90813_tm406
Tropical Medicine and International Health Evaluation of the SPf66 vaccine for malaria control whendelivered through the EPI scheme in Tanzania
C. J. Acosta1,2, C. M. Galindo1,2, D. Schellenberg1,2, J. J. Aponte1, E. Kahigwa3, H. Urassa2, J. R. M. Armstrong
Schellenberg2,5, H. Masanja2, R. Hayes6, A. Y. Kitua2,4, F. Lwilla7, H. Mshinda2, C. Menendez1, M. Tanner5 and
P. L. Alonso1
1 Unidad de Epidemiologia y Bioestadistica, Hospital Clinic/IDIBAPS, Barcelona, Spain2 Ifakara Health Research and Development Centre, National Institute for Medical Research, Ifakara, Tanzania3 Saint Francis Designated District Hospital, Ifakara, Tanzania4 National Institute for Medical Research, Dar es Salaam, Tanzania5 Swiss Tropical Institute, Basel, Switzerland6 London School of Hygiene & Tropical Medicine, London, UK7 District Medical Officer, Kilombero, Tanzania Malaria control programmes need to protect young children, who bear the brunt of malaria disease and death in Africa. The development of a vaccine is a priority if improved and sustained malariacontrol is to be achieved. The best use of a vaccine in Africa will be achieved if it can be delivered throughthe expanded programme of immunization (EPI). We conducted a trial designed to evaluate the efficacy ofSPf66 vaccine for malaria control when delivered through the EPI scheme in Tanzania.
The study was a two-arm, double blind, individually randomized placebo controlled trial involv- ing 1207 infants. The primary objective of the trial was to estimate the efficacy of three doses of SPf66 givenat 1, 2 and 7 months of age in preventing clinical episodes of malaria. These were documented through ahealth facility-based passive case detection system.
Among 1207 randomized children, overall compliance for third dose was 91%. SPf66 was safe, immunogenic and did not interfere with the humoral immune responses to EPI vaccines. There were 294 chil-dren among SPf66 recipients and 288 among placebo recipients with at least one malaria episode, yielding avaccine efficacy estimate of 2% (95% CI: 216, 16; P 5 0.84).
conclusion This has been the first trial of a malaria vaccine among very young infants. It provides informa- tion on the safety of peptide vaccines administered at this early age as well as their capacity to induceimmune responses without negatively interacting with EPI vaccines. Given the modest protection previouslydocumented in older age groups and the lack of efficacy in younger infants, this vaccine in its current alum-based formulation does not appear to have a role in malaria control in sub-Saharan Africa. The lack ofefficacy found in this trial also raises concerns about potential difficulties of inducing protective immuneresponses against malaria through immunization in infants.
keywords malaria vaccine, infants, EPI, SPf 66, Plasmodium falciparum
correspondence Dr P.L. Alonso, Unidad de Epidemiologia y Bioestadistica, Hospital Clinic, Villarroel
170, 08036 Barcelona, Spain. E-mail: [email protected]
stituting a major obstacle to the economic development of the continent and a contributor to poverty. The last few years The current world malaria situation is probably no better have witnessed a renewed awareness of the unacceptable state than 30 years ago. Plasmodium falciparum malaria is still of malaria control worldwide and particularly in sub-Saharan thought to be directly responsible for 1–3 million deaths of Africa. This has led to the formulation of new initiatives, children every year in sub-Saharan Africa, as well as con- such as Roll Back Malaria, aiming to reduce the burden of 1999 Blackwell Science Ltd Tropical Medicine and International Health C. J. Acosta et al. Evaluation of the SPf66 vaccine for malaria control
this disease with currently existing tools. However, the de- the adjacent Ifakara Mother & Child Health (MCH) Clinic.
velopment of a vaccine is thought to be a priority if improved SFDDH has 375 beds, 70 of which are for paediatric patients.
and sustained malaria control is to be achieved.
In Kilombero District, 85% of all infants complete the full To date, only two antigens have been tested for efficacy national EPI scheme (Font et al. unpublished observation) among populations living in endemic areas and subject to which consists of BCG/OPV at birth, DTP/OPV at age 1, 2 natural exposure to P. falciparum (Graves 1997). One is and 3 months, then measles at 9 months.
