Microgeographic variations in Burkitt's lymphoma incidence correlate with differences in malnutrition, malaria and Epstein-Barr virus.

BACKGROUND: Endemic Burkitt's lymphoma (eBL) has been associated with Epstein-Barr virus (EBV) and holoendemic Plasmodium falciparum malaria. But recent evidence suggests that other risk factors are involved. METHODS: We hypothesised that selenoprotein glutathione peroxidase (GPx), a surrogate of nutritional status, is an important biomarker for eBL risk. We measured plasma GPx, anthropometric markers of malnutrition, EBV viral loads and malaria parasitaemia in children aged 1-9 years (n=258) from two locations in Nyanza Province, Kenya, with higher-than-expected and lower-than-expected incidence of eBL. The study participants were malaria asymptomatic children from the community. RESULTS: Children from eBL high-incidence areas had significantly lower GPx levels, high EBV viral load and more evidence of chronic malnutrition than children from eBL low-incidence areas (all P<0.001). Additionally, GPx levels were significantly lower in children with the highest EBV viral load and for those with P. falciparum infections (P=0.035 and P=0.004, respectively). CONCLUSIONS: These results suggest that selenium deficiency may be a risk factor for eBL.

Distinct pattern of class and subclass antibodies in immune complexes of children with cerebral malaria and severe malarial anaemia.

Plasmodium falciparum infection can lead to deadly complications such as severe malaria-associated anaemia (SMA) and cerebral malaria (CM). Children with severe malaria have elevated levels of circulating immune complexes (ICs). To further investigate the quantitative differences in antibody class/subclass components of ICs in SMA and CM, we enrolled 75 children with SMA and 32 children with CM from hospitals in western Kenya and matched them to 74 and 52 control children, respectively, with uncomplicated symptomatic malaria. Total IgG IC levels were always elevated in children with malaria upon enrollment, but children with CM had the highest levels of any group. Conditional logistic regression showed a borderline association between IgG4-containing IC levels and increased risk of SMA (OR = 3.11, 95% CI 1.01-9.56, P = 0.05). Total IgG ICs (OR = 2.84, 95% CI 1.08-7.46, P = 0.03) and IgE-containing ICs (OR = 6.82, OR 1.88-24.73, P < or = 0.01) were associated with increased risk of CM. These results point to differences in the contribution of the different antibody class and subclass components of ICs to the pathogenesis of SMA and CM and give insight into potential mechanisms of disease.

Determinants of under nutrition among school age children in a Nairobi peri-urban slum.

BACKGROUND: Malnutrition is a major public health concern affecting a significant number of school age children influencing their health, growth and development, and school academic performance. OBJECTIVE: To establish the determinants of under nutrition among school age children between 6-12 years in a low-income urban community. DESIGN: A cross-sectional descriptive study. SETTING: Kawangware peri-urban slum, Nairobi, Kenya. SUBJECTS: Three hundred and eighty four school children aged 6-12 years. RESULTS: A total of 4.5% were wasted, 14.9% underweight and 30.2% stunted. The children who were over nine years of age were more underweight (72.4%, p = 0.000) and stunted (77.2%, p = 0.000) than those below eight years. The girls were more wasted (29.1%, p = 0.013) than the boys (18.2%), whereas the boys were more stunted (65.7%, p = 0.003) than the girls (50.7%). The other variables found to have had significant association with the nutritional status of the children were: monthly household income (p = 0.008), food prices (p = 0.012), morbidity trends (p = 0.045), mode of treatment (p = 0.036) and school attendance (p = 0.044). CONCLUSION: The findings of this study show evidently that there is under nutrition among school age children, with stunting being the most prevalent. The Ministry of Education and Ministry of Health therefore need to develop policies which can alleviate under nutrition among school age children. We also recommend that awareness be created among the school age children, parents and teachers, on the dietary requirements of both boys and girls.

Home Management of Diarrhea among Underfives in a Rural Community in Kenya: Household Perceptions and Practices

