Seasonal vaccination against malaria: a potential use for an imperfect malaria vaccine.

In many parts of the African Sahel and sub-Sahel, where malaria remains a major cause of mortality and morbidity, transmission of the infection is highly seasonal. Seasonal malaria chemoprevention (SMC), which involves administration of a full course of malaria treatment to young children at monthly intervals during the high transmission season, is proving to be an effective malaria control measure in these areas. However, SMC does not provide complete protection and it is demanding to deliver for both families and healthcare givers. Furthermore, there is a risk of the emergence in the future of resistance to the drugs, sulfadoxine-pyrimethamine and amodiaquine, that are currently being used for SMC. Substantial progress has been made in the development of malaria vaccines during the past decade and one malaria vaccine, RTS,S/AS01, has received a positive opinion from the European Medicines Authority and will soon be deployed in large-scale, pilot implementation projects in sub-Saharan Africa. A characteristic feature of this vaccine, and potentially of some of the other malaria vaccines under development, is that they provide a high level of efficacy during the period immediately after vaccination, but that this wanes rapidly, perhaps because it is difficult to develop effective immunological memory to malaria antigens in subjects exposed previously to malaria infection. A potentially effective way of using malaria vaccines with high initial efficacy but which provide only a short period of protection could be annual, mass vaccination campaigns shortly before each malaria transmission season in areas where malaria transmission is confined largely to a few months of the year

Efficacy, safety, tolerability of Dihydroartemisinine-Piperaquine and Sulfadoxine-Pyrimethamine plus Amodiaquine for Seasonal Malaria Chemoprevention (SMC) in children in Burkina Faso

Children in areas of highly seasonal malaria transmission in the Sahel should receive SMC with sulfadoxine-pyrimethamine plus amodiaquine (SPAQ). These drugs retain their efficacy in the areas where SMC is recommended, but alternative regimens are needed if SMC is used in other areas or if these drugs start to lose efficacy. The aim of this study was to investigate the suitability of dihydroartemisin-piperaquine (DHAPQ) for SMC, using a non-inferiority trial design. 1500 children randomized to receive SPAQ or DHAPQ monthly from August to October, and a cohort of untreated children outside the trial, were followed-up for malaria. SPAQ was more efficacious than DHAPQ, but the difference was within the margin set for non-inferiority. Both regimens gave a very high level of protection lasting 4 weeks. Protection was related to dosage. Both regimens were well tolerated, incidence of mild adverse events decreased in successive months, consistent with toleration to study drugs. In malaria cases, the frequency of the CVIET haplotype of pfcrt, the 86Y polymorphism of pfmdr1, and pfdhfr59 and dhps437 mutations, was greater among children who received SPAQ than in untreated children. However the number of cases, and the prevalence of parasitaemia, was much lower in treated children, reducing the scope for SMC to select for resistance. The frequency of the CVIET haplotype of PfCRT, thought to be associated with resistance to PQ, was not increased in children treated with DHAPQ. There was an enormous burden of malaria in the untreated children. SMC with SPAQ should be introduced for children in Burkina Faso without delay. DHAPQ is a potential alternative regimen in areas where SPAQ cannot be used but there are some drawbacks associated with its use. There is a need to develop alternative long-acting drugs with simple regimens that can be used for chemoprevention of malaria

Serodiagnosis of Schistosoma mansoni infections in an endemic area of Burkina Faso: performance of several immunological tests with different parasite antigens.