SPf66, a multistage, multicomponent synthetic peptide. TheCochrane collaboration's systematic review currently includessix double blind, randomized placebo controlled trials (DB- Study design
RCTs) carried out in South America, Africa and Asia. Meta-analysis revealed overall vaccine efficacy estimates of 23% The study was a two-arm, double blind, individually ran- (95% CI: 12, 32) in reducing the incidence of the first or only domized placebo controlled trial involving 1207 infants. An attack of clinical P. falciparum malaria and of 39% (95% CI: independent Data and Safety Monitoring Board (DSMB) 30, 47) for the total number of episodes. The review con- regularly monitored all aspects of the trial following agreed cludes that this vaccine, the first one to have reduced the risk Standard Operating Procedures.
of malaria among children living in endemic areas, deserves Given that this was the first time the vaccine was given to very young infants, preliminary safety data were collected on Malaria control programmes need to protect young chil- the first 98 infants. The DSMB performed an analysis on dren, who bear the brunt of malaria disease and death in these infants (groups 1 (n 5 46) and 2 (n 5 52)) before the Africa (World Bank 1993). The only functioning structure for remainder of the cohort (group 3 (n 5 1109)) was recruited.
the delivery of vaccines to children in most countries is the Children in group 1 were excluded if they had low birth Expanded Programme of Immunization (EPI). The costs and weight, any sign of neonatal infection or asphyxia, any gross logistics of setting up an alternative structure for the delivery congenital malformation or abnormal clinical parameters of a new vaccine would be formidable.
before vaccination. Children in groups 2 and 3 were only As part of the programme to evaluate SPf66 as a potential excluded if they required admission to hospital on the day of tool for malaria control in Africa, initiated in 1992, we con- dose 1. No twins were recruited to avoid misidentification. A ducted a trial designed to evaluate the efficacy of SPf66 when detailed description of the recruitment criteria of groups 1 delivered alongside the EPI. The rationale is based on the and 2 and of the assessment of safety is presented elsewhere results of the previous trial in Tanzania (Alonso et al. 1994), (Schellenberg et al. 1999).
which yielded a moderate but significant protective effect The primary objective of the trial was to estimate the ef- among 1–5 year-olds, and on the fact that none of the pre- ficacy of three doses of SPf66 given at 1, 2 and 7 months of vious trials included children of an age compatible with de- age in preventing clinical episodes of malaria. It was esti- livery of the vaccine through the EPI.
mated that 1200 infants would provide 90% power to detect avaccine efficacy of 25% at the 5% significance level (two-sided test). A clinical malaria episode in a child attending the health facility was defined as an axillary temperature$ 37.5 °C together with asexual P. falciparum parasitaemia Study site and population
of any density. This case definition has an estimated sen- The trial was conducted in the town of Ifakara, Kilombero sitivity and specificity of 100% and 88%, respectively district, southern Tanzania. The area is described in detail (Menendez et al. 1997). The trial adopted a pragmatic elsewhere (Menendez et al. 1997). The estimated number of approach by assessing the safety and efficacy of SPf66, as infective bites per person per year in the Kilombero valley is would be the case if it was in routine use and delivered more than 300 (Smith et al. 1993). The incidence of clinical through the EPI structure.
malaria rises steeply after the first month of life (Kitua et al.
SPf66 is a synthetic hybrid polymer solubilized in sterile 1996) and the incidence in infants attending local health saline solution and adsorbed onto aluminium hydroxide facilities for malaria and severe anaemia, a common manifes- (Moreno & Patarroyo 1989). The product used in this trial tation of malaria, are 0.7 and 0.6 episodes per child year, was the same as the one used in the previous Tanzanian study respectively (Menendez et al. 1997). Malaria control is based (Alonso et al. 1994). Both vaccine and placebo were bottled in on prompt diagnosis and chloroquine treatment, although identical 5-dose clear glass vials. Each dose of vaccine con- 60% of parasite strains show resistance at day 7 (Hatz et al.
sisted of 500 mg of peptide adsorbed to 0.312 mg of alu- 1998). Government health facilities in Ifakara are limited to minium hydroxide in a volume of 0.125 ml. The placebo the Saint Francis Designated District Hospital (SFDDH) and consisted of aluminium hydroxide alone.
