Eliminating morbidity caused by neglected tropical diseases by 2030.

The objective of this manuscript is to provide selective examples of the work of the Pan American Health Organization/World Health Organization (PAHO/WHO) Collaborating Centre for Research and Training in Parasite Epidemiology and Control which contribute to the WHO goal of eliminating neglected tropical diseases by 2030. This PAHO/WHO CC specifically aligns its activities with the Sustainable Development Goals and with the goals outlined in the WHO Road Map for Neglected Tropical Diseases 2021-2030. Its role is to contribute to advancing global action on NTDs, primarily through policy development and knowledge translation. Three important projects have recently been completed: 1. Finalizing the Monitoring and Evaluation Framework for the NTD Road Map (published May 2021; this PAHO/WHO CC was a member of the working group); 2. Developing new guidelines for the preventive chemotherapy of Taenia solium taeniasis (published September 2021; this PAHO/WHO CC was co-Chair; and 3. Formulating a policy brief on deworming for adolescent girls and women of reproductive age (published January 2022; this PAHO/WHO CC is co-lead). These projects are the result of the integration of expertise and experience from multiple partners, including from PAHO and WHO (where both organizations provided key leadership), this PAHO/WHO CC, government ministries, civil society organizations and universities, among others. In conclusion, this PAHO/WHO CC contributes timely guidance to country-led evidence-informed public health policy, to cost-effective program implementation and to the identification of priority research topics - all focused, ultimately, on eliminating NTD-attributable morbidity by 2030.

El objetivo de este artículo es proporcionar ejemplos seleccionados de la labor del centro colaborador de investigación y capacitación en epidemiología y control de parásitos de la Organización Panamericana de la Salud/Organización Mundial de la Salud (OPS/OMS), que contribuye al objetivo de la OMS de eliminar las enfermedades tropicales desatendidas para el 2030. Este centro colaborador de la OPS/OMS alinea sus actividades específicamente con los Objetivos de Desarrollo Sostenible y con los objetivos descritos en la Hoja de ruta sobre enfermedades tropicales desatendidas 2021-2030 de la OMS. Su función es contribuir al avance de las medidas mundiales sobre las enfermedades tropicales desatendidas, principalmente mediante la elaboración de políticas y la traducción de conocimiento. Recientemente se han completado tres proyectos importantes: 1) finalización del marco de seguimiento y evaluación de la Hoja de ruta sobre enfermedades tropicales desatendidas (publicado en mayo del 2021; este centro colaborador de la OPS/OMS formó parte del grupo de trabajo); 2) elaboración de nuevas directrices para la quimioterapia preventiva de la teniasis por Taenia solium (publicado en septiembre del 2021; este centro colaborador fue copresidente); y 3) formulación de un informe de políticas sobre la desparasitación de las adolescentes y las mujeres en edad reproductiva (publicado en enero del 2022; este centro colaborador fue coautor). Estos proyectos son el resultado de la integración del conocimiento y la experiencia de múltiples asociados, como la OPS y la OMS (ambas organizaciones ofrecieron un liderazgo clave), este centro colaborador de la OPS/OMS, así como varios ministerios gubernamentales, organizaciones de la sociedad civil y universidades, entre otros. En conclusión, este centro colaborador de la OPS/OMS ofrece orientaciones oportunas para las políticas de salud pública basadas en la evidencia lideradas por los países, la ejecución de programas costo-efectivos y la determinación de los temas de investigación prioritarios, todo ello destinado, en última instancia, a eliminar la morbilidad atribuible a las enfermedades tropicales desatendidas para el 2030.

