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Biomedical subjects

P L Alonso

Publications and source records attributed to P L Alonso.

At least 19 recordsLinked to original sources
PubMed2007

Safety and immunogenicity of the RTS,S/AS02A candidate malaria vaccine in children aged 1-4 in Mozambique.

BACKGROUND: The development of a malaria vaccine remains a public health priority for sub-Saharan Africa. RTS,S/AS02A candidate malaria vaccine has been shown to be safe and immunogenic in previous studies in adults and staggered dose-escalation studies in children in The Gambia. However, genetic features and the intensity of malaria transmission may modify the safety and immune response of a vaccine. OBJECTIVE: We carried out a phase I, double-blind randomized controlled trial in 60 children aged 1-4 in Mozambique to evaluate the safety, reactogenicity and immunogenicity of the paediatric vaccine dose (fixed 25 microg RTS,S in 0.25 ml) of RTS,S/AS02A, prior to undertaking a planned larger phase IIb proof-of-concept of efficacy study in the same population. METHOD: Children were randomized to receive either RTS,S/AS02A or Engerix-B vaccine. Monitoring of safety and reactogenicity included detailed clinical and laboratory analyses and assessment of adverse events (AEs). RESULTS: The RTS,S/AS02A was found to be safe and well tolerated. Serious adverse events were balanced between both groups and none was related to vaccination. The frequency of adverse events reported with RTS, S/AS02A was comparable to previous studies in children. Grade 3 AEs were infrequent (one case of pain, one of fever in each group and some swelling greater than 20 mm in diameter), transient and resolved without sequelae. RTS,S/AS02A was highly immunogenic for anti-circumsporozoite protein antibody response and induced a strong anti-hepatitis-B surface antigen response.

Alanine Transaminase↗
PubMed2006

Community incidences of respiratory infections in an actively followed cohort of children <1 year of age in Manhiça, a rural area of southern Mozambique.

OBJECTIVE: To estimate the community incidence-rates of respiratory infections among infants in Manhiça, southern Mozambique, and to determine risk factors associated with these infections. METHODS: A cohort of children <1 year of age were visited at home every week until they turned one. During the visits, field workers recorded signs/symptoms of respiratory infections and tested the children for malaria parasites when they had fever. RESULTS: Between 1 July 1998 and 30 June 1999, 1,044 children contributed with 23,726 weeks at risk. Children met the criteria for acute respiratory infection in 19.2% of the visits, for lower respiratory infection in 0.9% and for severe lower respiratory infection in 0.2%. The crude incidence rate measured for acute respiratory infections was 23.0, that for lower respiratory infection was 0.9 and that for severe lower respiratory infection was 0.2 per 100-person-week-at-risk. The risk of acute and lower respiratory infection was inversely related to age. Females were at significantly lower risk for all three conditions than males. A trend of increased risk of severe lower respiratory infection was noted among children born during the rainy season (adjusted rate ratio = 1.95, P = 0.122 in only 47 episodes). Malaria was strongly associated with an increased risk of all three respiratory infections [rate ratio of 2.35, 10.90 and 13.82 (P < 0.001) in the adjusted analysis, respectively]. Thirty-five children died during the follow-up period; 20% of them from lower respiratory infection. Conclusions Respiratory infections are a major cause of morbidity and mortality among infants in rural Mozambique. Our study provides a better understanding of the associated determinants.

Acute Disease↗
PubMed2006

Malaria: burden of disease.

Despite more than 100 years since Laveran described plasmodium species and Ross confirmed that they were transmitted by female anopheline mosquitoes, malaria remains a leading cause of morbidity and mortality worldwide. Although the areas where transmission takes place have reduced, and they are by now confined to the inter tropical areas, the number of people living at risk has grown to about 3 billion, and is expected to go on increasing. Not only does malaria cause around 500 million cases every year, and between 1 and 3 million deaths, but it also carries a huge burden that impairs the economic and social development of large parts of the planet. The failed attempt to eradicate malaria gave way to the control policy that was followed by a huge resurgence of malaria during the late 70s and 80s. Together with the emergence and spread of resistance to chloroquine and the weak health infrastructure in many of the endemic countries, particularly in Africa, the malaria situation worsened worldwide. The last decade of the 20th century was witness to the international community becoming increasingly aware of the unacceptable situation that the burden of malaria represented to large parts of the world. Renewed efforts to describe the problem, design and evaluate new control strategies, design and develop new drugs, better understand the biology of the parasite and the immunity it induces in the human host, develop candidate vaccines, together with new financial support constitute renewed hope that may lead to new trends in global health.

