Evaluation of an algorithm for integrated management of childhood illness in an area of Vietnam with dengue transmission

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1 Tropical Medicine and International Health volume 9 no 5 pp may 2004 Evaluation of an algorithm for integrated management of childhood illness in an area of Vietnam with dengue transmission Cao Xuan Thanh Phuong 1, Ngo Thi Nhan 1, Rachel Kneen 2,3, Delia Bethell 2,3, Le Thi Dep 1, Nguyen Thi Thuy Nga 1, Pham Thi Thu Thuy 1, Truong Dinh Luat 1, Tom Solomon 2,3, Bridget Wills 2,3, Christopher M. Parry 2,3 and The Dong Nai/WHO Study Team* 1 Dong Nai Paediatric Centre, Bien Hoa, Vietnam 2 The University of Oxford Clinical Research Unit, Hospital for Tropical Diseases, Ho Chi Minh City, Vietnam 3 Centre for Tropical Medicine, John Radcliffe Hospital, Oxford, UK Summary objectives To determine whether nurses, using the WHO/UNICEF algorithm for integrated management of childhood illness (IMCI), modified to include dengue infection, satisfactorily classified children in an area endemic for dengue haemorrhagic fever (DHF). methods Nurses assessed and classified, using the modified IMCI algorithm, a systematic sample of 1250 children aged 2 months to 10 years (n ¼ 1250) presenting to a paediatric hospital in Dong Nai Province, Vietnam. Their classification was compared with that of a paediatrician, blind to the result of the nurses assessment, which could be modified in the light of simple investigations, e.g. dengue serology. results In children aged 2 59 months (n ¼ 859), the nurses were able to classify, using the modified chart, the presenting illness in >99% of children and found more than one classification in 70%. For the children with pneumonia, diarrhoea, dengue shock syndrome, severe DHF and severe disease requiring urgent admission, the nurse s classification was >60% sensitive and >85% specific compared with that of the paediatrician. For the nurse s classification of DHF the specificity was 50 55% for the children <5 years and in children with definitive dengue serology. Alterations in the DHF algorithm improved specificity at the expense of sensitivity. conclusion Using the IMCI chart, nurses classified appropriately many of the major clinical problems in sick children <5 years in southern Vietnam. However, further modifications will be required in the fever section, particularly for dengue. The impact of using the IMCI chart in peripheral health stations remains to be evaluated. keywords dengue haemorrhagic fever, integrated management of childhood illness, Vietnam, fever, pneumonia, diarrhoea Introduction An estimated 12 million children aged <5 years die each year in resource-poor countries and 70% of these deaths are due to communicable diseases or malnutrition (Nicoll 2000). The WHO and UNICEF have designed and developed the Integrated Management of Childhood Illness (IMCI) strategy to address these global problems (Gove * Tran Thi Thanh Huynh, Doan Thi Kim Lien, Ngo Thi Anh Tuyet, Tran Thi Cam Tu, Do Hoang An Loc, Nguyen Thi Kim Nhung, Nguyen Van Quyen, Eric A. F. Simoes, Nicholas P. J. Day, Nicholas J. White, Jeremy J. Farrar. 1997; Lambrechts et al. 1999; Nicoll 2000). The strategy has three components: to optimize family and community practices in relation to child health, particularly careseeking behaviour; to improve case management of the sick child at first level facilities; and finally to facilitate such improvements by focussing on aspects of local health care systems such as drug supply and programme management. To improve the case management of sick children, an IMCI chart has been developed for use in first level health facilities. It is designed to allow health workers (who have undergone a specific training course) to assess, classify, treat and if appropriate, refer to hospital, sick children under 5 years old using only clinical signs. The chart was ª 2004 Blackwell Publishing Ltd 573

