GUIDE BOOK. SD BIOLINE Malaria Antigen Rapid Test series. Standard Diagnostics, Inc.

Transcription

1 GUIDE BOOK SD BIOLINE Malaria Antigen Rapid Test series Standard Diagnostics, Inc.

2 TABLE OF CONTENTS I. PRODUCT INFORMATION 3 II. BACKGROUND INFORMATION 7 III. CLINICAL FEATURES AND TREATMENT 12 IV. COMPARISON WITH OTHER DIAGNOSTIC METHODS 13 V. THE USE OF MALARIA RAPID TEST 15 Standard Diagnostics, Inc. 2 of 15

3 I. PRODUCT INFORMATION SD BIOLINE Malaria Ag One step differential diagnosis by detecting pldh antigen from Malaria Plasmodium falciparum and other species (P.vivax, P.malariae, P.ovale) in human whole blood Cat.No. 05FK40 Tests/ kit 25 tests/ kit Kit Contents test devices, assay diluent, Capillary tube and package insert Optional : alcohol swab, lancet Specimen Whole blood Percent accuracy P.f P.pan Sensitivity 96.8% 95.5% Specificity 99.5% Test procedure Interpretation Standard Diagnostics, Inc. 3 of 15

4 SD BIOLINE Malaria Ag Pf One step diagnosis by detecting HRPII antigen from Malaria Plasmodium falciparum in human whole blood Cat.No. 05FK50 Tests/ kit 25 tests/ kit Kit Contents test devices, assay diluent, Capillary tube and package insert Optional : alcohol swab, lancet Specimen Whole blood Percent accuracy Sensitivity 99.7% Specificity 99.5% Test procedure Add 5ul of blood into sample well Add 4 drops of assay diluent Interpret test results into assay diluent well in 20~30 minutes. Interpretation Standard Diagnostics, Inc. 4 of 15

5 SD BIOLINE Malaria Ag Pf/Pan One step differential diagnosis by detecting HRP-II antigen from Malaria Plasmodium falciparum and pldh antigen from other species (P.vivax, P.malariae, P.ovale) in human whole blood Cat.No. 05FK60 Tests/ kit 25 tests/ kit Kit Contents test devices, assay diluent, Capillary tube and package insert Optional : alcohol swab, lancet Specimen Whole blood Percent accuracy P.f P.pan Sensitivity 99.7% 95.5% Specificity 99.5% Test procedure Interpretation Standard Diagnostics, Inc. 5 of 15

6 Summary Cat. No. Item Method Detection Result Line Sensitivity Specificity 05FK40 Malaria Ag pldh P.f P.pan(v,m,o) 05FK50 Malaria Ag Pf HRP-2 P.f only 05FK60 Malaria Ag Pf/Pan pldh : P.pan P.f HRP-2 : P.f P.pan(v,m,o) 3 Line P.f 96.8 % (121/125) (C/ P.f/ P.pan) P.pan 95.5 % (106/111) 2 Line 99.7% (C/ T) (367/368) 3 Line P.f 99.7 % (367/368) (C/ P.f/ P.pan) P.pan 95.5 % (106/111) 99.5% (199/200) 99.5% (199/200) 99.5% (199/200) Packing Information Cat. No. 05FK40 05FK50 05FK60 Product Name SD BIOLINE Malaria Ag SD BIOLINE Malaria Ag Pf SD BIOLINE Malaria Ag Pf/Pan Kit Contents Type of Specimen Run time for test result interpretation Packaging Information Test devices, Assay diluent, Capillary tube and Insert ( Optional : alcohol swab, lancet ) Whole blood 20~30minutes 25Tests per kit 35Kits per carton Dimensions: 222 x 135 x 71 mm Test Kit Package Volume: 2128 cm³ Weight: 280 g Dimensions: 53 x 48 x 40 cm Shipping Carton Volume: 101,760 cm³ Weight: 17 kg Storage Conditions Self Life 2 ~ 30 at room temperature 24months Standard Diagnostics, Inc. 6 of 15

