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Biomedical subjects

A Y Kitua

Publications and source records attributed to A Y Kitua.

17 recordsLinked to original sources
PubMed2006

Implication of diethylcarbamazine induced morbidity and the role of cellular responses associated with bancroftian filariasis pathologies.

Pre and post-diethylcarbamazine treatment clinical expression, microfilaraemia prevalence and cellular responses were investigated in individuals in Tanga, Tanzania. Fifty-seven male individuals (aged = 15 years old) were identified for further studies on IL-4, IL-6, IL-8. IFN-gamma, IL-beta, TNF-alpha and nitric oxide in plasma and hydrocoele fluid. Microfilarial prevalence in the examined individuals was 12% with a geometric mean intensity (GMI) of 838 mff/ml in a community with a population of 1018 individuals. Microfilaraemic hydrocoele stage II and III were the most frequent pathologies observed with prevalence of 17.5% and 42. 1 %, respectively. All study individuals treated with diethylcarbamazine (DEC) standard dose of 6 mg/kg experienced post-treatment adverse events. There was no direct relationship between elevated IL-6 and the occurrence and severity of clinical adverse effects post-treatment. The findings from this study suggests that, blood elevated cytokine profile is not the main etiological factor in the inflammatory responses developing after treatment of bancroftian filariasis infections and pathology with DEC. Plasma levels of cellular (cytokines) responses during treatment revealed a proportion of symptomatic patients. Prior to treatment, patients with hydroecoele had high levels of IL-6 than those without the pathology. In conclusion these findings do not support the hypothesis that pro-inflammatory cytokines are directly responsible for adverse events to DEC chemotherapy in bancroftian filariasis infections and pathologies such as hydrocoele, lymphoedema and elephantiasis.

Adolescent↗
PubMed2006

The relationship between malaria parasitaemia and availability of healthcare facility in Mpwapwa district, central Tanzania.

A study was carried out in six villages located at different altitudes in Mpwapwa district of central Tanzania to determine malaria parasitaemia and transmission levels in villages with or without health care facilities. A total of 1119 schoolchildren (age = 5.9-12.3 years) were examined for malaria parasitaemia. Plasmodiumfalciparum was the predominant malaria species accounting for 92.8% of all species. The average malaria prevalence rate among schoolchildren was 25.8% (range 1.5-53.8%). The geometric mean parasite densities for P.falciparum was 361 (N = 286). Higher malaria prevalence was observed in villages at lower (< 1000 m) than at intermediate (1000-1500m) or higher (> 1500m) altitudes. Schoolchildren in areas with health care facilities were less at risk of acquiring malaria by 33.4% as compared with those living in areas without health facilities. Mean packed cell volume in schoolchildren was 38.5% (range = 35.2-41.0%). Splenomegaly was observed in 18.1% (0-40.2%) of the schoolchildren examined and it was higher among those in villages without health care facilities. Anopheles gambiae sensu lato was the only malaria vector found in the district and was found in all villages and at all altitudes. Sporozoite rate in An. gambiae s.l. ranged from 0-10.5%, with the lowland villages recording the highest rates. This study indicates that altitude and geographical accessibility to healthcare service are important determinants of malaria infection among rural communities in Tanzania.

Altitude↗
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↗
PubMed1999

Antibodies against Plasmodium falciparum vaccine candidates in infants in an area of intense and perennial transmission: relationships with clinical malaria and with entomological inoculation rates.

Serum immunoglobulin (Ig)G1, IgG3 and total IgG were assessed by immunoabsorbent assay in 198 infants from a Tanzanian village highly endemic for Plasmodium falciparum. Antibodies were measured against epitopes of the circumsporozoite protein (the repetitive epitope (NANP)50 and a construct of the flanking regions (CS27IC)), the malaria vaccine SPf66, and two constructs of the merozoite surface protein-1 (MSP-1), a 19-kDa fragment from the C-terminal domain (MSP-119) and an N-terminal fragment spanning blocks 1-6 (H6-p190 M-1/6-H6). IgG1 and total IgG titres showed similar age profiles, all decreasing for the first 2 months of life. Anti-(NANP)50 titres remained very low throughout the first year of life, while anti-CS27IC antibody appeared to peak around 7 months of age. Only a slight tendency to increase with age was observed for levels of the other antibodies studied. IgG3 titres except for H6-p190(1/6), were very low initially and remained very low throughout the first year of life. Clinical malaria incidence at the village dispensary was analysed prospectively in relation to antibody. No IgG1 or total IgG titre showed protective effects, but low IgG3 against p190(1/6) appeared to be a risk factor in some age groups. Given the large number of antibodies tested, this single indication of possible protection could merely be chance. There were no strong associations between antibody titres and entomologically assessed sporozoite exposure suggesting that transmission-reducing interventions may have little effect on antibody levels in such children.

