Neonatal mortality in a rural area of The Gambia.

Childhood mortality in Upper River Division, The Gambia is high, 99 per 1000 mid-year population, and 27% of deaths occur is the neonatal period. The aims of the present study were to describe patterns of neonatal death and to identify risk factors. Cause of death was investigated using a neonatal post-mortem questionnaire, and a population-based, matched case-control study was conducted to identify potential risk factors. The neonatal mortality rate in Upper River Division was 39 per 1000 live births (95% CI 36.8-41.2). The rates in the early and late neonatal periods were 21.0 (19.4-22.6) and 18.0 (16.5-19.5), respectively. Infection accounted for 57% of all deaths. In the early neonatal period, 30% of deaths were due to prematurity. Only 55% of babies who died presented for treatment and 84% died at home. Risk factors for neonatal death were primiparity (OR 2.18), previous stillbirth (OR 3.19), prolonged labour (OR 2.80) and pre-lacteal feeding (OR 3.38). A protective effect was seen in association with delivery by a trained traditional birth attendant (OR 0.34) and the application of shea nut butter, a traditional medicine, to the cord stump (OR 0.07). This study has identified the need to understand the reasons underlying the widespread use of pre-lacteal feeds and the barriers to health service use in this community in order to plan effective interventions.

Changes in the pattern of infant and childhood mortality in upper river division, The Gambia, from 1989 to 1993.

A surveillance system was used to detect births and deaths in children in a large, rural, West African population from 1989 to 1993. Cause of death was investigated using post-mortem questionnaires. Overall infant (age 0-11 months) and child (age 1-4 years) mortality rates of 80.1 and 18.8 per 1000 per year were recorded. These were reasonably consistent over the period of surveillance. The most frequent cause of death in infants was acute respiratory infection (ARI), whereas in children it was malaria: these two conditions accounted for 41% of the deaths in children under 5 years old. Other leading causes of death were acute gastroenteritis, malnutrition, and septicaemia. Deaths attributed to ARI decreased over the 5-year period, but mortality rates from other causes were either unchanged or increased slightly. Mortality from all causes peaked in the rainy season and was slightly higher in villages which were part of a primary health care programme than in those which were not. There were also no differences between male and female mortality rates beyond one year of age. Despite the introduction of a number of health interventions, there has been no major change in the overall pattern of mortality in children in a rural area of The Gambia. Malaria and ARI remain the main causes of death.

Can malaria chemoprophylaxis be restricted to first pregnancies?

The harmful effects of malaria are most pronounced during first pregnancies and chemoprophylaxis is most effective when given at this time. However, restriction of chemoprophylaxis to first pregnancies might lead to enhanced susceptibility to malaria during second pregnancies. We have investigated this possibility by studying the outcome of second pregnancies in 165 Gambian women who had received either malaria chemoprophylaxis with Maloprim or placebo during their first pregnancy. Many of these primigravidae did not present until the third trimester of pregnancy so that some are likely to have experienced a malaria infection before they started medication. The prevalence of malaria infection of the blood and of the placenta during second pregnancies was similar in women who had received chemoprophylaxis during their first pregnancy and in those who had not, and the mean birth weights of babies born to women in each group were almost identical. Thus, in areas where the epidemiology of malaria is similar to that of The Gambia and where most women present relatively late in pregnancy, it may be possible to restrict malaria chemoprophylaxis to first pregnancies with consequent savings in cost and a reduction in drug pressure on Plasmodium falciparum.

The distribution of birth weights in Gambian women who received malaria chemoprophylaxis during their first pregnancy and in control women.

The distribution of birth weights among the infants of 172 Gambian primigravidae who had received chemoprophylaxis with Maloprim (pyrimethamine+dapsone) during pregnancy was compared with that of the infants of 149 primigravidae who had received placebo. Administration of chemoprophylaxis led to a reduction in the prevalence of low birth weight babies and to an increase in the median birth weight. However, these changes were not accompanied by a comparable increase in the prevalence of high birth weight babies. The perinatal mortality rate was lower, although not significantly so, among the babies of women who had received chemoprophylaxis. Thus, no evidence was found to support the view that administration of chemoprophylaxis might increase the risks of delivery by causing cephalo/pelvic disproportion.

