Genomic surveillance of the Lambda SARS-CoV-2 variant in a global phylogenetic context.

The massive sequencing of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and global genomic surveillance strategies allowed the detection of many variants of concern and interest. The variant of interest Lambda (C.37), which originated in South America, has been the most prevalent in Peru and Chile, but its dispersion in other continents still remains unknown. The current study aims to determine the phylogenetic relationship among C.37 isolates worldwide, focusing on spike mutations to understand the spread of Lambda in pandemics. A total of 7441 sequences identified as C.37 were downloaded from the GISAID database; local analysis was carried out to identify spike mutations and phylogenetic analysis was carried out to determine the rate of spread of the virus. Our results showed some spike mutations of Lambda that allowed us to detect small local outbreaks in different countries that occurred in the past and identify several clades that have not yet been designated. Although the lineage C.37 is not epidemiologically relevant in Europe or North America, the endemic behavior of this variant in Peru had a major impact on the second SARS-CoV-2 wave.

Genomic analysis reveals a rapid spread and predominance of lambda (C.37) SARS-COV-2 lineage in Peru despite circulation of variants of concern.

The pandemic generated by SARS-Cov-2 has caused a large number of cases and deaths in the world, but South America has been one of the continents that were most hard hit. The appearance of new variants causes concern because of the possibility that they may evade the protection generated by vaccination campaigns, their greater capacity to be transmitted, or their higher virulence. We analyzed the circulating variants in Peru after improving our Genomic Surveillance program. The results indicate a steep increase of the lambda lineage (C.37) until becoming predominant between January and April 2021, despite the cocirculation of other variants of concern or interest. Lambda lineage deserves close monitoring and could probably become a variant of concern in the near future.

Developing evidence briefs for policy: a qualitative case study comparing the process of using a guidance-contextualization workbook in Peru and Uganda.

BACKGROUND: Translating research evidence from global guidance into policy can help strengthen health systems. A workbook was developed to support the contextualization of the WHO's 'Optimizing health worker roles to improve maternal and newborn health' (OptimizeMNH) guidance. This study evaluated the use of the workbook for the development of evidence briefs in two countries - Peru and Uganda. Findings surrounding contextual factors, steps in the process and evaluation of the workbook are presented. METHODS: A qualitative embedded case study was used. The case was the process of using the workbook to support the contextualization of global health systems guidance, with local evidence, to develop evidence briefs. Criterion sampling was used to select the countries, participants for interviews and documents included in the study. A template-organizing style and constant comparison were used for data analysis. RESULTS: A total of 19 participant-observation sessions and 8 interviews were conducted, and 50 documents were reviewed. Contextual factors, including the cadres, or groups, of health workers available in each country, the way the problem and its causes were framed, potential policy options to address the problem, and implementation considerations for these policy options, varied substantially between Peru and Uganda. However, many similarities were found in the process of using the workbook. Overall, the workbook was viewed positively and participants in both countries would use it again for other topics. CONCLUSIONS: Organizations that produce global guidance, such as WHO, need to consider institutionalizing the application of the workbook into their guidance development processes to help users at the national/subnational level create actionable and context-relevant policies. Feedback mechanisms also need to be established so that the evidence briefs and health policies arising from global guidance are tracked and the findings coming out of such guideline contextualization processes can be taken into consideration during future guidance development and research priority-setting.

Development of a clinical prediction rule for tuberculous meningitis in adults in Lima, Peru.

OBJECTIVES: Diagnosis of tuberculous meningitis (TM) is a challenge in countries with a high burden of the disease and constrained resources and clinical prediction rules (CPRs) could be of assistance. We aimed at developing a CPR for diagnosis of TM in a Latin American setting with high tuberculosis incidence and a concentrated HIV epidemic. METHODS: We enrolled adult patients with clinical suspicion of TM attending two hospitals in Lima, Peru. We obtained information on potential anamnestic, clinical and laboratory predictive findings that are easy to collect and promptly available. We independently diagnosed TM according to a composite reference standard that included a series of microbiological tests. We performed bivariate analysis and constructed a logistic regression model to select the predictive findings associated with TM. With the selected predictors included in the model, we developed a score-based CPR. We assessed its internal validity and diagnostic performance. RESULTS: Of 155 analysed patients, 59 (38%) had TM. The CPR we derived includes three predictors: cough for 14 days or more, 10-500 cells in CSF and adenosine deaminase ≥ 6 U/l in CSF. It classifies patients into high-, moderate- or low-score groups and has an overall area under the ROC curve of 0.87. 59% of patients were assigned to either the high- or the low-score group, permitting prompt decision-making. In patients in the high-score group, it attains a positive likelihood ratio for TM of 10.6 and in patients with low scores, a negative likelihood ratio of 0.10. Bootstrap analysis indicated high internal validity. CONCLUSION: This CPR could support decision-making in patients with clinical suspicion of TM. External validation and further assessment of its clinical impact are necessary before application in other settings.

