Malaria Journal - Latest Articles

Haemoglobin dynamics in Papuan and non-Papuan adults in northeast Papua, Indonesia, with acute, uncomplicated vivax or falciparum malaria

Walter Taylor — 2013-06-19T00:00:00Z

Background: Haemoglobin (Hb) recovers slowly in malaria and may be influenced by naturally acquired immunity. Hb recovery was compared in malaria immune, indigenous Papuan and non-Papuan adults with limited malaria exposure. Methods: Hb concentrations were measured on Days (D) 0, 3, 7, and 28 in 57 Papuans and 105 non-Papuans treated with chloroquine, doxycycline or both drugs for acute, uncomplicated Plasmodium vivax (n = 64) or Plasmodium falciparum (n = 98). Results: Mean (SD, range) D0 Hb was 12.7 (2.2, 7--21.3) g/dL and was similar in P. falciparum infected Papuans and non-Papuans: 12.2 vs. 12.8 g/dL (P = 0.15) but significantly lower in: (i) P. vivax-infected Papuans vs. P. vivax-infected non-Papuans: 11.4 vs. 13.47 g/dL [[increment] = -2.07 (95% CI: --3.3 -- --0.8), P = 0.0018], (ii) all patients with splenomegaly (vs. those without splenomegaly): 12.16 vs. 13.01 g/dL [[increment] = -0.85 (-1.6-- --0.085), P = 0.029], and (iii) all females vs. all males: 10.18 vs. 13.01 g/dL [[increment] = -2.82 (-3.97 -- --1.67), P < 0.0001].Multiple regression identified female sex (P = 0.000), longer illness duration (P = 0.015) (P. falciparum patients) and Papuan ethnicity (P = 0.017) (P. vivax patients) as significant factors for a lower D0 Hb.Mean D28 Hb increased to 13.6 g/dL [[increment] = 1.01 (0.5-1.5) vs. D0 Hb, P = 0.0001]. It was: (i) positively correlated with the D0 Hb (adjusted R2 = 0.24, P = 0.000), and was significantly lower in P. vivax infected Papuans vs. non-Papuans: 12.71 vs. 14.46 g/dL [[increment] = -1.7 (-2.95-- --0.5, P = 0.006). Conclusions: Haemoglobin recovery was related to baseline Hb. Vivax-infected malaria immune Papuans had persistently lower Hb concentrations compared to non-Papuans with limited malaria exposure. This haematological disadvantage remains unexplained.

Living on the edge: a longitudinal study of Anopheles funestus in an isolated area of Mozambique

J Derek Charlwood — 2013-06-17T00:00:00Z

Background: Understanding the survival strategies of malaria vectors at the edges of their distribution, where they are under stress from environmental conditions, may lead to the development of novel control techniques and may help predict the effects of climate change on these mosquitoes. Methods: The population dynamics of an isolated population of Anopheles funestus from the peninsula of Linga Linga in southern Mozambique was studied over a period of 104 weeks from March 2009 to May 2011 by 917 light-trap and 390 exit collections, mostly in an area close to a seasonal pond. Results: Over the sampling period, 3,684 An. funestus females were caught. Densities decreased with increasing distance from the pond. In 2009 and 2010, a single annual peak in An. funestus density coincident with the single annual peak in rainfall was observed, but a clear population peak was absent during the first 21 weeks of 2011. In between population peaks, An. funestus remained present at low densities. In light trap collections, the proportion of gravid mosquitoes was significantly higher during the 'low season' (the period between peaks) than during the peak season (RR = 4.3, p<0.001). In contrast, in exit collections, the proportion of gravid mosquitoes was significantly lower during low season than during the peak season (RR = 0.64, p<0.01). Also, in light traps, the proportion of part-fed females was higher during the low season than during the peak season (RR = 4.5, p<0.001), whereas this was inversed for engorged females (RR = 0.46, p<0.05).Thirteen out of 289 (4.5%) An. funestus tested positive in the sporozoite ELISA. The proportion of sporozoite positive females was higher during the low season (6.25%, six out of 96) than during the peaks (3.63%, seven out of 193), but this difference was not significant. Conclusions: It is suggested that a proportion of the mosquito population may become gonotrophically discordant during the long dry season resulting in enhanced mosquito survival and sustained malaria transmission.

