A pediatric HIV outbreak in Pakistan.

Background: Following reports of an outbreak of HIV infection among children in Larkana District, Pakistan, an international team investigated the extent and cause of the outbreak between April and June 2019. Aims: To investigate the incidence of HIV among children in Larkana District, Pakistan and describe the distribution of cases by time, place and person. Methods: Self-referred persons were tested for HIV using the national testing protocol. Local epidemiology of HIV was reviewed to generate hypotheses. An infection prevention and control (IPC) team conducted site visits and reviewed IPC practices. Results: Between 25 April and 27 June 2019, a total of 30 191 persons were tested for HIV in Larkana District, and 876 of them tested positive. Of those who tested positive, 719 (82%) were children aged <15 years. Traditional skin piercing procedures and transmission from high-risk populations to children were ruled out during the investigation. Informative interviews with parents or guardians of a convenience sample of 211 children aged <15 years showed that 99% of children had an injection or infusion for medical treatment within the past 12 months. Our investigation identified lack of HIV prevalence data for the general population including tuberculosis patients and those who attended antenatal care services. Conclusions: Investigations indicate that unsafe healthcare practices in formal and informal healthcare settings as the most likely cause of the 2019 outbreak of HIV infection in Larkana, Pakistan. Measures should be taken to improve IPC practices at the facility level, especially in pediatric and antenatal care clinics.

Assessing sex differences in viral load suppression and reported deaths using routinely collected program data from PEPFAR-supported countries in sub-Saharan Africa.

BACKGROUND: In sub-Saharan Africa, more women than men access HIV testing and treatment and may have better viral load suppression (VLS). We utilized routinely reported aggregated HIV program data from 21 sub-Saharan African countries to examine sex differences in VLS and death rates within antiretroviral therapy (ART) programs supported by the United States President's Emergency Plan for AIDS Relief (PEPFAR). METHODS: We included VLS and reported death data for persons aged 15 + years on ART from October-December 2020 disaggregated by sex and age for each subnational unit (SNU). We used linear mixed-model regression to estimate VLS proportion and negative binomial mixed-model regression to estimate the rates of death and death plus interruptions in treatment (IIT). All models were weighted for SNU-level ART population size and adjusted for sex, age, HIV/tuberculosis coinfection, country, and SNU; models for reported deaths and deaths plus IIT were also adjusted for SNU-level VLS. RESULTS: Mean VLS proportion was higher among women than men (93.0% vs. 92.0%, p-value < 0.0001) and 50 + than 15-49 age group (93.7% vs. 91.2%, p-value < 0.0001). The mean rate of reported deaths was higher among men than women (2.37 vs. 1.51 per 1000 persons, p-value < 0.0001) and 50 + than 15-49 age group (2.39 vs. 1.50 per 1000, p-value < 0.0001); the mean rate of reported deaths plus IIT was higher among men (30.1 in men vs. 26.0 in women per 1000, p-value < 0.0001) and higher among 15-49 than 50 + age group (34.7 vs. 22.6 per 1000, p-value < 0.0001). CONCLUSIONS: The mean rate of reported deaths was higher among men in most models despite adjusting for VLS. Further exploration into differences in care-seeking behaviors; coverage of screening, prophylaxis, and/or treatment of opportunistic infections; and more extensive testing options for men to include CD4 is recommended.

Iatrogenic ANA: An emerging source of expensive diagnostic confusion.

Intravenous immune globulin (IVIg) therapy has been shown to be useful in a multitude of disorders. IVIg is produced from pooled human plasma; therefore, autoantibodies found in the general population are also present in IVIg and transferred to those being transfused. This can prove a particular hazard for screening and diagnostic tests based on autoantibodies. We present a patient who was found to have a positive antinuclear antibody (ANA) titer after multiple IVIg transfusions, resulting in diagnostic confusion and unnecessary workup. A 45-year-old gentleman was diagnosed with atypical CIDP, initiated on a course of IVIg, and sent for inpatient rehabilitation. However, recovery was complicated by multiple readmissions for recurrent weakness, and as part of the workup for other etiologies, an ANA was found to be positive. Sub-serologies and paraneoplastic autoantibody panel were negative. In the absence of clinical symptoms, we recommended continued monitoring and repeat ANA testing 6 months after the last dose of IVIg; as any drug needs 5 half-lives to be eliminated from the body. Clinicians should consider any recent IVIg treatments when evaluating the pre-test probability of detecting an underlying connective tissue disease with ANA screening. Indiscriminate ANA levels in patients recently given IVIg lead to unnecessary and expensive further testing and consultation.

