RESUMO
A series of new 2,4-bis[(substituted-aminomethyl)phenyl]quinoline, 1,3-bis[(substituted-aminomethyl)phenyl]isoquinoline, and 2,4-bis[(substituted-aminomethyl)phenyl]quinazoline derivatives was designed, synthesised, and evaluated in vitro against three protozoan parasites (Plasmodium falciparum, Leishmania donovani, and Trypanosoma brucei brucei). Biological results showed antiprotozoal activity with IC50 values in the µM range. In addition, the in vitro cytotoxicity of these original molecules was assessed with human HepG2 cells. The quinoline 1c was identified as the most potent antimalarial candidate with a ratio of cytotoxic to antiparasitic activities of 97 against the P. falciparum CQ-sensitive strain 3D7. The quinazoline 3h was also identified as the most potent trypanosomal candidate with a selectivity index (SI) of 43 on T. brucei brucei strain. Moreover, as the telomeres of the parasites P. falciparum and Trypanosoma are possible targets of this kind of nitrogen heterocyclic compounds, we have also investigated stabilisation of the Plasmodium and Trypanosoma telomeric G-quadruplexes by our best compounds through FRET melting assays.
Assuntos
Antiprotozoários/química , Antiprotozoários/farmacologia , Desenho de Fármacos , Quinolinas/química , Quinolinas/farmacologia , Antiprotozoários/síntese química , Células Hep G2 , Humanos , Leishmania donovani/efeitos dos fármacos , Plasmodium falciparum/efeitos dos fármacos , Quinolinas/síntese química , Relação Estrutura-Atividade , Trypanosoma brucei brucei/efeitos dos fármacosRESUMO
BACKGROUND: As resistance to marketed anti-malarial drugs continues to spread, the need for new molecules active on Plasmodium falciparum-resistant strains grows. Pure (S) enantiomers of amino-alcohol quinolines previously displayed a good in vitro anti-malarial activity. Therefore, a more thorough assessment of their potential clinical use through a rodent model and an in vitro evaluation of their combination with artemisinin was undertaken. METHODS: Screening on a panel of P. falciparum clones with varying resistance profiles and regional origins was performed for the (S)-pentyl and (S)-heptyl substituted quinoline derivatives, followed by an in vitro assessment of their combination with dihydroartemisinin (DHA) on the 3D7 clone and an in vivo assay in a mouse model infected with Plasmodium berghei. Their haemolytic activity was also determined. RESULTS: A steady anti-malarial activity of the compounds tested was found, whatever the resistance profile or the regional origin of the strain. (S)-quinoline derivatives were at least three times more potent than mefloquine (MQ), their structurally close parent. The in vitro combination with DHA yielded an additive or synergic effect for both that was as good as that of the DHA/MQ combination. In vivo, survival rates were similar to those of MQ for the two compounds at a lower dose, despite a lack of clearance of the parasite blood stages. A 50% haemolysis was observed for concentrations at least 1,000-fold higher than the antiplasmodial IC50s. CONCLUSIONS: The results obtained make those two (S)-amino-alcohol quinoline derivatives good candidates for the development of new artemisinin-based combination therapy (ACT), hopefully with fewer neurologic side effects than those currently marketed ACT, including MQ.
