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Background: Since 2006, artemisinin-based combination therapies (ACT) have been used to treat uncomplicated Plasmodium falciparum malaria in Senegal, as recommended by WHO. Recently, decreased parasite clearance with artemisinin derivatives has been reported in Cambodia and Thailand. The effectiveness of artemisinin derivatives in Africa must be monitored. This study was conducted to evaluate the efficacy and the tolerability of three ACT widely used in Senegal., Methods: From October 2010 to February 2011, a descriptive and analytical sequential study was conducted in adults and children to evaluate these three combinations: artemether-lumefantrine (AL), artesunate-amodiaquine (ASAQ), and dihydroartemisinin-piperaquine (DHAPQ). The study took place at the health posts of Deggo and Pikine and the health center of Guédiawaye, in the suburbs of Dakar. The primary endpoint was the PCR-corrected adequate clinical and parasitological response (ACPR) at day 28 (D28); the secondary endpoints included ACPR at D42, clearance times for parasites, fever, and gametocytes, and the incidence of adverse events., Results: The study included 393 patients: 139 in the AL group, 130 in the ASAQ group, and 124 in the DHAPQ group. In the intent-to-treat population, PCR-corrected ACPR at day 28 was 92.8% in the AL, 89.2% in the ASAQ, and 91.1% in the DHAPQ (p = 0.58) groups, and in the per-protocol population, 98.4%, 98.3%, and 100% respectively (p = 0.39). At D42, ACPR was 99.2% in the AL, and 99.1% in each of the ASAQ and DHAPQ arms (p = 1). No early therapeutic failure (ETF) was observed. The combinations were well tolerated, with no serious adverse events reported during the follow-up period., Conclusion: These combinations are still effective and well-tolerated. Continued monitoring is nonetheless essential to detect early artemisinin resistance in Africa.

Seasonal malaria chemoprevention (SMC) is defined as the intermittent administration of full treatment courses of an antimalarial drug to children during the peak of malaria transmission season with the aim of preventing malaria-associated mortality and morbidity. SMC using sulfadoxine-pyrimethamine (SP) combined with amodiaquine (AQ) is a promising strategy to control malaria morbidity in areas of highly seasonal malaria transmission. However, a concern is whether SMC can delay the natural acquisition of immunity toward malaria parasites in areas with intense SMC delivery. To investigate this, total IgG antibody (Ab) responses to Plasmodium falciparum antigens glutamate-rich protein R0 (GLURP-R0) and apical membrane antigen 1 (AMA-1) were measured by enzyme-linked immunosorbent assay in Senegalese children under the age of 10 years in 2010 living in Saraya and Velingara districts (with SMC using SP + AQ [SMC+] since 2007) and Tambacounda district (without SMC (SMC-)). For both P. falciparum antigens, total IgG response were significantly higher in the SMC- compared with the SMC+ group (for GLURP-R0, P < 0.001 and for AMA-1, P = 0.001). There was as well a nonsignificant tendency for higher percentage of positive responders in the SMC- compared with the SMC+ group (for GLURP-R0: 22.2% versus 14.4%, respectively [P = 0.06]; for AMA-1: 45.6% versus 40.0%, respectively [P = 0.24]). Results suggest that long-term malaria chemoprevention by SMC/SP + AQ have limited impact on the development of acquired immunity, as tested using the P. falciparum antigens GLURP-R0 and AMA-1. However, other factors, not measured in this study, may interfere as well., (© The American Society of Tropical Medicine and Hygiene.)

