Malaria Bulletin: A Compendium of Current Literature

Acta Trop. 2009 Feb;109(2):108-17. Plasmodium falciparum gametocyte sex ratios in symptomatic children treated with antimalarial drugs. Sowunmi A, Balogun ST, Gbotosho GO, Happi CT. Department of Pharmacology & Therapeutics and Institute for Medical Research and Training, University of Ibadan, Nigeria. The sex ratios of Plasmodium falciparum gametocytes, defined as the proportion of gametocytes in peripheral blood that were male, were evaluated in 1609 children with acute, symptomatic, uncomplicated malaria, preand post-treatment with various antimalarial drugs, over an 8-year period (1999-2006) in an endemic area of southwest Nigeria. Gametocyte carriage on presentation was 10% (162 children). In 162 children in whom 5797 gametocytes were sexed on presentation, the weighted mean sex ratio was 0.18 (95% confidence interval 0.13-0.25). Following therapy, in 446 children in whom 38,519 gametocytes were sexed, the weighted mean sex ratio was 0.38 (95% CI 0.33-0.43) on day 3 and 0.70 (95% CI 0.63-0.75) (P<0.000001) by day 7 after therapy commenced. Non-artemisinin monotherapy significantly increased sex ratio producing a male-biased ratio, but artemisinin combination therapy significantly reduced the sex ratio producing a female biased ratio. Pre-treatment sex ratio correlated negatively with haematocrit (r=-0.229, P=0.003) or gametocytaemia (r=-0.435, P<0.0001) but not with other clinical or parasitological parameters. The ratio of the sex-specific half lives male:female, the 'gametocyte maleness index' (GMI), was >1 with non-artemisinin monotherapy but <1 with artesunate and artemisinin-based combinations. In a multiple regression model, anaemia, low gametocytaemia, and enrolment before 2004 were independent predictors of a male-biased sex ratio pre-treatment. A pre-treatment haematocrit <25%, enrolment before 2004 and treatment with non-artemisinin monotherapy were independent predictors of a male-biased sex ratio 7 days postinitiation of therapy. These findings may have implications for malaria management efforts in sub-Saharan Africa. Acta Trop. 2009 Feb;109(2):146-51. Efficacy of monotherapies and artesunate-based combination therapies in children with uncomplicated malaria in Somalia. Warsame M, Atta H, Klena JD, Waqar BA, Elmi HH, Jibril AM, Hassan HM, Hassan AM. Division of International Health, Karolinska Institutet, Stockholm, Sweden. [email protected] In order to guide the antimalarial treatment policy of Somalia, we conducted therapeutic efficacy studies of routinely used antimalarial monotherapies as well as artemisinin-based combination therapies (ACTs) for uncomplicated malaria in three sentinel sites during 2003-2006. Therapeutic efficacy of chloroquine (CQ), amodiaquine (AQ) and sulfadoxine/pyrimetahmine (SP) monotherapies, and artesunate plus SP (AS+SP) or AQ (AS+AQ) were evaluated in children 6 months to 10 years old with uncomplicated malaria. For the assessment of the monotherapies, 2003 WHO protocol with 14-day follow-up was used while the 2005 WHO protocol with 28-day follow-up was used for testing the ACTs. Of the monotherapies, CQ performed very Environmental Health at USAID – Malaria Bulletin, March 2009 4 poorly with treatment failures varying from 76.5% to 88% between the sites. AQ treatment failure was low except for Janale site with treatment failure of 23.4% compared to 2.8% and 8% in Jamame and Jowhar, respectively. For SP, treatment failures from 7.8% to 12.2% were observed. A 28-day test of artemisinin-based combinations, AS+SP and AS+AQ, proved to be highly efficacious with cure rates of 98-100% supporting the choice of AS+SP combination as first line treatment for uncomplicated malaria for Somalia. Acta Trop. 2009 Feb;109(2):118-23. Effect of temperature and inter-specific competition on the development and survival of Anopheles gambiae sensu stricto and An. arabiensis larvae. Kirby MJ, Lindsay SW. School of Biological and Biomedical Sciences, Durham University, Science Laboratories, UK. [email protected] The two major African malaria vectors Anopheles gambiae sensu stricto and An. arabiensis are sibling species that occupy different climatic niches but are frequently found in the same larval habitats. Differences in survival and development of the aquatic larval stages of these