Spatial distribution of malaria problem in three regions of Ethiopia

Dawit Ayele — 2013-06-17T00:00:00Z

Background: The transmission of malaria is the leading public health problem in Ethiopia. From the total area of Ethiopia, more than 75 % is malarious. The aim of this study was to identify socio-economic, geographic and demographic risk factors of malaria based on the rapid diagnosis test (RDT) survey results and produce the prevalence map of the area illustrating variation in malaria risk. Methods: This study accounts for spatial correlation in assessing the effects of socio- economic, demographic and geographic factors on the prevalence of malaria in Ethiopia. A total of 224 clusters of about 25 households each were selected from the Amhara, Oromiya and Southern Nation Nationalities and People's (SNNP) regions of Ethiopia. A generalized linear mixed model with spatial covariance structure was used to analyse the data where the response variable was the presence or absence of malaria using the RDT. Results: The results showed that households in the SNNP region were found to be at more risk than Amhara and Oromiya regions. Moreover, households which have toilet facilities clean drinking water, and a greater number of rooms and mosquito nets in the rooms, have less chance of having household members testing positive for RDT. Moreover, from this study, it can be suggested that incorporating spatial variability is necessary for understanding and devising the most appropriate strategies to reduce the risk of malaria.

Host immune constraints on malaria transmission: insights from population biology of within-host parasites

Philip McQueen — 2013-06-15T00:00:00Z

Background: Plasmodium infections trigger complex immune reactions from their hosts against several life stages of the parasite, including gametocytes. These immune responses are highly variable, depending on age, genetics, and exposure history of the host as well as species and strain of parasite. Although the effects of host antibodies that act against gamete stages in the mosquito (due to uptake in the blood meal) are well documented, the effects of host immunity upon within-host gametocytes are not as well understood. This report consists of a theoretical population biology-based analysis to determine constraints that host immunity impose upon gametocyte population growth. The details of the mathematical models used for the analysis were guided by published reports of clinical and animal studies, incorporated plausible modalities of immune reactions to parasites, and were tailored to the life cycles of the two most widespread human malaria pathogens, Plasmodium falciparum and Plasmodium vivax. Results: For the same ability to bind and clear a target, the model simulations suggest that an antibody attacking immature gametocytes would tend to lower the overall density of transmissible mature gametocytes more than an antibody attacking the mature forms directly. Transmission of P. falciparum would be especially vulnerable to complete blocking by antibodies to its immature forms since its gametocytes take much longer to reach maturity than those of P. vivax. On the other hand, antibodies attacking the mature gametocytes directly would reduce the time the mature forms can linger in the host. Simulation results also suggest that varying the standard deviation in the time necessary for individual asexual parasites to develop and produce schizonts can affect the efficiency of production of transmissible gametocytes. Conclusions: If mature gametocyte density determines the probability of transmission, both Plasmodium species, but especially P. falciparum, could bolster this probability through evasion or suppression of host immune responses against the immature gametocytes. However, if the long term lingering of mature gametocytes at low density in the host is also important to ensure transmission, then evasion or suppression of antibodies against the mature stages would bolster probability of transmission as well.

Blackwater fever in Congolese children: a report of clinical, laboratory features and risk factors

Joseph Bodi — 2013-06-15T00:00:00Z

Background: Blackwater fever (BWF) is one of the severe forms of malaria. This complication was first described among non-immune European expatriates in the malaria endemic areas. Recently, resurgence of this form of malaria has been reported among the indigenous populations. The objective of this study was to investigate the risk factors among BWF patients. Methods: A case--control study was conducted between in four hospitals located in Kinshasa, Democratic Republic of Congo from January 2010 to December 2011. One hundred and twenty nine children were recruited with 43 (cases) and 86 (control). Results: No significant difference in the gender and age distribution was observed between the case and control). The sex-ratio male to female in the case group and control group was respectively 1:1.0 and 1:1.1. The mean age was 8.62 years (SD = 3.84) in patients with haemoglobinuria and 8.55 years (SD = 3.77) in the control group. No difference in frequency of co-infection with Plasmodium falciparum and Plasmodium malariae was observed between the two groups. Significant differences in haemoglobin, haematocrit, creatinine, urea and platelets levels were observed between the two groups (p < 0.001), but not for blood group and lactate dehydrogenase (LDH) level. Majority of the BWF cases occurred during the rainy season (88.4%). Treatment with quinine (95.3%) was significantly associated with cases (p < 0.001). Seven (16.2%) of the haemoglobinuric children developed acute renal failure. Conclusion: Rainy season, low parasitaemia and quinine ingestion were the major risk factors significantly associated with haemoglobinuria. Acute renal failure was observed as the major complication of BWF.

