Pulmonary Hypertension in Adults and Children with Sickle Cell Disease in Nigeria: Prevalence, Clinical Characteristics and Role of Endemic Tropical Infections.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 3793-3793
Author(s):  
Zakari Y. Aliyu ◽  
Sachdev Vandana ◽  
Aisha I. Mamman ◽  
Aliyu Babadoko ◽  
Peter Akpanpe ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Pulmonary Hypertension ◽  
Sickle Cell Disease ◽  
Diastolic Blood Pressure ◽  
Blood Urea Nitrogen ◽  
Sickle Cell ◽  
The United States ◽  
Sub Saharan Africa ◽  
Cell Disease ◽  
Urea Nitrogen

Abstract Pulmonary hypertension has a prevalence of 30% in patients with sickle cell disease (SCD) in the United States with mortality rates of 40% at 40 months after diagnosis. The global burden of SCD is highest in sub-Saharan Africa where more than 200,000 children are born with the disease annually. The prevalence of pulmonary hypertension among individuals with SCD in Africa has not been previously reported. We performed Doppler echocardiographic assessments of pulmonary-artery systolic pressure in 206 consecutive hydroxyurea sickle cell patients at steady state in Nigeria, West Africa (101 males and 105 females; age range 10–52, mean [+/−SD] age, 21.5 +/− 7.7 years; 196 homozygous sickle cell and 10 compound heterozygotes SC). A control group consisted of 93 healthy Nigerians. Hemoglobin gentotype was determined by electrophoresis and DNA sequencing. Pulmonary hypertension was defined prospectively as a tricuspid regurgitant jet velocity (TRV) of at least 2.5 m per second. We collected clinical data on the patients and controls, and blood specimens for clinical laboratory measurements. Doppler-defined pulmonary hypertension occurred in 25% of sickle cell patients (21% with TRV 2.5 – 2.9 m/sec, 4% with TRV ≥ 3 m/sec). The presence of pulmonary hypertension was inversly associated with age (p=0.04) and hemoglobin (p=0.0016), and positively associated with reticulocyte count, serum levels of lactose dehydrogenase (p=0.03), creatine kinase, and blood urea nitrogen and systolic (p=0.03) and diastolic blood pressure (p=0.002) in bivariate analyses. In a multivariate linear regression model age, diastolic blood pressure and blood urea nitrogen had significant independent associations with pulmonary hypertension. There were no significant associations of HIV/AIDS, hepatitis B and C co infections and malarial parasitemia rate with pulmonary hypertension. Our findings suggest that pulmonary hypertension is common among sickle cell patients in Africa and it appears to be a complication of chronic hemolysis and vasculopathy. The prevalence of pulmonary hypertension decreases with age in Nigerian SCD patients, in sharp contrast to U.S. SCD patients, who demonstrate increasing prevalence with age. The public health implications of this finding are significant considering the potential number of individuals at risk for this complication. Large prospective cohort studies to determine the outcome of pulmonary hypertension in sickle cell patients in Africa are needed.

scholarly journals Antimicrobial Resistance and Sickle Cell Protein Analysis in Invasive Non-Typhoidal Salmonella Isolated From Outpatient and Hospitalized Children Below 16 Years in Informal Settlements in Nairobi Kenya

2020 ◽  
Author(s):  
Susan Kavai ◽  
Cecilia Mbae ◽  
Celestine Wanjiku ◽  
Ronald Ngetich ◽  
Zillah Wakio ◽  
...  
Keyword(s):  
Sickle Cell Disease ◽  
Salmonella Typhimurium ◽  
Sickle Cell ◽  
Informal Settlements ◽  
The United States ◽  
Sub Saharan Africa ◽  
Cell Protein ◽  
Cell Disease ◽  
Resistance Phenotype ◽  
Stool Samples

