¿Neurologist's contribution to the diagnosis of sine materia respiratory insufficiency: case report¿

ABSTRACT: Right-to-left shunt (RLS) can be the reason of marked hypoxemia, this diagnosis of respiratory insufficiency is usually difficult to make by Respiratory Physicians as it develops in absence of an intrinsic lung disease. We report a case of RLS in a patient with a hepatopulmonary syndrome caused by chronic autoimmune cholangitis which was suspected clinically by physical examination and by standard CT imaging and MIP reconstruction of the pulmonary vascular bed. Repeated previous transthoracic echocardiography (TTE) studies didn't reveal the shunts. The final diagnosis was performed by a minimally invasive doppler transcranial examination with the use of agitated saline as contrast solution. Transcranial Colour-Coded Duplex Sonography (TCCS) with saline contrast medium injection is described to have an higher sensitivity compared with TTE and comparable with transesophageal echocardiography (TEE) in RLS diagnosis. The collaboration of Neurologists to this diagnosis of respiratory insufficiency is really important, as the examination is simple, well tolerated in comparison with the discomfort associated with transesophageal echocardiography, and of minimal invasivity in comparison with angiography which is the ultimate diagnostic procedure in this clinical scenario. TCCS with saline contrast medium injection, should be performed for the diagnosis of chronic hypoxemia for which causes are not detected with routine clinical examinations, in order to confirm RLS.     

What can the residents of malaria endemic countries do to protect themselves against malaria?

The incidence of malaria may vary substantially between adjacent communities and within an individual community, even in areas of high malaria transmission. Analysis of the factors responsible for these local variations in the incidence of malaria may identify potential control measures. Factors shown to be associated with local protection against malaria in some situations include house position, house design, the use of insect repellents and mechanical barriers such as bednets and curtains. The efficacy of insecticide treated nets and curtains in preventing mortality and morbidity from malaria, at least in the short-term, has been demonstrated convincingly. However, other measures of personal protection have not been evaluated in large trials which have clinical malaria as their endpoint. Such trials are needed to see if new malaria control tools can be identified that will assist current international efforts to improve malaria control, especially in Africa. The millions of non-immune travellers who visit malaria endemic areas each year need to protect themselves against malaria and the ways in which they can do this most effectively have been studied extensively. However, less attention has been paid to the local population of malaria endemic areas. What steps can they adopt to provide personal protection against malaria and how effective are these measures? Clues to which measures might be effective can come from study of the reasons for local variations in the incidence of malaria.     

Dendritic cells: The Trojan horse of malaria?

Malaria, caused by Plasmodium spp., is responsible for over 200 million infections worldwide and 650,000 deaths annually. Until recently, it was thought that blood-stage parasites survived and replicated in hepatocytes and red blood cells exclusively. We recently showed that blood-stage parasites could infect, survive and replicate within plasmacytoid dendritic cells of the spleen and that these cells could release infective parasites. Here we discuss the implications of this novel niche in the spleen.     

Top-down or bottom-up regulation of intra-host blood-stage malaria: do malaria parasites most resemble the dynamics of prey or predator?

Knowledge of the factors that limit parasite numbers offers hope of improved intervention strategies as well as exposing the selective forces that have shaped parasite life-history strategies. We develop a theoretical framework with which to consider the intra-host regulation of malaria parasite density. We analyse a general model that relates timing and magnitude of peak parasite density to initial dose under three different regulatory processes. The dynamics can be regulated either by top-down processes (upgradable immune regulation), bottom-up processes (fixed immune response and red blood cell (RBC) limitation) or a mixture of the two. We define and estimate the following key parameters: (i) the rate of RBC replenishment; (ii) the rate of destruction of uninfected RBCs; and (iii) the maximum parasite growth rate. Comparing predictions of this model with experimental results for rodent malaria in laboratory mice allowed us to reject functional forms of immune upregulation and/or effects of RBC limitation that were inconsistent with the data. Bottom-up regulation alone was insufficient to account for observed patterns without invoking either localized depletion of RBC density or merozoite interference. By contrast, an immune function upregulated in proportion to either merozoite or infected RBC density was consistent with observed dynamics. An immune response directed solely at merozoites required twice the level of activation of one directed at infected RBCs.     

Is the incidence of malaria decreasing in endemic area of Turkey?

Much international business and tourism travels occur, as well as the deployment of soldiers to other places. The aim of this study was both to determine incidence of malaria in the military hospital, Diyarbakir, southeast region of Turkey, and to point out the incidence of this disease. During the study period (1997-2004), 609 cases were found in a military hospital, which is in an endemic area for vivax malaria. This article review trends in current malaria status as well as possible factors for the decreasing prevalence throughout the study period.     

