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 isunder-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

Do clinicians adhere to practice guidelines? A descriptive study at a referral hospital in Kenya

Background: Clinical guidelines when implemented correctly have shown to improve disease outcomes. This study describes utilization of Kenya National guidelines in managing ante partum haemorrhage (APH) in 3rd trimester.Objective: To describe adherence to clinical guideline in management of antepartum haemorrhage at Garissa Provincial General Hospital Design: Crossectional mixed methods studySetting: Garissa Provincial General HospitalSubjects: Medical records of patients managed for APH between 2002 and 2012 and Key Informant Interviews (KIIs) of Health workers.Results: 36.1% of the cases assessed were managed with strict adherence to guidelines. 90% of health care workers had high levels of awareness of the existence of guidelines and sited utilization challenges attributed to resource inadequacies.Conclusion: Clinicians are skilled on APH guidelines, but adherence levels are still low. Therefore, continuous appraisal of clinical practices, availing equipment, facilities and supplies to reinforce adherence is recommended

Predictors of mortality in HIV-1 infected children on antiretroviral therapy in Kenya: a prospective cohort

<p>Abstract</p> <p>Background</p> <p>Among children, early mortality following highly active antiretroviral therapy (HAART) remains high. It is important to define correlates of mortality in order to improve outcome.</p> <p>Methods</p> <p>HIV-1-infected children aged 18 months-12 years were followed up at Kenyatta National Hospital, Nairobi after initiating NNRTI-based HAART. Cofactors for mortality were determined using multivariate Cox regression models.</p> <p>Results</p> <p>Between August 2004 and November 2008, 149 children were initiated on HAART of whom 135 were followed for a total of 238 child-years (median 21 months) after HAART initiation. Baseline median CD4% was 6.8% and median HIV-1-RNA was 5.98-log₁₀copies/ml. Twenty children (13.4%) died at a median of 35 days post-HAART initiation. Mortality during the entire follow-up period was 8.4 deaths per 100 child-years (46 deaths/100 child-years in first 4 months and 1.0 deaths/100 child-years after 4 months post-HAART initiation). On univariate Cox regression, baseline hemoglobin (Hb) <9 g/dl, weight-for-height z-score (WHZ) < -2, and WHO clinical stage 4 were associated with increased risk of death (Hb <9 g/dl HR 3.00 [95% C.I. 1.21-7.39], p = 0.02, WHZ < -2 HR 3.41 [95% C.I. 1.28-9.08], p = 0.01, and WHO clinical stage 4, HR 3.08 [1.17-8.12], p = 0.02). On multivariate analysis Hb < 9 g/dl remained predictive of mortality after controlling for age, baseline CD4%, WHO clinical stage and weight-for-height z-score (HR 2.95 (95% C.I. 1.04-8.35) p = 0.04).</p> <p>Conclusion</p> <p>High early mortality was observed in this cohort of Kenyan children receiving HAART, and low baseline hemoglobin was an independent risk factor for death.</p

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

Viral Evolution and Cytotoxic T Cell Restricted Selection in Acute Infant HIV-1 Infection

Antiretroviral therapy-naive HIV-1 infected infants experience poor viral containment and rapid disease progression compared to adults. Viral factors (e.g. transmitted cytotoxic T- lymphocyte (CTL) escape mutations) or infant factors (e.g. reduced CTL functional capacity) may explain this observation. We assessed CTL functionality by analysing selection in CTL-targeted HIV-1 epitopes following perinatal infection. HIV-1 gag, pol and nef sequences were generated from a historical repository of longitudinal specimens from 19 vertically infected infants. Evolutionary rate and selection were estimated for each gene and in CTL-restricted and non-restricted epitopes. Evolutionary rate was higher in nef and gag vs. pol, and lower in infants with non-severe immunosuppression vs. severe immunosuppression across gag and nef. Selection pressure was stronger in infants with non-severe immunosuppression vs. severe immunosuppression across gag. The analysis also showed that infants with non-severe immunosuppression had stronger selection in CTL-restricted vs. non-restricted epitopes in gag and nef. Evidence of stronger CTL selection was absent in infants with severe immunosuppression. These data indicate that infant CTLs can exert selection pressure on gag and nef epitopes in early infection and that stronger selection across CTL epitopes is associated with favourable clinical outcomes. These results have implications for the development of paediatric HIV-1 vaccines

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.National Institutes of HealthRevisión por pare

Prioritising the most needed paediatric antiretroviral formulations: the PADO4 list

Despite considerable progress in paediatric HIV treatment and timely revision of global policies recommending the use of more effective and tolerable antiretroviral regimens, optimal antiretroviral formulations for infants, children, and adolescents remain limited. The Paediatric Antiretroviral Drug Optimization group reviews medium-term and long-term priorities for antiretroviral drug development to guide industry and other stakeholders on formulations most needed for low-income and middle-income countries. The group convened in December, 2018, to assess progress since the previous meeting and update the list of priority formulations. Issues relating to drug optimisation for neonatal prophylaxis and paediatric treatment, and those relating to the investigation of novel antiretrovirals in adolescents and pregnant and lactating women were also discussed. Continued focus on identifying, prioritising, and providing access to optimal antiretroviral formulations suitable for infants, children, and adolescents is key to ensuring that global HIV treatment targets can be met

