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M Cot

Publications and source records attributed to M Cot.

At least 37 records · Page 2Linked to original sources

Genetic control of blood infection levels in human malaria: evidence for a complex genetic model.

There is now accumulating evidence for the involvement of genetic factors in the control of immune response against malaria. These arguments come from numerous animal models, from population studies showing associations of red blood cell genetic defects as well as HLA antigens with severe malaria, and from familial studies including a recent segregation analysis, which led to detection of a major gene effect predisposing to high infection levels. The heterogeneity and complexity of this genetic control is one of the main findings of these previous studies, and probably a major cause of the difficulty in developing an effective malaria vaccine. A segregation analysis of blood infection levels is performed here in 44 pedigrees living in the tropical rain forest of southern Cameroon and exposed to high vectorial transmission intensity. The results confirm the existence of complex genetic factors controlling blood infection levels in human malaria but are not consistent with the parent-offspring transmission of a single Mendelian gene. This study also shows the dramatic effect of age on infection levels and its interaction with a putative major gene suggesting that genetic related differences are much more important in children than in adults. Further genetic studies focused on children may help to identify the nature of the genetic factors involved in the expression of human malaria, by means of linkage analyses using both familial information and genetic markers.

Adolescent↗

Prevalence of and risk factors for anemia in young children in southern Cameroon.

Anemia during childhood remains a major public health challenge in sub-Saharan Africa. To determine the prevalence of and the main risk factors for anemia in young children, we conducted a longitudinal survey in Ebolowa in southern Cameroon. Children were enrolled in two cohorts and followed during a three-year period: the first cohort was composed of 122 children from 0 to 36 months of age and the second cohort was composed of 84 children from 24 to 60 months of age. The two cohorts were followed weekly for symptomatic malaria, monthly for both symptomatic and asymptomatic malaria, and every six months for hematologic data; the children were grouped into six-month age groups. The prevalence of anemia (hemoglobin [Hb] level < 11 g/dl) was the highest in the six-month-old age group (47%) and the age-related evolution clearly showed a decrease in the prevalence from three years of age. Thus, 42% of the children less than three years of age were anemic, while 21% of the children between three and five years of age were anemic. The lowest mean +/- SD Hb content (10.7 +/- 2.1 g/dl) was observed in the six-month-old children and a regular improvement in the Hb level occurred from six months to three years of age. A stabilization was observed at a level of approximately 12 g/dl. At any age, there was no difference in mean Hb levels between children with AS and AA Hb genotypes. Hookworm infection was diagnosed in two children in the study population. Results of a multivariate analysis showed that placental malaria infection was the strongest risk factor for anemia in the six-month-old children (odds ratio [OR] = 3.6; 95% confidence interval [CI] = 1.1-12.3) and was independent of the frequency of parasitemia, parasitemia at the time of Hb measurement, or microcytosis. In the one-year-old age group, microcytosis was a significant factor related to anemia (OR = 2.8, 95% CI = 1-7.8) pointing out the role of iron deficiency at this age. Parasitemia at the time of Hb measurement was significantly associated with anemia in all age groups (except in 54- and 60-month-old groups). Strategies to decrease the prevalence of anemia in young children in southern Cameroon should include chemoprophylaxis for pregnant women, prevention of acquired malaria infection in both pregnancy and infancy, and prevention of nutritional iron deficiency.

Anemia↗

Linkage analysis of blood Plasmodium falciparum levels: interest of the 5q31-q33 chromosome region.

