Introduction

  • Sickle cell disease (SCD) is a major health care and societal problem that affects millions of people worldwide.

  • In low-income countries like Malawi, basic facilities for management are lacking, systematic screening is not present, and diagnosis is often made late.

  • Before January 2015, children suspected of having SCD at Kamuzu Central Hospital (KCH; a referral hospital in Lilongwe) were seen in the general pediatric clinic together with children with various chronic medical conditions.

  • The diagnosis was made clinically, with a few children diagnosed by Sickledex; the supply of drugs was erratic, and time was limited for patient and caregiver SCD education.

  • In January 2015, a weekly dedicated Sickle Cell Clinic was established at KCH, and hemoglobin electrophoresis capabilities were introduced.

  • The clinic together with a concurrent observational study aims to establish a prospective longitudinal SCD cohort in Malawi and determine clinical characteristics, acute and chronic complications, and the laboratory profile of patients with confirmed SCD.

Methods

  • Study participants were recruited from a general pediatric clinic, the children’s ward at KCH, and surrounding health facilities (Figure 1).

  • Clinical and laboratory data were collected longitudinally at 6-month intervals during routine care. Loss-to-follow-up was defined as no study visit in 12 months.

  • Statistical analyses were performed using SAS software.

  • Written informed consent was obtained from parents of all enrolled children. Children age 7 to 17 years also provided informed assent prior to study participation.

  • The study was approved by the University of North Carolina-Chapel Hill institutional review board and the Malawi National Health Science Review Committee.

Capacity building

  • Because the SCD clinic is now available, hemoglobin electrophoresis can be used to make the diagnosis in individuals suspected of having SCD at KCH (Figures 2 and 3).

  • Laboratory technicians have been trained to perform hemoglobin electrophoresis and interpret results. The site laboratory is now capable of conducting large-scale screening studies for SCD.

  • Having a dedicated team of nurses and clinicians running the Sickle Cell Clinic every week has led to better understanding of the disease and enhanced knowledge and skills in patient care.

Results

Figure 1.

Enrollment of new participants and loss-to-follow-up by year (N = 157).

Figure 1.

Enrollment of new participants and loss-to-follow-up by year (N = 157).

Table 1.

Demographic and follow-up characteristics of the study cohort

CharacteristicCount%n*
Male 79 51.6 153 
Female 74 48.4 153 
Lilongwe District 120 90.2 133 
Lost to follow-up (after 12 months) 54 34.4 157 
Deceased 3.8 157 
HbSS 155 98.7 157 
HbSc 0.6 157 
HbFS 0.6 157 
 Median Range or IQR n* 
Age at enrollment, years Range, 0-20 148 
Duration of follow-up, months 27 IQR, 24-36 135 
No. of follow-up study visits IQR, 2-4 157 
CharacteristicCount%n*
Male 79 51.6 153 
Female 74 48.4 153 
Lilongwe District 120 90.2 133 
Lost to follow-up (after 12 months) 54 34.4 157 
Deceased 3.8 157 
HbSS 155 98.7 157 
HbSc 0.6 157 
HbFS 0.6 157 
 Median Range or IQR n* 
Age at enrollment, years Range, 0-20 148 
Duration of follow-up, months 27 IQR, 24-36 135 
No. of follow-up study visits IQR, 2-4 157 

HbFS, fetal hemoglobin sickle cell; HbSc, sickle cell hemoglobin C; HbSS, homozygous sickle cell; IQR, interquartile range.

*

n represents total number of patients in the subgroup.

Table 2.

Lifetime medical history at enrollment

No. of patients (N = 154)*%
Malaria 58 37.7 
Tuberculosis 5.2 
Pneumonia 1.3 
Anemia 96 62.3 
Fever 13 8.4 
Pain crisis 72 46.8 
Jaundice 77 50.0 
Shortness of breath 23 14.9 
Chest pain 32 20.8 
Joint pain 79 51.3 
Dactylitis 47 30.5 
Total No. of blood transfusions   
 1-5 18 11.7 
 6-10 0.6 
 11-20 
 21-30 
 31-50 
Hospital admissions 1 (median) 0-8 (range) 
Pneumococcal vaccine 20 13.0 
No. of patients (N = 154)*%
Malaria 58 37.7 
Tuberculosis 5.2 
Pneumonia 1.3 
Anemia 96 62.3 
Fever 13 8.4 
Pain crisis 72 46.8 
Jaundice 77 50.0 
Shortness of breath 23 14.9 
Chest pain 32 20.8 
Joint pain 79 51.3 
Dactylitis 47 30.5 
Total No. of blood transfusions   
 1-5 18 11.7 
 6-10 0.6 
 11-20 
 21-30 
 31-50 
Hospital admissions 1 (median) 0-8 (range) 
Pneumococcal vaccine 20 13.0 
*

Not all participants had medical history information recorded.

