Search

Engineered gene drives, which bias their own inheritance to increase in frequency in target populations, are being developed to control mosquito malaria vectors. Such mosquitoes can belong to complexes of both vector and nonvector species that can produce fertile interspecific hybrids, making vertical gene drive transfer (VGDT) to sibling species biologically plausible. While VGDT to other vectors could positively impact human health protection goals, VGDT to nonvectors might challenge biodiversity ones. Therefore, environmental risk assessment of gene drive use in species complexes invites more nuanced considerations of target organisms and nontarget organisms than for transgenes not intended to increase in frequency in target populations. Incorporating the concept of target species complexes offers more flexibility when assessing potential impacts from VGDT.

A relatively rare congenital malformation, hematocolpos is the progressive accumulation of menstrual blood in the vaginal cavity at puberty. It is often the consequence of a hymen imperforation. It is clinically manifested by cyclic pelvic pain and primary amenorrhea and, more rarely, by a pelvic mass syndrome. The diagnosis is primarily clinical. Ultrasound and magnetic resonance imaging (MRI) are additional tests to confirm hematolcolpos and exclude other associated genitourinary malformations. Treatment consists of a hymenotomy to drain the hematocolpos. The age of discovery of hematocolpos varies from 13 to 14 years. We report a case of hematocolpos secondary to hymenal imperforation diagnosed in a 17-year-old girl with periodic pelvic pain, primary amenorrhea and a pelvic mass. A first ultrasound trap had evoked a large ovarian cyst but the repeat pelvic ultrasound in our hospital confirmed the diagnosis of hematocolpos.

Introduction: La fistule ouraquienne (FO) ou fistule ombilico-vesicale resulte d’un defaut d’obliteration totale du canalallantoidien au cinquieme mois de gestation. Il en decoule un ecoulement d’urines plus ou moins permanent par l’ombilicapres la naissance. Cet ecoulement est d’autant plus important que la pathologie est associee a une obstruction du bas appareil urinaire.Observation: Nous rapportons une observation de FO associee a des valves de l’uretre posterieur chez un garcon de 8 mois ayant une symptomatologie particuliere et nous discuterons de l’impact d’une telle association sur la fonction renale.Conclusion: L’association de pathologies peut avoir parfois un impact benefique.

Current mark–release–recapture methodologies are limited in their ability to address complex problems in vector biology, such as studying multiple groups overlapping in space and time. Additionally, limited mark retention, reduced post‐marking survival and the large effort in marking, collection and recapture all complicate effective insect tracking.We have developed and evaluated a marking method using a fluorescent dye (SmartWater®) combined with synthetic DNA tags to informatively and efficiently mark adult mosquitoes using an airbrush pump and nebulizer. Using a handheld UV flashlight, the fluorescent marking enabled quick and simple initial detection of recaptures in a field‐ready and non‐destructive approach that when combined with an extraction‐free PCR on individual mosquito legs provides potentially unlimited marking information.This marking, first tested in the laboratory with Anopheles gambiae s.l. mosquitoes, did not affect survival (median ages 24–28 days, p‐adj > 0.25), oviposition (median eggs/female of 28.8, 32.5, 33.3 for water, green, red dyes, respectively, p‐adj > 0.44) or Plasmodium competence (mean oocysts 5.56–10.6, p‐adj > 0.95). DNA and fluorescence had 100% retention up to 3 weeks (longest time point tested) with high intensity, indicating marks would persist longer.We describe a novel, simple, no/low‐impact and long‐lasting marking method that allows separation of multiple insect subpopulations by combining unlimited length and sequence variation in the synthetic DNA tags. This method can be readily deployed in the field for marking multiple groups of mosquitoes or other insects.

Artificial induction of labor (AIL) is the set of techniques intended to induce childbirth in order to reduce maternal-fetal mortality. The aim of this paper was to study the maternal and fetal prognosis after the artificial induction of labor with misoprostol. It was a descriptive prospective study conducted from September 1, 2018 to February 28, 2019 at the maternity unit of the Referral Health Center (RHC) in commune I of Bamako. It was about any pregnant woman at term who had received misoprostol as part of the artificial induction of labor. 102 cases of artificial induction with misoprostol 200 μg were collected out of 3641 deliveries, or a frequency of 2.8%. The age group 28 - 32 years accounted for 56.86% with an average age of 28.8 years. Multiparous represented 54.90% of the number. The history of diabetes and hypertension involved 37.25% of the pregnant women. The main indication was premature rupture of membranes (PRM) (40.2%). Induction was performed between the 37th and 41st week of amenorrhea (69.6%). The trigger index according to BISHOP was greater than 7 (50.98%). Induction was done only with 3/4 of misoprostol tablet 200 μg (43.14%). The average labor time was 7 hours (89.22%). The vaginal birth concerned 92.16% of pregnant women. An APGAR10 was noted in 97.85% of newborns after 05 minutes. AIL with misoprostol was practiced at the Center. The main indication was the premature rupture of the membranes. It improves the maternal and fetal prognosis.

