Antibody response to 17D yellow fever vaccine in Ghanaian infants.

OBJECTIVES: To assess the seroresponses to yellow fever vaccination at 6 and 9 months of age; assess any possible adverse effects of immunization with the 17D yellow fever vaccine in infants, particularly at 6 months of age. METHODS: Four hundred and twenty infants who had completed BCG, OPV and DPT immunizations were randomized to receive yellow fever immunization at either 6 or 9 months. A single dose of 0.5 ml of the reconstituted vaccine was administered to each infant by subcutaneous injection. To determine the yellow fever antibody levels of the infants, each donated 1 ml whole blood prior to immunization and 3 months post-immunization. Each serum sample was titred on Vero cells against the vaccine virus. FINDINGS: The most common adverse reactions reported were fever, cough, diarrhoea and mild reactions at the inoculation site. The incidences of adverse reactions were not statistically different in both groups. None of the pre-immunization sera in both age groups had detectable yellow fever antibodies. Infants immunized at 6 months recorded seroconversion of 98.6% and those immunized at 9 months recorded 98% seroconversion. The GMT of their antibodies were 158.5 and 129.8, respectively. CONCLUSIONS: The results indicate that seroresponses to yellow fever immunization at 6 and 9 months as determined by seroconversion and GMTs of antibodies are similar. The findings of good seroresponses at 6 months without significant adverse effects would suggest that the 17D yellow fever vaccine could be recommended for use in children at 6 months in outbreak situations or in high risk endemic areas.

Health centre versus home presumptive diagnosis of malaria in southern Ghana: implications for home-based care policy.

A study was conducted in 1997 to compare the accuracy of presumptive diagnosis of malaria in children aged 1-9 years performed by caretakers of the children to that of health centre staff in 2 ecological zones in southern Ghana. Similar symptoms were reported in the children at home and at the health centre. In the home setting, symptoms were reported the same day that they occurred, 77.6% of the children with a report of fever were febrile (axillary temperature > or = 37.5 degrees C) and 64.7% of the reports of malaria were parasitologically confirmed. In the health centre, the median duration of symptoms before a child was seen was 3 days (range 1-14 days), 58.5% of the children with a report of fever were febrile and 62.6% of the clinically diagnosed cases were parasitologically confirmed. In the 2 settings almost all the infections were due to Plasmodium falciparum. Parasite density was 3 times higher in the health centre cases compared to the home-diagnosed cases. Early and appropriate treatment of malaria detected in children by caretakers may prevent complications that arise as a result of persistence of symptoms and attainment of high parasitaemic levels.

Comparison of AIK-C measles vaccine in infants at 6 months with Schwarz vaccine at 9 months: a randomized controlled trial in Ghana.

In a randomized controlled trial in a measles endemic area, standard-dose (4.0 log10pfu) AIK-C measles vaccine administered at 6 months of age was compared to standard-dose Schwarz vaccine (3.7log10pfu) given at 9 months. Seroconversion rates at 3 and 6 months after immunization in the two groups were comparable and similar. The geometric mean titres achieved were, however, significantly higher in the Schwarz group (P < 0.05). No immediate serious side-effects were observed with either vaccine. We conclude that standard-dose AIK-C measles vaccine can be recommended for measles immunization in children below 9 months of age, especially in highly endemic and high-risk areas in developing countries.

PIP: The seroresponse of standard-dose heat-stable AIK-C measles vaccine administered to infants at 6 months of age was compared to that of standard-dose Schwarz vaccine administered at 9 months of age in a measles-endemic area in West Africa. The study was conducted in Asamankese, the capital town of Ghana's East Akim District. Infants 24-27 weeks of age who had been attending the Asamankese maternal-child health clinic regularly and had received all the required immunizations were enrolled and randomly assigned to receive the AIK-C (n = 184) or the Schwarz (n = 193) vaccine. No severe adverse reactions were reported during the 10-day follow-up period in either vaccine group. In the AIK-C group, 96.9% of infants who were seronegative at preimmunization and 79.4% of those with preexisting antibodies had seroconverted by 3 months after immunization; at 6 months after immunization, these rates were 97.3% and 100%, respectively. In the Schwarz group, 98.2% of infants seronegative at immunization and 100% of those with preexisting antibodies seroconverted by 3 months after immunization; at 6 months, these rates were 99.1% and 80%, respectively. Although the geometric mean titres achieved were significantly higher in the Schwarz vaccine group, these titres were above the protective level of 200 mIU in the AIK-C group. Administration of measles vaccine at a younger age may be more easily incorporated into current Expanded Program on Immunization schedules.

