Infections In African Children Research Articles

The Spectrum of Pathogens Associated with Infections in African Children with Severe Acute Malnutrition: A Scoping Review.

Understanding the interplay between infections and severe acute malnutrition is critical in attaining good clinical outcomes when managing malnourished children. However, review studies describing the profile of the associated pathogens in the malnourished African paediatric population are sparse in the literature. We aimed to identify the spectrum of pathogens from studies reporting infections in severely malnourished African children, as well as the antibiotic resistance pattern and clinical outcomes. A systematic literature review of the PubMed database was conducted following PRISMA guidelines from January 2001 to June 2024. The search algorithm was ((marasmus) OR (kwashiorkor) OR (severe acute malnutrition) OR (protein energy malnutrition)) AND (Africa). For a more comprehensive retrieval, an additional search algorithm was deployed: ((HIV) OR (tuberculosis)) AND (severe acute malnutrition). We included 60 studies conducted between 2001 and 2024. Most of the studies were from East Africa (n = 45, 75%) and Southern Africa (n = 5, 8.3%). A total of 5845 pathogens were identified comprising 2007 viruses, 2275 bacteria, 1444 parasites, and 119 fungal pathogens. The predominant pathogens were HIV, Mycobacterium tuberculosis, and malaria parasites accounting for 33.8%, 30%, and 24.2% of pathogens identified. Antibiotic susceptibility testing was documented in only three studies. Fatality rates were reported in 45 studies and ranged from 2% to 56% regardless of the category of pathogen. This review affirms the deleterious effect of infections in malnourished patients and suggests a gross underdiagnosis as studies were found from only 17 (31.5%) African countries. Moreover, data on fungal infections in severely malnourished African children were nearly absent despite this population being at risk. Thus, there is an urgent need to prioritize research investigating African children with severe acute malnutrition for fungal infections besides other pathogens and improve the availability of diagnostic tools and the optimized usage of antibiotics through the implementation of antimicrobial stewardship programmes.

Respiratory adenovirus infections in children: a focus on Africa.

Lower respiratory tract infections (LRTIs) are an important cause of child morbidity and mortality globally, especially in children under the age of 5 years in Africa. Respiratory viruses, including human adenoviruses (HAdVs), are common causes of LRTIs in children. This review aims to shed light on the epidemiology, clinical manifestations, sequelae, and treatment options specific to adenovirus respiratory infections in African children. Recent evidence has challenged the perception that adenovirus is a negligible cause of LRTIs. Studies show HAdV emerging as the third most common viral pathogen in fatal pneumonias among under-5 children in low-income and middle-income African countries, contributing to 5.5% of all pneumonia deaths and ranking second in hospital-associated viral pneumonia deaths. Predominant HAdV serotypes associated with disease differ by country and region, and have changed over time. Risk factors for increased disease severity and long-term respiratory sequelae in previously healthy African children with HAdV LRTIs are not well established. Although respiratory viruses, including HAdV, are recognized contributors to LRTIs, the prevalence and impact of adenovirus infections have been under-recognized and understated. Available data suggests that African children, particularly those under 5 years old, are at risk of severe sequelae from respiratory HAdV infections. Long-term sequelae, including bronchiectasis and postinfectious bronchiolitis obliterans, further underscore the significant impact of HAdV infections. However, the scarcity of comprehensive data hampers our understanding of the extent of the impact of HAdV infections on child lung health in Africa. We recommend scaled-up HAdV surveillance, ensuring its consistent inclusion in population-level LRTI assessments, and expanded and equitable access to diagnostics for early recognition of African children at risk of developing chronic sequelae and death. Enhanced understanding of adenovirus epidemiology and clinical outcomes and the availability of therapeutic options are essential for informed public health strategies and clinical care.