Introduction: A newborn is preterm when it is born before 37 weeks of amenorrhoea. Preterm births account for 11.1% of live births worldwide, 60% of which are in South Asia and sub-Saharan Africa. Preterm birth is the leading cause of neonatal mortality and the second leading cause of mortality in children under 5 years of age. The aim of this study was to investigate prematurity in the neonatology unit of the Mali Hospital. Materials and Methods: This was a cross-sectional, descriptive study from January 2012 to December 2015 of premature newborns from 28 to 36 weeks of amenorrhea in the neonatology unit of Mali Hospital. Results: From January 2012 to December 2015, we recorded 1692 inpatient newborns, including 614 preterm newborns, a frequency of 36.29%. The sex ratio was 1.43 in favor of boys. The average age of the mothers was 23.9 years with a minimum of 15 and a maximum of 47 years. The majority were housewives (92.7%). The pregnancy was poorly monitored in 51.8% of the mothers. The average gestational age was 32.9 days with extremes of 25 and 36 days. The most frequent mode of delivery was vaginal delivery (93.2%), with late prematurity in 51.5%, moderate prematurity (24.4%), extreme prematurity (18.7%) and very premature (5.4%). The mean birth weight was 1464 g with a standard deviation of 485 g and 2751 g. Prematurity was associated with neonatal infection in 49.4% of newborns, perinatal anoxia (13.9%) and hypotrophy (2.6%). The most frequent maternal risk factors were fever (83.4%), twinship (38.9%) and high blood pressure (8.6%). The average length of hospitalization was 9.75 days with extremes of 0 and 68 days. We recorded a cure rate of 57.7%, a death rate of 35.7% and a dropout rate of 6.7%. Conclusion: Prematurity is frequent in the neonatology unit of the Mali Hospital. We observed a high frequency among women of extreme age and low socio-economic and educational level. In our study we also noted a high mortality rate proportional to gestational age.

Summary: A malignant tumour that develops from the bronchial epithelium and then invades the lungs. It ranks third after colorectal and breast cancer. In Mali, computed tomography (CT) is the main imaging tool used at all stages of treatment. We had initiated this study with the objective of specifying the place of CT in the diagnosis of primary bronchopulmonary cancer at the hospital of Mali. Method: This is a prospective and descriptive study conducted by the Medical Imaging and Thoracic Surgery departments at Mali Hospital from March 2014 to February 2015. All the patients who have benefited from a CT scan and presenting at least one histologically confirmed bronchopulmonary tumor were included. Results: We were recruiting 60 patients with bronchopulmonary cancers out of 500 referred for a thoracic CT scan performed, a frequency of 12%. There was one male patient with a sex ratio of 4H/1F. The average age was 60 years. The history of smoking was 85%. The symptoms were dominated by general condition (63.33%), cough (25%) and haemoptysis (58.33%). CT scans were performed in all patients. The lesions were located more in the lower lobes (71%). The tumours were: heterogeneous tissue density (70%), spiculated contours (80%), and the histology was more non-small cell carcinoma. Conclusion: The incidence of bronchopulmonary cancer is very high and its prognosis is poor at an advanced stage. The evaluative role of CT and biopsy guidance has given it a place of choice in its management. The diagnosis of certainty remains histology.

Uterine leiomyomas (myomas) are the most common benign tumors of the female genital tract. They affect 20% to 25% of women of childbearing age and are 3 to 9 times more common in black women. We initiated this study in order to report the socio-demographic aspects and the indications for leiomyomas surgery at Hopital du Mali. This was a retro-prospective descriptive study, conducted in the gynecology department of Hopital du Mali from January 1, 2015 to December 31, 2019. Any patients, regardless of their age, in whom a leiomyomas had been detected and surgically treated were included. We had collected 180 cases of surgery for leiomyomas out of 950 surgical procedures, with a frequency of 18.94%. The 36 - 45 age group represented 45% of our patients with an average age of 35 years. Nulligravida accounted for 48.9% and nulliparous (60%). The main reason for consultation was the desire to become pregnant (53.33%). A history of myomectomy was found out in 15.55% of patients. Pelvic ultrasound figured out 64.44% interstitial myomas. Myomectomy was performed in 88.88% of cases and hysterectomy in 11.12% of cases. Among our patients 39.37% had become pregnant. Operative complications were dominated by anemia 14.44%. Leiomyoma was the histological tissue found in all cases of myomectomy. The average duration of hospitalization was 3 days. Conclusion: Leiomyomas surgery is the first scheduled gynecological surgical activity. Laparotomy remains the primary route of entry. The indications are dominated by the desire for pregnancy.

Objective: To describe the screening for uterine cancer by visual methods. Method: We conducted a prospective and descriptive study over a period of 12 months from January to December 2020. Direct observation of providers and interview of patients were performed for data collection. Results: Out of 3400 patients, 1024 were enrolled for the study, or 30.11%. The average age of the patients was 41 years with the extremes of 17 to 87 years. Women aged 40 to 45 were the most represented with 58.78%, (n = 602). Housewives 85.83% (n = 879), they had a primary education level in 71.09% of cases (n = 728), the vast majority were married 92.28% (n = 945). Multiparous represented 58.78% (n = 602) of the sample, nulliparous 18.26% (n = 187), women living in rural areas 30.17% (n = 309), in urban areas 69.82% (n = 715). The test was positive in 43 patients (4.19%) but squamocylindrical junction was not visible in 17% of cases. The preparation of acetic acid and lugol: good preparation in 100% of cases; the conditions of use are not respected in 27% for acetic acid and 38% for lugol. Conclusion: Routine screening for cervical cancer (SCC) by visual methods is essential to decrease the incidence of invasive cervical cancer.

