Chemoprophylaxis, diagnosis, treatments, and discharge management of COVID-19: An evidence-based clinical practice guideline(updated version)

The novel severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)is the cause of a rapidly spreading illness,coronavirus disease 2019(COVID-19),affecting more than seventeen million people around the world.Diagnosis and treatment guidelines for clinicians caring for patients are needed.In the early stage,we have issued"A rapid advice guideline for the diagnosis and treatment of 2019 novel coronavirus(2019-nCoV)infected pneumonia(standard version)";now there are many direct evidences emerged and may change some of previous recommendations and it is ripe for develop an evidence-based guideline.We formed a working group of clinical experts and methodologists.The steering group members proposed 29 questions that are relevant to the management of COVID-19 covering the following areas:chemoprophylaxis,diagnosis,treatments,and discharge management.We searched the literature for direct evidence on the management of COVID-19,and assessed its certainty generated recommendations using the Grading of Recommendations,Assessment,Development and Evaluation(GRADE)approach.Recommendations were either strong or weak,or in the form of ungraded consensus-based statement.Finally,we issued 34 statements.Among them,6 were strong recommendations for,14 were weak recommendations for,3 were weak recommendations against and 11 were ungraded consensus-based statement.They covered topics of chemoprophylaxis(including agents and Traditional Chinese Medicine(TCM)agents),diagnosis(including clinical manifestations,reverse transcription-polymerase chain reaction(RT-PCR),respiratory tract specimens,IgM and IgG antibody tests,chest computed tomography,chest X-ray,and CT features of asymptomatic infections),treatments(including lopinavirritonavir,umifenovir,favipiravir,interferon,remdesivir,combination of antiviral drugs,hydroxychloroquine/chloroquine,interleukin-6 inhibitors,interleukin-1 inhibitors,glucocorticoid,qingfei paidu decoction,lianhua qingwen granules/capsules,convalescent plasma,lung transplantation,invasive or noninvasive ventilation,and extracorporeal membrane oxygenation(ECMO)),and discharge management(including discharge criteria and management plan in patients whose RT-PCR retesting shows SARS-CoV-2 positive after discharge).We also created two figures of these recommendations for the implementation purpose.We hope these recommendations can help support healthcare workers caring for COVID-19 patients.

Epilepsy triggered by mefloquine in an adult traveler to Uganda

We report a case of a traveler who visited Uganda for 8 d, and took mefloquine one tablet/week for malaria prophylaxis. After the second dose, he suffered from two episodes of loss of consciousness with seizures, therefore mefloquine was discontinued. During the flight back after full recovery, seizures reoccurred while he was on board, he was disembarked in Addis Ababa and then transferred to Nairobi. After repatriation to Italy, he experienced four other similar episodes. The patient was still on full dose anticonvulsant therapy one year and a half after, as any attempt at reduced dose was unsuccessful. Currently, three agents(mefloquine, atovaquone/proguanil, and doxycycline) are recommended for malaria chemoprophylaxis, with similar efficacy but different adverse event profiles, regimens, and prices. Considering that mefloquine is associated with a higher risk of neurologic and psychiatric adverse events than the alternative regimens, we suggest considering mefloquine as a second line choice after atovaquone/progua-nil and doxycycline for short-term travelers.

The need for preventive and curative services for malaria when the military is deployed in endemic overseas territories: a case study and lessons learned

Background: Sri Lanka has been free from indigenous malaria since November 2012 and received the WHO certificate for malaria-free status in September 2016. Due to increased global travel, imported malaria cases continue to be reported in the country. Military personnel returning home from international peace-keeping missions in malaria endemic countries represent a key risk group in terms of imported malaria. The present study intended to characterize the potential causes of a malaria outbreak among the Sri Lankan security forces personnel deployed in the Central African Republic(CAR).Methods: Data were collected from a cross-sectional survey distributed among Sri Lankan Air Force personnel who had returned from United Nations peace-keeping missions in the CAR region. A pre-tested questionnaire was used for the data collection, and focus group discussions were also conducted.Results: One hundred twenty male Air Force personnel were interviewed(out of a group of 122 officers and airmen). All participants were deployed in the CAR for 14 months and were aware of the existence of chemoprophylaxis against malaria. The majority of the subjects(92.5%, 111/120) also knew that prophylaxis should be started prior to departure. However, the regular use of chemoprophylaxis was reported by only 61.7%(74/120) of the sample. Overall, 30.8% of the participants(37/120) had 44 symptomatic episodes of malaria during deployment, and one person succumbed to severe malaria. All cases were associated with noncompliance with chemoprophylaxis.Conclusion: Better coordination with overseas healthcare services and the establishment of directly observed chemoprophylaxis may help to avoid similar outbreaks in the future.

