Jpr.mazums.ac.ir

Malaria in Children, Prospects and Challenges
1Department of Pediatric Infectious Diseases, Faculty of Medicine, Mazandaran University of Medical Sciences, Sari,
Iran
2School of Public Health and Health Sciences Research Center, Mazandaran University of Medical Sciences, Sari, Iran
3Liverpool School of Tropical Medicine, Liverpool, UK
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ABSTRACT

Article type:
Malaria is still the number one killer especially among the young children and is responsible for one death per minute in the world. Overall, between 250-500 million cases of the disease occur worldwide causing more than one million deaths annually about 90% of which in children under five years of age. Although the spread of the disease is worldwide but it is seen mostly in tropical and subtropical regions of all continents and is more so in sub-Saharan Africa. Five parasite species transmitted by more than 70 potent Anopheles mosquito vectors are responsible for the occurrence of the disease and its spread. There have beenseveral approaches for malaria diagnosis, management and prevention as a whole and in children (as the most vulnerable group) in particular with various degrees of success. In this context works undertaken by international organizations such as Roll Back Malaria, Global Fund, UNICEF, as well as None for Profit international agencies and also at the national levels are promising in malaria control. However, drug and insecticide resistance, constraints in access to health care, poverty and the like are among the main challenges ahead. In this review paper the situation of malaria and its management measures with especial reference to children are discussed. Introduction
Malaria is still the most important infectious
Africa where the majority of the cases (more disease in the world, inflicting 250-500 million than 90%) are composed of children aged 6 people claiming the lives of about one million. months to 5 years.1, 3 Children are considered as one of the main vulnerable groups as they are population lives in countries where the disease naive immunologically for malaria parasite is endemic, and almost every country in the world encounters imported malaria.1, 2 More than 90% of the cases occur in Sub-Saharan cause as many as 10% of all deaths in children.1 *Corresponding Author: AhmadaliEnayati, Professor, PhD of Medical Entomology Mailing Address: Vice Chancellor for Research and Technology, Moallem Sq. Moallem St. Sari, Mazandaran Province, Iran Tel: +98 151 3257230 Fax: +98 151 3261244 Email: [email protected] Malaria in Children, Prospects and Challenges Burden of Malaria
stage in 2010, and adopted a nation-wide In 1900, more than 77% of the world population in 140 countries were at risk of malaria5 and the mortality rate at the time was 19.4 per 10,000 Malaria in Mazandaran
population. In Africa, the infant malaria specific Malaria in Mazandaran is under control since mortality rate was 9.5 per 1000 prior to 1960 6, the end of the GMEC in 1967.8, 10 The total though this statistics dramatically reduced to number of cases from 1997 to 2012 was 844, of which 822 P. vivax, 16 P. falciparum and 1 P. malaria. Of 844 cases, 641 were imported. published in 2011, there were 655,000 malaria Unlike the usual trend, the majority of the cases deaths worldwide in 2010, compared to 781,000 are adults. Babulsar and Tonekabon followed in 2009.1 It has been estimated that 91% of by Amol reported the highest number of the deaths in 2010 were in the African Region, followed by the South-East Asia (6%) and There are many reasons why the situation of Eastern Mediterranean Regions (3%). About malaria in the south and north being more or 86% of deaths globally were in children under 5 less the same before the GMEC, are now so years of age.1 However, in a recent research, it different. They include: higher number of more potent Anopheles species often with multi organization(WHO) estimate was in fact an insecticide resistance in the south compared underestimation and it is closer to reality that with the north; presence of more potent drug 1.24 million people died from malaria in 2010.2 resistant P. falciparum only in the south; Malaria in Iran
socioeconomic and cultural characteristics of There are eight Anopheles species transmitting the two regions (this has a direct impact on the the disease in Iran the most important of which are An. stephensi and An. culicifacious. The efforts); lack of adequate public health most frequent parasites are P. Vivax and P. infrastructure and access to health care; longer Falciparum leaving the third species, P. transmission season; border problem with Malaria, consisting only 3-4%.8 The situation of endemic areas of Pakistan and Afghanistan.8 malaria in Iran before the Global Malaria Malaria transmission
except the deserts, all areas were endemic with Mosquito bite
high annual incidence.8 However, after the The disease is exclusively transmitted through campaign, the disease has been marginalized to the bite of female Anopheles mosquitoes that the southern and more so to the south eastern occurs between dusk and down. More than 400 parts of the country. The number of cases in species of Anopheles exist in the world but only Iran was about 100 thousand a decade ago, but about 70 species are vectors and only 30 of it has dropped since and reached under 10 which are more important and potent.11 After thousand in recent years.9 The total number of confirmed cases in 2010 was 3031 of which 1847 were locally acquired and 1184 were imported cases.1 Iran moved to the elimination gametocytes. Upon taking a blood meal from a patient mosquito acquires these sexual forms and plays host to the sexual stage of the plasmodial life predominant species in Africa, central America, cycle. After 10-12 days and completing the Indian Subcontinent, and southeast Asia, P. sporogony, sporozoites are transmitted to a new human host through an infectious bite of a region, Bangladesh, Central America, India, Pakistan, and Sri Lanka, P. malaria predominate in Southeast Asia, South America, and Oceania, Blood transfusion
