635 research outputs found
Cost implications of improving malaria diagnosis: findings from north-eastern Tanzania.
No full textBACKGROUND: Over diagnosis of malaria contributes to improper treatment, wastage of drugs and resistance to the few available drugs. This paper attempts to estimate the rates of over diagnosis of malaria among children attending dispensaries in rural Tanzania and examines the potential cost implications of improving the quality of diagnosis. METHODOLOGY/PRINCIPAL FINDINGS: The magnitude of over diagnosis of malaria was estimated by comparing the proportion of outpatient attendees of all ages clinically diagnosed as malaria to the proportion of attendees having a positive malaria rapid diagnostic test over a two month period. Pattern of causes of illness observed in a or=5 year age group in the lower transmission site (RR 14.0 95%CI 8.2-24.2). In the low transmission site the proportion of morbidity attributable to malaria was substantially lower in <2 year old cohort compared to children seen at routine care system. (0.08% vs 28.2%; p<0.001). A higher proportion of children were diagnosed with ARI in the <2 year old cohort compared to children seen at the routine care system ( 42% vs 26%; p<0.001). Using a RDT reduced overall drug and diagnostic costs by 10% in the high transmission site and by 15% in the low transmission site compared to total diagnostic and drug costs of treatment based on clinical judgment in routine health care system. IMPLICATIONS: The introduction of RDTs is likely to lead to financial savings. However, improving diagnosis to one disease may lead to over diagnosis of another illness. Quality improvement is complex but introducing RDTs for the diagnosis of malaria is a good start
Laboratory and experimental hut evaluation of mosquito net and indoor residual spray (IRS) insecticides for improved malaria control
No full textSince the start of Roll Back Malaria (RBM) in 1998 funding for malaria control has increased dramatically, resulting in the current peak of $2.5billion spent on global malaria control annually. Vector control has been a major source of expenditure, with the focus in sub-Saharan Africa being free Long-Lasting Insecticidal Net (LLIN) distribution and Indoor Residual Spraying (IRS). Use of pyrethroid insecticides in agriculture and rapid scaling up of pyrethroid LLINs and IRS for malaria vector control has led to the development and spread of pyrethroid resistance in Anopheles gambiae malaria vectors. In community use, the level of insecticide resistance at which malaria control is compromised remains uncertain, but experimental hut trials in Benin, an area of high frequency pyrethroid resistance, showed that holed pyrethroid Insecticide Treated Nets (ITNs) failed to protect sleepers from being bitten and no longer had a mass killing effect on malaria vectors. If LLINs and IRS are to remain effective it is essential that new public health insecticides are developed to address the growing problem of resistance. All insecticides that are currently recommended by the World Health Organization Pesticide Evaluation Scheme (WHOPES) for LLIN or IRS belong to just four classes of chemistry that act on nerve and muscle targets; namely pyrethroid, organophosphate (OP), carbamate, and organochlorine (DDT). The Global Plan for Insecticide Resistance Management (GPIRM) states that in areas of pyrethroid resistance or high LLIN coverage, alternative insecticide classes should be used for IRS in a rotation. Rotation of insecticides is very difficult to implement due to a lack of new public health insecticides. The Stockholm Convention on Persistent Organic Pollutants (POPs) came into effect in 2004, yet the use of DDT (classified as a POP) for malaria control has been allowed to continue under exemption since then due to a perceived absence of equally effective and efficient alternatives. Alternative classes of insecticide for IRS such as pirimiphos-methyl (OP) and bendiocarb (carbamate) have a relatively short residual duration of action (2-6 months according to WHOPES). In areas of year-round transmission, multiple spray cycles are required resulting in significantly higher costs for malaria control programs and user fatigue. For continued cost-effectiveness of IRS programs it is important to develop new longer-lasting formulations of currently available insecticides, while also developing insecticides with new modes of action. Pyrethroids are the only insecticides that are currently recommended by WHOPES for LLIN. Therefore, it is essential to develop and evaluate new insecticides for LLIN before effectiveness of pyrethroid LLIN is compromised.
