Sickle cell disease (SCD) is highly prevalent in sub-Saharan Africa, including Lesotho where it accounts for substantial morbidity and mortality. SCD is a life-threatening genetic disorder that is best managed when diagnosed early by newborn screening. The incidence and cases are not reported in Lesotho. Newborn screening which is paramount for early diagnosis and enrolment of affected children into a comprehensive care programme is not available in Lesotho. Up to now, this strategy has been greatly impaired in resource-poor countries, because screening methods are technologically and financially intensive; affordable, reliable, and accurate methods are needed. We aimed to test the feasibility of implementing a sickle cell disease screening programme using innovative point-of-care test devices into existing immunization programmes in primary health-care settings. Goal; increase sickle cell disease awareness, diagnosis and management in Lesotho from 0- 20% by 25% Mission: To improve care of all Sickle Cell Disease patients for their better future and to lower the prevalence of the disease through multi=sectoral, multi-faced coordinated approach towards screening and awareness strategies Vision: Eliminate sickle cell disease as a public health problem in Lesotho. There is need for increasing the awareness about the disease in the community, implementation of mass screening activities for early identification, building a strong network of diagnosis and linkages, implementing robust monitoring system, strengthening the existing primary health care mechanism to incorporate SCD related strategies, capacity building of primary, secondary and tertiary health care teams and building cost-effective intensive interventions at higher care facilities.

1. Sickle cell disease
Sejojo Phaaroe FIBMS(UK) ; MGSc: CT(IAC) : MLSc(CNAA ) Ie : AHMP(YALE);
+266 50468036
Registered Charted -Medical Scientist- UK
Cytologist - International Academy of Cytology #6467
NLP Practitioner (Neuroscience ) GSF
Lead , Technical Assessor and Master Trainer- ISO15189 SADC -EU.
SADCAS Technical Advisor- ISO17025

2. Learning Objectives
• At the end of this session participants are expected to be able to:
 Describe sickle cell disease and types of sickle cell anaemia
 Describe epidemiology, risk factors and pathogenesis of sickle cell disease
 Recognize clinical presentation of sickle cell disease
 Perform clinical and laboratory assessment of patients with sickle cell disease
 Diagnose SCD including awareness of the clinical and laboratory features of
the various forms of SCD.
 Guide SCD-affected families on how to maintain health and reduce the risk of
complications due to SCD.

3. Learning Objectives (2)
 Manage complications of SCD such as pain, fever, acute chest
syndrome, stroke, etc.
 Safely transfer those with severe complications to a higher level of
care
• Provide pharmacological and nonpharmacological treatment to
patients with sickle cell disease
• learn how to Implement referral pathway for patients with sickle
cell disease
• Conduct regular follow up monitoring to patients with sickle cell
• know why it is important to integrate sickle cell disease in to NCD
integration programs
• POLICIES AND REGULATORY FRAMEWORKS FOR NCDs INTEGRATION IN LESOTHO

5. HAEMOGLOBINOPATHIES-
Sickle cell and thalassemias are two types of genetic
blood disorders.
HAEMOGLOBINOPATHIES
SICKLE CELL THALASSIEMIA

6. Altered
amino acid (G-V)
altered protein
variant - betha
globulin
on chain
affected HGB
itseself
HB GENE
sickle cell
both alpha
betha chains
excess synthesis of
normal globulin
chain
disturbed globulin
sysnthesis rate
betha-globin gene
control production
of b globin
thalassimia

7. Definition of Sickle Cell Disease
• Sickle cell anemia is a genetic disorder whereby red blood cells are
abnormally shaped, causing problems with the flow of blood through the
body as well as transport of oxygen throughout the body
• inheritance is Autosomal because its a blood disorder and systemic disorder
• its caused by mutation on B-chain of the globulin chain , where red blood cells
(RBCs) become sickle/crescent shaped
• Cells get destroyed in narrowed thin blood capillaries , RE system and cause
anaemia Blockage in thin layers body

12. cell Disease-(SCD) in short
• Sickle Cell Disease-(SCD) is one of the disorders in a broad group of
hemoglobinopathies
• People with this disease have atypical hemoglobin molecules called
hemoglobin S, which can distort red blood cells into a sickle, or
crescent, shape.
cells are
sticky

