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 Table of Contents  
ORIGINAL ARTICLE
Year : 2021  |  Volume : 28  |  Issue : 3  |  Page : 218-224

Profile of bacterial pathogens causing infections in children with sickle cell anaemia in Maiduguri


1 Department of Paediatrics, University of Maiduguri, University of Maiduguri Teaching Hospital, Maiduguri, Borno State, Nigeria
2 Department of Medical Microbiology, University of Maiduguri, University of Maiduguri Teaching Hospital, Maiduguri, Borno State, Nigeria

Date of Submission21-Apr-2021
Date of Decision04-Sep-2021
Date of Acceptance10-Sep-2021
Date of Web Publication22-Oct-2021

Correspondence Address:
Dr. Halima Abubakar Ibrahim
Department of Paediatrics, University of Maiduguri Teaching Hospital, PMB 1414, Maiduguri, Borno State
Nigeria
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/npmj.npmj_531_21

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  Abstract 


Background: Sickle cell disease (SCD) is a major cause of morbidity and mortality in African children. Infection has been found to be a major cause of hospitalisation, a major precipitant of crises and one of the greatest causes of death among SCD patients at all ages. Objectives: The objective of the study was to determine the prevalence of bacterial infection, pattern of the isolates and the antibiotic sensitivity of isolated bacteria among children with sickle cell anaemia (SCA). Materials and Methods: A cross-sectional study carried out in the University of Maiduguri Teaching Hospital. A total of 242 hospitalised children with SCA with symptoms and signs of infection were recruited for the study using consecutive sampling technique. Sociodemographic and clinical data were obtained. Blood, urine, aspirates, swabs and cerebrospinal fluid samples were collected based on their clinical presentation and subjected to microbiological analysis. Results: A total of 242 patients were studied. The age range was 9 months–15 years, with a mean age of 6.36 years ± 3.75 years. Male-to-female ratio was 1:1.14, with 41.7% of them belonging to low social class. Seventy seven of the 242 had confirmed bacterial infection giving an incidence of bacterial infection in SCA patients of 31.8%. Gram-negative organisms accounted for 64.5% of the isolates and they include Salmonella, Klebsiella, Escherichia coli and Coliforms. However, Staphylococcus aureus (32.9%) was the most frequent microorganism isolated, followed by Salmonella, (20.3%), Klebsiella (12.6%) and Coliforms (12.6%). Amoxicillin-clavulanate, cefixime and gentamicin showed more than 50% activity against the isolated bacterial pathogens while chloramphenicol was found to have low activity against Salmonella. Conclusion: High index of suspicion of bacterial infection should be borne in mind of the attending physician when children with SCA present with features of infection. Detailed clinical evaluation and appropriate sample collection for microbiological analysis are recommended. Empirical treatment should be started on SCA patients who have clinical evidence of infection and should be broad enough to cover for common bacterial pathogens.

Keywords: Bacteria, children, sickle cell anaemia


How to cite this article:
Ibrahim HA, Yakubu YM, Farouk AG, Ambe P, Gadzama GB. Profile of bacterial pathogens causing infections in children with sickle cell anaemia in Maiduguri. Niger Postgrad Med J 2021;28:218-24

How to cite this URL:
Ibrahim HA, Yakubu YM, Farouk AG, Ambe P, Gadzama GB. Profile of bacterial pathogens causing infections in children with sickle cell anaemia in Maiduguri. Niger Postgrad Med J [serial online] 2021 [cited 2021 Dec 1];28:218-24. Available from: https://www.npmj.org/text.asp?2021/28/3/218/328771




