[Sexuality assessment of homozygous adult sickle cell patients with a history of priapism in Senegal]. / Évaluation de la sexualité des drépanocytaires adultes homozygotes ayant des antécédents de priapisme au Sénégal.

OBJECTIVES: The objective of this study was to evaluate the sexuality of SS sickle cell patients with a history of priapism. METHODS: This was a case-control study of adult SS sickle cell patients. The occurrence of priapism as well as the nature of the priapism had been investigated. The patients were subdivided into three groups: Group 1 (no priapism), Group 2 (intermittent priapism) and Group 3 (acute priapism). The patients' sexuality was studied using the IIEF-15 questionnaire. RESULTS: We interviewed 191 SS sickle cell patients. The mean age was 27.1±7.1 years. Priapism was observed in 43.5 %. Only 77 patients were eligible for the IIEF15 questionnaire. Groups 1 and 2 performed significantly better than group 3 on erectile function (EF) and orgasmic function (OF) scores. There was no significant difference in the EF and OF scores between groups 1 and 2. No significant difference was observed between the three groups for the scores of sexual desire (SD), intercourse satisfaction (IS), and overall satisfaction (OS). The impairment of erectile function in group 2 was related to the age of the first episode of priapism and the last episode. The impairment of erectile function in group 3 was related to the duration of evolution (P<0.05). CONCLUSION: This study shows that priapism is responsible for impaired erectile function in SS adult sickle cell patients. A program to prevent intermittent episodes of priapism should be put in place.

Detection of kdr and ace-1 mutations in wild populations of Anopheles arabiensis and An. melas in a residual malaria transmission area of Senegal.

In the central western Senegal, malaria transmission has been reduced low due to the combination of several effective control interventions. However, despite this encouraging achievement, residual malaria transmission still occurring in few areas, mainly ensured by An. arabiensis and An. melas. The resurgence or the persistence of the disease may have originated from the increase and the spread of insecticide resistance genes among natural malaria vectors populations. Therefore, assessing the status and mechanisms of insecticides resistance among targeted malaria vectors is of highest importance to better characterize factors underlying the residual transmission where it occurs. Malaria vectors were collected from three selected villages using nocturnal human landing catches (HLC) and pyrethrum spray collections (PSC) methods. An. gambiae s.l. specimens were identified at the species level then genotyped for the presence of kdr-west (L1014F), kdr-east (L1014S) and ace-1R mutations by qPCR. An. arabiensis (69.36%) and An. melas (27.99%) were the most common species of the Gambiae complex in the study area. Among An. arabiensis population, the allelic frequency of the kdr-east (22.66%) was relatively higher than for kdr-west mutation (9.96%). While for An. melas populations, the overall frequencies of both mutations were very low, being respectively 1.12% and 0.40% for the L1014S and L1014F mutations. With a global frequency of 2%, only the heterozygous form of the G119S mutation was found only in An. arabiensis and in all the study sites. The widespread occurrence of the kdr mutation in both An. arabiensis and An. melas natural populations, respectively the main and focal vectors in the central-western Senegal, may have contributed to maintaining malaria transmission in the area. Thus, compromising the effectiveness of pyrethroids-based vector control measures and the National Elimination Goal. Therefore, monitoring and managing properly insecticide resistance became a key programmatic intervention to achieve the elimination goal where feasible, as aimed by Senegal. Noteworthy, this is the first report of the ace-1 mutation in natural populations of An. arabiensis from Senegal, which need to be closely monitored to preserve one of the essential insecticide classes used in IRS to control the pyrethroids-resistant populations.

Correction: Safety of Seasonal Malaria Chemoprevention (SMC) with Sulfadoxine-Pyrimethamine plus Amodiaquine when Delivered to Children under 10 Years of Age by District Health Services in Senegal: Results from a Stepped-Wedge Cluster Randomized Trial.

[This corrects the article DOI: 10.1371/journal.pone.0162563.].

Safety of Seasonal Malaria Chemoprevention (SMC) with Sulfadoxine-Pyrimethamine plus Amodiaquine when Delivered to Children under 10 Years of Age by District Health Services in Senegal: Results from a Stepped-Wedge Cluster Randomized Trial.