13. Hemoglobin
• Hemoglobin is a tetramer composed of two α-globin and two non- α -globin chains
working in conjunction with heme to transport oxygen in the blood
• Normal adult hemoglobin (HbA) is designated αA 2 : βA 2
• Variant hemoglobin is derived from gene abnormalities affecting the α-globin genes
(HBA1 or HBA2) or β-globin (HBB) structural genes (exons)
• More than a thousand hemoglobin variants have been identified relative to changes
in the globin chains. in genomics
• Qualitative changes correspond to amino acid substitutions resulting in
hemoglobinopathies. in proteonomics
• Quantitative changes like amino acid insertions, deletions or mutations in the
intervening sequences (introns) correspond to thalassemia and result in decreased
globin chain production -NGS ADVOCACY

14. Inheritance of sickle cell disease
• People who have sickle cell anemia inherit two faulty
hemoglobin genes
• — hemoglobin S — from each parent.
• Sickle cell disease can also occur when a child inherits one
hemoglobin S gene from one parent and another faulty
hemoglobin gene,
• such as beta (β) thalassemia,
• hemoglobin C,
• hemoglobin D, or
• hemoglobin E, from the second parent.

15. • A person has sickle cell trait when they inherit hemoglobin S
gene from one parent and a normal hemoglobin gene
(hemoglobin A ) from the other.
• They are a carrier of the hemoglobin S gene and can pass it
on when they have a child.
• People who have sickle cell trait are generally healthy.

17. Sickle Cell Trait

18. Epidemiology
 Sickle gene originates from Africa and India
 Historically, it has been traced back to a Ghanaian family who suffered from signs and symptoms suggestive of SCD
in the year 1670 [1].
 It was, however, not until 1910 when Dr. James B. Herrick brought attention to a peculiar case of a dental student
who had what is now known as SCD [2].
 It is estimated that 5% of the world’s population carry genetic imprints responsible for hemoglobinopathies
(primarily sickle cell and thalassemia)
 its now spreading worldwide (1 per 625 live births in America, Medscape)
 Highest incidence are found in Subsaharan Africa, India and Middle East
 There is sickle cell in Lesotho 1989 ( Sejojo Phaaroe etal) DANIDA/WHO
 Median age to acquire renal failure is 23.1 years and life expectancy is 27 years regardless of dialysis (medscape) ie.
SCD

21. global burden
• Global Burden of Diseases, Injuries, and Risk Factors Study (GBD)
2021 --------assessment of prevalence of sickle cell disease and
mortality burden by age and sex for 204 countries 2000 to 2021.
• total births of babies with sickle cell disease increased globally by
13·7%
• The number of people living with sickle cell disease globally increased
by 41·4% (38·3–44·9), from 5·46 million (4·62–6·45) in 2000 to 7·74
million (6·51–9·2) in 2021

22. • COVID-19 has been a powerful reminder of the importance of integrated molecular disease surveillance systems
in advancing public health systems. Scientists from around the world have published open-source analyses of
next-generation sequencing data for SARS-CoV-2, the virus that causes COVID-19, collaborating to further track
the spread of the pathogen and to provide information for critical response efforts. In the coming months and
years, NGS will continue to contribute to better understanding of SARS-CoV-2 including how it may evolve over
time, which has important implications for vaccine and drug development.COVID-19 has been a powerful
reminder of the importance of integrated molecular disease surveillance systems in advancing public health
systems. Scientists from around the world have published open-source analyses of next-generation sequencing
data for SARS-CoV-2, the virus that causes COVID-19, collaborating to further track the spread of the pathogen
and to provide information for critical response efforts. In the coming months and years, NGS will continue to
contribute to better understanding of SARS-CoV-2 including how it may evolve over time, which has important
implications for vaccine and drug development. COVID-19 has been a powerful reminder of the importance of
integrated molecular disease surveillance systems in advancing public health systems. Scientists from around
the world have published open-source analyses of next-generation sequencing data for SARS-CoV-2, the virus
that causes COVID-19, collaborating to further track the spread of the pathogen and to provide information for
critical response efforts. In the coming months and years, NGS will continue to contribute to better
understanding of SARS-CoV-2 including how it may evolve over time, which has important implications for
vaccine and drug development.

