[show abstract][hide abstract] ABSTRACT: Effective mass drug administration (MDA) with anti-malarial drugs can clear the human infectious reservoir for malaria and thereby interrupt malaria transmission. The likelihood of success of MDA depends on the intensity and seasonality of malaria transmission, the efficacy of the intervention in rapidly clearing all malaria parasite stages and the degree to which symptomatic and asymptomatic parasite carriers participate in the intervention. The impact of MDA with the gametocytocidal drug combination sulphadoxine-pyrimethamine (SP) plus artesunate (AS) plus primaquine (PQ, single dose 0.75 mg/kg) on malaria transmission was determined in an area of very low and seasonal malaria transmission in northern Tanzania.
In a cluster-randomized trial in four villages in Lower Moshi, Tanzania, eight clusters (1,110 individuals; cluster size 47- 209) were randomized to observed treatment with SP+AS+PQ and eight clusters (2,347 individuals, cluster size 55- 737) to treatment with placebo over three days. Intervention and control clusters were 1 km apart; households that were located between clusters were treated as buffer zones where all individuals received SP+AS+PQ but were not selected for the evaluation. Passive case detection was done for the entire cohort and active case detection in 149 children aged 1-10 year from the intervention arm and 143 from the control arm. Four cross-sectional surveys assessed parasite carriage by microscopy and molecular methods during a five-month follow-up period.
The coverage rate in the intervention arm was 93.0% (1,117/1,201). Parasite prevalence by molecular detection methods was 2.2-2.7% prior to the intervention and undetectable during follow-up in both the control and intervention clusters. None of the slides collected during cross-sectional surveys had microscopically detectable parasite densities. Three clinical malaria episodes occurred in the intervention (n = 1) and control clusters (n = 2).
This study illustrates the possibility to achieve high coverage with a three-day intervention but also the difficulty in defining suitable outcome measures to evaluate interventions in areas of very low malaria transmission intensity. The decline in transmission intensity prior to the intervention made it impossible to assess the impact of MDA in the chosen study setting.
[show abstract][hide abstract] ABSTRACT: Male circumcision (MC) has been shown to be effective against heterosexual acquisition of HIV infection and is being scaled up as an additional strategy against HIV in several countries of Africa. However, the policy environment (whether to formulate new specific policy on MC or adapts the existing ones); and the role of various stakeholders in the MC scale up process in Tanzania was unclear. We conducted this study as part of a situation analysis to understand the attitudes of policy makers and other key community and health authority decision makers towards MC, policy and regulatory environment, and the readiness of a health system to accommodate scaling up of MC services.
We conducted 36 key informants' interviews with a broad range of informants including civil servants, religious leaders, cultural and traditional gatekeepers and other potential informants. Study informants were selected at the national level, regional, district and community levels to represent both traditionally circumcising and non-circumcising communities.
Study informants had positive attitudes and strong beliefs towards MC. Key informants in traditionally non-circumcising districts were willing to take their sons for medically performed MC. Religious leaders and traditional gatekeepers supported MC as it has been enshrined in their holy scripts and traditional customs respectively. Civil servants highlighted the need for existence of enabling policy and regulatory environment in the form of laws, regulations and guidelines that will ensure voluntary accessibility, acceptability, quality and safety for those in need of MC services. Majority of informants urged the government to make improvements in the health system at all levels to ensure availability of adequate trained personnel, infrastructure, equipment, and supplies for MC scale up, and insisted on the involvement of different MC stakeholders as key components in effective roll out of medically performed MC programme in the country.
Findings from the situation analysis in Tanzania have shown that despite the absence of a specific policy on MC, basic elements of enabling policy environment at national, regional, district and community levels are in place for the implementation of MC scale up programme.
BMC Public Health 06/2011; 11:506. · 2.08 Impact Factor
[show abstract][hide abstract] ABSTRACT: The World Health Organisation and the Joint United Nations Programme on AIDS recommend male circumcision (MC) as an additional intervention against HIV infection. Various sub-Saharan African countries are at different stages of rolling out MC programmes. Despite initial fears, studies conducted among traditionally non-circumcising communities in Africa have shown that MC is widely accepted as a biomedical intervention. However, little is known on how traditionally circumcising communities where MC carries considerable social meaning and significance would respond to such programmes. This study was conducted among a traditionally circumcising community in Tarime district in Tanzania as part of a national situation analysis prior to initiating a national MC programme. It employed key informant interviews and focus group discussions for data collection. Results show that the Kurya ethnic group practice MC as a rite of passage from childhood to adulthood. Each clan organises its own circumcision ceremony, which takes place every even numbered years. Clan leaders and traditional circumcisers are central to its organisation. Among the Kurya, there is high regard for traditional MC as it is perceived as upholding cultural practice and identity. It also embodies notions of bravery since anaesthetics are not used. On the other hand, medical MC is not viewed as prestigious since anaesthetics are used to suppress pain. Social pressure for traditional MC is applied through ridiculing of those uncircumcised or circumcised at health facilities. In general, there are positive attitudes towards MC as it is perceived as enhancing personal hygiene and having a protective effect against sexually transmitted infections. For the success of nation-wide MC programmes, there is need to develop programmes that incorporate both clinical and sociocultural interests.