O objetivo deste manuscrito é fornecer exemplos seletivos do trabalho do Centro Colaborador de Pesquisa e Treinamento em Epidemiologia e Controle de Parasitos da Organização Pan-Americana da Saúde/Organização Mundial da Saúde (OPAS/OMS) que contribuem para a meta da OMS de eliminar até 2030 as doenças tropicais negligenciadas. Este CC da OPAS/OMS alinha especificamente suas atividades com os Objetivos de Desenvolvimento Sustentável e com as metas delineadas no Roteiro da OMS para Doenças Tropicais Negligenciadas 2021-2030. Seu papel é contribuir para o avanço da ação global contra doenças tropicais negligenciadas, principalmente por meio do desenvolvimento de políticas e da tradução de conhecimentos. Três importantes projetos foram concluídos recentemente: 1. Finalização da Estrutura de Monitoramento e Avaliação do Roteiro para as DTN (publicada em maio de 2021 ­ este CC da OPAS/OMS foi membro do grupo de trabalho); 2. Desenvolvimento de novas diretrizes para a quimioprofilaxia da teníase por Taenia solium (publicado em setembro de 2021 ­ este CC da OPAS/OMS foi copresidente); e 3. Formulação de orientação para políticas de desparasitação para adolescentes e mulheres em idade reprodutiva (publicado em janeiro de 2022 ­ este CC da OPAS/OMS foi cogestor). Esses projetos são o resultado da integração de conhecimentos e experiência de múltiplos parceiros, incluindo a OPAS e a OMS (onde ambas as organizações forneceram liderança essencial), este CC da OPAS/OMS, ministérios governamentais, organizações da sociedade civil e universidades, entre outros. Em suma, este CC da OPAS/OMS contribui com orientações oportunas para uma política de saúde pública liderada pelos países e informada com base em evidências, para a implementação de programas com boa relação custo-benefício e para a identificação de tópicos prioritários de pesquisa ­ todos focados, em última análise, na eliminação da morbidade atribuível às DTN até 2030.

Tafenoquine versus Primaquine to Prevent Relapse of Plasmodium vivax Malaria.

BACKGROUND: Tafenoquine, a single-dose therapy for Plasmodium vivax malaria, has been associated with relapse prevention through the clearance of P. vivax parasitemia and hypnozoites, termed "radical cure." METHODS: We performed a phase 3, prospective, double-blind, double-dummy, randomized, controlled trial to compare tafenoquine with primaquine in terms of safety and efficacy. The trial was conducted at seven hospitals or clinics in Peru, Brazil, Colombia, Vietnam, and Thailand and involved patients with normal glucose-6-phosphate dehydrogenase (G6PD) enzyme activity and female patients with moderate G6PD enzyme deficiency; all patients had confirmed P. vivax parasitemia. The patients were randomly assigned, in a 2:1 ratio, to receive a single 300-mg dose of tafenoquine or 15 mg of primaquine once daily for 14 days (administered under supervision); all patients received a 3-day course of chloroquine and were followed for 180 days. The primary safety outcome was a protocol-defined decrease in the hemoglobin level (>3.0 g per deciliter or ≥30% from baseline or to a level of <6.0 g per deciliter). Freedom from recurrence of P. vivax parasitemia at 6 months was the primary efficacy outcome in a planned patient-level meta-analysis of the current trial and another phase 3 trial of tafenoquine and primaquine (per-protocol populations), and an odds ratio for recurrence of 1.45 (tafenoquine vs. primaquine) was used as a noninferiority margin. RESULTS: A protocol-defined decrease in the hemoglobin level occurred in 4 of 166 patients (2.4%; 95% confidence interval [CI], 0.9 to 6.0) in the tafenoquine group and in 1 of 85 patients (1.2%; 95% CI, 0.2 to 6.4) in the primaquine group, for a between-group difference of 1.2 percentage points (95% CI, -4.2 to 5.0). In the patient-level meta-analysis, the percentage of patients who were free from recurrence at 6 months was 67.0% (95% CI, 61.0 to 72.3) among the 426 patients in the tafenoquine group and 72.8% (95% CI, 65.6 to 78.8) among the 214 patients in the primaquine group. The efficacy of tafenoquine was not shown to be noninferior to that of primaquine (odds ratio for recurrence, 1.81; 95% CI, 0.82 to 3.96). CONCLUSIONS: Among patients with normal G6PD enzyme activity, the decline in hemoglobin level with tafenoquine did not differ significantly from that with primaquine. Tafenoquine showed efficacy for the radical cure of P. vivax malaria, although tafenoquine was not shown to be noninferior to primaquine. (Funded by GlaxoSmithKline and Medicines for Malaria Venture; GATHER ClinicalTrials.gov number, NCT02216123 .).

Single-Dose Tafenoquine to Prevent Relapse of Plasmodium vivax Malaria.

