Role of Rigid Endoscopic Detorsion in the Management of Sigmoid Volvulus

Introduction: Sigmoid Volvulus (SV) is a common cause of bowel obstruction in Africa, affecting a relatively young and healthy population. There has been little research regarding the use of endoscopic detorsion in the management of SV from East Africa. The aim of this study was to determine the outcome of patients with SV managed by endoscopic detorsion at a single institution over a 9 year period.Methods: A retrospective review of all patients admitted with SV at Tenwek Hospital in Bomet, Kenya from January 2006 to October 2014 was done. Data were collected on demographics, clinical presentation, operative findings, management, and outcome.Results: There were 159 cases with a mean age of 41.1 years (range 15-87). Rigid endoscopic detorsion was attempted in 125 (79%) patients. The success, early recurrence, and mortality rate for rigid endoscopic detorsion was 79%, 6%, and 0% respectively. Eleven (13%, n=99) patients declined surgery after successful endoscopic detorsion, while 87 patients had semi-elective surgery, an average of 3.5 days post detorsion. Sixty patients had emergency surgery, with gangrenous bowel noted in 43 (72%) cases. Patients undergoing emergency surgery had a higher morbidity rate (27% vs. 5%, p=0.0002), and a higher mortality rate (12% vs. 0, p=0.002) compared to those having semi-elective surgery due to the presence of gangrenous bowel.Conclusion: Rigid endoscopic detorsion is appropriate in the initial management of any stable patient with clinical and radiological features suggestive of sigmoid volvulus without features of peritonitis.Keywords: Sigmoid Volvulus, Endoscopic Detorsion, Rigid Sigmoidoscopy, Outcomes

Case reduction and cost-effectiveness of the RTS,S/AS01 malaria vaccine alongside bed nets in Lilongwe, Malawi

Background: RTS,S/AS01, the most advanced vaccine against malaria, is now undergoing pilot implementation in Malawi, Ghana, and Kenya where an estimated 360,000 children will be vaccinated each year. In this study we evaluate RTS,S/AS01 alongside bed net use and estimate cost-effectiveness. Methods: RTS,S/AS01 phase III trial and bed net prevalence data were used to determine the effect of vaccination in the urban/periurban and rural areas of Lilongwe, Malawi. Cost data were used to calculate the cost-effectiveness of various interventions over three years. Findings: Since bed nets reduce malaria incidence and homogeneous vaccine efficacy was assumed, participants without bed nets received greater relative benefit from vaccination with RTS,S/AS01 than participants with bed nets. Similarly, since malaria incidence in rural Lilongwe is higher than in urban Lilongwe, the impact and cost-effectiveness of vaccine interventions is increased in rural areas. In rural Lilongwe, we estimated that vaccinating one child without a bed net would prevent 2·59 (1·62 to 3·38) cases of malaria over three years, corresponding to a cost of $10·08 (7·71 to 16·13) per case averted. Alternatively, vaccinating one child with a bed net would prevent 1·59 (0·87 to 2·57) cases, corresponding to$16·43 (10·16 to 30·06) per case averted. Providing RTS,S/AS01 to 30,000 children in rural Lilongwe was estimated to cost $782,400 and to prevent 58,611 (35,778 to 82,932) cases of malaria over a three-year period. Joint interventions providing both vaccination and bed nets (to those without them) were estimated to prevent additional cases of malaria and to be similarly cost-effective, compared to vaccine-only interventions. Interpretation: To maximize malaria prevention, vaccination and bed net distribution programs could be integrated. Funding: Impacts of Environment, Host Genetics and Antigen Diversity on Malaria Vaccine Efficacy (1R01AI137410-01

RTS,S vaccination is associated with reduced parasitemia and anemia among children diagnosed with malaria in the outpatient department of a district hospital in rural Malawi