Assuntos
Antimaláricos/farmacologia , Antimaláricos/uso terapêutico , Artemisininas/farmacologia , Artemisininas/uso terapêutico , Malária/tratamento farmacológico , Plasmodium falciparum/efeitos dos fármacos , Quinolinas/farmacologia , Quinolinas/uso terapêutico , Animais , Antimaláricos/toxicidade , Artemisininas/toxicidade , Modelos Animais de Doenças , Sinergismo Farmacológico , Quimioterapia Combinada , Eritrócitos/efeitos dos fármacos , Feminino , Hemólise , Concentração Inibidora 50 , Camundongos Endogâmicos BALB C , Testes de Sensibilidade Parasitária , Quinolinas/toxicidade , Análise de Sobrevida , Resultado do TratamentoRESUMO
BACKGROUND: Chloroquine (CQ) was the main malaria therapy worldwide from the 1940s until the 1990s. Following the emergence of CQ-resistant Plasmodium falciparum, most African countries discontinued the use of CQ, and now promote artemisinin-based combination therapy as the first-line treatment. This change was generally initiated during the last decade in West and Central Africa. The aim of this study is to describe the changes in CQ susceptibility in this African region, using travellers returning from this region as a sentinel system. METHODS: The study was conducted by the Malaria National Reference Centre, France. The database collated the pfcrtK76T molecular marker for CQ susceptibility and the in vitro response to CQ of parasites from travellers' isolates returning from Senegal, Mali, Ivory Coast or Cameroon. As a proxy of drug pressure, data regarding CQ intake in febrile children were collated for the study period. Logistic regression models were used to detect trends in the proportions of CQ resistant isolates. RESULTS: A total of 2874 parasite isolates were genotyped between 2000-2011. The prevalence of the pfcrt76T mutant genotype significantly decreased for Senegal (from 78% to 47%), Ivory Coast (from 63% to 37%), Cameroon (from 90% to 59%) and remained stable for Mali. The geometric mean of the 50% inhibitory concentration (IC50) of CQ in vitro susceptibility and the proportion of resistant isolates (defining resistance as an IC50 value > 100 nM) significantly decreased for Senegal (from 86 nM (59%) to 39 nM (25%)), Mali (from 84 nM (50%) to 51 nM (31%)), Ivory Coast (from 75 nM (59%) to 29 nM (16%)) and Cameroon (from 181 nM (75%) to 51 nM (37%)). Both analyses (molecular and in vitro susceptibility) were performed for the 2004-2011 period, after the four countries had officially discontinued CQ and showed an accelerated decline of the resistant isolates for the four countries. Meanwhile, CQ use among children significantly deceased in this region (fixed effects slope = -0.3, p < 10-3). CONCLUSIONS: An increase in CQ susceptibility following official withdrawal of the drug was observed in travellers returning from West and Central African countries. The same trends were observed for molecular and in vitro analysis between 2004-2011 and they correlated to the decrease of the drug pressure.
Assuntos
Antimaláricos/uso terapêutico , Cloroquina/uso terapêutico , Malária Falciparum/tratamento farmacológico , Plasmodium falciparum/efeitos dos fármacos , Adolescente , Adulto , África Central , África Ocidental , Idoso , Idoso de 80 Anos ou mais , Criança , Pré-Escolar , Resistência a Medicamentos , Feminino , Genótipo , Humanos , Lactente , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Testes de Sensibilidade Parasitária , Plasmodium falciparum/genética , Plasmodium falciparum/isolamento & purificação , Viagem , Adulto JovemRESUMO
A series of novel 2,9-bis[(substituted-aminomethyl)]-4,7-phenyl-1,10-phenanthroline derivatives was designed, synthesized, and evaluated in vitro against three protozoan parasites (Plasmodium falciparum, Leishmania donovani and Trypanosoma brucei brucei). Pharmacological results showed antiprotozoal activity with IC50 values in the sub and µM range. In addition, the in vitro cytotoxicity of these original molecules was assessed with human HepG2 cells. The substituted diphenylphenanthroline 1l was identified as the most potent antimalarial derivative with a ratio of cytotoxic to antiparasitic activities of 505.7 against the P. falciparum CQ-resistant strain W2. Against the promastigote forms of L. donovani, the phenanthrolines 1h, 1j, 1n and 1o were the most active with IC50 from 2.52 to 4.50 µM. The phenanthroline derivative 1o was also identified as the most potent trypanosomal candidate with a selectivity index (SI) of 91 on T. brucei brucei strain. FRET melting and native mass spectrometry experiments evidenced that the nitrogen heterocyclic derivatives bind the telomeric G-quadruplexes of P. falciparum and Trypanosoma. Moreover, as the telomeres of the parasites P. falciparum and Trypanosoma could be considered to be possible targets of this kind of nitrogen heterocyclic derivatives, their potential ability to stabilize the parasitic telomeric G-quadruplexes have been determined through the FRET melting assay and by native mass spectrometry.
RESUMO
In a multicenter study, potassium dichromate-preserved stools from patients infected with Cryptosporidium parvum (n = 20), C. hominis (n = 20), and other Cryptosporidium species (n = 10) and 60 controls were examined using four immunochromatographic assays. Assay sensitivity ranged between 50.1% and 86.7% for C. parvum and C. hominis but was <35% for other species.
