Accurate Diagnosis Of Malaria Research Articles

Falciparum malaria and HIV-1 in hospitalized adults in Maputo, Mozambique: does HIV-infection obscure the malaria diagnosis?

BackgroundThe potential impact of HIV-1 on falciparum malaria has been difficult to determine because of diagnostic problems and insufficient epidemiological data.MethodsIn a prospective, cross-sectional study, clinical and laboratory data was registered consecutively for all adults admitted to a medical ward in the Central Hospital of Maputo, Mozambique, during two months from 28th October 2006. Risk factors for fatal outcome were analysed. The impact of HIV on the accuracy of malaria diagnosis was assessed, comparing "Presumptive malaria", a diagnosis assigned by the ward clinicians based on fever and symptoms suggestive of malaria in the absence of signs of other infections, and "Verified malaria", a malaria diagnosis that was not rejected during retrospective review of all available data.ResultsAmong 333 included patients, fifteen percent (51/333) had "presumptive malaria", ten percent (28 of 285 tested persons) had positive malaria blood slides, while 69.1% (188/272) were HIV positive. Seven percent (n = 23) had "verified malaria", after the diagnosis was rejected in patients with neck stiffness or symptom duration longer than 2 weeks (n = 5) and persons with negative (n = 19) or unknown malaria blood slide (n = 4). Clinical stage of HIV infection (CDC), hypotension and hypoglycaemia was associated with fatal outcome. The "presumptive malaria" diagnosis was rejected more frequently in HIV positive (20/31) than in HIV negative patients (2/10, p = 0.023).ConclusionThe study suggests that the fraction of febrile illness attributable to malaria is lower in HIV positive adults. HIV testing should be considered early in evaluation of patients with suspected malaria.

Determinants of the accuracy of rapid diagnostic tests in malaria case management: evidence from low and moderate transmission settings in the East African highlands

BackgroundThe accuracy of malaria diagnosis has received renewed interest in recent years due to changes in treatment policies in favour of relatively high-cost artemisinin-based combination therapies. The use of rapid diagnostic tests (RDTs) based on histidine-rich protein 2 (HRP2) synthesized by Plasmodium falciparum has been widely advocated to save costs and to minimize inappropriate treatment of non-malarial febrile illnesses. HRP2-based RDTs are highly sensitive and stable; however, their specificity is a cause for concern, particularly in areas of intense malaria transmission due to persistence of HRP2 antigens from previous infections.MethodsIn this study, 78,454 clinically diagnosed malaria patients were tested using HRP2-based RDTs over a period of approximately four years in four highland sites in Kenya and Uganda representing hypoendemic to mesoendemic settings. In addition, the utility of the tests was evaluated in comparison with expert microscopy for disease management in 2,241 subjects in two sites with different endemicity levels over four months.ResultsRDT positivity rates varied by season and year, indicating temporal changes in accuracy of clinical diagnosis. Compared to expert microscopy, the sensitivity, specificity, positive predictive value and negative predictive value of the RDTs in a hypoendemic site were 90.0%, 99.9%, 90.0% and 99.9%, respectively. Corresponding measures at a mesoendemic site were 91.0%, 65.0%, 71.6% and 88.1%. Although sensitivities at the two sites were broadly comparable, levels of specificity varied considerably between the sites as well as according to month of test, age of patient, and presence or absence of fever during consultation. Specificity was relatively high in older age groups and increased towards the end of the transmission season, indicating the role played by anti-HRP2 antibodies. Patients with high parasite densities were more likely to test positive with RDTs than those with low density infections.ConclusionRDTs may be effective when used in low endemicity situations, but high false positive error rates may occur in areas with moderately high transmission. Reports on specificity of RDTs and cost-effectiveness analyses on their use should be interpreted with caution as there may be wide variations in these measurements depending upon endemicity, season and the age group of patients studied.