2 designed for use in African countries, where malaria, measles and malnutrition are the biggest health problems. It requires adaptation for use in south-east Asia where dengue haemorrhagic fever (DHF) is a major cause of childhood morbidity and mortality (Ngo et al. 2001). Following discussion between WHO and local paediatricians in Vietnam, the chart was modified to incorporate common signs in dengue infection, and then evaluated at a provincial paediatric hospital in southern Vietnam. Although the IMCI chart concerns children aged 2 59 months, dengue occurs commonly in children aged between 5 and 10 years. The study was therefore extended to include children aged up to 10 years. Materials and methods The study was performed at Dong Nai Paediatric Centre, Bien Hoa City. This 350-bed paediatric hospital serves the local community and is a referral hospital for the southern province of Dong Nai. Five consecutive children attending the hospital receiving room each morning were enrolled in the study for 5 days a week during the course of 1 year. Children (>2 months up to 10 years) were seen if they were in the first presentation of an acute illness. Children were excluded if they attended with trauma or a suspected surgical problem, if they were referred from another district hospital and had been given parenteral drugs or fluids, if they were attending for a follow-up appointment or if they had a chronic condition. Informed consent was obtained from the child s parent or guardian. The Ethical and Scientific Committees of Dong Nai Paediatric Centre and The Hospital for Tropical Diseases, Ho Chi Minh City, approved the study. The modified IMCI chart requires first an assessment of general danger signs followed by classification of the main symptoms using specific criteria (Table 1) (Gove 1997). Children classified with general danger signs, severe pneumonia, diarrhoea with severe dehydration, dengue shock syndrome or severe DHF, severe malaria, a severe febrile disease, severe complicated measles, mastoiditis, severe malnutrition or anaemia should be referred urgently to hospital. The remainder receive treatment locally, guided by the chart. Five nurses were trained to assess and classify the child s illness as if they were a health care worker seeing the child in a peripheral health station. The nurses were trained using the standard 11-day course and the training material supplied by the WHO designed for use with the IMCI chart in Africa. In addition, new signs for dengue included in the chart adapted for Vietnam were taught with the help of a specially prepared video. The nurses interviewed the parents and children in a study room. Specially designed forms were completed at the time by the nurses, and then posted into a locked box so they could not be altered or seen by the medical staff. Children who were so ill as to require urgent attention were assessed while being stabilized in the emergency room. A single nurse evaluated each patient and each nurse evaluated approximately the same number of patients over the course of the study. A junior paediatrician, unaware of the result of the nurse s assessment, then assessed the child. Four junior paediatricians were trained to take a standard history and examination and then classify the child s illness using the same diagnostic categories as the IMCI chart. Although not all children merited admission on clinical grounds, the parents or guardians of the children were encouraged to allow their children to be admitted to hospital so that relevant investigations could be completed. For those children who agreed to be admitted, the disease classification was modified by a senior paediatrician after review of the results of initial laboratory and radiological investigations. On the day of admission, blood was drawn for a haematocrit, white cell count and differential count, a platelet count and a Giemsa-stained thick and thin blood film for malaria and serum was stored at )20 C for viral serology. A blood culture was performed in children with general danger signs or with a fever lasting >7 days without an obvious focus. A lumbar puncture was performed in any child with signs consistent with a neurological infection or with general danger signs. Microbiology investigations used standard laboratory methods (Murray et al. 1995). Children with a classification of pneumonia or with general danger signs were chest X-rayed. Children with typical dengue shock syndrome, and thus included in the group with general danger signs, did not have blood or CSF cultures, or a chest X-ray, unless otherwise indicated. A convalescent serum sample was taken at the time of hospital discharge and stored at )20 C for viral serology. Serology for dengue and Japanese encephalitis virus (JEV) was measured by antibody capture ELISA (Vaughn et al. 1997). Paired specimens were considered satisfactory if they were taken at least 4 days apart. For single specimens, 40 U of immunoglobulin M (IgM) to dengue (with a dengue IgM greater than the JEV IgM) was considered evidence of dengue infection. For paired sera, a rise from <15 to >30 U of IgM to dengue was considered evidence of dengue infection. A dengue IgM:IgG ratio of 1.8:1 defined a primary infection whilst a ratio of <1.8:1 indicated the child had previously been infected with a different dengue virus serotype, or another flavivirus (a secondary infection). A twofold increase in IgG to dengue 574 ª 2004 Blackwell Publishing Ltd