[Good practices and ethical principles: as necessary as ever]. / Buenas prácticas y principios éticos: más necesarios que nunca.

We are going through a moment in which acts of disregard to the ethics in the public function are being disclosed at all levels. It is important to know the codes of ethics and good practices of each of the functions performed. In the field of scientific publications, it is highly recommended that all researchers who wish to publish their studies get to know the good scientific practices and the basic ethical principles of publications in science. The vast majority of medical journals are guided by the recommendations of the International Committee of Medical Journal Editors (ICMJE) and with respect to ethical shortcomings, by the guidelines of the COPE (Committee on Ethics in Publications). Frequent examples of scientific misconduct that can be found in local magazines are problems of authorship, redundant publication and plagiarism and lack of declaration of conflict of interest. In the present article we provide links to self-learning resources on these topics and we emphasize the importance of their wide dissemination.

Performance of clinical prediction rules for diagnosis of pleural tuberculosis in a high-incidence setting.

OBJECTIVES: Diagnosis of pleural tuberculosis (PT) is still a challenge, particularly in resource-constrained settings. Alternative diagnostic tools are needed. We aimed at evaluating the utility of Clinical Prediction Rules (CPRs) for diagnosis of pleural tuberculosis in Peru. METHODS: We identified CPRs for diagnosis of PT through a structured literature search. CPRs using high-complexity tests, as defined by the FDA, were excluded. We applied the identified CPRs to patients with pleural exudates attending two third-level hospitals in Lima, Peru, a setting with high incidence of tuberculosis. Besides pleural fluid analysis, patients underwent closed pleural biopsy for reaching a final diagnosis through combining microbiological and histopathological criteria. We evaluated the performance of the CPRs against this composite reference standard using classic indicators of diagnostic test validity. RESULTS: We found 15 eligible CPRs, of which 12 could be validated. Most included ADA, age, lymphocyte proportion and protein in pleural fluid as predictive findings. A total of 259 patients were included for their validation, of which 176 (67%) had PT and 50 (19%) malignant pleural effusion. The overall accuracy of the CPRs varied from 41% to 86%. Two had a positive likelihood ratio (LR) above 10, but none a negative LR below 0.1. ADA alone at a cut-off of ≥40 IU attained 87% diagnostic accuracy and had a positive LR of 6.6 and a negative LR of 0.2. CONCLUSION: Many CPRs for PT are available. In addition to ADA alone, none of them contributes significantly to diagnosis of PT.

Algorithm for the diagnosis of smear-negative pulmonary tuberculosis in high-incidence resource-constrained settings.

OBJECTIVES: Diagnosis of smear-negative pulmonary tuberculosis (SNPT) remains a challenge, particularly in resource-constrained settings. We evaluated a diagnostic algorithm that combines affordable laboratory tools and a clinical prediction rule (CPR). METHODS: We derived, based on published evidence, a diagnostic algorithm for SNPT. Sputum concentration constitutes its first step. In suspects with negative results, SNPT probability is classified with a CPR as low (excluded), high (confirmed) or intermediate. For intermediate patients, sputum Middlebrook 7H9 liquid culture is performed, and they are assessed after 2 weeks. If clinically deteriorated, with still negative liquid culture, bronchoscopy is offered. Otherwise, results of Middlebrook 7H9 culture are awaited. We prospectively evaluated this algorithm against a reference standard of solid and liquid cultures in two reference hospitals in Lima, Peru. RESULTS: 670 SNPT suspects were included from September 2005 to March 2008. The prevalence of SNPT was 27% according to the reference standard. The algorithm's overall accuracy was 0.94 (95% CI 0.91-0.95), its sensitivity was 0.88 (95% CI 0.82-0.92) and its specificity, 0.96 (95% CI 0.94-0.98). Sputum concentration, the CPR, Middlebrook 7H9 sputum culture and bronchoscopic samples defined a diagnosis of SNPT according to the algorithm in 57 (37%), 25 (16%), 63 (41%) and 8(5%) of patients, respectively. 65% of patients were diagnosed within 3 weeks. CONCLUSIONS: The algorithm was accurate for SNPT diagnosis. Sputum concentration, CPR and selective Middlebrook 7H9 culture are essential components.