Human T-cell recognition of synthetic peptides representing conserved and variant sequences from the merozoite surface protein 2 of Plasmodium falciparum.

Merozoite surface protein 2 (MSP2) is a malaria vaccine candidate currently undergoing clinical trials. We analyzed the peripheral blood mononuclear cell (PBMC) response to synthetic peptides corresponding to conserved and variant regions of the FCQ-27 allelic form of MSP2 in Ghanaian individuals from an area of hyperendemic malaria transmission and in Danes without exposure to malaria. PBMC from 20-39% of Ghanaians responded to each of the peptides by proliferation and 29-36% had PBMC which produced interferon-gamma (IFN-gamma) in response to peptide stimulation. In Danes, there was no proliferation to two of the peptides and only PBMC from 5% of the individuals proliferated to the other three peptides. IFN-gamma production was not detected to any peptide. In both Danes and Ghanaians in only a few instances was IL-4 detected in the PBMC cultures. Overall PBMC from 79% of the Ghanaians responded by proliferation and/or cytokine secretion to at least one of three peptides tested, whereas responses were only observed in 14% of Danes (P = 0.002). These data suggest that the Ghanaians had expanded peripheral blood T-cell populations recognizing the peptides as a result of natural infection. The findings are encouraging for the development of a vaccine based on these T-epitope containing regions of MSP2, as the peptides were broadly recognized suggesting that they can bind to diverse HLA alleles and also because they include conserved MSP2 sequences. Immunisation with a vaccine construct incorporating the sequences present in these peptides could thus be expected to be immunogenic in a high percentage of individuals and lead to the establishment of memory T-cells, which can be boosted through natural infection.

Malaria-related beliefs and behaviour in southern Ghana: implications for treatment, prevention and control.

A research infrastructure was established in two ecological zones in southern Ghana to study the variables of malaria transmission and provide information to support the country's Malaria Action Plan (MAP) launched in 1992. Residents' beliefs and practices about causes, recognition, treatment and prevention of malaria were explored in two ecological zones in southern Ghana using epidemiological and social research methods. In both communities females constituted more than 80% of caretakers of children 1-9 years and the illiteracy rate was high. Fever and malaria, which are locally called Asra or Atridi, were found to represent the same thing and are used interchangeably. Caretakers were well informed about the major symptoms of malaria, which correspond to the current clinical case definition of malaria. Knowledge about malaria transmission is, however, shrouded in many misconceptions. Though the human dwellings in the study communities conferred no real protection against mosquitoes, bednet usage was low while residents combatted the nuisance of mosquitoes with insecticide sprays, burning of coils and herbs, which they largely considered as temporary measures. Home treatment of malaria combining herbs and over-the-counter drugs and inadequate doses of chloroquine was widespread. There is a need for a strong educational component to be incorporated into the MAP to correct misconceptions about malaria transmission, appropriate treatment and protection of households. Malaria control policies should recognize the role of home treatment and drug shops in the management of malaria and incorporate them into existing control strategies.

Randomized controlled trial of acellular diphtheria, pertussis and tetanus vaccines in southern Ghana.

A randomized controlled trial of acellular diphtheria/pertussis/tetanus (ADPT) freeze-dried and liquid vaccines in infants was conducted in a peri-urban community (Ashaiman) in southern Ghana. Immunogenicity of the acellular vaccines, persistence of antibodies and adverse reactions were compared with those achieved with a whole-cell diphtheria-pertussis-tetanus (DPT) vaccine. The incidence of pertussis in the vaccine groups and prevalence of pertussis in children under 5 years of age in the study area were also determined. The acellular vaccines produced significantly fewer local and systemic reactions. Local reactions such as swelling and redness were observed in 2% (8/399) to 2.3% (9/385) of the acellular vaccine recipients as against 31% (122/394) in the whole-cell vaccine group. Fever ( > or = 37.5 degrees C) occurred in 7.27% (29/399) to 9.8% (38/385) in the acellular vaccine groups compared with 36.6% (145/394) in the whole-cell vaccine group. Geometric mean titres (GMTs), measured by ELISA, to pertussis toxin (PT) and filamentous haemagglutinin (FHA) were significantly higher in the acellular vaccine groups than in the whole-cell DPT (WCDPT) group. There were no significant differences in the GMTs of tetanus and diphtheria antitoxins between the two groups after each vaccination. Twelve months after primary vaccination, GMTs to PT in the freeze-dried, liquid ADPT groups and the WCDPT group have fallen from 56.23, 62.63 and 44.97 ELISA U/ml to 6.08, 6.18 and 11.30 ELISA U/ml, respectively. GMTs to FHA in all the vaccine groups also dropped during the same period from 49.94, 41.73 and 20.74 ELISA U/ml to 7.26, 7.72 and 5.91 ELISA U/ml, respectively. In this comparative controlled trial, the ADPT vaccines were more immunogenic, with less local and systemic reactions, than the WCDPT vaccine but there was a considerable drop in antibody titres in all the vaccine groups 12 months after primary vaccination. However, the levels of titres of anti-PT and anti-FHA antibodies in all the three vaccines that confer protection are not known. Further studies are necessary to provide this information in order to assess the need for subsequent booster doses after primary immunization with both ADPT and WCDPT vaccines.

