Bacteremia in Childhood Life-Threatening Infections in Urban Gambia: EUCLIDS in West Africa.

BACKGROUND: The limited availability of microbiology services in sub-Saharan Africa impedes accurate diagnosis of bacterial pathogens and understanding of trends in prevalence and antibiotic sensitivities. We aimed to characterize bacteremia among hospitalized children in The Gambia and to identify factors associated with bacteremia and mortality. METHODS: We prospectively studied children presenting with suspected severe infection to 2 urban hospitals in The Gambia, between January 2013 and September 2015. Demographic and anthropometric data, clinical features, management, and blood culture results were documented. Urine screens for antibiotic activity were performed in a subset of participants. RESULTS: Of 411 children enrolled (median age, 29 months; interquartile range, 11-82), 79.5% (325 of 409) reported prehospital antibiotic use. Antimicrobial activity by urinary screen for antibiotic activity was detected in 70.8% (n = 80 of 113). Sixty-six bacterial pathogens were identified in 65 (15.8%) participants and Staphylococcus aureus predominated. Gram-positive organisms were more commonly identified than Gram-negative (P < .01). Antibiotic resistance against first-line antimicrobials (ampicillin and gentamicin) was common among Gram-negative bacteria (39%; range, 25%-100%). Factors significantly associated with bacteremia included the following: gender, hydration status, musculoskeletal examination findings, admission to the Medical Research Council The Gambia at London School of Hygiene & Tropical Medicine hospital, and meeting sepsis criteria. Those associated with increased mortality were presence of a comorbidity, clinical pallor, tachypnea, and altered consciousness. Tachycardia was associated with reduced mortality. CONCLUSIONS: The bacteremia rate in children with suspected childhood life-threatening infectious diseases in The Gambia is high. The pattern of pathogen prevalence and antimicrobial resistance has changed over time compared with previous studies illustrating the importance of robust bacterial surveillance programs in resource-limited settings.

Substantially reduced pre-patent parasite multiplication rates are associated with naturally acquired immunity to Plasmodium falciparum.

Naturally acquired immunity to Plasmodium falciparum's asexual blood stage reduces parasite multiplication at microscopically detectable densities. The effect of natural immunity on initial prepatent parasite multiplication during the period following a new infection has been uncertain, contributing to doubt regarding the utility of experimental challenge models for blood-stage vaccine trials. Here we present data revealing that parasite multiplication rates during the initial prepatent period in semi-immune Gambian adults are substantially lower than in malaria-naive participants. This supports the view that a blood-stage vaccine capable of emulating the disease-reducing effect of natural immunity could achieve a detectable effect during the prepatent period.

Safety and immunogenicity of the malaria candidate vaccines FP9 CS and MVA CS in adult Gambian men.

We assessed the safety and immunogenicity of prime-boost vectors encoding the Plasmodium falciparum circumsporozoite (CS) protein expressed either in the attenuated fowl-pox virus (FP9) or modified vaccinia virus Ankara (MVA). Thirty-two adult Gambians in groups of four to eight received one, two or three doses of FP9 CS and/or MVA CS. No serious adverse event was observed following vaccination. The most immunogenic regimen was two doses of FP9 followed by a single dose of MVA 4 weeks later (an average of 1000 IFN-gamma spot forming units/million PBMCs). This level of effector T-cell responses appears higher than that seen in previously reported studies of CS-based candidate malaria vaccines.

Efficacy of RTS,S/AS02 malaria vaccine against Plasmodium falciparum infection in semi-immune adult men in The Gambia: a randomised trial.

