Prevention of diarrhoea in young children in developing countries.

Reviews/Analyses Prevention of diarrhoea in young children in developing countries S.R.A. Huttly,1 S.S. Morris,2 & V. Pisani3 An updated review of nonvaccine interventions for the prevention of childhood diarrhoea in developing countries is presented. The importance of various key preventive strategies (breast-feeding, water supply and sanitation improvements) is confirmed and certain aspects of others (promotion of personal and domestic hygiene, weaning education/food hygiene) are refined. Evidence is also presented to suggest that, subject to cost-effectiveness examination, two other strategies - vitamin A supplementation and the prevention of low birth weight- should be promoted to the first category of interventions, as classified by Feachem, i.e. those which are considered to have high effectiveness and strong feasibility. Introduction The main target of diarrhoea control programmes in developing countries is successful case-manage- ment, primarily through the use of oral rehydration therapy (ORT) and promotion of appropriate feed- ing during and after an episode of diarrhoea. Preven- tive strategies for morbidity are needed, however, if the estimated annual thousand million episodes of diarrhoea among under-5-year-olds are to be re- duced and further decreases in the 3.3 million diarrhoea-related deaths are to be achieved (1). A systematic review of potential interventions for the control of diarrhoeal diseases was initiated by WHO in 1982 (2). A total of 18 interventions were evalu- ated and classified into three groups based on an assessment of their effectiveness and feasibility (3) and the cost-effectiveness of the seven interventions that were identified to have high effectiveness and reasonably strong feasibility was assessed (4, 5). Subsequently, various questions raised in these reviews have been addressed. In particular, we pre- pared an updated review of nonvaccine, diarrhoeal interventions for the Xth World Congress of Gas- ' Senior Lecturer, Maternal and Child Epidemiology Unit, London School of Hygiene and Tropical Medicine, Keppel Street, London WC1 E 7HT, England. Requests for reprints should be sent to Dr Huttly at this address. 2 Lecturer, Maternal and Child Epidemiology Unit, London School of Hygiene and Tropical Medicine, London, England. 3 Programme Officer, Iringa, United Republic of Tanzania. Reprint No. 5766 troenterology, and present here a summary of our findings. Focusing on the questions raised in the original reviews, the four nonvaccine interventions identified as being adequately feasible and effective are covered: promotion of breast-feeding; improving weaning practices; improving water supply and sani- tation; and promotion of personal and domestic hygiene. Two preventive strategies that were identi- fied as requiring further research are also included: vitamin A supplementation and the prevention of low birth weight. A third, food hygiene, is included here as part of the assessment of improving weaning food practices. Promotion of breast-feeding Several updates of Feachem & Koblinsky's review (6), which was carried out in 1984, have been pub- lished (7-10). They identified good quantification of the effect of breast-feeding on diarrhoea mortality among infants in various socioeconomic settings as the highest research priority. Other research needs included clarification of the levels of protection against diarrhoeas of different etiologies and assess- ment of the relationship between feeding mode and both diarrhoea severity and persistent diarrhoea. Mortality from diarrhoea In a landmark study in southern Brazil, Victora et al. (11, 12) found that, compared with exclusively breast-fed (EBF) infants, those who were partially Bulletin of the World Health Organization, 1997, 75 (2): 163-174 © World Health Organization 1997 163 S.R.A. Huttly et al. breast-fed (PBF) had a 4.2 times higher risk of death caused by diarrhoea, which increased to 14.2 times higher for those not receiving any breast milk (NBF). Protection was greatest among infants aged 0-2 months (relative risk (RR) for PBF = 5.3 and for NBF = 23.3). Each additional daily feed of breast milk reduced the risk of diarrhoea death by 20%. There was no evidence that the protective effect per- sisted after weaning. Breast-feeding also afforded protection against deaths from persistent diarrhoea (RR for PBF = 4.3 and for NBF = 10.0) and possibly for those from dysenteric infection (RR for PBF = 4.9 and NBF = 3.0) (13). In Bangladesh, Briend et al. (14) found that among malnourished children, breast-feeding pro- tected against death from all causes up to 3 years of age. Although the number of deaths was small, breast-feeding protected against death due to bloody diarrhoea (RR = 0.19) and chronic nonbloody diar- rhoea (RR = 0.11). Also, in Guinea-Bissau breast- feeding protected against death among older child- ren (15). After adjustment for confounding, children aged 12-35 months who were not breast-fed had a risk of death 3.5 times greater than that of their breast-fed counterparts; no breakdown by cause of death was given, but diarrhoea morbidity rates were high (up to eight episodes per child per year) and thus as in many countries in sub-Saharan Africa, diarrhoea is probably a major cause of death among young children in Guinea-Bissau. Protection was therefore probably afforded against diarrhoeal deaths. In Ethiopia, infants who were not breast- fed experienced a tenfold increase in diarrhoea mor- tality (16). Comparison of children who died because of diarrhoea and those who survived a diarrhoeal epi- sode confirms that breast-feeding protects against case fatality. In India, children aged -18 months who were hospitalized for diarrhoea were 2.7 times more likely to die if they were not breast-fed (17). The protective effect declined with age, the odds ratio being 6.0 for those aged 0-6 months, 2.6 for those aged 7-12 months, and 1.8 for those aged 13- 18 months. Breast-feeding also afforded more pro- tection among children suffering from persistent diarrhoea, those who were malnourished, and those who had no other major infection. In Rwanda, chil- dren under 2 years of age who had been admitted to hospital for diarrhoea were more than three times as likely to die if they were weaned than if they were breast-fed (18). Etiology of diarrhoea In infants breast-feeding affords protection against symptomatic infection with Shigella spp. (8, 19-21), Vibrio cholerae (8, 20, 22), Campylobacter spp. (21, 23), Salmonella spp. (8, 21) and enterotoxigenic Escherichia coli producing heat-labile toxin (LT- ETEC) (24). Protection against cholera, and Shigella spp. appears to extend into the second and third years of life, albeit at a lower level than in infancy. In Bangladesh, breast-feeding was found to reduce the severity of infection with Shigella spp. (25) and V. cholerae (22). It is not clear whether breast-feeding offers protection against rotavirus, although breast- fed cases may experience less severe episodes (19). Severity of diarrhoea As indicated above, breast-feeding protects against the severity of cholera and Shigella spp. infections. Substantial protection is also offered against hospi- talization for diarrhoea. For example, in Iraq, young infants who were bottle-fed