1999 Blackwell Science Ltd Tropical Medicine and International Health C. J. Acosta et al. Evaluation of the SPf66 vaccine for malaria control
Informed consent, enrolment, blinding and vaccination
apart. In order to preserve the immunization schedule used inprevious trials, which administered the third dose 180 days Information about the trial was given to mothers resident in after dose 1, a new vaccination contact was introduced for Ifakara when they brought their children for their first con- the third SPf66 dose, at the routine clinic visit for the 7-month tact with the EPI. Further information regarding the purpose weighing (Figure 1).
of the trial, the procedures involved, potential risks and theuse of placebo was given to parents/guardians immediatelyafter the first dose of DTP/OPV was given. Comprehension was assessed with a set of standard questions. Following wit-nessed written informed consent, infants were recruited to the Identity photocards were issued after dose 1 and used at every trial and received dose 1.
subsequent contact. Children were examined twice in the The DSMB coded vials with the letters A to F. A random hour after vaccination and symptoms and signs of local and list of the letters arranged in blocks of 6 was used to assign a systemic reactions were documented. Children were also child to receive one of these letters, 3 of which corresponded examined after dose 3 of DTP/OPV and after measles vacci- to SPf66. At the time of the first vaccination a child was nation. A morbidity questionnaire was completed for group 1 assigned the next available unused letter. Although the SPf66 and 2 infants when visited at home, daily, for a week after and placebo were very similar, a person not involved in any vaccination. Parents were asked to attend the project clinic at other aspect of the trial drew up doses from the correspond- SFDDH if the child experienced health problems at any time.
ing vial and labelled syringes with the relevant letter in order The main purpose of this follow-up was to assess the inci- to assure the blindness. These activities were performed with dence of adverse effects.
a screen between the vaccine handler and the vaccinator. The Since mid-1994 a hospital surveillance system has been barrier prevented the vaccinator from seeing the preparation operating at SFDDH and the MCH (Menendez et al. 1997).
of the syringes and also prevented the vaccine handler from In brief, this system ensured that all study children who seeing the child to be vaccinated.
attended these health facilities were seen by project medical The vaccine was administered by subcutaneous injection personnel who provided round-the clock clinical cover. At into the opposite thigh to the site of the EPI vaccine given at each consultation, a questionnaire was completed which the same time. SPf66/placebo doses one and two were given at documented signs and symptoms. If the temperature was the same time as the first two doses of DTP/OPV, one month $ 37.5 °C, or if there was a history of fever in the preceding Passive case detection and demographic surveillance Figure 1 Study design and immunization schedule.
1999 Blackwell Science Ltd Tropical Medicine and International Health C. J. Acosta et al. Evaluation of the SPf66 vaccine for malaria control
24 h, a finger-prick blood sample was used to prepare thick Data management and statistical methods
and thin blood films for malaria parasite examination and to Data were double-entered into FoxPro databases (Microsoft measure the packed cell volume (PCV). For children who Corporation, US). Range, internal consistency and referential required admission a more detailed questionnaire was com- integrity checks were performed. All data collected up to 30 pleted. Children with parasitologically confirmed clinical September 1998 was included. The files were cleaned, locked malaria were treated following national guidelines with oral and handed to the DSMB in exchange for the code. A detailed chloroquine and/or sulphadoxine-pyrimethamine, or par- analytical plan was drawn up by the investigators and ap- enteral quinine if required.
proved by the DSMB before the code was handed over.
Cross-sectional surveys were conducted to measure para- The primary efficacy analysis was based on Cox regression sitaemia, packed cell volume (PCV), chloroquine consump- models of the risk of first or only episode of clinical malaria tion and haemoglobin trait at 8, 10 and 24 months of age.
starting 30 days after dose 3 until the end of the study or Serum samples were collected to assess serological responses censoring due to withdrawal or death. Vaccine efficacy (VE) to EPI vaccines and SPf66 as detailed elsewhere (Galindo was estimated from the hazard ratio (HR) as VE 5 100 et al. unpublished observation).
