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Low-density and asymptomaticWe analysed individual participant data from population-based surveys that measuredWe pooled 24,986 observations from six sites in Brazil and Peru.AsymptomaticUS National Institutes of Health, Fundação de Amparo à Pesquisa do Estado de São Paulo, and Belgium Development Cooperation.

Beside diagnostic uncertainties due to the lack of a perfect gold standard test for Helicobacter pylori infection, the diagnosis and the prevalence estimation for this infection encounter particular challenges in Africa including limited diagnostic tools and specific genetic background. We developed and evaluated the accuracy of an enzyme-linked immunosorbent assay (ELISA) system tailored for H. pylori genetics in Africa (HpAfr-ELISA). Strains belonging to main genetic populations infecting Africans were exploited as sources for whole-cell antigens to establish in-house the ELISA system. A phase II unmatched case-control study explored the diagnostic accuracy of the HpAfr-ELISA using a training set of samples collected from dyspeptic patients from Kinshasa, the Democratic Republic of Congo (DRC) who had been tested with invasive standard tests (i.e., histology, culture, and rapid urease test) in 2017. Then the assay was cross-validated through a community-based survey assessing the prevalence of H. pylori and associated factors in 425 adults from Mbujimayi, DRC in 2018. Bayesian inferences were used to deal with statistical uncertainties of estimates (true prevalence, sensitivity, and specificity) in the study population. At its optimal cut-off-value 20.2 U/mL, the assay achieved an estimated sensitivity of 97.6% (95% credible interval [95%CrI]: 89.2; 99.9%) and specificity of 90.5% (95%CrI: 78.6; 98.5). Consistent outcomes obtained at repeated tests attested the robustness of the assay (negative and positive agreements always > 70%). The true prevalence of H. pylori was estimated 53.8% [95%CrI: 42.8; 62.7%]. Increasing age (adjusted odds ratio [aOR] > 1.0 [95% confidence interval (CI): > 1.0; 1.1]; p, Author summary Enzyme-linked immunosorbent assay (ELISA) systems are useful tools for mass screening of Helicobacter pylori infection but their use encounters important challenges in Africa. This is mainly due to the specific genetic background of African H. pylori that may jeopardize the accuracy of currently available ELISA kits. In this study, we developed a new ELISA system, i.e. HpAfr-ELISA, based on pooled antigens of H. pylori that represent main genetic populations colonizing Africa. This new assay could be validated analytically using training samples collected in H. pylori positive and negative patients from the Democratic Republic of Congo (DRC). Then, the tool was successfully applied to a real-world community-based mass survey aiming at assessing the epidemiology of H. pylori in a rural area of the DRC. The characteristics of the HpAfr-ELISA assay indicated good robustness and high performances for detection of H. pylori. Statistical modeling enabled estimating the true latent prevalence of H. pylori infection and identifying factors predicting the exposition to the infection in the study population. This outcome will be useful for drawing efficient health policies and optimally allocating available resources to fight the H. pylori infection and related complications (e.g., gastric cancer) in the study area and globally in Africa.

This is the first study to assess the risk of co-endemic Plasmodium vivax and Plasmodium falciparum transmission in the Peruvian Amazon using boosted regression tree (BRT) models based on social and environmental predictors derived from satellite imagery and data. Yearly cross-validated BRT models were created to discriminate high-risk (annual parasite index API > 10 cases/1000 people) and very-high-risk for malaria (API > 50 cases/1000 people) in 2766 georeferenced villages of Loreto department, between 2010–2017 as other parts in the article (graphs, tables, and texts). Predictors were cumulative annual rainfall, forest coverage, annual forest loss, annual mean land surface temperature, normalized difference vegetation index (NDVI), normalized difference water index (NDWI), shortest distance to rivers, time to populated villages, and population density. BRT models built with predictor data of a given year efficiently discriminated the malaria risk for that year in villages (area under the ROC curve (AUC) > 0.80), and most models also effectively predicted malaria risk in the following year. Cumulative rainfall, population density and time to populated villages were consistently the top three predictors for both P. vivax and P. falciparum incidence. Maps created using the BRT models characterize the spatial distribution of the malaria incidence in Loreto and should contribute to malaria-related decision making in the area.

Background. Remote rural riverine villages account for most of the reported malaria cases in the Peruvian Amazon. As transmission decreases due to intensive standard control efforts, malaria strategies in these villages will need to be more focused and adapted to local epidemiology. Methods. By integrating parasitological, entomological, and environmental observations between January 2016 and June 2017, we provided an in-depth characterization of malaria transmission dynamics in 4 riverine villages of the Mazan district, Loreto department. Results. Despite variation across villages, malaria prevalence by polymerase chain reaction in March 2016 was high (>25% in 3 villages), caused by Plasmodium vivax mainly and composed of mostly submicroscopic infections. Housing without complete walls was the main malaria risk factor, while households close to forest edges were more commonly identified as spatial clusters of malaria prevalence. Villages in the basin of the Mazan River had a higher density of adult Anopheles darlingi mosquitoes, and retained higher prevalence and incidence rates compared to villages in the basin of the Napo River despite test-and-treat interventions. Conclusions. High heterogeneity in malaria transmission was found across and within riverine villages, resulting from interactions between the microgeographic landscape driving diverse conditions for vector development, housing structure, and human behavior. This work was supported by the Consejo Nacional de Ciencia, Tecnologia e Innovacion Tecnologica (grant number 008-2014-FONDECYT); the Academie de Recherche et d'Enseignement Superieur-Commission de la Cooperation au Developpement of Belgium (grant number ARES-CCD, PRD-Peru 2014-2019 to N. S., A. L. C., and A. R. A.); World Health Organization Special Programme for Research and Training in Tropical Diseases (grant number 201460655 to D. G.); and National Institutes of Health, National Institute of Allergy and Infectious Diseases (grant numbers U19AI089681 to J. M. V. and R01AI110112 to J. E. C.). A. R. A. is a Postdoctoral Researcher of the Fonds de la Recherche Scientifique (FNRS, Belgium).

Background Malaria is highly heterogeneous: its changing malaria microepidemiology needs to be addressed to support malaria elimination efforts at the regional level. Methods A 3-year, population-based cohort study in 2 settings in the Peruvian Amazon (Lupuna, Cahuide) followed participants by passive and active case detection from January 2013 to December 2015. Incidence and prevalence rates were estimated using microscopy and polymerase chain reaction (PCR). Results Lupuna registered 1828 infections (1708 Plasmodium vivax, 120 Plasmodium falciparum; incidence was 80.7 infections/100 person-years (95% confidence interval [CI] , 77.1–84.5). Cahuide detected 1046 infections (1024 P vivax, 20 P falciparum, 2 mixed); incidence was 40.2 infections/100 person-years (95% CI, 37.9–42.7). Recurrent P vivax infections predominated onwards from 2013. According to PCR data, submicroscopic predominated over microscopic infections, especially in periods of low transmission. The integration of parasitological, entomological, and environmental observations evidenced an intense and seasonal transmission resilient to standard control measures in Lupuna and a persistent residual transmission after severe outbreaks were intensively handled in Cahuide. Conclusions In 2 exemplars of complex local malaria transmission, standard control strategies failed to eliminate submicroscopic and hypnozoite reservoirs, enabling persistent transmission.

The spread of Plasmodium falciparum isolates carrying mutations in the kelch13 (Pfkelch13) gene associated with artemisinin resistance (PfART-R) in southeast Asia threatens malaria control and elimination efforts. Emergence of PfART-R in Africa would result in a major public health problem. In this systematic review, we investigate the frequency and spatial distribution of Pfkelch13 mutants in Africa, including mutants linked to PfART-R in southeast Asia. Seven databases were searched (PubMed, Embase, Scopus, African Journal Online, African Index Medicus, Bioline, and Web of Science) for relevant articles about polymorphisms of the Pfkelch13 gene in Africa before January, 2019. Following PRISMA guidelines, 53 studies that sequenced the Pfkelch13 gene of 23 100 sample isolates in 41 sub-Saharan African countries were included. The Pfkelch13 sequence was highly polymorphic (292 alleles, including 255 in the Pfkelch13-propeller domain) but with mutations occurring at very low relative frequencies. Non-synonymous mutations were found in only 626 isolates (2·7%) from west, central, and east Africa. According to WHO, nine different mutations linked to PfART-R in southeast Asia (Phe446Ile, Cys469Tyr, Met476Ile, Arg515Lys, Ser522Cys, Pro553Leu, Val568Gly, Pro574Leu, and Ala675Val) were detected, mainly in east Africa. Several other Pfkelch13 mutations, such as those structurally similar to southeast Asia PfART-R mutations, were also identified, but their relevance for drug resistance is still unknown. This systematic review shows that Africa, thought to not have established PfART-R, reported resistance-related mutants in the past 5 years. Surveillance using PfART-R molecular markers can provide valuable decision-making information to sustain the effectiveness of artemisinin in Africa.