BACKGROUND: It is recommended that children aged 3 months to five years of age living in areas of seasonal transmission in the sub-Sahel should receive Seasonal Malaria Chemoprevention (SMC) with sulfadoxine-pyrimethamine plus amodiaquine (SPAQ) during the malaria transmission season. The purpose of this study was to evaluate the safety of SMC with SPAQ in children when delivered by community health workers in three districts in Senegal where SMC was introduced over three years, in children from 3 months of age to five years of age in the first year, then in children up to 10 years of age. METHODS: A surveillance system was established to record all deaths and all malaria cases diagnosed at health facilities and a pharmacovigilance system was established to detect adverse drug reactions. Health posts were randomized to introduce SMC in a stepped wedge design. SMC with SPAQ was administered once per month from September to November, by nine health-posts in 2008, by 27 in 2009 and by 45 in 2010. RESULTS: After three years, 780,000 documented courses of SMC had been administered. High coverage was achieved. No serious adverse events attributable to the intervention were detected, despite a high level of surveillance. CONCLUSIONS: SMC is being implemented in countries of the sub-Sahel for children under 5 years of age, but in some areas the age distribution of cases of malaria may justify extending this age limit, as has been done in Senegal. Our results show that SMC is well tolerated in children under five and in older children. However, pharmacovigilance should be maintained where SMC is implemented and provision for strengthening national pharmacovigilance systems should be included in plans for SMC implementation. TRIAL REGISTRATION: ClinicalTrials.gov NCT 00712374.

Efficacy of sulfadoxine-pyrimethamine for the treatment of uncomplicated falciparum malaria in southern Mauritania.

BACKGROUND: Until 2006, the Mauritanian Ministry of Health recommended chloroquine and sulfadoxine-pyrimethamine for first- and second-line treatment of uncomplicated malaria, respectively. This study assessed the clinical efficacy of sulfadoxine-pyrimethamine in Kobeni as first-line treatment. MATERIALS AND METHODS: This study included 55 patients with Plasmodium falciparum infections, who were treated with sulfadoxine-pyrimethamine and followed up for 28 days. Isolates were genotyped to distinguish between recrudescence and reinfection. Treatment success rates and survival were analysed per protocol to evaluate drug efficacy. RESULTS: After inclusion, 2 patients were excluded for protocol violations, and 3 patients were lost to follow-up. Of the remaining 50 patients (per protocol population), 43 (86%) had adequate clinical and parasitological responses. Of the 7 patients with treatment failure, 5 (10%) were early failures, while 2 (4%) had initially responded and had late clinical failure on day 7, associated with recrudescence. With the exception of one adult weighing 91 kg, all treatment failures occurred in children aged from 7 to 12 years. CONCLUSIONS: Sulfadoxine-pyrimethamine monotherapy was moderately effective but insufficiently reliable in view of the relatively high rate of early treatment failure. The high prevalence of chloroquine resistance found in earlier studies and the results of the present study on sulfadoxine-pyrimethamine justify the change in national policy and systematic use of artemisinin-based combination therapy for first-line treatment of P. falciparum malaria in Mauritania.

[Identification of anopheles breeding sites in the residual foci of low malaria transmission «hotspots¼ in Central and Western Senegal]. / Identification des gîtes larvaires d'anophèles dans les foyers résiduels de faible transmission du paludisme « hotspots ¼ au centre-ouest du Sénégal.

