Diagnostic practices and estimated burden of tuberculosis among children admitted to 13 government hospitals in Kenya: An analysis of two years' routine clinical data.

BACKGROUND: True burden of tuberculosis (TB) in children is unknown. Hospitalised children are low-hanging fruit for TB case detection as they are within the system. We aimed to explore the process of recognition and investigation for childhood TB using a guideline-linked cascade of care. METHODS: This was an observational study of 42,107 children admitted to 13 county hospitals in Kenya from 01Nov 15-31Oct 16, and 01Nov 17-31Oct 18. We estimated those that met each step of the cascade, those with an apparent (or "Working") TB diagnosis and modelled associations with TB tests amongst guideline-eligible children. RESULTS: 23,741/42,107 (56.4%) met step 1 of the cascade (≥2 signs and symptoms suggestive of TB). Step 2(further screening of history of TB contact/full respiratory exam) was documented in 14,873/23,741 (62.6%) who met Step 1. Step 3(chest x-ray or Mantoux test) was requested in 2,451/14,873 (16.5%) who met Step 2. Step 4(≥1 bacteriological test) was requested in 392/2,451 (15.9%) who met Step 3. Step 5("Working TB" diagnosis) was documented in 175/392 (44.6%) who met Step 4. Factors associated with request of TB tests in patients who met Step 1 included: i) older children [AOR 1.19(CI 1.09-1.31)]; ii) co-morbidities of HIV, malnutrition or pneumonia [AOR 3.81(CI 3.05-4.75), 2.98(CI 2.69-3.31) and 2.98(CI 2.60-3.40) respectively]; iii) sicker children, readmitted/referred [AOR 1.24(CI 1.08-1.42) and 1.15(CI 1.04-1.28) respectively]. "Working TB" diagnosis was made in 2.9%(1,202/42,107) of all admissions and 0.2%(89/42,107) were bacteriologically-confirmed. CONCLUSIONS: More than half of all paediatric admissions had symptoms associated with TB and nearly two-thirds had more specific history documented. Only a few amongst them got TB tests requested. TB was diagnosed in 2.9% of all admissions but most were inadequately investigated. Major challenges remain in identifying and investigating TB in children in hospitals with access to Xpert MTB/RIF and a review is needed of existing guidelines

High frequency of Polio-like Enterovirus C strains with differential clustering of CVA-13 and EV-C99 subgenotypes in a cohort of Malawian children

Enteroviruses (EVs) are among the most commonly detected viruses infecting humans worldwide. Although the prevalence of EVs is widely studied, the status of EV prevalence in sub-Saharan Africa remains largely unknown. The objective of our present study was therefore to increase our knowledge on EV circulation in sub-Saharan Africa. We obtained 749 fecal samples from a cross-sectional study conducted on Malawian children aged 6 to 60 months. We tested the samples for the presence of EVs using real time PCR, and typed the positive samples based on partial viral protein 1 (VP1) sequences. A large proportion of th

Research Article (New England Journal of Medicine) Severe anemia in Malawian children

Background: Severe anemia is a major cause of sickness and death in African children, yet the causes of anemia in this population have been inadequately studied.Methods: We conducted a case–control study of 381 preschool children with severe anemia (hemoglobin concentration, <5.0 g per deciliter) and 757 preschool children without severe anemia in urban and rural settings in Malawi. Causal factors  previously associated with severe anemia were studied. The data were examined by multivariate analysis and structural equation modeling.Results: Bacteremia (adjusted odds ratio, 5.3; 95% confidence interval [CI], 2.6 to 10.9), malaria (adjusted odds ratio, 2.3; 95% CI, 1.6 to 3.3), hookworm (adjusted odds ratio, 4.8; 95% CI, 2.0 to 11.8), human immunodeficiency virus infection (adjusted odds ratio, 2.0; 95% CI, 1.0 to 3.8), the G6PD−202/−376 genetic disorder (adjusted odds ratio, 2.4; 95% CI, 1.3 to 4.4), vitamin A deficiency (adjusted odds ratio, 2.8; 95% CI, 1.3 to 5.8), and vitamin B12 deficiency (adjusted odds ratio, 2.2; 95% CI, 1.4 to 3.6) were associated with severe anemia. Folate deficiency, sickle cell disease, and laboratory signs of an abnormal  inflammatory response were uncommon. Iron deficiency was not prevalent in case patients (adjusted odds ratio, 0.37; 95% CI, 0.22 to 0.60) and was negatively associated with bacteremia. Malaria was associated with severe anemia in the urban site (with seasonal transmission) but not in the rural site (where malaria was holoendemic). Seventy-six percent of hookworm infections were found in children under 2 years of age.Conclusions: There are multiple causes of severe anemia in Malawian preschool children, but folate and iron deficiencies are not prominent among them. Even in the presence of malaria parasites, additional or alternative causes of severe anemia should be considered