Equivalent susceptibility of anopheles gambiae M and S molecular forms and anopheles arabiensis to plasmodium falciparum infection in Burkina Faso

Awa Gnémé — 2013-06-14T00:00:00Z

Background: The Anopheles gambiae sensu lato (s.l.) species complex in Burkina Faso consists of Anopheles arabiensis, and molecular forms M and S of Anopheles gambiae sensu stricto (s.s.). Previous studies comparing the M and S forms for level of infection with Plasmodium falciparum have yielded conflicting results. Methods: Mosquito larvae were sampled from natural pools, reared to adulthood under controlled conditions, and challenged with natural P. falciparum by experimental feeding with blood from gametocyte carriers. Oocyst infection prevalence and intensity was determined one week after infection. DNA from carcasses was genotyped to identify species and molecular form. Results: In total, 7,400 adult mosquitoes grown from wild-caught larvae were challenged with gametocytes in 29 experimental infections spanning four transmission seasons. The overall infection prevalence averaged 40.7% for A. gambiae M form, 41.4% for A. gambiae S form, and 40.1% for A. arabiensis. There was no significant difference in infection prevalence or intensity between the three population groups. Notably, infection experiments in which the population groups were challenged in parallel on the same infective blood displayed less infection difference between population groups, while infections with less balanced composition of population groups had lower statistical power and displayed apparent differences that fluctuated more often from the null average. Conclusion: The study clearly establishes that, at the study site in Burkina Faso, there is no difference in genetic susceptibility to P. falciparum infection between three sympatric population groups of the A. gambiae s.l. complex. Feeding the mosquito groups on the same infective blood meal greatly increases statistical power. Conversely, comparison of the different mosquito groups between, rather than within, infections yields larger apparent difference between mosquito groups, resulting from lower statistical power and greater noise, and could lead to false-positive results. In making infection comparisons between population groups, it is more accurate to compare the different groups after feeding simultaneously upon the same infective blood.

A good night's sleep and the habit of net use: perceptions of risk and reasons for bed net use in Bukoba and Zanzibar

Hannah Koenker — 2013-06-13T00:00:00Z

Background: Intensive malaria control interventions in the United Republic of Tanzania have contributed to reductions in malaria prevalence. Given that malaria control remains reliant upon continued use of long-lasting insecticidal bed nets (LLINs) even when the threat of malaria has been reduced, this qualitative study sought to understand how changes in perceived risk influence LLIN usage, and to explore in more detail the benefits of net use that are unrelated to malaria. Methods: Eleven focus group discussions were conducted in Bukoba Rural district and in Zanzibar Urban West district in late 2011. Participants were males aged 18 and over, females between the ages of 18 and 49, and females at least 50 years old. Results: The perceived risk of malaria had decreased among the respondents, and malaria control interventions were credited for the decline. Participants cited reductions in both the severity of malaria and in their perceived susceptibility to malaria. However, malaria was still considered a significant threat. Participants' conceptualization of risk appeared to be an important consideration for net use. At the same time, comfort and aspects of comfort (getting a good night's sleep, avoiding biting pests) appeared to play a large role in personal decisions to use nets consistently or not. Barriers to comfort (feeling uncomfortable or trapped; perceived difficulty breathing, or itching/rashes) were frequently cited as reasons not to use a net consistently. While it was apparent that participants acknowledged the malaria-prevention benefits of net use, the exploration of the risk and comfort determinants of net use provides a richer understanding of net use behaviours, particularly in a setting where transmission has fallen and yet consistent net use is still crucial to maintaining those gains. Conclusion: Future behaviour change communication campaigns should capitalize on the non-malaria benefits of net use that provide a long-term rationale for consistent use even when the immediate threat of malaria transmission has been reduced.

Determination of artemether and lumefantrine in anti-malarial fixed-dose combination tablets by microemulsion electrokinetic chromatography with short-end injection procedure