Absence of asymptomatic malaria in schoolchildren of Quibdó, Chocó

Asymptomatic malaria is characteristic of high intensity transmission areas in Africa but unusual in low transmission areas in Latin America. Nevertheless, asymptomatic malaria has been reported to be frequent in areas in Latin America with high and moderate intensity of transmission. Asymptomatic malaria can affect both individuals who carry parasites and are cryptic carrier reservoirs for the community. Individuals chronically infected with malaria parasites are usually unidentifiable by most malaria control programmes. In order to identify whether asymptomatic individuals harboring malaria parasites are an important reservoir of infection in Quibdó, Chocó, the prevalence of asymptomatic malaria was assessed in schoolchildren. This study was part of a major study of the epidemiology of malaria in Quibdó. A total of 255 children from 5 schools were examined, of which 223 were included in the analysis. Children reported headache (34%), cough (32%), and diarrhoea (9%). None of the children presented a positive thick smear. In addition, IFA tests in a subsample of 25 children were negative. By these criteria, the prevalence of asymptomatic malaria in Quibdó schoolchildren is 0% (95%C.I.: 0.0-1.4). Although asymptomatic malaria in adults possibly occurs, a very low prevalence is predicted.     

Serology: a robust indicator of malaria transmission intensity?

To estimate the burden of malarial disease, and evaluate the likely effects of control strategies, requires reliable predictions of malaria transmission intensity. It has long been suggested that antimalarial antibody prevalences could provide a more accurate estimate of transmission intensity than traditional measures such as parasite prevalence or entomological inoculation rates, but there has been no systematic evaluation of this approach. Now, the availability of well characterized malarial antigens allows us to test whether serological measurements provide a practical method for estimating transmission. Here we present a suggested methodology, highlight the advantages and shortcomings of serological measurements of malaria transmission and identify areas in which further work is desirable.     

Mosquitoes and transmission of malaria parasites – not just vectors

The regional malaria epidemics of the early 1900s provided the basis for much of our current understanding of malaria epidemiology. Colonel Gill, an eminent malariologist of that time, suggested that the explosive nature of the regional epidemics was due to a sudden increased infectiousness of the adult population. His pertinent observations underlying this suggestion have, however, gone unheeded. Here, the literature on Plasmodium seasonal behaviour is reviewed and three historical data sets, concerning seasonal transmission of Plasmodium falciparum, are examined. It is proposed that the dramatic seasonal increase in the density of uninfected mosquito bites results in an increased infectiousness of the human reservoir of infection and, therefore, plays a key role in "kick-starting" malaria parasite transmission.     

How useful is PCR in the diagnosis of malaria?

Polymerase chain reaction (PCR) assays are the most sensitive and specific method to detect malaria parasites, and have acknowledged value in research settings. However, the time lag between sample collection, transportation and processing, and dissemination of results back to the physician limits the usefulness of PCR in routine clinical practice. Furthermore, in most areas with malaria transmission, factors such as limited financial resources, persistent subclinical parasitaemia, inadequate laboratory infrastructures in the poorer, remote rural areas preclude PCR as a diagnostic method. Even in affluent, non-endemic countries, PCR is not a suitable method for routine use. Nonetheless, PCR could be clinically useful in selected situations.     

Why model malaria?

The past 30 years have seen little tangible progress in alleviating the worldwide burden of malaria. Ellis McKenzie here discusses some of the history, problems and prospects of mathematical models of malaria, and the contributions that models might make towards progress. He argues that models can be powerful tools for integrating information from different disciplines, and that advances in computer modeling can complement and extend classic approaches.     

Knowlesi malaria: newly emergent and of public health importance?

Several questions on public health impact have arisen from the discovery of a large focus of the simian malaria parasite, Plasmodium knowlesi, in the human population. P. knowlesi malaria is not newly emergent and was overlooked until molecular tools to distinguish between P. knowlesi and the morphologically similar Plasmodium malariae became available. Knowlesi malaria is a zoonosis that is widely distributed in Southeast Asia and can be fatal. Information on knowlesi malaria should be included in medical and public health guidelines to encourage the accurate diagnosis and treatment of patients, and monitor the incidence and distribution of cases. A complete emergence of P. knowlesi into the human population could be overwhelming and, although challenging, the prevention of this situation deserves serious consideration.     

Delayed cerebellar ataxia: a new complication of falciparum malaria?

Twelve cases of an unusual phenomenon of ataxia were investigated in otherwise well, conscious patients recovering from a febrile attack of presumed falciparum malaria. The ataxia occurred as the fever was subsiding, usually after an afebrile period of two to four days. The delay between onset of fever and the ataxia was three to four weeks. Peripheral blood of all the patients contained gametocytes of Plasmodium falciparum, and in some cases ring stages. The ataxia was most noticeable in the legs and the clinical picture suggested selective impairment of the cerebellar system. Signs of improvement appeared in a few weeks but complete recovery took one to four months. The most likely pathogenic mechanism of the ataxia in these cases was an immune reaction triggered by the malaria parasite and affecting the cerebellum or its connections, or both.     

