Early impact of 13-valent pneumococcal conjugate vaccine on pneumococcal meningitis—Burkina Faso, 2014–2015

Objectives

We evaluate early impact of 13-valent pneumococcal conjugate vaccine (PCV13) on pneumococcal meningitis in Burkina Faso.

Randomized Noninferiority Trial of Dihydroartemisinin-Piperaquine Compared with Sulfadoxine-Pyrimethamine plus Amodiaquine for Seasonal Malaria Chemoprevention in Burkina Faso

The WHO recommends that children living in areas of highly seasonal malaria transmission in the Sahel subregion should receive seasonal malaria chemoprevention (SMC) with sulfadoxine-pyrimethamine plus amodiaquine (SPAQ). We evaluated the use of dihydroartemisinin-piperaquine (DHAPQ) as an alternative drug that could be used if SPAQ starts to lose efficacy. A total of 1,499 children 3 to 59 months old were randomized to receive SMC with SPAQ or DHAPQ over 3 months. The primary outcome measure was the risk of clinical malaria (fever or a history of fever with a parasite density of at least 3,000/μl). A cohort of 250 children outside the trial was followed up as a control group. Molecular markers of drug resistance were assessed. The risk of a malaria attack was 0.19 in the DHAPQ group and 0.15 in the SPAQ group, an odds ratio of 1.33 (95% confidence interval [CI], 1.02 to 1.72). Efficacy of SMC compared to the control group was 77% (67% to 84%) for DHAPQ and 83% (74% to 89%) for SPAQ. pfdhfr and pfdhps mutations associated with antifolate resistance were more prevalent in parasites from children who received SPAQ than in children who received DHAPQ. Both regimens were highly efficacious and well tolerated. DHAPQ is a potential alternative drug for SMC. (This trial is registered at ClinicalTrials.gov under registration no. {"type":"clinical-trial","attrs":{"text":"NCT00941785","term_id":"NCT00941785"}}NCT00941785.)     

Polymorphisms in the K13-Propeller Gene in Artemisinin-Susceptible Plasmodium falciparum Parasites from Bougoula-Hameau and Bandiagara,Mali

Artemisinin-resistant Plasmodium falciparum malaria has been documented in southeast Asia and may already be spreading in that region. Molecular markers are important tools for monitoring the spread of antimalarial drug resistance. Recently, single-nucleotide polymorphisms (SNPs) in the PF3D7_1343700 kelch propeller (K13-propeller) domain were shown to be associated with artemisinin resistance in vivo and in vitro. The prevalence and role of K13-propeller mutations are poorly known in sub-Saharan Africa. K13-propeller mutations were genotyped by direct sequencing of nested polymerase chain reaction (PCR) amplicons from dried blood spots of pre-treatment falciparum malaria infections collected before and after the use of artemisinin-based combination therapy (ACT) as first-line therapy in Mali. Although K13-propeller mutations previously associated with delayed parasite clearance in Cambodia were not identified, 26 K13-propeller mutations were identified in both recent samples and pre-ACT infections. Parasite clearance time was comparable between infections with non-synonymous K13-propeller mutations and infections with the reference allele. These findings suggest that K13-propeller mutations are present in artemisinin-sensitive parasites and that they preceded the wide use of ACTs in Mali.     

Cardiovascular properties of aqueous extract from Mitragyna inermis (wild)

Aqueous extracts of Mitragyna inermis (AEMI) used traditionally as antihypertensive agents produced a concentration-dependent (0.1-3 mg/ml) ex vivo increase in cardiac contractile response and coronary flow but did not modify heart rate in the rat. Interestingly, AEMI produced relaxation in isolated porcine coronary artery at concentration up to 3 mg/ml that was exclusively dependent on the presence of endothelium. This relaxation involved partial depolarization (KCl 20, 40 mM) and NO synthase inhibitor-sensitive mechanisms but was not sensitive to the blockade of cyclo-oxygenase pathway. In contrast, the relaxant effect of AEMI was not dependent on the presence of endothelium in rat tail artery. Taken together, the present study demonstrates hypotensive, cardiotropic and vasodilatory properties of AEMI that contribute to better understanding of its beneficial effect against cardiovascular diseases.     

Ex Vivo Responses of Plasmodium falciparum Clinical Isolates to Conventional and New Antimalarial Drugs in Niger

Little is known about resistance of Plasmodium falciparum to antimalarials in Sahelian countries. Here we investigated the drug susceptibilities of fresh isolates collected in Niger post-deployment of artemisinin-based combination therapies (ACTs). We found that the parasites remained highly susceptible to new (dihydroartemisinin, lumefantrine, pyronaridine, and piperaquine) and conventional (amodiaquine and chloroquine) antimalarial drugs. The introduction of ACTs in 2005 and their further deployment nationwide have therefore not resulted in a decrease in P. falciparum susceptibilities to these antimalarials.     