  Introduction Top


Sickle cell disease (SCD) is a genetic disorder characterised by various combinations of haemoglobin S paired with another abnormal structural β chain haemoglobin variant or β thalassemia.[1] The homozygous form of the disease (HbSS) is the severe form and is termed sickle cell anaemia (SCA). According to the WHO estimates, SCD could account for up to 15% of mortality in children below 5 years of age in Africa[2] imposing heavy physiological, mental and financial burdens on affected persons and their relatives. Mortality and morbidity can be substantially reduced by early diagnosis and supportive care.[3] Nigeria has the highest birth prevalence of SCD in the world, with an estimated 150,000 annual births of babies with SCA.[2] Children with SCD have repeated episodes of painful crisis, anaemia and increased susceptibility to infections, with an estimated 50%–90% risk of dying before age 5 years.[2],[4]

Despite much research into the disease, major problems of SCD patients are still painful crises, anaemia and infections. Infection has been found to be a major cause of hospitalisation, a major precipitant of crises and one of the greatest causes of death among SCA patients at all ages particularly in less developed nations like Nigeria.[5],[7],[8] Increased risk of infection among SCA patients is as a result of deficiency in opsonin activity, abnormal neutrophil kinetics and loss of splenic function. In Africa, malaria a major precipitant of crisis frequently coexists with bacterial infections. In areas where antimalarial prophylaxis is adequate, bacterial infections become the dominant problem.[9]

Several organisms including Streptococcus pneumonia, Haemophilus influenzae type b and non-typhi Salmonella have been recognised as important causative agents through studies undertaken in the USA.[6],[10],[11],[12],[13] In the USA, before introduction of pneumococcal conjugate vaccine, children with SCD younger than 3 years had a 53 times greater risk of invasive pneumococcal disease compared with general population.[14] With parental education, penicillin prophylaxis, pneumococcal vaccination and aggressive treatment with intravenous antibiotics for febrile episodes, life expectancy in developed countries increased to 45–55 years,[3],[12] as opposed to 42–48 years in the 1980s.[15] Life expectancy in the African setting, however, is probably <20 years.[1] Scarcity of data has impeded development of evidence-based guidelines in Africa where 80% of all children with the disease are born.[16]

Studies conducted across Africa and particularly Nigeria[9],[17],[18],[19],[20] show a differing spectrum of bacterial isolates from those in developed countries like USA. This study determined the bacterial isolates responsible for infections in children with SCD in Maiduguri North Eastern Nigeria and the antibiotic sensitivity pattern of the isolates.


  Materials and Methods Top


The study was carried out at the Emergency Paediatrics Unit and the Paediatric Medical Wards of University of Maiduguri Teaching Hospital (UMTH), Maiduguri, Borno state, Nigeria, after obtaining ethical approval on 18th June 2014 from Research and Ethics Committee of the Hospital. Informed written consent was obtained from the parents/guardians of all the subjects.

Maiduguri is located in a semi-arid zone lying between latitude 11.5° N and longitude 13.5° E with a sunny weather and a temperature that may be as high as 41°C or more, especially in the hot dry season, and an annual rainfall of 1.14 mm to 771.90 mm. It is a cosmopolitan city with Kanuri, Shuwa-Arab, Marghi, Bura, Fulani and Hausa as the major residents while settlers from other parts of the country as well as neighbouring countries are also found. Islam and Christianity are the major religions.

The study population was made up of children with SCA aged 6 months to 15 years, hospitalised at the UMTH. The study was hospital-based and cross-sectional in design. It was conducted from November 2015 to February 2017, after ethical approval was granted by the hospital's research and ethical committee. The sample size was calculated based on reported prevalence of bacterial infections among SCD children of 60% reported from Zaria, Northern Nigeria.[9]

Kish's formula,[21] was used:



Where: nf = the desired sample size when population is <10,000.

n = the desired sample size when the population is more than 10,000.

N = the estimate of the population size. Average annual population of SCA patients in UMTH is 550.



n = is the minimum sample size when population is > 10,000.

Z = standard normal deviate, usually set at 1.96 corresponding to 95% confidence interval.