BACKGROUND: Treatment of Plasmodium vivax malaria requires the clearing of asexual parasites, but relapse can be prevented only if dormant hypnozoites are cleared from the liver (a treatment termed "radical cure"). Tafenoquine is a single-dose 8-aminoquinoline that has recently been registered for the radical cure of P. vivax. METHODS: This multicenter, double-blind, double-dummy, parallel group, randomized, placebo-controlled trial was conducted in Ethiopia, Peru, Brazil, Cambodia, Thailand, and the Philippines. We enrolled 522 patients with microscopically confirmed P. vivax infection (>100 to <100,000 parasites per microliter) and normal glucose-6-phosphate dehydrogenase (G6PD) activity (with normal activity defined as ≥70% of the median value determined at each trial site among 36 healthy male volunteers who were otherwise not involved in the trial). All patients received a 3-day course of chloroquine (total dose of 1500 mg). In addition, patients were assigned to receive a single 300-mg dose of tafenoquine on day 1 or 2 (260 patients), placebo (133 patients), or a 15-mg dose of primaquine once daily for 14 days (129 patients). The primary outcome was the Kaplan-Meier estimated percentage of patients who were free from recurrence at 6 months, defined as P. vivax clearance without recurrent parasitemia. RESULTS: In the intention-to-treat population, the percentage of patients who were free from recurrence at 6 months was 62.4% in the tafenoquine group (95% confidence interval [CI], 54.9 to 69.0), 27.7% in the placebo group (95% CI, 19.6 to 36.6), and 69.6% in the primaquine group (95% CI, 60.2 to 77.1). The hazard ratio for the risk of recurrence was 0.30 (95% CI, 0.22 to 0.40) with tafenoquine as compared with placebo (P<0.001) and 0.26 (95% CI, 0.18 to 0.39) with primaquine as compared with placebo (P<0.001). Tafenoquine was associated with asymptomatic declines in hemoglobin levels, which resolved without intervention. CONCLUSIONS: Single-dose tafenoquine resulted in a significantly lower risk of P. vivax recurrence than placebo in patients with phenotypically normal G6PD activity. (Funded by GlaxoSmithKline and Medicines for Malaria Venture; DETECTIVE ClinicalTrials.gov number, NCT01376167 .).

Neutralizing antibody responses over time in demographically and clinically diverse individuals recovered from SARS-CoV-2 infection in the United States and Peru: A cohort study.

BACKGROUND: People infected with Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) experience a wide range of clinical manifestations, from asymptomatic and mild illness to severe illness and death, influenced by age and a variety of comorbidities. Neutralizing antibodies (nAbs) are thought to be a primary immune defense against the virus. Large, diverse, well-characterized cohorts of convalescent individuals provide standardized values to benchmark nAb responses to past SARS-CoV-2 infection and define potentially protective levels of immunity. METHODS AND FINDINGS: This analysis comprises an observational cohort of 329 HIV-seronegative adults in the United States (n = 167) and Peru (n = 162) convalescing from SARS-CoV-2 infection from May through October 2020. The mean age was 48 years (range 18 to 86), 54% of the cohort overall was Hispanic, and 34% identified as White. nAb titers were measured in serum by SARS-CoV-2.D614G Spike-pseudotyped virus infection of 293T/ACE2 cells. Multiple linear regression was applied to define associations between nAb titers and demographic variables, disease severity and time from infection or disease onset, and comorbidities within and across US and Peruvian cohorts over time. nAb titers peaked 28 to 42 days post-diagnosis and were higher in participants with a history of severe Coronavirus Disease 2019 (COVID-19) (p < 0.001). Diabetes, age >55 years, male sex assigned at birth, and, in some cases, body mass index were also independently associated with higher nAb titers, whereas hypertension was independently associated with lower nAb titers. nAb titers did not differ by race, underlying pulmonary disease or smoking. Two months post-enrollment, nAb ID50 (ID80) titers declined 3.5 (2.8)-fold overall. Study limitations in this observational, convalescent cohort include survivorship bias and missing early viral loads and acute immune responses to correlate with the convalescent responses we observed. CONCLUSIONS: In summary, in our cohort, nAb titers after SARS-CoV-2 infection peaked approximately 1 month post-diagnosis and varied by age, sex assigned at birth, disease severity, and underlying comorbidities. Our data show great heterogeneity in nAb responses among people with recent COVID-19, highlighting the challenges of interpreting natural history studies and gauging responses to vaccines and therapeutics among people with recent infection. Our observations illuminate potential correlations of demographic and clinical characteristics with nAb responses, a key element for protection from COVID-19, thus informing development and implementation of preventative and therapeutic strategies globally. TRIAL REGISTRATION: ClinicalTrials.gov NCT04403880.