Background: In Senegal, a significant decrease of malaria transmission intensity has been noted the last years. Parasitaemia has become lower and, therefore, more difficult to detect by microscopy. In the context of submicroscopic parasitaemia, it has become relevant to rely on relevant malaria surveillance tools to better document malaria epidemiology in such settings. Serological markers have been proposed as an essential tool for malaria surveillance. This study aimed to evaluate the sero-epidemiological situation of Plasmodium falciparum malaria in two sentinel sites in Senegal., Methods: Cross-sectional surveys were carried out in Velingara (south Senegal) and Keur Soce (central Senegal) between September and October 2010. Children under 10 years old, living in these areas, were enrolled using two-level, random sampling methods. P. falciparum infection was diagnosed using microscopy. P. falciparum antibodies against circumsporozoite protein (CSP), apical membrane protein (AMA1) and merozoite surface protein 1&#95;42 (MSP1&#95;42) were measured by ELISA method. A stepwise logistic regression analysis was done to assess factors associated with P. falciparum antibodies carriage., Results: A total of 1,865 children under 10 years old were enrolled. The overall falciparum malaria prevalence was 4.99% with high prevalence in Velingara of 10.03% compared to Keur Soce of 0.3%. Symptomatic malaria cases (fever associated with parasitaemia) represented 17.37%. Seroprevalence of anti-AMA1, anti-MSP1&#95;42 and anti-CSP antibody was 38.12, 41.55 and 40.38%, respectively. The seroprevalence was more important in Velingara and increased with age, active malaria infection and area of residence., Conclusion: The use of serological markers can contribute to improved malaria surveillance in areas with declining malaria transmission. This study provided useful baseline information about the sero-epidemiological situation of malaria in Senegal and can contribute to the identification of malaria hot spots in order to concentrate intervention efforts., Trial Registration Number: PACTR201305000551876 ( http://www.pactr.org ).

Background: Given increasing rates of resistance to existing therapy, new options for treatment and prophylaxis of malaria are needed., Methods: Two randomised, comparative, non-inferiority studies were conducted in Africa, one double-blinded and one open-label. Adults with fever, a positive peripheral blood smear, and a positive rapid diagnostic test for Plasmodium falciparum were randomised in both studies to either azithromycin (AZ) 1,000 mg plus chloroquine (CQ) 600-mg base (AZCQ 1,000 mg) once daily for three days or mefloquine hydrochloride (MQ) 1,250 mg (split dose). In the first study, an additional regimen of AZ 500 mg plus CQ 600-mg base (AZCQ 500 mg) once daily for three days was included. All study participants were hospitalised until three consecutive daily blood smears were negative for asexual P. falciparum parasitaemia. Study participants were evaluated weekly for 42 days, with Day 28 polymerase chain reaction (PCR)-corrected parasitological clearance rate as primary endpoint., Results: A total of 467 subjects were randomised in the two studies. At 28 days' follow-up, PCR-corrected parasitological clearance rates in the per protocol population in the first study were 101/103 (98%) with AZCQ 1,000 mg compared with 102/103 (99%) with MQ (95% confidence interval [CI]: -5.2, 3.3). The AZCQ 500-mg regimen was stopped during an interim study review (six [86%] clearance of seven evaluable; two lost to follow-up). In the second study, clearance rates were similar: AZCQ 1,000 mg 107/107 (100%) vs MQ 111/112 (99%; 95% CI: -1.8, 3.6). Among the participating countries, in vitro CQ resistance based on pfcrt mutation frequency in the baseline isolates across both studies ranged from 20.8% (Zambia) to 96.1% (Uganda). Serious adverse events (AEs; all causality) were observed more frequently with MQ compared with AZCQ (four vs one, respectively), though discontinuations for AEs were similar (four vs three, respectively). Common AEs in the AZ-containing arms included pruritus, vomiting, dizziness, and headache., Conclusions: Among adults with symptomatic uncomplicated falciparum malaria in Africa, the combination of AZ 1,000 mg and CQ 600-mg base once daily for three days resulted in Day 28 PCR-corrected parasitological clearance rates of ≥98% and was non-inferior to treatment with MQ. AZCQ was well tolerated., Trial Registration: ClinicalTrials.gov identifiers NCT00082576 and NCT00367653.

