|Year : 2015 | Volume
| Issue : 2 | Page : 79-84
Epidemiology and Clinical Outcomes of Community Acquired Pneumococcal Infection in North-West Nigeria
Garba Iliyasu1, Abdulrazaq G Habib1, Aminu B Mohammed2, Mohammad M Borodo1
1 Department of Medicine, Faculty of Clinical Science, College of Health Sciences, Bayero University Kano, Kano, Nigeria
2 Department of Microbiology, Aminu Kano Teaching Hospital, Kano, Nigeria
|Date of Submission||23-Dec-2014|
|Date of Acceptance||12-Mar-2015|
|Date of Web Publication||20-May-2015|
Dr. Garba Iliyasu
Department of Medicine, College of Health Sciences, Bayero University Kano, Kano
Introduction: Pneumococcal infection is a leading cause of morbidity and mortality worldwide. There is a paucity of data on pneumococcal infection in Nigeria. We aimed to determine the epidemiology and clinical outcome of pneumococcal infection in a Tertiary Referral Center in Northwestern Nigeria. Materials and Methods: We conducted a prospective, hospital-based study on patients with community acquired pneumococcal infections. All studied subjects had clinical evaluation and relevant laboratory investigations. The outcome was defined as mortality. Analysis was carried out using descriptive statistics with differences and relationships determined using Student's t-test, Chi-squared and Fisher's exact tests as appropriate, with P < 0.05 regarded as significant. Result: Three hundred and two cases of bacteriologically proven community acquired pneumonia (241/302), bacteremia (38/302) and meningitis (23/302) were screened, out of which 125/241 (51.7%), 7/23 (30.4%) and 8/38 (21.1%) were pneumococcal pneumonia, pneumococcal meningitis and pneumococcal bacteremia, respectively. Most of the patients, 87/140 (69.3%) had comorbidity conditions. The overall mortality rate was 12.9%. Chronic heart disease (odds ratio [OR] = 1.143; 95% confidence interval [CI] = 0.032-0.638), human immunodeficiency virus infection (OR = 2.309; 95% CI = 1.258-4.241), age ≥65 years (OR = 6.397; 95% CI = 2.181-18.746), and infection with multi-drug resistant Pneumococcus (OR = 4.089; 95% CI = 1.274-13.125) were identified as independent risk factors for mortality. Conclusion: The Pneumococcus is a common cause of community acquired infections among adults in northwestern Nigeria, with associated high mortality.
Keywords: Community acquired, infection, Nigeria, pneumococcal
|How to cite this article:|
Iliyasu G, Habib AG, Mohammed AB, Borodo MM. Epidemiology and Clinical Outcomes of Community Acquired Pneumococcal Infection in North-West Nigeria. Sub-Saharan Afr J Med 2015;2:79-84
|How to cite this URL:|
Iliyasu G, Habib AG, Mohammed AB, Borodo MM. Epidemiology and Clinical Outcomes of Community Acquired Pneumococcal Infection in North-West Nigeria. Sub-Saharan Afr J Med [serial online] 2015 [cited 2019 Sep 21];2:79-84. Available from: http://www.ssajm.org/text.asp?2015/2/2/79/157429
| Introduction|| |
Streptococcus pneumoniae, otherwise call the Pneumococcus has remained an extremely important human bacterial pathogen since its initial recognition in the late 1800 s. Worldwide, it remains the most common cause of community-acquired pneumonia (CAP), sporadic bacterial meningitis and bacteremia. , It is an important public health concern throughout the world and as a leading cause of lower respiratory tract infection, its global burden in causing disease and deaths is comparable to that of the human immunodeficiency virus (HIV), malaria and tuberculosis.  Africa and Asia account for the greatest proportion of pneumococcal infection worldwide, and together they account for 66% of cases worldwide.  Nigeria accounts for 5% of the total burden at the third place after India and China.  Since no population-based data on pneumococcal infection in most developing countries are available, the estimates of disease burden are based on small clinical studies, vaccine trials, extrapolation from data in developed countries, and studies of persons at high risk for disease. Incidence rate of 416 and 388/100,000 were reported among children <5 and 3 years in Mozambique and Gambia, respectively. , While in Europe and the United States, the annual incidence of invasive pneumococcal infections (IPI) ranges from 10 to 100/100,000 with a mortality rate of 10-50%; the highest values were seen in elderly subjects aged 65 years or more.  In a prospective study of adults with bacteremic pneumococcal pneumonia in Canada, an overall incidence of 9.7 cases/100,000 population was found.  The World Health Organization estimated that 1.6 million people die from pneumococcal disease every year,  with developing countries bearing the greatest burden. 
