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Herrera S.,Caucaseco Scientific Research Center | Ochoa-Orozco S.A.,Caucaseco Scientific Research Center | Gonzalez I.J.,Foundation for Innovative New Diagnostics FIND | Peinado L.,Health Management Consultant City | And 3 more authors.
PLoS Neglected Tropical Diseases | Year: 2015

Malaria remains endemic in 21 countries of the American continent with an estimated 427,000 cases per year. Approximately 10% of these occur in the Mesoamerican and Caribbean regions. During the last decade, malaria transmission in Mesoamerica showed a decrease of ~85%; whereas, in the Caribbean region, Hispaniola (comprising the Dominican Republic [DR] and Haiti) presented an overall rise in malaria transmission, primarily due to a steady increase in Haiti, while DR experienced a significant transmission decrease in this period. The significant malaria reduction observed recently in the region prompted the launch of an initiative for Malaria Elimination in Mesoamerica and Hispaniola (EMMIE) with the active involvement of the National Malaria Control Programs (NMCPs) of nine countries, the Regional Coordination Mechanism (RCM) for Mesoamerica, and the Council of Health Ministries of Central America and Dominican Republic (COMISCA). The EMMIE initiative is supported by the Global Fund for Aids, Tuberculosis and Malaria (GFATM) with active participation of multiple partners including Ministries of Health, bilateral and multilateral agencies, as well as research centers. EMMIE’s main goal is to achieve elimination of malaria transmission in the region by 2020. Here we discuss the prospects, challenges, and research needs associated with this initiative that, if successful, could represent a paradigm for other malaria-affected regions. © 2015 Herrera et al.


Rodriguez J.C.P.,Ministry of Social Protection | Uribe G.A.,Ministry of Social Protection | Araujo R.M.,Pan American Health Organization | Narvaez P.C.,National Institute of Health | And 2 more authors.
Memorias do Instituto Oswaldo Cruz | Year: 2011

Malaria is currently one of the most serious public health problems in Colombia with an endemic/epidemic transmission pattern that has maintained endemic levels and an average of 105,000 annual clinical cases being reported over the last five years. Plasmodium vivax accounts for approximately 70% of reported cases with the remainder attributed almost exclusively to Plasmodium falciparum. A limited number of severe and complicated cases have resulted in mortality, which is a downward trend that has been maintained over the last few years. More than 90% of the malaria cases in Colombia are confined to 70 municipalities (about 7% of the total municipalities of Colombia), with high predominance (85%) in rural areas. The purpose of this paper is to review the progress of malaria-eradication activities and control measures over the past century within the eco-epidemiologic context of malaria transmission together with official consolidated morbidity and mortality reports. This review may contribute to the formulation of new antimalarial strategies and policies intended to achieve malaria elimination/eradication in Colombia and in the region.


Vallejo A.F.,Malaria Vaccine and Drug Development Center | Garcia J.,Malaria Vaccine and Drug Development Center | Amado-Garavito A.B.,Malaria Vaccine and Drug Development Center | Arevalo-Herrera M.,Caucaseco Scientific Research Center | And 3 more authors.
Malaria Journal | Year: 2016

Background: The use of molecular techniques has put in the spotlight the existence of a large mass of malaria sub-microscopic infections among apparently healthy populations. These sub-microscopic infections are considered an important pool for maintained malaria transmission. Methods: In order to assess the appearance of Plasmodium vivax gametocytes in circulation, gametocyte density and the parasite infectivity to Anopheles mosquitoes, a study was designed to compare three groups of volunteers either experimentally infected with P. vivax sporozoites (early infections; n = 16) or naturally infected patients (acute malaria, n = 16 and asymptomatic, n = 14). In order to determine gametocyte stage, a quantitative reverse transcriptase PCR (RT-qPCR) assay targeting two sexual stage-specific molecular markers was used. Parasite infectivity was assessed by membrane feeding assays (MFA). Results: In early infections P. vivax gametocytes could be detected starting at day 7 without giving rise to infected mosquitoes during 13 days of follow-up. Asymptomatic carriers, with presumably long-lasting infections, presented the highest proportion of mature gametocytes and were as infective as acute patients. Conclusions: This study shows the potential role of P. vivax asymptomatic carriers in malaria transmission should be considered when new policies are envisioned to redirect malaria control strategies towards targeting asymptomatic infections as a tool for malaria elimination. © 2016 Vallejo et al.