BACKGROUND: RTS,S/AS02 is a pre-erythrocytic malaria vaccine based on the circumsporozoite surface protein of Plasmodium falciparum fused to HBsAg, incorporating a new adjuvant (AS02). We did a randomised trial of the efficacy of RTS,S/AS02 against natural P. falciparum infection in semi-immune adult men in The Gambia. METHODS: 306 men aged 18-45 years were randomly assigned three doses of either RTS,S/AS02 or rabies vaccine (control). Volunteers were given sulfadoxine/pyrimethamine 2 weeks before dose 3, and kept under surveillance throughout the malaria transmission season. Blood smears were collected once a week and whenever a volunteer developed symptoms compatible with malaria. The primary endpoint was time to first infection with P. falciparum. Analysis was per protocol. FINDINGS: 250 men (131 in the RTS,S/AS02 group and 119 in the control group) received three doses of vaccine and were followed up for 15 weeks. RTS,S/AS02 was safe and well tolerated. P. falciparum infections occurred significantly earlier in the control group than the RTS,S/AS02 group (Wilcoxon's test p=0.018). Vaccine efficacy, adjusted for confounders, was 34% (95% CI 8.0-53, p=0.014). Protection seemed to wane: estimated efficacy during the first 9 weeks of follow-up was 71% (46-85), but decreased to 0% (-52 to 34) in the last 6 weeks. Vaccination induced strong antibody responses to circumsporozoite protein and strong T-cell responses. Protection was not limited to the NF54 parasite genotype from which the vaccine was derived. 158 men received a fourth dose the next year and were followed up for 9 weeks; during this time, vaccine efficacy was 47% (4-71, p=0.037). INTERPRETATION: RTS,S/AS02 is safe, immunogenic, and is the first pre-erythrocytic vaccine to show significant protection against natural P. falciparum infection.

Unique T cell effector functions elicited by Plasmodium falciparum epitopes in malaria-exposed Africans tested by three T cell assays.

Natural immunity to malaria is characterized by low level CD4 T cell reactivity detected by either lymphoproliferation or IFN-gamma secretion. Here we show a doubling in the detection rate of responders to the carboxyl terminus of circumsporozoite protein (CS) of Plasmodium falciparum by employing three T cell assays simultaneously: rapid IFN-gamma secretion (ex vivo ELISPOT), IFN-gamma secretion after reactivation of memory T cells and expansion in vitro (cultured ELISPOT), and lymphoproliferation. Remarkably, for no individual peptide did a positive response for one T cell effector function correlate with any other. Thus these CS epitopes elicited unique T cell response patterns in malaria-exposed donors. Novel or important epitope responses may therefore be missed if only one T cell assay is employed. A borderline correlation was found between anti-CS Ab levels and proliferative responses, but no correlation was found with ex vivo or cultured IFN-gamma responses. This suggested that the proliferating population, but not the IFN-gamma-secreting cells, contained cells that provide help for Ab production. The data suggest that natural immunity to malaria is a complex function of T cell subgroups with different effector functions and has important implications for future studies of natural T cell immunity.

A principal target of human immunity to malaria identified by molecular population genetic and immunological analyses.

New strategies are required to identify the most important targets of protective immunity in complex eukaryotic pathogens. Natural selection maintains allelic variation in some antigens of the malaria parasite Plasmodium falciparum. Analysis of allele frequency distributions could identify the loci under most intense selection. The merozoite surface protein 1 (Msp1) is the most-abundant surface component on the erythrocyte-invading stage of P. falciparum. Immunization with whole Msp1 has protected monkeys completely against homologous and partially against non-homologous parasite strains. The single-copy msp1 gene, of about 5 kilobases, has highly divergent alleles with stable frequencies in endemic populations. To identify the region of msp1 under strongest selection to maintain alleles within populations, we studied multiple intragenic sequence loci in populations in different regions of Africa and Southeast Asia. On both continents, the locus with the lowest inter-population variance in allele frequencies was block 2, indicating selection in this part of the gene. To test the hypothesis of immune selection, we undertook a large prospective longitudinal cohort study. This demonstrated that serum IgG antibodies against each of the two most frequent allelic types of block 2 of the protein were strongly associated with protection from P. falciparum malaria.

A prospective evaluation of a clinical algorithm for the diagnosis of malaria in Gambian children.

