Metabolomic Changes in Serum of Children with Different Clinical Diagnoses of Malnutrition.

BACKGROUND: Mortality in children with severe acute malnutrition (SAM) remains high despite standardized rehabilitation protocols. Two forms of SAM are classically distinguished: kwashiorkor and marasmus. Children with kwashiorkor have nutritional edema and metabolic disturbances, including hypoalbuminemia and hepatic steatosis, whereas marasmus is characterized by severe wasting. The metabolic changes underlying these phenotypes have been poorly characterized, and whether homeostasis is achieved during hospital stay is unclear. OBJECTIVES: We aimed to characterize metabolic differences between children with marasmus and kwashiorkor at hospital admission and after clinical stabilization and to compare them with stunted and nonstunted community controls. METHODS: We studied children aged 9-59 mo from Malawi who were hospitalized with SAM (n = 40; 21 with kwashiorkor and 19 with marasmus) or living in the community (n = 157; 78 stunted and 79 nonstunted). Serum from patients with SAM was obtained at hospital admission and 3 d after nutritional stabilization and from community controls. With the use of targeted metabolomics, 141 metabolites, including amino acids, biogenic amines, acylcarnitines, sphingomyelins, and phosphatidylcholines, were measured. RESULTS: At admission, most metabolites (128 of 141; 91%) were lower in children with kwashiorkor than in those with marasmus, with significant differences in several amino acids and biogenic amines, including those of the kynurenine-tryptophan pathway. Several phosphatidylcholines and some acylcarnitines also differed. Patients with SAM had profiles that were profoundly different from those of stunted and nonstunted controls, even after clinical stabilization. Amino acids and biogenic amines generally improved with nutritional rehabilitation, but most sphingomyelins and phosphatidylcholines did not. CONCLUSIONS: Children with kwashiorkor were metabolically distinct from those with marasmus, and were more prone to severe metabolic disruptions. Children with SAM showed metabolic profiles that were profoundly different from stunted and nonstunted controls, even after clinical stabilization. Therefore, metabolic recovery in children with SAM likely extends beyond discharge, which may explain the poor long-term outcomes in these children. This trial was registered at isrctn.org as ISRCTN13916953.

Under-five protein energy malnutrition admitted at the University of Nigeria Teaching Hospital, Enugu: a 10 year retrospective review.

OBJECTIVE: To determine the prevalence, risk factors, co-morbidities and case fatality rates of Protein Energy Malnutrition (PEM) admissions at the paediatric ward of the University of Nigeria Teaching Hospital Enugu, South-east Nigeria over a 10 year period. DESIGN: A retrospective study using case Notes, admission and mortality registers retrieved from the Hospital's Medical Records Department. SUBJECTS: All children aged 0 to 59 months admitted into the hospital on account of PEM between 1996 and 2005. RESULTS: A total of 212 children with PEM were admitted during the period under review comprising of 127 (59.9%) males and 85 (40.1%) females. The most common age groups with PEM were 6 to 12 months (55.7%) and 13 to 24 months (36.8%). Marasmus (34.9%) was the most common form of PEM noted in this review. Diarrhea and malaria were the most common associated co-morbidities. Majority (64.9%) of the patients were from the lower socio-economic class. The overall case fatality rate was 40.1% which was slightly higher among males (50.9%). Mortality in those with marasmic-kwashiokor and in the unclassified group was 53.3% and 54.5% respectively. CONCLUSION: Most of the admissions and case fatality were noted in those aged 6 to 24 months which coincides with the weaning period. Marasmic-kwashiokor is associated with higher case fatality rate than other forms of PEM. We suggest strengthening of the infant feeding practices by promoting exclusive breastfeeding for the first six months of life, followed by appropriate weaning with continued breast feeding. Under-five children should be screened for PEM at the community level for early diagnosis and prompt management as a way of reducing the high mortality associated with admitted severe cases.

Prenatal factors contribute to the emergence of kwashiorkor or marasmus in severe undernutrition: evidence for the predictive adaptation model.