The RTS,S/AS01 malaria vaccine was recently approved by the World Health Organization, but real-world effectiveness is still being evaluated. We measured hemoglobin concentration and parasite density in vaccinated and unvaccinated children who had been diagnosed with malaria by rapid diagnostic test (mRDT) in the outpatient department of a rural hospital in Malawi. Considering all mRDT positive participants, the mean hemoglobin concentration among unvaccinated participants was 9.58 g/dL. There was improvement to 9.82 g/dL and 10.36 g/dL in the 1 or 2 dose group (p = 0.6) and the 3 or 4 dose group (p = 0.0007), respectively. Among a microscopy positive subset of participants, mean hemoglobin concentration of unvaccinated participants was 9.55 g/dL with improvement to 9.82 g/dL in the 1 or 2 dose group (p = 0.6) and 10.41 g/dL in the 3 or 4 dose group (p = 0.003). Mean parasite density also decreased from 115,154 parasites/μL in unvaccinated children to 87,754 parasites/μL in children who had received at least one dose of RTS,S (p = 0.04). In this study population, vaccination was associated with significant improvements in both hemoglobin concentration and parasite density in the setting of real-world administration of the RTS,S/AS01 vaccine

EUS-derived criteria for distinguishing benign from malignant metastatic solid hepatic masses

Background Detection of hepatic metastases during EUS is an important component of tumor staging. Objective To describe our experience with EUS-guided FNA (EUS-FNA) of solid hepatic masses and derive and validate criteria to help distinguish between benign and malignant hepatic masses. Design Retrospective study, survey. Setting Single, tertiary-care referral center. Patients Medical records were reviewed for all patients undergoing EUS-FNA of solid hepatic masses over a 12-year period. Interventions EUS-FNA of solid hepatic masses. Main Outcome Measurements Masses were deemed benign or malignant according to predetermined criteria. EUS images from 200 patients were used to create derivation and validation cohorts of 100 cases each, matched by cytopathologic diagnosis. Ten expert endosonographers blindly rated 15 initial endosonographic features of each of the 100 images in the derivation cohort. These data were used to derive an EUS scoring system that was then validated by using the validation cohort by the expert endosonographer with the highest diagnostic accuracy. Results A total of 332 patients underwent EUS-FNA of a hepatic mass. Interobserver agreement regarding the initial endosonographic features among the expert endosonographers was fair to moderate, with a mean diagnostic accuracy of 73% (standard deviation 5.6). A scoring system incorporating 7 EUS features was developed to distinguish benign from malignant hepatic masses by using the derivation cohort with an area under the receiver operating curve (AUC) of 0.92; when applied to the validation cohort, performance was similar (AUC 0.86). The combined positive predictive value of both cohorts was 88%. Limitations Single center, retrospective, only one expert endosonographer deriving and validating the EUS criteria. Conclusion An EUS scoring system was developed that helps distinguish benign from malignant hepatic masses. Further study is required to determine the impact of these EUS criteria among endosonographers of all experience

The public health impact and cost-effectiveness of the R21/Matrix-M malaria vaccine: a mathematical modelling study

Background The R21/Matrix-M vaccine has demonstrated high efficacy against Plasmodium falciparum clinical malaria in children in sub-Saharan Africa. Using trial data, we aimed to estimate the public health impact and cost-effectiveness of vaccine introduction across sub-Saharan Africa. Methods We fitted a semi-mechanistic model of the relationship between anti-circumsporozoite protein antibody titres and vaccine efficacy to data from 3 years of follow-up in the phase 2b trial of R21/Matrix-M in Nanoro, Burkina Faso. We validated the model by comparing predicted vaccine efficacy to that observed over 12–18 months in the phase 3 trial. Integrating this framework within a mathematical transmission model, we estimated the cases, malaria deaths, and disability-adjusted life-years (DALYs) averted and cost-effectiveness over a 15-year time horizon across a range of transmission settings in sub-Saharan Africa. Cost-effectiveness was estimated incorporating the cost of vaccine introduction (dose, consumables, and delivery) relative to existing interventions at baseline. We report estimates at a median of 20% parasite prevalence in children aged 2–10 years (PfPR2–10) and ranges from 3% to 65% PfPR2–10. Findings Anti-circumsporozoite protein antibody titres were found to satisfy the criteria for a surrogate of protection for vaccine efficacy against clinical malaria. Age-based implementation of a four-dose regimen of R21/Matrix-M vaccine was estimated to avert 181 825 (range 38 815–333 491) clinical cases per 100 000 fully vaccinated children in perennial settings and 202 017 (29 868–405 702) clinical cases per 100 000 fully vaccinated children in seasonal settings. Similar estimates were obtained for seasonal or hybrid implementation. Under an assumed vaccine dose price of USD 3, the incremental cost per clinical case averted was USD 7 (range 4–48) in perennial settings and USD 6 (3–63) in seasonal settings and the incremental cost per DALY averted was USD 34 (29–139) in perennial settings and USD 30 (22–172) in seasonal settings, with lower cost-effectiveness ratios in settings with higher PfPR2–10. Interpretation Introduction of the R21/Matrix-M malaria vaccine could have a substantial public health benefit across sub-Saharan Africa. Funding The Wellcome Trust, the Bill & Melinda Gates Foundation, the UK Medical Research Council, the European and Developing Countries Clinical Trials Partnership 2 and 3, the NIHR Oxford Biomedical Research Centre, and the Serum Institute of India, Open Philanthropy