Diagnosis of clinical malaria remains difficult, especially in areas where a high proportion of the asymptomatic population have parasitaemia, for the symptoms and signs of malaria overlap with those of other common childhood diseases, such as acute lower respiratory tract infections. However, a study of symptoms and signs in a group of children who presented to Farafenni Health Centre, The Gambia with a history of recent fever identified a group of signs and symptoms which were strong predictors of malaria as opposed to other febrile illnesses. Using these predictors, an algorithm was developed which could be used by fieldworkers and which had a similar sensitivity and specificity for the diagnosis of malaria as that of an experienced paediatrician working without laboratory support. This algorithm has been validated prospectively on 518 children who presented to the Medical Research Council clinic at Basse, The Gambia with fever or a history of recent fever during a 10-month period. A fieldworker obtained a detailed history from the parent or guardian of each child and performed a clinical examination which included measurement of axillary temperature and respiratory rate. Packed cell volume was measured and a thick smear was examined for malaria parasites. A malaria score, based on the presence or absence of malaria-related signs and symptoms, was determined for 382 children who were seen at the clinic during the high transmission season. Using the cut-off score which was optimal during the previous retrospective study, a sensitivity of 70% and a specificity of 77% for a diagnosis of malaria was obtained. The optimal cut-off score for the Basse population was a score of 7; this gave a sensitivity of 88% and a specificity of 62%, figures comparable to those obtained by an experienced paediatrician without laboratory support.

High-throughput sequence typing of T-cell epitope polymorphisms in Plasmodium falciparum circumsporozoite protein.

We report a method for typing polymorphisms at the T-cell epitopes within the Th2R and Th3R regions of the Plasmodium falciparum circumsporozoite protein (CSP). This method combines the use of PCR and sequence specific oligonucleotide probes (PCR-SSOP), and allows the identification of single nucleotide polymorphisms in these epitope regions. PCR-SSOP is a robust and a high-throughput sequence typing technique which has the same specificity and fidelity as direct sequencing. This method has been developed specifically for the assessment of the protective efficacy of RTS,S/SBAS2 vaccine against the 3D7 strain of P. falciparum (RTS,S/SBAS2 vaccine contains a part of the 3D7 CSP protein) in a phase IIb trial in Gambia which has been completed recently. PCR-SSOP could be used to determine the allelic frequencies of other parasite antigens and their geographical distribution.

Efficacy of artesunate plus pyrimethamine-sulphadoxine for uncomplicated malaria in Gambian children: a double-blind, randomised, controlled trial.

BACKGROUND: Resistance to cheap effective antimalarial drugs, especially to pyrimethaminesulphadoxine (Fansidar), is likely to have a striking impact on childhood mortality in sub-Sharan Africa. The use of artesunate (artesunic acid) [corrected] in combination with pyrimethamine-sulphadoxine may delay or prevent resistance. We investigated the efficacy, safety, and tolerability of this combined treatment. METHODS: We did a double-blind, randomised, placebo-controlled trial in The Gambia. 600 children with acute uncomplicated Plasmodium falciparum malaria, aged 6 months to 10 years, at five health centres were randomly assigned pyrimethaminesulphadoxine (25 mg/500 mg) with placebo; pyrimethamine-sulphadoxine plus one dose of artesunate (4mg/kg bodyweight); or pyrimethamine-sulphadoxine plus one dose 4 mg/kg bodyweight artesunate daily for 3 days. Children were visited at home each day after the start of treatment until parasitaemia had cleared. FINDINGS: The combined treatment was well tolerated. No adverse reactions attributable to treatment were recorded. By day 1, only 178 (47%) of 381 children treated with artesunate were still parasitaemic, compared with 157 (81%) of 195 children in the pyrimethamine-sulphadoxine alone group (relative risk 1.7 [95% CI 1.5-2.0], p<0.001). Treatment-failure rates at day 14 were 3.1% in the pyrimethamine sulphadoxine alone group, and 3.7% in the one-dose artesunate group (risk difference -0.6% [-4.2 to 3.0]) and 1.6% in the three-dose group (1.5 [1.5-4.5], p=0.048). Symptoms resolved faster in children who received artesunate, but there was no additional benefit for three doses of artesunate over one dose. Children given artesunate were less likely to be gametocytaemic after treatment. INTERPRETATION: The combined treatment was safe, well tolerated, and effective. The addition of artesunate to malaria treatment regimens in Africa results in lower gametocyte rates and may lower transmission rates.