Background Increasing resistance of Plasmodium falciparum to sulfadoxine-pyrimethamine (SP) threatens its usefulness for intermittent preventive treatment in pregnancy (IPTp-SP). The prophylactic effects of IPTp-SP on maternal malaria and adverse pregnancy outcomes were evaluated in Kingasani Hospital, Kinshasa in the Democratic Republic of Congo (DRC). Methods Laboring women (n = 844) and respective newborns were investigated. Blood samples collected from women were tested for malaria using rapid diagnostic test (RDT), blood smears examination, and real-time PCR. The hemoglobin level was measured by HemoCue© analyzer. A PCR-RFLP method was applied for detecting N51I, C59R, and S108N mutations on dhfr along with A437G and K540E mutations on dhps in P. falciparum positive samples. Logistic regression models assessed relationships between IPTp-SP uptake and pregnancy outcomes. Results P. falciparum malaria was detected at delivery in 10.8% of women and was statistically associated with fever during the pregnancy (OR = 2.9 [1.5; 6.3]; p = 0.004) and maternal anemia (OR = 3.9 [2.4; 6.3]; p < 0.001). One out of five parasites was a quintuple mutant encoding dhfr mutations 51I, 59R, and 108 N along with dhps mutations 437G and 540E. The molecular profile of parasites (i.e., 32.6% of parasites carrying dhps K540E) was suitable with continued use of SP for IPTp. IPTp-SP uptake was not associated with reduced maternal malaria, fever reported in pregnancy, or fetal deaths (p > 0.05). Conversely, three or more doses of SP were associated with reduced maternal anemia at delivery (OR = 0.4 [0.2; 0.9]; p = 0.024), shortened gestation (OR = 0.4 [0.2; 0.8]; p = 0.009), and low-birth weights (OR = 0.2 [0.1; 0.5]; p < 0.001). Conclusion IPTp-SP was not associated with reduced maternal malaria in our study, but evidence was found of a prophylactic effect against adverse pregnancy outcomes. To counteract further loss of clinical effects of IPTp-SP in the study population, alternative strategies able to improve its anti-malarial efficacy such as combination of SP with partner molecules should be implemented.

Background Malaria is one of the major causes of childhood death in sub-Saharan countries. A reliable estimation of malaria prevalence is important to guide and monitor progress toward control and elimination. The aim of the study was to estimate the true prevalence of malaria in children under five in the Democratic Republic of the Congo, Uganda and Kenya, using a Bayesian modelling framework that combined in a novel way malaria data from national household surveys with external information about the sensitivity and specificity of the malaria diagnostic methods used in those surveys—i.e., rapid diagnostic tests and light microscopy. Methods Data were used from the Demographic and Health Surveys (DHS) and Malaria Indicator Surveys (MIS) conducted in the Democratic Republic of the Congo (DHS 2013–2014), Uganda (MIS 2014–2015) and Kenya (MIS 2015), where information on infection status using rapid diagnostic tests and/or light microscopy was available for 13,573 children. True prevalence was estimated using a Bayesian model that accounted for the conditional dependence between the two diagnostic methods, and the uncertainty of their sensitivities and specificities obtained from expert opinion. Results The estimated true malaria prevalence was 20% (95% uncertainty interval [UI] 17%–23%) in the Democratic Republic of the Congo, 22% (95% UI 9–32%) in Uganda and 1% (95% UI 0–3%) in Kenya. According to the model estimations, rapid diagnostic tests had a satisfactory sensitivity and specificity, and light microscopy had a variable sensitivity, but a satisfactory specificity. Adding reported history of fever in the previous 14 days as a third diagnostic method to the model did not affect model estimates, highlighting the poor performance of this indicator as a malaria diagnostic. Conclusions In the absence of a gold standard test, Bayesian models can assist in the optimal estimation of the malaria burden, using individual results from several tests and expert opinion about the performance of those tests. Electronic supplementary material The online version of this article (10.1186/s12936-018-2211-y) contains supplementary material, which is available to authorized users.

Malaria has steadily increased in the Peruvian Amazon over the last five years. This study aimed to determine the parasite prevalence and micro-geographical heterogeneity of Plasmodium vivax parasitaemia in communities of the Peruvian Amazon. Four cross-sectional active case detection surveys were conducted between May and July 2015 in four riverine communities in Mazan district. Analysis of 2785 samples of 820 individuals nested within 154 households for Plasmodium parasitaemia was carried out using light microscopy and qPCR. The spatio-temporal distribution of Plasmodium parasitaemia, dominated by P. vivax, was shown to cluster at both household and community levels. Of enrolled individuals, 47% had at least one P. vivax parasitaemia and 10% P. falciparum, by qPCR, both of which were predominantly sub-microscopic and asymptomatic. Spatial analysis detected significant clustering in three communities. Our findings showed that communities at small-to-moderate spatial scales differed in P. vivax parasite prevalence, and multilevel Poisson regression models showed that such differences were influenced by factors such as age, education, and location of households within high-risk clusters, as well as factors linked to a local micro-geographic context, such as travel and occupation. Complex transmission patterns were found to be related to human mobility among communities in the same micro-basin.

Background The global decline of malaria burden and goals for elimination has led to an increased interest in the fine-scale epidemiology of malaria. Micro-geographic heterogeneity of malaria infection could have implications for designing targeted small-area interventions. Methods Two-year longitudinal cohort study data were used to explore the spatial and spatio-temporal distribution of malaria episodes in 2040 children aged

BACKGROUND. Serological tools for the accurate detection of recent malaria exposure are needed to guide and monitor malaria control efforts. IgG responses against Plasmodium vivax and P. falciparum merozoite surface protein-10 (MSP10) were measured as a potential way to identify recent malaria exposure in the Peruvian Amazon. METHODS. A field-based study included 470 participants in a longitudinal cohort who completed a comprehensive evaluation: light microscopy and PCR on enrollment, at least 1 monthly follow-up by light microscopy, a second PCR, and serum and dried blood spots for serological analysis at the end of the follow-up. IgG titers against novel mammalian cell–produced recombinant PvMSP10 and PfMSP10 were determined by ELISA. RESULTS. During the follow-up period, 205 participants were infected, including 171 with P. vivax, 26 with P. falciparum, 6 with infections by both species but at different times, and 2 with mixed infections. Exposure to P. vivax was more accurately identified when serological responses to PvMSP10 were obtained from serum (sensitivity, 58.1%; specificity, 81.8%; AUC: 0.76) than from dried blood spots (sensitivity, 35.2; specificity, 83.5%; AUC: 0.64) (PAUC < 0.001). Sensitivity was highest (serum, 82.9%; dried blood spot, 45.7%) with confirmed P. vivax infections occurring 7–30 days before sample collection; sensitivity decreased significantly in relation to time since last documented infection. PvMSP10 serological data did not show evidence of interspecies cross-reactivity. Anti-PfMSP10 responses poorly discriminated between P. falciparum–exposed and nonexposed individuals (AUC = 0.59; P > 0.05). CONCLUSION. Anti-PvMSP10 IgG indicates recent exposure to P. vivax at the population level in the Amazon region. Serum, not dried blood spots, should be used for such serological tests. FUNDING. Cooperative agreement U19AI089681 from the United States Public Health Service, NIH/ National Institute of Allergy and Infectious Diseases, as the Amazonian International Center of Excellence in Malaria Research.

Background Case management is one of the principal strategies for malaria control. This study aimed to estimate the economic costs of uncomplicated malaria case management and explore the influence of health-seeking behaviours on those costs. Methods A knowledge, attitudes and practices (KAP) survey was applied to 680 households of fifteen communities in Mazan-Loreto in March 2017, then a socio-economic survey was conducted in September 2017 among 161 individuals with confirmed uncomplicated malaria in the past 3 months. Total costs per episode were estimated from both provider (Ministry of Health, MoH) and patient perspectives. Direct costs were estimated using a standard costing estimation procedure, while the indirect costs considered the loss of incomes among patients, substitute labourers and companions due to illness in terms of the monthly minimum wage. Sensitivity analysis evaluated the uncertainty of the average cost per episode. Results The KAP survey showed that most individuals (79.3%) that had malaria went to a health facility for a diagnosis and treatment, 2.7% received those services from community health workers, and 8% went to a drugstore or were self-treated at home. The average total cost per episode in the Mazan district was US$ 161. The cost from the provider’s perspective was US$ 30.85 per episode while from the patient’s perspective the estimated cost was US$ 131 per episode. The average costs per Plasmodium falciparum episode (US$ 180) were higher than those per Plasmodium vivax episode (US$ 156) due to longer time lost from work by patients with P. falciparum infections (22.2 days) than by patients with P. vivax infections (17.0 days). The delayed malaria diagnosis (after 48 h of the onset of symptoms) was associated with the time lost from work due to illness (adjusted mean ratio 1.8; 95% CI 1.3, 2.6). The average cost per malaria episode was most sensitive to the uncertainty around the lost productivity cost due to malaria. Conclusions Despite the provision of free malaria case management by MoH, there is delay in seeking care and the costs of uncomplicated malaria are mainly borne by the families. These costs are not well perceived by the society and the substantial financial impact of the disease can be frequently undervalued in public policy planning.

