-throughput 16S rRNA metagenomic assay validated for detecting bacterial zoonotic pathogens. We enrolled febrile patients admitted to 2 referral hospitals in Moshi, Tanzania, during September 2007-April 2009. Among 788 participants, median age was 20 (interquartile range 2-38) years. We performed PCR amplification of V1-V2 variable region 16S rRNA on cell pellet DNA, then metagenomic deep-sequencing and pathogenic taxonomic identification. We detected bacterial zoonotic pathogens in 10 (1.3%) samples: 3 with Rickettsia typhi, 1 R. conorii, 2 Bartonella quintana, 2 pathogenic Leptospira spp., and 1 Coxiella burnetii. One other sample had reads matching a Neoerhlichia spp. previously identified in a patient from South Africa. Our findings indicate that targeted 16S metagenomics can identify bacterial zoonotic pathogens causing severe febrile illness in humans, including potential novel agents.

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

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

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.

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

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

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

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

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

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 Leptospira species and genotypes among patients hospitalized with fever in Tanzania and compared these with Leptospira genotypes detected among animals in Tanzania to infer potential sources of human infection. We performed lipL32 real-time PCR to detect the presence of pathogenic Leptospira in acute-phase plasma, serum, and urine samples obtained from study participants with serologically confirmed leptospirosis and participants who had died with febrile illness. Leptospira blood culture was also performed. In positive specimens, we performed species-specific PCR and compared participant Leptospira secY sequences with Leptospira reference sequences and sequences previously obtained from animals in Tanzania. We detected Leptospira DNA in four (3.6%) of 111 participant blood samples. We detected Leptospira borgpetersenii (one participant, 25.0%), Leptospira interrogans (one participant, 25.0%), and Leptospira kirschneri (one participant, 25.0%) (one [25%] undetermined). Phylogenetic comparison of secY sequence from the L. borgpetersenii and L. kirschneri 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 Leptospira species is causing human infection. Although our analysis suggests a close relationship between Leptospira genotypes found in people and livestock, continued efforts are needed to obtain more Leptospira genetic material from human leptospirosis cases to help prioritize Leptospira species and genotypes for control.

Risk factors for human acute leptospirosis in northern Tanzania.

INTRODUCTION: Leptospirosis is a major cause of febrile illness in Africa but little is known about risk factors for human infection. We conducted a cross-sectional study to investigate risk factors for acute leptospirosis and Leptospira seropositivity among patients with fever attending referral hospitals in northern Tanzania. METHODS: We enrolled patients with fever from two referral hospitals in Moshi, Tanzania, 2012-2014, and performed Leptospira microscopic agglutination testing on acute and convalescent serum. Cases of acute leptospirosis were participants with a four-fold rise in antibody titers, or a single reciprocal titer ≥800. Seropositive participants required a single titer ≥100, and controls had titers <100 in both acute and convalescent samples. We administered a questionnaire to assess risk behaviors over the preceding 30 days. We created cumulative scales of exposure to livestock urine, rodents, and surface water, and calculated odds ratios (OR) for individual behaviors and for cumulative exposure variables. RESULTS: We identified 24 acute cases, 252 seropositive participants, and 592 controls. Rice farming (OR 14.6), cleaning cattle waste (OR 4.3), feeding cattle (OR 3.9), farm work (OR 3.3), and an increasing cattle urine exposure score (OR 1.2 per point) were associated with acute leptospirosis. CONCLUSIONS: In our population, exposure to cattle and rice farming were risk factors for acute leptospirosis. Although further data is needed, these results suggest that cattle may be an important source of human leptospirosis. Further investigation is needed to explore the potential for control of livestock Leptospira infection to reduce human disease.

Incidence of human brucellosis in the Kilimanjaro Region of Tanzania in the periods 2007-2008 and 2012-2014.

Background: 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.

Risk Factors for Human Brucellosis in Northern Tanzania.

Little is known about the epidemiology of human brucellosis in sub-Saharan Africa. This hampers prevention and control efforts at the individual and population levels. To evaluate risk factors for brucellosis in northern Tanzania, we conducted a study of patients presenting with fever to two hospitals in Moshi, Tanzania. Serum taken at enrollment and at 4-6 week follow-up was tested by Brucella microagglutination test. Among participants with a clinically compatible illness, confirmed brucellosis cases were defined as having a ≥ 4-fold rise in agglutination titer between paired sera or a blood culture positive for Brucella spp., and probable brucellosis cases were defined as having a single reciprocal titer ≥ 160. Controls had reciprocal titers < 20 in paired sera. We collected demographic and clinical information and administered a risk factor questionnaire. Of 562 participants in the analysis, 50 (8.9%) had confirmed or probable brucellosis. Multivariable analysis showed that risk factors for brucellosis included assisting goat or sheep births (Odds ratio [OR] 5.9, 95% confidence interval [CI] 1.4, 24.6) and having contact with cattle (OR 1.2, 95% CI 1.0, 1.4). Consuming boiled or pasteurized dairy products was protective against brucellosis (OR 0.12, 95% CI 0.02, 0.93). No participants received a clinical diagnosis of brucellosis from their healthcare providers. The under-recognition of brucellosis by healthcare workers could be addressed with clinician education and better access to brucellosis diagnostic tests. Interventions focused on protecting livestock keepers, especially those who assist goat or sheep births, are needed.