Abstract Background: Invasive Non-typhoidal Salmonella (iNTS) disease continues to be a major public health problem, especially in sub Saharan Africa where incidence rates are 227 cases [range 152-341] per 100,000 population. Populations at risk of iNTS include adults with HIV infection, malnourished children, those with recent malaria or sickle-cell anaemia (SCA). Individuals with SCA are at an increased risk of invasive bacterial infections with the proportion of deaths from infection reported to be as high as 38% in the United States and 29% in Jamaica. In Kenya, iNTS disease is particularly a major challenge in poor informal settlements with infants and young children less than 5 years of age being the most affected; mortality rates can be 20-25% unless prompt treatment is administered. Methods Our study was conducted in 3 outpatient sites and 1 inpatient site, the outpatient sites were all located within Mukuru informal settlement, a densely populated slum, 15km East of Nairobi City. Blood and stool samples from children with fever alone and with fever and diarrhea were collected for processing for presence of iNTS using basic microbiology procedures. Dry blood spots were also taken and processed for sickle cell protein markers using High performance liquid chromatography (HPLC). Results A total of 22,246 blood and stool samples were collected from children < 16 years of age with fever/with or without diarrhea, for a period of 6 years and subjected to microbiological culture and detection of bacterial pathogens. Out of these 741 (3.3%) tested positive for Salmonella species. A total of 338/741(41%) NTS were isolated across all the sites; these consisted of 158/741(21%) Salmonella Enteritidis and 180/741 (24%) Salmonella Typhimurium. The most common resistance phenotype was ampicillin, cotrimoxazole and chloramphenicol (35.03%). We had 12/338 (3.6%) isolates (11 of them being Salmonella Typhimurium) that were ESBL producers conferring resistance to 3rd generation cephalosporins (Amp C β-lactamases) while only 0.3% were resistant to ciprofloxacin. A total of 118 (35.03%) isolates were MDR. Out of 2684 dry blood samples subjected to HPLC for investigation of sickle cell disease traits, 1820/2684 (67%) had normal hemoglobin (Hb AA/ Hb AF); (162/2684 (6%) tested positive for Sickle Cell Traits (Hb AS/Hb AFS); while 4/2684 (0.2%) tested positive for Sickle cell disease (Hb FS). Conclusion The high MDR resistance phenotype in iNTS isolates and emerging resistance to third generation cephalosporins is of great concern in management of iNTS in our settings. Sickle cell disease was not a major factor among children with iNTS disease and no significant association with iNTS was observed.

scholarly journals Prospective Newborn Screening for Sickle Cell Disease and Other Inherited Blood Disorders in Central Malawi

2021 ◽  
Vol 66 ◽  
Author(s):  
Gerald Tegha ◽  
Hillary M. Topazian ◽  
Portia Kamthunzi ◽  
Thad Howard ◽  
Zondwayo Tembo ◽  
...  
Keyword(s):  
Sickle Cell Disease ◽  
Newborn Screening ◽  
Sickle Cell ◽  
Early Identification ◽  
G6pd Deficiency ◽  
The United States ◽  
Sub Saharan Africa ◽  
Cell Disease ◽  
Hematological Disorders ◽  
Alpha Thalassemia

Objectives: Newborn screening in the United States and Europe allows early identification of congenital disorders but does not yet exist in most low-resource settings, especially in sub-Saharan Africa. Newborn screening can identify multiple inherited hematological disorders, but feasibility and effectiveness for Africa are not fully determined.Methods: Surplus dried blood spot collected in Central Malawi through the HIV Early Infant Diagnosis surveillance program were repurposed and tested by isoelectric focusing for sickle cell disease and trait. Additional genetic testing identified G6PD deficiency and alpha thalassemia.Results: Testing of 10,529 cards revealed an overall sickle cell trait prevalence of 7.0% (range 3.9–9.7% by district); 10 of 14 infants identified with sickle cell disease (prevalence 0.1%) were located and received care at a specialized clinic. Subsequent testing of 1,329 randomly selected cards identified alpha thalassemia trait in 45.7% of samples, and G6PD deficiency in 20.4% of males and 3.4% of females, with 29.0% of females as heterozygous carriers.Conclusion: Inherited hematological disorders are common in Central Malawi; early identification through newborn screening can improve clinical outcomes and should be supported throughout Africa.

scholarly journals Establishing Sickle Cell Diagnostics and Characterizing a Pediatric Sickle Cell Disease Cohort in Malawi

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 2070-2070
Author(s):  
Jonathan Brett Heimlich ◽  
Godwin Chipoka ◽  
Portia Kamthunzi ◽  
Yuri D. Fedoriw ◽  
Nigel S. Key ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Sickle Cell Disease ◽  
Sickle Cell ◽  
Joint Pain ◽  
Clinical Care ◽  
Diagnostic Methods ◽  
Sub Saharan Africa ◽  
Age Group ◽  
Cell Disease ◽  
Sub Saharan