Background In Vietnam, the importance of vivax malaria relative to falciparum during the past decade has steadily increased to 50%. This, together with the spread of multidrug-resistant Plasmodium falciparum, is a major challenge for malaria elimination. A 2-year prospective cohort study to assess P. vivax morbidity after radical cure treatment and related risk factors was conducted in Central Vietnam. Methods and findings The study was implemented between April 2009 and December 2011 in four neighboring villages in a remote forested area of Quang Nam province. P. vivax-infected patients were treated radically with chloroquine (CQ; 25 mg/kg over 3 days) and primaquine (PQ; 0.5 mg/kg/day for 10 days) and visited monthly (malaria symptoms and blood sampling) for up to 2 years. Time to first vivax recurrence was estimated by Kaplan–Meier survival analysis, and risk factors for first and recurrent infections were identified by Cox regression models. Among the 260 P. vivax patients (61% males [159/260]; age range 3–60) recruited, 240 completed the 10-day treatment, 223 entered the second month of follow-up, and 219 were followed for at least 12 months. Most individuals (76.78%, 171/223) had recurrent vivax infections identified by molecular methods (polymerase chain reaction [PCR]); in about half of them (55.61%, 124/223), infection was detected by microscopy, and 84 individuals (37.67%) had symptomatic recurrences. Median time to first recurrence by PCR was 118 days (IQR 59–208). The estimated probability of remaining free of recurrence by month 24 was 20.40% (95% CI [14.42; 27.13]) by PCR, 42.52% (95% CI [35.41; 49.44]) by microscopy, and 60.69% (95% CI [53.51; 67.11]) for symptomatic recurrences. The main risk factor for recurrence (first or recurrent) was prior P. falciparum infection. The main limitations of this study are the age of the results and the absence of a comparator arm, which does not allow estimating the proportion of vivax relapses among recurrent infections. Conclusion A substantial number of P. vivax recurrences, mainly submicroscopic (SM) and asymptomatic, were observed after high-dose PQ treatment (5.0 mg/kg). Prior P. falciparum infection was an important risk factor for all types of vivax recurrences. Malaria elimination efforts need to address this largely undetected P. vivax transmission by simultaneously tackling the reservoir of P. falciparum and P. vivax infections., In a cohort study in 4 villages in Vietnam, Thanh Vinh Pham and colleagues investigate outcomes 1-2 years following a high dose primaquine regimen to treat P. vivax malaria., Author summary Why was this study done? WHO currently recommends a 14-day primaquine (PQ) regimen at 0.5 mg/kg/day together with chloroquine (CQ; 25 mg/kg over 3 days) for the radical cure of P. vivax infections in Southeast Asia. Between 2007 and 2009, Vietnam introduced a high-dose PQ regimen shortened to 10 days in an attempt to improve patient compliance. A 2-year one-arm cohort study was conducted between May 2009 and December 2011 in four remote villages of Central Vietnam to determine the incidence and risk factors for vivax recurrence after the new radical cure regimen. What did the researchers do and find? 260 P. vivax-infected patients were enrolled between May 2009 and December 2010, received directly observed 10-day treatment, and were followed up monthly for up to 24 months. During scheduled and unscheduled visits, participants were examined, and blood samples were systematically taken for light microscopy (LM) and polymerase chain reaction (PCR) analysis. All LM-detected vivax infections (patent) were treated with CQ alone, while PQ was given at the end of individual follow-up. Time-to-event analysis showed that by month 24, only 20% of patients remained free of vivax recurrences detected by PCR, while this was 40% for patent (by LM) recurrences. The majority of recurrences were submicroscopic and asymptomatic because only 38% of patients had symptomatic recurrences. The main risk factors for P. vivax recurrences were prior P. falciparum infections, especially submicroscopic, and prior treatment of vivax infections with CQ. What do these findings mean? Despite the age (10 years) of the data collected, the results of this cohort study remain relevant to the current malaria situation in Vietnam, where the elimination of vivax malaria and of multidrug-resistant P. falciparum are major challenges. A substantial proportion of the vivax malaria reservoir is not detected by current surveillance strategies in Vietnam, i.e., passive and re-active case detection based on LM/rapid diagnostic tests (RDTs). Prior P. falciparum infections (including submicroscopic) and vivax infections treated with CQ alone were significant risk factors for vivax recurrences. To further improve vivax elimination efforts in Vietnam, new treatment strategies (i.e., single-dose radical treatment) and more sensitive diagnostic tools (i.e., field PCR/ultrasensitive RDTs) simultaneously tackling falciparum and vivax malaria infections are needed.

Background: Faced with the resurgence of malaria, malaria surveillance in the Peruvian Amazon incorporated consecutive active case detection (ACD) interventions using light microscopy (LM) as reactive measure in communities with an unusual high number of cases during high transmission season (HTS). We assessed the effectiveness in malaria detection of this local ACD-based strategy. Methods: A cohort study was conducted in June&ndash, July 2015 in Mazan, Loreto. Four consecutive ACD interventions at intervals of 10 days were conducted in four riverine communities (Gamitanacocha, Primero de Enero, Libertad and Urco Mira&ntilde, o). In each intervention, all inhabitants were visited at home, and finger-prick blood samples collected for immediate diagnosis by LM and on filter paper for later analysis by quantitative real-time polymerase chain reaction (qPCR). Effectiveness was calculated by dividing the number of malaria infections detected using LM by the number of malaria infections detected by delayed qPCR. Results: Most community inhabitants (88.1%, 822/933) were present in at least one of the four ACD interventions. A total of 451 infections were detected by qPCR in 446 participants (54.3% of total participants), five individuals had two infections. Plasmodium vivax was the predominant species (79.8%), followed by P. falciparum (15.3%) and P. vivax-P. falciparum co-infections (4.9%). Most qPCR-positive infections were asymptomatic (255/448, 56.9%). The ACD-strategy using LM had an effectiveness of 22.8% (detection of 103 of the total qPCR-positive infections). Children aged 5&ndash, 14 years, and farming as main economic activity were associated with P. vivax infections. Conclusions: Although the ACD-strategy using LM increased the opportunity of detecting and treating malaria infections during HTS, the number of detected infections was considerably lower than the real burden of infections (those detected by qPCR).

Introduction: Efforts have been made to reduce HIV/AIDS-related mortality by delivering antiretroviral therapy (ART) treatment. However, HIV patients in resource-poor settings are still dying, even if they are on ART treatment. This study aimed to explore the factors associated with HIV/AIDS-related mortality in Southwestern Ethiopia. Method: A non-concurrent retrospective cohort study which collected data from the clinical records of adult HIV/AIDS patients, who initiated ART treatment and were followed between January 2006 and December 2010, was conducted, to explore the factors associated with HIV/AIDS-related mortality at Jimma University Specialized Hospital (JUSH). Survival times (i.e., the time from the onset of ART treatment to the death or censoring) and different characteristics of patients were retrospectively examined. A best-fit model was chosen for the survival data, after the comparison between native semi-parametric Cox regression and parametric survival models (i.e., exponential, Weibull, and log-logistic). Result: A total of 456 HIV patients were included in the study, mostly females (312, 68.4%), with a median age of 30 years (inter-quartile range (IQR): 23-37 years). Estimated follow-up until December 2010 accounted for 1245 person-years at risk (PYAR) and resulted in 66 (14.5%) deaths and 390 censored individuals, representing a median survival time of 34.0 months ( IQR: 22.8-42.0 months). The overall mortality rate was 5.3/100 PYAR: 6.5/100 PYAR for males and 4.8/100 PYAR for females. The Weibull survival model was the best model for fitting the data (lowest AIC). The main factors associated with mortality were: baseline age (>35 years old, AHR = 3.8, 95% CI: 1.6-9.1), baseline weight (AHR = 0.93, 95% CI: 0.90-0.97), baseline WHO stage IV (AHR = 6.2, 95% CI: 2.2-14.2), and low adherence to ART treatment (AHR = 4.2, 95% CI: 2.5-7.1). Conclusion: An effective reduction in HIV/AIDS mortality could be achieved through timely ART treatment onset and maintaining high levels of treatment adherence. ispartof: International Journal of Environmental Research and Public Health vol:14 issue:3 ispartof: location:Switzerland status: published