Impact of primary health care on child morbidity and mortality in rural Ghana: the Gomoa experience [corrected].

The impact of a combination of PHC intervention activities on child survival, growth, morbidity and mortality was assessed in three selected rural communities (Gomoa Fetteh, Gomoa Onyadze/Otsew Jukwa and Gomoa Mprumem) in the Central Region of Ghana from 1987 to 1990. EPI, provision of basic essential drugs and supplies for the treatment of common childhood diseases, treatment of the sick child, growth monitoring, health education, provision of antenatal services, family planning, training and supervision of Community Health Workers, disease surveillance and special studies were the major PHC strategies used to improve the health of the child and the pregnant woman in the three communities. These activities in their totality have had significant impact on morbidity and mortality in children under five and on maternal mortality in children under five and on maternal mortality over the study period 1987 to 1990. Although malaria, acute respiratory infections and diarrhoea diseases continue to be major causes of childhood morbidity, deaths due to these diseases have dramatically declined. Measles and other vaccine preventable diseases no longer contribute significantly to childhood morbidity and mortality. Infant and under five mortality have been reduced from 114.6/1000 and 155.6/1000 live births to 40.8/1000 and 61.2/1000 live births respectively. The crude birth rates however, remain almost the same over the five year period (43 to 48/1000 pop.) but crude death rates have declined (11 to 12.4/1000 pop.).(ABSTRACT TRUNCATED AT 250 WORDS)

Randomized, controlled trial of trivalent oral poliovirus vaccine (Sabin) starting at birth in Ghana.

To evaluate the efficacy of the schedule currently recommended for immunization with trivalent oral poliovirus vaccine (TOPV) (i.e., at birth, 6 weeks, 10 weeks, and 14 weeks after birth), we randomly assigned 452 infants into test (231 infants) and control (221 infants) groups. The test group received TOPV as currently recommended, and the dose at birth was omitted for the control group. At 10, 14, and 18 weeks of age, the levels of poliovirus neutralizing antibodies as well as seroconversion rates were consistently higher for the test group than for the control group. The final seroconversion rates against poliovirus types 1, 2, and 3 were 83.5%, 91% and 83%, respectively, for the test group and 75%, 83.2%, and 79.1%, respectively, for the control group. The TOPV immunization schedule starting at birth therefore produced better results. Seroconversion rates as well as antibody levels were highest in infants with low maternal antibodies.

Antibody response to measles immunization in rural Ghanaian infants.

We investigated optimal age of measles immunization in infants aged 3-11 months in rural villages of Ghana, and determined seroconversion rate in the same infant population following further attenuated measles vaccination with Schwarz vaccine. The prevalence of passively acquired antibody was 11 per cent in infants younger than 6 months, 10 per cent in infants 6 months old, and 3 per cent in infants 7 months old or older. Seroconversion rates in each age group were less than 50, 87, and 92 per cent, respectively. We then immunized 47 7-month-old infants. The seroconversion rate was 92 per cent in this group. There were no clinical adverse effects due to the vaccination. We conclude that measles vaccination could be administered effectively at the age of 7 months with an excellent seroconversion rate.

Species composition and inversion polymorphism of the Anopheles gambiae complex in some sites of Ghana, west Africa.

Samples of Anopheles gambiae s.1. were collected from eight localities belonging to four of the five main ecological strata of Ghana. Analysis of ovarian polytene chromosomes revealed the presence of A. gambiae s.s. in all the sites studied, while A. arabiensis was detected only in the extreme northern locality of Navrongo and A. melas in some southern sites. Anopheles arabiensis showed a degree of inversion polymorphism comparable to the one observed in other West African countries. The analysis of the chromosomal polymorphism of A. gambiae s.s. showed the presence of the FOREST form in the rain forest localities and the SAVANNA form in the coastal savanna sites. The MOPTI form occurred sympatrically with the SAVANNA form in the northernmost locality. The possible influence of the presence of various taxa of the A. gambiae complex and of their intra-specific variants on malaria vectorial system is discussed.