The performance of indirect haemagglutination assays (IHA), enzyme-linked immunosorbent assays (ELISA) and indirect immunofluorescent antibody tests (IFAT) were compared with 450 sera from a Schistosoma mansoni-endemic area in Burkina Faso. All participants in this survey provided at least one sample each of stool, urine and serum. From those with an egg-negative Kato-Katz thick smear, a second stool sample was examined. IHA was based on either extracts of adult S. mansoni worms (SmIHA) or S. japonicum egg antigen (SjIHA). For ELISA, three antigen preparations were used, namely: (i) soluble S. mansoni adult worm antigens (SWAP); (ii) soluble S. mansoni egg antigens (SEA); and (iii) a cationic exchange fraction of S. mansoni eggs (CEF6). IFAT was performed with S. mansoni male worm sections. Among the egg-excretors, the sensitivity of ELISA was high and egg antigens performed slightly better (SEA, 96%; CEF6, 97%) than worm antigen (94%). Sensitivity of IHA was satisfactory with homologous (Sm, >85%), but not heterologous (Sj, 56%) parasite antigen. In IFAT, the parenchyma-associated fluorescence showed high sensitivity (95%), but gut-associated fluorescence, which is known to be a sensitive diagnostic marker for schistosome-infected European travelers, was observed only in 76% of a sub-sample of 100 of the endemic sera. Among sera from egg-negative individuals, many gave positive reactions in several or all of the tests employed. These reactions (formally "false positive") are considered to represent true infections, since chemotherapy had not yet been delivered to this population. For the purpose of further surveys in Burkina Faso or other resource-poor settings, we suggest IHA as an accurate diagnostic test and propose to further improve its performance by including egg rather than worm antigens

Artemether-lumefantrine versus amodiaquine plus sulfadoxine-pyrimethamine for uncomplicated falciparum malaria in Burkina Faso: a randomised non-inferiority trial.

BACKGROUND: Artemisinin-based combination regimens are widely advocated for malarial treatment, but other effective regimens might be cheaper and more readily available. Our aim was to compare the risk of recurrent parasitaemia in patients given artemether-lumefantrine with that in those given amodiaquine plus sulfadoxine-pyrimethamine for uncomplicated malaria. METHODS: We enrolled 521 patients aged 6 months or older with uncomplicated falciparum malaria in Bobo-Dioulasso, Burkina Faso. Patients were randomly assigned to receive standard doses of either artemether-lumefantrine (261) or amodiaquine plus sulfadoxine-pyrimethamine (260) for 3 days. Primary endpoints were the risks of treatment failure within 28 days, either unadjusted or adjusted by genotyping to distinguish recrudescence from new infection. The study is registered at controlled-trials.gov with the identifier ISRCTN54261005. FINDINGS: Of enrolled patients, 478 (92%) completed the 28-day study. The risk of recurrent symptomatic malaria was lowest in the group given amodiaquine plus sulfadoxine-pyrimethamine (1.7%vs 10.2%; risk difference 8.5%; 95% CI 4.3-12.6; p=0.0001); as was the risk of recurrent parasitaemia (4.7%vs 15.1%; 10.4%; 5.1-15.6; p=0.0002). Nearly all recurrences were due to new infections. Recrudescences were four late treatment failures with artemether-lumefantrine and one early treatment failure with amodiaquine plus sulfadoxine-pyrimethamine. Both regimens were safe and well tolerated, with pruritus more common with amodiaquine plus sulfadoxine-pyrimethamine than with artemether-lumefantrine. Each regimen selected for new isolates with mutations that have been associated with decreased drug susceptibility. INTERPRETATION: Amodiaquine plus sulfadoxine-pyrimethamine was more effective than was artemether-lumefantrine for the treatment of uncomplicated malaria. For regions of Africa where amodiaquine plus sulfadoxine-pyrimethamine continues to be effective, this less expensive and more available regimen should be considered as an alternative to blanket recommendations for artemisinin-based combination treatment for malaria

Different methodological approaches to the assessment of in vivo efficacy of three artemisinin-based combination antimalarial treatments for the treatment of uncomplicated falciparum malaria in African children.

