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Bacteraemia among severely malnourished children infected and uninfected with the human immunodeficiency virus-1 in Kampala, Uganda

Bacteraemia among severely malnourished children infected and uninfected with the human... Background: To establish the magnitude of bacteraemia in severely malnourished children, and describe the types of bacteria and antimicrobial sensitivity by HIV status. Method: Isolates were recovered from 76 blood specimens. Antibiotic susceptibility tests were performed using commercial antibiotic disks and demographic and clinical findings were recorded. Results: Of the 450 children 63% were male; median age 17.0 months (inter quartile range, IQR 12–24) and 57% had oedema. 151 (36.7 %) of 411 tested HIV-positive; 76 (17.1%) of 445 blood specimens grew bacterial isolates; 58% were Gram negative – S. typhimurium (27.6%) and S. enteriditis (11.8%). Staph. aureus (26.3%) and Strep. pneumoniae (13.2%) were the main Gram positive organisms. There was no difference in the risk of bacteraemia by HIV status, age < 24 months, male sex, or oedema, except for oral thrush (OR 2.3 CI 1.0–5.1) and hypoalbuminaemia (OR 3.5 CI 1.0– 12.1). Isolates from severely immuno-suppressed children (CD4% <15%) were more likely to grow Salmonella enteriditis (OR 5.4; CI 1.6 – 17.4). The isolates were susceptible (≥ 80%) to ciprofloxacin, ceftriaxone and gentamicin; with low susceptibility to chlorampenicol, ampicillin (< 50%) and co- trimoxazole (<25%). Suspicion of bacteraemia had 95.9% sensitivity and 99.2% specificity. Among bacteraemic children, mortality was higher (43.5% vs 20.5%) in the HIV-positive; OR 3.0 (95%CI 1.0, 8.6). Conclusion: Bacteraemia affects 1 in every 6 severely malnourished children and carries high mortality especially among the HIV-positive. Given the high level of resistance to common antibiotics, there is need for clinical trials to determine the best combinations of antibiotics for management of bacteraemia in severely malnourished children. Page 1 of 7 (page number not for citation purposes) BMC Infectious Diseases 2006, 6:160 http://www.biomedcentral.com/1471-2334/6/160 The plates were then incubated at 37°C for 18 – 24 hours. Background Despite recent efforts aimed at reducing child mortality in Blood and chocolate agar plates were incubated under car- resource poor countries, 11 million children under the bon dioxide. Culture bottles that did not show turbidity age of five years die each year, mainly from infections and were further incubated for up to 10 days. A total of 21/445 malnutrition [1]. Bacterial infections occur frequently in (4.7%) of the blood specimens grew contaminants. malnourished children and carry high case fatality. In Uganda, there is only one documented study of blood Identification of culture isolates were done according to stream bacterial infection among severely malnourished standard methods, for Gram negatives, AP120E was used children [2], and that study was carried out during the pre- followed by serological identification of salmonella spe- HIV/AIDS era. Whether the HIV/AIDS pandemic has cies and coagulate test for Staphylococcus aureus, Optochin changed the pattern of bacterial infection and antimicro- for Streptococcus pneumoniae and X and V factors for Hae- bial sensitivity is unknown. In Mulago, Uganda's national mophilus influenzae. The Kirby-Bauer diffusion method referral hospital, severe malnutrition has the highest case was used to test the susceptibility to the isolates on fatality compared to other paediatric illnesses, but the role Muller-Hinton Agar-2 [4]. Commonly prescribed antibi- of bacteraemia in this is not clear. The objective of the cur- otics were tested and graded as sensitive or resistant (Fa. rent study was to establish the magnitude of bacteraemia Biomeriuex, France). Resistance was defined by the zone in severely malnourished children, and to describe the diameter below that given in standard operating proce- types of bacteria and antimicrobial sensitivity by HIV sta- dure (NCCLS 2003). For example, all enterobacteriaceae tus. are resistant to ampicillin when the zone diameter is less than 13 mm and considered sensitive when the zone diameter is greater than 17 mm. Methods We enrolled 450 children with severe malnutrition HIV serology tests defined as symmetrical oedema involving at least the feet or severe wasting (weight for height less than 3 SD) or Blood was taken in 5 ml EDTA vacutainer tubes (Becton both. The children were aged below 60 months and Dickinson, Franklin lakes, NJ USA) every morning admitted to the paediatric wards of Mulago, Uganda's between 8–11 am by venipuncture and transported national referral and teaching hospital. Two hundred and within 4 hours to the Uganda Virus Research Institute twenty were enrolled in September – November 2003 and (UVRI) laboratory, Entebbe for serological testing. HIV 230 children in September – December 2004. The caregiv- testing was performed using a standard HIV algorithm of ers of these children gave informed consent. Anthropo- two enzyme-linked immunoassays (EIA) in parallel. metric measurements were taken according to the WHO Western blot, real time polymerase chain reaction (RT- standard techniques and compared with National Centre PCR) was performed to confirm a positive EIA test for for Health Statistics (NCHS) reference population [3] children below 18 months old and children with indeter- Severe malnutrition was defined as weight-for-height (or minate results on EIA. Complete blood counts, including length for children less than 2 years) of < -3 z-score and/ differential counts, were done using a Beckman Coulter or presence of oedema. Children with a length below 49 counter. cm were excluded from the study as the NCHS reference does not provide reference values for these children. A Ethical considerations Informed consent for participation in the study, including medical officer collected the children's demographic and health characteristics using a clinical history, physical HIV testing, was obtained from the care givers who examination and laboratory examinations of blood and received pre-test and post-test counselling from an experi- urine specimens and chest x-ray at admission. enced multilingual study counsellor. The study was approved by the Regional Committee for Medical Ethics, Blood culture and sensitivity Bergen, Norway (REK Vest), Makerere University Faculty Blood specimens were obtained from 445 of the 450 chil- of Medicine Ethics and Research Committee, Mulago dren. Two millilitres of blood were drawn from a periph- Hospital Ethics Committee and the Uganda National eral vein under aseptic condition after cleaning the skin Council for Science and Technology. with 70% alcohol and 2% tincture of iodine. Statistics Each blood sample was inoculated into 2 culture bottles The sample size was calculated using the formula by Kish each containing 20 ml of Brain Heart Infusion Broth and [4]. Assuming a prevalence of bacteraemia among severely incubated at 37°C for 24 hours after which bottles were malnourished children to be 50%, also reported else- observed for turbidity. From bottles showing turbidity, where [5] and a margin of error of 5% and 95% confi- Gram's stain was done and inoculation made on to 7% dence, the minimum sample size for establishing the sheep blood, chocolate and MacConkey agar, respectively. prevalence of bacteraemia was 380. Page 2 of 7 (page number not for citation purposes) BMC Infectious