Chloroquine↗
PubMed2005

Plasmodium species mixed infections in two areas of Manhiça district, Mozambique.

We compared the distribution patterns of individual Plasmodium species and mixed-species infections in two geographically close endemic areas, but showing environmental differences. Comparisons concerned circulating Plasmodium infections in both human and mosquito vector populations in the dry and wet seasons, at a micro-epidemiological level (households). Both areas revealed a very high overall prevalence of infection, all year-round and in all age groups. Plasmodium falciparum was the predominant species, being found in the vast majority of infected individuals regardless of the presence of other species. Plasmodium malariae and Plasmodium ovale occurred almost exclusively in mixed infections. Seasonal variation in P. malariae prevalence was observed in one area but not in the other. A decrease in P. malariae prevalence concurred with a marked increase of P. falciparum prevalence. However this was strongly dependent on age and when analysing infections at the individual level, a different pattern between co-infecting species was unveiled. Regarding transmission patterns, in both areas, P. falciparum gametocytes predominated in single infections regardless of age and P. malariae gametocyte carriage increased when its overall prevalence decreased.

Adolescent↗
PubMed2004

Efficacy of chloroquine, amodiaquine, sulphadoxine-pyrimethamine and combination therapy with artesunate in Mozambican children with non-complicated malaria.

This paper reports a two-phase study in Manhiça district, Mozambique: first we assessed the clinical efficacy and parasitological response of Plasmodium falciparum to chloroquine (CQ), sulphadoxine-pyrimethamine (SP) and amodiaquine (AQ), then we tested the safety and efficacy in the treatment of uncomplicated malaria, of three combinations: AQ + SP, artesunate (AR) + SP and AQ + AR. Based on the WHO (1996, WHO/MAL/96.1077) in vivo protocol, we conducted two open, randomized, clinical trials. Children aged 6-59 months with axillary body temperature > or = 37.5 degrees C and non-complicated malaria were randomly allocated to treatment groups and followed up for 21 days (first and second trial) and 28 days (first trial). The therapeutic efficacy of AQ (91.6%) was better than that of SP (82.7%) and CQ (47.1%). After 14 days, 69% of the strains were parasitologically resistant to CQ, 21.4% to SP and 26% to AQ. Co-administration of AQ + SP, AR + SP and AQ + AR was safe and had 100% clinical efficacy at 14-day follow-up. The combination therapies affected rapid fever clearance time and reduced the incidence of gametocytaemia during follow-up.

Amodiaquine↗
PubMed2001

Prevalence of the K76T mutation in the putative Plasmodium falciparum chloroquine resistance transporter (pfcrt) gene and its relation to chloroquine resistance in Mozambique.

K76T, a mutation in the Plasmodium falciparum chloroquine (CQ) resistance transporter protein, has been implicated in resistance to CQ. A modified 14-day in vivo test to estimate the CQ resistance level was done in southern Mozambique: 21 (42%) of 50 subjects who completed the follow-up were CQ susceptible. Use of msa2-restriction fragment length polymorphism (RFLP) genotyping to differentiate new from recrudescent infections made little difference in the estimated prevalence of resistance. The K76T mutation prevalence was estimated by RFLP-polymerase chain reaction and sequencing, and its relation to parasitological CQ resistance was explored on day 0 samples: 51 of 56 pretreatment samples presented the T76 codon, and it was present in 100% of children with parasitological resistance. T76 also was present in 18 of 23 subjects in whom the infection resolved after CQ treatment. These findings show a high prevalence of the K76T mutation among wild isolates but also suggest additional factors responsible for CQ resistance.

Animals↗
PubMed2001

Placental malaria is associated with cell-mediated inflammatory responses with selective absence of natural killer cells.