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This thesis consisted of a sequence of tests to evaluate the efficacy of several new formulations of WHOPES recommended insecticides and novel insecticides both in the laboratory and against wild mosquitoes entering experimental huts.
Specifically these studies have shown that:
Addition of eave baffles in experimental huts succeeded in reducing the potential for mosquito escape and is preferable to the assumption of doubling veranda catch to allow for unrecorded escapes (research paper 2).
A Capsule Suspension (CS) formulation of pirmiphos-methyl used for IRS showed a significant improvement in terms of longevity on mud, concrete and plywood when compared with the previously recommended Emulsifiable Concentrate (EC) formulation in laboratory and experimental hut bioassays (research paper 3).
A new formulation of deltamethrin with polymeric binder (SC-PE) for IRS showed only a slight improvement over the existing Water Dispersible Granules (WG) formulation in bioassays, but both formulations equalled DDT in experimental huts and should provide annual mosquito control. Deltamethrin SC-PE or WG should only be considered for use by malaria control programs where there is low pyrethroid LLIN coverage (research paper 4).
In experimental hut trials, chlorfenapyr (pyrrole) IRS was equivalent to alphacypermethrin against pyrethroid susceptible An. arabiensis but superior against pyrethroid-resistant Cx. quinquefasciatus. The unique non-neurological mode of action shows no cross-resistance to existing resistance mechanisms and should be successful for control of pyrethroid resistant mosquitoes (research paper 5).
In experimental hut trials, chlorfenapyr ITNs produced relatively high mortality rates of pyrethroid susceptible An. arabiensis but due to low irritability there was only a small reduction in blood-feeding (research paper 8). Mortality rates were similar to those produced by deltamethrin ITN.
Unlike neurotoxic insecticides, such as pyrethroids and carbamates, chlorfenapyr owes its toxicity to the disruption of molecular pathways which enable cellular respiration to occur. Conventional 3 minute contact bioassay based on WHOPES guidelines is suitable for pyrethroids but does not predict field performance of
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chlorfenapyr, which is metabolic in nature and sensitive to temperature and the phase of the insect’s circadian activity rhythm (research paper 9).
Combining chlorfenapyr with a more excito-repellent pyrethroid on mosquito nets produced higher levels of blood-feeding inhibition than chlorfenapyr alone, in tunnel tests with both pyrethroid susceptible and resistant strains of Cx. quinquefasciatus (research paper 10).
Restricting insecticide to particular surfaces of the nets (top only or sides only) indicated that An. arabiensis contacts both the top and sides of a mosquito net during host-seeking behaviour. These results support the rationale behind the ‘2-in-1’ mosquito net, in which the top of the net is treated with a non-pyrethroid insecticide and the sides with pyrethroid (research paper 11)
Epidemiology of Subpatent Plasmodium Falciparum Infection: Implications for Detection of Hotspots with Imperfect Diagnostics.
No full textAt the local level, malaria transmission clusters in hotspots, which may be a group of households that experience higher than average exposure to infectious mosquitoes. Active case detection often relying on rapid diagnostic tests for mass screen and treat campaigns has been proposed as a method to detect and treat individuals in hotspots. Data from a cross-sectional survey conducted in north-western Tanzania were used to examine the spatial distribution of Plasmodium falciparum and the relationship between household exposure and parasite density. Dried blood spots were collected from consenting individuals from four villages during a survey conducted in 2010. These were analysed by PCR for the presence of P. falciparum, with the parasite density of positive samples being estimated by quantitative PCR. Household exposure was estimated using the distance-weighted PCR prevalence of infection. Parasite density simulations were used to estimate the proportion of infections that would be treated using a screen and treat approach with rapid diagnostic tests (RDT) compared to targeted mass drug administration (tMDA) and Mass Drug Administration (MDA). Polymerase chain reaction PCR analysis revealed that of the 3,057 blood samples analysed, 1,078 were positive. Mean distance-weighted PCR prevalence per household was 34.5%. Parasite density was negatively associated with transmission intensity with the odds of an infection being subpatent increasing with household exposure (OR 1.09 per 1% increase in exposure). Parasite density was also related to age, being highest in children five to ten years old and lowest in those > 40 years. Simulations of different tMDA strategies showed that treating all individuals in households where RDT prevalence was above 20% increased the number of infections that would have been treated from 43 to 55%. However, even with this strategy, 45% of infections remained untreated. The negative relationship between household exposure and parasite density suggests that DNA-based detection of parasites is needed to provide adequate sensitivity in hotspots. Targeting MDA only to households with RDT-positive individuals may allow a larger fraction of infections to be treated. These results suggest that community-wide MDA, instead of screen and treat strategies, may be needed to successfully treat the asymptomatic, subpatent parasite reservoir and reduce transmission in similar settings
