Performance of ¿VIKIA Malaria Ag Pf/Pan¿ (IMACCESS®), a new malaria rapid diagnostic test for detection of symptomatic malaria infections

ABSTRACT: BACKGROUND: Recently, IMACCESS[REGISTERED SIGN] developed a new malaria test (VIKIA Malaria Ag Pf/Pan[TRADE MARK SIGN]), based on the detection of falciparum malaria (HRP-2) and non-falciparum malaria (aldolase). METHODS: The performance of this new malaria rapid diagnostic test (RDT) was assessed using 1,000 febrile patients seeking malaria treatment in four health centres in Cambodia from August to December 2011. The results of the VIKIA Malaria Ag Pf/Pan were compared with those obtained by microscopy, the CareStart Malaria[TRADE MARK SIGN] RDT (AccessBio[REGISTERED SIGN]) which is currently used in Cambodia, and real-time PCR (as "gold standard"). RESULTS: The best performances of the VIKIA Malaria Ag Pf/Pan[TRADE MARK SIGN] test for detection of both Plasmodium falciparum and non-P. falciparum were with 20--30 min reading times (sensitivity of 93.4% for P. falciparum and 82.8% for non-P. falciparum and specificity of 98.6% for P. falciparum and 98.9% for non-P. falciparum) and were similar to those for the CareStart Malaria[TRADE MARK SIGN] test. CONCLUSIONS: This new RDT performs similarly well as other commercially available tests (especially the CareStart Malaria[TRADE MARK SIGN] test, used as comparator), and conforms to the World Health Organization's recommendations for RDT performance. It is a good alternative tool for the diagnosis of malaria in endemic areas.     

Should Malaria Treatment Be Guided by a Point of Care Rapid Test? A Threshold Approach to Malaria Management in Rural Burkina Faso

Background

In Burkina Faso, rapid diagnostic tests for malaria have been made recently available. Previously, malaria was managed clinically. This study aims at assessing which is the best management option of a febrile patient in a hyperendemic setting. Three alternatives are: treating presumptively, testing, or refraining from both test and treatment. The test threshold is the tradeoff between refraining and testing, the test-treatment threshold is the tradeoff between testing and treating. Only if the disease probability lies between the two should the test be used.

Methods and Findings

Data for this analysis was obtained from previous studies on malaria rapid tests, involving 5220 patients. The thresholds were calculated, based on disease risk, treatment risk and cost, test accuracy and cost. The thresholds were then matched against the disease probability. For a febrile child under 5 in the dry season, the pre-test probability of clinical malaria (3.2%), was just above the test/treatment threshold. In the rainy season, that probability was 63%, largely above the test/treatment threshold. For febrile children >5 years and adults in the dry season, the probability was 1.7%, below the test threshold, while in the rainy season it was higher (25.1%), and situated between the two thresholds (3% and 60.9%), only if costs were not considered. If they were, neither testing nor treating with artemisinin combination treatments (ACT) would be recommended.

Conclusions

A febrile child under 5 should be treated presumptively. In the dry season, the probability of clinical malaria in adults is so low, that neither testing nor treating with any regimen should be recommended. In the rainy season, if costs are considered, a febrile adult should not be tested, nor treated with ACT, but a possible alternative would be a presumptive treatment with amodiaquine plus sulfadoxine-pyrimethamine. If costs were not considered, testing would be recommended.     

Evaluation of the PathoTec ?Rapid I-D System”

The 10 biochemical test strips included in the PathoTec Rapid I-D System were evaluated for accuracy as compared to standard tests and for efficacy in identification of 193 gram-negative bacilli. The test agreement was 100% for oxidase and phenylalanine deaminase, 99% for indole, nitrate, and Voges-Proskauer, 98% for malonate, 97% for lysine decarboxylase, 90% for urease, 84% for H(2)S, and 75% for esculin hydrolysis. Most of the commonly isolated Enterobacteriaceae were identified correctly within 4 h. Errors in identification of Proteus morganii and P. rettgeri occurred because of positive H(2)S tests on the PathoTec strips with these organisms.     