Vallejo A.F.,Caucaseco Scientific Research Center | Martinez N.L.,Caucaseco Scientific Research Center | Gonzalez I.J.,Foundation for Innovative New Diagnostics FIND | Arevalo-Herrera M.,Caucaseco Scientific Research Center | And 2 more authors.
PLoS Neglected Tropical Diseases | Year: 2015

First, a passive case detection (PCD) study on 278 febrile patients recruited in Tierralta (department of Cordoba) was conducted to assess the diagnostic performance of the mLAMP method. Second, an active case detection (ACD) study on 980 volunteers was conducted in 10 sentinel sites with different epidemiological profiles. Whole blood samples were processed for microscopic and mLAMP diagnosis. Additionally RT-PCR and nested RT-PCR were used as reference tests. In the PCD study, P. falciparum accounted for 23.9% and P. vivax for 76.1% of the infections and no cases of mixed-infections were identified. Microscopy sensitivity for P. falciparum and P. vivax were 100% and 86.1%, respectively. mLAMP sensitivity for P. falciparum and P. vivax was 100% and 91.4%, respectively. In the ACD study, mLAMP detected 65 times more cases than microscopy. A high proportion (98.0%) of the infections detected by mLAMP was from volunteers without symptoms.mLAMP sensitivity and specificity were comparable to RT-PCR. LAMP was significantly superior to microscopy and in P. vivax low-endemicity settings and under minimum infrastructure conditions, it displayed sensitivity and specificity similar to that of single-well RT-PCR for detection of both P. falciparum and P. vivax infections. Here, the dramatically increased detection of asymptomatic malaria infections by mLAMP demonstrates the usefulness of this new tool for diagnosis, surveillance, and screening in elimination strategies.Most commonly used malaria diagnostic tests, including microscopy and antigen-detecting rapid tests, cannot reliably detect low-density infections which are frequent in low transmission settings. Molecular methods such as polymerase chain reaction (PCR) are highly sensitive but remain too laborious for field deployment. In this study, the applicability of a malaria diagnosis kit based on loop-mediated isothermal amplification (mLAMP) was assessed in malaria endemic areas of Colombia with Plasmodium vivax predominance. © 2015 Vallejo et al.


Lopez-Perez M.,Caucaseco Scientific Research Center | Alvarez A.,Caucaseco Scientific Research Center | Gutierrez J.B.,University of Georgia | Moreno A.,Emory University | And 2 more authors.
American Journal of Tropical Medicine and Hygiene | Year: 2015

Information about the prevalence of malarial anemia in areas of low-malaria transmission intensity, like Latin America, is scarce. To characterize the malaria-related anemia, we evaluated 929 malaria patients from three sites in Colombia during 2011-2013. Plasmodium vivax was found to be the most prevalent species in Tierralta (92%), whereas P. falciparum was predominant in Tumaco (84%) and Quibdó(70%). Although severe anemia (hemoglobin < 7 g/dL) was almost absent (0.3%), variable degrees of non-severe anemia were observed in 36.9%of patients. In Tierralta, hemoglobin levels were negatively associated with days of illness. Moreover, in Tierralta and Quibdó, the number of previous malaria episodes and hemoglobin levels were positively associated. Both Plasmodium species seem to have similar potential to induce malarial anemia with distinct cofactors at each endemic setting. The target age in these low-transmission settings seems shifting toward adolescents and young adults. In addition, previous malaria experience seems to induce protection against anemia development. Altogether, these data suggest that early diagnosis and prompt treatment are likely preventing more frequent and serious malaria-related anemia in Colombia. Copyright © 2015 by The American Society of Tropical Medicine and Hygiene.