Introduction: Diarrheal disease is a major cause of morbidity and mortality among under-fives especially in rural and peri-urbancommunities in developing countries. Home management of diarrhea is one of the key household practices targeted for enhancement in the Community Integrated Management of Childhood Illness (C-IMCI) strategy. Objective: The aim of this study was to determine the perceptions of mothers/caregivers regarding the causes of diarrhea among under-fives and how it was managed in the home before seeking help from Community Health Workers or health facilities. Design: A household longitudinal study was conducted in Nyando district; Kenya in 2004-2006 adopting both qualitative and quantitative approaches. Subjects: A total of 927 mothers/caregivers of under-fives participated in the study. Main outcome measures: Perceived causes of childhood diarrhoea; action taken during diarrhea; fluid intake; recognition of signs of dehydration; feeding during convalescence; adherence to treatment and advice. Results: Majority of the respondents 807(87.1) reported that their children had suffered from diarrhea within the last 2 weeks before commencement of the study. Diarrhea was found to contribute to 48of child mortality in the study area. Perceived causes of diarrhea were: unclean water 524(55.6); contaminated food 508(54.9); bad eye 464 (50.0); false teeth 423(45.6) and breast milk 331(35.8). More than 70of mothers decreased fluid intake during diarrhea episodes. The mothers perceived wheat flour; rice water and selected herbs as anti-diarrheal agents. During illness; 239(27.8) of the children were reported not to have drunk any fluids at all; 487(52.5) drunk much less and only 93(10.0) were reported to have drunk more than usual. A significant 831(89.6) withheld milk including breast milk with the notion that it enhanced diarrhea. Conclusion: Based on these findings; there is need to develop and implement interactive communication strategies for the health workers and mothers to address perceptions and miscon- ceptions and facilitate positive change in the household practice on management of diarrhea among under-fives

Role of child health clinics in promoting use of insecticide-treated nets among children under five years in Nyamira district, Kenya.

BACKGROUND: Maternal child health clinics are the ideal places to meet and sensitise all the mothers with children under five years on the use of insecticide-treated nets in the prevention of malaria. OBJECTIVE: To determine whether child health clinics are promoting the use of insecticide-treated nets in malaria prevention among children. DESIGN: Cross-sectional, descriptive study. SETTING: Eight health centres in Nyamira District. SUBJECTS: Four hundred mothers bringing their children aged five years and below to the child health clinics between August and October 2003. RESULTS: Two hundred and eighty four mothers (71%) had not received any information on the use of insecticide-treated nets while at the MCH clinics. Only 50% of the clinics had bed nets/ITNs posters mounted on their premises. Out of those clinics with posters, only in 50% of them had bed net posters seen. Very few mothers (36.2%) had seen the bed net/ITNs posters. None of the healthcare providers used bed net/ITNs posters to educate the mothers. None of the insecticide-treated net leaflets were issued. CONCLUSION: Despite the fact that maternal child health clinics were well placed in promoting the use of insecticide-treated nets to the mothers who brought their under five year children, very little was being done to this effect. MCH clinics need to be more aggressive in motivating mothers to use insecticide-treated nets.

Mothers' knowledge on malaria and vector management strategies in Nyamira District, Kenya.

BACKGROUND: Maternal knowledge on malaria and vector control measures are important because they enable mothers make an informed choice on the method of malaria control to use for their children under five years. OBJECTIVE: To determine the mothers' knowledge on malaria and vector control measures particularly use of insecticide treated nets. DESIGN: Cross sectional, descriptive study. SETTING: Eight health centres in Nyamira District, Kenya. SUBJECTS: Four hundred mothers bringing their children aged five years and below to the child health clinics. RESULTS: Mothers had a problem of defining malaria. Majority of them (91.8%) recognised mosquitoes as causing malaria. About 30% associated malaria with dirt, dirty compounds, dirty food/utensils, unboiled water and uncooked food. Many mothers identified basic malaria symptoms such as headache (70%), fever (68.8%), cold (65%), body or joint pain (65.5%) and abdominal pain/ vomiting (0.5%). Mothers (40.8%)were less knowledgeable on most vulnerable groups to malaria. A large number of mothers (55.5%) used nothing to protect themselves and their children under five years from mosquito bites. The radio (69%) tuned in the local language, played a very important role in the mothers' knowledge about the use of mosquito nets and insecticide treated nets. CONCLUSION: By virtue of the fact that majority of mothers (91.8%) recognised that mosquitoes caused malaria, it was an indicator that they were knowledgeable of its existence. Mothers were also informed of most of the malaria vector control measures particularly use of bed nets and insecticide treated nets. However, the general usage of those measures was very low.

Vaccinations with live-attenuated Leishmania major promastigotes and challenge infection with L. major in BALB/c mice.