N¿Cho Amin — 2013-06-13T00:00:00Z

Background: Artemether-lumefantrine (AL) combination therapy is now the most used anti-malarial treatment in the world. Quality control of AL formulations is still a major challenge in developing countries. Until now, only liquid chromatographic methods have been reported in the literature for their analysis. Capillary electrophoretic methods, which present various advantages (low price of capillary, low volumes of electrolyte consumption), may be an alternative to liquid chromatography methods. In this paper, a reliable method was developed and validated for the determination of AL in commercial fixed-dose combination tablets commercialized in Cote d'Ivoire. Methods: Artemether and lumefantrine were determined by microemulsion electrokinetic chromatography using short-end injection procedure. The two analytes were extracted from tablets by acidified methanol. Pyrimethamine was used as internal standard. Separation was carried out in an uncoated fused silica capillary, 30 cm long x 50 mum internal diameter, using an effective length of 10 cm and a microemulsion composed of octane, butanol, sodium dodecyl sulfate and borate buffer as background electrolyte, a - 500 V.cm-1 electric field and a detection wavelength of 214 nm. Results: Artemether, lumefantrine and pyrimethamine were separated in 6 min. The method was reliable with respect to selectivity towards formulation excipients, linearity of the response function (r2 > 0.998), recovery studies from synthetic tablets (in the range 99--101%), repeatability (relative standard deviation 1--3%, n = 7 analytical procedures). Application to four commercial formulations containing 20/120 mg of AL per tablet gave a content in good agreement with the declared content. However, the electropherogram of one tablet formulation showed the presence of an ingredient which was not declared. Conclusion: The developed MEEKC method can be proposed as an alternative method to liquid chromatography for the determination of artemether and lumefantrine in fixed-dose combination tablet formulations.

Population genetics analysis during the elimination process of Plasmodium falciparum in Djibouti

Bouh Khaireh — 2013-06-13T00:00:00Z

Background: Case management of imported malaria within the context of malaria pre-elimination is increasingly considered to be relevant because of the risk of resurgence. The assessment of malaria importation would provide key data i) to select countries with propitious conditions for pre-elimination phase and ii) to predict its feasibility. Recently, a sero-prevalence study in Djibouti indicated low malaria prevalence, which is propitious for the implementation of pre-elimination, but data on the extent of malaria importation remain unknown. Methods: Djiboutian plasmodial populations were analysed over an eleven-year period (1998, 1999, 2002 and 2009). The risk of malaria importation was indirectly assessed by using plasmodial population parameters. Based on 5 microsatellite markers, expected heterozygosity (H.e.), multiplicity of infection, pairwise Fst index, multiple correspondence analysis and individual genetic relationship were determined. The prevalence of single nucleotide polymorphisms associated with pyrimethamine resistance was also determined. Results: Data indicated a significant decline in genetic diversity (0.51, 0.59, 0.51 and 0 in 1998, 1999, 2002 and 2009, respectively) over the study period, which is inconsistent with the level of malaria importation described in a previous study. This suggested that Djiboutian malaria situation may have benefited from the decline of malaria prevalence that occurred in neighbouring countries, in particular in Ethiopia. The high Fst indices derived from plasmodial populations from one study period to another (0.12 between 1999 and 2002, and 0.43 between 2002 and 2009) suggested a random sampling of parasites, probably imported from neighbouring countries, leading to oligo-clonal expansion of few different strains during each transmission season. Nevertheless, similar genotypes observed during the study period suggested recurrent migrations and imported malaria. Conclusion: In the present study, the extent of genetic diversity was used to assess the risk of malaria importation in the low malaria transmission setting of Djibouti. The molecular approach highlights i) the evolution of Djiboutian plasmodial population profiles that are consistent and compatible with Djiboutian pre-elimination goals and ii) the necessity to implement the monitoring of plasmodial populations and interventions at the regional scale in the Horn of Africa to ensure higher efficiency of malaria control and elimination.

Malaria and protective behaviours: is there a malaria trap?

Jean-Claude Berthélemy — 2013-06-13T00:00:00Z

Background: In spite of massive efforts to generalize efficient prevention, such as insecticide-treated mosquito nets (ITN) or long-lasting insecticidal nets (LLINs), malaria remains prevalent in many countries and ITN/LLINs are still only used to a limited extent. Methods: This study proposes a new model for malaria economic analysis by combining economic epidemiology tools with the literature on poverty traps. A theoretical model of rational protective behaviour in response to malaria is designed, which includes endogenous externalities and disease characteristics. Survey data available for Uganda provide empirical support to the theory of prevalence-elastic protection behaviours, once endogeneity issues related to epidemiology and poverty are solved. Results: Two important conclusions emerge from the model. First, agents increase their protective behaviour when malaria is more prevalent in a society. This is consistent with the literature on "prevalence-elastic behaviour". Second, a 'malaria trap' defined as the result of malaria reinforcing poverty while poverty reduces the ability to deal with malaria can theoretically exist and the conditions of existence of the malaria trap are identified. Conclusions: These results suggest the possible existence of malaria traps, which provides policy implications. Notably, providing ITN/LLINs at subsidized prices is not sufficient. To be efficient an ITN/LLINs dissemination campaigns should include incentive of the very poor for using ITN/LLINs.