News for Africa Doc

Background: Two thirds of all falciparum malaria cases reported in the United Kingdom (UK) are acquired in West Africa (WA). To ensure recommendations and guidelines for malaria prophylaxis in travellers to West Africa correlate to the risk of infection, a study was undertaken to examine recent trends and predict future patterns of imported malaria acquired by UK residents visiting West Africa and West African visitors to the UK between 1993 and 2006. Methods and Results Using passenger numbers and malaria surveillance reports, the data revealed a 2.3-fold increase in travel to West Africa with a five-fold increase in travelers visiting friends and relatives (VFR). Malaria incidence fell through the study period, the greatest decline noted in VFR with a fall from 196 cases/1,000 person-years to 52 cases/1,000 person-years, 9.8% per year p<0.0001. The risk for travellers from the UK visiting for other reasons declined 2.7 fold, at an annual decrease of 7.0%, with the incidence in West African visitors to the UK falling by 2.3 fold, a rate of 7.9% annually.DiscussionThe reduction in incidence among all three groups of travellers may be explained by several factors; changing chemoprophylaxis usage and / or increased travel in urban areas where malaria risk has declined over the past decade, or widespread reduction in malaria transmission in West Africa. Conclusion: With the reduction in malaria incidence seen in both visitors to and from West Africa, the most rational explanation for these findings is a fall in malaria transmission in West Africa, which may require a change in prophylaxis policy for UK travelers over the next 5-10 years.

Background: Intermittent preventive treatment with sulphadoxine-pyrimethamine (SP) is recommended for reducing the risk of malaria in pregnancy and its consequences on mothers and babies (IPTp-SP). Indicators of implementation and effects of IPTp-SP were collected in a rural clinic in Southern Senegal. Methods: Women seen routinely at the antenatal clinic (ANC) of a rural dispensary during 2000-2007. Deployment of IPTp-SP started in January 2004. Inspection of antenatal and outpatient clinic registries of the corresponding period. Results: Between 1st January 2000 and 30th April 2007, 1,781 women of all gravitidities and parities attended the ANC with 965 deliveries (606 and 398 respectively since 1st January 2004, when IPTp-SP was started.) 69% of women were seen >3 times; 95% received at least one dose and 70% two doses of SP (from 61% in 2004 to 86% in 2007). The first visit, first and second dose of SP occurred at a median week 20, 22 and 31. The probability of receiving two doses was >80% with >3 antenatal visits and a first dose of SP by week 20. The prevalence of maternal malaria was low and similar pre- (0.7%) and during IPTp (0.8%). Effects on of low birth weight (LBW, <2.5kg) were non-statistically significant. The prevalence of LBW was 10.8% pre- and 7.7% during IPTp deployment (29% risk reduction, p=0.12). Unfavourable pregnancy outcomes numbered 72 (7.5% of pregnancies with known outcome), including 30 abortions and 42 later deaths (late foetal deaths, stillbirth, peri-natal) of which 13 with one or more malformations (1.35% of all recorded deliveries). Conclusions: The implementation of IPTp-SP was high. Early attendance to ANC favours completion of IPTp-SP. The record keeping system in place is amenable to data extraction and linkage. A model was developed that predicts optimal compliance to two SP doses, and could be tested in other settings. Maternal malaria was infrequent and unaffected by IPTp-SP. The risk of LBW was lower during IPT implementation but the difference was non-significant and could have other explanations.

Background: The use of artemisinin derivatives has increased exponentially with the deployment of artemisinin combination therapy (ACT) in all malarious areas. They are highly effective and are considered safe, but in animal studies artemisinin derivatives produce neurotoxicity targeting mainly the auditory and vestibular pathways. The debate remains as to whether artemisinin derivatives induce similar toxicity in humans. Methods: This prospective study assessed the effects on auditory function of a standard 3-day oral dose of artesunate (4 mg/kg/day) combined with mefloquine (25 mg/kg) in patients with acute uncomplicated falciparum malaria treated at the Shoklo Malaria Research Unit, on the Thai-Burmese border. A complete auditory evaluation with tympanometry, audiometry and auditory brainstem responses (ABR) was performed before the first dose and seven days after initiation of the antimalarial treatment. Results: Complete auditory tests at day 0 (D0) and day 7 (D7) were obtained for 93 patients. Hearing loss (threshold > 25 dB) on admission was common (57%) and associated with age only. No patient had a threshold change exceeding 10 dB between D0 and D7 at any tested frequency. No patient showed a shift in Wave III peak latency of more than 0.30 msec between baseline and D7. Conclusions: Neither audiometric or the ABR tests showed clinical evidence of auditory toxicity seven days after receiving oral artesunate and mefloquine.

