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Pedro L Alonso

Publications and source records attributed to Pedro L Alonso.

At least 19 recordsLinked to original sources
PubMed2007

Seasonal variations in maternal mortality in Maputo, Mozambique: the role of malaria.

OBJECTIVE: To evaluate the impact of malaria on maternal death through the analysis of the seasonal variations of crude and malaria-specific maternal mortality rates. METHODS: All maternal deaths and live births occurring at Maputo Central Hospital, located in an urban area, between January 2001 and December 2003, were retrospectively recorded. Clinical diagnoses of the causes of death and period of the year were analysed. RESULTS: Two hundred and seventy-eight deaths were recorded. The overall crude maternal mortality rate was 995/100 000 live births. Malaria was the most frequent cause of maternal death, accounting for 23%. Crude and malaria-specific maternal mortality rates showed a similar pattern of seasonal variation, with peaks at the beginning and the end of the malaria transmission season. The malaria-specific maternal mortality rate was significantly higher during the rainy seasons (rate ratio 1.919; 95% CI 1.061, 3.470; P = 0.031). CONCLUSIONS: Malaria may contribute to maternal mortality in highly endemic countries in sub-Saharan Africa, at least in urban areas. Efforts to improve malaria control in pregnancy may have an impact on maternal mortality in sub-Saharan Africa.

Adult↗
PubMed2006

RTS,S/AS02A malaria vaccine does not induce parasite CSP T cell epitope selection and reduces multiplicity of infection.

OBJECTIVE: The candidate malaria vaccine RTS,S/AS02A is a recombinant protein containing part of the circumsporozoite protein (CSP) sequence of Plasmodium falciparum, linked to the hepatitis B surface antigen and formulated in the proprietary adjuvant system AS02A. In a recent trial conducted in children younger than age five in southern Mozambique, the vaccine demonstrated significant and sustained efficacy against both infection and clinical disease. In a follow-up study to the main trial, breakthrough infections identified in the trial were examined to determine whether the distribution of csp sequences was affected by the vaccine and to measure the multiplicity of infecting parasite genotypes. DESIGN: P. falciparum DNA from isolates collected during the trial was used for genotype studies. SETTING: The main trial was carried out in the Manhiça district, Maputo province, Mozambique, between April 2003 and May 2004. PARTICIPANTS: Children from the two cohorts of the main trial provided parasite isolates as follows: children from Cohort 1 who were admitted to hospital with clinical malaria; children from Cohort 1 who were parasite-positive in a cross-sectional survey at study month 8.5; children from Cohort 2 identified as parasite-positive during follow-up by active detection of infection. OUTCOME: Divergence of DNA sequence encoding the CSP T cell-epitope region sequence from that of the vaccine sequence was measured in 521 isolates. The number of distinct P. falciparum genotypes was also determined. RESULTS: We found no evidence that parasite genotypes from children in the RTS,S/AS02A arm were more divergent than those receiving control vaccines. For Cohort 1 (survey at study month 8.5) and Cohort 2, infections in the vaccine group contained significantly fewer genotypes than those in the control group, (p = 0.035, p = 0.006), respectively, for the two cohorts. This was not the case for children in Cohort 1 who were admitted to hospital (p = 0.478). CONCLUSIONS: RTS,S/AS02A did not select for genotypes encoding divergent T cell epitopes in the C-terminal region of CSP in this trial. In both cohorts, there was a modest reduction in the mean number of parasite genotypes harboured by vaccinated children compared with controls, but only among those with asymptomatic infections.

Journal Article↗
PubMed2006

Relationship between haemoglobin and haematocrit in the definition of anaemia.