IFN-\u03bb4 is associated with increased risk and earlier occurrence of several common infections in African children

Genetic polymorphisms within the IFNL3/IFNL4 genomic region, which encodes type III interferons, have been strongly associated with clearance of hepatitis C virus. We hypothesized that type III interferons might be important for the immune response to other pathogens as well. In a cohort of 914 Malian children, we genotyped functional variants IFNL4-rs368234815, IFNL4-rs117648444, and IFNL3-rs4803217 and analyzed episodes of malaria, gastrointestinal, and respiratory infections recorded at 30,626 clinic visits from birth up to 5 years of age. Compared to children with the rs368234815-TT/TT genotype (IFN-λ4-Null), rs368234815-dG allele was most strongly associated with an earlier time-to-first episode of gastrointestinal infections (p = 0.003). The risk of experiencing an infection episode during the follow-up was also significantly increased with rs368234815-dG allele, with OR = 1.53, 95%CI (1.13–2.07), p = 0.005 for gastrointestinal infections and OR = 1.30, 95%CI (1.02–1.65), p = 0.033 for malaria. All the associations for the moderately linked rs4803217 (r2 = 0.78 in this set) were weaker and lost significance after adjusting for rs368234815. We also analyzed all outcomes in relation to IFN-λ4-P70S groups. Our results implicate IFN-λ4 and not IFN-λ3 as the primary functional cause of genetic associations with increased overall risk and younger age at first clinical episodes but not with recurrence or intensity of several common pediatric infections.

#53: High Burden of Serious Bacterial Infections in African Children Treated for Cancer

Abstract Background Infectious complications in children treated for cancer contribute to their morbidity and mortality. There is a paucity of studies on the incidence, microbiological etiology, risk factors, and outcome of serious bacterial infections in African children treated for cancer. Aim The aim of the study was to delineate the epidemiology of infectious morbidity and mortality in South African children with cancer. Methods This prospective, single-center, longitudinal-cohort study enrolled children one-19 years old hospitalized for cancer treatment at the Paediatric Oncology Unit, Chris Hani Baragwanath Academic Hospital, Soweto, South Africa. Children were investigated for infection as part of the standard of care. Results In total, 169 children were enrolled, 82 with hematological malignancy (HM), 87 with a solid tumor (ST), median age was 68.5 months and 10.7% were living with HIV. The incidence (per 100 child-years) of septic episodes (SE) and microbiologically confirmed SE (MSCE) was 101 (138 vs. 70, P < 0.001) and 70.9 (99.1 vs. 47.3; P < 0.001), respectively; higher in children with HM than ST. The incidence of MCSE in children with high-risk HM (137.7) was 4.32-fold greater compared with those with medium-risk HM (30.3; P < 0.001). Children with metastatic ST had a higher incidence (84.4) of MSCE than those with localized ST (33.6; aOR: 2.52; P < 0.001). The presence of an indwelling catheter was 3-fold (P < 0.001) more likely to be associated with MCSE compared with those without. There was no association for age group, nutritional status or HIV-status, and incidence of MCSE. The incidence of gram-positive (GPB) and gram-negative (GNB) SEs was 48.5 and 37.6, respectively, and higher in children with an HM. The most commonly identified GPB were Coagulase-negative Staphylococci, Streptococcus viridans and Enterococcus faecium; while the most common GNB were Escherichia coli, Acinetobacter baumannii, and Pseudomonas species. The median CRP was higher in children with MSCE compared with those with culture-negative SE (CNSE) (116.5 vs. 92; P < 0.001) in both HM (132.5 vs. 117; P < 0.001) and ST (87.5 vs. 46; P < 0.001). The procalcitonin was higher in those with MSCE compared with those with CNSE (2.30 vs. 1.40; P < 0.001) in both HM (2.95 vs. 1.60; P = 0.002) and ST (2.10 vs. 1.20; P < 0.001). The case fatality risk was 40.4%; 80% was attributed to sepsis. Of these, 35 (72.92%) had HM and 34 of the 35 (97.14%) had HR-HM. Children with HM had an overall sepsis CFR of 42.68%. Four (30.77%) of the 13 sepsis-related deaths in STs had metastatic disease and 8 (16.67%) of the total number of sepsis-related deaths were in children living with HIV. There was no association between malnutrition or HIV-positivity and death. The odds of dying from sepsis were higher in children with profound (aOR 3.96; P = 0.004) and prolonged (aOR 3.71; P = 0.011) neutropenia. Pneumonia (58.85% vs. 29.23%; aOR 2.38; P = 0.025) and tuberculosis (70.83% vs. 34.91%; aOR 4.3; P = 0.005) were independently associated with a higher CFR. Conclusion The current study emphasizes the high burden of sepsis in African children treated for cancer, and especially HM, and highlights the association of tuberculosis and pneumonia as independent predictors of death in children with cancer.

