Effectiveness of three commonly used transition phase diets in the inpatient management of children with severe acute malnutrition: a pilot randomized controlled trial in Malawi.

BACKGROUND: The case fatality rate of severely malnourished children during inpatient treatment is high and mortality is often associated with diarrhea. As intestinal carbohydrate absorption is impaired in severe acute malnutrition (SAM), differences in dietary formulations during nutritional rehabilitation could lead to the development of osmotic diarrhea and subsequently hypovolemia and death. We compared three dietary strategies commonly used during the transition of severely malnourished children to higher caloric feeds, i.e., F100 milk (F100), Ready-to-Use Therapeutic Food (RUTF) and RUTF supplemented with F75 milk (RUTF + F75). METHODS: In this open-label pilot randomized controlled trial, 74 Malawian children with SAM aged 6-60 months, were assigned to either F100, RUTF or RUTF + F75. Our primary endpoint was the presence of low fecal pH (pH ? 5.5) measured in stool collected 3 days after the transition phase diets were introduced. Secondary outcomes were duration of hospital stay, diarrhea and other clinical outcomes. Chi-square test, two-way analysis of variance and logistic regression were conducted and, when appropriate, age, sex and initial weight for height Z-scores were included as covariates. RESULTS: The proportion of children with acidic stool (pH ?5.5) did not significantly differ between groups before discharge with 30, 33 and 23% for F100, RUTF and RUTF + F75, respectively. Mean duration of stay after transitioning was 7.0 days (SD 3.4) with no differences between the three feeding strategies. Diarrhea was present upon admission in 33% of patients and was significantly higher (48%) during the transition phase (p < 0.05). There was no significant difference in mortality (n = 6) between diets during the transition phase nor were there any differences in other secondary outcomes. CONCLUSIONS: This pilot trial does not demonstrate that a particular transition phase diet is significantly better or worse since biochemical and clinical outcomes in children with SAM did not differ. However, larger and more tightly controlled efficacy studies are needed to confirm these findings. TRIAL REGISTRATION: ISRCTN13916953 Registered: 14 January 2013

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(sup -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 B(sub 12) 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 considere

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, &lt;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

Management issues in malnourished children with HIV and Tuberculosis (TB)

GB is a 4 month old male currently living with his aunt. His mother is deceased and nothing is known about the mother’s health or the birth history. Over the last 4 weeks, GB developed worsening watery non-bloody diarrhea and felt warm to his caregivers. Over the last week his oral intake decreased significantly; he is being fed formula and phala (soft maize porridge)

Task sharing within a managed clinical network to improve child health in Malawi

The Ministry of Health, Malawi, for its full support and collaboration during the development and implementation of this programme, including providing salaries for MOH staff during training. Deutsche Gesellschaft für Internationale Zusammenarbeit (GIZ) GmbH for scholarships for BSc for CO PCH 2013–2014 intake and the salary of a paediatrician to provide training to this cadre. University of St Andrews Global Health Implementation programme for funding BSc PCH 2013–2017. University of Edinburgh for funding BSc PCH 2013–2016. The Scottish Government for funding the virtual learning environment for this cadre. Nchima Trust for funding BSc PCH 2014 intake. ELMA Philanthropies for funding MMED scholarships for specialist paediatricians. ELMA Philanthropies for funding BSc 2015–2018 intake, funding for supervision and mentoring visitsBackground Eighty per cent of Malawi’s 8 million children live in rural areas, and there is an extensive tiered health system infrastructure from village health clinics to district hospitals which refers patients to one of the four central hospitals. The clinics and district hospitals are staffed by nurses, non-physician clinicians and recently qualified doctors. There are 16 paediatric specialists working in two of the four central hospitals which serve the urban population as well as accepting referrals from district hospitals. In order to provide expert paediatric care as close to home as possible, we describe our plan to task share within a managed clinical network and our hypothesis that this will improve paediatric care and child health. Presentation of the hypothesis Managed clinical networks have been found to improve equity of care in rural districts and to ensure that the correct care is provided as close to home as possible. A network for paediatric care in Malawi with mentoring of non-physician clinicians based in a district hospital by paediatricians based at the central hospitals will establish and sustain clinical referral pathways in both directions. Ultimately, the plan envisages four managed paediatric clinical networks, each radiating from one of Malawi’s four central hospitals and covering the entire country. This model of task sharing within four hub-and-spoke networks may facilitate wider dissemination of scarce expertise and improve child healthcare in Malawi close to the child’s home. Testing the hypothesis Funding has been secured to train sufficient personnel to staff all central and district hospitals in Malawi with teams of paediatric specialists in the central hospitals and specialist non-physician clinicians in each government district hospital. The hypothesis will be tested using a natural experiment model. Data routinely collected by the Ministry of Health will be corroborated at the district. This will include case fatality rates for common childhood illness, perinatal mortality and process indicators. Data from different districts will be compared at baseline and annually until 2020 as the specialists of both cadres take up posts. Implications of the hypothesis If a managed clinical network improves child healthcare in Malawi, it may be a potential model for the other countries in sub-Saharan Africa with similar cadres in their healthcare system and face similar challenges in terms of scarcity of specialists.Publisher PDFPeer reviewe

Challenges in the Management of HIV-Infected Malnourished Children in Sub-Saharan Africa

