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Melioidosis in Northern Tanzania: an Important Cause of Febrile Illness?

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Melioidosis in Northern Tanzania: an Important Cause of Febrile Illness? Melioidosis and serological evidence of exposure to Burkholderia pseudomallei among patients with fever, northern Tanzania Michael Maze Department of Medicine University of Otago, Christchurch Melioidosis Melioidosis caused by Burkholderia pseudomallei • Challenging to identify when cultured Soil reservoir, with human infection from contact with contaminated water Most infected people are asymptomatic: 1 clinical illness for 4,500 antibody producing exposures Febrile illness with a variety of presentations and bacteraemia is present in 40-60% of people with acute illness Estimated 89,000 deaths globally Gavin Koh CC BY-SA 4.0, https://commons.wikimedia.org/w/index.php?curid=4975784 Laboratory diagnosis of febrile inpatients, northern Tanzania, 2007-8 (n=870) Malaria (1.6%) Bacteremia (9.8%) Mycobacteremia (1.6%) Fungemia (2.9%) Brucellosis (3.5%) Leptospirosis (8.8%) Q fever (5.0%) No diagnosis (50.1%) Spotted fever group rickettsiosis (8.0%) Typhus group rickettsiosis (0.4%) Chikungunya (7.9%) Crump PLoS Neglect Trop Dis 2013; 7: e2324 Predicted environmental suitability for B. pseudomallei in East Africa Large areas of Africa are predicted to be highly suitable for Burkholderia pseudomallei East Africa is less suitable but pockets of higher suitability including northern Tanzania Northern Tanzania Increasing suitability for B. pseudomallei Limmathurotsakul Nat Microbiol. 2016;1(1). Melioidosis epidemiology in Africa Paucity of empiric data • Scattered case reports • Report from Kilifi, Kenya identified 4 bacteraemic cases from 66,000 patients who had blood cultured1 • 5.9% seroprevalence among healthy adults in Uganda2 • No reports from Tanzania 1. Limmathurotsakul Nat Microbiol. 2016;1(1). 2. Frazer J R Army Med Corps. 1982;128(3):123-30. Study Aim Determine the prevalence of melioidosis prevalence and B. pseudomallei exposure in northern Tanzania Methods – Blood culture surveillance Prospective hospital based surveillance during 2007-08, 2012-14 and 2016-19 Kilimanjaro Christian Medical Centre (630 bed hospital) and Mawenzi Regional Hospital (430 bed hospital) Enrolled all patients with a febrile illness Methods – Blood culture surveillance Blood inoculated into BacT Alert standard (10ml) or paediatric bottles (4ml) Isolates identified using API20NE biochemical identification system All isolated non-glucose fermenting gram-negative bacilli were tested by B. pseudomallei latex agglutination test Methods – Serological testing Participants admitted within 30 days of rainfall during 2012-2014 Acute serum, and convalescent serum 4-6 weeks after enrolment B. pseudomallei indirect haemaglutination testing • Probable acute melioidosis: ≥4 fold rise in reciprocal antibody titres • B. pseudomallei seropositivity: single titre ≥40 Characteristics of participants undergoing blood culture, Tanzania, 2012-14 (N=3,699) N n (%) Demographic characteristics Age, median (IQR) years 3,598 19.6 (1.9, 39.2) Male sex 3,595 1,788 (49.7) Risk factors Rainfall in 30 days prior to admission, median (IQR) mm 1,738 24.0 (1.8, 67.7) Farming occupation 1,445 261 (18.1) Self reported HIV-infected or positive HIV serology 2,605 428 (16.4) Clinical history Illness duration, median (IQR) days 3,334 5 (3,14) Dyspnoea 2,595 813 (31.3) Rash or cutaneous lesion 1,445 117 (8.1) Blood culture results, Tanzania, 2007-2019 1832 (70.2%) of 2,607 had adequately filled blood culture bottles 5 (0.1%) non-enteric gram negative bacteria isolated 0 B. pseudomallei Characteristics of participants undergoing Burkholderia pseudomallei indirect haemagglutination testing, Tanzania, 2012-14 (N=323) n (%) Demographic characteristics Age, median (IQR) years 27 (5,40) Male sex 142 (44.0) Risk factors Rainfall in 30 days prior to admission, median (IQR) mm 46 (27,2) Farming occupation 66 (20.6) Self reported HIV-infected 44 (13.6) Clinical history Fever duration, median (IQR) days 4 (2,7) Dyspnea 101 (31.4) Rash or cutaneous lesion 24 (8.4) Distribution of Burkholderia pseudomallei indirect hemagglutination test reciprocal antibody titers among febrile patients, Tanzania, 2012-14 250 Seropositivity cut-off 200 57 (17.7%) seropositive 150 2 (0.6%) probable melioidosis 100 50 Numberof participants 0 <10 10 20 40 80 160 320 640 1,280 10,240 Reciprocal indirect hemagglutination assay antibody titer to B. pseudomallei Interpretation: Blood culture No positive blood cultures among >3,500 patients over 12 years • Most single bottle inoculation • 30% culture bottles inadequately filled • Culture of blood only Unlikely to be a major cause of febrile illness in the region Does not preclude the presence of melioidosis • In Kenya: 4 cases from 66,000 blood cultures Interpretation: Serology 18% seropositive by IHA is high by global standards • Similar to serosurveys in Australia • 5.9% seropositive among healthy adults in Kampala, Uganda 1982 Seropositivity indicates exposure to B. pseudomallei, but cross- reactivity with B. mallei or environmental Burkholderia possible Deliberately biased sample, as presence of exposure was previously unknown Conclusions and next steps High prevalence of B. pseudomallei exposure but absence of confirmed bacteraemic melioidosis is notable Unlikely that melioidosis is a major cause of fever in northern Tanzania Ongoing blood culture surveillance and environmental sampling warranted Acknowledgements University of Otago: John Crump, Katrina Frances G. Cotter, Sandy Smith and MacGibbon Sharples Scholarships US National Institutes of Health-National Science Kilimanjaro Christian Medical Centre: Foundation Ecology of Infectious Disease program Blandina Mmbaga, Venance Maro, Kajiru (R01TW009237) US National Institutes of Health, Kilonzo, Francis Karia, Research Team National Institute for Allergy and Infectious Duke University: Matt Rubach, Manuela Diseases (R01 AI121378) Carugati, Holly Biggs, Deng Madut Biotechnology & Biological Sciences Research Council (BB/J010367/1, BB/L018926, BB/L017679, BB/L018845) Tanzania Ministry of Health: Wilbrod Saganda, Bingileki Lwezaula US Centers for Disease Control & Prevention: Renee Galloway, William Nicholson, Robyn Stoddard, Alex Hoffmaster, Mindy Elrod.
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