Background: Adequate malaria diagnosis and treatment remain major difficulties in rural sub-Saharan Africa. These issues deserve renewed attention in the light of first-line treatment with expensive artemisinin-combination therapy (ACT) and changing patterns of transmission intensity. This study describes diagnostic and treatment practices in Mto wa Mbu, an area that used to be hyperendemic for malaria, but where no recent assessments of transmission intensity have been conducted. Methods: Retrospective and prospective data were collected from the two major village health clinics. The diagnosis in prospectively collected data was confirmed by microscopy. The level of transmission intensity was determined by entomological assessment and by estimating sero-conversion rates using anti-malarial antibody responses. Results: Malaria transmission intensity by serological assessment was equivalent to < 1 infectious bites per person per year. Despite low transmission intensity, >40% of outpatients attending the clinics in 2006-2007 were diagnosed with malaria. Prospective data demonstrated a very high overdiagnosis of malaria. Microscopy was unreliable with <1% of slides regarded as malaria parasite-positive by clinic microscopists being confirmed by trained research microscopists. In addition, many 'slide negatives' received anti-malarial treatment. As a result, 99.6% (248/249) of the individuals who were treated with ACT were in fact free of malaria parasites. Conclusions: Transmission intensity has dropped considerably in the area of Mto wa Mbu. Despite this, most fevers are still regarded and treated as malaria, thereby ignoring true causes of febrile illness and over-prescribing ACT. The discrepancy between the perceived and actual level of transmission intensity may be present in many areas in sub-Saharan Africa and calls for greater efforts in defining levels of transmission on a local scale to help rational drug-prescribing behaviour.

Background: Malaria epidemics remain a significant public health issue in the East African highlands. The aim of this study was to monitor temporal variations in vector densities in relation to changes in meteorological factors and malaria incidence at four highland sites in Kenya and Uganda and to evaluate the implications of these relationships for epidemic prediction and control. Methods: Mosquitoes were collected weekly over a period of 47 months while meteorological variables and morbidity data were monitored concurrently. Mixed-effects Poisson regression was used to study the temporal associations of meteorological variables to vector densities and of the latter to incidence rates of Plasmodium falciparum. Results: Anopheles gambiae s.s. was the predominant vector followed by Anopheles arabiensis. Anopheles funestus was also found in low densities. Vector densities remained low even during periods of malaria outbreaks. Average temperature in previous month and rainfall in previous two months had a quadratic and linear relationship with An. gambiae s.s. density, respectively. A significant statistical interaction was also observed between average temperature and rainfall in the previous month. Increases in densities of this vector in previous two months showed a linear relationship with increased malaria incidence. Conclusions: Although epidemics in highlands often appear to follow abnormal weather patterns, interactions between meteorological, entomological and morbidity variables are complex and need to be modelled mathematically to better elucidate the system. This study showed that routine entomological surveillance is not feasible for epidemic monitoring or prediction in areas with low endemicity. However, information on unusual increases in temperature and rainfall should be used to initiate rapid vector surveys to assess transmission risk.