3 Table 1 Diagnostic classifications by the modified integrated management of childhood illness (IMCI) algorithm General danger signs Cough or difficulty in breathing Severe pneumonia Pneumonia No pneumonia (cough or cold) Diarrhoea Diarrhoea with severe dehydration Diarrhoea with some dehydration Diarrhoea with no dehydration Persistent diarrhoea Dysentery Fever Dengue risk Dengue shock syndrome (DSS) Severe Dengue Haemorrhagic Fever (severe DHF) DHF Malaria risk Very severe febrile disease Malaria likely No malaria risk Very severe febrile disease Measles Severe complicated measles Measles without eye or mouth complications Measles Ear problem Mastoiditis Acute ear infection Chronic ear infection Malnutrition and anaemia Severe malnutrition or severe anaemia Anaemia or very low weight No anaemia and not very low weight History of being unable to drink or breastfeed, vomits everything or convulsions. Child is lethargic or unconscious General danger sign or chest indrawing or stridor in a calm child Fast breathing (child aged 2 11 months: 50 breaths/min; child aged 12 months: 40 breaths/min) No signs of pneumonia or very severe disease Two or more of the following: lethargic or unconscious, sunken eyes, unable to drink or drinking poorly, skin pinch goes back very slowly Two or more of the following: restless or irritable, sunken eyes, drinking eagerly or thirsty, skin pinch goes back slowly Insufficient signs to classify as dehydrated Diarrhoea for 14 days or more. +/) dehydration Diarrhoea with blood in the stool By history or feels hot or temperature 37.5 C axilla Child 6 months and lives in a dengue risk district or has been in a dengue risk district in the last 2 weeks Cold, clammy extremities or pulse not detectable or weak and fast pulse Lethargic or restless or right upper abdominal tenderness or nose bleeding or gum bleeding or black vomit or black stools Petechiae or skin haemorrhages or high continuous fever for 3 days or more Lives in a malaria district or has been in a malaria risk district in the last 6 months Any general danger sign or stiff neck or bulging fontanelle Microscopy not available and no runny nose and no DHF and no measles and no other cause of fever Any general danger sign or stiff neck or bulging fontanelle Generalized rash and one of cough or runny nose or red eyes Any general danger sign or clouding of cornea or deep extensive mouth ulcers Pus draining from eyes or mouth ulcers Measles now or within the last 3 months Ear pain or discharge Tender swelling behind the ear Pus draining from the ear and discharge is reported for <14 days or ear pain Pus is draining from the ear and discharge is reported for 14 days or more Visible severe wasting or clouding of cornea or severe palmar pallor or oedema of both feet Some palmar pallor or very low weight for age Not very low weight for age and no other signs of malnutrition to a level of 100 U, in the absence of an IgM to dengue of 40 U, was accepted as evidence of a secondary infection. Acute dengue was ruled out if the dengue IgM was <40 U with an IgG of <100 U on day 7 or more of the illness, or on the day after defervescence (the first day with the temperature consistently <38 C) (Vaughn et al. 1997). The serology was considered indeterminate if the result could not be classified according to the guidelines above. This was usually because there was no convalescent serum sample or the acute and convalescent sample were <4 days apart. The clinical features of the children with definitive dengue serology were compared with those who had indeterminate serology to ensure that those with definitive dengue serology were representative of the group as a whole. Continuous variables were given as median with the 90% range and compared by the Mann Whitney U-test. Proportions were compared with the chi-square test, or Fishers exact test. The disease classification arrived at using the modified chart for the children aged 2 59 months was compared with the classification of the paediatrician aided by the initial laboratory and radiological investigations. The sensitivity, specificity, positive and negative predictive value of each classification was evaluated. For the DHF section of the chart, a similar analysis was performed for ª 2004 Blackwell Publishing Ltd 575