P. ovale and P. knowlesi (the least common Blood transfusion is also a relatively important species) are transmitted primarily in Africa.19,4 route especially in malarious areas. In these Most malaria cases acquired in Africa are due to P. falciparum. P. vivax dominates in Asia allows donors to have parasitemia without any fever or other clinical manifestations 14. In this In Iran, P. falciparum dominates in the south case, transmission is by merozoites, which do plus P. vivax and P. malariae malaria, while P. not enter the liver cells, hence curing the acute vivax is the only parasite species in the north.8 attack results in complete cure due to the lack of Malaria symptoms
Congenital malaria
erythrocyticshizogony period and also the first Prenatal or perinatal transmission of malaria round of erythrocyticshizogony. This period from a nonimmune mother to the fetus or baby depends on the species of the parasite and is is called congenital malaria. It may cause usually 9-14 days for P. falciparum, 12-17 days abortions, miscarriages, stillbirths, premature for P. vivax, 16-18 days for P. ovale, and 18-40 births, intrauterine growth retardation, and days for P. malariae. The classical clinical neonatal deaths. The signs or symptoms usually manifestations of malaria include shiver and occurring a couple of weeks after birth include chill for about one hour followed by a period of fever, restlessness, drowsiness, pallor, jaundice, about 6 hours of high temperature coupled with poor feeding, vomiting, diarrhea, cyanosis, and flushed skin, headache, body ache, fatigue, nausea and vomiting, diarrhea and a final phase Cryptic malaria
hours.4Spleenomegaly, hepatomegaly, jaundice, The category of cryptic malaria includes cases anemia, thrombocytopenia, acute kidney failure identified. Airport malaria, one kind of cryptic important symptoms of malaria. The patient malaria, occurs in proximity to international feels relatively well between the episodes of the Other routs of malaria transmission
The periodicity of malarial fever and other Malaria also can be transmitted through the use symptoms depends on the time required for the erythrocyticshizogonyand is definite for each transplantation is another malarial transmission species. P. malariae needs 72 hours for each cycle, hence the name quartan malaria (three days without high fever followed by one day Malaria parasitology
showing the symptoms). P. vivax and P. ovale There are five species of malaria parasites take 48 hours for one cycle and cause fever every two days (tertian malaria). P. falciparum Malaria in Children, Prospects and Challenges and P. knowlesi require only 24 h for their Rapid test
cycles to complete; hence the patient feels the Immunochromatographic tests based on the symptoms every other day.12 However, in case capture of the parasite antigens from the of mixed infection and also the parasites not peripheral blood using either monoclonal or being synchronized, this periodicity may not be polyclonal antibodies against the parasite antigen targets have been developed in the last decade to facilitate the diagnosis of malaria Severe malaria
where proper microscopy is not possible and Although there is not a gold standard for the basic laboratory materials and equipments are definition of severe malaria, it is considered severe if the following WHO criteria are immunochromatographic tests can target the present: Impaired consciousness, prostration, histidine-rich protein 2 of P. falciparum, a pan- respiratory distress, multiple seizures, jaundice, malarial Plasmodium aldolase, and the parasite hemoglobinuria, abnormal bleeding, severe anemia, circulatory collapse and pulmonary edema.4 The criteria in children emphasize Antibody detection
more on consciousness, severe anemia, and Malaria antibodies have limited value in respiratory distress.20 Malaria caused by P. diagnosing malaria in individual patients. That vivax is usually mild and rarely life threatening may have a role in the diagnosis of hyperactive compared with P. falciparum , however recent reports suggest that in some areas of Indonesia Differential diagnosis
P. falciparum mainly due to severe anemia and Due to the nature of the signs and symptoms of malaria, the differential diagnosis of malaria includes viral infections such as influenza and Malaria Diagnosis
Classic method
The gold standard of malaria diagnosis is by microscopic examination of Giemsa-stained Schistosomiasis, Acute MyelocyticLeukemia, thick or thin smear of peripheral blood despite leptospirosis, tuberculosis, relapsing fever, typhoid fever and yellow fever. 25, 28,4 There is techniques.12, 22 Thick smear allows scanning also considerable clinical overlap between large number of erythrocytes for a rapid septicaemia, pneumonia and severe malaria. As diagnosis of infection and thin smear helps in it is often impossible to rule out septicaemia in establishing the species of the parasite.4 a shocked or severely ill obtunded child, where Polymerase Chain Reaction
possible, blood should always be taken on Although morphologically distinguishable, PCR admission for culture, and if there is any doubt, strategies have been developed to diagnose P. empirical antibiotic treatment should be started knowlesi and P. malariaecannot be diagnosed morphologically, therefore, polymerase chain Complications of malaria in children