Effectiveness of the BBIBP-CorV vaccine in preventing infection and death in health care workers in Peru 2021.

BACKGROUND: During 2021, Peru started the vaccination against SARS-CoV-2 using the BBIBP-CorV inactivated virus vaccine for health care workers (HCW). We aim to evaluate the effectiveness of the BBIBP-CorV vaccine to prevent SARS-CoV-2 infection and deaths among HCWs. METHODS: Retrospective cohort study, from February 9 to June 30, 2021, using national registries of health care workers, laboratory tests for SARS-CoV-2 and deaths. We calculated the vaccine effectiveness for preventing laboratory-confirmed SARS-CoV-2 infection, COVID-19-mortality, and all-cause mortality among partially immunized and fully immunized HCWs. An extension of Cox proportional hazards regression was used to model the mortality results, and Poisson regression was used to model SARS-CoV-2 infection. RESULTS: The study included 606,772 eligible HCWs, the mean age was 40 (IQR: 33.0, 51.0). In fully immunized HCW, the effectiveness for preventing all-cause mortality was 83.6 (95% CI: 80.2 to 86.4), 88.7 (95% CI: 85.1 to 91.4) for preventing COVID-19 mortality, and 40.3 (95% CI 38.9 to 41.6) for preventing SARS-CoV-2 infection. CONCLUSION: The BBIBP-CorV vaccine showed high levels of effectiveness for preventing all-cause and COVID-19 deaths among fully immunized HCW. These results were consistent within different subgroups and sensitivity analyses. However, the effectiveness for preventing infection was suboptimal in this particular setting.

Relative vaccine effectiveness of the booster dose of COVID-19 vaccine for preventing death in individuals with a primary regimen based on the BBIBP-CorV, ChAdOx1-S, or BNT162b2 vaccines during the Omicron wave in Peru: A nested case-control study using national population data.

BACKGROUND: Studies have reported evidence about the effectiveness of a third dose with BNT162b2 for preventing hospitalization and death by COVID-19. However, there is little evidence regarding other primary vaccine schedules such as BBIBP-CorV and ChAdOx1-S. We estimated the relative vaccine effectiveness (RVE) of the booster dose versus the primary regimens of COVID-19 vaccines based on BBIBP-CorV, ChAdOx1-S, or BNT162b2 for preventing death during the Omicron wave in Peruvian adult people. METHODS: We carried out a nested case-control study with a risk set sampling of controls using data from Peru between December 20, 2021, and February 20, 2022 (during the Omicron wave). Data on vaccination, COVID-19 tests and deaths were collected from national surveillance databases. We performed conditional logistic regression models to estimate the RVE on the adult population. In addition, we executed sub-group analysis per age group (18 to 59 years, and 60 years or more) and per primary regime (based on BNT162b2, BBIBP-CorV, or ChAdOx1-S). RESULTS: Of the 11,188,332 people eligible to enter the study 1,974 met the case definition (death from COVID-19) and were matched to 9,183 controls. The overall RVE of a third dose to prevent death was 87.2% (84.2%-89.7%), which varied according to the primary regime (87.3% for BNT162b2, 82.0% for BBIPB-CorV-2, and 79.5% for ChAdOx-S). In older adults, the RVE was 87.1%, without significant variations according to the primary regime (86.1% for BNT162b2, 86.1 for BBIBP-CorV, and 82% for ChAdOx-S). CONCLUSIONS: The booster) dose of vaccine against COVID-19 had a high RVE for preventing death by COVID-19 in the Peruvian population in all primary regimes of vaccines during the Omicron wave. This effect was consistent in people over 60 years of age, the group most vulnerable to die from this infection.

IgG antibody response by ELISA using Wuhan and Lambda variant antigens in BBIBP-CORV vaccinated health care workers. / Anticuerpos IgG determinados mediante ELISA desarrollados con antígenos de linajes Wuhan y Lambda en trabajadores de salud vacunados con BBIBP-CORV.

