Newborn Sickle Cell Screening

Charles Kiyaga MSc, MPhil

National EID/NBS Coordinator

Central Public Health Laboratories

Ministry of Health – Uganda

Early Infant HIV Diagnosis (EID) Program

served as a Precursor for Sickle Cell NBS

• The national EID program targeting HIV exposed infants started in 2006 working

with 8 partner run laboratories with molecular capacity.

• To make the program more efficient and cost effective, the Ministry of Health

decided to consolidate the labs into one managed under the public system in 2011.

• To make the centralized EID lab accessible a sample transport network was

formed.

• This improved efficiency and reduced TAT from 2 months to 2 weeks, reduced the

unit cost per test from $40 to $18, and improved MOH oversight and coordination

of the program

The National Sample Transport System

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In order to increase access to the central EID laboratory, and quality lab services in general,

MoH decided to invest in a sample transport system. This system involves setting up local area

networks centered around major hospitals, and health centers which we called hubs.

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Route

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DNA PCR

Laboratory

HUB

• Each hub operated with in 30 to 40km radius reaching 25 to 35 health facilities

• Each hub is given a motorbike and a rider who through scheduled routes visits 5 to 8 health

facilities a day picking sample and dropping results of the previous visit.

• The hub will run those tests they have capacity for, and refer highly specialized ones to CPHL

• Map of Uganda with the total 100 functional

hubs, reaching over 3000 health facilities

which is over 90% of national coverage.

Structure of the hub network Map showing current Hub Distribution

The bike and rider given to each hub

The Hub-based National Specimens and Result

Transportation Network

Sickle Cell Disease in Africa and Uganda

Uganda

•Population: 36 million

•Birth rate: 1,600,000 per year

•Sickle prevalence is very high

•Estimated ~20,000 births/year

•However, 80% are dead by 5yrs

•Contributes ~15% of the U5MR

Piel FB, et al. Nat Commun 2010;1:104

Multiple origins with Africa and

also the Arab-Indian region

Inheritance of a single sickle

mutation (one parent) is sickle trait

and protects against malaria

Inheriting two sickle mutations

(from both parents) causes

homozygous sickle cell disease

400,000 babies with sickle cell

disease are born each year and

most are in sub-Saharan Africa

70 to 80% don’t live to see their 5th

birthday.

Sickle Cell Challenges in Uganda

• Limited data regarding the sickle cell burden

• Lack of knowledge among healthcare workers and

public, not recognized or accurately diagnosed

• Not on non-communicable disease agenda

• No national policy and strategy

• No newborn screening, lack of access to care

Sickle Cell Survey Proposal

• Establish Partnerships

MOH/CPHL, Makerere University

Cincinnati Children’s Hospital

• Country-wide surveillance study

Map the burden of SCT and SCD

Build local capacity, raise awareness

Ride on the already existing EID infrastructure

• Surveillance Study � sickle cell newborn screening

Sickle Cell Laboratory

Space at the CPHL was renovated and fully equipped

Laboratory set-up and training of CPHL personnel by

Cincinnati team, plan for ongoing training and monitoring

Short-term goals to build local capacity and determine

feasibility for high-volume testing

In February 2014, the Sickle Cell Laboratory was opened

Uganda Sickle Surveillance Study

Primary objective was to describe the current prevalence

and distribution of SCD in Uganda

We hypothesized that there is a large sickle cell burden

across Uganda, but with substantial geographic variability

Design and Methods:

•One year cross-sectional study

•Use dried blood spots collected in EID program

•Perform hemoglobin electrophoresis using isoelectric

(IEF) technique on 75,000-100,000 samples

US3 Results

~100,000 samples

Overall 13.3% trait

Overall 0.7% disease

High burden districts

Comorbidities: HIV, Age

Allows targeted screening

Highest Prevalence Districts

• 49 of the 112 districts have sickle cell trait >15.0%

• 8 districts have sickle cell trait >20.0%

• 14 districts contain 47% of the sickle cell disease

• Screening should focus on highest burden regions

Sickle Cell Newborn Screening

Where to begin screening?

•12-14 highest burden districts

•Mid Northern and Central regions

•Maternity wards for in-hospital births

•Healthcare facilities, immunization clinics

Whom to screen?

•All newborns within the hub

•Include children under 2 years in

high burden districts

Sickle Cell Training

West Nile

SCT 13.8%Mid Northern

SCT 19.2%North East

SCT 15.8%

Training at regional referral hospitals:

•1 full day of training per site

•Coordinated through sample

transport hub system

•Invite physicians, nurses, lab

techs, sample transport

coordinators

•Comprehensive sickle cell

curriculum developed

•Establishment of a local sickle cell clinics in targeted

sites

Targeted Screening Results

West Nile

SCT 13.8%Mid Northern

SCT 19.2%North East

SCT 15.8%

• Since the completion of the US3 study, 12 hub sites have now received sickle cell training and have begun targeted sickle cell screening

• Over 35,000 samples have been collected on children <2 years of age, from high-burden districts using the EID sample transport system

• ~20% sickle cell trait is confirmed in the East Central and Mid Northern regions of Uganda, with >1% disease

• Co-morbidity with HIV is supported by our new data

• Site training and follow-up training occurs with support of PerkinElmer and Cincinnati Children’s Hospital

Next Steps: Sickle Cell Laboratory

The new Uganda National Sickle Cell Laboratory:

•High efficiency

• ~2,000 samples per week)

• >99% accuracy for trait and disease

•Runs samples 5 days/week

•Doubled capacity in equipment, space,

and additional personnel

•Targeted screening from high-burden

districts and all HIV+ samples

•Beginning DNA-based diagnostics

Long-Term Goals in Uganda

West Nile

SCT 13.8%Mid Northern

SCT 19.2%North East

SCT 15.8%

• Continue scaling up targeted screening in high-burden

districts

• Improve clinical care with district hospital clinics but

also incorporate sickle cell into primary health care

• Increase public awareness by media and ad campaigns

• Establish national guidelines and encourage MOH to

write formal national sickle cell strategy

• Universal sickle cell screening with appropriate

intervention, education, and treatment

• Use sickle cell screening as a precursor for other NBS

interventions

End

Acknowledgements

•Thanks to our collaborating partners Cincinnati

Children’s Hospital based in the US for the

technical and logistical support

•Thanks to Perkin Elmer for the logistical

support.

•To Makerere University for supporting the

study