AIDS Care 04/2011; 23(9):1111-6. · 1.60 Impact Factor
[show abstract][hide abstract] ABSTRACT: Data from traditionally circumcising communities show that non-circumcised males and those circumcised in the medical settings are stigmatised. This is because traditional circumcision embodies local notions of bravery as anaesthetics are not used. This study was conducted to assess the acceptability of safe medical circumcision before the onset of sexual activity for HIV infection risk reduction in a traditionally circumcising community in Tanzania.
A cross-sectional study was conducted among males and females aged 18-44 years in traditionally circumcising communities of Tarime District in Mara Region, North-eastern Tanzania. A face-to-face questionnaire was administered to females to collect information on the attitudes of women towards circumcision and the preferred age for circumcision. A similar questionnaire was administered to males to collect information on socio-demographic, preferred age for circumcision, factors influencing circumcision, client satisfaction, complications and beliefs surrounding the practice.
Results were available for 170 males and 189 females. Of the males, 168 (98.8%) were circumcised and 61 (36.3%) of those circumcised had the procedure done in the medical setting. Of those interviewed, 165 (97.1%) males and 179 (94.7%) females supported medical male circumcision for their sons. Of these, 107 (64.8%) males and 130 (72.6%) females preferred prepubertal medical male circumcision (12 years or less). Preference for prepubertal circumcision was significantly associated with non-Kurya ethnic group, circumcision in the medical setting and residence in urban areas for males in the adjusted analysis. For females, preference for prepubertal circumcision was significantly associated non-Kurya ethnic group and being born in urban areas in the adjusted analysis.
There is a shift of preference from traditional male circumcision to medical male circumcision in this traditionally circumcising population. However, this preference has not changed the circumcision practices in the communities because of the community social pressure. Male circumcision national program should take advantage of this preference of medical male circumcision by introducing safe and affordable circumcision services and mobilising communities in a culturally sensitive manner to take up circumcision services.
BMC Public Health 01/2011; 11:373. · 2.08 Impact Factor
[show abstract][hide abstract] ABSTRACT: Variation in the risk of malaria within populations is a frequently described but poorly understood phenomenon. This heterogeneity creates opportunities for targeted interventions but only if hot spots of malaria transmission can be easily identified.
We determined spatial patterns in malaria transmission in a district in northeastern Tanzania, using malaria incidence data from a cohort study involving infants and household-level mosquito sampling data. The parasite prevalence rates and age-specific seroconversion rates (SCRs) of antibodies against Plasmodium falciparum antigens were determined in samples obtained from people attending health care facilities.
Five clusters of higher malaria incidence were detected and interpreted as hot spots of transmission. These hot spots partially overlapped with clusters of higher mosquito exposure but could not be satisfactorily predicted by a probability model based on environmental factors. Small-scale local variation in malaria exposure was detected by parasite prevalence rates and SCR estimates for samples of health care facility attendees. SCR estimates were strongly associated with local malaria incidence rates and predicted hot spots of malaria transmission with 95% sensitivity and 85% specificity.
Serological markers were able to detect spatial variation in malaria transmission at the microepidemiological level, and they have the potential to form an effective method for spatial targeting of malaria control efforts.
The Journal of Infectious Diseases 06/2010; 201(11):1764-74. · 5.85 Impact Factor
[show abstract][hide abstract] ABSTRACT: Naturally acquired immune responses against sexual stages of P. falciparum can reduce the transmission of malaria from humans to mosquitoes. These antigens are candidate transmission-blocking vaccines but little is known about the acquisition of sexual stage immunity after exposure to gametocytes, or their longevity and functionality. We conducted a longitudinal study on functional sexual stage immune responses.
Parasitaemic individuals (n = 116) were recruited at a health centre in Lower Moshi, Tanzania. Patients presented with gametocytes (n = 16), developed circulating gametocytes by day 7 (n = 69) or between day 7 and 14 (n = 10) after treatment or did not develop gametocytes (n = 21). Serum samples were collected on the first day of gametocytaemia and 28 and 84 days post-enrolment (or d7, 28, 84 after enrolment from gametocyte-negative individuals). Antibody responses to sexual stage antigens Pfs230 and Pfs48/45 were detected in 20.7% (72/348) and 15.2% (53/348) of the samples, respectively, and were less prevalent than antibodies against asexual stage antigens MSP-1(19) (48.1%; 137/285) and AMA-1 (52.4%; 129/246)(p<0.001). The prevalence of anti-Pfs230 (p = 0.026) and anti-Pfs48/45 antibodies (p = 0.017) increased with longer duration of gametocyte exposure and had an estimated half-life of approximately 3 months. Membrane feeding experiments demonstrated a strong association between the prevalence and concentration of Pfs230 and Pfs48/45 antibodies and transmission reducing activity (TRA, p<0.01).