Sara Alert: An automated symptom monitoring tool for COVID-19 in 11 jurisdictions in the United States, June - August, 2021.

Objectives: Health department personnel conduct daily active symptom monitoring for persons potentially exposed to SARS-CoV-2. This can be resource-intensive. Automation and digital tools can improve efficiency. We describe use of a digital tool, Sara Alert, for automated daily symptom monitoring across multiple public health jurisdictions. Methods: Eleven of the 20 U.S. public health jurisdictions using Sara Alert provided average daily activity data during June 29 to August 30, 2021. Data elements included demographics, communication preferences, timeliness of symptom monitoring initiation, responsiveness to daily messages, and reports of symptoms. Results: Participating jurisdictions served a U.S. population of over 22 million persons. Health department personnel used this digital tool to monitor more than 12,000 persons per day on average for COVID-19 symptoms. On average, monitoring began 3.9 days following last exposure and was conducted for an average of 5.7 days. Monitored persons were frequently < 18 years old (45%, 5,474/12,450) and preferred communication via text message (47%). Seventy-four percent of monitored persons responded to at least one daily automated symptom message. Conclusions: In our geographically diverse sample, we found that use of an automated digital tool might improve public health capacity for daily symptom monitoring, allowing staff to focus their time on interventions for persons most at risk or in need of support. Future work should include identifying jurisdictional successes and challenges implementing digital tools; the effectiveness of digital tools in identifying symptomatic individuals, ensuring appropriate isolation, and testing to disrupt transmission; and impact on public health staff efficiency and program costs.

Digital Tools Adopted by Public Health Agencies to Support COVID-19 Case Investigation and Contact Tracing, United States, 2020-2021.

During the COVID-19 pandemic, public health agencies implemented an array of technologies and digital tools to support case investigation and contact tracing. Beginning in May 2020, the Association of State and Territorial Health Officials compiled information on digital tools used by its membership, which comprises 59 chief health officials from each of the 50 states, 5 US territories, 3 freely associated states, and the District of Columbia. This information was presented online through a publicly available technology and digital tools inventory. We describe the national landscape of digital tools implemented by public health agencies to support functions of the COVID-19 response from May 2020 through May 2021. We also discuss how public health officials and their informatics leadership referenced the information about the digital tools implemented by their peers to guide and refine their own implementation plans. We used a consensus-based approach through monthly discussions with partners to group digital tools into 5 categories: surveillance systems, case investigation, proximity technology/exposure notification, contact tracing, and symptom tracking/monitoring. The most commonly used tools included the National Electronic Disease Surveillance System Base System (NBS), Sara Alert, REDCap, and Maven. Some tools such as NBS, Sara Alert, REDCap, Salesforce, and Microsoft Dynamics were repurposed or adapted for >1 category. Having access to the publicly available technology and digital tools inventory provided public health officials and their informatics leadership with information on what tools other public health agencies were using and aided in decision making as they considered repurposing existing tools or adopting new ones.

Evaluating COVID-19 Exposure Notification Effectiveness With SimAEN: A Simulation Tool Designed for Public Health Decision Making.

OBJECTIVES: Exposure notification (EN) supplements traditional contact tracing by using proximity sensors in smartphones to record close contact between persons. This ledger is used to alert persons of potential SARS-CoV-2 exposure, so they can quarantine until their infection status is determined. We describe a model that estimates the impact of EN implementation on reducing the spread of SARS-CoV-2 and on the workload of public health officials, in combination with other key public health interventions such as traditional contact tracing, face mask wearing, and testing. METHODS: We created an agent-based model, Simulated Automated Exposure Notification (SimAEN), to explore the effectiveness of EN to slow the spread of SARS-CoV-2. We varied selected simulation variables, such as population adoption of EN and EN detector sensitivity configurations, to illustrate the potential effects of EN. We executed 20 simulations with SimAEN for each scenario and derived results for each simulation. RESULTS: When more sensitive versus more specific EN configurations were compared, the effective reproductive number, RE, was minimally affected (a decrease <0.03). For scenarios with increasing levels of EN adoption, an increasing number of additional infected persons were identified through EN, and total infection counts in the simulated population decreased; RE values for this scenario decreased with increasing EN adoption (a decrease of 0.1 to 0.2 depending on the scenario). CONCLUSIONS: Estimates from SimAEN can help public health officials determine which levels of EN adoption in combination with other public health interventions can maximize prevention of COVID-19 while minimizing unnecessary quarantine in their jurisdiction.