INTRODUCTION: Anaemia is the most frequent haematological disorder in childhood. The notion that defines naemia does not change throughout life, although parameters used for its evaluation show significant variations during childhood. Haematocrit (Hct) (%) is usually defined as three times the value of haemoglobin (Hgb) (g/dl), while the clinical definition of anaemia is related to either an abnormal Hct or Hgb value. OBJECTIVE: To evaluate the agreement between Hgb and Hct values in the definition of anaemia, the relationship between these two parameters and their age-dependence. METHODS: The Hct and Hgb paired values from children aged 2-18 months from Ifakara (Tanzania) and children aged 1-4 years from Manhiça (Mozambique) were analysed. Haematological determinations of the Manhiça samples were done using a KX-21N cell counter (Kobe, Japan) and Ifakara samples were analysed in a semiautomatic cell counter (Sysmex F800 microcell counter, TOA Medical Electronics, Kobe, Japan). The kappa-statistic was used to calculate the agreement between anaemia definitions in each group. Crude and multivariate relationship between Hct and Hgb levels were analysed by linear regression model estimation. The age-dependence of the crude ratio (Hct/Hgb) was analysed using linear regression models and fractional polynomials. RESULTS: The prevalences of mild and moderate anaemia as defined by Hgb levels in the Manhiça group were 61% and 6%, respectively, and 41% and 2% by Hct. In the Ifakara group these were 74% and 10%, respectively, by Hgb and 42% and 3% by Hct, respectively. Agreement between mild and moderate anaemia definitions made up from Hgb or from Hct levels were from fair to moderate. Hct levels decreased with age for high Hgb levels, whereas they increased for low Hgb levels. The classification of cases is improved when higher age-related cut-off values for Hct are used. The crude relationship between Hct and Hgb levels was significantly different from 3, and this was modified by age. The evaluation of the age-dependence ratio (Hct/Hgb) showed a non-linear relationship with an asymptotic trend to 3. CONCLUSIONS: Measurement of haematocrit count is easy and can be performed in most rural health care centres. However, the corresponding Hgb levels cannot be derived with an acceptable accuracy using the value 3 as a conversion factor. Furthermore, the commonly assumed 'equivalent' cut-off points for anaemia definitions need to be re-evaluated.

Age Distribution↗
PubMed2006

Haematological and biochemical indices in young African children: in search of reference intervals.

INTRODUCTION: The reference intervals of haematological and biochemical indices currently used in Africa are derived from data collected from populations living in industrialized countries. Few studies have been performed in Africa questioning the validity of these values when applied to local African populations. OBJECTIVE: To provide reference intervals of haematological [haemoglobin (Hb), white blood cells (WBC), haematocrit (Htc) and platelets] and biochemical indices (ALT, creatinine and bilirubin) for children aged 1-4 from a rural area of southern Mozambique. METHODS: Reference intervals were developed using the 2.5 and 97.5 centiles. Partition tests were performed to evaluate age and gender differences. Quantile regression models were estimated for those variables in which age partition was recommended. Deviances from linearity in the estimated models were evaluated using fractional polynomials of first or second degree. Agreement to classify normality, using the estimated reference intervals or values in use in a western paediatric hospital, was made using the kappa statistic. RESULTS: Reference intervals for Hb, WBC, Htc, platelets, ALT and creatinine show significant differences by age. Gender differences were observed for creatinine values, while for bilirubin there were no significant differences for age or gender. Estimated Hb and Htc reference intervals in African children were lower than the accepted western ones, while ALT values were higher in the former. Agreement between normal classification, using the estimated intervals or the western values, was from slight to fair. CONCLUSIONS: Reference intervals of haematological and biochemical indices based on results from western individuals of the same age are not in agreement with the estimated values for African children. These observed values should not be used as a rule to define normality, but are the ones usually found in this population where anaemia, malaria and high mortality rates are also common.

Age Distribution↗
PubMed2006

Dissemination of Salmonella enterica serotype agona and multidrug-resistant Salmonella enterica serotype typhimurium in Cuba.

The molecular epidemiology, antimicrobial susceptibility, and mechanisms of resistance of 34 Salmonella spp. strains causing acute gastroenteritis, isolated from different provinces in Cuba, were determined. Sixty-four percent of the strains showed multiresistance. Salmonella typhimurium was the most frequent with 15 strains (44%), 13 of which belonged to phagotype 104 and presented similar genetic profiles of pulsed field gel electrophoresis. High levels of resistance to tetracycline (53%), spectinomycin (50%), ampicillin (44%), and chloramphenicol (41%) were found. Resistance to tetracycline was associated with the tet G and tet A genes. Resistance to ampicillin was caused by the presence of beta-lactamases, mainly the CARB type. The floR gene was the main mechanism of resistance to chloramphenicol. Our results showed an antimicrobial susceptible clone of Salmonella enterica serotype Agona in two separate regions. This is the first report of the widespread dissemination of a multiresistant clone of S. enterica serotype Typhimurium definitive phage type 104 in Cuba.