Abstract Sickle cell disease (SCD) is highly prevalent in sub-Saharan Africa; however, there are relatively few studies describing the clinical profile for children with laboratory-confirmed SCD. Prior to December 2014, neither neonatal screening nor standardized methods for SCD diagnosis were routinely available in Malawi, as hemoglobin electrophoresis and alternative diagnostic methods were absent. We describe implementation of hemoglobin electrophoresis for children with clinically suspected SCD at Kamuzu Central Hospital, one of two national teaching hospitals in Malawi. Children with clinically suspected SCD were recruited January - May 2015 and underwent comprehensive clinical and laboratory characterization. 137 total patients were recruited and 117 were confirmed to have HbSS disease. Among children who were being cared for as SCD prior to enrollment, 86% had HbSS suggesting generally accurate clinical diagnosis by local providers. Baseline clinical parameters and self-reported SCD complications for the study population are displayed in Table 1. Of those with confirmed SCD, median age was 7.3 years (IQR 2.7-10.4) with 53% males. Prior malaria was reported by 39% of patients, and was higher in the 0-5 age group compared with the over 5 age group (46% vs. 31%, p=0.03). The most commonly reported SCD complications were anemia (72%), joint pain (56%), jaundice (52%), and acute pain episodes (50%). Children with confirmed SCD had median hemoglobin of 7.3 g/dL (IQR 6.9-7.9), total bilirubin of 1.7 mg/dL (IQR 1.1-2.6) and lactate dehydrogenase of 658 IU/L (IQR 527-773). Urinalysis demonstrated 26% of patients with blood and 7% with proteinuria by dipstick. As of May 2015, more than 250 samples for enrolled children as well as routine clinical care had been batch-processed weekly with an average turn-around time of 36 hours for results. Three Malawian laboratory technicians were trained to perform hemoglobin electrophoresis, all of whom have been performing the test independently since April 2015. Our findings highlight a need for wider implementation of resource-appropriate diagnostics as an essential foundation for care and research. Children had substantial clinical and laboratory evidence of SCD-related morbidity. Earlier diagnosis can improve care for this population by facilitating earlier therapeutic interventions, as well as providing a basis for research to better understand SCD-related morbidity in sub-Saharan Africa. These efforts can ultimately inform management strategies to improve outcomes and increase life expectancy among children with SCD in Malawi. Table 1. All (n=117) Male (n= 62) Female (n=55) p value Age years, median (IQR) 7.3 (2.7-10.4) 5.3 (2.3-9.4) 8.9 (4.2-11.9) 0.004 Height cm, median (IQR, n) 115 (88-131, 60) 111 (89-128, 36) 119.5 (93-140, 24) 0.21 Weight kg, median (IQR, n) 19 (13-27, 108) 16.5 (12-23.6, 58) 21 (14-30, 50) 0.01 Blood Pressure Systolic mmHg, median (IQR, n) 103 (98-110, 83) 101 (94-108, 43) 103 (99-110, 40) 0.37 Blood Pressure Diastolic mmHg, median (IQR, n) 60 (55-65, 83) 58 (53-65, 43) 61 (56-68, 40) 0.13 Heart Rate BPM, median (IQR, n) 104 (91-118, 114) 105 (94-123, 61) 104 (88-112, 53) 0.15 O2 Saturation %, median (IQR, n) 93 (88-97, 108) 91 (85-96, 59) 95 (91-98, 49) 0.004 % Hypoxemic (SPO2 < 90%), n (%) 36 (30.7) 26 (41.9) 10 (18.2) 0.005 Body Temperature Celsius, median (IQR, n) 37 (36.7-37.4, 91) 37 (36.7-37, 46) 37 (36.4-37.2, 45) 0.22 Positive History of: Malaria, n (%) 45 (38.5) 22 23 0.34 0-5 years, n (%) 25 (46.3) - - 0.03 6-18 years, n (%) 20 (31.7) - - Pneumonia, n (%) 29 (24.8) 10 (16.1) 19 (34.5) 0.02 HIV, n (%) 0 0 0 - Anemia, n (%) 84 (71.8) 49 (79.0) 35 (63.6) 0.06 Pallor, n (%) 16 (13.7) 7 (11.3) 9 (16.4) 0.43 Jaundice, n (%) 61 (52.1) 33 (53.2) 28 (50.9) 0.82 Received Blood Transfusion, n (%) 87 (74.4) 47 (75.8) 40 (72.7) 0.47 Days since last transfusion, median (IQR) 316 (133-1144) 240 (111-410) 577 (180-1784) 0.03 Pain episodes, n (%) 58 (49.6) 27 (43.5) 31 (56.4) 0.16 Joint pain, n (%) 66 (56.4) 33 (53.2) 33 (60.0) 0.34 Dactylitis, n (%) 41 (35.0) 19 (30.6) 22 (40.0) 0.29 Leg ulcers, n (%) 5 (4.3) 5 (8.1) 0 0.03 Stroke, n (%) 10 (8.5) 5 (8.1) 5 (9.1) 0.84 Nocturnal Enuresis, n (%) 24 (20.5) 12 (19.4) 12 (21.8) 0.74 Disclosures No relevant conflicts of interest to declare.

