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Biomedical subjects

D K Koech

Publications and source records attributed to D K Koech.

At least 19 recordsLinked to original sources
PubMed2003

CD4T lymphocyte subsets and disease manifestation in children with and without HIV born to HIV-1 infected mothers.

OBJECTIVE: To understand the natural history of HIV-1 infection in children in terms of evolution of childhood clinical manifestations versus the immune status, we prospectively studied children with and without maternally transmitted HIV-1 infection born to mothers infected with HIV-1 for two years between March 1998 and March 2000. DESIGN: A prospective cohort study. SETTING: An institutional children's home. SUBJECTS: Fifty nine children (26 males and 33 females) with and without maternally transmitted HIV-1 infection born to mothers infected with HIV-1 and adopted in institutional children home. METHODS: HIV-1 status of children under nine months was confirmed by polymerase chain reaction(PCR). ELISA for HIV-1 antibody in serum/plasma was used to confirm HIV-infection status for children aged < or = 18 months. Children were visited every three months between March and June 2000. At every visit blood was collected for total white cell count, haemoglobin and CD4+ and CD8+ T cell counts. The institutional doctor routinely examined children and treated all ailments. Clinical data were recorded. MEASURES: HIV-DNA, anti-HIV antibodies, total white blood count, total T cell counts, CD4 and CD8 T cell subset counts, frequency of childhood manifestations of infection. RESULTS: The children were aged between 4.5 and 13 years. The baseline haematological and immunological profiles (mean, mode) were: HIV-1 sero-converters (WBC 7151,7150; HB 11.6, 12.0; CD4+ 686, 795; CD8+ 2168, 1507) and HIV-1 de-seroconverters (mean, mode) were: (WBC 8386, 7150; HB 11.7, 12.8; CD4+ 735, 795; CD8+ 2168, 1507). The commonest causes of illnesses among the HIV-1 children were URTI (85.3%), TB(56.1 %), pneumonia (56.2%), tonsillitis (34.1%), parotiditis (28%) and acute otitis media (25%). The distribution of clinical manifestations was similar between the two categories of children, except URTI, whose prevalence was significantly increased among HIV-1 infected children (p-value=0.006). Among the HIV-1 infected children, only TB, parotiditis, and acute otitis media (AOM) were significantly associated with decreased CD4+ T cell count (p<0.05) resulting from HIV infection. CONCLUSIONS: HIV infection in children predisposes them to common childhood infections that can be used as markers of immune decline. TB, AOM, URTI may be early indicators of suspicion that would enable selective screening for HIV infection in children.

Biomarkers↗
PubMed2002

Maternal immune responses and risk of infant infection with HIV-1 after a short course Zidovudine in a cohort of HIV-1 infected pregnant women in rural Kenya.

