Salim Mwarumba

Bacteraemia complicating severe malaria in children

Bacteraemia associated with severe malaria in childhood is a sporadically reported phenomenon but its incidence and clinical importance are unknown. We have reviewed clinical and laboratory data from 783 Kenyan children sequentially admitted with a primary diagnosis of severe malaria. The overall incidence of bacteraemia in children with severe malaria was 7.8% (95% CI 5.5-10.0); however, in children under 30 months of age the incidence was 12.0% (95% CI 8.3-15.7). The presence of bacteraemia was associated with a 3-fold increase in mortality (33.3% vs. 10.4%, P < 0.001). We conclude that invasive bacterial disease may contribute to the pathophysiology of the clinical syndrome of severe malaria in an important subgroup of children. We recommend that young children with severe malaria be treated with broad-spectrum antibiotics in addition to antimalarial drugs.

Bacteraemia in Kenyan children with sickle-cell anaemia: a retrospective cohort and case–control study

Summary Background In sub-Saharan Africa, more than 90% of children with sickle-cell anaemia die before the diagnosis can be made. The causes of death are poorly documented, but bacterial sepsis is probably important. We examined the risk of invasive bacterial diseases in children with sickle-cell anaemia. Methods This study was undertaken in a rural area on the coast of Kenya, with a case–control approach. We undertook blood cultures on all children younger than 14 years who were admitted from within a defined study area to Kilifi District Hospital between Aug 1, 1998, and March 31, 2008; those with bacteraemia were defined as cases. We used two sets of controls: children recruited by random sampling in the same area into several studies undertaken between Sept 1, 1998, and Nov 30, 2005; and those born consecutively within the area between May 1, 2006, and April 30, 2008. Cases and controls were tested for sickle-cell anaemia retrospectively. Findings We detected 2157 episodes of bacteraemia in 38 441 admissions (6%). 1749 of these children with bacteraemia (81%) were typed for sickle-cell anaemia, of whom 108 (6%) were positive as were 89 of 13 492 controls (1%). The organisms most commonly isolated from children with sickle-cell anaemia were Streptococcus pneumoniae (44/108 isolates; 41%), non-typhi Salmonella species (19/108; 18%), Haemophilus influenzae type b (13/108; 12%), Acinetobacter species (seven of 108; 7%), and Escherichia coli (seven of 108; 7%). The age-adjusted odds ratio for bacteraemia in children with sickle-cell anaemia was 26·3 (95% CI 14·5–47·6), with the strongest associations for S pneumoniae (33·0, 17·4–62·8), non-typhi Salmonella species (35·5, 16·4–76·8), and H influenzae type b (28·1, 12·0–65·9). Interpretation The organisms causing bacteraemia in African children with sickle-cell anaemia are the same as those in developed countries. Introduction of conjugate vaccines against S pneumoniae and H influenzae into the childhood immunisation schedules of African countries could substantially affect survival of children with sickle-cell anaemia. Funding Wellcome Trust, UK.

Diagnosis of acute bacterial meningitis in children at a district hospital in sub-Saharan Africa

BACKGROUND The diagnosis of acute bacterial meningitis in children is difficult in sub-Saharan Africa, because the clinical features overlap with those of other common diseases, and laboratory facilities are inadequate in many areas. We have assessed the value of non-laboratory tests and incomplete laboratory data in diagnosing childhood acute bacterial meningitis in this setting. METHODS We prospectively studied 905 children undergoing lumbar puncture at a rural district hospital in Kenya over 1 year. We related microbiological findings and cerebrospinal-fluid (CSF) laboratory measurements to tests that would typically be available at such a hospital. FINDINGS Acute bacterial meningitis was proven in 45 children (5.0% [95% CI 3.7-6.6]) and probable in 26 (2.9% [1.9-4.2]). 21 of the 71 cases of proven or probable acute bacterial meningitis had neither neck stiffness nor turbid CSF. In eight of 45 children with proven disease the CSF leucocyte count was less than 10x10(6)/L or leucocyte counting was not possible because of blood-staining. The presence of either a leucocyte count of 50x10(6)/L or more or a CSF/blood glucose ratio of 0.10 or less detected all but two of the 45 children with proven acute bacterial meningitis; these two samples were grossly blood-stained. INTERPRETATION The diagnosis of childhood acute bacterial meningitis is likely to be missed in a third of cases at district hospitals in sub-Saharan Africa without adequate and reliable laboratory resources. CSF culture facilities are expensive and difficult to maintain, and greater gains could be achieved with facilities for accurate leucocyte counting and glucose measurement.