species at different temperatures may help explain adult distribution. The development time from first instar larva to adult at constant water temperatures (25, 30 and 35 degrees C) was measured in these two species when reared together in the same container (ratio 1:1) and separately. Survival to adult was highest in both species reared at 25 degrees C and decreased with increasing temperature. More adult An. gambiae s.s. were produced at 25 degrees C than An. arabiensis (80% interquartile range (78-88) versus 68% (63-78)) but this situation was reversed at 35 degrees C (7% (3-17) versus 33% (27-32)). The survival of An. gambiae s.s. when reared alone was similar to that when reared in the presence of An. arabiensis. In marked contrast An. arabiensis suffered reduced survival when raised with An. gambiae s.s. at 30 degrees C (20% (7-57)) than when reared independently (57% (45-72)). Mean age at eclosion and adult size decreased for both species with increasing water temperature, however An. arabiensis larvae developed at a slower rate and resulted in larger adults than An. gambiae s.s. throughout. The apparent greater production of An. arabiensis at high water temperatures and An. gambiae s.s. at lower water temperatures may in part explain the spatial and temporal distribution of the two species. Acta Trop. 2009 Feb;109(2):159-62. The major insect lipoprotein is a lipid source to mosquito stages of malaria parasite. Atella GC, Bittencourt-Cunha PR, Nunes RD, Shahabuddin M, Silva-Neto MA. Instituto de Bioquímica Médica, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil. [email protected] Once mosquito midgut barrier was crossed malaria parasite faces a extensive metabolic developmental program in order to ensure its transmission. In the hemolymph of the mosquito the dynamics of lipid metabolism is conducted by a major lipoprotein, lipophorin (Lp). It was recently shown that Lp is engaged in the mosquito immune response to parasite infection. However, it is not clear if Lp is uptaken by the parasite. Here, we show that oocysts are able to uptake Environmental Health at USAID – Malaria Bulletin, March 2009 5 mosquito Lp. The uptake of FITC-labeled Lp was demonstrated in midgut-associated oocysts. Alternatively, to confirm Lp incorporation by oocysts we have conducted another set of experiments with iodinated Lp ((125)I-Lp). Oocysts were able to incorporate (125)I-Lp and the process is both time and temperature dependent. This set of results indicated that no matter oocysts are attached to mosquito midgut wall they bear a lipid sequestering machinery from its surroundings. Phospholipid transfer to sporozoites was also demonstrated. In conclusion, these results demonstrate for the first time that malaria parasite undergoes lipid uptake while in the invertebrate host. Acta Trop. 2009 Feb;109(2):87-97. A review on Anopheles culicifacies: from bionomics to control with special reference to Indian subcontinent. Barik TK, Sahu B, Swain V. Department of Zoology, University of Delhi, India. Anopheles culicifacies, is a complex of five isomorphic sibling species A, B, C, D and E and is considered to be the major malaria vector in the Indian subcontinent. Despite numerous studies, it is difficult to have a global view of the ecological and bionomical characteristics of the individual sibling species, as different identification methods have been used. Major biological and ecological trends such as the high plasticity of behaviour and the sympatry of species are addressed. In spite of the availability of rapid molecular identification tools, we still lack important information concerning the biological characteristics of each sibling species. Resistance to insecticide is alarming as it has developed quadruple resistance in two states of India. An intensified and appropriate intervention measure to interrupt transmission is the call of the day. The authors focus on (1) reviewing the vectorial aspects of An. culicifacies (2) discussing recently published data on bionomics of each sibling species, (3) identifying lacunae in the understanding of the Culicifacies complex, and (4) exploring the possibility of proper control measures. Our understanding of the bionomics of all the five sibling species would certainly help, keeping in mind the climatic changes we are to face in the