Does the Diagnostic Accuracy of the 13C‐Urea Breath Test Vary with Age Even After the Application of Urea Hydrolysis Rate?

Background: Endogenous CO₂ production may be a possible explanation for higher false‐positive results reported for ¹³C‐urea breath test (UBT) in children below 6 years. In this study, we evaluated whether age affects the diagnostic accuracy of the ¹³C‐UBT even after the application of urea hydrolysis rate (UHR) in children. Methods: A total of 612 ¹³C‐UBTs and endoscopic biopsies were performed on children divided into two groups; children under 6 years (n = 126) and children aged 6–18 years (n = 486). For ¹³C‐UBT, 75 mg ¹³C‐urea was ingested, and breath sample was collected 30 minutes later. Delta over baseline (DOB) was determined, and UHR was calculated to normalize the DOB values for endogenous CO₂ production. Results: There was significant difference between the DOB values of children under 6 years and those of children over 6 years in H. pylori‐positive (p = .029) and ‐negative groups (p = .002). On applying the UHR, no significant difference was observed between the UHR values of children under 6 years and those of children over 6 years in H. pylori‐positive (p = .877) and ‐negative groups (p = .427). In 12.6% children under 6 years, false‐positive results were observed on applying the DOB, and in 9.0% on applying the UHR (p = .125). Conclusions: The ¹³C‐UBT is a noninvasive method exhibiting high diagnostic accuracy with both UHR as well as DOB. However, high false‐positive results for ¹³C‐UBT were noted in children below 6 years on applying both UHR as well as DOB. Thus, this may not only be due to the effects of endogenous CO₂ production but also due to other factors.     

When Do Latent Class Models Overstate Accuracy for Diagnostic and Other Classifiers in the Absence of a Gold Standard?

Latent class models are increasingly used to assess the accuracy of medical diagnostic tests and other classifications when no gold standard is available and the true state is unknown. When the latent class is treated as the true class, the latent class models provide measures of components of accuracy including specificity and sensitivity and their complements, type I and type II error rates. The error rates according to the latent class model differ from the true error rates, however, and empirical comparisons with a gold standard suggest the true error rates often are larger. We investigate conditions under which the true type I and type II error rates are larger than those provided by the latent class models. Results from Uebersax (1988, Psychological Bulletin 104, 405-416) are extended to accommodate random effects and covariates affecting the responses. The results are important for interpreting the results of latent class analyses. An error decomposition is presented that incorporates an error component from invalidity of the latent class model.     

Is There a Risk of Suburban Transmission of Malaria in Selangor,Malaysia?

Background

The suburban transmission of malaria in Selangor, Malaysia’s most developed and populous state still remains a concern for public health in this region. Despite much successful control efforts directed at its reduction, sporadic cases, mostly brought in by foreigners have continued to occur. In addition, cases of simian malaria caused by Plasmodium knowlesi, some with fatal outcome have caused grave concern to health workers. The aim of this study was to investigate the possibility of local malaria transmission in suburban regions of Selangor, which are adjacent to secondary rainforests.

Findings

A malaria survey spanning 7 years (2006 - 2012) was conducted in Selangor. A total of 1623 laboratory confirmed malaria cases were reported from Selangor’s nine districts. While 72.6% of these cases (1178/1623) were attributed to imported malaria (cases originating from other countries), 25.5% (414/1623) were local cases and 1.9% (31/1623) were considered as relapse and unclassified cases combined. In this study, the most prevalent infection was P. vivax (1239 cases, prevalence 76.3%) followed by P. falciparum (211, 13.0%), P. knowlesi (75, 4.6%), P. malariae (71, 4.4%) and P. ovale (1, 0.06%). Mixed infections comprising of P. vivax and P. falciparum were confirmed (26, 1.6%). Entomological surveys targeting the residences of malaria patients’ showed that the most commonly trapped Anopheles species was An. maculatus. No oocysts or sporozoites were found in the An. maculatus collected. Nevertheless, the possibility of An. maculatus being the malaria vector in the investigated locations was high due to its persistent occurrence in these areas.