Safety, efficacy and pharmacokinetics profile of antimalarial drugs in pregnancy : pharmacoepidemiology studies
No full textBackground: Malaria in pregnancy is an important public health problem in sub Saharan Africa. It is known to be the most common and preventable cause of harmful birth outcomes in malaria endemic areas. It is therefore important for a pregnant woman to be treated with safe and effective antimalarial medication. Drug safety in pregnancy is of a greater concern due to limited safety data available in this vulnerable group. This is because pregnant women are not involved in clinical trials related to drug development process due to safety reasons and hence, most of these medicines come to market with limit information available about their safety in pregnancy. Hence, establishing a drug safety monitoring mechanism would be important to generate safety data when a given medicine is already in the market, especially medications against tropical diseases.
Pregnant women are at increased risk of malaria infection and illness than non-pregnant individuals due to physiological, hormonal and immunological changes that occur in their body after conception. The changes are also responsible for various therapeutic challenges that face this vulnerable group. This explains the presence of significant alteration of antimalarial pharmacokinetic (PK) properties in pregnancy and hence lead to a reduced drug blood concentration, which will ultimately lower antimalarial cure rate. Another factor that affects antimalarial effectiveness in pregnancy is parasite resistance against sulfadoxine-pyrimethamine (SP), a drug that is used for intermittent preventive treatment of malaria in pregnancy (IPTp).
The objectives of the thesis were to assess the magnitude of drugs exposure during pregnancy in relation to pregnancy outcomes, to describe the feasibility of establishing active pharmacovigilance system in developing countries using Health Demographic Surveillance System (HDSS) platform, to determine safety of artemether-lumefantrine (AL) exposure in first trimester of pregnancy, to evaluate pharmacokinetics and pharmacodynamics properties of artemether-lumefantrine in pregnant and non-pregnant women, and to determine the effectiveness of IPTp-SP in prevention of placental malaria, maternal anaemia and low birth weight in areas with different malaria transmission intensity.
Method: Three different study designs were used independently to respond to different specific objectives of this thesis; (i) a longitudinal follow up study was conducted to generate artemether/lumefantrine (AL) safety data in first trimester secondary to its inadvertent exposure in two Health Demographic Surveillance System (HDSS) areas in Tanzania. Pregnant women with gestational age ? 20 weeks were enrolled and followed up on monthly bases until delivery. Drugs exposures during the entire pregnancy period were also recorded. The latter was used to document the feasibility of establishing active pharmacovigilance system using HDSS platform in one of the studied HDSS area. (ii) To determine AL PK, a prospective study involving pregnant in second and third trimester and non-pregnant women, both with uncomplicated P falciparum malaria. Plasma samples were collected at pre-defined dates for bioassay to determine drug level. Participants were followed up on pre-defined schedule visits until day 42. Inter- and intra-individual variability was assessed and covariated effects quantified using a nonlinear mixed-effect modeling approach (NONMEM®). (iii) Another prospective study enrolling pregnant women to assess the effectiveness of IPTp in two areas with different malaria transmission intensity. Pregnant women were recruited in the labor ward and structured questionnaire was used for interview. Placental parasitaemia was screened by using both light microscope and real-time quantitative PCR.
Findings
Pharmacovigilance system
91% (994 of 1089) of pregnant women who were piloted to assess feasibility of establishing active PV system completed the follow up until delivery. 98% of pregnant women reported to have taken at least one medication during pregnancy, mainly drugs provided in the antenatal program. Other most reported drugs were analgesics (24%), antibiotics (17%) and antimalarials (15%), excluding IPTp. Iron and folate supplementations were associated with decreased risk of miscarriage/stillbirth (OR 0.1; 0.08 – 0.3).