The fibroids affect 20% to 25% of women of reproductive age and are 3 to 9 times more common in black women. We’ll talk about giant fibroids (GFs) when uterine height reaches or exceeds the navel. We have initiated this study in order to report the epidemioclinical and therapeutic aspects of giant fibroids at the Hopital du Mali. A descriptive retro-prospective study, conducted in the service of gynecology of the Hopital du Mali from November 2017 to December 2018 were included in this study, any patients, regardless of their age, having developed a fibroid, the uterin e height of the patient reaching or exceeding the umbilicus on physical examination and who were on surgical treatment. We had collected 30 cases of GFs out of the 92 patients who had undergone myomectomies, with a frequency of 32.60%. The age group 25 - 29 years accounted for 46.6% with an average age of 35 years. Housewives represented 50% and nulligravida made up 33% of our patients. Desire to become pregnant was the main reason for consultation in 34.4% of cases. The uterine height was between 25 and 29 cm on physical examination in 46.66% of cases. Myomectomy was performed in 76.64% and hysterectomy in 23.3% of cases. The size of the nuclei after surgery was over 25 cm in 48.66% of our patients. Conclusion: The giant fibroid (GF) is a common cause of myomectomy. The treatment is either hysterectomy or myomectomy and depends on the indications.

Slow spinal compressions are due to the development of an expansive process in the spinal canal. It is a very common pathology, the diagnosis of which is mainly clinical. However, magnetic resonance imaging occupies an essential place in the site diagnosis and etiological research in the management. Non-traumatic spinal cord compression is a diagnostic and therapeutic emergency, requiring early and appropriate management. MRI is the benchmark imaging examination for this pathology. No similar previous MRI study in Mali. We undertook this work with the aim to determine the place of MRI in the diagnosis of spinal cord compressions in Mali hospital. Method and Patients: This was a descriptive retrospective study, carried out at the hospital’s medical imaging department from January 1, 2017 to December 31, 2018 (02 years). It involved all patients, regardless of sex and age, sent for an MRI examination of the spine, and in whom spinal cord compression was diagnosed. We used a 0.35T low-field MRI machine with solid-state antennas. Results: We collected 179 cases of spinal cord compression MRI out of 585 spinal MRI performed, (frequency of 30.59%). The average age was 53.5 years with a male predominance (sex ratio 3.7). Motor disorders were the most common reason for examination (41%). We used the T1 T2 sagittal and T2 axial sequences. IV injection of gadolinium was performed in 48% of patients. The topographic lesions were: cervical (54.7%), thoracic (31.3%) and several segments (9.5%). The lesions concerned the compartments: extradural (79.3%), intradural (4.5%), and intramedullary (16.2%). The processes were degenerative (57.5%). tumorous (29.6%), infectious (12.3%) and vascular (0.6%). Conclusion: MRI is the benchmark imaging test for the management of non-traumatic spinal cord injury. Myelo-CT can be an alternative in the absence or in case of MRI contraindication.

Infertility is a socio-cultural drama in Africa, especially in Mali and remains difficult for couples to overcome. Laparoscopy, also called minimally invasive surgery or keyhole surgery, is an operative technique that permits to explore the pelvis and perform an appropriate therapeutic procedure. The objective of our work was to assess the role of laparoscopic surgery in the treatment of female infertility at Hopital du Mali. It was a retrospective descriptive study that was conducted over a period of 5 years (January 2013 to December 2018). Any patients followed for infertility and who underwent laparoscopic surgery in the gynecology department over a period of two (2) years were included. The outcome of laparoscopic surgery was evaluated in terms of conception of pregnancy. We had collected 103 infertile patients out of 2984, with a frequency of 3.45%. The mean age of our patients was 30.2 years. Housewives and out-of-school women accounted for 68.93% and 54.37% respectively. Nulligravida represented 41.75%. Regarding infertility, it was primary in 41.75% and secondary in 58.25%, with an average duration of 6.2 years. Systematic chlamydial serology was positive in 62.14% of our patients. Hysterosalpingography (HSG) revealed bilateral tubal obstruction in 53.33% of cases. Laparoscopy found tubal adhesions in 97.80% of cases. Adhesiolysis was the main procedure performed with 84.47% bilateral tubal patency achieved in the methylene blue test. Among our patients who had contracted a pregnancy (22.99%), 85% had carried their pregnancies to term. Tubal damage was the main cause of infertility. Adhesiolysis remains the main laparoscopic procedure for treatment.

Teenage pregnancy is common in Mali due to the high rate of unwanted pregnancies and early marriages. The general objective of this study was to study emergency cesarean delivery in adolescent girls at the referral health center (RHC) in commune I of the district of Bamako. It was a descriptive study with prospective data collection from January 1 to December 31, 2018. Any adolescent girls in whom an emergency caesarean section was performed were included. The data were entered and analyzed on SPSS 20.3. Results: we have collected 616 adolescent parturients, 202 caesareans were performed in emergency, with a frequency of 32.8%. The average age was 17 with the extremes of 13 and 19. Early marriage was found out in 95.5% of our patients, 40 adolescent girls were primiparous (20%), 4 of whom had an inter-reproductive interval of less than a year. The main indications for cesarean section were fetal distress in 71 cases (35%), fetal-pelvic disproportion, scar uterus in the border pelvis (11% each), breech presentation in 15 cases (7%). Anemia (10.4%) was the main complication, followed by vascular pedicle attack (5.94%), infection of the operating site (1.5%) and a bladder wound (0.99%). Fetal mortality was 1.4% and neonatal 3.8%. Conclusion: the association between adolescence and caesarean section in emergency constitutes risk factors which increase maternal and neonatal morbidity and mortality. Fighting these factors improves the survival of the mother and the newborn.