Despite efforts made over decades by the Peruvian government to eliminate malaria, Plasmodium vivax remains a challenge for public health decision-makers in the country. The uneven distribution of its incidence, plus its complex pattern of dispersion, has made ineffective control measures based on global information that lack the necessary detail to understand transmission fully. In this sense, population genetic tools can complement current surveillance. This study describes the genetic diversity and population structure from September 2012 to March 2015 in three geographically distant settlements, Cahuide (CAH), Lupuna (LUP) and Santa Emilia (STE), located in the Peruvian Amazon. A total 777 P. vivax mono-infections, out of 3264, were genotyped. Among study areas, LUP showed 19.7% of polyclonal infections, and its genetic diversity (Hexp) was 0.544. Temporal analysis showed a significant increment of polyclonal infections and Hexp, and the introduction and persistence of a new parasite population since March 2013. In STE, 40.1% of infections were polyclonal, with Hexp = 0.596. The presence of four genetic clusters without signals of clonal expansion and infections with lower parasite densities compared against the other two areas were also found. At least four parasite populations were present in CAH in 2012, where, after June 2014, malaria cases decreased from 213 to 61, concomitant with a decrease in polyclonal infections (from 0.286 to 0.18), and expectedly variable Hexp. Strong signals of gene flow were present in the study areas and wide geographic distribution of highly diverse parasite populations were found. This study suggests that movement of malaria parasites by human reservoirs connects geographically distant malaria transmission areas in the Peruvian Amazon. The maintenance of high levels of parasite genetic diversity through human mobility is a critical barrier to malaria elimination in this region., Author summary Plasmodium vivax transmission is heterogeneous and discontinuous in the Peruvian Amazon. Such heterogeneity is the result of factors that include, but are not restricted to, the environment, public policies, and characteristics of the parasite, the vector, and human activities. All these factors make P. vivax transmission resilient to interventions. In order to achieve the goals of control and local elimination, P. vivax surveillance must inform how those factors sustain disease transmission in order to focalize and synchronize control strategies. In this study, we implemented molecular surveillance complemented with population genetic tools in the areas of Cahuide, Lupuna, and Santa Emilia located in the Peruvian Amazon. In particular, we characterize the transmission and the parasite genetic variation in these sites from September 2012 to March 2015. The changes in parasite diversity, the wide geographic dispersion of parasite subpopulation and the introduction of a new parasite clone or subpopulation in Lupuna documented in this study suggest that connectivity among the different endemic areas, likely due to human mobility, sustains disease transmission in the region hindering the success of control measures. This information must be considered in the design of current control strategies.

Malaria remains a major public health problem in the Peruvian Amazon where the persistence of high-risk transmission areas (hotspots) challenges the current malaria control strategies. This study aimed at identifying significant space-time clusters of malaria incidence in Loreto region 2002–2013 and to determine significant changes across years in relation to the control measures applied. Poisson regression and purely temporal, spatial, and space-time analyses were conducted. Three significantly different periods in terms of annual incidence rates (AIR) were identified, overlapping respectively with the pre-, during, and post- implementation control activities supported by PAMAFRO project. The most likely space-time clusters of malaria incidence for P. vivax and P. falciparum corresponded to the pre- and first two years of the PAMAFRO project and were situated in the northern districts of Loreto, while secondary clusters were identified in eastern and southern districts with the latest onset and the shortest duration of PAMAFRO interventions. Malaria in Loreto was highly heterogeneous at geographical level and over time. Importantly, the excellent achievements obtained during 5 years of intensified control efforts totally vanished in only 2 to 3 years after the end of the program, calling for sustained political and financial commitment for the success of malaria elimination as ultimate goal.

Background Understanding the dynamics of malaria transmission in diverse endemic settings is key for designing and implementing locally adapted and sustainable control and elimination strategies. A parasitological and epidemiological survey was conducted in September–October 2012, as a baseline underlying a 3-year population-based longitudinal cohort study. The aim was to characterize malaria transmission patterns in two contrasting ecological rural sites in the Peruvian Amazon, Lupuna (LUP), a riverine environment, and Cahuide (CAH), associated with road-linked deforestation. Methods After a full population census, 1941 individuals 3 years and older (829 in LUP, 1112 in CAH) were interviewed, clinically examined and had a blood sample taken for the detection of malaria parasites by microscopy and PCR. Species-specific parasite prevalence was estimated overall and by site. Multivariate logistic regression models assessed risk factors for parasite infection by PCR, while SaTScan detected spatial clusters of PCR-positive individuals within each site. In addition, data from routine malaria surveillance in the period 2009–2012 were obtained. Results Parasite prevalence by PCR was higher in CAH than in LUP for Plasmodium vivax (6.2% vs. 3.9%) and for Plasmodium falciparum (2.6% vs. 1.2%). Among PCR-confirmed infections, asymptomatic (Asy) parasite carriers were always more common than symptomatic (Sy) infections for P. vivax (Asy/Sy ratio: 2/1 in LUP and 3.7/1 in CAH) and for P. falciparum (Asy/Sy ratio: 1.3/1 in LUP and 4/1 in CAH). Sub-patent (Spat) infections also predominated over patent (Pat) infections for both species: P. vivax (Spat/Pat ratio: 2.8/1 in LUP and 3.7/1 in CAH) and P. falciparum malaria (Spat/Pat ratio: 1.9/1 in LUP and 26/0 in CAH). For CAH, age, gender and living in a household without electricity were significantly associated with P. vivax infection, while only age and living in a household with electricity was associated with P. falciparum infection. For LUP, only household overcrowding was associated with P. falciparum infection. The spatial analysis only identified well-defined clusters of P. vivax and P. falciparum infected individuals in CAH. Reported malaria incidence indicated that malaria transmission has long occurred in LUP with primarily seasonal patterns, and confirmed a malaria outbreak in CAH since May 2012. Conclusions This parasitological and epidemiological baseline assessment demonstrates that malaria transmission and parasite prevalence is heterogeneous in the Peruvian Amazon, and influenced by local socio-demographics and ecological contexts. Riverine and road construction/deforestation contexts must be taken into account in order to carry out effective anti-malaria control and elimination efforts. Electronic supplementary material The online version of this article (doi:10.1186/s12936-017-1957-y) contains supplementary material, which is available to authorized users.

Introduction: A large proportion of the Ethiopian population (approximately 68%) lives in malaria risk areas. Millions of long-lasting insecticide treated nets (LLINs) have been distributed as part of the malaria prevention and control strategy in the country. This study assessed the ownership, access and use of LLNs in the malaria endemic southwest Ethiopia. Methods: A community-based cross-sectional study was conducted in southwest Ethiopia during October–November 2015, including 836 households from sixteen villages around Gilgel-Gibe dam area. Indicators of ownership, access and use of LLINs were derived following the Roll Back Malaria (RBM) guidelines. Factors associated with failure for both LLIN access and use were analysed at household level using a multivariate logistic regression model. Results: The proportion of households with at least one LLIN was 82.7% (95% CI: 80.0, 85.1). However, only 68.9% (95% CI: 65.6, 71.9) had enough LLINs to cover all family members (with ≥one LLIN for every two persons). While 75.3% (95% CI: 68.4, 83.0) of the population was estimated to have accessed to LLINs, only 63.8% (95% CI: 62.3, 65.2) reported to have used a LLIN the previous night. The intra-household gap (i.e., households owning at least one LLIN, but unable to cover all family members) and the behavioral gap (i.e., household members who did not sleep under a LLIN despite having access to one) were 16.8% and 10.5%, respectively. Age, marital status and education of household heads, as well as household size and cooking using firewood were associated with the access to enough LLINs within households. Decreased access to LLINs at households was the main determinant for not achieving ≥80% household members sleeping under a LLIN the previous night. Other associated factors were household size and education level of household head. Conclusions: LLIN coverage levels in study villages remain below national targets of 100% for ownership and 80% for use. The access to enough LLINs within the households is the main restriction of LLIN use in the study area.

Malaria in Peru, dominated by Plasmodium vivax, remains a public health problem. The 1990s saw newly epidemic malaria emerge, primarily in the Loreto Department in the Amazon region, including areas near to Iquitos, the capital city, but sporadic malaria transmission also occurred in the 1990s-2000s in both north-coastal Peru and the gold mining regions of southeastern Peru. Although a Global Fund-supported intervention (PAMAFRO, 2005-2010) was temporally associated with a decrease of malaria transmission, from 2012 to the present, both P. Vivax and Plasmodium falciparum malaria cases have rapidly increased. The Peruvian Ministry of Health continues to provide artemesininbased combination therapy for microscopy-confirmed cases of P. Falciparum and chloroquine-primaquine for P. Vivax. Malaria transmission continues in remote areas nonetheless, where the mobility of humans and parasites facilitates continued reintroduction outside of ongoing surveillance activities, which is critical to address for future malaria control and elimination efforts. Ongoing P. Vivax research gaps in Peru include the following: identification of asymptomatic parasitemics, quantification of the contribution of patent and subpatent parasitemics to mosquito transmission, diagnosis of nonparasitemic hypnozoite carriers, and implementation of surveillance for potential emergence of chloroquine- and 8-aminoquinoline-resistant P. Vivax. Clinical trials of tafenoquine in Peru have been promising, and glucose-6-phosphate dehydrogenase deficiency in the region has not been observed to be a limitation to its use. Larger-scale challenges for P. Vivax (and malaria in general) in Peru include logistical difficulties in accessing remote riverine populations, consequences of government policy and poverty trends, and obtaining international funding for malaria control and elimination. Copyright © 2016 by The American Society of Tropical Medicine and Hygiene.