Anti-Bacterial Agents↗
PubMed2006

Malaria: deploying a candidate vaccine (RTS,S/AS02A) for an old scourge of humankind.

Malaria is an infectious disease caused by the protist Plasmodium spp. and it currently kills more than one million people annually. The burden of malaria is concentrated in sub-Saharan Africa, India, and Southeast Asia. The parasite's resistance to commonly used anti-malarial drugs has worsened the situation in the poorest countries. The World Health Organization (WHO) estimates that more than 100 countries suffer from endemic malaria episodes. In addition to numerous control measures and treatments, several vaccines are at different research stages and trials. We have assayed RTS,S/AS02A, a pre-erythrocytic candidate vaccine that has shown promising protection levels in phase IIb trials in Mozambique. The vaccine is directed against the sporozoite form of the parasite, which is injected by the mosquito Anopheles spp. The vaccine induces a strong antibody response and stimulates Th1 cells-a subset of helper T cells that participates in cell-mediated immunity. Recent interest by international funding agencies has provided new inputs into initiatives and programs to fight malaria, which, under normal welfare and adequate social development conditions, is a curable disease.

Animals↗
PubMed2005

Duration of protection with RTS,S/AS02A malaria vaccine in prevention of Plasmodium falciparum disease in Mozambican children: single-blind extended follow-up of a randomised controlled trial.

BACKGROUND: RTS,S/AS02A is a pre-erythrocytic stage malaria vaccine that provides partial protection against infection in malaria-naive adult volunteers and hyperimmune adults. A previous report showed that this vaccine reduced risk of clinical malaria, delayed time to new infection, and reduced episodes of severe malaria over 6 months in African children. An important remaining issue is the durability of protection against clinical disease in these children. METHODS: We did a randomised, controlled, phase IIb trial of RTS,S/AS02A given at 0, 1, and 2 months in 2022 Mozambican children aged 1-4 years. We previously determined vaccine efficacy (VE) against clinical malaria in a double-blind phase that included study months 2.5-8.5 (VE(2.5-8.5)). We now report VE in a single-blind phase up to month 21 (VE(8.5-21)). The primary endpoint was time to first or only clinical episode of Plasmodium falciparum malaria (axillary temperature 37.5 degrees C and P falciparum asexual parasitaemia >2500 per microL) detected through a passive case detection system. We also determined VE for other case definitions and for episodes of severe malaria. This study is registered with the ClinicalTrials.gov identifier NCT00197041. FINDINGS: During the single-blind phase, VE(8.5-21) was 28.9% (95% CI 8.4-44.8; p=0.008). At month 21, prevalence of P falciparum infection was 29% lower in the RTS,S/AS02A group than in the control (p=0.017). Considering the entire study period, VE(2.5-21) was 35.3% (95% CI 21.6-46.6; p<0.0001) and VE(2.5-21) for severe malaria was 48.6% (95% CI 12.3-71.0; p=0.02). INTERPRETATION: These results show that RTS,S/AS02A confers partial protection in African children aged 1-4 years living in rural endemic areas against a range of clinical disease caused by P falciparum for at least 18 months, and confirm the potential of malaria vaccines to become credible control tools for public-health use.

Animals↗
PubMed2004

Polarisation microscopy increases the sensitivity of hemozoin and Plasmodium detection in the histological assessment of placental malaria.

The histological study of the placenta is useful in the diagnosis of malaria during pregnancy. However, the scarcity of parasites and pigment in many malarial infections renders their identification difficult. We have tested the accuracy of standard and polarisation microscopy in the evaluation of 500 placental specimens from an area of high malarial endemicity in Tanzania. Standard microscopy showed a low sensitivity (50.3% for parasites, 40.5% for pigment), due to poor detection rates in cases with scant parasites (12.7% for <1%; 97.8% for >5% parasitised erythrocytes, P < 0.001 ) or minimal pigment deposition (42.4% versus 84.5% when severe, P < 0.001 ). The use of polarisation microscopy significantly increased the sensitivity of detection of pigment to 100% and parasites to 98.1% because of the marked birefringence of hemozoin present in mature stage parasites which accumulate in the placenta. Formalin pigment shares many properties with hemozoin, but the use of neutral buffered formalin prevented the formation of formalin pigment in placentas even after long periods of fixation. In conclusion, polarisation microscopy is a simple tool that markedly increases the sensitivity of the detection of malaria infection in the placenta and has good specificity when used on tissues fixed in neutral formalin. This method can be useful to investigators working in the malaria field.