BACKGROUND: Severe acute malnutrition in childhood manifests as oedematous (kwashiorkor, marasmic kwashiorkor) and non-oedematous (marasmus) syndromes with very different prognoses. Kwashiorkor differs from marasmus in the patterns of protein, amino acid and lipid metabolism when patients are acutely ill as well as after rehabilitation to ideal weight for height. Metabolic patterns among marasmic patients define them as metabolically thrifty, while kwashiorkor patients function as metabolically profligate. Such differences might underlie syndromic presentation and prognosis. However, no fundamental explanation exists for these differences in metabolism, nor clinical pictures, given similar exposures to undernutrition. We hypothesized that different developmental trajectories underlie these clinical-metabolic phenotypes: if so this would be strong evidence in support of predictive adaptation model of developmental plasticity. METHODOLOGY/PRINCIPAL FINDINGS: We reviewed the records of all children admitted with severe acute malnutrition to the Tropical Metabolism Research Unit Ward of the University Hospital of the West Indies, Kingston, Jamaica during 1962-1992. We used Wellcome criteria to establish the diagnoses of kwashiorkor (n = 391), marasmus (n = 383), and marasmic-kwashiorkor (n = 375). We recorded participants' birth weights, as determined from maternal recall at the time of admission. Those who developed kwashiorkor had 333 g (95% confidence interval 217 to 449, p<0.001) higher mean birthweight than those who developed marasmus. CONCLUSIONS/SIGNIFICANCE: These data are consistent with a model suggesting that plastic mechanisms operative in utero induce potential marasmics to develop with a metabolic physiology more able to adapt to postnatal undernutrition than those of higher birthweight. Given the different mortality risks of these different syndromes, this observation is supportive of the predictive adaptive response hypothesis and is the first empirical demonstration of the advantageous effects of such a response in humans. The study has implications for understanding pathways to obesity and its cardio-metabolic co-morbidities in poor countries and for famine intervention programs.

Impaired glucose absorption in children with severe malnutrition.

OBJECTIVE: To quantify intestinal glucose absorption in children with two types of severe malnutrition, kwashiorkor and marasmus, compared with healthy children. STUDY DESIGN: Children with kwashiorkor (n = 6) and marasmus (n = 9) and control subjects (n = 3) received a primed (13 mg/kg), constant infusion (0.15 mg/kg/min) of [6,6H2]glucose for 4.5 hours. Two hours after start of the infusion an oral bolus of glucose 1.75 g/kg labeled with [U-13C]glucose 10 mg/g was given and was followed by periodic blood sampling. Mathematical modeling was applied to determine oral glucose absorption. RESULTS: Median total glucose absorption was 5.9 mmol/kg, interquartile range (IQR) 4.5-6.7 mmol/kg and 4.4 (IQR 2.9-5.9) mmol/kg in children with kwashiorkor and marasmus compared with 7.7 (IQR 5.8-9.0) mmol/kg in control subjects; P = .03 compared with marasmus). Children with the lowest glucose absorption were found specifically in the kwashiorkor group and marasmic children with hypoalbuminemia. Severe impairment in absorption correlated with urinary 8-hydroxydeoxyguanosine secretion (r = -0.62, P = .01). CONCLUSIONS: Severe malnutrition is associated with an impaired glucose absorption and decreased glucose absorption correlates with oxidative stress in these children.

Probiotics and prebiotics for severe acute malnutrition (PRONUT study): a double-blind efficacy randomised controlled trial in Malawi.

BACKGROUND: Severe acute malnutrition affects 13 million children worldwide and causes 1-2 million deaths every year. Our aim was to assess the clinical and nutritional efficacy of a probiotic and prebiotic functional food for the treatment of severe acute malnutrition in a HIV-prevalent setting. METHODS: We recruited 795 Malawian children (age range 5 to 168 months [median 22, IQR 15 to 32]) from July 12, 2006, to March 7, 2007, into a double-blind, randomised, placebo-controlled efficacy trial. For generalisability, all admissions for severe acute malnutrition treatment were eligible for recruitment. After stabilisation with milk feeds, children were randomly assigned to ready-to-use therapeutic food either with (n=399) or without (n=396) Synbiotic2000 Forte. Average prescribed Synbiotic dose was 10(10) colony-forming units or more of lactic acid bacteria per day for the duration of treatment (median 33 days). Primary outcome was nutritional cure (weight-for-height >80% of National Center for Health Statistics median on two consecutive outpatient visits). Secondary outcomes included death, weight gain, time to cure, and prevalence of clinical symptoms (diarrhoea, fever, and respiratory problems). Analysis was on an intention-to-treat basis. This trial is registered as an International Standard Randomised Controlled Trial, number ISRCTN19364765. FINDINGS: Nutritional cure was similar in both Synbiotic and control groups (53.9% [215 of 399] and 51.3% [203 of 396]; p=0.40). Secondary outcomes were also similar between groups. HIV seropositivity was associated with worse outcomes overall, but did not modify or confound the negative results. Subgroup analyses showed possible trends towards reduced outpatient mortality in the Synbiotic group (p=0.06). INTERPRETATION: In Malawi, Synbiotic2000 Forte did not improve severe acute malnutrition outcomes. The observation of reduced outpatient mortality might be caused by bias, confounding, or chance, but is biologically plausible, has potential for public health impact, and should be explored in future studies. FUNDING: Department for International Development (DfID).

