Short report: molecular markers associated with Plasmodium falciparum resistance to sulfadoxine-pyrimethamine in the Democratic Republic of Congo.

Sulfadoxine-pyrimethamine (SP) is the first line antimalarial treatment in the Democratic Republic of Congo. Using polymerase chain reaction, we assessed the prevalence of mutations in the dihydrofolate reductase (dhfr) (codons 108, 51, 59) and dihydropteroate synthase (dhps) (codons 437, 540) genes of Plasmodium falciparum, which have been associated with resistance to pyrimethamine and sulfadoxine, respectively. Four hundred seventy-four patients were sampled in Kilwa (N = 138), Kisangani (N = 112), Boende (N = 106), and Basankusu (N = 118). The proportion of triple mutations dhfr varied between sites but was always > 50%. The proportion of dhps double mutations was < 20%, with some sites as low as 0.9%. A quintuple mutation was present in 12.8% (16/125) samples in Kilwa; 11.9% (13/109) in Kisangani, 2.9% (3/102) in Boende, and 0.9% (1/112) in Basankusu. These results suggest high resistance to pyrimethamine alone or combined with sulfadoxine. Adding artesunate to SP does not seem a valid alternative to the current monotherapy

High Efficacy of Two Artemisinin-Based Combinations (Artesunate + Amodiaquine and Artemether + Lumefantrine) in Caala, Central Angola.

In April 2004, 137 children 6-59 months of age with uncomplicated Plasmodium falciparum (Pf) malaria (Caala, Central Angola) were randomized to receive either artemether-lumefantrine (Coartem) or artesunate + amodiaquine (ASAQ). After 28 days of follow-up, there were 2/61 (3.2%) recurrent parasitemias in the Coartem group and 4/64 (6.2%) in the ASAQ group (P = 0.72), all classified as re-infections after PCR genotyping (cure rate = 100% [95%CI: 94-100] in both groups). Only one patient (ASAQ group) had gametocytes on day 28 versus five (Coartem) and three (ASAQ) at baseline. Compared with baseline, anemia was significantly improved after 28 days of follow-up in both groups (Coartem: from 54.1% to 13.4%; ASAQ: from 53.1% to 15.9%). Our findings are in favor of a high efficacy of both combinations in Caala. Now that Coartem has been chosen as the new first-line anti-malarial, the challenge is to insure that this drug is available and adequately used

Extrafine beclomethasone/formoterol in severe COPD patients with history of exacerbations

The FORWARD study is a randomised, double-blind trial that compares the efficacy and safety of 48 weeks treatment with extrafine beclomethasone dipropionate/formoterol fumarate (BDP/FOR), 100/6 μg pMDI, 2 inhalations BID, vs. FOR 12 μg pMDI, 1 inhalation BID, in severe COPD patients with a history of exacerbations. Co-primary endpoints were exacerbation rate over 48 weeks and pre-dose morning FEV1 at 12 weeks. The ITT population included 1186 patients (69% males, mean age 64 years) with severe airflow limitation (mean post-bronchodilator FEV1 42% predicted). Salbutamol as rescue therapy, theophylline and tiotropium (if stable regimen prior to screening) were allowed. Compared to FOR, BDP/FOR: (1) reduced the exacerbation rate (rate ratio: 0.72 [95% confidence interval 0.62–0.84], p < 0.001); (2) improved pre-dose morning FEV1 (mean difference: 0.069 L [0.043–0.095] p < 0.001); (3) prolonged the time to first exacerbation; (4) improved the SGRQ total score. The percentage of patients with adverse events was similar (52.1% with BDP/FOR and 49.2% with FOR). Pneumonia incidence was low, slightly higher with BDP/FOR (3.8%) than with FOR (1.8%). No difference for laboratory values, ECG or vital signs. Extrafine BDP/FOR significantly reduces the exacerbation rate and improves lung function of patients with severe COPD and history of exacerbations as compared to FOR alone

Differential effects of azithromycin, doxycycline and co-trimoxazole in ingested blood on the vectorial capacity of malaria mosquitoes

Background.  The gut microbiota of malaria vector mosquitoes grows after a blood meal and limits Plasmodium infection. We previously showed that penicillin and streptomycin in the ingested blood affect bacterial growth and positively impact mosquito survival and permissiveness to Plasmodium. In this study, we examine the effects of doxycycline, azithromycin, and co-trimoxazole. All 3 antibiotics are used in mass drug administration programs and have antimicrobial activities against bacteria and various stages of malaria parasites. Methods.  The effects of blood meal supplementation with antibiotics on the mosquito microbiota, lifespan, and permissiveness to Plasmodium falciparum were assessed. Results.  Ingestion of any of the 3 antibiotics significantly affected the mosquito microbiota. Azithromycin decreased P falciparum infection load and mosquito lifespan, whereas at high concentrations, doxycycline increased P falciparum infection load. Co-trimoxazole negatively impacted infection intensity but had no reproducible effect on mosquito lifespan. Conclusions.  Our data suggest that the overall effect of antibiotic treatment on parameters critical for mosquito vectorial capacity is drug specific. The negative effect of azithromycin on malaria transmission is consistent with current efforts for disease elimination, whereas additional, larger scale investigations are required before conclusions can be drawn about doxycycline