Maternal postpartum deworming and infant milk intake: Secondary outcomes from a trial.

The World Health Organization recommends deworming to reduce soil-transmitted helminth (STH)-attributable morbidity in women of reproductive age, including pregnant and lactating women, to reduce blood loss, iron deficiency anaemia and nutrient malabsorption. This study assessed the impact of maternal postpartum deworming with albendazole approximately 1 day after delivery on infant milk intake among a subset of 216 randomly selected mother-infant pairs recruited into a large trial in Peru. Infant milk intake was measured using the deuterium-oxide method at 1- and 6-month postpartum. Maternal STH infection was measured at 6-month postpartum. At 1-month postpartum, mean intake was 756 ± 16 and 774 ± 18 mL day-1 in the albendazole and placebo groups, respectively (mean difference: -18 mL day-1 ; 95% CI: -65, 30). At 6-month postpartum, mean intake was 903 ± 16 and 908 ± 18 mL day-1 in the albendazole and placebo groups, respectively (mean difference: -5 mL day-1 ; 95% CI: -52, 43). There was no statistically significant difference in milk intake between groups at either time point. At 6-month postpartum, mothers infected with Trichuris trichiura had infants with higher milk intakes (adjusted mean difference: 70 mL day-1 ; 95% CI: 20, 120) compared with uninfected mothers. However, there was no statistically significant difference in infant milk intake between mothers who had moderate-and-heavy intensity infection compared with the comparison group (mothers with no and light intensity infection). A lower prevalence and intensity of infection, and inclusion of uninfected mothers in both arms of the trial, resulting in effect dilution, may explain the null findings.

Bayesian Methods for Exposure Misclassification Adjustment in a Mediation Analysis: Hemoglobin and Malnutrition in the Association Between Ascaris and IQ.

BACKGROUND: Soil-transmitted helminth infections have been found to be associated with child development. The objective was to investigate hemoglobin levels and malnutrition as mediators of the association between Ascaris infection and intelligence quotient (IQ) scores in children. METHODS: We conducted a longitudinal cohort study in Iquitos, Peru, between September 2011 and July 2016. A total of 1760 children were recruited at 1 year of age and followed up annually to 5 years. We measured Ascaris infection and malnutrition at each study visit, and hemoglobin levels were measured as of age 3. The exposure was defined as the number of detected Ascaris infections between age 1 and 5. We measured IQ scores at age 5 and used Bayesian models to correct exposure misclassification. RESULTS: We included a sample of 781 children in the analysis. In results adjusted for Ascaris misclassification, mean hemoglobin levels mediated the association between Ascaris infection and IQ scores. The natural direct effects (not mediated by hemoglobin) (95% CrI) and natural indirect effects (mediated by hemoglobin) (95% CrI) were compared with no or one infection: -0.9 (-4.6, 2.8) and -4.3 (-6.9, -1.6) for the effect of two infections; -1.4 (-3.8, 1.0) and -1.2 (-2.0, -0.4) for three infections; and -0.4 (-3.2, 2.4) and -2.7 (-4.3, -1.0) for four or five infections. CONCLUSION: Our results are consistent with the hypothesis that hemoglobin levels mediate the association between Ascaris infection and IQ scores. Additional research investigating the effect of including iron supplements in STH control programs is warranted.

Diffuse Multibacillary Leprosy of Lucio and Latapí with Lucio's Phenomenon, Peru.

Diffuse multibacillary leprosy of Lucio and Latapí is mainly reported in Mexico and Central America. We report a case in a 65-year-old man in Peru. He also had Lucio's phenomenon, characterized by vascular thrombosis and invasion of blood vessel walls by leprosy bacilli, causing extensive skin ulcers.

International Sexual Partnerships May Be Shaped by Sexual Histories and Socioeconomic Status.

Exchange sex and higher education were associated with an increased likelihood of international sexual partnerships (ISPs). Exchange sex and older age were associated with an increased likelihood of condomless sex in ISPs. Educational and socioeconomic factors may create unbalanced power dynamics that influence exchange sex and condomless sex in ISPs.

