Etiological characterization of acute undifferentiated febrile illness in Apartadó and Villeta municipalities, Colombia, during COVID-19 pandemic.

Background: Acute undifferentiated febrile illness (AUFI) is one of the leading causes of illness in tropical regions. Although malaria is the most important cause, other pathogens such as Dengue (DENV), Leptospira and recently, Coronavirus Disease 2019 (COVID-19) have gained importance. In Colombia, few studies aimed to identify the etiology of AUFI. Most of them performed in Apartadó and Villeta municipalities, identifying the active circulation of several pathogens. Thus, we conducted a cross-sectional study in these municipalities to characterize the etiologies of AUFI during COVID-19 pandemic. Methods: An active surveillance was conducted between September and December 2021 in local hospitals of Apartadó and Villeta municipalities. Febrile patients were enrolled after voluntarily agreeing to participate in the study. Ten different etiologies were evaluated through direct, serological, molecular and rapid diagnostic methods. Results: In Apartadó a confirmed etiology was found in 60% of subjects, DENV (25%) being the most frequent, followed by leptospirosis (16.7%), malaria (10%), COVID-19 (8.3%), spotted fever group (SFG) rickettsiosis (6.7%) and Chikungunya (1.7%). In Villeta, a specific etiology was confirmed in 55.4% of patients, of which SFG rickettsiosis (39.3%) was the most frequent, followed by leptospirosis (21.4%), DENV (3.6%) and malaria (1.8%). No cases due to Mayaro, Yellow Fever, Oropouche and Venezuelan Equine Encephalitis viruses were detected. Conclusion: We confirm the relevance of dengue fever, leptospirosis, SFG rickettsiosis, COVID-19 and malaria as causes of AUFI in the municipality of Apartadó, and highlight the great importance of SFG rickettsiosis as the main cause of AUFI in the municipality of Villeta.

Multiplex Reverse Transcription Polymerase Chain Reaction Combined with a Microwell Hybridization Assay Screening for Arbovirus and Parasitic Infections in Febrile Patients Living in Endemic Regions of Colombia.

Acute febrile syndrome is a frequent reason for medical consultations in tropical and subtropical countries where the cause could have an infectious origin. Malaria and dengue are the primary etiologies in Colombia. As such, constant epidemiological surveillance and new diagnostic tools are required to identify the causative agents. A descriptive cross-sectional study was conducted to evaluate the circulation and differential diagnosis of six pathogens in two regions of Colombia. The results obtained via multiplex reverse transcription polymerase chain reaction combined with a microwell hybridization assay (m-RT-PCR-ELISA) were comparable to those obtained using rapid tests conducted at the time of patient enrollment. Of 155 patients evaluated, 25 (16.1%) and 16 (10.3%) were positive for malaria and dengue, respectively; no samples were positive for any of the other infectious agents tested. In most cases, m-RT-PCR-ELISA confirmed the results previously obtained through rapid testing.

Diversity of the Bacterial and Viral Communities in the Tropical Horse Tick, Dermacentor nitens, in Colombia.

Ticks are obligatory hematophagous ectoparasites that transmit pathogens among various vertebrates, including humans. The microbial and viral communities of ticks, including pathogenic microorganisms, are known to be highly diverse. However, the factors driving this diversity are not well understood. The tropical horse tick, Dermacentor nitens, is distributed throughout the Americas and it is recognized as a natural vector of Babesia caballi and Theileria equi, the causal agents of equine piroplasmosis. In this study, we characterized the bacterial and viral communities associated with partially fed Dermacentor nitens females collected using a passive survey on horses from field sites representing three distinct geographical areas in the country of Colombia (Bolivar, Antioquia, and Cordoba). RNA-seq and sequencing of the V3 and V4 hypervariable regions of the 16S rRNA gene were performed using the Illumina-Miseq platform (Illumina, San Diego, CA, USA). A total of 356 operational taxonomic units (OTUs) were identified, in which the presumed endosymbiont, Francisellaceae/Francisella spp., was predominantly found. Nine contigs corresponding to six different viruses were identified in three viral families: Chuviridae, Rhabdoviridae, and Flaviviridae. Differences in the relative abundance of the microbial composition among the geographical regions were found to be independent of the presence of Francisella-like endosymbiont (FLE). The most prevalent bacteria found in each region were Corynebacterium in Bolivar, Staphylococcus in Antioquia, and Pseudomonas in Cordoba. Rickettsia-like endosymbionts, mainly recognized as the etiological agent of rickettsioses in Colombia, were detected in the Cordoba samples. Metatranscriptomics revealed 13 contigs containing FLE genes, suggesting a trend of regional differences. These findings suggest regional distinctions among the ticks and their bacterial compositions.

Diversity of the bacterial and viral communities in the tropical horse tick, Dermacentor nitens in Colombia.