Diseases 2006, 6:160 http://www.biomedcentral.com/1471-2334/6/160 The statistical analysis was done using SPSS version 13 Although 36.7% of the children tested positive for HIV-1, (SPSS Inc, Chicago, IL 60606, USA). For continuous vari- there was no significant difference in the proportion of ables medians were used to measure central tendency and children who had bacteraemia by HIV status, age-group, inter quartile range (IQR) for the spread of the dependent sex or presence of oedema (Table 1). However, the pro- variables. For categorical variables, proportions were com- portion of children with oral thrush who had bacterial pared using the chi-squared or Fisher's exact test where infection was twice that of the children without oral appropriate. The children were grouped by their gender thrush. Only oral thrush and hypoalbuminaemia (male, female), age groups in months (≤24 months and > remained significant after adjusting for other factors in a 24 months; ≤12 months and > 12 months), presence of multiple regression analysis. oedema, HIV test result (positive or negative) and blood culture result (bacteraemia or no bacteraemia). Logistic Of the 76 blood specimens growing bacterial isolates, 44 regression analysis was used to identify factors independ- (58%) had Gram negative organisms, predominantly Sal- ently associated with bacteraemia. monella species and E. coli (table 2). Among the Gram pos- itive organisms, Staphylococcus aureus and Streptococcus Kaplan-Meier life tables and curves were used to deter- pneumoniae predominated, table 2. There was no signifi- mine survival functions and display data. Cox's propor- cant difference in the types or subtypes of blood bacterial tional hazards model was used to compare survival with organisms by HIV status. However, blood specimens from and without bacteraemia adjusted for age-group, sex, type severely immuno-suppressed children (CD4% <15%) of severe malnutrition and independent variables that had were more likely to grow Salmonella enteriditis species than p values below 0.2 in the univariate analysis. Children those from children with higher CD4% (OR 5.4, 95% CI were censored on the day of death. A 2-tailed p-value of < 1.7–17), even after adjusting for HIV status (OR 9.0; 95% 0.05 was considered significant. CI 1.7–48). Of the 12/55 (28%) HIV negative children with CD4% of <15%, nine (75%) were aged between 9– 23 months. Results Of the 450 severely malnourished children studied, 62.4% were males and the median age was 17.0 months Blood specimens from children with oral thrush were (IQR 12–24, ranges 4 – 60). More than half (56%) of the more likely to grow Salmonella typhimurium (14.3%, 5/35) children presented with oedema, and there was no differ- than those from children with with no oral thrush (4.6%, ence by sex; OR 1.02 (95% CI 0.7–1.5). Commonly diag- 13/280); (OR, 3.4, CI 1.14 – 10). nosed infections on admission included respiratory tract Isolates susceptibility to antibiotics infections (positive x-ray findings) and diarrhoea. Seventy six (17.1%) of the 445 blood specimens cultured, grew The bacterial isolates were mainly susceptible (≥ 80%) to bacterial isolates. ciprofloxacin, ceftriaxone, gentamicin and erythromycin. Table 1: Characteristics, clinical and laboratory diagnosis and outcome of severely malnourished children below 60 months of age by presence or absence of blood stream infections, Mulago hospital, Uganda. Blood bacterial pathogens Odds Ratio (95% Confidence interval) Characteristics Present n/total (%) Absent n/total (%) Unadjusted Adjusted Age ≤ 24 months 59/353 (16.7) 17/92 (18.5) 0.89 (0.49–1.61) 0.78 (0.40–1.54) Sex: male 48/279 (17.2) 28/166 (16.9) 1.02 (0.61–1.71) 0.99 (0.54–1.80) Oedema 47/251 (18.7) 29/194 (14.9) 1.31 (0.79–2.18) 1.55 (0.81–2.96) Hypothermia 3/24 (12.5) 21/327 (18.6) 0.62 (0.18–2.15) Oral thrush 15/54 (27.8) 61/391 (15.6) 2.08 (1.08–4.01)* 2.31 (1.04–5.11)* Acute diarrhoea† 16/91 (17.6) 75/354 (21.2) 1.05 (0.57–1.92) Persistent diarrhoea†† 15/81 (18.5) 66/364 (18.1) 1.13 (0.61–2.11) Respiratory infections 47/277 (17.0) 15/93 (16.1) 1.06 (0.56–2.01) Bacteruria 13/79 (16.5) 47/207 (22.7) 0.96 (0.49–1.89) Severe anaemia 2/56 (9.1) 20/253 (07.9) 2.3 (0.53–10.2) Malaria 5/36 (13.9) 71/406 (17.5) 0.76 (0.29–2.03) Hypokalaemia 38/178 (21.4) 38/262 (14.5) 1.60 (0.78–2.17) 1.44 (0.79–2.61) Hypoalbuminaemia 71/367 (19.3) 5/73 (6.9) 3.26 (1.27–8.39)* 3.54 (1.04–12.1)* Positive HIV status 30/149 (20.1) 39/259 (15.1) 0.42 (0.84–2.41) 1.67 (0.88–3.15) CD4<15% 15/58 (13.8) 58/274 (21.2) 0.61 (0.27–1.36) 1.99 (0.76–5.22) * p-value < 0.05, † frequent loose watery stools lasting ≤ 14 days, †† frequent loose watery stools lasting >14 days Page 3 of 7 (page number not for citation purposes) BMC Infectious Diseases 2006, 6:160 http://www.biomedcentral.com/1471-2334/6/160 Table 2: Number and percentages of bacterial pathogens isolated from blood specimens of severely malnourished children below 60 months of age at admission to, Mulago Hospital by HIV status Bacteria pathogens HIV+ n/total (%) HIV -ve n/total (%) Odds ratio (95% CI) Gram positive (Total = 27) 14 (52) 13 (48) 1.31 (0.49 – 3.48) Staphylococcus Aureus (n = 13) 8 (62) 5 (38) Coagulase negative (n = 5) 3 (60) 2 (40) Streptococcus pneumoniae (n = 9) 5 (56) 4 (44) Gram negative (Total = 41) 17 (42) 24 (58) 0.76 (0.29 – 2.03) Salmonella Enteriditis (n = 9) 3 (33) 6 (67) Typhimurium (n = 19) 8 (42) 11 (58) Typhi(n = 5) 2 (40) 3 (60) Escherichia coli(n = 6) 3 (50) 3 (50) Haemophilus. Influenzae (n = 2) 1(50) 1 (50) They had low susceptibility to chlorampenicol, ampicillin was still apparent when the survival of the children with (< 50%) and co-trimoxazole (< 25%), table 3. Susceptibil- bacteraemia was analyzed by the log rank test (p = 0.02). ity to ceftazidime, ampicillin and chloramphenicol was For the children without bacteraemia, the test of equality significantly higher for bacterial pathogens isolated from of survival distributions by HIV status was not significant HIV positive compared to the HIV negative (table 4). (p = 0.07, figure 1). Intermediate resistance to specific antibiotics was also observed (2 to ceftriaxone, 1 to ceftaxidime, 3 to cefurox- Discussion ime, 2 to ampicillin and 1 to chloramphenicol). In this study we report the pattern of bacteraemia amongst severely malnourished children in Mulago hospital, Mortality Uganda, where the prevalence of HIV infection among Although the mortality among the 76 children who had paediatric patients is high [7]. The prevalence of bacterae- bacteraemia was higher (28.9% vs. 23.0%) than among mia of 17% among the severely malnourished children in the 369 without bacteraemia, the difference was not sig- the current study is about the same as the 13% reported by nificant; OR 1.4 (95% CI 0.8–2.4), table 5. Philipps and Wharton [2] in the same hospital in the pre- HIV/AIDS era, and comparable to the 18.7% recently Among the children with bacteraemia, mortality was reported from Nairobi by Nooran et al [8]. Nonetheless, a higher (43.5% vs. 20.5%) in the HIV positive than the positive HIV test did not significantly increase the preva- HIV negative; OR 3.0 (95% CI 1.01–8.6). This difference lence of bacteraemia. This is in keeping with several stud- Table 3: Number and percentages of susceptibility of bacterial pathogen isolated from blood specimens of severely malnourished children below 60 months of age to selected antibiotics by HIV status. Staphylococcus Streptococcus Salmonella Escherichia Coli Haemophilus Pneumoniae † ‡ Antimicrobials Aureus CoN n/total (%) Typhi Enteriditis T. murium n/total (%) Influenza n/total (%) n/total (%) n/total (%) n/total (%) n/total (%) n/total (%) Co-trimoxazole 4/17 (23) 0/3 (0) 0/11 (0) 1/5 (20) 2/9 (22) 6/21 (29) 0/6 (0) 0/2 (0) Ampicillin 13/20 (65) 2/5 (40) 7/12 (58) 1/5 (20) 2/9 (22) 0/21 (0) 1/6 (17) 0/2 (0) Augmentin* 12/14 (86) 2/3 (67) 10/11 (91) 3/5 (60) 2/8 (25) 4/21 (19) 1/6 (17) 1/2 (50) Chloramphenicol 12/19 (63) 3/5 (60) 8/11 (73) 0/5 (0) 3/9 (33) 6/21 (29) 3/6 (50) 1/2 (50) Cloxacillin 3/5 (60) 0/1 (0) 5/8 (62) - - - - - Cefuroxime 7/14 (50) 0/4 (0) 4/10 (40) 2/5 (40) 8/9 (89) 12/21 (57) 4/5 (80) 0/2 (0) Ceftaxidime 9/15 (60) 1/3 (33) 5/6 (83) 1/5 (20) 0/2 (0) 4/7 (57) 1/4 (25) 1/1 (100) Erythromycin 8/13 (61) 2/3 (67) 6/6 (100) - - - - 1/1 (100) Gentamicin 15/17 (88) 4/5 (80) 3/7 (43) 4/5 (80) 9/9 (100) 16/21 (76) 5/6 (83) 1/2 (50) Ceftriaxone 13/19 (68) 4/4 (100) 8/11 (73) 4/5 (80) 9/9 (100) 19/21 (91) 5/5 (100) 2/2 (100) Ciprofloxacin 9/10 (90) 4/5 (80) 3/4 (75) 5/5 (100) 2/2 (100) 7/7 (100) 3/3 (100) 1/1 (100) † ‡ * Amoxicillin-clav, Coagulase Negative, Typhimurium Page 4 of 7 (page number not for citation purposes) BMC Infectious Diseases 2006, 6:160 http://www.biomedcentral.com/1471-2334/6/160 Table 4: Number and percentages of susceptibility of bacterial pathogen isolated from blood specimens of severely malnourished children below 60 months of age to selected antibiotics by HIV status. HIV status Antibiotics positive negative n/total (%) n/total(%) Odds ratio (95% CI) Co-trimoxazole 5/24 (21) 9/39 (23) 0.90 (0.25 – 3.24) Ampicillin 16/30 (53) 12/39 (31) 0.33 (0.12 – 0.93) Augmentin 14/25 (56) 19/37 (51) 1.04 (0.38 – 2.87) Chloramphenicol 16/29 (55) 14/39 (36) 0.35 (0.13 – 0.95) Cloxacillin 2/4 (50) 4/7 (57) 1.33 (0.11 – 16.0) Cefuroxime 16/21 (76) 24/37 (65) 0.88 (0.31 – 2.45) Ceftazidime 13/18 (72) 8/17 (47) 0.21 (0.05 – 0.9) Erythromycin 8/12 (67) 8/8 (100) 2.67 (0.24 – 30.1) Gentamicin 21/27 (78) 29/36 (81) 1.09 (0.32 – 3.71) Ceftriaxone 27/32 (84) 35/39 (90) 0.16 (0.02 – 1.42) Ciprofloxacin 14/15 (93) 14/15 (93) 1.0 (0.06 – 17.6) ies of bacteraemia in the HIV/AIDS era [8,9], but different monella enteriditis [14] and this, in turn, promotes the pro- from Berkeley's [10] study in which HIV and malnutrition duction of HIV in the macrophages of the gastrointestinal were independent risk factors for bacteraemia. This differ- tract mucosal cells, thus completing a vicious cycle. ence might be due to the fact that the current study was Although some of the non typhoidal salmonella in the carried out on only severely malnourished children with a current study were unusual, they were all from the blood high risk of dying. cultures and from patients residing in the slums of Kam- pala city. Gram negative organisms, especially non typhoidal salmo- nella species, were the predominant cause of bacteraemia We also found a high proportion of Gram positive organ- in severely malnourished children, supporting early isms particularly Staphylococcus aureus. The reason for the results from Uganda [2] and recent studies from Kenya, predominance of Staphylococcus aureus in this series is not Malawi and Ethiopia [8,11-13]. clear as there was no associated skin ulceration. It is pos- sible that vitamin A deficiency in severely malnourished Although there was no difference in the types of bacterial patients [15] might have contributed to this. Several stud- organisms by HIV status, blood specimens from severely ies have suggested that vitamin A deficiency predisposes immuno-suppressed children were more likely to grow to Staphylococcus aureus through phagocyte dysfunction Salmonella enteriditis. The mechanism for this is not very and decreased complement activity [16]. In Uganda, the clear and may include the difficulty in clearing salmonella national health program includes Vitamin A supplemen- infections from infected macrophages and weak immune tation twice a year for all the children below 5 years of age, system, HIV may predispose the host to infection with Sal- from the age of 9 months. Vitamin A is also routinely Table 5: Number and percentages of outcome of severely malnourished children who had bacterial blood stream infections at admission to Mulago hospital, Uganda Outcome status Dead Alive Organism n (%) n (%) OR (95% CI) Staphylococcus aureus 3 (20) 12 (80) 1.8 (2.8 – 6.7) Coagulase negative 1 (20) 4 (80) 1.7 (0.2 – 16) Streptococcus 4 (40) 6 (60) 1.8 (0.5 – 07) pneumoniae Haemophilus influenza 1 (50) 1 (50) - Salmonella enteriditis 1 (11) 8 (92) 3.6 (0.4 – 31) Salmonella typhi 0 (0) 5 (100) - Salmonella typhimurium 6 (29) 15 (71) 1.0 (0.3 – 3.1) Escherichia coli 6 (100) 0 (0) 4.4 (2.8 – 6.7) Page 5 of 7 (page number not for citation purposes) BMC Infectious Diseases 2006, 6:160 http://www.biomedcentral.com/1471-2334/6/160 Kaplan-Meier Figure 1 survival curves of HIV positive and HIV negative children by blood culture positive and negative result Kaplan-Meier survival curves of HIV positive and HIV negative children by blood culture positive and negative result. given as treatment to all children suffering from measles, significantly resistant to many of the antibiotics tested tuberculosis, severe malnutrition and severe pneumonia. when compared to the isolates from HIV-negative patients Other possible risk factors that could have contributed to [18]. However a recent study from Thailand, of antimicro- Staphylococcus aureus include concurrent viral infections, bial susceptibility tests of bacterial pathogens from blood chronic lung diseases in HIV positive children and prior cultures of HIV-infected patients, found that Salmonella hospitalization. However, none of the children had been species were highly sensitive to amoxicillin/clavulanate, hospitalized two weeks prior to the study. gentamicin, and ciprofloxacin [19]. The difference in sen- sitivity patterns of salmonellae species may probably be We found a very low proportion of H. influenzae infection attributed to difference in accessibility and use of antibi- in these children and this may be explained by the incor- otics. poration of HiB vaccine into the expanded programme on immunization (EPI) in Uganda from 2002. These results leave us in an important dilemma. The organisms exhibited very low in vitro susceptibility to one Our study demonstrated high bacterial resistance to com- of the drugs (ampicillin) currently recommended in com- monly used antibiotics such as co-trimoxazole, ampicillin bination with gentamicin for the management of pre- and chloramphenicol among both HIV positive and HIV sumed bacteraemia in severely malnourished children. negative children. These findings raise great concern as However they showed high susceptibility to gentamicin ampicillin, in combination with gentamicin, is routinely and ciprofloxacin. This calls for further studies to deter- given to all children admitted with severe malnutrition at mine the most feasible combination of antibiotics for the Mulago hospital [17] However there was high susceptibil- management of bacteraemia in severely malnourished ity to ciprofloxacin, ceftriaxone and gentamicin regardless children in this setting. In conformity with other studies, of HIV test status and this concurs with recent finding our study did not find clinical signs or symptoms that from Kenya [8]. could be reliably used to predict bacteraemia [9,20]. Surprisingly, blood isolates from HIV infected children The mortality among severely malnourished children were more susceptible to ampicillin and