OBJECTIVES: . To evaluate the IgG antibody response by ELISA using Wuhan and Lambda antigens in health care workers with and without history of SARS-CoV-2 infection prior to immunization with the first and second doses of Sinopharm vaccine (BBIBP-CorV). MATERIALS AND METHODS: . An analytical study was carried out in health care workers over 18 years of age. Fifty-one participants with history and 100 participants without history of SARS-CoV-2 infection, who received two doses of Sinopharm vaccine, were included. IgG antibodies were assessed 21 days after the first dose, 21 days after the second dose and 3 months after the second dose by in-house ELISA using the complete antigen of the Wuhan variant (B.1.1) and lambda variant (C-37) of SARS-CoV-2 virus. RESULTS: . Both groups showed a large increase in the percentage of people with antibodies after the second dose, however, this percentage decreased 3 months after the second dose. The difference between the antibody index measured by ELISA with Wuhan variant antigen versus the ELISA with lambda variant was significant (p<0.001). CONCLUSIONS: . There is a significant increase in the presence of IgG type antibodies after 15 days of the second dose of BBIBP-CorV vaccination in participants without previous infection and a decrease after 3 months of the second dose in the ratio of IgG antibody reactivity indexes in ELISAs with the variant antigen as with ELISAs with the lambda variant.

OBJETIVOS.: Evaluar la respuesta de anticuerpos IgG determinada mediante ELISA utilizando antígenos de los linajes Wuhan y Lambda en trabajadores de la salud con y sin antecedente de infección por SARS-CoV-2 previa a la inmunización con la primera y segunda dosis de la vacuna Sinopharm (BBIBP-CorV). MATERIALES Y MÉTODOS.: Se realizó un estudio analítico en trabajadores de salud mayores de 18 años. Se incluyeron 51 participantes con antecedente y 100 participantes sin antecedente de infección por SARS-CoV-2, quienes recibieron dos dosis de la vacuna Sinopharm. Los anticuerpos IgG se evaluaron 21 días después de la primera dosis, 21 días después de la segunda dosis y 3 meses después de la segunda dosis mediante una prueba de ELISA in house desarrollado utilizando el antígeno completo del linaje Wuhan (B) y del linaje Lambda(C.37) del virus de SARS-CoV-2. RESULTADOS.: En ambos grupos se observó un incremento del porcentaje de personas con anticuerpos luego de la segunda dosis, sin embargo, este porcentaje disminuyó luego de 3 meses de la segunda dosis. Se halló una diferencia significativa entre el índice de anticuerpos medido por ELISA con el antígeno del linaje Wuhan versus el ELISA con el linaje Lambda (p<0,001). CONCLUSIONES.: Existe un aumento significativo de la presencia de anticuerpos tipo IgG luego de 15 días de la segunda dosis de la vacunación con BBIP-CORV en los participantes sin infección previa y una disminución, luego de 3 meses de la segunda dosis, de la razón de índices de reactividad de anticuerpos IgG en los ELISA desarrollados con el antígeno de la variante como en los ELISA desarrollados con la variante Lambda.

Immunogenicity and reactogenicity of a third dose of BNT162b2 vaccine for COVID-19 after a primary regimen with BBIBP-CorV or BNT162b2 vaccines in Lima, Peru.

BACKGROUND: The administration of a third (booster) dose of COVID-19 vaccines in Peru initially employed the BNT162b2 (Pfizer) mRNA vaccine. The national vaccination program started with healthcare workers (HCW) who received BBIBP-CorV (Sinopharm) vaccine as primary regimen and elderly people previously immunized with BNT162b2. This study evaluated the reactogenicity and immunogenicity of the "booster" dose in these two groups in Lima, Peru. METHODS: We conducted a prospective cohort study, recruiting participants from November to December of 2021 in Lima, Peru. We evaluated immunogenicity and reactogenicity in HCW and elderly patients previously vaccinated with either two doses of BBIBP-CorV (heterologous regimen) or BTN162b2 (homologous regimen). Immunogenicity was measured by anti-SARS-CoV-2 IgG antibody levels immediately before boosting dose and 14 days later. IgG geometric means (GM) and medians were obtained, and modeled using ANCOVA and quantile regressions. RESULTS: The GM of IgG levels increased significantly after boosting: from 28.5±5.0 AU/mL up to 486.6±1.2 AU/mL (p<0.001) which corresponds to a 17-fold increase. The heterologous vaccine regimen produced higher GM of post-booster anti-SARS-CoV-2 IgG levels, eliciting a 13% increase in the geometric mean ratio (95%CI: 1.02-1.27) and a median difference of 92.3 AU/ml (95%CI: 24.9-159.7). Both vaccine regimens were safe and well tolerated. Previous COVID-19 infection was also associated with higher pre and post-booster IgG GM levels. CONCLUSION: Although both boosting regimens were highly immunogenic, two doses of BBIBP-CorV boosted with BTN162b2 produced a stronger IgG antibody response than the homologous BNT162b2 regimen in the Peruvian population. Additionally, both regimens were mildly reactogenic and well-tolerated.