Malaria incidence has markedly declined in the Mbour, Fatick, Niakhar and Bambey districts (central and western Senegal) thanks to a scaling up of effective control measures namely LLINs (Long Lasting Insecticide Treated Net), ACTs (Artesunate Combination Therapy) and promoting care seeking. However malaria cases are now maintained by foci of transmission called hotspots. We evaluate the role of anopheles breeding sites in the identification of malaria hotspots in the health districts of Mbour, Fatick, Niakhar and Bambey. Surveys of breeding sites were made in 6 hotspot villages and 4 non-hotspot villages. A sample was taken in each water point with mosquito larvae by dipping method and the collected specimens were identified to the genus level. Additional parameters as name of the village and breeding sites, type of collection, original water turbidity, presence of vegetation, proximity to dwellings, geographic coordinates, sizes were also collected. Sixty-two water collections were surveyed and monitored between 2013 and 2014. Temporary natural breeding sites were predominant regardless of the epidemiological status of the village. Among the 31 breeding sites located within 500 meters of dwellings in hotspots villages, 70% carried Anopheles larvae during the rainy season while 43% of the 21 breeding sites located at similar distances in non-hotspot villages carried Anopheles larvae during the same period (P = 0.042). At the end of the rainy season, the trend is the same with 27% of positive breeding sites in hotspots and 14% in non-hotspots villages. The breeding sites encountered in hotspots villages are mostly small to medium size and are more productive by Anopheles larvae than those found in non-hotspot area. This study showed that the high frequency of smallest and productive breeding sites around and inside the villages can create conditions of residual transmission.

[Pneumocystis pneumonia biological diagnosis at Fann Teaching Hospital in Dakar, Senegal]. / Diagnostic biologique de la pneumonie à Pneumocystis au centre hospitalier universitaire de Fann, Dakar, Sénégal.

BACKGROUND: Data relative to Pneumocystis pneumonia in sub-Saharan Africa are not well known. Weakness of the technical material and use of little sensitive biological tools of diagnosis are among the evoked reasons. The objective of this study is to update the data of the disease at the Fann Teaching Hospital in Dakar and to estimate biological methods used in diagnosis. MATERIALS AND METHODS: A descriptive longitudinal study was carried out from January 5th, 2009 to October 31st, 2011 in the parasitology and mycology laboratory of the Fann Teaching Hospital in Dakar. The bronchoalveolar lavages received in the laboratory were examined microscopically for Pneumocystis jirovecii by indirect fluorescent assay or after Giemsa or toluidine blue O staining. RESULTS: One hundred and eighty-three bronchoalveolar lavages withdrawn from 183 patients were received in the laboratory. Sixteen were positive for P. jirovecii at 9% frequency. Four among these patients were HIV positive. Indirect fluorescent assay allowed finding of P. jirovecii among 16 patients while Giemsa staining discovered P. jirovecii only in a single patient. No case was diagnosed by toluidine blue O staining. CONCLUSION: Pneumocystis pneumonia in Parasitology and Mycology Laboratory of Fann Teaching Hospital at Dakar was mainly diagnosed among HIV patients.

Genome-wide association study of antibody responses to Plasmodium falciparum candidate vaccine antigens.

We conducted a genome-wide association study (GWAS) of antibody responses directed to three Plasmodium falciparum vaccine candidate antigens (MSP1, MSP2 and GLURP) previously associated with different patterns of protection against malaria infection in Senegalese children. A total of 174 950 single-nucleotide polymorphisms (SNPs) were tested for association with immunoglobulin G1 (IgG1) responses directed to MSP1 and to GLURP and with IgG3 responses to MSP2 FC27 and to MSP2 3D7. We first performed a single-trait analysis with each antibody response and then a multiple-trait analysis in which we analyzed simultaneously the three immune responses associated with the control of clinical malaria episodes. Suggestive associations (P<1 × 10(-4)) were observed for 25 SNPs in MSP1 antibody response analysis or in multiple-trait analysis. According to the strength of their observed associations and their functional role, the following genes are of particular interest: RASGRP3 (2p22.3, P=7.6 × 10(-6)), RIMS1 (6q13, P=2.0 × 10(-5)), MVB12B (9q33.3, P=8.9 × 10(-5)) and GNPTAB (12q23.2, P=7.4 × 10(-5)). Future studies will be required to replicate these findings in other African populations. This work will contribute to the elucidation of the host genetic factors underlying variable immune responses to P. falciparum.

