Biomedical subjects

Saadou Issifou

Publications and source records attributed to Saadou Issifou.

At least 19 recordsLinked to original sources

PubMed2006

No variation in the prevalence of point mutations in the Pfcrt and Pfmdr1 genes in isolates from Gabonese patients with uncomplicated or severe Plasmodium falciparum malaria.

In Lambaréné (Gabon), where a high level of Plasmodium falciparum resistance to chloroquine has been reported, we assessed the relationship between polymorphisms in the P. falciparum chloroquine resistance transporter (Pfcrt) and multidrug resistance-1 (Pfmdr1) genes and the clinical severity of malaria. Ninety-one and 60 P. falciparum isolates from children with uncomplicated or severe malaria were collected in 1996 and 2002, respectively. Single nucleotide mutations at codon 76 in the Pfcrt gene and at codons 86, 184, 1034, 1042, and 1246 in the Pfmdr1 gene were assessed by PCR-RFLP. All P. falciparum isolates presented the Pfcrt K76T mutation, whatever the clinical status. A high prevalence (>80%) of the Pfmdr1 86Tyr and 184Phe mutations was detected at both time points and in both clinical groups. We did not identify any specific mutation in the Pfmdr1 gene associated with the severity of disease, and the multiplicity of P. falciparum infection was also similar in both groups. Our results showed no change in the polymorphism of Pfcrt and Pfmdr1 genes in P. falciparum isolates collected in 1996 and 2002, and the severity of the disease was not associated with specific mutations neither in the Pfcrt nor in the Pfmdr1 genes in the study site.

Animals↗

PubMed2006

Short course of quinine plus a single dose of sulfadoxine/pyrimethamine for Plasmodium falciparum malaria.

BACKGROUND: Quinine remains the treatment of choice in hospitalized malaria cases; however, adverse reactions and the long treatment duration of 7 days often hamper its adequate use. Shortening the treatment by adding sulfadoxine/pyrimethamine may enhance compliance and reduce side effects. We aimed to assess the efficacy of a 3-day course of quinine plus a single dose of sulfadoxine/pyrimethamine for the treatment of non-severe hospitalized malaria cases in Lambaréné, Gabon. METHODS: Fifty children aged between 2 and 7 years received quinine dihydrochloride (12 mg/kg every 12 hours for 72 hours), and then a single dose of oral SP (500 mg/25 mg tablet) was given according to weight category. The children were hospitalized for the duration of the treatment and until two consecutive blood smears were negative for malaria parasites. The follow-up period lasted 28 days. RESULTS: Parasites were cleared after 66 hours (SD: 15 hours) and the fever after 46 hours (SD: 24 hours). All patients evaluable by day 28 were negative for malaria parasites (100% efficacy rate, 95% CI: 0.92-1). Only two patients out of 49 had gametocytemia on days 7 and 14. There was no adverse event probably or possibly attributable to the study drugs. CONCLUSIONS: A very high efficacy can be reached using a 3-day course of quinine plus a single dose of sulfadoxine/pyrimethamine for the treatment of non-severe hospitalized malaria cases in our study area.

Animals↗

PubMed2006

Fosmidomycin plus clindamycin for treatment of pediatric patients aged 1 to 14 years with Plasmodium falciparum malaria.

Fosmidomycin plus clindamycin was shown to be efficacious in the treatment of uncomplicated Plasmodium falciparum malaria in a small cohort of pediatric patients aged 7 to 14 years, but more data, including data on younger children with less antiparasitic immunity, are needed to determine the potential value of this new antimalarial combination. We conducted a single-arm study to improve the precision of efficacy estimates for an oral 3-day fixed-ratio combination of fosmidomycin and clindamycin at 30 and 10 mg/kg of body weight, respectively, every 12 hours for the treatment of uncomplicated P. falciparum malaria in 51 pediatric outpatients aged 1 to 14 years. Fosmidomycin plus clindamycin was generally well tolerated, but relatively high rates of treatment-associated neutropenia (8/51 [16%]) and falls of hemoglobin concentrations of > or =2 g/dl (7/51 [14%]) are of concern. Asexual parasites and fever were cleared within median periods of 42 h and 38 h, respectively. All patients who could be evaluated were parasitologically and clinically cured by day 14 (49/49; 95% confidence interval [CI], 93 to 100%). The per-protocol, PCR-adjusted day 28 cure rate was 89% (42/47; 95% CI, 77 to 96%). Efficacy appeared to be significantly reduced in children aged 1 to 2 years, with a day 28 cure rate of only 62% for this small subgroup (5/8). The inadequate efficacy in children of <3 years highlights the need for continued systematic studies of the current dosing regimen, which should include randomized trial designs.