Confirmed Severe Acute Respiratory Syndrome Coronavirus 2 Reinfections After a Second Wave With Predominance of Lambda in Lima and Callao, Peru.

Background: Coronavirus disease 2019 (COVID-19) infection is a major public health problem in the world and reinfections are becoming more frequent. Our main objective was to describe the epidemiological, clinical, and genomic characteristics of the confirmed cases of reinfection by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in the capital of Lima and Callao, Peru. Methods: We searched in the Peruvian laboratory information system from April 2020 up to May 2021, looking for cases having 2 positive molecular tests for SARS-CoV-2 with more than 90 days between them. We performed genomic sequencing to the available pairs of samples and described the clinical characteristics, epidemiological impact, and genomic analysis of the confirmed reinfections. Results: There were 1 694 164 people with a positive diagnostic test for SARS-CoV-2 in Lima/Callao during the study period. Of these, 1695 had 2 positive molecular tests with more than 90 days between them. Two hundred eleven had both samples available for genomic analysis according to our selection criteria, and these were retrieved and submitted to sequencing. Thirty cases were confirmed to be SARS-CoV-2 reinfections with 2 different lineages in the 2 episodes. The variant Lambda (C.37) was the most common during the second infection and accounted for 19 (63.3%) of the 30 cases. Conclusions: We report 30 cases of confirmed SARS-CoV-2 reinfections. The Lambda variant was the most common cause of the second infections, in concordance with its predominant circulation during Peru's second wave. This report describes the largest series of confirmed reinfections by SARS-CoV-2 in Latin America.We describe the epidemiological, clinical, and genomic characteristics of the confirmed cases of reinfection by severe acute respiratory syndrome coronavirus 2 in Lima and Callao, durante la segunda ola en Peru. The Lambda variant (C.37) was the most common cause of the second infections.

Evaluation of clinical prediction rules for respiratory isolation of inpatients with suspected pulmonary tuberculosis.

BACKGROUND: In the framework of hospital infection control, various clinical prediction rules (CPRs) for respiratory isolation of patients with suspected pulmonary tuberculosis (PTB) have been developed. Our aim was to evaluate their performance in an emergency department setting with a high prevalence of PTB. METHODS: We searched the MEDLINE and OVID databases to identify CPRs to predict PTB. We used a previously collected database containing clinical, radiographical, and microbiological information on patients attending an emergency department with respiratory complaints, and we applied each CPR to every patient and compared the result with culture for Mycobacterium tuberculosis as the reference standard. We also simulated the proportion of isolated suspects and missed cases for PTB prevalences of 5% and 30%. RESULTS: We withheld 13 CPRs for evaluation. We had complete data on 345 patients. Most CPRs achieved a high sensitivity but very low specificity and very low positive predictive value. Mylotte's score, which includes results of sputum smear as a predictive finding, was the best-performing CPR. It attained a sensitivity of 88.9% and a specificity of 63.9%. However, at a 30% PTB prevalence, 498 of 1000 individuals with suspected PTB would have to be isolated; 267 of these cases would be true PTB cases, and 33 cases would be missed. Two consecutive sputum smears had a sensitivity of 75.6% and a specificity of 99.7%. CONCLUSIONS: In a setting with a high prevalence of PTB, only 1 of the 13 assessed CPRs demonstrated high sensitivity combined with satisfactory specificity. Our results highlight the need for local validation of CPRs before their application.

Performance of an algorithm based on WHO recommendations for the diagnosis of smear-negative pulmonary tuberculosis in patients without HIV infection.