Assuntos
Antígenos de Protozoários/análise , Técnicas de Laboratório Clínico/métodos , Criptosporidiose/diagnóstico , Cryptosporidium/isolamento & purificação , Fezes/parasitologia , Parasitologia/métodos , Criptosporidiose/parasitologia , Cryptosporidium/imunologia , Humanos , Imunoensaio/métodos , Sensibilidade e EspecificidadeRESUMO
BACKGROUND: Malaria is reportedly receding in different epidemiological settings, but local long-term surveys are limited. At Mlomp dispensary in south-western Senegal, an area of moderate malaria transmission, year-round, clinically-suspected malaria was treated with monotherapy as per WHO and national policy in the 1990s. Since 2000, there has been a staggered deployment of artesunate-amodiaquine after parasitological confirmation; this was adopted nationally in 2006. METHODS: Data were extracted from clinic registers for the period between January 1996 and December 2010, analysed and modelled. RESULTS: Over the 15-year study period, the risk of malaria decreased about 32-times (from 0.4 to 0.012 episodes person-year), while anti-malarial treatments decreased 13-times (from 0.9 to 0.07 treatments person-year) and consultations for fever decreased 3-times (from 1.8 to 0.6 visits person-year). This was paralleled by changes in the age profile of malaria patients so that the risk of malaria is now almost uniformly distributed throughout life, while in the past malaria used to concern more children below 16 years of age. CONCLUSIONS: This study provides direct evidence of malaria risk receding between 1996-2010 and becoming equal throughout life where transmission used to be moderate. Infection rates are no longer enough to sustain immunity. Temporally, this coincides with deploying artemisinin combinations on parasitological confirmation, but other contributing causes are unclear.
Assuntos
Amodiaquina/administração & dosagem , Antimaláricos/administração & dosagem , Artemisininas/administração & dosagem , Malária/tratamento farmacológico , Malária/epidemiologia , Adolescente , Adulto , Idoso , Criança , Pré-Escolar , Combinação de Medicamentos , Feminino , Humanos , Incidência , Lactente , Recém-Nascido , Malária/transmissão , Masculino , Pessoa de Meia-Idade , Senegal/epidemiologia , Adulto JovemRESUMO
BACKGROUND: We prepared a novel series of enantiopure mefloquine analogues with pyrrolo[ 1,2-a]quinoxaline core in order to fight Plasmodium falciparum resistant strain. OBJECTIVES: To observe the influence of pyrrolo[1,2-a]quinoxaline core versus quinoline core on the antimalarial activity. METHOD: Four enantiopure aminoalcoholpyrrolo[1,2-a]quinoxalines 2 were synthetized via Sharpless asymmetric dihydroxylation reaction in eight steps. Their antimalarial activity was evaluated on two Plasmodium falciparum strains 3D7 and W2 with a SYBR Green I fluorescence-based method and their cytotoxicity was measured on four cell lines HepG2, THP-1, CHO and HFF. RESULTS: IC50 values of the four compounds 2 were close to the micromolar against the two P. falciparum strains. They were more active against P. falciparum strain W2 vs. P. falciparum strain 3D7. (R)- enantiomers were always more active than their (S)-counterpart whatever the strain. Selectivity indexes of compounds 2 were lower than 100. CONCLUSION: A novel series of enantiopure aminoalcohols with pyrrolo[1,2-a]quinoxaline core were synthesized in eight steps. They displayed IC50 values close to the micromolar against two P. falciparum strains 3D7 and W2. Although, In this series, 2,8-bistrifluoromethylquinoline was a best core than pyrrolo[1,2-a]quinoxaline for an optimal antimalarial activity, the pyrroloquinoxaline 2b showed an interesting antimalarial activity.