23. AFRICAN
NO CASES
KNOWN
FOR

24. efforts for Lesotho
• Sickle cell disease mortality burden is highest in children, especially in countries with
the greatest under-5 mortality rates
• establish comprehensive NCDs integration strategies to address morbidity and
mortality associated with sickle cell disease, attainment of SDG 3.1, 3.2, and 3.4
• provide community engagement strategies, health education, family pedigrams ,
multi-sectoral inteventions. eg in early childhood programs
• urgent need for routine and sustained surveillance efforts in Lesotho
• data management to fill Widespread data gaps
• Global organisational efforts to fight diseases, such as measles and tuberculosis,
have contributed to cause-specific mortality declines in children younger than 5
years, yet sickle cell disease has had no such global push
• further research to assess the contribution of conditions associated with sickle cell
disease, and widespread deployment of evidence-based prevention and treatment
for those with sickle cell disease

25. • Universal newborn screening combined with preventive treatment is
feasible and effective even in low-resource locations like Lesotho.
• Early diagnosis of sickle cell disease to allow for risk mitigation and
early treatment intervention, which most likely explains some
improvement in survival

27. Pathogenesis 1
 SCD is caused by a point mutation at position 6 of the beta haemoglobin
gene in which a hydrophilic glutamic acid is replaced by valine
 The susceptible RBCs once subjected to an oxygen tension of <40mmHg
for about 2-4 minutes they become deoxygenated
 HYPROXIA

31.  Deoxygenated haemoglobin undergoes hydrophobic interaction with adjacent sickle
haemoglobin forming large polymer and thus RBC becomes less deformable and acquire
sickle shape
 Rigid RBCs obstruct microvasculature causing tissue hypoxia which precipitates further
sickling
 Sickle cells rapidly haemolyze and have a life span of about 10- 20 days IN STEAD OF 120
DAYS
 The initiation of polymerization may be incomplete and reversible if re-oxygenation occurs
early in the process
 Repetitive exposure to alternating deoxygenated and oxygenated states can lead to
membrane distortion, oxidative damage and irreversible sickling

32. L
RAAS= regulates blood pressure by increasing sodium (salt) reabsorption,
water reabsorption (retention) and vascular tone (the degree to which your
blood vessels constrict, or narrow)
LOW O2 TENSION
STIMULATES
ERYTHOPOETIN

34. Organ Systems Involved
The renin-angiotensin-aldosterone system is ubiquitous with the
involvement of multiple organ systems, especially the kidneys, lungs,
systemic vasculature, adrenal cortex, and brain

35. Clinical Spectrum of SCD

36. Signs and symptoms
• Signs and symptoms of sickle cell disease usually begin in early childhood.
• Characteristic features of this disorder include a low number of red blood
cells (anemia), low wwc
• periodic episodes of pain. --vascular integrity
• The severity of symptoms varies from person to person( mild , moderate ,
severe)
• It causes frequent infections,
• swelling in the hands and legs, pain,
• severe tiredness, and delayed growth or puberty.

37. signs and symptoms of sickle cell anemia vary
between individuals.
• Some of the commonly noted symptoms include:
• Irritability or fussiness in babies
• Severe fatigue or tiredness
• Frequent episodes of pain, also known as crises, in different parts of the body
• Swelling of hands and feet, associated with pain
• Frequent infections
• Delayed growth noted in children and adults
• Vision problems

38. Clinical Manifestation of Sickle Cell Disease
 Chief cause for admission of patients is Sickle cell crises
 This includes the following:
• Vaso-occlusive crisis
1. Pain Crisis---------------------pain
2. Splenic sequestration-----------------splenomegaly
3. Acute Chest Syndrome----------pain
4. Aplastic Crisis--------------------anaemia
5. Hemolytic Crisis------------------ blood fragidity , bilirubin ,

39. Clinical Manifestation of Sickle Cell (2)
 The most common clinical manifestation is pain, which occurs unpredictably and is often excruciating
 Acute manifestations that may rapidly become life-threatening include
 bacterial sepsis ( b-hemolytic strep, stapplococus, other enterobacteriacae , )
severe anaemia,
acute chest syndrome,
and stroke
 Other acute complications include
 aplastic crises and
 priapism ---