OBJECTIVE: To evaluate the performance of an algorithm based on WHO recommendations for diagnosis of smear-negative pulmonary tuberculosis in HIV-negative patients. METHODS: We recruited HIV-negative patients with clinical suspicion of tuberculosis who had had three negative sputum smears in Lima, Peru. All included subjects underwent a complete anamnesis, physical examination and chest X-ray, and had a sputum specimen cultured in Ogawa, Middlebrook 7H9 media and MGIT®. We applied an algorithm based on WHO recommendations to classify patients as having tuberculosis or not. The diagnostic performance of the algorithm was evaluated comparing its results against the reference standard of a positive culture for M. tuberculosis in either of the media used. RESULTS: A total of 264 of the 285 patients included (92.6%) completed evaluation and follow up. Of these, 70 (26.5%) had a positive culture for M. tuberculosis. Clinical response to a broad spectrum course of antibiotics was good in 32 of these 70 patients (45.7; 95%CI 34.0-57.4%). Overall, the algorithm attained a sensitivity of 22.9% (95% CI 13.1-32.7%) and a specificity of 95.4 % (95% CI 92.4-98.3%) compared to culture results. The positive likelihood ratio was 4.93 and the negative likelihood ratio was 0.81. CONCLUSIONS: The sensitivity and negative likelihood ratio of the algorithm is poor. It should be re-evaluated, and possibly adapted to local circumstances before further use. The clinical response to an antibiotic trial is the most important component to reassess. We also suggest considering performing chest X-ray earlier in the diagnostic work-up.

Whole genome analysis of extensively drug resistant Mycobacterium tuberculosis strains in Peru.

Peru has the highest burden of multidrug-resistant tuberculosis in the Americas region. Since 1999, the annual number of extensively drug-resistant tuberculosis (XDR-TB) Peruvian cases has been increasing, becoming a public health challenge. The objective of this study was to perform genomic characterization of Mycobacterium tuberculosis strains obtained from Peruvian patients with XDR-TB diagnosed from 2011 to 2015 in Peru. Whole genome sequencing (WGS) was performed on 68 XDR-TB strains from different regions of Peru. 58 (85.3%) strains came from the most populated districts of Lima and Callao. Concerning the lineages, 62 (91.2%) strains belonged to the Euro-American Lineage, while the remaining 6 (8.8%) strains belonged to the East-Asian Lineage. Most strains (90%) had high-confidence resistance mutations according to pre-established WHO-confident grading system. Discordant results between microbiological and molecular methodologies were caused by mutations outside the hotspot regions analysed by commercial molecular assays (rpoB I491F and inhA S94A). Cluster analysis using a cut-off ≤ 10 SNPs revealed that only 23 (34%) strains evidenced recent transmission links. This study highlights the relevance and utility of WGS as a high-resolution approach to predict drug resistance, analyse transmission of strains between groups, and determine evolutionary patterns of circulating XDR-TB strains in the country.

Allelic and genotypic frequencies of NAT2, CYP2E1, and AADAC genes in a cohort of Peruvian tuberculosis patients.

BACKGROUND: We determined the frequency of genetic polymorphisms in three anti-TB drug metabolic proteins previously reported: N-acetyltransferase 2 (NAT2), cytochrome P450 2E1 (CYP2E1), and arylacetamide deacetylase (AADAC) within a Peruvian population in a cohort of TB patients. METHODS: We genotyped SNPs rs1041983, rs1801280, rs1799929, rs1799930, rs1208, and rs1799931 for NAT2; rs3813867 and rs2031920 for CYP2E1; and rs1803155 for AADAC in 395 participants completed their antituberculosis treatment. RESULTS: Seventy-four percent of the participants are carriers of slow metabolizer genotypes: NAT2*5, NAT2*6, and NAT2*7, which increase the sensitivity of INH at low doses and increase the risk of drug-induced liver injuries. Sixty-four percent are homozygous for the wild-type CYP2E1*1A allele, which could increase the risk of hepatotoxicity. However, 16% had a NAT2 fast metabolizer phenotype which could increase the risk of acquiring resistance to INH, thereby increasing the risk of multidrug-resistant (MDR) or treatment failure. The frequency of rs1803155 (AADAC*2 allele) was higher (99.9%) in Peruvians than in European American, African American, Japanese, and Korean populations. CONCLUSIONS: This high prevalence of slow metabolizers for isoniazid in the Peruvian population should be further studied and considered to help individualize drug regimens, especially in countries with a great genetic diversity like Peru. These data will help the Peruvian National Tuberculosis Control Program develop new strategies for therapies.

