Resource availability for the management of maternal sepsis in Malawi, other low-income countries, and lower-middle-income countries

ObjectiveTo assess the availability of key resources for the management of maternal sepsis and evaluate the feasibility of implementing the Surviving Sepsis Campaign (SSC) recommendations in Malawi and other low-resource settings.MethodsA cross-sectional study was conducted at health facilities in Malawi, other low-income countries, and lower-middle-income countries during January-March 2016. English-speaking healthcare professionals (e.g. doctors, nurses, midwives, and administrators) completed a questionnaire/online survey to assess the availability of resources for the management of maternal sepsis.ResultsHealthcare centers (n=23) and hospitals (n=13) in Malawi showed shortages in the resources for basic monitoring (always available in 5 [21.7%] and 10 [76.9%] facilities, respectively) and basic infrastructure (2 [8.7%] and 7 [53.8%], respectively). The availability of antibiotics varied between Malawian healthcare centers (9 [39.1%]), Malawian hospitals (8 [61.5%]), hospitals in other low-income countries (10/17 [58.8%]), and hospitals in lower-middle-income countries (39/41 [95.1%]). The percentage of SSC recommendations that could be implemented was 33.3% at hospitals in Malawi, 30.3% at hospitals in other low-income countries, and 68.2% at hospitals in lower-middle-income countries.ConclusionThe implementation of existing SSC recommendations is unrealistic in low-income countries because of resource limitations. New maternal sepsis care bundles must be developed that are applicable to low-resource settings

The impact of training non-physician clinicians in Malawi on maternal and perinatal mortality : a cluster randomised controlled evaluation of the enhancing training and appropriate technologies for mothers and babies in Africa (ETATMBA) project

Background: Maternal mortality in much of sub-Saharan Africa is very high whereas there has been a steady decline in over the past 60 years in Europe. Perinatal mortality is 12 times higher than maternal mortality accounting for about 7 million neonatal deaths; many of these in sub-Saharan countries. Many of these deaths are preventable. Countries, like Malawi, do not have the resources nor highly trained medical specialists using complex technologies within their healthcare system. Much of the burden falls on healthcare staff other than doctors including non-physician clinicians (NPCs) such as clinical officers, midwives and community health-workers. The aim of this trial is to evaluate a project which is training NPCs as advanced leaders by providing them with skills and knowledge in advanced neonatal and obstetric care. Training that will hopefully be cascaded to their colleagues (other NPCs, midwives, nurses). Methods/design: This is a cluster randomised controlled trial with the unit of randomisation being the 14 districts of central and northern Malawi (one large district was divided into two giving an overall total of 15). Eight districts will be randomly allocated the intervention. Within these eight districts 50 NPCs will be selected and will be enrolled on the training programme (the intervention). Primary outcome will be maternal and perinatal (defined as until discharge from health facility) mortality. Data will be harvested from all facilities in both intervention and control districts for the lifetime of the project (3–4 years) and comparisons made. In addition a process evaluation using both quantitative and qualitative (e.g. interviews) will be undertaken to evaluate the intervention implementation. Discussion: Education and training of NPCs is a key to improving healthcare for mothers and babies in countries like Malawi. Some of the challenges faced are discussed as are the potential limitations. It is hoped that the findings from this trial will lead to a sustainable improvement in healthcare and workforce development and training. Trial registration: ISRCTN6329415

Viruses causing lower respiratory symptoms in young children: Findings from the ORChID birth cohort