There is accumulating evidence for the involvement of genetic factors in the human response to malaria infection, mostly based on results obtained in studies of severe clinical malaria. The role of major gene(s) controlling blood parasitemia levels in human malaria has also been detected by means of segregation analysis. To confirm and to localize such gene(s), we performed a sib-pair linkage analysis investigating the role of five candidate chromosomal regions: 6p21 (HLA-tumor necrosis factor region), 2q13-q21 (genes coding for interleukin-1 alpha and beta), 14q11 (locus coding for the alpha chain of T cell antigen receptor), 7q35 (gene cluster for the beta subunit of T cell receptor), and 5q31-q33, which includes several candidate genes and was recently linked to a locus controlling infection levels by Schistosoma mansoni, denoted as SM1. The analysis was carried out on nine families from a southern Cameroon village, and the phenotype under study was blood infection levels with Plasmodium falciparum. No linkage was found with any of the four markers outside the 5q31-q33 region. A trend in favor of linkage was observed in the distal part of the 5q31-q33 region, especially with the marker D5S636 (P < 0.05 using the Monte Carlo P value), which was the marker that provided the highest evidence for linkage with SM1. These results suggest that a locus influencing P. falciparum levels in malaria could be located in the same genetic region as that containing SM1, indicating that the 5q31-q33 region may be critical in the control of different parasite infections.

Adolescent↗

Maternal placental infection with Plasmodium falciparum and malaria morbidity during the first 2 years of life.

In areas endemic for malaria, pregnant women frequently present with a placenta that has been parasitized by Plasmodium falciparum, an infection associated with a reduction in the birth weight of the offspring. However, the impact of placental infection on malaria-related morbidity during the infant's first years of life has not been investigated. Between 1993 and 1995, 197 children in southern Cameroon were followed weekly clinically and monthly parasitologically. The dates of first positive blood smear and the evolution of the parasite prevalence rates were compared between infants born to mothers presenting with (n = 42) and without (n = 155) P. falciparum infection of the placenta. Infants born to placenta-infected mothers were more likely to develop a malaria infection between 4 and 6 months of age; then the difference progressively disappeared. Similarly, parasite prevalence rates were higher in placenta-infected infants from 5 to 8 months of age. Thus, malarial infection of the placenta seems to result in a higher susceptibility of infants to the parasite. This was not related to maternally transmitted antibodies, as specific antibody levels were similar in both groups of infants. A better understanding of the involved mechanisms may have important implications for the development of malaria control strategies.

Animals↗

Immune response to Plasmodium falciparum antigens in Cameroonian primigravidae: evolution after delivery and during second pregnancy.

Mechanisms responsible for the increase in malaria susceptibility during pregnancy, and in particular during the first pregnancy, have not been elucidated. T and B cell responses to leucoagglutinin, bacille Calmette-Guerin (BCG) and to six Plasmodium falciparum antigens were longitudinally investigated in 33 pregnant women during their first pregnancy, after delivery, and during second pregnancy. Parasitological data obtained from the same women during and after the first pregnancy demonstrated the higher risk of P. falciparum infection during this pregnancy. Plasma levels of antibodies to Pf155/ RESA were lower during pregnancy than after delivery. Conversely, antibodies to P. falciparum asexual blood stages were higher during pregnancy than after delivery, suggesting that during pregnancy the regulation of antibody production may be variously impaired depending upon the antigens. The most striking finding of the present study is the impairment of the IL-2 cellular response during the first pregnancy. Conversely, proliferative responses, as well as IL-4 and interferon-gamma (IFN-gamma) responses, were either unaffected or moderately enhanced. No difference in humoral and cellular responses was observed between first and second pregnancy. The impairment of the IL-2 responses involved the response to malaria peptides and proteins, as well as the response to non-malarial antigens and to the mitogen leucoagglutinin. Thus, the alteration of malaria immunity might rather fall into the general frame of the depression of cellular immunity during pregnancy than involve a specific malaria phenomenon.

Amino Acid Sequence↗

Isotypic analysis of maternally transmitted Plasmodium falciparum-specific antibodies in Cameroon, and relationship with risk of P. falciparum infection.