Microscopic observation drug susceptibility assay for tuberculosis screening before isoniazid preventive therapy in HIV-infected persons.

BACKGROUND: Active tuberculosis (TB) must be excluded before initiating isoniazid preventive therapy (IPT) in persons infected with human immunodeficiency virus (HIV), but currently used screening strategies have poor sensitivity and specificity and high patient attrition rates. Liquid TB culture is now recommended for the detection of Mycobacterium tuberculosis in individuals suspected of having TB. This study compared the efficacy, effectiveness, and speed of the microscopic observation drug susceptibility (MODS) assay with currently used strategies for TB screening before IPT in HIV-infected persons. METHODS: A total of 471 HIV-infected IPT candidates at 3 hospitals in Lima, Peru, were enrolled in a prospective comparison of TB screening strategies, including laboratory, clinical, and radiographic assessments. RESULTS: Of 435 patients who provided 2 sputum samples, M. tuberculosis was detected in 27 (6.2%) by MODS culture, 22 (5.1%) by Lowenstein-Jensen culture, and 7 (1.6%) by smear. Of patients with any positive microbiological test result, a MODS culture was positive in 96% by 14 days and 100% by 21 days. The MODS culture simultaneously detected multidrug-resistant TB in 2 patients. Screening strategies involving combinations of clinical assessment, chest radiograph, and sputum smear were less effective than 2 liquid TB cultures in accurately diagnosing and excluding TB (P<.01). Screening strategies that included nonculture tests had poor sensitivity and specificity. CONCLUSIONS: MODS culture identified and reliably excluded cases of pulmonary TB more accurately than other screening strategies, while providing results significantly faster than Lowenstein-Jensen culture. Streamlining of the ruling out of TB through the use of liquid culture-based strategies could help facilitate the massive up-scaling of IPT required to reduce HIV and TB morbidity and mortality.

Infectious agents in biological samples from patients with Guillain-Barré syndrome in Peru, 2018-2019. / Agentes infecciosos en muestras biológicas de pacientes con síndrome de Guillain-Barré en Perú, 2018-2019.

OBJECTIVE: To describe the results of laboratory tests performed on biological samples from patients with Guillain-Barré syndrome (GBS) submitted to the Instituto Nacional de Salud (INS) between 2018 and 2019. MATERIALS AND METHODS: We conducted an observational study on patients with GBS, by using data from the epidemiological surveillance system. Biological samples, previously analyzed at the INS, were obtained to study arboviruses, respiratory viruses, enteroviruses and enterobacteria, among others. RESULTS: A total of 2,051 specimens were obtained from 906 patients with GBS. Three patients tested positive for dengue and three for Zika. In 19 patients, the stool culture was positive for Campylobacter jejuni. Phylogenetic analysis of 10 Campylobacter jejuni strains classified them as genotype ST2993, which was previously reported in China and associated to a GBS outbreak. Twelve cerebrospinal fluid samples tested positive for enterovirus by PCR in 2018, but none could be verified by culture or complete genome sequencing during the study. One patient was positive for influenza A, two for influenza B, two for adenovirus, five for respiratory syncytial virus, and ten for rinovirus. CONCLUSION: Several pathogens were found in samples from patients with GBS. However, we found that the genotype ST2993 of Campylobacter jejuni was the most likely causal agent, a pathogen that is related to GBS outbreaks in different continents. It is necessary to confirm this hypothesis with additional analytical studies and it is important to describe the transmission mechanism of C. jejuni genotype ST2993 in order to implement prevention and control measures.