© 2018 Article author(s). Introduction Viral acute respiratory infections (ARIs) cause substantial child morbidity. Sensitive molecular-based assays aid virus detection, but the clinical significance of positive tests remains uncertain as some viruses may be found in both acutely ill and healthy children. We describe disease-pathogen associations of respiratory viruses and quantify virus-specific attributable risk of ARIs in healthy children during the first 2 years of life. Methods One hundred fifty-eight term newborn babies in Brisbane, Australia, were recruited progressively into a longitudinal, community-based, birth cohort study conducted between September 2010 and October 2014. A daily tick-box diary captured predefined respiratory symptoms from birth until their second birthday. Weekly parent-collected nasal swabs were batch-tested for 17 respiratory viruses by PCR assays, allowing calculation of virus-specific attributable fractions in the exposed (AFE) to determine the proportion of virus-positive children whose ARI symptoms could be attributed to that particular virus. Results Of 8100 nasal swabs analysed, 2646 (32.7%) were virus-positive (275 virus codetections, 3.4%), with human rhinoviruses accounting for 2058/2646 (77.8%) positive swabs. Viruses were detected in 1154/1530 (75.4%) ARI episodes and in 984/4308 (22.8%) swabs from asymptomatic periods. Respiratory syncytial virus (AFE: 68% (95% CI 45% to 82%)) and human metapneumovirus (AFE: 69% (95% CI 43% to 83%)) were strongly associated with higher risk of lower respiratory symptoms. Discussion The strong association of respiratory syncytial virus and human metapneumovirus with ARIs and lower respiratory symptoms in young children managed within the community indicates successful development of vaccines against these two viruses should provide substantial health benefits

Something Old, Something New: Ion Channel Blockers as Potential Anti-Tuberculosis Agents

Tuberculosis (TB) remains a challenging global health concern and claims more than a million lives every year. We lack an effective vaccine and understanding of what constitutes protective immunity against TB to inform rational vaccine design. Moreover, treatment of TB requires prolonged use of multi-drug regimens and is complicated by problems of compliance and drug resistance. While most (Mtb) bacilli are quickly killed by the drugs, the prolonged course of treatment is required to clear persistent drug-tolerant subpopulations. Mtb's differential sensitivity to drugs is, at least in part, determined by the interaction between the bacilli and different host macrophage populations. Therefore, to design better treatment regimens for TB, we need to understand and modulate the heterogeneity and divergent responses that Mtb bacilli exhibit within macrophages. However, developing drugs is a long and expensive process. An alternative approach to expedite the development of new TB treatments is to repurpose existing drugs that were developed for other therapeutic purposes if they also possess anti-tuberculosis activity. There is growing interest in the use of immune modulators to supplement current anti-TB drugs by enhancing the host's antimycobacterial responses. Ion channel blocking agents are among the most promising of the host-directed therapeutics. Some ion channel blockers also interfere with the activity of mycobacterial efflux pumps. In this review, we discuss some of the ion channel blockers that have shown promise as potential anti-TB agents

Single cell analysis of M. tuberculosis phenotype and macrophage lineages in the infected lung

In this study, we detail a novel approach that combines bacterial fitness fluorescent reporter strains with scRNA-seq to simultaneously acquire the host transcriptome, surface marker expression, and bacterial phenotype for each infected cell. This approach facilitates the dissection of the functional heterogeneity of M. tuberculosis-infected alveolar (AMs) and interstitial macrophages (IMs) in vivo. We identify clusters of pro-inflammatory AMs associated with stressed bacteria, in addition to three different populations of IMs with heterogeneous bacterial phenotypes. Finally, we show that the main macrophage populations in the lung are epigenetically constrained in their response to infection, while inter-species comparison reveals that most AMs subsets are conserved between mice and humans. This conceptual approach is readily transferable to other infectious disease agents with the potential for an increased understanding of the roles that different host cell populations play during the course of an infection

Examples of risk tools for pests in Peanut (Arachis hypogaea) developed for five countries using Microsoft Excel