4 the whole group of children aged 2 months to 10 years limited to those with definitive serology. To assess the newly devised clinical dengue signs for inter-observer variability, the assessment by the nurse was compared with that of the admitting paediatrician by the kappa statistic (j) (Altman 1991), a chance corrected measure of agreement. The kappa statistic ranges between 0 and 1, with 1 representing perfect agreement and 0 representing no more agreement than would be expected to occur on the basis of chance alone. Agreement was considered poor if the kappa value was 0.20, fair for , moderate for , good for , and very good for Data were analysed using EpiInfo version 6.0 (Centers for Disease Control and Prevention, Atlanta, GA, USA) and SPSS version 10.0 for Windows (SPSS Inc., Chicago, IL, USA). Results During the 12-month period, (December 1996 to December 1997) 1250 children were enrolled. The median (90% range) age of the children was 36 months (range: 6 108) and 695 (55.6%) were male. Fourteen of the 1250 children refused hospital admission and 38 of those children admitted later self-discharged from hospital before resolution of their symptoms. The median (90% range) duration of admission was 3 days (range: 1 8). For the children with fever the median (90% range) duration of fever prior to admission was 3 days (range: 1 7). None of the children died, but two children were transferred to a tertiary referral hospital because of suspected encephalitis. Dengue serology results At the time of the initial assessment, 1174/1250 (93.9%) of the children had fever or a history of fever. Definitive dengue serology results were available for 871 children, including 823 (70.1%) of the 1174 children who had fever or a history of fever. For 775 (89%) children, dengue was ruled out. Ninety-six (11%) children had acute dengue infection, 23 (24%) of which were primary and 73 (76%) were secondary. The median (90% range) age of the seropositive children was 72 months (range: ). Children with primary infection were younger than those with secondary infection [48 months (24 118) vs. 72 months (17 120), P ¼ 0.001]. Table 2 compares the clinical characteristics of the children with definitive dengue serology and those whose serology was indeterminate. In general, the two groups were comparable. The duration of fever before admission was slightly longer in the children with definitive serology and the proportion of children with a final diagnosis of pneumonia greater. As the duration of admission for children with a final diagnosis of pneumonia was longer than for children without pneumonia [5 days (2 9) vs. 3 days (1 7), P < 0.001], this group had more opportunities to have a convalescent sample taken. Symptom or sign Definitive dengue serology (n ¼ 871) Indeterminate dengue serologyà (n ¼ 379) P value Age (months)* 36 (6 108) 36 (6 108) 0.46 No. of male (%) 488 (56.0) 207 (54.6) 0.64 Duration of fever (days) 3 (0 7) 2 (0 5) <0.001 Temperature ( C) 38.0 ( ) 38.0 ( ) 0.79 Haematocrit (%) 35 (28 42) 35 (28 42) 0.80 White cell count ( 10 9 /l) 8.0 ( ) 8.0 ( ) 0.56 % Neutrophils 54 (30 75) 56 (30 70) 0.77 Platelet count ( 10 9 /l) 160 ( ) 160 ( ) 0.82 No. of patients with diagnosis 85 (9.8) 50 (13.2) 0.07 of dengue (%) No. of patients with diagnosis 170 (19.5) 54 (14.2) 0.03 of pneumonia (%) No. of patients with diagnosis diarrhoea/dysentery (%) 158 (18.1) 76 (20.1) 0.86 Table 2 Comparison of the clinical characteristics of children with and without definitive dengue serology. Children aged 2 months to 10 years (n ¼ 1250) * Continuous variables expressed as median (90% interval). Proportions expressed as number (percentage). à An indeterminate dengue serology result was one that could not be clearly classified as consistent with dengue infection or one in which dengue could be ruled out. This was usually because there was no convalescent serum sample or the acute and convalescent sample were <4 days apart. 576 ª 2004 Blackwell Publishing Ltd