Risk factors for IPI include; extremes of age, certain racial and ethnic groups, and underlying medical conditions such as diabetes mellitus, chronic heart disease (CHD), chronic pulmonary disease, chronic renal failure, alcohol abuse, functional (such as sickle cell anemia) or anatomic asplenia etc. ,,,, HIV infection can also substantially increase the risk of pneumococcal infection. , Among adults aged 18-55 years with HIV infection, Breiman et al.,  found that African Americans, current smokers, and persons who had close contact with children were at increased risk.
Knowledge on pneumococcal infection among the adult population in Nigeria is lacking. The main objective of this study was to describe the epidemiology and outcome of community-acquired pneumococcal infections among adults, as seen in a Tertiary Referral Hospital in North-western Nigeria.
| Materials and Methods|| |
We conducted a prospective study among patients attending Aminu Kano Teaching Hospital (AKTH) between June 2009 and January 2011. All adult 18 years and above with a diagnosis of either CAP, meningitis or bacteremia were included. The hospital provides tertiary care and serves as a major referral center for other states in North-western Nigeria and neighboring Niger republic. It has 550 beds and offers specialist inpatient and outpatient care, across various specialties.
All adult patients who were admitted over the study period with features compatible with CAP, meningitis and bacteremia were screened for inclusion. Patients <18 years and those who did not consent were excluded from the study. A sputum specimen was collected in a clean, sterile container from patients with the clinical diagnosis of pneumonia. Blood samples were collected from all the patients and inoculated directly into each of brain-heart infusion and thioglycolate culture medium, with the use of standard aseptic procedures for aerobic and anaerobic cultures, respectively. All those who presented with clinical features of compatible with meningitis had a lumbar puncture provided no contraindications exist. The cerebrospinal fluid (CSF) samples were collected in a clean, sterile container and were sent to the laboratories for microbiological analysis, cell count and for glucose and protein measurement. A blood sample was drawn for random plasma glucose measurement just before the lumbar puncture was performed, for comparison with the CSF glucose level. All Samples were taken before administering antibiotic whenever feasible and transported to the laboratory immediately. All patients who consented were screened for HIV infection using two consecutive rapid tests (determine and unigold). Posttest counseling was done for those who tested positive and enrolled in to HIV care program, those that tested negative were enlightened on how to remain negative.
The laboratory operates 24 h/day and is able to process CSF specimen within 30 min of receipt. All samples of sputum and CSF were inoculated onto 5% sheep blood agar and incubated at 37°C. Inoculated plates were incubated in a candle jar so as to create a reduced oxygen tension (5-10% additional CO 2 tension). Inoculated blood culture bottles were incubated in the laboratory at 37°C and observed for bacterial growth within 24-72 h and then until day 7 if there was no bacterial growth earlier. Inoculated media were sub-cultured onto blood agar plates and incubated as per CSF and sputum twice, on days 2 and 3 after incubation. Plates were examined for growth, by the use of standard procedures. Samples of all typical pneumococcal colonies obtained were subjected to further identification methods (presence of α-haemolysis, colony morphology and ethylhydrocupreine hydrochloride (optochin) sensitivity. Only samples with microbiologically proven isolates were finally selected for the study.
Microbial susceptibility tests were carried out on all confirmed pneumococcal isolates to penicillin G, cefotaxime, ceftriaxone, tetracycline, trimethoprim/sulfamethoxazole, erythromycin, ofloxacin and chloramphenicol using E-test strips (AB BIODISK, Sweden). Minimum inhibitory concentration was measured and strains were divided into resistant, intermediate or sensitive according to the Clinical and Laboratory Standard Institute guidelines.  Multi-drug resistant (MDR) Pneumococcus was defined as resistance to at least ≥3 classes of antibiotics. 
pneumococcal pneumonia was defined based on clinical plus chest radiographic findings consistent with pneumonia, in addition to a positive culture of S. pneumonia from an ideal sputum specimen defined as the presence of more than 25 white cells and <10 squamous epithelial cells per low power field. Pneumococcal meningitis was defined as isolation of S. pneumoniae from a CSF sample in a patient with clinical evidence of meningitis. Pneumococcal bacteremia was defined as isolation of S. pneumonia from the blood sample collected aseptically.