IntroductionMalaria has been the leading cause of morbidity and mortality for several decades in Mali, with an increase from 2017 to 2020 (2,884,837 confirmed cases and 1,454 deaths). On the recommendation of the World Health Organization (WHO) and in the interests of efficient use of resources, Mali has begun a process of stratifying the health districts to target malaria control strategies.MethodMalaria, entomological and environmental data were collected through the local health information system (LHIS), the Demographic and Health Survey (DHS 2018), research institutions and MALI-METEO services. The WHO has recommended stratification at the district level consisted of assigning each district to one of 4 classes according to criteria based on incidence adjusted for attendance rate. Variables associated with monthly malaria incidence at the district level were identified using a general additive non-linear regression model.ResultsFrom 2017 to 2019, the median incidence across 75 health districts of Mali was 129.34 cases per 1,000 person-year (IQR=86.48). The results showed different periods of high malaria transmission in health districts level and durations varying from 2 to 6 months, showing a double peak for some health districts, which were located in the flooded areas. environmental variables such as rainfall, vegetation index (NDVI), maximum temperature and relative humidity were significantly associated at malaria incidence with a lag of around one month. A strata defines a geographical area with similar epidemiological, environmental and socio-economic factors. Stratification resulted in 12 health districts of very low transmission, 19 low transmission, 20 moderate transmission and 24 in high transmission areas. The number of rounds of season malaria chemoprevention will be based on the number of months in the high transmission period.ConclusionThis first stratification in Mali will allow targeting malaria control strategies. This approach will be dynamic and revised yearly in order to integrate information from the national epidemiological surveillance.

Fibroids affect 20% to 25% of reproductive-age women, and black women are 3 to 9 times more likely to develop them. When uterine height approaches or exceeds the navel, we're talking about giant fibroids. This research was started at the Hôpital du Mali to report on the epidemioclinical and therapeutic aspects of giant fibroids. A descriptive retro-prospective study, conducted in the service of gynecology of the Hôpital du Mali from November 2017 to December 2018 were included in this study, any patients, regardless of their age, having developed a fibroid, the uterine height of the patient reaching or exceeding the umbilicus on physical examination and who were on surgical treatment. We had collected 30 cases of GFs out of the 92 patients who had undergone myomectomies, with a frequency of 32.60%. The age group 25 - 29 years accounted for 46.6% with an average age of 35 years. Housewives represented 50% and nulligravida made up 33% of our patients. Desire to become pregnant was the main reason for consultation in 34.4% of cases. On physical inspection, 46.66 % of the time, the uterine height was between 25 and 29 cm. In 76.64 percent of cases, myomectomy was performed, while hysterectomy was performed in 23.3 %. The size of the nuclei after surgery was over 25 cm in 48.66% of our patients. Conclusion: The giant fibroid (GF) is a common cause of myomectomy. The treatment is either hysterectomy or myomectomy and depends on the indications. Hysterectomy should be reserved for the etiologies: excessive volume of fibroids, postmenopausal women and multiple gravida.

Background: Over the past decade, three strategies have reduced severe malaria cases and deaths in endemic regions of Africa, Asia, and the Americas, specifically: 1] artemisinin-based combination therapies (ACTs), 2] insecticide-treated bed nets (ITNs) , and 3] intermittent preventive treatment with sulfadoxine-pyrimethamine in pregnancy (IPTp. The rationale for this study was to examine communities in Dangassa, Mali where in 2015 two additional control strategies were implemented: ITN universal coverage and Seasonal Malaria Chemoprevention (SMC) among children less than five years. Methods: This was a prospective study based on a rolling longitudinal cohort of 1,401 subjects participating in biannual smear surveys for the prevalence of asymptomatic P. falciparum infection and continuous surveillance for the incidence of human disease (uncomplicated malaria). Entomologic collections were performed to examine the intensity of transmission based on pyrethroid spray catches, human landing catches, and enzyme-linked immunosorbent assay (ELISA) testing for circumsporozoite antigen. Results: A total of 1,401 participants of all ages were enrolled in the study in 2012 after random sampling of households from the community census list. Prevalence of infection was extremely high in Dangassa varying from 9.5% to 62.8% at the start of the rainy season and from 15.1% to 66.7% at the end of the rainy season. Likewise, the number of vectors per house, biting rates, sporozoïtes rates and entomologic inoculation rates (EIR) were substantially greater in Dangassa. Discussion: The findings for this study are consistent with the progressive implementation of effective malaria control strategies in Dangassa. At baseline (2012-2014), prevalence of P. falciparum was above 60% followed by a significant year-to-year decease starting in 2015. Incidence of uncomplicated infected was greater among children < five years while asymptomatic infection was more frequent among the five to fourteen years old. A significant decrease in entomological inoculation rate was also observed from 2015 to 2020. Likewise, vectors’ density, sporozoïtes rates, and entomologic inoculation rates decrease substantially during the study period. Conclusion: Efficient Implementation of two main malaria prevention strategies in Dangassa substantially contribute to a reduction of both asymptomatic and symptomatic malaria in Dangassa from 2015 to 2020

Stakeholder engagement is an essential pillar for the development of innovative public health interventions, including genetic approaches for malaria vector control. Scientific terminologies are mainly lacking in local languages, yet when research activities involve international partnership, the question of technical jargon and its translation is crucial for effective and meaningful communication with stakeholders. Target Malaria, a not-for-profit research consortium developing innovative genetic approaches to malaria vector control, carried out a linguistic exercise in Mali, Burkina Faso and Uganda to establish the appropriate translation of its key terminology to local languages of sites where the teams operate. While reviewing the literature, there was no commonly agreed approach to establish such glossary of technical terms in local languages of the field sites where Target Malaria operates. Because of its commitment to the value of co-development, Target Malaria decided to apply this principle for the linguistic work and to take the opportunity of this process to empower communities to take part in the dialogue on innovative vector control. The project worked with linguists from other institutions (whether public research ones or private language centre) who developed a first potential glossary in the local language after better understanding the project scientific approach. This initial glossary was then tested during focus groups with community members, which significantly improved the proposed translations by making them more appropriate to the local context and cultural understanding. The stepwise process revealed the complexity and importance of elaborating a common language with communities as well as the imbrication of language with cultural aspects. This exercise demonstrated the strength of a co-development approach with communities and language experts as a way to develop knowledge together and to tailor communication to the audience even in the language used.