Immunosuppression, particularly of cell-mediated responses, has classically been thought to play a major role in the increased susceptibility to malaria observed in pregnant women. An immunohistochemical characterization of the inflammatory infiltrate in a group of 41 placentas from women living in a Plasmodium falciparum-hyperendemic area in Tanzania revealed a marked increase in the number of monocytes and macrophages and cytotoxic T cells in the intervillous space of placentas with active malaria infection, compared with noninfected placentas, placentas from women with past infection, and a control group of placentas from Spain. This increase was associated with the severity of the infection. High numbers of monocytes and macrophages were associated with low birth weight. We also detected a complete absence of NK cells in the intervillous space in all placentas. This apparently physiological absence of NK cells may contribute to hindering the clearance of the parasite. These results indicate that placental malaria does not appear to be associated with cell-mediated immunosuppression. The role of the absence of NK cells in increased susceptibility to malaria needs to be further elucidated.

Animals↗
PubMed2001

Diagnostic accuracy and case management of clinical malaria in the primary health services of a rural area in south-eastern Tanzania.

Malaria control continues to rely on the diagnosis and prompt treatment of both suspected and confirmed cases through the health care structures. In south-eastern Tanzania malaria is one of the leading causes of morbidity and mortality. The absence of microscopic examination in most of the health facilities implies that health workers must rely on clinical suspicion to identify the need of treatment for malaria. Of 1558 randomly selected paediatric consultations at peripheral health facilities throughout Kilombero District, 41.1% were diagnosed by the attending health worker as clinical malaria cases and 42.5% prescribed an antimalarial. According to our malaria case definition of fever or history of fever with asexual falciparum parasitaemia of any density, 25.5% of all children attending the health services had malaria. This yielded a sensitivity of 70.4% (IC95% = 65.9-74.8%) and a specificity of 68.9% (IC95% = 66.2-71.5%). Accordingly, 30.4% of confirmed cases left with no antimalarial treatment. Among malaria-diagnosed patients, 10% were underdosed and 10.5% were overdosed. In this area, as in many African rural areas, the low diagnostic accuracy may imply that the burden of malaria cases may be overestimated. Greater emphasis on the functioning and quality of basic health services in rural endemic areas is required if improved case management of malaria is to help roll back this scourge.

Antimalarials↗
PubMed2001

Serum antibodies to oxidized low-density lipoprotein in pregnant women with preeclampsia and chronic hypertension: lack of correlation with lipid peroxides.

OBJECTIVES: To evaluate the circulating levels of antibodies to oxidized low-density lipoprotein (LDL) and their correlation with the lipid peroxide/vitamin E ratio in pregnant women with preeclampsia and chronic hypertension. METHODS: Antibodies to oxidized LDL were measured by enzyme-linked immunoassay, lipid peroxides (malondialdehyde), and vitamin E were measured by high-pressure liquid chromatography. Patients were 25 healthy pregnant women, 20 previously nonhypertensive women diagnosed with preeclampsia, and 20 women with uncomplicated chronic hypertension. RESULTS: Serum levels of antibodies to LDL in preeclamptic patients were similar to controls, whereas women with chronic hypertension showed a trend for increased mean levels. Lipid peroxides in serum were significantly increased and vitamin E levels were significantly decreased in preeclampsia with respect to nonhypertensive pregnancy, but no differences were observed for chronic hypertensive women. CONCLUSIONS: Our results suggest that preeclampsia is not accompanied by increased levels of antibodies to oxidized LDL. By contrast, and according to previous studies in nonpregnant patients, chronic hypertensive patients showed a trend for elevated levels.

Antibodies↗
PubMed2001

Prenatal risk factors of wheezing at the age of four years in Tanzania.