42. pressure and
flow mechanics

45. Pediatric Problems
• All children presenting with
unexplained acute illness
• acute neurological symptoms,
• loss of vision,
• collapse,
• respiratory symptoms,
• hepatosplenomegaly,
• jaundice,
• swollen limbs,
family history of SCD and sepsis
should be tested for SCD

46. aplastic anemia

48. SCD
differential diagnosis
• Hereditary spherocytosis
• Thalassaemia
• toxic haemolytic anaemia- β strepp, staff , clostridium welshi, other
infections e.g TB, syphilis
• malnutrition
• malaria - protozoal infection
• Legg-Calve-Perthes disease
• k+ cloride, lead,sulphonimides,naphtalene, glyphosate chemical
poisoning
• medication; Methyldopa,nitrofurantoin, phenylhydrazide,
• G6P Deficiency
• HDNB Combs antibodies -
• cancer- wilm tumour , leukemia,
• SLE
• certain plants extracts- and traditional medicines concoctions - vicia
vara,
• polycythaemia vera
• hemoglobinuria
• paroxymal hemoglobinuria

50. - Causes of Nephrotic Syndrome - in SCD
• Usually caused by damage to glomeruli in the kidneys as a result
of certain diseases such as:
• Minimal change disease (a kidney disease)
• Focal segmental glomerulosclerosis
• Membranous nephropathy
• Diabetic kidney disease
• Systemic lupus erythematosus
• Amyloidosis
• Blood clot in a kidney vein
• Heart failure

51. The risk factors :
• Certain medical conditions such as diabetes, lupus, amyloidosis,
reflux nephropathy and other kidney diseases
• Certain infections such as HIV, hepatitis B, hepatitis C, COVID 19, SVD
and malaria.
• Certain medications such as nonsteroidal anti-inflammatory drugs
• alchohol, drugs that cause autosomal gene abberations in pregnancy

52. NCD’s INTEGRATION DEMAND FOR LESOTHO
• lobbying for Funding to conduct full scale prevelance survey , Awareness
and demand creation ( Family peridgrees and genomics) EU-AFRICA4 MED)
• develop screening protocols and integration in to STG
• capacity building and mentoship program of Health professionals and Med
LAB on SCD diagnosis and Management and monitoring treatment
• conduct Community-Based Chronic Disease Care integration of SCD
• Capacitating lay village health workers (VHWs) to deliver essential services
at the community level to improve access to and outcomes of NCD’s in
LMICs
• develop an Integrated SCD program Country wide
• conduct population NGS on SCD for Lesotho

53. • If untreated for a prolonged period it may lead to
• Blood clots-occur due to loss of proteins that prevent clotting
• High blood cholesterol and elevated blood triglycerides- due to
release of more cholesterol and triglycerides by the liver as it
produces albumin
• Poor nutrition-due to loss of proteins which can result in malnutrition
• High blood pressure- due to uremia
• Acute kidney failure
• Chronic kidney disease – leads to loss of kidney function gradually

54.  Starts suddenly, very severe, and it may last for several hours
 Commonly long bones are affected, but in the 1st 18 months can involve metatarsals and
metacarpals causing dactylitis (painfull swelling hands and feet)
Splenic sequestration
• Sequestration causes worsening of baseline anemia and increase risk of infection by
encapsulated organism
• This includes H. influenza, S. pneumoniae, S. typhi and N. meningitidis
 Acute chest syndrome
o Commonly characterized by chest pain, fever, cough, tachypnea, pulmonary infiltrates,
hypoxemia
o Medical emergency is commonly precipitated by chest infections in children

55. Vaso-oclusive Crises cont
 Due to obstruction of microvasculature by rigid sickle cells
 Painful crises- can affect any part but is chiefly experienced in the
abdomen, bones, joints and soft tissues

56. Aplastic
 Worsening of baseline anemia due to infection of parvovirus B-19
 This is single stranded RNA virus that is acquired by respiratory
droplets and a special philia for erythrocytes progenitor
 Thus, switches off RBC production and causes drastic drop of
reticulocyte counts

57. Hemolytic Crisi
 Accelerated breakdown of RBC that occurs with co-existence of G6PD deficiency
 G6PD is a recessive X linked disorder that results to deficiency of the enzyme
reqiured for formation glutathione in Pyruvate Phosphorylation pathway
 Glutathione is required for clearing free radicals to prevent oxidative damage

58. Factors that can Precipitate SC -lifestyle
 Infections
 Low oxygen tension
 Concomitant medical conditions (e.g., sarcoidosis, diabetes mellitus, herpes)
 Dehydration
 Acidosis
 Extreme physical exercise
• Physical or psychologic stress
• Alcohol and drugs
• Pregnancy
• Cold weather

59. nu
nutritional??????