Objetivos. Evaluar la posesión, retención y uso de mosquiteros tratados con insecticida de larga duración (MTILD) luego de un año de su distribución en Loreto, Perú. Materiales y métodos. De julio a septiembre de 2007 se distribuyeron 26 185 MTILD Olyset Net® en 194 comunidades objetivo de Loreto, que protegieron a 45 331 personas. Posteriormente, se realizaron visitas de monitoreo (primera en diciembre de 2007 y segunda en julio de 2008) a los hogares de una muestra de 60 comunidades objetivo (30,9% del total), colectándose mediante un cuestionario semiestructurado los datos necesarios para el cálculo de indicadores de posesión, retención y uso de los MTILD. Resultados. En ambas visitas, la posesión de MTILD en hogares fue elevada (99,9% y 98,7%, respectivamente). La razón MTILD/persona disminuyó de 0,58 al momento de la distribución a 0,51 en la segunda visita, estimándose una retención al año de MTILD de 87%. En la primera visita, 99,0% de los niños Objectives. To assess long-lasting insecticide - treated bednet (LLITN) ownership, retention and usage one year after their distribution in Loreto, Peru. Materials and methods. From July to September 2007, 26,185 LLITNs Olyset Net ® were delivered in 194 targeted communities in the Peruvian Amazon region, covering 45,331 people. Two cross-sectional community-based surveys in December 2007 and July 2008 were undertaken in a sample of 60 targeted communities (30.9% out of the total). A semi-structured questionnaire was used to collect necessary data to calculate LLITN ownership, retention and usage indicators. Results. High LLITN household ownership was showed in both surveys (99.9% and 98.7%, respectively). LLITN/ person ratio decreased from 0.58 at the end of the LLITN delivery to 0.51 in the second survey, estimating LLITN retention of 87% after 1 year of intervention. In the first survey, 99.0% of all children

Objetivos. Evaluar la competencia de los microscopistas en el diagnóstico de la malaria mediante paneles de láminas estandarizados en la Amazonía peruana. Materiales y métodos. Estudio transversal, realizado entre los meses de julio y septiembre de 2007, en 122 establecimientos de salud de primer nivel de atención de la Amazonía peruana. En el marco del Proyecto PAMAFRO, se evaluó las competencias en el diagnóstico de malaria en 68 microscopistas sin experiencia (un año), utilizando paneles estandarizados de 20 láminas siguiendo las recomendaciones de la Organización Mundial de la Salud (OMS). Se definió concordancia como el porcentaje de aciertos que tuvo el microscopista en los diagnósticos (identificación de especie del parásito). Un microscopista con concordancia ≥90% (≥18 láminas acertadas) fue definido como "experto", 80 a 1 year) using standardized sets of 20 blood smear slides according to the World Health Organization (WHO) recommendations. A correct diagnosis (correct species identification) was defined as "agreement", a microscopist was qualified as an "expert" if they have an agreement ≥90% (≥ 18 slides with correct diagnosis), as a "referent" with an agreement between 80% and

Most cases of gastric cancers occur in non-industrialized countries but there is scarce information about the epidemiology of this illness in these countries. Our study examined whether there was a variation in the prevalence of gastric cancer in Lima, Peru over the last 2 decades. Subjects older than 29 years of age were included. They underwent an esophagogastroduedonoscopy at 3 socioeconomically different health facilities in Lima: a county hospital (7,168 subjects), a Peruvian-Japanese Clinic (14,794 individuals) and a private hospital (4,893 individuals). Birth cohort prevalence of gastric cancer was used. Regression models were calculated to predict the future prevalence of gastric cancer. It was found that the birth cohort prevalence of gastric cancer decreased in Peru from 22.7 to 2% (p < 0.001), from 12 to 0.5% (p < 0.001), and from 6.5 to 0.1% (p < 0.001) in the low, middle and high socioeconomic group, respectively. The prevalence of intestinal metaplasia decreased from 44.3 to 12.5% (p < 0.001), from 28.4 to 5% (p < 0.001), and from 19.4 to 2.2% (p < 0.001) in the low, middle and high socioeconomic status, respectively. These trends will likely persist over the future decades. Nevertheless, the prevalence of gastric cancer remains high in subjects older than 59 years of age in the low socioeconomic status. It is concluded that the prevalence of gastric cancer is decreasing in Peru, similar to the current trend undergoing in industrialized nations. However, there are still specific groups with high prevalence that might benefit from screening for early detection and treatment.

Background The identification of epidemiological pattern of infection with Plasmodium falciparum and Plasmodium vivax in malaria-endemic area, where multiple episodes are common, is important for intervention programmes. Methods A longitudinal cohort study based on weekly house-to-house visits was conducted between July 2008 and June 2010 in 2040 children less than 10 years of age, living nearby the Gilgel-Gibe hydroelectric power dam reservoir in order to determine factors associated with increased P. vivax and P. falciparum incidence. Two types of multivariate frailty models were applied (using time-to-first malaria episode data and time-to-recurrent malaria episode data), allowing the estimation of adjusted hazard ratios (AHR) of potential risk factors (gender, age, proximity to the dam reservoir, and season) for species-specific malaria incidence. Results Of 2040 children in 96 weeks of follow up, 864 children experienced at least one malaria episode: 685 due to P. falciparum in 548 children, and 385 due to P. vivax in 316 children. Plasmodiumvivax and P. falciparum malaria incidence rates were 8.2 (95 % CI: 7.3–9.1) and 14.6 (95 % CI: 13.4–15.6) per 1000 children per month, respectively. According to the time-to-recurrent event models, children aged ≥7 years had a lower risk of presenting P. vivax episodes (AHR = 0.6; 95 % CI: 0.4–0.9), but a higher risk of P. falciparum episodes, when compared with children under ≤3 years (AHR = 1.2; 95 % CI: 1.1–1.6). In addition, P. vivax (AHR = 2.7; 95 % CI: 2.2–3.5) and P. falciparum (AHR = 16.9; 95 % CI: 14.3–20.2) episodes were respectively 2.7 and 16.9 times more frequent in the dry season than in the long rainy season. Conclusions The analysis of all malaria episodes (first and recurrent episodes) in the malaria cohort suggests different species-specific patterns of malaria disease in children, with mild seasonality in the incidence of P. vivax episodes mostly observed in younger age groups, and with marked seasonality in the incidence of P. falciparum episodes mainly seen in older children. Electronic supplementary material The online version of this article (doi:10.1186/s12936-016-1253-2) contains supplementary material, which is available to authorized users.

