sulfamethoxazole prophylaxis on long term clinical impact of malaria infection among HIV infected adults on successful ART in Blantyre Malawi Felix Mkandawire Randy G Mungwira Titus H Divala ID: 641270 Download Presentation
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sulfamethoxazole. prophylaxis on long term clinical impact of malaria infection among HIV infected adults on successful ART in Blantyre, Malawi. . Felix Mkandawire. , . Randy G. . Mungwira. ,. Titus H. Divala.
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Effects of daily trimethoprim-
Presentation on theme: "Effects of daily trimethoprim-"— Presentation transcript:
Effects of daily trimethoprim-sulfamethoxazole prophylaxis on long term clinical impact of malaria infection among HIV infected adults on successful ART in Blantyre, Malawi
Titus H. Divala
Terrie E. Taylor, Jane
J. van Oosterhout
, Matthew B. Laurens, Miriam K. LauferSlide2
Malaria and HIVCombined 2 million deaths annually Highest
in sub-Saharan Africa Proportion of global incidence 88% of malaria cases and 90% of malaria deathsHIV 70% Geographical overlap: high risk of coinfection
1. WHO Annual report - 2008
, 2. UNAIDS report –
2010, 3. WHO- 2015Slide3
Malaria and HIV immunosuppressionRisk of malaria disease increases slightly with immunosuppressionCotrimoxazole preventive therapy
revents OI’sreduces the risk of malaria4 Laufer et al. - 2006, 5 WHO guidelines – 2006, 6.
et al. – 2016,
et al. – 2016Slide4
Role of CPT after ARTAntiretroviral therapy (ART) now widely available in sub-Saharan AfricaHighly effective in leading to immune recoveryAfter immune reconstitution, is CPT still beneficial?
Why consider CPT discontinuation?
Side effects, pill burden,
cost, antimicrobial resistanceSlide5
With ART success, can CPT be discontinued?What we know about CPT discontinuation Two clinical trials:
Most significant morbidity was increased malaria infection
Also increase in diarrhea
No increased risk of other OIsWhat is unknownMechanism of clinical malaria susceptibility Impact on asymptomatic malaria
et al 2016, 2.
et al. 2016Slide6
Goals of this studyWhat is the impact of discontinuing CPT on Clinical susceptibility to malaria infectionAsymptomatic malaria infectionUsing data from an on-going clinical trialSlide7
Study site and settingNdirande Health Centre, Blantyre, MalawiParticipants selected from:
randomized, open-label controlled trial of daily
cotrimoxazole or weekly chloroquine among adults on ART Small subgroup selected for immunology sub-studySlide8
Cohort selection from TSCQParticipants from the CPT and No CPT arm
Non-pregnant adults aged ≥18 years
≥6 months on ART and CPT
Clinically stable: no acute illnessEvidence of successful ART and immune recoveryHIV viral load <400 copies/ml, CD4 count >250 cells/mm3Slide9
Study proceduresFollow up: every 4 weeks for 6 monthsAlso evaluated when sickData collectedHistory: Malaria symptoms or signs,
Examination: malaria signs Diagnostic specimensBlood smear if symptoms of malaria were presentDried blood spots on filter paper for qPCR at every visitSlide10
Molecular detection of malariaQiagen extraction of dried blood spots on Whatman 3M filter paperReal-time PCR detection of P. falciparum 18s rRNA geneStandard curves evaluated for each runSlide11
Outcome definitionsClinical malariaMalaria symptoms plus positive blood smearAsymptomatic malariaNo malaria-like symptoms plus positive Real-time PCRSlide12
Baseline characteristics were similar between groups
Study profileEnrolled: 61
Accrued: 17 PYO
# F/paper analyzed
Accrued: 14 PYO
Clinical: 1 case
# F/paper analyzed
Clinical and asymptomatic malariaClinical malaria6/100 PYO (CPT) vs 29/100
CPT)Incidence rate ratio 5.0 [95%-CI 0.5 to 246.4]No episodes of asymptomatic malaria detected in either groupSlide15
Discussion: Clinical malariaMore episodes of clinical malaria in the “no CPT” group Difference not statistically significant Small sample size
Results of clinical disease incidence confirm previous findingsSlide16
Discussion: Asymptomatic malariaNo episode of asymptomatic malaria detectedAll infections manifested clinicallyUnusual in BlantyreRecent adult population survey
% (120/2613) parasitaemia prevalence by qPCRAll most all were asymptomatic5 Walldorf et al. - 2015Slide17
Does CPT impact malaria immunity?CPT successfully prevented most Malaria infectionsWe expected to find some degree of asymptomatic malaria Demonstrated by surveillance studies in same areaHowever, all malaria infection → symptomatic disease
By preventing malaria, CPT may have impacted immunity to malaria disease.
Rebound effect described in some but not all previous prophylaxis studiesSlide18
Strengths and limitationsStrengthsDetailed clinical and laboratory data from RCT settingGood active and passive malaria surveillance
Sample sizeLow transmission areaDid not measure malaria immunitySlide19
ConclusionCPT discontinuation after long term useAssociated with increased risk of clinical malariaNo infections were asymptomatic
immunityFinal analysisHigher power with inclusion of more TSCQ study participantsExplore impact on malaria immunityPlan to evaluate serological responseSlide20
Ndirande Health Center
participantsBlantyre Malaria Project Study nurses led by M. Funsani Study clinicians led L. KhondeLaboratory led by R.