Epidemiology of Leptospirosis in Africa: A Systematic Review of a Neglected Zoonosis and a Paradigm for 'One Health' in Africa.

Leptospirosis is an important but neglected bacterial zoonosis that has been largely overlooked in Africa. In this systematic review, we aimed to summarise and compare current knowledge of: (1) the geographic distribution, prevalence, incidence and diversity of acute human leptospirosis in Africa; and (2) the geographic distribution, host range, prevalence and diversity of Leptospira spp. infection in animal hosts in Africa. Following Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines, we searched for studies that described (1) acute human leptospirosis and (2) pathogenic Leptospira spp. infection in animals. We performed a literature search using eight international and regional databases for English and non-English articles published between January 1930 to October 2014 that met out pre-defined inclusion criteria and strict case definitions. We identified 97 studies that described acute human leptospirosis (n = 46) or animal Leptospira infection (n = 51) in 26 African countries. The prevalence of acute human leptospirosis ranged from 2 3% to 19 8% (n = 11) in hospital patients with febrile illness. Incidence estimates were largely restricted to the Indian Ocean islands (3 to 101 cases per 100,000 per year (n = 6)). Data from Tanzania indicate that human disease incidence is also high in mainland Africa (75 to 102 cases per 100,000 per year). Three major species (Leptospira borgpetersenii, L. interrogans and L. kirschneri) are predominant in reports from Africa and isolates from a diverse range of serogroups have been reported in human and animal infections. Cattle appear to be important hosts of a large number of Leptospira serogroups in Africa, but few data are available to allow comparison of Leptospira infection in linked human and animal populations. We advocate a 'One Health' approach to promote multidisciplinary research efforts to improve understanding of the animal to human transmission of leptospirosis on the African continent

Antimicrobial resistance patterns of phenotype Extended Spectrum Beta-Lactamase producing bacterial isolates in a referral hospital in northern Tanzania

Background: Production of Extended Spectrum Beta-Lactamase (ESBL) by bacteria is a chronic problem in a health care set up. In order to have adequate information for treatment of bacterial infections especially ESBL producing isolates, it is crucial to understand the trends in the antibiotic-resistance pattern, occurrence and their geographical spread.  The objective of this study was to determine the antimicrobial resistance pattern among phenotype ESBL producing isolates in northern Tanzania.Methods: From July 2013 to January 2014, urine, pus and blood samples were collected from patients suspected to have bacterial infections at Kilimanjaro Christian Medical Centre in Moshi, Tanzania. The isolates were identified based on standard laboratory procedures. Antimicrobial susceptibility tests were carried out using various antimicrobial discs as per the recommendations of Clinical Laboratory Standard Institute.Results: A total of 330 specimens were collected. They consisted of 46 urine, 264 pus (from wound) and 20 blood samples. Among isolated bacteria, ESBL producers were 29.7% (98) and non-producers were 70.5% (232).  Escherichia coli and Klebsiella pneumoniae were the most isolated bacteria and dominant ESBL producers.  ESBL production was highly associated with moderate condition at discharge and longer periods of admission. More than 60% of the ESBL producing E. coli were resistant to ceftazidime, cefpodoxime, cefotaxime, amoxycilin, ciprofloxacin, and gentamycin. More than 80% of ESBL producing K. pneumonia and Proteus mirabilis were resistant to ceftazidime and cefotaxime. Fifty four percent of ESBL producing K. pneumonia were resistant to gentamycin.Conclusion: This study shows that ESLB phenotypes among Gram-negative bacteria are common among patients attending a tertiary hospital in northern in Tanzania. The findings suggest that clinical microbiology laboratories should take into account the diagnosis of ESBL producers in order to define the degree of the problem so as to establish a proper treatment protocol

Neurological disorders in Northern Tanzania: A 6-year prospective hospital-based case series