In a longitudinal study, anti-Pfs230 and Pfs48/45 antibodies developed rapidly after exposure to gametocytes and were strongly associated with transmission-reducing activity. Our data indicate that the extent of antigen exposure is important in eliciting functional transmission-reducing immune responses.
PLoS ONE 01/2010; 5(11):e14114. · 3.73 Impact Factor
[show abstract][hide abstract] ABSTRACT: Intermittent preventive treatment in infants (IPTi) is a new malaria control tool. However, it is uncertain whether IPTi works mainly through chemoprophylaxis or treatment of existing infections. Understanding the mechanism is essential for development of replacements for sulfadoxine-pyrimethamine (SP) where it is no longer effective. This study investigated how protection against malaria given by SP, chlorproguanil-dapsone (CD) and mefloquine (MQ), varied with time since administration of IPTi.
A secondary analysis of data from a randomised, placebo-controlled trial in an area of high antifolate resistance in Tanzania was conducted. IPTi using SP, CD, MQ or placebo was given to 1280 infants at 2, 3 and 9 months of age. Poisson regression with random effects to adjust for potential clustering of malaria episodes within children was used to calculate incidence rate ratios for clinical malaria in defined time strata following IPTi. The short-acting antimalarial CD gave no protection against clinical malaria, whereas long-acting MQ gave two months of substantial protection (protective efficacy (PE) 73.1% (95% CI: 23.9, 90.5) and 73.3% (95% CI: 0, 92.9) in the first and second month respectively). SP gave some protection in the first month after treatment (PE 64.5% (95% CI: 10.6, 85.9)) although it did not reduce the incidence of malaria up to 12 months of age. There was no evidence of either long-term protection or increased risk of malaria for any of the regimens.
Post-treatment chemoprophylaxis appears to be the main mechanism by which IPTi protects children against malaria. Long-acting antimalarials are therefore likely to be the most effective drugs for IPTi, but as monotherapies could be vulnerable to development of drug resistance. Due to concerns about tolerability, the mefloquine formulation used in this study is not suitable for IPTi. Further investigation of combinations of long-acting antimalarials for IPTi is needed.
PLoS ONE 01/2010; 5(3):e9467. · 3.73 Impact Factor
[show abstract][hide abstract] ABSTRACT: Malaria infection induces oxidative stress in the host cells. Antioxidant enzymes such as glutathione S-transferases (GSTs) are responsible for fighting reactive oxygen species and reduction of oxidative stress. Common GST polymorphisms have been associated with susceptibility to different diseases whose pathologies involve oxidative stress. In this study, we tested the hypothesis that GST polymorphisms that lead to reduced or lack of enzyme activity are associated with severe Plasmodium falciparum malarial anemia. We studied the genotypic distribution of GSTM1, GSTT1, and GSTP1 polymorphisms between mild malaria (N = 107) and severe malarial anemia (N = 50) in Tanzanian children. We did not find a significant relationship with the GSTT1 polymorphism. GSTM1-null was higher in the severe malaria anemia group but the difference was not significant (P = 0.08). However, a significant association of GSTP1 I105V genotype with severe malarial anemia was discovered (26.0% against 10.3% mild malaria, P = 0.004). We concluded that GSTP1 and possibly GSTM1 may protect against severe falciparum malaria in children.
The American journal of tropical medicine and hygiene 09/2009; 81(2):363-5. · 2.53 Impact Factor
[show abstract][hide abstract] ABSTRACT: Administration of sulfadoxine-pyrimethamine at times of vaccination-intermittent preventive treatment in infants (IPTi)-is a promising strategy to prevent malaria. However, rising resistance to this combination is a concern. We investigated a shortacting and longacting antimalarial drug as alternative regimens for IPTi.
We undertook a double-blind, placebo-controlled trial of IPTi in an area of high resistance to sulfadoxine-pyrimethamine at sites of moderate (n=1280 infants enrolled) and low (n=1139) intensity of malaria transmission in Tanzania. Infants aged 8-16 weeks were randomly assigned in blocks of 16 to sulfadoxine (250 mg) plus pyrimethamine (12.5 mg; n=319 in moderate-transmission and 283 in low-transmission sites), chlorproguanil (15 mg) plus dapsone (18.75 mg; n=317 and 285), mefloquine (125 mg; n=320 and 284), or placebo (n=320 and 284), given at the second and third immunisations for diphtheria, pertussis, and tetanus, and for measles. Research team and child were masked to treatment. Recruitment was stopped early at the low-transmission site because of low malaria incidence. The primary endpoint was protective efficacy against all episodes of clinical malaria at 2-11 months of age. Analysis was by intention to treat. This study is registered with ClinicalTrials.gov, number NCT00158574.