BACKGROUND: Currently there is no vaccine available in use against any form of leishmaniases worldwide. OBJECTIVE: To assess potential of a live-attenuated Leishmania major promastigates, for protection against a challenge infection with L. major in BALB/c mice. DESIGN: A laboratory based study. SETTING: Study was carried out at Centre for Biotechnology Research and Development, Kenya Medical Research Institute, Nairobi. RESULTS: The greatest protection against challenge with L. major was seen in mice immunised with live parasites (P < 0.001) compared to vaccinations with heat killed or soluble antigens. In general, immunised mice produced high level of antileishmanial antibodies and T cell stimulation to their respective antigens. CONCLUSIONS: Our live-attenuated parasites produced by serial sub-culture of L. major parasites 118 times showed the capacity to induce appropriate cell-mediated immune responses and protection against L. major infection in BALB/c mice. Data also suggests that these parasites do not revert to virulence when injected subcutaneously in mice.

Maternal use of insecticide-treated nets in the prevention of malaria among children under five years in Nyamira district, Kenya.

BACKGROUND: Insecticide treated nets (ITNs) have been proved as one of the most effective ways of reducing malaria morbidity and mortality in children and pregnant women. Proper use and care of insecticide treated nets reduce malaria health risk to children. OBJECTIVE: To determine maternal use of insecticide treated nets in the prevention of malaria among children under five years in Nyamira district. DESIGN: Cross-sectional, descriptive study. SETTING: Eight health centres in Nyamira district. SUBJECTS: Four hundred mothers bringing their children aged five years and below to the child health clinics between August and October 2003. RESULTS: There was very low usage of mosquito nets (33.8%) with the proportion of under five using bed nets and insecticide treated nets being 33.3% and 23.8% respectively. The possibility of a mother having an insecticide treated net was significantly related with the level of education of the mother (p = 0.003), occupation (p = 0.001) and knowledge (p = 0.000). Among the reasons given by mothers regarding non usage of insecticide treated nets included lack of money, they were expensive, ignorance and carelessness. CONCLUSION: There was low use of ITNs (23.8%) among children. There is need for health information, education and communication campaigns to sensitise the mothers on most risk groups from malaria so as to create awareness of who needed more protection through use of ITNs. There is need for ITNs intervention projects for malaria prevention in the area.

Anti-plasmodial activity of some Kenyan medicinal plant extracts singly and in combination with chloroquine.

Sixty organic and aqueous extracts of eleven plants used for the control of malaria by local communities in Kisii District, Kenya were screened for in vitro anti-plasmodial activity. The plants selection was based on existing ethnobotanical information and interviews with local communities. The extracts were tested against chloroquine sensitive and resistant laboratory adapted strains of Plasmodium falciparum. The study revealed that 63.6% of the plants were active (IC50 < or = 100 microg/mL). Extracts of four plants, Ekebergia capensis, Stephania abyssinica, Ajuga remota and Clerodendrum myricoides gave IC50 values below 30 microg/mL against both chloroquine sensitive and resistant P. falciparum strains. Combination of extracts of E. capensis and C. myricoides with chloroquine against the multi-drug resistant P. falciparum isolate (V1/S) revealed synergistic effect. The plants which showed activity may be useful as sources for novel anti-plasmodial compounds.

Leishmania major-Phlebotomus duboscqi interactions: inhibition of anti-LPG antibodies and characterisation of two proteins with shared epitopes.

OBJECTIVES: To assess the effect of monoclonal antibodies (MABS) raised against L. major derived LPG on L. major development in vitro and in its natural vector P. duboscqi. Also determine whether LPG molecule and the sand fly the gut lysates have shared epitopes. DESIGN: A laboratory based study. SETTING: Colony bred P. duboscqi sand flies and all other experiments were done under laboratory conditions. METHODS: Laboratory reared sand flies were allowed to feed beneath a blood filled membrane feeder containing 1 x 10(6) amastigotes in 20 microl mixed with 0.5 ml of defibrinated rabbit blood with a 1:100 dilution of anti-LPG MABS. Control blood contained a similar number of amastigotes but no MABS. At least five female previously fed sand flies were later dissected on days two, four, and six post-feeding and examined for promastigote forms and parasite loads in the sand fly mid gut. In vitro, the same number of amastigotes in 100 microl complete Schneider's Drosophila medium was mixed in a 96 well plate with either 100 microl of 1:100 anti-LPG MABS, 1:1000 anti LPG MABS or undiluted sera from L. major infected mice. The control well contained a similar number of amastigotes but no antibodies added. Following an overnight incubation in a CO2 incubator at 37 degrees C and growth at 26 degrees C, parasites were assessed at 3, 6 and 24 hour intervals for changes in their developmental forms. RESULTS: 1:100 dilution of anti-LPG MABS when mixed with amastigotes were effective in reducing L. major development at the early log phase or procyclic stage both in vitro and within the sand fly (p<0.05). The control cultures or sand flies that fed on amastigotes alone and no MABS supported full parasite development up to the metacyclic stage. Results also showed that flies, which had fed on MABS, showed low parasitemia levels of 2+, compared to a high density of 4+ for their controls (p<0.5). CONCLUSIONS: These findings showed that anti-LPG MABS were effective in reducing sand fly infections. This study also showed that P. duboscqi gut lysates and proteins present in L. major-derived LPG share two common proteins of molecular weights 105 kDa and 106 kDa. Further analysis of these individual proteins from the gut should be studied with a view of determining their vaccine potential.