Epidemiology of Human Metapneumovirus-associated Lower Respiratory Tract Infections in African Children: Systematic Review and Meta-analysis.

Human metapneumovirus (hMPV) has been associated with upper and lower respiratory tract infections (LRTI) in children and adults. This systematic review evaluated the epidemiology of hMPV-associated LRTI, including severe acute respiratory infection (SARI) hospitalization or clinically diagnosed severe pneumonia, in African children under 5 years of age. We searched Science Direct, PubMed, Cochrane Central, Scopus, and WHO regional databases using the terms "("Human metapneumovirus" AND "Africa") OR ("hMPV" AND "Africa")" up to September 17, 2020. Other sources included ClinicalTrials.gov to obtain unpublished data. Studies were included if children were less than 5 years of age and hospitalized with hMPV-associated LRTI, SARI or if clinically diagnosed with severe pneumonia in the community. The main outcomes were prevalence of hMPV identified among children with hospitalized LRTI or SARI. We further calculated odds ratios for hMPV in cases with LRTI compared with non-LRTI controls. Pooled results were calculated using a random-effects model. Thirty studies were eligible for inclusion in the review. The prevalence of hMPV-LRTI/SARI among hospitalized and severe pneumonia cases was 4.7% [95% confidence interval (CI): 3.9-5.6, I2 = 95.0]. The case-control studies indicated that hMPV was 2.0-fold (95% CI: 0.9-4.4) more likely to be identified in LRTI cases (10.3%) than controls (6.0%). Three of 5 studies reported hMPV-associated LRTI case fatality risk, with a pooled estimate of 1.3% (95% CI: 0.3-2.9; I2 = 49). hMPV was associated with approximately 5% of LRTI/SARI hospitalizations or severe pneumonia cases in Africa.

Weighted gene co-expression network analysis and drug-gene interaction bioinformatics uncover key genes associated with various presentations of malaria infection in African children and major drug candidates.

Malaria is a fatal parasitic disease with unelucidated pathogenetic mechanism. Herein, we aimed to uncover genes associated with different clinical aspects of malaria based on the GSE1124 dataset that is publicly accessible by using WGCNA. We obtained 16 co-expression modules and their correlations with clinical features. Using the MCODE tool, we identified THEM4, STYX, VPS36, LCOR, KIAA1143, EEA1, RAPGEF6, LOC439994, ZBTB33, PTPN22, ESCO1, and KLF3 as hub genes positively associated with Plasmodium falciparum infection (ASPF). These hub genes were involved in the biological processes of endosomal transport, regulation of natural killer cell proliferation, and KEGG pathways of endocytosis and fatty acid elongation. For the purple module negatively correlated with ASPF, we identified 19 hub genes that were involved in the biological processes of positive regulation of cellular protein catabolic process and KEGG pathways of other glycan degradation. For the salmon module positively correlated with severe malaria anemia (SMA), we identified 17 hub genes that were among those driving the biological processes of positive regulation of erythrocyte differentiation. For the brown module positively correlated with cerebral malaria (CM), we identified eight hub genes and these genes participated in phagolysosome assembly and positive regulation of exosomal secretion, and animal mitophagy pathway. For the tan module negatively correlated with CM, we identified four hub genes that were involved in CD8-positive, alpha-beta T cell differentiation and notching signaling pathway. These findings may provide new insights into the pathogenesis of malaria and help define new diagnostic and therapeutic approaches for malaria patients.