Cespedes N.,Malaria Vaccine and Drug Development Center | Cespedes N.,University of Lausanne | Cespedes N.,University of Valle | Arevalo-Herrera M.,Malaria Vaccine and Drug Development Center | And 7 more authors.
Vaccine | Year: 2013

Background: Plasmodium vivax circumsporozoite (PvCS) protein is a major sporozoite surface antigen involved in parasite invasion of hepatocytes and is currently being considered as vaccine candidate. PvCS contains a dimorphic central repetitive fragment flanked by conserved regions that contain functional domains. Methods: We have developed a chimeric 137-mer synthetic polypeptide (PvCS-NRC) that includes the conserved region I and region II-plus and the two natural repeat variants known as VK210 and VK247. The antigenicity of PvCS-NRC was tested using human sera from PNG and Colombia endemic areas and its immunogenicity was confirmed in mice with different genetic backgrounds, the polypeptide formulated either in Alum or GLA-SE adjuvants was assessed in inbred C3H, CB6F1 and outbred ICR mice, whereas a formulation in Montanide ISA51 was tested in C3H mice. Results: Antigenicity studies indicated that the chimeric peptide is recognized by a high proportion (60-70%) of residents of malaria-endemic areas. Peptides formulated with either GLA-SE or Montanide ISA51 adjuvants induced stronger antibody responses as compared with the Alum formulation. Sera from immunized mice as well as antigen-specific affinity purified human IgG antibodies reacted with sporozoite preparations in immunofluorescence and Western blot assays, and displayed strong in vitro inhibition of sporozoite invasion (ISI) into hepatoma cells. Conclusions: The polypeptide was recognized at high prevalence when tested against naturally induced human antibodies and was able to induce significant immunogenicity in mice. Additionally, specific antibodies were able to recognize sporozoites and were able to block sporozoite invasion in vitro. Further evaluation of this chimeric protein construct in preclinical phase e.g. in Aotus monkeys in order to assess the humoral and cellular immune responses as well as protective efficacy against parasite challenge of the vaccine candidate must be conducted. © 2013 Elsevier Ltd.


Orjuela L.I.,National University of Colombia | Orjuela L.I.,Grupo Of Entomologia Instituto Nacional Of Salud | Ahumada M.L.,Grupo Of Entomologia Instituto Nacional Of Salud | Avila I.,Instituto Departamental Of Salud Of Narino | And 3 more authors.
Malaria Journal | Year: 2015

Background: Anopheles calderoni was first recognized in Colombia in 2010 as this species had been misidentified as Anopheles punctimacula due to morphological similarities. An. calderoni is considered a malaria vector in Peru and has been found naturally infected with Plasmodium falciparum in Colombia. However, its biting behaviour, population dynamics and epidemiological importance have not been well described for Colombia. Methods: To assess the contribution of An. calderoni to malaria transmission and its human biting behaviour and spatial/temporal distribution in the southwest of Colombia, human landing catches (HLC) and larval collections were carried out in a cross-sectional, entomological study in 22 localities between 2011 and 2012, and a longitudinal study was performed in the Boca de Prieta locality in Olaya Herrera municipality between July 2012 and June 2013. All mosquitoes determined as An. calderoni were tested by ELISA to establish infection with Plasmodium spp. Results: Larvae of An. calderoni were found in four localities in 12 out of 244 breeding sites inspected. An. calderoni adults were collected in 14 out of 22 localities during the cross-sectional study and represented 41.3% (459 of 1,111) of the collected adult specimens. Other species found were Anopheles albimanus (54.7%), Anopheles apicimacula (2.1%), Anopheles neivai (1.7%), and Anopheles argyritarsis (0.2%). In the localities that reported the highest malaria Annual Parasite Index (>10/1,000 inhabitants) during the year of sampling, An. calderoni was the predominant species (>90% of the specimens collected). In the longitudinal study, 1,528 An. calderoni were collected by HLC with highest biting rates in February, May and June 2013, periods of high precipitation. In general, the species showed a preference to bite outdoors (p < 0.001). In Boca de Prieta, two specimens of An. calderoni were ELISA positive for Plasmodium circumsporozoite protein: one for P. falciparum and one for Plasmodium vivax VK-210. This represents an overall sporozoite rate of 0.1% and an annual entomological inoculation rate of 2.84 infective bites/human/year. Conclusions: This study shows that An. calderoni is a primary malaria vector in the southwest of Colombia. Its observed preference for outdoor biting is a major challenge for malaria control. © 2015 Orjuela et al.