Household cost of malaria overdiagnosis in rural Mozambique

BackgroundIt is estimated that over 70% of patients with suspected malaria in sub-Saharan Africa, diagnose and manage their illness at home without referral to a formal health clinic. Of those patients who do attend a formal health clinic, malaria overdiagnosis rates are estimated to range between 30–70%.MethodsThis paper details an observational cohort study documenting the number and cost of repeat consultations as a result of malaria overdiagnosis at two health care providers in a rural district of Mozambique. 535 adults and children with a clinical diagnosis of malaria were enrolled and followed over a 21 day period to assess treatment regimen, symptoms, number and cost of repeat visits to health providers in patients misdiagnosed with malaria compared to those with confirmed malaria (determined by positive bloodfilm reading).ResultsDiagnosis based solely on clinical symptoms overdiagnosed 23% of children (<16y) and 31% of adults with malaria. Symptoms persisted (p = 0.023) and new ones developed (p < 0.001) in more adults than children in the three weeks following initial presentation. Adults overdiagnosed with malaria had more repeat visits (67% v 46%, p = 0.01–0.06) compared to those with true malaria. There was no difference in costs between patients correctly or incorrectly diagnosed with malaria. Median costs over three weeks were $0.28 for those who had one visit and $0.76 for ≥ 3 visits and were proportionally highest among the poorest (p < 0.001)ConclusionOverdiagnosis of malaria results in a greater number of healthcare visits and associated cost for adult patients. Additionally, it is clear that the poorest individuals pay significantly more proportionally for their healthcare making it imperative that the treatment they receive is correct in order to prevent wastage of limited economic resources. Thus, investment in accurate malaria diagnosis and appropriate management at primary level is critical for improving health outcomes and reducing poverty.

A Review of Malaria Diagnostic Tools: Microscopy and Rapid Diagnostic Test (RDT)

The absolute necessity for rational therapy in the face of rampant drug resistance places increasing importance on the accuracy of malaria diagnosis. Giemsa microscopy and rapid diagnostic tests (RDTs) represent the two diagnostics most likely to have the largest impact on malaria control today. These two methods, each with characteristic strengths and limitations, together represent the best hope for accurate diagnosis as a key component of successful malaria control. This review addresses the quality issues with current malaria diagnostics and presents data from recent rapid diagnostic test trials. Reduction of malaria morbidity and drug resistance intensity plus the associated economic loss of these two factors require urgent scaling up of the quality of parasite-based diagnostic methods. An investment in anti-malarial drug development or malaria vaccine development should be accompanied by a parallel commitment to improve diagnostic tools and their availability to people living in malarious areas.

Malaria diagnosis under field conditions in the Venezuelan Amazon

To improve practical, accurate diagnosis of malaria in the Amazon rainforest of Venezuela, two rapid diagnostic tests (RDT) (OptiMAL-IT) and FalciVax) and a laboratory light microscope, used in the field with a battery-operated head lamp as an external light source, were evaluated against the standard laboratory microscope procedure for malaria detection. One hundred and thirty-six Yanomami patients were studied for the presence of malaria parasites. Thirty-three patients (24%) were positive for malaria (Plasmodium falciparum, P. vivax, P. malariae). Twenty-one (64%) of the positive patients had <100 parasites/microl. Both RDTs showed poor sensitivity (24.2% for OptiMAL-IT) and 36.4% for FalciVax) but good specificity (99% both for OptiMAL-IT) and FalciVax). Field and laboratory microscopy showed sensitivities of 94% and 91%, respectively. The kappa coefficient was 0.90, indicating a high agreement between field and laboratory microscopy. We conclude that (i) adequate slide reading cannot be substituted by either of the two RDTs in the Venezuelan Amazon and (ii) the use of a light source such as that described above makes slide reading more feasible than hitherto in remote areas without electricity.