How Severe Anaemia Might Influence the Risk of Invasive Bacterial Infections in African Children.

Severe anaemia and invasive bacterial infections are common causes of childhood sickness and death in sub-Saharan Africa. Accumulating evidence suggests that severely anaemic African children may have a higher risk of invasive bacterial infections. However, the mechanisms underlying this association remain poorly described. Severe anaemia is characterized by increased haemolysis, erythropoietic drive, gut permeability, and disruption of immune regulatory systems. These pathways are associated with dysregulation of iron homeostasis, including the downregulation of the hepatic hormone hepcidin. Increased haemolysis and low hepcidin levels potentially increase plasma, tissue and intracellular iron levels. Pathogenic bacteria require iron and/or haem to proliferate and have evolved numerous strategies to acquire labile and protein-bound iron/haem. In this review, we discuss how severe anaemia may mediate the risk of invasive bacterial infections through dysregulation of hepcidin and/or iron homeostasis, and potential studies that could be conducted to test this hypothesis.

High Burden of Serious Bacterial Infections in African Children Treated for Cancer.

Infections in children treated for cancer contribute to morbidity and mortality. There is a paucity of studies on the incidence, etiology, risk factors and outcome of bacterial infections in African children treated for cancer. The aim of the study was to delineate the epidemiology of infectious morbidity and mortality in children with cancer. The study enrolled children 1-19 years old with cancer and infections. Children were investigated for infection as part of standard of care. One hundred sixty-nine children were enrolled, 82 with hematologic malignancies and 87 with solid tumors and 10.7% were HIV infected. The incidence (per 100 child-years) of septic episodes (101) microbiologically confirmed (70.9) septic episodes, Gram-positive (48.5) and Gram-negative (37.6) sepsis was higher in children with hematologic malignancies than in those with solid tumors. The most common Gram-positive bacteria were Coagulase-negative Staphylococci, Streptococcus viridans and Enterococcus faecium, while the most common Gram-negative bacteria were Escherichia coli, Acinetobacter baumannii and Pseudomonas species. The C-reactive protein and procalcitonin was higher in microbiologically confirmed sepsis. The case fatality risk was 40.4%; 80% attributed to sepsis. The odds of dying from sepsis were higher in children with profound [adjusted odds ratio (aOR) = 3.96; P = 0.004] or prolonged neutropenia (aOR = 3.71; P = 0.011) and profound lymphopenia (aOR = 4.09; P = 0.003) and independently associated with pneumonia (53.85% vs. 29.23%; aOR = 2.38; P = 0.025) and tuberculosis (70.83% vs. 34.91%; aOR = 4.3; P = 0.005). The study emphasizes the high burden of sepsis in African children treated for cancer and highlights the association of tuberculosis and pneumonia as independent predictors of death in children with cancer.

Central Nervous System Virus Infection in African Children with Cerebral Malaria.

We aimed to identify the contribution of central nervous system (CNS) viral coinfection to illness in African children with retinopathy-negative or retinopathy-positive cerebral malaria (CM). We collected cerebrospinal fluid (CSF) from 272 children with retinopathy-negative or retinopathy-positive CM and selected CSF from 111 of these children (38 retinopathy positive, 71 retinopathy negative, 2 retinopathy unknown) for analysis by metagenomic next-generation sequencing. We found CSF viral coinfections in 7/38 (18.4%) retinopathy-positive children and in 18/71 (25.4%) retinopathy-negative children. Excluding HIV-1, human herpesviruses (HHV) represented 61% of viruses identified. Excluding HIV-1, CNS viral coinfection was equally likely in children who were retinopathy positive and retinopathy negative (P = 0.1431). Neither mortality nor neurological morbidity was associated with the presence of virus (odds ratio [OR] = 0.276, 95% CI: 0.056-1.363). Retinopathy-negative children with a higher temperature, lower white blood cell count, or being dehydrated were more likely to have viral coinfection. Level of consciousness at admission was not associated with CNS viral coinfection in retinopathy-negative children. Viral CNS coinfection is unlikely to contribute to coma in children with CM. The herpesviruses other than herpes simplex virus may represent incidental bystanders in CM, reactivating during acute malaria infection.

