Plasmodium falciparum gametocyte carriage in asymptomatic children in western Kenya.

Contains fulltext : 58662.pdf ( ) (Open Access)BACKGROUND: Studies on Plasmodium falciparum gametocyte development and dynamics have almost exclusively focused on patients treated with antimalarial drugs, while the majority of parasite carriers in endemic areas are asymptomatic. This study identified factors that influence gametocytaemia in asymptomatic children in the absence and presence of pyrimethamine-sulphadoxine (SP) antimalarial treatment. METHODS: A cohort of 526 children (6 months-16 years) from western Kenya was screened for asexual parasites and gametocytes and followed weekly up to four weeks. Children with an estimated parasitaemia of > or =1,000 parasites/microl were treated with SP according to national guidelines. Factors associated with gametocyte development and persistence were determined in untreated and SP-treated children with P. falciparum mono-infection. RESULTS: Gametocyte prevalence at enrollment was 33.8% in children below five years of age and decreased with age. In the absence of treatment 18.6% of the children developed gametocytaemia during follow-up; in SP-treated children this proportion was 29.8%. Age, high asexual parasite density and gametocyte presence at enrollment were predictive factors for gametocytaemia. The estimated mean duration of gametocytaemia for children below five, children from five to nine and children ten years and above was 9.4, 7.8 and 4.1 days, respectively. CONCLUSION: This study shows that a large proportion of asymptomatic untreated children develop gametocytaemia. Gametocytaemia was particularly common in children below five years who harbor gametocytes for a longer period of time. The age-dependent duration of gametocytaemia has not been previously shown and could increase the importance of this age group for the infectious reservoir

The presence of Plasmodium falciparum gametocytes in human blood increases the gravidity of Anopheles gambiae mosquitoes

We conducted a field study in an area of endemic malaria transmission in western Kenya to determine whether mosquitoes that feed on gametocyte-infected blood but do not become infected have reduced or enhanced fecundity in comparison to mosquitoes fed on uninfected blood. Fifteen paired membrane-feeding experiments were conducted in which two strains of Anopheles gambiae mosquitoes were simultaneously fed on either Plasmodium falciparum¿infected blood from children or uninfected control blood from adults. The presence of noninfecting gametocytes in blood increased the probability that An. gambiae would produce eggs after one blood meal by sixfold (odds ratio for control relative to infected blood group 0.16; 95% CI 0.10¿0.23). This result could not be explained by variation in blood meal size or hemoglobin content between hosts. When children cleared their infections, the difference in gravidity between mosquitoes fed on their blood and uninfected adults disappeared, suggesting this phenomenon is due to the presence of Plasmodium gametocytes in blood and not to host-specific factors such as age. This result was observed in two mosquito strains that differ in their innate fecundity, suggesting it may apply generally. To our knowledge, this is the first time that Plasmodium has been implicated as enhancing vector gravidit

TRANSMISSION BLOCKING VACCINE STUDIES IN LEISHMANIASIS: 11. EFFECT OF IMMUNISATION USING LEISHMANIA MAJOR DERIVED 63 KILODALTON GLYCOPROTEIN, LIPOPHOSPHOGLYCAN AND WHOLE PARASITE ANTIGENS ON THE COURSE OF L. MAJOR INFECTION IN BALBIC MICE

Background: Safe, effective and inexpensive vaccines may be the most practical tool for controlof any form of leishmaniasis. Leishmaniasis produces a state of pre-immunition which is theunderlying mechanism for prolonged immunity to re-infection. Low doses of parasites has beenshown to beable to induce protection in mice. It is not known, however, how immunesel-a froma susceptible host imrnunised with Leishmania-derived antigens when taken in by the sandflyaffects the development and the subsequent transmission of the parasite to naive hosts.Objective: To monitor the course of disease in BALBlc mice following challenge using L.rnajor infected P. duboscqi which had previously fed on immunised mice.Methods: BALBIc mice were immunised adequately withLeishrnania major-derived antigensnamely, crude whole parasite (WPA), recombinant 63 kilodalton glycoprotein (rgp63),lipophosphoglycan (LPG;) ancl a cocktail composed of rgp63 plus LPG antigens. Laboratoryreared Phlebotornus duboscqi sandflies, the natural vector for L. major were later allwwed tofeed on immunised animals, interrupted and allowed to continue feeding on infected animalsfor an equal amount of time until they became fully engorged. The sandflies were maintainedon apples as a carbohydrate source in an insectary maintained at a temperature of 2S°C and80% relative humidity. On the seventh day these sandflies were used to infect naivc B:ALB/c mice and the course of infection followed for a period of at least three months.Results: Mice infected usingsandflies which had previously fed on WPA or rgp63-immunizedmice showed disease exacerbation as the infection progressed, whereas those infected usingsandflies which had previously fed on LPG-immunised mice had the least lesion sizescompared to control mice infected using sandflies which had fed on saline immunised mice(p<0.05).Conclusions: Results from this study indicate that the course of L. major infection in BALBIc mice was dependent on the infective dose of parasites transmitted by the sandflies. R~:sultsfrom this study suggests that sub-infective doses of the parasite from sandflies previously fedon animals immunised with Leishmania-derived antigens needs to be evaluated for theirpotential in vaccine development against Leishmania infections