P = proportion of children with SCA that develop infection. For this study, the value of P was taken from a previous study in Zaria by Akuse.[9]

P = 0.60, q = (1.0 – P) = 0.40, d = level of precision = 0.05 (5%)

The calculated sample size was 220. Attrition of 10% was added making the total sample size to be 242.

Study population included children with SCA hospitalised at the Emergency Paediatrics Unit and Paediatric Medical Ward of the UMTH. They were recruited consecutively after satisfying the inclusion criteria until the sample size was reached. Inclusion criteria are patients diagnosed with SCA aged 6 months to 15 years with symptoms and signs suggestive of infection. Exclusion criteria include those with known coexisting immunosuppressive conditions such as HIV infection, malignancies, cytotoxic therapy and prolonged steroid therapy; those on antibiotics for more than 48 h before hospitalisation and those that did not give consent/ascent.

On enrolment, a pro-forma detailing sociodemographic variables, clinical history and physical examination was completed by investigator for each patient after pre-testing. Patient's age, gender, indicators of socioeconomic status such as occupation and educational level of both parents and presenting complaints were obtained. Social class was assigned to each patient using the Oyedeji Social Classification Scheme. Histories of antimalarial prophylaxis, recent use of antibiotics (within the previous 48 h) were also obtained. Examination findings, clinical diagnosis and relevant investigations to be done were entered into the pro-forma. Axillary temperature was used for this study and a value of 37.5°C and above was considered as febrile. Samples (blood culture specimen, cerebrospinal fluid [CSF] specimen, urine specimen, pus aspirate and swabs) were collected and taken to the laboratory by the investigator.

Specimen culture

Laboratory procedures were carried out in conjunction with the Medical Microbiologists and Medical Laboratory Scientists after the investigator had been educated.

  1. Blood specimen: The BACTEC PEDS bottles were incubated at 37°C. The initial subculture was carried out after 48 h of incubation on sheep blood agar and MacConkey agar. The agar plates were incubated under aerobic condition at 37°C for 18–24 h. Where the first subculture was negative, a second subculture was done after another 72 h. Where there was no growth after the second subculture, it was reported as 'No Bacterial Growth'.
  2. CSF specimen: CSF fluid was cultured directly onto chocolate and sheep blood agar. The sheep blood agar was then incubated aerobically at 35°C–37°C for 18–24 h, while the chocolate agar plate was incubated in a candle extinction jar to provide an atmosphere of increased carbon dioxide concentration for the possible isolation of Haemophilus influenzae, Neisseria Meningitidis and Streptococcus pneumoniae. Macroscopy, microscopy and gram stain were then carried out on the remaining sample.[22]
  3. Urine specimen: Urine specimen was divided into two. Half was inoculated directly onto sheep blood agar and cysteine lactose electrolyte deficient agar. This was incubated aerobically at 35°C–37°C for 18–24 h. The other half was used for macroscopy, microscopy and Gram staining.
  4. Throat swab: This was inoculated onto blood agar and MacConkey; it was then incubated at 35°C–37°C for 18–24 h, aerobically.
  5. Pus aspirate and swab: This was inoculated onto sheep blood agar and MacConkey and subsequently incubated at 35°C–37°C for 18–24 h both aerobically and anaerobically. The remaining sample was then used for microscopy and Gram staining.


Bacterial identification and characterisation

Preliminary screening test

The colonial morphology of the respective isolates was identified and noted on the respective agar plates. They were then subjected to Gram staining according to standard methods.[23]

Confirmatory test

Gram-negative organisms were subjected to confirmatory methods of identification based on colonial morphology and biochemical reactions of sugars. Gram-positive cocci were subjected to confirmatory methods using the catalase and coagulase biochemical tests.[24]

Antimicrobial susceptibility testing using disc diffusion method

The modified Kirby–Bauer method was utilised.[25] Antibiotic sensitivity testing was done using the commercially available oxoid single discs comprising of cephalexin (30 μg), cefuroxime (30 μg), cefixime (5 μg), ceftriaxone (30 μg), gentamicin (10 μg), penicillin (1unit), erythromycin (30 μg), cotrimoxazole (1.25/23.75 μg), amoxicillin (10 μg), amoxicillin plus clavulanic acid (AMC) 30 μg, streptomycin (10 μg) and chloramphenicol (30 μg).