[Evaluation of the efficacy and safety of three 2-drug combinations for the treatment of uncomplicated Plasmodium falciparum malaria in Senegal: artesunate-amodiaquine, dihydroartemisinin-piperaquine, and artemether-lumefantrine]. / Évaluation de l'efficacité et de la tolérance des combinaisons artésunate-amodiaquine, dihydroartémisinine-pipéraquine et artéméther-luméfantrine pour le traitement du paludisme à Plasmodium falciparum non compliqué au Sénégal.

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.

[Acceptability of indoor residual spraying in the Central-Western of Senegal]. / Étude de l'acceptabilité de l'aspersion intradomiciliaire d'insecticide à effet rémanent dans le centre-ouest du Sénégal.

The recent decline of malaria transmission in central-western of Senegal after a scaling up of control measures gives an open window for interventions toward malaria elimination. As a consequence, malaria transmission is now occurring as hotspots. The aim of the project is to evaluate whether target control measures combining indoor residual spraying (IRS) with chemoprophylaxis can virtually eliminate malaria in hotspots. Targeted villages located in four (4) health districts (Mbour, Fatick, Niakhar and Bambey) were sprayed in august 2013 with Actellic® 300 CS (Pirimiphosmethyl). Our objective in this study is to evaluate the acceptability of IRS in the population. IRS is a very complex intervention that requires strong adhesion of populations. After its implementation, 370 households have been interviewed. The results of this survey showed good acceptability of IRS using Actellic® 300 CS, with 97.8% of beneficiaries who declared that IRS is good and even excellent for the community. Despite inconveniences that may arise during intervention, including the preparation of structures to be treated, 98% of respondents were not disturbed in their daily activities. 98.6% of responders declared that sprayers were working with professionalism and almost all households (99.7%) are willing to accept IRS next year. The survey revealed a good acceptability of indoor residual spraying in hot spots located in central-western of Senegal; spraying with Actellic® 300 CS did not cause a problem to the targeted populations. Finally, there is great satisfaction in the population due a huge reduction of mosquito nuisances.

[Profile of cytokines associated with protection against malaria episodes during pregnancy in hypo-endemic area in Senegal]. / Profil des cytokines associées à la protection contre les accès palustres au cours de la grossesse en zone hypo-endémique au Sénégal.

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.

[Cryptosporidiosis in Senegalese children: prevalence study and use of ELISA serologic diagnosis]. / La cryptosporidiose de l'enfant au Sénégal : étude de la prévalence et apport du diagnostic sérologique par ELISA.

This is a prospective, descriptive and analytic study conducted from July 2011 to September 2011 at the Children National Hospital Albert Royer of Dakar and at the Vélingara Health District. It was focused on children under 15 without reference to HIV status. For each child, a sample of stool was examined by the Ziehl-Neelsen modified staining and by ELISA using the "Cryptosporidium Antigen Detection Microwell ELISA kit" designed to detect Cryptosporidium spp antigens. The aim of our study was to determine the prevalence of cryptosporidiosis in rural and hospital areas and to measure the performance of the ELISA kit that we used. Out of the 375 stool examinations performed with the Ziehl-Neelsen modified staining, 17 had revealed the presence of Cryptosporidium spp (4.53%). The prevalence in rural areas was 2% while the hospital prevalence was 7.4%, of which 1.8% (1/57) were from urban areas and 9.8% (12/122) from suburban areas. No positive case was observed in children over 10 years. By ELISA, 23 positives cases were reported corresponding to a prevalence of 6.13% (1.8% in children living in urban areas, 13.1% in children from suburban areas and 3%living in rural areas).The correlation of this assay with the Ziehl-Neelsen modified staining, considered as the reference method, found that this assay had a sensitivity of 58.82% and a high specificity reaching 96.37%. The positive predictive value (PPV) was 43.4% while the negative predictive value was 98%. Cryptosporidiosis is a significant cause of parasitic infection among children in Senegal. Antigen detection of Cryptosporidium spp by ELISA in stool can be a complementary tool in the diagnosis of cryptosporidiosis.

[Identification of three Candida africana strains in Senegal]. / Identification de trois souches de Candida africana au Sénégal.