OBJECTIVOS : Evaluar cinco elementos importantes de la calidad de atención (espacio físico, equipamiento, personal, tiempo para la atención, y consejería) en servicios de crecimiento y desarrollo (CRED) de 18 establecimientos de salud (EE. SS.) en nueve regiones con altos índices de pobreza en Perú. MATERIALES Y MÉTODOS. : Estudio cuali-cuantitativo realizado en Amazonas, Apurímac, Ayacucho, Cajamarca, Cusco, Huánuco, Huancavelica, Puno y Ucayali, que incluyó la observación directa (OD) durante la atención de CRED, grupos focales (GF) con usuarios (uno por establecimiento de salud), y entrevistas en profundidad (EEP) con trabajadores de salud (dos por establecimiento de salud). RESULTADOS : Se realizaron 18 OD para la verificación de ambientes y equipos, 23 OD de turnos completos de atención, 67 acompañamientos a usuarios de los servicios de CRED, 18 GF (118 madres participantes), y 36 EEP. Las madres y los profesionales de salud coincidieron en que existen limitaciones de infraestructura, equipamiento, materiales y personal que afectarían una atención de CRED de calidad. La demora en la atención, el incumplimiento de horarios, y la falta de calidez en la atención son los aspectos que generaron mayor insatisfacción en los usuarios. Solo en 24,3% del tiempo total de los turnos observados se realizaron actividades que generaron beneficio al usuario. Por su parte, la consejería estaría cumpliendo el objetivo de promover el mejoramiento de las prácticas de cuidado del niño. CONCLUSIONES : El estudio ha permitido identificar debilidades y áreas de oportunidad para reorientar los servicios de CRED, en el marco de la política de fortalecimiento del primer nivel de atención del sector Salud. [Quali-quantitative study on healthcare for children below the age of 3 at health establishments in nine underdeveloped regions of Peru]. OBJECTIVES: To assess five elements of healthcare quality (physical space, equipment, personnel, waiting time, and counseling) in growth and development services (GDS) at 18 healthcare establishments in nine regions of Peru with high rates of poverty. MATERIALS AND METHODS: A quali-quantitative study was carried out in the Amazonas, Apurímac, Ayacucho, Cajamarca, Cusco, Huánuco, Huancavelica, Puno, and Ucayali regions, that included direct observation (DO) during medical assistance in GDS, focus groups (FG, one user per healthcare establishment), and in-depth interviews (IDI) with healthcare workers (two per healthcare establishment). RESULTS: There were 18 DOs carried out to assess environment and equipment, 23 DOs of complete service shifts, 67 accompaniments to users during medical assistance in GDS, 18 FGs (118 participating mothers), and 36 IDIs. Both mothers and healthcare professionals agreed that there were limitations in infrastructure, equipment, materials, and personnel that impacted quality medical assistance in GDS. Delays in medical assistance, failure to comply with schedules, and lack of friendliness when providing medical care were the aspects that produced the greatest user dissatisfaction. Only 24.3% of the total amount of time spent at the healthcare establishment corresponded to beneficial activities for the user, although the Health Department was meeting the objective to promote improvement of childcare practices. CONCLUSIONS: The study was useful in identifying weaknesses and strengths that may help redirect GDS efforts within the framework of policies aimed at strengthening first-class medical assistance.

INTRODUCCIÓN: Para acelerar el descenso de la mortalidad de la niñez se debe enfrentar con éxito la mortalidad neonatal mediante la implementación de intervenciones oportunas y efectivas. OBJETIVOS: Identificar mediante una evaluación cualitativa potenciales retrasos y fallos en la atención materno-neonatal de neonatos fallecidos entre julio y diciembre del 2011 en Huánuco y Ucayali, Perú. MATERIALES Y MÉTODOS: Estudio cualitativo que incluyó 22 entrevistas en profundidad a madres de neonatos fallecidos en el periodo de estudio, usando una guía semi-estructurada basada en el cuestionario estándar de autopsia verbal recomendada por la Organización Mundial de la Salud. La entrevista incluyó además preguntas para identificar retrasos en la atención siguiendo el modelo de las tres demoras: a) en la toma de decisión para la búsqueda de atención, b) en la búsqueda de atención por limitado acceso a los servicios de salud, y c) en la misma atención en los servicios de salud. RESULTADOS : La mayoría de los retrasos fueron en la misma atención, asociados a fallos en prácticas materno-neonatales clave: valoración del trabajo de parto, atención del parto, diagnóstico del recién nacido y manejo del recién nacido sano y con complicaciones. CONCLUSIÓN: El estudio ha identificado retrasos y fallos frecuentes en la atención materno-neonatal en los mismos servicios de salud estudiados que requieren acciones correctivas para la reducion en la mortalidad neonatal. [Delays in maternal-neonatal care: qualitative assessment of neonatal deaths in reference health facilities of the Peruvian Ministry of Health ] INTRODUCTION: Accelerating the decrease of child mortality involves facing the neonatal mortality effectively by the implementation of opportune and appropriate interventions. OBJECTIVES: To identify potential delays in the maternal-neonatal care through a qualitative assessment of neonatal deaths between July and December, 2011 in Huanuco and Ucayali, Peru. MATERIALS AND METHODS: Qualitative study that included 22 in-depth interviews with mothers of newborns who died during the study period, using a semi-structured guide based on the standard questionnaire of verbal autopsy recommended by World Health Organization. Additional questions were included to indentify delays in the attention following the three-delays model: a) in the decision making for seeking medical care, b) in seeking care due to limited access to health services, and c) in receiving medical care at the health facility. RESULTS: Most of delays were in the health services, and were associated with failures in key maternal-neonatal practices: labor assessment, delivery care, diagnosis of the newborn, and management of healthy and critically ill newborns. CONCLUSION: The study has identified delays and failures in the maternal-neonatal care in the same study health facilities, which require corrective actions in order to have a positive impact on neonatal mortality.

BACKGROUND: Peru has presented a decreasing malaria trend during the last decade, particularly in areas on northwestern coast; however, a limited number of cases continues to be reported yearly mainly in malaria hotspots. METHODS: A two-phase study was conducted to identify spatial and temporal clusters of incident Plasmodium vivax malaria, as well as to determine risk factors associated with households (HH) presenting P. vivax malaria episodes in an urban area of the northwestern Peruvian Coast from June 2008 to May 2010. In the first stage, a full census of the study population was conducted, including geo-referencing of reported P. vivax episodes. In the second stage, a population-based case-control study allowed the identification of risk factors associated with HHs reporting episodes. A total of 117 case HHs with reported P. vivax and 117 control HHs without malaria episodes were assessed. A semi-structured questionnaire was used to interview the head of households and to collect data on HH location and structure, availability of public services, preventive malaria measures, family member with outdoor occupation (farmer, moto-taxi driver), and other HH characteristics. Univariate and multivariate logistic regression analyses were performed to determine case-HH risk factors. SaTScan was used to detect spatial and temporal P. vivax malaria clusters. RESULTS: The most likely spatial cluster of malaria incidence included 1,040 people (22.4% of total population) in 245 HHs (24.6% of total HHs) accounting for 283 malaria episodes (40.1% of total episodes) during the study period (RR = 2.3, p < 0.001). A temporal cluster was also identified from April 12, 2009 to July 4, 2009 accounting for 355 malaria episodes (50.4% of total episodes) (RR = 7.2, p = 0.001). Factors significantly associated with case HHs compared with control HHs were: proximity to water drain < 200 metres (OR = 2.3, 95% CI: 1.3, 4.0); HH size >5 individuals (OR = 1.8, 95% CI: 1.0, 3.2); lack of potable water (OR = 1.8, 95% CI: 1.1, 3.2); and having domestic and peridomestic animals (OR = 3.6, 95% CI: 1.3, 9.5). CONCLUSION: Plasmodium vivax malaria incidence is highly heterogeneous in space and time in the urban study area with important geographical and housing risk factors associated with symptomatic episodes.

Background With low and markedly seasonal malaria transmission, increasingly sensitive tools for better stratifying the risk of infection and targeting control interventions are needed. A cross-sectional survey to characterize the current malaria transmission patterns, identify hotspots, and detect recent changes using parasitological and serological measures was conducted in three sites of the Peruvian Amazon. Material and Methods After full census of the study population, 651 participants were interviewed, clinically examined and had a blood sample taken for the detection of malaria parasites (microscopy and PCR) and antibodies against P. vivax (PvMSP119, PvAMA1) and P. falciparum (PfGLURP, PfAMA1) antigens by ELISA. Risk factors for malaria infection (positive PCR) and malaria exposure (seropositivity) were assessed by multivariate survey logistic regression models. Age-specific seroprevalence was analyzed using a reversible catalytic conversion model based on maximum likelihood for generating seroconversion rates (SCR, λ). SaTScan was used to detect spatial clusters of serology-positive individuals within each site. Results The overall parasite prevalence by PCR was low, i.e. 3.9% for P. vivax and 6.7% for P. falciparum, while the seroprevalence was substantially higher, 33.6% for P. vivax and 22.0% for P. falciparum, with major differences between study sites. Age and location (site) were significantly associated with P. vivax exposure; while location, age and outdoor occupation were associated with P. falciparum exposure. P. falciparum seroprevalence curves showed a stable transmission throughout time, while for P. vivax transmission was better described by a model with two SCRs. The spatial analysis identified well-defined clusters of P. falciparum seropositive individuals in two sites, while it detected only a very small cluster of P. vivax exposure. Conclusion The use of a single parasitological and serological malaria survey has proven to be an efficient and accurate method to characterize the species specific heterogeneity in malaria transmission at micro-geographical level as well as to identify recent changes in transmission.