Selection of Drug Resistance-Mediating Plasmodium falciparum Genetic Polymorphisms by Seasonal Malaria Chemoprevention in Burkina Faso

Seasonal malaria chemoprevention (SMC), with regular use of amodiaquine plus sulfadoxine-pyrimethamine (AQ/SP) during the transmission season, is now a standard malaria control measure in the Sahel subregion of Africa. Another strategy under study is SMC with dihydroartemisinin plus piperaquine (DP). Plasmodium falciparum single nucleotide polymorphisms (SNPs) in P. falciparum crt (pfcrt), pfmdr1, pfdhfr, and pfdhps are associated with decreased response to aminoquinoline and antifolate antimalarials and are selected by use of these drugs. To characterize selection by SMC of key polymorphisms, we assessed 13 SNPs in P. falciparum isolated from children aged 3 to 59 months living in southwestern Burkina Faso and randomized to receive monthly DP or AQ/SP for 3 months in 2009. We compared SNP prevalence before the onset of SMC and 1 month after the third treatment in P. falciparum PCR-positive samples from 120 randomly selected children from each treatment arm and an additional 120 randomly selected children from a control group that did not receive SMC. The prevalence of relevant mutations was increased after SMC with AQ/SP. Significant selection was seen for pfcrt 76T (68.5% to 83.0%, P = 0.04), pfdhfr 59R (54.8% to 83.3%, P = 0.0002), and pfdhfr 108N (55.0% to 87.2%, P = 0.0001), with trends toward selection of pfmdr1 86Y, pfdhfr 51I, and pfdhps 437G. After SMC with DP, only borderline selection of wild-type pfmdr1 D1246 (mutant; 7.7% to 0%, P = 0.05) was seen. In contrast to AQ/SP, SMC with DP did not clearly select for known resistance-mediating polymorphisms. SMC with AQ/SP, but not DP, may hasten the development of resistance to components of this regimen. (This study has been registered at ClinicalTrials.gov under registration no. {"type":"clinical-trial","attrs":{"text":"NCT00941785","term_id":"NCT00941785"}}NCT00941785.)     

Sentinel surveillance of influenza in Burkina Faso: identification of circulating strains during 2010–2012

Background

Although influenza surveillance has recently been improved in some sub-Saharan African countries, no information is yet available from Burkina Faso.

Objectives

Our study was the first to determine the prevalence of influenza viruses circulating in Burkina Faso through a sentinel surveillance system.

Methods

We conducted sentinel surveillance with oropharyngeal (OP) swabs collected from outpatients (1 month to 83 years) from six sites in Bobo-Dioulasso and Ouagadougou, among patients meeting the WHO/CDC case definition for influenza-like illness (ILI; fever ≥38°C, and cough and/or sore throat in the absence of other diagnosis) from July 2010 to May 2012. Influenza viruses were detected by real-time RT-PCR using CDC primers, probes, and protocols.

Results

The first three ILI cases were enrolled each day; of 881 outpatients with ILI enrolled and sampled, 58 (6·6%) tested positive for influenza viruses (29 influenza A and 29 influenza B). Among the influenza A viruses, 55·2% (16/29) were influenza A (H1N1)pdm09 and 44·8% (13/29) were seasonal A (H3N2). No cases of seasonal A/H1N1 were detected. Patients within 0–5 years and 6–14 years were the most affected, comprising 41·4% and 22·4% laboratory-confirmed influenza cases, respectively. Influenza infections occurred during both the dry, dusty Harmattan months from November to March and the rainy season from June to October with peaks in January and August.

Conclusions

This surveillance was the first confirming the circulation of influenza A (H1N1)pdm09, A/H3N2, and influenza B viruses in humans in Burkina Faso.     

Disseminated adenovirus infection after autologous stem cell transplant

Adenovirus is an infrequent but challenging viral complication of transplantation that is rarely reported after autologous stem cell transplant. We present a case of disseminated adenovirus infection in a woman who received an autologous stem cell transplant for treatment of multiple sclerosis. After presenting with post‐transplant episodic diarrhea and viremia, endoscopic biopsies and immunohistochemical staining confirmed the diagnosis of disseminated adenovirus infection. Her symptoms and viremia resolved after treatment with cidofovir. This case demonstrates that a high index of suspicion, a systematic clinical approach, and immunohistochemical tissue staining are necessary to diagnose disseminated adenovirus infection in an unexpected host.