Parasite virulence and disease patterns in Plasmodium falciparum malaria.

Heterogeneity in parasite virulence is one of several factors that have been proposed to contribute to the wide spectrum of disease severity in Plasmodium falciparum malaria. We used observed age-structured patterns of disease to define a population structure of P. falciparum, where the latter contains several independently transmitted antigenic types or "strains" that each induce some degree of strain-specific antidisease immunity upon infection. Patterns of incidence of severe and mild disease may be explained by assuming that a majority of these strains are associated with mild disease and that although severe malarial anemia is a complication occurring in a certain proportion of early infections with "mild" parasites, cerebral malaria is caused by a few distinct highly virulent strains. Considerable variation in parasite virulence, as a major factor of disease severity in malaria, is made possible by the absence of competition between the various parasite strains, arising from weak shared immune responses. The theoretical framework presented in this paper can explain other epidemiological observations, such as the results of interventions with insecticide-impregnated bednets.

Comparison of mortality between villages with and without Primary Health Care workers in Upper River Division, The Gambia.

Health services utilization was analysed in a rural area of the The Gambia. In general, health workers were consulted frequently. However, verbal autopsies showed that children who died had rarely consulted health workers, particularly if they came from villages where such workers were not posted. Traditional healers were consulted frequently, independently of the presence of a village health worker. The relationship between cause specific mortality and the utilization of health services is discussed. Childhood mortality was similar in villages with or without a primary health care worker at the time of the study.

PIP: The study aim was to evaluate the impact of mortality and primary health care (PHC) services utilization prior to death, based on data from the mortality surveillance system in the Upper River Division (URD) of The Gambia. The sample of villages with greater than 400 persons included 355 villages with a voluntary village health workers (VHW) and/or a trained traditional birth attendant (TBA), and 9 villages without. Recording of births and deaths was accomplished by one registrar for every 200 children or under, and totaled 373 village registrars and 8 field workers covering a population of 133,000. Cause of death for children aged 5 years was determined by 3 physicians and collected for senior field assistants. Morbidity data for children was gathered from monthly forms completed by VHWs and BAs. VHWs and TBAs were trained 6=8 weeks at Basse Hospital and 4-6 weeks at Bansang Regional Hospital, respectively, with periodic retraining. Local PHC centers provided health education, environmental health education, immunization, nutrition, treatment and referral. There were 6 health centers in URD, which was the base of operations for travel to 5-6 sites 1-2 times per month for running clinics, evaluation of referred patients, and supervision of PHC activities. There were 16, 216 episodes of malaria, 6111 episodes of respiratory infection (ALRI), and 6380 episodes of acute gastroenteritis reported through the PHC system. That means .63, .23, and .25 episodes per person per year, respectively. More than 50% of cases of ALRI involved consultation with VHWs. There were 915 deaths among children aged 5 years in one year. Of the 94% reports on the deaths made by relatives, there were 85% dying at home, and 8% dying at a health center or hospitals. 13% (117) were inpatients during a portion of the precipitating illness. Survivors of illnesses were higher among those children receiving consultation with the VHW. Only 33% of children who died had consulted a VHW during the final illness. TBAs reported 50% of deaths recorded by the surveillance system. TBAs are selectively consulted.

The immunogenicity and safety of Haemophilus influenzae type b-tetanus toxoid conjugate vaccine in Gambian infants.

In developing countries, Haemophilus influenzae type b is a major cause of meningitis and pneumonia in the 1st year of life. The safety and immunogenicity of a Haemophilus influenzae type b polysaccharide-tetanus toxoid conjugate vaccine (PRP-T) were evaluated in two studies of Gambian infants. In the first study, 131 infants were recruited and randomized into three groups to receive PRP-T at 1 and 3 months (group A), PRP-T at 2 and 4 months (group B) or no PRP-T (group C). The liquid form of PRP-T was used. The geometric mean titre (GMT) of anti-PRP antibody 1 month after the second dose was 0.26 microgram/ml in group A and 0.41 microgram/ml in group B. In the second study, 66 infants were given PRP-T in the lyophilized form at 2, 3 and 4 months of age. The GMT 1 month after the first dose was 0.09 microgram/ml, after the second 0.74 microgram/ml and after the third 2.32 micrograms/ml. After the third dose, 72% of children had antibody levels greater than 1.0 microgram/ml and 93% greater than 0.15 microgram/ml. No serious side-effects were observed and the rate of adverse reactions was consistent with the concurrent administration of diphtheria-tetanus-pertussis (DPT) vaccine.