Ticks are obligatory hematophagous ectoparasites that transmit pathogens among various vertebrates, including humans. The composition of the microbial and viral communities in addition to the pathogenic microorganisms is highly diverse in ticks, but the factors driving the diversity are not well understood. The tropical horse tick, Dermacentor nitens , is distributed throughout the Americas and it is recognized as a natural vector of Babesia caballi and Theileria equi , the causal agents of equine piroplasmosis. We characterized the bacterial and viral communities associated with partially-fed D. nitens females collected by a passive survey on horses from field sites representing three distinct geographical areas in Colombia (Bolivar, Antioquia, and Cordoba). RNA-seq and sequencing of the V3 and V4 hypervariable regions of the 16S rRNA gene were performed using the Illumina-Miseq platform. A total of 356 operational taxonomic units (OTUs) were identified, in which the presumed endosymbiotic Francisellaceae/ Francisella spp. was predominantly found. Nine contigs corresponding to six different viruses were identified in three viral families: Chuviridae, Rhabdoviridae, and Flaviviridae. Differences in the relative abundance of the microbial composition among the geographical regions were found to be independent of the presence of Francisella -Like Endosymbiont (FLE). The most prevalent bacteria found on each region were Corynebacterium in Bolivar, Staphylococcus in Antioquia, and Pseudomonas in Cordoba. Rickettsia -like endosymbionts, mainly recognized as the etiological agent of rickettsioses in Colombia were detected in the Cordoba samples. Metatranscriptomics revealed 13 contigs containing FLE genes, suggesting a trend of regional differences. These findings suggest regional distinctions among the ticks and their bacterial compositions.

A molecular barcode and web-based data analysis tool to identify imported Plasmodium vivax malaria.

Traditionally, patient travel history has been used to distinguish imported from autochthonous malaria cases, but the dormant liver stages of Plasmodium vivax confound this approach. Molecular tools offer an alternative method to identify, and map imported cases. Using machine learning approaches incorporating hierarchical fixation index and decision tree analyses applied to 799 P. vivax genomes from 21 countries, we identified 33-SNP, 50-SNP and 55-SNP barcodes (GEO33, GEO50 and GEO55), with high capacity to predict the infection's country of origin. The Matthews correlation coefficient (MCC) for an existing, commonly applied 38-SNP barcode (BR38) exceeded 0.80 in 62% countries. The GEO panels outperformed BR38, with median MCCs > 0.80 in 90% countries at GEO33, and 95% at GEO50 and GEO55. An online, open-access, likelihood-based classifier framework was established to support data analysis (vivaxGEN-geo). The SNP selection and classifier methods can be readily amended for other use cases to support malaria control programs.

Performance of the hematology analyzer XN-31 prototype in the detection of Plasmodium infections in an endemic region of Colombia.

Early and accurate diagnosis is critical in reducing the morbidity and mortality associated with malaria. Microscopy (MI) is the current diagnostic gold standard in the field; however, it requires expert personnel, is time-consuming, and has limited sensitivity. Although rapid diagnostic tests for antigen detection (RDTs) are an alternative to diagnosis, they also have limited sensitivity and produce false positive results in detecting recent past infection. The automated hematology analyzer XN-31 prototype (XN-31p) (Sysmex Corporation, Kobe, Japan) is able to identify plasmodium-infected erythrocytes, count parasitemia and perform complete blood-cell counts within one minute. The performance of the XN-31p in diagnosing malaria was evaluated and compared with real-time polymerase chain reaction (qPCR), MI and RDT in an endemic area of Colombia where Plasmodium falciparum and Plasmodium vivax are present. Acute febrile patients were enrolled from July 2018 to April 2019 in Quibdó, Colombia. Malaria diagnoses were obtained from MI and RDT in the field and later confirmed by qPCR. Venous blood samples in EDTA were processed with an XN-31p in the field. Sensitivity, specificity, positive/negative predictive values, and the likelihood ratios of positive and negative tests were calculated with respect to the results from qPCR, MI and RDT. The intraclass correlation coefficient (ICC) and Bland-Altman plot were used to evaluate the concordance in the parasitemia with respect to MI. A total of 1,754 subjects were enrolled. The mean age was 27.0 years (IQR 14-44); 89.6% were Afro-Colombians, 94.3% lived in urban areas and 0.91% were pregnant. With respect to qPCR, the XN-31p showed a sensitivity of 90% (95% CI 87.24-92.34) and a specificity of 99.83% (95% CI 99.38-99.98) in detecting Plasmodium spp.; both parameters were equivalent to those for MI and RDT. Using MI as the reference, the XN-31p showed a sensitivity of 98.09% (95% CI 96.51-99.08), a specificity of 99.83% (95% CI 99.4-99.98), an ICC of 0.85 (95% CI 0.83-0.87) and an average difference of - 3096 parasites/µL when compared with thick-smear MI and an ICC of 0.98 (95% CI 0.97-0.98) and an average difference of - 0.0013% when compared with thin-smear MI. The XN-31p offers a rapid and accurate alternative method for diagnosing malaria in clinical laboratories in areas where P. falciparum and P. vivax cocirculate.

State of Artemisinin and Partner Drug Susceptibility in Plasmodium falciparum Clinical Isolates from Colombia.