Comparison of the Estimated Incidence of Acute Leptospirosis in the Kilimanjaro Region of Tanzania between 2007-08 and 2012-14.

BACKGROUND: The sole report of annual leptospirosis incidence in continental Africa of 75-102 cases per 100,000 population is from a study performed in August 2007 through September 2008 in the Kilimanjaro Region of Tanzania. To evaluate the stability of this estimate over time, we estimated the incidence of acute leptospirosis in Kilimanjaro Region, northern Tanzania for the time period 2012-2014. METHODOLOGY AND PRINCIPAL FINDINGS: Leptospirosis cases were identified among febrile patients at two sentinel hospitals in the Kilimanjaro Region. Leptospirosis was diagnosed by serum microscopic agglutination testing using a panel of 20 Leptospira serovars belonging to 17 separate serogroups. Serum was taken at enrolment and patients were asked to return 4-6 weeks later to provide convalescent serum. Confirmed cases required a 4-fold rise in titre and probable cases required a single titre of ≥800. Findings from a healthcare utilisation survey were used to estimate multipliers to adjust for cases not seen at sentinel hospitals. We identified 19 (1.7%) confirmed or probable cases among 1,115 patients who presented with a febrile illness. Of cases, the predominant reactive serogroups were Australis 8 (42.1%), Sejroe 3 (15.8%), Grippotyphosa 2 (10.5%), Icterohaemorrhagiae 2 (10.5%), Pyrogenes 2 (10.5%), Djasiman 1 (5.3%), Tarassovi 1 (5.3%). We estimated that the annual incidence of leptospirosis was 11-18 cases per 100,000 population. This was a significantly lower incidence than 2007-08 (p<0.001). CONCLUSIONS: We estimated a much lower incidence of acute leptospirosis than previously, with a notable absence of cases due to the previously predominant serogroup Mini. Our findings indicate a dynamic epidemiology of leptospirosis in this area and highlight the value of multi-year surveillance to understand leptospirosis epidemiology.

Evaluation of in-hospital management for febrile illness in Northern Tanzania before and after 2010 World Health Organization Guidelines for the treatment of malaria.

OBJECTIVE: 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.

Estimating leptospirosis incidence using hospital-based surveillance and a population-based health care utilization survey in Tanzania.

BACKGROUND: The incidence of leptospirosis, a neglected zoonotic disease, is uncertain in Tanzania and much of sub-Saharan Africa, resulting in scarce data on which to prioritize resources for public health interventions and disease control. In this study, we estimate the incidence of leptospirosis in two districts in the Kilimanjaro Region of Tanzania. METHODOLOGY/PRINCIPAL FINDINGS: We conducted a population-based household health care utilization survey in two districts in the Kilimanjaro Region of Tanzania and identified leptospirosis cases at two hospital-based fever sentinel surveillance sites in the Kilimanjaro Region. We used multipliers derived from the health care utilization survey and case numbers from hospital-based surveillance to calculate the incidence of leptospirosis. A total of 810 households were enrolled in the health care utilization survey and multipliers were derived based on responses to questions about health care seeking in the event of febrile illness. Of patients enrolled in fever surveillance over a 1 year period and residing in the 2 districts, 42 (7.14%) of 588 met the case definition for confirmed or probable leptospirosis. After applying multipliers to account for hospital selection, test sensitivity, and study enrollment, we estimated the overall incidence of leptospirosis ranges from 75-102 cases per 100,000 persons annually. CONCLUSIONS/SIGNIFICANCE: We calculated a high incidence of leptospirosis in two districts in the Kilimanjaro Region of Tanzania, where leptospirosis incidence was previously unknown. Multiplier methods, such as used in this study, may be a feasible method of improving availability of incidence estimates for neglected diseases, such as leptospirosis, in resource constrained settings.

Etiology of severe non-malaria febrile illness in Northern Tanzania: a prospective cohort study.

INTRODUCTION: 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. METHODS AND FINDINGS: 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. CONCLUSIONS: 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.

