HIV-1 Incidence, Adherence, and Drug Resistance in Individuals Taking Daily Emtricitabine/Tenofovir Disoproxil Fumarate for HIV-1 Pre-Exposure Prophylaxis: Pooled Analysis From 72 Global Studies.

BACKGROUND: Oral pre-exposure prophylaxis (PrEP) with emtricitabine/tenofovir disoproxil fumarate (F/TDF) has high efficacy against HIV-1 acquisition. Seventy-two prospective studies of daily oral F/TDF PrEP were conducted to evaluate HIV-1 incidence, drug resistance, adherence, and bone and renal safety in diverse settings. METHODS: HIV-1 incidence was calculated from incident HIV-1 diagnoses after PrEP initiation and within 60 days of discontinuation. Tenofovir concentration in dried blood spots (DBS), drug resistance, and bone/renal safety indicators were evaluated in a subset of studies. RESULTS: Among 17,274 participants, there were 101 cases with new HIV-1 diagnosis (0.77 per 100 person-years; 95% CI 0.63-0.94). In 78 cases with resistance data, 18 (23%) had M184I or V, one (1.3%) had K65R, and three (3.8%) had both mutations. In 54 cases with tenofovir concentration data from DBS, 45 (83.3%), 2 (3.7%), 6 (11.1%), and 1 (1.9%) had average adherence of <2, 2-3, 4-6, and ≥7 doses/week, respectively, and the corresponding incidence was 3.9 (95% CI 2.9-5.3), 0.24 (0.060-0.95), 0.27 (0.12-0.60), and 0.054 (0.008-0.38) per 100 person-years. Adherence was low in younger participants, Hispanic/Latinx and Black participants, cisgender women, and transgender women. Bone and renal adverse event incidence rates were 0.69 and 11.8 per 100 person-years, respectively, consistent with previous reports. CONCLUSIONS: Leveraging the largest pooled analysis of global PrEP studies to date, we demonstrate that F/TDF is safe and highly effective, even with less than daily dosing, in diverse clinical settings, geographies, populations, and routes of HIV-1 exposure.

HIV Preexposure Prophylaxis With Emtricitabine and Tenofovir Disoproxil Fumarate Among Cisgender Women.

Importance: Emtricitabine and tenofovir disoproxil fumarate (F/TDF) for HIV preexposure prophylaxis (PrEP) is highly effective in cisgender men who have sex with men (MSM) when adherence is high (>4 doses/week). Real-world effectiveness and adherence with F/TDF for PrEP in cisgender women is less well characterized. Objective: To characterize the effectiveness of F/TDF for PrEP and its relationship with adherence in cisgender women. Design, Setting, and Participants: Data were pooled from 11 F/TDF PrEP postapproval studies conducted in 6 countries that included 6296 cisgender women aged 15 to 69 years conducted from 2012 to 2020. HIV incidence was evaluated according to adherence level measured objectively (tenofovir diphosphate concentration in dried blood spots or tenofovir concentration in plasma; n = 288) and subjectively (electronic pill cap monitoring, pill counts, self-report, and study-reported adherence scale; n = 2954) using group-based trajectory modeling. Exposures: F/TDF prescribed orally once a day. HIV incidence was analyzed in subgroups based on adherence trajectory. Main Outcomes and Measures: HIV incidence. Results: Of the 6296 participants, 46% were from Kenya, 28% were from South Africa, 21% were from India, 2.9% were from Uganda, 1.6% were from Botswana, and 0.8% were from the US. The mean (SD) age at PrEP initiation across all studies was 25 (7) years, with 61% of participants being younger than 25 years. The overall HIV incidence was 0.72 per 100 person-years (95% CI, 0.51-1.01; 32 incident HIV diagnoses among 6296 participants). Four distinct groups of adherence trajectories were identified: consistently daily (7 doses/week), consistently high (4-6 doses/week), high but declining (from a mean of 4-6 doses/week and then declining), and consistently low (less than 2 doses/week). None of the 498 women with consistently daily adherence acquired HIV. Only 1 of the 658 women with consistently high adherence acquired HIV (incidence rate, 0.13/100 person-years [95% CI, 0.02-0.92]). The incidence rate was 0.49 per 100 person-years (95% CI, 0.22-1.08) in the high but declining adherence group (n = 1166) and 1.27 per 100 person-years (95% CI, 0.53-3.04) in the consistently low adherence group (n = 632). Conclusions and Relevance: In a pooled analysis of 11 postapproval studies of F/TDF for PrEP among cisgender women, overall HIV incidence was 0.72 per 100 person-years; individuals with consistently daily or consistently high adherence (4-6 doses/week) to PrEP experienced very low HIV incidence.

