Journal Article > ResearchFull Text
Int J Tuberc Lung Dis. 2010 December 1; Volume 14 (Issue 12); 1589-1595.
Minetti A, Camelique O, Hsa Thaw K, Thi SS, Swaddiwudhipong W, et al.
Int J Tuberc Lung Dis. 2010 December 1; Volume 14 (Issue 12); 1589-1595.
SETTING
Although tuberculosis (TB) is a curable disease, it remains a major global health problem and an important cause of morbidity and mortality among vulnerable populations, including refugees and migrants.
OBJECTIVE
To describe results and experiences over 20 years at a TB programme in refugee camps on the Thai-Burmese border in Tak Province, Thailand, and to identify risk factors associated with adverse outcomes (e.g., default, failure, death).
DESIGN
Retrospective review of routine records of 2425 patients admitted for TB treatment in the Mae La TB programme between May 1987 and December 2005.
RESULTS
TB cases notified among refugees decreased over 20 years. Among patients treated with a first-, second- or third-line regimen, 77.5% had a successful outcome, 13.5% defaulted, 7.6% died and 1.3% failed treatment. Multivariate analysis for new cases showed higher likelihood of adverse outcomes for patients who were Burmese migrants or Thai villagers, male, aged >15 years or with smear-negative pulmonary TB.
CONCLUSION
These findings suggest that treatment outcomes depend on the programme's capacity to respond to specific patients' constraints. High-risk groups, such as migrant populations, need a patient-centred approach, and specific, innovative strategies have to be developed based on the needs of the most vulnerable and marginalised populations.
Although tuberculosis (TB) is a curable disease, it remains a major global health problem and an important cause of morbidity and mortality among vulnerable populations, including refugees and migrants.
OBJECTIVE
To describe results and experiences over 20 years at a TB programme in refugee camps on the Thai-Burmese border in Tak Province, Thailand, and to identify risk factors associated with adverse outcomes (e.g., default, failure, death).
DESIGN
Retrospective review of routine records of 2425 patients admitted for TB treatment in the Mae La TB programme between May 1987 and December 2005.
RESULTS
TB cases notified among refugees decreased over 20 years. Among patients treated with a first-, second- or third-line regimen, 77.5% had a successful outcome, 13.5% defaulted, 7.6% died and 1.3% failed treatment. Multivariate analysis for new cases showed higher likelihood of adverse outcomes for patients who were Burmese migrants or Thai villagers, male, aged >15 years or with smear-negative pulmonary TB.
CONCLUSION
These findings suggest that treatment outcomes depend on the programme's capacity to respond to specific patients' constraints. High-risk groups, such as migrant populations, need a patient-centred approach, and specific, innovative strategies have to be developed based on the needs of the most vulnerable and marginalised populations.
Journal Article > ResearchFull Text
Malar J. 2013 July 17; Volume 12 (Issue 1); 250.; DOI:10.1186/1475-2875-12-250
Schramm B, Valeh P, Baudin E, Mazinda CS, Smith R, et al.
Malar J. 2013 July 17; Volume 12 (Issue 1); 250.; DOI:10.1186/1475-2875-12-250
BACKGROUND
Safety surveillance of widely used artemisinin-based combination therapy (ACT) is essential, but tolerability data in the over five years age group are largely anecdotal.
METHODS
Two open-label, randomized trials were conducted in Nimba County, Liberia: i) the main tolerability trial with 1,000 Plasmodium falciparum malaria patients aged over five years (Study-T), and, ii) an efficacy trial with a secondary objective of collecting tolerability data among 300 children age six to 59 months (Study-E). In both studies patients were randomized to fixed-dose artesunate-amodiaquine (ASAQ Winthrop®) or artemether-lumefantrine (AL, Coartem®), respectively. Clinical- and laboratory-adverse events (AEs) were recorded until day 28.
RESULTS
Study-T: most patients experienced at least one AE. Severe AEs were few, primarily asymptomatic blood system disorders or increased liver enzyme values. No treatment or study discontinuation occurred. Mild or moderate fatigue (39.8% vs 16.3%, p < 0.001), vomiting (7.1% vs 1.6%, p < 0.001), nausea (3.2% vs 1.0%, p = 0.01), and anaemia (14.9% vs 9.8%, p = 0.01) were more frequently recorded in the ASAQ versus AL arm. Study-E: mild or moderate AEs were common, including anaemia, fatigue, vomiting or diarrhoea. The few severe events were asymptomatic blood system disorders and four clinical events (pneumonia, malaria, vomiting and stomatitis).