AL safety
82% (1783 of 2167) of pregnant women who used and not used antimalarial drugs in first trimester were followed until delivery and recorded their pregnancy outcome. 319 (17.9%) used antimalarial drugs in first trimester and AL was the most frequent antimalarial used [53.9% (172 of 319)]. Others were 24.4 % quinine, 20.7% SP and 3.4% amodiaquine. Quinine exposure in first trimester was associated with increased risk of miscarriage/stillbirth (OR 2.5; 1.3 – 5.1) and premature birth (OR 2.6; 1.3 – 5.3). AL, SP and amodiaquine exposure were found not to be harmful.
PK analysis
33 pregnant women and 22 non-pregnant women with malaria were treated with AL (80/480mg) twice daily for 3 days. Lumefantrine (LF) bioavailability and metabolism rate into desmethyl-lumefantrine were respectively 34% lower and 78% higher in pregnant than in non-pregnant patients. Overall PCR uncorrected therapeutic failure was 18% in pregnant and 5% in non-pregnant women (OR 4.0; p value 0.22). A higher median day 7 LF concentration was associated with adequate clinical and parasitological response.
Effectiveness of IPTp
350 pregnant women were recruited and screened for placental parasitaemia (175 each from high and low malaria transmission areas). Prevalence of placenta parasitaemia was 16.6% in high transmission area and 2.3% in low transmission area. One or more doses of IPTp in high transmission area had 80% impact against placental malaria (OR 0.2; CI 0.06 – 0.7; p=0.015) and 60% in low transmission (OR 0.4; CI 0.04 – 4.5; p=0.478). Primigravida and residing in high transmission area were significant risk factors for placental malaria (OR 2.4; CI 1.1 – 5.0) and (OR 9.4; CI 3.2 – 27.7), respectively. The numbers needed to treat (NNT) was 4 (CI 2 – 4) women in high transmission area and 33 (CI 20 – 50) low transmission area to prevent one placental malaria. IPTp use was not statistically significant associated with decreased risk of maternal anaemia or low birth weight, regardless are of transmission intensity.
Conclusion:
Overall medicine use in pregnancy period is very high, including AL exposure in first trimester albeit this drug is not the first line treatment for malaria in early pregnancy. AL use in first trimester was safer as opposed to quinine, the first line drug which was associated with adverse pregnancy outcomes. We therefore recommend to consider other options than quinine for standard antimalarial drug in first trimester, and AL could be the best one.
HDSS platforms represent a reliable and feasible support to build on a pharmacovigilance system to assess safety of drugs in pregnancy since it has proved to be feasible. We recommend that pharmaceutical companies and other global financial bodies should invest more on the establishment of active pharmacovigilance system in pregnancy in tropical developing countries. The latter will boost safety data pool of newly marketed medicines and anti-infective agents for treating different illnesses in pregnancy.
LF bioavailability is significantly lowered in pregnant women due to altered PK properties as opposed to non-pregnant women in the same area. This may be responsible for therapeutic failure among pregnant women secondary to the observed low post-treatment prophylaxis. We recommend to evaluate a modified treatment regimen of malaria in pregnancy. ---------- Muhtasari
Utangulizi: Ugonjwa wa malaria kwa mama mjamzito ni tatizo kuu kwenye afya ya jamii hasa Africa kusini mwa jangwa la Sahara. Malaria ni miongoni mwa magonjwa yanayoweza kuzuilika. Ugonjwa huu unasababisha mazara makubwa sana kwa mtoto mchanga tokea akiwa tumboni kwa mama yake hasa sehemu zenye malaria kwa kiwango cha juu. Hivyo basi ni vema mama mjamzito atibiwe na dawa salama na zenye uwezo mkubwa wa kuangamiza vidudu vya malaria. Usalama wa dawa kwa mama mjamzito ni kitu chenye changamoto kubwa kutokana na uhaba wa takwimu muhimu za usalama wa dawa za malaria kwa wajawazito. Sababu kuu inatokana na mama wajawazito kutohusishwa kwenye majaribio ya dawa kipindi cha za mwanzoni pale ambapo dawa husika bado hazijapewa kibali cha kuingia sokoni kwa sababu ya kuhofia usalama wa kiafya hasa kwa mtoto aliyopo tumboni. Hilo linapelekea kwa dawa nyingi kuingia sokoni zikiwa na upungufu wa taarifa muhimu juu ya usalama wake kwa mama mjamzito. Kwa sababu hiyo, ni muhimu kuwa na mfumo wa kipekee wa kumfuatilia mama mjamzito pale atakapotumia dawa ambazo zipo tayari sokoni ili kuboresha taarifa za kiusalama kiafya kutokana na matumizi yake kipindi cha ujauzito.