7 II. BACKGROUND INFORMATION What is Malaria? Malaria is a common infection in hot, tropical areas but can also occur (rarely) in temperate climates. It is caused by any of four single-celled parasites of the Plasmodium species, which are carried by mosquitoes infected from biting someone who already has the disease. Malaria is then transmitted to other people when they are bitten by the infected mosquitoes. Where does Malaria Occur? Malaria typically is found in warmer regions of the world -- in tropical and subtropical countries. Higher temperatures allow the Anopheles mosquito to thrive. Malaria parasites, which grow and develop inside the mosquito, need warmth to complete their growth before they are mature enough to be transmitted to humans. Malaria occurs in over 100 countries and territories. More than 40% of the world s population is at risk. Large areas of Central and South America, Hispaniola (the Caribbean island that is divided between Haiti and the Dominican Republic), Africa, the Indian subcontinent, Southeast Asia, the Middle East, and Oceania are considered malaria-risk areas. Especially malaria is so common in Africa. In Africa south of the Sahara, the principal malaria mosquito, Anopheles gambiae, transmits malaria very efficiently. The type of malaria parasite most often found, Plasmodium falciparum, causes severe, potentially fatal disease. Lack of resources and political instability can prevent the building of solid malaria control programs. In addition, malaria parasites are increasingly resistant to anti-malarial drugs, presenting one more barrier to malaria control in that continent. Malaria Endemic Areas _ Malaria cases Standard Diagnostics, Inc. 7 of 15

8 Is Malaria A common Disease? Yes. The World Health Organization estimates that each year million cases of malaria occur and more than 1 million people die of malaria. Also malaria is a leading cause of death and disease worldwide, especially in developing countries. Most deaths occur in young children. For example, in Africa, a child dies from malaria every 30 seconds. Because malaria causes so much illness and death, the disease is a great drain on many national economies. Since many countries with malaria are already among the poorer nations, the disease maintains a vicious cycle of disease and poverty. No. Country Case Case rate Death Year 1 Uganda 12,343, % 8, Tanzania (United Rep. of) 10,712, % 14, Mozambique 5,087, % 3, Congo (Dem. Republic of) 4,386, % 16, Ghana 3,552, % 3, Sudan 3,084, % 2, Malawi 2,853, % 6, Nigeria 2,608, % 5, Madagascar 2,114, % Zambia 2,010, % 5, Anopheles Mosquitoes Malaria is transmitted among humans by female mosquitoes of the genus Anopheles. Female mosquitoes take blood meals to carry out egg production, and such blood meals are the link between the human and the mosquito hosts in the parasite life cycle. Of the approximately 430 known species of Anopheles, only transmit malaria in nature. The successful development of the malaria parasite in the mosquito (from the "gametocyte" stage to the "sporozoite" stage) depends on several factors. The most important is ambient temperature and humidity (higher temperatures accelerate the parasite growth in the mosquito) and whether the Anopheles survives long enough to allow the parasite to complete its cycle in the mosquito host ("sporogonic" or "extrinsic" cycle, duration 10 to 18 days). Differently from the human host, the mosquito host does not suffer noticeably from the presence of the parasites. < Anopheles mosquitoes > Standard Diagnostics, Inc. 8 of 15