The Burden of Acute Febrile Illness Attributable to Dengue Virus Infection in Sri Lanka: A Single-Center 2-Year Prospective Cohort Study (2016-2019).

We performed a 2-year prospective cohort study to determine the incidence of dengue in Angoda, Colombo district, Sri Lanka (NCT02570152). The primary objective was to determine the incidence of acute febrile illness (AFI) because of laboratory confirmed dengue (LCD). Secondary objectives were to determine AFI incidence because of non-LCD, describe AFI symptoms, and estimate AFI incidence because of LCD by dengue virus (DENV)-type and age group. Participants from households with at least one minor and one adult (≤50 years) were enrolled and followed with scheduled weekly visits and, in case of AFI, unscheduled visits. Blood was collected for DENV detection at AFI visits, and symptoms recorded during the 7-day period following AFI onset. A total of 2,004 participants were enrolled (971 children, and 1,033 adults). A total of 55 LCD episodes were detected (overall incidence of 14.2 per 1,000 person-years). Incidence was the highest among children < 5 years (21.3 per 1,000 person-years) and 5-11 years (22.7 per 1,000 person-years), compared with adults ≥ 18 years (9.2 per 1,000 person-years). LCD was mostly (83.6%) caused by DENV-2 (n = 46), followed by DENV-1 (n = 6) and DENV-3 (n = 3). Common symptoms of LCD were headache, fatigue, myalgia, loss of appetite, and arthralgia. Incidence of AFI because of non-LCD was 47.3 per 1,000 person-years. In conclusion, this study reports the LCD incidence for a DENV-2 dominated epidemic that is comparable to the incidence of suspected dengue reported passively for 2017, one of the worst outbreaks in recent history.

Incidence of dengue illness in Mexican people aged 6 months to 50 years old: A prospective cohort study conducted in Jalisco.

BACKGROUND AND OBJECTIVES: The burden of dengue virus (DENV), a mosquito-borne pathogen, remains difficult to assess due to misdiagnosis and underreporting. Moreover, the large proportion of asymptomatic dengue cases impairs comprehensive assessment of its epidemiology even where effective surveillance systems are in place. We conducted a prospective community-based study to assess the incidence of symptomatic dengue cases in Zapopan and neighboring municipalities in the state of Jalisco, Mexico. METHODS: Healthy subjects aged 6 months to 50 years living in households located in the Zapopan and neighboring municipalities were enrolled for a 24-month follow-up study (NCT02766088). Serostatus was determined at enrolment and weekly contacts were conducted via phone calls and home visits. Participants had to report any febrile episode lasting for at least two days. Suspected dengue cases were tested by reverse-transcriptase quantitative polymerase chain reaction (RT-qPCR), detection of non-structural protein 1 (NS1), anti-DENV immunoglobulin G and M (IgG and IgM) assays. RESULTS: A total of 350 individuals from 87 households were enrolled. The overall seroprevalence of anti-DENV IgG at enrolment was 19.4% (95% confidence interval [CI] 14.5-25.6) with the highest seroprevalence rate observed in the adult group. Over the 27-month study period from July 2016 to September 2018, a total of 18 suspected dengue cases were reported. Four cases were confirmed by RT-qPCR and serotyped as DENV-1. A fifth case was confirmed by the NS1 assay. The 13 remaining suspected cases were tested negative by these assays. Based on the 5 virologically confirmed cases, symptomatic dengue incidence proportion of 1.4% (95%CI 0.5-3.8) was estimated. No severe cases or hospitalizations occurred during the study. CONCLUSION: Community-based active surveillance was shown as efficient to detect symptomatic dengue cases. CLINICAL TRIAL REGISTRATION: NCT02766088.

A prospective, multicentre, cohort study to assess the incidence of dengue illness in households from selected communities in Brazil (2014-2018).

OBJECTIVES: To estimate the incidence of dengue infection across geographically distinct areas of Brazil. METHODS: This prospective, household-based, cohort study enrolled participants in five areas and followed them up for up to 4 years (2014-2018). Dengue seroprevalence was assessed at each scheduled visit. Suspected dengue cases were identified through enhanced passive and active surveillance. Acute symptomatic dengue infection was confirmed through reverse-transcriptase quantitative polymerase chain reaction in combination with an antigenic assay (non-structural protein 1) and serology. RESULTS: Among 3300 participants enrolled, baseline seroprevalence was 76.2%, although only 23.3% of participants reported a history of dengue. Of 1284 suspected symptomatic dengue cases detected, 50 (3.9%) were laboratory-confirmed. Based on 8166.5 person-years (PY) of follow-up, the incidence of laboratory-confirmed symptomatic infection (primary endpoint) was 6.1 per 1000 PY (95% confidence interval [CI]: 4.5, 8.1). Incidence varied substantially in different years (1.8-7.4 per 1000 PY). The incidence of inapparent primary dengue infection was substantially higher: 41.7 per 1000 PY (95% CI: 31.1, 54.6). CONCLUSIONS: Our findings, highlighting that the incidence of dengue infection is underestimated in Brazil, will inform the design and implementation of future dengue vaccine trials. CLINICAL TRIAL REGISTRATION: NCT01751139.