were most at risk, being 55 times more likely to be hospitalized for diarrhoea than their exclusively breast-fed counterparts (26). In southern Brazil, infants who started to receive supplements in addition to breast milk during the first week of life were five times more likely to be hospi- talized for diarrhoea by 3 months of age (27). For infants who stopped breast-feeding during the first week of life the corresponding relative risk was 12. Results from three case-control studies under- taken to establish risk factors for moderate or severe dehydrating diarrhoea in children aged 0-23 months have been collated (Kirkwood & Morris, unpub- lished data, 1992). These studies, conducted in Bangladesh, Brazil, and Egypt, showed that breast- feeding provided substantial protection against an episode of diarrhoea that resulted in life-threatening dehydration. After adjusting for appropriate con- founders, nonbreast-fed children were at a 2.3 times (Bangladesh) to 3.0 times (Brazil) greater risk of dehydration. In Brazil, the protective effect was greatest among young infants (<6 months), in Bang- ladesh among the age group 6-11 months, while in Egypt the impact was similar for all age groups. In Ethiopia odds ratios were 4.2 for nonbreast-fed and 2.9 for partially breast-fed relative to exclusively breast-fed children aged 0-6 months, although no adjustment for confounding was made (28). This protective effect was not evident in children aged 7-12 months. The evidence concerning breast-feeding and morbidity caused by persistent diarrhoea is mixed. In southern Brazil, infants who stopped breast- feeding in the first week of life had a five times higher risk than their breast-fed counterparts of persistent diarrhoea before 3 months of age (27). Several studies have compared cases of persistent and acute diarrhoea. Sazawal et al. found that exclusive WHO Bulletin OMS. Vol 75 1997164 Prevention of diarrhoea in young children breast-feeding appeared to offer substantial protec- tion against a persistent episode, although it was not statistically significant (29). Baqui et al. showed that reduced breast-feeding during an episode of diar- rhoea resulted in an almost two-fold increase in the risk of it becoming persistent (30). Also, Lanata et al. reported that the risk of an episode becoming per- sistent was higher among those not given breast milk during the first week of illness (OR = 1.6), but this was not significant (31). The findings of the above studies confirm the role played by breast-feeding in the prevention of diarrhoea. Although data on diarrhoea mortality are still relatively scarce, those that are available show the strong protective effect of breast-feeding and the results on protection against diarrhoea severity also support this finding. Exclusive breast-feeding during the early months of infancy appears to be of particu- lar importance, and although the value of prolonged breast-feeding has been questioned on nutritional grounds, the answer remains unclear (32). The pro- tective effect of breast-feeding among older children against infection with Shigella spp. and cholera, overall diarrhoea, and mortality, particularly among those who are malnourished, suggests that mothers should not be discouraged from breast-feeding this age group. The results on progression of diar- rhoea episodes to dehydration or to persistent epi- sodes endorse the continuation of breast-feeding during diarrhoea. These benefits have influenced thinking on breast-feeding policy in countries affected by human immunodeficiency virus (HIV). Despite the risk of vertical transmission of HIV infection in affected areas, in many situations the health risks of not breast-feeding far outweigh the potential number of lives saved through abandoning this practice (33). Improving weaning practices Ashworth & Feachem located no studies which measured directly the impact of weaning education on diarrhoeal disease (34). However, data from 12 countries suggested that weaning education can im- prove the nutritional status of infants and young chil- dren. Calculations of the impact on diarrhoea of a weaning education programme yielded estimated reductions of 2-12% in diarrhoea mortality. These estimates were based on the potential impact due to improved nutritional status, but did not include the impact that might be achieved through reduced food contamination. The latter was dealt with in a review by Esrey & Feachem (35); however, because of lack of adequate data, only tentative conclusions could be made on the impact of food hygiene practices on childhood diarrhoea. Research was urged into those practices that are risk factors for faecal contamina- tion (and therefore likely to be associated with diar- rhoea) and also into interventions to modify such risk-related practices. Certain food handling, preparation, and storage practices increase the risk of faecal contamination. For example, cooked foods stored at ambient tem- peratures for more than 3-4 hours have higher levels of bacterial pathogens than those stored for shorter periods (36-40). Use of cups rather than feeding bottles reduces contamination of weaning foods (38, 41). In Ghana, the effect of fermentation on the bacterial contamination of weaning foods contain- ing maize dough was examined (42). Unfermented dough samples were significantly more contami- nated; also, 6 hours and 12 hours after being pre- pared, porridge was more contaminated if it was made from unfermented dough. The feasibility of improving the hygiene levels of weaning food was investigated in a multidis- ciplinary project in north-east Brazil, in which novel methods were used to identify four key weaning food hygiene practices to target for change (43). The se- lection of behaviours was based on their prevalence, estimated feasibility for change, and anticipated im- pact on contamination of weaning foods; feasibility for change was then tested in a 1-month household micro-trial. Messages were developed to promote the following: washing hands before food prepara- tion; use of boiling water to reconstitute powdered milk; feeding of gruels using a cup and spoon instead of a bottle; and avoiding storing gruel and milk. In each case 15 mothers or caretakers were asked to adopt one of these behaviours for the trial period; a fifth group was asked to implement all four behav- iours. Most of the mothers were able to maintain the promoted practices for 1 month and at least half were able to practise the behaviour each time the baby was fed, thus demonstrating the feasibility of changing appropriate behaviours. Several studies are under way to investigate ways of increasing the energy intake of young chil- dren. In Jamaica, a preliminary trial showed that consumption of a thick energy-dense porridge was significantly lower than that of a traditional liquid porridge (average, 98 vs 139g-kg-'-day-1) but the energy intake was significantly higher (average, 402 vs 296kJ-kg-'-day-1). Amylase treatment of the thick energy-dense porridge, to reduce its viscosity, did not increase intakes further (44). Preliminary results from a weaning intervention in Peru show that the total amount of complementary food consumed varied inversely with its energy density; consumption was greater when more meals were offered (4 or Svs 3) (45). WHO Bulletin OMS. Vol 