PIP: This double-blind, randomized, controlled study investigated the efficacy, safety and tolerability of artesunate plus pyrimethamine-sulphadoxine for uncomplicated malaria among Gambian children. Combined use of artesunate and pyrimethamine-sulphadoxine was hypothesized to delay or prevent resistance, which proved to be effective in reducing childhood mortality in sub-Saharan Africa. A total of 600 children with acute uncomplicated Plasmodium falciparum malaria, 6 months to 10 years old, were randomly administered pyrimethamine-sulphadoxine (25 mg/500 mg) with placebo, 4 mg/kg body weight pyrimethamine-sulphadoxine plus 1 dose of artesunate, or pyrimethamine-sulphadoxine plus 4 mg/kg body weight artesunate for 3 days. Results indicate that combined treatment was well tolerated. On day 1, 178 of 381 children treated with artesunate were still parasitemic compared with 157 of 195 children in the pyrimethamine-sulphadoxine group. On the other hand, failure rates on day 14 were 3.1% in the pyrimethamine-sulphadoxine group and 3.7% in the 1-dose artesunate group and 1.6% in the 3-dose group. Insignificant differences were found among children administered 1-dose and 3-dose artesunate, and were found less likely to be gametocytemic after treatment. In conclusion, this study confirms the safety and efficacy of a combined treatment, which eventually results in lower gametocyte rates and lower transmission rates.

Serological responses of Gambian children to immunization with the malaria vaccine SPf66.

Antibody responses to the malaria vaccine SPf66 and to its constituent peptides were measured over a period of 2 years in Gambian children who had been immunized with SPf66 or with a control vaccine (inactivated polio vaccine). Three hundred and six of 308 children (99%) who had received three doses of SPf66 vaccine had antibodies to SPf66 at a level above that found in European controls who had not been exposed to malaria. Responses to the constituent peptides derived from 35.1, 55.1 and 83.1-kDa proteins were found in 88%, 97% and 97% of children, respectively; 26% had an antibody response to the NANP repeat peptide of circumsporozoite protein which is also included in the SPf66 vaccine. A response to SPf66 was found in 22% of children who had received the control vaccine. Antibody responses to NANP, 35.1, 55.1 and 83.1-kDa peptide were found in 3%, 33%, 49% and 33% of these children. Overall, no significant correlation was found between the level of anti-SPf66 antibody at the beginning of the malaria transmission season following vaccination and the subsequent risk of malaria. However, further analysis showed that among the control children who had acquired antibodies to SPf66 as a result of natural exposure to malaria, those with high levels of anti-SPf66 were less at risk of malaria, perhaps reflecting their greater previous exposure and thus immunity. In contrast, among children who had received three doses of SPf66, those with high antibody levels were at greater risk of have malaria during the subsequent malaria transmission season.

Acute bacterial meningitis in The Gambia: a four-year review of paediatric hospital admissions.

Over a 4 year period, 1991 to 1994, 420 patients with acute bacterial meningitis were admitted to a tertiary urban hospital in The Gambia. Organisms were isolated from the cerebrospinal fluid in 64 per cent of cases. In the neonatal period Streptococcus pneumoniae was the single most common organism isolated. Amongst infants and children the two major pathogens were Haemophilus influenzae and S. pneumoniae. In the first year of life, children with S. pneumoniae meningitis were younger than those with H. influenzae infection (median age 3 months versus 6 months, p < 0.00003) and they had a higher case fatality rate (37 per cent versus 17 per cent, p = 0.002). In view of the high case fatality rate, there is a need to review overall case management. This will include a review of more effective antibiotics, the possible role of dexamethasone, and the inclusion of efficacious vaccines against H. influenzae and S. pneumoniae disease.