The test was carried out on Mueller-Hinton agar according to the Clinical and Laboratory Standards Institute guidelines. Four to five colonies of 24-h pure culture isolates were inoculated into 5 ml sterile normal saline and turbidity adjusted to match a 0.5 McFarland standard.[26]

Data obtained were entered and analysed using Statistical Package for the Social Sciences version 20.0 (IBM SPSS statistics for windows version 20.0. Armonk, NY, USA: IBM Corp.). Tables were used for data presentation and study variables were compared using Chi-square (χ2) and student's t-test. A P < 0.05 was considered statistically significant at 95% confidence interval.


  Results Top


Two hundred and forty two children with SCA who satisfied the inclusion criteria were recruited for the study from November 2015 to February 2017. The sociodemographic characteristics of the study population are shown in [Table 1]. The ages ranged from 9 months to 15 years with majority of them in 1 to <10-year age group (70.3%). The mean age + SD of the children studied was 6.36 years ± 3.75. There were 113 (46.7%) males and 129 (53.3%) females giving a male-to-female (M:F) ratio of 1:1.14. There were more children from social class IV 101 (47.6%) than from other classes.
Table 1: Sociodemographic characteristics of the study population (n=242)

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Of the 242 SCA patients studied, 77 had confirmed bacterial infection giving an incidence of 31.8%. One hundred and forty nine (61.6%) of the patients studied had malaria parasitaemia of at least + while two hundred and thirty four (96.7%) were regular on prophylactic proguanil.

The main working diagnoses made at admission included septicaemia, 120 (49.6%), pneumonia 34 (14.0%), urinary tract infection 33 (13.6%) and osteomyelitis 33 (13.6%). Clinical diagnosis of pneumonia was made in 34 (14.0%) of the 242 patients. All had blood culture and chest radiographs. Twenty four had radiological evidence of pneumonia while in the remaining 12 patients, diagnosis was essentially clinical.

There were 33 patients with diagnosis of osteomyelitis of which 15 had periosteal reaction, 13 had pathological fractures and 5 had normal radiographs. All the 120 patients with suspected septicaemia had blood culture done. Only 46 were culture positive giving a yield of 38.3%. Clinical diagnosis of UTI was made in 33 (13.6%) out of the 242 patients. Of the 33 patients, 19 (57.6%) had positive cultures.

[Table 2] shows the distribution of the isolated organisms. Although there were more Gram-negative organisms than Gram-positive organisms, Staphylococcus aureus was the most common isolated organism 26 (32.9%). Candida was isolated from blood of one patient while Blastomyces dermatitidis was isolated from a cutaneous sinus of a patient with chronic osteomyelitis.
Table 2: Distribution of organisms isolated by type (n=79)

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[Table 3] shows the distribution of organisms by specimen. Staphylococcus aureus still remained the most common bacteria isolated from blood and aspirates and swabs. However, Coliforms were the most frequent bacteria from urine.
Table 3: Distribution of organisms by specimen (n=79)

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[Table 4] shows the relationship between rate of culture proven infection and crises. Two hundred and thirty (95%) patients had one form of crises or the other at presentation. [Table 4] shows that positive culture is significantly more likely in patients with mixed crises (58.8%). Patients with vaso-occlusive crises (VOC) and anaemic crises were more likely to have negative culture than positive culture.
Table 4: Rate of infection in relation to crises

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Social class was the only sociodemographic variable that was significantly associated with culture proven infections [Table 5]. Those with culture proven infections were more likely to be from social class V.
Table 5: Sociodemographic characteristics and rate of infections