Background: Evaluation of mosquito responses towards different trap-bait combinations in field trials is a time-consuming process that can be shortened by experiments in contained semi-field systems. Possible use of the BG Sentinel (BGS) trap to sample Anopheles gambiae s.s. was evaluated. The efficiency of this trap was compared with that of the Mosquito Magnet-X (MM-X) trap when baited with foot odour alone or combinations of foot odour with carbon dioxide (CO2) or lemongrass as behaviour-modifying cues. Methods: Female An. gambiae s.s. were released in an experimental flight arena that was placed in a semi-field system and left overnight. Catch rates for the MM-X and BGS traps were recorded. Data were analysed by fitting a generalized linear model to the (n+1) transformed catches. Results: Both types of traps successfully captured mosquitoes with all odour cues used. When the BGS trap was tested against the MM-X trap in a choice assay with foot odour as bait, the BGS trap caught about three times as many mosquitoes as the MM-X trap (P=0.002). Adding CO2 (500ml/min) to foot odour increased the number of mosquitoes caught by 268% for the MM-X (P<0.001) and 34% (P=0.051) for the BGS trap, compared to foot odour alone. When lemongrass leaves were added to foot odour, mosquito catches were reduced by 39% (BGS, P<0.001) and 38% (MM-X, P=0.353), respectively. Conclusions: The BGS trap shows high potential for field trials due to its simple construction and high catch rate when baited with human foot odour only. However, for rapid screening of different baits in a contained semi-field system the superior discriminatory power of the MM-X trap is advantageous.

Background: Most malaria-endemic countries are implementing a change in anti-malarial drug policy to artemisinin-based combination therapy (ACT). The impact of different drug choices and implementation strategies is uncertain. Data from many epidemiological studies in different levels of malaria endemicity and in areas with the highest prevalence of drug resistance like borders of Thailand are certainly valuable. Formulating an appropriate dynamic data-driven model is a powerful predictive tool for exploring the impact of these strategies quantitatively. Methods: A comprehensive model was constructed incorporating important epidemiological and biological factors of human, mosquito, parasite and treatment. The iterative process of developing the model, identifying data needed, and parameterization has been taken to strongly link the model to the empirical evidence. The model provides quantitative measures of outcomes, such as malaria prevalence/incidence and treatment failure, and illustrates the spread of resistance in low and high transmission settings. The model was used to evaluate different anti-malarial policy options focusing on ACT deployment. Results: The model predicts robustly that in low transmission settings drug resistance spreads faster than in high transmission settings, and treatment failure is the main force driving the spread of drug resistance. In low transmission settings, ACT slows the spread of drug resistance to a partner drug, especially at high coverage rates. This effect decreases exponentially with increasing delay in deploying the ACT and decreasing rates of coverage. In the high transmission settings, however, drug resistance is driven by the proportion of the human population with a residual drug level, which gives resistant parasites some survival advantage. The spread of drug resistance could be slowed down by controlling presumptive drug use and avoiding the use of combination therapies containing drugs with mismatched half-lives, together with reducing malaria transmission through vector control measures. Conclusions: This paper has demonstrated the use of a comprehensive mathematical model to describe malaria transmission and the spread of drug resistance. The model is strongly linked to the empirical evidence obtained from extensive data available from various sources. This model can be a useful tool to inform the design of treatment policies, particularly at a time when ACT has been endorsed by WHO as first-line treatment for falciparum malaria worldwide.

Background: The objective was to study the seasonal effect on the spatial distribution of the incidence of malaria in children under 10 years old living in the Manhica district, Mozambique. Methods: The data of the clinical malaria incidence were obtained from a study of two cohorts of children followed from December 1996 to July 1999. The cases were obtained by the active detection method. Hierarchical Bayesian models were used to model the incidence of malaria, including spatial correlation nested to climatic season. The models were compared with the deviance information criterion. The age and gender of the children were also taken into account. Results: The incidence of malaria is associated with age, period and climate season. The incidence presents a clear spatial pattern, with a higher incidence in the neighbourhoods situated in the north and northeast of the Manhica area. The transmission of malaria is highest during the wet season but the spatial pattern of malaria does not differ from that during the dry season. Conclusions: The incidence of malaria in Manhica presents a spatial pattern which is independent of the seasonal climatic conditions. The climate modifies the incidence of malaria in the entire region but does not change the spatial pattern of the incidence of this disease. These findings may be useful for the planning of malaria control activities. These activities can be performed taking account that the neighbourhoods with more incidence of malaria do not change over the annual climate seasons.