chlorampenicol with bacteraemia of 28.9% was comparable to findings than those from HIV negative children. This finding is at from other centres in sub-Saharan Africa [8,11,13]. Over- odds with results from an Ethiopian study which reported all, there was no significant association between bacterae- that isolates recovered from HIV-positive patients were mia and mortality in this vulnerable group of children. Page 6 of 7 (page number not for citation purposes) BMC Infectious Diseases 2006, 6:160 http://www.biomedcentral.com/1471-2334/6/160 diatrics and Child Health, Makerere University, Kampala, Uganda and the However among the children with bacteraemia, mortality Centre for International Health, University of Bergen Norway; NORAD was much higher in the HIV-positive than among the HIV- and the Norwegian government Quota Program. We also thank Dr Robert negative, table 5. This underscores the importance of early Downing, Uganda Viral Research Institute, Entebbe, Uganda for the HIV diagnosis and use of efficacious antibiotics [21]. In the tests. current study we did not observe any significant relation- ship between outcome and age of the children, which is References consistent with results of a recent study from Kenya [22]. 1. Horton R: The coming decade for global action on child health. Lancet 2006, 367(9504):3-5. 2. Phillips I, Wharton B: Acute bacterial infection in kwashiorkor A limitation of this study is the lack of information on and marasmus. Br Med J 1968, 1(589):407-9. 3. World Health Organization: Management of severe malnutrition, prior use of antimicrobials and previous history of hospi- in a manual for physicians and other senior health workers. talization that may be associated with bacterial resistance Geneva: WHO; 1999. 4. Bauer AW, Kirby WMM, Sherries JC, Turck M: Antibiotic suscepti- and types of isolates. However, the information on under- bility testing by a standardised single disk method. Amer J Clin lying diseases was collected using the clinical history, Pathol 1966, 45(4):493-496. 5. Kish L: Survey Sampling. New York: John Wiley and Sons; 1985. physical examination laboratory tests and chest x-ray. We 6. Nimri LF, Rawashdeh M, Meqdam MM: Bacteremia in children: eti- used isolates from two samples of children form two dif- ologic agents, focal sites, and risk factors. J Trop Pediatr 2001, 47(6):356-60. ferent years. However, the severely malnourished children 7. Marum LH, Tindyebwa D, Gibb D: Care of children with HIV infec- from the two samples came from the same community tion and AIDS in Africa. Aids 1997, 11(Suppl B):S125-34. 8. Noorani N, Macharia WM, Oyatsi D, Revathi G: Bacterial isolates in served by the hospital and the same methodology was severely malnourished children at Kenyatta National Hospital, used at the same seasonal periods, the same hospital set- Nairobi. East Afr Med J 2005, 82(7):343-8. 9. Norton EB, Archibald LK, Nwanyanwu OC, et al.: Clinical predictors ting and the same laboratories. The study was conducted of bloodstream infections and mortality in hospitalized in only one hospital in the country and may not be repre- Malawian children. Pediatr Infect Dis J 2004, 23(2):145-51. discussion 151–5 sentative of the larger Ugandan population. 10. Berkley JA, Lowe BS, Mwangi I, et al.: Bacteremia among children admitted to a rural hospital in Kenya. N Engl J Med 2005, 352(1):39-47. Further more, the selection of specific seasons may have a 11. Reed RP, Wegerhoff FO, Rothberg AD: Bacteraemia in malnour- bearing on the spectrum of pathogens identified as well as ished rural African children. Ann Trop Paediatr 1996, 16(1):61-8. 12. Shimeles D, Lulseged S: Clinical profile and pattern of infection in on the severity of malnutrition. The study was carried out Ethiopian children with severe protein-energy malnutrition. East Afr Med J 1994, 71(4):264-7. between September and December, which is the peak sea- 13. Berkowitz FE: Infections in children with severe protein energy son for severe malnutrition in Uganda. Unfortunately, it malnutrition. Pediatr Infect Dis J 1992, 11:750-759. was not possible to determine the effect of seasonality on 14. Mizel S, Kucera L, Richardson S, Ciacci F, Iyer N: Regulation of mac- rophage activation and human immunodeficiency virus pro- non-typhoidal salmonellae. duction by invasive Salmonella strains. Infect Immun 1995, 63(5):1820-1826. 15. Duncan B, Canfield L, Barber B, Greivenkamp J, Oriokot F, Naluyinda F: Conclusion The night vision threshold test (NVTT): a simple instrument for testing dark adaptation in young children. J Trop Pediatr 2000, Bacteraemia (both Gram negative and Gram positive 46(1):30-35. organisms) affects one in every 6 severely malnourished 16. Wiedermann U, Tarkowski A, Bremell T, Hanson L, Kahu H, Dahlgren U: Vitamin A deficiency predisposes to Staphylococcus aureus children and carries high mortality especially among the infection. Infect Immun 1996, 64(1):209-214. HIV-positive children. Given the high level of resistance to 17. World Health Organization: Management of severe malnutrition: a manual for physicians and other senior health workers. 1999 commonly used antibiotics, there is need for clinical trials edition. Geneva: WHO; 1999. to determine the most feasible combination of antibiotics 18. Wolday D, Erge W: Antimicrobial sensitivity pattern of Salmo- nella: comparison of isolates from HIV-infected and HIV-unin- (cheapest most effective, given orally) for the manage- fected patients. Trop Doct 1998, 28(3):139-141. ment of bacteraemia in severely malnourished children in 19. Srifuengfung S, Chokephaibulkit K, Yungyuen T, Tribuddharat C: Bac- teremia and antimicrobial susceptibilities in HIV-infected this setting. patients at Siriraj Hospital. Southeast Asian J Trop Med Public Health 2005, 36(2):347-351. 20. Bahwere P, Levy J, Hennart P, et al.: Community-acquired bactere- Competing interests mia among hospitalized children in rural central Africa. Int J The author(s) declare that they have no competing inter- Infect Dis 2001, 5(4):180-8. 21. Nathoo KJ, Chigonde S, Nhembe M, Ali MH, Mason PR: Community- ests. acquired bacteremia in human immunodeficiency virus- infected children in Harare, Zimbabwe. Pediatr Infect Dis J 1996, 15(12):1092-7. Authors' contributions 22. Kairuki S, Revathi G, Kariuki N, Kiiru J, Mwituria J, Muyodi J, Gothinji All authors participated in the design of the study, inter- JW, Kagendo D, Munyalo A, Hart CA: Invasive multidrug-resistant non-typhoidal salmonella infections in Africa: Zoonotic or pretation of the results, statistical analysis and writing the anthroponotic transmission? J Med Microbiol 2006, 55(part manuscript. HB supervised patient recruitment, follow-up 5):585-91. and data collection. All authors read and approved the final manuscript. Pre-publication history The pre-publication history for this paper can be accessed here: Acknowledgements We acknowledge financial support from the NUFU project 43/2002 Essen- http://www.biomedcentral.com/1471-2334/6/160/prepub tial Nutrition and child health, collaboration between the Department of Pae- Page 7 of 7 (page number not for citation purposes) http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png BMC Infectious Diseases Springer Journals

Bacteraemia among severely malnourished children infected and uninfected with the human immunodeficiency virus-1 in Kampala, Uganda

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Publisher
Springer Journals
Copyright
Copyright © 2006 by Bachou et al; licensee BioMed Central Ltd.