Suppressing pest populations below economically-damaging levels is an important element of sustainable peanut (Arachis hypogaea L.) production. Peanut farmers and their advisors often approach pest management with similar goals regardless of where they are located. Anticipating pest outbreaks using field history and monitoring pest populations are fundamental to protecting yield and financial investment. Microsoft Excel was used to develop individual risk indices for pests, a composite assessment of risk, and costs of risk mitigation practices for peanut in Argentina, Ghana, India, Malawi, and North Carolina (NC) in the United States (US). Depending on pests and resources available to manage pests, risk tools vary considerably, especially in the context of other crops that are grown in sequence with peanut, cultivars, and chemical inputs. In Argentina, India, and the US where more tools (e.g., mechanization and pesticides) are available, risk indices for a wide array of economically important pests were developed with the assumption that reducing risk to those pests likely will impact peanut yield in a positive manner. In Ghana and Malawi where fewer management tools are available, risks to yield and aflatoxin contamination are presented without risk indices for individual pests. The Microsoft Excel platform can be updated as new and additional information on effectiveness of management practices becomes apparent. Tools can be developed using this platform that are appropriate for their geography, environment, cropping systems, and pest complexes and management inputs that are available. In this article we present examples for the risk tool for each country.Fil: Jordan, David L.. University of Georgia; Estados Unidos. North Carolina State University; Estados UnidosFil: Buol, Greg S.. North Carolina State University; Estados UnidosFil: Brandenburg, Rick L.. North Carolina State University; Estados UnidosFil: Reisig, Dominic. North Carolina State University; Estados UnidosFil: Nboyine, Jerry. Council for Scientific and Industrial Research Savanna Agricultural Research Institute; GhanaFil: Abudulai, Mumuni. Council for Scientific and Industrial Research Savanna Agricultural Research Institute; GhanaFil: Oteng Frimpong, Richard. Council for Scientific and Industrial Research Savanna Agricultural Research Institute; GhanaFil: Mochiah, Moses Brandford. Council for Scientific and Industrial Research Crops Research Institute; GhanaFil: Asibuo, James Y.. Council for Scientific and Industrial Research Crops Research Institute; GhanaFil: Arthur, Stephen. Council for Scientific and Industrial Research Crops Research Institute; GhanaFil: Akromah, Richard. Kwame Nkrumah University Of Science And Technology; GhanaFil: Mhango, Wezi. Lilongwe University Of Agriculture And Natural Resources; MalauiFil: Chintu, Justus. Chitedze Agricultural Research Service, Lilongwe; MalauiFil: Morichetti, Sergio. Aceitera General Deheza; ArgentinaFil: Paredes, Juan Andres. Instituto Nacional de Tecnología Agropecuaria. Centro de Investigaciones Agropecuarias. Instituto de Patología Vegetal; Argentina. Instituto Nacional de Tecnología Agropecuaria. Centro de Investigaciones Agropecuarias. Unidad de Fitopatología y Modelización Agrícola - Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Unidad de Fitopatología y Modelización Agrícola; ArgentinaFil: Monguillot, Joaquín Humberto. Instituto Nacional de Tecnología Agropecuaria. Centro de Investigaciones Agropecuarias. Instituto de Patología Vegetal; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Singh Jadon, Kuldeep. Central Arid Zone Research Institute, Jodhpur; IndiaFil: Shew, Barbara B.. North Carolina State University; Estados UnidosFil: Jasrotia, Poonam. Indian Institute Of Wheat And Barley Research, Karnal; IndiaFil: Thirumalaisamy, P. P.. India Council of Agricultural Research, National Bureau of Plant Genetic Resources; IndiaFil: Harish, G.. Directorate Of Groundnut Research, Junagadh; IndiaFil: Holajjer, Prasanna. National Bureau Of Plant Genetic Resources, New Delhi; IndiaFil: Maheshala, Nataraja. Directorate Of Groundnut Research, Junagadh; IndiaFil: MacDonald, Greg. University of Florida; Estados UnidosFil: Hoisington, David. University of Georgia; Estados UnidosFil: Rhoads, James. University of Georgia; Estados Unido

A Randomized Trial of Prophylactic Antibiotics for Miscarriage Surgery.