Background: The aim of this study was to analyse willingness to pay (WTP) and ability to pay (ATP) for ACT for children below five years of age in a rural setting in Tanzania before the introduction of artemisinin-based combination therapy (ACT) as first-line treatment for uncomplicated malaria. Socio-economic factors associated with WTP and expectations on anti-malaria drugs, including ACT, were also explored. Methods: Structured interviews and focus group discussions were held with mothers, household heads, health-care workers and village leaders in Ishozi, Gera and Ishunju wards in north-west Tanzania in 2004. Contingent valuation method (CVM) was used with "take-it-or-leave-it" as the eliciting method, expressed as WTP for a full course of ACT for a child and households' opportunity cost of ACT was used to assess ATP. The study included descriptive analyses with multivariate adjustment for potential confounding factors. Results: Among 265 mothers and household heads, 244 (92%, CI=88%-95%) were willing to pay Tanzanian Shillings (TSh) 500 (US$ 0.46) for a child's dose of ACT, but only 55% (49%-61%) were willing to pay more than TSh 500. Mothers were more often willing to pay than male household heads (adjusted odds ratio=2.1, CI=1.2-3.6). Socio-economic status had no significant effect on WTP. The median annual non-subsidized ACT cost for clinical malaria episodes in an average household was calculated as US$ 6.0, which would represent 0.9% of the average total consumption expenditures as estimated from official data in 2001. The cost of non-subsidized ACT represented 7.0% of reported total annual expenditure on food and 33.0% of total annual expenditure on health care. "Rapid effect," "no adverse effect" and "inexpensive" were the most desired features of an anti-malarial drug. Conclusions: WTP for ACT in this study was less than its real cost and a subsidy is, therefore, needed to enable its equitable affordability. The decision taken in Tanzania to subsidize Coartema fully at governmental health care facilities and at a consumer price of TSh 300-500 (US$ 0.28-0.46) at special designated shops through the programme of Accredited Drug Dispensing Outlets (ADDOs) appears to be well founded.

Background: Anopheles funestus is a major malaria vector in southern Africa. Vector control efforts rely on the use of insecticide chemicals to significantly reduce the number of malaria vectors by targeting that portion of the female population that takes blood meals and subsequently rests indoors. It has been suggested that the intake of a blood meal may assist female mosquitoes to tolerate higher doses of insecticide through vigour tolerance. It is hypothesized that during the process of blood digestion, detoxification mechanisms required for the neutralizing of harmful components in the blood meal may also confer an increased ability to tolerate insecticide intoxication through increased enzyme regulation. Methods: Bottle bioassays using a range of concentrations of permethrin were performed on pyrethroid susceptible and resistant laboratory strains of An. funestus in order to detect differences in insecticide susceptibility following a single blood meal. Based on these results, a discriminating dosage was identified (double the lowest dosage that resulted in 100% mortality of the susceptible strain). Blood-fed and unfed females drawn from the resistant strain of An. funestus were then assayed against this discriminating dose, and the percentage mortality for each sample was scored and compared. Results: In the insecticide dose response assays, neither the fully susceptible nor the resistant strain of An. funestus showed any significant difference in insecticide susceptibility following a blood meal, regardless of the stage of blood meal digestion. A significant increase in the level of resistance was however detected in the resistant An. funestus strain following a single blood meal, based on exposure to a discriminating dose of permethrin. Conclusions: The fully susceptible An. funestus strain did not show any significant alteration in susceptibility to insecticide following a blood meal, suggesting that vigour tolerance through increased body mass (and increased dilution of internalized insecticide) does not play a significant role in tolerance to insecticide intoxication. The increase in insecticide tolerance in the pyrethroid-resistant strain of An. funestus following a blood meal suggests that insecticide detoxification mechanisms involved in insecticide resistance are stimulated by the presence of a blood meal prior to insecticide exposure, leading to enhanced expression of the resistance phenotype. This finding may be significant in terms of the methods used to control indoor resting populations of An. funestus, if the mass killing effect of insecticide application proves increasingly inadequate against blood-feeding females already carrying the insecticide resistance phenotype.