Background: Malarial infection in non immune pregnant women is a major risk factor for pregnancy failure. However in malaria endemic areas, intermittent preventive treatment (IPTp) have been adopted to prevent malaria in pregnancy women since 2003 in Senegal. The impact of IPT on the development of immunity is not very well documented. We conducted a prospective study at the Roi-Baudouin maternity hospital of Guediawaye in Senegal to assess IL10, IL12, TNFα and IFNγ cytokines production in pregnant women under IPTp. Cytokines were analyzed in 82 sera at inclusion and delivery. P. falciparum HRP2 antigen was detected in 17% of women included by rapid diagnostic test (RDT). At inclusion the mean of IL10 response was higher in P. falciparum negative women (8 UA) compare to RDT-positive women (7 UA) p=0.069 while in delivery the opposite was found p=0.014. Low production of inflammatory cytokines IL12, IFNγ and TNFα was noted in both groups. Between inclusion and delivery, a significant increase of IL-10 production was noted while a decrease of IFNγ and TNFα cytokine was noted. Thus, IL12 and IFNγ responses may synergistically associate as malaria immune response during pregnancy.

Our study investigated the possible impact of SP-IPT given to infants and children on the prevalence of SP-resistant haplotypes in the Plasmodium falciparum genes Pfdhfr and Pfdhps, comparing sites with and without IPTi/c. P. falciparum positive samples (N = 352) collected from children < 5 years were analyzed to determine the prevalence of SP resistance-related haplotypes by nested PCR followed by sequence-specific oligonucleotide probe-enzyme-linked immunosorbent assay. The prevalence of the Pfdhfr triple mutant haplotype (CIRN) increased in both groups, but only significantly in the IPTi/c group from 41% to 65% in 2011 (P = 0.005). Conversely, the Pfdhps 437G mutation decreased in both groups from 44.6% to 28.6% (P = 0.07) and from 66.7% to 47.5% (P = 0.02) between 2010 and 2011 in the control and the IPTi/c groups, respectively. A weak trend for decreasing prevalence of quadruple mutants (triple Pfdhfr + Pfdhps 437G) was noted in both groups (P = 0.15 and P = 0.34). During the two cross-sectional surveys some significant changes were observed in the SP resistance-related genes.

Senegal has since 2003 used sulphadoxine-pyrimethamine (SP) for Intermittent Preventive Treatment (IPT) of malaria in risk groups. However, the large-scale IPT strategy may result in increasing drug resistance. Our study investigated the possible impact of SP-IPT given to infants and children on the prevalence of SP-resistant haplotypes in the Plasmodium falciparum genes Pfdhfr and Pfdhps, comparing sites with and without IPTi/c. P. falciparum positives samples (n=352) were collected from children under 5years of age during two cross-sectional surveys in 2010 and 2011 in three health districts (two on IPTi/c and one without IPTi/c intervention) located in the southern part of Senegal. The prevalence of SP-resistance-related haplotypes in Pfdhfr and Pfdhps was determined by nested PCR followed by sequence-specific oligonucleotide probe (SSOP)-ELISA. The prevalence of the Pfdhfr double mutant haplotypes (CNRN and CICN) was stable between years at<10% in the control group (P=0.69), while it rose significantly in the IPTi/c group from 2% in 2010 to 20% in 2011 (P=0.008). The prevalence of the Pfdhfr triple mutant haplotype (CIRN) increased in both groups, but only significantly in the IPTi/c group from 41% to 65% in 2011 (P=0.005). Conversely, the Pfdhps 437G mutation decreased in both groups from 44.6% to 28.6% (P=0.07) and from 66.7% to 47.5% (P=0.02) between 2010 and 2011 in the control and the IPTi/c groups, respectively. Combined with Pfdhfr, there was a weak trend for decreasing prevalence of quadruple mutants (triple Pfdhfr+Pfdhps 437G) in both groups (P=0.15 and P=0.34). During the two cross-sectional surveys, some significant changes were observed in the SP-resistance-related genes. However, since these changes were observed in the two groups, the IPTi/c strategy does only seem to have limited impact on resistance development and other factors as well. However, continuous monitoring will be needed, due to the up-scaling of the IPTi/c strategy in Senegal according to WHO recommendations., (Copyright © 2013 Académie des sciences. Published by Elsevier SAS. All rights reserved.)