TRANSMISSION BLOCKING VACCINE STUDIES IN LElISHMANIASIS: I . LIPOPHOSPHOGLYCAN IS A PROMISING TRANSMISSION BLOCKING VACCINE MOLECULE AGAINST CUTANEOUS LEISHMANIASIS

Background: New strategies for control of leishmaniasis is needed as chemotherapy usingantimonial drugs is prolonged, expensive, associated with side effects and relapses. Vectorcontrol has limitations and a vaccine which may be the best approach is not available.Objectives: To assess the level of inhibition of promastigote development and gut morphologyin infected Phlebotomus dubotcqi sandflies fed on different groups of BALBlc mice immunisedwith rgp63, lipophosglycan (LPG) or their cocktail and whole parasite antigens preparedfrom L. major culture-derived promastigotes.Methods: BALBlc mice were immunised adequately with Leishmania major-derived antigensnamely, crude whole para5ite ( WPA), recombinant 63 kilodalton glycoprotein (rgp63), LPG anda cocktail composed of rgp63 plus LPG antigens . Laboratory reared Phlebotomus duboscqisandflies, the natural vector for I, major were later allowed to feed on immunised animals,interrupted and allowed to continue feeding on infected animals for an equal amount of tirne untilthey became fully engorged. The sandflies were maintained on apples as a carbohydrate sourcein an insectary maintained at a temperature of 2S°C and 80% relative humidity. Some of thesandflies were dissected on days 2,4 and 6 after feeding and observed using the light :and thetransmission electron microscopy for any changes in their gut morphology. The remainingsandflies werealldissectdon thesixthday post-feeding and examinedfor procyclics,necton~onads,haptomonads and metacyclic promastigote forms of Leishmania.Results: Sandflies which had previously fed on WPA, LPG plus rgp63 cocktail ant1 LPGimmunisedmice showed the lowest infection rates compared to control sandflies fed on salineimmunised mice (p<0.05). A significant number of procyclic promastigotes, th~e firstdevelopmental form of the parasite in culture as well as in the sandfly was observed insandflies which fed on LPG-immunised mice (pe0.05). The dominant parasite form insandflies which fed on rgp63 or LPG-immunised mice was the nectomonad form but very fewof the infective metacyclic forms (pe0.05). Control sandflies fed on saline immunised orinfected mice alone displayed a normal pattern of parasite development up to the metacyclicstage. Studies showed that two possible mechanisms through which immune sera fromimmunised mice may came inhibition of parasite development is by exflagellation ofnectomonad forms and degeneration of the sandfly midgut epithelium as revealed by lightand electron microscopy studies respectively.Conclusions: This studj has shown that immune-mediated transmission blocking rnay beapplied to Leishmania infections. Based on observation of the procyclic promastigoles, thedominance of the nectomonad forms, low infectivity rates in sandflies fed on LPG-immunisedmice, we concluded that LPG stands out to be a promising transmission blocking vaccinecandidate in leishmaniasis

Treatment failure of pyrimethamine-sulphadoxine and induction of Plasmodium falciparum gametocytaemia in children in western Kenya.

Item does not contain fulltextSub-Saharan Africa faces increasing levels of resistance of Plasmodium falciparum parasites to the first-line drug pyrimethamine-sulphadoxine (SP). Successful treatment with SP is reported to induce gametocytes and drug resistance may further increase gametocytaemia after treatment. Treatment success, gametocyte prevalence and gametocyte density were determined in 224 asymptomatic children in western Kenya on day 7 after treatment with SP. Treatment failure (R2 or R3 resistance) was observed in 22% of the children. The relative risk to show gametocytes on day 7 after treatment in children with treatment failure was 4.1 (95% CI 1.4-11.6) times higher compared to children with a sensitive infection, after adjustment for age and trophozoite density at the start of treatment. In addition, the gametocyte density was also higher upon SP treatment failure. These findings are reason for concern, as the increased gametocyte prevalence and density after SP treatment failure may increase the spread of SP-resistant strains in the population

Plasmodium falciparum malaria disease manifestations in humans and transmission to Anopheles gambiae: a field study in Western Kenya