The following clinical data of all patients with bacteriologically proven IPI were collected and analyzed: Demographic data, clinical features, co-morbidities, HIV serostatus, antibiotic susceptibility result and outcome (mortality) at 1-month after discharge. All patients were managed according to the hospital's standard protocol for IPI, and none of the patients received steroids.
Analysis was carried out using descriptive statistics with differences and relationships determined using Student's t-test, Chi-square and Fisher's exact tests as appropriate, with P ≤ 0.05 regarded as significant. Determinants and predictors were explored using univariate and multivariable analysis with unadjusted (crude) odds ratio (OR) and logistic regression adjusted, respectively. Statistical Package for Social Sciences version 16.0 was used (SPSS, Illinois Chicago, USA).
Ethical clearance was obtained from the ethics committee of AKTH. Informed consent was obtained from the patients or their legal representatives.
| Results|| |
The ages of the patients ranged from 18 to 82 years, with a mean age of 42.7 years (±18.74). The peak age groups were 55-64 years and ≥65 years [Figure 1]. There were 73/140 (52.1%) males and 67/140 (47.9%) females with a male-to-female ratio of 1.09. Out of the 140 patients, 98 (74.2%) consented for HIV screening and 19 (19.4%) were positive.
During the study period, 302 cases of bacteriologically proven community-acquired infections (241 pneumonia, 38 bacteremia, 23 meningitis) were screened, out of which 125/241 (51.7%), 7/23 (30.4%) and 8/38 (21.1%) were pneumococcal pneumonia, pneumococcal meningitis and pneumococcal bacteremia syndromes, respectively [Table 1]. This translates to 140/302 (46.4%) of the total community acquired infections seen during the study period. Of the 125 patients with pneumococcal pneumonia, there were 6 (4.8%) cases of bacteremic pneumonia. Pneumococcal vaccination was not documented in any of the patients.
Significant number of the patients, 67/140 (47.9%) had at least one comorbidity while 20 had at least two comorbid conditions. The most common being chronic pulmonary disease 23/67 (34.3%), HIV 19/67 (28.4%), sickle cell anemia 15/67 (22.4%), CHD 10/67 (14.9%). While 20/140 (14.3%) of the patients were smokers [Table 1].
Eight patients were lost to follow-up; all among those with pneumonia and 17 died; giving an overall mortality of 17/132 (12.9%), at 1-month. [Table 2] shows the outcomes for each pneumococcal syndrome; with the highest mortality seen in those with meningitis. Out of the 17 patients who died, 10/17 (58.8%) were aged 65 years or older while the remaining 7/17 (41.2%) were in the 15-64 year age brackets (P = 0.001), there was a slight peak at the 35-44 year age group with 3/17 (17.6%) deaths while no death was recorded in the 25-34 year age group. There was significantly higher mortality among those who were HIV positive compared to HIV negative patients (6/19 [31.6%] vs. 8/79 [10.1%], P = 0.016).
One hundred and thirty two pneumococcal isolates were tested against panels of commonly used antibiotics; 19/132 (14.4%) were resistant to at least one class of antibiotic, 42/132 (31.8%) were resistant to two classes of antibiotics while 71/132 (53.8%) were resistant to three or more classes of antibiotics (MDR). None of the isolates was susceptible to all the antibiotics tested. Most of the isolates were sensitive to ceftriaxone (96.2%), chloramphenicol (80.3%) and amoxicillin (78.8%), while most were resistant to trimethoprim/sulfamethoxazole (96.2%). Mortality was higher among those infected with MDR Pneumococcus (χ2 = 9.315, P = 0.003) [Table 3].
|Table 3: Outcomes, according to number of class of antibiotic resistance|
Click here to view
On multiple logistic regression analysis the only factors predictive of mortality were CHD (OR = 1.143; 95% CI = 0.032-0.638), HIV (OR = 2.309; 95% CI = 1.258-4.241), age ≥65 years (OR = 6.397; 95% CI = 2.181-18.746), and infection with MDR Pneumococcus (OR = 4.089; 95% CI = 1.274-13.125).
| Discussion|| |
There is a paucity of data on pneumococcal infection in Nigeria, even though there is a large body of information on the same subject from the western literature. This is primarily a clinical study on pneumococcal infection which addresses the epidemiology, pattern of presentation and clinical outcomes of the major pneumococcal syndromes, as observed in a Tertiary Teaching Hospital in North-western Nigeria.