PIP: In Sukuta, Gambia, in 1989, 128 newborns were randomly allocated to receive the liquid form of the Haemophilus influenzae type b (Hib) polysaccharide-tetanus toxoid (PRP-T) vaccine at 1 and 3 months (group A), 2 and 4 months (group B), or not to receive the vaccine (group C). All these children also received the oral polio vaccine and the diphtheria-pertussis-tetanus (DPT) vaccine. In 1990, in Bakau, Gambia, 66 infants received the lyophilized form of the PRP-T vaccine at the same time as they received DPT vaccine: 2, 3, and 4 months. The investigators aimed to determine the safety and immunogenicity of PRP-T as a forerunner to the upcoming PRP-T efficacy trial in Gambia. In the 1989 study, the geometric mean titer (GMT) of anti-PRP antibody 1 month after the second dose was higher in group B than in group A (0.41 vs. 0.26 mcg/ml). In the 1990 study, the GMT of anti-PRP antibody was 0.09 mcg/ml after the first dose, 0.74 mcg/ml after the second dose, and 2.32 mcg/ml after the third dose. One month after the final dose, the lyophilized PRP-T vaccine yielded higher antibody levels than the liquid form. For example, 72% of infants in the lyophilized group had an antibody level greater than 1 mcg/ml compared with 18% for the liquid group. 93% of all infants in groups A and B had antibody levels above 0.15 mcg/ml, the level considered to provide immediate protection, compared with 53% for the liquid group. Serious side effects were not observed. The rate of adverse reactions correlated with the concurrent delivery of DPT vaccine. Advantages of the PRP-T vaccine include: it mixes well with DPT; if administered in a three-dose schedule to Gambian infants, it is safe and elicits a protective antibody response in most infants; and it also protects against Hib infection, a major cause of meningitis and pneumonia in infants and an important cause of major childhood-acquired disability in developing countries.

Safety and immunogenicity of Haemophilus influenzae type B-Neisseria meningitidis group B outer membrane protein complex conjugate vaccine mixed in the syringe with diphtheria-tetanus-pertussis vaccine in young Gambian infants.

To ensure compliance and to reduce costs it is important, especially in less developed countries, that programs of child immunization should require as few clinic attendances and as few injections as possible. Therefore we have investigated whether a Haemophilus influenzae type b conjugate vaccine could be given safely and effectively with diphtheria-tetanus-pertussis vaccine (DTP). One hundred twenty-six Gambian infants were given both polyribosylribitol phosphate (PRP)-outer membrane protein complex (PedvaxHIB) and DTP on the same day at 8, 12 and 16 weeks of age; 60 were given the vaccines mixed in the syringe and 66 were given the vaccines separately. To minimize the injection volume the dose of PRP-OMPC used in both groups was 7.5 micrograms, which is half the usual dose. There were no significant differences in anti-PRP antibody titers between the groups after 1, 2 or 3 doses. The geometric mean titers of antibody for the two groups combined were 0.29 micrograms/ml 1 month after the first dose, 1.03 micrograms/ml after the second dose and 1.11 micrograms/ml after the third dose. Concentrations of antibodies to diphtheria, tetanus and pertussis 1 month after the third dose were not significantly different between the two groups. Systemic side effects were reported with equal frequency in the two groups and were similar to those reported elsewhere for DTP. Tenderness at the injection site was more common where the combined injection (0.75 ml) had been given than where DTP alone (0.5 ml) had been given. The main drawback to the use of these 2 vaccines together is the complexity of the mixing procedure used in this clinical trial.

The pattern of infant and childhood mortality in Upper River Division, The Gambia.