The diagnosis of Plasmodium falciparum infection in Gambian children, by field staff using the rapid, manual, ParaSight-F test.

A rapid immunodiagnostic test for Plasmodium falciparum, the ParaSight-F test, was evaluated in the diagnosis of malaria in 139 children with uncomplicated malaria, who presented at the Medical Research Council's clinic at Basse in Upper River division, The Gambia. The aim was to evaluate the performance and usefulness of the test as a diagnostic method in a malaria-endemic area, when performed by a field worker. Compared with microscopy, the test had a sensitivity of 96.5%, a specificity of 90.5%, a negative predictive value of 94.2% and a positive predictive value of 94.3%. Because of its sensitivity, specificity and simplicity, the ParaSight-F test will be of value in situations where microscopy is not possible.

A trial of Fansidar plus chloroquine or Fansidar alone for the treatment of uncomplicated malaria in Gambian children.

Chloroquine can no longer be recommended as the first-line treatment for uncomplicated malaria in several parts of Africa because of the increasing prevalence of chloroquine resistance. However, chloroquine was a highly effective treatment for malaria not only because of its ability to kill parasites quickly but also because it is an anti-inflammatory drug. Therefore, we have investigated whether Fansidar (pyrimethamine/sulfadoxine) plus chloroquine is a more effective treatment for uncomplicated malaria than Fansidar alone. Four hundred and five Gambian children with uncomplicated Plasmodium falciparum malaria were studied in a randomized controlled trial. Significantly more children treated with Fansidar alone, compared to those treated with Fansidar plus chloroquine (19/203 vs. 2/202; P < 0.001), returned to the clinic with persistent symptoms during the first 3 d after treatment. Three children who had received Fansidar alone had fits, but none of the children treated with Fansidar plus chloroquine did so. At the day 7 follow-up, the parasite failure rate in the Fansidar alone group was 3/198 (1.5%), whilst in the Fansidar plus chloroquine group it was 3/201 (1.5%). At the day 28 follow-up, there was still no significant difference between the parasite failure rate in the Fansidar alone group (15/150; 10.0%) and the Fansidar plus chloroquine group (7/141; 5.0%) and the mean packed cell volume (PCV) in the 2 groups was similar. Thus, a combination of Fansidar plus chloroquine was a more effective symptomatic treatment than Fansidar given alone, but neither the parasite cure rate nor the PCV was enhanced by use of the combination.

An efficacy trial of the malaria vaccine SPf66 in Gambian infants--second year of follow-up.

In 1994, 630 Gambian infants were immunized with three doses of the synthetic polypeptide malaria vaccine SPf66 or with a control vaccine. No significant protection against first or total attacks of malaria was observed among the children who received SPf66. However, the period of follow-up was short. Thus, 532 children were followed for a second malaria transmission season during which 291 episodes of malaria were detected. Protective efficacies of SPf66 against first attacks of malaria and against all attacks of malaria were 8% [95% CI-20%, 30%] and 2% [95% CI-26% 24%] respectively. SPf66 did not provide any significant degree of protection to Gambian infants during a second year of follow-up.

A randomized controlled trial of artemether/benflumetol, a new antimalarial and pyrimethamine/sulfadoxine in the treatment of uncomplicated falciparum malaria in African children.