(12HR)%. Unadjusted vaccine efficacy estimates were com- Hospital-based surveillance was complemented with a pared with efficacy estimates adjusted for each baseline char- simple demographic surveillance system. Residence status acteristic in turn using the ratio of the two. Adjustments were and details of deaths occurring outside SFDDH were ob- made in the final model where adjusted and unadjusted esti- tained through home visits either monthly (groups 1 and 2) or mates differed by 15% or more. The proportional hazards bimonthly (group 3). To estimate the distance from the child's assumption was assessed using Cox regression models with home to the SFDDH, the position of each house was recorded using a GeoExplorer II Global Positioning System Secondary analyses included a sensitivity analysis of case (Trimble, UK) with differential correction.
definitions based on different parasite density cut-off as wellas an ‘intention to treat' analysis of all children randomized, from dose 1 until the end of the study or death, using Poissonregression models. For multiple malaria episodes and all Thick and thin blood films were stained and read according admissions to hospital, Poisson regression models with ran- to standard, quality-controlled procedures (Alonso et al.
dom effects were used to take account of between- and 1994) In short, blood slides were read twice by different within-child variation (Clayton 1998). As the probability of readers who were blind to the other slide result. A third read- an episode may depend on the previous history of events, the ing was done pending on whether there was a difference in number of previous episodes was included in the model as a Plasmodium falciparum positivity or the ratio of the densities time-dependent covariate using the log (previous 1 1) trans- was . 1.5 or , 0.67. If less than 30 parasites were counted formation (Lindsey 1995). For multiple malaria episodes, chil- and the difference in the number of parasites was . 10, a dren were not considered at risk for 30 days after the start of third reading was done. The definitive parasite reading was each episode. The analyses were done using STATA statistical based on the majority verdict for positivity and the geometric software (Stata Corp. 1997).
mean of the positive densities for positive slides. The packedcell volume (PCV) was measured using a Hawksley haem-atocrit reader after centrifugation of the microcapillary tubes. Haemoglobin electrophoresis was performed on cellu-lose acetate strips on samples collected at 8 months of age.
Figure 2 shows the trial profile. Baseline characteristics of the Urine was tested for 4-aminoquinolines using high-perfor- study groups were similar (Table 1). Overall compliance of mance thin-layered chromatography (HPTLC-Alufolien SPf66/placebo was 98.3% and 96.5% for second dose and Kieselgel 60 R Merck, Darmstadt, Germany). Antibodies 91.5% and 98.0% for third dose, respectively. Compliances against the SPf66 construct were determined using a FAST within 28 days of the expected date of immunization for ELISA, as described by Teuscher et al. (1994), in a random doses 2 and 3 were 95% and 80%, respectively. Seventy-two selection of serum samples collected one month after the children received dose 3 at the same time as measles vaccine.
third dose. These assays were run blind after the code was Safety data are described in detail elsewhere (Schellenberg broken. Humoral responses to some EPI vaccines were mea- et al. 1999). The frequencies of adverse reactions, abnormal sured in the first 100 serum samples collected from infants laboratory parameters (data not shown) outpatient atten- aged 4 months (for polio, diphtheria and tetanus) and dance, hospital admissions and deaths (Figure 2) were similar 10 months (for measles). Antibodies were determined follow- in SPf66 and placebo recipients. One child had a systemic ing procedures described elsewhere (Galazka 1990).
allergic reaction after the third dose of SPf66 which resolved 1999 Blackwell Science Ltd Tropical Medicine and International Health C. J. Acosta et al. Evaluation of the SPf66 vaccine for malaria control
Invited to participate 79 Do not fit inclusion criteria (13 March 1996–23 April 1997) Start time at risk Finish time at risk (30 September 1998) Figure 2 Trial profile. a, Clinical grounds on day of vaccincation; b, misvaccination.