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 ≥ 4-fold increase in microagglutination test titer, and probable brucellosis was defined as a single reciprocal titer ≥ 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 ≥ 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.

Histoplasmosis among hospitalized febrile patients in northern Tanzania.

Histoplasmosis may be common in East Africa but the diagnosis is rarely confirmed. We report 9 (0.9%) cases of probable histoplasmosis retrospectively identified among 970 febrile inpatients studied in northern Tanzania. Median (range) age was 31 (6, 44) years, 6 (67%) were female, 6 (67%) HIV-infected; 7 (78%) were clinically diagnosed with tuberculosis or bacterial pneumonia. Histoplasmosis is an important cause of febrile illness in Tanzania but is rarely considered in the differential diagnosis. Increased clinician awareness and availability of reliable diagnostic tests may improve patient outcomes.

Bacteremic disseminated tuberculosis in sub-saharan Africa: a prospective cohort study.

BACKGROUND: Disseminated tuberculosis is a major health problem in countries where generalized human immunodeficiency virus (HIV) infection epidemics coincide with high tuberculosis incidence rates; data are limited on patient outcomes beyond the inpatient period. METHODS: We enrolled consecutive eligible febrile inpatients in Moshi, Tanzania, from 10 March 2006 through 28 August 2010; those with Mycobacterium tuberculosis bacteremia were followed up monthly for 12 months. Survival, predictors of bacteremic disseminated tuberculosis, and predictors of death were assessed. Antiretroviral therapy (ART) and tuberculosis treatment were provided. RESULTS: A total of 508 participants were enrolled; 29 (5.7%) had M. tuberculosis isolated by blood culture. The median age of all study participants was 37.4 years (range, 13.6-104.8 years). Cough lasting >1 month (odds ratio [OR], 13.5; P< .001), fever lasting >1 month (OR, 7.8; P = .001), weight loss of >10% (OR, 10.0; P = .001), lymphadenopathy (OR 6.8; P = .002), HIV infection (OR, undefined; P < .001), and lower CD4 cell count and total lymphocyte count were associated with bacteremic disseminated tuberculosis. Fifty percent of participants with M. tuberculosis bacteremia died within 36 days of enrollment. Lower CD4 cell count (OR, 0.88; P = .049) and lower total lymphocyte count (OR, 0.76; P = .050) were associated with death. Magnitude of mycobacteremia tended to be higher among those with lower CD4 cell counts, but did not predict death. CONCLUSIONS: In the era of free ART and access to tuberculosis treatment, almost one half of patients with M. tuberculosis bacteremia may die within a month of hospitalization. Simple clinical assessments can help to identify those with the condition. Advanced immunosuppression predicts death. Efforts should focus on early diagnosis and treatment of HIV infection, tuberculosis, and disseminated disease.

Chikungunya and dengue fever among hospitalized febrile patients in northern Tanzania.

Consecutive febrile admissions were enrolled at two hospitals in Moshi, Tanzania. Confirmed acute Chikungunya virus (CHIKV), Dengue virus (DENV), and flavivirus infection were defined as a positive polymerase chain reaction (PCR) result. Presumptive acute DENV infection was defined as a positive anti-DENV immunoglobulin M (IgM) enzyme-linked immunsorbent assay (ELISA) result, and prior flavivirus exposure was defined as a positive anti-DENV IgG ELISA result. Among 870 participants, PCR testing was performed on 700 (80.5%). Of these, 55 (7.9%) had confirmed acute CHIKV infection, whereas no participants had confirmed acute DENV or flavivirus infection. Anti-DENV IgM serologic testing was performed for 747 (85.9%) participants, and of these 71 (9.5%) had presumptive acute DENV infection. Anti-DENV IgG serologic testing was performed for 751 (86.3%) participants, and of these 80 (10.7%) had prior flavivirus exposure. CHIKV infection was more common among infants and children than adults and adolescents (odds ratio [OR] 1.9, P = 0.026) and among HIV-infected patients with severe immunosuppression (OR 10.5, P = 0.007). CHIKV infection is an important but unrecognized cause of febrile illness in northern Tanzania. DENV or other closely related flaviviruses are likely also circulating.

Q fever, spotted fever group, and typhus group rickettsioses among hospitalized febrile patients in northern Tanzania.