Arevalo-Herrera M.,Caucaseco Scientific Research Center | Arevalo-Herrera M.,University of Valle | Lopez-Perez M.,Caucaseco Scientific Research Center | Medina L.,Asoclinic Inmunologia Ltda | And 3 more authors.
Malaria Journal | Year: 2015

Background: Malaria transmission in Latin America is generally hypoendemic and unstable, with Plasmodium vivax as the most prevalent species. However, only a few studies have been carried out in areas with low and unstable transmission, whereas the clinical profile of malaria has been broadly described in hyperendemic areas. The pattern of clinical manifestations and laboratory findings in low to moderate endemic areas of Colombia is reported here. Methods: A passive surveillance study was conducted between 2011 and 2013 involving 1,328 patients with Plasmodium falciparum, P. vivax or mixed malaria infections attending malaria points-of-care of four malaria endemic-areas with distinct transmission intensities and parasite distribution. Trained physicians recorded clinical symptoms and signs as well as socio-demographic characteristics of study participants. Haematological, biochemical and urine tests were performed at the time of diagnosis. Results: Out of 1,328 cases, 673 (50.7%) were caused by P. vivax; 650 (48.9%) were due to P. falciparum; and five (0.4%) patients had mixed infections (P. falciparum/P. vivax). Most patients (92.5%) presented with uncomplicated malaria characterized by fever, chills, headache, sweating, myalgia/arthralgia and parasitaemia ≤20,000 parasites/μL. Fever, tachycardia, pallor and abdominal pain on palpation were more frequent in P. falciparum patients, whereas mild hepatomegaly and splenomegaly were mostly observed with P. vivax. Non-severe anaemia (Hb 7.0-10.9 g/dL) was observed in 20% of the subjects, whereas severe anaemia (Hb∈;lt7.0 g/dL) was present in four patients. Half of the patients presented thrombocytopaenia regardless of parasite species. Leukopaenia, neutrophilia and monocytosis were frequently observed in patients infected with P. falciparum. Mild-to-moderate biochemical alterations were present in ~25% of the patients, particularly abnormal bilirubin in those with P. falciparum and abnormal transaminases in P. vivax malaria patients. Proteinuria was present in ~50% of the patients regardless of parasite species, whereas haemoglobinuria was more common in P. vivax infections. Only 7.5% of the cases were classified as clinically severe malaria, caused by both P. vivax and P. falciparum. Conclusions: The high prevalence of uncomplicated malaria associated with moderate parasitaemia suggests the importance of timely diagnosis and effective treatment and encourages new activities to further decrease complicated malaria cases and mortality. © 2015 Arévalo-Herrera et al.; licensee BioMed Central.


Herrera S.,Caucaseco Scientific Research Center | Herrera S.,Latin American Center for Malaria Research | Vallejo A.F.,Caucaseco Scientific Research Center | Vallejo A.F.,Latin American Center for Malaria Research | And 7 more authors.
Malaria Journal | Year: 2014