60. community outreach / clinic screening programs
Genogram

61. Urinalysis - comunity oureach package
• multi-system medical consultation
• BIOCHEMISTRY- PH, albumin, bilirubin, ketocis,glucose,
• MIROSCOPY - epithelial ccasts, yeasts, trichononads, cristals,
• CULTURE
• INFECTIONS
• RENAL
• LIVER
• BRAIN
• LUNGS
• SPLEEN
• ENDOCRINOLOGICAL- DM / HTN/

62. FREQUENT URINALYSIS IS GOLD STANDARD
Glucose
Bilirubin
Ketone
Specific Gravity
Blood
pH
Protein
Urobilinogen
Nitrite
Leukocyte Esterase

63. Diagnosis
Screening Tests Point of Care (POC)
tests
Confirmatory tests
Sickling Test (non-
diagnostic): All positive
sickling test must be
confirmed by the
approved point of care
tests.
tests released by Licensed
Medical Laboratory
Scientists
 Sickle SCAN®
 Hemotype SC™
 Hemoglobin
Electrophoresis
 Iso-Electric Focusing
(IEF)
 High-Performance
Liquid
Chromatography
(HPLC).

64. Precautionary Blood test and genetic tests
• If you do not know whether you make sickle hemoglobin, you can find out
by having your blood tested.
• You may also have a genetic test. This way, you can learn whether you
carry a genes — or have the trait — for sickle hemoglobin that you could
pass on to a child.
• Cytogenetics can help determine which type of sickle cell disease you
have or confirm a diagnosis if results from blood tests are not clear.
• Genetic testing can also tell whether you have one or two copies of the
sickle hemoglobin gene.

65. Prenatal screening- protocol
• Healthcare providers can also diagnose sickle cell disease before a
baby is born.
• This is done using a sample of either amniotic fluid (the liquid in the
sac surrounding a growing embryo) or tissue taken from the placenta
(the organ that attaches the umbilical cord to the womb).
• Testing before birth can be done as early as 8 to 10 weeks into the
pregnancy. This testing looks for the sickle hemoglobin gene rather
than the abnormal hemoglobin itself.
• This testing cannot predict the severity of the disease.

66. Newborn screening
• In newborn screening programs, drops of blood from a heel prick are
collected on a special type of paper.
• The hemoglobin from this blood is then tested in a lab. Newborn screening
results are sent to the provider who ordered the test and to your child’s
healthcare provider.
• Providers from a special follow-up newborn screening team will contact
you directly if your child has sickle cell disease. Your child’s providers will
then retest your child to make sure the diagnosis is correct.
• Newborn screening programs also find out whether your baby has
the sickle cell traitexternal link and is a carrier.
• If this is the case, counseling will be offered. Remember that when a child
has sickle cell trait or sickle cell disease, their future siblings or future
children may be at risk.

67. Clinical investigations
• Attacks are diagnosed clinically, i.e. there is no gold standard
diagnostic test
• Hemolysis (anemia and jaundice) is often present, although for
painful crises the diagnosis depends essentially on how the patient
describes the pain

68. Lab Investigations
• For Screening, Diagnosis and Confirmation
 Sickling test (Hemoglobin S solubility test and sodium metabisulfite test), not
for infants. Useful after 6 month from birth
 Newborn Screening: HPLC fractionation (High performance liquid
Chromatography) and thin Layer/Isoeletric focusing