All randomly assigned infants were analysed. At the moderate-transmission site, mefloquine had a protective efficacy of 38.1% (95% CI 11.8-56.5, p=0.008) against clinical malaria in infants aged 2-11 months, but neither sulfadoxine-pyrimethamine (-6.7%, -45.9 to 22.0) nor chlorproguanil-dapsone (10.8%, -24.6 to 36.1) had a protective effect. No regimen had any protective efficacy against anaemia or hospital admission. Mefloquine caused vomiting in 141 of 1731 (8%) doses given on day 1 (odds ratio vs placebo 5.50, 95% CI 3.56-8.46). More infants died in the chlorproguanil-dapsone and mefloquine groups (18 and 15, respectively) than in the sulfadoxine-pyrimethamine or placebo groups (eight deaths per group; p=0.05 for difference between chlorproguanil-dapsone and placebo).
IPTi with a longacting, efficacious drug such as mefloquine can reduce episodes of malaria in infants in a moderate-transmission setting. IPTi with sulfadoxine-pyrimethamine has no benefit in areas of very high resistance to this combination. The appropriateness of IPTi should be measured by the expected incidence of malaria and the efficacy, tolerability, and safety of the drug.
IPTi Consortium and the Gates Malaria Partnership.
The Lancet 09/2009; 374(9700):1521-32. · 39.06 Impact Factor
[show abstract][hide abstract] ABSTRACT: Sulphadoxine-pyrimethamine (SP) a widely used treatment for uncomplicated malaria and recommended for intermittent preventive treatment of malaria in pregnancy, is being investigated for intermittent preventive treatment of malaria in infants (IPTi). High levels of drug resistance to SP have been reported from north-eastern Tanzania associated with mutations in parasite genes. This study compared the in vivo efficacy of SP in symptomatic 6-59 month children with uncomplicated malaria and in asymptomatic 2-10 month old infants.
An open label single arm (SP) standard 28 day in vivo WHO antimalarial efficacy protocol was used in 6 to 59 months old symptomatic children and a modified protocol used in 2 to 10 months old asymptomatic infants. Enrolment was stopped early (87 in the symptomatic and 25 in the asymptomatic studies) due to the high failure rate. Molecular markers were examined for recrudescence, re-infection and markers of drug resistance and a review of literature of studies looking for the 581G dhps mutation was carried out. In symptomatic children PCR-corrected early treatment failure was 38.8% (95% CI 26.8-50.8) and total failures by day 28 were 82.2% (95% CI 72.5-92.0). There was no significant difference in treatment failures between asymptomatic and symptomatic children. 96% of samples carried parasites with mutations at codons 51, 59 and 108 in the dhfr gene and 63% carried a double mutation at codons 437 and 540. 55% carried a third mutation with the addition of a mutation at codon 581 in the dhps gene. This triple: triple haplotype maybe associated with earlier treatment failure.
In northern Tanzania SP is a failed drug for treatment and its utility for prophylaxis is doubtful. The study found a new combination of parasite mutations that maybe associated with increased and earlier failure.
PLoS ONE 02/2009; 4(2):e4569. · 3.73 Impact Factor
[show abstract][hide abstract] ABSTRACT: Adequate malaria diagnosis and treatment remain major difficulties in rural sub-Saharan Africa. These issues deserve renewed attention in the light of first-line treatment with expensive artemisinin-combination therapy (ACT) and changing patterns of transmission intensity. This study describes diagnostic and treatment practices in Mto wa Mbu, an area that used to be hyperendemic for malaria, but where no recent assessments of transmission intensity have been conducted.
Retrospective and prospective data were collected from the two major village health clinics. The diagnosis in prospectively collected data was confirmed by microscopy. The level of transmission intensity was determined by entomological assessment and by estimating sero-conversion rates using anti-malarial antibody responses.
Malaria transmission intensity by serological assessment was equivalent to < 1 infectious bites per person per year. Despite low transmission intensity, > 40% of outpatients attending the clinics in 2006-2007 were diagnosed with malaria. Prospective data demonstrated a very high overdiagnosis of malaria. Microscopy was unreliable with < 1% of slides regarded as malaria parasite-positive by clinic microscopists being confirmed by trained research microscopists. In addition, many 'slide negatives' received anti-malarial treatment. As a result, 99.6% (248/249) of the individuals who were treated with ACT were in fact free of malaria parasites.
Transmission intensity has dropped considerably in the area of Mto wa Mbu. Despite this, most fevers are still regarded and treated as malaria, thereby ignoring true causes of febrile illness and over-prescribing ACT. The discrepancy between the perceived and actual level of transmission intensity may be present in many areas in sub-Saharan Africa and calls for greater efforts in defining levels of transmission on a local scale to help rational drug-prescribing behaviour.