Sustaining a hygiene education intervention to prevent and control geohelminth infections at schools in the Peruvian Amazon.

The World Health Organization currently recommends that school-based deworming programs include health hygiene education as a complementary measure. However, the sustainability and long-term impact of such hygiene education had yet to be assessed. In July 2012, this cross-sectional study was conducted in 18 primary schools in the Peruvian Amazon to gauge continuing adherence to a health hygiene education intervention introduced 2 years earlier to reduce soil-transmitted helminth infections. Due in large part to high teacher turn-over, only 9 of 47 (19.1%) teachers were still implementing the intervention. Health hygiene education interventions must, therefore, be designed to ensure sustainability in order to contribute to the overall effectiveness of school-based deworming programs.

Quantifying how single dose Ad26.COV2.S vaccine efficacy depends on Spike sequence features.

In the ENSEMBLE randomized, placebo-controlled phase 3 trial (NCT04505722), estimated single-dose Ad26.COV2.S vaccine efficacy (VE) was 56% against moderate to severe-critical COVID-19. SARS-CoV-2 Spike sequences were determined from 484 vaccine and 1,067 placebo recipients who acquired COVID-19. In this set of prespecified analyses, we show that in Latin America, VE was significantly lower against Lambda vs. Reference and against Lambda vs. non-Lambda [family-wise error rate (FWER) p < 0.05]. VE differed by residue match vs. mismatch to the vaccine-insert at 16 amino acid positions (4 FWER p < 0.05; 12 q-value ≤ 0.20); significantly decreased with physicochemical-weighted Hamming distance to the vaccine-strain sequence for Spike, receptor-binding domain, N-terminal domain, and S1 (FWER p < 0.001); differed (FWER ≤ 0.05) by distance to the vaccine strain measured by 9 antibody-epitope escape scores and 4 NTD neutralization-impacting features; and decreased (p = 0.011) with neutralization resistance level to vaccinee sera. VE against severe-critical COVID-19 was stable across most sequence features but lower against the most distant viruses.

Preexposure chemoprophylaxis for HIV prevention in men who have sex with men.

BACKGROUND: Antiretroviral chemoprophylaxis before exposure is a promising approach for the prevention of human immunodeficiency virus (HIV) acquisition. METHODS: We randomly assigned 2499 HIV-seronegative men or transgender women who have sex with men to receive a combination of two oral antiretroviral drugs, emtricitabine and tenofovir disoproxil fumarate (FTC-TDF), or placebo once daily. All subjects received HIV testing, risk-reduction counseling, condoms, and management of sexually transmitted infections. RESULTS: The study subjects were followed for 3324 person-years (median, 1.2 years; maximum, 2.8 years). Of these subjects, 10 were found to have been infected with HIV at enrollment, and 100 became infected during follow-up (36 in the FTC-TDF group and 64 in the placebo group), indicating a 44% reduction in the incidence of HIV (95% confidence interval, 15 to 63; P=0.005). In the FTC-TDF group, the study drug was detected in 22 of 43 of seronegative subjects (51%) and in 3 of 34 HIV-infected subjects (9%) (P<0.001). Nausea was reported more frequently during the first 4 weeks in the FTC-TDF group than in the placebo group (P<0.001). The two groups had similar rates of serious adverse events (P=0.57). CONCLUSIONS: Oral FTC-TDF provided protection against the acquisition of HIV infection among the subjects. Detectable blood levels strongly correlated with the prophylactic effect. (Funded by the National Institutes of Health and the Bill and Melinda Gates Foundation; ClinicalTrials.gov number, NCT00458393.).

A cross-sectional study of knowledge of sex partner serostatus among high-risk Peruvian men who have sex with men and transgender women: implications for HIV prevention.