Delayed parasite clearance time observed in Southeast Asia provided the first evidence of Plasmodium falciparum resistance to artemisinins. The ex vivo ring-stage survival assay (RSA) mimics parasite exposure to pharmacologically relevant artemisinin concentrations. Mutations in the C-terminal propeller domain of the putative kelch protein Pf3D7_1343700 (K13) are associated with artemisinin resistance. Variations in the pfmdr1 gene are associated with reduced susceptibility to the artemisinin partner drugs mefloquine (MQ) and lumefantrine (LF). To clarify the unknown landscape of artemisinin resistance in Colombia, 71 patients with uncomplicated P. falciparum malaria were enrolled in a non-randomized observational study in three endemic localities in 2014-2015. Each patient's parasite isolate was assessed for ex vivo RSA, K13-propeller mutations, pfmdr1 copy number, and pfmdr1 mutations at codons 86, 184, 1034, 1042, and 1246, associated with reduced susceptibility, and 50% inhibitory concentration (IC50) for other antimalarial drugs. Ex vivo RSAs were successful in 56% (40/71) of samples, and nine isolates showed survival rates > 1%. All isolates had wild-type K13-propeller sequences. All isolates harbored either of two pfmdr1 haplotypes, NFSDD (79.3%) and NFSDY (20.7%), and 7.1% of isolates had > 1 pfmdr1 gene. In vitro IC50 assays showed that variable proportions of isolates had decreased susceptibility to chloroquine (52.4%, > 100 nM), amodiaquine (31.2%, > 30 nM), MQ (34.3%, > 30 nM), and LF (3.2%, > 10 nM). In this study, we report ex vivo RSA and K13 data on P. falciparum isolates from Colombia. The identification of isolates with increased ex vivo RSA rates in the absence of K13-propeller mutations and no positivity at day three requires further investigation.

Association of variants in IL1B, TLR9, TREM1, IL10RA, and CD3G and Native American ancestry on malaria susceptibility in Colombian populations.

Host genetics is an influencing factor in the manifestation of infectious diseases. In this study, the association of mild malaria with 28 variants in 16 genes previously reported in other populations and/or close to ancestry-informative markers (AIMs) selected was evaluated in an admixed 736 Colombian population sample. Additionally, the effect of genetic ancestry on phenotype expression was explored. For this purpose, the ancestral genetic composition of Turbo and El Bagre was determined. A higher Native American ancestry trend was found in the population with lower malaria susceptibility [odds ratio (OR) = 0.416, 95% confidence interval (95% CI) = 0.234-0.740, P = 0.003]. Three AIMs presented significant associations with the disease phenotype (MID1752, MID921, and MID1586). The first two were associated with greater malaria susceptibility (D/D, OR = 2.23, 95% CI = 1.06-4.69, P = 0.032 and I/D-I/I, OR = 2.14, 95% CI = 1.18-3.87, P = 0.011, respectively), and the latter has a protective effect on the appearance of malaria (I/I, OR = 0.18, 95% CI = 0.08-0.40, P < 0.0001). After adjustment by age, sex, municipality, and genetic ancestry, genotype association analysis showed evidence of association with malaria susceptibility for variants in or near IL1B, TLR9, TREM1, IL10RA, and CD3G genes: rs1143629-IL1B (G/A-A/A, OR = 0.41, 95% CI = 0.21-0.78, P = 0.0051), rs352139-TLR9 (T/T, OR = 0.28, 95% CI = 0.11-0.72, P = 0.0053), rs352140-TLR9 (C/C, OR = 0.41, 95% CI = 0.20-0.87, P = 0.019), rs2234237-TREM1 (T/A-A/A, OR = 0.43, 95% CI = 0.23-0.79, P = 0.0056), rs4252246-IL10RA (C/A-A/A, OR = 2.11, 95% CI = 1.18-3.75, P = 0.01), and rs1561966-CD3G (A/A, OR = 0.20, 95% CI = 0.06-0.69, P = 0.0058). The results showed the participation of genes involved in immunological processes and suggested an effect of ancestral genetic composition over the traits analyzed. Compared to the paisa population (Antioquia), Turbo and El Bagre showed a strong decrease in European ancestry and an increase in African and Native American ancestries. Also, a novel association of two single nucleotide polymorphisms with malaria susceptibility was identified in this study.

Acciones necesarias para la eliminación de la malaria en Colombia / Actions needed for malaria elimination in Colombia

La malaria o paludismo sigue representando una carga de enfermedad para las comunidades de los diferentes territorios de Colombia, de los cuales Chocó, Nariño, Córdoba y Antioquia son los departamentos donde más casos se notifican (el 73 % de 77 172 casos de malaria no complicada en 2019); además, en el país se informaron 1342 casos graves (1). El Ministerio de Salud de Colombia se adhirió a la Iniciativa Regional para la Eliminación de la Malaria (IREM), creada en 2014. En diciembre de 2019, esta iniciativa priorizó acciones en 12 municipios de Chocó, Nariño y Valle del Cauca. Sin embargo, la situación social en los territorios indica que no están dadas las condiciones que permitan este logro en el país.

Malaria continues to represent a burden of disease for communities in the different territories of Colombia, of which Chocó, Nariño, Córdoba and Antioquia are the departments where most cases are reported (73% of 77 172 cases of uncomplicated malaria in 2019); in addition, 1342 severe cases were reported in the country (1). The Colombian Ministry of Health joined the Regional Initiative for the Elimination of Malaria (IREM), created in 2014. In December 2019, this initiative prioritized actions in 12 municipalities in Chocó, Nariño and Valle del Cauca. However, the social situation in the territories indicates that the conditions are not in place to allow this achievement in the country.

Antibody Responses Against Anopheles darlingi Immunogenic Peptides in Plasmodium Infected Humans.