5 Table 3 Comparison of the classification by modified IMCI algorithm classification and paediatricians. Children aged 2 59 months (n ¼ 859) Classify by chart Yes Yes No No Classified by doctor Yes No Yes No Sens Spec PPV NPV Severe illness requiring urgent hospital admission Severe pneumonia Pneumonia Cough/cold Diarrhoea with dehydration Diarrhoea with no dehydration Persistent diarrhoea Dysentery Dengue shock syndrome Severe DHF DHF Severe malaria Malaria Measles Sens, sensitivity; Spec, specificity; PPV, positive predictive value; NPV, negative predictive value. IMCI chart results for children aged 2 59 months A total of 859 (69%) children were aged between 2 and 59 months. The median (90% range) age in this group was 19 months (range: 5 48) and 486 (57%) were male. The general danger signs used by the modified IMCI algorithm were recorded by the nurses in 25 (2.9%) of the children: a convulsion in 23/25 children; lethargy in one child; and another child was unable to drink. The nurses, using the modified IMCI chart, classified 68 of 859 (7.9%) children as having severe disease requiring urgent admission whereas the admission doctor classified 38 of 859 (6.5%) as requiring urgent admission. The main complaints were fever (792, 92%), cough (525, 61%) and diarrhoea (226, 26%) and the nurses were able to make a classification in >99% of children. Children were classified into more than one category in 604 of 859 (70%) of cases. Table 3 compares the classification of the nurses, using the modified chart, with the disease classification of the paediatricians with the aid of admission investigations in the children aged 2 59 months. The sensitivity of the nurses varied between 60% and 100% for the classification of children with severe illness requiring hospital admission, pneumonia, diarrhoea, DSS, severe DHF and DHF but was <60% for measles and malaria. The specificity for all classifications was >85% except for cough/cold and DHF. Dengue classification for the children aged 2 months to 10 years The sensitivity and specificity of the nurses diagnoses, using the modified chart, for the classification of each grade of DHF for all the children aged 2 months to 10 years with definitive dengue serology is in Table 4. The nurses Table 4 Comparison of the classification of DHF by the modified IMCI algorithm and the paediatricians. Children aged 2 months to 10 years with definitive dengue serology (n ¼ 871). Results with the modified IMCI chart, and with a proposed further modification for the classification of severe DHF and DHF Classify by chart Yes Yes No No Classified by doctor Yes No Yes No Sens Spec PPV NPV Dengue shock syndrome Severe DHF DHF Severe DHF/severe dengue (fever and mucosal bleeding)* DHF/probable dengue (fever and skin bleeding)* Sens, sensitivity; Spec, specificity; PPV, positive predictive value; NPV, negative predictive value. * Alternative modification of the IMCI DHF classification. ª 2004 Blackwell Publishing Ltd 577

6 classified five times as many children as having DHF using the modified IMCI chart as the paediatrician. A further modification of the chart was explored in which children with any duration of fever and evidence of mucosal bleeding were classified as severe DHF, and those with any duration of fever and evidence of skin bleeding were classified as DHF (Table 4). This alteration improved the specificity of the DHF classification but reduced its sensitivity. The sensitivity and specificity of the severe DHF classification was virtually unchanged. Similar results were obtained if the analysis was extended to include all children, rather than just those with definitive serology. Forty of the children aged 2 months to 10 years had dengue shock syndrome at the time of admission or developed it during the course of their admission. The nurses, using the modified chart, classified correctly all 20 children with DSS on admission. However, three of the remaining 20 children who developed DSS during the course of their admission were classified by the nurses using the modified IMCI chart at the time of admission as unlikely to have DHF. These three children presented with a high fever on day 2 of their illness. Each of these children developed skin petechiae on day 3 or 4 of their illness, and then shock on day 4 or 5. The degree of agreement between the nurses and doctors in the assessment of clinical features used for the DHF classification are in Table 5. The chance-corrected level of agreement was good for recording the duration of fever, the presence of mucosal or skin bleeding, a weak or absent pulse and cold extremities. The agreement for abdominal pain or tenderness was only fair and that for lethargy and restlessness poor. Other medical problems The other principal diagnoses made in the children aged 2 59 months were viral syndrome (190), febrile convulsion (16), tonsillitis (10), gingivostomatitis (eight), suspected pertussis (five), chronic otitis media (four), mumps (four), suspected typhoid fever (four) and skin infections (four). Only one child had acute otitis media. The weight for age was more than 3 standard deviations below the NCHS/CDC growth