OBJECTIVE: To investigate the effects of short-course nucleoside reverse transcriptase inhibitor (Zidovudine, ZDW/AZT) on maternal immune responses and risk of infant infection with HIV-1 among rural-based mothers in western Kenya. DESIGN: A prospective cohort study involving HIV-1 seropositive pregnant mothers and their infants. SUBJECTS: One hundred and seven HIV-1 seropositive asymptomatic pregnant women and their infants. METHODS: After informed consent, the women were enrolled at gestation age between 16-24 weeks. For cultural and economic reasons, all mothers were allowed to breast feed their infants. Short-course antepartum regime of AZT was administered to all mothers starting at 36 weeks gestation until start of labour. Maternal absolute CD4+ T cell subset assays were performed before 3rd trimester (about 36 weeks gestation) and after a 4-week therapy of AZT (at least one month post-nuptially). Infant HIV-1 status was determined by HIV-1 DNA polymerase chain reaction (PCR) on samples sequentially taken at 1, 2, 3, 4, 6 and 9 months and confirmed by serology at 18 months of age. INTERVENTIONS: Antepartum short-course orally administered AZT: 300mg twice-daily starting at 36 weeks gestation until start of labour, 300mg at labour onset and 300mg every three hours during labour until delivery. MAIN OUTCOME MEASURES: Maternal CD4+ T cell counts before and after AZT treatment. Determination of infant HIV-1 infection status. RESULTS: Among 107 women sampled, only 59 received full dose of AZT and thus qualified for present analysis. Of these, 12 infected their children with HIV, while 47 did not. Comparison of CD4+ T cells before and after AZT treatment scored a significant rise in all mothers (P = 0.01). This increase in CD4+ T cells was not significant among mothers who infected their infants with HIV-1 (P = 0.474). However, a significant rise in CD4+ T cells following AZT therapy was observed only in mothers who did not transmit HIV-1 to their infants (P=0.014). CONCLUSION: These data suggest that a rise in the CD4+ T cell counts following short AZT regimen, now widely in use in resource-weak countries, may be evidence of the active suppression of the replication of HIV. However, further studies to examine the multi-factorial effect of CD4+ lymphocytes and pregnancy on MTCT of HIV need to be carried out to help fully explain the effect of AZT on immune response and whether the CD4+T cell count can be used as a true test of immunological normalisation during antiretroviral therapy.

Adult↗
PubMed2001

Transmission blocking vaccine studies in leishmaniasis: I. Lipophosphoglycan is a promising transmission blocking vaccine molecule against cutaneous leishmaniasis.

BACKGROUND: New strategies for control of leishmaniasis is needed as chemotherapy using antimonial drugs is prolonged, expensive, associated with side effects and relapses. Vector control 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 morphology in infected Phlebotomus duboscqi sandflies fed on different groups of BALB/c mice immunised with rgp63, lipophosglycan (LPG) or their cocktail and whole parasite antigens prepared from L. major culture-derived promastigotes. METHODS: BALB/c mice were immunised adequately with Leishmania major-derived antigens namely, crude whole parasite (WPA), recombinant 63 kilodalton glycoprotein (rgp63), LPG and a cocktail composed of rgp63 plus LPG antigens. Laboratory reared Phlebotomus duboscqi sandflies, the natural vector for L. major were later allowed to feed on immunised animals, interrupted and allowed to continue feeding on infected animals for an equal amount of time until they became fully engorged. The sandflies were maintained on apples as a carbohydrate source in an insectary maintained at a temperature of 25 degrees C and 80% relative humidity. Some of the sandflies were dissected on days 2, 4 and 6 after feeding and observed using the light and the transmission electron microscopy for any changes in their gut morphology. The remaining sandflies were all dissected on the sixth day post-feeding and examined for procyclics, nectomonads, haptomonads and metacyclic promastigote forms of Leishmania. RESULTS: Sandflies which had previously fed on WPA, LPG plus rgp63 cocktail and LPG-immunised mice showed the lowest infection rates compared to control sandflies fed on saline immunised mice (p < 0.05). A significant number of procyclic promastigotes, the first developmental form of the parasite in culture as well as in the sandfly was observed in sandflies which fed on LPG-immunised mice (p < 0.05). The dominant parasite form in sandflies which fed on rgp63 or LPG-immunised mice was the nectomonad form but very few of the infective metacyclic forms (p < 0.05). Control sandflies fed on saline immunised or infected mice alone displayed a normal pattern of parasite development up to the metacyclic stage. Studies showed that two possible mechanisms through which immune sera from immunised mice may cause inhibition of parasite development is by exflagellation of nectomonad forms and degeneration of the sandfly midgut epithelium as revealed by light and electron microscopy studies respectively. CONCLUSIONS: This study has shown that immune-mediated transmission blocking may be applied to Leishmania infections. Based on observation of the procyclic promastigotes, the dominance of the nectomonad forms, low infectivity rates in sandflies fed on LPG-immunised mice, we concluded that LPG stands out to be a promising transmission blocking vaccine candidate in leishmaniasis.