Background: This study investigated the pharmacokinetics of fosmidomycin when given in combination with clindamycin at two dosage regimens in patients with acute uncomplicated falciparum malaria. Methods: A total of 70 patients with acute uncomplicated Plasmodium falciparum malaria who fulfilled the enrolment criteria were recruited in the pharmacokinetic study. Patients were treated with two different dosage regimens of fosmidomycin in combination with clindamycin as follows: Group I: fosmidomycin (900 mg) and clindamycin (300 mg) every 6 hours for 3 days (n= 25); and Group II: fosmidomycin (1,800 mg) and clindamycin (600 mg) every 12 hours for 3 days (n=54). Results: Both regimens were well tolerated with no serious adverse events. The 28-day cure rates for Group I and Group II were 91.3 and 89.7%, respectively. Steady-state plasma concentrations of fosmidomycin and clindamycin were attained at about 24 hr after the first dose. The pharmacokinetics of both fosmidomycin and clindamycin analysed by model-independent and model-dependent approaches were generally in broad agreement. There were marked differences in the pharmacokinetic profiles of fosmidomycin and clindamycin when given as two different combination regimens. In general, most of the dose-dependent pharmacokinetic parameters (model-independent Cmax: 3.74 vs 2.41 ug/ml; Cmax-ss: 2.80 vs 2.08 ug/ml; Cmax-min-ss: 2.03 vs 0.71 ug/ml; AUC: 23.31 vs 10.63 ug.hr/ml (median values) were significantly higher in patients who received the high dose regimen (Group II). However, Cmin-ss was lower in this group (0.80 vs 1.37 ug/ml), resulting in significantly higher fluctuations in the plasma concentrations of both fosmidomycin and clindamycin following multiple dosing (110.0 vs 41.9%). Other pharmacokinetic parameters, notably total clearance (CL/F), apparent volume of distribution (V/F, Vz/F) and elimination half-life (t1/2z, t1/2e) were also significantly different between the two dosage regimens. In addition, the dose-dependent pharmacokinetics of both fosmidomycin and clindamycin tended to be lower in patients with recrudescence responses in both groups. Conclusions: The findings may suggest that dosing frequency and duration have a significant impact on outcome. The combination of fosmidomycin (900 mg) and clindamycin (300-600 mg) administered every six hours for a minimum of five days would constitute the lowest dose regimen with the shortest duration of treatment and which could result in a cure rate greater than 95%.

Background: A sound local understanding of preventive measures and health-seeking behaviour is important for the effective control of malaria. The purpose of this study was to assess the knowledge, attitudes, practices and beliefs of 'malaria' and its control in two rural communities of central Cote d'Ivoire, and to examine associations between 'malaria' and the households' socioeconomic status. Methods: A cross-sectional household survey was carried out, using a combination of qualitative and quantitative methods. People's socioeconomic status was estimated, employing a household asset-based approach. Results: Malaria was identified as djekouadjo, the local folk name of the disease. Although people were aware of malaria-related symptoms and their association with mosquitoes, folk perceptions were common. In terms of treatment, a wide array of modern and traditional remedies was employed, often in combination. Individuals with a sound knowledge of the causes and symptoms of malaria continued to use traditional treatments and only a few people sleep under bed nets, whereas folk beliefs did not necessarily translate into refusal of modern treatments. Perceived causes of malaria were linked to the household's socioeconomic status with wealthier individuals reporting mosquitoes more frequently than poorer households. Bed nets were more frequently used in wealthier social strata, whereas other protective measures - perceived to be cheaper - were more prominent among the poorest. Conclusion: Equitable access to resources at household, community and health system levels are essential in order to enable community members to prevent and treat malaria. There is a need for community-based approaches that match health care services with poor people's needs and resources.

Background: Across tropical Africa the bulk of malaria-related morbidity and mortality is particularly high during childhood. Classical malariometric surveys have relied on assessing malaria infection prevalence. The last comprehensive evaluation of the malaria situation in Mozambique was carried out during the 1950s. This aims to characterize the malaria transmission intensities and to estimate the disease burden that may help guide control programme. Methods: Between February 2002 and April 2003, a house-to-house survey, was carried out in 24 districts randomly selected. A total of 8,816 children aged below 10 years old were enrolled. Finger prick and blood collection were performed to prepare thick and thin films for malaria parasite species identification, density and haemoglobin concentration. Axillary temperature was also measured. Prevalence of infection, parasite density and anaemia were estimated for age groups category in each region/stratum. Comparisons between proportions were made using Chi-square test or Fisher exact. Relationship between age groups, region/stratum and parasite prevalence, density was determined using linear regression. All survey mean estimations were adjusted for sampling weights, clustering and stratification. Results: Malaria parasite prevalence was 58.9% (5.190/8.816), the majority of blood smears 52.4% (4,616/8,816) were due to Plasmodium falciparum and geometric mean parasite density was 1,211 parasites/_l (95% CI, 1,141 - 1.286). Gametocytes prevalence, only for P. falciparum was 5.6% (518/8,816). The burden was highest in the northern regions and in the coastal stratum. Parasite infection and geometric mean parasite density peaked during the second year of life and thereafter decreased with increasing age. Mean haemoglobin concentrations was 9.9 g/dl (95% CI 9.5 - 10.2). Anaemia prevalence was 69.8% (6.257/8.816) and among anaemic children 11.5% (743/6.257) were severely anaemic. Anaemia rose dramatically during the first year of life to peak among children in the 12 - 23 months age group. Highest levels of anaemia were recorded in both northern and central-northern regions 77.9% and 79.4% respectively. Conclusions: This survey confirms that malaria especially that caused by P. falciparum, remains endemic throughout the country. The burden of malaria disease and anaemia-related malaria during childhood constitute a major public health problem and warrant integrated and collaborative interventions towards its control.