We report here the results of a randomized double blind trial comparing coartemether (CGP56697), a combination of artemether and benflumetol, with pyrimethamine/sulfadoxine (P/S). Two hundred eighty-seven children 1-5 years of age with uncomplicated falciparum malaria were enrolled at two centers in The Gambia between July 1996 and December 1996. Following treatment, children were visited at home every 24 hr until a blood film free of asexual parasites was obtained. Genotyping of parasites was used to distinguish recrudescence from new infections. Three days after the start of treatment, 133 (100%) of the CGP56697-treated children compared with 128 (93.4%) of children treated with P/S had cleared their parasites (P = 0.003). The day 15 cure rate was 93.3% for CGP56697 and 97.7% for P/S (P = 0.13). Within the third and fourth week after initiation of therapy, 20 children treated with CGP56697 and one of the P/S-treated children returned with second malaria episodes (P < 0.0001). Genotyping suggested that the majority (19 of 23 [82.6%]) of these second episodes were due to new infections, supporting the World Health Organization recommendation that longer follow-up is not relevant for the assessment of drug efficacy. At the two-week follow-up, 28.9% of the P/S treated children but none of the CGP56697-treated children carried gametocytes (P < 0.0001). This study showed that CGP56697 is safe in African children with acute uncomplicated falciparum malaria, clears parasites more rapidly than P/S, and results in fewer gametocyte carriers. More frequent new infections within the third and fourth week following treatment with CGP56697 than treatment with P/S are likely to be due to the short prophylactic effect of CGP56697.

Changes in the pattern of infant and childhood mortality in upper river division, The Gambia, from 1989 to 1993.

A surveillance system was used to detect births and deaths in children in a large, rural, West African population from 1989 to 1993. Cause of death was investigated using post-mortem questionnaires. Overall infant (age 0-11 months) and child (age 1-4 years) mortality rates of 80.1 and 18.8 per 1000 per year were recorded. These were reasonably consistent over the period of surveillance. The most frequent cause of death in infants was acute respiratory infection (ARI), whereas in children it was malaria: these two conditions accounted for 41% of the deaths in children under 5 years old. Other leading causes of death were acute gastroenteritis, malnutrition, and septicaemia. Deaths attributed to ARI decreased over the 5-year period, but mortality rates from other causes were either unchanged or increased slightly. Mortality from all causes peaked in the rainy season and was slightly higher in villages which were part of a primary health care programme than in those which were not. There were also no differences between male and female mortality rates beyond one year of age. Despite the introduction of a number of health interventions, there has been no major change in the overall pattern of mortality in children in a rural area of The Gambia. Malaria and ARI remain the main causes of death.

Management of severe malarial anaemia in Gambian children.

The optimum management of children with severe malarial anaemia is still uncertain. Hence, we have undertaken a study to determine whether iron treatment is as effective at restoring haemoglobin levels one month after presentation as blood transfusion without iron treatment in children with moderately severe malarial anaemia. Two hundred and eighty-seven children with a packed cell volume (PCV) < 15% and malaria infection were recruited into the study; 173 children were assigned to receive blood transfusion because they had a PCV < 12% and/or signs of respiratory distress and the remaining 114 children were allocated at random to receive either blood transfusion (58) or treatment with oral iron (56) for 28 d. Twenty-four children died, 23 in the most severely anaemic group. Fifteen children (65%) died before transfusion was given and most deaths occurred within the first 4 h of admission. One child died in the iron treatment group and 10 subsequently required transfusion. Among the severely anaemic children, those with respiratory distress were at greater risk of death than those without respiratory distress. After 28 d, haematological restoration was significantly better in children who had received iron than in those treated by blood transfusion (P = 0.02). Children who received malaria chemoprophylaxis after discharge from hospital had fewer episodes of malaria and subsequent admissions to a hospital or health centre than those who did not. Children with severe anaemia and clinical signs of respiratory distress must be identified quickly and transfused as soon as possible. However, for less severely anaemic children who are clinically stable, iron therapy offers an alternative to transfusion provided such children can be kept under surveillance and transfused subsequently should this become necessary.

Follow-up of Gambian children recruited to a pilot safety and immunogenicity study of the malaria vaccine SPf66.