Mortuary and hospital-based HIV mortality surveillance among decedents in a low-resource setting: lessons from Western Kenya.

BACKGROUND: Lack of dependable morbidity and mortality data complicates efforts to measure the demographic or population-level impact of the global HIV/AIDS epidemic. Mortuary-based mortality surveillance can address gaps in vital statistics in low-resource settings by improving accuracy of measuring HIV-associated mortality and indicators of access to treatment services among decedents. This paper describes the process and considerations taken in conducting mortuary and hospital-based HIV mortality surveillance among decedents in Kenya. MAIN TEXT: We conducted HIV mortuary and hospital-based mortality surveillance at two of the largest mortuaries in Kisumu County, Kenya (April 16-July 12, 2019). Medical charts were reviewed for documentation of HIV status among eligible decedents. HIV testing was done on blood and oral fluid samples from decedents with undocumented HIV status and those whose medical records indicated HIV-negative test results > 3 months before death. A panel of experts established the cause of death according to the International Classification of Diseases, 10th Revision rules. Civil registry data for the year 2017 were abstracted and coded to corresponding ICD-10 codes. Of the 1004 decedents admitted to the two mortuaries during the study period, 49 (4.9%) were unavailable because they had been transferred to other facilities or dispatched for burial before enrolment. Of the 955 available decedents, 104 (10.9%) were ineligible for the study. Blood samples were collected from 659 (77.4%) decedents, and 654 (99.2%) were tested for HIV. Of the 564 decedents eligible for the OraQuick® validation sub-study, 154 were eligible for oral sample collection, and 132 (85.7%) matched pre- and post-embalming oral samples were collected and tested. Of the 851 eligible decedents, 241 (28.3%) had evidence of HIV infection: 119 had a diagnosis of HIV infection recorded in their patient files, and 122 had serological evidence of HIV infection. CONCLUSION: This study shows that in low-resource settings, conducting hospital and mortuary-based surveillance is feasible and can be an alternative source of mortality data when civil registry data are inadequate.

An Epidemic of Pediatric HIV From Reuse of Infusion Equipment in Pakistan.

BACKGROUND: From April to June 2019, a total of 909 new HIV infections were identified in Larkana, Pakistan; 86% was children younger than 15 years. To identify the possible transmission links in this outbreak, a case-control study was conducted in June 2019. METHODS: For cases, we selected a systematic random sample of 100 HIV-positive children from the screening list. We chose 2 age-matched and sex-matched controls from the neighborhood of each HIV-positive case. All selected children were tested using the World Health Organization-approved rapid diagnosis test algorithm. We interviewed the parents of each selected child about previous exposures to parenteral treatment and compared exposures of case and control children using conditional logistic regression. RESULTS: The ages of the selected children ranged from 1 month to 10 years. More than 90% of both HIV+ and HIV- children had received outpatient health care from MBBS-qualified private physicians. Eighty-three percent of HIV+ children versus 46% of HIV- children had received health care from one private physician [adjusted odds ratio (aOR) = 29, 95% confidence interval (95% CI): 10 to 79]. Intravenous infusions during the last outpatient visit were reported by 29% of case versus 7% of controls (aOR 57, 95% CI: 2.9 to >1000), whereas no case children and 17% of control children had received only intramuscular injections (aOR 0, 95% CI: 0 to 41). Among cases, 94% had been given infusions through a drip set compared with 85% of control children (aOR = 7.7, 95% CI: 2.3 to 26). Infusions had been administered with reused IV drip sets in 70% of cases compared with 8% of controls (aOR = 197, 95% CI: 16 to 2400). DISCUSSION: Private physicians reusing intravenous drip sets to treat outpatients seen in private practice were responsible for this HIV epidemic. Mapping and regulation of private practitioners were suggested.

Same-day discharge after transcatheter mitral valve repair using MitraClip in a tertiary community hospital: a case series.

BACKGROUND: Due to the current Coronavirus Disease 2019 (COVID-19) pandemic, there is a realization for innovation in procedures and protocols to minimize hospital stay and at the same time ensure continued evidence-based treatment delivered to the patients. We present a same-day discharge protocol for transcatheter mitral valve repair (TMVR) using MitraClip under general anaesthesia in a six-patient case series. This protocol aims to reduce the length of hospital stay, thereby minimizing potential for nosocomial COVID-19 infections and to promote safe discharge with cautious follow-up. CASE SUMMARY: Six patients with severe symptomatic mitral valve (MV) regurgitation underwent successful transfemoral MV repair using standard procedures. Following repair, patients were monitored on telemetry in the recovery area for 3 h, ambulated to assess vascular access stability and underwent post-procedural transthoracic echocardiogram to assess for any pericardial effusion or post-procedural prosthetic mitral stenosis. CONCLUSION: Same-day discharge after TMVR is possible when done cautiously with close follow-up, can minimize hospital stay, improve resource utilization, and reduce risk of nosocomial COVID-19 infection.