Infection with HIV, and oftentimes coinfection with TB, complicates the care of severely malnourished children in sub-Saharan Africa. These superimposed infections challenge clinicians faced with a population of malnourished children for whose care evidence-based guidelines have not kept up. Even as the care of HIV-uninfected malnourished children has improved dramatically with the advent of community-based care and even as there are hopeful signs that the HIV epidemic may be stabilizing or ameliorating, significant gaps remain in the care of malnourished children with HIV. Here we summarize what is currently known, what remains unknown, and what remains challenging about how to treat severely malnourished children with HIV and TB

Glycerol and acetaminophen as adjuvant therapy did not affect the outcome of bacterial meningitis in Malawian children

We investigated the benefit of 2 candidate adjunctive therapies in bacterial meningitis: glycerol, which has shown promise in earlier studies, and acetaminophen, which is reportedly beneficial in adult septicemia. In a hospital in Blantyre, Malawi, we enrolled 360 children aged ≥ 2 months with proven bacterial meningitis (36% HIV infected) in a double-blind, randomized, placebo-controlled trial of glycerol and acetaminophen in a 2 × 2 factorial design. Of 4 groups, first group received oral glycerol, second received rectal acetaminophen, third received both therapies and the fourth received placebos only. Adjuvant therapies were given for the first 48 hours of antibiotic therapy. Endpoints were mortality and neurological sequelae. Baseline findings were similar across all groups, except that many children had prior antibiotics in the acetaminophen group and many were anemic in the acetaminophen and glycerol group. Outcomes were similar for all groups. We found no benefit from oral glycerol or rectal acetaminophen in, mostly pneumococcal, meningitis in Malawian children

Methods for conducting a double-blind randomized controlled clinical trial of three days versus five days of amoxicillin dispersible tablets for chest indrawing childhood pneumonia among children two to 59 months of age in Lilongwe, Malawi: a study protocol

Abstract Background Pneumonia is the leading infectious cause of death in children under 5 years of age around the globe. In addition to preventing pneumonia, there is a critical need to provide greater access to appropriate and effective treatment. Studies in Asia have evaluated the effectiveness of 3 days of oral amoxicillin for the treatment of fast-breathing pneumonia; however, further evidence is needed to determine if 3 days of oral amoxicillin is also effective for the treatment of chest indrawing pneumonia. Methods This is a double-blind, randomized, non-inferiority trial with the objective to assess the effectiveness of shorter duration amoxicillin dispersible tablet (DT) treatment of chest indrawing childhood pneumonia in a malaria-endemic region of Malawi. The primary objective of this study is to determine whether 3 days of treatment with oral amoxicillin DT in HIV-uninfected Malawian children two to 59 months of age with chest indrawing pneumonia is as effective as 5 days of treatment. The study will enroll 2000 children presenting to Kamuzu Central or Bwaila District Hospitals in Lilongwe, Malawi. Each child will be randomized to either 3 days of amoxicillin DT followed by 2 days of placebo DT or 5 days of amoxicillin DT. Children in the study will be hospitalized for 48 h after enrollment and will have scheduled study visits at Days 2, 4, 6 and 14. Treatment failure by Day 6 is the primary outcome. We hypothesize that the rates of treatment failure will be similar in both arms and that 3 days of treatment will be non-inferior to 5 days of amoxicillin DT for chest indrawing pneumonia using a relative non-inferiority margin of 1.5. This trial was approved by the Western Institutional Review Board and Malawi College of Medicine Research and Ethics Committee. Discussion Given the paucity of data from Africa, African-based research is necessary to establish appropriate duration of treatment with amoxicillin DT for chest indrawing childhood pneumonia in malaria-endemic settings in the region. An expanded evidence base will contribute to future iterations of World Health Organization Integrated Management of Childhood Illness guidelines. Trial registration NCT02678195: Pre-results. Date registered February 9, 2016

Impact of Human Immunodeficiency Virus Infection on the Etiology and Outcome of Severe Pneumonia in Malawian Children

Background: HIV infection is a major risk factor for death in childhood pneumonia in HIV-endemic regions. Improved case management and preventive strategies require better understanding of the impact of HIV on causes, clinical presentation, and outcome. Methods: A prospective, clinical descriptive study of Malawian infants and children with severe pneumonia included blood culture and nasopharyngeal aspiration for diagnosis of pneumocystis pneumonia (PcP). A select group with consolidation on chest radiograph, and without severe hypoxia or hyperinflation, also had lung aspirate taken for culture and identification of bacterial deoxyribonucleic acid by real-time polymerase chain reaction (PCR). Results: There were 327 study patients with a median age of 11 months (range, 2 months-14 years). HIV prevalence was 51%. There were 58 cases of confirmed bacterial pneumonia, of which the most common bacterial isolates were Streptococcus pneumoniae and Salmonella typhimurium. Of the 54 lung aspirates, only 2 were positive on culture but 27 were positive for bacterial deoxyribonucleic acid by PCR. PcP was confirmed in 16 patients, and was associated with young age, severe hypoxia, HIV infection, and a very poor outcome. The overall case-fatality rate was 10% despite presumptive therapy for PcP and routine broad-spectrum antibiotic treatment appropriate for local antimicrobial susceptibility data. Most of the deaths occurred in infants of 2 to 6 months of age and PcP was associated with 57% of these deaths. Conclusions: PcP is a major barrier in reducing the case-fatality rate of severe pneumonia in infants of HIV-endemic communities. The use of PCR on lung aspirate specimens greatly increased the diagnostic yield