In malaria-endemic areas, infants are relatively protected against malaria infection. Such protection is though to be related principally to the transplacental transfer of maternal antibodies. We measured total and Plasmodium falciparum-specific IgG (including subclasses), IgM, and IgE antibodies in 154 paired maternal-cord serum samples from an area of meso- to hyperendemic malaria in South Cameroon. Among peripheral mother blood samples, total IgG and IgM were detected in all samples, IgE in all but two. Plasmodium falciparum-specific IgG were detected in all serum samples, IgM and IgE in > 75% of samples. The prevalence rates of anti-P. falciparum IgG subclasses varied from 75% to 97%. With the exception of P. falciparum-specific IgG, all antibody class and subclass levels were lower in cord blood than in peripheral mother blood. Plasmodium falciparum-specific IgG1 and IgG3 isotypes were transferred to the offspring more often and more efficiently than IgG2 and IgG4. The detection of total and P. falciparum-specific IgM and IgE in some cord serum samples demonstrated that fetuses can mount humoral response against malaria parasites. We also determined whether transplacentally acquired antibodies protect against malaria infection by relating the antibody levels at birth to the risk of acquiring P. falciparum infection during the first 6 months of life. Among various classes and subclasses of P. falciparum-specific antibodies, only IgG2 were related to a decrease in the risk of acquiring a P. falciparum peripheral blood infection from birth to 6 months of age.

Adolescent↗

Risk factor for neonatal tetanus in west Burkina Faso: a case control study.

A case-control study was carried out to identify risk factors for neonatal tetanus in rural Burkina Faso. Each of the 31 cases identified prospectively were matched with two controls. Risk factors such as the instrument used to cut the umbilical cord and the qualification of the midwives were only identified in the univariate analysis. The multifactorial analysis identified factors commonly believed to be associated with neonatal tetanus: lack of mother's immunization and place of birth other than maternity clinics. However, applying karite nut butter on the umbilical cord was found to be a strong independent factor associated with neonatal tetanus. Immunization of mothers against tetanus should be enforced. Health education must take into consideration sociocultural realities of these populations.

Burkina Faso↗

Malaria cellular immune responses in neonates from Cameroon.

T cell responses to leucoagglutinin, PPD, and seven Plasmodium falciparum blood stages antigens were investigated in 164 cord blood samples from Cameroonian neonates. In vitro T cell responses were measured by lymphocyte proliferation, and IL-2, IFN-gamma, and IL-4 release in the presence of crude schizont extract, purified Pf155/RESA protein, and synthetic peptides from Pf155/ RESA. Following culture in presence of leucoagglutinin or PPD, proliferation and cytokine production were very low, as compared to adults from the same area. Interestingly, following stimulation of cord blood lymphocytes by malaria antigens, the percentage of responders and the mean level of positive responses were of the same order than those observed in adults for IL-2 production, while proliferative and IL-4 responses were only marginally decreased. Conversely, IFN-gamma production was highly reduced, as compared to adults. Our results demonstrate that prenatal immune priming to malarial antigens is common in this area and that the fetal immune system is able to respond to antigenic stimuli, as cells proliferate and generate cytokines. As cord blood lymphocytes may be induced to differentiate into effector cells producing predominantly Th1 or Th2 cytokines, malaria during pregnancy might direct the functional capacity of fetal T cells to respond to further infection.

Adult↗

Humoral and cellular immune responses to synthetic peptides from the Plasmodium falciparum blood-stage antigen, Pf155/RESA, in Cameroonian women.

T- and B-cell responses to the Plasmodium falciparum blood-stage antigen Pf155/RESA were investigated in 104 Cameroonian women, half of whom were pregnant. We used purified protein and six synthetic peptides representing T- and B-cell epitopes. In vitro T-cell responses were measured by proliferation and IL2, IFN-gamma, and IL4 release. B-cell responses were assessed by plasma antibodies. All peptides induced a cellular response in some individuals. A proliferative response was induced in 25% of the donors by Pf155/RESA, and in 7 to 11% by any peptide. Cytokine release occurred in 23 to 30% of the Pf155/RESA-stimulated cultures, and in 8 to 25% of the peptide-stimulated cultures. Overall, each peptide induced a cellular response (proliferation and/or cytokine release) in 44% of the donors. T-cells from 23% of the donors failed to respond to any peptide. Responding cells did not usually respond in all readouts, and proliferation and release of any of the three cytokines were not correlated. Similarly, antibody and T-cell responses were not related. Selected epitopes of Pf155/RESA, an important vaccine candidate, are well recognized in naturally exposed individuals and are able to activate T-cells to proliferate and to produce various lymphokines in numerous individuals from a malaria endemic area.