Background: In Thailand, South Africa and Zanzibar, a decrease in malaria morbidity was observed following the introduction of artemisinin-based combination therapy (ACT). In Senegal, therapeutic trials supervised the in vivo efficacy of artesunate plus amodiaquine from 1999 to 2005 at the M'lomp village dispensary. The trends in malaria morbidity in this village were evaluated from 2000 to 2002. Methods: Each year, between July and December inclusive, fevers treated with antimalarials and slide-proven, uncomplicated malaria cases were collected from dispensary health records. Data were also collected in 1998, just prior to ACT introduction. Pearson's chi square tests and Student tests were used to compare two percentages or two means respectively (alpha=0.05). Results: Between 1998 and 2002, the total number of fevers treated with antimalarials and their repetitiveness progressively decreased: From 2824 to 945 fevers and from 17.6% to 9.7% (RR1998-2002=0.55; [0.44-0.69]; p<0.0001) respectively. Considering uncomplicated malaria cases only, a decrease was observed in their total number between 2001 and 2002, from 953 to 570 cases. The incidence rate and repetitiveness also decreased. The incidence rate fell from 46.1% in 2001 to 37.5% in 2002 (p<0.0001) and the repetitiveness decreased from 13.0% in 2000 to 6.6% in 2002 (RR2000-2002=0.51; [0.35-0.72]; p=0.0001). Conclusion: The percentage of uncomplicated malaria cases treated with ACT increased, from 18.9% in 2000 to 64.0% in 2002, making it tempting to conclude an impact on malaria morbidity. Nonetheless, the decline in incidence rate of uncomplicated malaria was slight and a lower recorded rainfall was reported in 2002 which could also explain this decline. The context in which ACT is introduced affects the impact on malaria morbidity. In M'lomp, in contrast to studies in Thailand, South Africa and Zanzibar, ACT coverage of malaria cases was low and no vector control measure was deployed. Moreover, the malaria transmission level is higher. In sub-Saharan countries, in order to optimize the impact on malaria morbidity, ACT deployment must be supported, on the one hand, by a strengthening of public health system to ensure a high ACT coverage and, on the other hand, by others measures, such vector control measures.

Background: Intra-specific variation in sperm length influences male reproductive success in several species of insects. In males of the malaria vector Anopheles gambiae, sperm length is highly variable but the significance of this variation is unknown. Understanding what determines the reproductive success of male mosquitoes is critical for controlling malaria, and in particular for replacing natural populations with transgenic, malaria-resistant mosquitoes. Methods: A laboratory population of A. gambiae males was tested for intra-specific variation in sperm length. A full-sib quantitative genetic design was used to test for a genetic component of sperm length in A. gambiae males and estimate its heritability. This study also tested for a relationship between sperm length and male reproductive success in A. gambiae. Male reproductive success was measured as the proportions of inseminated and ovipositing females. Results: There was intra-specific variation of sperm length in A. gambiae. There was no significant genetic variation in sperm length and its heritability was low (h2 = 0.18) compared to other insects. Sperm length was correlated with male body size (measured as wing length). Males with short sperm had significantly higher reproductive success than males with long sperm and this was independent of body size. Conclusions: This is the first study to demonstrate intra-specific variation in sperm length in A. gambiae and that males with short sperm have higher reproductive success. That sperm length influences female oviposition is important for any strategy considering the release of transgenic males.

