|Year : 2018 | Volume
| Issue : 3 | Page : 80-85
Prevalence and pattern of bacterial isolate in febrile children with sickle cell anemia in a tertiary hospital in Northern Nigeria
Abdullahi Musa1, Olufemi Gboye Ogunrinde1, Aisha Indo Mamman2, Yauba Muhammad Saad3, AbdulRasul Ibrahim4, Alhassan Mela Yakubu1
1 Department of Paediatrics, College of Health Sciences, Ahmadu Bello University, Zaria, Nigeria
2 Department of Haematology, College of Health Sciences, Ahmadu Bello University, Zaria, Nigeria
3 Department of Paediatrics, College of Medical Sciences, University of Maiduguri, Zaria, Nigeria
4 Department of Medical Microbiology, College of Health Sciences, Ahmadu Bello University, Zaria, Nigeria
|Date of Web Publication||29-Jul-2019|
Department of Paediatrics, College of Medical Sciences, Ahmadu Bello University/Teaching Hospital, Zaria
Context: Bacterial infections constitute a major cause of morbidity and mortality in children with sickle cell anemia (SCA). These children have increased susceptibility to bacterial infections, the pattern of which varies with place and time. Knowledge of local pattern of bacterial infection in SCA will facilitate empirical management. Aims: This article aims to determine the prevalence and pattern of bacterial isolates and their in vitro antibiotic sensitivities in febrile children with SCA. Settings and Design: A comparative cross-sectional study was conducted at Ahmadu Bello University Teaching Hospital, Zaria, Nigeria. Methods and Material: Two hundred and thirty-two febrile children with SCA between 6 months and 15 years and another 232 febrile children with AA phenotype were investigated for bacterial infections. Blood and urine cultures were done in all the patients and other cultures were performed based on the patients’ clinical presentation. Statistical Analysis Used: Data was analyzed using Epi Info statistical software. Results: Bacterial cultures were positive in 34 (14.7%) of children with SCA and 40 (17.2%) of the controls. The three most frequently isolated pathogens among both children with and without SCA were Staphylococcus aureus (23.5%; 25.0%), Escherichia coli (23.5%; 20.0%), and Klebsiella spp. (14.7%; 17.5%). Bacterial infection was significantly more common in children less than 5 years with SCA (χ2 = 3.98, df = 1, P = 0.046). Most of the organisms isolated were sensitive to third-generation cephalosporins. Conclusions: Gram-negative bacteria were the most common isolates in febrile children with SCA. Boys less than 5 years have higher positivity rates. In children with SCA admitted with suspected bacterial infection, third-generation cephalosporins should be the antibiotic of choice for empirical treatment.
Keywords: Bacterial isolate, children, fever, sickle cell anemia
|How to cite this article:|
Musa A, Ogunrinde OG, Mamman AI, Saad YM, Ibrahim A, Yakubu AM. Prevalence and pattern of bacterial isolate in febrile children with sickle cell anemia in a tertiary hospital in Northern Nigeria. Sub-Saharan Afr J Med 2018;5:80-5
|How to cite this URL:|
Musa A, Ogunrinde OG, Mamman AI, Saad YM, Ibrahim A, Yakubu AM. Prevalence and pattern of bacterial isolate in febrile children with sickle cell anemia in a tertiary hospital in Northern Nigeria. Sub-Saharan Afr J Med [serial online] 2018 [cited 2019 Oct 20];5:80-5. Available from: http://www.ssajm.org/text.asp?2018/5/3/80/263561
| Introduction|| |
Bacterial infection remains one of the major causes of morbidity and mortality in children with sickle cell anemia (SCA) and this situation is due to the increased susceptibility of these children to bacterial infections caused by encapsulated organisms.,, Loss of splenic function is one of several factors believed to contribute to this increased susceptibility.