Background: The burden of neurological disorders is large and altered by the HIV epidemic. Objectives: We describe the pattern of neurological disorders and their association with HIV infection in adult patients attending a consultant hospital in Northern Tanzania. Methods: In this prospective cross-sectional study, we collected data on adult neurological referrals over a 6-year period between 2007-13. The odds of HIV infection, across neurological categories adjusted for age and sex, was calculated. Results: Of 2037 participants, 54.8% were male and 45.2% were female. The median age of participants was 43 years. The results for HIV screening were available for 992/2037 (48.7%) patients, of whom 306 (30.8%) were seropositive. The most frequent neurological disorders were cerebrovascular disease (19.9%), paraplegia (13.6%), and peripheral neuropathies (8%). Taken together CNS infection accounted for 278/2037 (13.6%). The adjusted odds (aOR) of HIV infection was highest amongst infections; brain abscesses (aOR 107, 95% CI 35.1-470.4) and meningitis/encephalitis (aOR 40.1, 95% CI 13.6-172.9), but also raised in cerebrovascular disease, paraplegia, peripheral neuropathies, cranial nerve palsies, seizures, cerebllar disorders, movement disorders, motor neuron disease and headache. Conclusion: The main pattern of neurological disorders in Northern Tanzania is presented. The odds of HIV infection was highest in CNS infections and in a wide range of non-communicable neurological disorders.publishedVersio

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

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

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

Test site predicts HIV care linkage and antiretroviral therapy initiation: a prospective 3.5 year cohort study of HIV-positive testers in northern Tanzania

Abstract Background Linkage to HIV care is crucial to the success of antiretroviral therapy (ART) programs worldwide, loss to follow up at all stages of the care continuum is frequent, and long-term prospective studies of care linkage are currently lacking. Methods Consecutive clients who tested HIV-positive were enrolled from four HIV testing centers (1 health facility and 3 community-based centers) in the Kilimanjaro region of Tanzania as part of the larger Coping with HIV/AIDS in Tanzania (CHAT) prospective observational study. Biannual interviews were conducted over 3.5 years, assessing care linkage, retention, and mental health. Bivariable and multivariate logistic regression analyses were conducted to determine associations with early death (prior to the second follow up interview) and delayed (>6 months post-test) or failed care linkage. Results A total of 263 participants were enrolled between November, 2008 and August, 2009 and 240 participants not already linked to care were retained in the final dataset. By 6 months after enrollment, 169 (70.4 %) of 240 participants had presented to an HIV care and treatment facility; 41 (17.1 %) delayed more than 6 months, 15 (6.3 %) died, and 15 (6.3 %) were lost to follow up. Twenty-six patients died before their second follow up visit and were analyzed in the early death group (10.8 %). Just 15 (9.6 %) of those linked to care had started ART within 6 months, but 123 (89.1 %) of patients documented to be ART eligible by local guidelines had started ART by the end of 3.5 years. On multivariate analysis, male gender (OR 1.72; 95 % CI 1.08, 2.75), testing due to illness (OR 1.63; 95 % CI 1.01, 2.63), and higher mean depression scale scores (4 % increased risk per increase in depression score; 95 % CI 1 %, 8 %) were associated with early death. Testing at a community versus a hospital-based site (OR 2.89; 95 % CI 1.79, 4.66) was strongly associated with delaying or never entering care. Conclusions Nearly 30 % of the cohort did not have timely care linkage, ART initiation was frequently delayed, and testing at a hospital outpatient department versus community-based testing centers was strongly associated with successful care linkage

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

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

The Effect of Switching to Second-Line Antiretroviral Therapy on the Risk of Opportunistic Infections Among Patients Infected With Human Immunodeficiency Virus in Northern Tanzania

Background. Due to the unintended potential misclassifications of the World Health Organization (WHO) immunological failure criteria in predicting virological failure, limited availability of treatment options, poor laboratory infrastructure, and healthcare providers’ confidence in making switches, physicians delay switching patients to second-line antiretroviral therapy (ART). Evaluating whether timely switching and delayed switching are associated with the risk of opportunistic infections (OI) among patients with unrecognized treatment failure is critical to improve patient outcomes