[show abstract][hide abstract] ABSTRACT: Long-lasting insecticidal nets (LLINs) are advocated by WHO for protection against malaria. Of the three brands of LLINs currently approved by WHO, Olyset(R) is the only one currently granted full recommendation. With this type of LLIN, the insecticide (permethrin) is incorporated into the polyethylene fibre during manufacture and diffuses from the core to the surface, thereby maintaining surface concentrations. It has not been determined for how long Olyset nets remain protective against mosquitoes in household use.
Examples of Olyset nets, which had been in use in Tanzanian villages for seven years, were tested in experimental huts against naturally entering Anopheles gambiae and Anopheles funestus mosquitoes. Performance was compared with new Olyset nets, conventionally treated ITNs (either newly treated with alphacypermethrin or taken from local villages after 1.5 years of use) and untreated nets. All nets were artificially holed except for the seven-year Olyset nets, which had developed holes during prolonged domestic use.
Anopheles funestus and An. gambiae in NE Tanzania are susceptible to pyrethroids. The new Olyset nets caused high mortality against An. funestus (73.9%) and An. gambiae (62.7%) in experimental huts. The seven-year Olyset nets caused 58.9% mortality against An. funestus and 40.0% mortality against An. gambiae. The freshly treated alphacypermethrin nets also caused high mortality against An. funestus (70.6%) and An. gambiae (72.0%); this decreased to 58.4% and 69.6% respectively after 1.5 years of use. The new Olyset nets inhibited blood-feeding by 40-50%. The 7 year Olyset nets showed no feeding inhibition over that shown by the untreated nets. The alphacypermethrin treated nets failed to inhibit blood-feeding after 1.5 years of use. However iHhhdn laboratory tunnel tests samples of all types of treated net including the 7 year Olyset inhibited blood-feeding by more than 95%.
After seven years of use Olyset nets were still strongly insecticidal. Mosquito mortality decreased by only 20-35% over this period. However, Olyset would not provide personal protection after seven years unless it was in good condition and all holes fully repaired.
[show abstract][hide abstract] ABSTRACT: To measure pyrethroid susceptibility in populations of malaria vectors and nuisance-biting mosquitoes in Tanzania and to test the biological efficacy of current insecticide formulations used for net treatment.
Anopheles gambiae Giles s.l., An. funestus Giles s.l. and Culex quinquefasciatus Say were collected during three national surveys and two insecticide-treated net (ITN) studies in Tanzania. Knockdown effect and mortality were measured in standard WHO susceptibility tests and ball-frame bio-efficacy tests. Test results from 1999 to 2004 were compared to determine trends in resistance development.
Anopheles gambiae s.l. and An. funestus s.l. were highly susceptible to permethrin (range 87-100%) and deltamethrin (consistently 100%) in WHO tests in 1999 and 2004, while Culex quinquefasciatus susceptibility to these pyrethroids was much lower (range 7-100% and 0-84% respectively). Efficacy of pyrethroid-treated nets was similarly high against An. gambiae s.l. and An. funestus s.l. (range 82-100%) while efficacy against Cx. quinquefasciatus was considerably lower (range 2-100%). There was no indication of development of resistance in populations of An. gambiae s.l. or An. funestus s.l. where ITNs have been extensively used; however, susceptibility of nuisance-biting Cx. quinquefasciatus mosquitoes declined in some areas between 1999 and 2004.
The sustained pyrethroid susceptibility of malaria vectors in Tanzania is encouraging for successful malaria control with ITNs. Continued monitoring is essential to ensure early resistance detection, particularly in areas with heavy agricultural or public health use of insecticides where resistance is likely to develop. Widespread low susceptibility of nuisance-biting Culex mosquitoes to ITNs raises concern for user acceptance of nets.