next few years. Acta Trop. 2009 Feb;109(2):124-30. Competitive interactions between larvae of the malaria mosquitoes Anopheles arabiensis and Anopheles gambiae under semi-field conditions in western Kenya. Paaijmans KP, Huijben S, Githeko AK, Takken W. Laboratory of Entomology, Wageningen University, The Netherlands. [email protected] The present paper reports the occurrence of competition between larvae of the malaria mosquito sibling species Anopheles arabiensis and An. gambiae under ambient conditions in western Kenya. Larvae of both species were reared at the same density and under the same food conditions outdoors in single-species and mixed-species populations (species ratio 1:1) in transparent cups that floated in small and large semi-natural pools, which experienced different diurnal variations in water temperature. In a second experiment, both species were reared at similar densities and under the same food conditions in trays in either single-species or mixed-species populations at different proportions (species Environmental Health at USAID – Malaria Bulletin, March 2009 6 ratio 1:1, 1:3 or 3:1). Competition affected the development rate of both species in an opposite way: the development time of larvae of An. arabiensis increased whereas the development time of larvae of An. gambiae decreased in the presence of its sibling species. In small pools larvae developing in mixed-species populations experienced a higher mortality than larvae reared in single-species populations, whereas no such effect was observed in the large pools. In both species the time to pupation was longer and emerging females were larger in the small pools. Larval mortality of An. arabiensis was lower in the small pools compared to the large pools, whereas An. gambiae showed the opposite trend. Overall An. arabiensis showed reduced development rates, higher mortality rates and emerged with a larger body size compared to An. gambiae. The implication of these competitive interactions between larvae of An. arabiensis and An. gambiae under semi-filed conditions needs to be considered in the design and implementation of programmes that aim to reduce malaria transmission as competition may alter the species composition in the field. Am J Trop Med Hyg. 2009 Feb;80(2):236-8. Short report: a multiplex PCR assay for simultaneous genotyping of kdr and ace-1 loci in Anopheles gambiae. Kazanidou A, Nikou D, Grigoriou M, Vontas J, Skavdis G. Department of Molecular Biology and Genetics, Democritus University of Thrace, Alexandroupolis, Greece. [email protected] The selection of insecticide-resistant genotypes in Anopheles gambiae, the most important malaria vector in Africa, makes disease control problematic in several endemic areas. The early detection and monitoring of resistance associated mutations in field mosquito populations is essential for the application of successful insecticide-based control interventions. Currently, the surveillance of these mutations is performed using individual assays, some of which require sophisticated and expensive equipment. Here we describe a novel multiplex polymerase chain reaction-based assay for detecting simultaneously the five single nucleotide polymorphisms in the voltage-gated sodium channel and the ace-1 genes, which have been associated with the mosquito response to most commonly used insecticides. Am J Trop Med Hyg. 2009 Feb;80(2):228-35. Studies on the Salvador I strain of Plasmodium vivax in non-human primates and anopheline mosquitoes. Collins WE, Sullivan JS, Strobert E, Galland GG, Williams A, Nace D, Williams T, Barnwell JW. Division of Parasitic Diseases, National Center for Zoonotic, Vector Borne and Enteric Diseases, Geographic Medicine and Health Promotion and Animal Resources Branches, Centers for Disease Control and Prevention, Atlanta, Georgia, USA. [email protected] A review is presented on studies conducted in New World monkeys and chimpanzees with the Salvador I strain of Plasmodium vivax. This isolate has been adapted to Aotus and Saimiri (squirrel) monkeys and developed as a model for the testing of antimalarial vaccines. After the injection of 10,000 sporozoites, the median prepatent period in S. boliviensis monkeys was 21.5 days. In 103 Environmental Health at USAID – Malaria Bulletin, March 2009 7 sporozoite-induced infections in