Table 3.

Medications at enrollment visit and as a proportion of all return visits

MedicationFirst visitAll return visits
No. (N = 151)*%No. (N = 451)%
Folic acid 21 13.9 438 97.1 
Fansidar 18 11.9 414 91.8 
Azithromycin, penicillin V, amoxicillin 19 12.6 441 97.8 
Hydroxyurea 3.3 126 27.9 
MedicationFirst visitAll return visits
No. (N = 151)*%No. (N = 451)%
Folic acid 21 13.9 438 97.1 
Fansidar 18 11.9 414 91.8 
Azithromycin, penicillin V, amoxicillin 19 12.6 441 97.8 
Hydroxyurea 3.3 126 27.9 
*

Not all participants had medical history information recorded.

Table 4.

Physical examination characteristics at enrollment and at last recorded study visit

CharacteristicFirst visitLast visit
No. (N = 151)*%No. (N = 138)%
Jaundice 4.6 11 8.0 
Frontal bossing 2.7 13 9.4 
Murmur 1.3 6.5 
Hepatomegaly 26 17.2 19 13.8 
Splenomegaly 3.3 10 7.3 
Clubbing 2.7 1.5 
Leg ulcers 2.9 
Dactylitis 1.3 
Joint swelling 1.3 
CharacteristicFirst visitLast visit
No. (N = 151)*%No. (N = 138)%
Jaundice 4.6 11 8.0 
Frontal bossing 2.7 13 9.4 
Murmur 1.3 6.5 
Hepatomegaly 26 17.2 19 13.8 
Splenomegaly 3.3 10 7.3 
Clubbing 2.7 1.5 
Leg ulcers 2.9 
Dactylitis 1.3 
Joint swelling 1.3 
*

Not all participants had medical history information recorded.

The most recent study follow-up visit (excluding the enrollment visit).

Table 5.

Laboratory results at first and last recorded follow-up visits

Laboratory testFirst visit*Last visit
No. of tests doneMedianRangeNo. of tests doneMedianRange
Hemoglobin (g/dL) 137 7.4 5.1-10.4 140 7.6 3.6-13.0 
Serum creatinine (mg/dL) 137 0.3 0.1-1.2 105 0.36 0.14-7.22 
Lactate dehydrogenase (U/L) 136 653 309-1748 104 638.5 204-2117 
  No. of positive tests %  No. of positive tests % 
Urine protein 145 11 7.6 164 15 9.2 
Blood in urine 145 54 26.2 164 49 29.9 
Laboratory testFirst visit*Last visit
No. of tests doneMedianRangeNo. of tests doneMedianRange
Hemoglobin (g/dL) 137 7.4 5.1-10.4 140 7.6 3.6-13.0 
Serum creatinine (mg/dL) 137 0.3 0.1-1.2 105 0.36 0.14-7.22 
Lactate dehydrogenase (U/L) 136 653 309-1748 104 638.5 204-2117 
  No. of positive tests %  No. of positive tests % 
Urine protein 145 11 7.6 164 15 9.2 
Blood in urine 145 54 26.2 164 49 29.9 
*

Not all participants had medical history information recorded.

Figure 2.

Isoelectric focusing electrophoresis unit.

Figure 2.

Isoelectric focusing electrophoresis unit.

Figure 3.

Isoelectric focusing gel.

Figure 3.

Isoelectric focusing gel.

Conclusion

Most children presented with a history of malaria, a major cause of morbidity and mortality in children with SCD in Malawi. Anemia and a history of blood transfusion were common in patients who presented with SCD. Screening children who present with anemia may lead to early diagnosis of SCD. Parents are educated about the importance of prophylaxis, prompt treatment of infections, immunizations, and mosquito netting. Our cohort shows a low death rate, but the rate of loss to follow-up is concerning. A community tracking program of bringing patients back to care and ascertainment of health status including verbal autopsies is needed.

Acknowledgements

The authors thank Robert Krysiak, Godwin Chipoka, Zondwayo Tembo, and Yacinta Majawa (University of North Carolina Project-Malawi).

This work was funded by the Fulbright-Fogarty Training Program, National Institutes of Health Fogarty International Center, National Heart, Lung, and Blood Institute (U01HL117659).

Authorship

Conflict-of-interest disclosure: N.K. received research funding from UniQure BV. K.A. received research funding from Pfizer and Global Blood Therapeutics; received honoraria from Modus Therapeutics, Global Blood Therapeutics, Novartis Pharmaceuticals, and Bioverativ; served as a member of the board of directors or on advisory committees for Global Blood Therapeutics; and served as a member of various entities of Bioverativ. The remaining authors declare no competing financial interests.

Correspondence: Portia Kamthunzi, University of North Carolina Project-Malawi, Lilongwe, Malawi; e-mail: pkamthunzi@unclilongwe.org.