9 Life Cycle In nature, malaria parasites spread by infecting successively two types of hosts: humans and female Anopheles mosquitoes. In humans, the parasites grow and multiply first in the liver cells and then in the red cells of the blood. In the blood, successive broods of parasites grow inside the red cells and destroy them, releasing daughter parasites ("merozoites") that continue the cycle by invading other red cells. The blood stage parasites are those that cause the symptoms of malaria. When certain forms of blood stage parasites ("gametocytes") are picked up by a female Anopheles mosquito during a blood meal, they start another, different cycle of growth and multiplication in the mosquito. After days, the parasites are found (as "sporozoites") in the mosquito's salivary glands. When the Anopheles mosquito takes a blood meal on another human, the sporozoites are injected with the mosquito's saliva and start another human infection when they parasitize the liver cells. Thus the mosquito carries the disease from one human to another (acting as a "vector"). Differently from the human host, the mosquito vector does not suffer from the presence of the parasites. Malaria Parasites Malaria parasites are micro-organisms that belong to the genus Plasmodium. There are more than 100 species of Plasmodium, which can infect many animal species such as reptiles, birds, and various mammals. Only four species of Plasmodium infect humans in nature. (There are some other species which can, exceptionally or under experimental conditions, infect humans.) The four species infecting humans are: *P.falciparum *P.vivax Plasmodium falciparum, which is found worldwide in tropical and subtropical areas. It is the only species that can cause severe, potentially fatal malaria. It is estimated that every year 700,000 to 2.7 million people are killed by P. falciparum, especially in Africa where this species predominates. Plasmodium falciparum can cause severe malaria because it multiples rapidly in the blood, and can thus cause severe blood loss (anemia). In addition, the infected parasites can clog small blood vessels. When this occurs in the brain, cerebral malaria results, a complication that can be fatal. Plasmodium vivax, which is found mostly in Asia, Latin America, and in some parts of Africa. Because of the population densities especially in Asia it is probably the most prevalent human malaria parasite. While P. vivax only exceptionally causes death (most often due to rupture of an enlarged spleen), it can cause symptoms that are incapacitating. Thus, P. vivax contributes substantially to the disease burden (morbidity) of malaria, with a resulting social and economic impact. Plasmodium vivax (as well as P. ovale) has dormant liver stages ("hypnozoites") that can activate and invade the blood ("relapse") several months or years after the infecting mosquito bite. Standard Diagnostics, Inc. 9 of 15

10 The two other species are less frequently encountered: *P.ovale *P.malariae Plasmodium ovale, which is found mostly in Africa (especially West Africa) and the islands of the western Pacific. It is biologically and morphologically very similar to P. vivax. However, differently from P. vivax, it can infect individuals who are negative for the Duffy blood group, which is the case for many residents of sub Saharan Africa. This explains the greater prevalence of P. ovale (rather than P. vivax ) in most of Africa. Plasmodium malariae, found worldwide, is the only human malaria parasite species that has a quartan cycle (three-day cycle). (The three other species have a tertian, two-day cycle). Plasmodium malariae causes a longlasting, chronic infection that in some cases can last a lifetime. In some patients P. malariae can cause serious complications such as the nephrotic syndrome. Countries and Territories With malaria s Areas The following list shows all countries where malaria occurs. In some of these countries, malaria is present only in certain areas or up to a particular altitude. In many countries, malaria has a seasonal pattern. These details are provided in the Country list, together with information on the predominant malaria species, status of resistance to antimalarial drugs and recommended chemoprophylactic regimen. (* = P. vivax risk only) Afghanistan Algeria* Angola Argentina * Armenia * Azerbaijan * Bangladesh Belize Benin Bhutan Bolivia Botswana Brazil Burkina Faso Burundi Cambodia Cameroon Cape Verde Central African Republic Chad China Colombia Comoros Congo Congo, Democratic Republic of the (former Zaire) Costa Rica Cote d Ivoire Djibouti Dominican Republic Ecuador Egypt El Salvador Equatorial Guinea Eritrea Ethiopia French Guiana Gabon Gambia Georgia * Ghana Guatemala Guinea Guinea-Bissau Guyana Haiti Honduras India Indonesia Iran, Islamic Republic of Iraq * Kenya Korea, Democratic People s Republic of * Korea, Republic of * Kyrgyzstan Lao People s Democratic Republic Liberia Madagascar Malawi Malaysia Mali Mauritania Mauritius * Mayotte Mexico Morocco * Mozambique Myanmar Namibia Nepal Nicaragua Niger Nigeria Oman Pakistan Panama Standard Diagnostics, Inc. 10 of 15