Background Implementation and upscale of effective malaria vector control strategies necessitates understanding the multi-factorial aspects of transmission patterns. The primary aims of this study are to determine the vector composition, biting rates, trophic preference, and the overall importance of distinguishing outdoor versus indoor malaria transmission through a study at two communities in rural Mali. Methods Mosquito collection was carried out between July 2012 and June 2016 at two rural Mali communities (Dangassa and Koïla Bamanan) using pyrethrum spray-catch and human landing catch approaches at both indoor and outdoor locations. Species of Anopheles gambiae complex were identified by polymerase chain reaction (PCR). Enzyme-Linked -Immuno-Sorbent Assay (ELISA) were used to determine the origin of mosquito blood meals and presence of Plasmodium falciparum sporozoite infections. Results A total of 11,237 An. gambiae sensu lato (s.l.) were collected during the study period (5239 and 5998 from the Dangassa and Koïla Bamanan sites, respectively). Of the 679 identified by PCR in Dangassa, Anopheles coluzzii was the predominant species with 91.4% of the catch followed by An. gambiae (8.0%) and Anopheles arabiensis (0.6%). At the same time in Koïla Bamanan, of the 623 An. gambiae s.l., An. coluzzii accounted for 99% of the catch, An. arabiensis 0.8% and An. gambiae 0.2%. Human Blood Index (HBI) measures were significantly higher in Dangassa (79.4%; 95% Bayesian credible interval (BCI) [77.4, 81.4]) than in Koïla Bamanan (15.9%; 95% BCI [14.7, 17.1]). The human biting rates were higher during the second half of the night at both sites. In Dangassa, the sporozoite rate was comparable between outdoor and indoor mosquito collections. For outdoor collections, the sporozoite positive rate was 3.6% (95% BCI [2.1–4.3]) and indoor collections were 3.1% (95% BCI [2.4–5.0]). In Koïla Bamanan, the sporozoite rate was higher indoors at 4.3% (95% BCI [2.7–6.3]) compared with outdoors at 2.4% (95% BCI [1.1–4.2]). In Dangassa, corrected entomological inoculation rates (cEIRs) using HBI were 13.74 [95% BCI 9.21–19.14] infective bites/person/month (ib/p/m) at indoor, and 18.66 [95% BCI 12.55–25.81] ib/p/m at outdoor. For Koïla Bamanan, cEIRs were 1.57 [95% BCI 2.34–2.72] ib/p/m and 0.94 [95% BCI 0.43–1.64] ib/p/m for indoor and outdoor, respectively. EIRs were significantly higher at the Dangassa site than the Koïla Bamanan site. Conclusion The findings in this work may indicate the occurrence of active, outdoor residual malaria transmission is comparable to indoor transmission in some geographic settings. The high outdoor transmission patterns observed here highlight the need for additional strategies to combat outdoor malaria transmission to complement traditional indoor preventive approaches such as long-lasting insecticidal nets (LLINs) and indoor residual spraying (IRS) which typically focus on resting mosquitoes.

BackgroundCurrent mark release recapture methodologies are limited in their ability to address complex problems in vector biology, such as studying multiple groups overlapping in space and time. Additionally, limited mark retention, reduced post-marking survival, and the large effort in marking, collection and recapture, all complicate effective insect tracking.MethodWe have developed and evaluated a marking method using a fluorescent dye (Smartwater®) combined with synthetic DNA tags to informatively and efficiently mark adult mosquitoes using an airbrush pump and nebulizer. Using handheld UV flashlights, the fluorescent marking enabled quick and simple initial detection of recaptures in a simple, field-ready, and non-destructive approach that when combined with a simple, extraction-free PCR on individual mosquito legs provides potentially unlimited marking information.ResultsThis marking, first tested in the laboratory with Anopheles gambiae s.l. mosquitoes, did not affect survival (median ages 24-28 days, p-adj > 0.25), oviposition (median eggs/female of 28.8, 32.5, 33.3 for water, green, red dyes, respectively, p-adj > 0.44), or Plasmodium competence (mean oocysts 5.56 to 10.6, p-adj > 0.95). DNA and fluorescence had 100% retention up to 3 weeks (longest time point tested) with high intensity, indicating marks would persist longer.ConclusionsWe describe a novel, simple, no/low-impact, and long-lasting marking method that allows separation of multiple insect subpopulations by combining unlimited length and sequence variation in the synthetic DNA tags. This method can be readily deployed in the field for marking multiple groups of mosquitoes or other insects.