The etiological agents of bacterial infection in children vary from place to place. Organisms like Streptococcus pneumoniae and Haemophilus influenzae, which cause vaccine-preventable infections, are often reported to be the major causes of bacterial infections in these patients in the developed countries.,,,, This has led to the use of preventive measures against such organisms like pneumococcal vaccine, H. influenzae (Hib) vaccine, and routine use of penicillin prophylaxis in children with significant reduction in morbidity and mortality. However, most studies from Africa have not revealed either of these organisms as the leading cause of infection in these patients.,,, In Nigeria, different studies have shown organisms such as Staphylococcus aureus, Escherichia More Details coli, Klebsiella spp., and Salmonella More Details spp. as leading causes with varying degrees of sensitivities to different antibiotics.,,, All these studies did not determine the effect of age, considering that the pathology of sickle cell disease is progressive.
The present study, therefore, aimed to compare the prevalence and pattern of bacterial isolates and their antibiotic sensitivities in febrile children of various age groups, with and without SCA in Ahmadu Bello University Teaching Hospital (ABUTH), Zaria. The information generated from the study will provide a basis for empirical treatment of children with bacterial infections.
| Patients and methods|| |
This was a descriptive cross-sectional study conducted over 11 months at the Department of Paediatrics and Institute of Child Health, Banzazzau, both of ABUTH, Zaria. Consecutively enrolled febrile (axillary temperature of ≥37.5°C) children with SCA between the ages of 6 months and 15 years were studied. Age and sex-matched febrile children with confirmed hemoglobin phenotype AA were enrolled as controls from the pediatric outpatient clinic and emergency pediatric unit of the same hospital. Children who had been on antibiotics within the week preceding enrolment into the study and those with other forms of sickle cell disease other than SCA were excluded. Ethical approval was obtained from the ABUTH Health Research Ethics Committee and a written informed consent was also obtained from parents/guardians of the patients. History recorded at enrolment included age, sex, antibiotic use, prophylactic use of penicillin, and vaccination with Hib vaccine or pneumococcal conjugate vaccine. Physical examination was done at presentation and temperature was recorded at triage.
All patients had blood specimen and urine samples taken for culture and sensitivity. Other samples such as cerebrospinal fluid, stool, wound, and ear swabs were taken as indicated by the child’s clinical diagnosis. One milliliter of blood was immediately transferred into a bottle containing 10 mL of sterile thioglycolate broth using a new needle. The specimen was then incubated at 37°C for 48 h after which the first subculture onto blood, chocolate, and MacConkey agar was performed.
The agar plates were then incubated under aerobic and anaerobic conditions. The chocolate agar was incubated in an atmosphere of increased carbon dioxide concentration using extinction jar to promote the growth of Neisseria More Details meningitides and H. influenzae. After 24 h, the plates were examined for growth, which, if visible colonies, were then identified using Gram stain, and biochemical and serological tests using standard techniques.
Urine microscopy was done immediately and also a well-mixed urine specimen was inoculated onto blood and MacConkey agar plates and incubated aerobically at 37°C for 24 to 48 h. Significant bacteriuria was diagnosed in patients with 105 CFU/mL or more of bacterial growth from midstream urine or clean catch. Any growth of bacteria from a suprapubic aspirate was also considered as significant. Any growth detected was identified by biochemical and serological tests. Sensitivity was determined using antibiotic discs.
Hemoglobin electrophoresis was determined for all the patients using cellulose acetate paper with a buffer at a pH of 8.0 to 9.0 as described by Dacie and Lewis.
Frequency tables were used to illustrate the data obtained. Chi-square test was used for bivariate analysis to compare categorical variables and a P value of less than 0.05 was considered statistically significant.
| Results|| |
A total of 232 patients with SCA and an equal number of controls were studied. Of the 232 patients studied in each group, 144 (62.1%) were males giving a male to female ratio of 1.64:1 [[Table 1]]. Patients and controls aged less than 5 years were 169 (72.8%) each whereas those older than 5 years were 63 (27.2%) each. The mean age was 4.2 ± 3.6 years in both the studied populations.