A system has been established to document births and deaths in children in a large, rural, West African population, using community reporters. Causes of death in children under the age of 5 years were investigated using post-mortem questionnaires completed by field assistants. There was a marked seasonal incidence of all major causes of death with peak rates in the rainy season. Acute lower respiratory infections (ALRI) were the most frequent cause of death in children under 5 years of age. Other major causes of death were malaria, acute gastro-enteritis and chronic diarrhoea with malnutrition. Mortality from all the major causes of death decreased with increasing village size. Our findings have implications for interventions against childhood mortality.

PIP: In preparation for the trial of a conjugated polysaccharide vaccine immunogenic in young children in The Gambia, a surveillance system was established in Upper River Division (URD) to detect deaths from all causes and from acute lower respiratory infections (ALRI) in children under five years old. The URD is the eastern-most administrative area in The Gambia, with a 1989 estimated population of 133,000. Field workers complete questionnaires on the basis of information provided by the mother or guardian of an under-five year old child dead since one month. The goal is to learn about the sequence and duration of events which took place during the child's last illness. 915 under-five year old deaths were reported over the period July 1988 to June 1989, for which post-mortem questionnaires were completed for all but 44 for various logistic reasons. Peak rates for all major causes of death were observed in the rainy season, ALRI were the most frequent cause of death, and other major causes of death included malaria, acute gastro-enteritis, and chronic diarrhea with malnutrition. Mortality from all the major causes decreased with increasing village size. The authors discuss the implications of these findings for interventions against childhood mortality.

Treponemal infection and the outcome of pregnancy in a rural area of The Gambia, west Africa.

Of 826 pregnant women studied in a rural area of The Gambia, 77 (9.3%) were seropositive for a treponemal infection (positive rapid plasma reagin [RPR] and Treponema pallidum hemagglutination [TPHA] test). The perinatal death rate recorded prospectively in babies of 77 seropositive women (39.0/1000 births) was less than that among babies of 720 seronegative women (77.6/1000 births; odds ratio, 0.48; 95% confidence interval, 0.15-1.57). No increase in mortality or morbidity was found among the children of 39 seropositive women compared with the children of 39 control women. Seropositivity was found in only 20 (1.1%) of 1872 children less than 14 years old residing in the same community. The finding that the babies of rural Gambian women seropositive for syphilis are not at risk of early death is of importance in determining the priority that should be given to establishing antenatal screening programs in The Gambia and neighboring communities.

Malaria chemoprophylaxis, birth weight and child survival.

Study of the effects of malaria chemoprophylaxis given during pregnancy on birthweight and investigation of the influence of birthweight on child survival suggest that, in a rural area of The Gambia, chemoprophylaxis given during pregnancy might reduce infant mortality by about one-fifth in the children of primigravidae but by less than 5% in the children of multigravidae. In malaria endemic areas, primigravidae should be protected against malaria not only for their own sake but also for that of their infants.

PIP: Over 3 years, researchers randomly assigned more than 1775 pregnant women (many in their 3rd trimester of pregnancy) from 41 villages near Farafenni, The Gambia, to receive either Maloprim (malaria chemoprophylaxis of pyrimethamine and dapsone) or a placebo to determine Maloprim's effects on birth weight and child survival. All births occurred at home. Field workers went to each home as soon as possible after delivery to weigh the newborns. The relative risks for neonatal and infant mortality were 23 for infants weighing less than 2000 gms and 12 for those who weighed at least 2500 gms. While they were 2.1 and 0.8, respectively, for infants weighing between 2000 and 2500 gms. 33.3% of low birth weight infants of primigravidae died compared with 19% of those of multigravidae. Taking Maloprim during pregnancy reduced infant mortality by 18% for infants of primigravidae and only 4% for infants of multigravidae. It reduced neonatal deaths by 42% for infants of primigravidae and by just 6% for infants of multigravidae. These results suggested that health workers should distribute antimalarial medicine to all primigravidae. Chemoprophylaxis along with other malaria control efforts, such as insecticide impregnated bed nets or a malaria vaccine, would protect mothers and their infants.

Orthodontic abnormalities in patients with eating disorders.