Mama mjamzito anahatari kubwa ya kuambukizwa ugonjwa wa malaria pamoja na kuuguwa kuliko mama ambaye hana ujauzito. Hili linatokana na mabadiliko kipindi cha ujauzito ambayo yanasababishwa na kupunguwa kwa kinga ya mwili na mabadiliko ya homoni mwilini mwake. Mabadiliko haya yanachangia pia kuathiri ufanisi wa dawa mwilini kwake kupambana na vijidudu vya malaria na hivyo kupunguza uwezo wa uponyaji. Usugu wa dawa dhidi ya vijidudu vya malaria, kwa mfano dawa ya SP huchangia pia kuathiri uwezo wa kumponya mgonjwa wa malaria.
Dhumini kuu la utafiti huu ni (i) kujuwa wingi wa dawa anazotumia mama mjamzito ukilinganisha na matokeo ya mimba yake, (ii) kuonyesha uwezekano wa kuwa na mfumo pekee wa kudhibitisha matumizi ya dawa ambao utaweza kufuatilia usalama na matumizi ya dawa kwa ujumla kwa mama mjamzito, kwenye nchi inayoendelea kwa kutumia mfumo wa HDSS (Health Demographic Surveillance System), (iii) kuhakiki usalama wa matumizi ya dawa mseto (ALU) ya malaria kipindi cha mimba changa, (iv) kutathimini unyambulisho wa dawa ya mseto mwilini mwa mgonjwa sambamba na kulinganisha ufanisi wake wa kuangamiza vijidudu vya malaria, na (v) kutathimini ufanisi wa dawa ya SP ambayo mama mjamzito anapatiwa kliniki kama inasaidia kuangamiza vijidudu vya malari kwenye kondo la uzazi, kuzuia upungufu wa damu kwa mama na mtoto kutozaliwa na kilo pungufu kwenye maeneo yenye viwango tofauti vya maambukizo ya malaria.
Methodolojia: Njia tatu tofauti zilitumika kupata majibu husika ya malengo ya utafiti huu; (i) Kufuatilia mama wajawazito tokea kipindi cha mwanzo cha ujauzito wao hadi wanapojifungua na kurekodi taarifa za matumizi ya dawa (ikiwemo dawa mseto) na matokeo ya ujauzito. Zoezi hili lilifanyika kwenye vituo vya HDSS huko Rufiji na Kigoma mjini. (ii) Unyambulisho wa ufanisi wa dawa mseto uliwahusisha wanawake ambao ni wajawazito (wenye umri wa mimba kuanzia wiki 13 na kuendelea) na wale wasio wajawazito lakini wote wakiwa wametambulika hawana malaria kali. Walipewa dawa mseto na kutolewa damu kwa kipindi tofauti tofauti ndani ya siku 42 za kuwafuatilia ili kupima kiwango cha dawa kwenye damu na kuhakiki vijidudu vya malaria vinavyo angamia. (iii) Kuhakiki ufanisi wa SP kama kinga ya malaria kwa mama mjamzito (IPTp) ilihusisha kuwatambua akina mama wajawazito wakiwa kwenye hospitali mbili tofauti ambazo zipo kwenye maeneo yanye viwango tofauti vya uambukizaji wa malaria. Utambuzi wa akinamama hawa ulikuwa muda mfupi kabla hawajajifungua na ulihusisha kukusanya damu toka kwenye kondo la uzazi mara tu baada ya kujifungua na kupima kama kuna maambukizi ya vijidudu vya malaria.