reference (World Health Organisation Working Group 1986) in eight (0.9%) of the children under 5 years, and between 2 and 3 standard deviations below the reference in 13 (1.5%). One of the children under 5 years was severely anaemic with a haematocrit <15%; 74 (8.6%) had a haematocrit <30%. The median (90% range) haematocrit in this group was 34% (30 40). For the children under 5 years, those with a weight for age 2 or more standard deviations below the reference did not overlap with those with a haematocrit <30%. In the children aged from 5 to 10 years the median (90% range) haematocrit was 37% (32 42). All CSF cultures and blood cultures were negative in the children <5 years. Salmonella typhi was isolated in three children aged 5 10 years. Discussion The IMCI chart is an attempt to combine various diseasespecific algorithms into a single approach, which will address most of the potentially life-threatening illnesses among children under 5 years in resource-poor countries. It is designed to assist health workers at first level facilities in the appropriate management and assessment of a sick child. It must be able to address the majority of presenting complaints and identify children with severe illness who require rapid referral to hospital. In this study, nurses using the modified IMCI chart were able to classify the presenting illness in >99% of children and found more than one classification in 70%. This highlights the importance of an integrated approach to the diagnosis and treatment of sick children. It is also important that the modified chart identifies sick children who need prompt referral to hospital. Nurses using the modified chart Nurse Yes Yes No No Agreement Doctor Yes No Yes No (%) Kappa statistic Fever duration 3 days Abdominal pain or tenderness Mucosal bleeding* Skin bleeding Lethargy or restlessness Weak or absent pulse Cold extremities Table 5 Comparison of nurse and doctor recording of admission symptoms and signs used to classify children with DHF. Children aged 2 months to 10 years (n ¼ 1250) * Nose or gum bleeding, haematemesis, lower gastrointestinal bleeding or melaena. Skin haemorrhages or spontaneous petechiae. 578 ª 2004 Blackwell Publishing Ltd

7 classified 68 (7.9%) of the children as severely ill and requiring urgent admission to hospital. The sensitivity of this classification, in comparison with the paediatrician, was almost 95%. Only two of 38 children whom the paediatrician considered severely ill, were not similarly classified by the nurses using the modified chart. In both cases, the severity of pneumonia was underestimated by the nurses. The sensitivity and specificity of the nurses, using the modified chart, for detecting DSS at the time of admission was excellent. However, three (15%) of a total of 20 children who went on to develop DSS whilst in hospital were initially classified by the nurses as being unlikely to have dengue. All three children presented early in the course of the disease (day 2 of illness) and according to the chart guidelines, would have been reviewed in 1 or 2 days time, for evidence of skin or mucosal bleeding. In each child, skin petechiae did develop in the subsequent 2 days, prior to the onset of shock. The major problem with the modified chart was with the classification of fever. Many children with fever were incorrectly classified as having dengue or malaria and the chart over-classified DHF to a major degree. Many of the children were classified as having DHF because of fever for 3 or more days without evidence of skin bleeding. Children with suspected DHF require daily follow-up in the health centre because they are at risk of developing DSS. Classification of a large number of children with DHF could overburden the health centre staff during the dengue season and improvements in specificity would therefore be useful. The terminology used in the chart proved to be a source of confusion. It is generally accepted that the critical feature, which differentiates between patients with DF and those with DHF is the presence of increased vascular permeability, and that bleeding, whether skin or mucosal, occurs in both groups of patients. Detection of increased vascular permeability prior to the development of shock is not practical in community settings. Given this limitation, the two clinical scenarios, which can be identified and should prompt early hospital referral are firstly signs of impending or established shock, and secondly the presence of mucosal bleeding. In both these situations, careful monitoring is essential and specific