Quality of care provided to febrile children presenting in rural private clinics on the Kenyan coast.

BACKGROUND: Private sector health facilities are diverse in nature, and offer widely varying quality of care (QOC). OBJECTIVES: The study aimed to describe the QOC provided to febrile children at rural private clinics on the Kenyan coast and stakeholder perspectives on standards of practice and opportunities for change. METHODS: Data collection methods were structured observations of consultations; interviews with users on exit from clinic and at home and in depth interviews with private practitioners (PP) and district health managers. FINDINGS: Private clinics have basic structural features for health care delivery. The majority of the clinics in this study were owned and run by single-handed trained medical practitioners. Amongst 92 observed consultations, 62% of diagnoses made were consistent with the history, examinations and tests performed. 74% of childhood fevers were diagnosed as malaria, and 88% of all prescriptions contained an antimalarial drug. Blood slides for malaria parasites were performed in 55 children (60%). Of those whose blood slide was positive (n=27), 52% and 48% were treated with a nationally recommended first or second line antimalarial drug, respectively. Where no blood slide was done (n=37), 73% were prescribed a nationally recommended first line and 27% received a second line antimalarial drug. Overall, 68 % of antimalarial drugs were prescribed in an appropriate dose and regime. Both private practitioners and district health managers expressed the view that existing linkages between the public and private health sectors within the district are haphazard and inadequate. CONCLUSIONS: Although rural PPs are potentially well placed for treatment of febrile cases in remote settings, they exhibit varying QOC. Practitioners, users and district managers supported the need to develop interventions to improve QOC. The study identifies the need to consider involvement of the for-profit providers in the implementation of the IMCI guidelines in Kenya.

In vitro antiplasmodial activity of some plants used in Kisii, Kenya against malaria and their chloroquine potentiation effects.

Fifty-five organic and aqueous extracts of 11 plants used in malaria therapy in Kisii District, Kenya were tested in vitro against chloroquine (CQ)-sensitive and resistant strains of Plasmodium falciparum. Of the plants tested, 73% were active (IC(50) < 100 microg/ml). Three plants, Vernonia lasiopus, Rhamnus prinoides and Ficus sur afforded extracts with IC(50) values ranging less than 30 microg/ml against both CQ-sensitive and resistant strains. Combination of some extracts with CQ against the multi-drug resistant P. falciparum isolate V1/S revealed some synergistic effect. The plant extracts with low IC(50) values may be used as sources for novel antimalarial compounds to be used alone or in combination with CQ.

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.

Leishmania donovani-derived lipophosphoglycan plus BCG induces a Th1 type immune response but does not protect Syrian golden hamsters (Mesocricetus auratus) and BALB/c mice against Leishmania donovani.

The efficacy of Leishmania donovani-derived lipophosphoglycan (LPG) plus Mycobacterium bovis Bacille Calmette-Guerin (BCG) as a vaccine candidate against visceral leishmaniosis in susceptible BALB/c mouse and Syrian golden hamster (Mesocricetus auratus) models was investigated. Following a triple vaccination with a total dose of 150 microl BCG plus 60 microg or 30 microg of LPG for hamsters and BALB/c mice respectively, there were no noticeable side effects both locally and systemically; implying that the molecule was safe at this dosage level. Vaccinated animals demonstrated an activation of both the humoral as well as cell-mediated responses to LPG, which correlated with resistance against the disease. Protection by LPG plus BCG, was however, poor as the remaining immunized animals showed disease progression leading to severity of the disease as illustrated by emaciation, mass loss and heavy splenic parasitaemia in hamsters. These data nevertheless suggest that it may be rewarding to further evaluate the potential of LPG as a vaccine candidate in leishmaniosis using other adjuvants, which may enhance its immunogenicity.

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.

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.

An analysis of haematological parameters in patients and individual residents of a Plasmodium falciparum malaria holoendemic area of western Kenya.