Assessing the burden of dengue among household members in Alaminos, Laguna, the Philippines: a prospective cohort study.

Background: The incidence of dengue is increasing rapidly and is a challenging health issue in the Philippines. Epidemiological data are largely based on a passive-surveillance reporting system, which leads to substantial under-reporting of cases. Objectives: To estimate dengue infection and disease incidence prospectively at the community level in an endemic area of the Philippines using an active surveillance strategy. Methods: We implemented active surveillance in the highly endemic community of Alaminos, Laguna. The study consisted of a 1-year follow-up with 2 visits scheduled at the start and end of the study, as well as regular active surveillance in between and unscheduled visits for suspected cases. Blood samples were collected and analyzed to detect dengue during the first scheduled visit and all unscheduled visits, and clinical examination was performed at all visits (registered at clinicaltrials.gov NCT02766088). Results: We enrolled 500 participants, aged from 6 months to 50 years; 76.2% were found positive for immunoglobulin G (95% confidence interval [CI], 71.9-80.0), with 92.0% among those aged 9-17 years. Active (weekly) surveillance identified 4 virologically confirmed cases of dengue (incidence proportion 0.8; 95% CI 0.3-2.1); all in participants aged ≤14 years. Conclusions: Routine surveillance programs such as sentinel sites are needed to characterize the entire clinical spectrum of symptomatic dengue, disease incidence, and transmission in the community.

An epidemiological study to assess Plasmodium falciparum parasite prevalence and malaria control measures in Burkina Faso and Senegal.

BACKGROUND: Malariometric information is needed to decide how to introduce malaria vaccines and evaluate their impact in sub-Saharan African countries. METHODS: This cross-sectional study (NCT01954264) was conducted between October and November, 2013, corresponding to the high malaria transmission season, in four sites with Health and Demographic Surveillance Systems (DSS) [two sites with moderate-to-high malaria endemicity in Burkina Faso (Nouna and Saponé) and two sites with low malaria endemicity in Senegal (Keur Socé and Niakhar)]. Children (N = 2421) were randomly selected from the DSS lists of the study sites and were stratified into two age groups (6 months-4 years and 5-9 years). A blood sample was collected from each child to evaluate parasite prevalence of Plasmodium falciparum and other Plasmodium species and gametocyte density by microscopy, and rapid diagnosis test in the event of fever within 24 h. Case report forms were used to evaluate malaria control measures and other factors. RESULTS: Plasmodium falciparum was identified in 707 (29.2%) children, with a higher prevalence in Burkina Faso than Senegal (57.5 vs 0.9% of children). In Burkina Faso, prevalence was 57.7% in Nouna and 41.9% in Saponé in the 6 months-4 years age group, and 75.4% in Nouna and 70.1% in Saponé in the 5-9 years age group. Infections with other Plasmodium species were rare and only detected in Burkina Faso. While mosquito nets were used by 88.6-97.0 and 64.7-80.2% of children in Burkina Faso and Senegal, other malaria control measures evaluated at individual level were uncommon. In Burkina Faso, exploratory analyses suggested that use of malaria treatment or any other medication within 14 days, and use of insecticide spray within 7 days decreased the prevalence of malaria infection; older age, rural residence, natural floor, grass/palm roof, and unavailability of electricity in the house were factors associated with increased malaria occurrence. CONCLUSIONS: Plasmodium falciparum infection prevalence in children younger than 10 years was 57.5% in Burkina Faso and 0.9% in Senegal, and variability was observed, among others, by age, study site and malaria control measures.

Using collaborative learning to improve diabetes care and outcomes: the VIDA project.