Many anorexic and bulimic patients induce vomiting by inserting their fingers in the oral cavity. We hypothesized that finger pressure could lead to tooth movement, eventually resulting in the development of orthodontic abnormalities, particularly open-bite. Twenty-four females with eating disorders and 24 matched controls underwent orthodontic examination and completed a dental questionnaire. Orthodontic abnormalities were more commonly found in the eating disorder group and open-bite was the most common abnormality seen. The presence of open-bite or other orthodontic abnormality was not associated with patient reports of self-induced vomiting, which would suggest that digital pressure was not the causative factor. The dental appearances indicated that the skeletal base pattern was abnormal in many cases. The findings could, in part, be accounted for by the fact that patients with eating disorders were less likely than controls to have completed courses of orthodontic treatment. Alternatively, the orthodontic abnormality may have contributed to the development of an eating disorder. Further study of this area is proposed.

Malaria in a peri-urban area of The Gambia.

A clinical and entomological survey of malaria was carried out in Bakau, a peri-urban coastal settlement in The Gambia, from June 1988-May 1989. Only 41 of a cohort of 560 children, aged from three months to nine-years-old, experienced a clinical episode of malaria during the observation period. The majority of cases were identified at clinics and not by regular community surveillance. In Bakau Old Town episodes of malaria were more common on the periphery of the settlement, adjacent to typical anopheline breeding sites, than in the centre. Overall malaria cases were not significantly clustered in space and time, although three pairs of cases among children sleeping in the same room at the same time were identified. A cross-sectional survey in November, at the end of the rainy season, revealed a point prevalence parasitaemia of 2.0% and a spleen rate of 0.3%. All malariometric parameters measured were much lower than any found in comparable studies undertaken in rural areas of the country, reflecting the low number of malaria vectors, Anopheles gambiae complex mosquitoes, found in Bakau. Chloroquine consumption, sleeping under bednets, houses with ceilings, the use of insecticide aerosols and burning traditional mosquito repellents may all have contributed to the low prevalence of malaria in the study area.

Evaluation of a primary health care programme in The Gambia. II. Its impact on mortality and morbidity in young children.

Mortality and morbidity in children under 5 years of age were measured in 41 villages and hamlets in a rural area of The Gambia for a 1-year period before and for a 3-year period after the introduction of a primary health care (PHC) programme into 15 of the larger villages in the area. Both infant mortality and child mortality rates fell during the post-intervention period but declines were similar in PHC and in non-PHC villages suggesting that factors such as an up-grading of the Farafenni dispensary, improvements in transport and the survey itself may have played an important part in bringing about these changes. Measurements of morbidity showed a lower prevalence of diarrhoea, vomiting or severe cough in PHC villages after the introduction of the PHC programme. Introduction of the PHC programme had no significant effect on nutritional status or on vaccine coverage. Significant improvements in the health of children in the Farafenni study area have taken place during the past 5 years but the PHC programme is probably only one of the factors that have brought about these changes.

Evaluation of a primary health care programme in The Gambia. I. The impact of trained traditional birth attendants on the outcome of pregnancy.

In 1983 a primary health care (PHC) programme was introduced into the Farafenni area of The Gambia; an important component of this programme was the identification and training of a traditional birth attendant (TBA) in each village with a population of 400 or greater. The outcome of pregnancy has been documented among women resident in 15 villages which joined the PHC programme and in 26 which were too small to do so, for 1 year before and for 3 years after the start of the programme. In PHC villages 65% of women were assisted at delivery by a trained TBA during the post-implementation period and the proportion of women who delivered in a hospital or health centre increased. Both maternal and neonatal death rates fell in PHC villages during the post-intervention period, declining to about half the levels recorded during pre-intervention surveys during the last year of the study. In non-PHC villages there was also a fall in the maternal death rate but little change in the neonatal death rate. Trained traditional birth attendants probably played some part in improving the outcome of pregnancy in the Farafenni area but other factors, such as improvements in transport, may also have contributed.

Lack of an association between acute gastroenteritis, acute respiratory infections and malaria in young Gambian children.