Conclusions

Malaria cases reported in this study were mostly imported cases. However the co-existence of local cases and potential Plasmodium spp. vectors should be cause for concern. The results of this survey reflect the need of maintaining closely monitored malaria control programs and continuous extensive malaria surveillance in Peninsula Malaysia.     

Performance of the CareStart? G6PD Deficiency Screening Test,a Point-of-Care Diagnostic for Primaquine Therapy Screening

Development of reliable, easy-to-use, rapid diagnostic tests (RDTs) to detect glucose-6-phosphate dehydrogenase (G6PD) deficiency at point of care is essential to deploying primaquine therapies as part of malaria elimination strategies. We assessed a kit under research and development called CareStart™ G6PD deficiency screening test (Access Bio, New Jersey, USA) by comparing its performance to quantitative G6PD enzyme activity using a standardized spectrophotometric method (‘gold standard’). Blood samples (n = 903) were collected from Cambodian adults living in Pailin province, western Cambodia. G6PD enzyme activities ranged from 0 to 20.5 U/g Hb (median 12.0 U/g Hg). Based on a normal haemoglobin concentration and wild-type G6PD gene, the normal values of G6PD enzymatic activity for this population was 3.6 to 20.5 U/g Hg (95^th percentiles from 5.5 to 17.2 U/g Hg). Ninety-seven subjects (10.7%) had <3.6 U/g Hg and were classified as G6PD deficient. Prevalence of deficiency was 15.0% (64/425) among men and 6.9% (33/478) among women. Genotype was analyzed in 66 G6PD-deficient subjects and 63 of these exhibited findings consistent with Viangchang genotype. The sensitivity and specificity of the CareStart™ G6PD deficiency screening test was 0.68 and 1.0, respectively. Its detection threshold was <2.7 U/g Hg, well within the range of moderate and severe enzyme deficiencies. Thirteen subjects (1.4%, 12 males and 1 female) with G6PD enzyme activities <2 U/g Hg were falsely classified as “normal” by RDT. This experimental RDT test here evaluated outside of the laboratory for the first time shows real promise, but safe application of it will require lower rates of falsely “normal” results.     

A Diagnostic Accuracy Study of Xpert?MTB/RIF in HIV-Positive Patients with High Clinical Suspicion of Pulmonary Tuberculosis in Lima,Peru

Background

Diagnosis of pulmonary tuberculosis (TB) among human immunodeficiency virus (HIV) patients remains complex and demands easy to perform and accurate tests. Xpert®MTB/RIF (MTB/RIF) is a molecular TB diagnostic test which is rapid and convenient; the test requires minimal human resources and reports results within two hours. The majority of performance studies of MTB/RIF have been performed in high HIV burden settings, thus TB diagnostic studies among HIV patients in low HIV prevalence settings such as Peru are still needed.

Methodology/Principal Findings

From April 2010 to May 2011, HIV-positive patients with high clinical suspicion of TB were enrolled from two tertiary hospitals in Lima, Peru. Detection of TB by MTB/RIF was compared to a composite reference standard Löwenstein-Jensen (LJ) and liquid culture. Detection of rifampicin resistance was compared to the LJ proportion method. We included 131 patients, the median CD4 cell count was 154.5 cells/mm³ and 45 (34.4%) had TB. For TB detection among HIV patients, sensitivity of MTB/RIF was 97.8% (95% CI 88.4–99.6) (44/45); specificity was 97.7% (95% CI 91.9–99.4) (84/86); the positive predictive value was 95.7% (95% CI 85.5–98.8) (44/46); and the negative predictive value, 98.8% (95% CI 93.6–99.8) (84/85). MTB/RIF detected 13/14 smear-negative TB cases, outperforming smear microscopy [97.8% (44/45) vs. 68.9% (31/45); p = 0.0002]. For rifampicin resistance detection, sensitivity of MTB/RIF was 100% (95% CI 61.0–100.0) (6/6); specificity was 91.0% (95% CI 76.4–96.9) (30/33); the positive predictive value was 66.7% (95% CI 35.4–87.9) (6/9); and the negative predictive value was 100% (95% CI 88.7 –100.0) (30/30).