Subject
Medicine & Public Health; Infectious Diseases; Parasitology; Medical Microbiology; Tropical Medicine; Internal Medicine
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1471-2334
DOI
10.1186/1471-2334-6-160
pmid
17090299
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Abstract

Background: To establish the magnitude of bacteraemia in severely malnourished children, and describe the types of bacteria and antimicrobial sensitivity by HIV status. Method: Isolates were recovered from 76 blood specimens. Antibiotic susceptibility tests were performed using commercial antibiotic disks and demographic and clinical findings were recorded. Results: Of the 450 children 63% were male; median age 17.0 months (inter quartile range, IQR 12–24) and 57% had oedema. 151 (36.7 %) of 411 tested HIV-positive; 76 (17.1%) of 445 blood specimens grew bacterial isolates; 58% were Gram negative – S. typhimurium (27.6%) and S. enteriditis (11.8%). Staph. aureus (26.3%) and Strep. pneumoniae (13.2%) were the main Gram positive organisms. There was no difference in the risk of bacteraemia by HIV status, age < 24 months, male sex, or oedema, except for oral thrush (OR 2.3 CI 1.0–5.1) and hypoalbuminaemia (OR 3.5 CI 1.0– 12.1). Isolates from severely immuno-suppressed children (CD4% <15%) were more likely to grow Salmonella enteriditis (OR 5.4; CI 1.6 – 17.4). The isolates were susceptible (≥ 80%) to ciprofloxacin, ceftriaxone and gentamicin; with low susceptibility to chlorampenicol, ampicillin (< 50%) and co- trimoxazole (<25%). Suspicion of bacteraemia had 95.9% sensitivity and 99.2% specificity. Among bacteraemic children, mortality was higher (43.5% vs 20.5%) in the HIV-positive; OR 3.0 (95%CI 1.0, 8.6). Conclusion: Bacteraemia affects 1 in every 6 severely malnourished children and carries high mortality especially among the HIV-positive. Given the high level of resistance to common antibiotics, there is need for clinical trials to determine the best combinations of antibiotics for management of bacteraemia in severely malnourished children. Page 1 of 7 (page number not for citation purposes) BMC Infectious Diseases 2006, 6:160 http://www.biomedcentral.com/1471-2334/6/160 The plates were then incubated at 37°C for 18 – 24 hours. Background Despite recent efforts aimed at reducing child mortality in Blood and chocolate agar plates were incubated under car- resource poor countries, 11 million children under the bon dioxide. Culture bottles that did not show turbidity age of five years die each year, mainly from infections and were further incubated for up to 10 days. A total of 21/445 malnutrition [1]. Bacterial infections occur frequently in (4.7%) of the blood specimens grew contaminants. malnourished children and carry high case fatality. In Uganda, there is only one documented study of blood Identification of culture isolates were done according to stream bacterial infection among severely malnourished standard methods, for Gram negatives, AP120E was used children [2], and that study was carried out during the pre- followed by serological identification of salmonella spe- HIV/AIDS era. Whether the HIV/AIDS pandemic has cies and coagulate test for Staphylococcus aureus, Optochin changed the pattern of bacterial infection and antimicro- for Streptococcus pneumoniae and X and V factors for Hae- bial sensitivity is unknown. In Mulago, Uganda's national mophilus influenzae. The Kirby-Bauer diffusion method referral hospital, severe malnutrition has the highest case was used to test the susceptibility to the isolates on fatality compared to other paediatric illnesses, but the role Muller-Hinton Agar-2 [4]. Commonly prescribed antibi- of bacteraemia in this is not clear. The objective of the cur- otics were tested and graded as sensitive or resistant (Fa. rent study was to establish the magnitude of bacteraemia Biomeriuex, France). Resistance was defined by the zone in severely malnourished children, and to describe the diameter below that given in standard operating proce- types of bacteria and antimicrobial sensitivity by HIV sta- dure (NCCLS 2003). For example, all enterobacteriaceae tus. are resistant to ampicillin when the zone diameter is less than 13 mm and considered sensitive when the zone diameter is greater than 17 mm. Methods We enrolled 450 children with severe malnutrition HIV serology tests defined as symmetrical oedema involving at least the feet or severe wasting (weight for height less than 3 SD) or Blood was taken in 5 ml EDTA vacutainer tubes (Becton both. The children were aged below 60 months and Dickinson, Franklin lakes, NJ USA) every morning admitted to the paediatric wards of Mulago, Uganda's between 8–11 am by venipuncture and transported national referral and teaching hospital. Two hundred and within 4 hours to the Uganda Virus Research Institute twenty were enrolled in September – November 2003 and (UVRI) laboratory, Entebbe for serological testing. HIV 230 children in September – December 2004. The caregiv- testing was performed using a standard HIV algorithm of ers of these children gave informed consent. Anthropo- two enzyme-linked immunoassays (EIA) in parallel. metric measurements were taken according to the WHO Western blot, real time polymerase chain reaction (RT- standard techniques and compared with National Centre PCR) was performed to confirm a positive EIA test for for Health Statistics (NCHS) reference population [3] children below 18 months old and children with indeter- Severe malnutrition was defined as weight-for-height (or minate results on EIA. Complete blood counts, including length for children less than 2 years) of < -3 z-score and/ differential counts, were done using a Beckman Coulter or presence of oedema. Children with a length below 49 counter. cm were excluded from the study as the NCHS reference does not provide reference values for these children. A Ethical considerations Informed consent for participation in the study, including medical officer collected the children's demographic and health characteristics using a clinical history, physical HIV testing, was obtained from the care givers who examination and laboratory examinations of blood and received pre-test and post-test counselling from an experi- urine specimens and chest x-ray at admission. enced multilingual study counsellor. The study was approved by the Regional Committee for Medical Ethics, Blood culture and sensitivity Bergen, Norway (REK Vest), Makerere University Faculty Blood specimens were obtained from 445 of the 450 chil- of Medicine Ethics and Research Committee, Mulago dren. Two millilitres of blood were drawn from a periph- Hospital Ethics Committee and the Uganda National eral vein under aseptic condition after cleaning the skin Council for Science and Technology. with 70% alcohol and 2% tincture of iodine. Statistics Each blood sample was inoculated into 2 culture bottles The sample size was calculated using the formula by Kish each containing 20 ml of Brain Heart Infusion Broth and [4]. Assuming a prevalence of bacteraemia among severely incubated at 37°C for 24 hours after which bottles were malnourished children to be 50%, also reported else- observed for turbidity. From bottles showing turbidity, where [5] and a margin of error of 5% and 95% confi- Gram's stain was done and inoculation made on to 7% dence, the minimum sample size for establishing the sheep blood, chocolate and MacConkey agar, respectively. prevalence