Rapid susceptibility testing of Mycobacterium tuberculosis by the Mycobacteria Growth Indicator Tube (MGITAST SIRE)

ObjectiveTo evaluate the reliability of the Mycobacteria Growth Indicator Tube (MGITAST) for susceptibility testing of Mycobacterium tuberculosis.MethodsSeventy strains of M. tuberculosis were tested for susceptibility to streptomycin, isoniazid, rifampicin and ethambutol by comparing MGITAST results to those obtained by the method of proportion (MOP) on Lowenstein–Jensen (LJ) and Middlebrook 7H10 media. The 7H10 MOP was considered the method of reference.ResultsThe turnaround time for MGITAST was 6.2days (5–10days) and for MOP it was 18–21days. With rifampicin, MGITAST agreed for all isolates with both MOP. For streptomycin, MGITAST and 7H10 MOP agreed for 64 isolates (91.4%); 61 were susceptible and three resistant. LJ MOP and 7H10 MOP agreed for 64 isolates (92.2%); 62 were susceptible and three resistant. With isoniazid, both MOP agreed for all isolates, while MGITAST and 7H10 MOP had two discrepancies. For ethambutol, MGITAST and 7H10 MOP were concordant for 66 isolates; 65 were susceptible and one resistant. Both MOP were concordant for 67 isolates; 66 were susceptible and one resistant.ConclusionsBased on these results, MGITAST is a time-saving method and can be used as an alternative to the BACTEC System. MGITAST is reliable as far as rifampicin and isoniazid are concerned; however, additional studies are needed for streptomycin and ethambutol

Strengthening human genetics research in Africa: report of the 9th meeting of the African Society of Human Genetics in Dakar in May 2016.

The 9th meeting of the African Society of Human Genetics, in partnership with the Senegalese Cancer Research and Study Group and the Human Heredity and Health in Africa (H3Africa) Consortium, was held in Dakar, Senegal. The theme was Strengthening Human Genetics Research in Africa. The 210 delegates came from 21 African countries and from France, Switzerland, UK, UAE, Canada and the USA. The goal was to highlight genetic and genomic science across the African continent with the ultimate goal of improving the health of Africans and those across the globe, and to promote the careers of young African scientists in the field. A session on the sustainability of genomic research in Africa brought to light innovative and practical approaches to supporting research in resource-limited settings and the importance of promoting genetics in academic, research funding, governmental and private sectors. This meeting led to the formation of the Senegalese Society for Human Genetics

Anti-malarial prescriptions in three health care facilities after the emergence of chloroquine resistance in Niakhar, Senegal (1992–2004)

<p>Abstract</p> <p>Background</p> <p>In the rural zone of Niakhar in Senegal, the first therapeutic failures for chloroquine (CQ) were observed in 1992. In 2003, the national policy regarding first-line treatment of uncomplicated malaria was modified, replacing CQ by a transitory bi-therapy amodiaquine/sulphadoxine-pyrimethamine (AQ/SP), before the implementation of artemisinin-based combination therapy (ACT) in 2006.</p> <p>The aims of the study were to assess the evolution of anti-malarial prescriptions in three health care facilities between 1992 and 2004, in parallel with increasing CQ resistance in the region.</p> <p>Methods</p> <p>The study was conducted in the area of Niakhar, a demographic surveillance site located in a sahelo-sudanese region of Senegal, with mesoendemic and seasonal malaria transmission. Health records of two public health centres and a private catholic dispensary were collected retrospectively to cover the period 1992–2004.</p> <p>Results</p> <p>Records included 110,093 consultations and 292,965 prescribed treatments. Twenty-five percent of treatments were anti-malarials, prescribed to 49% of patients. They were delivered all year long, but especially during the rainy season, and 20% of patients with no clinical malaria diagnosis received anti-malarials. Chloroquine and quinine represented respectively 55.7% and 34.6% of prescribed anti-malarials. Overall, chloroquine prescriptions rose from 1992 to 2000, in parallel with clinical malaria; then the CQ prescription rate decreased from 2000 and was concomitant with the rise of SP and the persistence of quinine use. AQ and SP were mainly used as bi-therapy after 2003, at the time of national treatment policy change.</p> <p>Conclusion</p> <p>The results show the overall level of anti-malarial prescription in the study area for a considerable number of patients over a large period of time. Even though resistance to CQ rapidly increased from 1992 to 2001, no change in CQ prescription was observed until the early 2000s, possibly due to the absence of an obvious decrease in CQ effectiveness, a lack of therapeutic options or a blind follow-up of national guidelines.</p

Evaluation of Two Strategies for Community-Based Safety Monitoring during Seasonal Malaria Chemoprevention Campaigns in Senegal, Compared with the National Spontaneous Reporting System.