Genetic Diversity ofPlasmodium falciparumHistidine‐Rich Protein 2 (PfHRP2) and Its Effect on the Performance of PfHRP2‐Based Rapid Diagnostic Tests

Rising costs of antimalarial agents are increasing the demand for accurate diagnosis of malaria. Rapid diagnostic tests (RDTs) offer great potential to improve the diagnosis of malaria, particularly in remote areas. Many RDTs are based on the detection of Plasmodium falciparum histidine-rich protein (PfHRP) 2, but reports from field tests have questioned their sensitivity and reliability. We hypothesize that the variability in the results of PfHRP2-based RDTs is related to the variability in the target antigen. We tested this hypothesis by examining the genetic diversity of PfHRP2, which includes numerous amino acid repeats, in 75 P. falciparum lines and isolates originating from 19 countries and testing a subset of parasites by use of 2 PfHRP2-based RDTs. We observed extensive diversity in PfHRP2 sequences, both within and between countries. Logistic regression analysis indicated that 2 types of repeats were predictive of RDT detection sensitivity (87.5% accuracy), with predictions suggesting that only 84% of P. falciparum parasites in the Asia-Pacific region are likely to be detected at densities < or = 250 parasites/microL. Our data also indicated that PfHRP3 may play a role in the performance of PfHRP2-based RDTs. These findings provide an alternative explanation for the variable sensitivity in field tests of malaria RDTs that is not due to the quality of the RDTs.

Cerebral malaria is frequently associated with latent parasitemia among the semi-immune population of eastern Sudan

The accurate diagnosis of malaria starts with clinical suspicion, confirmed by reliable laboratory results. A hospital-based study, described here, was carried out in a malaria mesoendemic area in eastern Sudan, where the inhabitants are semi-immune to malaria, and the fever threshold of parasitemia is not above the detection level of microscopy. Thus, we hypothesized that patients with symptoms highly suggestive of cerebral malaria (CM), but aparasitemic by microscopy, may have submicroscopic parasitemia. Patients in our malaria clinic were screened by microscopy, and 120 individuals were selected for the study, including febrile patients with and without microscopically detectable parasitemia, and apparently healthy individuals. In the two former groups there were patients with severe anemia and deep coma. Polymerase chain reaction (PCR) for parasite detection and ELISA tests for measuring serum antibody levels were carried out on all blood samples. A majority of the febrile patients who were parasite negative by microscopy showed the presence of a Plasmodium falciparum infection by PCR. The occurrence of P. falciparum infection with parasitemia below the detection level of microscopy was recognized more often in patients with CM symptoms than in those with severe malarial anemia (SMA), and in older rather than younger patients. Patients clinically suspected (CS) of having CM ( CSCM) mostly were infected with a single clone, and a large proportion of them acquired antibodies (Abs) against merozoite surface protein (MSP) antigens (Ags). The therapeutic response to quinine treatment was comparable between patients with CSCM and CM. In conclusion, uniquely in this setting, CM can be associated with sub-patent parasitemia; thus, a diagnostic tool more sensitive than microscopy is needed.

Imported malaria notified in New South Wales and the Australian Capital Territory, including trends in notifications ofPlasmodium falciparum, 1989 to 2003

Malaria is the most common tropical parasitic infection imported into NSW. This article presents a review of all cases of malaria diagnosed and notified in NSW and the Australian Capital Territory from 1989 to the end of 2003. Of the four species of malaria infecting humans, Plasmodium falciparum, P. vivax, P. ovale and P. malariae, P. falciparum is most likely to be associated with serious illness and death. Therefore, trends in the occurrence of this species over the period are examined. This information is of value to clinicians and public health professionals in highlighting both the importance of rapid and accurate diagnosis of malaria and the changing trends in the origin of imported cases.

Accurate Clinical Diagnosis of Malaria in a Postflood Epidemic: A Field Study in Mozambique

To determine the positive predictive value (PPV) of a clinical diagnosis vs laboratory testing for malaria in a remote field setting following a natural disaster. During an observational study, as part of a disaster response in Mozambique, patients were clinically diagnosed and treated for malaria. The population included native tribes in remote areas and displaced persons in refugee camps representing all age groups, male and female. The diagnosis was made if patients exhibited at least 3 of the following historical features: fever, chills, headache, and nausea/vomiting (N/V). In addition they had to have either a tactile fever or palpable spleen. At the conclusion of the mission, 28 patients were prospectively tested with an antigen-capture assay for P. falciparum to determine the PPV of clinical diagnosis vs definitive laboratory testing. During the study period, 1215 of 4064 (30%) patients were diagnosed with malaria based on clinical presentation. On our final day, 28 consecutive patients with a clinical diagnosis of malaria were tested using an antigen-capture assay for P. falciparum. Of those, 25 tested positive-yielding a PPV of 89% (CI 0.78-1.01). In a remote field setting where malaria is endemic/epidemic, diagnosis of malaria based on selected historical and physical findings is possible with a high positive predictive value.