OBJETIVO: Describir los resultados de los exámenes de laboratorio realizados en muestras biológicas de pacientes con síndrome de Guillain-Barré (SGB), recibidas en el Instituto Nacional de Salud (INS) entre los años 2018 y 2019. MATERIALES Y MÉTODOS: Se realizó un estudio observacional en pacientes con SGB notificados en el sistema de vigilancia epidemiológica. Se obtuvieron muestras biológicas analizadas en el INS para investigar arbovirus, virus respiratorios, enterovirus y enterobacterias, entre otros. RESULTADOS: Se recibió un total de 2051 especímenes clínicos de 906 pacientes con SGB. Tres pacientes dieron positivo al dengue y tres pacientes al Zika. En 19 pacientes, el cultivo en heces fue positivo para Campylobacter jejuni. El análisis filogenético de diez cepas de Campylobacter jejuni las clasificó como genotipo ST2993, reportado previamente en China y asociado a un brote de SGB. En 2018, hubo 12 muestras que habían dado positivo al PCR para enterovirus en el líquido cefalorraquídeo, pero ninguna pudo corroborarse con el cultivo respectivo ni con secuenciamiento de genoma completo. Un paciente dio positivo por virus de la influenza A, dos por virus de la influenza B, dos por adenovirus, cinco por virus respiratorio sincicial, y diez por rinovirus. CONCLUSIÓN: Se han encontrado diversos agentes patógenos en especímenes de pacientes con SGB, sin embargo, la presencia de Campylobacter jejuni genotipo ST2993, un patógeno relacionado a brotes de SGB en varios continentes, sería el probable agente causal. Es necesario confirmar esta hipótesis con estudios analíticos y determinar la cadena de transmisión de este agente para implementar las medidas de prevención y control.

Evaluation of a rapid serological test for detection of IgM and igG antibodies against SARS-CoV-2 under field conditions. / Evaluación en condiciones de campo de una prueba serológica rápida para detección de anticuerpos IgM e IgG contra SARS-CoV-2.

OBJECTIVE: To determine the additional diagnostic performance of a rapid serological test for detection of IgM and IgG antibodies compared to the real-time polymerase chain reaction (RT-PCR) test; for detection of SARS-CoV-2. MATERIALS AND METHODS: A cross-sectional study was carried out including patients hospitalized for COVID-19 in 3 hospitals, health workers exposed to the infection and outpatients who met suspicious case criteria, all of which underwent the molecular test (RT-PCR) and the rapid serological test. The additional diagnostic performance of rapid serological test was evaluated in comparison to molecular tests. Likewise, an approximation was made to the sensitivity and specificity of the rapid serological test. RESULTS: 144 people were included. With the rapid test, 19.4% of positive results were obtained compared to 11.1% in the molecular test (p = 0.03). The rapid serological test detected 21 cases that had been negative by the initial (RT-PCR), providing an additional diagnostic performance of 56.8% compared to the RT-PCR. The additional diagnostic performance was 50.0% during the first week, 70.0% during the second week and 50.0% during the third week of symptom onset. The sensitivity of the rapid serological test was 43.8% and the specificity of 98.9%. CONCLUSIONS: The rapid serological test was able to detect a greater number of cases than those detected by the molecular test especially after the second week of onset of symptoms. It also showed high specificity. It is therefore useful as a complementary test to RT-PCR, especially during the second and third week of illness.

OBJETIVOS: Determinar el rendimiento diagnóstico adicional de una prueba serológica rápida que detecta anticuerpos IgM e IgG contra SARS-CoV-2 en relación a la reacción en cadena de polimerasa reversa en tiempo real (RT-PCR). MATERIALES Y MÉTODOS: Se realizó un estudio transversal incluyendo pacientes hospitalizados por COVID-19 en tres hospitales, trabajadores de salud expuestos a la infección y pacientes ambulatorios que cumplían criterios de caso sospechoso, a quienes se les realizó la prueba molecular (RT-PCR) y la prueba serológica rápida. Se evaluó el rendimiento diagnóstico adicional de las prueba serológica rápida en relación a la molecular. Asimismo, se realizó la estimación de sensibilidad y especificidad de dichas pruebas. RESULTADOS: Se incluyeron 144 personas. La prueba serológica rápida obtuvo un 19,4% de resultados positivos en comparación con un 11,1% en la prueba molecular (p=0,03). La prueba serológica rápida detectó 21 casos que habían resultado negativos por el RT-PCR inicial y el rendimiento diagnóstico adicional fue de 56,8% en comparación al RT-PCR. El rendimiento diagnóstico adicional fue 50,0% durante la primera semana, 70,0% durante la segunda y 50,0% durante la tercera semana de inicio de síntomas. La sensibilidad de la prueba serológica rápida fue de 43,8% y la especificidad del 98,9%. CONCLUSIONES: La prueba serológica rápida logró detectar un mayor número de casos respecto a la molecular, sobre todo a partir de la segunda semana de inicio de síntomas. Además, presentó una alta especificidad. Los resultados mostrarían su utilidad como prueba complementaria a la prueba molecular, especialmente durante la segunda y tercera semana de enfermedad.