BACKGROUND: A study was undertaken to assess the interactions between prenatal exposures, early life infections, atopic predisposition, and allergen exposures in the development of wheezing up to the age of 4 years in a tropical region of Africa. METHODS: The study subjects comprised children born at the district hospital in Ifakara, Tanzania during a 1 year period who were participating in a trial of iron supplementation and malaria chemoprophylaxis during the first year of life and followed for up to 4 years. From this group of subjects, 658 (79%) participated in the interview at 18 months and 528 (64%) in a second interview at 4 years. Wheezing was measured with the ISAAC questionnaire. A hospital based inpatient and outpatient surveillance system was set up to document all attendance by study children for any cause, including episodes of clinical malaria and lower respiratory tract infections. Total IgE levels and malaria parasites were measured in maternal and cord blood. Total IgE was also measured at 18 months of age. Indoor environmental levels of Der p I and Fel d I were determined using an enzyme linked immunosorbent assay at the same time as the interview at the age of 18 months. RESULTS: The prevalence of wheezing at 4 years is common in Ifakara (14%, range 13-15%). The presence of malaria parasites in cord blood (odds ratio, OR = 6.84, 95% CI 1.84 to 24.0) and maternal asthma (OR = 8.47, 95% CI 2.72 to 26.2) were positively associated with wheezing at the age of 4 years, and cord blood total IgE was negatively associated (OR = 0.24, 95% CI 0.07 to 0.85) (all p<0.05). Parasitaemia at birth was not related to total IgE levels in cord blood (p=0.6). Clinical episodes of malaria during infancy were not associated with wheezing, and nor were levels of indoor aeroallergens. CONCLUSION: These findings suggest that events occurring during pregnancy may play a role in the future appearance of wheezing, although the results must be interpreted with caution because of the small numbers studied.

Allergens↗
PubMed2001

Cholera outbreak in southern Tanzania: risk factors and patterns of transmission.

To identify risk factors and describe the pattern of spread of the 1997 cholera epidemic in a rural area (Ifakara) in southern Tanzania, we conducted a prospective hospital-based, matched case- control study, with analysis based on the first 180 cases and 360 matched controls. Bathing in the river, long distance to water source, and eating dried fish were significantly associated with risk for cholera. Toxigenic Vibrio cholerae O1, biotype El Tor, serotype Ogawa, was isolated in samples from Ifakara's main water source and patients' stools. DNA molecular analyses showed identical patterns for all isolates.

Adolescent↗
PubMed2001

Effect of malaria on soluble transferrin receptor levels in Tanzanian infants.

The diagnosis of iron deficiency anemia in malaria endemic areas is complicated by the influence of the infection on the laboratory tests conventionally used to assess iron status. Determination of soluble transferrin receptor (sTfR) levels has been shown to be a sensitive indicator of iron deficiency in adults and is not affected by a range of infectious and inflammatory conditions. The utility of sTfR levels in the diagnosis of iron deficiency in malaria endemic areas remains unresolved. Three hundred and fourteen infants in a rural area of southern Tanzania living under conditions of intense and perennial malaria transmission were studied to determine the utility of sTfR plasma levels in the assessment of iron deficiency anemia. Independent of the presence of anemia, malaria parasitemia was associated with a significant increase in sTfR plasma levels that were even higher than those found in iron deficiency anemia. We conclude that the measurement of sTfR levels does not have a role in the diagnosis of iron deficiency anemia in young children exposed to malaria infection.

Anemia, Iron-Deficiency↗
PubMed2000

The impact of placental malaria on gestational age and birth weight.

Maternal malaria is associated with reduced birth weight, which is thought to be effected through placental insufficiency, which leads to intrauterine growth retardation (IUGR). The impact of malaria on preterm delivery is unclear. The effects of placental malaria-related changes on birth weight and gestational age were studied in 1177 mothers (and their newborns) from Tanzania. Evidence of malaria infection was found in 75.5% of placental samples. Only massive mononuclear intervillous inflammatory infiltration (MMI) was associated with increased risk of low birth weight (odds ratio ¿OR, 4.0). Maternal parasitized red blood cells and perivillous fibrin deposition both were associated independently with increased risk of premature delivery (OR, 3.2; OR, 2.1, respectively). MMI is an important mechanism in the pathogenesis of IUGR in malaria-infected placentas. This study also shows that placental malaria causes prematurity even in high-transmission areas. The impact of maternal malaria on infant mortality may be greater than was thought previously.

Birth Weight↗
PubMed2000

Clinical evaluation of an in-house IS6110 polymerase chain reaction for diagnosis of tuberculosis.