Antibiotics for eradicating meningococcal carriages:Network meta-analysis and investigation of evidence inconsistency

AIMTo compare different antibiotics for eradicating the carriage of Neisseria meningitidis （N. meningitidis ）, and to investigate heterogeneity and evidence inconsistency.METHODSFrom a search of PubMed and published systematic reviews, we identifed 23 trials evaluating 15 antibiotics that could be connected in a trial network. The outcome of interest is the eradication of N. meningitidis . We used WinBUGS to conduct random-effects, mixed treatment comparisons. Heterogeneity and evidence inconsistency was investigated by meta-regression modelling and examining characteristics of trial participants and inter-ventions evaluated.RESULTS Rifampin, ciprofloxacin, minocycline, ceftriaxone, and azythromycin were statistically significantly （P 〈 0.05） more effective than placebo. The probability of being the best was 67.0% for a combination of rifampin and minocycline, 25.0% for ceftriaxone, 1.7% for azythromycin, and below 1% for the remaining regimens. Signifcant inconsistency between the direct and indirect estimates was observed for the comparison of rifampin and ciprofoxacin （ P 〈 0.01）, which may be caused by different types of carriers and different doses of ciprofoxacin.CONCLUSIONA range of prophylactic antibiotic regimens are effective for eradicating meningococcal carriages, and treatment choice will depend on the individual priorities of the patients and physicians. In clinical situations where complete eradication is considered to be of the utmost importance, a combination of rifampin and minocycline seems to offer the highest likelihood of success. Ceftriaxone as a single intramuscular injection is also likely to be more effective as compared with the other two antibiotics （ciprofoxacin or rifampin） recommended by the current guidelines.

Debunking the myths perpetuating low implementation of isoniazid preventive therapy amongst human immunodeficiency virus-infected persons

Isoniazid preventive therapy(IPT) is the administration of isoniazid(INH) to people with latent tuberculosis(TB) infection(LTBI) to prevent progression to active TB disease. Despite being life-saving for human immunodeficiency virus(HIV)-infected persons who do not have active TB, IPT is poorly implemented globally due to misconceptions shared by healthcare providers and policy makers. However, amongst HIV-infected patients especially those living in resource-limited settings with a high burden of TB, available evidence speaks for IPT: Among HIV-infected persons, active TB- the major contraindication to IPT, can be excluded with symptom screening; chest X-ray and tuberculin skin testing are unreliable and often lead to logistic delays resulting in increased numbers of people with LTBI progressing to active TB; the use of IPT has not been found to increase the risk of the development of INH mono-resistance; IPT is cost-effective and cheaper than the cost of treating cases of active TB that would develop without IPT; ART and IPT have an additive effect on the prevention of TB, and both are safe and beneficial even in children. In order to sustain the recorded gains from ART scale-up and to further reduce TB-related morbidity and mortality, more efforts are needed to scale-up IPT implementation globally.

