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Biomedical subjects

K A Koram

Publications and source records attributed to K A Koram.

At least 19 recordsLinked to original sources
PubMed2003

Does apolipoprotein E polymorphism influence susceptibility to malaria?

Outcome of infection varies greatly among people, and in the case of three very different viruses, it is determined by apolipoprotein E (APOE) genotype. APOE might affect outcome of malaria infection also, since apoE protein and the protozoon (like the viruses) share cell entry mediators (heparan sulphate proteoglycans and/or specific apoE receptors). APOE polymorphisms give rise to protein variants that differ in binding strength to these mediators; thus, the extent of competition between apoE and protozoon for cell entry, and hence magnitude of protozoan damage, might depend on apoE isoform. Genotypes of infants infected with malaria were examined. It was found that APOE epsilon 2 homozygotes became infected at an earlier age than those carrying the other genotypes, the difference being statistically significant. Parasite densities, all of which were low, did not differ significantly. This effect, although based on small numbers, suggests that APOE epsilon 2 may be a risk factor for early infection.

Animals↗
PubMed2002

Absolute levels and ratios of proinflammatory and anti-inflammatory cytokine production in vitro predict clinical immunity to Plasmodium falciparum malaria.

The relationship between malaria-related outcomes and cytokine production in whole blood cultures associated with cellular immune responses and immunity to Plasmodium falciparum malaria was examined in a study in southern Ghana. Production of malaria-specific interferon (IFN)-gamma was associated with reduced risk of fever and clinical malaria. Protective IFN-gamma responses were induced by live schizonts but not by dead parasites. Production of malaria-specific tumor necrosis factor (TNF)-alpha was associated with reduced risk of fever during follow-up. Baseline levels of TNF-alpha and phytohemagglutinin (PHA)-induced interleukin (IL)-10 were positively associated with hemoglobin concentration. IL-12 production was associated with reduced risk of parasitemia. PHA-induced transforming growth factor-beta production was associated with reduced risk of fever during follow-up. High ratios of proinflammatory to anti-inflammatory cytokines were associated with increased risk of fever and higher hemoglobin concentrations. Thus, absolute levels and ratios of proinflammatory and anti-inflammatory cytokines influence susceptibility to infection, clinical disease, and anemia. These data contradict data from cross-sectional clinical studies and indicate a need for detailed analysis of the relationship between cellular immunity to malaria and resistance to disease.

Adolescent↗
PubMed2001

Frequent and persistent, asymptomatic Plasmodium falciparum infections in African infants, characterized by multilocus genotyping.

To determine the duration and complexity of naturally acquired Plasmodium falciparum infections in small children, a longitudinal cohort study of 143 newborns was conducted in coastal Ghana. On average, children experienced 2 episodes of infection in their first 2 years of life, the median duration of an asymptomatic infection was <4 weeks, and estimates of the mean number of parasite genotypes per infection were 1.15-2.28. Nevertheless, 40% of the children experienced infections lasting </=12 weeks, and both the duration and complexity of infections increased with age. The longest period of continual infection was 64 weeks, and the maximum persistence of a single parasite genotype was 40 weeks. Thus, malaria infections in infants <5 months old tend to be asymptomatic and rapidly cleared; persistent asymptomatic parasitemia is more common in children >5 months old. The ability of very young children to clear or control malaria infections indicates the presence of effective innate or immune antiparasite mechanisms.

Age Factors↗
PubMed2001

Novel Plasmodium falciparum clones and rising clone multiplicities are associated with the increase in malaria morbidity in Ghanaian children during the transition into the high transmission season.

A survey of Plasmodium falciparum infection and clone multiplicity in Ghanaian children was carried out to study the effect of the onset of the malaria transmission season on disease incidence. Fortnightly blood samples were collected from 40 children living in the rural town of Dodowa, between February and August 1998. P. falciparum parasite densities were calculated and PCR genotyping was carried out using the polymorphic MSP-1 and MSP-2 genes as target loci for the estimation of the number of parasite clones in each sample. The average clone number was estimated using maximum likelihood techniques and the minimum number of clones per patient was analysed for the effects of age, sex, season, minimum number of clones per child, level of parasitaemia and parasite genotype. The statistical analysis indicated that the more clones a child carried, the more likely they were to have a clinical malaria episode. This was true after adjusting for age and season effects and for the measured circulating parasitaemia. The probability of clinical disease also increased if the MSP-1 MAD 20 and the MSP-2 FC 27 alleles were present. This longitudinal analysis thus indicates that the probability of a Ghanaian child having a symptomatic malaria episode is positively associated with both increasing numbers and novel types of P. falciparum clones.