A Preliminary Study of Pneumonia Etiology Among Hospitalized Children in Kenya

Abstract Background. Pneumonia is the leading cause of childhood death in the developing world. Higher-quality etiological data are required to reduce this mortality burden. Methods. We conducted a case-control study of pneumonia etiology among children aged 1–59 months in rural Kenya. Case patients were hospitalized with World Health Organization–defined severe pneumonia (SP) or very severe pneumonia (VSP); controls were outpatient children without pneumonia. We collected blood for culture, induced sputum for culture and multiplex polymerase chain reaction (PCR), and obtained oropharyngeal swab specimens for multiplex PCR from case patients, and serum for serology and nasopharyngeal swab specimens for multiplex PCR from case patients and controls. Results. Of 984 eligible case patients, 810 (84%) were enrolled in the study; 232 (29%) had VSP. Blood cultures were positive in 52 of 749 case patients (7%). A predominant potential pathogen was identified in sputum culture in 70 of 417 case patients (17%). A respiratory virus was detected by PCR from nasopharyngeal swab specimens in 486 of 805 case patients (60%) and 172 of 369 controls (47%). Only respiratory syncytial virus (RSV) showed a statistically significant association between virus detection in the nasopharynx and pneumonia hospitalization (odds ratio, 12.5; 95% confidence interval, 3.1–51.5). Among 257 case patients in whom all specimens (excluding serum specimens) were collected, bacteria were identified in 24 (9%), viruses in 137 (53%), mixed viral and bacterial infection in 39 (15%), and no pathogen in 57 (22%); bacterial causes outnumbered viral causes when the results of the case-control analysis were considered. Conclusions. A potential etiology was detected in >75% of children admitted with SP or VSP. Except for RSV, the case-control analysis did not detect an association between viral detection in the nasopharynx and hospitalization for pneumonia.

Causes and outcome of young infant admissions to a Kenyan district hospital

Aims: To provide a comprehensive description of young infant admissions to a first referral level health facility in Kenya. These data, currently lacking, are important given present efforts to standardise their care through the integrated management of childhood illness (IMCI) and for prioritising both health care provision and disease prevention strategies. Methods: Prospective, 18 month observational study in a Kenyan district hospital of all admissions less than 3 months of age to the paediatric ward. Results: A total of 1080 infants were studied. Mortality was 18% overall, though in those aged 0–7 days it was 34%. Within two months of discharge a further 5% of infants aged <60 days on admission had died. Severe infection and prematurity together accounted for 57% of inpatient deaths in those aged <60 days, while jaundice and tetanus accounted for another 27%. S pneumoniae, group B streptococcus, E coli, and Klebsiella spp. were the most common causes of invasive bacterial disease. Hypoxaemia, hypoglycaemia, and an inability to feed were each present in more than 20% of infants aged 0–7 days. Both hypoxaemia and the inability to feed were associated with inpatient death (OR 3.8 (95% CI 2.5 to 5.8) and 7.4 (95% CI 4.8 to 11.2) respectively). Conclusions: Young infants contribute substantially to paediatric inpatient mortality at the first referral level, highlighting the need both for basic supportive care facilities and improved disease prevention strategies.

Risk and causes of paediatric hospital-acquired bacteraemia in Kilifi District Hospital, Kenya: a prospective cohort study

Summary Background In sub-Saharan Africa, community-acquired bacteraemia is an important cause of illness and death in children. Our aim was to establish the magnitude and causes of hospital-acquired (nosocomial) bacteraemia in African children. Methods We reviewed prospectively collected surveillance data of 33 188 admissions to Kilifi District Hospital, Kenya, between April 16, 2002, and Sept 30, 2009. We defined bacteraemia as nosocomial if it occurred 48 h or more after admission. We estimated the per-admission risk, daily rate, effect on mortality, and microbial cause of nosocomial bacteraemia and analysed risk factors by multivariable Cox regression. The effect on morbidity was measured as the increase in hospital stay by comparison with time-matched patients without bacteraemia. Findings The overall risk of nosocomial bacteraemia during this period was 5·9/1000 admissions (95% CI 5·2–6·9) but we recorded an underlying rise in risk of 27% per year. The incidence was 1·0/1000 days in hospital (0·87–1·14), which is about 40 times higher than that of community-acquired bacteraemia in the same region. Mortality in patients with nosocomial bacteraemia was 53%, compared with 24% in community-acquired bacteraemia and 6% in patients without bacteraemia. In survivors, nosocomial bacteraemia lengthened hospital stay by 10·1 days (3·0–17·2). Klebsiella pneumoniae, Escherichia coli, Staphylococcus aureus, Acinetobacter spp, group D streptococci, and Pseudomonas aeruginosa accounted for three-quarters of nosocomial infections. Nosocomial bacteraemia was significantly associated with severe malnutrition (hazard ratio 2·52, 95% CI 1·79–3·57) and blood transfusion in children without severe anaemia (4·99; 3·39–7·37). Interpretation Our findings show that although nosocomial bacteraemia is rare, it has serious effects on morbidity and mortality, and the microbiological causes are distinct from those of community-acquired bacteraemia. Nosocomial infections are largely unrecognised or undocumented as a health risk in low-income countries, but they are likely to become public health priorities as awareness of their occurrence increases and as other prominent childhood diseases are progressively controlled. Funding Wellcome Trust.

