Clinical standards for drug-susceptible TB in children and adolescents.

BACKGROUND: These clinical standards aim to provide guidance for diagnosis, treatment, and management of drug-susceptible TB in children and adolescents.METHODS: Fifty-two global experts in paediatric TB participated in a Delphi consensus process. After eight rounds of revisions, 51/52 (98%) participants endorsed the final document.RESULTS: Eight standards were identified: Standard 1, Age and developmental stage are critical considerations in the assessment and management of TB; Standard 2, Children and adolescents with symptoms and signs of TB disease should undergo prompt evaluation, and diagnosis and treatment initiation should not depend on microbiological confirmation; Standard 3, Treatment initiation is particularly urgent in children and adolescents with presumptive TB meningitis and disseminated (miliary) TB; Standard 4, Children and adolescents should be treated with an appropriate weight-based regimen; Standard 5, Treating TB infection (TBI) is important to prevent disease; Standard 6, Children and adolescents should receive home-based/community-based treatment support whenever possible; Standard 7, Children, adolescents, and their families should be provided age-appropriate support to optimise engagement in care and clinical outcomes; and Standard 8, Case reporting and contact tracing should be conducted for each child and adolescent.CONCLUSION: These consensus-based clinical standards, which should be adapted to local contexts, will improve the care of children and adolescents affected by TB.

The journey to improve the prevention and management of childhood tuberculosis: the Kenyan experience.

Child tuberculosis (TB) cases in Kenya, a high TB burden country, constitute more than one tenth of all TB cases. This paper describes Kenya's efforts in the past decade to increase awareness about policy, improve leadership and combat the multiple challenges faced in the diagnosis and management of children presumed to have TB. We describe the increasing advocacy and involvement of paediatricians and the child health sector with the National TB Programme, and the resulting improvement in leadership, policy, child-specific guidelines and training materials, health worker capacity, and the implementation of prevention and cure of child TB.

Incidence and correlates of tuberculosis IGRA conversion among HIV-infected postpartum women.

SETTING: Prevention of maternal-to-child transmission program at a tertiary care hospital in Nairobi, Kenya. The risk of acquiring Mycobacterium tuberculosis infection among peripartum human immunodeficiency virus (HIV) infected women is poorly defined. OBJECTIVE: To determine the incidence of and co-factors for interferon-gamma release assay (IGRA) conversion among postpartum HIV-infected women using T-SPOT.TB. DESIGN: We used data and cryopreserved peripheral blood mononuclear cells from a historical cohort of HIV-infected women enrolled at 32 weeks' gestation and followed for 1 year postpartum between 1999 and 2005. RESULTS: Of 89 women initially IGRA-negative during pregnancy, 11 (12.4%) became positive, 53 (59.5%) remained negative and 25 (28.1%) were indeterminate at 1 year postpartum. Mean interferon-gamma (IFN-γ) response among converters increased from ~1 to >50 spot-forming cells/well (P = 0.015). IGRA conversion was significantly associated with partner HIV infection, flush toilets, maternal illness and cough during follow-up, but not maternal CD4 count or HIV viral load. CONCLUSION: The high rates of IGRA conversion seen among HIV-infected postpartum women in our study are similar to those of other groups at high risk for M. tuberculosis infection. This has important implications for M. tuberculosis infection screening strategies and provision of preventive therapy for the health of women and their infants.

ADHERENCE TO PNEUMONIA GUIDELINES FOR CHILDREN 2 - 59 MONTHS AT GARRISA PROVINCIAL GENERAL HOSPITAL.

BACKGROUND: Clinical Practice Guidelines for childhood illnesses including pneumonia in Kenya are contained in the Ministry of Health Basic Paediatric Protocols. In the presence of a cough and/ or difficulty in breathing and increased respiratory rate for age, pneumonia is diagnosed. In addition to these the presence of lower chest wall indrawing denotes severe pneumonia; The presence of cyanosis, inability to drink/ breastfeed, grunting, level of consciousness using the AVPU scale less than A in addition to the aforementioned is classified as very severe pneumonia. Recommended management is intravascular Crystalline penicillin, gentamycin and oxygen for severe pneumonia, intravascular crystalline penicillin for severe pneumonia and oral amoxyl or cotrimaxole for pneumonia. These guidelines have been disseminated through the Emergency Triage And Treatment Plus (ETAT +) coursesheld since 2007. Implementation of guidelines into care has been shown to reduce case fatality from pneumonia by 36%. OBJECTIVES: To evaluate the level of adherence and factors affecting adherence to the National guidelines on management of pneumonia in children aged two to fifty nine months at Garissa provincial General Hospital, Kenya. DESIGN: Retrospective hospital based cross sectional study. SETTING: Paediatric Department of Garissa Provincial General Hospital (PGH) in Kenya. SUBJECTS: Hospital medical records of children aged two to fifty nine months diagnosed with pneumonia between January and June 2012 were reviewed. Data abstracted from the records included demographic information, recorded clinical signs and symptoms, disease classification and treatment. RESULTS: Records of 91 childrenwere reviewed. Theirmedian age was 12 months (IQR 6 - 18 months). There were more boys than girls with a male to female ratio of 1.25:1. Forty-eight of the participants (52.8%) had severe pneumonia. Guideline adherence was assessed at three levels; assessment of clinical signs and symptoms reflected by their recording, correct disease severity classification and correct treatment prescribed. There were a minimum of two and a maximum of six clinical sign and symptoms recorded. The average level of adherence was 42.9% (SD ± 17.3).Documented correct classification of disease severity was 56.6% and recommended treatment of pneumonia was 27.7%. The presence of a co-morbidity and severe disease was associated with better adherence to the assessment tasks (p = 0.033 and p = 0.021 respectively). Disease severity was associated with better adherence to the disease classification task (p = < 0.001) and treatment task (p = 0.02). CONCLUSION: Adherence to guidelines was low at all assessed levels. Overall, disease severity was associated with better guideline adherence. Presence of co-morbidities improved disease assessment.