The most common complications in children are severe anemia.29,30 impaired consciousness (including distress (due to metabolic acidosis) 32, 33, treated netting, it would not exceed the multiple seizures34-36, Black Water Fever and jaundice 37 leading to poor prognosis. 3839In any case, it does not justify the underestimation of should be used properly and in the right time the risks posed by P. vivax as new case studies and place. In doing so, bednets should be revealed that this latter is not far behind the tucked in under the mattress, vulnerable groups former in causing severe malaria especially in especially children should be under the bednets early in the night and care must be taken to avoid contact of bare arms and legs to the nets Malaria management
as mosquitoes can blood feed from them against Malaria can be prevented and once contracted should be treated1 and in fact treatment of the disease is also a method of prevention as it Repellents
prevents the mosquitoes to get infected while Different chemicals such as Diethyl-meta- blood feeding from the ill individual.42 toluamide(DEET)in formulations like spray, cream, lotion and fumigants are commercially Vector Control
available to be used personally to keep the Applying indoor residual spraying (IRS) and mosquitoes away. Application of every 3-4 distribution of long lasting insecticide treated hours of any formulation of DEET less than bednets (LLINs) are generally applicable for 40% to exposed areas of skin except eyes and mouth is recommended. In infants, hands are a) Indoor Residual Spraying (IRS)
frequently put in mouth, so they are not to be IRS is defined as the application of stable formulations of insecticides on the inside of houses to kill mosquitoes that come in contact Chemoprophylaxis
intermittent
presumptive therapy
Application of non-residual formulations like aerosols in houses especially children’s presumptive therapy (IPT) are available to bedrooms before retiring at night is also control malaria.61-63 Chemoprophylaxis, which recommended for temporary malaria control.45, is defined as subtherapeutic doses of an 46 It is recommended to apply the spray well antimalarial drug, and IPT, the use of full before the children are put in the room to sleep treatment doses of drugs given at a few pre- specified time points are chemoprevention b) Insecticide treated nets (ITNs)
methods available. IPT is given to pregnant Although untreated bednets have been used for women and is being considered for infants and mosquitoes nuisance as well as malaria control, children in areas of high transmission where 11, 47-54 but ITNs are far more effective than many will be infected.3 The drugs used for the untreated nets in reducing malaria especially in chemoprophylaxis of malaria are given in Table children less than 5 years of age.47Pyrethroids are the insecticides of choice for treatment due to their low mammalian toxicity. They are Treatment
extremely safe for household use and even if an There are several different categories of drugs infant chews a relatively large area of the for malaria treatment including those with Malaria in Children, Prospects and Challenges blood schizontocidal effects e.gchloroquine and resulting in low-birth weight which contributes amodiaquine, and primaquine with gametocidal substantially to child deaths.77 As vulnerable effect as well as activity against hypnozoites. 40, groups, young children (under 5 years) and pregnant women should be at the centre of The artemisinin- derivative drugs such as malaria control programmes in highly endemic artemether, arteether and artesunate have recently been commercialized 68 and used in Vaccines
Development of an effective malaria vaccine effectiveness in combination with other classic has been a longstanding but difficult objective. antimalarials is documented by several studies There are three parasite stages targeted by Malaria treatment in Iran
including a) pre-erythrocytic vaccines which Based on the WHO recommended treatment for target the sporozoites to prevent them from malaria, IranianCenters for Disease Control and invading hepatocytes (neutralizing antibody) or Prevention (CDC) issues and updates guidelines to destroy them once inside the hepatocytes 78, for malaria treatment is summarized in Table 2. b) Blood stage vaccines which inactivate the Information is given for pediatrics malaria merozoites during the relatively short time that they are in the blood stream, or target malaria Malaria immunity
antigens expressed on the surface of red blood Although incomplete, immunity acquired by cells 78-80, c) Transmission-blocking vaccines which prevent from the sexual stage of the especially in endemic and hyperendemic areas parasite 81 and d) Anti P. vivax malaria vaccine may prevent severe disease but still allowing with only two vaccine candidates being tested future infection. Individuals with sickle cell The 1st malaria vaccine to have any degree of erythrocytes lacking Duffy blood group antigen efficacy is the RTS'S vaccine, which is based on are resistant to P. vivax, and erythrocytes the circumsporozoite protein of P. falciparum. containing hemoglobin F (fetal hemoglobin) are In various clinical trials, this vaccine has shown resistant to P. falciparum. The latter plus the an efficacy of 26-56% against uncomplicated passive maternal antibody, are the reasons why malaria and 38-50% against severe malaria in newborns rarely become ill with malaria in young children in malaria endemic areas in hyperendemic areas.75 Children 3 mo to 2-5 yr periods as long as 45 mo after vaccination. The of age have little specific immunity to malaria vaccine is now in large phase III trials. 4, 83, 84 species and therefore the disease takes most of Prospects of malaria control
hyperendemic areas. Immunity is subsequently Roll Back Malaria (RBM) Partnership