Bacterial isolates in the study groups
Of the 232 patients with SCA, 34 (14.7%) had positive bacterial cultures compared to 40 (17.2%) of the 232 controls. The higher prevalence was, however, noticed only among children of 5 to 9 years. The difference in the rates of bacterial isolation between the two groups was, however, not statistically significant (χ2 = 0.58, df = 1, P = 0.45). Among children with SCA, there was a significantly higher yield of bacteria in patients aged less than 5 years [30 (17.8%) of 169] compared to those older than 5 years [4 (6.3%) of 63] (χ2 = 3.98, df = 1, P = 0.046). Boys with SCA less than 5 years had significantly higher rate of bacterial isolates [21 (23.9%) of 88] than their female counterparts [6 (9.4%) of 64] (χ2 = 5.29, df = 1, P = 0.02). None of the patients studied in either the SCA group or the controls had more than one organism isolated.
Gram-negative bacteria as a group accounted for 22 (64.7%) of the 34 isolates among patients with SCA and 23 (57.5%) of 40 isolates among the controls. Of these, E. coli was the most common isolate accounting for 8 (23.5%) of the total isolates among the patients with SCA and 10 (25%) among the controls [[Table 2]]. When the organisms were compared according to the age group, 87.5% of the E. coli and 62.5% of the Staph. aureus and 50% of the Strep. pneumoniae were isolated from under fives among the SCA group. Among the controls, 75% of the E. coli and 50% of the Staph. aureus and 87.5% Strep. pneumoniae were from under fives.
There were 12 gram-positive organisms isolated in the patients with SCA, which accounted for 35.3% of the isolates compared to 17 (42.5%) among the controls. Staph. aureus was isolated in 8 (23.5%) and Strep. pneumoniae was isolated in only 4 (11.8%) of the patients with SCA. Among the controls, Staph. aureus was isolated in 10 (25%) and Strep. pneumoniae in 7 (17.5%) patients.
Use of preventive measures among patients with SCA
Among the 232 children with SCA studied, only 20 (8.6%) were using penicillin routinely as a preventive measure against infection. Of those using penicillin, none had a positive bacterial culture. None of the patients studied received Hib vaccine or pneumococcal vaccine.
Antibiotic sensitivity pattern
[[Table 3] and [Table 4]] showed the in vitro sensitivity pattern of the bacteria isolated from the patients with SCA and controls, respectively. Overall, the organisms were most sensitive to ceftriaxone (90.6%) in the SCA group and ceftazidime (100%) in the control group. The organisms were least sensitive to erythromycin among the SCA children with overall sensitivity of 6.3% and to cotrimoxazole in the control group with overall sensitivity of 7.7%. E. coli and Staph. aureus isolated had good sensitivity to all the antibiotics except penicillin and nitrofurantoin. Isolates of Strep. pneumoniae were sensitive to most of the antibiotics including penicillin (75%), chloramphenicol (100%), and ceftriazone (100%). The Strep. pneumoniae was, however, resistant to cotrimoxazole and ciprofloxacin.
|Table 3 In vitro antibiotic sensitivity pattern of bacterial agents isolated in children with SCA|
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|Table 4 In vitro antibiotic sensitivity pattern of the bacterial agents isolated in the patients without SCA|
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H. influenzae was sensitive to most of the antibiotics tested but resistant to penicillin, cotrimoxazole, and clavulanic acid-potentiated amoxycillin among the control group. The Pseudomonas isolated was highly resistant to most of the antibiotics but 100% sensitive to gentamicin, ciprofloxacin, ceftriazone, and ceftazidime.
| Discussion|| |
The overall prevalence of bacterial isolation among febrile children with SCA was lower than those without SCA in our study. The fact that there was a higher yield of bacteria in the children without SCA contradicts findings from other studies., This may be because the children without SCA are more likely to present to hospital when they are severely ill compared to patients with SCA, most of whom seek care because of acute illnesses associated with the SCA or malaria, all of which can cause fever and, as such, less likely to yield bacteria on culture.