Malaria Screening of Blood Donors in Saudi Arabia

Transfusion-associated malaria is a potentially serious complication that continues to pose risks in blood bank settings. There is a need for effective malaria screening of blood donations to improve on the current exclusion policies of potentially infected carriers on the basis of clinical and travel history. We evaluated the potential usefulness of ELISA screening for malaria antibody and P. falciparum antigen among Saudi blood donors. A total of 1756 donors were studied, 1100 from the malaria endemic Southern Region and 656 donors from the known malaria-free Riyadh area. The overall antibody prevalence for the antibody was 7.6%, in comparison to only 0.17% for the antigen. In the endemic region, the antibody positivity rate of 9.1% was almost double the rate in the non-endemic area (4.8%). There was no difference in the antigen prevalence rates; 0.18% in endemic and 0.15% in nonendemic areas. In malaria endemic countries like Saudi Arabia, excluding antibody-positive donations would result in too much wastage of blood units. However, antigen malaria testing appears to offer a potential utility, as only few donations would be rejected.

DIAGNOSIS OF MALARIA BY DETECTION OF PLASMODIAL LACTATE DEHYDROGENASE WITH AN IMMUNODOT ENZYME ASSAY

We have previously demonstrated, using polyclonal and monoclonal antibodies, that the lactate dehydrogenase (LDH) of malaria parasites is immunologically distinct from the host enzyme. The polyclonal antibodies, produced against the affinity purified plasmodial LDH (pLDH) in rabbits, showed specificity to LDH of malaria parasites. In the present study, these anti-pLDH polyclonal antibodies were used to develop an immunodiagnostic test (immunodot enzyme assay of plasmodial LDH) based on the detection of parasite LDH in patient blood. The immunodot enzyme assay of plasmodial LDH was evaluated using blood samples from patients with malaria or other infections. Out of 502 microscopically positive malaria blood samples, 497 blood samples showed positive immunodot assays of pLDH while all the 423 microscopically negative cases were found negative by our test. The blood samples from other infections and non-endemic controls were negative by the immunodot enzyme assay of pLDH. This LDH based test was also found negative in blood samples of cured patients 7 days after chloroquine treatment. The test is simple to perform, can be read visually, econimal, highly specific with a sensitivity of ∼99% and is thus suitable for accurate diagnosis of malaria in field conditions.

An easier and more accurate diagnosis of malaria and filariasis through the use of the skin scarification smear.

SummaryThe superficial scarification of the scapular region is advocated in order to obtain a thin smear of dermal juice which, stained with Giemsa, provides an easy and more accurate means, both quantitatively and qualitatively, of diagnosing malaria parasites as well as the microfilarias of both blood and skin.

The Treatment of Pernicious Anemia and Other Macrocytic Anemias With Vitamin B12

Malaria is a mosquito-borne disease caused by five species of Plasmodium parasites. Accurate diagnosis of malaria plays an essential part in malaria control. With traditional diagnostic methodologies, malaria control programs have achieved remarkable success during the past decade, and are now heading toward malaria elimination in many areas. This new situation, however, calls for novel diagnostics with improved sensitivity, throughput, and reduced cost for active screening of malaria parasites, as all transfected individuals have to be identified in order to block transmission. In this chapter, we provide a brief introduction of malaria, the requirement of diagnostic advances in the age of malaria elimination, and a comprehensive overview of the currently available molecular malaria diagnostics, ranging from well-known tests to platforms in early stages of evaluation. We also discussed several practical issues for the application of molecular tests in malaria identification.