Animals↗
PubMed2001

Do maternally acquired antibodies protect infants from malaria infection?

Neonates and infants are relatively protected from clinical malaria, but the mechanism of this protection is not well understood. Maternally derived antibodies are commonly believed to provide protection against many infectious diseases, including malaria, for periods of up to 6-9 months but several recent epidemiological studies have produced conflicting results regarding a protective role of passively acquired antimalarial antibodies. In this article, we review the epidemiological evidence for resistance of young infants to malaria, summarize the data on antimalarial antibody levels and specificity and their association with protection from malaria infection or clinical disease, and explore alternative explanations for resistance to malaria in infants.

Antibodies, Protozoan↗
PubMed2001

Incidence of symptomatic and asymptomatic Plasmodium falciparum infection following curative therapy in adult residents of northern Ghana.

Adult residents of holoendemic malaria regions in Africa have a naturally acquired immunity (NAI) to malaria that renders them more resistant to new infections, limits parasitemia, and reduces the frequency and severity of illness. Given such attributes, it is not clear how one might evaluate drug or vaccine efficacy in adults without serious confounding. To determine symptomatic and asymptomatic malaria attack rates in adults of northern Ghana, 197 men and women underwent curative therapy for any pre-existing malaria infections at the start of the high transmission (wet) season. They were monitored for first parasitemia and first clinical episode of infection by Plasmodium falciparum over a 20-week period (May-October 1996). The cumulative incidence of primary infection by P. falciparum was 0.98 and incidence density of infection was calculated to be 7.0 cases/person-year. Symptoms were reported by 19.5% of the individuals at the time of first recurrent parasitemia. Incidence of infection, parasite density, and the frequency of symptoms were comparable in males and females. The results suggest that NAI did not provide these adults with significant defense against rapid re-infection and suggest that this population-infection design could serve to demonstrate the efficacy of a drug or vaccine in preventing parasitemia.

Adolescent↗
PubMed2001

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.

Antibodies, Viral↗
PubMed2000

Naturally acquired antibodies to the glutamate-rich protein are associated with protection against Plasmodium falciparum malaria.

The development of effective malaria vaccines depends on the identification of targets of well-defined protective immune responses. Data and samples from a longitudinal study of a cohort of children from coastal Ghana were used to investigate the role of antibody responses to 3 regions of the Plasmodium falciparum glutamate-rich protein (GLURP). The data show that levels of the GLURP-specific IgG that occurs in the nonrepeat region of the antigen are significantly correlated with clinical protection from P. falciparum malaria, after correction for the confounding effect of age. Furthermore, levels of cytophilic antibodies were found to be of particular importance for protection, lending support to the hypothesis that antibody-dependent cellular inhibition is the important element in GLURP-specific protective immunity.

Adolescent↗
PubMed2000

High frequency of circulating gamma delta T cells with dominance of the v(delta)1 subset in a healthy population.

TCR gamma delta(+) cells constitute <5% of all circulating T cells in healthy, adult Caucasians, and V(delta)1(+) cells constitute a minority of these cells. In contrast to TCR alpha beta(+) cells, their repertoire is selected extrathymically by environmental antigens. Although increased frequencies of V(delta)1(+) cells are found in several diseases, their function remains obscure. Here we show that the frequency of peripheral blood gamma delta T cells in healthy West Africans is about twice that of Caucasians, mainly due to a 5-fold increase in V(delta)1(+) cells, which is consequently the dominant subset. No age dependency of V(delta)1 frequencies was identified and the V(delta)1(+) cells in the African donors did not show preferential V(gamma) chain usage. Analysis of the CDR3 region size did not reveal any particular skewing of the V(delta)1 repertoire, although oligoclonality was more pronounced in adults compared to children. The proportions of CD8(+), CD38(+) and CD45RA(hi)CD45RO(-) cells within the V(delta)1(+) subset were higher in the African than in the European donors, without obvious differences in expression of activation markers. No significant correlations between levels of V(delta)1(+) cells and environmental antigens or immunological parameters were identified. Taken together, the evidence argues against a CDR3-restricted, antigen-driven expansion of V(delta)1(+) cells in the African study population. Our study shows that high frequencies of TCR gamma delta(+) cells with dominance of the V(delta)1(+) subset can occur at the population level in healthy people, raising questions about the physiological role of V(delta)1(+) T cells in the function and regulation of the immune system.