75 1997 165 S.R.A. Huttly et al. All these results can contribute to the formula- tion of effective weaning intervention strategies for the prevention of diarrhoea morbidity. As with promotion of breast-feeding, however, change in be- haviour is involved, which poses particular chal- lenges for health promotion workers. Improving water supplies and sanitation Unlike many of the other preventive strategies, im- provement of water supplies and sanitation has been the subject of intervention studies worldwide. The original review carried out by Esrey et al. in 1985 summarized results from 67 studies in 28 countries to assess the impact of improved water supplies and sanitation (46). In 1991 Esrey et al. reviewed a fur- ther 17 studies and obtained very similar findings a 22% (range, 0-100%) median reduction in diar- rhoea morbidity, 26% (range, 0-68%) from those studies considered to be more rigorous (47). Several other recent studies (48-51) have reported similar reductions. A median reduction of 65% (range, 43- 79%) was estimated for diarrhoea-specific mortality, although none of the three studies involved were classified as rigorous (47). Based on the results of six rigorous studies, a median reduction of 55% (range, 20-82%) in overall child mortality was found. These reductions, based on a relatively small number of studies, must, however, be interpreted with caution. Water and sanitation would be expected to have little impact on several other major causes of overall infant and child mortality. Thus, a measure which reduced diarrhoea-specific mortality by 65%, would not be expected to have such a sizeable impact on overall mortality. Esrey et al. also examined the health impact according to the type of intervention (46). Their find- ings suggest that improvements in water quantity and in excreta disposal may be more significant than improvements in water quality alone. However, this was less clear in the later review (47), in which the more rigorous studies were examined separately, although the number of studies involved was small. A recent analysis of data from demographic and health surveys conducted in eight countries dem- onstrated that improvements in sanitation had a greater impact on diarrhoea prevalence than improvements in water supply (52). These findings were based on comparisons between studies; how- ever, within-study results also support this idea, par- ticularly in favour of water availability (48-50, 53, 54). Nevertheless, the limitations of ascribing health impact to one particular component of an integrated intervention programme have to be recognized. Some intervention studies have assessed the impact of improved services according to the pres- ence of other factors. For mortality (55, 56) and morbidity (57) the impact was greater among infants not breast-fed. In Malaysia, sanitation had a greater impact on infant mortality among the children of illiterate mothers (58), whereas in Lesotho the re- verse was true for the impact on diarrhoea morbidity (50). A number of reasons have been proposed to account for the range of impacts achieved with water supply and sanitation interventions, and have been summarized by Huttly (59). The relatively low priority assigned to water supply and sanitation im- provements has been challenged by Briscoe (60), who describes as misleading those cost-effectiveness analyses that fail to take account of the multiple health benefits, direct or indirect, of sanitary im- provements. This author also concludes that the long-term effects on child survival are probably sub- stantial, in addition to the more immediate impacts on morbidity. Thus, while it is clearly complex, im- proving water supplies and sanitation facilities in development activities seems justified (60, 61). The challenges are great, with approximately a thousand million people remaining unserved by improved water supplies and 1.7 thousand million being un- served by adequate sanitation (62). Promotion of personal and domestic hygiene As described above, improvements in water quantity may have more impact on diarrhoea than im- provements in water quality alone, and this has been attributed to better personal and domestic hygiene. As a consequence, the promotion of hygienic be- haviours is receiving increased attention as a pre- ventive strategy against diarrhoeal diseases. In 1984 Feachem (63) found only three relevant studies whose health impact could be assessed. Since then, several more studies have appeared, which permits a better assessment, and significant developments are occurring in the design and evaluation of such interventions. Of 10 studies which aimed specifically at im- proving hygiene practices (64), all showed a positive impact on diarrhoeal morbidity in young children (Table 1), with a median reduction of 33% (range, 11-89%). Five studies focused specifically on hand-washing (median reduction, 35%), while the remainder dealt with a range of behaviours, in- cluding hand-washing, (median reduction, 26%). Three projects that were implemented as integrated water supply, sanitation, and hygiene education WHO Bulletin OMS. Vol 75 1997166 Prevention of diarrhoea in young children Table 1: Impact of hygiene behaviour interventions on diarrhoea morbidity, according to type of behavioural intervention Hand-washing: Several behaviours: Location % reduction in morbidity Location % reduction in morbidity USA (ref. 87) 48 Bangladesh (ref. 88) ca. 40 Burma (ref. 89) 30 Zaire (ref. 90) 11 Bangladesh (ref. 91) 35 Thailand (ref. 92) 34 India (ref. 93) 32 Bangladesh (ref. 94) 26 Indonesia (ref. 95) 89 Guatemala (ref. 96) 14 Median % reduction 35 Median % reduction 26 programmes attempted to relate their health im- pact to the behaviours being promoted. Their over- all impact on diarrhoea was approximately the same as that for water supply and sanitation im- provements or hygiene improvements alone. These integrated projects, however, generally had less in- tensive hygiene promotion than the dedicated hygiene projects. The results suggest that a greater health impact may be achieved if a single behaviour, in this case hand-washing, is targeted. The number of studies remains relatively small, however, but it is clear that individual hygiene education campaigns should not promote too many different messages. In conse- quence, WHO has recently identified three key water-related behaviours for promotion (65): cleans- ing of hands - especially after defecation, after cleaning babies and young children's bottoms, and before eating and before preparing food; sanitary disposal of faeces - especially those of young chil- dren and babies, and those with diarrhoea; and maintaining drinking-water free from faecal con- tamination. Advances have also been made in the development of methods for the more efficient pro- motion of hygiene behaviour change as well as in tools for evaluation of changes (66). The results ap- pear promising, especially for communities where substantial hardware improvements remain distant. Vitamin A supplementation In 1987, Feachem reviewed the relationship between vitamin A deficiency and diarrhoea in young chil- dren (67), a topic of considerable interest follow- ing the report of Sommer et al. (68) that vitamin A supplementation reduced child mortality by 34%. Studies were urged to investigate further