1999 Blackwell Science Ltd Tropical Medicine and International Health C. J. Acosta et al. Evaluation of the SPf66 vaccine for malaria control
Table 1 Baseline characteristics
Table 2 Number of clinical episodes of P. falciparum per child from
30 days after dose 3
SPf66 (n 5 550)* Placebo (n 5 541)* Episodes* per child Vaccine (n 5 550) Placebo (n 5 541) Age (days) at randomization Weight/age z-score at randomization *Fever $ 37.58C and parasites.
–5.8 to –0.41 cines; two infants (both SPf66 recipients) against diphtheria, Distance to SFDDH (km) from child's home 4 (3 placebo, 1 SPf66) against tetanus and 6 against measles (3 placebo, 3 SPf66). More detailed information on immuno- genicity and interactions is reported elsewhere (Galindo et al.
Age (days) at dose 3 Breastfed at dose 3 Between randomization and 30 days after dose 3, 29% (159/550) of the vaccine group and 32% (175/541) of the placebo group had one or more episodes of clinical malaria Age (days) at measles vaccination (x2 5 1.5; P 5 0.22). Table 2 shows the number and distribu- tion of malaria episodes among vaccine and placebo recipi- ents starting 30 days after dose 3. The primary analysis is restricted to 541 placebo and 550 SPf66 recipients who Reported net use† received all three doses and whose time at risk started 30 days after the third dose. There were 294 first or only episodes among SPf66 recipients and 288 among placebo recipients, yielding an adjusted vaccine efficacy estimate of 2% (95% Chloroquine use‡ CI: 216, 16; P 5 0.84) (Table 3). The Kaplan Meier curve is presented in Figure 3. Secondary endpoints, including the intention-to-treat analysis as well as sensitivity analysis of different parasite density cut-offs, are presented in Table 3.
*Denominator except for chloroquine use and Hb genotype; †At home visit after dose 3; ‡At age 10 months, n 5 104 for SPf66 and 98for placebo; ¶At age 10 months, n 5 100 for SPf66 and 102 for We have reported the first trial of a synthetic peptide vaccine administered at 1, 2 and 7 months of age alongside the EPIvaccines. SPf66 was safe, immunogenic and did not modify rapidly after a single dose of intramuscular promethazine.
the humoral responses to polio, tetanus, diphtheria and SPf66 was immunogenic with 98% (47/48) of SPf66 recipients measles vaccines. However, SPf66 did not reduce the risk of positive for anti-SPf66 antibodies 1 month after dose 3 com- clinical malaria among Tanzanian children living in this area pared with 12% (6/50) of placebo recipients (P , 0.001).
of high perennial transmission.
Geometric mean titres (GMT) in SPf66-seropositive children This study was not intended to validate the results of any were also higher in SPf66 recipients (1181 in SPf66 vs. 64 in former trial but to progress down the critical path of vaccine placebo; P , 0.001). All vaccine and placebo recipients devel- evaluation for public health use. It was part of a comprehen- oped protective titres for polio 3 (85/85). Few children tested sive programme to evaluate the potential of SPf66 which had did not develop protective titres against some other EPI vac- demonstrated a 31% efficacy among Tanzanian children aged 1999 Blackwell Science Ltd Table 3 Annual incidence of clinical episodes of P. falciparum malaria and estimated vaccine efficacy
ropical Medicine and Inter RR Vaccine efficacy (95% CI) Child-years incidence Child-years incidence Evaluation of the SPf66 vaccine f
Primary analysis: First/only episodes 0.98 202.4% (215,17) 0.772 201.7% (216,16) 0.841 Cox† of fever* withparasitaemia Secondary analyses: First/only episodes 0.98 201.8% (217,18) 0.836 201.8% (217,18) 0.843 Cox† of fever* ¶sitaemia. 5,000/mlFirst/only episodes 0.97 203.0% (218,20) 0.754 203.2% (217,20) 0.739 Cox† or malaria contr
parasitaemia. 20,000/mlFirst/only episodes 1.12 211.8% (248,15) 0.431 029.8% (245,17) 0.510 Cox‡ of severe anaemia(PCV , 25%) All admissions to 0.91 209% (23,20) 0.152 213.1% (21,25) 0.92 207.7% (25,19) 0.237 206.7% (26,18) 0.89 210.6% (24,23) 0.139 209.0% (24,21) fever* & parasitaemia. 5,000/mlAll episodes of 0.83 216.5% (1,29) 0.035 213.8% (0,26) fever* & parasitaemia * $ 37.5 8C; † adjusted for weight-for-age at randomization, distance to SFDHH, and net use after dose 3; ‡ adjusted for weight-for-age at randomization; ¶ Random effects Poisson models, adjusted for the previous number of episodes as a time variable covariate.