Conclusions/Significance

In HIV patients in our population with a high clinical suspicion of TB, MTB/RIF performed well for TB diagnosis and outperformed smear microscopy.     

MRI Findings for Frozen Shoulder Evaluation: Is the Thickness of the Coracohumeral Ligament a Valuable Diagnostic Tool?

Background

Recent studies have demonstrated that the coracohumeral ligament (CHL) is shortened and thickened in a frozen shoulder. We analyzed the rate in CHL visualization between patients with frozen shoulder and normal volunteers using Magnetic Resonance Imaging (MRI) to determine the CHL thickness in the patients with a frozen shoulder.

Methods and Findings

There were 72 shoulder joints in 72 patients (50 femles and 22 males with a mean age of 53.5 years) with clinical evidence and MR imaging evidence of frozen shoulder. These were prospectively analyzed to identify and measure the maximum thickness of the CHL. The control group, which included 120 shoulder joints in 60 normal volunteer individuals (30 females and 30 males with a mean age of 50.5 years) was also referred for MR imaging. A chi-square test was used to analyze the data of the rate of CHL visualization between the patients with frozen shoulder and the control group. A two-way ANOVA was used to analyze the mean maximal thickness of CHL. The CHL was visualized in 110 out of 120 shoulders in the control group (91.7%), and in 57 out of 72 shoulders for the frozen shoulder group (79.2%), there was significant difference, using a chi-square test (P<0.05). The CHL was not visualized in 10 out of 120 shoulders in the control group (8.3%), and 15 out of 72 shoulders in the frozen shoulder group (20.8%), there was a significant difference (P<0.05). The CHL thickness (3.99±1.68 mm) in the patients with frozen shoulder was significantly greater than that thickness (3.08±1.32 mm) in the control group, using a two-way ANOVA (P<0.001). The CHL thickness (3.52±1.52 mm, n = 97) in the female shoulders was no significantly greater than that thickness (3.22±1.49 mm, n = 70) in the male shoulders, using a two-way ANOVA (P>0.05).

Conclusions

MR Imaging is a satisfactory method for CHL depiction, and a thickened CHL is highly suggestive of frozen shoulder.     

Is “Appearing Chronically Ill” a Sign of Poor Health? A Study of Diagnostic Accuracy

Objective

To determine the sensitivity and specificity of a physician’s assessment that a patient “appears chronically ill” for the detection of poor health status.

Methods

The health status of 126 adult outpatients was determined using the 12-Item Short Form Health Survey (SF-12). Physician participants (n = 111 residents and faculty) viewed photographs of each patient participant and assessed whether or not the patient appeared chronically ill. For the entire group of physicians, the median sensitivity and specificity of “appearing chronically ill” for the detection of poor health status (defined as SF-12 physical health score below age group norms by at least 1 SD) were calculated. The study took place from February 2009 to January 2011.

Results

Forty-two participants (33%) had an SF-12 physical health score ≥1 SD below age group norms, and 22 (18%) had a score ≥2 SD below age group norms. When poor health status was defined as an SF-12 physical score ≥1 SD below age group norms, the median sensitivity was 38.1% (IQR 28.6–47.6%), specificity 78.6% (IQR 69.0–84.0%), positive likelihood ratio 1.64 (IQR 1.42–2.15), and negative likelihood ratio 0.82 (IQR 0.74–0.87). For an SF-12 physical score ≥2 SD below age group norms, the median sensitivity was 45.5% (IQR 36.4–54.5%), specificity 76.9% (IQR 66.3–83.7%), positive likelihood ratio 1.77 (IQR 1.49–2.25), and negative likelihood ratio 0.75 (IQR 0.66–0.86).