Matokea: (i) Mfumo wa ukusanyaji taarifa ya matumizi ya dawa kipindi chote cha ujauzito. Asilimia 90 (994/1089) ya mama wajawazito waliweza kufuatiliwa mpaka walipo jifunguwa. Jumla ya 98% waliripoti kutumia walau aina moja ya dawa kipindi cha ujauzito, hasa zikiwa dawa zinazotolewa kwenye mpango maalumu wa mama na mtoto. Dawa nyingi zikiwa ni dawa za kuzuia maumivu (24%), antibayotiki (17%) na dawa za kutibu malaria (15%). Imeonekana dawa za kuongeza wingi wa dama zinahusiana na kupunguza hatari ya mimba kuharibika na mtoto kuzaliwa njiti.
(ii) Usalama wa dawa mseto: Jumla ya mama wajawazito 1783 kati ya 2167 (82%) waliyotumia na ambao hawajatumia dawa za malaria kipindi cha miezi mitatu ya mwanzo ya ujauzito walifuatiliwa na kurekodi matokeo yao ya ujauzito wao. 319 (17.9%) walitumia dawa za malaria kipindi hicho cha mwanzo cha ujauzito na kati ya hawa 53.9% walitumia dawa mseto. Wengine walitumia quinine (24.4%), SP (20.7%) na amodiaquine (3.4%). Matumizi ya quinine kipindi cha miezi mitatu ya mwanzo ya mimba yalihusishwa na kuharibika kwa mimba na kuzaa mtoto njiti. Dawa ya mseto, SP na amodiaquine zilionyesha kutokuwa na mathara yeyote.
(iii) Unyambulisho wa ufanisi ya dawa mseto: Utafiti huu ulihusisha wajawazito 33 na wanawake wasio wajawazito 22 waliyo na malaria na kutibiwa na dozi kamili ya dawa mseto mara mbili kutwa kwa siku 3. Sehemu ya dawa ya mseto ilionekana kuwa pungufu kwa wajawazito ukilinganisha na wale wasiyo wajawazito. Kwenye kipindi cha kuwafuatiliya wagonjwa (ndani ya siku 42), 18% ya wajawazito na 5% ya wasiyo wajawazito waligundulika kuwa bado wana vijidudu vya malaria. Kuwa na kiwango kikubwa cha dawa ya mseto kwenye mzunguko wa damu ulihusishwa na kupona malaria kwa ufasaha.
(iv) Ufanisi wa SP kama kinga ya malaria kwa mama mjamzito. Jumla ya mama wajawazito 350 walihusiswa kwenye utafiti huu, 175 toka kila sehemu yenye malaria ya kwa kiwango cha juu na pia toka kwenye sehemu ya malaria kwa kiwango cha chini. Maambukizo ya malaria kwenye kondo la uzazi ilikuwa 16.6% kwenye eneo la malaria cha kiwango cha juu na 2.3% kwenye eneo lenye malaria kwa kiwango cha chini. Matumizi ya SP yalionyesha uwezekano wa kuzuia maambukizi ya kondo la uzazi hasa eneo lenye malaria ya juu. Kuwa na ujauzito wa kwanza na kuishi eneo lenye malaria ya juu ni kiambata hatarishi cha kupata maambukizo ya kondo la uzazi
Hitimisho: Kwa ujumla matumizi ya dawa kipindi cha ujauzito yapo kwenye kiwangu cha juu, ikiwemo matumizi ya dawa mseto kwenye kipindi cha mimba changa, japokuwa dawa hii siyo chaguo la kwanza kwenye tiba ya malaria kwenye kipindi hichi. Dawa mseto imeonekana kuwa salama zaidi kuliko quinine hivyo ni bora kuanza kufikiria jinsi itakavyoweza kupendekezwa kwa matumizi kipindi cha mimba changa.