BACKGROUND: Use of different methods for assessing the efficacy of artemisinin-based combination antimalarial treatments (ACTs) will result in different estimates being reported, with implications for changes in treatment policy. METHODS: Data from different in vivo studies of ACT treatment of uncomplicated falciparum malaria were combined in a single database. Efficacy at day 28 corrected by PCR genotyping was estimated using four methods. In the first two methods, failure rates were calculated as proportions with either (1a) reinfections excluded from the analysis (standard WHO per-protocol analysis) or (1b) reinfections considered as treatment successes. In the second two methods, failure rates were estimated using the Kaplan-Meier product limit formula using either (2a) WHO (2001) definitions of failure, or (2b) failure defined using parasitological criteria only. RESULTS: Data analysed represented 2926 patients from 17 studies in nine African countries. Three ACTs were studied: artesunate-amodiaquine (AS+AQ, N = 1702), artesunate-sulphadoxine-pyrimethamine (AS+SP, N = 706) and artemether-lumefantrine (AL, N = 518).Using method (1a), the day 28 failure rates ranged from 0% to 39.3% for AS+AQ treatment, from 1.0% to 33.3% for AS+SP treatment and from 0% to 3.3% for AL treatment. The median [range] difference in point estimates between method 1a (reference) and the others were: (i) method 1b = 1.3% [0 to 24.8], (ii) method 2a = 1.1% [0 to 21.5], and (iii) method 2b = 0% [-38 to 19.3].The standard per-protocol method (1a) tended to overestimate the risk of failure when compared to alternative methods using the same endpoint definitions (methods 1b and 2a). It either overestimated or underestimated the risk when endpoints based on parasitological rather than clinical criteria were applied. The standard method was also associated with a 34% reduction in the number of patients evaluated compared to the number of patients enrolled. Only 2% of the sample size was lost when failures were classified on the first day of parasite recurrence and survival analytical methods were used. CONCLUSION: The primary purpose of an in vivo study should be to provide a precise estimate of the risk of antimalarial treatment failure due to drug resistance. Use of survival analysis is the most appropriate way to estimate failure rates with parasitological recurrence classified as treatment failure on the day it occurs

HRP2 and pLDH-Based Rapid Diagnostic Tests, Expert Microscopy, and PCR for Detection of Malaria Infection during Pregnancy and at Delivery in Areas of Varied Transmission: A Prospective Cohort Study in Burkina Faso and Uganda.

BACKGROUND: Intermittent screening and treatment (IST) of malaria during pregnancy has been proposed as an alternative to intermittent preventive treatment in pregnancy (IPTp), where IPTp is failing due to drug resistance. However, the antenatal parasitaemias are frequently very low, and the most appropriate screening test for IST has not been defined. METHODOLOGY/PRINCIPAL FINDINGS: We conducted a multi-center prospective study of 990 HIV-uninfected women attending ANC in two different malaria transmission settings at Tororo District Hospital, eastern Uganda and Colsama Health Center in western Burkina Faso. Women were enrolled in the study in the second or third trimester of pregnancy and followed to delivery, generating 2,597 blood samples for analysis. Screening tests included rapid diagnostic tests (RDTs) targeting histidine-rich protein 2 (HRP2) and parasite lactate dehydrogenase (pLDH) and microscopy, compared to nPCR as a reference standard. At enrolment, the proportion of pregnant women who were positive for P. falciparum by HRP2/pan pLDH RDT, Pf pLDH/pan pLDH RDT, microscopy and PCR was 38%, 29%, 36% and 44% in Uganda and 21%, 16%, 15% and 35% in Burkina Faso, respectively. All test positivity rates declined during follow-up. In comparison to PCR, the sensitivity of the HRP2/pan pLDH RDT, Pf pLDH/pan pLDH RDT and microscopy was 75.7%, 60.1% and 69.7% in Uganda, 55.8%, 42.6% and 55.8% in Burkina Faso respectively for all antenatal visits. Specificity was greater than 96% for all three tests. Comparison of accuracy using generalized estimating equation revealed that the HRP2- detecting RDT was the most accurate test in both settings. CONCLUSIONS/SIGNIFICANCE: The study suggests that HRP2-based RDTs are the most appropriate point-of-care test currently available for use during pregnancy especially for symptomatic women, but will still miss some PCR-positive women. The clinical significance of these very low density infections needs to be better defined

Knowledge, Attitude, and Practice of Health Care Workers in the Management of Peptic Ulcer at the Paul VI and the Bogodogo District Hospitals, in Burkina Faso