As a result of widespread antimalarial drug resistance, all African countries with endemic malaria have, in recent years, changed their malaria treatment policy. In Senegal, the health authorities changed from chloroquine (CQ) to a combination of sulfadoxine-pyrimethamine (SP) plus amodiaquine (AQ) in 2003. Since 2006, the artemisinin combination therapies (ACTs) artemether-lumefantrine (AL) and artesunate plus amodiaquine (AS/AQ) were adopted for uncomplicated malaria treatment. After several years of CQ withdrawal, the current study wished to determine the level of CQ resistance at the molecular level in selected sites in Senegal, because the scientific community is interested in using CQ again. Finger prick blood samples were collected from Plasmodium falciparum-positive children below the age of 10 years (N = 474) during cross-sectional surveys conducted in two study sites in Senegal with different malaria transmission levels. One site is in central Senegal, and the other site is in the southern part of the country. All samples were analyzed for single nucleotide polymorphisms (SNPs) in the P. falciparum CQ resistance transporter gene (Pfcrt; codons 72-76) using polymerase chain reaction (PCR) sequence-specific oligonucleotide probe (SSOP) enzyme-linked immunosorbent assay (ELISA) and real-time PCR methods. In total, the 72- to 76-codon region of Pfcrt was amplified in 449 blood samples (94.7%; 285 and 164 samples from the central and southern sites of Senegal, respectively). In both study areas, the prevalence of the Pfcrt wild-type single CVMNK haplotype was very high; in central Senegal, the prevalence was 70.5% in 2009 and 74.8% in 2010, and in southern Senegal, the prevalence was 65.4% in 2010 and 71.0% in 2011. Comparing data with older studies in Senegal, a sharp decline in the mutant type Pfcrt prevalence is evident: from 65%, 64%, and 59.5% in samples collected from various sites in 2000, 2001, and 2004 to approximately 30% in our study. A similar decrease in mutant type prevalence is noted in other neighboring countries. With the continued development of increased CQ susceptibility in many African countries, it may be possible to reintroduce CQ in the near future in a drug combination; it could possibly be given to non-vulnerable groups, but it demands close monitoring of possible reemergence of CQ resistance development.

The impact of intermittent presumptive treatment (IPT) on the immunity of pregnant women in Senegal is still not very well known. We conducted a prospective study at the Roi-Baudouin maternity of Guediawaye in Senegal to assess IgG antibodies production against MSP1, GLURP and DBL5 in pregnant women under IPT. Blood samples were collected from the participating women at inclusion and delivery. Samples were analyzed after centrifugation for the detection of IgG antibodies in sera by Elisa. Informed consent was given by each study participant prior to their inclusion. A total of 101 eligible women aged from 18 to 44 were included in this study. Multigravidae women represented 70.3% of the study population, whereas primigravidae accounted for 29.7%. The IgG level decreased slightly from inclusion to delivery for the women with regard to anti-MSP1 (83.1at inclusion versus 79.5 at delivery, p = 0.52) as well as anti-GLURP-R2 (84.1 at inclusion versus 75.9 at delivery, p = 0.16). After adjustment for number of pregnancies, there was a significant decrease in the production of anti-VAR2CSA between inclusion and delivery (p < 0.05). By reducing the incidence of malaria during pregnancy, IPT reduced the acquisition of placental parasites antibodies suppressors which could delay the development of protective immunity against malaria. The application of IPT in pregnant women would thus be more appropriate in hypoendemic areas where malaria exposure is lower.

Background: In view of the high level of chloroquine resistance in many countries, WHO has recommended the use of combination therapy with artemisinin derivatives in the treatment of uncomplicated malaria due to Plasmodium falciparum. Four antimalarial drug combinations, artesunate plus amodiaquine (Arsucam), artesunate plus mefloquine (Artequin), artemether plus lumefantrine (Coartem; four doses and six doses), and amodiaquine plus sulphadoxine-pyrimethamine, were studied in five health districts in Senegal., Methods: This is a descriptive, analytical, open, randomized study to evaluate the efficacy and tolerability of these four antimalarial combinations in the treatment of uncomplicated falciparum malaria using the 2002 WHO protocol., Results: All drug combinations demonstrated good efficacy. On day 28, all combinations resulted in an excellent clinical and parasitological response rate of 100% after correction for PCR results, except for the four-dose artemether-lumefantrine regimen (96.4%). Follow-up of approximately 10% of each treatment group on day 42 demonstrated an efficacy of 100%.The combinations were well tolerated clinically and biologically. No unexpected side-effect was observed and all side-effects disappeared at the end of treatment. No serious side-effect requiring premature termination of treatment was observed., Conclusion: The four combinations are effective and well-tolerated.