Animals↗
PubMed2001

Transmission blocking vaccine studies in leishmaniasis: II. Effect of immunisation using Leishmania major derived 63 kilodalton glycoprotein, lipophosphoglycan and whole parasite antigens on the course of L. major infection in BALB/c mice.

BACKGROUND: Safe, effective and inexpensive vaccines may be the most practical tool for control of any form of leishmaniasis. Leishmaniasis produces a state of pre-immunition which is the underlying mechanism for prolonged immunity to re-infection. Low doses of parasites has been shown to be able to induce protection in mice. It is not known, however, how immune sera from a susceptible host immunised with Leishmania-derived antigens when taken in by the sandfly affects the development and the subsequent transmission of the parasite to naive hosts. OBJECTIVE: To monitor the course of disease in BALB/c mice following challenge using L. major infected P. duboscqi which had previously fed on immunised mice. METHODS: BALB/c mice were immunised adequately with Leishmania major-derived antigens namely, crude whole parasite (WPA), recombinant 63 kilodalton glycoprotein (rgp63), lipophosphoglycan (LPG) and a cocktail composed of rgp63 plus LPG antigens. Laboratory reared Phlebotomus duboscqi sandflies, the natural vector for L. major were later allowed to feed on immunised animals, interrupted and allowed to continue feeding on infected animals for an equal amount of time until they became fully engorged. The sandflies were maintained on apples as a carbohydrate source in an insectary maintained at a temperature of 25 degrees C and 80% relative humidity. On the seventh day these sandflies were used to infect naive BALB/c mice and the course of infection followed for a period of at least three months. RESULTS: Mice infected using sandflies which had previously fed on WPA or rgp63-immunized mice showed disease exacerbation as the infection progressed, whereas those infected using sandflies which had previously fed on LPG-immunised mice had the least lesion sizes compared 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 BALB/c mice was dependent on the infective dose of parasites transmitted by the sandflies. Results from this study suggests that sub-infective doses of the parasite from sandflies previously fed on animals immunised with Leishmania-derived antigens needs to be evaluated for their potential in vaccine development against Leishmania infections.

Animals↗
PubMed1999

Diagnosis of Wuchereria bancrofti infection by the polymerase chain reaction employing patients' sputum.

A preliminary evaluation of the diagnostic potential of a polymerase chain reaction (PCR) assay using diurnally collected sputum from bancroftian filariasis patients is described. A new set of PCR primers amplifying a 254-bp-long sequence termed AccI, derived from a long dispersed repeated sequence and SspI primers previously employed for PCR-based diagnosis were employed in this study with similar results. Of the 34 sputum samples from patients, 32 (94%) were PCR positive. Of the 18 patients with low to high microfilaremia (21-1560 microfilariae/ml), 16 (88.8%) were PCR positive. Of the remaining 16 patients, 6 with very low microfilaremia (2-6 microfilariae/ml) and 10 without microfilaremia, all (100%) were PCR positive. Two PCR-positive cases among the 13 endemic normal individuals tested (15.4%) may represent cases of occult filariasis. PCR amplification was also demonstrated with one PCR-positive sputum aliquot when mixed with 14 sputum aliquots from uninfected (PCR-negative) individuals. The potential diagnostic merits of the sputum-PCR assay are discussed.

Animals↗
PubMed1999

Impact of the crayfish Procambarus clarkii on Schistosoma haematobium transmission in Kenya.