Many clinical symptoms of malaria are associated with alterations in certain haematological parameters during acute and subclinical infections. Total leucocyte and erythrocyte counts, haemoglobin concentration, haematocrit and other minor indices, were investigated in five cohort groups of individuals resident in a malaria hyperendemic area of western Kenya. The groups included age- and sex-matched adults with acute Plasmodium falciparum malaria, aparasitaemic adults, children with acute malaria, aparasitaemic children and asymptomatic-parasitaemic school children. The study aimed at defining what constitutes immunity to malaria which may be important in the critical evaluation of malaria vaccine antigens. Anaemia was more severe in adults and children with acute malaria than in their age- and sex-matched aparasitaemic and asymptomatic-aparasitaemic school children. Lymphocyte counts were significantly higher in asymptomatic-aparasitaemic school children than in aparasitaemic adults, suggesting a possible functional role for lymphocytes in the anti-disease immunity in the former group.

Cellular immune responses of schistosomiasis patients are altered by human immunodeficiency virus type 1 coinfection.

In vitro studies suggest that CD4(+) cells with a T helper 2 (Th2) phenotype better support human immunodeficiency virus type 1 (HIV-1) replication than do cells of the Th1 phenotype. As a result, Th2-type immune responses may be substantially affected by HIV-1 coinfection. To test this hypothesis, a comparison was done of proliferation and cytokine production by peripheral blood mononuclear cells from patients with schistosomiasis who were positive or negative for HIV-1. Patients with schistosomiasis with HIV-1 coinfections had significantly lower interleukin (IL)-4 and IL-10 production than did HIV-1-negative individuals. In contrast, interferon-gamma production levels were similar between the 2 groups. Furthermore, in patients with HIV-1, a decrease in CD4(+) T cells was correlated with an increased Th1:Th2 cytokine production ratio. The effect of praziquantel treatment on proliferation and cytokine responses also differed between HIV-1 infection groups. Thus, HIV-1 infection affects immune response patterns of patients with schistosomiasis.

Vervet monkeys vaccinated with killed Leishmania major parasites and interleukin-12 develop a type 1 immune response but are not protected against challenge infection.

Leishmania major is a protozoan parasite that causes chronic cutaneous lesions that often leave disfiguring scars. Infections in mice have demonstrated that leishmanial vaccines that include interleukin-12 (IL-12) as an adjuvant are able to induce protective immunity. In this study, we assessed the safety, immunopotency, and adjuvant potential of two doses of IL-12 when used with a killed L. major vaccine in vervet monkeys. The induction of cell-mediated immunity following vaccination was determined by measuring delayed-type hypersensitivity, in vitro lymphocyte proliferation, and gamma interferon (IFN-gamma) production. Protection was assessed by challenging the animals with L. major parasites and monitoring the course of infection. At low doses of IL-12 (10 microg), a small increase in the parameters of cell-mediated immunity was observed, relative to those in animals that received antigen without IL-12. However, none of these animals were protected against a challenge infection. At higher doses of IL-12 (30 microg), a substantial increase in Leishmania-specific immune responses was observed, and monkeys immunized with antigen and IL-12 exhibited an IFN-gamma response that was as great as that in animals that had resolved a primary infection and were immune. Nevertheless, despite the presence of correlates of protection, the disease course was only slightly altered, and protection was low compared to that in self-cured monkeys. These data suggest that protection against leishmaniasis may require more than the activation of Leishmania-specific IFN-gamma-producing T cells, which has important implications for designing a vaccine against leishmaniasis.

A low interleukin-10 tumor necrosis factor-alpha ratio is associated with malaria anemia in children residing in a holoendemic malaria region in western Kenya.

The balance between Th1 cytokines (tumor necrosis factor [TNF]-alpha, interferon [IFN]-gamma) and Th2 cytokines (interleukin [IL]-10, -4) may be critical in the development of severe falciparum malaria. Therefore, plasma concentrations of these cytokines were determined in children with various manifestations of malaria. Plasma levels of IFN-gamma and IL-4 were undetectable in most children. However, TNF-alpha and IL-10 were significantly elevated in children with high-density parasitemia and malaria anemia compared with children in control groups. In children with mild malaria, IL-10, but not TNF-alpha, was significantly elevated. While the highest concentrations of TNF-alpha were found in children with malaria anemia, IL-10 levels were highest in children with high-density uncomplicated malaria. The mean ratio of IL-10 to TNF-alpha was significantly higher in children with mild and high-density parasitemia (4.64, P<.005) than in children with malaria anemia (1.77). Thus, higher levels of IL-10 over TNF-alpha may prevent development of malaria anemia by controlling the excessive inflammatory activities of TNF-alpha.