of bacteraemia was 380. Page 2 of 7 (page number not for citation purposes) BMC Infectious Diseases 2006, 6:160 http://www.biomedcentral.com/1471-2334/6/160 The statistical analysis was done using SPSS version 13 Although 36.7% of the children tested positive for HIV-1, (SPSS Inc, Chicago, IL 60606, USA). For continuous vari- there was no significant difference in the proportion of ables medians were used to measure central tendency and children who had bacteraemia by HIV status, age-group, inter quartile range (IQR) for the spread of the dependent sex or presence of oedema (Table 1). However, the pro- variables. For categorical variables, proportions were com- portion of children with oral thrush who had bacterial pared using the chi-squared or Fisher's exact test where infection was twice that of the children without oral appropriate. The children were grouped by their gender thrush. Only oral thrush and hypoalbuminaemia (male, female), age groups in months (≤24 months and > remained significant after adjusting for other factors in a 24 months; ≤12 months and > 12 months), presence of multiple regression analysis. oedema, HIV test result (positive or negative) and blood culture result (bacteraemia or no bacteraemia). Logistic Of the 76 blood specimens growing bacterial isolates, 44 regression analysis was used to identify factors independ- (58%) had Gram negative organisms, predominantly Sal- ently associated with bacteraemia. monella species and E. coli (table 2). Among the Gram pos- itive organisms, Staphylococcus aureus and Streptococcus Kaplan-Meier life tables and curves were used to deter- pneumoniae predominated, table 2. There was no signifi- mine survival functions and display data. Cox's propor- cant difference in the types or subtypes of blood bacterial tional hazards model was used to compare survival with organisms by HIV status. However, blood specimens from and without bacteraemia adjusted for age-group, sex, type severely immuno-suppressed children (CD4% <15%) of severe malnutrition and independent variables that had were more likely to grow Salmonella enteriditis species than p values below 0.2 in the univariate analysis. Children those from children with higher CD4% (OR 5.4, 95% CI were censored on the day of death. A 2-tailed p-value of < 1.7–17), even after adjusting for HIV status (OR 9.0; 95% 0.05 was considered significant. CI 1.7–48). Of the 12/55 (28%) HIV negative children with CD4% of <15%, nine (75%) were aged between 9– 23 months. Results Of the 450 severely malnourished children studied, 62.4% were males and the median age was 17.0 months Blood specimens from children with oral thrush were (IQR 12–24, ranges 4 – 60). More than half (56%) of the more likely to grow Salmonella typhimurium (14.3%, 5/35) children presented with oedema, and there was no differ- than those from children with with no oral thrush (4.6%, ence by sex; OR 1.02 (95% CI 0.7–1.5). Commonly diag- 13/280); (OR, 3.4, CI 1.14 – 10). nosed infections on admission included respiratory tract Isolates susceptibility to antibiotics infections (positive x-ray findings) and diarrhoea. Seventy six (17.1%) of the 445 blood specimens cultured, grew The bacterial isolates were mainly susceptible (≥ 80%) to bacterial isolates. ciprofloxacin, ceftriaxone, gentamicin and erythromycin. Table 1: Characteristics, clinical and laboratory diagnosis and outcome of severely malnourished children below 60 months of age by presence or absence of blood stream infections, Mulago hospital, Uganda. Blood bacterial pathogens Odds Ratio (95% Confidence interval) Characteristics Present n/total (%) Absent n/total (%) Unadjusted Adjusted Age ≤ 24 months 59/353 (16.7) 17/92 (18.5) 0.89 (0.49–1.61) 0.78 (0.40–1.54) Sex: male 48/279 (17.2) 28/166 (16.9) 1.02 (0.61–1.71) 0.99 (0.54–1.80) Oedema 47/251 (18.7) 29/194 (14.9) 1.31 (0.79–2.18) 1.55 (0.81–2.96) Hypothermia 3/24 (12.5) 21/327 (18.6) 0.62 (0.18–2.15) Oral thrush 15/54 (27.8) 61/391 (15.6) 2.08 (1.08–4.01)* 2.31 (1.04–5.11)* Acute diarrhoea† 16/91 (17.6) 75/354 (21.2) 1.05 (0.57–1.92) Persistent diarrhoea†† 15/81 (18.5) 66/364 (18.1) 1.13 (0.61–2.11) Respiratory infections 47/277 (17.0) 15/93 (16.1) 1.06 (0.56–2.01) Bacteruria 13/79 (16.5) 47/207 (22.7) 0.96 (0.49–1.89) Severe anaemia 2/56 (9.1) 20/253 (07.9) 2.3 (0.53–10.2) Malaria 5/36 (13.9) 71/406 (17.5) 0.76 (0.29–2.03) Hypokalaemia 38/178 (21.4) 38/262 (14.5) 1.60 (0.78–2.17) 1.44 (0.79–2.61) Hypoalbuminaemia 71/367 (19.3) 5/73 (6.9) 3.26 (1.27–8.39)* 3.54 (1.04–12.1)* Positive HIV status 30/149 (20.1) 39/259 (15.1) 0.42 (0.84–2.41) 1.67 (0.88–3.15) CD4<15% 15/58 (13.8) 58/274 (21.2) 0.61 (0.27–1.36) 1.99 (0.76–5.22) * p-value < 0.05, † frequent loose watery stools lasting ≤ 14 days, †† frequent loose watery stools lasting >14 days Page 3 of 7 (page number not for citation purposes) BMC Infectious Diseases 2006, 6:160 http://www.biomedcentral.com/1471-2334/6/160 Table 2: Number and percentages of bacterial pathogens isolated from blood specimens of severely malnourished children below 60 months of age at admission to, Mulago Hospital by HIV status Bacteria pathogens HIV+ n/total (%) HIV -ve n/total (%) Odds ratio (95% CI) Gram positive (Total = 27) 14 (52) 13 (48) 1.31 (0.49 – 3.48) Staphylococcus Aureus (n = 13) 8 (62) 5 (38) Coagulase negative (n = 5) 3 (60) 2 (40) Streptococcus pneumoniae (n = 9) 5 (56) 4 (44) Gram negative (Total = 41) 17 (42) 24 (58) 0.76 (0.29 – 2.03) Salmonella Enteriditis (n = 9) 3 (33) 6 (67) Typhimurium (n = 19) 8 (42) 11 (58) Typhi(n = 5) 2 (40) 3 (60) Escherichia coli(n = 6) 3 (50) 3 (50) Haemophilus. Influenzae (n = 2) 1(50) 1 (50) They had low susceptibility to chlorampenicol, ampicillin was still apparent when the survival of the children with (< 50%) and co-trimoxazole (< 25%), table 3. Susceptibil- bacteraemia was analyzed by the log rank test (p = 0.02). ity to ceftazidime, ampicillin and chloramphenicol was For the children without bacteraemia, the test of equality significantly higher for bacterial pathogens isolated from of survival distributions by HIV status was not significant HIV positive compared to the HIV negative (table 4). (p = 0.07, figure 1). Intermediate resistance to specific antibiotics was also observed (2 to ceftriaxone, 1 to ceftaxidime, 3 to cefurox- Discussion ime, 2 to ampicillin and 1 to chloramphenicol). In this study we report the pattern of bacteraemia amongst severely malnourished children in Mulago hospital, Mortality Uganda, where the prevalence of HIV infection among Although the mortality among the 76 children who had paediatric patients is high [7]. The prevalence of bacterae- bacteraemia was higher (28.9% vs. 23.0%) than among mia of 17% among the severely malnourished children in the 369 without bacteraemia, the difference was not sig- the current study is about the same as the 13% reported by nificant; OR 1.4 (95% CI 0.8–2.4), table 5. Philipps and Wharton [2] in the same hospital in the pre- HIV/AIDS era, and comparable to the 18.7% recently Among the children with bacteraemia, mortality was reported from Nairobi by Nooran et al [8]. Nonetheless, a higher (43.5% vs. 20.5%) in the HIV positive than the positive HIV test did not significantly increase the preva- HIV negative; OR 3.0 (95% CI 1.01–8.6). This difference lence of bacteraemia. This is in keeping with several stud- Table 3: Number and percentages of susceptibility of bacterial pathogen isolated from blood specimens of