Background: Massive implementation of malaria diagnostics in low-resource countries is regarded as a pivotal strategy in control and elimination efforts. Although malaria rapid diagnostic tests (RDTs) are considered a viable alternative, there are still obstacles to the widespread implementation of this strategy, such as reporting constraints and lack of proper quality assurance of RDT-based programmes at point-of-care (POC). Methods. A prospective cohort of patients, seeking routine care for febrile episodes at health centres in malaria-endemic areas of Colombia, was used to assess the diagnostic performance of a device based on smartphone technology (Deki ReaderTM, former codename "GenZero"), that assists users at POC to process RDTs. After informed consent, patients were enrolled into the study and blood samples were collected for thick blood smear (TBS) and RDT. The RDT results were interpreted by both visual inspection and Deki Reader device and concordance between visual and device interpretation was measured. Microscopy corrected by real-time polymerase chain reaction (PCR) and microscopy were "gold standard" tests to assess the diagnostic performance. Results: In total, 1,807 patients were enrolled at seven health centres in malaria-endemic areas of Colombia. Thirty-three Plasmodium falciparum and 100 Plasmodium vivax cases were positive by corrected microscopy. Both sensitivity and specificity were 93.9% (95% CI 69.7-95.2) and 98.7% (95% CI 98.5-99.4) for P. falciparum, and 98.0% (95% CI 90.3-98.9) and 97.9% (95% CI 97.1-98.5) for P. vivax. Percentage concordance between visual and device interpretation of RDT was 98.5% and 99.0% for P. vivax and P. falciparum, respectively.The RDT, when compared to TBS, showed high sensitivity and specificity for P. falciparum in both visual and device interpretation, and good overall diagnostic performance for P. vivax. Comparison between PCR as gold standard and visual and device interpretation showed acceptable overall performance for both species. Conclusions: The diagnostic performance of the Deki Reader was comparable to visual interpretation of RDTs (without significant differences) for both malaria species. Providing standardized automated interpretation of RDTs at POC in remote areas, in addition to almost real-time reporting of cases and enabling quality control would greatly benefit large-scale implementation of RDT-based malaria diagnostic programmes. © 2014 Herrera et al.; licensee BioMed Central Ltd.


Chaparro P.,National Institute of Health of Colombia | Chaparro P.,National University of Colombia | Padilla J.,Ministry of Health and Social Protection of Colombia | Vallejo A.F.,Caucaseco Scientific Research Center | And 3 more authors.
Malaria Journal | Year: 2013

Background: Although malaria has presented a significant reduction in morbidity and mortality worldwide during the last decade, it remains a serious global public health problem. In Colombia, during this period, many factors have contributed to sustained disease transmission, with significant fluctuations in an overall downward trend in the number of reported malaria cases. Despite its epidemiological importance, few studies have used surveillance data to describe the malaria situation in Colombia. This study aims to describe the characteristics of malaria cases reported during 2010 to the Public Health Surveillance System (SIVIGILA) of the National Institute of Health (INS) of Colombia. Methods. A descriptive study was conducted using malaria information from SIVIGILA 2010. Cases, frequencies, proportions, ratio and measures of central tendency and data dispersion were calculated. In addition, the annual parasite index (API) and the differences between the variables reported in 2009 and 2010 were estimated. Results: A total of 117,108 cases were recorded by SIVIGILA in 2010 for a national API of 10.5/1,000 habitants, with a greater number of cases occurring during the first half of the year. More than 90% of cases were reported in seven departments (=states): Antioquia: 46,476 (39.7%); Chocó: 22,493 (19.2%); Cordoba: 20,182 (17.2%); Valle: 6,360 (5.4%); Guaviare: 5,876 (5.0%); Nariño: 4,085 (3.5%); and Bolivar: 3,590 (3.1%). Plasmodium vivax represented ∼71% of the cases; Plasmodium falciparum ∼28%; and few infrequent cases caused by Plasmodium malariae. Conclusions: Overall, a greater incidence was found in men (65%) than in women (35%). Although about a third of cases occurred in children <15 years, most of these cases occurred in children >5 years of age. The ethnic distribution indicated that about 68% of the cases occurred in mestizos and whites, followed by 23% in Afro-descendants, and the remainder (9%) in indigenous communities. In over half of the cases, consultation occurred early, with 623 complicated and 23 fatal cases. However, the overall incidence increased, corresponding to an epidemic burst and indicating the need to strengthen prevention and control activities as well as surveillance to reduce the risk of outbreaks and the consequent economic and social impact. © 2013 Chaparro et al.; licensee BioMed Central Ltd.

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