What is the function of MSP-I on the malaria merozoite?

In the absence o f any clear enzymatic activity, attempts to define the role of merozoite surface protein-I have focused mainly on analysis of its structure, on its interaction with the immune system and on binding assays. But how does our knowledge of the structure o f this protein contribute to functional studies? Are there data to suggest a role in the evasion of effective host immune responses? Binding studies have used the intact protein or various fragments and peptides, but do such approaches provide a reliable indicator of function? In this article, Tony Holder and Mike Blackman review these areas.     

Acidosis of severe falciparum malaria: heading for a shock?

Severe Plasmodium falciparum malaria encompasses a complex syndrome affecting many organs and causing physiological perturbations that have many features in common with children with sepsis. Among these, metabolic acidosis has emerged as a central feature of severe malaria and is the best independent predictor of a fatal outcome in both adults and children. There is now clear evidence that intravascular hypovolaemia (shock) is common in children with malarial acidosis. How it should be treated presents a therapeutic dilemma because acidosis often coexists with impaired consciousness (cerebral malaria). We summarize the results of recent clinical trials examining the safety and efficacy of volume expansion in children with 'cerebral malaria' complicated by acidosis.     

Evaluation of the Clearview<Superscript>®</Superscript> malaria pLDH malaria rapid diagnostic test in a non-endemic setting

Background

Malaria Rapid Diagnostic Tests (RDTs) are widely used to diagnose malaria. The present study evaluated a new RDT, the Clearview^® Malaria pLDH test targeting the pan-Plasmodium antigen lactate dehydrogenase (pLDH).

Methods

The Clearview^® Malaria pLDH test was evaluated on fresh samples obtained in returned international travellers using microscopy corrected by PCR as the reference method. Included samples were Plasmodium falciparum (139), Plasmodium vivax (22), Plasmodium ovale (20), Plasmodium malariae (7), and 102 negative.

Results

Overall sensitivity for the detection of Plasmodium spp was 93.2%. For P. falciparum, the sensitivity was 98.6%; for P. vivax, P. ovale and P. malariae, overall sensitivities were 90.9%, 60.0% and 85.7% respectively. For P. falciparum and for P. vivax, the sensitivities increased to 100% at parasite densities above 100/μl. The specificity was 100%. The test was easily to perform and the result was stable for at least 1 hour.

Conclusion

The Clearview^® Malaria pLDH was efficient for the diagnosis of malaria. The test was very sensitive for P. falciparum and P. vivax detection. The sensitivities for P. ovale and P. malariae were better than other RDTs

     

The decline of malaria in Finland – the impact of the vector and social variables

Background

Resistance to anti-malarial drugs hampers control efforts and increases the risk of morbidity and mortality from malaria. The efficacy of standard therapies for uncomplicated Plasmodium falciparum and Plasmodium vivax malaria was assessed in Chumkiri, Kampot Province, Cambodia.

Methods

One hundred fifty-one subjects with uncomplicated falciparum malaria received directly observed therapy with 12 mg/kg artesunate (over three days) and 25 mg/kg mefloquine, up to a maximum dose of 600 mg artesunate/1,000 mg mefloquine. One hundred nine subjects with uncomplicated vivax malaria received a total of 25 mg/kg chloroquine, up to a maximum dose of 1,500 mg, over three days. Subjects were followed for 42 days or until recurrent parasitaemia was observed. For P. falciparum infected subjects, PCR genotyping of msp1, msp2, and glurp was used to distinguish treatment failures from new infections. Treatment failure rates at days 28 and 42 were analyzed using both per protocol and Kaplan-Meier survival analysis. Real Time PCR was used to measure the copy number of the pfmdr1 gene and standard 48-hour isotopic hypoxanthine incorporation assays were used to measure IC₅₀ for anti-malarial drugs.

Results

Among P. falciparum infected subjects, 47.0% were still parasitemic on day 2 and 11.3% on day 3. The PCR corrected treatment failure rates determined by survival analysis at 28 and 42 days were 13.1% and 18.8%, respectively. Treatment failure was associated with increased pfmdr1 copy number, higher initial parasitaemia, higher mefloquine IC₅₀, and longer time to parasite clearance. One P. falciparum isolate, from a treatment failure, had markedly elevated IC₅₀ for both mefloquine (130 nM) and artesunate (6.7 nM). Among P. vivax infected subjects, 42.1% suffered recurrent P. vivax parasitaemia. None acquired new P. falciparum infection.

Conclusion

The results suggest that artesunate-mefloquine combination therapy is beginning to fail in southern Cambodia and that resistance is not confined to the provinces at the Thai-Cambodian border. It is unclear whether the treatment failures are due solely to mefloquine resistance or to artesunate resistance as well. The findings of delayed clearance times and elevated artesunate IC₅₀ suggest that artesunate resistance may be emerging on a background of mefloquine resistance.