Background: In 2015, peptic ulcer disease (PUD) was cause of 52.3% and 17% of digestive bleeding and death in respectively among in-hospital patients at the gastroenterology units of the main hospital in Ouagadougou. We aimed to assess the knowledge, attitudes and practices of the health care workers in the management of PUD.Subjects dan Method: It was a descriptive cross-sectional study with a prospective data collection implemented at the Paul VI and the Bogodogo District Hospitals in Ouagadougou (Burkina Faso) from December 15, 2015 to January 25, 2016. A questionnaire was administered to 134 health care workers including medical doctors, nurses and midwives.Results: The mean age was 33 years (Mean= 33.6; SD= 5.84). Females represented 61.9%. Knowledge levels were good to excellent for general knowledge, symptoms and treatment of PUD. Depending on the agent's qualification, knowledge levels were excellent in all areas for two-thirds to three-quarters of the general practitioners, except for knowledge of additional investigation analyses, where only 47.8% had an excellent knowledge. Depending on the level of education, the level of knowledge was at least good for more than 50% of the agents except for the knowledge of additional investigation analyses where only 45.2 % of the agents of secondary school level had a good knowledge. The main attitudes consisted in managing the patients in emergency and out of an emergency context in 45.8% and 42.2% of the cases, respectively. Regarding the practices, 51.5% of the HCWs systematically requested investigation analyses before starting an aetiological therapy.Conclusion: The PUD knowledge ranks from good to excellent. However, the frequent prescription of symptomatic treatments could be the cause of many complications. The promotion of continuous medical education is a good mitigation plan to resolve the issues of knowledge and competence regarding the PUD. Keywords: attitude, knowledge, peptic ulcer disease, practice Correspondence:Eric Nagaonlé Somé. Institut de Recherche en Sciences de la Santé (IRSS)/CNRST 10 BP 250 Ouagadougou 10 Burkina Faso. Email: [email protected]. Mobile phone: +22670751333

PlasmoView: a web-based resource to visualise global Plasmodium falciparum genomic variation.

Malaria is a global public health challenge, with drug resistance a major barrier to disease control and elimination. To meet the urgent need for better treatments and vaccines, a deeper knowledge of Plasmodium biology and malaria epidemiology is required. An improved understanding of the genomic variation of malaria parasites, especially the most virulent Plasmodium falciparum (Pf) species, has the potential to yield new insights in these areas. High-throughput sequencing and genotyping is generating large amounts of genomic data across multiple parasite populations. The resulting ability to identify informative variants, particularly single-nucleotide polymorphisms (SNPs), will lead to the discovery of intra- and inter-population differences and thus enable the development of genetic barcodes for diagnostic assays and clinical studies. Knowledge of genetic variability underlying drug resistance and other differential phenotypes will also facilitate the identification of novel mutations and contribute to surveillance and stratified medicine applications. The PlasmoView interactive web-browsing tool enables the research community to visualise genomic variation and annotation (eg, biological function) in a geographic setting. The first release contains over 600,000 high-quality SNPs in 631 Pf isolates from laboratory strains and four malaria-endemic regions (West Africa, East Africa, Southeast Asia and Oceania)

Asymptomatic Malaria Carriage in South-Western Burkina Faso: An Epidemiological Analysis

Background: Burkina Faso is challenged by rise in malaria incidence and insecticide and drug resistance. We investigated the prevalence of asymptomatic infection of Plasmodium falciparum. over three surveys.Subjects dan Method: We conducted repeated cross-sectional surveys in September and December 2016 and June 2017 in Diebougou health district. An initial census identified 4,028 subjects aged 6 months to 18 years. The independent variables included the age or date of birth, dependant were the area of residence, the use of bed nets, presence of not of parasites, the period of the surveys and the presence or absence of clinical signs/symptoms/fever, the gender. We used electronic case report forms for data collection, then uploaded into electronic tablets PCs, transferred to a central server. Data were analyzed with R version 3.4.3 software. Baseline chara