International audience; BACKGROUND:Pfs25H-EPA is a protein-protein conjugate transmission-blocking vaccine against Plasmodium falciparum that is safe and induces functional antibodies in malaria-naive individuals. In this field trial, we assessed Pfs25H-EPA/Alhydrogel for safety and functional immunogenicity in Malian adults.METHODS:This double-blind, randomised, comparator-controlled, dose-escalation trial in Bancoumana, Mali, was done in two staggered phases, an initial pilot safety assessment and a subsequent main phase. Healthy village residents aged 18-45 years were eligible if they had normal laboratory results (including HIV, hepatitis B, hepatitis C tests) and had not received a previous malaria vaccine or recent immunosuppressive drugs, vaccines, or blood products. Participants in the pilot safety cohort and the main cohort were assigned (1:1) by block randomisation to a study vaccine group. Participants in the pilot safety cohort received two doses of Pfs25H-EPA/Alhydrogel 16 μg or Euvax B (comparator vaccine), and participants in the main cohort received Pfs25H-EPA/Alhydrogel 47 μg or comparator vaccine (Euvax B for the first, second, and third vaccinations and Menactra for the fourth vaccination). Participants and investigators were masked to group assignment, and randomisation codes in sealed envelopes held by a site pharmacist. Vials with study drug for injection were covered by opaque tape and labelled with a study identification number. Group assignments were unmasked at final study visit. The primary outcomes were safety and tolerability for all vaccinees. The secondary outcome measure was immunogenicity 14 days after vaccination in the per-protocol population, as confirmed by the presence of antibodies against Pfs25H measured by ELISA IgG and antibody functionality assessed by standard membrane feeding assays and by direct skin feeding assays. This trial is registered with ClinicalTrials.gov, number NCT01867463.FINDINGS:Between May 15, and Jun 16, 2013, 230 individuals were screened for eligibility. 20 individuals were enrolled in the pilot safety cohort; ten participants were assigned to receive Pfs25H-EPA/Alhydrogel 16 μg, and ten participants were assigned to receive comparator vaccine. 100 individuals were enrolled in the main cohort; 50 participants were assigned to receive Pfs25H-EPA/Alhydrogel 47 μg, and 50 participants were assigned to receive comparator vaccine. Compared with comparator vaccinees, Pfs25H vaccinees had more solicited adverse events (137 events vs 86 events; p=0·022) and treatment-related adverse events (191 events vs 126 events, p=0·034), but the number of other adverse events did not differ between study vaccine groups (792 vs 683). Pfs25H antibody titres increased with each dose, with a peak geometric mean of 422·3 ELISA units (95% CI 290-615) after the fourth dose, but decreased relatively rapidly thereafter, with a half-life of 42 days for anti-Pfs25H and 59 days for anti-EPA (median ratio of titres at day 600 to peak, 0·19 for anti-Pfs25H vs 0·29 for anti-EPA; p=0·009). Serum transmission-reducing activity was greater for Pfs25H than for comparator vaccine after the fourth vaccine dose (p

Despite impressive progress, malaria continues to impose a substantial burden of mortality and morbidity, particularly in sub-Saharan Africa, and new tools will be needed to achieve elimination. Gene drive is a natural process by which some genes are inherited at a greater-than-Mendelian rate and can spread through a population even if they cause harm to the organisms carrying them. Many different synthetic gene drive systems have been proposed to suppress the number of mosquitoes and/or reduce vector competence. As with any control measure, due attention should be paid to the possible evolution of resistance. No gene drive construct has yet been reported that is ‘field-ready’ for release, and when such constructs are developed, they should be assessed on a case-by-case basis. Gene drive approaches to vector control promise to have a number of key features that motivate their continued development, and scrutiny, by all concerned.

Novel approaches to area-wide control of vector species offer promise as additional tools in the fight against vectored diseases. Evaluation of transgenic insect strains aimed at field population control in disease-endemic countries may involve international partnerships and should be done in a stepwise approach, starting with studies in containment facilities. The preparations of both new-build and renovated facilities are described, including working with local and national regulations regarding land use, construction, and biosafety requirements, as well as international guidance to fill any gaps in regulation. The examples given are for containment categorization at Arthropod Containment Level 2 for initial facility design, classification of wastes, and precautions during shipping. Specific lessons were derived from preparations to evaluate transgenic (non-gene drive) mosquitoes in West and East African countries. Documented procedures and the use of a non-transgenic training strain for trial shipments and culturing were used to develop competence and confidence among the African facility staff, and along the chain of custody for transport. This practical description is offered to support other research consortia or institutions preparing containment facilities and operating procedures in conditions where research on transgenic insects is at an early stage.

Genetic strategies for large scale pest or vector control using modified insects are not yet operational in Africa, and currently rely on import of the modified strains to begin preliminary, contained studies. Early involvement of research teams from participating countries is crucial to evaluate candidate field interventions. Following the recommended phased approach for novel strategies, evaluation should begin with studies in containment facilities. Experiences to prepare facilities and build international teams for research on transgenic mosquitoes revealed some important organizing themes underlying the concept of “facilities readiness,” or the point at which studies in containment may proceed, in sub-Saharan African settings. First, “compliance” for research with novel or non-native living organisms was defined as the fulfillment of all legislative and regulatory requirements. This is not limited to regulations regarding use of transgenic organisms. Second, the concept of “colony utility” was related to the characteristics of laboratory colonies being produced so that results of studies may be validated across time, sites, and strains or technologies; so that the appropriate candidate strains are moved forward toward field studies. Third, the importance of achieving “defensible science” was recognized, including that study conclusions can be traced back to evidence, covering the concerns of various stakeholders over the long term. This, combined with good stewardship of resources and appropriate funding, covers a diverse set of criteria for declaring when “facilities readiness” has been attained. It is proposed that, despite the additional demands on time and resources, only with the balance of and rigorous achievement of each of these organizing themes can collaborative research into novel strategies in vector or pest control reliably progress past initial containment studies.