71. Lab Investigation (2)
 Abnormal hemoglobin forms are detected on hemoglobin electrophoresis a form of gel electrophoresis on
which the various types of hemoglobin move at varying speed
 Sickle cell hemoglobin (HbSS) and Hemoglobin C with sickling (HbSC) the two most common forms can be
identified from there
 urinalysiis - BIOCHEMISTRY , MICROSCOPY CULTURE AND SENSITIVITY
 FBC- CBC----blood films including Malaria, Howel joel bodies, reticulocyte count
 direct combs test, aminoscenthesis
 LFTSs, KFT’s, Cadiac FTs, Endocrinology ( s’e-aldosterone, T4/T3, ca+,mg+, renin, angitensin
 Kidney function tests including renin, angitension1, 11 aldosterone , tryptophan and NSEs
 Cultures and sensitivities including TORCH,
 Cytogenetics. immunocytochemistry ( perl perressioan blue, NSE, silver stains,amyloid, reticulin etc)
 NGS
 PRECISION MEDICINE -

72. • DNA analysis ---------cytogenetics
• Other tests that may be used to help evaluate someone who is suspected of having or who is known
to have sickle cell trait or disease include:
• Complete blood Count (CBC)
• Blood Smear differential and malaria - (era of climate change and travel episodes )
• Neurological tests SILVER STAINS, (agentaffin and argirophill cells) , TRYPTOPHAN , NSE
• blood gases and Electrolytes- always when infussions and transfusions are done
• Chest X-ray in Acute Chest Syndrome
• Trans-Cranial Doppler Ultrasound (TCD),MRI (with or without angiography) and Neuro-
psychometric studies (NPM)

73. RETICULOCYTES COUNT- in peripheral hospitals
• To perform a reticulocyte count, you can follow these steps123:
• Collect a few drops of blood in EDTA.
• Incubate the blood with new methylene blue solution.
• Prepare a thin smear on a glass slide from the mixture.
• Count the reticulocytes under the microscope.
• Alternatively, you can perform a reticulocyte count with an automated
instrument (hematology analyzer)4.

84. TREATMENT
• aimed at avoiding pain episodes, relieving symptoms, and preventing complications.
• Treatments might include medications and blood transfusions.
• For some children and teenagers, a stem cell transplant might cure the disease .
• Hydroxyurea is a medication that can reduce the frequency of painful crises and might reduce
the need for blood transfusions and hospitalizations .
• glutamine oral powder is another drug that has been recently approved by the FDA for the
treatment of sickle cell anemia. It helps in reducing the frequency of pain crises 1.
• Crizanlizumab is a drug that can help reduce the frequency of pain crises in adults and children
older than 16 1. otherwise use WHO pain step ladder for opioids -PALLIATIVE CARE
• Voxelotor is another drug that can lower the risk of anemia and improve blood flow throughout
the body 1.
• Children with sickle cell anemia might receive penicillin between the ages of about 2 months old
until at least age 5 years. Doing so helps prevent infections, such as pneumonia, which can be
life-threatening to children with sickle cell anemia

85. HTN Standard treatment guidelines +EDL
• ACE inhibitors
• ARBs
• CCBs Amlodipine
• BBs lopressor
• Renin inhibitors
ENALAPRIL,
LISINOPRIL,
PER9NDOPRIL,
RAMIPRIL

86. Follow up Patients with Sickle Cell Disease
• Take history and family gengogram/ pedigre
• Full and thorough Examination
• Blood tests: at each visit (already said visits are yearly for older well children
• Provide / Organise / Prescribe / Check
• USE MED LAB MEDLAB MED LAB
• Follow-up appointment to be booked

87. palliative care

88. Routine Medications for SCD
Drug Dose: Adult Dose: Child
Penicillin V Not given <1yr: 62.5mg BD
1-3yrs: 125mg BD
>3yrs: 250mg
> 5yrs: not usually given as prophylaxis
Folic acid 5mg or 1mg as available OD <1yr: 1.25mg OD
1-3yrs: 2.5mg OD
>3yrs: 5mg OD
Analgesia 2-week supply for PRN use Paracetamol 1g QDS, Ibuprofen 400mg
QDS
Paracetamol 15mg/kg QDS,
Ibuprofen 5mg/kg TDS
Ferrous sulphate if MCH<25pg 200mg TDS 2mg/kg TDS for 6 weeks, then check Hb level and ferritin.
Mebendazole after every 3 months 200mg
400mg stat dose
1-2years
2years
Malaria prophylaxis Low transmission
Use insecticide treated nets
Prompt diagnosis and treatment

89. Next Genomic sequencing
• Next-generation sequencing (NGS) is a new technology used for DNA
and RNA sequencing and variant/mutation detection.
• NGS can sequence hundreds and thousands of genes or whole
genome in a short period of time.
• The sequence variants/mutations detected by NGS have been widely
used for disease diagnosis, prognosis, therapeutic decision, and
follow up of patients.
• The capacity of its massive parallel sequencing offers new
opportunities for personalized precision medicine.