In order to evaluate the in vivo efficacy of chloroquine in the treatment of P. falciparum malaria, studies have been carried out in Richard-Toll, Fatick and Tambacounda, 3 areas where dynamics of transmission, population movements, as well as prophylactic and curative practises are different. Failure rates in treatment were 13% in site 1 (Richard-Toll) where medical pressure and population movements are high. In sites 2 and 3 (Fatick and Tambacounda), the failure rate was 3%. Even if medical pressure is lower in the latter site (Tambacounda), the higher transmission could be a factor in the spreading of resistance. A surveillance system and better use of chloroquine must be undertaken.

This prospective one-year study was conducted as a preliminary phase to setting up a protocol for economic appraisal of management of severe malaria at Albert Royer Children's Hospital in Dakar, Senegal. Data was routinely collected using a standardized checklist. The four key indicators chosen for this study were nurse workload, adequacy of care (number of patients receiving adequate care), direct cost, and mortality rate. The mean daily care workload was estimated to be 27.2 minutes. This indicator assesses the relationship between supply and demand. Based on 5 criteria, care was considered as adequate in 54.5 p. 100 of patients. This indicator is helpful in judging the effectiveness of the therapeutic modalities used. The direct cost of treating severe malaria was estimated to be 45963 CFA francs. This indicator will be useful in establishing controls to reduce costs. The mortality rate was 12.2 p. 100. Comparison of this rate with previous years suggests little improvement in the outcome of malaria management at the institution. This indicator must be taken into account in the ongoing quality control program. Overall these findings should enable institutional decision-making to improve management of severe malaria based on objective measurable data.

To assess epidemiological, clinical and therapeutic features of severe malaria among adults in Dakar (Senegal), we carried out a 5-year retrospective study in Infectious Diseases Ward (January 1992-December 1996). Over this period, 222 cases of severe malaria were included according to WHO definition criteria, 120 of them (54%) being adult patients. Monthly distribution of cases showed 2 peaks, on October and November. Most of the patients were males (sex-ratio = 2.1) and lived in urban area (91.7%). The mean age was 28.9 years (range = 16-73 years). Clinically, all of the cases presented with stage II coma. Association existed with convulsion (20%), severe anaemia (29.2%), renal failure (19.2%), hypoglycaemia (17.5%) and jaundice (34%). Patients were treated using quinine intravenously. Case fatality rate reached 26.7%, indicating life-threatening potential of malaria in adults living in urban area.

In order to determine the prevalence of malaria and its epidemiological characteristics, a survey was carried out in 11 villages situated in all the Basin of River Senegal (B.R.S.). 3306 (0-14 years) children are examined. The results show that malaria is hypo-endemic in the B.R.S. with a plasmodic index of 8.6% and a splenic index of 9.9%. But these malariametric indexes change according to the areas visited. Thus, malaria prevails at a hypo-endemic level in Dagana and Podor districts while at a medium if not hyperendemic level in Matam and Bakel districts. The plasmodial index also change according to age reaching a maximum within children from 10 to 14 years. As for the spleen index, it is low among children from 10-14 years. As for the spleen index, it is low among children from 0 to 4 years old, then increases among those aging from 5 to 9 years, before decreasing within children ranging from 10 to 14 years. P.falciparum is the most prevalent species, representing 96% of the cases; it is followed by P.malarioe (3%) and P.ovale (1%). If our results are compared with those obtained before by other authors, we can conclude that the recent hydro-agricultural plannings carried out in the area, have not yet provoked an increase of the cases of malaria. But, in order to avoid this risk, it is necessary to take from now some preventive measures.