the poten- tial of vitamin A supplementation. There is now scarcely any doubt that prophylac- tic supplementation with synthetic vitamin A can reduce at least diarrhoea mortality rates in young children. The evidence to support this assertion comes from the results of five large-scale, commu- nity-based, randomized controlled trials of vitamin A supplementation in young children (Table 2). A further three similar studies have only reported ef- fects on all-cause mortality, but their pooled results are no different from those of the other five studies. The estimates of the effect of vitamin A supple- mentation on diarrhoea mortality are remarkably consistent across the five different studies, despite the diversity of settings and methodologies adopted. Only one study failed to show a beneficial impact on diarrhoea mortality (100). This study also found no overall impact on all causes of death combined (in marked contrast to the other four studies, which found that vitamin A supplementation was associ- ated with reductions in the range 19-54%); however, total vitamin A intake was significantly associated with both all-cause and diarrhoea-specific mortality - children at the 90th percentile of the distribution of total vitamin A intake experienced a reduction of ca. 75% in the risk of diarrhoea mortality relative to children at the 10th percentile, after adjusting for socioeconomic confounding (relative risk, 0.25; 95% confidence interval (CI): 0.10-0.65) (69). Table 2: Impact of prophylactic vitamin A supplemen- tation on diarrhoea mortality Location Relative riska Nepal, highlands (ref. 97) 0.65 (0.44-0.95)b Nepal, lowlands (ref. 98) 0.61 South India (ref. 99) 0.48 (0.24-0.96) Sudan (ref. 100) 1.01 (0.68-1.49) Ghana (ref. 101) Acute diarrhoea 0.66 (0.47-0.92) Chronic diarrhoea/malnutrition 0.67 (0.38-1.18) a Vitamin A: placebo group. b Figures in parentheses are 95% confidence intervals. WHO Bulletin OMS. Vol 75 1997 167 S.R.A. Huttly et al. Two meta-analyses have attempted to synthe- size the results from studies carried out in Nepal, India, and Sudan (70, 71). Both conclude that vita- min A supplementation is associated with a signi- ficant reduction in diarrhoea-specific mortality, with summary relative risks of 0.71 (95% CI = 0.57-0.88) and 0.69 (95% CI = 0.57-0.84). The inclusion of the results from a study carried out in Ghana would presumably have reduced these relative risk esti- mates still further (closer to the levels of 0.66/0.67 found in that study). Supplementation with synthe- tic vitamin A may therefore reduce diarrhoea mor- tality rates in young children by approximately one third. There has also been considerable interest in establishing the magnitude of the effect of prophy- lactic vitamin A supplementation on the incidence, duration, and severity of diarrhoea. The most reli- able information on these outcomes arises from four intensive, prospective studies (Table 3). One other study with intensive morbidity sur- veillance has provided data only on the mean daily prevalence, rather than the incidence, of diarrhoea (75). Mean daily prevalences of 15.9% in the vita- min-A-supplemented group and 15.5% in the pla- cebo group were found, giving a prevalence ratio of 0.98. Three further studies evaluated the impact on diarrhoea prevalence at single points in time follow- ing the administration of vitamin A or placebo. One study in Haiti (72) found that at 2-8-weeks' post- dosing (2-week period prevalence) the prevalence ratio was 1.09, while another in Indonesia (73) found that at 9-13-months' post-dosing the prevalence ra- tio was 0.89. A small study in Thailand (74) found that the cumulative incidence of diarrhoea appeared to be reduced by approximately 40% over the first 2- months' post-dosing but did not fall over the follow- ing 2-month period (RR = 1.19). Although many of the morbidity studies have been criticized on methodological grounds, and have failed to provide adequately detailed analyses of their results, taken together they seem to indicate fairly unequivocally that vitamin A supplementation has no impact, ben- Table 3: Impact of prophylactic vitamin A supplemen- tation on the incidence of diarrhoea Location Frequency of visits Relative riska Brazil (ref. 102) 3 per week 0.94 (0.90-0.98)b South India (ref. 103) 1 per week 0.99c Indonesia (ref. 104) Every other day 1.06 (0.96-1.19) China (ref. 105) 1 per 2 weeks 0.41 a Vitamin A: placebo group. b Figures in parentheses are 95% confidence intervals. c Age adjusted. eficial or otherwise, on the incidence or prevalence of diarrhoea. The only plausible explanation for the marked reduction in diarrhoea mortality that has been ob- served in the larger mortality studies is that vitamin A supplementation reduces the severity of diarrhoeal disease; however, little information is available to verify this hypothesis. The most detailed account pub- lished so far (102) appears to indicate that the impact of vitamin A supplementation increases with the se- verity of the diarrhoea episode, with incidence ratios of 0.97 for mild (1-2 days' duration), 0.91 for moder- ate (:3 days' duration, with a mean of -4 liquid or semi-liquid motions per 24h) and 0.80 for severe diarrhoea (-3 days' duration, with a mean of -5 liquid or semi-liquid motions per 24h). The authors of this study also report a strong trend in the impact of vitamin A supplementation on the number of days with -3, -4, -5 or -6 liquid stools. In a similar study in Ghana (75), a significant reduction in diar- rhoea associated with signs of dehydration was de- tected in children supplemented with vitamin A (RR = 0.85); none the less the association between vitamin A supplementation and diarrhoea severity is poorly understood. No information is available on etiology- specific impacts of vitamin A supplementation. Four studies that gave very large doses of syn- thetic vitamin A to children hospitalized with mea- sles are a further source of information on the impact on diarrhoeal disease of raising vitamin A levels in young children (76-79). Three of these studies re- ported that during hospitalization children treated with vitamin A had shorter durations of diarrhoea (77-79), and Coutsoudis et al. reported less frequent and less severe diarrhoea at 6-weeks' and 6-months' post-discharge, although the number of children in this study were very small and the differences are not statistically significant (78). The above results show that vitamin A supple- mentation is a very promising preventive strategy for the control of diarrhoeal diseases. Improving the vi- tamin A status among young children in developing countries on a widespread scale is currently a chal- lenge for which a variety of different strategies are available. While capsule distribution, food fortifica- tion and dietary modification are all physiologically capable of improving children's vitamin A stores, their impact at the programme level will depend on the feasibility of achieving broad population cover- age at sustainable costs. Prevention of low birth weight The prevention of low birth weight (LBW), i.e. <2500g, as a measure against diarrhoeal diseases WHO Bulletin OMS. Vol 75 1997168 Prevention of diarrhoea in young children in young children was reviewed by Ashworth & Feachem in 1985 (80), who were unable to locate any satisfactory data