The incidence of acute gastrointestinal and acute respiratory infections was measured in 2 groups of approximately 750 Gambian children aged 3-59 months during a 3-year period. One group of children was partially protected against malaria by fortnightly chemoprophylaxis with Maloprim whilst children in the other group were infected much more frequently. Mortality from acute gastroenteritis and from acute respiratory infections was similar in the 2 groups. The proportions of children in each group who complained of gastrointestinal or severe respiratory symptoms on morbidity surveillance were also similar. Thus, no evidence was found to suggest that malaria plays either a direct or indirect role in causing acute gastrointestinal or respiratory infections in young children in The Gambia.

The effects of malaria chemoprophylaxis given by traditional birth attendants on the course and outcome of pregnancy.

A trial of malaria chemoprophylaxis given by traditional birth attendants was undertaken in a rural area of The Gambia where access to antenatal clinics is difficult. Women received one or more doses of Maloprim or placebo from a traditional birth attendant during 1049 of 1208 pregnancies (87%) recorded in 16 villages over a 3-year period. Primigravidae who received Maloprim had a lower parasite rate and a significantly higher mean packed cell volume than primigravidae who received placebo, and their babies were significantly heavier (6% low birth weight vs 22%). In multigravidae chemoprophylaxis reduced malaria parasitaemia but it had no beneficial effect on haemoglobin level and much less effect on birth weight than was observed in primigravidae. However, the mean birth weight of babies born to grandemultigravidae who received chemoprophylaxis was significantly higher than that of babies born to grandemultigravidae who did not.

A comparative study of Lapudrine (chlorproguanil) and Maloprim (pyrimethamine and dapsone) as chemoprophylactics against malaria in Gambian children.

A comparison has been made of Lapudrine (chlorproguanil) and Maloprim (pyrimethamine +dapsone) as malaria chemoprophylactics when given every two weeks for 3 years to Gambian children under the age of 5 years. Both drugs produced falls in spleen and malaria parasite rates and an increase in packed cell volume. Maloprim, but not chlorproguanil, significantly reduced the incidence of episodes of fever accompanied by malaria parasitaemia. Children who received Maloprim, but not those who received chlorproguanil, grew better than children in the placebo group. This finding suggests that brief clinical episodes of malaria are more important in impairing growth than more prolonged periods of asymptomatic parasitaemia. No serious side-effect attributable to either drug was observed. After chemoprophylaxis had been given for 3 malaria transmission seasons the level of resistance of Plasmodium falciparum to pyrimethamine and to chlorproguanil was about 10%.

The effects of antimalarials and folate supplements on haematological indices and red cell folate levels in Gambian children.

Haematological indices and red cell folate levels (RCF) were measured during two annual surveys in a group of Gambian children aged 3 months-5 years who were participating in a trial of malaria chemoprophylaxis with Maloprim or chlorproguanil given with or without folate supplements. Chlorproguanil was given in an adult dose of 20 mg, Maloprim as one quarter or one half of the adult dose of 25 mg pyrimethamine and 100 mg dapsone. Antimalarials and folate supplements were given fortnightly. About 20% of children had low RCF levels (less than 100 ng/ml). Among children who did not receive supplementation with folate there were no significant differences in mean RCF levels between children who received Maloprim, chlorproguanil or placebo. Among children who received folate supplements, the mean RCF was significantly lower among those receiving chlorproguanil than among the controls. Mean RCF values were similar in children who received Maloprim or placebo. If chlorproguanil is used for malaria chemoprophylaxis in young children an age-related dose should be used.

Comparison of two strategies for control of malaria within a primary health care programme in the Gambia.

Two drug strategies for the control of malaria in children aged 3-59 months have been compared in a rural area of The Gambia--treatment of presumptive episodes of clinical malaria with chloroquine by village health workers, and treatment combined with fortnightly chemoprophylaxis with 'Maloprim' (pyrimethamine/dapsone) which was also given by village health workers. Treatment alone did not have any significant effect on mortality or morbidity from malaria. In contrast, treatment and chemoprophylaxis reduced overall mortality in children aged 1-4 years, mortality from probable malaria, and episodes of fever associated with malaria parasitaemia. A high level of compliance with chemoprophylaxis was obtained and no harmful consequences of chemoprophylaxis were observed.