A primate model of severe malarial anaemia: a comparative pathogenesis study

Severe malarial anaemia (SMA) is the most common life-threatening complication of Plasmodium falciparum infection in African children. SMA is characterised by haemolysis and inadequate erythropoiesis, and is associated with dysregulated inflammatory responses and reduced complement regulatory protein levels (including CD35). However, a deeper mechanistic understanding of the pathogenesis requires improved animal models. In this comparative study of two closely related macaque species, we interrogated potential causal factors for their differential and temporal relationships to onset of SMA. We found that rhesus macaques inoculated with blood-stage Plasmodium coatneyi developed SMA within 2 weeks, with no other severe outcomes, whereas infected cynomolgus macaques experienced only mild/ moderate anaemia. The abrupt drop in haematocrit in rhesus was accompanied by consumption of haptoglobin (haemolysis) and poor reticulocyte production. Rhesus developed a greater inflammatory response than cynomolgus macaques, and had lower baseline levels of CD35 on red blood cells (RBCs) leading to a significant reduction in the proportion of CD35+ RBCs during infection. Overall, severe anaemia in rhesus macaques infected with P. coatneyi has similar features to SMA in children. Our comparisons are consistent with an association of low baseline CD35 levels on RBCs and of early inflammatory responses with the pathogenesis of SMA.

Efficacy and Side Effects of Topical Applications of Two Different Solutions in the Treatment of Molluscum Contagiosum in a City in Africa: An Open, Randomized, Comparative Clinical Trial

AbstractMolluscum contagiosum (MC) is one of the most common viral infections in African children. However, there is no work investigating the treatment of MC in dark skinned children in Africa. In this study, we aimed to compare efficacy and side effects of topical application of 10% potassium hydroxide (KOH) and 16.7% salicylic acid (SAL) and lactic acid (LAC) combination in the treatment of MC in Sudan, Africa. This is a prospective, randomized, and comparative study. The inclusion criterion was the presence of at least 10 lesions. The exclusion criteria were the use of any topical MC treatment during the last 2 weeks, immunosuppression, periorbital and perioral involvement, the history of hypersensitivity to any kind of keratolytics, and the presence of concomitant bacterial skin infections. The main efficacy outcome was the complete remission or partial remission. Three visits were performed: baseline visit (diagnosis, randomization, and therapy initiation), visit 1 for follow-up (at 15–30 days after initiation of therapy and for study end), and visit 2 for postclearing assessment (at 60th day after the initiation of therapy). Chi-squared (χ2) test was used. All patients (n = 101) participating completed the 60 days of follow-up period. Post 60 days of treatment, the rates of complete resolution in 55 patients treated with 10% KOH solution and 47 patients treated with 16.7% SAL + LAC combination solution were 87.0 and 85.1% (p > 0.05), respectively. The rates of partial resolution in the group treated with KOH solution and in patients treated with SAL + LAC combination solution were 12.9% and 14.8% (p > 0.05), respectively. Major side effects in KOH group were burning sensation or stinging during application (48.1%, p = 0.0009) and hypopigmentation (38.8%, p = 0.007) while it was desquamation (23.4%, p > 0.05) in the SAL + LAC combination group. Results indicate both 10% KOH solution and SAL + LAC combination solution showed good efficacy in the treatment of MC in African children. Neither 10% KOH nor the SAL + LAC combination solution was found superior to other in the treatment, while the latter was noted to have fewer side effects. Permanent hypopigmentation is an important and undesired side effect of 10% KOH treatment.