Administration, Oral↗

PubMed2006

Simplified multi-organ dysfunction score predicts disability in African children with Plasmodium falciparum malaria.

In this prospective study, we assessed the simplified multi-organ dysfunction score (sMODS) in 485 consecutive African children, hospitalized with Plasmodium falciparum malaria. Children were grouped according to their ability to walk unaided (Group 1, N = 414), sit unaided (Group 2, N = 63), or inability of both (Group 3, N = 8) before contracting malaria. The sMODS on admission to hospital was highly correlated with prolonged disease duration in Groups 1 and 2 (Spearman r = 0.79 and r = 0.78, respectively). A sMODS of > or = 16 was indicative for prolonged disease duration in Group 1 (> 48 hours of inability to walk, sensitivity of 87%, specificity of 82%) and Group 2 (> 24 hours of inability to sit, sensitivity of 100%, and specificity of 78%.). The simplified MODS is a simple and sensitive measure merit of severity of illness in children with P. falciparum malaria and allows early prognostic evaluation.

Child, Preschool↗

PubMed2006

Microscopic and sub-microscopic Plasmodium falciparum infection, but not inflammation caused by infection, is associated with low birth weight.

Pregnancy-associated malaria is one of the leading causes of low birth weight in malaria endemic areas. In this study, 145 parturient women residing in areas endemic for Plasmodium falciparum in Lambaréné, Gabon, were recruited into the study after delivery, and the association of maternal P. falciparum infection, inflammatory response, and birth weight was studied. At delivery, 10% (15) of the mothers (12 were positive in both peripheral and placental blood smears, 1 was positive in peripheral blood only, and 2 were positive in placenta blood only) were positive for P. falciparum by microscopy and 23% (30) by real-time polymerase chain reaction (PCR). The level of C-reactive protein (CRP) was significantly elevated in microscopically P. falciparum-positive pregnant women (34 mg/L; 95% CI: 3-458) but not in those with sub-microscopic infections (6 mg/L; 95% CI: 1-40) compared with those free of P. falciparum infection (7 mg/L; 95% CI: 1-43). In a multivariate analysis, the presence of microscopic (adjusted OR = 28.6, 95% CI = 4.8-169.0) or sub-microscopic (adjusted OR = 13.2, 95% CI = 2.4-73.0) P. falciparum infection in pregnant women and age of mothers < 21 years (adjusted OR = 9.7 CI = 1.0-89.7), but not CRP levels, were independent predictors for low birth weight. This finding may have important operational implications and emphasizes the need for appropriate diagnostic methods in studies evaluating the outcome of pregnancy-associated malaria.

Adolescent↗

PubMed2005

Influence of carriage of hemoglobin AS and the Fc gamma receptor IIa-R131 allele on levels of immunoglobulin G2 antibodies to Plasmodium falciparum merozoite antigens in Gabonese children.

BACKGROUND: To extend our previous findings showing an imbalanced distribution of immunoglobulin G2 (IgG2) antibodies to Plasmodium falciparum merozoite surface protein 2 (MSP2) and a higher frequency of infection with multiple P. falciparum strains in Gabonese children with sickle cell trait (hemoglobin AS), human Fc gamma receptor (Fc gamma R) IIa (CD32) polymorphism and the rate of in vitro invasion of red blood cells (RBCs) from subjects with either hemoglobin AA or AS by multiple P. falciparum strains were investigated. METHODS: Fc gamma RIIa mutation at amino acid position 131 (arginine or histidine) was detected by polymerase chain reaction, and in vitro cultures for parasites were used to assess the invasion rate. RESULTS: Fc gamma RIIa polymorphism is normally distributed in this population, with no preferential carriage by children with hemoglobin AS. Lower levels of IgG2 subclass antibodies to MSP2 peptides were independently associated with the Fc gamma RIIa-R131 allele and with carriage of hemoglobin AS. Our data suggest that IgG3 antibody responses to MSP2 epitopes could be exacerbated by lower IgG2 levels in children with hemoglobin AS. CONCLUSIONS: The higher rate of invasion of RBCs in the presence of multiple strains may indicate that several invasion pathways are solicited simultaneously, and the longer persistence of ring forms in RBCs from the subjects with hemoglobin AS might reflect a slower multiplication phase, leading to a longer circulation and enhanced phagocytosis of these nonpathogenic parasite forms. This may contribute to the protection against P. falciparum malaria observed in children with hemoglobin AS.