BACKGROUND: Seasonal malaria chemoprevention (SMC) using sulfadoxine-pyrimethamine plus amodiaquine has been introduced in 12 African countries. Additional strategies for safety monitoring are needed to supplement national systems of spontaneous reporting that are known to under represent the incidence of adverse reactions. OBJECTIVES: This study aimed to determine if adverse event (AE) reporting could be improved using a smartphone application provided to village health workers, or by active follow-up using a symptom card provided to caregivers. METHODS: Two strategies to improve reporting of AEs during SMC campaigns were evaluated, in comparison with the national system of spontaneous reporting, in 11 health post areas in Senegal. In each health post, an average of approximately 4000 children under 10 years of age received SMC treatment each month for 3 months during the 2015 malaria transmission season-a total of 134,000 treatments. In three health posts (serving approximately 14,000 children), caregivers were encouraged to report any adverse reactions to the nurse at the health post or to a community health worker (CHW) in their village, who had been trained to use a smartphone application to report the event (enhanced spontaneous reporting). In two health posts (approximately 10,000 children), active follow-up of children at home was organized after each SMC campaign to ask about AEs that caregivers had been asked to record on a symptom card (active surveillance). Six health posts (approximately 23,000 children) followed the national system of spontaneous reporting using the national reporting (yellow) form. Each AE report was assessed by a panel to determine likely association with SMC drugs. RESULTS: The incidence of reported AEs was 2.4, 30.6, and 21.6 per 1000 children treated per month, using the national system, enhanced spontaneous reporting, and active surveillance, respectively. The most commonly reported symptoms were vomiting, fever, and abdominal pain. The incidence of vomiting, known to be caused by amodiaquine, was similar using both innovative methods (10/1000 in the first month, decreasing to 2.5/1000 in the third month). Despite increased surveillance, no serious adverse drug reactions were detected. CONCLUSION: Training CHWs in each village and health facility staff to report AEs using a mobile phone application led to much higher reporting rates than through the national system. This approach is feasible and acceptable, and could be further improved by strengthening laboratory investigation and the collection of control data immediately prior to SMC campaigns

Evolution of malaria mortality and morbidity after the emergence of chloroquine resistance in Niakhar, Senegal

Background: Recently, it has been assumed that resistance of Plasmodium to chloroquine increased malaria mortality. The study aimed to assess the impact of chemoresistance on mortality attributable to malaria in a rural area of Senegal, since the emergence of resistance in 1992, whilst chloroquine was used as first-line treatment of malaria, until the change in national anti-malarial policy in 2003. Methods: The retrospective study took place in the demographic surveillance site (DSS) of Niakhar. Data about malaria morbidity were obtained from health records of three health care facilities, where diagnosis of malaria was based on clinical signs. Source of data concerning malaria mortality were verbal autopsies performed by trained fieldworkers and examined by physicians who identified the probable cause of death. Results: From 1992 to 2004, clinical malaria morbidity represented 39% of total morbidity in health centres. Mean malaria mortality was 2.4 parts per thousand and 10.4 parts per thousand among total population and children younger than five years, respectively, and was highest in the 1992-1995 period. It tended to decline from 1992 to 2003 (Trend test, total population p = 0.03, children 0-4 years p = 0.12 - children 1-4 years p = 0.04 - children 5-9 years p = 0.01). Conclusion: Contrary to what has been observed until 1995, mortality attributable to malaria did not continue to increase dramatically in spite of the growing resistance to chloroquine and its use as first-line treatment until 2003. Malaria morbidity and mortality followed parallel trends and rather fluctuated accordingly to rainfall