Background: Intermittent preventive treatment of malaria in infants (IPTi) reduces the incidence of clinical malaria. However, before making decisions about implementation, it is essential to ensure that IPTi is acceptable, that it does not adversely affect attitudes to immunization or existing health seeking behaviour. This paper reports on the reception of IPTi during the first implementation study of IPTi in southern Tanzania. Methods: Data were collected through in-depth interviews, focus group discussions and participant observation carried out by a central team of social scientists and a network of key informants/interviewers who resided permanently in the study sites. Results: IPTi was generally acceptable. This was related to routinization of immunization and resonance with traditional practices. Promoting "health" was considered more important than preventing specific diseases. Many women thought that immunization was obligatory and that health staff might be unwilling to assist in the future if they were non-adherent. Weighing and socialising were important reasons for clinic attendance. Non-adherence was due largely to practical, social and structural factors, many of which could be overcome. Reasons for non-adherence were sometimes interlinked. Health staff and "road to child health" cards were the main source of information on the intervention, rather than the specially designed posters. Women did not generally discuss child health matters outside the clinic, and information about the intervention percolated slowly through the community. Although there were some rumours about sulphadoxine pyrimethamine (SP), it was generally acceptable as a drug for IPTi, although mothers did not like the way tablets were administered. There is no evidence that IPTi had a negative effect on attitudes or adherence to the expanded programme on immunisation (EPI) or treatment seeking or existing malaria prevention. Conclusions: In order to improve adherence to both EPI and IPTi local priorities should be taken into account. For example, local women are often more interested in weighing than in immunization, and they view vaccination and IPTi as vaguely "healthy" rather preventing specific diseases. There should be more emphasis on these factors and more critical consideration by policy makers of how much local knowledge and understanding is minimally necessary in order to make interventions successful.

Background: There have been many reports on the population genetic structures of Plasmodium falciparum from different endemic regions, but few studies have examined the characteristics of isolates from patients with different clinical outcomes. The population genetic structures of P. falciparum isolates from patients with either severe or uncomplicated malaria were examined. Methods: Twelve microsatellite DNA loci from P. falciparum were used to assess the population genetic structures of 50 isolates (i.e., 25 isolates from patients with severe malaria and 25 from patients with uncomplicated malaria) collected in the Thai-Myanmar border area between 2002 and 2005. Results: Genetic diversity and effective population sizes were greater in the uncomplicated malaria group than in the severe malaria group. Evidence of genetic bottlenecks was not observed in either group. Strong linkage disequilibrium was observed in the uncomplicated malaria group. The groups demonstrated significant genetic differentiation (P < 0.05), and allele frequencies for 3 of the 12 microsatellite loci differed significantly between the two groups. Conclusions: These findings suggest that the genetic structure of P. falciparum populations in patients with severe malaria differs from that in patients with uncomplicated malaria. The microsatellite loci used in this study were presumably unrelated to antigenic features of the parasites, but, these findings suggest that some loci may influence the clinical outcome of malaria.

Background: In order to establish a successful infection in the human host, the malaria parasite Plasmodium falciparum must establish interactions with a variety of human proteins on the surface of different cell types, as well as with proteins inside the host cells. To better understand this aspect of malaria pathogenesis, a study was conducted with the goal of identifying interactions between proteins of the parasite and those of its human host. Methods: A modified yeast two-hybrid methodology that preferentially selects protein fragments that can be expressed in yeast was used to conduct high-throughput screens with P. falciparum protein fragments against human liver and cerebellum libraries. The resulting dataset was analyzed to exclude interactions that are not likely to occur in the human host during infection. Results: An initial set of 2,200 interactions was curated to remove proteins that are unlikely to play a role in pathogenesis based on their annotation or localization, and proteins that behave promiscuously in the two-hybrid assay, resulting in a final dataset of 456 interactions. A cluster that implicates binding between P. falciparum PFE1590w/ETRAMP5, a putative parasitophorous vacuole membrane protein, and human apolipoproteins ApoA, ApoB and ApoE was selected for further analysis. Different isoforms of ApoE, which are associated with different outcomes of malaria infection, were shown to display differential interactions with PFE1590w. Conclusions: A dataset of interactions between proteins of P. falciparum and those of its human host was generated. The preferential interaction of the P. falciparum PFE1590w protein with the human ApoE epsilon3 and ApoE epsilon4 isoforms, but not the ApoE epsilon2 isoform, supports the hypothesis that ApoE genotype affects risk of malaria infection. The dataset contains other interactions of potential relevance to disease that may identify possible vaccine candidates and drug targets.