Iron Status and Associated Malaria Risk Among African Children.

BackgroundIt remains unclear whether improving iron status increases malaria risk, and few studies have looked at the effect of host iron status on subsequent malaria infection. We therefore aimed to determine whether a child’s iron status influences their subsequent risk of malaria infection in sub-Saharan Africa.MethodsWe assayed iron and inflammatory biomarkers from community-based cohorts of 1309 Kenyan and 1374 Ugandan children aged 0–7 years and conducted prospective surveillance for episodes of malaria. Poisson regression models were fitted to determine the effect of iron status on the incidence rate ratio (IRR) of malaria using longitudinal data covering a period of 6 months. Models were adjusted for age, sex, parasitemia, inflammation, and study site.ResultsAt baseline, the prevalence of iron deficiency (ID) was 36.9% and 34.6% in Kenyan and Ugandan children, respectively. ID anemia (IDA) affected 23.6% of Kenyan and 17.6% of Ugandan children. Malaria risk was lower in children with ID (IRR, 0.7; 95% confidence interval [CI], 0.6, 0.8; P < .001) and IDA (IRR, 0.7; 95% CI, 0.6, 0.9; P = .006). Low transferrin saturation (<10%) was similarly associated with lower malaria risk (IRR, 0.8; 95% CI, 0.6, 0.9; P = .016). However, variation in hepcidin, soluble transferrin receptors (sTfR), and hemoglobin/anemia was not associated with altered malaria risk.ConclusionsID appears to protect against malaria infection in African children when defined using ferritin and transferrin saturation, but not when defined by hepcidin, sTfR, or hemoglobin. Additional research is required to determine causality.Clinical Trials RegistrationISRCTN32849447

Cooking and season as risk factors for acute lower respiratory infections in African children: a cross-sectional multi-country analysis.

BackgroundAcute lower respiratory infections (ALRI) are a leading cause of death among African children under five. A significant proportion of these are attributable to household air pollution from solid fuel use.MethodsWe assessed the relationship between cooking practices and ALRI in pooled datasets of Demographic and Health Surveys conducted between 2000 and 2011 in countries of sub-Saharan Africa. The impacts of main cooking fuel, cooking location and stove ventilation were examined in 18 (n = 56,437), 9 (n = 23,139) and 6 countries (n = 14,561) respectively. We used a causal diagram and multivariable logistic mixed models to assess the influence of covariates at individual, regional and national levels.ResultsMain cooking fuel had a statistically significant impact on ALRI risk (p<0.0001), with season acting as an effect modifier (p = 0.034). During the rainy season, relative to clean fuels, the odds of suffering from ALRI were raised for kerosene (OR 1.64; CI: 0.99, 2.71), coal and charcoal (OR 1.54; CI: 1.21, 1.97), wood (OR 1.20; CI: 0.95, 1.51) and lower-grade biomass fuels (OR 1.49; CI: 0.93, 2.35). In contrast, during the dry season the corresponding odds were reduced for kerosene (OR 1.23; CI: 0.77, 1.95), coal and charcoal (OR 1.35; CI: 1.06, 1.72) and lower-grade biomass fuels (OR 1.07; CI: 0.69, 1.66) but increased for wood (OR 1.32; CI: 1.04, 1.66). Cooking location also emerged as a season-dependent statistically significant (p = 0.0070) determinant of ALRI, in particular cooking indoors without a separate kitchen during the rainy season (OR 1.80; CI: 1.30, 2.50). Due to infrequent use in Africa we could, however, not demonstrate an effect of stove ventilation.ConclusionsWe found differential and season-dependent risks for different types of solid fuels and kerosene as well as cooking location on child ALRI. Future household air pollution studies should consider potential effect modification of cooking fuel by season.