Pathophysiological Mechanisms of Severe Anaemia in Malawian Children

BACKGROUND: Severe anaemia is a major cause of morbidity and mortality in African children. The aetiology is multi-factorial, but interventions have often targeted only one or a few causal factors, with limited success. METHODS AND FINDINGS: We assessed the contribution of different pathophysiological mechanisms (red cell production failure [RCPF], haemolysis and blood loss) to severe anaemia in Malawian children in whom etiological factors have been described previously. More complex associations between etiological factors and the mechanisms were explored using structural equation modelling. In 235 children with severe anaemia (haemoglobin<3.2 mMol/L [5.0 g/dl]) studied, RCPF, haemolysis and blood loss were found in 48.1%, 21.7% and 6.9%, respectively. The RCPF figure increased to 86% when a less stringent definition of RCPF was applied. RCPF was the most common mechanism in each of the major etiological subgroups (39.7-59.7%). Multiple aetiologies were common in children with severe anaemia. In the final model, nutritional and infectious factors, including malaria, were directly or indirectly associated with RCPF, but not with haemolysis. CONCLUSION: RCPF was the most common pathway leading to severe anaemia, from a variety of etiological factors, often found in combination. Unlike haemolysis or blood loss, RCPF is a defect that is likely to persist to a significant degree unless all of its contributing aetiologies are corrected. This provides a further explanation for the limited success of the single factor interventions that have commonly been applied to the prevention or treatment of severe anaemia. Our findings underline the need for a package of measures directed against all of the local aetiologies of this often fatal paediatric syndrome

Long Term Outcome of Severe Anaemia in Malawian Children

Severe anaemia is a common, frequently fatal, condition in African children admitted to hospital, but its long term outcome is unknown. Early reports that survivors may be at risk of additional late morbidity and mortality may have significant implications for child survival in Africa. We assessed the short and long term outcome of severe anaemia in Malawian children and identified potential risk factors for death and further severe anaemia. For 18 months, we followed up children (6-60 months old) presenting to hospital with severe anaemia (haemoglobin <or=5 g/dl) and their hospital and community controls with the aim to compare all cause mortality and severe anaemia recurrence rates between the groups, and to identify risk factors for these adverse outcomes. A total of 377 cases, 377 hospital controls and 380 community controls were recruited. Among cases, the in-hospital mortality was 6.4% and post-discharge all cause mortality was 12.6%, which was significantly greater than in hospital controls (2.9%) or community controls (1.4%) (Log rank test, p <0.001). The incidence of recurrence of severe anaemia among the cases was 0.102 per child-year (95% Confidence Interval 0.075-0.138), and was significantly higher than the 0.007 per child-year (95% CI 0.003-0.015) in the combined controls (p <0.0001). HIV was the most important risk factor both for post-discharge mortality (Hazard Ratio 10.5, 95% CI 4.0-27.2) and for recurrence of severe anaemia (HR 5.6, 95% CI 1.6-20.1). Severe anaemia carries a high 'hidden' morbidity and mortality occurring in the months after initial diagnosis and treatment. Because severe anaemia is very common, this is likely to contribute importantly to overall under-five mortality. If not adequately addressed, severe anaemia may be an obstacle to achievement of the Millennium development goal No.4 on child survival. Strategies to diagnose and properly treat HIV infected children early most likely will reduce the high post-discharge mortality in severe anaemi

Marked Reduction in Prevalence of Malaria Parasitemia and Anemia in HIV-Infected Pregnant Women Taking Cotrimoxazole With Or Without Sulfadoxine-Pyrimethamine Intermittent Preventive Therapy during Pregnancy in Malawi

Background. Effectiveness of cotrimoxazole (CTX) compared with sulfadoxine-pyrimethamine (SP) intermittent-preventive-therapy (IPTp) for malaria in HIV-infected pregnant women is unknown. We examined effectiveness of CTX with or without SP-IPTp versus SP-IPTp at reducing malaria parasitemia and anemia

Nodding Syndrome: The Unresolved Mystery of a Pediatric Disease in Sub-Saharan Africa

Nodding syndrome is a mysterious neurologic illness of unknown etiology, presenting with distinctive clinical features often at early age. Currently, it affects children in restricted geographical areas in South Sudan, Northern Uganda and Southern Tanzania and is associated with high mortality and morbidity, especially in the children with severe disease. In this paper, we will give an outline of what is known about nodding syndrome with respect to epidemiology, clinical presentation, etiology and treatment. In addition, a possible approach to resolving the mystery is presented

Anaemia, iron deficiency and susceptibility to infections

Anaemia, iron deficiency and infections are three major causes of childhood morbidity and mortality throughout the world, although they predominantly occur in resource limited settings. As the three conditions may have the same underlying aetiologies, they often occur simultaneously and may interact. Being an essential component in erythropoiesis, iron is also essential for proper functioning of the host immune system as well as an essential nutrient for growth of various pathogens, including non-typhoid salmonella. This has resulted in a treatment dilemma in which iron is needed to treat the iron deficient anaemia and improve the immune system of the host (child), but the same treatment may also put the child at an increased, potentially fatal, infection ris