Animals↗
PubMed2004

The effects of short-term iron supplementation on iron status in infants in malaria-endemic areas.

Iron deficiency and Plasmodium falciparum malaria are the two main causes of anemia in young children in region endemic for this disease. The impact on iron status of prophylactic oral iron supplementation (2 mg/kg/day from two to six months of age) and the duration of this effect were assessed in a group of 832 Tanzanian infants exposed to P. falciparum malaria. Iron parameters and red blood cell indices were assessed at 2, 5, 8, and 12 months of age. Infants who received iron supplements had a significantly lower prevalence of iron deficiency (P < 0.01 at 5 months and P < 0.001 at 8 and 12 months). Red blood cell indices (mean corpuscular volume, mean cell hemoglobin, and mean cell hemoglobin concentration) were increased in children receiving iron supplementation and they did not differ between those protected and unprotected against malaria. The prevalence of ferropenia was similar in children protected against malaria and in those who were not protected and did not receive iron supplements (34.7% versus 37.3% at 12 months of age). We concluded that iron supplementation between the ages of 2-6 months improves iron status at least up to 12 months of age. Malaria infection does not contribute to iron deficiency.

Anemia, Iron-Deficiency↗
PubMed2003

Antibody response after RSV infection in children younger than 1 year of age living in a rural area of Mozambique.

Serological responses have been studied in respiratory syncytial virus (RSV) infected children < 1 year of age attending the outpatient department of the Manhiça District Hospital (Mozambique). Molecular characterization of viral RNA in nasopharyngeal aspirates from the infected children indicated a high level of genetic uniformity among the infecting viruses, all of which belonged to a single genotype of RSV group A. A representative virus strain, Moz00, was isolated from one of the infants and was used, together with the group A strain A2 and the group B strain 8/60, as antigens in the quantification of infant antibody responses. In this study, 97.5% (39/40) and 96.4% (27/28) of infected children produced an antibody response against Moz00 detected by the membrane fluorescent antibody test (MFAT) and the neutralization test (NT), respectively. Seroconversion rates decreased when the A2 and 8/60 strains were used as antigen in MFAT (95.4% and 88.2%, respectively) or NT (81.8% and 54.5%, respectively), indicating that antibody responses had both group- and strain-specific components. Antibodies in convalescent sera of infected children were compared with maternally derived antibodies detected in a group of children also < 1 year of age, but with no evidence of RSV infection. The convalescent sera exhibited reduced neutralizing capacity when the 8/60 strain was used as antigen (P = 0.028), suggesting that the infant antibody response lacks neutralizing capacity against strains of the heterologous virus group. Restricted cross-reactivity and neutralizing capacity of antibodies generated by young children might be expected to induce only moderate protection in subsequent epidemics against genetically distant strains.

Amino Acid Sequence↗
PubMed2003

Plasmodium falciparum multiple infections in Mozambique, its relation to other malariological indices and to prospective risk of malaria morbidity.

We describe the frequency of Plasmodium falciparum clones infecting individuals living in a rural area of southern Mozambique and analyse the relationship between multiplicity of infection, age and other malariometric indices, including prospective risk of clinical malaria. The genotyping was based on the use of restriction fragment length polymorphism-polymerase chain reaction (RFLP-PCR) analysis of P. falciparum merozoite surface protein 2 (msp2). We analysed 826 samples collected during five cross-sectional surveys from residents of Manhiça ranging in age from 4 months to 83 years. We also determined the multiplicity of infection in samples obtained from 6-month-old infants (n = 79) and children <10 years (n = 158) who were then treated and followed prospectively for 1 year or 75 weeks, respectively. Multiplicity of infection did not vary significantly during the first year of life, but increased thereafter, and decreased during adulthood to the levels found in infants. With increasing multiplicity of infection, there was a statistically significant decrease in the risk of submicroscopic infections. There was also a significant correlation between multiplicity of infection and parasite density in infants, children <4 years of age and adults, suggesting that high densities increase the probability of discriminating more clones in complex infections. We found that the relationship between multiple infections and malaria morbidity is age-dependent. In infants, the risk of subsequent episodes of clinical malaria was related to the parasite density but not to baseline multiplicity of infection. In older children, however, the more clones a child carried, the more likely they were to have a clinical malaria episode, and this was true after adjusting for parasite densities. This change in the association between multiplicity and risk of clinical malaria may indicate a shift in the host response to P. falciparum.