Background The landscape of mosquito-borne disease risk has changed dramatically in recent decades, due to the emergence and reemergence of urban transmission cycles driven by invasive Aedes aegypti and Ae. albopictus. Insecticide resistance is already widespread in the yellow fever mosquito, Ae. Aegypti; is emerging in the Asian tiger mosquito Ae. Albopictus; and is now threatening the global fight against human arboviral diseases such as dengue, yellow fever, chikungunya, and Zika. Because the panel of insecticides available for public health is limited, it is of primary importance to preserve the efficacy of existing and upcoming active ingredients. Timely implementation of insecticide resistance management (IRM) is crucial to maintain the arsenal of effective public health insecticides and sustain arbovirus vector control. Methodology and principal findings This Review is one of a series being generated by the Worldwide Insecticide resistance Network (WIN) and aims at defining the principles and concepts underlying IRM, identifying the main factors affecting the evolution of resistance, and evaluating the value of existing tools for resistance monitoring. Based on the lessons taken from resistance strategies used for other vector species and agricultural pests, we propose a framework for the implementation of IRM strategies for Aedes mosquito vectors. Conclusions and significance Although IRM should be a fixture of all vector control programs, it is currently often absent from the strategic plans to control mosquito-borne diseases, especially arboviruses. Experiences from other public health disease vectors and agricultural pests underscore the need for urgent action in implementing IRM for invasive Aedes mosquitoes. Based on a plan developed for malaria vectors, here we propose some key activities to establish a global plan for IRM in Aedes spp., Author summary Arthropod-borne viruses transmitted by Aedes aegypti and Ae. albopictus represent a major public health concern at a global scale. The insecticidal treatments exerted on both species have selected for various resistance mechanisms within wild populations. Although the impact of insecticide resistance on the efficacy of vector control operations remains broadly unknown, it is of primary importance to implement strategies for preserving the efficacy of treatments and reducing the pathogen transmission during epidemics. For this purpose, there are urgent needs for new tools for vector control and insecticide resistance monitoring to improve the management of insecticide resistance in Aedes species.

Shifting the malaria priorities from a paradigm of control and elimination to a goal of global eradication calls for renewed attention to the interruption of malaria transmission. Sustained progress toward eradication will require both improved understanding of infectious reservoirs and efficient development of novel transmission-blocking interventions, such as rapidly acting and highly efficacious therapeutics and vaccines. Here, we review the direct skin feeding assay (DSF), which has been proposed as a valuable tool for measuring the in natura transmission of malaria parasites from human hosts to mosquito vectors across heterogeneous populations. To capture the methodological breadth of this assay’s use, we first systematically review and qualitatively synthesize previously published investigations using DSFs to study malaria transmission in humans. Then, using a recent Phase 1 trial in Mali of the Pfs25H-EPA/Alhydrogel® vaccine candidate (NCT01867463) designed to interrupt Plasmodium falciparum transmission as a case study, we describe the potential opportunities and current limitations of utilizing the endpoints measured by DSF in making early clinical decisions for individually randomized transmission-interrupting intervention candidates. Using simulations based on the data collected in the clinical trial, we demonstrate that the capacity of the DSF to serve as an evaluative tool is limited by the statistical power constraints of the “effective sample size” (i.e. the number of subjects that are capable of transmitting at the time of feeding). Altogether, our findings suggest DSFs have great potential utility for assessing the public health impacts of emerging antimalarial tools, but additional research is needed to address issues of scalability and to establish correlation with community-wide clinical endpoints as well as complementary in vitro measures, such as standard membrane feeding assays.

Bioinformatics and data science research have boundless potential across Africa due to its high levels of genetic diversity and disproportionate burden of infectious diseases, including malaria, tuberculosis, HIV and AIDS, Ebola virus disease, and Lassa fever. This work lays out an incremental approach for reaching underserved countries in bioinformatics and data science research through a progression of capacity building, training, and research efforts. Two global health informatics training programs sponsored by the Fogarty International Center (FIC) were carried out at the University of Sciences, Techniques and Technologies of Bamako, Mali (USTTB) between 1999 and 2011. Together with capacity building efforts through the West Africa International Centers of Excellence in Malaria Research (ICEMR), this progress laid the groundwork for a bioinformatics and data science training program launched at USTTB as part of the Human Heredity and Health in Africa (H3Africa) initiative. Prior to the global health informatics training, its trainees published first or second authorship and third or higher authorship manuscripts at rates of 0.40 and 0.10 per year, respectively. Following the training, these rates increased to 0.70 and 1.23 per year, respectively, which was a statistically significant increase (p < 0.001). The bioinformatics and data science training program at USTTB commenced in 2017 focusing on student, faculty, and curriculum tiers of enhancement. The program’s sustainable measures included institutional support for core elements, university tuition and fees, resource sharing and coordination with local research projects and companion training programs, increased student and faculty publication rates, and increased research proposal submissions. Challenges reliance of high-speed bandwidth availability on short-term funding, lack of a discounted software portal for basic software applications, protracted application processes for United States visas, lack of industry job positions, and low publication rates in the areas of bioinformatics and data science. Long-term, incremental processes are necessary for engaging historically underserved countries in bioinformatics and data science research. The multi-tiered enhancement approach laid out here provides a platform for generating bioinformatics and data science technicians, teachers, researchers, and program managers. Increased literature on bioinformatics and data science training approaches and progress is needed to provide a framework for establishing benchmarks on the topics.

The molecular mechanisms and genetic architecture that facilitate adaptive radiation of lineages remain elusive. Polymorphic chromosomal inversions, due to their recombination-reducing effect, are proposed instruments of ecotypic differentiation. Here, we study an ecologically diversifying lineage of Anopheles gambiae, known as the Bamako chromosomal form based on its unique complement of three chromosomal inversions, to explore the impact of these inversions on ecotypic differentiation. We used pooled and individual genome sequencing of Bamako, typical (non-Bamako) An. gambiae and the sister species Anopheles coluzzii to investigate evolutionary relationships and genomewide patterns of nucleotide diversity and differentiation among lineages. Despite extensive shared polymorphism and limited differentiation from the other taxa, Bamako clusters apart from the other taxa, and forms a maximally supported clade in neighbour-joining trees based on whole-genome data (including inversions) or solely on collinear regions. Nevertheless, FST outlier analysis reveals that the majority of differentiated regions between Bamako and typical An. gambiae are located inside chromosomal inversions, consistent with their role in the ecological isolation of Bamako. Exceptionally differentiated genomic regions were enriched for genes implicated in nervous system development and signalling. Candidate genes associated with a selective sweep unique to Bamako contain substitutions not observed in sympatric samples of the other taxa, and several insecticide resistance gene alleles shared between Bamako and other taxa segregate at sharply different frequencies in these samples. Bamako represents a useful window into the initial stages of ecological and genomic differentiation from sympatric populations in this important group of malaria vectors.