Kupitia HDSS imeonyesha inaweza kusaidia kuwa na mfumo wa uhakika na kuaminika wa kukusanya taarifa muhimu za matumizi ya dawa kwa mama mjamzito kwenye nchi masikini. Hivyo ni bora makampuni ya dawa, wafadhili kwa kushirikiana na taasisi za afya ndani na nje ya nchi wafikirie jinsi ya kufadhili mfumo huu ili kusaidia kuboresha takwimu za usalama wa dawa kwa mama wajawazito.
Imethibitika kuwa dawa mseto inapunguwa kwa kiasi kikubwa mwilini mwa mwanamke mjamzito ukilinganisha na mwanamke asiyo mjamzito. Hili huenda ikapelekea mama mjamzito kutopona kwa ufasaa na kupungukiwa uwezekano wa kukabiliyana na maambukizo mapya ya malaria kipindi cha usoni hasa baada ya kumaliza dozi ya malaria. Hivyo tunapendekeza kupitiwa upya dozi ya malaria inayotumika sasa na mama mjamzito na kushauri upatikanaji wa dozi mpya kwa hili kundi la wajawazito
Feeding and Resting Behaviour of Malaria Vector, Anopheles Arabiensis with Reference to Zooprophylaxis.
No full textThe most important factor for effective zooprophylaxis in reducing malaria transmission is a predominant population of a strongly zoophilic mosquito, Anopheles arabiensis. The feeding preference behaviour of Anopheline mosquitoes was evaluated in odour-baited entry trap (OBET). Mosquitoes were captured daily using odour-baited entry traps, light traps and hand catch both indoor and in pit traps. Experimental huts were used for release and recapture experiment. The mosquitoes collected were compared in species abundances. Anopheles arabiensis was found to account for over 99% of Anopheles species collected in the study area in Lower Moshi, Northern Tanzania. In experimental release/capture trials conducted at the Mabogini verandah huts, An. arabiensis was found to have higher exophilic tendency (80.7%) compared to Anopheles gambiae (59.7%) and Culex spp. (60.8%). OBET experiments conducted at Mabogini collected a total of 506 An. arabiensis in four different trials involving human, cattle, sheep, goat and pig. Odours from the cattle attracted 90.3% (243) compared to odours from human, which attracted 9.7% (26) with a significant difference at P = 0.005. Odours from sheep, goat and pig attracted 9.7%, 7.2% and 7.3%, respectively. Estimation of HBI in An. arabiensis collected from houses in three lower Moshi villages indicated lower ratios for mosquitoes collected from houses with cattle compared to those without cattles. HBI was also lower in mosquitoes collected outdoors (0.1-0.3) compared to indoor (0.4-0.9). In discussing the results, reference has been made to observation of exophilic, zoophilic and feeding tendencies of An. arabiensis, which are conducive for zooprophylaxis. It is recommended that in areas with a predominant An. arabiensis population, cattle should be placed close to dwelling houses in order to maximize the effects of zooprophylaxis. Protective effects of human from malaria can further be enhanced by keeping cattle in surroundings of residences
Trends in the selection of insecticide resistance in Anopheles gambiae s.l. mosquitoes in northwest Tanzania during a community randomized trial of longlasting insecticidal nets and indoor residual spraying.