The use of home-based therapy with ready-to-use therapeutic food to treat malnutrition in a rural area during a food crisis.

When the international community declared a famine in Malawi in January of 2006, emergency food aid reached only populations with pre-existing health care services. To treat the widespread childhood malnutrition in Machinga district, a rural area lacking health care facilities, in February 2006 five outpatient therapeutic programs were implemented that utilized home-based therapy and ready-to-use therapeutic food. Children with severe malnutrition, defined as the presence of edema and/or a weight-for-height less than 70% of the reference standard, were enrolled in the program. Two senior clinical nurses trained village health aides in each of the five communities. Children visited the health aides biweekly. During the visits, health aides collected demographic and anthropometric information and distributed a 2-week supply of ready-to-use therapeutic food, providing 175 kcal/kg/d. Treatment continued for 8 weeks; children were discharged before 8 weeks if they reached a weight-for-height more than 100% of the reference standard, or required admission to the hospital due to systemic infection or recurrence of edema. Of the 826 children enrolled, 775 (93.7%) recovered, 13 (1.8%) remained malnourished, 30 (3.6%) defaulted, and 8 (0.9%) died. Mean weight gained was 2.7+/-3.7 g/kg/d, height gained 0.3+/-0.9 mm/d, and mid-upper arm circumference gained 0.2+/-0.3 mm/d. Home-based therapy with ready-to-use therapeutic food administered by village health aides is an effective approach to treating malnutrition during food crises in areas lacking health services.

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

Fraction of all hospital admissions and deaths attributable to malnutrition among children in rural Kenya.

BACKGROUND: Malnutrition is common in the developing world and associated with disease and mortality. Because malnutrition frequently occurs among children in the community as well as those with acute illness, and because anthropometric indicators of nutritional status are continuous variables that preclude a single definition of malnutrition, malnutrition-attributable fractions of admissions and deaths cannot be calculated by simply enumerating individual children. OBJECTIVE: We determined the malnutrition-attributable fractions among children admitted to a rural district hospital in Kenya, among inpatient deaths and among children with the major causes of severe disease. DESIGN: We analyzed data from children between 6 and 60 mo of age, comprising 13,307 admissions, 674 deaths, 3068 admissions with severe disease, and 562 community controls by logistic regression, using anthropometric z scores as the independent variable and admission or death as the outcome, to calculate the probability of admission as a result of "true malnutrition" for individual cases. Probabilities were averaged to calculate attributable fractions. RESULTS: Z scores < -3 were insensitive for malnutrition-attributable deaths and admissions, and no single threshold was both specific and sensitive. The overall malnutrition-attributable fraction for in-hospital deaths was 51% (95% CI: 42%, 61%) with midupper arm circumference. Similar malnutrition-attributable fractions were seen for the major causes of severe disease (severe malaria, gastroenteritis, lower respiratory tract infection, HIV, and invasive bacterial disease). CONCLUSIONS: Despite global improvements, malnutrition still underlies half of the inpatient morbidity and mortality rates among children in rural Kenya. This contribution is underestimated by using conventional clinical definitions of severe malnutrition.

Improving the management of severe acute malnutrition in an area of high HIV prevalence.