Conclusions

Our study suggests that a physician’s assessment that a patient “appears chronically ill” has poor sensitivity and modest specificity for the detection of poor health status in adult outpatients. The associated likelihood ratios indicate that this assessment may have limited diagnostic value.     

Malaria immunity in infants: a special case of a general phenomenon?

Newborn infants in endemic areas are markedly resistant to Plasmodium falciparum malaria. Consequently, severe disease is rare during the first few months of life, and infections tend to be low density and relatively asymptomatic during this period. Although this is generally ascribed to passively transferred immunity, attempts to identify the targets and mechanisms of this protection have been unsuccessful. The implications of the hypothesis that the progression from resistance through susceptibility and back to resistance during infancy and early childhood reflects the gradual acquisition of IgG to variant surface antigens (VSAs), while protection from maternal VSA-specific IgG steadily fades, are discussed here.     

Do Diagnosis Delays Impact Receipt of Test Results? Evidence from the HIV Early Infant Diagnosis Program in Uganda

Background

There is scant evidence on the association between diagnosis delays and the receipt of test results in HIV Early Infant Diagnosis (EID) programs. We determine the association between diagnosis delays and other health care system and patient factors on result receipt.

Methods

We reviewed 703 infant HIV test records for tests performed between January 2008 and February 2009 at a regional referral hospital and level four health center in Uganda. The main outcome was caregiver receipt of the test result. The primary study variable was turnaround time (time between sample collection and result availability at the health facility). Additional variables included clinic entry point, infant age at sample collection, reported HIV status and receipt of antiretroviral prophylaxis for prevention of mother-to-child transmission. We conducted a pooled analysis in addition to separate analyses for each facility. We estimated the relative risk of result receipt using modified Poisson regression with robust standard errors.

Results

Overall, the median result turnaround time, was 38 days. 59% of caregivers received infant test results. Caregivers were less likely to receive results at turnaround times greater than 49 days compared to 28 days or fewer (ARR = 0.83; 95% CI = 0.70–0.98). Caregivers were more likely to receive results at the PMTCT clinic (ARR = 1.81; 95% CI = 1.40–2.33) and less likely at the pediatric ward (ARR = 0.54; 95% CI = 0.37–0.81) compared to the immunization clinic. At the level four health center, result receipt was half as likely among infants older than 9 months compared to 3 months and younger (ARR= 0.47; 95% CI = 0.25–0.93).

Conclusion

In this study setting, we find evidence that longer turnaround times, clinic entry point and age at sample collection may be associated with receipt of infant HIV test results.     

Are Participants in a Street-Based HIV Testing Program Able to Perform Their Own Rapid Test and Interpret the Results?

Objective

Availability of over-the-counter rapid HIV tests could improve access to testing those reluctant or unable to use current services. We aimed to evaluate the feasibility of HIV self-testing using a finger-stick whole-blood rapid test (Determine™ HIV Combo) to detect both antigen and antibody.

Methods

Before being tested, 313 participants in a street-based testing program were given adapted instructions and a test kit, and performed the self-test without supervision. These participants, together with another 207 who performed supervised self-testing, received additional instructions on how to interpret the test results shown in six colour photos and filled out a questionnaire. Logistic regression and generalized estimating equations (GEE) were used in the statistical analysis.

Results

About 8.0% (95%CI:4.8%–11.2%) obtained an invalid self-test. An invalid result was inversely associated with male participants who had sex with men (OR = 0.3;95%CI:0.1–1.0). Of the 3111 photos interpreted,4.9% (95%CI:4.1–5.7) were incorrect. Only 1.1% (95%CI:0.3–1.8) of the positive results were interpreted as negative. Age 30 or older (OR = 2.1; 95%CI:1.2–3.7), having been born in Latin America (OR = 1.6; 95%CI:1.1–2.2),and not having university education (OR = 2.1;95%CI:1.2–3.7) were associated with misinterpreting test results in the GEE. Participant''s perceptions of both their proficiency when conducting the test and interpretation were related with actual outcomes. Most participants (83.9%) were more motivated than before to use the self-test in the future, and 51.7% would pay >10 Euros for the test if it was sold in pharmacies.