CONCLUSION
Both ASAQ and AL were well tolerated in patients of all age groups. No unexpected AEs occurred. Certain mild or moderate AEs were more frequent in the ASAQ arm. Standardised safety surveillance should continue for all forms of ACT.
TRIAL REGISTRATION
The protocols were registered with Current Controlled Trials, under the identifier numbers ISRCTN40020296, ISRCTN51688713, (http://www.controlled-trials.com).
Safety surveillance of widely used artemisinin-based combination therapy (ACT) is essential, but tolerability data in the over five years age group are largely anecdotal.
METHODS
Two open-label, randomized trials were conducted in Nimba County, Liberia: i) the main tolerability trial with 1,000 Plasmodium falciparum malaria patients aged over five years (Study-T), and, ii) an efficacy trial with a secondary objective of collecting tolerability data among 300 children age six to 59 months (Study-E). In both studies patients were randomized to fixed-dose artesunate-amodiaquine (ASAQ Winthrop®) or artemether-lumefantrine (AL, Coartem®), respectively. Clinical- and laboratory-adverse events (AEs) were recorded until day 28.
RESULTS
Study-T: most patients experienced at least one AE. Severe AEs were few, primarily asymptomatic blood system disorders or increased liver enzyme values. No treatment or study discontinuation occurred. Mild or moderate fatigue (39.8% vs 16.3%, p < 0.001), vomiting (7.1% vs 1.6%, p < 0.001), nausea (3.2% vs 1.0%, p = 0.01), and anaemia (14.9% vs 9.8%, p = 0.01) were more frequently recorded in the ASAQ versus AL arm. Study-E: mild or moderate AEs were common, including anaemia, fatigue, vomiting or diarrhoea. The few severe events were asymptomatic blood system disorders and four clinical events (pneumonia, malaria, vomiting and stomatitis).
CONCLUSION
Both ASAQ and AL were well tolerated in patients of all age groups. No unexpected AEs occurred. Certain mild or moderate AEs were more frequent in the ASAQ arm. Standardised safety surveillance should continue for all forms of ACT.
TRIAL REGISTRATION
The protocols were registered with Current Controlled Trials, under the identifier numbers ISRCTN40020296, ISRCTN51688713, (http://www.controlled-trials.com).
Journal Article > ResearchFull Text
Lancet. 2008 April 14; Volume 366 (Issue 9482); DOI:10.1016/S0140-6736(05)66792-X
Nathan N, Borel T, Djibo A, Evans D, Djibo S, et al.
Lancet. 2008 April 14; Volume 366 (Issue 9482); DOI:10.1016/S0140-6736(05)66792-X
BACKGROUND: In sub-Saharan Africa in the 1990s, more than 600,000 people had epidemic meningococcal meningitis, of whom 10% died. The current recommended treatment by WHO is short-course long-acting oily chloramphenicol. Continuation of the production of this drug is uncertain, so simple alternatives need to be found. We assessed whether the efficacy of single-dose treatment of ceftriaxone was non-inferior to that of oily chloramphenicol for epidemic meningococcal meningitis. METHODS: In 2003, we undertook a randomised, open-label, non-inferiority trial in nine health-care facilities in Niger. Participants with suspected disease who were older than 2 months were randomly assigned to receive either chloramphenicol or ceftriaxone. Primary outcome was treatment failure (defined as death or clinical failure) at 72 h, measured with intention-to-treat and per-protocol analyses. FINDINGS: Of 510 individuals with suspected disease, 247 received ceftriaxone, 256 received chloramphenicol, and seven were lost to follow-up. The treatment failure rate at 72 h for the intention-to-treat analysis was 9% (22 patients) for both drug groups (risk difference 0.3%, 90% CI -3.8 to 4.5). Case fatality rates and clinical failure rates were equivalent in both treatment groups (14 [6%] ceftriaxone vs 12 [5%] chloramphenicol). Results were also similar for both treatment groups in individuals with confirmed meningitis caused by Neisseria meningitidis. No adverse side-effects were reported. INTERPRETATION: Single-dose ceftriaxone provides an alternative treatment for epidemic meningococcal meningitis--its efficacy, ease of use, and low cost favour its use. National and international health partners should consider ceftriaxone as an alternative first-line treatment to chloramphenicol for epidemic meningococcal meningitis.