UNLABELLED: The prevalence of diabetes in Mexico among those 20-64 years of age has increased from 7.2% in 1993 to 10.7% in 2000. National population-based surveys in Mexico demonstrated that 50% of the total population with diabetes had blood glucose levels of 200mg/dl or higher. Thus, diabetes care has become one of the most important public health challenges in this country. The aim of the study was to improve the quality of diabetes care in primary health care centers using the chronic care model and the breakthrough series (BTS) collaborative methodology. METHODS: Ten public health centers in the cities of Xalapa and Veracruz were randomly selected to participate in the project. Five of the health centers were randomly assigned to receive the intervention (intervention group) and the other five followed usual care (usual care group). The intervention was evaluated by A1c test before and after the intervention in both groups of patients. Patients were followed for 18 months from November 2002 to May 2004. Results were adjusted for the clustering of patients within practices and baseline measure. RESULTS: The proportion of people with good glycemic control (A1c<7%) among those in the intervention group increased from 28% before the intervention to 39% after the intervention. The proportion of patients achieving three or more quality improvement goals increased from 16.6% to 69.7% (p<0.001) among the intervention group while the usual care group experienced a non-significant decrease from 12.4% to 5.9% (p=0.118). The focus on the primary care team and the participation of people with diabetes were strategic elements incorporated into the methodology, expected to ensure sustainability of continued improvement of health outcomes. CONCLUSIONS: The intervention introduced modifications to solve problems identified by health teams in their practice and improved process and outcome measures of quality diabetes care. Most of the actions were directed at four components of the chronic care model: self-management support, decision support, delivery system design, and clinical information systems.

Effect of transport interval on out-of-hospital cardiac arrest survival in the OPALS study: implications for triaging patients to specialized cardiac arrest centers.

STUDY OBJECTIVE: To identify any association between out-of-hospital transport interval and survival to hospital discharge in victims of out-of-hospital cardiac arrest. METHODS: Data from the Ontario Prehospital Advanced Life Support Study (January 1, 1991, to December 31, 2002), an Utstein-compliant registry of out-of-hospital cardiac arrest patients from 21 communities, were analyzed. Logistic regression identified factors that were independently associated with survival in consecutive adult, nontraumatic, out-of-hospital cardiac arrest patients and in the subgroup with return of spontaneous circulation. RESULTS: A total of 18,987 patients met criteria and 15,559 (81.9%) had complete data for analysis (study group). Return of spontaneous circulation was achieved in 2,299 patients (14.8%), and 689 (4.4%) survived to hospital discharge. Median transport interval was 4.0 minutes (25th quartile 3.0 minutes; 75th quartile 6.2 minutes) for survivors and 4.2 minutes (25th quartile 3.0, 75th quartile 6.2) for nonsurvivors. Logistic regression revealed multiple factors that were independently associated with survival: witnessed arrest (odds ratio 2.61; 95% confidence interval [CI] 2.05 to 3.34), bystander cardiopulmonary resuscitation (odds ratio 2.22; 95% CI 1.82 to 2.70), initial rhythm of ventricular fibrillation/tachycardia (odds ratio 2.22; 95% CI 1.97 to 2.50), and shorter emergency medical services (EMS) response interval (odds ratio 1.26; 95% CI 1.20 to 1.33). There was no association between transport interval and survival in either the study group (odds ratio 1.01; 95% CI 0.99 to 1.05) or the return of spontaneous circulation subgroup (odds ratio 1.04; 95% CI 0.99, 1.08). CONCLUSION: In a large out-of-hospital cardiac arrest study from demographically diverse EMS systems, longer transport interval was not associated with decreased survival. Given the growing evidence showing major influence from specialized postarrest care, these findings support conducting clinical trials that assess the effectiveness and safety of bypassing local hospitals to take patients to regional cardiac arrest centers.

Hazmat disaster preparedness in Hong Kong: what are the hazardous materials on Lantau, Lamma, and Hong Kong Islands?

OBJECTIVE: Hazmat disaster preparedness is critical, especially as Hong Kong prepares for major international events, such as the 2008 Olympic Equestrian Games. No published medical study describes the identities and quantities of hazardous materials (HMs) in Hong Kong and lists what antidotes are needed for these dangerous goods (DGs). This study describes what HMs are most common in Hong Kong to prioritize disaster preparedness and training. DESIGN: A descriptive, cross-sectional study. SETTING: The Hong Kong Special Administrative Region, specifically Lantau, Lamma, and Hong Kong Islands. SAMPLE: The Hong Kong Fire Services Department (HKFSD) Dangerous Goods Database (DGD). INTERVENTIONS: Descriptive statistical analyses with Stata 9.2. MAIN OUTCOME MEASURES: Identifying and quantifying HMs in the HKFSD DGD. RESULTS: Most HMs do not have antidotes. The most common HMs with recognized antidotes are carbon monoxide, methylene chloride, fluorides, cyanides, nitriles, hydrazine, methanol, and nitrates. The most common categories of DGs are substances giving off inflammable vapors, compressed gases, and corrosive and poisonous substances. CONCLUSIONS: Hazmat disaster preparedness and training should emphasize these most common categories of DGs. Disaster planning should ensure adequate antidotes for HMs with recognized antidotes, ie, oxygen for carbon monoxide and methylene chloride; calcium gluconate and calcium chloride for fluorides; hydroxocobalamin or amyl nitrite, sodium nitrite, and sodium thiosulfate for cyanides and nitriles; pyridoxine for hydrazine; fomepizole or ethanol for methanol; and methylene blue for methemoglobinemia produced by nitrates. Supportive care is essential for patients exposed to HMs because most DGs do not have antidotes.