The prevalence of bacterial infections among febrile children with SCA at 14.7% in our study is low when compared to earlier studies from Nigeria and other African countries that ranged from 28.4% to 60%.,,, The reason for the lower prevalence may be because of increased awareness of children with SCA and their parents over time, as a result of regular clinic follow-up, on how to prevent crisis and infection, as has been shown by Rahimy et al. It may also suggest the fact that the prevalence of infection has reduced in the environment, because of improved sanitation and personal hygiene as asserted by Mara et al. A more recent study by Wierenga et al. from Jamaica got a much lower prevalence of 6.1%, likely because they used 39°C or more as the definition of fever; thus, they may have excluded some bacteremic cases with lower degrees of fever. Also they reported routine use of benzathine penicillin among the patients as a form of prophylactic measure against infection. Even though the use of penicillin was not significant in our study, it is worth mentioning that none of the patients on routine penicillin had positive bacterial isolate.
Bacterial infection in the present study was found to be significantly more common in children with SCA under the age of 5 years than in those older than 5 years, as reported in the earlier studies.,,,, This may be because of improvement in personal care and hygiene with increasing age as reported by Rahimy et al.
Staph. aureus, E. coli, and Klebsiella species were the most common organisms isolated in the present study, a finding that was similar to earlier studies from Africa,,, but contrasted with those from the developed world that showed Strep. pneumoniae and H. influenzae to be the most common pathogens.,,,,, An explanation may be that Staph. aureus, E. coli, and Klebsiella species these prevail in our community due to environmental factors such as high humidity and poor sanitary standards, which obtains in our environment, and these may supersede pneumococcus as the leading cause of bacterial infection. Also Staph. aureus, E. coli, and Klebsiella species are easier to culture than are fastidious organisms such as pneumococcus and H. influenzae; in laboratories with few resources, this differential culture sensitivity might bias the distribution of the pathogens detected.
Another possible explanation is that the early loss of splenic function seen mainly in nonmalarial endemic areas may leave children with SCA susceptible to pneumococcal infection, and that the reverse might be the case in malarial endemic areas with persistent antigenic stimulation from malaria resulting in prolongation of splenic function in these children.,
The present study showed that the predominant organisms isolated were most sensitive to third-generation cephalosporins and gentamicin that is similar to findings in some previous studies., This may be due to the fact that these drugs are not commonly abused because they are expensive and are administered parenterally. All the Staph. aureus isolated were also sensitive to the third-generation cephalosporins that are antibiotics with effect mostly against gram-negative organisms.
Penicillin, cotrimoxazole, and erythromycin were the least sensitive drugs in this study. This may be because they are cheap and also available in substandard or fake preparations leading to development of resistance in the community. This study showed that chloramphenicol still has good effect against H. influenzae and Strep. pneumoniae as all the H. influenzae and pneumococcus isolated were sensitive.
Our study has shown that bacterial infection in children with SCA is lower than previously reported and that bacterial isolates were similar in children with and without SCA. Also, third-generation cephalosporins should be used empirically in children in our environment suspected with bacterial infection before the result of antibiotic sensitivity becomes available. Further studies are needed to demonstrate the usefulness of preventive measures against bacterial infections in SCA.
Presentation at a meeting
This study was presented at the African Field Epidemiology Network (AFENET) Conference, Ethiopia, in 2013.
The authors thank the children who participated in this study. The authors also acknowledge the contributions of the staffs of the Departments of Haematology and Microbiology especially Peter A. Abunimye, Abdulhadi Abubakar, Suleiman Mukhtar, and Iliya Kigbu for their technical assistance.
Financial support and sponsorship
This study was supported by the McArthur Foundation.
Conflicts of interest
There are no conflicts of interest.
| References|| |
Onwubalili JK. Sickle cell disease and infection. J Infect 1983;7:2-20.
Booth C, Inusa B, Obaro SK. Infection in sickle cell disease: a review. Int J Infect Dis 2010;14:e2–12.
Lobel JS, Bove KE. Clinicopathologic characteristics of septicemia in sickle cell disease. Am J Dis Child 1982;136:543-7.
