Same-day Initiation Research Articles

A fast and highly sensitive blood culture PCR method for clinical detection of Salmonella enterica serovar Typhi

BackgroundSalmonella Typhi causes an estimated 21 million new cases of typhoid fever and 216,000 deaths every year. Blood culture is currently the gold standard for diagnosis of typhoid fever, but it is time-consuming and takes several days for isolation and identification of causative organisms. It is then too late to initiate proper antibiotic therapy. Serological tests have very low sensitivity and specificity, and no practical value in endemic areas. As early diagnosis of the disease and prompt treatment are essential for optimal management, especially in children, a rapid sensitive detection method for typhoid fever is urgently needed. Although PCR is sensitive and rapid, initial research indicated similar sensitivity to blood culture and lower specificity. We developed a fast and highly sensitive blood culture PCR method for detection of Salmonella Typhi, allowing same-day initiation of treatment after accurate diagnosis of typhoid.MethodsAn ox bile tryptone soy broth was optimized for blood culture, which allows the complete lysis of blood cells to release intracellular bacteria without inhibiting the growth of Salmonella Typhi. Using the optimised broth Salmonella Typhi bacteria in artificial blood samples were enriched in blood culture and then detected by a PCR targeting the fliC-d gene of Salmonella Typhi.ResultsTests demonstrated that 2.4% ox bile in blood culture not only lyzes blood cells completely within 1.5 hours so that the intracellular bacteria could be released, but also has no inhibiting effect on the growth of Salmonella Typhi.Three hour enrichment of Salmonella Typhi in tryptone soya broth containing 2.4% ox bile could increase the bacterial number from 0.75 CFU per millilitre of blood which is similar to clinical typhoid samples to the level which regular PCR can detect. The whole blood culture PCR assay takes less than 8 hours to complete rather than several days for conventional blood culture.ConclusionsThis novel blood culture PCR method is superior in speed and sensitivity to both conventional blood culture and PCR assays. Its use in clinical diagnosis may allow early detection of the causative organism and facilitate initiation of prompt treatment among patients with typhoid fever.

Letter to the Editor: Responding to the Human Resource Crisis: Peer Health Workers, Mobile Phones, and HIV Care in Rakai, Uganda.

Dear Editor: Two challenges to successful antiretroviral therapy (ART) scale-up in resource-limited settings (RLS) are human resource and healthcare infrastructure limitations.1 We read with interest the modeling study by Barnighausen et al. which describes the complexities of ensuring adequate human resources to treat HIV/AIDS (HRHA).2 The authors suggest that factors needed to achieve universal ART coverage include “changes in the nature or organization of care,” training health workers with skills specific to the developing world to reduce emigration, and developing systems that decrease the number of traditional HRHA required to treat a fixed number of patients. The Rakai Health Sciences Program (RHSP) PEPFAR-funded ART program has been actively pursuing innovative HIV care strategies that directly address these important points. In 2006, we piloted a novel program utilizing peer health workers (PHW) and mobile phones to monitor patients in a rural ART program in Rakai, Uganda. In May 2006, the RHSP ART program recruited and trained nineteen PHWs. These PHWs are persons living with HIV themselves and receiving care through the program. Each PHW was assigned approximately 15–20 patients with whom they would typically conduct biweekly home visits. At visits, PHWs documented a review of symptoms (headache, fever, etc.), a missed pills by self-report, and a pill count, along with providing adherence counseling, health education, and social support. Documentation was returned to higher-trained providers for review and triage. PHWs were supplied bikes, identifying t-shirts, and compensation for part-time employment. Over a 6-month pilot period, PHWs completed documentation on 3,642 home visits (approximately 7.5 visits per PHW per week). Nine PHWs were additionally trained to use mobile phones to send real-time text messages containing clinical and adherence data to higher-trained providers for review and triage. These texts were numeric codes produced by converting home visit data, e.g., yes=1, no=0. PHWs could also place calls to a central toll-free clinic phone with any concerns. Due to limited electrical power, a lead-acid battery system was used to charge phones. All technology used was available in-country. These nine PHWs successfully sent 1,177 text messages (approximately 5 per PHW per week) over the pilot period. PHWs also made 101 calls to the central clinic over the study period, mostly for guidance on illnesses, urgent care needs, and concerns about drug side effects. A Likert scale (1–5, 1=strongly agree, 5=strongly disagree) survey administered to 39 PEPFAR clinical staff (response rate = 100%) found 44% (17/39) strongly agreed and 56% (22/39) agreed that the PHW and mobile phone intervention had improved the overall health of patients; 20% (8/39) strongly agreed and 49% (19/39) agreed it had improved patient adherence. Direct per PHW program startup costs were approximately $115 USD with monthly maintenance costs approximately $15 USD. The mobile phone intervention per PHW startup costs were an additional $100 USD with monthly maintenance costs of approximately $10 USD. We found that a simple and inexpensive clinical and adherence monitoring intervention leveraging PHWs empowered with mobile phones could be successfully implemented in a rural RLS. PHWs are currently an underutilized resource which may provide one solution to increasing HRHA.3 As the numbers of potential PHWs are inherently related to the prevalence of HIV, these individuals represent a flexible and sustainable work force that is unlikely to emigrate and able to remain proportional in size to the epidemic. This PHW work force can concentrate its efforts on monitoring and supporting patients on ART, while the limited number of more highly trained health workers (e.g., nurses and clinical and medical officers) can focus their time on more clinically demanding tasks. Further operations research is needed to better understand PHW effects on HIV care outcomes, which responsibilities are appropriate to task-shift to PHWs, determine acceptable training and evaluation standards, assess cost-effectiveness, and evaluate the sustainability of PHW-based programs. A unique aspect to our PHW program was the use of a mobile phone intervention as a simple support strategy. The mobile phones allowed us to use local technology to improve communications between PHWs and higher-level providers in a rural setting with poor transport infrastructure. Mobile phone coverage has rapidly expanded in Africa and other RLSs over the past several years, providing opportunities such as this one to creatively use this tool to improve health care by optimizing the way care is organized and delivered.4–6 Addressing the HRHA limitations will require a multifaceted and sustained approach. A valuable and vital component to this approach involves people living with HIV themselves. Interventions utilizing PHWs and mobile phone technology may offer one practical strategy for expanding and improving HIV care in environments with limited health workers and infrastructure.