on LBW as a determinant of diar- rhoea morbidity or mortality. They concluded, how- ever, for developing countries where diarrhoea is a major cause of infant and child death that LBW is probably associated with diarrhoea mortality. Subse- quently, several studies have been conducted that permit examination of the association between LBW and diarrhoea. Mortailty from diarrhoea Two studies, both conducted in southern Brazil, have assessed the association between LBW and diarrhoea mortality in infants. The first involved over 200 infant deaths among a birth cohort of almost 6000 children, 25 of which were due to diarrhoea. Despite the relatively small number of deaths, an inverse relationship was found between birth weight and diarrhoea mortality (81). Death rates ranged from 12 per 1000 in children weigh- ing <2000g at birth to 2 per 1000 for those weigh- ing ¢'3500g. The relative risk of infant death due to diarrhoea associated with LBW was 2.5 (95% CI = 0.9-6.7), while that for infant death due to all causes was 11.0 (95% CI = 8.7-14.4). Among deaths not due to perinatal causes, however, the relative risks were broadly the same. In a second study, using the case-control approach, risk factors for post-perinatal mortality were investigated by comparing cases with healthy neighbourhood con- trols (82). After adjustment for confounding fac- tors, LBW infants had twice the risk of death due to diarrhoea (odds ratio (OR) = 2.0; 90% CI = 1.1-4.4) than those weighing :2500g at birth. A similar odds ratio was found for deaths due to respiratory infec- tions, but that for deaths due to other infec- tious diseases was greater (OR = 5.0; 90% CI = 1.3- 18.6). Another study from Brazil examined prognostic factors for deaths due to diarrhoea in Rio de Janeiro by comparing those children <12 months of age who were hospitalized for diarrhoea and died (cases) with those also hospitalized for diarrhoea but who sur- vived (controls) (83). LBW infants were three times as likely to die than those weighing -2500g at birth. No data from developing countries were found on the effect of LBW on death as a result of diarrhoea after the first year of life. Morbidity from diarrhoea Several studies have examined the association be- tween hospitalization for diarrhoea and LBW. A small case-control study in Sri Lanka found a signifi- cant inverse relationship between birth weight and risk of hospitalization for diarrhoea, which persisted after adjustment for confounding (84). The results also suggest that LBW may be associated with an increased risk of diarrhoea morbidity beyond the first year of life. This has been borne out by subse- quent studies (see Table 4). All but one of these studies, which had a small sample size, reported at least a doubling in the risk of diarrhoea morbidity associated with LBW. Further analyses of data from Brazil (85) showed that this risk was more apparent among those LBW children who were born small-for-gestational age than among those born preterm. Also, this association was not present in later childhood (hospitalizations during 24-48 months of age). In Papua New Guinea, Bukenya et al. also showed that the LBW effect was highest in children aged <18 months and absent in those -3 years (108). No studies were found that examined the im- pact of an intervention to improve birth weight on diarrhoea morbidity or mortality, and any likely im- pact therefore remains theoretical (80). The conse- quences of low birth weight are multifactorial and the above evidence again emphasizes the need for its prevention. Kramer identified several public health interventions likely to have an impact on birth weight (86). The potential impacts on diarrhoea morbidity and mortality, as well as the many other benefits, suggest that these preventive strategies de- serve evaluation of their effectiveness, feasibility and cost. Table 4: Impact of low birth weight on diarrhoea morbidity Location Outcome Effect measure Brazil (ref. 106) Hospitalization for diarrhoea Risk ratio = 1.95 Thailand (ref. 107) Hospitalization for diarrhoea Odds ratio approx. 4 Brazil (ref. 108) Hospitalization for dehydrating diarrhoea Odds ratio approx. 3 Gambia (ref. 109) Clinic attendance for diarrhoea No association India (ref. 110) Diarrhoea prevalence Prevalence ratio approx. 3 Papua New Guinea (ref. 111) Diarrhoea incidence Rate ratio approx. 2 WHO Bulletin OMS. Vol 75 1997 169 S.R.A. Huttly et al. Conclusions The results of the present review confirm the im- portance of some key preventive strategies (breast- feeding, water supply and sanitation improvements), refine some others (promotion of personal and do- mestic hygiene, weaning education/food hygiene), and offer evidence that, subject to cost-effectiveness examination, two other strategies - vitamin A supplementation and the prevention of low birth weight - should be promoted. Martines et al. (5) suggest that over the coming years, the effectiveness and cost-effectiveness of many of these preventive strategies will improve since nonvaccine interven- tions involve behaviour change and public health education to achieve this will become more effective. No national diarrhoeal disease control programme is likely to implement all potential preventive stra- tegies, the choice depending on a number of factors such as different etiologies, existing infrastructure, and government priorities (5). Effective implemen- tation of these preventive strategies calls for in- volvement of a range of sectors (agriculture, water supply and sanitation), more so than for case- management. Acknowledgement S.R.A.H. and S.S.M. gratefully acknowledge the financial support provided by the United Kingdom Overseas Devel- opment Administration. Resume Prevention de la diarrhee chez le jeune enfant dans les pays en d6veloppement The prise en charge r6ussie est le principal objectif des programmes de lutte antidiarrh6ique dans les pays en d6veloppement; toutefois, il faut des strat6gies pr6ventives si l'on veut reduire le fardeau de la morbidit6 chez le jeune enfant. L'OMS a entam6 l'6tude systematique de 18 interventions pr6ventives potentielles en 1982, ce qui a permis de classer les interventions en trois groupes, selon leur efficacite et leur faisabilit6.3 Le pr6sent article d6crit une etude actualis6e qui porte sur sept interven- tions autre que vaccinales. Les r6sultats confirment et renforcent le r6le tres protecteur de l'allaitement au sein en ce qui concerne la mortalit6 et la morbidite diarrheiques. L'allaitement au sein exclusif durant les premiers mois de la vie semble etre particulierement im- portant et bien que l'on ait mis en doute la valeur nutritionnelle d'un allaitement au sein prolong6, il ne faut pas decourager les meres d'allaiter leur nouveau-n6. Plusieurs 6tudes ont fait progresser la comprehension des pratiques de sevrage am6liorees et de l'hygiene alimentaire, meme si la quantifica- tion de l'impact sur la diarrhee demeure limitee. De nombreuses etudes ayant trait a l'effet, sur la mor- bidite diarrheique, de l'amelioration des systemes d'approvisionnement en eau et d'assainissement ont 6te effectn6es ces dix dernieres ann6es et nous ont permis de mieux comprendre l'impact de ces systemes. En consequence, une attention accrue est accord6e a la promotion de comportements hygieniques en tant que strategie pr6ventive. Dix etudes visant plus precisement a ameliorer les pratiques d'hygiene ont signal6 l'impact positif de celles-ci la morbidite diarrheique, avec une r6duction moyenne de 33%. Des progres sont realis6s en ce qui concerne a la fois l'elaboration de methodes permettant de promouvoir plus effi- cacement les changements comportementaux en matiere d'hygiene et la conception d'instruments d'6valuation. Les resultats semblent prometteurs a ce jour, notamment pour les communautes ou l'am6lioration notable de l'equipement est encore lointaine. 