Alleles↗

PubMed2005

Artesunate-clindamycin versus quinine-clindamycin in the treatment of Plasmodium falciparum malaria: a randomized controlled trial.

BACKGROUND: Artemisinin-based drug combinations are the mainstay in the fight against drug-resistant malaria in Africa. Currently available antimalarial drug combinations that include artemisinins are pharmacokinetically unmatched and are therefore potentially increasing the risk of selection of resistant mutants in areas in which the rate of transmission of malaria is high. We tested the potential value of artemisinin-based combination therapy with a short elimination half-life for the treatment of uncomplicated Plasmodium falciparum malaria in sub-Saharan Africa. METHODS: We conducted an open-label, randomized, controlled clinical trial to evaluate the efficacy and tolerability of oral artesunate-clindamycin therapy given twice daily for 3 days (artesunate, 2 mg/kg, and clindamycin, 7 mg/kg, per dose), compared with a standard quinine-clindamycin regimen given twice daily for 3 days (quinine, 15 mg/kg, and clindamycin, 7 mg/kg, per dose), for the treatment of uncomplicated falciparum malaria in 100 Gabonese children aged 3-12 years. The primary end point of the study was the polymerase chain reaction-corrected cure rate for the per-protocol population. RESULTS: The activity of artesunate-clindamycin was comparable to that of quinine-clindamycin in the per-protocol analysis of cure rates at day 28 of follow-up (87% versus 94%). No serious adverse events were reported, and tolerability was good and was similar in both groups. Times to clearance of fever and clearance of parasites were significantly shorter in the artesunate-clindamycin group. CONCLUSIONS: Artesunate-clindamycin and other matching artemisinin-based combinations with a short plasma half-life merit further attention for use in regions in which the rate of transmission of malaria is high.

Antimalarials↗

PubMed2005

Clinical and parasitological characteristics of puerperal malaria.

BACKGROUND: Women with semi-immunity to malaria who live in regions where the disease is endemic are at increased risk for more frequent and severe episodes of malaria during pregnancy. Recent findings indicate that this increased risk might persist beyond delivery, but the underlying mechanisms for this change in risk are poorly understood. METHODS: One hundred fifty women were included in a cohort study in Lambaréné, Gabon, and were actively followed up weekly for 10 weeks after delivery, as were nonpregnant control women who had been matched to them by location and age. Parasites in samples of placenta and blood were genotyped by use of polymerase chain reaction amplification of the merozoite surface antigen 2 gene and the subtelomeric variable open reading frame gene of Plasmodium falciparum. RESULTS: Eleven puerperal women had cases of clinical malaria, compared with 1 control woman (rate ratio, 9.8; P=.006). Eighteen puerperal women had P. falciparum parasitemia, compared with 6 control women (rate ratio, 2.7; P=.03). Five of 16 puerperal women (31%) with parasitemia on follow-up had identical parasites in their placentas and blood, and 11 of these cases (69%) were the result of reinfection. Puerperal women remained at equal risk for the development of parasitemia throughout the first 10 weeks after delivery. Use of bed nets, use of chloroquine prophylaxis during pregnancy, presence of malaria episodes during pregnancy, gravidity, and age were not associated with the acquisition of parasitemia during follow-up. CONCLUSIONS: Compared with nonpregnant women, puerperal women have a considerably increased risk for the development of malaria and/or parasitemia. This increased risk is caused both by the recurrence of P. falciparum parasitemia and by the increased susceptibility to new infections, although the latter plays a more significant role.

Adult↗

PubMed2005

Malaria and asymptomatic parasitaemia in Gabonese infants under the age of 3 months.

We determined the incidence of both malaria and asymptomatic parasitaemia in infants under the age of 3 months within the framework of a longitudinal cohort study in Lambaréné, Gabon, between December 2002 and July 2004. Of 878 infants who were included at birth, we identified malaria in three infants and, additionally, asymptomatic parasitaemia in six infants. The malaria incidence density was 1.1/1000 person-months or 0.1% of observations. Our findings underpin the notion that the incidence of malaria and parasitaemia in infants below the age of 3 months is very low.

Adult↗

PubMed2005

Short-course regimens of artesunate-fosmidomycin in treatment of uncomplicated Plasmodium falciparum malaria.