The Louisiana red swamp crayfish, Procambarus clarkii, which was introduced into east Africa in the 1950s or 1960s, has since widely dispersed. Previous work by our group has shown that P. clarkii can reduce populations of the molluscan intermediate hosts of human schistosomes through predatory and competitive interactions. Here, we investigate whether crayfish can reduce populations of Bulinus africanus and consequently, Schistosoma haematobium prevalence in school children. Children from 6 primary schools in the Machakos and Kitui Districts of Kenya were selected for study. Schools were divided into 3 experimental-control pairs. At experimental schools, crayfish were introduced into nearby aquatic habitats harboring Bulinus africanus snails and serving as S. haematobium transmission sites. Snail habitats near control schools did not receive crayfish. Six months after crayfish introduction, all infected children were treated with praziquantel. Children were then monitored quarterly for 2 years, at which time infection and reinfection rates were compared statistically between the paired schools. In one such pair, crayfish failed to establish, resulting in neither snail control nor a reduction in transmission. At the second pair of schools, the numbers of snails were decreased by the presence of crayfish, but a clear difference in infection rates in children could not be detected, primarily because drought conditions kept overall transmission rates low. At the third school pair, crayfish established well in experimental habitats, snail numbers decreased precipitously, and children at the experimental school were significantly less likely to acquire S. haematobium infections than children at the control school. Our results indicate that under certain environmental circumstances, P. clarkii exerts a significant impact on the transmission of human schistosomiasis in Kenya. Important questions remain regarding the impact of P. clarkii on Kenyan freshwater ecosystems, not the least of which is its potential to significantly influence the epidemiology of schistosomiasis in east Africa.

Adolescent↗
PubMed1999

Evaluation of a standardized direct agglutination test (DAT) for the diagnosis of visceral leishmaniasis in Kenya.

A prototype test kit being developed, by the World Health Organization (WHO), for the diagnosis of visceral leishmaniasis (VL) was evaluated in the Baringo district of Rift Valley province in Kenya. The screening of approximately 10,000 individuals for the signs of VL produced 305 suspected cases. These cases and 304 controls matched for sex and age (+/- 2 years) were then tested with the kit, which is based on a direct agglutination test (DAT). The evaluation was a three-stage process. The first stage, the field screening, involved screening filter-paper samples of dried blood from the suspects and controls at a DAT titre of 1:500. The second stage, the laboratory titration, involved screening of the same individuals by testing freshly eluted filter-paper samples at 1:500 to 1:2000 dilution. In the third stage, the full-scale titration, all samples that had been positive at 1:2000 were titrated at 1:500-1:512,000. All the suspects giving DAT titres of 1:2000 or higher were considered positive for VL. This diagnosis was checked, whenever possible, by the examination of smears and/or cultures of splenic aspirates for leishmanial parasites. Those found to be parasitologically positive were put on a standard treatment regime of 20 mg sodium stibogluconate (Pentostam)/kg.day. Although 42 (13.8%) of the 305 clinical suspects investigated were DAT-positive (at 1:2000), it was only possible to take splenic aspirates from 32. Four (12.5%) of these 32 were apparently false-positives by DAT, as no parasites could be detected in their splenic aspirates. The others provided positive smears and cultures (27 cases) or a negative smear but a positive culture (one case). It was possible to re-examine two of the four serologically positive but parasitologically negative VL suspects at a 3-month follow-up: neither had a palpable spleen, one had seroconverted and the other had much lower DAT titre (1:32,000) than when investigated previously (1:128,000). All the parasitologically confirmed cases remained DAT-positive (1:2000) at this follow-up. The low cut-off titre (1:2000) and the simple procedure should make the kit suitable for use by health workers at all levels of primary-health care, including those with limited training and skills, for screening rural communities at risk of VL.

Adolescent↗
PubMed1998

Experimental control of the schistosome-transmitting snail Biomphalaria pfeifferi by the ampullariid snail Pila ovata.