severely malnourished children below 60 months of age to selected antibiotics by HIV status. Staphylococcus Streptococcus Salmonella Escherichia Coli Haemophilus Pneumoniae † ‡ Antimicrobials Aureus CoN n/total (%) Typhi Enteriditis T. murium n/total (%) Influenza n/total (%) n/total (%) n/total (%) n/total (%) n/total (%) n/total (%) Co-trimoxazole 4/17 (23) 0/3 (0) 0/11 (0) 1/5 (20) 2/9 (22) 6/21 (29) 0/6 (0) 0/2 (0) Ampicillin 13/20 (65) 2/5 (40) 7/12 (58) 1/5 (20) 2/9 (22) 0/21 (0) 1/6 (17) 0/2 (0) Augmentin* 12/14 (86) 2/3 (67) 10/11 (91) 3/5 (60) 2/8 (25) 4/21 (19) 1/6 (17) 1/2 (50) Chloramphenicol 12/19 (63) 3/5 (60) 8/11 (73) 0/5 (0) 3/9 (33) 6/21 (29) 3/6 (50) 1/2 (50) Cloxacillin 3/5 (60) 0/1 (0) 5/8 (62) - - - - - Cefuroxime 7/14 (50) 0/4 (0) 4/10 (40) 2/5 (40) 8/9 (89) 12/21 (57) 4/5 (80) 0/2 (0) Ceftaxidime 9/15 (60) 1/3 (33) 5/6 (83) 1/5 (20) 0/2 (0) 4/7 (57) 1/4 (25) 1/1 (100) Erythromycin 8/13 (61) 2/3 (67) 6/6 (100) - - - - 1/1 (100) Gentamicin 15/17 (88) 4/5 (80) 3/7 (43) 4/5 (80) 9/9 (100) 16/21 (76) 5/6 (83) 1/2 (50) Ceftriaxone 13/19 (68) 4/4 (100) 8/11 (73) 4/5 (80) 9/9 (100) 19/21 (91) 5/5 (100) 2/2 (100) Ciprofloxacin 9/10 (90) 4/5 (80) 3/4 (75) 5/5 (100) 2/2 (100) 7/7 (100) 3/3 (100) 1/1 (100) † ‡ * Amoxicillin-clav, Coagulase Negative, Typhimurium Page 4 of 7 (page number not for citation purposes) BMC Infectious Diseases 2006, 6:160 http://www.biomedcentral.com/1471-2334/6/160 Table 4: Number and percentages of susceptibility of bacterial pathogen isolated from blood specimens of severely malnourished children below 60 months of age to selected antibiotics by HIV status. HIV status Antibiotics positive negative n/total (%) n/total(%) Odds ratio (95% CI) Co-trimoxazole 5/24 (21) 9/39 (23) 0.90 (0.25 – 3.24) Ampicillin 16/30 (53) 12/39 (31) 0.33 (0.12 – 0.93) Augmentin 14/25 (56) 19/37 (51) 1.04 (0.38 – 2.87) Chloramphenicol 16/29 (55) 14/39 (36) 0.35 (0.13 – 0.95) Cloxacillin 2/4 (50) 4/7 (57) 1.33 (0.11 – 16.0) Cefuroxime 16/21 (76) 24/37 (65) 0.88 (0.31 – 2.45) Ceftazidime 13/18 (72) 8/17 (47) 0.21 (0.05 – 0.9) Erythromycin 8/12 (67) 8/8 (100) 2.67 (0.24 – 30.1) Gentamicin 21/27 (78) 29/36 (81) 1.09 (0.32 – 3.71) Ceftriaxone 27/32 (84) 35/39 (90) 0.16 (0.02 – 1.42) Ciprofloxacin 14/15 (93) 14/15 (93) 1.0 (0.06 – 17.6) ies of bacteraemia in the HIV/AIDS era [8,9], but different monella enteriditis [14] and this, in turn, promotes the pro- from Berkeley's [10] study in which HIV and malnutrition duction of HIV in the macrophages of the gastrointestinal were independent risk factors for bacteraemia. This differ- tract mucosal cells, thus completing a vicious cycle. ence might be due to the fact that the current study was Although some of the non typhoidal salmonella in the carried out on only severely malnourished children with a current study were unusual, they were all from the blood high risk of dying. cultures and from patients residing in the slums of Kam- pala city. Gram negative organisms, especially non typhoidal salmo- nella species, were the predominant cause of bacteraemia We also found a high proportion of Gram positive organ- in severely malnourished children, supporting early isms particularly Staphylococcus aureus. The reason for the results from Uganda [2] and recent studies from Kenya, predominance of Staphylococcus aureus in this series is not Malawi and Ethiopia [8,11-13]. clear as there was no associated skin ulceration. It is pos- sible that vitamin A deficiency in severely malnourished Although there was no difference in the types of bacterial patients [15] might have contributed to this. Several stud- organisms by HIV status, blood specimens from severely ies have suggested that vitamin A deficiency predisposes immuno-suppressed children were more likely to grow to Staphylococcus aureus through phagocyte dysfunction Salmonella enteriditis. The mechanism for this is not very and decreased complement activity [16]. In Uganda, the clear and may include the difficulty in clearing salmonella national health program includes Vitamin A supplemen- infections from infected macrophages and weak immune tation twice a year for all the children below 5 years of age, system, HIV may predispose the host to infection with Sal- from the age of 9 months. Vitamin A is also routinely Table 5: Number and percentages of outcome of severely malnourished children who had bacterial blood stream infections at admission to Mulago hospital, Uganda Outcome status Dead Alive Organism n (%) n (%) OR (95% CI) Staphylococcus aureus 3 (20) 12 (80) 1.8 (2.8 – 6.7) Coagulase negative 1 (20) 4 (80) 1.7 (0.2 – 16) Streptococcus 4 (40) 6 (60) 1.8 (0.5 – 07) pneumoniae Haemophilus influenza 1 (50) 1 (50) - Salmonella enteriditis 1 (11) 8 (92) 3.6 (0.4 – 31) Salmonella typhi 0 (0) 5 (100) - Salmonella typhimurium 6 (29) 15 (71) 1.0 (0.3 – 3.1) Escherichia coli 6 (100) 0 (0) 4.4 (2.8 – 6.7) Page 5 of 7 (page number not for citation purposes) BMC Infectious Diseases 2006, 6:160 http://www.biomedcentral.com/1471-2334/6/160 Kaplan-Meier Figure 1 survival curves of HIV positive and HIV negative children by blood culture positive and negative result Kaplan-Meier survival curves of HIV positive and HIV negative children by blood culture positive and negative result. given as treatment to all children suffering from measles, significantly resistant to many of the antibiotics tested tuberculosis, severe malnutrition and severe pneumonia. when compared to the isolates from HIV-negative patients Other possible risk factors that could have contributed to [18]. However a recent study from Thailand, of antimicro- Staphylococcus aureus include concurrent viral infections, bial susceptibility tests of bacterial pathogens from blood chronic lung diseases in HIV positive children and prior cultures of HIV-infected patients, found that Salmonella hospitalization. However, none of the children had been species were highly sensitive to amoxicillin/clavulanate, hospitalized two weeks prior to the study. gentamicin, and ciprofloxacin [19]. The difference in sen- sitivity patterns of salmonellae species may probably be We found a very low proportion of H. influenzae infection attributed to difference in accessibility and use of antibi- in these children and this may be explained by the incor- otics. poration of HiB vaccine into the expanded programme on immunization (EPI) in Uganda from 2002. These results leave us in an important dilemma. The organisms exhibited very low in vitro susceptibility to one Our study demonstrated high bacterial resistance to com- of the drugs (ampicillin) currently recommended in com- monly used antibiotics such as co-trimoxazole, ampicillin bination with gentamicin for the management of pre- and chloramphenicol among both HIV positive and HIV sumed bacteraemia in severely malnourished children. negative children. These findings raise great concern as However they showed high susceptibility to gentamicin ampicillin, in combination with gentamicin, is routinely and ciprofloxacin. This calls for further studies to deter- given to all children admitted with severe malnutrition at mine the most feasible combination of antibiotics for the Mulago hospital [17] However there was high susceptibil- management of bacteraemia in severely malnourished ity to ciprofloxacin, ceftriaxone and gentamicin regardless children in this setting. In conformity with other studies, of HIV test status and this concurs with recent finding our study did