Insecticide Residues in Cotton, Sorghum and Fallow Soil from the Nuba Mountains Cotton Corporation of South Kordofan State, Sudan.

BACKGROUND: Soil is the final depot of most environmental contaminants, including pesticides. Soil may be contaminated by pesticides as a result of direct application or drift during spray activities. Soil contamination with pesticide residues may affect the quality of food crops, animal products, and soil micro-organisms which may in turn negatively affect human health and the environment. OBJECTIVES: The main objective of the current study was to determine the soil residues of commonly used pesticides in rain-fed crops grown by the Nuba Mountains Cotton Corporation (NMCC) in South Kordofan state of Western Sudan. METHODS: Four locations (representing the four directions around the state capital Kadugli) were chosen for sample collection: Alefain (East Kadugli), Elmashaish (West Kadugli), Ed Dalling uncultivated area (North Kadugli) and Lagawa (Southwest Kadugli). Nine soil samples were randomly taken from each location representing areas under cotton, sorghum, and uncultivated land covered with natural vegetation. Soil samples were analyzed by gas chromatography (GC) equipped with electron capture detector (ECD) and GC-mass spectrometry (MS). RESULTS: The results generally indicated that organophosphate levels were greater than organochlorine and pyrethroids with heptachlor, malathion, and dimethoate present in all samples analyzed, while the level of p,p-dichlorodiphenyltrichloroethane (DDT) was below the detection limit. Endosulfan α and ß isomers were detected in some samples. Dimethoate had the highest level (22.02 mg/kg), while ß endosulfan was found at the lowest level (0.015 mg/kg). Generally, samples collected from cotton soils showed higher residue levels compared to sorghum soil with average concentrations of 307.25 mg/kg versus 58.63 mg/kg, respectively. Almashaish showed the highest residues levels followed by Alefain, Lagawa, and Ed Dalling with total residues of 57.56 mg/kg, 26.34 mg/kg, 22.63 mg/kg, and 17.07 mg/kg, respectively. CONCLUSIONS: The current study sheds light on the residue levels of some of the commonly used pesticides in the cotton rain-fed scheme in South Kordofan State, western Sudan. The study calls for regular residue monitoring in various environmental components in the area and suggests possible management measures. COMPETING INTERESTS: The authors declare no competing financial interests.

Sofosbuvir Resistance-associated Substitutions in the Palm Domain of HCV-NS5B RNA Dependent RNA Polymerase; Study of two Sofosbuvir non-responders.

OBJECTIVE: In current study we performed sequencing of palm domain of HCV-NS5B gene, its ancestral analysis along with amino acids substitution analysis. These analysis were done to find the molecular basis of the viral resistance against Sofosbuvir drug. METHODS: Blood samples from individuals with chronic Hepatitis C infection that were resistant to Sofosbuvir were collected. The samples were processed for their molecular characterization that included RNA extraction, Complementary DNA (cDNA) synthesize, nested PCR, gel elution, Sequencing, ancestral and 3D structure analysis. RESULTS: Evolutionary analysis revealed that current study sequences (QAU-01, QAU-02) clustered with a previously studied sequence, KY971494.1. Moreover, we reports multiple novel amino acid substitutions in the palm domain of NS5B gene such as Ile116Val, Asn117Gly, Glu246Ala, Val252Ala, Glu258Gln, Cys262Leu, Ser269Arg, Ala272Thr, Ile293Leu, Lys304Arg, Asn307Gly, Ala338Val and Arg345Gly in our query sequence (QAU-01). At 246 and 269 position in (QAU-02), no substitution was observed. CONCLUSIONS: We have noticed that the current sequences are relatively emerging and could have been originated from aforementioned sequence recently. Based on the current results, we suggests that these substitutions could be associated with structural or functional impairment of protein and could also be may be considered as resistance associated substitutions (RAS) to Sofosbuvir drug.

Transcatheter aortic valve replacement same-day discharge for selected patients: a case series.