11 ne fait maintenant pratiquement aucun doute que la compl6mentation prophylactique par de la vitamine A de synthese permet de r6duire les taux de mortalite diarrheique chez le jeune enfant. 11 semble toutefois que la compl6mentation par de la vitamine A n'ait aucun impact sur l'incidence ou la prevalence de la diarrhee et il a ete sugg6re qu'elle devait par consequent reduire la gravite de la maladie, bien que l'on dispose seulement d'infor- mations limit6es pour verifier cette hypothese. On a actuellement davantage d'indices montrant l'impact de l'insuffisance ponderale a la naissance a la fois sur la morbidit6 et la mortalit6 diarrh6iques. Les resultats suggerent que ces deux der- nieres strategies - promotion de comportements hygi6niques et complementation par de la vitamine A de synthese - devraient, apres analyse du rap- port couVIefficacite, etre ajout6es a la premi6re cat6gorie d'interventions de Feachem. Aucun programme national de lutte antidiarrheique ne semble en mesure de mettre en oeuvre toutes les strategies de pr6vention potentielles, le choix d6pendant de plusieurs facteurs tels que des 6tiologies diff6rentes, les infrastructures existantes et les priorites gouvernementales. Davantage en- core que pour la prise en charge des cas, I'appli- cation efficace de ces strategies de prevention exige la participation de plusieurs secteurs autres celui de la sant6. WHO Bulletin OMS. Vol 75 1997170 Prevention of diarrhoea in young children References 1. Bern C et al. The magnitude of the global problem of diarrhoeal disease: a ten-year update. Bulletin of the World Health Organization, 1992, 70: 705- 714. 2. Feachem RG, Hogan RC, Merson MH. Diarrhoeal disease control: reviews of potential interventions. Bulletin of the World Health Organization, 1983, 61: 637-640. 3. Feachem RG. Preventing diarrhoea: what are the policy options. Health policy and planning, 1986, 1: 109-117. 4. Phillips MA, Feachem RGA, Mills A. Options for diarrhoeal diseases control: the cost and cost- effectiveness of selected interventions for the pre- vention of diarrhoea. London, Evaluation and Plan- ning Centre for Health Care, 1987. 5. Martines J, Phillips M, Feachem RG. Diarrheal dis- eases. In: Jamison DT et al., eds. Disease control priorities in developing countries. Oxford, Oxford University Press, 1993. 6. Feachem RG, Koblinsky M. Interventions for the control of diarrhoeal diseases among young children: promotion of breast-feeding. Bulletin of the World Health Organization, 1984, 62: 271-291. 7. Huffman SL, Combest C. Role of breast-feeding in the prevention and treatment of diarrhoea. Journal of diarrhoeal diseases research, 1990, 8: 68-81. 8. Jason JM, Nieburg P, Marks JS. Mortality and infectious disease associated with infant-feeding practices in developing countries. Pediatrics, 1984, 4 (suppl.): 702-727. 9. Research on improving infant feeding practices to prevent diarrhoea or reduce its severity: Memoran- dum from a JHU/WHO meeting. Bulletin of the World Health Organization, 1989, 67: 27-33. 10. de Zoysa I, Rea M, Martines J. Why promote breastfeeding in diarrhoeal disease control pro- grammes? Health policy and planning, 1991, 6: 371- 379. 11. Victora CG et al. Evidence for protection by breast- feeding against infant deaths from infectious dis- eases in Brazil. Lancet, 1987, 21: 319-322. 12. Victora CG et al. Infant feeding and deaths due to diarrhea: a case-control study. American journal of epidemiology, 1989, 129: 1032-1041. 13. Victora CG et al. Deaths due to dysentery, acute and persistent diarrhoea among Brazilian infants. Acta paediatrica, 1992 (suppl. 381): 7-11. 14. Briend A, Wojtyniak B, Rowland MGM. Breast feeding, nutritional state, and child survival in rural Bangladesh. British medicaljournal, 1988, 296: 879- 881. 15. Molbak K et al. Prolonged breastfeeding, diarrhoeal disease, and survival of children in Guinea-Bissau. British medical journal, 1994, 308: 1403-1406. 16. Shamebo D et al. The Butajira Rural Health Project in Ethiopia: a nested case-referent (control) study of under-5 mortality and its health and behavioural de- terminants. Annals of tropical paediatrics, 1994, 14: 201-209. 17. Sachdev HPS et al. Does breastfeeding influence mortality in children hospitalized with diarrhoea? Journal of tropical pediatrics, 1991, 37: 275- 279. 18. Lepage P, Munyakazi C, Hennart P. Breastfeeding and hospital mortality in children in Rwanda. Lancet, 1981,1: 409-411. 19. Faruque A et al. Community-based evaluation of the effect of breast-feeding on the risk of microbiol- ogically confirmed or clinically presumptive shige- Ilosis in Bangladeshi children. Pediatrics, 1992, 90: 406-411. 20. Glass RI, Stoll BJ. The protective effect of human milk against diarrhea: a review of studies from Bang- ladesh. Acta paediatrica Scandinavica, 1989 (suppl. 351): 131-136. 21. Osisanya JOS et al. Acute diarrhoeal disease in Nigeria: detection of enteropathogens in a rural sub- Saharan population. Transactions of the Royal Soci- ety of Tropical Medicine and Hygiene, 1988, 82: 773-777. 22. Clemens JD et al. Breast feeding and the risk of severe cholera in rural Bangladeshi children. Ameri- can joumal of epidemiology, 1990, 131: 400-41 1. 23. Ruiz-Palacios GM et al. Protection of breast-fed infants against Campylobacter diarrhea by antibod- ies in human milk. Joumal of pediatrics, 1990, 116: 707-713. 24. Long KZ et al. Proportional hazards analysis of diarrhea due to enterotoxigenic Escherichia coli and breast feeding in a cohort of urban Mexican children. American journal of epidemiology, 1994, 139: 193- 205. 25. Clemens JD et al. Breast feeding as a determinant of severity in shigellosis. American journal of epide- miology, 1986, 123: 710-720. 26. Mahmood DA, Feachem RG, Huttly SRA. Infant feeding and risk of severe diarrhoea in Basrah city, Iraq: a case-control study. Bulletin of the World Health Organization, 1989, 67: 701-706. 27. Martines JC. The interrelationships between feeding mode, malnutrition and diarrhoeal morbidity in early infancy among the urban poor in southern Brazil. PhD thesis, University of London, 1988. 28. Lulseged S. Predictors of moderate to severe dehydration in acute diarrhoeal disease: a case- control study. Ethiopian medical journal, 1992, 30: 69-78. 29. Sazawal S, Bhan MK, Bhandari N. Type of milk feeding during acute diarrhoea and the risk of persistent diarrhoea: a case-control study. Acta paediatrica, 1992 (suppl. 381): 93-97. 30. Baqui AH et al. Epidemiological and clinical charac- teristics of acute and persistent diarrhoea in rural Bangladeshi children. Acta paediatrica, 1992 (suppl. 381): 15-21. 31. Lanata CF et al. Feeding during acute diarrhea as a risk factor for persistent diarrhea. Acta paediatrica, 1992 (suppl. 381): 98-103. 