1999 Blackwell Science Ltd Tropical Medicine and International Health C. J. Acosta et al. Evaluation of the SPf66 vaccine for malaria control
Figure 3 Kaplan Meier curve for first or
only clinical malaria episodes. ——— SPf66;----------Placebo.
Proportion of children free of disease Years (after third dose + 30 days) 1–5 years. The rationale of this trial was based on three con- setting, but in younger children. The most likely explanation for the different results is that very young infants have differ- • the high risk of malaria morbidity and mortality during ent immunological reactions to SPf66, or possibly malaria the first year of life, especially in areas of high transmis- antigens in general, rendering them less receptive to vaccina- tion attempts. This age dependence in the response is a real • the realization that a malaria vaccine will be of maxi- possibility, as suggested by the lower titres reached among mum use in Africa if it can be integrated in the current vaccinees in this trial or as is the case for pneumococcal poly- schedule of immunization; saccharide vaccines (Temple et al. 1991). An analysis of the • the level of protection documented in the first trial, kinetics and the quality of antibody response is in progress.
although modest, still warranted further testing of this Should age, maturation of the immune system, interference vaccine in the same setting.
with maternal antibodies or prior exposure be important Why has the vaccine failed to protect young infants when determinants of the capacity to induce protective responses the same product in the same area given to older children against malaria, these would have implications for malaria reduced their risk of malaria? First of all, the confidence vaccine design and implementation strategies in the future.
intervals for efficacy estimates from the two Tanzanian trials SPf66 has been the most extensively tested malaria vaccine overlap. As a result it could be argued that the results are to date. Phase III trials have been carried out in South compatible and that the differences may be due to chance.
America, Asia and Africa. A full review of these results is However, in the first Tanzanian trial, all the results – includ- beyond the scope of this paper, but are available from the ing the primary outcome – consistently supported the finding Cochrane Collaboration (Graves 1997). In Africa, there has of a positive result. These included efficacy against first or only been one other trial beside the two Tanzanian studies only malaria episodes, including different parasite cut-offs in previously discussed. In The Gambia, an area of moderate the sensitivity analysis (Alonso et al. 1994) as well as multiple and seasonal malaria transmission, a phase III trial was car- episodes persisting during extended follow-up (Alonso et al.
ried out among children aged 6–12 months at the time of the 1996). There was also a 21% reduction in geometric mean first dose. The lack of efficacy documented in that trial sup- parasite density in SPf66 recipients (Alonso et al. 1996) and a ports the notion that age may be an important determinant in reduction in the number of concurrent P. falciparum infec- inducing protective immunity with this vaccine.
tions (Beck et al. 1997). Just as the findings in the former trial In conclusion, we have conducted the first trial of a malaria were consistent and positive, the various indicators assessed vaccine among very young infants subject to intense P. falci- in the current trial tended to corroborate the lack of efficacy parum malaria, and provided information on the safety of in young infants. The role of chance cannot be excluded, but peptide vaccines administered to young infants as well as of we consider it an unlikely explanation for the discrepant esti- their capacity to induce immune responses without negatively mates of efficacy in the two Tanzanian trials.
interacting with EPI vaccines. The documented lack of ef- Secondly, the two Tanzanian studies afford a unique oppor- ficacy raises concerns about potential difficulties of inducing tunity to assess the importance of age in determining the ef- protective immune responses against malaria through immu- ficacy of SPf66. The same vaccine was used in the same nization in infants. Given the modest protection documented 1999 Blackwell Science Ltd Tropical Medicine and International Health C. J. Acosta et al. Evaluation of the SPf66 vaccine for malaria control
in older age groups and the lack of efficacy in the younger Beck HP, Felger I, Huber W et al. (1997) Analysis of multiple infants, this vaccine in its current alum-based formulation Plasmodium falciparum infections in Tanzanian children during the does not appear to have a role in malaria control in sub- phase III trial of the malaria vaccine SPf66. Journal of Infectious Saharan Africa.