acquired, and severe cases of malaria become less common.4In areas of intense malaria 1998, with the goal of halving malaria deaths by transmission, most cases of severe malarial 2010, and halving it again by 2015 by a) anemia and deaths occur in infants and young strengthening the aggressive control of malaria children because of their exposure and lack of in its heartland, b) shrinking the malaria map immunity.3, 76 In stable transmission areas, the major effect is malaria-related anemia in the continue researching and developing new tools, mother and presence of parasites in the placenta insecticides, and eventually a vaccine.85, 86 Beyond 2015:Malaria mortality stays near zero International organizations such as the WHO, through universal coverage for all populations at risk, and countries currently in the pre- international donors plus 20 African Heads of elimination stage will achieve elimination.91 State in Abuja, Nigeria in April 2000 pledged Bill and Mellinda Gates Foundation and
malaria control.86, 87 Although this was an Innovative
Consortium
enthusiastic programme, in practice adequate resources has not gone through the plan of Like several other international charitable and non-for-profit organization, IVCC sponsored by committed to research and development in Millennium Development Goals
malaria control aiming at producing new tools This covers a whole host of different goals like LLINs, new insecticide molecules as well including malaria. Target 6C indicates that as a front for malaria vaccine among other malaria transmission should be halted by 2015 and begun to reverse the incidence of malaria and other major diseases. 88, 89 Management of Member States Commitment to Malaria
other diseases such as HIV by providing NNRT Elimination
drugs reduced the incidence and recurrence of The 23 countries of the Eastern Mediterranean malaria.90 Based on WHO world malaria report Region are in various stages of malaria control: in 2011, there were 655 000 malaria deaths worldwide in 2010, compared to 7,81,000 in transmission and are in the control stage 2009.1 However in a recent research it was revealed that 1.24 million people died from countries with geographically limited malaria transmission are in the elimination stage (the Global Malaria Action Plan
Islamic Republic of Iran, and Saudi Arabia). By 2010, 80% of people at risk from malaria Egypt, Oman and the Syrian Arab Republic are should use locally appropriate vector control in the prevention of reintroduction stage and the malaria patients should be diagnosed and treated with effective anti-malarial treatments; Challenges Facing Malaria Control
Drug resistance
reduced by 50% from 2000 levels: to less than Chloroquine resistance was first reported in P. 175-250 million cases and 500,000 deaths falciparum from Colombia and Thailand in By 2015: through universal coverage with effectiveness in many high-transmission areas effective interventions, global and national in 1980s. Latter resistance extended to other mortality is near zero and global incidence is reduced to less than 85-125 million cases per pyrimethamine.94 As a result, artemisinin year; the incidence is halted and begun to derivatives have been introduced in recent years but the first cases of artemisinin resistance have already been reported in Cambodia.95, 96 Malaria in Children, Prospects and Challenges The consequence of these situations are lack of Insecticide resistance
health infrastructure, modifications in the The phenomenon is caused by several different ecological conditions that may result in changes mechanisms including biochemical or site in the populations and behavior of vectors qualitatively or quantitatively different enzymes immunity level and the physical, physiological that detoxify insecticide molecules 97 or and immunity vigor of the people especially children, which make individuals especially molecules so that they are no longer susceptible children and even more so girls more prone to to them.98 As pyrethroid insecticides are the only group available for ITNs and LLINs, pyrethroid resistance has particularly different Community resistance
impacts on the personal protection provided by In many societies interventions such as IRS, ITNs and IPT face resistance for different reasons. IRS especially after several years of Mobile population
operation, is not welcome as it requires Mobile populations usually live in temporary preparations in the houses, it may alter the color shelters where mosquitoes may enter readily. In of the walls and also has bad smell. ITNs may these situations, personal protection is of high not be accepted as they may block the free air importance especially for more vulnerable stream which is a problem in tropical weather. groups like pregnant women and children.107-109 IPT may not be accepted due to fear of side effects.111 Though behaviors like feeling Refugees
obliged for receiving health care such as Displaced people are at higher risk of a whole vaccine may pave the way for implementing host of infectious diseases including malaria as the health infrastructure is no longer present and the means of malaria protection may not be Access to healthcare and socioeconomic
vulnerable to diseases as the situation may In many regions of the world populations in remote areas lack adequate access to healthcare physiological and immunity vigor.107-109 as communities are small and scattered and appropriate road is lacking.112 Another problem Border malaria
is gradual transition from free healthcare to Being neighbor to malaria endemic countries more private sector healthcare which seeks and cross-border malaria is a challenge in community partnership. Poverty is another issue malaria management. Iran has common borders 113-115 and most communities resist this with Afghanistan and Pakistan in the east and privatization by not acquisition of the care with several Persian Gulf states in the south owing to their economic status.116 Literacy level which makes the country vulnerable to border is a major determinant in seeking healthcare.117 malaria through immigrants (mostly illegal) crossing the border. The parasites they carry are Forest malaria