Aging↗
PubMed1999

Evaluation of the SPf66 vaccine for malaria control when delivered through the EPI scheme in Tanzania.

BACKGROUND: 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 malaria control is to be achieved. The best use of a vaccine in Africa will be achieved if it can be delivered through the expanded programme of immunization (EPI). We conducted a trial designed to evaluate the efficacy of SPf66 vaccine for malaria control when delivered through the EPI scheme in Tanzania. METHODS: The study was a two-arm, double blind, individually randomized placebo controlled trial involving 1207 infants. The primary objective of the trial was to estimate the efficacy of three doses of SPf66 given at 1, 2 and 7 months of age in preventing clinical episodes of malaria. These were documented through a health facility-based passive case detection system. RESULTS: 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 children among SPf66 recipients and 288 among placebo recipients with at least one malaria episode, yielding a vaccine efficacy estimate of 2% (95% CI: -16, 16; P = 0.84). CONCLUSION: This has been the first trial of a malaria vaccine among very young infants. It provides information on the safety of peptide vaccines administered at this early age as well as their capacity to induce immune responses without negatively interacting with EPI vaccines. Given the modest protection previously documented 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 of efficacy found in this trial also raises concerns about potential difficulties of inducing protective immune responses against malaria through immunization in infants.

Double-Blind Method↗
PubMed1998

Immune responses to Plasmodium falciparum antigens during a malaria vaccine trial in Tanzanian children.

Among Tanzanian children living in an area of intense and perennial malaria transmission, prevalence of naturally acquired IgG antibodies that recognize SPf66, NANP, p190 and a 19 kDa fragment of the merozoite surface protein-1 (MSP-1) is high and increases with age. This possibly reflects the high level of natural exposure of the children to P. falciparum. The prevalences of IgG antibodies that recognize the three putative merozoite derived sequences contained in the malaria vaccine SPf66 (83.1, 55.1 and 35.1) is low but also show some age dependence. Three doses of the SPf66 vaccine induce a strong IgG antibody response against both the SPf66 construct, NANP and the three individual peptides. Vaccination with SPf66 did not result in an increase of anti19 kDa fragment antibodies. This reflects the specificity of the humoral immune response induced by the SPf66 construct. Among vaccinated children, antibody titres against SPf66 decreased over time following the third dose. However, 18 months after the third dose, SPf66 recipients still had significantly higher IgG titres and stimulation indices of peripheral blood mononuclear cells (PBMC) than placebo recipients. Within the vaccine group, there is a trend for increasing anti-SPf66 IgG titre to be associated with decreasing risk of clinical malaria but this was not statistically significant. Results also show the difficulties of establishing whether antibody responses are related to protection in field trials in endemic areas.

Animals↗
PubMed1998

Incidence of Plasmodium falciparum infection in infants in relation to exposure to sporozoite-infected anophelines.

The relationship of the incidence of Plasmodium falciparum infection to entomologic inoculation rates (EIRs) was studied in 163 children less than one year of age in a Tanzanian village to determine likely effects of transmission-reducing interventions on infection incidence. A total of 66,727 Anopheles gambiae s.l. and 17,620 An. funestus mosquitoes were caught in 1,056 light trap collections from 139 houses over a period of more than two years. Time period-specific human biting rates were estimated for 11 village neighborhoods. Sporozoites were detected by ELISA in 4.4% of the An. funestus and 2.5% of the An. gambiae s.l. Eight hundred seventeen pairs of blood slides with approximately two-week intervals between slides were used to estimate incidence of parasitemia by fitting reversible catalytic models to parasite positivity data. Estimated EIRs during the four weeks preceding each intersurvey interval averaged 1.6 (SD = 2.1) per adult per night. Parasites were present at the end of 31% of the 443 intervals that commenced with a parasite-negative slide. Attack rates were comparable with those in western Kenya, and the proportion of bites resulting in human infections was strongly dependent on mosquito density. Incidence of infection increased with the EIR up to approximately one bite from a sporozoite-carrying mosquito per adult per night. However, higher levels of transmission observed locally in the wet season did not result in a correspondingly higher incidence. These data suggest that transmission-reducing measures cannot be expected to reduce incidence of infection at the highest levels of EIR.