11 Papua New Guinea Paraguay Peru Philippines Rwanda Sao Tome and Principe Saudi Arabia Senegal Sierra Leone Solomon Islands Somalia South Africa Sri Lanka Sudan Suriname Swaziland Syrian Arab Republic * Tajikistan Tanzania, United Republic of Thailand Timor-Leste Togo Turkey * Turkmenistan * Uganda Uzbekistan Vanuatu Venezuela Viet Nam Yemen Zambia Zimbabwe Standard Diagnostics, Inc. 11 of 15

12 III. CLINICAL FEATURES AND TREATMENT Signs and Symptoms of Malaria? Symptoms of malaria include fever and flu-like illness, including shaking chills, headache, muscle aches, and tiredness. Nausea, vomiting, and diarrhea may also occur. Malaria may cause anemia and jaundice (yellow coloring of the skin and eyes) because of the loss of red blood cells. Infection with one type of malaria, Plasmodium falciparum, if not promptly treated, may cause kidney failure, seizures, mental confusion, coma, and death. NOTE : Any traveler who becomes ill with a fever or flu-like illness while traveling to Africa and up to 1 year after visiting Africa should be considered as malaria inspection. It might take longer than 1 year after infection to windows period of malaria How soon will A person Feel sick After being Bitten by An infected Mosquito? For most people, symptoms begin 10 days to 4 weeks after infection, although a person may feel ill as early as 7 days or as late as 1 year later. Two kinds of malaria, P. vivax and P. ovale, can relapse. In P. vivax and P. ovale infections, some parasites can remain dormant in the liver for several months up to about 4 years after a person is bitten by an infected mosquito. When these parasites come out of hibernation and begin invading red blood cells ( relapse ), the person will become sick. What is the Treatment for Malaria? Malaria can be cured with prescription drugs. The type of drugs and length of treatment depend on which kind of malaria is diagnosed, where the patient was infected, the age of the patient, whether the patient is pregnant, and how severely ill the patient is at start of treatment. Isn't there a Malaria Vaccine? And if not, Why? There is currently no malaria vaccine approved for human use. The malaria parasite is a complex organism with a complicated life cycle. Its antigens are constantly changing and developing a vaccine against these varying antigens is very difficult. In addition, scientists do not yet totally understand the complex immune responses that protect humans against malaria. However, many scientists all over the world are working on developing an effective vaccine. Because other methods of fighting malaria, including drugs, insecticides, and bed nets, have not succeeded in eliminating the disease, the search for a vaccine is considered to be one of the most important research projects in public health. Standard Diagnostics, Inc. 12 of 15

13 IV. COMPARISON WITH OTHER DIAGNOSTIC METHODS What is the Diagnosis of Malaria? 1. Clinical Diagnosis Clinical Diagnosis is based on the patient's symptoms and on physical findings at examination. The first symptoms of malaria (most often fever, chills, sweats, headaches, muscle pains, nausea and vomiting) are often not specific and are also found in other diseases (such as the "flu" and common viral infections). Also, the physical findings are often not specific (elevated temperature, perspiration, tiredness). In severe malaria (caused by Plasmodium falciparum), clinical findings (confusion, coma, neurologic focal signs, severe anemia, respiratory difficulties) are more striking and may increase the suspicion index for malaria. Thus, in most cases the early clinical findings in malaria are not common and need to be confirmed by a laboratory test. 2. Microscopic Diagnosis Malaria parasites can be identified by examining under the microscope a drop of the patient's blood, spread out as a "blood smear" on a microscope slide. Prior to examination, the specimen is stained (most often with the Giemsa stain) to give to the parasites a distinctive appearance. This technique remains the gold standard for laboratory confirmation of malaria. However, it depends on the quality of the reagents, of the microscope, and on the experience of the laboratorian 3. Rapid Test Various test kits are available to detect antigens/antibodies derived from malaria parasites. Such immunologic ("immunochromatographic") tests most often use a dipstick or cassette format, and provide results in 2-10 minutes. These "Rapid Diagnostic Tests" (RDTs) offer a useful alternative to microscopy in situations where reliable microscopic diagnosis is not available. Malaria RDTs are currently used in some clinical settings and programs. However, before malaria RDTs can be widely adopted, several issues remain to be addressed, including improving their accuracy; lowering their cost; and ensuring their adequate performance under adverse field conditions. Malaria RDTs are currently not approved by the U. S. Food and Drug Administration (FDA) for use in the United States. The World Health Organization's Regional Office for the Western Pacific (WHO/WPRO) provides technical information, including a list of commercially available malaria RDTs 4. Molecular Diagnosis Parasite nucleic acids are detected using polymerase chain reaction (PCR). This technique is more accurate than microscopy. However, it is expensive, and requires a specialized laboratory (even though technical advances will likely result in field-operated PCR machines). 5. Serological Diagnosis Serology detects antibodies against malaria parasites, using either indirect immunofluorescence (IFA) or enzyme-linked immunosorbent assay (ELISA). Serology does not detect current infection but rather measures past experience. 6. Drug Resistance Tests Drug resistance tests are performed in specialized laboratories to assess the susceptibility to Standard Diagnostics, Inc. 13 of 15