Journal Article > ResearchFull Text
Trop Med Int Health. 2006 April 1; Volume 11 (Issue 4); DOI:10.1111/j.1365-3156.2006.01580.x
Rolland E, Checchi F, Pinoges LLP, Balkan S, Guthmann JP, et al.
Trop Med Int Health. 2006 April 1; Volume 11 (Issue 4); DOI:10.1111/j.1365-3156.2006.01580.x
OBJECTIVE: To compare the cost-effectiveness of malaria treatment based on presumptive diagnosis with that of malaria treatment based on rapid diagnostic tests (RDTs). METHODS: We calculated direct costs (based on experience from Ethiopia and southern Sudan) and effectiveness (in terms of reduced over-treatment) of a free, decentralised treatment programme using artesunate plus amodiaquine (AS + AQ) or artemether-lumefantrine (ART-LUM) in a Plasmodium falciparum epidemic. Our main cost-effectiveness measure was the incremental cost per false positive treatment averted by RDTs. RESULTS: As malaria prevalence increases, the difference in cost between presumptive and RDT-based treatment rises. The threshold prevalence above which the RDT-based strategy becomes more expensive is 21% in the AS + AQ scenario and 55% in the ART-LUM scenario, but these thresholds increase to 58 and 70%, respectively, if the financing body tolerates an incremental cost of 1 euro per false positive averted. However, even at a high (90%) prevalence of malaria consistent with an epidemic peak, an RDT-based strategy would only cost moderately more than the presumptive strategy: +29.9% in the AS + AQ scenario and +19.4% in the ART-LUM scenario. The treatment comparison is insensitive to the age and pregnancy distribution of febrile cases, but is strongly affected by variation in non-biomedical costs. If their unit price were halved, RDTs would be more cost-effective at a malaria prevalence up to 45% in case of AS + AQ treatment and at a prevalence up to 68% in case of ART-LUM treatment. CONCLUSION: In most epidemic prevalence scenarios, RDTs would considerably reduce over-treatment for only a moderate increase in costs over presumptive diagnosis. A substantial decrease in RDT unit price would greatly increase their cost-effectiveness, and should thus be advocated. A tolerated incremental cost of 1 euro is probably justified given overall public health and financial benefits. The RDTs should be considered for malaria epidemics if logistics and human resources allow.
Journal Article > ResearchFull Text
PLOS One. 2012 November 7; Volume 7 (Issue 11); DOI:10.1371/journal.pone.0049091
Bastard M, Pinoges LLP, Balkan S, Szumilin E, Ferreyra C, et al.
PLOS One. 2012 November 7; Volume 7 (Issue 11); DOI:10.1371/journal.pone.0049091
Ensuring long-term adherence to therapy is essential for the success of HIV treatment. As access to viral load monitoring and genotyping is poor in resource-limited settings, a simple tool to monitor adherence is needed. We assessed the relationship between an indicator based on timeliness of clinic attendance and virological response and HIV drug resistance.
Journal Article > ResearchFull Text
Malar J. 2013 July 17; Volume 12 (Issue 1); 251.; DOI:10.1186/1475-2875-12-251
Schramm B, Valeh P, Baudin E, Mazinda CS, Smith R, et al.
Malar J. 2013 July 17; Volume 12 (Issue 1); 251.; DOI:10.1186/1475-2875-12-251
BACKGROUND
Prospective efficacy monitoring of anti-malarial treatments is imperative for timely detection of resistance development. The in vivo efficacy of artesunate-amodiaquine (ASAQ) fixed-dose combination (FDC) was compared to that of artemether-lumefantrine (AL) among children aged six to 59 months in Nimba County, Liberia, where Plasmodium falciparum malaria is endemic and efficacy data are scarce.
METHODS
An open-label, randomized controlled non-inferiority trial compared the genotyping adjusted day 42 cure rates of ASAQ FDC (ASAQ Winthrop®) to AL (Coartem®) in 300 children aged six to 59 months with uncomplicated falciparum malaria. Inclusion was between December 2008 and May 2009. Randomization (1:1) was to a three-day observed oral regimen (ASAQ: once a day; AL: twice a day, given with fatty food). Day 7 desethylamodiaquine and lumefantrine blood-concentrations were also measured.