No full textAnopheles gambiae s.l. (Diptera: Culicidae) in Muleba, Tanzania has developed high levels of resistance to most insecticides currently advocated for malaria control. The kdr mutation has almost reached fixation in An. gambiae s.s. in Muleba. This change has the potential to jeopardize malaria control interventions carried out in the region. Trends in insecticide resistance were monitored in two intervention villages using World Health Organization (WHO) susceptibility test kits. Additional mechanisms contributing to observed phenotypic resistance were investigated using Centers for Disease Control (CDC) bottle bioassays with piperonylbutoxide (PBO) and S,S,S-tributyl phosphorotrithioate (DEF) synergists. Resistance genotyping for kdr and Ace-1 alleles was conducted using quantitative polymerase chain reaction (qPCR). In both study villages, high phenotypic resistance to several pyrethroids and DDT was observed, with mortality in the range of 12-23%. There was a sharp decrease in mortality in An. gambiae s.l. exposed to bendiocarb (carbamate) from 84% in November 2011 to 31% in December 2012 after two rounds of bendiocarb-based indoor residual spraying (IRS). Anopheles gambiae s.l. remained susceptible to pirimiphos-methyl (organophosphate). Bendiocarb-based IRS did not lead to the reversion of pyrethroid resistance. There was no evidence for selection for Ace-1 resistance alleles. The need to investigate the operational impact of the observed resistance selection on the effectiveness of longlasting insecticidal nets and IRS for malaria control is urgent
Medication exposure during pregnancy: a pilot pharmacovigilance system using health and demographic surveillance platform
No full textThere is limited safety information on most drugs used during pregnancy. This is especially true for medication against tropical diseases because pharmacovigilance systems are not much developed in these settings. The aim of the present study was to demonstrate feasibility of using Health and Demographic Surveillance System (HDSS) as a platform to monitor drug safety in pregnancy.; Pregnant women with gestational age below 20 weeks were recruited from Reproductive and Child Health (RCH) clinics or from monthly house visits carried out for the HDSS. A structured questionnaire was used to interview pregnant women. Participants were followed on monthly basis to record any new drug used as well as pregnancy outcome.; 1089 pregnant women were recruited; 994 (91.3%) completed the follow-up until delivery. 98% women reported to have taken at least one medication during pregnancy, mainly those used in antenatal programmes. Other most reported drugs were analgesics (24%), antibiotics (17%), and antimalarial (15%), excluding IPTp. Artemether-lumefantrine (AL) was the most used antimalarial for treating illness by nearly 3/4 compared to other groups of malaria drugs. Overall, antimalarial and antibiotic exposures in pregnancy were not significantly associated with adverse pregnancy outcome. Iron and folic acid supplementation were associated with decreased risk of miscarriage/stillbirth (OR 0.1; 0.08-0.3).; Almost all women were exposed to medication during pregnancy. Exposure to iron and folic acid had a beneficial effect on pregnancy outcome. HDSS proved to be a useful platform to establish a reliable pharmacovigilance system in resource-limited countries. Widening drug safety information is essential to facilitate evidence based risk-benefit decision for treatment during pregnancy, a major challenge with newly marketed medicines
Biochemical basis of permethrin resistance in Anopheles arabiensis from Lower Moshi, north-eastern Tanzania.
No full textBACKGROUND: Development of resistance to different classes of insecticides is a potential threat to malaria control. With the increasing coverage of long-lasting insecticide-treated nets in Tanzania, the continued monitoring of resistance in vector populations is crucial. It may facilitate the development of novel strategies to prevent or minimize the spread of resistance. In this study, metabolic-based mechanisms conferring permethrin (pyrethroid) resistance were investigated in Anopheles arabiensis of Lower Moshi, Kilimanjaro region of north-eastern Tanzania. METHODS: WHO susceptibility test kits were used to detect resistance to permethrin in An. arabiensis. The levels and mechanisms of permethrin resistance were determined using CDC bottle bioassays and microplate (biochemical) assays. In bottle bioassays, piperonyl butoxide (PBO) and s,s,s-tributyl phosphorotrithioate (DEF) were used as synergists to inhibit mixed function oxidases and non-specific esterases respectively. Biochemical assays were carried out in individual mosquitoes to detect any increase in the activity of enzymes typically involved in insecticide metabolism (mixed function oxidases, alpha- and beta-esterases). RESULTS: Anopheles arabiensis from the study area was found to be partially resistant to permethrin, giving only 87% mortality in WHO test kits. Resistance ratios at KT50 and KT95 were 4.0 and 4.3 respectively. The permethrin resistance was partially synergized by DEF and by PBO when these were mixed with permethrin in bottle bioassays and was fully synergized when DEF and PBO were used together. The levels of oxidase and beta-esterase activity were significantly higher in An. arabiensis from Lower Moshi than in the laboratory susceptible strain. There was no difference in alpha-esterase activity between the two strains. CONCLUSION: Elevated levels of mixed function oxidases and beta-esterases play a role in detoxification of permethrin in the resistant An. arabiensis population of Lower Moshi
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