Schistosoma mansoni and HIV-1 infection: Is there any association?

Humphrey D. Mazigo, PhD

Global adult prevalence of HIV and schistosomiasis (Bastinduy et al., 2014)

• Globally, 35.3M (≥15 years) are infected with HIV-1 infection, of these, 23.5M (68%) live in SSA (UNAIDS.,2013)

• Globally, 779M in 76 countries are at risk for schistosomiasis and 207M are infected, 90% live in sub-Saharan Africa (Steinmann et al.,2006; Hotez et al., 2007)

INTRODUCTION

• The DALYs lost due to schistosomiasis are estimated at 4.5M

• The DALYs lost due to HIV infection is >80M• Combined DALYs results into significant morbidities and mortalities

Global burden of diseases

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“The big three”

Neglected tropical diseases (NTDs)

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Hotez et al. (2006)

Hotez et al.,2006; 2014

Schistosomiasis in Tanzania• Two spp S. mansoni and S. haematobium are endemic and widely spread in country

• S. mansoni is wide spread along the large water bodies

• S. haematobium is mainly in small water bodies

• National prevalence: 52% but varies between regions

• Health effect of S. mansoni infection: Peri-portal fibrosis, hepatomegaly, splenomegaly and hepatosplenomegaly and death associatted with portal hypertension, oesophageal varices and hemetemesis

Mazigo et al., 2012; Rollinson et al., 2012

Life cycle of Schistosomiasis

HIV-1 in Tanzania

• National prevalence is 5.2% and varies

between regions

• Age: 15 – 49 yrs – 5%

• Sex: Female 6% and males 4%

• Residential: Urban 7% vs rural 4%

• Fishing villages along the Lake Victoria

shores marked as highly risk groups

THMIS: 2013/14

HIV-1 and S. mansoni co-infections

•Because of the overlap of HIV-1 and S. mansoni in SSA, half of 25M HIV infected individuals may be co-infected (Secor 2000: Bentwich et al., 2000)

•Hypothesis:- co-infection of HIV-1 and S. mansoni may enhance virulence of each other within a co-infected host (Lawn 2001; Wolday 2002)

•But, the role played by concurrent HIV-1 infection as accelerating factor for S. mansoni infection, related morbidities and PZQ treatment outcome remain a topic of further studies

HIV-1 and S. mansoni co-infections

The effects of HIV-1 on schistosomiasis

CD4+ T cell reductions by HIV-1:- - Alters eggs excretion efficiency (Karanja et al., 1997)

- Decrease fibrogenesis, hence, severe hepatic morbidities (Mwinzi et al., 2001)

- Increases susceptible to re-infection with Schistosomes (Karanja et al., 2002)

- Low CD4+ T cell counts are associated with reduced levels of eosinophils which are necessary for resistance to repeated schistosomal infections (Ganley et al., 2006)

HIV-1 and S. mansoni co-infections

The effects of schistosomiasis in HIV-1

• Infections with schistosomes cause chronic stimulation of the immune system with a strong bias towards Th2 CD4+ response (Pearce et al., 1991).

• Th2 response to Schistosomes Ag down-regulates Th1-type responses which are necessary for efficient antiviral CD8+ CTL prod.(McElroy et al., 2005).

• HIV replicates more rapidly in activated T cells with Schistosomes Ag and CD4+ T cells lines are more easily affected than Th1 (Lawn et al., 1991).

• In Ethiopia, a study of HIV-1 infected and uninfected, helminth infection was associated with increased T- cell activation (Kassu, 2003).

• In HIV-uninfected indiv. increased T-cell activation make them more susceptible to HIV infection (Kassu, 2003).

Is S. mansoni associatted with HIV-1 infection

Is S. mansoni associatted with HIV-1 infection

Odd of developing immunological failure were 4 times greater in patients with SM/HIV-1 co-infection

Is S. mansoni infection associated with HIV infection?

Does PZQ treatment have impact on HIV-1 markers?

Factors associated with S. mansoni infectionVariable No. infected Prevalence (%) CPR APR

Sex

Female 382 40.29 1 1

Male 472 56.14 1.39(1.26-1.54) 1.27(1.14-1.42)

Occupation

SME 129 44.14 1 1

Peasants 561 45.11 1.02(0.89-1.16) 1.06(0.86-1.24)

Fishing 164 66.28 1.52(1.42-1.59) 1.27(1.06-1.53)

Village

Igombe 176 40.42 1 1

Igalagala 141 55.47 1.37(1,31-1.44) 1.31(1.12-1.52)

Kayenze 351 54.24 1.34(1.24-1.44) 1.32(1.15-1.51)

Sangabuye 186 41.24 1.02(0.88-1.78) 1.06(0.89-1.25)

HIV-1

Negative 804 48.12 1 1

Positive 50 39.52 0.92(0.78-1.09) 1.01(0.84-1.21)

Factors associated with intensities of S. mansoni infection

Intensity of S. mansoni infection was not associated with HIV-1 infection

(AOR = 0.84,95% CI; 0.56 – 1.25)

• The intensity of S.mansoni infection was associated with :- Male gender (AOR = 1.65,95% CI; 1.32-2.08, P<0.0001)

Young ages (21–30yrs; AOR = 1.68,95% CI; 1.14-2.48,P<0.01)

Involvement in fishing activities (AOR = 1.62,95%CI; 1.10-2.41, P<0.01)

Being illiterate (AOR = 1.33,95% CI;1.07 – 1.66, P<0.014)

Living in the study villages.