RESULTS
The day 42 genotyping-adjusted cure rate estimates were 97.3% [95% CI: 91.6-99.1] for ASAQ and 94.2% [88.1-97.2] for AL (Kaplan-Meier survival estimates). The difference in day 42 cure rates was -3.1% [upper limit 95% CI: 1.2%]. These results were confirmed by observed proportion of patients cured at day 42 on the per-protocol population. Parasite clearance was 100% (ASAQ) and 99.3% (AL) on day 3. The probability to remain free of re-infection was 0.55 [95% CI: 0.46-0.63] (ASAQ) and 0.66 [0.57-0.73] (AL) (p = 0.017).
CONCLUSIONS
Both ASAQ and AL were highly efficacious and ASAQ was non-inferior to AL. The proportion of patients with re-infection was high in both arms in this highly endemic setting. In 2010, ASAQ FDC was adopted as the first-line national treatment in Liberia. Continuous efficacy monitoring is recommended.
TRIAL REGISTRATION
The protocols were registered with Current Controlled Trials, under the identifier numbers ISRCTN51688713, ISRCTN40020296.
Prospective efficacy monitoring of anti-malarial treatments is imperative for timely detection of resistance development. The in vivo efficacy of artesunate-amodiaquine (ASAQ) fixed-dose combination (FDC) was compared to that of artemether-lumefantrine (AL) among children aged six to 59 months in Nimba County, Liberia, where Plasmodium falciparum malaria is endemic and efficacy data are scarce.
METHODS
An open-label, randomized controlled non-inferiority trial compared the genotyping adjusted day 42 cure rates of ASAQ FDC (ASAQ Winthrop®) to AL (Coartem®) in 300 children aged six to 59 months with uncomplicated falciparum malaria. Inclusion was between December 2008 and May 2009. Randomization (1:1) was to a three-day observed oral regimen (ASAQ: once a day; AL: twice a day, given with fatty food). Day 7 desethylamodiaquine and lumefantrine blood-concentrations were also measured.
RESULTS
The day 42 genotyping-adjusted cure rate estimates were 97.3% [95% CI: 91.6-99.1] for ASAQ and 94.2% [88.1-97.2] for AL (Kaplan-Meier survival estimates). The difference in day 42 cure rates was -3.1% [upper limit 95% CI: 1.2%]. These results were confirmed by observed proportion of patients cured at day 42 on the per-protocol population. Parasite clearance was 100% (ASAQ) and 99.3% (AL) on day 3. The probability to remain free of re-infection was 0.55 [95% CI: 0.46-0.63] (ASAQ) and 0.66 [0.57-0.73] (AL) (p = 0.017).
CONCLUSIONS
Both ASAQ and AL were highly efficacious and ASAQ was non-inferior to AL. The proportion of patients with re-infection was high in both arms in this highly endemic setting. In 2010, ASAQ FDC was adopted as the first-line national treatment in Liberia. Continuous efficacy monitoring is recommended.
TRIAL REGISTRATION
The protocols were registered with Current Controlled Trials, under the identifier numbers ISRCTN51688713, ISRCTN40020296.
Journal Article > ResearchFull Text
Ann Trop Paediatr. 2008 March 1; Volume 28 (Issue 1); DOI:10.1179/146532808X270635
Dubray C, Ibrahim SA, Abdelmutalib M, Guerin PJ, Dantoine F, et al.
Ann Trop Paediatr. 2008 March 1; Volume 28 (Issue 1); DOI:10.1179/146532808X270635
BACKGROUND: Systemic antibiotics are routinely prescribed for severe acute malnutrition (SAM). However, there is no consensus regarding the most suitable regimen. In a therapeutic feeding centre in Khartoum, Sudan, a randomised, unblinded, superiority-controlled trial was conducted, comparing once daily intramuscular injection with ceftriaxone for 2 days with oral amoxicillin twice daily for 5 days in children aged 6-59 months with SAM. METHODS: Commencing with the first measured weight gain (WG) following admission, the risk difference and 95% confidence interval (95% CI) for children with a WG > or = 10 g/kg/day were calculated over a 14-day period. The recovery rate and case fatality ratio (CFR) between the two groups were also calculated. RESULTS: In an intention-to-treat analysis of 458 children, 53.5% (123/230) in the amoxicillin group and 55.7% (127/228, difference 2.2%, 95% CI -6.9-11.3) in the ceftriaxone group had a WG > or = 10 g/kg/day during a 14-day period. Recovery rate was 70% (161/230) in the amoxicillin group and 74.6% (170/228) in the ceftriaxone group (p=0.27). CFR was 3.9% (9/230) and 3.1% (7/228), respectively (p=0.67). Most deaths occurred within the 1st 2 weeks of admission. CONCLUSION: In the absence of severe complications, either ceftriaxone or amoxicillin is appropriate for malnourished children. However, in ambulatory programmes, especially where there are large numbers of admissions, ceftriaxone should facilitate the work of medical personnel.