18-month occurrence of severe events among early diagnosed HIV-infected children before antiretroviral therapy in Abidjan, Côte d'Ivoire: A cohort study

<p>Abstract</p> <p>Objective</p> <p>To assess the 18-month field effectiveness on severe events of a pediatric package combining early HIV-diagnosis and targeted cotrimoxazole prophylaxis in HIV-infected children from age six-week before the antiretroviral era, in Abidjan, Côte d'Ivoire.</p> <p>Methods</p> <p>Data from two consecutive prevention of HIV mother-to-child transmission programs were compared: the ANRS 1201/1202 Ditrame-Plus cohort (2001–2005) and the pooled data of the ANRS 049a Ditrame randomized trial and its following open-labeled cohort (1995–2000), used as a reference group. HIV-infected pregnant women ≥ 32–36 weeks of gestation were offered a short-course peri-partum antiretroviral prophylaxis (ZDV in Ditrame, and ZDV ± 3TC+single-dose (sd) NVP in Ditrame-Plus). Neonatal prophylaxis was provided in Ditrame-Plus only: 7-day ZDV and sdNVP 48–72 h after birth. A 6-week pediatric HIV-RNA diagnosis was provided on-line in the Ditrame-Plus while it was only oriented on clinical symptoms in Ditrame. Six-week HIV-infected children received a daily cotrimoxazole prophylaxis in Ditrame-Plus while no prophylaxis was provided in Ditrame. The determinants of severe events (death or hospitalization > 1 day) were assessed in a Cox regression model.</p> <p>Results</p> <p>Between 1995 and 2003, 98 out of the 1121 live-births were diagnosed as HIV-infected in peri-partum: 45 from Ditrame-Plus and 53 from Ditrame. The 18-month Kaplan-Meier cumulative probability of presenting a severe event was 66% in Ditrame-Plus (95% confidence interval [95%CI]: 50%–81%) and 77% in Ditrame (95%CI: 65%–89%), Log Rank test: p = 0.47. After adjustment on maternal WHO clinical stage, maternal death, 6-week pediatric viral load, birth-weight, and breastfeeding exposure, the 18-month risk of severe event was lower in Ditrame-Plus than in Ditrame (adjusted Hazard Ratio (aHR): 0.55, 95%CI: 0.3–1.1), although the difference was not statistically significant; p = 0.07). Maternal death was the only variable determinant of the occurrence of severe events in children (aHR: 3.73; CI: 2.2–11.2; p = 0.01).</p> <p>Conclusion</p> <p>Early cotrimoxazole from 6 weeks of age in HIV-infected infants seemed to reduce probability of severe events but the study lacked statistical power to prove this. Even with systematic cotrimoxazole prophylaxis, infant morbidity and mortality remained high pointing towards a need for early pediatric HIV-diagnosis and antiretroviral treatment in Africa.</p

HIV-Specific Antibodies Capable of ADCC Are Common in Breastmilk and Are Associated with Reduced Risk of Transmission in Women with High Viral Loads

There are limited data describing the functional characteristics of HIV-1 specific antibodies in breast milk (BM) and their role in breastfeeding transmission. The ability of BM antibodies to bind HIV-1 envelope, neutralize heterologous and autologous viruses and direct antibody-dependent cell cytotoxicity (ADCC) were analyzed in BM and plasma obtained soon after delivery from 10 non-transmitting and 9 transmitting women with high systemic viral loads and plasma neutralizing antibodies (NAbs). Because subtype A is the dominant subtype in this cohort, a subtype A envelope variant that was sensitive to plasma NAbs was used to assess the different antibody activities. We found that NAbs against the subtype A heterologous virus and/or the woman's autologous viruses were rare in IgG and IgA purified from breast milk supernatant (BMS) – only 4 of 19 women had any detectable NAb activity against either virus. Detected NAbs were of low potency (median IC50 value of 10 versus 647 for the corresponding plasma) and were not associated with infant infection (p = 0.58). The low NAb activity in BMS versus plasma was reflected in binding antibody levels: HIV-1 envelope specific IgG titers were 2.2 log10 lower (compared to 0.59 log10 lower for IgA) in BMS versus plasma. In contrast, antibodies capable of ADCC were common and could be detected in the BMS from all 19 women. BMS envelope-specific IgG titers were associated with both detection of IgG NAbs (p = 0.0001)and BMS ADCC activity (p = 0.014). Importantly, BMS ADCC capacity was inversely associated with infant infection risk (p = 0.039). Our findings indicate that BMS has low levels of envelope specific IgG and IgA with limited neutralizing activity. However, this small study of women with high plasma viral loads suggests that breastmilk ADCC activity is a correlate of transmission that may impact infant infection risk

Track A Basic Science

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/138319/1/jia218438.pd