BACKGROUND: Knowledge of a sex partner's HIV serostatus can influence sexual behavior and inform harm-reduction strategies. We sought to determine how often Peruvian men who have sex with men (MSM) and transgender women (TW) knew the HIV serostatus of their sex partners, if this knowledge was associated with any predictive factors or unprotected anal intercourse (UAI), and if UAI was associated with partner serostatus. METHODS: We analyzed data from the 2008 Peruvian MSM Sentinel Surveillance Survey. Data were collected by CASI about each participant's three most recent male sex partners. Primary outcome was knowledge of a partner's HIV test result. Multivariate analysis assessed the effect of age, education, sexual identity, number of male partners, alcohol use during intercourse, type of partnership and length of partnership using logistic regression. RESULTS: 735 participants provided data on 1,643 of their most recent sex partners from the last 3 months. 179/735 (24.4%) of all participants knew HIV test results for at least one of their 3 most recent partners, corresponding to 230/1643 (14.0%) of all sexual partnerships in the last 3 months. In multivariate analysis, casual (OR: 0.27, 95% CI: 0.17-0.42) and exchange sex (OR: 0.31, 95% CI: 0.11-0.88) partners, compared to stable partners, were negatively associated with knowledge of partner serostatus, whereas relationships lasting longer than one night (<3 months OR: 2.20, 95% CI: 1.39-3.51; 3 months to 1 year OR: 3.00, 95% CI: 1.80-5.01; ≥ 1 year OR: 4.13, 95% CI: 2.40-7.10) were positively associated with knowledge of partner serostatus. Knowledge of partner serostatus was not associated with unprotected anal intercourse with that partner. CONCLUSIONS: Few MSM and TW in Peru know their partners' HIV serostatus. Our findings suggest that the type and length of partnership influence the likelihood of knowing a partner's serostatus. Further research should explore the contexts and practices of partner communication, their effect on sexual behavior, and interventions to promote discussion of HIV testing and serostatus as an HIV prevention strategy in this population.

Extended follow-up confirms early vaccine-enhanced risk of HIV acquisition and demonstrates waning effect over time among participants in a randomized trial of recombinant adenovirus HIV vaccine (Step Study).

BACKGROUND: The Step Study tested whether an adenovirus serotype 5 (Ad5)-vectored human immunodeficiency virus (HIV) vaccine could prevent HIV acquisition and/or reduce viral load set-point after infection. At the first interim analysis, nonefficacy criteria were met. Vaccinations were halted; participants were unblinded. In post hoc analyses, more HIV infections occurred in vaccinees vs placebo recipients in men who had Ad5-neutralizing antibodies and/or were uncircumcised. Follow-up was extended to assess relative risk of HIV acquisition in vaccinees vs placebo recipients over time. METHODS: We used Cox proportional hazard models for analyses of vaccine effect on HIV acquisition and vaccine effect modifiers, and nonparametric and semiparametric methods for analysis of constancy of relative risk over time. RESULTS: One hundred seventy-two of 1836 men were infected. The adjusted vaccinees vs placebo recipients hazard ratio (HR) for all follow-up time was 1.40 (95% confidence interval [CI], 1.03-1.92; P= .03). Vaccine effect differed by baseline Ad5 or circumcision status during first 18 months, but neither was significant for all follow-up time. The HR among uncircumcised and/or Ad5-seropositive men waned with time since vaccination. No significant vaccine-associated risk was seen among circumcised, Ad5-negative men (HR, 0.97; P=1.0) over all follow-up time. CONCLUSIONS: The vaccine-associated risk seen in interim analysis was confirmed but waned with time from vaccination.

[Acute gastrointestinal involvement in dengue disease by serotype 4: a case report and literature review]. / Compromiso gastrointestinal agudo en pacientes con dengue por serotipo 4: Comunicación de un caso y revisión de la literatura.

Dengue fever is the world's most important arboviral disease, presenting a wide clinical spectrum. We report for the first time in Peru, a case caused by dengue virus serotype 4 with significant gastrointestinal involvement (acute acalculous cholecystitis and acute hepatitis). In addition we carried out a review of the literature atypical presentation illustrating the importance of the characteristics of abdominal pain (right upper quadrant); presence of Murphy's sign, ultrasound, and liver enzymes levels, for appropriate diagnosis and clinical management.

Antibiotic point prevalence survey and antimicrobial resistance in hospitalized patients across Peruvian reference hospitals.

