Fig 1.
Flow chart of study population.
Chart shows the selection of patients for this case-control study, nested within a previous prospective study on HIV-schistosoma co-infection. A number of Schisto-IRIS patients (17/26) were excluded due to sample or data issues, resulting in 9 patients selected with clinical data and non-haemolitic samples available at each time point. Additional Schisto+HIV+ (n = 9) and Schisto-HIV+ (n = 9) patients were randomly selected as controls, except for allowing comparable gender distribution between groups.
Fig 2.
Chart shows a time line of patient follow-up during the study. Before enrolment, adult HIV+ patients who were ART naïve and receiving voluntary counseling and testing (VCT) were screened for TB, malaria and hepatitis B virus (HBV), and soil transmitted helminths (STH). Patients then underwent clinical and lab-investigations at baseline (i.e. prior to starting ART and PZQ treatment), and at 2 weeks, 1 month and 3 months after starting ART. Additional screening for signs of S. mansoni infection by ultrasound were performed at baseline and month 3. aPatients initiated ART and PZQ treatment in close proximity to each other, prior the week 2 visit. Since patients had to be referred to the ART-treatment center, some patients received PZQ before starting ART and some shortly after. bKato Katz smear was performed at each visit by performing 2 smears on 1 stool sample for quantitative evaluation of S. manoni, Ascaris lumbricoides, Trichuris trichuria, hookworm, while S. haematobium eggs were evaluated by a urine filtration method.
Table 1.
Working case definition of paradoxical Schistosoma-IRIS with S. mansoni.
Table 2.
Provisional case definition of unmasking Schistosoma-IRIS in patients with ART-associated Schistosomiasis due to S. mansoni.
Fig 3.
Graph shows CD4 counts before and during ART in Schisto-IRIS patients (red circles), Schisto+HIV+ controls (blue triangles) and Schisto-HIV+ controls (green squares). The significant change over for each patient group was calculated using the Friedman test (p-values shown in graphs), with Dunn’s multiple comparison post-hoc tests to indicate differences between time points (indicated by horizontal bars with an asterisk). B = baseline, W2 = week 2, M1 = month 1, and M3 = month 3.
Fig 4.
Correlation of treatment interval with onset of IRIS.
Graph shows a correlation between ART-PZQ interval and onset of IRIS symptoms (#days since ART initiation), negative values indicate PZQ treatment prior to ART and dotted line represents 0 days interval.
Table 3.
Clinical characteristics of study population.
Table 4.
Description of symptoms in Schisto-IRIS patients.
Fig 5.
Time analysis of MMPs and TIMPs.
Graphs show plasma levels of (A) MMP-1, (B) MMP-7, (C) MMP-10, (D) TIMP-1, and (E) TIMP-2 before and during ART in Schisto-IRIS patients (red circles), Schisto+HIV+ controls (blue triangles) and Schisto-HIV+ controls (green squares). The significant change over time for each patient group was calculated using the Friedman test (p-values shown in graphs), with Dunn’s multiple comparison post-hoc tests to indicate differences between time points (indicated by horizontal bars with an asterisk). B = baseline, W2 = week 2, M1 = month 1, and M3 = month 3.
Table 5.
Plasma levels of MMPs & TIMPs during follow-up of 3 patient groups.
Fig 6.
Time analysis of CRP, I-FABP and sCD14.
Graphs show plasma levels of (A) CRP, (B) I-FABP and (C) sCD14 before and during ART in Schisto-IRIS patients (red circles), Schisto+HIV+ controls (blue triangles) and Schisto-HIV+ controls (green squares). The significant change over time for each patient group was calculated using the Friedman test (p-values shown in graphs), with Dunn’s multiple comparison post-hoc tests to indicate differences between time points when applicable (indicated by horizontal bars with an asterisk). One Schisto-HIV+ patient did not have sufficient sample volume for CRP determination. B = baseline, W2 = week 2, M1 = month 1, and M3 = month 3.
Table 6.
Plasma levels of TIMPs, CRP and I-FABP during follow-up of 3 patient groups.
Fig 7.
Time analysis of 8 anti-nuclear antibodies.
Graphs show semi-quantitative values of plasma levels of ANAs, calculated as a ratio of positive cut-off control (index value). Index values of (A) U1 snRNP, (B) snRNP/Sm complex, (C) Sm, (D) SS-A, (E) SS-B, (F) Scl 70, (G) CenpB and (H) Jo-1 before and during 1 month of ART are shown in Schisto-IRIS patients (red circles) and Schisto+HIV+ controls (blue triangles). The significant change over time for each patient group was calculated using the Wilcoxon-signed rank test (p-values shown in graphs). B = baseline, M1 = month 1.