Adult↗
PubMed2000

Lack of association between maternal antibody and protection of African infants from malaria infection.

Maternally derived antibodies are believed to protect infants against infection, but there is little direct evidence for a protective role of passively acquired antibodies against malaria. A longitudinal study of malaria infection in 143 infants was conducted in a region of southern Ghana where Plasmodium falciparum is endemic. Infants born in the high-transmission season were less likely to become infected in the first 20 weeks of life than children born in the low-transmission season. Plasma, obtained at birth, was tested for immunoglobulin G (IgG) and IgG subclasses to P. falciparum schizonts and recombinant circumsporozoite antigen, MSP-1(19), MSP-2, AMA-1, and Pf155 (also called ring-infected erythrocyte surface antigen). Antibody levels at birth were not associated with resistance to malaria infection. On the contrary, antibodies at birth were positively associated with infection, indicating that high levels of maternally derived antibodies represent a marker for intensity of exposure to malaria infection in infants. However, all five children who experienced high-density infections (>100 parasites/microl of blood) were seronegative for MSP-1(19) at the time of infection.

Adolescent↗
PubMed2000

Severe anemia in young children after high and low malaria transmission seasons in the Kassena-Nankana district of northern Ghana.

Malaria and anemia accounted for 41% and 18% respectively of hospital deaths in the Kassena-Nankana district of northern Ghana during 1996. We measured hemoglobin (Hb), malaria prevalence, and anthropometric indices of 6--24-month-old infants and young children randomly selected from this community at the end of the high (May-October, n = 347) and low (November-April, n = 286) malaria transmission seasons. High transmission season is characterized by rainfall (the equivalent of 800-900 mm/yr.), while the remaining months receive less than 50 mm/yr. Severe anemia, defined as Hb < 6.0 g/dL, was 22.1% at the end of the high transmission season compared to 1.4% at the end of the low transmission season (Odds Ratio [OR] = 20.1; 95% CI: 7.1-55.3). Parasitemia was 71% and 54.3% at these time points (OR = 2.1; 95% CI: 1.5-2.9). Nutritional anemia appeared to have little impact upon this seasonal difference since anthropometric indices were comparable. Although the relative contributions of other causes of severe anemia were not assessed, repeated malaria infections may be a primary determinant of severe anemia among infants and young children during the high transmission season.

Anemia↗
PubMed1999

Lymphatic filariasis related perceptions and practices on the coast of Ghana: implications for prevention and control.

A qualitative study to investigate lymphatic filariasis related perceptions and practices that may be relevant for the design of appropriate health education and control programmes was conducted in four endemic villages in coastal Ghana. The villagers were aware of the common manifestations of filariasis, such as adenolymphangitis (ADL), lymphoedema, elephantiasis and hydrocele, which were specifically described with local terminology. ADL attacks were identified as the most dreaded health problem in the communities, and elephantiasis and hydrocele also ranked high in importance among reported diseases. Generally the respondents did not accept the mosquito theory of transmission, but they believed in other physical, and in spiritual and hereditary causes. Hydrocele was considered to have no link to the other disease manifestations. The manifestations were most often treated with herbal preparations which were used orally, smeared on affected parts or given as enema. In some cases the affected parts were scarified before herbal preparations were applied. The manifestations affected the work output of its victims and subjected them to hardships such as teasing, unsuitability for marriage, sexual dysfunction and divorce. Although the etiology was seen as different, the local perception of the developmental process of elephantiasis closely paralleled that of the biomedical understanding. It is suggested that this coincidence is used as an entry point for health education, to advance a broader biomedical knowledge on etiology, transmission and treatment options, and thereby to ensure co-operation of the target populations in the control of this complex disease.