Asymptomatic Plasmodium falciparum malaria prevalence among adolescents and adults in Malawi, 2015–2016

Malaria remains a significant cause of morbidity and mortality in Malawi, with an estimated 18–19% prevalence of Plasmodium falciparum in children 2–10 years in 2015–2016. While children report the highest rates of clinical disease, adults are thought to be an important reservoir to sustained transmission due to persistent asymptomatic infection. The 2015–2016 Malawi Demographic and Health Survey was a nationally representative household survey which collected dried blood spots from 15,125 asymptomatic individuals ages 15–54 between October 2015 and February 2016. We performed quantitative polymerase chain reaction on 7,393 samples, detecting an overall P. falciparum prevalence of 31.1% (SE = 1.1). Most infections (55.6%) had parasitemias ≤ 10 parasites/µL. While 66.2% of individuals lived in a household that owned a bed net, only 36.6% reported sleeping under a long-lasting insecticide-treated net (LLIN) the previous night. Protective factors included urbanicity, greater wealth, higher education, and lower environmental temperatures. Living in a household with a bed net (prevalence difference 0.02, 95% CI − 0.02 to 0.05) and sleeping under an LLIN (0.01; − 0.02 to 0.04) were not protective against infection. Our findings demonstrate a higher parasite prevalence in adults than published estimates among children. Understanding the prevalence and distribution of asymptomatic infection is essential for targeted interventions

Low Complexity of Infection Is Associated With Molecular Persistence of Plasmodium falciparum in Kenya and Tanzania

Background Plasmodium falciparum resistance to artemisinin-based combination therapies (ACTs) is a threat to malaria elimination. ACT-resistance in Asia raises concerns for emergence of resistance in Africa. While most data show high efficacy of ACT regimens in Africa, there have been reports describing declining efficacy, as measured by both clinical failure and prolonged parasite clearance times. Methods Three hundred children aged 2–10 years with uncomplicated P. falciparum infection were enrolled in Kenya and Tanzania after receiving treatment with artemether-lumefantrine. Blood samples were taken at 0, 24, 48, and 72 h, and weekly thereafter until 28 days post-treatment. Parasite and host genetics were assessed, as well as clinical, behavioral, and environmental characteristics, and host anti-malarial serologic response. Results While there was a broad range of clearance rates at both sites, 85% and 96% of Kenyan and Tanzanian samples, respectively, were qPCR-positive but microscopy-negative at 72 h post-treatment. A greater complexity of infection (COI) was negatively associated with qPCR-detectable parasitemia at 72 h (OR: 0.70, 95% CI: 0.53–0.94), and a greater baseline parasitemia was marginally associated with qPCR-detectable parasitemia (1,000 parasites/uL change, OR: 1.02, 95% CI: 1.01–1.03). Demographic, serological, and host genotyping characteristics showed no association with qPCR-detectable parasitemia at 72 h. Parasite haplotype-specific clearance slopes were grouped around the mean with no association detected between specific haplotypes and slower clearance rates. Conclusions Identifying risk factors for slow clearing P. falciparum infections, such as COI, are essential for ongoing surveillance of ACT treatment failure in Kenya, Tanzania, and more broadly in sub-Saharan Africa