Adult↗

Mother-to-child transmission of human immunodeficiency virus type 1 and type 2 and dual infection: a cohort study in Banfora, Burkina Faso.

A prospective cohort study on the mother-to-child transmission of human immunodeficiency virus type 1 (HIV1), type 2 (HIV2) and dual positivity (HIV1 + HIV2) was carried out in Banfora, West Burkina Faso. The study samples consist of 117 newborns of HIV-seropositive women matched to 234 newborns of HIV-seronegative women. Among cases, 91 were born of HIV1-seropositive mothers, 15 were born of HIV2-seropositive mothers and 11 were born of HIV1 and HIV2 dual-seropositive mothers and were included in an 18-month follow-up. Calculation of the mother-to-child transmission rate was according to the recommendations of the European Economic Community working group. The HIV1 mother-to-child transmission rate was estimated to be 27.8% (95% confidence interval (CI) 24.5 to 32.4) with one method and 25.5% (95% CI 13.5 to 37.5) with a second method. For HIV2, this rate was estimated to be 29.5% (95% CI 26.0 to 39.8) and was not statistically different from the HIV1 mother-to-child transmission rate. No case of transmission was observed in children born of dual seropositive mothers. Survival rate at month 18 was significantly lower for children born of HIV1 mothers: 83.7% (95% CI 78.2 to 92.2). Survival rates were similar between children born of HIV2-seropositive (86.7), dual HIV1 + 2-positive (100) and seronegative mothers (92.0%). Findings suggest a higher mother-to-child transmission rate of HIV2 in children born in Burkina Faso than in Europe and a low clinical expression of HIV2 in children.

AIDS Serodiagnosis↗

Longitudinal survey of Loa loa filariasis in southern Cameroon: long-term stability and factors influencing individual microfilarial status.

A longitudinal, one-year survey of Loa loa infection was carried out in an endemic area of southern Cameroon. Parasitologic samplings (calibrated thick blood smears) were performed every two months to study the evolution of loiasis infection at both the population and the individual level. The mean number of measurements by subject was 3.8 (range 1-6). At the population level, prevalence of infection and microfilarial load were found to be very stable over time. This observation is consistent with the existence of an important reserve of parasitic material available for vectors and the maintenance of high levels of transmission. At the individual level, both the microfilarial status (microfilaremic/nonmicrofilaremic) and the level of parasitemia showed a remarkable stability over time. Age was the relevant factor that influenced the individual microfilarial status in the whole population. When only microfilaremic individuals were taken into account, age did not influence the level of microfilaremia, suggesting that loiasis could be considered as a noncumulative disease. The stability of individual microfilarial status and the pattern of infection variations observed with age support the view that genetic factors might be involved in host defense mechanisms against loiasis infection.

Adolescent↗

Increase of birth weight following chloroquine chemoprophylaxis during the first pregnancy: results of a randomized trial in Cameroon.

A randomized trial was carried out from 1991 to 1993 among women attending an antenatal clinic in Ebolowa, Cameroon where malaria is hyperendemic and transmission occurs at a high level all year round. All pregnant women attending the clinic for their first prenatal visit between October 1991 and November 1992 were alternately assigned to chloroquine (CQ) or control (CT) groups. Chloroquine was given under observation at a weekly oral dose of 300 mg. At delivery, smears from maternal, cord, and placental blood were made and stained with Giemsa for parasites. An in vivo chloroquine sensitivity investigation was carried out on women attending the postnatal consultation to evaluate the level of chloroquine resistance in the target population. The efficacy of chloroquine was moderate in placental infection (39.2% infected in the CQ group versus 57.8% in the CT group: P = 0.05), probably because of a resistance to chloroquine estimated to be 10.9%. In the CQ group, the mean birth weight was significantly higher (P = 0.02) and the proportion of low birth weight newborns was lower (10.5% versus 27.7%; P = 0.02). A strong correlation between placental infection and birth weight was observed: the mean birth weight difference between infected and noninfected placentae was 359 g (P < 0.0001) and the proportion of low birth weight new born babies was 35.6% versus 5.9% (P = 0.0001). In Cameroon, in spite of a moderate resistance to chloroquine, this drug proved to be highly effective in increasing birth weight when administered to primigravidae. We therefore think such a prophylaxis should be recommended only to primigravidae in high transmission areas.

