A. K. Bradley

MENINGOCOCCAL DISEASE AND SEASON IN SUB-SAHARAN AFRICA

Abstract The incidence of meningococcal disease varies seasonally in both tropical and temperate countries. This association is most apparent in sub-Saharan Africa, where almost all epidemics start in the dry season and abate during the rains. Meningococcal carriage rates do not vary with season either in Africa or in temperate countries, suggesting that seasonal factors have little influence on the frequency of meningococcal transmission. It is suggested that changes in the ratio of clinical to subclinical cases of infection are more important than changes in the frequency of transmission in producing seasonal variations in the incidence of meningococcal disease. Some evidence to support this hypothesis was obtained during an epidemic of group A meningococcal disease in northern Nigeria in 1977-79.

Deaths in infancy and early childhood in a well-vaccinated, rural, West African population.

A survey of deaths in children under the age of 7 years was made over a 1-year period in a rural area of The Gambia with few facilities for curative medicine but with a good record of infant immunizations. One hundred and eighty-four deaths were investigated. Only 12% of deaths occurred in a hospital or health centre but an attempt was made to establish a cause of death by interviewing the family of each dead child and by examining any health records that were available. The infant mortality rate was 142 per 1000 live births and the child mortality rate (death in children aged 1-4 years) 43 per 1000 per year. Acute respiratory infections, malaria and chronic diarrhoea with marasmus were the most frequent causes of death after the 1st month of life. Few children died of diseases that could have been prevented by routine immunizations. An effective immunization programme has probably had some effect on deaths in infancy and early childhood but it will be necessary to find ways of preventing deaths from malaria, acute respiratory infections and chronic diarrhoea/marasmus at the primary health care level if infant and childhood mortality are to be reduced further in rural areas of The Gambia.

Malaria chemoprophylaxis with chloroquine in young Nigerian children. I. Its effect on mortality, morbidity and the prevalence of malaria.

One hundred and ninety-eight Nigerian children who received weekly chemoprophylaxis with chloroquine from shortly after birth until the age of one year or two years and 185 age-matched controls were studied. Chemoprophylaxis with chloroquine was partially, but not completely, effective in controlling malaria. Clinical malaria was documented significantly less frequently in protected children than in control children, and only 9% of random blood films obtained from protected children were positive for Plasmodium falciparum while 41% of random blood films from control children were positive for this parasite. Mean malaria antibody levels were lower in protected than in control children; for ELISA and precipitin antibodies the difference between the two groups was less marked at two years than at one year. Mortality was similar among protected and among control children. No rebound mortality or morbidity was observed after chemoprophylaxis was stopped.

Malaria chemoprophylaxis with chloroquine in young Nigerian children. III. Its effect on nutrition.

The nutrition of a group of Nigerian children who received weekly chemoprophylaxis with chloroquine during their first one or two years of life was compared with the nutrition of a group of children exposed frequently to malaria. Fewer episodes of severe malnutrition and fewer deaths from malnutrition occurred among protected than among control children. Protected children tended to be taller and heavier than control children and to have a larger mid-upper arm circumference. Mean serum albumin and pre-albumin levels were higher in protected than in control children. However differences between the two groups were small and only in a few instances were they statistically significant.

Failure of meningococcal vaccination to stop the transmission of meningococci in Nigerian schoolboys.

A combined group A and group C meningococcal polysaccharide vaccine was given to 438 Nigerian schoolboys shortly before an outbreak of group A meningococcal disease occurred in their school. Four months after vaccination the carriage rate of group A meningococci among vaccinated subjects (11%) was no different from that found among the controls (12%), although a good antibody response to both components of the vaccine was observed. One case of group A meningococcal disease was recorded amongst 438 vaccinated subjects while five cases occurred among 874 controls.

Malaria chemoprophylaxis with chloroquine in young Nigerian children. IV: Its effect on haematological measurements

Haematological measurements were made in 198 Nigerian children aged three months to two years who received weekly malaria chemoprophylaxis with chloroquine from shortly after birth until the age of one or two years and in 185 age-matched control children. Children protected against malaria had a higher mean haemoglobin level and a higher packed cell volume than control children, and they showed fewer abnormalities of their red cells. Total and differential white blood cell counts, mean plasma folate and mean serum ferritin concentrations were similar in both groups of children. However, the geometric mean red cell folate level of children exposed to malaria was significantly higher than the mean level of control children; and it may be that malaria raises the red cell folate through intracellular synthesis by malaria parasites. Children with malaria parasitaemia had a significantly lower haemoglobin and packed cell volume and a significantly higher geometric mean red cell folate and ferritin level than children without parasitaemia. Serum ferritin is probably an unreliable index of iron status in children with malaria.

Malaria chemoprophylaxis with chloroquine in young Nigerian children: II. Effect on the immune response to vaccination

The immune response of 198 young Nigerian children protected against malaria by chemoprophylaxis with chloroquine to immunization with triple, poliomyelitis, measles, typhoid, meningococcal and BCG vaccines was compared with the immune response to vaccination of 185 control children. Good responses to triple, measles and BCG vaccines were shown by children in both groups; poorer responses were obtained to poliomyelitis, typhoid and meningococcal vaccines. The response to immunization of protected children was similar to that observed among control children for all the vaccines tested except for meningococcal polysaccharide vaccine. Protected children showed a significantly greater antibody response to both group A and group C meningococcal polysaccharides than control children. This finding supports the results of previous studies which have shown that the immune response to meningococcal polysaccharide vaccines is adversely affected both by acute malaria and by asymptomatic malaria parasitaemia.

The immune response to vaccination in undernourished and well-nourished Nigerian children.

The immune response of young Nigerian children to a full course of infant immunizations was studied in relation to their nutritional state at the time of vaccination. No significant correlations were found between anthropometric measurements made at the time of vaccination and the antibody response to triple, polio, measles, meningococcal and typhoid vaccines. Significant correlations were found between serum pre-albumin levels and the response to group A meningococcal polysaccharide vaccine and between serum albumin levels and the response to group C meningococcal polysaccharide vaccine. These correlations may reflect the depressive effect of malaria both on serum albumin and pre-albumin levels and on immune responsiveness to meningococcal polysaccharides. No significant correlations were found between nutritional state at the time of BCG vaccination and the development of a positive tuberculin reaction five weeks later. We conclude that under-nutrition has little or no effect on the immune response to vaccines used in routine infant immunization programmes.

Malaria and haemoglobin genotype in young northern Nigerian children

Plasmodium falciparum and P. malariae were found less frequently in blood obtained from Nigerian children under the age of two years who had the haemoglobin genotype AS than in blood films obtained from those who had the genotype AA. However, differences between the two groups were statistically significant only for P. falciparum asexual forms. The prevalence of malaria antibodies, as measured by an ELISA, did not differ significantly between the two groups.

A comparison of chloroquine and pyrimethamine as malaria chemoprophylactics in young Nigerian children

The efficacy of chloroquine and pyrimethamine as malaria chemoprophylactics was investigated in young Nigerian children. Chloroquine resistance had not been documented in the study area; pyrimethamine resistance was probably present but uncommon. Children who received weekly chemoprophylaxis with pyrimethamine had a lower prevalence of malaria parasitaemia and malaria antibodies than children who received weekly chemoprophylaxis with chloroquine. Pyrimethamine given monthly gave a comparable degree of protection to chloroquine given weekly. Chloroquine frequently induced vomiting in young children and this may have impaired its efficacy as a prophylactic. We conclude that, in an area where neither chloroquine nor pyrimethamine resistance is prevalent, pyrimethamine is a better chemoprophylactic for young children than chloroquine.