32. Grummer-Strawn LM. Does prolonged breast- feeding impair child growth? A critical review. Pediatrics, 1993, 91: 766-771. WHO Bulletin OMS. Vol 75 1997 171 S.R.A. Huttly et al. 33. Del Fante P et al. HIV, breast-feeding and under-5 mortality: modelling the impact of policy decisions for or against breast-feeding. Journal of tropical medi- cine and hygiene, 1993, 96: 203-21 1. 34. Ashworth A, Feachem RG. Interventions for the control of diarrhoeal diseases among young children: weaning education. Bulletin of the World Health Organization, 1985, 63: 1115-1127. 35. Esrey SA, Feachem RG. Interventions for the con- trol of diarrhoeal diseases among young children: promotion of food hygiene. Unpublished document WHO/CDD/89.30 (available upon request from Divi- sion of Child Health and Development, World Health Organization, 1211 Geneva 27, Switzerland). 36. Rowland MGM, Barrell RAE, Whitehead RG. Bac- terial contamination of traditional Gambian weaning foods. Lancet, 1978, 1: 136-138. 37. Black RE et al. Contamination of weaning foods and transmission of enterotoxigenic Escherichia cofi diar- rhoea in young children in rural Bangladesh. Trans- actions of the Royal Society of Tropical Medicine and Hygiene, 1982, 76: 259-264. 38. Black RE et al. Incidence and etiology of infantile diarrhea and major routes of transmission in Hua- scar, Peru. American joumal of epidemiology, 1989, 129: 785-799. 39. Henry FJ et al. Bacterial contamination of weaning foods and drinking water in rural Bangladesh. Epide- miology and infection, 1990, 104: 79-85. 40. Motarjemi Y et al. Contaminated weaning food: a major risk factor for diarrhoea and associated malnu- trition. Bulletin of the World Health Organization, 1993, 71: 79-92. 41. Phillips I et al. Methods and hygiene of infant feed- ing in an urban area of Uganda. Journal of tropical pediatrics, 1969, 15: 167-171. 42. Mensah PPA et al. Fermentation of cereals for re- duction of bacterial contamination of weaning foods in Ghana. Lancet, 1990, 336: 140-143. 43. Monte CMG. Improving weaning food hygiene prac- tices in a slum area of Fortaleza, north-east Brazil: a new approach. PhD thesis, University of London, 1993. 44. Stephenson DM et al. Weaning food viscosity and energy density: their effects on ad libitum con- sumption and energy intakes in Jamaican children. American journal of clinical nutrition, 1 994, 60: 465- 469. 45. Programme for Control of Diarrhoeal Diseases. Ninth Programme Report 1992-1993. Unpublished document WHO/CDD/94.46, 1994 (available upon request from Division of Child Health and Develop- ment, World Health Organization, 1211 Geneva 27, Switzerland). 46. Esrey SA, Feachem RG, Hughes JM. Interventions for the control of diarrhoeal diseases among young children: improving water supplies and excreta dis- posal facilities. Bulletin of the World Health Organi- zation, 1985, 63: 757-772. 47. Esrey SA et al. Effects of improved water supply and sanitation on ascariasis, diarrhoea, dracun- culiasis, hookworm infection, schistosomiasis, and trachoma. Bulletin of the World Health Organization, 1991, 69: 609-621. 48. Huttly SRA et al. The Imo State (Nigeria) drinking water supply and sanitation project II: Impact on dracunculiasis, diarrhoea and nutritional status. Transactions of the Royal Society of Tropical Medi- cine and Hygiene, 1990, 84: 316-321. 49. Aziz KMA et al. Reduction in diarrhoeal diseases in children in rural Bangladesh by environmental and behavioural modifications. Transactions of the Royal Society of Tropical Medicine and Hygiene, 1990, 84: 433-438. 50. Daniels DL et al. A case-control study of the impact on diarrhoea morbidity of improved sanitation in Lesotho. Bulletin of the World Health Organization, 1990, 68: 455-463. 51. Mertens TE et al. Childhood diarrhoea in Sri Lanka: a case-control study of the impact of improved water sources. Tropical medicine and parasitology, 1990, 41: 98-104. 52. Esrey SA. Water, waste and well-being: a multi- country study. American journal of epidemiology, 1996, 143: 608-623. 53. Gorter AC et al. Water supply, sanitation and diarrhoeal disease in Nicaragua: results from a case-control study. Intemational journal of epidemi- ology, 1991, 20: 527-533. 54. Victora CG et al. Water supply, sanitation and hous- ing in relation to the risk of infant mortality from diarrhoea. International journal of epidemiology, 1988, 17: 651-654. 55. Butz et al. Environmental factors in the relationship between breasffeeding and infant mortality: the role of water and sanitation in Malaysia. American journal of epidemiology, 1984, 119: 516-525. 56. Habicht J-P, Da Vanzo J, Butz WP. Mother's milk and sewage: their interactive effects on infant mortal- ity. Pediatrics, 1988, 81: 456-461. 57. VanDerslice J, Popkin B, Briscoe J. Drinking- water quality, sanitation and breast-feeding: their in- teractive effects on infant health. Bulletin of the World Health Organization, 1994, 72: 589-601. 58. Esrey SA, Habicht J-P. Maternal literacy modifies the effect of toilets and piped water on infant survival in Malaysia. American journal of epidemiology, 1988, 127: 1079-1087. 59. Huttly SRA. Water, sanitation and health in develop- ing countries. In: Golding AMB et al., eds. Water and public health. London, Smith Gordan, 1994: 251- 258. 60. Briscoe J. A role for water supply and sanitation in the child survival revolution. Bulletin of the Pan American Health Organization, 1987, 21: 93-105. 61. Okun DA. The value of water supply and sanitation in development: an assessment. American journal of public health, 1988, 78: 1463-1467. 62. World Bank. World development report: develop- ment and the environment. New York, Oxford Uni- versity Press, 1992: 112. 63. Feachem RG. Interventions for the control of diarrhoeal diseases among young children: pro- motion of personal and domestic hygiene. Bulletin 172 WHO Bulletin OMS. Vol 75 1997 Prevention of diarrhoea in young children of the World Health Organization, 1984, 62: 467- 476. 64. Pisani V. Improving personal and domestic hygiene: does it reduce diarrhoeal disease? MSc dissertation, London School of Hygiene and Tropical Medicine, 1994. 65. Improving water and sanitation hygiene behaviours for the reduction of diarrhoeal disease: the report of an informal consultation. Unpublished document. WHO/CWS/90.7/WHO/CDD/93.5, 1993 (available upon request from Division of Child Health and Development, World Health Organization, 1211 Geneva 22, Switzerland). 66. Boot MT, Cairncross AM. Actions speak: the study of hygiene behaviour in water supply and sanitation projects. The Hague, IRC Water and Sanitation Cen- tre, 1993. 67. Feachem RG. Vitamin A deficiency and diarrhoea: a review of interrelationships and their implications for the control of xerophthalmia and diarrhoea. Tropical diseases bulletin, 1987, 84: R1-R1i6. 68. Sommer A et al. Impact of vitamin A supplementa- tion on childhood mortality: a randomized controlled community trial. Lancet, 1986, 1: 1169-1173. 69. Fawzi WW et al. Dietary vitamin A intake and the risk of mortality among children. American journal of clini- cal nutrition, 1994, 59: 401-408. 70. Beaton GH et al. Effectiveness of vitamin A supple- mentation in the control ofyoung child morbidity and mortality in developing countries. Toronto, University of Toronto, 1992. 71. Fawzi WW et al. Vitamin A supplementation and child mortality: a meta-analysis. Journal of the American Medical Association, 1993, 269: 898- 903. 