Background Loop-mediated isothermal DNA amplification (LAMP) methodology offers an opportunity for point-of-care (POC) molecular detection of asymptomatic malaria infections. However, there is still little evidence on the feasibility of implementing this technique for population screenings in isolated field settings. Methods Overall, we recruited 1167 individuals from terrestrial (‘road’) and hydric (‘riverine’) communities of the Peruvian Amazon for a cross-sectional survey to detect asymptomatic malaria infections. The technical performance of LAMP was evaluated in a subgroup of 503 samples, using real-time Polymerase Chain Reaction (qPCR) as reference standard. The operational feasibility of introducing LAMP testing in the mobile screening campaigns was assessed based on field-suitability parameters, along with a pilot POC-LAMP assay in a riverine community without laboratory infrastructure. Results LAMP had a sensitivity of 91.8% (87.7–94.9) and specificity of 91.9% (87.8–95.0), and the overall accuracy was significantly better among samples collected during road screenings than riverine communities (p≤0.004). LAMP-based diagnostic strategy was successfully implemented within the field-team logistics and the POC-LAMP pilot in the riverine community allowed for a reduction in the turnaround time for case management, from 12–24 hours to less than 5 hours. Specimens with haemolytic appearance were regularly observed in riverine screenings and could help explaining the hindered performance/interpretation of the LAMP reaction in these communities. Conclusions LAMP-based molecular malaria diagnosis can be deployed outside of reference laboratories, providing similar performance as qPCR. However, scale-up in remote field settings such as riverine communities needs to consider a number of logistical challenges (e.g. environmental conditions, labour-intensiveness in large population screenings) that can influence its optimal implementation.

BackgroundWhile coverage of long-lasting insecticide-treated nets (LLIN) has steadily increased, a growing number of studies report gaps between net ownership and use. We conducted a mixed-methods social science study assessing the importance of net preference and use after Olyset® LLINs were distributed through a mass campaign in rural communities surrounding Iquitos, the capital city of the Amazonian region of Peru.MethodsThe study was conducted in the catchment area of the Paujil and Cahuide Health Centres (San Juan district) between July 2007 and November 2008. During a first qualitative phase, participant observation and in-depth interviews collected information on key determinants for net preference and use. In a second quantitative phase, a survey among recently confirmed malaria patients evaluated the acceptability and use of both LLINs and traditional nets, and a case control study assessed the association between net preference/use and housing structure (open vs. closed houses).ResultsA total of 10 communities were selected for the anthropological fieldwork and 228 households participated in the quantitative studies. In the study area, bed nets are considered part of the housing structure and are therefore required to fulfil specific architectural and social functions, such as providing privacy and shelter, which the newly distributed Olyset® LLINs ultimately did not. The LLINs' failure to meet these criteria could mainly be attributed to their large mesh size, transparency and perceived ineffectiveness to protect against mosquitoes and other insects, resulting in 63.3% of households not using any of the distributed LLINs. Notably, LLIN usage was significantly lower in houses with no interior or exterior walls (35.2%) than in those with walls (73.8%) (OR = 5.2, 95CI [2.2; 12.3], pConclusionNet preference can interfere with optimal LLIN use. In order to improve the number of effective days of LLIN protection per dollar spent, appropriate quantitative and qualitative methods for collecting information on net preference should be developed before any LLIN procurement decision is made.

BACKGROUND: Where malaria endemicity is low, control programmes need increasingly sensitive tools for monitoring malaria transmission intensity (MTI) and to better define health priorities. A cross-sectional survey was conducted in a low endemicity area of the Peruvian north-western coast to assess the MTI using both molecular and serological tools. METHODS: Epidemiological, parasitological and serological data were collected from 2,667 individuals in three settlements of Bellavista district, in May 2010. Parasite infection was detected using microscopy and polymerase chain reaction (PCR). Antibodies to Plasmodium vivax merozoite surface protein-119 (PvMSP1₁₉) and to Plasmodium falciparum glutamate-rich protein (PfGLURP) were detected by ELISA. Risk factors for exposure to malaria (seropositivity) were assessed by multivariate survey logistic regression models. Age-specific antibody prevalence of both P. falciparum and P. vivax were analysed using a previously published catalytic conversion model based on maximum likelihood for generating seroconversion rates (SCR). RESULTS: The overall parasite prevalence by microscopy and PCR were extremely low: 0.3 and 0.9%, respectively for P. vivax, and 0 and 0.04%, respectively for P. falciparum, while seroprevalence was much higher, 13.6% for P. vivax and 9.8% for P. falciparum. Settlement, age and occupation as moto-taxi driver during previous year were significantly associated with P. falciparum exposure, while age and distance to the water drain were associated with P. vivax exposure. Likelihood ratio tests supported age seroprevalence curves with two SCR for both P. vivax and P. falciparum indicating significant changes in the MTI over time. The SCR for PfGLURP was 19-fold lower after 2002 as compared to before (λ1 = 0.022 versus λ2 = 0.431), and the SCR for PvMSP1₁₉ was four-fold higher after 2006 as compared to before (λ1 = 0.024 versus λ2 = 0.006). CONCLUSION: Combining molecular and serological tools considerably enhanced the capacity of detecting current and past exposure to malaria infections and related risks factors in this very low endemicity area. This allowed for an improved characterization of the current human reservoir of infections, largely hidden and heterogeneous, as well as providing insights into recent changes in species specific MTIs. This approach will be of key importance for evaluating and monitoring future malaria elimination strategies.

To assess long-lasting insecticide - treated bednet (LLITN) ownership, retention and usage one year after their distribution in Loreto, Peru.From July to September 2007, 26,185 LLITNs Olyset Net ® were delivered in 194 targeted communities in the Peruvian Amazon region, covering 45,331 people. Two cross-sectional community-based surveys in December 2007 and July 2008 were undertaken in a sample of 60 targeted communities (30.9% out of the total). A semi-structured questionnaire was used to collect necessary data to calculate LLITN ownership, retention and usage indicators.High LLITN household ownership was showed in both surveys (99.9% and 98.7%, respectively). LLITN/ person ratio decreased from 0.58 at the end of the LLITN delivery to 0.51 in the second survey, estimating LLITN retention of 87% after 1 year of intervention. In the first survey, 99.0% of all children5 years and 96,0% of pregnant women slept under a LLITN the previous night, while in the second survey, 77.7% of children5 years and 66.3% of pregnant women slept under a LLITN the previous night. Big mesh size of LLITN had low people's acceptability, reaching only 39.0% in the second survey.Although universal LLITN household ownership remained high, their LLITN usage levels have decreased during one-year follow-up period.

Most cases of gastric cancers occur in non-industrialized countries but there is scarce information about the epidemiology of this illness in these countries. Our study examined whether there was a variation in the prevalence of gastric cancer in Lima, Perú over the last 2 decades. Subjects older than 29 years of age were included. They underwent an esophagogastroduedonoscopy at 3 socioeconomically different health facilities in Lima: a county hospital (7,168 subjects), a Peruvian-Japanese Clinic (14,794 individuals) and a private hospital (4,893 individuals). Birth cohort prevalence of gastric cancer was used. Regression models were calculated to predict the future prevalence of gastric cancer. It was found that the birth cohort prevalence of gastric cancer decreased in Perú from 22.7 to 2% (p0.001), from 12 to 0.5% (p0.001), and from 6.5 to 0.1% (p0.001) in the low, middle and high socioeconomic group, respectively. The prevalence of intestinal metaplasia decreased from 44.3 to 12.5% (p0.001), from 28.4 to 5% (p0.001), and from 19.4 to 2.2% (p0.001) in the low, middle and high socioeconomic status, respectively. These trends will likely persist over the future decades. Nevertheless, the prevalence of gastric cancer remains high in subjects older than 59 years of age in the low socioeconomic status. It is concluded that the prevalence of gastric cancer is decreasing in Perú, similar to the current trend undergoing in industrialized nations. However, there are still specific groups with high prevalence that might benefit from screening for early detection and treatment.

To determine the prevalence of peptic ulcer and gastric adenocarcinoma in a population of middle and high socio-economic status in Lima, Peru, between 1985 and 2002.The prevalence of gastroduodenal ulcer and gastric adenocarcinoma was determined after studying by esophagogastroduodenoscopy 31,446 patients at the Policlínico Peruano Japonds (PPJ) between 1985 and 2002. All patients had chronic upper gastrointestinal symptoms and had endoscopically proven diagnosis of active peptic ulcer or histological diagnosis of gastric adenocarcinoma.Analysis of PPJ population identified a decrease in the prevalence of gastric ulcer and duodenal ulcer from 3.15% and 5.05% respectively in 1985, to 1.62% and 2.00% respectively in 2002. Gastric adenocarcinoma prevalence also decreased from 3.19% in 1988 to 0.92% in 2002. The prevalences of gastric ulcer (OR = 1.49, 95% IC 1.26-1.77, p0.001), duodenal ulcer (OR = 1.32, 95% IC 1.15-1.51, p0.001) and gastric adenocarcinoma (OR = 1.53, 95% IC 1.25-1.86, p0.001), decreased in the last eight years.Over the study period, there was a significant decrease in the prevalence of peptic ulcer and gastric adenocarcinoma at the Policlinico Peruano Japonés, where patients from middle and high socio economic status are attended.