often resistant to most antimalarial drugs. 8 Forest malaria dominates in many parts of Southeast Asia, Africa, and South America and Disasters and civil unrest
is more difficult to control than non-forest Table 1. drugs used for the chemoprophylaxis of malaria
Drug
Pediatric dose
Comments
Begin 1-2 days before travel to malarious areas. Take daily at the same time each day while in the malarious area and for 7 days after leaving such areas. Contraindicated in (creatinine clearance <30 mL/minute). >30-40 kg: 3 ped tab/day >40 kg: 1 adult tablet daily Begin 1-2 weeks before travel to malarious areas. Take weekly on the same day of the week while in themalarious area and for 4 Begin 1-2 days before travel to malarious day while in the malarious area and for 4 weeks after leaving such areas. Contraindicated in children <8 years of age and pregnant women. Begin 1-2 weeks before travel to malarious areas. Take weekly on the same day of the week while in the malarious area and for 4 Begin 1-2 weeks before travel to malarious tablet once/week; >31-45 kg: ¾ tablet once/week; 45 kg: 1 tablet once/week salt) up to adult dose orally, areas. Take daily at same time each day while in malarious area and for 7 days after persons with G6PDa deficiency, and during pregnancyand lactation unless the infant being breastfed has documented normal G6PD level. salt) up to adult dose orally, prolonged exposure to P. vivax and P. ovale or both. Contraindicated in persons lactation unless the infant being breastfed Malaria in Children, Prospects and Challenges malaria. The vectors are often partially or in16 out of 64 provinces, in Bel´em, Par´a, a forest fringe area of Brazil, in the forested areas notnormally enter houses protected by IRS or of equatorial Africa, in Thailand, Cambodia, LLINs. The situation particularly in India, with54 million population involved, in Vietnam Table 2. Iranian CDC guideline for pediatric malaria treatment
Clinical diagnosis/species
Drug resistance status
Pediatric dose
Day 1: 10 mg/kg Day 2: 10 mg/kg Day 3: 5 mg/kg Primaquine: 0.25 mg/kg/day for 14 days Or 0.75 mg/kg/week for 8 weeks Day 1: Artesunate 4 mg/kg plus fansidar 25 Day 2: Artesunate 4 mg/kg Day 3: Artesunate 4 mg/kg Day 2: 10 mg/kg Day 3: 5 mg/kg plus Primaquine 0.75 mg/kg 25-35 kg: 3 tabs po bid for 3 days >35 kg: 4 tabs po bid for 3 days Plus Clindamycin 10 mg/kg did for 7 days treatment failure) Severe falciparum malaria Quinin 15 mg/kg first IV dose followed by 10 mg/kg tid for 3 days Artesunate 2.4 mg/kg every 12 hours for three doses followed by once daily for 3 days Conclusion
management of the disease have dramatically There have been several ups and downs to malaria management since its discovery in the early 20th century. Major successes were in the sanitation period in the middle of the 20th behavioral issues, the prospect of malaria century followed by the GMEC in the 60s and management is promising through scientific discoveries of new tools and techniques in malaria management, international cooperation international organizations. During the years, and community participation in implementing 13. Service MW. Medical Entomology for students. 4 ed. Conflict of Interest
Cambridge: Cambridge University Pressl; 2008. 14. Enevold A, Nkya W, Theisen M, Vestergaard L, Jensen A, Staalsoe T, et al. Potential impact of host immunity on malaria treatment outcome in Tanzanian Funding/Support
children infected with Plasmodium falciparum. Malaria Journal. 2007; 6(1): 153. 15. Mwaniki MK, Talbert AW, Mturi FN, Berkley JA, Kager P, Marsh K, et al. Congenital and neonatal References
malaria in a rural Kenyan district hospital: an eight-year analysis. Malar J. 2010; 9: 313. 1. WHO. World malaria report Switzerland; 2011. 16. Karch S, Dellile MF, Guillet P, Mouchet J. African 2. Murray CJ, Rosenfeld LC, Lim SS, Andrews KG, malaria vectors in European aircraft. The Lancet. Foreman KJ, Haring D, et al. Global malaria mortality between 1980 and 2010: a systematic analysis. Lancet 17. Tarantola AP, Rachline AC, Konto C, Houzé S, Lariven S, Fichelle A, et al. Occupational malaria 3. Hsiang MS, Panosian C, Dorsey G. Understanding following needlestick injury Emerg Infect Dis 2004 Malaria. In: Feachem RGM, Phillips AA, Targett GA, editors. Shrinking the Malaria Map a Prospectus on http://wwwnc.cdc.gov/eid/article/10/10/04-0277.htm Malaria Elimination. San Francisco: The Global 18. Rodriguez M, Tome S, Vizcaino L, Fernandez- Castroagudin J, Otero-Anton E, Molina E, et al. 4. Krause PJ. Malaria (Plasmodium). In: Behrman RE, Malaria Infection through Multiorgan Donation: An Kliegman RM, Jenson HB, editors. Nelson Textbook Update From Spain. LIVER TRANSPLANTATION of Pediatrics. 17th Edition ed: Saunders; 2011. p. 19. Barber BE, William T, Jikal M, Jilip J, Dhararaj P, 5. Hay SI, Guerra CA, Tatem AJ, Noor AM, Snow RW. Menon J, et al. Plasmodium knowlesi malaria in The global distribution and population at risk of children. Emerg Infect Dis. 2011; 17(5): 814-20. malaria: past, present, and future. The Lancet 20. Anstey NM, Price RN. Improving Case Definitions Infectious Diseases. 2004; 4(6): 327-36. for Severe Malaria. PLoS Med. 2007; 4(8): e267. 6. Snow RW, Trape J-F, Marsh K. The past, present and 21. Tjitra E, Anstey NM, Sugiarto P, Warikar N, future of childhood malaria mortality in Africa. Kenangalem E, Karyana M, et al. Multidrug-Resistant Trends in Parasitology. 