Adults of the African ampullariid snail Pila ovata were examined for their ability to control laboratory populations of the pulmonate snail Biomphalaria pfeifferi, a widespread, intermediate host of the human pathogen Schistosoma mansoni in sub-Saharan Africa. In a 6-week experiment conducted in large (100 x 60 x 60 cm) outdoor tanks containing floating macrophytes (Nymphaea caerula) and initially set up with one adult ampullariid for every three adult pulmonates, the numbers of B. pfeifferi egg masses were always about half those in similar tanks without P. ovata. Although, by week 6, the numbers of B. pfeifferi in the control tanks (without ampullariids) had increased 5-fold, from an initial mean of 30 snails/tank, there was no significant increase in the numbers of B. pfeifferi in the experimental tanks (containing ampullariids). Results of experiments conducted in indoor glass aquaria indicated that adult P. ovata rapidly attacked egg masses or neonates (< 2.5 mm shell diameter) of B. pfeifferi but had no effect on the adults. The adult ampullariids also significantly decreased cover by floating macrophytes over a 6-week period compared with that in similar but ampullariid-free aquaria. This decrease in plant cover is relevant to biological control of the schistosome vectors as macrophytes serve as food, shelter and oviposition sites for pulmonate snails. The present result indicate the ability of P. ovata to inhibit multiplication of B. pfeifferi populations, at least under laboratory conditions, both directly, through predation, and indirectly, by competition for resources. Pila ovata may therefore prove useful in the biological control of medically important, pulmonate snails.

Animals↗
PubMed1997

Quality control of Kato slide counts for Schistosoma mansoni: a review of 12 years' experience in Kenya.

A total of 19 annual or biannual audits were performed over a 12-year period by an independent microscopist on randomized subsamples of Kato slides examined for Schistosoma mansoni eggs by Kenyan microscopists from the Division of Vector-borne Diseases (DVBD). The recounts were invariably lower than the originals owing to some deterioration of the preparations between counts, but the two were strongly correlated: significant regressions of recounts on counts taking up 80-90% of the observed variance. Observer bias differed significantly between microscopists but remained stable over time, whereas repeatability of recounts on counts dropped slightly in periods of maximum work load but did not vary systematically with time. Approximately 7% of the counts and recounts disagreed on the presence or absence of eggs, but less than a third of these were negatives that were found positive on recount. False negatives dropped to 1.3% if duplicate counts were considered. The performance of the Kenyan microscopists was remarkably high and consistent throughout the 12-year period. This form of quality control is suitable for projects where limited funds preclude full-time supervisors using more sophisticated systems.

Animals↗
PubMed1997

An evaluation of surveillance of malaria at primary health care level in Kenya.

As less than twenty five per cent of persons suffering from malaria seek formal treatment in most of sub-Saharan Africa, Facility-based morbidity statistics are inadequate for monitoring malaria control programmes. This explorative study assessed whether a health centre equipped with a microscope and trained personnel could monitor malaria transmission within its catchment area. The study was conducted at Chemase Health Centre in Nandi District in Kenya, an area holoendemic for malaria with Anopheles gambiae as the main vector and Plasmodium falciparum as the commonest cause of malaria. From first August to 31 October 1991, first seven children under five years of age on each working day accompanied by their mothers to the maternal and child health clinic were studied. A general examination was performed by a Registered Clinical Officer (Medical Assistant) and thin and thick blood smears made, stained with Giemsa stain and examined for malaria parasites by a Medical Laboratory Technologist. Mothers were interviewed by enrolled community nurses on antimalarial measures they were using in their homes. Four hundred and fifty five children mostly under five years of age, consisting of 48.1% males and 51.9% females, were studied. Malaria parasites were present in 209 (45.9%) blood smears of the children. The percentage of blood smears positive for malaria parasites was high in children below 36 months of age. There was a tendency for low percentage of blood smears positive for malaria in children whose mothers reported using mosquito nets or insecticide sprays. The study did not interrupt the routine of the health centre. Periodic monitoring of new malaria illnesses. and percentage of blood smears positive for malaria parasites in children aged 0 to 35 months should be introduced into health centre practice in Kenya. This catchment area approach could be used to monitor malaria control programmes as well as predicting malaria epidemics.

Age Distribution↗
PubMed1996

A simple method for maintaining, detecting and recovering virulent Leishmania donovani in hamsters.