The Pneumococcus is the commonest cause of CAP, meningitis and bacteremia worldwide. , In this study, it represented 46.4% of CAP, community acquired meningitis and community acquired bacteremia, with pneumonia being the commonest syndrome 125/140 (89.3%). This is similar to a report by Rueda et al., where they found a rate of 85%, 5.1% and 3.7% for pneumonia, bacteremia and meningitis, respectively.  A higher rate of bacteraemia and meningitis in children compared to adults has been previously reported.  In the past three decades, studies of the etiology of CAP in Nigeria reported Pneumococcus as the most common cause. ,,, It was also shown to be the most prevalent isolate among patients with community acquired sporadic meningitis in northeastern Nigeria.  Data on the prevalence of community acquired pneumococcal bacteremia in Nigeria is scanty, however this study highlighted the significance of Pneumococcus as an important cause of community acquired bacteremia in northwestern Nigeria, which is in keeping with reports from other parts of the world.  Pneumococcal infection is believed to have been under-reported in Nigeria because of the fastidious nature of the organism and the use of human blood for preparation of blood agar. We used sheep blood in this study. Our case definition for pneumococcal pneumonia was limited to clinical findings, chest X-ray features and isolation of S. pneumonia from sputum specimen, because of the restriction in our ethical approval. This was a major limitation as our data might not have described true invasive pneumococcal pneumonia.
Invasive pneumococcal infection is known to be a disease of the very young and the elderly.  We noted a significant number of patients within the 55-64 year age group and 65 years and above. The lower number among those aged ≥65 years may be explained by the low life expectancy in Nigeria with fewer people above 65 years of age, while the small peak at 35-45 year age group may have been as a result of the high HIV (identified as one of the major risk factors in this study) prevalence within this age group, this pattern was also observed by Kyaw et al. in Australia.  There was also a notable higher incidence among males compared to females, with a relative increase in number of females over males between 18 and 44 years (female reproductive age group). Female gender has been previously shown to be a risk factor for pneumococcal infections, because of close proximity to children. ,,
Although it was a hospital based study, high rate of HIV infection (19.4%) was observed among the patients studied when compared with Nigerian prevalence of 5%.  HIV infection has been associated with increased risk of IPI in several studies. ,,,
The overall mortality rate of 12.6% was lower than the mortality rate of 39% reported in the 1980 s in Zaria, Nigeria,  this might be as a result of the differences in the study population and probable change in the serotype and virulence of the pneumococcal strain involved. Mortality rate of 12% and 16% were reported by Klemets et al.  and Rueda et al. Mortality in IPI varies according to the syndrome, with meningitis having the most fatal outcome followed by bacteremic pneumonia. We found statistically significant higher mortality among patients with meningitis and less among those with nonbacteremic pneumonia. Poor outcome in pneumococcal meningitis has been linked to the persistence of bacteria and their products in the CSF following effective antibiotic treatment in contrast to rapid clearance in meningococcal meningitis.  Even though the number of patients with bacteremic pneumococcal pneumonia in our study was small, the mortality among this group was relatively high, which is similar to what has been reported elsewhere. ,, In addition to being at higher absolute risk for disease, older adults are also at much higher risk of death following IPI. , This is reflected in our study where the mortality in those aged ≥65 years was significantly higher compared to those <65 years.
There is documented evidence that pneumococcal infections outside the central nervous system, caused by pneumococci with reduced susceptibility to penicillin respond well to penicillin given in appropriate doses.  Majority of the patients in this study had pneumonia, this could have explained the lack of independent association between penicillin resistance and mortality, however there was a statistically significant increase in mortality among those infected with MDR Pneumococcus (P < 0.003).
Human immunodeficiency virus-infected patients in Africa are vulnerable to severe recurrent infection with Pneumococcus; they also have higher mortality.  In our analysis, mortality was significantly higher among those who were HIV positive, compared to HIV negative patients, this has been shown in other studies. , Degree of immunosuppression has been shown to be the most relevant factor associated with mortality;  this a major limitation in our finding.
Using logistic regression, age ≥65 years, CHD, HIV, and infection with MDR pneumococci were identified as predictors of mortality, which is in agreement with most studies. ,,,,,,
| Conclusion|| |
Streptococcus pneumonia is a common cause of community-acquired infection among adult in North-western Nigeria, and mortality rate is high. Resistance to commonly used antibiotics is common which also impacts on the outcome. The findings of this study underscore the need for pneumococcal vaccination among at-risk individuals and provide important baseline data on antimicrobial resistance for continuous surveillance in this region. There is also a need for a community based pneumococcal disease surveillance including pneumococcal serotypes for effective vaccine introduction in Nigeria.
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[Table 1], [Table 2], [Table 3]