Infants with late breast milk acquisition of HIV-1 generate interferon-gamma responses more rapidly than infants with early peripartum acquisition.

Infants infected with HIV-1 after the first month of life have a lower viral set-point and slower disease progression than infants infected before 1 month. We investigated the kinetics of HIV-1-specific CD8(+) T lymphocyte secretion of interferon (IFN)-gamma in infants infected before 1 month of life compared with those infected between months 1 and 12 (late infection). HIV-1 infection was assessed at birth and at months 1, 3, 6, 9 and 12 and timing of infection was determined by HIV-1 gag DNA from dried blood spots and verified by plasma HIV-1 RNA levels. HIV-1 peptide-specific IFN-gamma responses were measured by enzyme-linked immunospot at months 1, 3, 6, 9 and 12. Timing of development of IFN-gamma responses was compared using the log-rank test and Kaplan-Meier survival curves. Infants infected late developed HIV-1-specific CD8(+) T cell responses 2.8 months sooner than infants infected peripartum: 2.3 versus 5.1 months after HIV-1 infection (n = 52, P = 0.04). Late-infected infants had more focused epitope recognition than early-infected infants (median 1 versus 2 peptides, P = 0.03); however, there were no differences in the strength of IFN-gamma responses. In infants infected with HIV-1 after the first month of life, emergence of HIV-1-specific CD8(+) IFN-gamma responses is coincident with the decline in viral load, nearly identical to what is observed in adults and more rapid than in early-infected infants.

Hypo-phosphataemia in children under five years with kwashiorkor and marasmic kwashiorkor.

BACKGROUND: Severe malnutrition contributes up to 50% of childhood mortality in developing countries is frequently characterised by electrolyte depletion, including low total body phosphate. During therapeutic re-feeding, electrolyte shift from extracellular to intra-cellular compartments may induce hypo-phosphataemia (hypo-P) with resultant increased morbidity and mortality. This biochemical imbalance is under-recognised, and the frequency of this problem among African malnourished children is unclear. OBJECTIVES: To determine the magnitude of hypo-phosphataemia in children under five years of age presenting to Kenyatta National Hospital with kwashiorkor and marasmic kwashiorkor and to evaluate the relationship between hypo-phosphataemia and nutritional intervention during the first five days of treatment. DESIGN: Short longitudinal survey. SETTING: The General Paediatric wards of the Kenyatta National Hospital (KNH), Nairobi. SUBJECTS: Children under five years of age presenting with kwashiorkor or marasmic kwashiorkor at KNH were recruited into the study. MAIN OUTCOME MEASURES: Low serum phosphate level (< 1.20 mmol/l) and patient outcome (survival or death) during the first five days of treatment. RESULTS: One hundred and sixty five children were enrolled between June 2005 and February 2006 of which 107 (64%) had kwashiorkor and 58 (36%) had marasmic kwashiorkor. They were of mean age 20 months (range 3-60), and 95 (58%) were male. The prevalence of hypo-phosphataemia was 86% on admission, increased to 90% and 93% on day one and two respectively, and then declined to 90% by the fourth day. At admission 6% were hypo-phosphataemic, increasing to 18% and 22% on day one and two respectively, and declining to 11% by day four. On admission mean serum phosphate was below normal at 0.91 mmol/l, declined significantly to 0.67 mmol/l and to a nadir of 0.63 mmol/l after the first and second day of treatment respectively, then rose slightly to 0.75 mmol/l on the fourth day (p < 0.001 comparing each follow-up mean level with the admission level). There was a positive association between severity of nadir serum phosphate level and mortality (p = 0.028). There were no deaths among children with normal nadir serum phosphate levels. However, among children with mild, moderate and severe nadir hypo-phosphataemia, 8,14 and 21% died respectively. Children with dermatosis and hypomagnesaemia showed a trend for association with mortality (p = 0.082 and 0.099 respectively). CONCLUSION: Hypo-phosphataemia is frequent among children with kwashiorkor and marasmic kwashiorkor presenting at KNH. Serum phosphate levels decline significantly during the first two days of nutritional intervention, and severity of