The ability of hamsters (Mesocricetus auratus) to retain amastigotes of Leishmania donovani at cutaneous sites was examined. Following intradermal inoculation of L. donovani stationary phase culture promastigotes in fore and hind footpads, nasal area and belly skin, cultures of aspirates taken fortnightly from these sites showed that amastigotes can survive in the skin for up to 10 months without visceralizing. Hairless cutaneous sites were better at retaining L. donovani amastigotes than the hairy belly skin. L. donovani promastigotes cultivated from aspirates of sites of inoculation were highly virulent. The skin is suggested as one of the sites where viscerotropic L. donovani can remain cryptic for a long time before the infection either visceralizes or is aborted. Skins of hamsters when inoculated intradermally can serve as an easy site for maintaining, detecting and recovering virulent L. donovani without killing the hamster.

Animals↗
PubMed1996

Animal reservoirs of leishmaniasis in Marigat, Baringo District, Kenya.

A total of 1128 rodents belonging to seven genera were examined for leishmanial parasites over a period of sixteen months. Parasites were isolated from 36 (12.5%) Tatera robusta, 3 (0.5%) Arvicanthis niloticus, and 2 (0.8%) Mastomys natalensis. All isolates were characterised by isoenzyme analysis using nine enzymes. The enzymes examined were: malate dehydrogenase (MDH), phosphoglucomutase (PGM), glucose phosphate isomerase (GPI), isocitrate dehydrogenase (ICD), nucleoside hydrolase (NH), glucose 6-phosphate dehydrogenase (G6PD), mannose phosphate isomerase (MPI), malic enzyme (ME) and 6-phosphogluconate dehydrogenase (6PGD). The enzyme profiles from these isolates were compared with those from Leishmania reference strains and also with isolates of Leishmania major from man and sandfly, P. duboscqci from the same area. All the isolates except one from a Mastomys were identified as L. major. The isolate from Mastomys was trypanosome-like and remains unidentified. The results in this study show that Tatera robusta is the main reservoir of cutaneous leishmaniasis in Baringo District. None of the animals trapped were found infected with Leishmania donovani suggesting that rodents do not play a role in the transmission of visceral leishmaniasis in this area.

Animals↗
PubMed1996

Some emerging issues on the malaria problem in Kenya.

Malaria in Kenya has been characterised by marked variability in its epidemiology, partly reflecting the obstacles and progress made in the control strategies. The impact of anti-vector activities in the 1970s and before have been observed for variable lengths of time afterwards. Malaria has re-emerged in areas previously with little or no transmission. The recovery of infective Anopheles gambiae vector in higher altitudes affirms the potential for transmission in areas where epidemics have been known to occur. Morbidity and mortality patterns in the otherwise endemic lowlands have become increasingly severe, an observation which would be attributed to the increasing inefficacy of chloroquine. Efforts to promote personal protection suffer substantial setbacks in sustainability inspite of apparent acceptability. There are indications that the mosquito vector susceptibility to permethrin and other insecticides will now require continual monitoring in order to detect development of significant resistance. In this communication, we review some emergent issues in malaria transmission in Kenya and the potential for control as adduced from historical and contemporary perspectives.

Altitude↗
PubMed1996

Field trial of permethrin impregnated sisal curtains in malaria control in western Kenya.

A trial to determine the effectiveness of sisal eaves-curtains impregnated with permethrin for malaria control was conducted in the malaria holoendemic western Kenya between 1991 and 1993. Indoor resting densities of Anopheles gambiae s.l. and Anopheles funestus were reduced by 90.9% and 93.8% respectively in protected houses. The entomological inoculation rate (EIR) was reduced by 72% in the intervention village. There was no significant reduction in vector longevity or survival as shown by the sustained high sporozoite rates. Monthly bioassays for retained insecticidal potency of permethrin on the fibre indicated vector mortality rates above 95% over the period. Of 283 and 240 children followed up from the intervention and control villages, a mean malaria prevalence of 43.2% and 52.2% respectively was observed over the trial period (p < 0.01). The prevalence rose to 73.5% and 75.7% (p = 0.541) respectively after the removal of the curtains. No significant differences were observed in the mean parasite density between the groups or between the proportions with parasite density exceeding 2,500 per microliter and with or without fever. The prevalence of splenomegaly was significantly lower in the intervention group compared to the control, both during (p = 0.005) and after the intervention (p < 0.001). There was no significant difference in the mean change in haematocrit at the end of the intervention. We observe that permethrin impregnated sisal curtains effectively retain permethrin, alter favourably the indoor vector density and EIR, and could provide a reduction in malaria prevalence.