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As shown in [Table 6], majority of the isolated pathogens exhibited high sensitivity to amoxicillin clavulanate, gentamicin and cefixime. However, the pathogens demonstrated very low sensitivity to cephalexin, penicillin, amoxicillin and erythromycin.
Table 6: In vitro antibiotic sensitivity of isolated bacteria

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  Discussion Top


From this study, there were only 8 (3.3%) infants. This low figure could be due to the fact that most children are not routinely screened for SCD early in life and are only diagnosed when they present with symptoms. Symptoms of SCD are usually evident from 6 months of age by which time there is significant decline in HbF. This calls for establishment of routine screening programmes which can aid early diagnosis of SCD and institution of measures to prevent morbidity and mortality. Another reason could be that most of the children die from severe infections without being diagnosed as the peak age for severe infections is 6 months to 3 years.

Majority of the children were in social class IV 101 (41.7%). The North Eastern part of the country has suffered from effects of insurgency for years, leading to loss of lives, destruction of properties and displacement of people. This has undoubtedly worsened the socioeconomic condition of the people. With Borno and Yobe states having highest prevalence of the sickle cell trait, it is not surprising to find most of the children in low social class.

When compared with the rate of culture-positive infection, only social class had a statistically significant association with demographic indices. There was no statistically significant association with age and sex. Children from social class V were more likely to have culture-positive infection than other classes. This social class is characterised by lack of parental education and poverty. These factors could affect access to quality health care early in the course of illness as a result they end up presenting much later with complicated illnesses. An earlier study by Okany and Akinyanju in Lagos,[27] Nigeria, reported that socioeconomic status has a modifying influence on the severity of SCD with lower status being associated with more severe illness.

Although the incidence of infection in this study is high, it is lower than the reported incidences of 60% in Zaria,[9] 82% in Lagos[17] and 74.6% in Ibadan[19] but higher than those reported from Ilesa (21.7),[20] Uganda (28.4%)[18] and United States (16% and 3.8%).[28],[29] The plausible reason for the lower incidence in this study could be due to the fact that some procedures for obtaining specimens such as lung and Bone aspiration which could have yielded more growth were not done in this study due to their invasive nature. These procedures were carried out in the study from Zaria[9] where the incidence of bacterial infections was 60%. In addition, diagnosis of proven infection in this study was based on laboratory results rather than on clinical signs and symptoms as contained in the studies from Lagos[17] and Ibadan.[19] Laboratory diagnosis is more specific and only culture proven infections are confirmatory. This will prevent erroneous use of antibiotics which would have increased the financial burden on the caregivers, exposed the patient to side effects of the antibiotics and promoted development of resistance to the antibiotic. Malaria frequently coexists with bacterial infections in Africa and in areas where antimalarial prophylaxis is adequate, bacterial infections become the dominant problem.[9] However, in this study, the incidence of malaria parasitaemia was high (61.6%) making it a major differential diagnosis among the patients and leaving few of them with bacterial infection. Makani et al.[30] in a 5-year prospective study for malaria parasitaemia in Tanzanian patients with SCA reported that although malaria infection was not common among outpatients with SCD, its presence in those hospitalised was associated with increased risk of mortality. Patients with SCD will benefit more from intensification in chemoprophylaxis, environmental manipulation and prompt and effective treatment of malaria during severe illnesses.

The finding that Staphylococcus aureus was the most common organism isolated in this study is comparable with findings from other studies in Nigeria[9],[19],[31] and Uganda.[18] This may be due to the fact that individuals with white cell dysfunction like in SCD have an increased susceptibility to Staphylococcus aureus infection.[32] Another reason could be geographical difference as Staphylococcus aureus has been found to be the most common pathogen of osteomyelitis in patients with SCD in Nigeria and the Middle East.[33] In this study, 33% of the patients had clinical diagnosis of osteomyelitis.