90. testing platforms
•Space capacity is minimal, test menus
are multi-pex multi-integrated for EID,
Viral load, HIV,, MTB and HPV SVD,
COVID 19 and other infectious
diseases.
•GENOMIC TESTING IN CANCER AND
OTHER NCDs

91. Population genomics
• large-scale application of genomic technologies to study
populations of individuals. For example, population
genomics research can be used to study human ancestry,
migrations and health conditions .
• Population Genomics. Basically, population genomics
allows Medical scientists to understand how groups are
related over time.
• It also allows scientists to understand our ancestral
backgrounds and how that ancestral background has been
shaped over time, in terms of the environment that our
ancestors have lived their lives.

92. Pathway ideal of referral

93. Process or algorithms for follow-up Affected
individuals
• : Notification of a family about a (presumptive) serious health
problem in an otherwise healthy appearing newborn is not a trivial
task. Ideally, notification should be done in person or by live phone
call.
• The initial conversation should be expected to raise anxiety, and
cause disappointment and sadness at a time of joy;
• it may also stir anger or denial.

94. cont
• The messenger should be someone familiar with the clinical course of SCD
in infants, young children and adults, and be able to answer basic questions
about SCD and ready to provide reassurance and support for the family.
• The processes and algorithms for notification and follow-up often place the
primary care service as the medical home,
• presuming that staff is able to interpret screening results and take
appropriate actions when a baby with a positive screen is reported.
• Reporting individuals with abnormal screening results to a dedicated
follow-up agency and/or sickle cell treatment center will increase the
timeliness of appropriate care

96. Pharmacological Treatment
• Febrile illness
 Children with fever are screened for bacteraemia i.e. complete blood count,
reticulocyte count and blood culture taken
 Younger children (varies from center to center) are admitted for intravenous
antibiotics while older children with reassuring white cell counts are managed at
home with oral antibiotics
 Children with previous bacteraemic episodes should be admitted

97. Pharmacological Treatment (2)
Painful (vaso-occlusive) crises
 Most patients with sickle cell disease have intensely painful episodes called
vasoocclusive crises
 Painful crises are treated symptomatically with analgesics; pain management
requires opioid administration at regular intervals until the crisis has settled

98. Pharmacological Treatment (3)
Painful (vaso-occlusive) crises
 For milder crises a subgroup of patients are managed by NSAIDs (such as
diclofenac or naproxen)
 For more severe crises most patients require inpatient management for
intravenous opioids; patient-controlled analgesia (PCA)

99. Pharmacological Treatment (4)
Painful (vaso-occlusive) crises
 Diphenhydramine is effective for the itching associated with the opioid use
 NB: analgesia, Oxygen, hydration and warmth

100. Pharmacological Treatment (5)
Acute chest crises
• Management is similar to vaso-occlusive crises with the addition of antibiotics
(usually a quinolone or macrolide)
• When the pulmonary infiltrates worsen or the oxygen requirement increases,
simple blood transfusion or exchange transfusion is indicated

101. Pharmacological Treatment (6)
Acute chest crises
• Exchange transfusion involves the exchange of a significant portion of the patients red cell mass for normal
red cells, which decreases the percent hemoglobin S in the patient's blood
Hydroxyurea
• The first approved drug for the causative treatment of sickle cell anemia

102. Pharmacological Treatment (7)
• Hydroxyurea had previously been used as a chemotherapy agent, and
there is some concern that long-term use may be harmful
• it is likely that the benefits outweigh the risk
 Splenic Sequestration Crisis
 Treatment includes early intervention and maintenance of hemodynamic
stability using isotonic fluid or blood transfusions.

