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A Collaborative Health Research and Service Program in northern Tanzania

A Collaborative Health Research and Service Program in northern Tanzania. John A. Crump, MB, ChB, DTM&H Assistant Professor of Medicine Division of Infectious Diseases and International Health Senior Lecturer, Kilimanjaro Christian Medical College. Overview. Tanzania

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A Collaborative Health Research and Service Program in northern Tanzania

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  1. A Collaborative Health Research and Service Program in northern Tanzania John A. Crump, MB, ChB, DTM&H Assistant Professor of Medicine Division of Infectious Diseases and International Health Senior Lecturer, Kilimanjaro Christian Medical College

  2. Overview • Tanzania • Medicine collaboration in Tanzania • Philosophy and core values • Training • Research • Past research accomplishments • Current research portfolio • Focus on febrile illness studies • Future directions

  3. Tanzania • Population 33 million • Area 886,000 km2 • Human development index rank 162nd • Per capita GDP USD 251 • HIV seroprevalence 7.0%

  4. History of collaboration in Tanzania • 1986-1994 Coast • Muhimbili National Hospital, Dar es Salaam • Mid-1990s northern Tanzania • Kilimanjaro Christian Medical Centre, Moshi • Medical resident rotations • 2002 scale-up of activities • Place faculty, develop research program • KIWAKUKKI, Moshi • Kibong’oto National Tuberculosis Hospital, Sanya Juu • Mawenzi Regional Hospital, Moshi • HIV prevention, treatment and care

  5. Survival of KIWAKKUKI home-based care clients, 2003-2005, n=226 Tillekeratne LG, et al. World AIDS Conference 2006, Abstract MoPe0303

  6. Philosophy and core values • Research with service • Training • Patient care and public health • True collaboration • Long-term commitment • Decades not years, months or days • Progress may be slow • Fair weather and foul • International health as a discipline • >100 year history • International health best practiced from ‘the field’ • Minimize ‘public health tourism’

  7. Department of Medicine Trainees

  8. Tanzanian trainees 2002-present

  9. ‘Research with Service’

  10. Cost-effectiveness of free versus co-pay HIV voluntary counseling and testing • Would provision of free HIV voluntary counseling and testing (VCT) in Tanzania be cost-effective?

  11. Methods • 813 VCT clients • KIWAKKUKI • May– Nov 2003 • Before, during, after free VCT campaign • Cost-effectiveness model • Number of tests per day • Costs of testing • Benefits of knowing HIV serostatus: infections averted, access to treatment

  12. Persons receiving VCT per day KIWAKKUKI VCT, 2003n=813 Mean daily volume prior to free testing Mean 15.0 p<0.0001 Mean daily volume during free testing Mean daily volume after free testing Mean 7.1 p<0.0001 Number of clients Mean 4.1 June July August September October November 2003 Thielman NM, et al. Am J Public Health 2006; 96: 114-9

  13. Cost-Effectiveness of VCT Thielman NM, et al. Am J Public Health 2006; 96: 114-9

  14. Simple, low cost approaches to identifying patients with CD4 count <200 cells/mm3 • How can we identify HIV-infected adults with CD4 count <200/mm3 in settings where laboratory capacity is limited?

  15. Methods • 202 subjects recently diagnosed with HIV referred • VCT centers • Aug 2004 – Jun 2005 • WHO staging history and examination, anthropometry and simple lab tests • ESR • CBC • CD4 count by manual Beckman Coulter method • Bivariable analysis to predict CD4 <200/mm3 • Partition tree analysis of significant variables

  16. Distribution of CD4 count by WHO stage, Moshi, Tanzania, 2004-5 CD4 count mm3* WHO stage *Interquartile range, range Morpeth SC, et al. CROI 2005, Boston, Ma., Abstract 638

  17. Number of recently diagnosed HIV-infected persons who would be triaged to treatment using 4 different strategies, by CD4-count stratum *Receiver-operator characteristics area-under-the-curve Morpeth SC, et al. CROI 2005, abstract 638a

  18. Trimethoprim-sulfamethoxazole study • What effect is use of TMP-SXT prophylaxis in persons with symptomatic HIV disease in Africa having on emergence of antimicrobial resistance?

  19. Methods • 184 subjects recently diagnosed with HIV referred • VCT centers • Aug 2004 – Dec 2005 • Prospective observational cohort study • Arm A: HIV-uninfected • Arm B: HIV-infected, asymptomatic (no TMP-SXT) • Arm C: HIV-infected, symptomatic (TMP-SXT) • Follow-up • Baseline • Weeks 1, 2, 4, 24 • Stool • Screened for Escherichia coli not susceptible to TMP-SXT

  20. Results • Baseline non-susceptibility was high • Arm A: 26 (57%) of 46 • Arm B: 28 (70%) of 40 • Arm C: 41 (67%) of 61 • Introduction on TMP-SXT rapidly led to non-susceptibility • >95% of Arm C patients had non-susceptible E. coli within 1 week of TMP-SXT • Arm C vs. Arm A p=0.007 • Arm C vs. Arm B p=0.020

  21. Antiretroviral drug resistance and adherence study (ADAR) • How common is virologic failure in patients receiving ART in Tanzania and who fails and why?

  22. Methods • Retrospective cohort study • 150 HIV-infected adult patients, June-August 2005 • FDC D4T/3TC/NVP ≥ 6 months • Consecutive patients presenting for follow up • Standardized questionnaire • Sociodemographics • Economic conditions • HIV and ART knowledge, beliefs, disclosure • Adherence • Access to care • Plasma • HIV RNA quantitation

  23. Risk Factors for Virologic FailureMultivariable Analysis* *Model controlled for age and gender and included variables with p<0.1 from biavriable analysis Ramadhani HO, et al. World AIDS Conference 2006, abstract ThLb0213

  24. Self-Funded ART and Virologic Failure • Persons paying for ART were more likely to be maladherent r=0.54, p<0.001

  25. Tuberculosis and HIV Immune Reconstitution Syndrome Trial (THIRST) • Is it better to start ART immediately or to defer ART in patients co-infected with tuberculosis?