We present the results of our investigations in the epidemiology of H. pylori infection in Peru during the last two decades. The prevalence of Helicobacter pylori infection in Lima is decreasing in people of middle and high socioeconomic status and continues stationary in people of low socioeconomic status. This decrease is similar in Peruvian and Japanese population in this city, and is associated to the decrease of the gastrointestinal diseases related to this bacterium: peptic ulcer and stomach adenocarcinoma. The infection is slightly greater in males and is acquired in early ages of life. Via oro-fecal and water contamination are probably the most important transmission ways. In our country, so far, there is no evidence to assure that some races have higher pre-disposition to acquire the infection. There are no differences in the infection by H. pylori among coast, mountain or jungle populations; and people who live in high altitudes have more atrophic chronic gastritis secondary to H. pylori infection than people who live at sea level.

Objetivos: Investigar un brote de síndrome febril en el distrito de Punchao mediante una evaluación clínica, laboratorial y entomológica para conocer los factores asociados a la aparición de dicho brote. Materiales y métodos: Debido al reporte de tres pacientes con cuadro clínico febril asociado a cefalea, mialgias y postración en la semana epidemiológica Nº41 del año 2000, procedentes del distrito de Punchao, Humalíes, Huánuco y ante la información de presentación inusual de pacientes febriles en la última semana en dicho lugar, se decidió investigar la naturaleza y características del brote. Se definió como caso a todo paciente con cuadro febril agudo y uno de estos síntomas: cefalea, mialgias o postración; procediéndose a la búsqueda activa de éstos y a la evaluación de presencia de anticuerpos para rickettsias en suero mediante inmunofluorescencia indirecta (IFI). Se capturaron roedores y se colectaron ectoparásitos en las viviendas (roedores, animales domésticos y humanos), a fin de identificar la presencia de Rickettsias en ellos mediante IFI, aislamiento o PCR. Resultados: No se logró el aislamiento del agente causal. Se evidenció circulación de la Rickettsia sp. (serología positiva) tanto en humanos (en casos y en no casos) como en roedores. Se evidenció mayor presencia de malos hábitos de aseo y condiciones inadecuadas de saneamiento básico en los casos (respecto a los no casos) y una disminución de los casos luego del inicio de las medidas de control. Conclusiones: Las evidencias encontradas permitieron identificar un brote de tifus en Punchao, no pudiéndose determinar la especie involucrada debido a que no se aisló el agente causal. Objectives: To assess an outbreak of febrile syndrome in Punchao district through a clinical, laboratorial and entomological evaluation and to find out the factors associated to the occurrence of such outbreak. Materials and methods: Due to the report of three patients from Punchao, Huamalíes (Huanuco) presenting with fever associated to headache, myalgia and postration, on the 41st epidemiological week 2000; and because of an inusual presentation of feverish patients in the last week in such site; we decided to investigate the nature and characteristics of the outbreak. We define as case every patient with a time of illness less than 15 days with fever and one of these symptoms: headache, myalgias and postration and we started actively to look for these cases and to assess the presence of anti-Rickettsias antibodies in serum using IFI. We captured rodents and collected ectoparasites in houses (in rodents, domestic animals and humans), with the purpose of identifying Rickettsias using IFI, isolation and/or PCR. Results: We could not isolate the causal agent. The circulation of Rickettsia (positive serology) in humans (cases and no cases) and in rodents was confirmed. A greater presence of bad habits of cleanliness and inadequate conditions of basic sanitation in cases (in relation to no cases) and a decrease in the number of cases after the beginning of control measures, was evident. Conclusions: The evidences found allowed the identification of a typhus outbreak in Punchao; however, the determination of the involucrated species was not possible because the causal agent was not isolated.

Objetivos: determinar la distribución geográfica de los serotipos del virus dengue en el Perú en el año 2001 e identificar las manifestaciones clínicas asociadas a dichos serotipos a partir de las muestras que ingresaron al Instituto Nacional de Salud (INS) de Lima, Perú. Materiales y métodos: en este estudio transversal analítico se incluyó 236 pacientes, cuyas muestras sanguíneas resultaron confirmatorias de dengue por el método del aislamiento viral, realizado en el laboratorio de arbovirus y rickettsias durante el año 2001. Los datos clínicos de estos pacientes fueron extraídos de las fichas epidemiológicas enviadas por los establecimientos de salud en el ámbito nacional notificantes al INS. Resultados: los cuatro serotipos del dengue estuvieron circulando en el Perú en el año 2001 (DEN-3 y DEN-4 recientemente identificados)La mayoría de los pacientes (76,7%) refirieron no haber tenido anteriormente dengue. Los pacientes con infección por el serotipo DEN-2 presentaron mayores síntomas y signos que aquellos infectados con DEN-1 y DEN-3; siendo este último serotipo el que produjo menor sintomatología en los pacientes. Conclusiones: los cuatro serotipos del dengue están circulando en el país. El serotipo DEN-2 sería responsable de cuadros clínicos con mayor sintomatología o severidad. Objectives: To determine the geographic distribution of the serotypes of dengue virus in Peru in 2001 and to identify the clinical features associated to these serotypes from samples assessed at the National Institute of Health (NIH) in Lima, Perú. Materials and Methods: This analytical cross- sectional study included 236 patients with a confirmed diagnosis of dengue, obtained by viral isolation in the Arbovirus and Rickettsias Laboratory during 2001. The clinical data of these patients was obtained from the epidemilogical formats sent by the health care services to the NIH. Results: The 4 dengue serotypes circulated in Peru during 2001 (DEN-3 and DEN-4 were recently identificated). Most of the patients (76,7%) reported that they did not have previous dengue infections.The patients with infections by DEN-2 serotype had more symptoms and signs than the patients with DEN-1 and DEN-3. Conclusions: The 4 dengue serotypes are currently circulating in Peru. DEN-2 serotype would be responsible of more severe clinical presentations.

INTRODUCCIÓN : A pesar de la disminución de la pobreza en Perú, la prevalencia de la anemia infantil en el país continúa siendo alta. OBJETIVO : Determinar los factores sociodemográficos y las características del cuidado materno-infantil asociadas con la anemia en niños de seis a 35 meses de edad en Perú. MATERIALES Y MÉTODOS : Se hizo un estudio observacional que incluyó los datos sobre hemoglobina sanguínea registrados en la Encuesta Demográfica y de Salud Familiar (ENDES), 2007-2013, en niños entre los seis y los 35 meses de edad. Mediante un análisis multivariado de regresión logística, se identificaron los factores asociados con la anemia, definida como una hemoglobina corregida por altitud, menor de 11 mg/dl. RESULTADOS : La prevalencia de anemia fue alta (47,9 %). Se identificaron doce factores asociados con la anemia: factores sociodemográficos como vivir fuera de Lima y Callao; en un hogar con bajo nivel socioeconómico; tener una madre adolescente y con bajo nivel educativo; ser de sexo masculino con edad menor de 24 meses y antecedentes de fiebre reciente, y factores relacionados con el cuidado materno-infantil como la falta de control prenatal en el primer trimestre, la falta de suplemento de hierro durante el embarazo o administrado durante un periodo breve, parto en el domicilio, diagnóstico de anemia en la madre en el momento de la encuesta y ausencia de tratamiento antiparasitario preventivo en el niño. CONCLUSIONES : La ENDES proporcionó información valiosa sobre los factores asociados con la anemia en niños de seis a 35 meses, cuyo conocimiento debe mejorar la cobertura y la efectividad de prácticas adecuadas de cuidado materno-infantil. [Factors associated with anemia in children under three years of age in Perú: analysis of the Encuesta Demográfica y de Salud Familiar, ENDES, 2007-2013] INTRODUCTION: Despite the reduction of poverty in Perú, the prevalence of anemia in the country remains high. OBJECTIVE: To identify socio-demographic, child and maternal-child care factors associated with anemia in children between 6 and 35 months in Perú. MATERIALS AND METHODS: We conducted an analytical and descriptive study that included registered data from the national survey on demography and family health, 2007-2013, on children between 6 and 35 months old, including the measurement of blood hemoglobin. Anemia was confirmed by hemoglobin-altitude corrected values below 11 mg/dl. We used multivariate logistic regression models to assess potential associated factors for anemia. RESULTS: Anemia prevalence was high (47.9%). Twelve factors were independently associated with anemia in children: Socio-demographic factors such as living outside Lima and Callao, in a low socioeconomic household, and having an adolescent mother with low education level; child-related factors as being male, younger than 24 months of age, and having fever in the previous two weeks, and maternal-child care factors such as lack of prenatal control in the first trimester of pregnancy, lack or short period of iron supplementation during pregnancy, house delivery, anemia detection at the moment of the survey, and lack of intestinal anti-parasite preventive treatment in the child. CONCLUSIONS: The analysis of survey data provided valuable information about factors associated with anemia in children between 6 and 35 months, which can be used to increase the coverage and effectiveness of maternal-child care practices.