The peptidoglycan recognition proteins PGRPLA and PGRPLB regulate Anopheles immunity to bacteria and affect infection by Plasmodium

Peptidoglycan recognition proteins (PGRPs) form a family of immune regulators that is conserved from insects to mammals. In the malaria vector mosquito Anopheles coluzzii , the peptidoglycan receptor PGRPLC activates the Imd pathway limiting both t he microbiota load and Plasmodium infection. Here, we carried out an RNAi screen to examine the rol e of all seven Anopheles PGRPs in infections with Plasmodium berghei and Plasmodium falciparum . We show that, in addition to PGRPLC, PGRPLA and PGRPS2/S3 also participate in antiparas itic defenses, and that PGRPLB promotes mosquito permissiveness to P. falciparum . We also demonstrate that following a mosquito blood feeding, which promotes growth of the gut microbiota, PGRPLA and PGRPLB positively and negatively regulate the activation of the Imd pathway, respective ly. Our data demonstrate that PGRPs are important regulators of the mosquito epithelial immunity and vector comp etence

MUAC as the sole discharge criterion from community‐based management of severe acute malnutrition in Burkina Faso

The use of mid upper arm circumference (MUAC) measurement to screen and determine eligibility for admission to therapeutic feeding programs has been established, but evidence and programmatic experience to inform guidance on the use of MUAC as a discharge criterion is limited. We present results from a large‐scale nutritional program using MUAC for admission and discharge and compare program outcomes and response to treatment when determining eligibility for discharge by proportional weight gain versus discharge by MUAC. The study population included all children admitted to the Ministry of Health therapeutic feeding program supported by Médecins Sans Frontières in northern Burkina Faso from September 2007 to December 2011 (n = 50,841). Recovery was high overall using both discharge criteria, with low risks of death, nonresponse, and transfer to inpatient care and high daily gains in weight, MUAC, weight‐for‐height Z score, and height. When discharge was made by MUAC only, recovery increased, while all adverse program outcomes and length of stay decreased, with increasing MUAC on admission. MUAC‐based programming, where MUAC is integrated into program screening, admission, and discharge, is one of several new approaches that can be used to target resources to the most at‐risk malnourished children and improve program efficiency and coherency. This analysis provides additional programmatic experience on the use of MUAC‐based discharge criterion, but more work may be needed to inform optimal discharge thresholds across settings

Against the Odds: Psychomotor Development of Children Under 2 years in a Sudanese Orphanage.

Providing abandoned children the necessary medical and psychological care as possible after their institutionalization may minimize developmental delays. We describe psychomotor development in infants admitted to an orphanage in Khartoum, Sudan, assessed at admission and over an 18-month follow-up. Psychological state and psychomotor quotients were determined using a simplified Neonatal Behavior Assessment Scale (NBAS), the Brunet-Lezine and Alarm distress baby (ADBB) scale. From May-September 2005, 151 children were evaluated 2, 4, 9, 12 and 18 months after inclusion. At admission, ∼15% of children ≤1 month had a regulation impairment according to the NBAS, and 33.8% presented a distress state (ADBB score >5). More than 85% (129/151) recovered normal psychomotor development. The results of the program reinforce the importance of early detection of psychological disorders followed by rapid implementation of psychological case management to improve the development of young children in similar institutions and circumstances

Setting up an enhanced surveillance of newly acquired hepatitis C infection in men who have sex with men: a pilot in London and South East region of England.

Preliminary findings suggest ongoing HCV transmission among MSM infected with human immunodeficiency virus (HIV) and that enhanced surveillance for newly acquired HCV in MSM is feasible

A user-friendly software to easily count Anopheles egg batches

BACKGROUND: Studies on malaria vector ecology and development/evaluation of vector control strategies often require measures of mosquito life history traits. Assessing the fecundity of malaria vectors can be carried out by counting eggs laid by Anopheles females. However, manually counting the eggs is time consuming, tedious, and error prone. METHODS: In this paper we present a newly developed software for high precision automatic egg counting. The software written in the Java programming language proposes a user-friendly interface and a complete online manual. It allows the inspection of results by the operator and includes proper tools for manual corrections. The user can in fact correct any details on the acquired results by a mouse click. Time saving is significant and errors due to loss of concentration are avoided. RESULTS: The software was tested over 16 randomly chosen images from 2 different experiments. The results show that the proposed automatic method produces results that are close to the ground truth. CONCLUSIONS: The proposed approaches demonstrated a very high level of robustness. The adoption of the proposed software package will save many hours of labor to the bench scientist. The software needs no particular configuration and is freely available for download on: http://w3.ualg.pt/∼hshah/eggcounter/