Fosmidomycin is effective against malaria, but it needs to be given for > or =4 days when used alone. We conducted a study of 50 children with Plasmodium falciparum malaria to evaluate the safety and efficacy of consecutively shortened regimens of artesunate-fosmidomycin (1 to 2 mg/kg of body weight and 30 mg/kg of body weight, respectively; doses given every 12 hours). All dosing regimens were well tolerated. Artesunate-fosmidomycin acted rapidly, resulting in consolidated geometric mean parasite and fever clearance times of 24 h and 15 h, respectively. Treatment regimens of > or =2 days led to cure ratios of 100% by day 14 (39/39; 95% confidence interval [95% CI], 91% to 100%). Most importantly, the 3-day regimen achieved 100% cure on day 28 (10/10; 95% CI, 69% to 100%). Treatment with artesunate-fosmidomycin was associated with transient grade I or II neutropenia (absolute neutrophil counts of 750 to 1,200/microl and 400 to 749/microl, respectively) in six or two patients, respectively. Artesunate-fosmidomycin demonstrates the feasibility and potential value of short-course artemisinin-based combination chemotherapy with rapidly eliminated combination partners.

Antimalarials↗

PubMed2005

Short report: Piloting paperless data entry for clinical research in Africa.

Direct data entry, using handheld computers, may simplify and streamline data management, especially in remote settings. We compared the accuracy of data entry using the current standard practice (a paper-based case report form with double data entry) with that using a personal digital assistant (PDA) in a clinical study in rural Gabon. The rate of discrepant entries was 1.7%. Categorical data (presented in "pull down" menus on the PDA) were more commonly discrepant than were continuous "typed in" data (2.4% versus 1.2%; P = 0.001). Both systems functioned smoothly and no data were lost. The clinicians involved in this study preferred the handheld computers, and their use will be considered in future studies in an African clinical research network.

Africa↗

PubMed2005

Effectiveness of quinine monotherapy for the treatment of Plasmodium falciparum infection in pregnant women in Lambaréné, Gabon.

Pregnant women participating in a longitudinal immuno-epidemiologic survey in Lambaréné, Gabon, and presenting with Plasmodium falciparum parasitemia at monthly blood smear examinations were offered treatment with oral 7-day quinine monotherapy according to national health guidelines. A total of 50 pregnant women were offered 7-day oral quinine sulfate 10 mg/kg thrice daily. Clinical examinations and laboratory tests were performed on Days 28 and 56 to assess the effectiveness of this standard regimen. By Day 28, the effectiveness of the 7-day quinine regimen was 60% (95% confidence interval: 46-72%). We conclude that a 7-day course of quinine has a poor effectiveness and that alternative treatment regimens for malaria in pregnant women should be assessed.

Adult↗

PubMed2005

Assessment of a simplified method for counting leukocytic malaria pigment.

Severe and fatal malaria is associated with the increased presence of malaria hemozoin in peripheral phagocytes. Large studies of this relationship are hampered by the fact that identifying and counting phagocytes on thick blood smears is time consuming. Distinguishing which mononuclear cells are monocytes and which granulocytes are neutrophils requires time and careful training. In this study, we evaluated a simplified method in which only the proportions of hemozoin-containing mononuclear cells and granulocytes are counted. Thick blood films from 471 Gabonese children with malaria were evaluated. We found a linear relationship and a strong correlation between the proportions of hemozoin-containing monocytes versus mononuclear cells (r = 0.85) and neutrophils versus polymorphonuclear cells (r = 0.93), respectively. The two methods had similar predictive values, as estimated by receiver operating characteristics curves. This simplified method can be used to estimate the amount of extra-erythrocytic pigment in peripheral blood, and we suggest that it may be particularly suitable for very large studies.

Animals↗

PubMed2005

5-day nonobserved artesunate monotherapy for treating uncomplicated Falciparum malaria in young Gabonese children.

Despite different recommendations from WHO and national authorities, artesunate monotherapy is increasingly used for treating African children with malaria. A 5-day course of oral artesunate (first day: 4 mg/kg body weight, observed intake; and 2 mg/kg body weight on the following days with nonobserved drug intake) yielded a PCR-corrected Day 28 cure rate of 90% (45 of 50 patients; CI 78-97%) in Gabonese children aged between 2 and 18 months. Artesunate was well tolerated, and no severe adverse events were reported.

Animals↗

PubMed2004

Fosmidomycin-clindamycin for the treatment of Plasmodium falciparum malaria.