The success of vector control strategies aiming to decrease disease transmission via the release of sterile or genetically-modified male mosquitoes critically depends on mating between laboratory-reared males and wild females. Unfortunately, mosquito colonization, laboratory rearing, and genetic manipulations can all negatively affect male competitiveness. Heterosis is commonly used to produce domestic animals with enhanced vigor and homogenous genetic background and could therefore potentially improve the mating performance of mass-reared male mosquitoes. Here, we produced enhanced hybrid males of the malaria mosquito Anopheles coluzzii by crossing two strains colonized >35 and 8 years ago. We compared the amount of sperm and mating plug proteins they transferred to females, as well as their insemination rate, reproductive success and longevity under various experimental conditions. Across experiments, widespread adaptations to laboratory mating were detected in the older strain. In large-group mating experiments, no overall hybrid advantage in insemination rates and the amount of sperm and accessory gland proteins transferred to females was detected. Despite higher sperm activity, hybrid males did not appear more fecund. However, individual-male mating and laboratory-swarm experiments revealed that hybrid males, while inseminating fewer females than older inbred males, were significantly more fertile, producing larger mating plugs and drastically increasing female fecundity. Heterotic males also showed increased longevity. These results validate the use of heterosis for creating hybrid males with improved fitness from long-established inbred laboratory strains. Therefore, this simple approach could facilitate disease control strategies based on male mosquito releases with important ultimate benefits to human health.

International audience; The Zika crisis drew attention to the long-overlooked problem of arboviruses transmitted by Aedes mosquitoes in Africa. Yellow fever, dengue, chikungunya and Zika are poorly controlled in Africa and often go unrecognized. However, to combat these diseases, both in Africa and worldwide, it is crucial that this situation changes. Here, we review available data on the distribution of each disease in Africa, their Aedes vectors, transmission potential, and challenges and opportunities for Aedes control. Data on disease and vector ranges are sparse, and consequently maps of risk are uncertain. Issues such as genetic and ecological diversity, and opportunities for integration with malaria control, are primarily African; others such as ever-increasing urbanization, insecticide resistance and lack of evidence for most control-interventions reflect problems throughout the tropics. We identify key knowledge gaps and future research areas, and in particular, highlight the need to improve knowledge of the distributions of disease and major vectors, insecticide resistance, and to develop specific plans and capacity for arboviral disease surveillance, prevention and outbreak responses.

International audience; Major efforts are currently underway to develop novel, complementary methods to combat mosquito-borne diseases. Mosquito genetic control strategies (GCSs) have become an increasingly important area of research on account of their species-specificity, track record in targeting agricultural insect pests, and their environmentally non-polluting nature. A number of programs targeting Aedes and Anopheles mosquitoes, vectors of human arboviruses and malaria respectively, are currently being developed or deployed in many parts of the world. Operationally implementing these technologies on a large scale however, beyond proof-of-concept pilot programs, is hampered by the absence of adequate sex separation methods. Sex separation eliminates females in the laboratory from male mosquitoes prior to release. Despite the need for sex separation for the control of mosquitoes, there have been limited efforts in recent years in developing systems that are fit-for-purpose. In this special issue of Parasites and Vectors we report on the progress of the global Coordinated Research Program on Exploring genetic, molecular, mechanical and behavioural methods for sex separation in mosquitoes that is led by the Insect Pest Control Subprogramme of the Joint FAO/IAEA Division of Nuclear Techniques in Food and Agriculture with the specific aim of building efficient sex separation systems for mosquito species. In an effort to overcome current barriers we briefly highlight what we believe are the three main reasons why progress has been so slow in developing appropriate sex separation systems: the availability of methods that are not scalable, the difficulty of building the ideal genetic systems and, finally, the lack of research efforts in this area.

Malaria transmission-blocking vaccines (TBV) have been evaluated in field trials in Mali since 2013. However, the assays currently used to measure serum antibody TB activity (TBA) after vaccination are highly variable, in part due to the lack of optimization and standardization for field assays in which mosquitoes feed on gametocytemic blood. Herein, we report a study conducted in Bancoumana village, Mali, where we identify and optimize the parameters that contribute to successful mosquito feeding outcomes in both direct skin feeds (DSFs) and direct membrane feeding assays (DMFA). These parameters include: 1) mosquito age, 2) duration of mosquito starvation prior to feeding, 3) membrane selection for DMFA, 4) anatomical location of DSF feeding (arm, calf, and ankle), and 5) time of day for DSF (dawn or dusk). We found that younger mosquitoes were significantly associated with higher feeding, survival, and infection rates. Longer starvation times were positively, but not significantly, associated with higher infection rates, but were negatively associated with feeding and survival. Membrane type and body location did not affect infection outcome significantly. Although dusk was found to be associated with higher infection rates, this may be confounded by the time from positive blood smear. Based on these findings, we make specific recommendations for optimal feeding parameters in the different assay types to maximize the chance of detecting parasite transmission in a standardized manner.