Introduction: Malaria is still an important vector-borne disease in the New World tropics. Despite the recent decline in malaria due to Plasmodium falciparum infection in Africa, a rise in Plasmodium infections has been detected in several low malaria transmission areas in Latin America. One of the main obstacles in the battle against malaria is the lack of innovative tools to assess malaria transmission risk, and the behavioral plasticity of one of the main malaria vectors in Latin America, Anopheles darlingi. Methods: We used human IgG antibodies against mosquito salivary gland proteins as a measure of disease risk. Whole salivary gland antigen (SGA) from Anopheles darlingi mosquitoes was used as antigen in Western blot experiments, in which a ~65 kDa protein was visualized as the main immunogenic band and sent for sequencing by mass spectrometry. Apyrase and peroxidase peptides were designed and used as antigens in an ELISA-based test to measure human IgG antibody responses in people with different clinical presentations of malaria. Results: Liquid chromatography-mass spectrometry revealed 17 proteins contained in the ~65 kDa band, with an apyrase and a peroxidase as the two most abundant proteins. Detection of IgG antibodies against salivary antigens by ELISA revealed a significant higher antibody levels in people with malaria infection when compared to uninfected volunteers using the AnDar_Apy1 and AnDar_Apy2 peptides. We also detected a significant positive correlation between the anti-peptides IgG levels and antibodies against the Plasmodium vivax and P. falciparum antigens PvMSP1 and PfMSP1. Odd ratios suggest that people with higher IgG antibodies against the apyrase peptides were up to five times more likely to have a malaria infection. Conclusion: Antibodies against salivary peptides from An. darlingi salivary gland proteins may be used as biomarkers for malaria risk.

Malaria in Pregnancy in Endemic Regions of Colombia: High Frequency of Asymptomatic and Peri-Urban Infections in Pregnant Women with Malaria.

Background: Malaria in pregnancy (MiP) has been associated with adverse pregnancy outcomes. There is limited information on MiP in low transmission regions as Colombia. This study aimed to describe the epidemiology of MiP through active surveillance of infections by microscopy and polymerase chain reaction (PCR). Methods: A cross-sectional study was conducted between May 2016 and January 2017 in five municipalities (Apartadó, Turbo, El Bagre, Quibdó, and Tumaco) in Colombia. Pregnant women self-presenting at health centers for antenatal care visits, seeking medical care for suspected malaria, or delivery, were enrolled. Diagnosis of Plasmodium spp was made in peripheral and placental blood samples by microscopy and PCR. Results: A total of 787 pregnant women were enrolled; plasmodial infection was diagnosed by microscopy in 4.2% (95% CI 2.8-5.6; 33/787) or by nPCR in 5.3% (95% CI 3.8-6.9; 42/787) in peripheral blood. Most of the infections were caused by P. falciparum (78.5%), and 46% were afebrile (asymptomatic). Women in the first and second trimester of pregnancy were more likely to be infected (aOR = 3.06, 95%CI = 1.6 - 5.8). To live in the urban/peri-urban area (aOR = 3.04, 95%CI = 1.4 - 6.56), to have a history of malaria during last year (aOR = 5.45, 95%IC = 2.16 - 13.75), and the infrequent bed net usage (aOR = 2.8, 95%CI = 1.31 - 5.97) were associated with the infection. Pregnant infected women had a higher risk of anaemia (aOR = 2.18, 95%CI = 1.15 - 4.12) and fever (aOR = 14.2, 95%CI = 6.89 - 29.8). Conclusion: The screening for malaria during antenatal care in endemic areas of Colombia is highly recommended due to the potential adverse effects of Plasmodium spp. infection in pregnancy and as an important activity for the surveillance of asymptomatic infections in the control of malaria.

Microscopic and submicroscopic Plasmodium infections in indigenous and non-indigenous communities in Colombia.

BACKGROUND: The indigenous population is considered a highly susceptible group to malaria because individuals usually live in areas with high exposure to Anopheles and poverty, and have limited access to health services. There is a great diversity of indigenous communities in Colombia living in malaria-endemic areas; however, the burden of infection in these populations has not been studied extensively. This study aimed to determine the prevalence of Plasmodium infections in indigenous and non-indigenous communities in two malaria-endemic areas in Colombia. METHODS: A community-based cross-sectional survey was conducted in seven villages of Turbo and El Bagre municipalities; three of these villages were indigenous communities. Inhabitants of all ages willing to participate were included. Sociodemographic and clinical data were recorded as well as household information. The parasitological diagnosis was performed by microscopy and nested PCR. The prevalence of microscopy and submicroscopic infection was estimated. An adjusted GEE model was used to explore risk factors associated with the infection. RESULTS: Among 713 participants, 60.7% were from indigenous communities. Plasmodium spp. was detected in 30 subjects (4.2%, CI 95% 2.9-5.9); from those, 29 were in the indigenous population, 47% of infections were afebrile, and most of them submicroscopic (10/14). Microscopic and submicroscopic prevalence was 2.5% (CI 95% 1.6-3.9) and 1.7% (CI 95% 0.9-2.9), respectively. In El Bagre, all infections occurred in indigenous participants (3.9%, CI 95% 2.2-7.1), and 81% were submicroscopic. By contrast, in Turbo, the highest prevalence occurred in indigenous people (11.5%; CI 95%: 7.3-17.5), but 88.8% were microscopic. Living in an indigenous population increased the prevalence of infection compared with a non-indigenous population (PR 19.4; CI 95% 2.3-166.7). CONCLUSION: There is a high proportion of Plasmodium infection in indigenous communities. A substantial proportion of asymptomatic and submicroscopic carriers were detected. The identification of these infections, not only in indigenous but also in the non-indigenous population, as well as their associated factors, could help to implement specific malaria strategies for each context.