not find clinical signs or symptoms that from Kenya [8]. could be reliably used to predict bacteraemia [9,20]. Surprisingly, blood isolates from HIV infected children The mortality among severely malnourished children were more susceptible to ampicillin and chlorampenicol with bacteraemia of 28.9% was comparable to findings than those from HIV negative children. This finding is at from other centres in sub-Saharan Africa [8,11,13]. Over- odds with results from an Ethiopian study which reported all, there was no significant association between bacterae- that isolates recovered from HIV-positive patients were mia and mortality in this vulnerable group of children. Page 6 of 7 (page number not for citation purposes) BMC Infectious Diseases 2006, 6:160 http://www.biomedcentral.com/1471-2334/6/160 diatrics and Child Health, Makerere University, Kampala, Uganda and the However among the children with bacteraemia, mortality Centre for International Health, University of Bergen Norway; NORAD was much higher in the HIV-positive than among the HIV- and the Norwegian government Quota Program. We also thank Dr Robert negative, table 5. This underscores the importance of early Downing, Uganda Viral Research Institute, Entebbe, Uganda for the HIV diagnosis and use of efficacious antibiotics [21]. In the tests. current study we did not observe any significant relation- ship between outcome and age of the children, which is References consistent with results of a recent study from Kenya [22]. 1. Horton R: The coming decade for global action on child health. Lancet 2006, 367(9504):3-5. 2. Phillips I, Wharton B: Acute bacterial infection in kwashiorkor A limitation of this study is the lack of information on and marasmus. Br Med J 1968, 1(589):407-9. 3. World Health Organization: Management of severe malnutrition, prior use of antimicrobials and previous history of hospi- in a manual for physicians and other senior health workers. talization that may be associated with bacterial resistance Geneva: WHO; 1999. 4. Bauer AW, Kirby WMM, Sherries JC, Turck M: Antibiotic suscepti- and types of isolates. However, the information on under- bility testing by a standardised single disk method. Amer J Clin lying diseases was collected using the clinical history, Pathol 1966, 45(4):493-496. 5. Kish L: Survey Sampling. New York: John Wiley and Sons; 1985. physical examination laboratory tests and chest x-ray. We 6. Nimri LF, Rawashdeh M, Meqdam MM: Bacteremia in children: eti- used isolates from two samples of children form two dif- ologic agents, focal sites, and risk factors. J Trop Pediatr 2001, 47(6):356-60. ferent years. However, the severely malnourished children 7. Marum LH, Tindyebwa D, Gibb D: Care of children with HIV infec- from the two samples came from the same community tion and AIDS in Africa. Aids 1997, 11(Suppl B):S125-34. 8. Noorani N, Macharia WM, Oyatsi D, Revathi G: Bacterial isolates in served by the hospital and the same methodology was severely malnourished children at Kenyatta National Hospital, used at the same seasonal periods, the same hospital set- Nairobi. East Afr Med J 2005, 82(7):343-8. 9. Norton EB, Archibald LK, Nwanyanwu OC, et al.: Clinical predictors ting and the same laboratories. The study was conducted of bloodstream infections and mortality in hospitalized in only one hospital in the country and may not be repre- Malawian children. Pediatr Infect Dis J 2004, 23(2):145-51. discussion 151–5 sentative of the larger Ugandan population. 10. Berkley JA, Lowe BS, Mwangi I, et al.: Bacteremia among children admitted to a rural hospital in Kenya. N Engl J Med 2005, 352(1):39-47. Further more, the selection of specific seasons may have a 11. Reed RP, Wegerhoff FO, Rothberg AD: Bacteraemia in malnour- bearing on the spectrum of pathogens identified as well as ished rural African children. Ann Trop Paediatr 1996, 16(1):61-8. 12. Shimeles D, Lulseged S: Clinical profile and pattern of infection in on the severity of malnutrition. The study was carried out Ethiopian children with severe protein-energy malnutrition. East Afr Med J 1994, 71(4):264-7. between September and December, which is the peak sea- 13. Berkowitz FE: Infections in children with severe protein energy son for severe malnutrition in Uganda. Unfortunately, it malnutrition. Pediatr Infect Dis J 1992, 11:750-759. was not possible to determine the effect of seasonality on 14. Mizel S, Kucera L, Richardson S, Ciacci F, Iyer N: Regulation of mac- rophage activation and human immunodeficiency virus pro- non-typhoidal salmonellae. duction by invasive Salmonella strains. Infect Immun 1995, 63(5):1820-1826. 15. Duncan B, Canfield L, Barber B, Greivenkamp J, Oriokot F, Naluyinda F: Conclusion The night vision threshold test (NVTT): a simple instrument for testing dark adaptation in young children. J Trop Pediatr 2000, Bacteraemia (both Gram negative and Gram positive 46(1):30-35. organisms) affects one in every 6 severely malnourished 16. Wiedermann U, Tarkowski A, Bremell T, Hanson L, Kahu H, Dahlgren U: Vitamin A deficiency predisposes to Staphylococcus aureus children and carries high mortality especially among the infection. Infect Immun 1996, 64(1):209-214. HIV-positive children. Given the high level of resistance to 17. World Health Organization: Management of severe malnutrition: a manual for physicians and other senior health workers. 1999 commonly used antibiotics, there is need for clinical trials edition. Geneva: WHO; 1999. to determine the most feasible combination of antibiotics 18. Wolday D, Erge W: Antimicrobial sensitivity pattern of Salmo- nella: comparison of isolates from HIV-infected and HIV-unin- (cheapest most effective, given orally) for the manage- fected patients. Trop Doct 1998, 28(3):139-141. ment of bacteraemia in severely malnourished children in 19. Srifuengfung S, Chokephaibulkit K, Yungyuen T, Tribuddharat C: Bac- teremia and antimicrobial susceptibilities in HIV-infected this setting. patients at Siriraj Hospital. Southeast Asian J Trop Med Public Health 2005, 36(2):347-351. 20. Bahwere P, Levy J, Hennart P, et al.: Community-acquired bactere- Competing interests mia among hospitalized children in rural central Africa. Int J The author(s) declare that they have no competing inter- Infect Dis 2001, 5(4):180-8. 21. Nathoo KJ, Chigonde S, Nhembe M, Ali MH, Mason PR: Community- ests. acquired bacteremia in human immunodeficiency virus- infected children in Harare, Zimbabwe. Pediatr Infect Dis J 1996, 15(12):1092-7. Authors' contributions 22. Kairuki S, Revathi G, Kariuki N, Kiiru J, Mwituria J, Muyodi J, Gothinji All authors participated in the design of the study, inter- JW, Kagendo D, Munyalo A, Hart CA: Invasive multidrug-resistant non-typhoidal salmonella infections in Africa: Zoonotic or pretation of the results, statistical analysis and writing the anthroponotic transmission? J Med Microbiol 2006, 55(part manuscript. HB supervised patient recruitment, follow-up 5):585-91. and data collection. All authors read and approved the final manuscript. Pre-publication history The pre-publication history for this paper can be accessed here: Acknowledgements We acknowledge financial support from the NUFU project 43/2002 Essen- http://www.biomedcentral.com/1471-2334/6/160/prepub tial Nutrition and child health, collaboration between the Department of Pae- Page 7 of 7 (page number not for citation purposes)

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