14 antimalarial drugs of parasites collected from a specific patient. Two main laboratory methods are available: - In vitro tests: The parasites are grown in culture in the presence of increasing concentrations of drugs; the drug concentration that inhibits parasite growth is used as endpoint; - Molecular characterization: molecular markers assessed by PCR or gene sequencing allow also the prediction, to some degree, of resistance to some drugs; however, the predictive values of these molecular tests are still being evaluated. Microscopy vs Rapid Test Microscopy Rapid test Requirements Equipment Microscope None Electricity Preferred, not necessary None Supplies Blood collection, staining reagents, supplies, water All supplies included in kit Training Trained microscopist Only minimal training required Performance Test Duration minimum 1 hr. 20~30 mins. Labour-Intensiveness High Low Technical Specifications Detection threshold 5~10 parasites/μl 50~100 parasites/μl Detection of all species Yes Yes Quantification Possible Not Possible Detection of sequestered parasites No Yes Microscopy Rapid test Advantages Disadvantages Sensitive Informative Labour-intensive Need equipments and well trained technicians. Time-consuming (around 1 hr.) Simple and easy to perform Rapid No equipment required Can be false positive after treatment Non-quantitative Standard Diagnostics, Inc. 14 of 15

15 V. The Use of Malaria Rapid Tests The Use of Malaria Rapid Tests Malaria rapid test can assist in making a rapid, accurate diagnosis of malaria in circumstances where demonstration of parasitaemia has previously been impossible or where microscopy-based diagnosis may be unreliable. Rapid test may be useful in: diagnosis by health workers distant from good microscopy services remote diagnosis in organized workforces entering malaria-endemic areas (i.e. military or mining companies) outbreak investigation and surveys of parasite prevalence self-diagnosis by travelers entering endemic areas confirmation of diagnosis in hospital laboratories or medical clinics. Rapid test can offer significant benefits in malaria management if: a clear plan of action has been prepared to deal with the outcomes (i.e. drug treatment or appropriate further investigation) a clear benefit is demonstrated in health outcomes they are affordable there are adequate systems in place to ensure RDTs are used correctly and are in good condition. Focusing Item by Distribution Of species Species Sub-Saharan Africa West and Central East and Southern Asia Central America and Caribbean South America P.falciparum 88.2% 78.8% 4.2% 12.9% 29.2% Non-falciparum 11.8% 21.2% 95.8% 87.1% 70.8% P.vivax 1.2% 9.8% 95.6% 87.1% 70.6% P.malariae 2.2% 3.0% 0.0% 0.0% 0.2% P.ovale 8.4% 8.4% 0.2% 0.0% 0.0% According to the distribution of species, choose the suitable item among the 3 types of malaria antigen tests. Sub-Saharan Africa, Asia, Central America and Caribbean, 05FK40 Malaria Ag South America 05FK50 Malaria Ag Pf 05FK60 Malaria Ag Pf/Pan Sub-Saharan Africa Sub-Saharan Africa, Asia, Central America and Caribbean, South America Standard Diagnostics, Inc. 15 of 15