BACKGROUND: Peru reports higher levels than other countries in Latin America of resistance to antimicrobials among Gram-positive and Gram-negative bacteria, however data on antibiotic use in Peru are scarce. This study aims to estimate the prevalence and quality of antibiotic prescription in hospitalized patients and to determine the antibiotic susceptibility rates of bacteria causing key bacterial infections. METHODS: We carried out a point prevalence survey of antibiotic prescription at ten public hospitals in nine regions of Peru. Data was collected from patients hospitalized during a 3-week period, with details about antibiotic use, patient information, and antimicrobial susceptibility. RESULTS: 1620 patient charts were reviewed; in 924 cases antibiotics were prescribed (57.0 %, range 45.9-78.9 %). Most of the antibiotics (74.2 %) were prescribed as empirical treatment, only 4.4 % as targeted treatment. For 9.5 % of cases the reason for antibiotic use was unknown. Cephalosporins were the most prescribed (30.0 %), followed by carbapenems (11.3 %). Ninety-four blood cultures were positive for bacterial growth, 48.8 % of the Staphylococcus aureus were methicillin-resistant, among Escherichia coli and Klebsiella pneumoniae, 51.7 % and 72.7 % were resistant to third-generation cephalosporins (3GC), 3.4 % and 18.2 % were resistant to carbapenems, respectively. Among bacteria isolated from urine cultures (n = 639), 43.9 % of E. coli and 49.2 % of K. pneumoniae were resistant to 3GC, and 0.9 % of E. coli and 3.2 % of K. pneumoniae were resistant to meropenem. CONCLUSIONS: The overall proportion of hospitalized patients receiving antibiotics in hospitals from different regions in Peru was high, with only a small proportion receiving targeted treatment. Cephalosporins and carbapenems were the most frequently prescribed antibiotics, reflecting high resistance rates against 3GC and carbapenems in Enterobacterales isolated from blood and urine.

Quantifying how single dose Ad26.COV2.S vaccine efficacy depends on Spike sequence features.

It is of interest to pinpoint SARS-CoV-2 sequence features defining vaccine resistance. In the ENSEMBLE randomized, placebo-controlled phase 3 trial, estimated single-dose Ad26.COV2.S vaccine efficacy (VE) was 56% against moderate to severe-critical COVID-19. SARS-CoV-2 Spike sequences were measured from 484 vaccine and 1,067 placebo recipients who acquired COVID-19 during the trial. In Latin America, where Spike diversity was greatest, VE was significantly lower against Lambda than against Reference and against all non-Lambda variants [family-wise error rate (FWER) p < 0.05]. VE also differed by residue match vs. mismatch to the vaccine-strain residue at 16 amino acid positions (4 FWER p < 0.05; 12 q-value ≤ 0.20). VE significantly decreased with physicochemical-weighted Hamming distance to the vaccine-strain sequence for Spike, receptor-binding domain, N-terminal domain, and S1 (FWER p < 0.001); differed (FWER ≤ 0.05) by distance to the vaccine strain measured by 9 different antibody-epitope escape scores and by 4 NTD neutralization-impacting features; and decreased (p = 0.011) with neutralization resistance level to vaccine recipient sera. VE against severe-critical COVID-19 was stable across most sequence features but lower against viruses with greatest distances. These results help map antigenic specificity of in vivo vaccine protection.

High monoclonal neutralization titers reduced breakthrough HIV-1 viral loads in the Antibody Mediated Prevention trials.

The Antibody Mediated Prevention (AMP) trials (NCT02716675 and NCT02568215) demonstrated that passive administration of the broadly neutralizing monoclonal antibody VRC01 could prevent some HIV-1 acquisition events. Here, we use mathematical modeling in a post hoc analysis to demonstrate that VRC01 influenced viral loads in AMP participants who acquired HIV. Instantaneous inhibitory potential (IIP), which integrates VRC01 serum concentration and VRC01 sensitivity of acquired viruses in terms of both IC50 and IC80, follows a dose-response relationship with first positive viral load (p = 0.03), which is particularly strong above a threshold of IIP = 1.6 (r = -0.6, p = 2e-4). Mathematical modeling reveals that VRC01 activity predicted from in vitro IC80s and serum VRC01 concentrations overestimates in vivo neutralization by 600-fold (95% CI: 300-1200). The trained model projects that even if future therapeutic HIV trials of combination monoclonal antibodies do not always prevent acquisition, reductions in viremia and reservoir size could be expected.

Using conjoint analysis to measure the acceptability of rectal microbicides among men who have sex with men in four South American cities.