JUSTIFICATION: The frequency of candidiasis has increased dramatically in recent years. Candida albicans is the most common species. However, other species which are pathogenic and resistant to usual antifungal agents beginning to emerge. These include Candida dubliniensis and Candida africana, which share morphological similarities with Candida albicans. Thus, it is of interest to correctly identify the fungal isolates. OBJECTIVE: To seek these new species among Candida strains isolated in Dakar. MATERIAL AND METHODS: Oropharyngeal and vaginal swabs were performed at Fann Universitary Hospital in Dakar. The strains were identified by the germ tube test, the chlamydospore production test and an auxanogram. Then identification by PCR targeting the hyphal wall protein 1(hwp1) gene, was performed for the discrimination between Candida albicans, Candida dubliniensis and Candida africana. RESULTS: In total, 243 yeasts were isolated from samples including 231 in vaginal swab and 12 in oropharyngeal swab. Species identified by phenotypic methods are Candida albicans, which is the most frequent, Candida tropicalis, Candida glabrata, Candida dubliniensis, Candida kefyr and Candida lusitaniae. PCR performed on the 150 strains germ tube test positive identifies three Candida africana, 109 Candida albicans and no strain of Candida dubliniensis. CONCLUSION: This study isolates Candida africana for the first time in Senegal. Further studies on a larger sample will better know the actual proportion of these three species among the isolated yeasts.

Evaluation of serum boron levels and lipid profile in pregnancies with or without gestational diabetes.

AIMS: Animal research has demonstrated that boron has effects on triglycerides and glucose and may act as a metabolic regulator in several enzymatic systems. Gestational diabetes mellitus (GDM) is a prevalent obstetrical complication and the lack of data on maternal status of boron in normal/diabetic pregnancies, prompted us to undertake this study. METHODS: Maternal blood samples were collected during screening and diagnosis of GDM at 24-28 weeks. Serum lipids (total cholesterol, high-density cholesterol, low density cholesterol, triglycerides, lipoprotein-a, apolipoprotein-A-I and apolipoprotein-B) and boron levels were determined. Fifteen non-GDM and 19 GDM women constituted the study population. RESULTS: The mean age was 30.1±5 years. The median boron levels were 15.2 µg/L (0.0152 ppm; range, 8.4-25.4 µg/L). When GDM and non-GDM cases were compared for age, gravidity, parity, lipid profiles and serum boron levels, no significant differences were found (P>0.05). No correlation was found between lipids and boron levels. CONCLUSION: This preliminary study contributes to the limited information about the metabolic aspects of boron. Considering the evidence that boron acts as a regulator of energy substrate utilization, the effect of dietary boron on glucose metabolism deserves further research.

[Effect of intermittent presumptive treatment with sulfadoxine-pyrimethamine on the acquisition of anti-VAR2CSA antibodies in pregnant women living in a hypoendemic area in Senegal]. / Influence du traitement présomptif intermittent par la sulfadoxinepyriméthamine sur l'acquisition d'anticorps anti-VAR2CSA chez la femme enceinte vivant en zone hypoendémique au Sénégal.

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.

Schistosoma haematobium infection affects Plasmodium falciparum-specific IgG responses associated with protection against malaria.

We have previously shown that antibody responses directed to Plasmodium falciparum merozoite surface protein (MSP)-1, MSP-2 and glutamate-rich protein (GLURP) are associated with anti-malarial protection in residents of the Niakhar area of Senegal. In the same area, urinary schistosomiasis is frequent and we therefore assessed the possible influence of Schistosoma haematobium infection on these protective anti-malarial IgG responses. After adjustment for confounders, we found that the levels of IgG1 directed to MSP1 and GLURP were significantly lower in helminth carriers. The higher circulating levels of interleukin (IL)-10 present in the plasma of co-infected individuals were associated with decreased anti-plasmodial IgG responses, particularly of those directed to MSP-2. Our data thus reveal a modulation of P. falciparum-specific immune responses in the presence of a trematode helminth infection, potentially increasing infected individuals' risk of plasmodial infection or disease.

Canine visceral leishmaniasis caused by Leishmania infantum in Senegal: risk of emergence in humans?