BACKGROUND: The importance of Q fever, spotted fever group rickettsiosis (SFGR), and typhus group rickettsiosis (TGR) as causes of febrile illness in sub-Saharan Africa is unknown; the putative role of Q fever as a human immunodeficiency virus (HIV) coinfection is unclear. METHODS: We identified febrile inpatients in Moshi, Tanzania, from September 2007 through August 2008 and collected acute- and convalescent-phase serum samples. A ≥4-fold increase in immunoglobulin (Ig) G immunfluorescence assay (IFA) titer to Coxiella burnetii phase II antigen defined acute Q fever. A ≥4-fold increase in IgG IFA titer to Rickettsia conorii or Rickettsia typhi antigen defined SFGR and TGR, respectively. RESULTS: Among 870 patients, 483 (55.5%) were tested for acute Q fever, and 450 (51.7%) were tested for acute SFGR and TGR. Results suggested acute Q fever in 24 (5.0%) patients and SFGR and TGR in 36 (8.0%) and 2 (0.5%) patients, respectively. Acute Q fever was associated with hepato- or splenomegaly (odds ratio [OR], 3.1; P = .028), anemia (OR, 3.0; P = .009), leukopenia (OR, 3.9; P = .013), jaundice (OR, 7.1; P = .007), and onset during the dry season (OR, 2.7; P = .021). HIV infection was not associated with acute Q fever (OR, 1.7; P = .231). Acute SFGR was associated with leukopenia (OR, 4.1; P = .003) and with evidence of other zoonoses (OR, 2.2; P = .045). CONCLUSIONS: Despite being common causes of febrile illness in northern Tanzania, Q fever and SFGR are not diagnosed or managed with targeted antimicrobials. C. burnetii does not appear to be an HIV-associated co-infection.

Leptospirosis among hospitalized febrile patients in northern Tanzania.

We enrolled consecutive febrile admissions to two hospitals in Moshi, Tanzania. Confirmed leptospirosis was defined as a ≥ 4-fold increase in microscopic agglutination test (MAT) titer; probable leptospirosis as reciprocal MAT titer ≥ 800; and exposure to pathogenic leptospires as titer ≥ 100. Among 870 patients enrolled in the study, 453 (52.1%) had paired sera available, and 40 (8.8%) of these met the definition for confirmed leptospirosis. Of 832 patients with ≥ 1 serum sample available, 30 (3.6%) had probable leptospirosis and an additional 277 (33.3%) had evidence of exposure to pathogenic leptospires. Among those with leptospirosis the most common clinical diagnoses were malaria in 31 (44.3%) and pneumonia in 18 (25.7%). Leptospirosis was associated with living in a rural area (odds ratio [OR] 3.4, P < 0.001). Among those with confirmed leptospirosis, the predominant reactive serogroups were Mini and Australis. Leptospirosis is a major yet underdiagnosed cause of febrile illness in northern Tanzania, where it appears to be endemic.

Invasive bacterial and fungal infections among hospitalized HIV-infected and HIV-uninfected adults and adolescents in northern Tanzania.

BACKGROUND: few studies describe patterns of human immunodeficiency virus (HIV) co-infections in African hospitals in the antiretroviral therapy (ART) era. METHODS: we enrolled consecutive admitted patients aged ≥ 13 years with oral temperature of ≥ 38.0°C during 1 year in Moshi, Tanzania. A standardized clinical history and physical examination was done and hospital outcome recorded. HIV antibody testing, aerobic and mycobacterial blood cultures, and malaria film were performed. HIV-infected patients also received serum cryptococcal antigen testing and CD4(+) T lymphocyte count (CD4 cell count). RESULTS: of 403 patients enrolled, the median age was 38 years (range, 14-96 years), 217 (53.8%) were female, and 157 (39.0%) were HIV-infected. Of HIV-infected patients, the median CD4 cell count was 98 cells/µL (range, 1-1,105 cells/ µL), 20 (12.7%) were receiving ART, and 29 (18.5%) were receiving trimethoprim-sulfamethoxazole prophylaxis. There were 112 (27.7%) patients who had evidence of invasive disease, including 26 (23.2%) with Salmonella serotype Typhi infection, 24 (21.4%) with Streptococcus pneumoniae infection, 17 (15.2%) with Cryptococcus neoformans infection, 12 (10.7%) with Mycobacterium tuberculosis complex infection, 8 (7.1%) with Plasmodium falciparum infection, and 7 (6.3%) with Escherichia coli infection. HIV infection was associated with M. tuberculosis and C. neoformans bloodstream infection but not with E. coli, S. pneumoniae, or P. falciparum infection. HIV infection appeared to be protective against Salmonella. Typhi bloodstream infection (odds ratio, .12; P = .001). CONCLUSIONS: while Salmonella Typhi and S. pneumoniae were the most common causes of invasive infection overall, M. tuberculosis and C. neoformans were the leading causes of bloodstream infection among HIV-infected inpatients in Tanzania in the ART era. We demonstrate a protective effect of HIV against Salmonella. Typhi bloodstream infection in this setting. HIV co-infections continue to account for a large proportion of febrile admissions in Tanzania.