The aim of this study was to clinically validate a heminested polymerase chain reaction (PCR) method, based on the IS6110 insertion segment of Mycobacterium tuberculosis complex, for the diagnosis of tuberculosis. Samples of pulmonary, extrapulmonary and blood origin were collected prospectively from 331 patients. All samples were processed to detect acid-fast bacilli by direct stain, culture and PCR. The gold standard comparison was a clinically based final case definition of tuberculosis corresponding to group 3 of the American Thoracic Society's classification system. The sensitivities of stain, culture and PCR were 41%, 65% and 59%, respectively. Overall specificity exceeded 97% for all techniques. The combination of PCR and direct stain achieved a sensitivity similar to that of culture alone. The PCR method detected 74 of 95 (78%) culture-positive results. In a hospital setting, PCR could be a useful, reliable tool for diagnosis of tuberculosis and may be introduced as a complementary routine diagnostic laboratory method.

Culture Media↗
PubMed2000

Placental pathology in malaria: a histological, immunohistochemical, and quantitative study.

To characterize the histological changes in malarial placentas and their relationship with parity and maternal and cord parasitemias, we conducted a histological study on 1,179 placentas from Ifakara, Tanzania, an area with intense and perennial malaria transmission. Immunohistochemical and quantitative studies for CD45, fibrin, and villous area were performed in 60 cases. Four hundred fifteen placentas (35.2%) showed parasites (active infections); in 303 of them, parasites co-existed with pigment covered by fibrin (chronic infections), and in 112 only parasites were detected (acute infections). Four hundred seventy-five cases (40.3%) showed hemozoin deposition without parasites (past infections). Of women with parasitized placentas, 46.3% did not show parasites in the peripheral blood. Basal membrane thickening (P = .002), fibrinoid necrosis (P = .004), and prominence of syncytial knots (P = .031) were associated with active malarial infection. No quantitative differences for perivillous fibrin deposition or villous area were found. The most significant association with active malarial infection was intervillous infiltration by mononuclear inflammatory cells (P < .001). Chronic infections were associated with the most severe changes, particularly intervillous mononuclear inflammation (OR, 28.7; 95% CI = 16.0 to 51.5, P< .001). Past infections showed only minimal differences with noninfected placentas. Primiparas showed chronic infections more frequently than multiparas (52% v 15%, P < .001). They also showed significantly higher placental parasitemias and intervillous inflammatory infiltrate. In conclusion, placental histology is more sensitive than peripheral blood examination in detecting malarial infection during pregnancy. Most malarial infections recover during pregnancy, leaving few residual changes in the placenta. Intervillous inflammation is the most frequent finding associated with malaria and is especially severe in primiparas, suggesting that mechanisms other than immunosuppression are responsible for the high susceptibility in this group.

Female↗
PubMed2000

Malaria-related anaemia.

Malaria infection in humans by Plasmodium species is associated with a reduction in haemoglobin levels, frequently leading to anaemia. Plasmodium falciparum causes the most severe and profound anaemia, with a significant risk of death. This cannot be explained simply by the direct destruction of parasitized red blood cells at the time of release of merozoites, a process shared by all these species. In this review, Clara Menendez, Alan Fleming and Pedro Alonso focus on recent advances in our knowledge of the pathophysiology, epidemiology, management and prevention of anaemia from falciparum malaria.

Adult↗
PubMed2000

Apparent tolerance of Plasmodium falciparum in infants in a highly endemic area.

The incidence of fever among infants in the village of Idete in the Morogoro region of Tanzania was analyzed in relation to densities of Plasmodium falciparum parasites in the peripheral blood. Parasite densities in both fever cases and in asymptomatic infants, were compared and a Bayesian non-parametric mixture decomposition algorithm was used to estimate the proportion of fevers attributable to malaria and hence the incidence of clinical malaria. Age group-specific densities of peripheral parasitaemia showed little seasonality, but the clinical malaria incidence showed a clear peak in the wet season in children aged less than 9 months. Estimates of the parasitaemia-specific incidence of clinical malaria were used to quantify apparent tolerance of parasites, and indicated that clinical episodes occurred on average at lower parasite densities during the wet season than in the dry season. These patterns could reflect differences in levels of anti-toxic immunity, but the nature of the seasonal differences supports the alternative explanation that the variation in apparent tolerance may be an effect of changes in the ratio of peripheral parasite densities to the sequestered mass.

Age Factors↗