AIM: To assess the clinical outcomes of a combined approach to the treatment of severe acute malnutrition in an area of high HIV prevalence using: (i) an initial inpatient phase, based on WHO guidelines and (ii) an outpatient recovery phase using ready-to-use therapeutic food. METHODS: An operational prospective cohort study implemented in a referral hospital in Southern Malawi between May 2003 and 2004. Patient outcomes were compared with international standards and with audits carried out during the year preceding the study. RESULTS: Inpatient mortality was 18% compared to 29% the previous year. Programme recovery rate was 58.1% compared to 45% the previous year. The overall programme mortality rate was 25.7%. Of the total known HIV seropositive children, 49.5% died. CONCLUSIONS: Inpatient mortality and cure rates improved compared to pre-study data but the overall mortality rate did not meet international standards. Additional interventions will be needed if these standards are to be achieved.

Effects of antioxidants on glutathione levels and clinical recovery from the malnutrition syndrome kwashiorkor--a pilot study.

Kwashiorkor is a severe edematous form of malnutrition with high prevalence and lethality in many African countries, and repeatedly has been reported to be associated with oxidative stress. The therapy of kwashiorkor is still ineffective. In this pilot study, we tested the hypothesis that oral application of thiol-containing antioxidants increases glutathione status and is beneficial for the clinical recovery of kwashiorkor patients. The longitudinal clinical intervention study was carried out at St Joseph's Hospital, Jirapa, Ghana. Children with severe kwashiorkor were randomly assigned to either a standard treatment (ST) receiving a therapeutic protocol based on the recommendations of the WHO or to one of three study groups receiving in addition 2 x 600 mg reduced glutathione or 2 x 50 mg alpha-lipoic acid or 2 x 100 mg N-acetylcysteine per day. Patients were followed up clinically and biochemically for 20 days and compared with 37 healthy controls. Both glutathione and alpha-lipoic acid supplementation had positive effects on survival. Also, the blood glutathione concentrations correlated positively with survival rates. Furthermore, the initial skin lesions, glutathione and total protein concentrations were found to be strong predictors of survival. The data strongly suggest that a therapy restoring the antioxidative capacity by applying cysteine equivalents in the form of glutathione and/or alpha-lipoic acid is beneficial for biochemical and clinical recovery of kwashiorkor patients.

Assessment of severe malnutrition among hospitalized children in rural Kenya: comparison of weight for height and mid upper arm circumference.

CONTEXT: Severe malnutrition has a high mortality rate among hospitalized children in sub-Saharan Africa. However, reports suggest that malnutrition is often poorly assessed. The World Health Organization recommends using weight for height, but this method is problematic and often not undertaken in practice. Mid upper arm circumference (MUAC) and the clinical sign "visible severe wasting" are simple and inexpensive methods but have not been evaluated in this setting. OBJECTIVES: To evaluate MUAC and visible severe wasting as predictors of inpatient mortality at a district hospital in sub-Saharan Africa and to compare these with weight-for-height z score (WHZ). DESIGN, SETTING, AND PARTICIPANTS: Cohort study with data collected at admission and at discharge or death. Predictive values for inpatient death were determined using the area under receiver operating characteristic curves. Participants were children aged 12 to 59 months admitted to a district hospital in rural Kenya between April 1, 1999, and July 31, 2002. MAIN OUTCOME MEASURE: MUAC, WHZ, and visible severe wasting as predictors of inpatient death. RESULTS: Overall, 4.4% (359) of children included in the study died while in the hospital. Sixteen percent (1282/8190) of admitted children had severe wasting (WHZ < or =-3) (n = 756), kwashiorkor (n = 778), or both. The areas under the receiver operating characteristic curves for predicting inpatient death did not significantly differ (MUAC: 0.75 [95% confidence interval, 0.72-0.78]; WHZ: 0.74 [95% confidence interval, 0.71-0.77]) (P = .39). Although sensitivity and specificity for subsequent inpatient death were 46% and 91%, respectively, for MUAC less than or equal to 11.5 cm, 42% and 92% for WHZ less than or equal to -3, and 47% and 93% for visible severe wasting, the 3 indices identified different sets of children and were independently associated with mortality. Clinical features of malnutrition were significantly more common among children with MUAC less than or equal to 11.5 cm than among those with WHZ less than or equal to -3. CONCLUSIONS: MUAC is a practical screening tool that performs at least as well as WHZ in predicting subsequent inpatient mortality among severely malnourished children hospitalized in rural Kenya. Visible severe wasting is also a potentially useful sign at this level, providing appropriate training has been given.

Comparison of home-based therapy with ready-to-use therapeutic food with standard therapy in the treatment of malnourished Malawian children: a controlled, clinical effectiveness trial.