2001; 17(12): 593-7. <italic>Plasmodium vivax</italic> Associated with 7. Carter R, Mendis KN. Evolutionary and Historical Severe and Fatal Malaria: A Prospective Study in Aspects of the Burden of Malaria. Clinical Papua, Indonesia. PLoS Med. 2008; 5(6): e128. Microbilogy Review. 2002; 15(4): 564-94. 22. Maguire JD, Lederman ER, Barcus MJ, O'Meara WA, 8. Edrissian G. Malaria in Iran: Past and Present Jordon RG, Duong S, et al. Production and validation Situation. Iranian Journal of Parasitology. 2006; 1(1): of durable, high quality standardized malaria microscopy slides for teaching, testing and quality 9. Mohammadi M, Ansari-Moghaddam A, Raiesi A, assurance during an era of declining diagnostic Rakhshani F, Nikpour F, Haghdost A, et al. Baseline results of the first malaria indicator survey in Iran at 23. Mens PF, Moers AP, de Bes LM, Flint J, Sak JR, household level. Malar J. 2011; 10: 277. Keereecharoen L, et al. Development, validation and 10. Ghaffari S, Mahdavi SA, Moulana Z, Mouodi S, evaluation of a rapid PCR-nucleic acid lateral flow Karimi-Nia H, Bayani M, et al. Malaria in immuno-assay for the detection of Plasmodium and Mazandaran, Northern Iran: Passive Case Finding the differentiation between Plasmodium falciparum During 1997-2012. Iranian J Parasitol. 2012; 7(3): 82- and Plasmodium vivax. Malar J. 2012; 11: 279. 24. Sulistyaningsih E, Fitri LE, Loscher T, Berens-Riha 11. Enayati AA, Lines J, Hemingway J. Malaria N. Diagnostic difficulties with Plasmodium knowlesi management, past, present and future. Ann Rev infection in humans. Emerg Infect Dis. 2010; 16(6): 12. Wernsdorfer WH, McGregor I. Malaria: Principles 25. WHO. Guidelines for the treatment of malaria. and Practice of Malariology Edinburgh: Churchill Malaria in Children, Prospects and Challenges 26. Bisoffi Z, Gobbi F, Angheben A, Van den Ende J. 38. Gerardin P, Rogier C, Ka A, Jouvencel P, Diatta B, The Role of Rapid Diagnostic Tests in Managing Imbert P. Outcome of life-threatening malaria in Malaria. PLoS Med. 2009; 6(4): e1000063. African children requiring endotracheal intubation. 27. WHO. Malaria Rapid Diagnostic Test Performance. 39. Achidi E, Apinjoh T, Anchang-Kimbi J, Mugri R, 28. Zingman BS, Viner BL. Splenic complications in Ngwai A, Yafi C. Severe and uncomplicated malaria: case report and review. Clin Infect Dis. 1993; falciparum malaria in children from three regions and three ethnic groups in Cameroon: prospective study. 29. Phiri K, Esan M, van Hensbroek MB, Khairallah C, Faragher B, terKuile FO. Intermittent preventive 40. Reeder JC, Targett GA, Shanks GD, Greenwood BM. therapy for malaria with monthly artemether– Killing the parasite. In: Feachem RGM, Phillips AA, lumefantrine for the post-discharge management of Targett GA, editors. Shrinking the Malaria Map a severe anaemia in children aged 4–59 months in Prospectus on Malaria Elimination. San Francisco southern Malawi: a multicentre, randomised, placebo- The Global Health Group; 2009. p. 127-39. controlled trial. The Lancet Infectious Diseases. 2012; 41. Ajetunmobi W, Orimadegun A, Brown B, Afolabi N, Olabiyi F, Anetor J, et al. Haemoglobinuria among 30. Sowunmi A, Gbotosho GO, Happi CT, Fateye BA. children with severe malaria attending tertiary care in Factors contributing to anaemia after uncomplicated Ibadan, Nigeria. Malaria Journal. 2012; 11(1): 336. 42. Enayati AA, Lines J, Maharaj R, Hemingway J. Suppressing the vector. In: Feachem RGM, Phillips 31. Holding PA, Stevenson J, Peshu N, Marsh K. AA, Targett GA, editors. Shrinking the Malaria Map a Cognitive sequelae of severe malaria with impaired Prospectus on Malaria Elimination. San Francisco consciousness. Transactions of the Royal Society of The Global Health Group; 2009. p. 140-54. Tropical Medicine and Hygiene. 1999; 93(5): 529-34. 43. Macdonald G. The Epidemiology and Control of 32. Haydoura S, Mazboudi O, Charafeddine K, Bouakl I, Malaria,. Oxford: Oxford University Press; 1957. Baban TA, Taher AT, et al. Transfusion-related 44. WHO. Indoor residual spraying, use of indoor Plasmodium ovale malaria complicated by acute residual spraying for scaling upglobal malaria control respiratory distress syndrome (ARDS) in a non- and elimination. WHO/HTM/MAL/20061112. 2006. endemic country. Parasitology International. 2011; 45. Samuelsen H, Toé LP, Baldet T, Skovmand O. Prevention of mosquito nuisance among urban 33. Mukherjee T, Lavania AK. Acute respiratory distress populations in Burkina Faso. Social Science &amp; syndrome due to vivax malaria. Medical Journal 46. Pemba D, Kadangwe C. Mosquito Control Aerosols’ 34. Kihara M, Carter JA, Holding PA, Vargha-Khadem F, Scott RC, Idro R, et al. Impaired everyday memory Insecticides management/mosquito-control-aerosols- associated with encephalopathy of severe malaria: the efficacy-based-on-pyrethroids-constituents. role of seizures and hippocampal damage. Malar J. Perveen F, editor. Advances in Integrated Pest 35. Idro R, Otieno G, White S, Kahindi A, Fegan G, 47. Lengeler C. Insecticide-treated bed nets and curtains Ogutu B, et al. Decorticate, decerebrate and for preventing malaria. Cochrane Database Syst Rev. opisthotonic posturing and seizures in Kenyan children with cerebral malaria. Malar J. 2005; 4: 57. 48. Enayati AA, Hemingway J. Pyrethroid insecticide 36. Ikumi ML, Muchohi SN, Ohuma EO, Kokwaro GO, resistance and treated bednets efficacy in malaria Newton CRJC. Response to diazepam in children control. Pesticide Biochemistry and Physiology. 2006; with malaria induced seizures. Epilepsy Research. 49. Bockarie MJ, Tavul L, Kastens W, Michael E, Kazura 37. Silva Lima E, Fabbri C, de CássiaMascarenhasNetto JW. Impact of untreated bednets on prevalence of R, Lacerda MVG. Jaundice Is Associated with Wuchereriabancrofti transmitted by Anopheles farauti Oxidative Stress in Patients with Plasmodium Vivax in Papua New Guinea. Medical and Veterinary Malaria. Free Radical Biology and Medicine. 