Conclusions

This is the first study showing that blood-based self-testing with current technology is feasible in HIV-negative participants demanding the test and without prior training or supervision. Bearing in mind that it was conducted under difficult weather conditions and using a complex kit, over-the-counter tests could be a feasible option to complement current diagnostic strategies. More studies are needed to accommodate technology, minimise interpretation mistakes and provide on-line support.     

Diet and Feeding Ecology of Chimpanzees (Pan troglodytes) in Bulindi, Uganda: Foraging Strategies at the Forest–Farm Interface

Wild animals increasingly inhabit human-influenced environments such as forest fragments amid agricultural systems. Dietary studies provide a means of assessing wildlife responses to anthropogenic habitat changes. Chimpanzees are specialist frugivores that consume other plant parts, e.g., fibrous pith and leaves, in greater amounts during fruit shortages. I examined the plant diet and seasonal foraging strategies of chimpanzees inhabiting small forest fragments within a cultivated landscape in Uganda. I determined diet over 13 mo via systematic fecal analysis, supplemented by direct observation and feeding trace evidence. I identified important foods and examined their role as seasonal fallbacks. Diet composition and breadth were overall species typical. Chimpanzees were highly frugivorous and the fruit component of fecal samples exceeded that of nonfruit fiber in all months. Forest fruit availability fluctuated seasonally, including a 3-mo low fruiting season, when overall fruit intake declined. During this time chimpanzees pursued a mixed strategy of increasing fiber consumption and feeding more heavily on energy-rich cultivars, including those obtained through crop raiding. The data suggest that exploiting agricultural fruits helped chimpanzees maintain a fruit-dominated diet when forest fruit was scarce. No evidence suggested this disturbed forest–farm mosaic is a food-impoverished habitat for chimpanzees overall. Nevertheless, cultivar feeding creates conflict with people and the high nutritional quality of crops is likely offset by the inherent risk associated with obtaining them. This study adds to growing evidence of ecological and behavioral adaptability of Pan troglodytes in response to anthropogenic habitat alteration. Targeted conservation of key natural foods for wildlife —particularly fallbacks— would help reduce conflicts and improve the survival prospects of threatened species sharing environments with people.     

The Dynamics of Transmission and Spatial Distribution of Malaria in Riverside Areas of Porto Velho,Rond?nia,in the Amazon Region of Brazil

The study area in Rondônia was the site of extensive malaria epidemic outbreaks in the 19^th and 20^th centuries related to environmental impacts, with large immigration flows. The present work analyzes the transmission dynamics of malaria in these areas to propose measures for avoiding epidemic outbreaks due to the construction of two Hydroelectric Power Plants. A population based baseline demographic census and a malaria prevalence follow up were performed in two river side localities in the suburbs of Porto Velho city and in its rural vicinity. The quantification and nature of malaria parasites in clinical patients and asymptomatic parasite carriers were performed using microscopic and Real Time PCR methodologies. Anopheles densities and their seasonal variation were done by monthly captures for defining HBR (hourly biting rate) values. Main results: (i) malaria among residents show the riverside profile, with population at risk represented by children and young adults; (ii) asymptomatic vivax and falciparum malaria parasite carriers correspond to around 15% of adults living in the area; (iii) vivax malaria relapses were responsible for 30% of clinical cases; (iv) malaria risk for the residents was evaluated as 20–25% for vivax and 5–7% for falciparum malaria; (v) anopheline densities shown outdoors HBR values 5 to 10 fold higher than indoors and reach 10.000 bites/person/year; (vi) very high incidence observed in one of the surveyed localities was explained by a micro epidemic outbreak affecting visitors and temporary residents. Temporary residents living in tents or shacks are accessible to outdoors transmission. Seasonal fishermen were the main group at risk in the study and were responsible for a 2.6 fold increase in the malaria incidence in the locality. This situation illustrates the danger of extensive epidemic outbreaks when thousands of workers and secondary immigrant population will arrive attracted by opportunities opened by the Hydroelectric Power Plants constructions.     