Similar to findings from other studies in Nigeria,[9],[17],[19],[31] the Enterobacteriaceae (Salmonella, Klebsiella, Escherichia coli, Shigella, Proteus, Serratia and Citrobacter) were other organisms isolated from this study. This may be due to the fact that ischaemia and infarction of bowel permits Enterobacteriaceae to invade the intestinal wall and enter the blood stream, making them available for isolation. One hundred and sixty eight of the children studied had various forms of VOC including abdominal crises at presentation making the above finding possible.

Blastomyces dermatitidis was isolated from a patient with chronic osteomyelitis and multiple discharging sinuses who had received several antibacterials for suspected bacterial osteomyelitis without response. It is a known cause of fungal osteomyelitis acquired through inhalation of Conidia. Blastomycosis is more aggressive in immunocompromised patients such as those with SCD.[34]

Streptococcus pneumoniae was not isolated in any of the patients in this study. Studies done in other parts of Nigeria and some parts of Africa have reported a low rate[9],[18],[31] or no isolation[17],[19] of Streptococcus pneumoniae. Penicillin prophylaxis and pneumococcal vaccination could be possible reasons for the above finding. Although none of the patients studied was on penicillin prophylaxis, some of them especially the 'under five' might have received pneumococcal conjugate vaccine as part of routine National Program on Immunisation (NPI). However, the immunisation status (according to NPI schedule) of children in this study was not assessed. Prior use of antibiotics could be another reason but only 2.5% of the patients admitted to prior use of antibiotics. This figure is likely to be actually higher because patronising patent medicine stores are a common practice in this environment. Most of the children studied are from lower a social class which in turn correlates with low level of literacy among the parents. These parents may not be able to distinguish antibiotics from combinations of drugs received from the stores as such may say 'no' to prior use of antibiotics. Penicillins are common over the counter drugs which have activity against Streptococcus pneumoniae. Another reason for lack of isolation of Streptococcus pneumoniae could be due to reports of possible preservation of splenic function by persistent malarial stimulation in African children with SCD,[33] making them less susceptible to encapsulated organisms like Streptococcus pneumoniae.

In this study, when microbial culture rate was assessed, positive culture was only more likely in mixed crisis while culture in VOC and anaemic crises was more likely to be negative, suggesting that malaria rather than bacterial infection is a likely precipitant of crises in the later.

While proving infections by culture is very important, the antibiotic sensitivity of the isolated organism is very crucial for the management of the patient and policy making. Unlike some of the papers reviewed,[11],[13],[16],[17],[18],[19],[20],[35],[36] this study demonstrated antibiotic sensitivity pattern of the isolated bacteria. However, a 1996 study from Zaria[9] reported high sensitivities of isolated bacteria to ampiclox, gentamicin and first generation cephalosporins. The effectiveness of amoxicillin-clavulanate and cefixime against all the isolated organisms from this study is an advantage as it is useful in the choice of antibiotics for empirical treatment, especially when culture result is not readily available. The only drawback here is that cefixime which is a third generation cephalosporin with good activity against Gram-negative organisms is available only in oral form making it an unsuitable antibiotic, especially during the initial phase of treatment of severe infections where parenteral drugs are needed. The high level of sensitivity towards these drugs makes them a good choice because of their known safety profile in children. More so, gentamicin has been found to have excellent activity against 70% of the isolated organisms, making it a good alternative because of its availability and cost effectiveness. The observation of low sensitivity of Salmonella to chloramphenicol, a common antibiotic used when infection with this organism is suspected, is worrying. This finding could be explained by resistance to chloramphenicol as a result of widespread use. Choices of antibiotics should, however, generally be based on local antibiotic sensitivity patterns, availability of the drugs, cost of the drugs and clinical state of the patient.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
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  [Table 1], [Table 2], [Table 3], [Table 4], [Table 5], [Table 6]



 

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