Brousse V, Buffet P, Rees D. The spleen and sickle cell disease: the sick (led) spleen. Br J Haematol 2014;166:165-76.
Hongeng S, Williams JA, Harris S, Day SW, Wang WC. Recurrent Streptococcus pneumoniae
sepsis in children with sickle cell disease. J Pediatr 1997;130:814-6.
Wong WY, Overturf GD, Powars DR. Infection caused by Streptococcus pneumoniae
in children with sickle cell disease: epidemiology, immunologic mechanisms, prophylaxis and vaccination. Clin Infect Dis 1992;14:1124-36.
Kabins SA, Lerner C. Fulminant pneumococcemia and sickle cell anemia. J Am Med Assoc 1970;211:467-71.
Powars D, Overturf G, Turner E. Is there an increased risk of Haemophilus influenzae
septicemia in children with sickle cell anemia? Pediatrics 1983;71:927-31.
Serjeant GR. The natural history of sickle cell disease. Cold Spring Harb Perspect Med 2013;3:a011783.
Akinyanju O, Johnson AO. Acute illness in Nigerian children with sickle cell anaemia. Ann Trop Paediatr 1987;7:181-6.
Okounghae HO, Nwankwo MU, Offor EC. Pattern of bacteraemia in febrile children with sickle cell anaemia. Ann Trop Paediatr 1993;13:55-64.
Akuse RM. Variation in the pattern of bacterial infection in patients with sickle cell disease requiring admission. J Trop Pediatr 1996;42:318-23.
Kizito ME, Mworozi E, Ndugwa C, Serjeant GR. Bacteraemia in homozygous sickle cell disease in Africa: is pneumococcal prophylaxis justified? Arch Dis Child 2007;92:21-3.
Aken’ova YA, Bakare RA, Okunade MA. Septicaemia in sickle cell anaemia patients: the Ibadan experience. Central Afr J Med 1998;44:102-4.
Dacie JV, Lewis SM. Practical Haematology. 5th ed. Edinburgh: Churchill Livingstone; 1975.
Rahimy MC, Gangbo A, Ahouignan G, Adjou R, Deguenon C, Goussanou S et al.
Effect of a comprehensive clinical care program on disease course in severely ill children with sickle cell anemia in a sub-Saharan African setting. Blood 2003;102:834-8.
Mara D, Lane J, Scott B, Trouba D. Sanitation and health. PLoS Med 2010;7:1-7.
Wierenga KJJ, Hambleton IR, Wilson RM, Alexander H, Serjeant BE, Serjeant GR. Significance of fever in Jamaican patients with homozygous sickle cell disease. Arch Dis Child 2001;84:156-9.
Mallouh AA, Salamah MM. Pattern of bacterial infection in homozygous sickle cell disease.A report from Saudi Arabia. Am J Dis Child 1985;139:820-2.
Onwubalili JK. Sickle cell disease and infection. J Infect 1983;7:2-20.
Magnus SA, Hambleton IR, Moosdeen F, Serjeant GR. Recurrent infections in homozygous sickle cell disease. Arch Dis Child 1999;80:537-41.
Brown B, Dada-Adegbola H, Trippe C, Olopade O. Prevalence and etiology of bacteremia in febrile children with sickle cell disease at a Nigeria tertiary hospital. Mediterr J Hematol Infect Dis 2017;9:e2017039.
Overturf GD, Powars D, Baraff LF. Bacterial meningitis and septicaemia in sickle cell disease. Am J Dis Child 1977;131:784-7.
Ward J, Smith AH. Hemophilus influenzae bacteremia in children with sickle cell disease. J Pediatr 1976;88:261-3.
Adeleke AD, Adeolu OO, Jeje AA, Odesanmi AVO. Persistent gross splenomegaly in Nigerian patients with sickle cell anaemia, relationship to malaria. Ann Trop Paediat 1985;8:103-7.
Serjeant GR, Ndugwa CM. Sickle cell disease in uganda: a time for action. East Afr Med J 2003;80:384–7.
[Table 1], [Table 2], [Table 3], [Table 4]