Same-day initiation of the transdermal hormonal delivery system (contraceptive patch) versus traditional initiation methods

Introduction Published comparisons of oral contraceptive pill (OCP) initiation methods demonstrate that OCP initiation at the office visit (“Quick Start”) resulted in higher continuation rates into the second cycle. This trial was performed to investigate whether Quick Start with the contraceptive patch would provide similar results. Materials and Methods Sixty women were randomized to initiate use of the contraceptive patch using Quick Start (Group 1, n=30) or on the first day of their next menses (Group 2, n=30). Telephone contact at 6 weeks occurred to ensure that the second cycle had been initiated. A single follow-up visit was scheduled after completion of the third patch cycle. Results Continuation rates for Groups 1 and 2 were 97% and 93% (p=1.0), respectively, into the second cycle, and 93% and 90%, respectively, into the third cycle (p=1.0). Only approximately half of the subjects planned to continue using the patch after the study. Conclusion Quick Start for the contraceptive patch did not improve continuation rates into the second or third cycle.

Promoting the Safety and Use of Hormonal Contraceptives

Nearly one half of all pregnancies in the United States are unintended despite the availability of safe and effective contraceptives. The morbidity and mortality from unintended pregnancy are not insignificant. Currently available hormonal contraceptives are very effective, safe, and available for most American women. National and international institutions have removed the pelvic examination as a requirement for initiating the prescription for hormonal contraceptives, substituting instead a medical history and a blood pressure measurement. However, problems with uneven access, prescription requirements, conflicting information on the package instructions for initiating and continuing use, and incorrect perceptions of excess risk of contraceptive products may lead women to use them less than effectively or not at all. Newer progestins have been shown to have more risk of thrombosis than older formulations, instead of improved safety. In considering how hormonal contraceptives might be made safer, recommendations are made for improved availability and effective use. These include expanding the numbers and types of providers and the compensation for these services; reconsidering the need for prescription; revising labels to reflect the safety of the current formulations; communicating the safety of the current formulations; encouraging the use of the older progestins; exploring alternate schedules, such as extended or continuous oral contraceptive (OC) use; promoting same-day initiation of methods rather than waiting for menses; and ensuring universal access to emergency contraception as an adjunct to effective ongoing contraceptive methods.

The Schönlein-Henoch syndrome (anaphylactoid purpura) compared with certain features of nephritis and rheumatism.

<h3>Abstract</h3> <h3>Introduction</h3> Same-day initiation (SDI) of antiretroviral therapy (ART) for HIV consistently increases ART uptake, but concerns remain about higher attrition from care after initiation. We analysed twelve-month retention in the SLATE SDI trials. <h3>Methods</h3> SLATE I and SLATE II were individually randomized trials at public outpatient clinics in Johannesburg that enrolled patients not yet on ART and administered the SLATE I or II algorithm, which included a symptom self-report, medical history, brief physical examination, and readiness questionnaire, to assess eligibility for SDI. ART uptake and early retention have been reported. Using routine clinic records, we conducted a pooled analysis of retention in care and HIV viral suppression 14 months after study enrolment. <h3>Results and discussion</h3> We enrolled 1,193 study participants (standard arms, n=599, 50%; intervention arms, n=594, 50%) and analysed by originally assigned groups. By 14 months after study enrolment (equivalent to 12-month retention in care), 50% of intervention arm patients and 46% of standard arm patients remained in care at the initiating site (crude risk difference 4% (95% confidence interval −1% to 10%; crude relative risk 1.10 (0.97-1.23), with similar viral suppression between arms. Observed attrition from care at site by 14 months was high in both study arms, but we found no evidence that the offer of SDI led to greater overall attrition or lower rates of viral suppression one year after starting ART and may have led to small improvements. Same-day initiation may have shifted some attrition from before to after dispensing of the first dose of medication. <h3>Conclusions</h3> An offer of same-day initiation of ART, following a carefully designed protocol to identify patients who are eligible and ready to start treatment, is not inherently associated with an overall increase in patient attrition from care. <h3>Trial registration</h3> Clinicaltrials.govNCT02891135, registered September 1, 2016. First participant enrolled March 6, 2017 in South Africa. Clinicaltrials.govNCT03315013, registered October 19, 2017. First participant enrolled 14 March 2018.