Phase 1 Study in Malaria Na?ve Adults of BSAM2/Alhydrogel?+CPG 7909, a Blood Stage Vaccine against P. falciparum Malaria

A Phase 1 dose escalating study was conducted in malaria naïve adults to assess the safety, reactogenicity, and immunogenicity of the blood stage malaria vaccine BSAM2/Alhydrogel®+ CPG 7909. BSAM2 is a combination of the FVO and 3D7 alleles of recombinant AMA1 and MSP1₄₂, with equal amounts by weight of each of the four proteins mixed, bound to Alhydrogel®, and administered with the adjuvant CPG 7909. Thirty (30) volunteers were enrolled in two dose groups, with 15 volunteers receiving up to three doses of 40 µg total protein at Days 0, 56, and 180, and 15 volunteers receiving up to three doses of 160 µg protein on the same schedule. Most related adverse events were mild or moderate, but 4 volunteers experienced severe systemic reactions and two were withdrawn from vaccinations due to adverse events. Geometric mean antibody levels after two vaccinations with the high dose formulation were 136 µg/ml for AMA1 and 78 µg/ml for MSP1₄₂. Antibody responses were not significantly different in the high dose versus low dose groups and did not further increase after third vaccination. In vitro growth inhibition was demonstrated and was closely correlated with anti-AMA1 antibody responses. A Phase 1b trial in malaria-exposed adults is being conducted.

Trial Registration

Clinicaltrials.gov {"type":"clinical-trial","attrs":{"text":"NCT00889616","term_id":"NCT00889616"}}NCT00889616     

Rapid effects of aldosterone in primary cultures of cardiomyocytes – do they suggest the existence of a membrane-bound receptor?

Aldosterone acts on its target tissue through a classical mechanism or through the rapid pathway through a putative membrane-bound receptor. Our goal here was to better understand the molecular and biochemical rapid mechanisms responsible for aldosterone-induced cardiomyocyte hypertrophy. We have evaluated the hypertrophic process through the levels of ANP, which was confirmed by the analysis of the superficial area of cardiomyocytes. Aldosterone increased the levels of ANP and the cellular area of the cardiomyocytes; spironolactone reduced the aldosterone-increased ANP level and cellular area of cardiomyocytes. Aldosterone or spironolactone alone did not increase the level of cyclic 3',5'-adenosine monophosphate (cAMP), but aldosterone plus spironolactone led to increased cAMP level; the treatment with aldosterone?+?spironolactone?+?BAPTA-AM reduced the levels of cAMP. These data suggest that aldosterone-induced cAMP increase is independent of mineralocorticoid receptor (MR) and dependent on Ca²⁺. Next, we have evaluated the role of A-kinase anchor proteins (AKAP) in the aldosterone-induced hypertrophic response. We have found that St-Ht31 (AKAP inhibitor) reduced the increased level of ANP which was induced by aldosterone; in addition, we have found an increase on protein kinase C (PKC) and extracellular signal-regulated kinase 5 (ERK5) activity when cells were treated with aldosterone alone, spironolactone alone and with a combination of both. Our data suggest that PKC could be responsible for ERK5 aldosterone-induced phosphorylation. Our study suggests that the aldosterone through its rapid effects promotes a hypertrophic response in cardiomyocytes that is controlled by an AKAP, being dependent on ERK5 and PKC, but not on cAMP/cAMP-dependent protein kinase signaling pathways. Lastly, we provide evidence that the targeting of AKAPs could be relevant in patients with aldosterone-induced cardiac hypertrophy and heart failure.