Journal Article > ResearchFull Text
PLOS One. 2011 November 21; Volume 6 (Issue 11); e28112.; DOI:10.1371/journal.pone.0028112
Pujades-Rodriguez M, Dantony E, Pinoges LLP, Ecochard R, Etard JF, et al.
PLOS One. 2011 November 21; Volume 6 (Issue 11); e28112.; DOI:10.1371/journal.pone.0028112
BACKGROUND
To compare the incidence and timing of toxicity associated with the use of a reduced dose of stavudine from 40 to 30 mg in first-line antiretroviral therapy (ART) for HIV treatment and to investigate associated risk factors.
METHODS
Multicohort study including 23 HIV programs in resource-limited countries. Adults enrolled between January 2005 and December 2009. Four-year rates of all-cause and stavudine-specific toxicity were estimated. Multilevel mixed-effect Poisson and accelerated failure models were used to investigate factors associated with toxicity and timing of diagnosis.
FINDINGS
A total of 48,785 patients contributed 62,505 person-years of follow-up. Rate of all-cause toxicity was 7.80 (95%CI 7.59-8.03) per 100 person-years, but varied greatly across sites (range 0.41-21.76). Patients treated with stavudine 40 mg had higher rates of toxicity (adjusted rate ratio [aRR] 1.18, 95%CI 1.06-1.30 during the first year of ART; and 1.51, 95%CI 1.32-1.71 during the second year). Women, older age, initial advanced clinical stage, and low CD4 count were associated with increased toxicity rate ratios. Timing of lipodystrophy and peripheral neuropathy diagnosis were 12% and 13% shorter, respectively, in patients treated with stavudine 40 mg than in those receiving 30 mg stavudine dose (P = 0.03 and 0.07, respectively). INSTERPRETATION: Higher rates of drug-related toxicity were reported in patients receiving stavudine 40 mg compared with 30 mg, and the time to toxicity diagnosis was shorter in patients treated with the higher dose. Higher rates of toxicity were observed during the first two years of ART.
To compare the incidence and timing of toxicity associated with the use of a reduced dose of stavudine from 40 to 30 mg in first-line antiretroviral therapy (ART) for HIV treatment and to investigate associated risk factors.
METHODS
Multicohort study including 23 HIV programs in resource-limited countries. Adults enrolled between January 2005 and December 2009. Four-year rates of all-cause and stavudine-specific toxicity were estimated. Multilevel mixed-effect Poisson and accelerated failure models were used to investigate factors associated with toxicity and timing of diagnosis.
FINDINGS
A total of 48,785 patients contributed 62,505 person-years of follow-up. Rate of all-cause toxicity was 7.80 (95%CI 7.59-8.03) per 100 person-years, but varied greatly across sites (range 0.41-21.76). Patients treated with stavudine 40 mg had higher rates of toxicity (adjusted rate ratio [aRR] 1.18, 95%CI 1.06-1.30 during the first year of ART; and 1.51, 95%CI 1.32-1.71 during the second year). Women, older age, initial advanced clinical stage, and low CD4 count were associated with increased toxicity rate ratios. Timing of lipodystrophy and peripheral neuropathy diagnosis were 12% and 13% shorter, respectively, in patients treated with stavudine 40 mg than in those receiving 30 mg stavudine dose (P = 0.03 and 0.07, respectively). INSTERPRETATION: Higher rates of drug-related toxicity were reported in patients receiving stavudine 40 mg compared with 30 mg, and the time to toxicity diagnosis was shorter in patients treated with the higher dose. Higher rates of toxicity were observed during the first two years of ART.