72. Stansfield SK et al. Vitamin A supplementation and increased prevalence of childhood diarrhoea and acute respiratory infections. Lancet, 1993, 341: 578-582. 73. Abdeljaber MH et al. The impact of vitamin A sup- plementation on morbidity: a randomized community intervention trial. American journal of public health, 1991, 81(12): 1654-1656. 74. Bloem MW et al. Mild vitamin A deficiency and risk of respiratory tract diseases and diarrhea in pre- school and school children in northeastern Thailand. American journal of epidemiology, 1990, 131: 332- 339. 75. Arthur P et al. Impact of vitamin A supplementation on childhood morbidity in northern Ghana. Lancet, 1992, 339: 361-362. 76. Barclay AJG, Foster A, Sommer A. Vitamin A sup- plements and mortality related to measles: a randomised clinical trial. British medical journal, 1987, 294: 294-296. 77. Hussey GD, Klein M. A randomized, controlled trial of vitamin A in children with severe measles. New England journal of medicine, 1990, 323(3): 160-164. 78. Coutsoudis A, Broughton M, Coovadia HM. Vita- min A supplementation reduces measles morbidity in young African children: a randomized, placebo- controlled, double-blind trial. American joumal of clinical nutrition, 1991, 54: 890-895. 79. Ogaro FO et al. Effect of vitamin A on diarrhoeal and respiratory complications of measles. Tropical and geographical medicine, 1993, 45(6): 283-286. 80. Ashworth A, Feachem RG. Interventions for the control of diarrhoeal diseases among young children: prevention of low birth weight. Bulletin of the World Health Organization, 1985, 63:165-184. 81. Victora CG et al. Birthweight and infant mortality: a longitudinal study of 5914 Brazilian children. Interna- tional journal of epidemiology, 1987, 16: 239-245. 82. Victora CG et al. Influence of birth weight on mortal- ity from infectious diseases: a case-control study. Pediatrics, 1988, 81: 807-811. 83. Post CLA et al. [Prognostic factors for hospital deaths caused by diarrhoea or pneumonia in 1- year-olds: a case-control study]. Revista de saude publica, 1992, 26: 369-378 (in Portuguese). 84. Mertens TE, Cousens SC, Feachem RG. Evidence of a prolonged association between low birthweight and paediatric diarrhoea in Sri Lanka. Transactions of the Royal Society of Tropical Medicine and Hy- giene, 1987, 81: 196. 85. Barros FC et al. Comparison of the causes and consequences of prematurity and intrauterine growth retardation: a longitudinal study in southern Brazil. Pediatrics, 1992, 90: 238-244. 86. Kramer M. Determinants of low birth weight: meth- odological assessment and meta-analysis. Bulletin of the World Health Organization, 1987, 65: 663- 737. 87. Black RE et al. Handwashing to prevent diarrhoea in day-care centers. American joumal of epidemiology, 1981, 113: 445-451. 88. Alam N et al. Mothers' personal and domestic hy- giene and diarrhoea incidence in young children in rural Bangladesh. International journal of epidemiol- ogy, 1989, 18: 242-247. 89. Han AM, Hlaing T. Prevention of diarrhoea and dys- entery by hand washing. Transactions of the Royal Society of Tropical Medicine and Hygiene, 1989, 83: 128-131. 90. Haggerty PA. Community-based hygiene education to reduce diarrhoeal disease in rural Zaire: a pro- spective, longitudinal study. PhD Thesis, University of London, 1991. 91. Khan MU. Interruption of shigellosis by hand wash- ing. Transactions of the Royal Society of Tropical Medicine and Hygiene, 1982, 76: 164-168. 92. Pinfold JV. A hygiene intervention designed to re- duce the incidence of diarrhoeal disease in rural northeast Thailand. Final report. Department of Civil Engineering, University of Leeds, Leeds, England. 93. Sircar BK et al. Effect of handwashing on the inci- dence of diarrhoea in a Calcutta slum. Journal of diarrhoeal diseases research, 1987, 5: 112-114. 94. Ahmed NU et al. A longitudinal study of the impact of behavioural change intervention on cleanliness, diarrhoeal morbidity and growth of children in rural Bangladesh. Social science and medicine, 1993, 37: 159-171. WHO Bulletin OMS. Vol 75 1997 173 S.R.A. Huttly et al. 95. Wilson JM et al. Hand-washing reduces diarrhoea episodes: a study in Lombok, Indonesia. Transac- tions of the Royal Society of Tropical Medicine and Hygiene, 1991, 85: 819-821. 96. Torun B. Environmental and educational interven- tions against diarrhea in Guatemala. In: Chen LC, Scrimshaw NS, eds. Diarrhea and malnutrition: inter- actions, mechanisms, and interventions. New York, Plenum Press, 1982: 235-266. 97. Daulaire NMP et al. Childhood mortality after a high dose of vitamin A in a high-risk population. British medical journal, 1992, 304: 207-210. 98. West KP Jr, Pokhrel RP, Katz J. Efficacy of vita- min A in reducing preschool child mortality in Nepal. Lancet, 1991, 338: 67-71. 99. Rahmathullah L et al. Reduced mortality among children in southern India receiving a small weekly dose of vitamin A. New England journal of medicine, 1990, 323: 929-935. 100. Herrera MG et al. Vitamin A supplementation and child survival. Lancet, 1992, 340: 267-271. 101. Ghana VAST Study Team. Vitamin A supplementa- tion in northern Ghana: effects on clinic attendances, hospital admissions, and child mortality. Lancet, 1993, 342: 7-12. 102. Barreto ML et al. Effect of vitamin A supplementa- tion on diarrhoea and acute lower-respiratory tract infections in young children in Brazil. Lancet, 1994, 334: 228-231. 103. Rahmathullah L et al. Diarrhea, respiratory infec- tions, and growth are not affected by a weekly low- dose vitamin A supplement: a masked, controlled field trial in children in southern India. American journal of clinical nutrition, 1991, 54: 568-577. 104. Dibley MJ, Sadjimin T, Kjolhede C. Impact of high dose vitamin A supplementation on incidence and duration of diarrhea and acute respiratory infections in preschool Indonesian children. In: Toward Com- prehensive Programs to Reduce Vitamin A Defi- ciency. XV Intemational Vitamin A Consultative Group Meeting, Washington, DC. Washington, DC, The Nutrition Foundation, Inc., 1993: 88. 105. Cheng Lie et al. Impact of large-dose vitamin A supplementation on childhood diarrhoea, respiratory disease and growth. European joumal of clinical nu- trition, 1993, 47: 88-96. 106. Victora CG. Pneumonia, diarrhea and growth in the first 4 years of life: a longitudinal study of 5914 urban Brazilian children. American joumal of clinical nutri- tion, 1990, 52: 391-396. 107. Ittiravivongs A et al. Effect of low birth weight on severe childhood diarrhea. Southeast Asian joumal of tropical medicine and public health, 1991, 22: 557-562. 108. Victora CG et al. Breast-feeding, nutritional status, and other prognostic factors for dehydration among young children with diarrhoea in Brazil. Bulletin of the World Health Organization, 1992, 70: 467-475. 109. Downes B et al. Outcome of low birth weight infants in a West African village. Joumal of tropical pediatrics, 1991, 37: 106-1 10. 110. Das BK et al. Comparative outcome of low birth weight babies. Indian pediatrics, 1993, 30: 15-21. 111. Bukenya GB, Barnes T, Nwokolo N. Low birth- weight and acute childhood diarrhoea: evidence of their association in an urban settlement of Papua New Guinea. Annals of tropical paediatrics, 1991, 11: 357-362. 174 WHO Bulletin OMS. Vol 75 1997