A randomized controlled trial of two acellular pertussis-diphtheria-tetanus vaccines in primary immunization in Ghana: antibody responses and adverse reactions.

Two acellular pertussis vaccines combined with diphtheria and tetanus toxoids (APDT vaccines) were compared with a whole cell PDT (WCPDT) vaccine in primary immunization in Ghana. One is a liquid vaccine which is used for general immunization in Japan and the other is a freeze-dried vaccine newly developed as a heat-stable vaccine. Eighty-nine infants were recruited in the study. Sixty-eight who completed three doses of the immunization were assessed for immunological responses. Twenty-one dropped out because of sickness or moving from the study area. A total of 242 vaccinations in 89 infants were followed up for adverse reactions. Geometric mean titres (GMTs) to filamentous haemagglutinin in the two APDT vaccinees were significantly higher than in the WCPDT recipients. GMTs to pertussis toxin, diphtheria and tetanus toxoids were not significantly different among the three groups. Seropositive rates to pertussis antigens, tetanus and diphtheria toxoids were 94.4 to 100% in the two APDT vaccines. Systemic reactions within 7 days of inoculation were similarly low in the three groups, but significantly fewer infants had local reactions after either of the two APDT vaccines than after the WCPDT vaccine.

In vitro responses of P. falciparum parasites to chloroquine, amodiaquine and quinine in two ecological zones in Ghana.

Blood specimens were taken from 318 school children with at least 1,000 and not more than 80,000 P. falciparum asexual parasites per microliter of blood for a 30 hour in vitro microtest of P. falciparum asexual parasites responses to chloroquine, amodiaquine and quinine. The study was conducted in primary schools in four urban and three rural communities in the costal and forest zones in Ghana between June 1988 and December 1990. Chloroquine resistance was present in 58.7 pc (54/92) and 3.9 pc (4/103) of the successful in vitro tests in the coastal and forest zones respectively. Resistance to amodiaquine was recorded in 28.6 pc (12/42) of the successful tests in coastal zone. There was no resistance to quinine in any of the ecological zones. Concentrations of the three drugs in pmol required for 90 pc inhibition of schizont maturation were generally higher in communities in the coastal zone than those in the forest zone. The results suggest an increase in sensitivity or a reduction in resistance of P. falciparum to the drugs from the coast to the forest zone.

Seasonal characteristics of malaria infection in under-five children of a rural community in southern Ghana.

In a quarterly survey of malaria infection in the under-five children conducted at Gomoa Onyadze/Otsew Jukwa, a rural community in the Central Region of Ghana from December, 1986 to September, 1987, crude parasite rates ranged from 19.6 to 33.5 per cent in the dry season (December and March) and 33.0 to 44.0 per cent in the wet season (June and September). P. falciparum was the predominant parasite species by parasite formula analysis with higher rates in the rainy season (94.2 to 95.8 per cent) compared to that of the dry season (51.4 to 78.8 per cent). P. malariae (20.4 per cent), P. ovale (2.7 per cent) and mixed infection rates were higher in the dry season (December and March). As high as 30.4 to 44.8 per cent of positive parasite slides had parasite density of above 3200 per microliter of blood (above class 6 degree of parasitaemia). Depending on the season 7.2-27.3 per cent of children had parasite density above 25,600 per microliter of blood (above class 10 degree of parasitaemia).

Plasmodium falciparum: sensitivity to chloroquine in vivo in three ecological zones in Ghana.

4690 children aged 6-15 years in 5 urban and 4 rural communities in 3 ecological zones in Ghana were screened from June 1988 to December 1990 to provide suitable candidates for the World Health Organization standard in vivo test for susceptibility of Plasmodium falciparum to chloroquine. 1880 (40.1%) had parasitaemia, mostly (83.7-98.6%) due to P. falciparum infection. Of the 626 in vivo tests performed, 570 (91.1%) showed sensitivity to chloroquine and 56 (8.9%) responses were classified as resistant to chloroquine at RI (5.1%) and RII (3.8%). The resistance responses were commonest (17.1-22.7%) in the coastal zone, followed by the savanna zone (8.6-10.0%), and lowest in the forest zone (3.1-6.3%). The RII responses occurred mainly in communities in the coastal zone. There was no RIII resistance in any zone. The pattern of RI (early) and RII responses of P. falciparum to chloroquine in this study suggested an increase in sensitivity, or a reduction in resistance, of P. falciparum to chloroquine from the coast to the forest and northern savanna zones, and from the urban to the rural communities in each zone in Ghana.