Journal Article > ResearchFull Text
Trop Med Int Health. 2008 January 1; Volume 13 (Issue 1); DOI:10.1111/j.1365-3156.2007.01977.x
Olliaro PL, Pinoges LLP, Checchi F, Vaillant M, Guthmann JP
Trop Med Int Health. 2008 January 1; Volume 13 (Issue 1); DOI:10.1111/j.1365-3156.2007.01977.x
OBJECTIVE: Parasites may recur asymptomatically after initial clearance by antimalarial treatment. Current guidelines recommend treatment only when patients develop symptoms or at the end of follow-up. We wanted to assess prospectively the probability of becoming symptomatic and the risks of this practice. METHODS: We analysed data collected in 13 trials of uncomplicated paediatric malaria conducted in eight sub-Saharan African countries. These studies followed all cases of post-treatment asymptomatic parasitaemia until they developed symptoms or to the end of the 28-day follow-up period, at which time parasite genotypes were compared to pre-treatment isolates to distinguish between recrudescences and new infections. RESULTS: There were 425 asymptomatic recurrences after 2576 treatments with either chloroquine, sulfadoxine/pyrimethamine or amodiaquine, of which 225 occurred by day 14 and 200 between day 15 and day 28. By day 28, 42% developed fever (median time to fever = 5 days) and 30% remained parasitaemic but afebrile, while 23% cleared their parasites (outcome unknown in 4%). Young age, parasitaemia >/=500 parasites/microl; onset of parasitaemia after day 14, and treatment with amodiaquine were the main variables associated with higher risk of developing fever. CONCLUSION: In areas of moderate to intense transmission, asymptomatic recurrences of malaria after treatment carry a substantial risk of becoming ill within a few days and should be treated as discovered. Young children are at higher risk. The higher risk carried by cases occurring in the second half of follow-up may be explained by falling residual drug levels.
Journal Article > ResearchFull Text
PLoS Negl Trop Dis. 2008 December 2; Volume 2 (Issue 12); DOI:10.1371/journal.pntd.0000342
Guerin PJ, Naess LM, Fogg C, Rosenqvist E, Pinoges LLP, et al.
PLoS Negl Trop Dis. 2008 December 2; Volume 2 (Issue 12); DOI:10.1371/journal.pntd.0000342
BACKGROUND: Neisseria meningitidis serogroup A is the main causative pathogen of meningitis epidemics in sub-Saharan Africa. In recent years, serogroup W135 has also been the cause of epidemics. Mass vaccination campaigns with polysaccharide vaccines are key elements in controlling these epidemics. Facing global vaccine shortage, we explored the use of fractional doses of a licensed A/C/Y/W135 polysaccharide meningococcal vaccine. METHODS AND FINDINGS: We conducted a randomized, non-inferiority trial in 750 healthy volunteers 2-19 years old in Mbarara, Uganda, to compare the immune response of the full dose of the vaccine versus fractional doses (1/5 or 1/10). Safety and tolerability data were collected for all subjects during the 4 weeks following the injection. Pre- and post-vaccination sera were analyzed by measuring serum bactericidal activity (SBA) with baby rabbit complement. A responder was defined as a subject with a >/=4-fold increase in SBA against a target strain from each serogroup and SBA titer >/=128. For serogroup W135, 94% and 97% of the vaccinees in the 1/5- and 1/10-dose arms, respectively, were responders, versus 94% in the full-dose arm; for serogroup A, 92% and 88% were responders, respectively, versus 95%. Non-inferiority was demonstrated between the full dose and both fractional doses in SBA seroresponse against serogroups W135 and Y, in total population analysis. Non-inferiority was shown between the full and 1/5 doses for serogroup A in the population non-immune prior to vaccination. Non-inferiority was not shown for any of the fractionate doses for serogroup C. Safety and tolerability data were favourable, as observed in other studies. CONCLUSIONS: While the advent of conjugate A vaccine is anticipated to largely contribute to control serogroup A outbreaks in Africa, the scale-up of its production will not cover the entire "Meningitis Belt" target population for at least the next 3 to 5 years. In view of the current shortage of meningococcal vaccines for Africa, the use of 1/5 fractional doses should be considered as an alternative in mass vaccination campaigns. TRIAL REGISTRATION: ClinicalTrials.gov NCT00271479.