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic has resulted in drastic changes to the practice of medicine, requiring healthcare systems to find solutions to reduce the risk of infection. Using a case series, we propose a protocol for same-day discharge (SDD) for selected patients undergoing transcatheter aortic valve replacement (TAVR) using real-time remote cardiac monitoring. Six patients with severe symptomatic aortic stenosis underwent TAVR and were discharged on the same day. CASE SUMMARY: Six patients with symptomatic severe native or bioprosthetic aortic valve stenosis underwent a successful transfemoral TAVR using standard procedures, including the use of rapid atrial pacing to assess the need for permanent pacemaker implantation. Following TAVR, patients were monitored on telemetry in the recovery area for 3 h, ambulated to assess vascular access stability, and discharged with real-time remote cardiac monitoring if no new conduction abnormality was observed. The patients were seen by tele-visits within 2 days and 2 weeks after discharge. DISCUSSION: Amidst the COVID-19 pandemic, SDD following successful transfemoral TAVR may be feasible for selected patients and reduce potential COVID-19 exposure.

Signs, Symptoms, and Comorbidities Associated With Onset and Prognosis of COVID-19 in a Nursing Home.

BACKGROUND: Effective halting of outbreaks in skilled nursing facilities (SNFs) depends on the earliest recognition of cases. We assessed confirmed COVID-19 cases at an SNF impacted by COVID-19 in the United States to identify early indications of COVID-19 infection. METHODS: We performed retrospective reviews of electronic health records for residents with laboratory-confirmed SARS-CoV-2 during February 28-March 16, 2020. Records were abstracted for comorbidities, signs and symptoms, and illness outcomes during the 2 weeks before and after the date of positive specimen collection. Relative risks (RRs) of hospitalization and death were calculated. RESULTS: Of the 118 residents tested among approximately 130 residents from Facility A during February 28-March 16, 2020, 101 (86%) were found to test positive for SARS-CoV-2. At initial presentation, about two-thirds of SARS-CoV-2-positive residents had an abnormal vital sign or change in oxygen status. Most (90.2%) symptomatic residents had elevated temperature, change in mental status, lethargy, change in oxygen status, or cough; 9 (11.0%) did not have fever, cough, or shortness of breath during their clinical course. Those with change in oxygen status had an increased relative risk (RR) of 30-day mortality [51.1% vs 29.7%, RR 1.7, 95% confidence interval (CI) 1.0-3.0]. RR of hospitalization was higher for residents with underlying hepatic disease (1.6, 95% CI 1.1-2.2) or obesity (1.5, 95% CI 1.1-2.1); RR of death was not statistically significant. CONCLUSIONS AND IMPLICATIONS: Our findings reinforce the critical role that monitoring of signs and symptoms can have in identifying COVID-19 cases early. SNFs should ensure they have a systematic approach for responding to abnormal vital signs and oxygen saturation and consider ensuring common signs and symptoms identified in Facility A are among those they monitor.

Meta-Analysis and Trial Sequential Analysis of Randomized Controlled Trials for Multivessel PCI Versus Culprit Artery Only PCI in STEMI Without Cardiogenic Shock.

BACKGROUND: Traditionally ST-elevation myocardial infarction (STEMI) with multivessel coronary artery disease is treated with percutaneous coronary intervention (PCI) to culprit lesion only. The benefit of multivessel (MV) PCI among STEMI patients without cardiogenic shock is unclear. METHODS: PubMed, EMBASE, and Cochrane Database were searched from 1996 to 2019, for studies of patients with STEMI without cardiogenic shock, who underwent PCI. Only randomized controlled trials comparing culprit PCI to MV PCI vs culprit vessel PCI were included for pairwise meta-analysis. All-cause mortality, cardiac mortality, reinfarction, revascularization and major adverse cardiovascular events (MACE) were compared. Trial sequential analysis (TSA) was performed for outcome variables. RESULTS: Nine randomized controlled trials contributed 6930 patients meeting inclusion criteria. Three thousand three hundred seventy-six underwent MV PCI, and 3554 underwent culprit PCI. Our analysis demonstrated no significant difference in all-cause mortality. MV PCI had a lower risk of cardiac mortality, reinfarction, MACE and repeat revascularization compared to culprit PCI (P values <0.05). TSA showed futility for further trials to detect all-cause mortality benefit and lack of firm evidence of benefit in cardiac mortality and re-infarction, but firm evidence of benefit in revascularization and MACE. CONCLUSIONS: In conclusion, MV PCI strategy was beneficial in reducing cardiac mortality, reinfarction, repeat revascularization, and MACE but there was no all-cause mortality benefit when compared to culprit only PCI strategy. Evidence for benefit in cardiac mortality and re-infarction is not robust per TSA.