Adolescent↗
PubMed2002

Prevalence of respiratory syncytial virus IgG antibodies in infants living in a rural area of Mozambique.

A case control study was carried out in Manhiça (Mozambique). Serum samples were collected from infants < 1 year of age in hospital to assess the effect of serum antibodies on the incidence of respiratory syncytial virus (RSV) infection. Sera were collected from a total of 31 cases of RSV infection and paired uninfected controls matched for age and sex. Anti-RSV antibodies were assessed by a membrane fluorescent antibody test (MFAT) for immunoglobulin G (IgG) antibodies and by a neutralizing antibody test. IgG RSV antibodies were of higher prevalence and at higher levels in the control group when compared to the infected case group (P < 0.001), indicating an important role for IgG antibodies in protection. To assess infection before recruitment, IgA RSV antibodies were also measured by MFAT. IgA RSV antibody prevalence was very low in patients and controls (0/31 and 4/31 respectively), suggesting that most of the detected IgG RSV antibody in both groups was of maternal origin. Re-analysis of data from the subset of 27 matched, IgA RSV antibody negative infant pairs mirrored the full analysis indicating that maternal antibody has an important role in RSV protection. Similar results were obtained when neutralizing antibodies were measured and when the measurement was done against subgroup A virus strain A2, subgroup B virus strain 8/60 and a contemporary subgroup A isolate, Moz00. No significant differences in the reactivity of maternal antibodies with the three virus strains were observed. The data described below represent the first analysis of the role of maternal antibodies in reducing the risk of pediatric infection in developing countries. The results reinforce the concept of maternal vaccination for the control of RSV in very young children in whom the risk and severity of infection are the highest.

Adolescent↗
PubMed2002

Epidemiology and clinical presentation of respiratory syncytial virus infection in a rural area of southern Mozambique.

BACKGROUND: Respiratory syncytial virus (RSV) is a major cause of lower respiratory tract infection (LRTI) in infants throughout most of the world, but little is known about RSV infection in Africa where LRTI are among the leading causes of infant and childhood death. METHODS: The study took place in a rural district hospital in southern Mozambique between October, 1998, and May, 2000. From all children (n = 5635) <1 year of age presenting to an outpatient department with cough or nasal secretion and all children (n = 1307) <5 years of age admitted to hospital with a LRTI, a nasopharyngeal aspirate was collected and tested for RSV by enzyme-linked immunosorbent assay (Abbott). RESULTS: RSV infection was found in 8.6% of study infants in the outpatient department and 10.6% of admitted children with LRTI. Cases presented in predictable yearly outbreaks during the warm and rainy season. Lower respiratory tract involvement was frequent (59.7%). Cough, chest indrawing and increased respiratory rate were all independently related to RSV infection. Wheezing was infrequent. Bacterial coinfection (4.6%) and the case-fatality rate (3.4%) were low. CONCLUSIONS: There is a substantial burden of disease attributable to RSV infection in this rural African setting, with the highest incidence and severity occurring in young infants.

Bacterial Infections↗
PubMed2002

Malaria infection does not appear to modify the risk of bronchiolitis early in life.