2012; 50. Clarke SE, Bogh C, Brown RC, Pinder M, Walraven GE, Lindsay SW. Do untreated bednets protect against malaria? Trans R Soc Trop Med Hyg; 2001. treatment for children and timely home treatment for malaria control. Malaria Journal. 2009; 8(1): 292. 51. D'Alessandro U, Olaleye BO, McGuire W, Thomson 63. Nakibuuka V, Ndeezi G, Nakiboneka D, Ndugwa C, MC, Langerock P, Bennett S, et al. A comparison of the efficacy of insecticide-treated and untreated bednets in preventing malaria in Gambian children. chloroquine for malaria prophylaxis in children with Transactions of the Royal Society of Tropical sickle cell anaemia in Uganda: a randomized controlled trial. Malaria Journal. 2009; 8(1): 237. 52. Lindsay SW, Shenton FC, Snow RW, Greenwood 64. Vinetz JM, Clain J, Bounkeua V, Eastman RT, Fidock BM. Responses of Anopheles gambiae complex D. Chemotherapy of Malaria. In: Brunton LL, mosquitoes to the use of untreated bednets in The Gambia. Med Vet Entomol. 1989; 3(3): 253-62. pharmacological basis of therapeutics. 12 ed. New 53. Mwangi TW, Ross A, Marsh K, Snow RW. The effects of untreated bednets on malaria infection and 65. Desjardins RE, Doberstyn EB, Wernsdorfer WH. The morbidity on the Kenyan coast. Transactions of the treatment and prophylaxix of malaria. In: Wernsdorfer Royal Society of Tropical Medicine and Hygiene. WH, McGregor SI, editors. Malaria principles and 54. Russell TL, Lwetoijera DW, Maliti D, Chipwaza B, Kihonda J, Charlwood JD, et al. Impact of promoting 66. Winstanley PA. Chemotherapy for Falciparum longer-lasting insecticide treatment of bed nets upon Malaria: The Armoury, the Problems and the malaria transmission in a rural Tanzanian setting with Prospects. Parasitology Today. 2000; 16(4): 146-53. pre-existing high coverage of untreated nets. Malaria 67. Lalloo DG, Shingadia D, Pasvol G, Chiodini PL, Whitty CJ, Beeching NJ, et al. UK malaria treatment 55. Zaim M, Aitio A, Nakashima N. Safety of pyrethroid- guidelines. Journal of Infection. 2007; 54(2): 111-21. treated mosquito nets. Medical & Veterinary 68. vanAgtmael MA, Eggelte TA, van Boxtel CJ. Artemisinin drugs in the treatment of malaria: from 56. Curtis V, Kanki B. Bednets and malaria. Afr Health. medicinal herb to registered medication. Trends in Pharmacological Sciences. 1999; 20(5): 199-205. 57. Brown M, Hebert AA. Insect repellents: An overview. 69. Winstanley P, Ward S. Malaria chemotherapy. In: Molineux DH, editor. Control of human parasitic 58. Faulde MK, Albiez G, Nehring O. Insecticidal, diseases. London: Academic Press; 2007. p. 47-76. acaricidal and repellent effects of DEET- and IR3535- 70. Abuaku B, Duah N, Quaye L, Quashie N, Koram K. impregnated bed nets using a novel long-lasting Therapeutic efficacy of artemether-lumefantrine polymer-coating technique. Parasitol Res. 2010; combination in the treatment of uncomplicated malaria among children under 5 years in 3 ecological 59. Moore SJ, Darling ST, Sihuincha M, Padilla N, zones in Ghana. Malaria Journal. 2012; 11(Suppl 1): Devine GJ. A low-cost repellent for malaria vectors in the Americas: results of two field trials in Guatemala 71. Adjei G, Kurtzhals J, Rodrigues O, Alifrangis M, Hoegberg L, Kitcher E, et al. Amodiaquine- 60. N'Guessan R, Rowland M, Moumouni TL, Kesse NB, Carnevale P. Evaluation of synthetic repellents on uncomplicated malaria in Ghanaian children: a mosquito nets in experimental huts against randomized efficacy and safety trial with one year follow-up. Malaria Journal. 2008; 7(1): 127. Culexquinquefasciatus mosquitoes. Trans R Soc Trop 72. Ayede I, Falade A, Sowunmi A, Jansen F. An open randomized clinical trial in comparing two artesunate- 61. Ahorlu C, Koram K. Intermittent preventive treatment based combination treatments on Plasmodium for children (IPTC) combined with timely home falciparum malaria in Nigerian children: artesunate/ treatment for malaria control. Malaria Journal. 2012; sulphamethoxypyrazine/ pyrimethamine (fixed dose over 24 hours) versus artesunate/amodiaquine (fixed 62. Ahorlu C, Koram K, Seakey A, Weiss M. dose over 48 hours). Malaria Journal. 2010; 9(1): 378. Effectiveness of combined intermittent preventive 73. Betson M, Sousa-Figueiredo J, Clifford S, Atuhaire A, Arinaitwe M, Adriko M, et al. Artemther- Malaria in Children, Prospects and Challenges lumefantrine is partially effective for treating chronic 87. WHO. The Abuja declaration, The African Summit multi-species malaria in Ugandan pre-school children. on Roll Back Malaria. WHO/CDS/RBM/200346. Malaria Journal. 2012; 11(Suppl 1): P11. 74. WHO. Guidlines for the treatment of malaria. 88. UN. Millennium Development Goals: UN; 2000. 89. Moonasar D, Nuthulaganti T, Kruger PS, Mabuza A, 75. Bougouma E, Tiono A, Ouedraogo A, Soulama I, Rasiswi ES, Benson FG, et al. Malaria control in Diarra A, Yaro J-B, et al. Haemoglobin variants and South Africa 2000-2010: beyond MDG6. Malar J. Plasmodium falciparum malaria in children under five years of age living in a high and seasonal malaria 90. Achan J, Kakuru A, Ikilezi G, Ruel T, Clark TD, transmission area of Burkina Faso. Malaria Journal. Nsanzabana C, et al. Antiretroviral agents and prevention of malaria in HIV-infected Ugandan 76. Feachem RGA. Shrinking the Malaria Map, A Guide children. N Engl J Med. 2012; 367(22): 2110-8. on Malaria Elimination for Policy Makers. San 91. WHO. The Global Malaria Action Plan. Geneva: Francisco The Global Health Group; 2009. 77. Walther B, Miles D, Crozier S, Waight P, Palmero M, 92. Hemingway J, Beaty BJ, Rowland M, Scott TW, Ojuola O, et al. Placental Malaria is associated with reduced early life weight development of affected Consortium: improved control of mosquito-borne children independent of low birth weight. Malaria diseases. Trends in Parasitology. 2006; 22(7): 308-12. 