Tropical Medicine & International Health 10/2007; 12(9):1061-73. · 2.94 Impact Factor
[show abstract][hide abstract] ABSTRACT: Objective To measure pyrethroid susceptibility in populations of malaria vectors and nuisance-biting mosquitoes in Tanzania and to test the biological efficacy of current insecticide formulations used for net treatment.Methods Anopheles gambiae Giles s.l., An. funestus Giles s.l. and Culex quinquefasciatus Say were collected during three national surveys and two insecticide-treated net (ITN) studies in Tanzania. Knockdown effect and mortality were measured in standard WHO susceptibility tests and ball-frame bio-efficacy tests. Test results from 1999 to 2004 were compared to determine trends in resistance development.Results Anopheles gambiae s.l. and An. funestus s.l. were highly susceptible to permethrin (range 87–100%) and deltamethrin (consistently 100%) in WHO tests in 1999 and 2004, while Culex quinquefasciatus susceptibility to these pyrethroids was much lower (range 7–100% and 0–84% respectively). Efficacy of pyrethroid-treated nets was similarly high against An. gambiae s.l. and An. funestus s.l. (range 82–100%) while efficacy against Cx. quinquefasciatus was considerably lower (range 2–100%). There was no indication of development of resistance in populations of An. gambiae s.l. or An. funestus s.l. where ITNs have been extensively used; however, susceptibility of nuisance-biting Cx. quinquefasciatus mosquitoes declined in some areas between 1999 and 2004.Conclusion The sustained pyrethroid susceptibility of malaria vectors in Tanzania is encouraging for successful malaria control with ITNs. Continued monitoring is essential to ensure early resistance detection, particularly in areas with heavy agricultural or public health use of insecticides where resistance is likely to develop. Widespread low susceptibility of nuisance-biting Culex mosquitoes to ITNs raises concern for user acceptance of nets.Objectif Mesurer la sensibilité aux pyréthroïdes de populations de vecteurs de la malaria et de moustiques piqueurs nuisants en Tanzanie et Examiner l’efficacité biologique des formulations actuelles d’insecticides utilisés pour le traitement des filets.Méthodes Anopheles gambiae Giles s.l., An. funestus Giles s.l. et Culex quinquefasciatus Say ont été collectés au cours de trois surveillances nationales et de deux études sur les filets traités aux insecticides (ITNs) en Tanzanie. L’effet d’assommage et la mortalité ont été mesurés dans les essais standards de l’OMS pour la sensibilité et les essais de bio-efficacité de «ball-frame». Les résultats des essais de 1999 et de 2004 ont été comparés pour déterminer des tendances dans le développement de résistance.Résultats An. gambiae s.l. et An. funestus s.l. étaient fortement sensibles au perméthrine (87 à 100%) et au deltaméthrine (tous à 100%) dans les essais de l’OMS en 1999 et 2004, alors que la sensibilité de Culex quinquefasciatus à ces pyréthroïdes était beaucoup faible (de 7 à 100% et 0 à 84% respectivement). L’efficacité des ITNs était pareillement forte sur An. gambiae s.l. et An. funestus s.l. (82 à 100%) tandis que l’efficacité sur Cx. quinquefasciatus était considérablement plus faible (2 à 100%). Il n’y avait aucune indication de développement de résistance dans les populations de An. gambiae s.l. ou An. funestus s.l. sur lesquelles les ITNs ont été intensivement utilisés. Cependant, la sensibilité des moustiques piqueurs nuisants, Cx. quinquefasciatus, déclinait dans certains endroits entre 1999 et 2004.Conclusion La sensibilité constante des vecteurs de la malaria aux pyréthroïdes en Tanzanie est encourageant pour le contrôle efficace de la malaria avec l’utilisation des ITNs. La surveillance continue est essentielle pour assurer la détection tôt de la résistance, en particulier dans les endroits avec une utilisation massive des insecticides en agriculture et pour la santé publique où la résistance est susceptible de se développer. La faible sensibilité répandue des moustiques Culex piqueurs nuisants souligne le soucis pour l’acceptation des ITNs par les utilisateurs.Objetivo Medir la susceptibilidad a piretroides en poblaciones de vectores de malaria y otros mosquitos responsables de picaduras molestas en Tanzania y evaluar la eficacia biológica de los métodos actuales de formulación de insecticida utilizados para el tratamiento de redes mosquiteras.Métodos Se recolectaron Anopheles gambiae Giles s.l., An. funestus Giles s.l. y Culex quinquefasciatus Say durante tres estudios nacionales y dos estudios de redes mosquiteras impregnadas (RMI) en Tanzania. El efecto ‘Knockdown’ y la mortalidad fueron medidas mediante pruebas de susceptibilidad estándar de la OMS y pruebas de bioeficacia tipo ‘ball-frame’. Se compararon los resultados de las pruebas de 1999 con las de 2004, para determinar las tendencias en el desarrollo de resistencias.Resultados Anopheles gambiae s.l. y An. funestus s.l. eran altamente susceptibles frente a la permetrina (rango 87–100%) y la deltametrina (consistentemente 100%) en las pruebas de la OMS en 1999 y 2004, mientras que la susceptibilidad de Culex quinquefasciatus a estos piretroides era mucho menor (rango 7–100% y 0–84%, respectivamente). La eficacia de las RMI con piretroides era similar frente a An. gambiae s.l. y An. funestus s.l. (rango 82–100%) mientras que la eficacia frente a Cx. quinquefasciatus era considerablemente menor (rango 2–100%). No había indicación de desarrollo de resistencias en poblaciones de An. gambiae s.l. o An. funestus s.l. en lugares en los que las RMI habían sido usadas extensivamente; sin embargo, la susceptibilidad de mosquitos Cx. quinquefasciatus disminuyó en algunas áreas entre 1999 y 2004.Conclusión La susceptibilidad mantenida de los vectores de malaria frente a los piretroides en Tanzania es esperanzadora en lo que respecta a un posible control exitoso de la malaria con RMI. La monitorización continua es esencial para asegurar una detección temprana de resistencias, particularmente en áreas con un uso intensivo de insecticidas, bien sea agrícolas o por motivos de salud pública, en los cuales la resistencia podría desarrollarse. La baja susceptibilidad generalizada a RMI de los mosquitos Culex es preocupante, pudiendo influir en la aceptación que los usuarios tengan de las redes.