Risk Factors for Death in 632 Patients with Sickle Cell Anemia in the United States and United Kingdom

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 3240-3240 ◽  
Author(s):  
Mark T Gladwin ◽  
Robyn J Barst ◽  
J. Simon R. Gibbs ◽  
Marianna Hildesheim ◽  
Vandana Sachdev ◽  
...  
Keyword(s):  
Risk Factors ◽  
Pulmonary Hypertension ◽  
Sickle Cell Disease ◽  
Sickle Cell ◽  
Research Funding ◽  
Proportional Hazards ◽  
The United States ◽  
Right Heart Catheterization ◽  
Heart Catheterization ◽  
Cell Disease

Abstract Abstract 3240 The role of pulmonary hypertension as a common and attributable cause of mortality in patients with sickle cell disease remains controversial. To assess this question and explore risk factors for death in patients with sickle cell disease we evaluated 632 patients in the Walk-PHASST pulmonary hypertension screening cohort, recruited from nine different study sites in the United States and one site in the United Kingdom. Methods: Patient characteristics and their associations with mortality were analyzed with Cox proportional hazards regression analysis. Based on data from three right heart catheterization screenings studies that have recently been published, we defined the presence of pulmonary hypertension for this analysis by a Doppler-echocardiographic measurement of the tricuspid regurgitant jet velocity (TRV) ≥ 3.0 m/s, which has a 67–75% positive predictive value for a mean pulmonary artery pressure ≥ 25 mm Hg by right heart catheterization. This therefore represents a very conservative threshold for a large population screening study. Among subjects with a measurable TRV (n=572), 64 (11.2%) had measurements of ≥ 3.0 m/sec. Among those with measurable NT-proBNP (n=582), 140 (24.1%) had measurements ≥160 pg/mL, a value associated with both pulmonary hypertension and mortality. A total of 39 (7.4%) had both high TRV (≥3.0 m/sec) and high NT-proBNP (≥160 pg/mL). Results: Over a median follow-up time of 29 months, we observed 22 deaths. 50% (N=11) of these patients had a TRV≥ 3.0 m/sec. At 24 months the cumulative survival was 83% for patients with TRV ≥ 3.0 m/sec and 98% for patients with TRV < 3.0 m/sec (p<0.0001). The unadjusted hazard ratios for death were 11.14 (95% CI 4.1–30.1; p<0.0001) for patients with TRV above and below 3.0 m/sec and 4.55 (95% CI 1.8–11.3; p=0.001) for patients with NT-proBNP above and below 160 pg/mL. For patients with both high TRV (≥ 3.0 m/sec) and high NT-proBNP (≥ 160 pg/mL), the unadjusted hazard ratio was 14.86 (95% CI 5.5–39.9; p<0.0001). Overall, an increased risk of death was observed for both age and gender, with males at higher risk relative to females (HR=2.48, 95% CI 1.0–6.1; p=0.05), and patients older than 47 years (HR=2.02, 95% CI 1.1–3.8; p=0.03). Associations with mortality were also observed for chronic transfusions (HR=3.00, 95% CI 1.2–7.8; p=0.02) and a NYHA/WHO class value or III or IV (HR=4.52, 95% CI 1.4–14.3; p=0.01). Other variables associated with mortality in our cohort included a high hemolytic component, aspartate aminotransferase (AST), ferritin, and creatinine. Variables not associated with mortality included current hydroxyurea use, SC disease, self-reported history of painful episodes, and six-minute walk distance. In stepwise multiple proportional hazards regression analysis, the association between TRV and mortality remained significant after adjustment for all other risk factors, including ferritin, AST, creatinine and even NT-proBNP (HR 4.27, 95%CI 1.3–14.1; p=0.04). Conclusions: Using a more conservative cut-off value of TRV ≥ 3.0 m/sec as defining PH in a large screening population of sickle cell disease patients, PH occurs in approximately 10% of unselected screened patients and is associated with the highest unadjusted and adjusted risk for death of any measured variable. Disclosures: Gladwin: Bayer Corp: Consultancy, Research Funding; NIH and NHLBI: Research Funding; Gilead Sciences: Research Funding. Barst:Ventripoint: Stock options Other; Actelion, Eli Lilly, Gilead, Glaxo Smith-Kline (GSK), Medtronics, Bayer, Ikaria, Pfizer, Novartis, VentriPoint: Consultancy, Honoraria. Girgis:NIH/NHLBI: Research Funding, Travel support Other. Rosenzweig:NIH: Research Funding. Badesch:NIH: Research Funding. Lanzkron:NIH: Research Funding.

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