Dynamics of the Antibody Response to Plasmodium falciparum Infection in African Children

Acquired immune responses to malaria have widely been perceived to be short-lived, with previously immune individuals losing immunity when they move from malaria-endemic areas. However long-lived Plasmodium falciparum-specific antibody responses lasting for an individual's lifetime are frequently observed. We fit mathematical models of the dynamics of antibody titers to P. falciparum antigens from longitudinal cohort studies of African children to estimate the half-lives of circulating immunoglobulin G (IgG) antibodies and IgG antibody-secreting cells (ASCs). Comparison of antibody responses in the younger Ghanaian cohort and the older Gambian cohort suggests that young children are less able to generate the long-lived ASCs necessary to maintain the circulating antibodies that may provide protection against reinfection. Antibody responses in African children can be described by a model 15 including both short-lived ASCs (half-life range, 2-10 days), which are responsible for boosting antibody titers following infection, and long-lived ASCs (half-life range, 3-9 years), which are responsible for maintaining sustained humoral responses. The rapid decay of antibodies following exposure to malaria and the maintenance of sustained antibody responses can be explained in terms of populations of short-lived and long-lived ASCs.

Overview of the Effect and Epidemiology of Parasitic Central Nervous System Infections in African Children

Infections of the central nervous system are a significant cause of neurologic dysfunction in resource-limited countries, especially in Africa. The prevalence is not known and is most likely underestimated because of the lack of access to accurate diagnostic screens. For children, the legacy of subsequent neurodisability, which affects those who survive, is a major cause of the burden of disease in Africa. Of the parasitic infections with unique effect in Africa, cerebral malaria, neurocysticercosis, human African trypanosomiasis, toxoplasmosis, and schistosomiasis are largely preventable conditions, which are rarely seen in resource-equipped settings. This article reviews the current understandings of these parasitic and other rarer infections, highlighting the specific challenges in relation to prevention, diagnosis, treatment, and the complications of coinfection.

An Overview of the Effect and Epidemiology of Viral Central Nervous System Infections in African Children

Viral infections in Africa are common. Polio still persists in the continent despite vaccination campaigns. Many of the common viral infections, such as by the nonpolio enteroviruses, lack effective therapies and leave devastating sequelae to infected neonates and infants. Rarer conditions, such as by West Nile virus, have generated a fascinating conundrum as to how the virus spread to other parts of the world, such as the United States of America. This infection illustrates that these conditions should not be considered isolated to Africa alone but that they represent examples of potentially lethal infections which, although predominantly found in Africa, have the capacity to spread wider afield.

Detection and molecular characterisation of noroviruses in hospitalised children in Malawi, 1997–2007

Despite the increasing recognition of noroviruses as major pathogens associated with community-acquired diarrhoea in children, there are few studies from Africa. Long-term surveillance studies of rotavirus gastroenteritis in Malawian children have provided an opportunity to undertake a study of the importance and epidemiological features of norovirus infection in this population. Faecal specimens were collected from children <5 years of age admitted to hospital with acute diarrhoea, as well as from a comparison group of diarrhoea-free children, in Blantyre, Malawi between 1997 and 2007. Norovirus was detected using real-time PCR and strains genotyped by nucleotide sequence analysis. Norovirus was detected in 220/1,941 (11.3%) faecal specimens, comprising genogroup GI (1.8%), GII (9.4%) and mixed GI/GII (0.1%). The median age of children with norovirus was 6 months (range, 0-48 months). Norovirus was detected throughout the year, with peaks at the end of the rainy season (March) and towards the end of the dry season (August-November). Norovirus GII.4 was the most commonly detected genotype accounting for 70% of strains characterised, followed by GII.2 (6%), GII.6 (4%) and GII.12 (4%). Sub typing of GII.4 noroviruses demonstrated local circulation of strains prior to their subsequent detection in association with global epidemics of gastroenteritis. The prevalence of norovirus in children without diarrhoea was similar to the level in cases. This largest study to date of norovirus infection in African children indicates the potential role of paediatric surveillance in predicting the emergence of norovirus strains with global epidemic potential.