BACKGROUND: Childhood malnutrition is common in Malawi, and the standard treatment, which follows international guidelines, results in poor recovery rates. Higher recovery rates have been seen in pilot studies of home-based therapy with ready-to-use therapeutic food (RUTF). OBJECTIVE: The objective was to compare the recovery rates among children with moderate and severe wasting, kwashiorkor, or both receiving either home-based therapy with RUTF or standard inpatient therapy. DESIGN: A controlled, comparative, clinical effectiveness trial was conducted in southern Malawi with 1178 malnourished children. Children were systematically allocated to either standard therapy (186 children) or home-based therapy with RUTF (992 children) according to a stepped wedge design to control for bias introduced by the season of the year. Recovery, defined as reaching a weight-for-height z score > -2, and relapse or death were the primary outcomes. The rate of weight gain and the prevalence of fever, cough, and diarrhea were the secondary outcomes. RESULTS: Children who received home-based therapy with RUTF were more likely to achieve a weight-for-height z score > -2 than were those who received standard therapy (79% compared with 46%; P < 0.001) and were less likely to relapse or die (8.7% compared with 16.7%; P < 0.001). Children who received home-based therapy with RUTF had greater rates of weight gain (3.5 compared with 2.0 g . kg(-1) . d(-1); difference: 1.5; 95% CI: 1.0, 2.0 g . kg(-1) . d(-1)) and a lower prevalence of fever, cough, and diarrhea than did children who received standard therapy. CONCLUSION: Home-based therapy with RUTF is associated with better outcomes for childhood malnutrition than is standard therapy.

Intestinal and systemic infection, HIV, and mortality in Zambian children with persistent diarrhea and malnutrition.

BACKGROUND: Persistent diarrhea-malnutrition syndrome is a complex of infection and immune failure that involves protein, calorie and micronutrient depletion, and metabolic disturbances. We report an analysis of the impact of HIV infection on infectious disease, clinical presentation, and mortality in Zambian children with persistent diarrhea and malnutrition. METHODS: Two hundred children (94 boys and 106 girls, 6-24 months old) were examined on admission to the malnutrition ward of University Teaching Hospital in Lusaka, Zambia. There was then 1 month of follow-up. RESULTS: Antibodies to HIV were found in 108 of the children (54%). The common intestinal infections (Cryptosporidium parvum [26%] and nontyphoid Salmonella spp [18%]), septicemia (17%), and pulmonary tuberculosis confirmed by gastric lavage (13.5%) were not significantly more common in HIV-seropositive than in HIV-seronegative children. HIV-seropositive children were more likely to have marasmus whereas HIV-seronegative children were more likely to have kwashiorkor. Weight-for-age z scores at nadir (postedema) were lower in HIV-seropositive children (median, -4.4; interquartile range [IQR], -5.0 to -3.8) than in HIV-seronegative children (median, -3.7; IQR, -4.2 to -3.1; P < 0.0001). Height-for-age and weight-for-height z scores and mid-upper arm circumference showed a similar difference. Of the 200 children, 39 (19.5%) died within 28 days; cryptosporidiosis and marasmus were the only independent predictors of death. CONCLUSIONS: Although intestinal and systemic infections did not differ for HIV-seropositive and HIV-seronegative children, HIV influenced nutritional states of all children. Cryptosporidiosis and marasmus were associated with higher mortality.

The impact of the human immunodeficiency virus type 1 on the management of severe malnutrition in Malawi.

A study was undertaken in a central nutritional rehabilitation unit in southern Malawi to assess the impact of HIV infection on clinical presentation and case fatality rate. HIV seroprevalence in 250 severely malnourished children over 1 year of age was 34.4% and overall mortality was 28%. HIV infection was associated significantly more frequently with marasmus (62.2%) than with kwashiorkor (21.7%) (p < 0.0001). Breastfed children presenting with severe malnutrition were significantly more likely to be HIV-seropositive (p < 0.001). Clinical and radiological features were generally not helpful in distinguishing HIV-seropositive from HIV-seronegative children. The case fatality rate was significantly higher for HIV-seropositive children (RR 1.6 [95% CI 1.14-2.24]). The increasing difficulties of managing the growing impact of HIV infection on severely malnourished children in Malawi are discussed in the context of reduced support for nutritional rehabilitation units.

Intensive nursing care of kwashiorkor in Malawi.