Elephantiasis, Filarial↗
PubMed1998

Increased eosinophil activity in acute Plasmodium falciparum infection--association with cerebral malaria.

To assess the eosinophil response to Plasmodium falciparum infection a cohort of initially parasite-free Ghanaian children was followed for 3 months. Seven of nine children who acquired an asymptomatic P. falciparum infection showed increase in eosinophil counts, while a decrease was found in seven of nine children with symptomatic malaria, and no change was observed in 14 children who remained parasite-free. In a hospital-based study, paediatric patients with cerebral malaria (CM), severe anaemia (SA), or uncomplicated malaria (UM) had uniformly low eosinophil counts during the acute illness followed by eosinophilia 30 days after cure. Plasma levels of eosinophil cationic protein (ECP) and eosinophil protein X (EPX) were measured as indicators of eosinophil activation. In spite of the low eosinophil counts, ECP levels were increased on day 0 and significantly higher in patients with CM (geometric mean (95% confidence interval) 8.5 ng/ml (6.8-10.7 ng/ml)) than in SA (4.7 ng/ml (3.0-7.5 ng/ml)) and UM patients (4.3 ng/ml (3.6-5.3 ng/ml), P < 0.001). A similar pattern was found for EPX. It thus appears that the low eosinophil counts may be due to tissue sequestration and destruction rather than decreased production. The plasma levels of the granule proteins correlated with levels of tumour necrosis factor and soluble IL-2 receptor, implicating inflammatory responses and T cell activation as causes of the eosinophil activation. By contrast, the eosinophil induction did not appear to be part of a Th2-like response. Eosinophil granule proteins may be important in both control of malaria infection and the pathogenesis of severe malaria.

Animals↗
PubMed1998

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.

Age Factors↗
PubMed1997

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.

Antimalarials↗
PubMed1993

Entomological risk factors for severe malaria in a peri-urban area of The Gambia.

A study was undertaken of possible entomological risk factors for severe malaria in a peri-urban area of The Gambia. Households of children who had experienced a severe or a mild attack of malaria and of matched controls were visited and their characteristics recorded. Mosquitoes were then collected in the bedrooms of study subjects using both insecticide spray catches and light traps. Mud-walled buildings and bedrooms without ceilings were found more frequently in the households of children who had experienced malaria than in those of controls. Only one difference, which may have arisen by chance, was found between the households of severe and of mild malaria cases; animals were recorded significantly more frequently in the compounds of the severe cases. Mosquito catches reported on two occasions 2 weeks apart showed good reproducibility, indicating that measurements made at the time that a child presented with malaria were likely to reflect those that would have been present at the time that the child was infected. Anopheles gambiae s.l. was found on average more frequently in the bedrooms of children who had experienced malaria than in those of the controls but no difference was found in mosquito numbers between bedrooms of severe or mild cases of malaria. The human blood index and sporozoite rate were similar in mosquitoes caught in households of malaria cases and in those of controls. No evidence was found to support the hypothesis that the level of exposure to malaria-infected mosquitoes is a risk factor for the development of severe malaria.

Animals↗
PubMedDate not supplied

Socio-economic risk factors for malaria in a peri-urban area of The Gambia.

Successful control of malaria depends upon a detailed knowledge of its epidemiology, including knowledge of the social and economic factors that influence its prevalence. Little is known about the socio-economic factors that influence the prevalence of malaria in tropical Africa. Therefore, we undertook such a study in over 350 Gambian children with malaria resident in a peri-urban area with seasonal transmission, using the case-control approach. Malaria was associated with poor quality housing and crowding and with travel to rural areas, where the level of malaria transmission is higher than in urban centres. No association was found between the risk of malaria and the overall education level of parents or guardians of study children. However, the knowledge of malaria possessed by mothers of cases of malaria was less than that of controls, suggesting that further education of the study community on the causation of malaria and on ways of preventing it could be of value.

Case-Control Studies↗