BACKGROUND: The observation of an increased prevalence of allergic disorders coinciding with a decreasing frequency of infectious diseases in early childhood has led to the speculation that infections may prevent allergic sensitization. Information on the role of parasites in this context is limited. Bronchiolitis in infancy has been linked with asthmatic symptoms later in childhood, although the underlying cause of this association is unknown. METHODS: To test the hypothesis that early parasitic infections in infancy might prevent the development of allergic manifestations later in life, the effect of malaria infections during the first year of life on the risk of bronchiolitis was studied in 675 Tanzanian children at 18 months of age. The study was conducted as part of an intervention trial of malaria chemoprophylaxis and/or iron supplementation for the prevention of malaria and anemia in infants. RESULTS: The incidence of bronchiolitis up to 18 months of age in the 675 children was 0.58 episode per child per year. The risk factors analysis was based on 470 children with complete data. There was no difference in the incidence of bronchiolitis between those who had received malaria chemoprophylaxis during the first year of life and those who had not. However, the proportion of children who had bronchiolitis was lower among those who had had malaria episodes than among those who had not (48% vs. 55%, P = 0.05). CONCLUSIONS: This study does not support the hypothesis that reduced exposure to parasites may modulate the development of bronchiolitis early in life.

Age of Onset↗
PubMed2002

Field trials.

Explore the source record for details and available documents.

Humans↗
PubMed2002

The safety and efficacy of sulfadoxine-pyrimethamine, amodiaquine, and their combination in the treatment of uncomplicated Plasmodium falciparum malaria.

The safety and efficacy of amodiaquine (AQ), sulfadoxine-pyrimethamine (SP), and coadministered AQ+SP was assessed in 351 Tanzanian children (age range, 6-59 months) with uncomplicated Plasmodium falciparum malaria. This open, randomized study followed the 28-day World Health Organization (WHO) protocol and evaluated safety using clinical and laboratory parameters. Children receiving SP were more likely to vomit during follow-up (32% vs. 17%: P = 0.03), and SP alone resulted in prolonged fever clearance times. Although Day 7 and Day 14 clinical and parasitological cure rates were similar, by Day 28 45% of children treated with AQ demonstrated R1 resistance and 27.5% were clinical failures compared with 25% and 6.3%, respectively, for SP alone. Coadministered AQ+SP was safe, combined the greater clinical (96.2%) and parasitological (64.2%) efficacy of SP with the more rapid symptom resolution of AQ, and reduced the incidence of gametocytemia during follow-up (AQ+SP 12.6% vs. SP 29.9%; P = 0.001). The level of R1 resistance to SP may herald a rapid decline in its efficacy as SP drug pressure increases. Coadministration of AQ+SP may delay this.

Amodiaquine↗
PubMedDate not supplied

Efficacy of the RTS,S/AS02A vaccine against Plasmodium falciparum infection and disease in young African children: randomised controlled trial.

BACKGROUND: Development of an effective malaria vaccine could greatly contribute to disease control. RTS,S/AS02A is a pre-erythrocytic vaccine candidate based on Plasmodium falciparum circumsporozoite surface antigen. We aimed to assess vaccine efficacy, immunogenicity, and safety in young African children. METHODS: We did a double-blind, phase IIb, randomised controlled trial in Mozambique in 2022 children aged 1-4 years. The study included two cohorts of children living in two separate areas which underwent different follow-up schemes. Participants were randomly allocated three doses of either RTS,S/AS02A candidate malaria vaccine or control vaccines. The primary endpoint, determined in cohort 1 (n=1605), was time to first clinical episode of P falciparum malaria (axillary temperature > or =37.5 degrees C and P falciparum asexual parasitaemia >2500 per microL) over a 6-month surveillance period. Efficacy for prevention of new infections was determined in cohort 2 (n=417). Analysis was per protocol. FINDINGS: 115 children in cohort 1 and 50 in cohort 2 did not receive all three doses and were excluded from the per-protocol analysis. Vaccine efficacy for the first clinical episodes was 29.9% (95% CI 11.0-44.8; p=0.004). At the end of the 6-month observation period, prevalence of P falciparum infection was 37% lower in the RTS,S/AS02A group compared with the control group (11.9% vs 18.9%; p=0.0003). Vaccine efficacy for severe malaria was 57.7% (95% CI 16.2-80.6; p=0.019). In cohort 2, vaccine efficacy for extending time to first infection was 45.0% (31.4-55.9; p<0.0001). INTERPRETATION: The RTS,S/AS02A vaccine was safe, well tolerated, and immunogenic. Our results show development of an effective vaccine against malaria is feasible.

Animals↗