In the context of global warming and the risk of spreading arthropod-borne diseases, the emergence and reemergence of leishmaniasis should not be neglected. In Senegal, over the past few years, cases of canine leishmaniasis have been observed. We aim to improve the understanding of the transmission cycle of this zoonosis, to determine the responsible species and to evaluate the risk for human health. An epidemiological and serological study on canine and human populations in the community of Mont Rolland (Thiès area) was conducted. The data showed a high seroprevalence of canine leishmaniasis (>40%) and more than 30% seropositive people. The dogs' seroprevalence was confirmed by PCR data (concordance > 0.85, Kappa > 0.7). The statistical analysis showed strong statistical associations between the health status of dogs and seropositivity, the number of positive PCRs, clinical signs and the number of Leishmania isolates. For the first time, the discriminative PCRs performed on canine Leishmania strains clearly evidenced that the pathogenic agent is Leishmania infantum. The results obtained show that transmission of this species is well established in this area. That the high incidence of seropositivity in humans may be a consequence of infection with this species is discussed.

Amodiaquine dosage and tolerability for intermittent preventive treatment to prevent malaria in children.

Sulfadoxine-pyrimethamine with amodiaquine (SP-AQ) is a highly efficacious regimen for intermittent preventive treatment to prevent malaria in children (IPTc), but the amodiaquine component is not always well tolerated. We determined the association between amodiaquine dosage by body weight and mild adverse events (AEs) and investigated whether alternative age-based regimens could improve dosing accuracy and tolerability, using data from two trials of IPTc in Senegal, one in which AQ dose was determined by age and the other in which it was determined by weight category. Both dosage strategies resulted in some children receiving AQ doses above the recommended therapeutic range. The odds of vomiting increased with increasing amodiaquine dosage. In one study, incidence of fever also increased with increasing dosage. Anthropometric data from 1,956 children were used to predict the dosing accuracy of existing and optimal alternative regimens. Logistic regression models describing the probability of AEs by dosage were used to predict the potential reductions in mild AEs for each regimen. Simple amendments to current AQ dosing schedules based on the child's age could substantially increase dosing accuracy and thus improve the tolerability of IPTc using SP-amodiaquine in situations where weighing the child is impractical.

Dosing accuracy of artesunate and amodiaquine as treatment for falciparum malaria in Casamance, Senegal.

OBJECTIVES: Several products of artesunate plus amodiaquine (AS + AQ) are being deployed in malaria-endemic countries for treating uncomplicated falciparum malaria but dosing accuracy and consequential effects on efficacy and tolerability have not been examined. METHODS: Patients with parasitologically confirmed, uncomplicated falciparum malaria were treated and followed by research teams or local health centre staff in Casamance, Senegal. AS + AQ was given as: (i) loose combination (AS 50 mg, AQ 200 mg), dosed on body weight, or (ii) co-blistered product (AS 50 mg, AQ 153 mg) dosed by weight or age. Target doses were: (i) AS 4 (2-10) mg/kg/day and (ii) AQ 10 (7.5-15) mg/kg/day. Patients receiving therapeutic doses defined dosing accuracy. Treatment-emergent signs and symptoms (TESS) were recorded. RESULTS: A total of 3277 patients were treated with loose (n = 1972, weight-dosed) or co-blistered (n = 1305, 962 age-dosed, 343 weight-dosed) AS + AQ by the research team (n = 966) or clinic staff (n = 2311). AS was dosed correctly in >99% with all regimens. Loose AQ by weight was 98% correct. The co-blister AQ overdosed 18% of patients when dosed by age and underdosed 13% by weight. Low weight was an independent risk factor for overdosing. The co-blister had significantly more TESS than the loose product [117/1305 (9%) vs. 41/1972 (2%), relative risk = 4.3 (95% CI: 3.0-6.1, P < 0.0001)]. Age-based dosing accounted for the difference. TESS occurred mostly within one day (72%) and were mild or moderate (75%). CONCLUSION: Artesunate is easier to dose than AQ. Currently available age-dosed, co-blistered AS + AQ tends to overdose AQ and is less well tolerated than loose tablets. It is not the optimal presentation of AS + AQ.