Origin and Global Expansion of Mycobacterium tuberculosis Complex Lineage 3

Tuberculosis still causes 1.5 million deaths annually and is mainly caused by Mycobacterium tuberculosis complex strains belonging to three evolutionary modern lineages (Lineages 2–4). While Lineage 2 and Lineage 4 virtually conquered the world, Lineage 3 is particularly successful in Northern and Eastern Africa, as well as in Southern Asia, the suspected evolutionary origin of these strains. Here, we sought to understand how Lineage 3 strains came to the African continent. To this end, we performed routine genotyping to characterize over 2500 clinical isolates from 38 countries. We then selected a representative collection of 373 isolates for a whole-genome analysis and a modeling approach to infer the geographic origin of different sublineages. In fact, the origin of Lineage 3 could be located in India, and we found evidence for independent introductions of four distinct sublineages into North/East Africa, in line with known ancient exchanges and migrations between both world regions. Our study illustrates that the evolutionary history of humans and their pathogens are closely connected and further provides a systematic understanding of the genomic diversity of Lineage 3, which could be important for the development of new tuberculosis vaccines or new therapeutics.Mycobacterium tuberculosis complex (MTBC) Lineage 3 (L3) strains are abundant in world regions with the highest tuberculosis burden. To investigate the population structure and the global diversity of this major lineage, we analyzed a dataset comprising 2682 L3 strains from 38 countries over 5 continents, by employing 24-loci mycobacterial interspersed repetitive unit-variable number of tandem repeats genotyping (MIRU-VNTR) and drug susceptibility testing. We further combined whole-genome sequencing (WGS) and phylogeographic analysis for 373 strains representing the global L3 genetic diversity. Ancestral state reconstruction confirmed that the origin of L3 strains is located in Southern Asia and further revealed multiple independent introduction events into North-East and East Africa. This study provides a systematic understanding of the global diversity of L3 strains and reports phylogenetic variations that could inform clinical trials which evaluate the effectivity of new drugs/regimens or vaccine candidates.Peer Reviewe

Major Reduction in Anti-Malarial Drug Consumption in Senegal after Nation-Wide Introduction of Malaria Rapid Diagnostic Tests

BACKGROUND: While WHO recently recommended universal parasitological confirmation of suspected malaria prior to treatment, debate has continued as to whether wide-scale use of rapid diagnostic tests (RDTs) can achieve this goal. Adherence of health service personnel to RDT results has been poor in some settings, with little impact on anti-malarial drug consumption. The Senegal national malaria control programme introduced universal parasite-based diagnosis using malaria RDTs from late 2007 in all public health facilities. This paper assesses the impact of this programme on anti-malarial drug consumption and disease reporting. METHODS AND FINDINGS: Nationally-collated programme data from 2007 to 2009 including malaria diagnostic outcomes, prescription of artemisinin-based combination therapy (ACT) and consumption of RDTs in public health facilities, were reviewed and compared. Against a marked seasonal variation in all-cause out-patient visits, non-malarial fever and confirmed malaria, parasite-based diagnosis increased nationally from 3.9% of reported malaria-like febrile illness to 86.0% over a 3 year period. The prescription of ACT dropped throughout this period from 72.9% of malaria-like febrile illness to 31.5%, reaching close equivalence to confirmed malaria (29.9% of 584,873 suspect fever cases). An estimated 516,576 courses of inappropriate ACT prescription were averted. CONCLUSIONS: The data indicate high adherence of anti-malarial prescribing practice to RDT results after an initial run-in period. The large reduction in ACT consumption enabled by the move from symptom-based to parasite-based diagnosis demonstrates that effective roll-out and use of malaria RDTs is achievable on a national scale through well planned and structured implementation. While more detailed information on management of parasite-negative cases is required at point of care level to assess overall cost-benefits to the health sector, considerable cost-savings were achieved in ACT procurement. Programmes need to be allowed flexibility in management of these funds to address increases in other programmatic costs that may accrue from improved diagnosis of febrile disease

In Vitro and In Vivo Human Herpesvirus 8 Infection of Placenta

Herpesvirus infection of placenta may be harmful in pregnancy leading to disorders in fetal growth, premature delivery, miscarriage, or major congenital abnormalities. Although a correlation between human herpesvirus 8 (HHV-8) infection and abortion or low birth weight in children has been suggested, and rare cases of in utero or perinatal HHV-8 transmission have been documented, no direct evidence of HHV-8 infection of placenta has yet been reported. The aim of this study was to evaluate the in vitro and in vivo susceptibility of placental cells to HHV-8 infection. Short-term infection assays were performed on placental chorionic villi isolated from term placentae. Qualitative and quantitative HHV-8 detection were performed by PCR and real-time PCR, and HHV-8 proteins were analyzed by immunohistochemistry. Term placenta samples from HHV-8-seropositive women were analyzed for the presence of HHV-8 DNA and antigens. In vitro infected histocultures showed increasing amounts of HHV-8 DNA in tissues and supernatants; cyto- and syncitiotrophoblasts, as well as endothelial cells, expressed latent and lytic viral antigens. Increased apoptotic phenomena were visualized by the terminal deoxynucleotidyl transferase-mediated deoxyuridine nick end-labeling method in infected histocultures. Ex vivo, HHV-8 DNA and a latent viral antigen were detected in placenta samples from HHV-8-seropositive women. These findings demonstrate that HHV-8, like other human herpesviruses, may infect placental cells in vitro and in vivo, thus providing evidence that this phenomenon might influence vertical transmission and pregnancy outcome in HHV-8-infected women