The case fatality rate for children with kwashiorkor in central hospitals in Malawi was 30.5% (275/901) in 1995. The purpose of this study was to determine whether improved case management with intensive nursing care could lower this case fatality rate. A total of 75 children admitted with kwashiorkor in Blantyre, Malawi, received intensive nursing care. This included nursing in individual clean beds with blankets, a nurse:child ratio of 1:3, supervised feedings every 2 h, a paediatrician with expertise in treating kwashiorkor always available for consultation, laboratory evaluation for systemic infection and empiric use of ceftriaxone. Nineteen of these children died (25%). The causes of death were life threatening electrolyte abnormalities (hypokalaemia, hyponatraemia, hypophosphataemia) in nine cases, overwhelming infection in eight cases and congestive heart failure in two children. Children infected with the human immunodeficiency virus were more likely to die (9/20), as were children with life threatening electrolyte abnormalities (9/15) and children with more severe wasting. When compared with 225 children treated in the same year at the same institution, who were carefully matched for severity of kwashiorkor, intensive nursing did not improve overall survival.

Who dies from what? Determining cause of death in South Africa's rural north-east.

Information on cause of death is essential for rational public health planning, yet mortality data in South Africa is limited. In the Agincourt subdistrict, verbal autopsies (VA) have been used to determine cause of death. A VA is conducted on all deaths recorded during annual demographic and health surveillance. Trained lay fieldworkers interview a close caregiver to elicit signs and symptoms of the terminal illness. Each questionnaire is reviewed by three medical practitioners blind to each other's assessment, who assign a 'probable cause of death' where possible. Of 1001 deaths of adults and children identified between 1992 and 1995, 932 VAs were completed. The profile of deaths reflects a mixed picture: the 'unfinished agenda' of communicable disease and malnutrition (diarrhoea and kwashiorkor predominantly) are responsible for over half of deaths in under-fives, accidents are prominent in the 5-14 age-group, while the 'emerging agenda' of violence and chronic degenerative disease (particularly circulatory disease) is pronounced among the middle-aged and elderly. This profile shows the social and demographic transition to be well underway within a rural, underdeveloped population. Validation of VA findings demonstrate that the cause of death profile derived from VA can be used with confidence for planning purposes. Findings of note include the high death rates from kwashiorkor and violence, emerging AIDS and pulmonary tuberculosis, and circulatory deaths in the middle-aged and young elderly. A deeper understanding of the causal factors underlying these critical health problems is needed to strengthen policy and better target interventions.

Severe hypophosphatemia in children with kwashiorkor is associated with increased mortality.

Severe hypophosphatemia, serum phosphate concentration <0.32 mmol/L (<1.0 mg/dL), occurred in 8 of 68 (12%) of children with kwashiorkor within 48 hours of admission; 5 of 8 (63%) of these children died, compared with 13 of 60 (22%) children without severe hypophosphatemia (P <.02). Dermatosis and dehydration were significantly correlated with severe hypophosphatemia, but these clinical signs could not reliably predict fatal cases. Severe hypophosphatemia seems to be common and life-threatening in children with kwashiorkor in Malawi.

PIP: Severe hypophosphatemia, serum inorganic phosphate concentration of less than 0.32 mmol/l, is associated with leukocyte dysfunction, acute respiratory decompensation, cardiac arrhythmias, and heart failure. The condition has been described in children with kwashiorkor from South Africa, but not in children from Jamaica or India. In acute kwashiorkor in sub-Saharan Africa, the case fatality rate remains high, often over 20%, despite the implementation of standard treatment protocols. The authors examined whether severe hypophosphatemia was frequent at presentation or during initial refeeding among Malawian children with kwashiorkor and whether it was associated with a fatal outcome. All children under age 10 years who presented with kwashiorkor to the Queen Elizabeth Central Hospital in Blantyre during a 2-month period were eligible and enrolled in the study. 68 children with kwashiorkor were studied. Severe hypophosphatemia occurred in 8 (12%) children with kwashiorkor within 48 hours of admission. 5 of these 8 (63%) children died, compared with 13 of 60 (22%) children without severe hypophosphatemia. Dermatosis and dehydration were significantly correlated with severe hypophosphatemia, but these clinical signs could not reliably predict fatal cases. Severe hypophosphatemia appears to be common and life-threatening in children with kwashiorkor in Malawi.