Identification and Pilot Evaluation of Salivary Peptides from Anopheles albimanus as Biomarkers for Bite Exposure and Malaria Infection in Colombia.

Insect saliva induces significant antibody responses associated with the intensity of exposure to bites and the risk of disease in humans. Several salivary biomarkers have been characterized to determine exposure intensity to Old World Anopheles mosquito species. However, new tools are needed to quantify the intensity of human exposure to Anopheles bites and understand the risk of malaria in low-transmission areas in the Americas. To address this need, we conducted proteomic and bioinformatic analyses of immunogenic candidate proteins present in the saliva of uninfected Anopheles albimanus from two separate colonies-one originating from Central America (STECLA strain) and one originating from South America (Cartagena strain). A ~65 kDa band was identified by IgG antibodies in serum samples from healthy volunteers living in a malaria endemic area in Colombia, and a total of five peptides were designed from the sequences of two immunogenic candidate proteins that were shared by both strains. ELISA-based testing of human IgG antibody levels against the peptides revealed that the transferrin-derived peptides, TRANS-P1, TRANS-P2 and a salivary peroxidase peptide (PEROX-P3) were able to distinguish between malaria-infected and uninfected groups. Interestingly, IgG antibody levels against PEROX-P3 were significantly lower in people that have never experienced malaria, suggesting that it may be a good marker for mosquito bite exposure in naïve populations such as travelers and deployed military personnel. In addition, the strength of the differences in the IgG levels against the peptides varied according to location, suggesting that the peptides may able to detect differences in intensities of bite exposure according to the mosquito population density. Thus, the An. albimanus salivary peptides TRANS-P1, TRANS-P2, and PEROX-P3 are promising biomarkers that could be exploited in a quantitative immunoassay for determination of human-vector contact and calculation of disease risk.

IgG antibody response against Anopheles salivary gland proteins in asymptomatic Plasmodium infections in Narino, Colombia.

BACKGROUND: The humoral immune response against Anopheles salivary glands proteins in the vertebrate host can reflect the intensity of exposure to Anopheles bites and the risk of Plasmodium infection. In Colombia, the identification of exposure biomarkers is necessary due to the several Anopheles species circulating. The purpose of this study was to evaluate risk of malaria infection by measuring antibody responses against salivary glands extracts from Anopheles (Nyssorhynchus) albimanus and Anopheles (Nys.) darlingi and also against the gSG6-P1 peptide of Anopheles gambiae in people residing in a malaria endemic area in the Colombian Pacific coast. METHODS: Dried blood spots samples were eluted to measure the IgG antibodies against salivary gland extracts of An. albimanus strains STECLA (STE) and Cartagena (CTG) and An. darlingi and the gSG6-P1 peptide by ELISA in uninfected people and microscopic and submicroscopic Plasmodium carriers from the Colombia Pacific Coast. A multiple linear mixed regression model, Spearman correlation, and Mann-Whitney U-test were used to analyse IgG data. RESULTS: Significant differences in specific IgG levels were detected between infected and uninfected groups for salivary glands extracts from An. albimanus and for gSG6-P1, also IgG response to CTG and gSG6-P1 peptide were positively associated with the IgG response to Plasmodium falciparum in the mixed model. CONCLUSION: The CTG and STE An. albimanus salivary glands extracts are a potential source of new Anopheles salivary biomarkers to identify exposure to the main malaria vector and to calculate risk of disease in the Colombian Pacific coast. Also, the gSG6-P1 peptide has the potential to quantify human exposure to the subgenus Anopheles vectors in the same area.

Barriers to the care of febrile patients in a malaria endemic area. El Bagre (Antioquia, Colombia) 2016 / Barreras para la atención de pacientes febriles en una zona endémica de malaria. El Bagre (Antioquia, Colombia) 2016 / Barreiras para a atenção de pacientes febriles em uma zona endemica de malaria. O Bagre

Objective: identify constraints of patients with acute febrile syndrome to institutional care services access, emphasizing the identification of communication barriers. Method: this is a descriptive study that involves qualitative research techniques including malaria care service patients as well as assistance and administrative personnel of El Bagre town in Antioquia, Colombia in 2016. Semi-structured individual surveys, interviews and focus groups were used. Results: users listed difficulties including transportation, insufficient number of appointments and absence of personnel to access healthcare. Communication difficulties were related to the information provided in the paperwork and documents filled out to attend healthcare facilities, scarce information about diagnostic, control, and adherence to antimalarial treatment; additionally some patients did not use Spanish to communicate in oral or write form. Conclusion: the creation of health models based on structural transformations that encompass the needs of Healthcare System actors and communities is a must, which allows the establishment of foundations for a multicultural society project

Objetivo: Identificar limitaciones de los pacientes con síndrome febril agudo para acceder a los servicios de atención institucional, con énfasis en la identificación de barreras de comunicación.Método: Estudio descriptivo que involucra técnicas de investigación cualitativa con pacientes de los servicios de atención de la malaria y con personal asistencial y administrativo del municipio de El Bagre Antioquia, Colombia en el 2016. Se aplicaron encuestas semiestructuradas individuales, entrevistas y grupos focales. Los usuarios señalaron dificultades con el transporte, insuficiente número de citas y falta de personal para acceder a la atención. Resultados: Las dificultades de comunicación se relacionaron con la información suministrada sobre trámites y documentación para asistir a los puestos de salud, poca información sobre el diagnóstico, control y adherencia al tratamiento antimalárico y el no uso de algunos pacientes del español para comunicarse en forma verbal o escrita. Conclusiones: Esto exige crear modelos de salud basados en transformaciones estructurales que abarquen las necesidades de los actores del sistema de salud y las comunidades, permitiendo establecer las bases para un proyecto multicultural de sociedad.