Transmission of the malaria parasite Plasmodium is influenced by many different host, vector and parasite factors. Here we conducted a field study at Mbita, an area of endemic malaria in Western Kenya, to test whether parasite transmission to mosquitoes is influenced by the severity of malaria infection in its human host at the time when gametocytes, the transmission forms, are present in the peripheral blood. We examined the infectivity of 81 Plasmodium falciparum gametocyte carriers to mosquitoes. Of these, 21 were patients with fever and other malaria-related symptoms, and 60 were recruited among apparently healthy volunteers. Laboratory-reared Anopheles gambiae s.s. (local strain) were experimentally infected with blood from these gametocyte carriers by membrane-feeding. The severity of the clinical symptoms was greater in febrile patients. These symptomatic patients had higher asexual parasitaemia and lower gametocyte densities (P=0·05) than healthy volunteers. Ookinete development occurred in only 6 out of the 21 symptomatic patients, of which only 33·3% successfully yielded oocysts. The oocyst prevalence was only 0·6% in the 546 mosquitoes that were fed on blood from this symptomatic group, with mean oocyst intensity of 0·2 (range 0–2) oocysts per mosquito. In contrast, a higher proportion (76·7%) of healthy gametocyte carriers yielded ookinetes, generating an oocyst rate of 12% in the 1332 mosquitoes that fed on them (mean intensity of 6·3, range: 1–105 oocysts per mosquito). Statistical analysis indicated that the increased infectivity of asymptomatic gametocyte carriers was not simply due to their greater gametocyte abundance, but also to the higher level of infectivity of their gametocytes, possibly due to lower parasite mortality within mosquitoes fed on blood from healthy hosts. These results suggest that blood factors and/or conditions correlated with illness reduce P. falciparum gametocyte infectivity

Biological cost of tolerance to heavy metals in the mosquito Anopheles gambiae

The global rate of heavy metal pollution is rapidly increasing in different habitats. Anopheles malaria vector species appear to tolerate many aquatic habitats with metal pollutants, despite their normal proclivity for ‘clean’ water (i.e., generally water free of organic matter). Investigations were conducted to establish whether there are biological costs for tolerance to heavy metals in Anopheles gambiae Giles sensu stricto (Diptera: Culicidae), and to assess the potential impact of heavy metal pollution on mosquito ecology. Anopheles gambiae s.s. were selected for cadmium, copper or lead tolerance through chronic exposure of immature stages to solutions of the metals for three successive generations. Biological costs were assessed in the fourth generation by horizontal life table analysis. Tolerance in larvae to cadmium (as cadmium chloride, CdCl2), copper (as copper II nitrate hydrate, (Cu (NO 3 ) 2. 2·5H 2 O) and lead (as lead II nitrate, (Pb (NO 3 ) 2 ), monitored by changes in LC 50 concentrations of the metals, changed from, 6.07, 12.42 and 493.32 μg/L to 4.45, 25.02 and 516.69 μg/L, respectively, after 3 generations of exposure. The metal-selected strains had a significantly lower magnitude of egg viability, larval and pupal survivorship, adult emergence, fecundity and net reproductive rate than the control strain. The population doubling times were significantly longer and the instantaneous birth rates lower in most metal-selected strains relative to the control strain. Our results suggest that although An. gambiae s.s . displays the potential to develop tolerance to heavy metals, particularly copper, this may occur at a significant biological cost, which can adversely affect its ecological fitness

Feeding and survival of the malaria vector Anopheles gambiae on plants growing in Kenia

The propensity of the malaria vector mosquito Anopheles gambiae Giles (Diptera: Culicidae) to ingest sugars from various plants, and subsequent survival rates, were assessed with laboratory-reared males and females offered eight species of plants commonly cultivated and/or growing wild in western Kenya. In cages (no-choice bioassay), mosquitoes given the opportunity to feed on castorbean (Ricinus communis L.) had the longest survival times (mean and median survival time of 6.99 ± 0.23 and 5.67 ± 0.17 days, respectively), comparable to mosquitoes given 6% glucose (mean and median survival time of 8.70 ± 0.23 and 6.67 ± 0.33 days, respectively). Survival rates of An. gambiae were low on the other plants, comparable to mosquitoes given only water. Three plants: sweet potato (Ipomoea batatas L.), wild sage (Lantana camara L.) and castorbean provided levels of sugar ingestion by both sexes of An. gambiae detectable using the cold anthrone method, showing a positive correlation between median survival and sugar consumption (Spearman rank correlation coefficient = 0.905, P <0.0001). Equal numbers of males and females were released in an enclosed semi-field screenhouse system containing a range of local plants, but no host for blood, and allowed to feed ad libitum: 6.7 ± 0.5% (11/64) of those recaptured were found to contain detectable fructose (all females). Common plants are clearly a viable source of nutrition for adult female An. gambiae, as well as males, and may constitute and important resource for this important malaria vecto