103. Pharmacological Treatment (8)
• Splenic Sequestration Crisis
• Careful blood transfusions with red blood cells are recommended to treat
both the sequestration and the resultant anemia
 Blood transfusion aborts the red blood cell sickling in the spleen and allows
release of the patient’s blood cells that have become sequestered, often
raising the hemoglobin above baseline values

104. Pharmacological Treatment (9)
• Typically recommend only 5 mL/kg of red blood cells because the goal is to prevent
hypovolemia
• Blood transfusion that results in hemoglobin levels above 10 g/dL may put the
patient at risk for hyperviscosity syndrome because of the risk that that patient may
release the blood within the spleen
• If there is recurrent episode Prophylactic splenectomy is the only choice for
preventing future life threating episode.

105. Pharmacological Treatment (10)
Priapism
 The optimal treatment for acute priapism is unknown. Acutely, supportive therapy, such as a hot
shower, short aerobic exercise, or pain medication, is commonly used by patients at home
 Urology consultation is required to initiate this procedure, with appropriate input from a
hematologist
• A prolonged episode lasting >4 hrs should be treated by aspiration of blood from the corpora
cavernosa followed by irrigation with dilute epinephrine to produce immediate and sustained
detumescence

106. Pharmacological Treatment (12)
• Penicillin prophylaxis
• The most important intervention in the routine management of children with
SCD is penicillin prophylaxis to prevent pneumococcal infection, which
justifies newborn screening
• Penicillin is given twice daily from as 2months of age

107. Pharmacological Treatment (13)
• Children with SCD-SS are given Penicillin VK: 125mg by mouth twice
daily for those under 3yrs of age and 250mg twice daily for those 3
and older
• An alternative to oral penicillin is an injection IM of 1.2 million units
of long acting Bicillin (Penicillin G Benzathine) every 3 weeks

108. Pain Management
 Pain is the commonest acute complication in SCD
 Mild to Moderate Pain
 Use oral analgesics Paracetamol, Ibuprofen or diclofenac
 Encourage excessive oral fluids intake

109. latest treatments of sickle cell disease
• According to the National Heart, Lung, and Blood Institute (NHLBI), researchers are studying new
ways to prevent blood cells from sickling, which could help alleviate anemia and reduce the
frequency and severity of pain crises in people living with sickle cell disease
• One such study involves activating a protein in red blood cells called pyruvate kinase (PKR), which
supports cellular health and metabolism. Researchers found that stimulating PKR activity may
prevent or alleviate severe pain crises in people with sickle cell disease
• Another treatment option for sickle cell anemia is bone marrow or stem cell transplantation,
which can cure the disease in some patients
• However, these procedures are risky and are typically reserved for people with severe disease.
Gene therapy is another promising treatment option that may become available in the future 3.
• It’s important to note that treatment for sickle cell anemia is highly individualized and depends on
the severity of the disease and the patient’s overall health. If you or someone you know has sickle
cell anemia, it’s best to consult with a healthcare professional to determine the best course of
treatment.

110. Brainstorming
How do you follow up and monitor a child with sickle cell disease?

111. Key Points
 Sickle cell anemia is a genetic disorder whereby red blood cells are
abnormally shaped, causing problems with the flow of blood through
the body as well as transport of oxygen throughout the body
 Sickle cell anemia exists in Lesotho

112. Key Points (2)
 Clinical presentation of Sickle cell crises includes the following:
• Vaso-occlusive crisis
• Aplastic Crisis
• Hemolytic Crisis
• Treatment include pharmacological and non-pharmacological interventions
• Follow up monitoring have to be done closely by doing complete assessment and
treatment and counselling of parents
•

113. Population health and NGS
• We see population health as a broad concept encompassing not only
the elimination of diseases and injuries, but also the intersecting and
overlapping factors that influence health.
• These influencing factors include the environment, education,
mobility, policy and governance, poverty, racism, infrastructure,
access to technology, urban planning and many more.
• Together, these issues revolve around three major pillars — human
health, environmental resilience and social and economic equity —
that affect the lives of billions of people around the world.

114. Network
• Governing bodies must work with industry to maximise the
public benefits of precision medicine.
• This vital line of communication accelerates innovation by
ensuring that bold ideas fit within safety standards imposed
by regulatory agencies, before companies set on product
development and testing.

116. THANK YOU
Sejojo Phaaroe FIBMS
+266 50468036
email: thinktankentr@gmail.com
www.thinktankent.com