BACKGROUND: Surgical intervention is needed in some cases of spontaneous abortion to remove retained products of conception. Antibiotic prophylaxis may reduce the risk of pelvic infection, which is an important complication of this surgery, particularly in low-resource countries. METHODS: We conducted a double-blind, placebo-controlled, randomized trial investigating whether antibiotic prophylaxis before surgery to complete a spontaneous abortion would reduce pelvic infection among women and adolescents in low-resource countries. We randomly assigned patients to a single preoperative dose of 400 mg of oral doxycycline and 400 mg of oral metronidazole or identical placebos. The primary outcome was pelvic infection within 14 days after surgery. Pelvic infection was defined by the presence of two or more of four clinical features (purulent vaginal discharge, pyrexia, uterine tenderness, and leukocytosis) or by the presence of one of these features and the clinically identified need to administer antibiotics. The definition of pelvic infection was changed before the unblinding of the data; the original strict definition was two or more of the clinical features, without reference to the administration of antibiotics. RESULTS: We enrolled 3412 patients in Malawi, Pakistan, Tanzania, and Uganda. A total of 1705 patients were assigned to receive antibiotics and 1707 to receive placebo. The risk of pelvic infection was 4.1% (68 of 1676 pregnancies) in the antibiotics group and 5.3% (90 of 1684 pregnancies) in the placebo group (risk ratio, 0.77; 95% confidence interval [CI], 0.56 to 1.04; P = 0.09). Pelvic infection according to original strict criteria was diagnosed in 1.5% (26 of 1700 pregnancies) and 2.6% (44 of 1704 pregnancies), respectively (risk ratio, 0.60; 95% CI, 0.37 to 0.96). There were no significant between-group differences in adverse events. CONCLUSIONS: Antibiotic prophylaxis before miscarriage surgery did not result in a significantly lower risk of pelvic infection, as defined by pragmatic broad criteria, than placebo. (Funded by the Medical Research Council and others; AIMS Current Controlled Trials number, ISRCTN97143849.)

Prophylactic antibiotics to reduce pelvic infection in women having miscarriage surgery - The AIMS (Antibiotics in Miscarriage Surgery) trial: study protocol for a randomized controlled trial

Follow-up card. (DOCX 605 kb

Development and validation of quantitative PCR assays for HIV-associated cryptococcal meningitis in sub-Saharan Africa: a diagnostic accuracy study

Background: HIV-associated cryptococcal meningitis is the second leading cause of AIDS-related deaths, with a 10-week mortality rate of 25–30%. Fungal load assessed by colony-forming unit (CFU) counts is used as a prognostic marker and to monitor response to treatment in research studies. PCR-based assessment of fungal load could be quicker and less labour-intensive. We sought to design, optimise, and validate quantitative PCR (qPCR) assays for the detection, identification, and quantification of Cryptococcus infections in patients with cryptococcal meningitis in sub-Saharan Africa. Methods: We developed and validated species-specific qPCR assays based on DNA amplification of QSP1 (QSP1A specific to Cryptococcus neoformans, QSP1B/C specific to Cryptococcus deneoformans, and QSP1D specific to Cryptococcus gattii species) and a pan-Cryptococcus assay based on a multicopy 28S rRNA gene. This was a longitudinal study that validated the designed assays on cerebrospinal fluid (CSF) of 209 patients with cryptococcal meningitis at baseline (day 0) and during anti-fungal therapy (day 7 and day 14), from the AMBITION-cm trial in Botswana and Malawi (2018–21). Eligible patients were aged 18 years or older and presenting with a first case of cryptococcal meningitis. Findings: When compared with quantitative cryptococcal culture as the reference, the sensitivity of the 28S rRNA was 98·2% (95% CI 95·1–99·5) and of the QSP1 assay was 90·4% (85·2–94·0) in CSF at day 0. Quantification of the fungal load with QSP1 and 28S rRNA qPCR correlated with quantitative cryptococcal culture (R2=0·73 and R2=0·78, respectively). Both Botswana and Malawi had a predominant C neoformans prevalence of 67% (95% CI 55–75) and 68% (57–73), respectively, and lower C gattii rates of 21% (14–31) and 8% (4–14), respectively. We identified ten patients that, after 14 days of treatment, harboured viable but non-culturable yeasts based on QSP1 RNA detection (without any positive CFU in CSF culture). Interpretation: QSP1 and 28S rRNA assays are useful in identifying Cryptococcus species. qPCR results correlate well with baseline quantitative cryptococcal culture and show a similar decline in fungal load during induction therapy. These assays could be a faster alternative to quantitative cryptococcal culture to determine fungal load clearance. The clinical implications of the possible detection of viable but non-culturable cells in CSF during induction therapy remain unclear. Funding: European and Developing Countries Clinical Trials Partnership; Swedish International Development Cooperation Agency; Wellcome Trust/UK Medical Research Council/UKAID Joint Global Health Trials; and UK National Institute for Health Research