93. Wernsdorfer WH, Payne D. Ditesrug Sensitivity tests 78. Dubovsky F, Rabinovich NR. Malaria vaccines. In: in Malaria Paras. In: Wernsdorfer WH, McGregor SI, Plotkin SA, Orenstein WA, editors. Vaccines. Philadelphia: Saunders; 2004. p. 1283-9. Malariology. New York: Churcill Livingstone; 1988. 79. Good MF. towards a blood-stage vaccine for malaria: are we following all the leads? Nature Reviews 94. Mbugi E, Mutayoba B, Malisa A, Balthazary S, 80. Sutherland C. A Challenge for the Development of Malaria Vaccines: Polymorphic Target Antigens. falciparum malaria in Mlimba, Tanzania. Malaria 81. Carter R. Transmission blocking malaria vaccines. 95. Noedl H, Se Y, Schaecher K, Smith BL, Socheat D, Fukuda MM, et al. Evidence of Artemisinin-Resistant 82. Herrera S, Corradin G, Arévalo-Herrera M. An update Malaria in Western Cambodia. N Engl J Med. 2008; on the search for a Plasmodium vivax vaccine. Trends 96. Dondorp AM, Nosten F, Yi P, Das D, Phyo AP, 83. Leach A, Vekemans J, Lievens M, Ofori-Anyinam O, Tarning J, et al. Artemisinin resistance in Plasmodium Cahill C, Owusu-Agyei S, et al. Design of a phase III falciparum malaria. N Engl J Med. 2009; 361(5): 455- multicenter trial to evaluate the efficacy of the RTS,S/AS01 malaria vaccine in children across 97. Enayati AA, Ranson H, Hemingway J. Insect diverse transmission settings in Africa. Malaria glutathione transferases and insecticide resistance. 84. Lievens M, Aponte J, Williamson J, Mmbando B, 98. Enayati AA, Vatandoost H, Ladonni H, Townson H, Mohamed A, Bejon P, et al. Statistical methodology Hemingway J. Molecular evidence for a kdr-like for the evaluation of vaccine efficacy in a phase III pyrethroid resistance mechanism in the malaria vector multi-centre trial of the RTS,S/AS01 malaria vaccine in African children. Malaria Journal. 2011; 10(1): Veterinary Entomology. 2003; 17: 138–44. 99. Darriet F, Guillet P, N'Guessan R, Doannio JM, Koffi 85. Feachem RGA, Phillips AA, Targett GA. Shrinking A, Konan LY, et al. Impact of resistance of the Malaria Map, A Prospectus on Malaria Elimination. San Francisco The Global Health Group; deltamethrin on the efficacy of impregnated mosquito nets. Medicine Tropicale. 1998; 58(4): 349-54. 86. Narasimhan V, Attaran A. Roll back malaria? The 100. Darriet F, N'guessan R, Koffi AA, Konan L, scarcity of international aid for malaria control. Malar Doannio JM, Chandre F, et al. Impact of pyrethrin resistance on the efficacity of impregnated mosquito nets in the prevention of malaria: results of tests in 112. Bingham A, Gaspar F, Lancaster K, Conjera J, experimental cases with deltamethrin SC. Bull Collymore Y, Ba-Nguz A. Community perceptions of malaria and vaccines in two districts of Mozambique. 101. N'Guessan R, Darriet F, Doannio JM, Chandre F, Carnevale P. Olyset Net efficacy against pyrethroid- 113. Ahmed S, Haque R, Haque U, Hossain A. Knowledge on the transmission, prevention and Culexquinquefasciatus after 3 years' field use in C te treatment of malaria among two endemic populations d'Ivoire. Med Vet Entomol. 2001; 15(1): 97-104. of Bangladesh and their health-seeking behaviour. 102. N'Guessan R, Corbel V, Akogbéto M, Rowland M. Reduced efficacy of insecticide-treated nets and 114. de Castro M, Fisher M. Is malaria illness among indoor residual spraying for malaria control in young children a cause or a consequence of low socioeconomic status? evidence from the united Infectious Diseases. 2007; 13(2): 199-206. Republic of Tanzania. Malaria Journal. 2012; 11(1): 103. Chandre F, Darriet F, Duchon S, Finot L, Manguin S, Carnevale P, et al. Modifications of pyrethroid 115. Krefis A, Schwarz N, Nkrumah B, Acquah S, effects associated with kdr mutation in Anopheles Loag W, Sarpong N, et al. Principal component gambiae. Med Vet Entomol. 2000; 14(1): 81-8. analysis of socioeconomic factors and their 104. Chouaibou M, Simard F, Chandre F, Etang J, association with malaria in children from the Ashanti Darriet F, Hougard JM. Efficacy of bifenthrin- Region, Ghana. Malaria Journal. 2010; 9(1): 201. impregnated bednets against Anopheles funestus and 116. Kisia J, Nelima F, Otieno D, Kiilu K, Emmanuel pyrethroid-resistant Anopheles gambiae in North W, Sohani S, et al. Factors associated with utilization Cameroon. Malaria Journal. 2006; 11(5): 77. of community health workers in improving access to 105. Dabiré RK, Diabaté A, Baldet T, Paré-Toé L, malaria treatment among children in Kenya. Malaria Guiguemdé RT, Ouédraogo JB, et al. Personal protection of long lasting insecticide-treated nets in 117. Coldren RL, Prosser T, Ogolla F, Ofula VO, areas of Anopheles gambiaes.s. resistance to Adungo N. Literacy and recent history of diarrhoeaare pyrethroids. Malaria Journal. 2006; 5(12): 8. predictive of Plasmodium falciparum parasitaemia in 106. Doannio JM, Dossou-Yovo J, Diarrassouba S, Chauvancy G, Darriet F, Chandre F, et al. Efficacy of permethrin-impregnated Olyset Net mosquito nets in a zone with pyrethroid resistant vectors. I--Entomologic evaluation. Medicine Tropicale. 1999; 59(4): 349-54. 107. Rowland M, Nosten F. Malaria epidemiology and control in refugee camps and complex emergencies. Annals of Tropical Medicine & Parasitology. 2001; 95(8): 741- 54. 108. Nájera JA. Malaria control among refugees and 109. Anderson J, Doocy S, Haskew C, Spiegel P, Moss WJ. The burden of malaria in post-emergency refugee sites: A retrospective study. Confl Health. 2011; 5(1): 1752-505. 110. Watson JT, Gayer M, Connolly MA. Epidemics after natural disasters. Emerg Infect Dis. 2007; 13(1): 1-5. 111. Deribew A, Birhanu Z, Sena L, Dejene T, Reda A, Sudhakar M, et al. The effect of household heads training about the use of treated bed nets on the burden of malaria and anaemia in under-five children: a cluster randomized trial in Ethiopia. Malaria Journal. 2012; 11(1): 8.

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