Animals↗
PubMed1995

The chemotactic effect of Phlebotomus duboscqi (Diptera: Psychodidae) salivary gland lysates to murine monocytes.

The possibility that salivary gland lysates of Phlebotomus duboscqi are able to attract vertebrate monocytes was investigated. In vitro studies showed that salivary gland lysates of P. duboscqi, the vector of Leishmania major in Kenya, are chemotactic to mouse peritoneal monocytes. This attraction of monocytes by vector salivary gland lysates may form part of the mechanisms through which sandfly saliva ensures successful parasitization of macrophages in a susceptible host by Leishmania parasites.

Animals↗
PubMed1995

Vaccination of vervet monkeys against cutaneous leishmaniosis using recombinant Leishmania 'major surface glycoprotein' (gp63).

Vervet monkeys (Cercopithicus aethiops) were shown to give a positive delayed-type hypersensitivity (DTH) reaction to gp63, a major surface glycoprotein of Leishmania parasites, and also produce antibodies to the molecule following a triple vaccination with a total dose of 150 micrograms of recombinant gp63 mixed with Bacille Calmette Guerin (BCG). However, peripheral blood leucocytes (PBL) from these animals neither proliferated nor produced any interferon-gamma (IFN-gamma) following in vitro stimulation with the antigen. Analysis of lymphocyte subsets following vaccination did not reveal any striking phenotypic alteration of cellular sub-populations in PBL. When vaccinated animals were rechallenged, via the needle, with virulent Leishmania major promastigotes containing salivary gland extracts from vector sandflies, only partial protection was achieved. We concluded from these studies that rgp63 produced in Escherichia coli is a safe vaccine molecule which gives only partial protection following vaccination in the vervet monkey host. The molecule requires further improvement for vaccine and/or immunodiagnosis application.

Animals↗
PubMed1993

Leishmania donovani-reactive Th1- and Th2-like T-cell clones from individuals who have recovered from visceral leishmaniasis.

Infections in humans by Leishmania donovani parasites can result in a fatal disease, visceral leishmaniasis (VL), or in a self-limiting asymptomatic infection. In murine models of the infection employing Leishmania major, the course of the disease can be directed into a VL-like syndrome by interleukin-4 (IL-4)-producing Th2 cells, or cure may result by Th1 cells secreting gamma interferon (IFN-gamma). The present study examined the potential of human T cells to generate Th1 or Th2 responses to L. donovani. The profiles of IFN-gamma, IL-4, and lymphotoxin secretion after antigen stimulation were analyzed in a panel of L. donovani-reactive CD4+ human T-cell clones generated from individuals who had recovered from VL after antimonial treatment. Two of the T-cell clones produced large amounts of IL-4 without production of IFN-gamma, seven clones produced both IFN-gamma and IL-4, and eight produced only IFN-gamma. This is the first report of a Th1- and Th2-type response in human leishmaniasis. These results suggest that in analogy with murine models, there is a dichotomy in the human T-cell response to L. donovani infections. Preferential activation of IL-4-producing Th2-like cells may be involved in the exacerbation of human VL, whereas activation of IFN-gamma-producing Th1 cells may protect the host from severe disease. Identification of leishmanial antigens activating one or the other type of T cells will be important in the development of vaccines against leishmaniasis.

Animals↗