It has been demonstrated that fosmidomycin has good tolerability and rapid onset of action, but late recrudescences preclude its use alone; in vitro, clindamycin has been shown to act synergistically with fosmidomycin against Plasmodium falciparum. We conducted a study in pediatric outpatients with P. falciparum malaria in Gabon to evaluate the efficacy and safety of an oral combination of fosmidomycin-clindamycin of 30 mg/kg and 10 mg/kg of body weight, respectively, every 12 h. Patients 7-14 years old were recruited in cohorts of 10. The first 10 patients were treated for 5 days. The duration of treatment was then incrementally shortened in intervals of 1 day if >85% of the patients in a cohort were cured by day 14. All dosing regimens were well tolerated, and no serious adverse events occurred. Asexual parasites and fever rapidly cleared in all patients. Cure ratios of 100% on day 14 were achieved with treatment durations of 5 (10/10 patients), 4 (10/10 patients), 3 (10/10 patients), and 2 days (10/10 patients); 1 day of treatment led to a cure ratio of 50% (5/10 patients). Fosmidomycin-clindamycin is safe and well tolerated, and short-course regimens achieved high efficacy in children with P. falciparum malaria. Fosmidomycin-clindamycin is a promising novel treatment option for malaria.

Administration, Oral↗

PubMed2004

Impact of increasing consultation fees on malaria in Africa.

To evaluate the impact of the increase in consultation fees on malaria incidence in children presenting in the outpatient clinic of a privately funded hospital, we measured the impact of two fee increases on the number of pediatric outpatients. A 74% reduction in outpatients and a 78% reduction in malaria cases occurred in a course of four years. No differences were observed in an adjacent public hospital that does not charge consultation fees. This surprisingly strong effect may be the basis for increase in malaria morbidity and mortality, since in the time course of 4 years, an estimated 3000 children did not receive adequate malaria treatment in this region. Furthermore, it may drive parasite resistance, due to inadequate auto-medication.

Child↗

PubMed2004

Fosmidomycin-clindamycin for Plasmodium falciparum Infections in African children.

BACKGROUND: Fosmidomycin is a new antimalarial drug with a novel mechanism of action. Studies in Africa that have evaluated fosmidomycin as monotherapeutic agent demonstrated its excellent tolerance, but 3-times-daily treatment regimens of >or=4 days were required to achieve radical cure, prompting further research to identify and validate a suitable combination partner to enhance its efficacy. METHODS: We conducted a randomized, controlled, open-label study to evaluate the efficacy and safety of fosmidomycin combined with clindamycin (n=12; 30 and 5 mg/kg body weight every 12 h for 5 days, respectively), compared with fosmidomycin alone (n=12; 30 mg/kg body weight every 12 h for 5 days) and clindamycin alone (n=12; 5 mg/kg body weight every 12 h for 5 days) for the clearance of asymptomatic Plasmodium falciparum infections in schoolchildren in Gabon aged 7-14 years. RESULTS: Asexual parasites were rapidly cleared in children treated with fosmidomycin-clindamycin (median time, 18 h) and fosmidomycin alone (25 h) but slowly in children treated with clindamycin alone (71 h; P=.004). However, only treatment with fosmidomycin-clindamycin or clindamycin alone led to the radical elimination of asexual parasites as measured by day 14 and 28 cure rates of 100%. Asexual parasites reappeared by day 28 in 7 children who received fosmidomycin (day 14 cure rate, 92% [11/12; day 28 cure rate, 42% [5/12]). All regimens were well tolerated, and no serious adverse events occurred. CONCLUSION: The combination of fosmidomycin and clindamycin is well tolerated and superior to either agent on its own with respect to the rapid and radical clearance of P. falciparum infections in African children.

Antimalarials↗

PubMed2004

Depressed natural killer cell cytotoxicity against Plasmodium falciparum-infected erythrocytes during first pregnancies.

We measured natural killer (NK) cell cytotoxicity and cortisol and prolactin concentrations in peripheral venous blood samples obtained from pregnant Gabonese women at the time of delivery. The NK cell-mediated cytotoxicity against Plasmodium falciparum-infected erythrocytes in vitro was lower in samples obtained from primiparous women than in samples obtained from multiparous women; cortisol concentrations were significantly higher in primiparous women than in multiparous women, and prolactin concentrations were significantly lower. The highest cortisol concentrations were found in the plasma of P. falciparum-infected primiparous women. A positive correlation was found between cortisol concentration and parasite load; an inverse correlation was found between the magnitude of the NK cell cytolytic effect and cortisol production. A positive correlation was found between this effect and prolactin production. Thus, depressed NK cell cytotoxicity against P. falciparum-infected erythrocytes is correlated with high cortisol concentrations and may contribute to increased susceptibility to malaria during pregnancy.

Adult↗