splenectomized monkeys, the median maximum parasite count ranged from 2,139 to 202,368/microL, with a median maximum parasite count of 48,174/microL. Median maximum parasite counts in Aotus lemurinus griseimembra, A. nancymaae, A. azarae boliviensis, and A. vociferans monkeys were 19,902, 18,390, 21,420, and 18,210/microL, respectively and ranged from 124 to 156,000/microL. Mosquito infections were readily obtained in different species of Anopheles mosquitoes. The S. boliviensis monkey and Salvador I strain seems suitable for the testing of sporozoite and liver stage vaccines but not for blood-stage vaccines against P. vivax unless adapted further in spleen-intact Saimiri boliviensis monkeys. Am J Trop Med Hyg. 2009 Feb;80(2):218-27. Genetic variation among Plasmodium vivax isolates adapted to non-human primates and the implication for vaccine development. Ntumngia FB, McHenry AM, Barnwell JW, Cole-Tobian J, King CL, Adams JH. Global Health Infectious Disease Research, Department of Global Health, College of Public Health, University of South Florida, Tampa, Florida 33612, USA. Plasmodium vivax Duffy binding protein (DBP) is vital for parasite development, thereby making this molecule a good vaccine candidate. Preclinical development of a P. vivax vaccine often involves use of primate models prior to testing efficacy in humans, but primate isolates are poorly characterized. We analyzed the complete gene coding for the DBP in several P. vivax isolates that are used for experimental primate infections and compared these sequences with the Salvador I DBP isolate, which is being used for vaccine development. Our results affirm that primate-adapted isolates are genetically similar to P. vivax circulating in humans, but variability is greatest in the putative target of protective antibodies. In addition, some P. vivax isolates contain multiple genetically different clones. Testing a DBP vaccine may therefore be complicated by heterogeneity and diversity of the P. vivax isolates available for in vivo challenge. Am J Trop Med Hyg. 2009 Feb;80(2):215-7. Short report: chloroquine-resistant Plasmodium vivax in the Republic of Korea. Lee KS, Kim TH, Kim ES, Lim HS, Yeom JS, Jun G, Park JW. Department of Internal Medicine, Kwandong University College of Medicine, Seoul, Republic of Korea. The number of Plasmodium vivax malaria patients in the Republic of Korea and North Korea since the re-emergence of malaria in 1993 is estimated to be approximately one million. To cope with this situation, the Army of the Republic of Korea has performed chemoprophylaxis with hydroxychloroquine and primaquine since 1997. The cumulative number of soldiers in the Army of the Republic of Korea given chemoprophylaxis exceeded 1.4 million by 2007. Extensive chemoprophylaxis contributed to preventing a rapid increase of malaria patients in the Army of the Republic of Korea, but increased the possibility of the occurrence of chloroquine (CQ)-resistant P. vivax strains. In this study, treatment responses of P. vivax malaria patients in the Republic of Korea monitored during 2003-2007, and CQ resistance was confirmed in 2 of 484 enrolled patients. Our results are the first report of CQ-resistant P. vivax in a Environmental Health at USAID – Malaria Bulletin, March 2009 8 temperate region of Asia. Continuous surveillance is warranted to monitor the change in CQ resistance frequency of P. vivax in the Republic of Korea. Am J Trop Med Hyg. 2009 Feb;80(2):209-14. Assessment of insecticide-treated bednet use among children and pregnant women across 15 countries using standardized national surveys. Eisele TP, Keating J, Littrell M, Larsen D, Macintyre K. Department of International Health and Development, Tulane School of Public Health and Tropical Medicine, New Orleans, Louisiana 70112, USA. [email protected] Impact of insecticide-treated bednets (ITNs) on preventing malaria may be minimized if they are not used by vulnerable populations. Among ITN-owning households from 15 standardized national surveys from 2003 to 2006, we identify factors associated with ITN use among children younger than 5 years of age and make comparisons of ITN use among children and pregnant women across countries. Within ITN-owning households, many children and pregnant women are still not using them. Between-country analysis with linear