- Igalagala – (AOR=1.71,95%CI;1.23-2.40)

- Kayenze – (AOR=1.62,95%CI;1.23-2.13)

- Sangabuye – (AOR=1.38,95%CI;1.001-1.89)

Association between immune status and S. mansoni infections

Prevalence of PPF

The overall prevalence PPF (grades C-F) was 14.78%:

- 29.55% were grade C, 52.63% (130/247) D,14.17% (35/247) E

and 3.64% (9/247) were grade F

In relation to S. mansoni infection, of the individuals detected with PPF,

52.23% (129/247) had detectable eggs

PPF prevalence did not differ by prevalence (P=0.10) and infection

intensities of S. mansoni based on egg count (epg) (P=0.11)

Results

In relation to HIV-1 infection, 13.79% and 15.01% of the HIV-1

infected and uninfected individuals had PPF (P=0.72)

HIV-1 infected: n=4 had grade C, n = 8 had grade D and n = 4 had

grade E-F

Factors associated with PPF:-

Male gender (AOR = 2.27, P< 0.001), Age group 21–30 years (AOR = 2.45, P< 0.028) Residential time, 11–20 years (AOR = 3.52,P< 0.01) and ≥21yrs

(AOR =2.66,P< 0.01)

Comparison of the height adjusted mean deviations of organs in relation to infection with S. mansoni and HIV-1 infection status

In relation to HIV-1

OrganomegalyHIV-1 serostatus

F-ratio P-valuesHIV-1 negative infected with S. mansoni (N= 790) deviations from mean (95%CI)

HIV-1 positive co-infected with S. mansoni (N= 50) deviations from mean (95%CI)

LiverLeft liver lobe size 2.23 (2.11 – 2.36) 2.79 (2.23 – 3.37) -2.0702 0.039

Spleen

Spleen size 1.21 (1.08 – 1.34) 1.57 (1.14 – 2.00) -1.3664 0.17

Portal vein Diameter

Portal vein size 1.04 (0.97 – 1.12) 0.92 (0.69 – 1.16) 0.8072 0.42

The no correlation was observed (r=-0.16, P=0.084)

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3 4 5 6 7CD4+ cell counts (x 100cells/microLitre)

Fitted values Schistosoma mansoni GMepg(log +1)

Correlation between left liver lobe sizes and CD4+ in co-infected individuals

Predictors of left liver lobe hepatomegaly, splenomegaly and hepatosplenomegaly

• Left liver lobe measurements:- the age of the study participants (P<0.038), malaria infection (P<0.038) and intensities of S. mansoni infection (P<0.01). HIV-1 infection was not (P=0.069)

• Spleen measurements:- being male (P<0.002), fishing occupation (P<0.05), village of residence (living in Kayenze village, P<0.039 and Igalagala village, P<0.005), being infected with malaria parasite (P<0.018) and HIV-1 infection (P<0.05)

• Hepatosplenomegaly:- village of residence (living at Sangabuye village, AOR=2.09, P<0.022, Kayenze village, AOR=1.83, P<0.04: Igalagala, AOR=2.49, P<0.023) and being heavily infected with S. mansoni infection (AOR=1.13, 95%CI; P<0.041)

Objective 3a

Parasitological cure rates in relation to HIV-1 serostatus

• Overall parasitological cure rate: 61.80% (n=343/555)

• HIV-1 negative: 526 infected with S. mansoni at baseline, cure rate: 62.19% (329/555)

• HIV-1 + S. mansoni:- cure rate: 48.28% (14/29)

• No significance difference (P= 0.12)

Parasitological cure rates in relation to CD4+ cells counts

• Co-infected with CD4+ cell counts <350cells/µL: cure rate

43.75%(7/16)

• Co-infected with CD4+ cells counts ≥ 350cells/µL: cure rate: 66.67%(8/12).

Comparison of HIV-1 viral loads, CD4-Th2-lymphocytes and effects of praziquantel treatment among adults infected or not with S. mansoni in fishing villages of North-Western Tanzania. Infectious Diseases of Poverty

Results

Variables HIV-1 only (n=22) HIV-1 + S. mansoni

co-infected (n=28) F-test P-values

HIV-1 viral load (Mean log10 RNA copies/ml of plasma)

Baseline 5.98 ± 3.06

(95%CI: 4.79 – 7.17)

9.21 ± 1.91

(95%CI: 8.36 – 10.06)t =-4.72553 0.0001**

3 month 8.19 ± 2.17

(95%CI: 7.35-9.03)

9.44 ± 1.99

(95%CI: 8.55 – 10.32)t= - 2.0892 0.042**

6 month 10.49 ± 1.29

(95%CI: 9.99 – 10.99)

10.59 ± 1.44

(95%CI: 9.96 – 11.24)t= -0.2714 0.79

Conclusion

S. mansoni-related PPF, liver and spleen enlargements occur in the study population and with similar grades observed among co-infected and in S. mansoni only infected individuals

HIV-1 infection or CD4+ levels was not associated with increased risk of heavy intensity of S. mansoni infection or severe organomegally and had no effect on PZQ treatment outcomes

PZQ treatment had a significant effect on prevalence, intensity of infection and S. mansoni related morbidities but did not lead to any changes on CD4+ cell counts and plasma viral loads

No association between S. mansoni and HIV-1 infection. Further study are needed

Asanteni