  26. Methods • Randomized, controlled trial • 70 patients with HIV infection and smear-positive pulmonary tuberculosis • Initiate TB treatment then FDC ZDV/LMV/ABC after • 2 weeks • 8 weeks • Follow-up • 104 weeks

  27. CD4-positive lymphocyte responses CD4+ count (cells/mm3) p <0.0001 for temporal trends Entry Week 12 Week 36 Week 48 Week 24 n= 70 69 68 67 66 Shao HJ, et al. CROI 2006, Abstract 796

  28. Outcomes • 3 study subjects’ deaths were not thought to be related to study medications • ZDV/LMV/ABC was discontinued in 6 subjects - 2 with dose-limiting anemia, requiring substitution of stavudine for ZDV - 4 with suspected ABC hypersensitivity reactions • At week 48, 64 (96%) of 67 had HIV RNA <400 copies/mL • To date, no cases of TB-associated immune reconstitution syndrome have been observed

  29. HIV seroprevalence Kibong’oto Tuberculosis THIRST Hospitalized patients Mawenzi Regional ADAR KCMC HIV inpatient characteristics Sociodemographics (VCT) Tuberculosis symptoms HIV VCT clients HIV staging TMP-SXT Community-based subjects Cost-effectiveness HIV-seroincidence HIV HBC clients Sociodemographics (HBC) Morbidity and survival

  30. KCMC BIOTECHNOLOGY LABORATORY Microbiology Molecular Virology Cryopreservation Hematology and Chemistry Immunology

  31. Grant support for researchDuke-KCMC Collaboration, 2002-present Clinical Research Site Abbott (LPV/RTV) CHAVI CFAR (Clin Core) ISAAC Grant support (thousands of USD) AITRP GSK (THIRST) CIPRA R03 CFAR (ADAR) Roche Laboratories (VCT) CFAR (Cervical Ca) Year

  32. Adult HIV treatment studies

  33. Pediatric HIV treatment studies

  34. HIV vaccine-related research

  35. Community studies

  36. HIV co-infection studies

  37. HIV co-infection studies

  38. Febrile illness in northern Tanzania • Febrile illness accounts for 10-30% of admissions to hospital in northern Tanzania • HIV co-infection is common among inpatients • Community 7% (2004) • Medical inpatients 21% (2000) • Tuberculosis inpatients 41% (2000) • Laboratory capacity is limited • Fever is often managed empirically with antimalarials, even when slide negative • Causes of fever differ from those in the west • Little work has been done on prevention, diagnosis, and treatment of leading causes of fever

  39. 95% treated with quinine 66% received antibacterial Severe febrile illness hospital management, northern Tanzania Reyburn HG, et al. Brit Med J 2004; 329: 1212

  40. Muhimbili National Hospital, Dar es SalaamTanzania, 1995 Archibald LK, et al. Clin Infect Dis 1998; 26: 290

  41. Muhimbili National Hospital, Dar es SalaamTanzania, 1995 Archibald LK, et al. Clin Infect Dis 1998; 26: 290

  42. KCMC, Moshi, Tanzania, 2007

  43. Nested studies and goals • Causes of febrile illness in children admitted to hospital in a low transmission area of P.falciparum • To impact on Integrated Management of Childhood Illness (IMCI) algorithms • Disseminated tuberculosis diagnostics study • To improve the clinical and laboratory diagnosis of disseminated tuberculosis • Non-Typhi Salmonella in HIV case-control study • To inform prevention guidelines for HIV-associated non-Typhi Salmonella bacteremia in Africa

  44. Future directions • Continue to work on health problems of importance in Tanzania • Descriptive → interventional studies • Opportunistic → focused research plan • Expand the training program • Long-term training • Advanced degrees • Assist to foster a critical mass of researchers at KCMC • Independent investigators • Life-long collaborators

  45. Conclusions • Platform for HIV and infectious diseases research • Strong collaborative relationships with hospital, community, and other researchers • Emphasis on training • Track record of ‘research with service’ • Growing personnel and infrastructure • High quality laboratory facilities • Potential to underpin ambitious and growing research agenda • HIV treatment and prevention research • HIV co-infection research • Community studies

  46. Duke-KCMC Collaboration Team, Moshi, April 2007

  47. Duke University Medical Center John D. Hamilton, MD John A. Bartlett, MD Nathan M. Thielman, MD, MPH Charles Muiruri L. Barth Reller, MD, DTM&H G. Ralph Corey, MD Barton F. Haynes, MD Michael Merson, MD Anne B. Morrissey, MS Jean Gratz, MS Julia Giner, RN Jan Ostermann, PhD Gary M. Cox, MD Carol Dukes Hamilton, MD Coleen K. Cunningham, MD KIWAKKUKI Rehema A. Kiwera, AdvDipClinMed Dafrosa K. Itemba, BA Kilimanjaro Christian Medical Centre John F. Shao, MD, PhD Mark E. Swai, MD Humphrey J. Shao, MD Habib O. Ramadhani, MD Florida P. Muro, MD Bahati P. Msaki, MD Emmanual Balandya, MD Venance P. Maro, MD Grace D. Kinabo, MD Levina Msuya, MD Werner Schimana, MD Moses W. Sichangi, MSc Francis P. Karia, MBA Ahaz T. Kulanga, MBA Acknowledgements

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