Animals↗
PubMed1998

Relationships of malaria morbidity with exposure to Plasmodium falciparum in young children in a highly endemic area.

To study incidence of clinical Plasmodium falciparum malaria in relation to exposure to parasites, attendance of children less than eighteen months old at a village dispensary in a highly endemic area of Tanzania was recorded. Entomologic inoculation rates (EIRs), estimated as a function of time period and place of residence, exceeded one sporozoite positive bite per adult per night in some village neighborhoods during the wet season. Incidence of clinical P. falciparum malaria, defined either as fever with parasitemia or as fever with hyperparasitemia, increased with the EIR over the whole range of exposures. Each 10-fold increase in the EIR corresponded to a 1.6-fold increase in incidence of fever plus parasitemia (95% confidence interval = 1.4-2.0). Therefore reduction of human-vector contacts will probably reduce morbidity incidence even at very high exposures. Incidence showed little relationship to estimated cumulative numbers of inoculations since birth, but decreased steeply with estimated cumulative time infected with trophozoites. This suggests that clinical immunity depends mainly on the extent of exposure to blood-stage antigens, not on the diversity of inocula seen, and thus temporary reductions in human-vector contacts are unlikely to result in subsequent increases in morbidity.

Animals↗
PubMed1997

Randomised placebo-controlled trial of iron supplementation and malaria chemoprophylaxis for prevention of severe anaemia and malaria in Tanzanian infants.

BACKGROUND: Malaria and anaemia, especially that due to iron deficiency, are two leading causes of morbidity worldwide. Little is known about the relative contribution of Plasmodium falciparum infection and iron deficiency to the aetiology of anaemia in malaria-endemic areas. We undertook a randomised comparison of different strategies for control of anaemia and malaria in infants, including an assessment of the effect of iron supplementation on malaria susceptibility. METHODS: 832 infants born at one hospital in a malaria-hyperendemic area of Tanzania between January and October, 1995, were randomly assigned to group DI, receiving daily oral iron (2 mg/kg daily) plus weekly Deltaprim (3.125 mg pyrimethamine plus 25 mg dapsone); group IP, receiving iron plus weekly placebo; group DP, receiving daily placebo plus weekly Deltaprim; or group PP. supplementation was given from 8 to 24 weeks of age, and the weekly chemoprophylaxis from 8 to 48 weeks. The frequency of severe anaemia (packed-cell volume < 25%) and malaria episodes was assessed through a combination of passive case detection and cross-sectional surveys. FINDINGS: The groups that received iron supplementation had a lower frequency of severe anaemia than those that did not receive iron (0.62 vs 0.87 cases per person-year; protective efficacy 28.8% [95% CI 6.3-45.8). Iron supplementation had no effect on the frequency of malaria (0.87 vs 1.00 cases per person-year; protective efficacy 12.8% [-12.8 to 32.5]). The groups that received malaria prophylaxis had lower frequencies of both severe anaemia (0.45 vs 1.04 episodes per person-year; protective efficacy 57.3% [43.0-67.9]) and malaria (0.53 vs 1.34 episodes per person-year; protective efficacy 60.5% [48.2-69.9]) than the groups that did not receive prophylaxis. After the end of the intervention period, children who had received malaria chemoprophylaxis had higher rates of severe anaemia and malaria than non-chemoprophylaxis groups (relative risks 2.2 [1.3-3.7] and 1.8 [1.3-2.6]). INTERPRETATION: Malaria chemoprophylaxis during the first year of life was effective in prevention of malaria and anaemia but apparently impaired the development of natural immunity. Iron supplementation was effective in preventing severe anaemia without increasing susceptibility to malaria. Our findings support iron supplementation of infants to prevent iron-deficiency anaemia, even in malaria-endemic areas.

Adult↗
PubMed1997

The role of low level Plasmodium falciparum parasitaemia in anaemia among infants living in an area of intense and perennial transmission.