Objetivo: Identificar limitações dos pacientes com síndrome febril agudo para aceder aos serviços de atenção institucional, com ênfase na identificação de barreiras de comunicação. Método: Estudo descritivo que involucra técnicas de pesquisa qualitativa com pacientes dos serviços de atenção da malária e com equipe assistencial e administrativo do município do Bagre Antioquia, Colômbia no 2016. Fizeram-se enquetes semiestruturadas individuais, entrevistas e grupos focais. Os usuários sinalaram dificuldades com o transporte, insuficiente número de horas marcadas e falta de pessoal para aceder à atenção. Resultados: As dificuldades de comunicação se relacionaram com a informação subministrada sobre trâmites e documentação para chegar aos SUS (Sistema Único de Saúde), pouca informação sobre o diagnóstico, controle e aderência ao tratamento antimalárico e o não uso de alguns pacientes do espanhol para comunicar-se em forma verbal ou escrita. Conclusões: Isto exige criar modelos de saúde baseados em transformações estruturais que abarquem as necessidades dos atores do sistema de saúde e as comunidades, permitindo estabelecer as bases para um projeto multicultural de sociedade.

Severe malaria in pregnant women hospitalized between 2010 and 2014 in the Department of Antioquia (Colombia) / Malaria grave en mujeres gestantes hospitalizadas entre el 2010 y el 2014 en el departamento de Antioquia, Colombia.

Introduction: Malaria during pregnancy has a negative impact on maternal-neonatal health, with a high risk of clinic complications and mortality. High endemic areas are specially characterized by maternal anaemia and low birth weight. The clinical spectrum is little known in low endemic areas. Objective: To clinically and epidemiologically characterize malaria episodes in hospitalized pregnant women in the Department of Antioquia (Colombia) in the period 2010-2014. Materials and methods: Retrospective, cross-sectional, descriptive study with medical records of pregnant women with P. falciparum and P. vivax malaria. The WHO severe malaria diagnostic criteria and the Colombian Guía para la atención clínica integral del paciente con malaria (guidelines for comprehensive malaria treatment) were used. Results: We analyzed 111 cases, out of which 13.5% were classified as severe malaria according to the WHO criteria. Following the Colombian Guidelines, the proportion increased to 23.4%. Identified complications included hepatic dysfunction, anaemia, acidosis, and severe thrombocytopenia. No difference in the frequency of complications by Plasmodium species was observed; 39.4% of the cases presented general danger signs, pallor and jaundice being the most frequent; 40.5% showed danger signs for pregnancy, such as persistent headache, abdominal pain, and vaginal bleeding. Conclusions: Severe malaria is a highly frequent event in pregnant women, without differences by Plasmodium species. It shows early recognizable dangers signs. Hospital under-reporting was identified in 88% of severe cases as well as a lack of laboratory tests for a more comprehensive diagnosis. A protocol for the clinical diagnosis of pregnant women with malaria is required.

Introducción. La malaria (o paludismo) durante la gestación impacta negativamente la salud de la madre y del neonato, con alto riesgo de complicaciones clínicas y mortalidad. En las regiones de alta endemia se han caracterizado, especialmente, la anemia materna y el bajo peso al nacer, pero es poco conocido el espectro clínico en las zonas de baja endemia. Objetivo. Caracterizar clínica y epidemiológicamente los episodios de malaria en mujeres gestantes hospitalizadas en el departamento de Antioquia entre el 2010 y el 2014. Materiales y métodos. Se hizo un estudio descriptivo, transversal y retrospectivo, con historias clínicas de mujeres gestantes con malaria por Plasmodium falciparum y P. vivax. Se utilizaron los criterios diagnósticos de malaria complicada de la Organización Mundial de la Salud (OMS) y de la Guía para la atención clínica integral del paciente con malaria vigente en Colombia. Resultados. Se analizaron 111 casos; el 13,5 % se clasificó como complicación grave según los criterios de la OMS, porcentaje que ascendió a 23,4 % según los criterios de la guía colombiana. Las complicaciones detectadas fueron disfunción hepática, anemia, acidosis y trombocitopenia grave. No se observó diferencia en la frecuencia de las complicaciones según la especie de plasmodio. El 39,4 % de los casos presentó signos generales de peligro; la palidez y la ictericia fueron los más frecuentes. El 40,5 % presentó signos de peligro para la gestación como la cefalea persistente, el dolor abdominal y el sangrado vaginal. Conclusiones. La malaria grave se presenta con gran frecuencia en las mujeres gestantes, sin diferencia según la especie de plasmodio, y se manifiesta con signos de peligro precozmente reconocibles. Se encontró un subregistro hospitalario del 88 % de los casos graves y falta de exámenes de laboratorio para un diagnóstico más completo. Se requiere un protocolo para el diagnóstico clínico de las mujeres gestantes con malaria.