Background: The efficacy of intravenous quinine, which is the mainstay for treating severe malaria in children, is decreasing in South East Asia and Africa. Artemisinin derivatives are a potential alternative to quinine. However, their efficacy compared to quinine in treating severe malaria in children is not clearly understood. The objective of this review was to assess the efficacy of parenteral artemisinin derivatives versus parenteral quinine in treating severe malaria in children. Methods: All randomized controlled studies comparing parenteral artemisinin derivatives with parenteral quinine in treating severe malaria in children were included in the review. Data bases searched were: The Cochrane Central Register of Controlled Trials (The Cochrane Library Issue 4, 2007), MEDLINE (1966 to February 2008), EMBASE (1980 to February 2008), and LILACS (1982 to February 2008). Dichotomous variables were compared using risk ratios (RR) and the continuous data using weighted mean difference (WMD). Results: Twelve trials were included (1,524 subjects). There was no difference in mortality between artemisinin derivatives and quinine (RR= 0.90, 95% CI 0.73 to 1.12). The artemisinin derivatives resolved coma faster than quinine (WMD=-4.61, 95% CI: -7.21 to -2.00, fixed effect model), but when trials with adequate concealment only were considered this differences disappeared. There was no statistically significant difference between the two groups in parasite clearance time, fever clearance time, incidence of neurological sequelae and 28th day cure rate. One trial reported significantly more local reactions at the injection site with intramuscular quinine compared to artemether. None of the trials was adequately powered to demonstrate equivalence. Conclusions: There was no evidence that treatment of children with severe malaria with parenteral artemisinin derivatives was associated with lower mortality or long-term morbidity compared to parenteral quinine. Future studies require adequately powered equivalence trial design to decide whether both drugs are equally effective.

Background: Haematological changes associated with malaria in pregnancy are not well documented, and have focused predominantly on anaemia. Examined here is thrombocytopaenia in pregnant women infected with Plasmodium falciparum or Plasmodium vivax in a low transmission area on the north-western border of Thailand. Methods: In this observational study, the platelet counts was reviewed from routine complete blood counts (CBC) in a cohort of healthy and malaria infected pregnant women attending weekly antenatal clinics. In a previously published cohort study of Karen pregnant women (n=723), every woman had a CBC on admission. A platelet count of 75,000 /muL was the value at two standard deviations below the mean and this value was used to indicate thrombocytopaenia for this study. Differences in platelet count in non-pregnant and pregnant women were compared after matching for age, symptoms, malaria species and parasitaemia. Results: In total 974 pregnant women had 1,558 CBC measurements between February 2004 and September 2006. The median platelet counts (/muL) were significantly lower in patients with an episode of falciparum 134,000 [11,000-690,000] (N=694) or vivax malaria 184,000 [23,000-891,000] (N=523) compared to healthy pregnant women 256,000 [64,000-781,000] (N=255), P<0.05 for both comparisons. Plasmodium falciparum and P. vivax caused a 34% (95% CI 24-47) and 22% (95% CI 8-36) reduction in platelet count, respectively. Pregnant compared to non pregnant women were at higher risk (OR=2.27, 95%CI 1.16-4.4, P=0.017) for thrombocytopaenia. Platelets counts were higher in first compared with subsequent malaria infections within the same pregnancy. Malaria associated thrombocytopaenia had a median [range] time for recovery of 7 [2-14] days which did not differ by antimalarial treatment (P=0.858), or species (P=0.632) and was not associated with active bleeding. Conclusion: The thrombocytopaenic effects of acute uncomplicated falciparum and vivax malaria are significant. Pregnant women are more susceptible to thrombocytopaenia than non-pregnant women. Uncomplicated malaria associated thrombocytopaenia was never severe in this series and prompt treatment resulted in normalization of platelet counts within a week.