regression showed child ITN use increases as intra-household access to ITNs increases (P = 0.020, R2 = 0.404), after controlling for season and survey year. Results from within-country logistic regression analyses were consistent with between-country analysis showing intra-household access to ITNs is the strongest and most consistent determinant of use among children. The gaps in ITN use and possession will likely persist in the absence of achieving a ratio of no more than two people per ITN. Am J Trop Med Hyg. 2009 Feb;80(2):202-8. Influence of wasting and stunting at the onset of the rainy season on subsequent malaria morbidity among rural preschool children in Senegal. Fillol F, Cournil A, Boulanger D, Cissé B, Sokhna C, Targett G, Trape JF, Simondon F, Greenwood B, Simondon KB. Epidemiology and Prevention Research Unit, Institut de Recherche pour le Développement, Montpellier, France. [email protected] In sub-Saharan Africa, malaria and malnutrition are major causes of morbidity and mortality in children less than five years of age. To explore the impact of malnutrition on subsequent susceptibility to malaria, a cohort of 874 rural preschool children in Senegal was followed-up during one malaria transmission season from July through December. Data on nutritional status and Plasmodium falciparum parasitemia were collected at baseline. Malaria morbidity was monitored through weekly home visits. Wasted children (weight-for-height z-score < -2) were at lower risk of having at least one subsequent clinical malaria attack (odds ratio = 0.33; 95% confidence interval = 0.13-0.81, P = 0.02), whereas stunting (height-for-age z-score < -2) or being underweight (weight-for-age z-score < -2) was not associated with clinical malaria. Although non-biological explanations such as overprotection of wasted children by their mothers should be considered, immunomodulation according to nutritional status could explain the lower risk of malaria attack among wasted children. Environmental Health at USAID – Malaria Bulletin, March 2009 9 Am J Trop Med Hyg. 2009 Feb;80(2):199-201. Short report: comparison of chlorproguanil-dapsone with a combination of sulfadoxine-pyrimethamine and chloroquine in children with malaria in northcentral Nigeria. Ogunfowokan O, Dankyau M, Madaki AJ, Thacher TD. Department of Family Medicine, Jos University Teaching Hospital, Jos, Plateau State, Nigeria. [email protected] Effective and affordable treatment of malaria is critical in the face of resistance of Plasmodium falciparum to chloroquine (CQ) and sulfadoxine-pyrimethamine (SP). We conducted a randomized controlled trial comparing the efficacy of chlorproguanil-dapsone (CD) with a combination SP plus CQ in children in Nigeria less than five years of age with malaria. Of 264 children enrolled, 122 (89.7%) and 118 (92.2%) completed the study in the SP + CQ and CD groups, respectively. By day 3, 96 (78.7%) and 94 (79.7%) had cleared their parasitemia (P = 0.79), and 107 (87.7%) and 109 (92.4%) were symptom free (P = 0.32) in the SP + CQ and CD groups, respectively. Adequate clinical and parasitologic response at day 14 occurred in 111 (94.1%; 95% confidence interval [CI] = 91.6-95.7%) in the CD group and 113 (92.6%; 95% CI = 89.9-94.3%) in the SP + CQ group (P = 0.85). SP + CQ and CD had similar antimalarial efficacy and still provide affordable treatment of uncomplicated malaria in northcentral Nigeria. Am J Trop Med Hyg. 2009 Feb;80(2):194-8. Severe Plasmodium vivax malaria: a report on serial cases from Bikaner in northwestern India. Kochar DK, Das A, Kochar SK, Saxena V, Sirohi P, Garg S, Kochar A, Khatri MP, Gupta V. Department of Medicine, S. P. Medical College, Bikaner, Rajasthan, India. [email protected] Epidemiologic studies and clinical description of severe Plasmodium vivax malaria in adults living in malaria-endemic areas are rare and more attention is needed to understand the dynamics and its interaction with the immune system. This observational study included 1,091 adult patients admitted to medical wards of S. P. Medical College and associated group of hospitals in Bikaner, India from September 2003 through December 2005. The diagnosis of P. vivax malaria was established by peripheral blood film (PBF), rapid diagnostic test (RDT), and polymerase chain reaction (PCR), and severe malaria