Tropical Medicine & International Health 08/2007; 12(9):1061 - 1073. · 2.94 Impact Factor
[show abstract][hide abstract] ABSTRACT: Recently developed molecular gametocyte detection techniques have shown that submicroscopic Plasmodium falciparum gametocytes are common in symptomatic patients and can infect mosquitoes. The relevance for the infectious reservoir of malaria in the general population remains unknown. In this study, we investigated submicroscopic asexual parasitaemia and gametocytaemia in inhabitants of an area of hypoendemic and seasonal malaria in Tanzania.
Two cross-sectional malariometric surveys were conducted in the dry and wet seasons of 2005 in villages in lower Moshi, Tanzania. Finger prick blood samples were taken to determine the prevalence of P. falciparum parasites by microscopy, rapid diagnostic test and real-time nucleic acid sequence-based amplification (QT-NASBA).
2752 individuals participated in the surveys, of whom 1.9% (51/2721) had microscopically confirmed asexual parasites and 0.4% (10/2721) had gametocytes. In contrast, QT-NASBA revealed that 32.5% (147/453) of the individuals harboured asexual parasites and 15.0% (68/453) had gametocytes. No age dependency or seasonality was observed in submicroscopic parasite carriage.
Molecular detection techniques reveal that carriage of submicroscopic asexual parasite and gametocyte densities is relatively common in this low transmission area. Submicroscopic gametocytaemia is likely to be responsible for maintaining malarial transmission in the study area.
Tropical Medicine & International Health 05/2007; 12(4):547-53. · 2.94 Impact Factor
[show abstract][hide abstract] ABSTRACT: P. falciparum gametocytes may persist after treatment with sulphadoxine-pyrimethamine (SP) plus artesunate (AS) and contribute considerably to malaria transmission. We determined the efficacy of SP+AS plus a single dose of primaquine (PQ, 0.75 mg/kg) on clearing gametocytaemia measured by molecular methods.
The study was conducted in Mnyuzi, an area of hyperendemic malaria in north-eastern Tanzania. Children aged 3-15 years with uncomplicated P. falciparum malaria with an asexual parasite density between 500-100,000 parasites/microL were randomized to receive treatment with either SP+AS or SP+AS+PQ. P. falciparum gametocyte prevalence and density during the 42-day follow-up period were determined by real-time nucleic acid sequence-based amplification (QT-NASBA). Haemoglobin levels (Hb) were determined to address concerns about haemolysis in G6PD-deficient individuals.
108 individuals were randomized. Pfs25 QT-NASBA gametocyte prevalence was 88-91% at enrolment and decreased afterwards for both treatment arms. Gametocyte prevalence and density were significantly lower in children treated with SP+AS+PQ. On day 14 after treatment 3.9% (2/51) of the SP+AS+PQ treated children harboured gametocytes compared to 62.7% (32/51) of those treated with SP+AS (p<0.001). Hb levels were reduced in the week following treatment with SP+AS+PQ and this reduction was related to G6PD deficiency. The Hb levels of all patients recovered to pre-treatment levels or greater within one month after treatment.
PQ clears submicroscopic gametocytes after treatment with SP+AS and the persisting gametocytes circulated at densities that are unlikely to contribute to malaria transmission. For individuals without severe anaemia, addition of a single dose of PQ to an efficacious antimalarial drug combination is a safe approach to reduce malaria transmission following treatment.
PLoS ONE 01/2007; 2(10):e1023. · 3.73 Impact Factor
[show abstract][hide abstract] ABSTRACT: Molecular markers of insecticide resistance can provide sensitive indicators of resistance development in malaria vector populations. Monitoring of insecticide resistance in vector populations is an important component of current malaria control programmes. Knockdown resistance (kdr) confers resistance to the pyrethroid class of insecticides with cross-resistance to DDT through single nucleotide polymorphisms (SNPs) in the voltage-gated sodium channel gene.
To enable detection of kdr mutations at low frequency a method was developed that uses polymerase chain reaction (PCR) and enzyme-linked immunosorbent assay (ELISA)-based technology, allowing rapid, reliable and cost-effective testing of large numbers of individual mosquitoes. This was used to assay mosquitoes from sites in lower Moshi, Tanzania.