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the staff of the Ifakara Health Research and Development Graves P (1997) Human malaria vaccines: In Infectious Diseases Centre and the St Francis Designated District Hospital.
Module of the Cochrane Database Systematic Reviews. Updated Particular thanks go to the clinical officers whose work was 3 June 1997 (eds P Garner, H Gelband, P Olliaro & R Salinas) of central importance. We gratefully acknowledge the com- Available in the Cochrane Library (database on disk and CDROM).
petent assistance in data management of Gregory Kabadi and The Cochrane Collaboration; Issue 1 (4). Update Software, Oxford.
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Dr Vidal and Ms. Grace Lubomba.
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Research Clearance was issued by the Tanzania Com- Schellenberg D, Acosta CJ, Galindo CM et al. (1999) Safety in infants mission for Science and Technology (Ref. # CST/RCA.
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Smith T, Charlwood JD, Kihonda J et al. (1993) Absence of seasonal The trial was funded by the Spanish Agency for International variation in malaria parasitaemia in an area of intense seasonal transmission. Acta Tropica 54, 55–72.
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Temple K, Greenwood B, Inskip H, Hall A, Koskela M & Leinonen M Alonso PL, Smith T, Armstrong Schellenberg JRM et al. (1994) (1991) Antibody response to pneumococcal capsular polysaccha- Randomised trial of efficacy of SPf66 vaccine against Plasmodium ride vaccine in African children. Paediatrics Infectious Disease falciparum malaria in children in southern Tanzania. Lancet 344,
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The ways for development of environmentally safe solid composite propellants
Progress in Propulsion Physics 1 (2009) 63-80 DOI: 10.1051/eucass/200901063 © Owned by the authors, published by EDP Sciences, 2009 THE WAYS FOR DEVELOPMENT OF ENVIRONMENTALLY SAFE SOLID COMPOSITE PROPELLANTS D. B. Lempert, G. B. Manelis, and G. N. Nechiporenko The paper considers a wide set of issues concerning the creation of highenergetic solid composite propellants causing the minimal polluting e¨ecton the environment. Thereby, the level of toxicity of products of di¨er-ent compositions is discussed and propellants with perchlorates oxidizersare compared with propellants with halogen free oxidizers (mainly, am-monium dinitramide, HMX, CL-20). The main methods for creatingcompositions having a required performance and the highest energeticcharacteristics are also under discussion. The dependences of the spe-ci¦c impulse on the mode of formulation arrangement and on the com-pounds£ properties (i.e., formation enthalpy, density, element content)are demonstrated. The main principles for the maximal use of ener-getic potential of chemical substances are under consideration. Theseare the proper selection of the binder type which would be optimal forthe given mixture of oxidizer with fuel (or energetic) component and theopportunity of using metals and their hydrides (mainly, aluminum hy-dride (AH)). Main obstacles in using di¨erent kinds of compositions, aswell as advantages of speci¦c propellants are under consideration as well.A special attention is paid to the interrelationship between the energeticparameter and other performances (thermal stability, combustion law,sensitivity, and compatibility).
dktecoenonwovens.in
NONWOVENS BULLETIN Vol. No. 1 Issue No. 05 February 2015 DKTE Centre of Excellence in Nonwovens Plot No. 1, 2 and 3, Shri. Lakshmi Co-Operative Industrial Estate, Hatkanangle – Ichalkaranji ,Dt. Kolhapur – 416109 (MS) India Tel: +91 230 2366354 Email Website: www.dktecoenonwovens.in Nonwoven Bulletin Volume 01 Issue No. 05 / February 2015