A pilot safety and immunogenicity trial of the malaria vaccine SPf66 was undertaken in The Gambia in 1993. One hundred and fifty infants aged 6-11 months were immunized with either 0.5 mg or 1.0 mg of SPf66 produced either in Colombia or in the USA or with a control vaccine. Children who received SPf66 experienced more clinical attacks of malaria than did children in the control group during the first period of surveillance and the difference in incidence between children who had received high dose Colombian vaccine and the control children was statistically significant at the 5% level. During the 1995 malaria transmission season, 127 children from the original cohort of 150 were observed. During 18 weeks of intensive surveillance, the incidence of clinical malaria was again higher among children who had received SPf66 than among children who had received inactivated polio vaccine (6.23 vs 4.89 clinical attacks per 1000 days at risk), the effect being most marked among children who were in the high dose groups, but differences between groups were now no longer statistically significant.

PIP: 150 human subjects aged 6-11 months were involved in a pilot safety and immunogenicity trial of the malaria vaccine SPf66 conducted in The Gambia in 1993. The infants were immunized with either 0.5 mg or 1.0 mg of the vaccine produced in either Colombia or the US, or with a control vaccine. Children who received SPf66 experienced more clinical attacks of malaria than did children in the control group during the first period of surveillance, with the difference in incidence between children who had received high dose Colombian vaccine and the control children being statistically significant. 127 children from the original cohort of 150 were observed during the 1995 malaria transmission season. During 18 weeks of intensive surveillance, the incidence of clinical malaria was again higher among children who had received SPf66 than among children who had received inactivated polio vaccine. The effect was most marked among children in the high dose groups, although the intergroup differences were statistically insignificant. The SPf66 vaccine may have induced an immune response which made the immunized children more susceptible to malaria. It is also possible that the increased susceptibility to malaria among children who received SPf66 was a chance event following the randomization process. No enhancement of either disease frequency or severity was found in a much larger efficacy trial of Colombian SPf66 conducted among Gambian children during a 2-year follow-up period.

Predictors of mortality in Gambian children with severe malaria anaemia.

Severe malaria anaemia is a frequent cause of admission to hospital in tropical Africa and about 10% of children with this condition die. To determine ways in which mortality might be reduced we have studied risk factors for a fatal outcome in 173 children with severe malaria anaemia who were assigned to receive blood transfusion because they had a packed cell volume of less than 12% and/or signs of respiratory distress. Twenty-three children died (13%); in 15 cases (65%) death occurred before blood transfusion was given. The presence of respiratory distress was found to be the most important predictor of death. Children with severe malaria anaemia and signs of respiratory distress must therefore be transfused as soon as possible.

PIP: Severe anemia is a major cause of morbidity and mortality among children in Africa. In areas of moderate seasonal transmission, cerebral malaria is the dominant form of severe malaria. Severe malaria anemia is a frequent cause of admission to hospital in tropical Africa, and results in the death of about 10% of children with the condition. While children with severe malaria anemia can often be saved from death by blood transfusion, deaths from the condition continue to occur even in centers in which transfusion is available. Findings are presented from a study conducted at Royal Victoria Hospital, Banjul, the main referral hospital in The Gambia, to determine how such mortality may be reduced. The authors studied risk factors for a fatal outcome in 173 children of mean age 25.3 months with severe malaria anemia who were assigned to undergo blood transfusion because they had a packed cell volume of less than 12% and/or signs of respiratory distress. 15 of the 23 children who died did so before receiving transfused blood. The presence of respiratory distress was found to be the most important predictor of death. These findings suggest that children with severe malaria anemia and signs of respiratory distress should be transfused as soon as possible.

Toxic shock-like syndrome caused by adenovirus infection.

Adenovirus infections commonly occur in childhood and produce a wide range of clinical disease. The most common sites of infection are the respiratory and gastrointestinal tracts but involvement of cardiovascular, neurological, cutaneous, ophthalmic, renal, and hepatic systems can also occur. A case of toxic shock-like syndrome with symptoms of multiorgan involvement resulting from adenovirus infection is reported.