was categorized as per World Health Organization guidelines. Of 1,091 patients with malaria, 635 had P. falciparum malaria and 456 had P. vivax malaria. Among patients with severe manifestations, 40 had evidence of monoinfection of P. vivax malaria diagnosed by PBF, RDT, and PCR. Complications observed were hepatic dysfunction and jaundice in 23 (57.5%) patients, renal failure in 18 (45%) patients, severe anemia in 13 (32.5%) patients, cerebral malaria in 5 patients (12.5%), acute respiratory distress syndrome in 4 patients (10%), shock in 3 patients (7.5%), and hypoglycemia in 1 (2.5%) patient. Thrombocytopenia was observed in 5 (12.5%) patients, and multi-organ dysfunction was detected in 19 (47.5%) patients. Further large-scale multicentric epidemiologic studies are needed to define the basic pathology of this less known entity. Environmental Health at USAID – Malaria Bulletin, March 2009 10 Am J Trop Med Hyg. 2009 Feb;80(2):188-93. Methemoglobinemia and adverse events in Plasmodium vivax malaria patients associated with high doses of primaquine treatment. Carmona-Fonseca J, Alvarez G, Maestre A. Grupo Salud y Comunidad, Universidad de Antioquia, Medellín, Colombia. Primaquine (PQ) is recommended to prevent relapses in patients with Plasmodium vivax malaria infection. However, treatment with PQ causes methemoglobinemia. In this study, we measured the methemoglobin (MetHB) levels in three groups of subjects who received PQ treatment at 0.58, 0.83, or 1.17 mg/kg/d. A total of 112 subjects were studied. MetHB levels were detected at > or = 4% in 46-50% 1 day after PQ treatment in all three groups and 4-9% of subjects had MetHB levels > or = 4% 15 days after treatment. Only subjects receiving the highest doses of PQ had mild and brief adverse events, and 17% of them were associated with treatment. We conclude that when PQ is administered under certain conditions (i.e., normal glucose-6-phosphate dehydrogenase activity, in non-pregnant subjects and with a light meal), daily doses as high as 1.17 mg/kg do not represent a serious risk of high MetHB levels to patients. Antimicrob Agents Chemother. 2009 Feb 17. Reduced efficacy of intermittent preventive treatment of malaria in malnourished children. Danquah I, Dietz E, Zanger P, Reither K, Ziniel P, Bienzle U, Mockenhaupt FP. Institute of Tropical Medicine and International Health, Charité University Medicine Berlin, Germany; Institute of Biometry and Clinical Epidemiology, Charité University Medicine Berlin, Germany; Institute of Tropical Medicine, University of Tuebingen, Tuebingen, Germany; Department of Infectious Diseases and Tropical Medicine, University of Munich, Munich, Germany; Northern Region Malaria Project, Tamale, Ghana. Intermittent preventive treatment in infants with sulfadoxine-pyrimethamine (IPTi-SP) reduces malaria episodes by 20-59% across Africa. This protective efficacy, however, may be affected by the high frequency of malnutrition in African infants. We analyzed the impact of malnutrition as defined by anthropometry on the incidence of malaria and on the protective efficacy of IPTi in a cohort of 1200 children in hyperendemic northern Ghana. These children received IPTi-SP or placebo at 3, 9, and 15 months of age and were followed-up until 24 months of age. Malnutrition was present in 32%, 40%, and 50% of children at ages 3, 9, and 15 months, respectively. It was associated with increased risks of severe anemia and death but not of malaria. Although malaria slightly contributed to chronic malnutrition, IPTi did not substantially improve child growth. Importantly, the protective efficacies of IPTi in malnourished children were roughly half or even less of those observed in non-malnourished children. In the first year of life, IPTi reduced the incidence of malaria to a significantly lesser extent in infants who received both doses in a malnourished condition (25%; 95%CI, -7-48%) as compared to non-malnourished children (46%; 95%CI, 30-58%; P = 0.049). Moreover, in contrast to nutritionally advantaged children, the rate of severe malaria appeared to be increased in malnourished children who took IPTi. IPTi might exhibit reduced efficacy in regions of abundant malnutrition. There, concomitant nutrition programs may be needed to achieve the Environmental Health at USAID – Malaria Bulletin, March 2009 11