Seroprevalence of HBV and HCV among Children in the

Kilimanjaro Region, TanzaniaFlorida J. Muro, Suzanne P. Fiorillo, Christopher Odhiambo,

Coleen K. Cunningham, Ann M. Buchanan

KCMC-Duke CollaborationMoshi Tanzania

XIX International AIDS Conference, Washington, DC24 July 2012

Kilimanjaro Christian Medical CentreMoshi, Tanzania

BackgroundMore than 350 million people worldwide are infected

with hepatitis B virus (HBV), 170 million with hepatitis C virus (HCV)

HBV and HCV are more prevalent among HIV-infected individuals

HIV increases the speed of liver dysfunction among those with co-infection

Liver disease due to chronic hepatitis: increasing cause of morbidity and mortality among those with HIV

BackgroundChronic HBV infection risk:

up to a 90% risk with perinatal infection

25-30% risk with early childhood infection

< 5% risk among adults

HCV infection: chronic infection in 75-80% of adults

Data on hepatitis-HIV co-infection among African populations are scarce

Background

Three phases of chronic HBV infection:

Phase HBsAg HBeAg HBV DNA ALT FibrosisImmune Tolerant

Pos Pos High Nml No

Immune Active

Pos Pos High High Yes

Inactive Phase

Pos Neg Low Nml No

Children are typically in the immune tolerant phase.

ObjectiveTo determine Hepatitis B and Hepatitis C

prevalence in healthy HIV-negative and HIV-infected children in Kilimanjaro Region, Tanzania

MethodsBanked serum/plasma samples

HIV-uninfected, healthy children: 1 month -18 years N=385

HIV-infected children on HAART, 1-16 years N=158

HBV testing:Hepatitis B surface ag (HBsAg)Hepatitis B core antibody (HBcAb)Hepatitis B surface antibody (HBsAb)

Study Location: Moshi, Kilimanjaro Region, Tanzania, East Africa

Methods

HCV testing:Anti-HCV ELISA

Validation studies performed on all assays prior to useAll assays FDA-approvedDefinitions:

Any prior HBV infection: HBcAb or HBsAg +

Presumptive chronic HBV infection: HBsAg + at time of test

Results

543 serum/plasma samples tested385 HIV-negative158 HIV-infected

Evidence of any HBV infection: 4.2% (95% CI: 2.5, 5.9)Among HIV-negative children: 2.1%

(95% CI: 0.6, 3.5)Among HIV-infected children: 9.5%

(95% CI 4.9, 14.1)

Results

Children with HIV infection were more likely to have evidence of HBV infection

than HIV-negative children:

OR 4.9 (95% CI 2.1, 11.9)p < 0.0001

Results

*These 2 patients were HBcAb and HBsAb positive, likely reflecting maternal antibody transmission

Evidence of any HBV Infection by HIV Status and Age Group

Age < 12 months ≥ 1 < 5 years ≥ 5 < 13 years ≥13 <18 years

HIV-positive 0/1 (0.0%) 4/31 (12.9%) 9/109 (8.3%) 2/17 (11.8%)

95% CI -- (0.4, 25.4) (3.0, 13.5) (0.0, 28.8)

HIV-negative 2/41 (4.9%) 0/106 (0.0%) 2/150 (1.3%) 4/88 (4.5%)

95% CI (0.0, 11.8) -- (0.0, 3.2) (0.1, 9.0)

Overall 2*/42 (4.8%) 4/137 (2.9%) 11/259 (4.2%) 6/105 (5.7%)

95% CI (20, 11.5) (0.1, 5.8) (1.8, 6.7) (1.2, 10.2)

Results

Prevalence of presumed chronic HBV infection: 3.0% (1.6, 4.5) Among HIV-negative children: 1.3% (0.2, 2.5) Among HIV-infected children: 7.5% (3.2, 11.9)

Resolved infection (HBcAb and HBsAb positive) was found in 5 patients: 2 HIV-infected and 3 HIV-negative

Isolated HBcAb was found in two patients Hepatitis C: 541 samples tested by anti-HCV ELISA

0.0%

ResultsCharacteristics of HIV-Infected Children with and without Evidence of HBV-Coinfection

Patient Characteristics HBV Pos(n=15)

HBV Neg(n=143)

P-value

Mean (SD) Age, years 8.9 (3.8) 8.6 (3.6) 0.7

Female Gender, # (%) 7 (46.7%) 67 (46.9%) 0.9

Mean (SD) CD4 lymphocyte count 814 (434) 1,000 (566) 0.3

Mean (SD) CD4 percent 26.2 (9.4) 29.4 (8.9) 0.3

Lamivudine-containing HAART, # (%) 12 (80%) 119 (88.8%) 0.3

Results

< 12 mos ≥1 < 5 yrs ≥5 < 13 yrs ≥13 <18 yrs0

102030405060708090

HBV Protection by HBsAb+

N=138

N=259N=105

N=44

Conclusions

HCV was not found in this large pediatric cohort

HBV prevalence is high among HIV-infected children in the Kilimanjaro Region of Tanzania

Children with HIV are almost 5 times as likely to show evidence of infection than children without HIV

Conclusions

The prevalence of chronic HBV-HIV co-infection in this population (7.5%) is higher than that reported recently in many other pediatric populations: 3.3% Thailand 4.9% China 4% Kenya 1.2% Dar es Salaam, Tanzania

Though lower than some other African countries: Nigeria (7.7%) Namibia (8.7%) Ivory Coast (12.1%)

ConclusionsHigh prevalence of HIV-HBV co-infection in this

pediatric population Need for routine HBsAg screening of all HIV-infected

children Prior to HAART initiation

More comprehensive prevalence data needed – across all age groups

Prevention of HBV could be strengthened by wider vaccination coverageVaccinate high risk childrenBirth dose?

Limitations

Chronic hepatitis B could not be confirmedSamples tested at a single timepoint

Larger sample size needed to determine true prevalence of HIV-HBV co-infection among children in this region

The significance of isolated HBcAb in two patients is unclear

No measurement of HBV DNA

Further StudyFollow up study planned for a larger prospective study

of HIV-infected childrenUnanswered questions:

Best treatment options for HIV-HBV infected children?Already on HAART?

Immune tolerant disease Immune active disease

Initiating HAART? Immune tolerant disease Immune active disease

Acknowledgements

Co-authors: Florida Muro, Chris Odhiambo, Suzanne Fiorillo, Coleen Cunningham

Duke University Center for AIDS Research (CFAR)2010 developmental grant (5P30 AI064518) (AM

Buchanan)Duke Global Health Institute

Transition Award (FJ Muro)Kilimanjaro Christian Medical Centre LeadershipPatients and families in the Kilimanjaro Region