Serotype Distribution and Prevalence of Resistance to Benzylpenicillin in Three Representative Populations of Streptococcus pneumoniae Isolates from the Coast of Kenya

As surveillance data from sub-Saharan Africa are few, three representative populations of Streptococcus pneumoniae isolates were examined in Kenya for serotype distribution and Etest minimum inhibitory concentrations (MICs) of benzylpenicillin: (1) 75 lung aspirate or blood culture isolates from 301 consecutive adult patients with pneumonia, (2) 112 invasive isolates from continuous pediatric inpatient surveillance over 4 years, and (3) 97 nasopharyngeal isolates from systematically selected sick children. The proportions with benzylpenicillin MICs of > or = 0.1 microgram/mL were 0.27, 0.29, and 0.47, respectively. Vaccine-related serotypes accounted for 96% of invasive isolates from children and 90% of those from human immunodeficiency virus (HIV)-seropositive adults. Serotype 1 accounted for 44% of pneumococci from HIV-seronegative patients but only 5% of those from HIV-seropositive patients (P = .0002). Of serotype 1 isolates, 98% were susceptible to benzylpenicillin, but serogroups 13, 14, 19, and 23 were strongly associated with an MIC of > or = 0.1 microgram/mL.

Bacterial contamination of pediatric whole blood transfusions in a Kenyan hospital

BACKGROUND: Hospitalized children in sub‐Saharan Africa frequently receive whole blood transfusions for severe anemia. The risk from bacterial contamination of blood for transfusion in sub‐Saharan Africa is not known. This study assessed the frequency of bacterial contamination of pediatric whole blood transfusions at a referral hospital in Kenya.

Bacteraemia due to Staphylococcus aureus

Aims: To describe the clinical features and outcome of bacteraemia due to Staphylococcus aureus in children admitted to a rural Kenyan hospital. Methods: Retrospective case review of all children with a positive blood culture for S aureus admitted to Kilifi District Hospital, Kenya, between January 1996 and December 2001. Results: Ninety seven children (median age 17 months, range 1 day to 12 years; 46 male) with bacteraemia due to S aureus were identified, accounting for 5% of all positive blood cultures; 10 were considered to be nosocomially acquired. A focus that was clinically consistent with staphylococcal infection was identified in 52 cases; of these, 88% had multiple foci. Children with a focus were likely to be older, present later, and have a longer duration of hospital stay. Most children in this group (90%) received intravenous cloxacillin on admission in contrast to none of those without a focus. In the former group, mortality was only 6% compared to 47% among those without a focus; 10/13 neonates without an apparent staphylococcal focus died compared to none of the 11 with a focus. Eight of the 10 neonates in the former group died within 48 hours of admission, before empirical antibiotics could be changed to include cloxacillin. Conclusions: Children most at risk of death associated with bacteraemia due to S aureus are least likely to have clinical features traditionally associated with this infection.

Invasive bacterial infections in neonates and young infants born outside hospital admitted to a rural hospital in Kenya.

Background: Bacterial sepsis is thought to be a major cause of young infant deaths in low-income countries, but there are few precise estimates of its burden or causes. We studied invasive bacterial infections (IBIs) in young infants, born at home or in first-level health units (“outborn”) who were admitted to a Kenyan rural district hospital during an 8-year period. Methods: Clinical and microbiologic data, from admission blood cultures and cerebrospinal fluid cultures on all outborn infants aged less than 60 days admitted from 2001 to 2009, were examined to determine etiology of IBI and antimicrobial susceptibilities. Results: Of the 4467 outborn young infants admitted, 748 (17%) died. Five hundred five (11%) had IBI (10% bacteremia and 3% bacterial meningitis), with a case fatality of 33%. The commonest organisms were Klebsiella spp., Staphylococcus aureus, Streptococcus pneumoniae, Group B Streptococcus, Acinetobacter spp., Escherichia coli, and Group A Streptococcus. Notably, some blood culture isolates were seen in outborn neonates in the first week of life but not in inborns: Salmonella, Aeromonas, and Vibrio spp. Eighty-one percent of isolates were susceptible to penicillin and/or gentamicin and 84% to ampicillin and/or gentamicin. There was a trend to increasing in vitro antimicrobial resistance to these combinations from 2008 but without a worse outcome. Conclusions: IBI is common in outborn young infants admitted to rural African hospitals with a high mortality. Presumptive antimicrobial use is justified for all young infants admitted to the hospital.