From April to November 1994, we carried out a study in Rufisque, an urban area located in Dakar Region. During dry season, 5.32% of febrile outpatients were infected with Plasmodium falciparum with a mean parasitic density evaluated at 12,471 p/microliter. One case of cerebral malaria was noted. During raining season, malaria represented 58.75% of the fevers. Ten presented neurological signs; the mean parasitic density was high, 131,140 p/microliter. Two children died. Good efficiency of quinine was noted but chloroquine treatment failures was present: 50%. Generally malaria is less prevalent in urban areas. But in Rufisque ecological conditions are main factors which permit spreading of the disease. Prior measures of control such correct treatment of cases and good management of environment must be done.

The efficacy of quinine treatment for Plasmodium falciparum strains remains sound. However reports of decreased sensitivity and resistance of some strains in Asia and East Africa indicate that current treatment regimens should be re-adjusted. The purpose for the present study carried out in Dakar, Senegal, was to evaluate the local regimen for acute Plasmodium falciparum malaria using quinine at a dose of 20 mg/kg per day in two daily injections on 3 consecutive days. Thirty-seven patients with acute Plasmodium falciparum malaria including 10 severe cases were treated using the standard regimen and followed up clinically and parasitologically from Day 0 to Day 7. On Day 7 parasites were still detectable in the blood of four patients for a failure rate of 10.8%. Persistence of parasites despite disappearance of clinical symptoms suggests that the regimen should be increased to 25 mg/kg per day for at least for 3 days or longer if symptoms persist. Due to its adverse effects and cost (10 times higher than chloroquine treatment), quinine treatment should be prescribed only for patients with severe malaria forms.

In Touba, more important accessibility to antimalarial drugs and their uncontrolled use let to assure that the rate of malarial morbidity would be lower there than in other place in Senegal whereas the rate of chloroquine resistance would be higher. A checking survey of these assumptions has been carried out from october 15 to november 10, 1995 in Touba's health center. Among 227 feverish subjects investigated, 111 were Plasmodium falciparum carriers. Malarial bouts accounted for 48.9% of the feverish fits observed and for the major cause of consultation during the rainy season. These figures are higher than those usually observed in urban environment. Conversely, the rate of chloroquine resistance is lower than those observed in urban zones, since the therapeutic efficacy of chloroquine on Plasmodium falciparum was 100% in that survey.

The study of malarial seroprevalence in Dakar has interested 598 women among whom 377 pregnant and 221 non pregnant, between 15 to 45 years old and happens during the dry season, period of which malaria transmission is practically stopped in the locality. Among the tested serums by indirect immunofluorescence with Plasmodium falciparum asexual blood forms as antigen, 24.4% contained antimalarial antibodies. The serological index does'nt vary significantly according to the months during the dry season, the women age and their previous pregnancy number. On the contrary, the women who live in Dakar since less than 2 years, have e higher seropositivity rate of 33.7% than those who are there since more than 2 years, 20.0%. It is likewise for the women practicing chemoprophylaxy with chloroquine of whom 16.5% have antibodies against 26.0% among those who don't practice it. The seropositivity rate doesn't vary significantly according as the women are pregnant (24.7% of positive) or not pregnant (24.0% of positive). The weakness of the serological rate in the examined women, can be explained by the situation of Dakar in a weak malarial hypoendemic area. II shows that the major examined subjects have lost or have never had contact with Plasmodium what predispose them to make severe and complicated malarial attacks.

The comparison of the prevalence of malaria in pregnant and non pregnant women living in Dakar has interested 1819 women among whom 950 pregnant and 869 non pregnant. For all the examined women, the global plasmoidic index was 2.6% and the gametocytic index 0.1%. Plasmodium falciparum was the only observed species. According to the obtained results, pregnant women, with a plasmoidic index of 4.5% are more often parasited than the non pregnant women, only affected in a proportion of 0.5% Whatever the age, the number of previous pregnancy, the place of residence, the duration of the stay in Dakar may be, the pregnant women are always more often parasited than the non pregnant women and the registered differences are statistically significant. That situation could come from a greater receptivity of the pregnant women what is admitted by some authors. But a more important proportion of natives from rural area was observed among the pregnant women, from where a difference in the exposure to the risk of impaludation between the two groups that could explain the registered results. The global plasmoidic index of 2.6% obtained in the examined women, reflects well the present situation of the malaria endemy in Dakar, a weak hypo-endemic area.