Evaluating trauma care capabilities in Mexico with the World Health Organization's Guidelines for Essential Trauma Care publication.

OBJECTIVE: To identify affordable, sustainable methods to strengthen trauma care capabilities in Mexico, using the standards in the Guidelines for Essential Trauma Care, a publication that was developed by the World Health Organization and the International Society of Surgery to provide recommendations on elements of trauma care that should be in place in the various levels of health facilities in all countries. METHODS: The Guidelines publication was used as a basis for needs assessments conducted in 2003 and 2004 in three Mexican states. The states were selected to represent the range of geographic and economic conditions in the country: Oaxaca (south, lower economic status), Puebla (center, middle economic status), and Nuevo León (north, higher economic status). The sixteen facilities that were assessed included rural clinics, small hospitals, and large hospitals. Site visits incorporated direct inspection of physical resources as well as interviews with key administrative and clinical staff. RESULTS: Human and physical resources for trauma care were adequate in the hospitals, especially the larger ones. The survey did identify some deficiencies, such as shortages of stiff suction tips, pulse oximetry equipment, and some trauma-related medications. All of the clinics had difficulties with basic supplies for resuscitation, even though some received substantial numbers of trauma patients. In all levels of facilities there was room for improvement in administrative functions to assure quality trauma care, including trauma registries, trauma-related quality improvement programs, and uniform in-service training. CONCLUSIONS: This study identified several low-cost ways to strengthen trauma care in Mexico. The study also highlighted the usefulness of the recommended norms in the Guidelines for Essential Trauma Care publication in providing a standardized template by which to assess trauma care capabilities in nations worldwide.

Evaluating trauma care capabilities in Mexico with the World Health Organization's Guidelines for Essential Trauma Care publication

OBJETIVO: Identificar formas asequibles y sustentables de reforzar los recursos para la atención de heridos en México aplicando las pautas contenidas en Guidelines for Essential Trauma Care [Pautas para el tratamiento básico de los heridos], publicación de la Organización Mundial de la Salud y de la Sociedad Quirúrgica Internacional que contiene recomendaciones sobre los componentes de la atención de heridos que deben poseer los servicios de salud de distintos niveles en todos los países. MÉTODOS: Las pautas publicadas (Guidelines) sirvieron de base para llevar a cabo evaluaciones de las necesidades en tres estados mexicanos en 2003 y en 2004. Los estados se escogieron con la idea de que estuviese representada la amplia variedad de condiciones geográficas y económicas del país: Oaxaca (en el sur y de estrato económico inferior), Puebla (en el centro y con un estrato económico mediano) y Nuevo León (en el norte y con un estrato económico más alto). Se evaluaron dieciséis centros entre los cuales había puestos de salud rurales, hospitales pequeños y hospitales grandes. Se hicieron visitas a todos los centros para llevar a cabo la inspección directa de los recursos físicos en cada uno y entrevistar a miembros clave del personal administrativo y clínico. RESULTADOS: Los recursos humanos y físicos destinados a la atención de heridos eran de calidad satisfactoria en los hospitales, especialmente los más grandes. La encuesta reveló algunas deficiencias, tales como una escasez de succionadores rígidos, oxímetros de pulso y algunos medicamentos usados para tratar heridos. En todos los puestos se observaron dificultades con los equipos básicos de reanimación, a pesar de que algunos recibían un número bastante alto de heridos. En los centros de todos los niveles había margen para mejorar las funciones administrativas a fin de conseguir una atención de calidad que incluyese el mantenimiento de registros de heridos, programas para mejorar la atención de estos pacientes y uniformidad en el adiestramiento del personal durante el desempeño de sus funciones. CONCLUSIONES: En este estudio se identificaron varias formas baratas de reforzar la atención de pacientes heridos en México. También se subrayó la utilidad de las pautas recomendadas en la obra Guidelines for Essential Trauma Care como modelo estandarizado para evaluar los recursos para el tratamiento de heridos que poseen los países en cualquier parte del mundo.