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Schistosomiasis and HIV co-infection in fishing communities along Lake Victoria, Uganda

Schistosomiasis and HIV co-infection in fishing communities along Lake Victoria, Uganda. Pontiano Kaleebu Medical Research Council (MRC UK) Uganda Virus Research Institute (UVRI) ENTEBBE. Introduction. A wide geographic overlap in occurrence NTDs and HIV

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Schistosomiasis and HIV co-infection in fishing communities along Lake Victoria, Uganda

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  1. Schistosomiasis and HIV co-infection in fishing communities along Lake Victoria, Uganda PontianoKaleebu Medical Research Council (MRC UK) Uganda Virus Research Institute (UVRI) ENTEBBE

  2. Introduction • A wide geographic overlap in occurrence NTDs and HIV • Infection with S.mansoni may be associated with increased susceptibility to HIV infection and disease progression (earlier studies inconclusive) • Fishing communities in Uganda with high HIV infection rates and high S. mansoni prevalence (50%), suitable for investigation of interactions of HIV and worms

  3. Division of labour in the fishing community

  4. Project goals • Impact of S.mansonion HIV acquisition and associated immune responses in co-infected individuals (Case control study) • Impact of praziquantel treatment on HIV disease progression and immunological responses among individuals (Intervention study)

  5. Study area In 2009, 1000 HIV- at risk volunteers were enrolled from 5 fishing sites along lake Victoria to assess HIV incidence and study retention. • They were followed six monthly for 18 months • HIV prevalence 29%, incidence 5/100pyo) and high S. mansoni prevalence (50%)

  6. Case control study Objectives • To determine the odds of S.mansoni infection among 50 HIV incident cases compared to 150 HIV negative controls identified from a fisher folk cohort • To compare prevalence of S. mansoni infection status from stored blood samples at enrollment and at 18 months among 50 HIV incident cases and 150 HIV negative controls • To investigate innate and adaptive immune responses among HIV incident cases with worm infections

  7. Study design-nested case control 1000 HIV-1 negative 13-49 yrs at high risk of infection, visit: 1 2 3 4 (5) (Recalled volunteers for schistosomiasis Case-control study nested within the prospective cohort 50 HIV+ incident cases 150 HIV- controls) were enrolled 0 mo 6 mo 12 mo 18 mo Enrol HIV VCT Plasma Serum HIV VCT Plasma Serum HIV VCT Plasma Serum HIV VCT Plasma Serum HIV VCT Plasma Serum Kato Katz on 3 consecutive stool samples to ascertain S.mansoni infection among cases and controls at study exit 35 ml blood : 2.5 ml PAXgene tube ~30 ml PBMC + plasma 0.6 ml whole blood assay Circulating Anodic Antigen (CAA) test (van Dam / Corstjens) on stored plasma (visits 1,2,3,4)

  8. Results OR 1.05 95%CI (0.53 – 2.10) No evidence of association between S. mansoni infection and HIV sero-conversion CAA serum analysis is on-going to establish if S.mansoni infection occurred before HIV sero-conversion

  9. Innate signalling patterns in HIV – Schistosome co-infection Fisher Folk HIV-1 incidence study – schistosomiasis substudy Whole blood:RPMI (1:1) + innate stimuli: 24h sups IFN-γ TNF-α IFN-α IL-10 IL-13 cytokines (Luminex)

  10. Fisher Folk HIV-1 incidence study – schistosomiasis substudy Acquired responses Flow cytometry HIV PTE pools GAG (~1 μg/ml, 24 h, costim + BFA from start) POL ENV NEF NEG control SEB Schistosome antigens SEA (10 μg/ml, 24h*, BFA added AWA for last 6 h) NEG control If cells are sufficient: (2nd priority) pos/neg regulators panel [live CD3 CD4 CD8 CD160 LAG-3 PD-1 2B4 CTLA-4] (3rd priority) Tregs panel [live CD3 CD4 CD25 CD45RO FOXP3 CD127] (4th priority) differentiation panel [live CD3 CD4 CD8 CD27 CD45RA CD127 CCR7] (5th priority) cytotoxic panel [live CD8 Grm A Grm B GrmK Pf CD 45RA CD127]

  11. Cytotoxicity genes and Treg associated genes: enhanced in HIV+SM+ Marielle Haks et al. unpublished

  12. S. mansoni & HIV co-infected individuals have higher Th1 type responses to HIV than HIV mono infected CD4 - ENV CD4 - GAG HIV+ S. m.- HIV+ S. m.+ 1.5 % cells 1 % cells 1 P=0.04 .8 .6 .5 .4 .2 0 0 CD8 - ENV CD8 - GAG 3 2 P=0.04 1.5 2 % cells % cells 1 P=0.03 1 .5 0 0 SM+ SM- SM+ SM- SM+ SM- SM+ SM- SM+ SM- SM+ SM- SM+ SM- SM+ SM- SM+ SM- SM+ SM- SM+ SM- SM+ SM- SM+ SM- SM+ SM- TNF-α IL-2 IFN-γ + + + + + + + + + + + + + + + + + + + + + + + + Andrew Obuku 2012 (unpublished)

  13. Intervention study Objectives • Compare HIV progression (viral loads, CD4 count, clinical) among HIV+/S.mansoni+ patients treated with intensive (quarterly) Vs standard (annual) treatment with praziquantel • Compare immunological changes between the treatment arms over the study period

  14. Study design- RCT Participant recruitment starting this month and will be followed 3 monthly for 15 months

  15. Immunological and gene expression profile studies Innate and adaptive assays Luminex assays Flow cytometry RNA expression profiling (RT-MLPA; Illumina)

  16. Acknowledgements Funders: EDCTP; IAVI; MRC-UK; IDEA (EU) Fisherfolk and Intervention study investigators: P. Kaleebu, A. Kamali, J.Seeley, A. Gershim; L. Nielsen; J Mpendo; A. Elliott; P. Pala ; J Levin; J Nakiyinji-Miiro; G Pantaleo; S. Ding Schistosomiasis /HIV Immunology studies: P. Pala; A. Elliott; A. Obuku ; P Kaleebu; R Sekaly; M. Cameron; M. Haks; H. Smits; M. Perrau; A. Harari; S. Ding; G. Pantaleo

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