Adolescent↗

Malaria and pregnancy in Cameroonian primigravidae: humoral and cellular immune responses to Plasmodium falciparum blood-stage antigens.

To investigate the mechanisms underlying the increased susceptibility to malaria in pregnant women, we determined the level of malaria-specific immunity in primigravidae. Humoral and cellular in vitro responses to unpurified (a crude schizont extract and a gametocyte preparation) and purified (affinity-purified Pf155/ring-infected erythrocyte surface antigen [RESA]) Plasmodium falciparum proteins, an immunodominant 45/47-kilodalton antigen from Mycobacterium bovis, and leucoagglutinin were compared between 52 primigravidae and 52 nonpregnant women from a semirural area of Cameroon. In vitro cellular responses were investigated in terms of lymphocyte proliferation, as well as production of interleukin-2 (IL-2), interferon-gamma (IFN-gamma), and IL-4. Cells from primigravidae exhibited a reduced proliferative response to schizont and gametocyte antigens, as well as to the M. bovis antigen. Conversely, the IL-2 response to Pf155/RESA was reduced. Interleukin-4 and IFN-gamma production did not appear to be affected in primigravidae. Antibody levels were also similar between pregnant and nonpregnant women. Our results underline the importance of examining several parameters of T cell activation with different types of antigens for a correct evaluation of the ability of lymphocytes to respond to malaria.

Adolescent↗

[Role of genetic epidemiology in the study of infectious diseases. The example of malaria].

Genetic epidemiology is a new tool for the study of malaria, with interesting incidence in the comprehension of host/parasite interrelations. The existence of a co-dominant major gene, with a mendelian transmission, controlling the levels of parasitemia has been found out. This allele has a frequency of 24% which means that about 6% of the population is predisposed to high parasitemias. These studies show the interest to integrate the existence of a genetical variability in the development and the evaluation of malaria control programmes. They are offering new perspectives in therapeutics and in the elaboration of vaccinal strategies.

Animals↗

Risk factors for preterm delivery in Burkina Faso (west Africa).

The environmental and socioeconomic risk factors for preterm delivery were assessed in a West African urban population (Bobo-Dioulasso, Burkina Faso). The study population were 102 cases of preterm delivery matched with 102 controls obtained from 4124 sequential deliveries which occurred between May and October 1989 in the three maternity centres in the city. The univariate analysis identified the risk factors as age (< 20 years), primiparity, marital status (single), low frequency of antenatal visits, death of a previous child and level of education of the mother. The following risk factors identified by multivariate analysis (logistic regression) are consistent with those identified in previous studies: youth of the mother, primiparity (P = 0.01) and death of a previous child (P < 0.05). On the other hand, in this study, the level of education of the parent was identified as an independent risk factor (P < 0.001). This finding could be used to determine a target population for prevention programmes.

Adolescent↗

Risk factors of malaria infection during pregnancy in Burkina Faso: suggestion of a genetic influence.

A cohort of 570 untreated pregnant women from Burkina Faso was studied to assess the influence of epidemiologic factors on malaria infection, which was quantified as the mean of serial, season-adjusted parasitemia measurements (mean parasite density [MPD]) carried out during the last five months of gestation. A significant effect of the area of maternal residence on the MPD was found (P < 0.003) and was probably due to geographic differences in mosquito transmission conditions. The strong relationship observed between parity and malaria infection (P < 0.0001), with MPD levels decreasing as the number of gestations increased, confirms that primigravidae are a high-risk group whose protection should be a priority. After adjustment for two relevant epidemiologic factors (i.e., area of residence and parity), the residual MPD values fitted a mixture of two distributions. This result supports the view that a major gene is involved in the determination of malaria infection intensities and is consistent with the results of a recent familial study in Cameroon.

Adult↗