Malaria grave en mujeres gestantes hospitalizadas entre el 2010 y el 2014 en el departamento de Antioquia, Colombia / Severe malaria in pregnant women hospitalized between 2010 and 2014 in the Department of Antioquia (Colombia)

Resumen Introducción. La malaria (o paludismo) durante la gestación impacta negativamente la salud de la madre y del neonato, con alto riesgo de complicaciones clínicas y mortalidad. En las regiones de alta endemia se han caracterizado, especialmente, la anemia materna y el bajo peso al nacer, pero es poco conocido el espectro clínico en las zonas de baja endemia. Objetivo. Caracterizar clínica y epidemiológicamente los episodios de malaria en mujeres gestantes hospitalizadas en el departamento de Antioquia entre el 2010 y el 2014. Materiales y métodos. Se hizo un estudio descriptivo, transversal y retrospectivo, con historias clínicas de mujeres gestantes con malaria por Plasmodium falciparum y P. vivax. Se utilizaron los criterios diagnósticos de malaria complicada de la Organización Mundial de la Salud (OMS) y de la Guía para la atención clínica integral del paciente con malaria vigente en Colombia. Resultados. Se analizaron 111 casos; el 13,5 % se clasificó como complicación grave según los criterios de la OMS, porcentaje que ascendió a 23,4 % según los criterios de la guía colombiana. Las complicaciones detectadas fueron disfunción hepática, anemia, acidosis y trombocitopenia grave. No se observó diferencia en la frecuencia de las complicaciones según la especie de plasmodio. El 39,4 % de los casos presentó signos generales de peligro; la palidez y la ictericia fueron los más frecuentes. El 40,5 % presentó signos de peligro para la gestación como la cefalea persistente, el dolor abdominal y el sangrado vaginal. Conclusiones. La malaria grave se presenta con gran frecuencia en las mujeres gestantes, sin diferencia según la especie de plasmodio, y se manifiesta con signos de peligro precozmente reconocibles. Se encontró un subregistro hospitalario del 88 % de los casos graves y falta de exámenes de laboratorio para un diagnóstico más completo. Se requiere un protocolo para el diagnóstico clínico de las mujeres gestantes con malaria.

Abstract Introduction: Malaria during pregnancy has a negative impact on maternal-neonatal health, with a high risk of clinic complications and mortality. High endemic areas are specially characterized by maternal anaemia and low birth weight. The clinical spectrum is little known in low endemic areas. Objective: To clinically and epidemiologically characterize malaria episodes in hospitalized pregnant women in the Department of Antioquia (Colombia) in the period 2010-2014. Materials and methods: Retrospective, cross-sectional, descriptive study with medical records of pregnant women with P. falciparum and P. vivax malaria. The WHO severe malaria diagnostic criteria and the Colombian Guía para la atención clínica integral del paciente con malaria (guidelines for comprehensive malaria treatment) were used. Results: We analyzed 111 cases, out of which 13.5% were classified as severe malaria according to the WHO criteria. Following the Colombian Guidelines, the proportion increased to 23.4%. Identified complications included hepatic dysfunction, anaemia, acidosis, and severe thrombocytopenia. No difference in the frequency of complications by Plasmodium species was observed; 39.4% of the cases presented general danger signs, pallor and jaundice being the most frequent; 40.5% showed danger signs for pregnancy, such as persistent headache, abdominal pain, and vaginal bleeding. Conclusions: Severe malaria is a highly frequent event in pregnant women, without differences by Plasmodium species. It shows early recognizable dangers signs. Hospital under-reporting was identified in 88% of severe cases as well as a lack of laboratory tests for a more comprehensive diagnosis. A protocol for the clinical diagnosis of pregnant women with malaria is required.

Chloroquine-Primaquine Therapeutic Efficacy, Safety, and Plasma Levels in Patients with Uncomplicated Plasmodium vivax Malaria in a Colombian Pacific Region.

In Colombia, published studies for the treatment of uncomplicated Plasmodium vivax malaria with chloroquine-primaquine (CQ-PQ) are scarce. The aim of the study was to evaluate the therapeutic efficacy and safety profile of this combination. A clinical trial was performed in adults with uncomplicated P. vivax malaria using the 28-day World Health Organization validated protocol. Patients received supervised antimalarial treatment and the primary efficacy end point was the clinical and parasitological response. Safety was assessed through adverse events surveillance, and plasma levels of antimalarial drugs were measured. A total of 77 patients were included. Adequate clinical and parasitological response rate diagnosed by thick blood smear examination was achieved in 72 of 73 patients (98.6%) with a complete 28-day follow-up. There were two parasitological therapeutic failures (TFs) (2.9%) on day 28, established by polymerase chain reaction among 68 patients, one of them with a positive film. No adverse events were detected. After completing the antimalarial treatment, all patients reached adequate plasma concentrations of CQ and desethylchloroquine (DECQ), with medians of 302.9 and 104.0 ng/mL, respectively. Uncomplicated P. vivax malaria treatment with CQ-PQ standard treatment was effective and safe in the study population; TFs were not associated with low plasma levels of CQ and DECQ.

[Epidemiological surveillance activities for malaria in the colombian-peruvian border diagnostic network]. / Actividades de vigilancia epidemiológica de la malaria en la red diagnóstica de la frontera colombiana-peruana.