Conjoint Analysis (CJA), a statistical market-based technique that assesses the value consumers place on product characteristics, may be used to predict acceptability of hypothetical products. Rectal Microbicides (RM)-substances that would prevent HIV infection during receptive anal intercourse-will require acceptability data from potential users in multiple settings to inform the development process by providing valuable information on desirable product characteristics and issues surrounding potential barriers to product use. This study applied CJA to explore the acceptability of eight different hypothetical RM among 128 MSM in Lima and Iquitos, Peru; Guayaquil, Ecuador; and Rio de Janeiro, Brazil. Overall RM acceptability was highest in Guayaquil and lowest in Rio. Product effectiveness had the greatest impact on acceptability in all four cities, but the impact of other product characteristics varied by city. This study demonstrates that MSM from the same region but from different cities place different values on RM characteristics that could impact uptake of an actual RM. Understanding specific consumer preferences is crucial during RM product development, clinical trials and eventual product dissemination.

Campylobacter antimicrobial resistance in Peru: a ten-year observational study.

BACKGROUND: Campylobacter jejuni and Campylobacter coli are food-borne pathogens of great importance and feature prominently in the etiology of developing world enteritis and travellers' diarrhoea. Increasing antimicrobial resistant Campylobacter prevalence has been described globally, yet data from Peru is limited. Our objective was to describe the prevalence trends of fluoroquinolone and macrolide-resistant C. jejuni and C. coli stool isolates from three regions in Peru over a ten-year period. METHODS: Surveillance for enteric pathogens was conducted in Lima, Iquitos and Cusco between 2001 and 2010. Campylobacter stool isolates were tested for susceptibilities to ciprofloxacin, azithromycin and erythromycin. Susceptibilities were reviewed for 4652 isolates from Lima ( n = 3419), Iquitos ( n = 625) and Cusco ( n = 608). RESULTS: Comparing the study periods of 2001-2005 and 2006-2010, prevalence of ciprofloxacin-resistant C. jejuni isolates rose in the study areas of Lima (73.1% to 89.8%, p < 0.001) and Iquitos (24.1% to 48.9%, p < 0.001). Ciprofloxacin-resistant C. coli rates also increased in Lima (48.1% to 87.4%, p < 0.001) and Cusco (10.0% to 65.9%, p = 0.005). Small but significant increases in azithromycin-resistant and erythromycin-resistant C. jejuni prevalence were noted in Iquitos (2.2% to 14.9%, p < 0.001; 3.2% to 14.9%, p = 0.002), and erythromycin-resistant C. coli rates increased in Lima (0.0% to 5.3%, p = 0.038). The prevalence of C. jejuni isolates resistant to both ciprofloxacin and azithromycin increased in Iquitos (0.3% to 14.9%, p < 0.001) and Lima (0.3% to 1.6%, p = 0.011), and prevalence of C. jejuni isolates resistant to both ciprofloxacin and erythromycin rose in Iquitos (0.0% to 14.9%, p < 0.001). Ciprofloxacin and erythromycin resistant C. coli prevalence increased in Lima (0.0% to 5.3%, p = 0.034). CONCLUSIONS: These results have implications for the empirical management of enterocolitis in Peru. Ongoing surveillance is essential to guide appropriate antimicrobial use in this setting. Local epidemiological studies to explore the relationship between increasing antimicrobial resistance and agricultural or human antibiotic use may be valuable.

A hospital policy change toward delayed cord clamping is effective in improving hemoglobin levels and anemia status of 8-month-old Peruvian infants.

OBJECTIVE: To assess the effectiveness of a hospital policy change toward delayed cord clamping on infant hemoglobin (Hb) levels and anemia status at 4 and 8 months of age. METHODS: A cohort of Peruvian mothers and infants, originating from a pre/post study investigating a change in hospital policy from early to delayed cord clamping, was followed until 8 months postpartum. Infant hemoglobin levels and anemia status were measured at 4 and 8 months postpartum. RESULTS: Following the hospital policy change, adjusted mean infant Hb levels improved by 0.89 gdl(-1) [95% confidence interval (95% CI) 0.57-1.22] and anemia was significantly reduced (aOR = 0.38; 95% CI 0.19-0.78) at 8 months postpartum. CONCLUSIONS: A hospital policy change toward delayed cord clamping is effective in improving Hb levels and the anemia status of 8-month-old infants. Prior to scaling-up this intervention, issues related to training, monitoring, safety, additional long-term benefits and specific local conditions should be investigated.