Comprehension of Risk Factors of Malaria during Pregnancy among Pregnant Women Attending Antenatal Care in Malawi

A study was conducted to determine the comprehension of pregnant women on malaria risk factors during pregnancy. Comprehension of Malaria risks is important to ensure compliance to prevention methods and treatment by the pregnant women and hence optimizes the pregnancy outcomes. The study was conducted in 2012 at three health facilities, Queen Elizabeth Central Hospital, Ndirande health Centre and St. Joseph Mission Hospital in Malawi. The study design was descriptive and utilized quantitative data collection and analysis methods on a random sample of 316 antenatal mothers. The study targeted antenatal mothers who were aged between 15 and 49 years, in the gestation period of 28 to 36 weeks and able to converse in English or vernacular language. A structured questionnaire was used to collect data which were analyzed using SPSS version 16.0. Most of the participants (79.4%, n = 251) knew the risk factors of malaria during pregnancy but very few (18.4%, n = 58) knew about intermittent prevention treatment despite taking SP as prescribed. The motivation factors for taking SP were husband support and the desire to protect their babies and themselves from Malaria. Although the comprehension of the intermittent prevention treatment among the women was low, the women were motivated to adhere to the treatment when instructed by the healthcare workers due to the desire for good health for themselves and their unborn babies. Husbands were the most significant other that motivated the pregnant women to adhere to treatment. Results show that there is a need for healthcare workers to facilitate comprehension of intermittent prevention treatment among pregnant mothers.

Analysis of the chemoprophylactic effect on close contacts of patients with active tuberculosis and positive tuberculin skin tests

Objective:The current study analyzed the chemoprophylactic effect of isoniazide on close contacts of patients with active tuberculosis and positive tuberculin skin tests(TSTs).Methods:A total of 1206 close contacts of patients with active tuberculosis and strongly-pos-itive TSTs were enrolled.The patients had chest X-ray examinations.Patients without tuberculosis and other diseases were divided into the following groups:90 patients in the prophylaxis group,who were given 300 mg of isoniazid qd(3-5 mg/kg for children)over a 10-month treatment course;and 89 patients in the control group without drug therapy.Both groups were followed for 10 years.Results:(1)There were 568 patients with negative results and 638 with positive results,includ-ing 445 with ordinarily-and moderately-positive results,and 193 with strongly-positive results(a positive rate of 52.9%[638/1206]and a strongly-positive rate of 16.0%[193/1206]).Fourteen tuber-culosis patients were identified(tuberculosis detection rate of 1.1%).(2)During the 3-year period of follow-up,there were 4 patients in the prophylaxis group and 12 patients in the control group who acquired tuberculosis(a morbidity rate of 4.7%[4/84]and 13.4%[12/89],respectively),and the dif-ference was statistically significant(χ^(2)=3.916,P=0.048).Six patients in the prophylaxis group,all of whom were children,discontinued medication use during the course of treatment due to adverse drug reactions,for an adverse drug reaction occurrence rate of 6.6%(6/90),a medication completion rate of 93.3%(84/90),and a 3-year protection ratio of 64.6%.(3)During the 4-6 year period,there were two patients in the prophylaxis group and three patients in the control group who acquired tubercu-losis(a morbidity rate of 2.5%[2/78]and 4.1%[3/73],respectively),two in the prophylaxis group and four in the control group who were lost to follow-up(a loss to follow-up rate of 2.5%[2/80]and 5.1%[4/77],respectively),and the difference was not statistically significant(χ^(2)=0.006,P=0.940;χ^(2)=0.215,P=0.643).(4)During the 7-10 year study,there was one patient in the prophylaxis group and two patients in the control group who acquired tuberculosis(a morbidity rate of 1.3%[1/72]and 3.1%[2/64],respectively),and four in the prophylaxis group and six in the control group who were lost to follow-up(a loss to follow-up rate of 5.2%[4/76]and 8.5%[6/70],respectively),and the dif-ference was not statistically different(χ^(2)=0.011,P=0.918;χ^(2)=0.176,P=0.675).(5)Within 10 years,there were 7 patients in the prophylaxis group and 17 patients in the control group who acquired tu-berculosis(a morbidity rate of 8.3%[7/84]and 21.5%[17/79],respectively;χ^(2)=4.770,P=0.029),and 6 in the prophylaxis group and 10 in the control group were lost to follow-up(the loss to follow-up rate was 7.1%[6/84]and 11.2%[10/89],respectively;χ^(2)=0.863,P=0.353).Conclusion:Close contacts of patients with active tuberculosis are at high-risk for acquir-ing tuberculosis.It is safe and effective for patients with strongly-positive TST results to undergo isoniazid chemoprophylaxis for 10 months.