Children under one year of age in an area of intense and perennial Plasmodium falciparum transmission were followed up for one year to establish to what extent chronic, low parasitaemia was associated with severe anaemia. There was a significant increase in the prevalence of anaemia (PCV < or = 25%) with increase in parasite density. PCV levels were related not only to concurrent parasite density but also decreased with densities measured one month previously. At any point in time, the mean PCV level in infants with low parasitaemia (< 1000 parasites/microliter) was higher than that of infants with intermediate (1000-9999/microliter) and high parasite densities (> or 10000/microliter). After the age of 7 months, infants with low parasite densities tend to recover, probably as a result of developing immunity. At the age of 12 months, they have similar PCV levels to infants with no detectable parasitaemia by microscopy. The maintenance of low parasite density appears crucial to the survival of infants in malaria endemic areas. The findings suggest that interventions which lower parasite densities in areas of intense transmission reduce the development of severe malarial anaemia and thus malaria-related mortality and morbidity in infants.

Anemia↗
PubMed1997

Field trials of malaria vaccines.

Malaria due to Plasmodium falciparum is probably the most important infectious disease in the tropical world. About 2000 million people live in areas exposed to malaria and 300 million individuals are infected every year. In Africa south of the Sahara alone, over 1 million children die annually as a result of malaria. It is a difficult parasitic disease both to diagnose and control. It does not provide sterile immunity even after long exposure periods. However, acquisition of partial immunity allows over 60 per cent of individuals with long exposure to carry the parasite in their blood without symptoms, posing difficulties for case definition, malaria attributable morbidity and deaths. Further, it is extremely difficult to establish the extent to which malaria has influence over the adverse outcome of other infectious disease like measles and malnutrition. The complex life cycle of the parasite involving human and vector mosquitos as well as its allelic diversity and antigenic variations makes the development and implementation of effective malaria control intervention problematic. It is now becoming evident that multi-intervention approach may be the most appropriate way of combating malaria in view of the increasing resistance of the parasite to antimalarial drugs as well as vector mosquitoes to insecticides. Malaria vaccines will therefore play a major role in future malaria interventions. New malaria vaccine candidates will require testing in malaria endemic countries. Sufficient sites for testing potential malaria vaccines must be prepared. In this paper we discuss the necessary preparations required for field testing of malaria vaccines in tropical countries.

Animals↗
PubMed1996

Plasmodium falciparum malaria in the first year of life in an area of intense and perennial transmission.

A longitudinal study of Plasmodium falciparum malaria in infants in Idete village, south-eastern Tanzania, was conducted over a period of 14 months in order to determine the incidence of P. falciparum infection and clinical malaria in the first year of life. Of 1356 blood slides from cross-sectional surveys, 52.1% were positive for asexual stages of P. falciparum. There were marked increases in P. falciparum prevalence, parasite densities, overall fever incidence and the incidence of malaria fevers with age for the first 6 months of life. The average attack rate, estimated from a reversible catalytic model, was 0.029 per day with a slight increase with age but there was no initial period of protection against infection in neonates. Estimated average duration of infections was 64 days, with infections in older infants lasting much longer than those contracted during the first 2 months of life. These results support the hypotheses that the main effect of passively transferred maternal immunity to malaria is in the control of asexual stage parasites, and that the level of clinical immunity depends upon the extent of recent exposure to parasites. Infants as young as 4 months of age are at high risk of clinical attacks. Intervention programmes against malaria in areas of the highest transmission should therefore be designed to include this group.

Cohort Studies↗
PubMed1996

Duration of protection and age-dependence of the effects of the SPf66 malaria vaccine in African children exposed to intense transmission of Plasmodium falciparum.

The SPf66 synthetic vaccine is safe and partly efficacious against Plasmodium falciparum malaria among children 1-5 years old. The estimated vaccine efficacy [VE] for all clinical episodes over a period of 18 months after the third dose is 25% (95% confidence interval [CI], 1%-44%; P = .044). The observed temporal variations in efficacy could have been due to chance (likelihood ratio chi 2 = 13.8, 8 df; P = .086). Efficacy against clinical malaria did not vary significantly with age (chi 2 = 1.07, 4 df; P = .90). Overall parasite density was 21% lower in vaccine recipients than in the placebo group (95% CI, 0%-38%; P = .044). Further development of SPf66 may require trials to evaluate safety, immunogenicity, and efficacy when administered in the first year of life, together with other vaccines contained in the Expanded Programme of Immunization schedule.

Age Factors↗