Surgical aspects of bacterial infection in African children

Infections and their complications requiring surgical intervention are a frequent presentation in African children. Surgical site infection (SSI) is common with rates over 20%, even after clean procedures. The high rates of SSI are due in part to lack of infection control and surveillance policies in most hospitals in Africa. SSI is attended by complications, long hospital stay, and some mortality, but the economic consequences are unestimated. Typhoid fever and typhoid intestinal perforation are major problems with perforation rates of approximately 10%, which is higher in older children. The ideal surgical treatment is arguable, but simple closure and segmental resection are the present effective surgical options. Because of delayed presentation, complications after surgical treatment are high with a mortality approaching 41% in some parts of Africa. Nutrition for these patients remains a challenge. Acute appendicitis, although not as common in African children, often presents rather late with up to 50% of children presenting with perforation and other complications, and mortality is approximately 4% is some settings. Pyomyositis and necrotizing fasciitis are the more common serious soft-tissue infections, but early recognition and prompt treatment should minimize the occasional mortality. Though common in Africa, the exact impact of human immunodeficiency virus infection on the spectrum and severity of surgical infection in African children is not clear, but it may well worsen the course of infection in these patients.

Do multiple concurrent infections in African children cause irreversible immunological damage?

Much of the developing world, particularly sub-Saharan Africa, has high levels of morbidity and mortality associated with infectious diseases. The greatest risk of invasive disease is in the young, the malnourished and HIV-infected individuals. In many regions in Africa these vulnerable groups and the wider general population are under constant immune pressure from a range of environmental factors, under-nutrition and multiple concurrent infections from birth through to adulthood. Intermittent microbial exposure during childhood is required for the generation of naturally acquired immunity capable of protection against a range of infectious diseases in adult life. However, in the context of a resource-poor setting, the heavy burden of malarial, diarrhoeal and respiratory infections in childhood may subvert or suppress immune responses rather than protect, resulting in sub-optimal immunity. This review will explore how poor maternal health, HIV exposure, socio-economic and seasonal factors conspire to weaken childhood immune defences to disease and discuss the hypothesis that recurrent infections may drive immune dysregulation, leading to relative immune senescence and premature immunological aging.

The relationship between reported fever and Plasmodium falciparum infection in African children

BackgroundFever has traditionally served as the entry point for presumptive treatment of malaria in African children. However, recent changes in the epidemiology of malaria across many places in Africa would suggest that the predictive accuracy of a fever history as a marker of disease has changed prompting calls for the change to diagnosis-based treatment strategies.MethodsUsing data from six national malaria indicator surveys undertaken between 2007 and 2009, the relationship between childhood (6-59 months) reported fever on the day of survey and the likelihood of coincidental Plasmodium falciparum infection recorded using a rapid diagnostic test was evaluated across a range of endemicities characteristic of Africa today.ResultsOf 16,903 children surveyed, 3% were febrile and infected, 9% were febrile without infection, 12% were infected but were not febrile and 76% were uninfected and not febrile. Children with fever on the day of the survey had a 1.98 times greater chance of being infected with P. falciparum compared to children without a history of fever on the day of the survey after adjusting for age and location (OR 1.98; 95% CI 1.74-2.34). There was a strong linear relationship between the percentage of febrile children with infection and infection prevalence (R2 = 0.9147). The prevalence of infection in reported fevers was consistently greater than would be expected solely by chance and this increased with increasing transmission intensity. The data suggest that in areas where community-based infection prevalence in childhood is above 34-37%, 50% or more of fevers are likely to be associated with infection.ConclusionThe potential benefits of diagnosis will depend on the prevalence of infection among children who report fever. The study has demonstrated a predictable relationship between parasite prevalence in the community and risks of infection among febrile children suggesting that current maps of parasite prevalence could be used to guide diagnostic strategies in Africa.