Sequence-specific oligonucleotide probes (SSOP) were used for simultaneous detection of both East and West African kdr mutations with high specificity and sensitivity. Application of the SSOP-ELISA method to 1,620 field-collected Anopheles arabiensis from Tanzania identified the West African leucine-phenylalanine kdr mutation in two heterozygous individuals, indicating the potential for resistance development that requires close monitoring.
The presence of the West African kdr mutation at low frequency in this East African population of An. arabiensis has implications for the spread of the kdr gene across the African continent.
[show abstract][hide abstract] ABSTRACT: Mosquito traps known as Mbita traps made from modified bednets according to a design developed in Kenya were compared with Centers for Disease Control (CDC) light traps for their ability to catch anopheline and culicine mosquitoes in several different villages in northern Tanzania. The results confirmed those recently reported in Kenya, that Mbita traps catch significantly fewer mosquitoes than CDC traps. Statistical analysis using a Poisson log linear model with random effects for the trap counts showed that the ratio of the catches with the two types of trap was not consistent in the different villages. Thus, we doubt whether the Mbita trap would be a reliable substitute for CDC traps. In one trial, the catches made at different hours of the night with the two types of trap indicated that in villages where insecticide treated nets (ITNs) had been used for some years, somewhat more of the Anopheles biting occurred early and late in the night, whereas in villages with no history of ITN use, biting was concentrated in the middle of the night. This suggests that behavioural adaptation to avoid contact with ITNs may be beginning to evolve.
International Journal of Tropical Insect Science 08/2005; 25(03):208 - 213.
[show abstract][hide abstract] ABSTRACT: The antimalarial combination of sulfadoxine and pyrimethamine (SP) was introduced as first-line treatment for uncomplicated malaria in Tanzania during 2001 following 18 years of second-line use. The genetic determinants of in vitro resistance to the two drugs individually are shown to be point mutations at seven sites in the dihydrofolate reductase gene (dhfr) conferring resistance to pyrimethamine and five sites in the dihydropteroate synthase (dhps) gene conferring resistance to sulfadoxine. Different combinations of mutations within each gene confer differing degrees of insensitivity, but information about the frequency with which allelic haplotypes occur has been lacking because of the complicating effects of multiple infection. Here we used a novel high-throughput sequence-specific oligonucleotide probe-based approach to examine the present resistance status of three Plasmodium falciparum populations in northern Tanzania. By using surveys of asymptomatic infections and screening for the presence of all known point mutations in dhfr and dhps genes, we showed that just five dhfr and three dhps allelic haplotypes are present. High frequencies of both triple-mutant dhfr and double-mutant dhps mutant alleles were found in addition to significant interregional heterogeneity in allele frequency. In vivo studies have shown that the cooccurrence of three dhfr mutations and two dhps mutations in an infection prior to treatment is statistically predictive of treatment failure. We have combined data for both loci to determine the frequency of two-locus genotypes. The triple-dhfr/double-dhps genotype is present in all three regions with frequencies ranging between 30 and 63%, indicating that treatment failure rates are likely to be high.
Antimicrobial Agents and Chemotherapy 05/2003; 47(4):1347-54. · 4.57 Impact Factor
[show abstract][hide abstract] ABSTRACT: Sulfadoxine-pyrimethamine was first introduced for treatment of malaria in Africa during the early 1980s for cases when chloroquine treatment failed, and has since become the first-line treatment in many countries. Resistance to sulfadoxine-pyrimethamine is now increasing, especially in southeast Africa.
We characterised genetic change in dhfr and dhps genes in the Plasmodium falciparum population of KwaZulu-Natal, South Africa, during 1995-99, a period of rapid deterioration of the effectiveness of sulfadoxine-pyrimethamine. We assessed the evolutionary origin of the resistance by analysing polymorphic microsatellite repeats in the flanking region of the dhfr and dhps genes, which show whether resistance alleles originated through shared or independent ancestral mutation events. We then assessed the current extent of dispersal of dhfr and dhps resistance alleles by doing the same analysis in P falciparum sampled from communities in the Kilimanjaro region of northern Tanzania in 2001.
The large genetic change during 1995-99 in KwaZulu-Natal, South Africa, in both the health facility and the wider community surveys, was at the dhps locus, apparently because resistance at dhfr was established before 1995. The allelic determinants of resistance in this province share a common evolutionary origin with those found in Kilimanjaro, Tanzania, even though the two sites are 4000 km apart.
Three resistant dhfr alleles, and one resistant dhps allele, each derived from independent ancestral lineages, have been driven through through southeast Africa. The movement by the dhfr alleles (pyrimethamine resistance) preceded that of the dhps allele (sulfadoxine resistance). Our findings emphasise that gene flow rather than new mutations has been the most common originator of resistance in African countries.
The Lancet 05/2003; 361(9364):1174-81. · 39.06 Impact Factor