intervention may be required. Using the current terminology, patients referred to hospital with mucosal bleeding, classified as severe DHF by the chart, may turn out to have either DF or DHF once fully assessed, whilst at a community level in a dengue-endemic area, no patient can ever be classified to have DF. Use of the same terminology to describe different clinical entities is likely to cause confusion between community and hospital health care staff, and undermines the reliability of any epidemiological data collected (World Health Organisation 1997). As it is not possible for community health care workers to differentiate between DF and DHF without shock, it would be more appropriate if the IMCI terminology focused on a more practical system such as dengue with shock, severe dengue and probable dengue. Therefore, the chart could be modified in an alternative way. The classification of DSS/dengue with shock should be kept unchanged. The remaining children could be categorized as severe dengue, if they have fever of any duration combined with evidence of mucosal bleeding, or probable dengue, if they have fever of any duration combined with evidence of skin bleeding. This is the practical rule of thumb already used by many health care workers in dengue-endemic areas. It also means using the clinical signs that were reliably detected by the nurses (skin and mucosal bleeding) and avoiding those with poor reproducibility (abdominal pain, tenderness and lethargy or restlessness). This alteration improved the specificity of the DHF/probable dengue classification at the expense of sensitivity, with the sensitivity and specificity of the severe DHF/severe dengue classification virtually unchanged (Table 4). None of the children classified by the nurses, using the modified chart, as having malaria were found to have blood smear-positive malaria. Of the three children with confirmed malaria, two had been classified by the nurses as having pneumonia and one DHF. Malaria was previously common in this area (Cao et al. 1997) but the prevalence of malaria during this study period was very low. In southern Vietnam, there are still focal areas that have high malaria prevalence where the chart may be more helpful. There is a system of malaria smear microscopy at health centre level in Vietnam and this is probably a more reliable system for identifying children with malaria. Measles was diagnosed in nearly 4% of children despite a measles vaccination programme. Ear problems were very uncommon. Typhoid fever was also uncommon in contrast to the year before the study when there was an outbreak of typhoid fever in this area (Cao et al. 1999). Dehydration in the children with diarrhoea was rare and not severe. Other diseases not specifically covered by the IMCI chart occurred in small numbers. A very low weight for age was only present in 2.6% of the children and only 6.5% of children had a haematocrit <30%. This is very different from the situation in other Sub-Saharan African and Asian countries where the chart has been evaluated (Bern et al. 1997; Kalter et al. 1997; Perkins et al. 1997; Weber et al. 1997). No children had severe malnutrition and ª 2004 Blackwell Publishing Ltd 579

8 anaemia together and so it would be more appropriate in Asia to classify these two problems separately. There are several potential limitations of this study. The study was conducted in a hospital setting although the IMCI chart is designed for peripheral health stations. The extent to which the range of problems seen is comparable with those that would be seen in a health centre is not known. However, as many patients in Vietnam use hospitals as their first point of call with a medical problem, a high proportion of the problems will be typical of the primary health care clinic for which the chart is designed. There were fewer severely ill patients included in the study than we had expected. However, in this respect the pattern is likely to reflect more closely the pattern in peripheral health centres. There was clearly some interobserver variation in the detection of signs and symptoms between the five nurses using the chart to assess the children. However, we have tried to quantify this for the different variables using the kappa statistic. Although we were unable to establish a definite dengue serology result in 30% of the children, in fact the results for the performance of the dengue section of the chart for the children with definitive serology were similar to the children with indeterminate serology. Finally, we did not specifically