OBJECTIVE.: To describe the activities of the malaria diagnostic network and its quality control in the Colombian-Peruvian border to characterize the functioning of the epidemiological surveillance system. MATERIALS AND METHODS.: Descriptive study with a research focus on implementation. We visited border communities with health care centers or volunteers trained to diagnose malaria. The visited sites were georeferenced to know their distribution. With information from departmental public health laboratories, the quality component was analyzed and compliance with the national guidelines for malaria diagnostic networks in the border area of the two countries was evidenced. RESULTS.: Twenty-five Colombian and 18 Peruvian sites were visited, of which 25% had only microscopy posts, 56% made a diagnosis for malaria, and 19% only took samples and the plates were sent to a reference point for diagnosis. The Ministry of Health of the Amazon (Colombia) did not carry out direct supervision visits to the malaria diagnostic network during 2016-2017; the Regional Health Directorate of Loreto (Peru) has not carried out visits since 2015. Sixty percent of the diagnosis points in the Amazon and 29% in Loreto participated in quality assurance. CONCLUSIONS.: Lack of opportunity in the diagnosis was identified in 44% of the visited sites and deficiencies in the quality component of the border diagnostic network.

OBJETIVO.: Describir las actividades de la red de diagnóstico de malaria y su control de calidad en la frontera colombiana-peruana para caracterizar el funcionamiento del sistema de vigilancia epidemiológica. MATERIALES Y MÉTODOS.: Estudio descriptivo con enfoque de investigación en implementación. Se visitaron comunidades fronterizas con puestos de atención en salud o voluntarios entrenados para el diagnóstico de malaria. Se georreferenciaron los sitios visitados para conocer su distribución; con información de laboratorios de salud pública departamentales, se analizó el componente de calidad y se evidenció el cumplimiento de los lineamientos nacionales para las redes de diagnóstico de la malaria en la zona de frontera de los dos países. RESULTADOS.: Se visitaron 25 sitios colombianos y 18 peruanos, de los cuales, en el 25% solo había puestos de microscopía, el 56% realiza diagnóstico para malaria; y 19% realiza sólo toma de muestra y las láminas son enviadas a un punto de referencia para su diagnóstico. La Secretaria de Salud del Amazonas (Colombia) no desarrolló visitas de supervisión directa a la red de diagnóstico para malaria en 2016-2017, la Dirección Regional de Salud de Loreto (Perú) no lleva a cabo visitas desde el 2015. El 60% de los puntos de diagnóstico en el Amazonas y el 29% en Loreto participaron del aseguramiento de la calidad. CONCLUSIÓN.: Se identificó falta de oportunidad en el diagnóstico en el 44% de los sitios visitados y deficiencias en componente de calidad de la red de diagnóstico fronteriza.

Artemeter-Lumefantrine therapeutic efficacy, safety and plasma levels in patients with uncomplicated falciparum malaria from the Colombian Pacific region / Eficacia terapéutica, seguridad y niveles plasmáticos del Artemeter-Lumefantrine en pacientes con malaria falciparum no complicada de la región del Pacifico Colombiano

Introduction: In Colombia, the published studies for the treatment of uncomplicated Plasmodium falciparum malaria with Artemether-Lumefantrine are scarce. The aim of the study was to evaluate the therapeutic efficacy and safety profile of this combination. Methods: A clinical trial was performed in adults with uncomplicated P. falciparum malaria using the 28‑day World Health Organization validated protocol. Patients received supervised antimalarial treatment and the primary efficacy endpoint was the clinical and parasitological response. Safety was assessed through adverse events surveillance and plasmatic levels of antimalarial drugs were measured. Results: 88 patients were included. Adequate clinical and parasitological response rate of 100% on day 28 was achieved in 84 patients, diagnosed by thick blood smear examination. There were four parasitological therapeutic failures (5%) detected by polymerase chain reaction. Discusion: Therapeutic efficacy similar to previous studies was established with a slight increase in therapeutic failure. The serum levels of the antimalarials were adequate and the few cases of therapeutic failure were not related. Conclusion: Treatment of uncomplicated P. falciparum malaria with Artemeter-Lumefantrine was effective and safe in the study population. All patients reached adequate plasma concentrations of the drugs; therapeutic failures were not associated with low blood levels of the drug clinical trial.

Introducción: Son escasos los estudios en Colombia sobre eficacia del tratamiento para Plasmodium falciparum con la combinación Artemeter-Lumefantrina. El objetivo de este estudio fue evaluar la eficacia terapéutica y el perfil de seguridad de este tratamiento combinado. Métodos: Se realizó un ensayo clínico en adultos con malaria por P. falciparum no complicada, utilizando el esquema de 28 días recomendado por la Organización Mundial de la Salud (OMS). Los pacientes recibieron el tratamiento supervisado y el desenlace primario evaluado fue la respuesta clínica y parasitológica. La seguridad fue evaluada a través de vigilancia de efectos adversos y medición de niveles plasmáticos del medicamento. Resultados: Se incluyeron 88 pacientes. La tasa de curación clínica y parasitológica fue del 100% en 84 pacientes que tuvieron examen de gota gruesa al día 28. Hubo cuatro (5%) fallas parasitológicas detectada por reacción en cadena de polimerasa. Discusión: La eficacia terapéutica fue similar a la reportada en estudios previos con un ligero aumento de falla terapéutica. Los niveles plasmáticos de los antimalaricos fueron adecuados y no relacionados con la falla terapéutica. Conclusión: El tratamiento de malaria por P. falciparum no complicada con Artemeter-Lumefantrina fue efectiva y segura en la población estudiada. Todos los pacientes alcanzaron niveles en plasma adecuados y no se encontró asociación de falla terapéutica con bajos niveles en sangre.