address in this study how the chart would perform for the daily reassessment of patients. This is potentially a crucial element in the assessment in dengue because of the progressive nature of the disease. The main purpose of the study was to see if the overall chart, including the specific adaptations made for Vietnam, addressed the range of health problems in sick children and classified them safely. The chart covered the major clinical problems in local sick children. However, further modifications will be required in the fever section, in particular with respect to the classification of dengue and malaria. Whether the IMCI chart will be appropriate for implementation in peripheral health stations in Vietnam and the impact of that implementation on child health remains to be evaluated. Acknowledgements We are very grateful to the Director and staff of the Dong Nai Paediatric Centre for help and support during the study. We are also grateful to Dr Sandy Gove of the Division of Child Health and Development, WHO, who helped in the setting up of this study and Dr David Vaughn and Dr Timothy Endy at the Department of Virology, US Army Medical Component, Armed Forces Research Institute of Medical Sciences, Bangkok, Thailand, who performed the dengue serology. Dr Cao Xuan Thanh Phuong, who supervised the clinical aspects of this study, sadly died at the end of October This study was supported by the UNDP/World Bank/WHO Special Programme for Research and Training in Tropical Diseases Grant Award: ID and by the Wellcome Trust of Great Britain. References Altman DG (1991) Practical Statistics for Medical Research. Chapman and Hall, London. Bern C, Zucker JR, Perkins BA, Otieno J, Oloo AJ & Yip R (1997) Assessment of potential indicators for protein-energy malnutrition in the algorithm for integrated management of childhood illness. Bulletin of the World Health Organisation 75 (Suppl. 1), Cao XT, Bethell DB, Pham TP et al. (1997) Comparison of artemisinin suppositories, intramuscular artesunate, and intravenous quinine for the treatment of severe childhood malaria. Transactions of the Royal Society of Tropical Medicine and Hygiene 91, Cao XT, Kneen R, Nguyen TA et al. 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(2001) Acute management of dengue shock syndrome: a randomised double-blind comparison of four intravenous fluid regimens in the first hour. Clinical Infectious Diseases 32, Nicoll A (2000) Integrated management of childhood illness in resource-poor countries: an initiative from the World Health Organisation. Transactions of the Royal Society of Tropical Medicine and Hygiene 94, Perkins BA, Zucker JR, Otieno J et al. (1997) Evaluation of an algorithm for integrated management of childhood illness in an area of Kenya with high malaria transmission. Bulletin of the World Health Organisation 75 (Suppl. 1), Vaughn DW, Green S, Kalayanarooj S et al. (1997) Dengue in the early febrile phase: viraemia and antibody response. Journal of Infectious Diseases 176, Weber MW, Mullholland EK, Jaffar S, Troedsson H, Gove S & Greenwood BM (1997) Evaluation of an algorithm for the integrated management of childhood illness in an area with 580 ª 2004 Blackwell Publishing Ltd

9 seasonal malaria in the Gambia. Bulletin of the World Health Organization 75 (Suppl. 1), World Health Organization (1997) Dengue Haemorrhagic Fever: Diagnosis, Treatment, Prevention and Control, 2nd edn. WHO, Geneva. World Health Organization Working Group (1986). Use and interpretation of anthropometric indicators of nutritional status. Bulletin of the World Health Organization 64, Authors Christopher M. Parry, Department of Medical Microbiology and Genitourinary Medicine, University of Liverpool, Liverpool, L69 3GA, UK. Tel.: ; Fax: ; (corresponding author). Cao Xuan Thanh Phuong, Ngo Thi Nhan, Le Thi Dep, Nguyen Thi Thuy Nga, Pham Thi Thu Thuy and Truong Dinh Luat, Dong Nai Paediatric Centre, Bien Hoa, Dong Nai Province, Vietnam. Rachel Kneen, Department of Neurology, Royal Liverpool Children s Hospital (Alder Hey), Liverpool L12 2AP. rachel.kneen@blueyonder.co.uk Delia Bethell, Wellcome Research Unit, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand. nickd@tropmedres.ac.uk Tom Solomon, Department of Medical Microbiology and Genitourinary Medicine, University of Liverpool, Liverpool L69 3GA. tsolomon@liverpool.ac.uk Bridget Wills, The University of Oxford Clinical Research Unit, Hospital for Tropical Diseases 190 Ben Ham Tu, District 5, Ho Chi Minh City, Vietnam. Tel.: ; Fax: ; bridgetw@hcm.vnn.vn ª 2004 Blackwell Publishing Ltd 581