Assuntos
Amino Álcoois/farmacologia , Antimaláricos/farmacologia , Mefloquina/análogos & derivados , Mefloquina/farmacologia , Pirróis/farmacologia , Quinoxalinas/farmacologia , Amino Álcoois/síntese química , Amino Álcoois/química , Amino Álcoois/toxicidade , Animais , Antimaláricos/síntese química , Antimaláricos/química , Antimaláricos/toxicidade , Células CHO , Linhagem Celular Tumoral , Cloroquina/farmacologia , Cricetulus , Humanos , Mefloquina/química , Mefloquina/toxicidade , Plasmodium falciparum/efeitos dos fármacos , Pirróis/síntese química , Pirróis/química , Pirróis/toxicidade , Quinoxalinas/síntese química , Quinoxalinas/química , Quinoxalinas/toxicidade , EstereoisomerismoRESUMO
BACKGROUND: There are no data on the long term use of an artemisinin combination treatment in moderate or high transmission areas of Africa. METHODS AND FINDINGS: Artesunate plus amodiaquine (AS+AQ) was used to treat slide-proven Plasmodium falciparum-infected patients of all ages in the Oussouye district, Casamance, Senegal, over a period of six years (2000 to 2005). Efficacy, by Kaplan Meier survival analysis (n = 966), and safety (adverse event rates, n = 752) were determined over 28 days. A weight-based dosing regimen was used for the loose tablets during 2000-2003 (n = 731) and a commercially available co-blister was used during 2004-2005 (n = 235). Annual crude (non PCR corrected) rates remained stable over the study period [range 88.5-96.7%; overall 94.6 (95% CI 92.9-95.9)]. Nine co-blister treated patients (0.9%) withdrew because of drug-related adverse events; seven had gastrointestinal complaints of whom two were hospitalized for vomiting. By Day 28, the mean total bilirubin (n = 72), AST (n = 94) and ALT (n = 95) values decreased. Three patients had Day 28 AST/ALT values > 40 < 200 IU/L. Changes in white cell counts were unremarkable (n = 87). CONCLUSION: AS+AQ in combination was highly efficacious and well-tolerated in this area and justifies the decision to use it as first line treatment. Long-term monitoring of safety and efficacy should continue.
Assuntos
Amodiaquina/uso terapêutico , Antimaláricos/uso terapêutico , Artemisininas/uso terapêutico , Malária Falciparum/tratamento farmacológico , Segurança , Sesquiterpenos/uso terapêutico , Amodiaquina/administração & dosagem , Amodiaquina/efeitos adversos , Amodiaquina/farmacologia , Animais , Antimaláricos/administração & dosagem , Antimaláricos/efeitos adversos , Antimaláricos/farmacologia , Artesunato , Combinação de Medicamentos , Humanos , Malária Falciparum/epidemiologia , Malária Falciparum/parasitologia , Pacientes Ambulatoriais , Plasmodium falciparum/efeitos dos fármacos , Plasmodium falciparum/genética , Plasmodium falciparum/crescimento & desenvolvimento , Senegal/epidemiologia , Resultado do TratamentoRESUMO
Cryptosporidium parvum, Tyzzer, 1912 is identified as a common cause of diarrhoea in immunocompetent individuals. In immunocompromised, especially HIV-infected subjects, cryptosporidiosis causes severe chronic diarrhoea. In this study, nitazoxanide (NTZ) was compared for curative activity with sinefungin (SNF) and paromomycin (PRM) in immunosuppressed rats, a screening model for anticryptosporidial agents. NTZ at either 50 mg/kg/day, 100 mg/kg/day or 200 mg/kg/day resulted in seven days in a dose-dependent inhibition of oocyst shedding similar to that obtained with SNF (10 mg/kg/day) and PRM (100 mg/kg/day). Further discontinuation of SNF or PRM 100 mg/kg/day therapy resulted in early relapse of oocyst shedding which reached the pre-treatment levels in 2-4 days. In contrast, seven days after discontinuation of therapy, shedding inhibition was unchanged in NTZ-treated rats. Data prompt further assessment of the activity of NTZ on sequestered C. parvum.
Assuntos
Adenosina/análogos & derivados , Antiprotozoários/farmacologia , Criptosporidiose/tratamento farmacológico , Cryptosporidium parvum/crescimento & desenvolvimento , Tiazóis/farmacologia , Adenosina/farmacologia , Animais , Criptosporidiose/imunologia , Modelos Animais de Doenças , Fezes/parasitologia , Hospedeiro Imunocomprometido , Masculino , Nitrocompostos , Contagem de Ovos de Parasitas , Paromomicina/farmacologia , Ratos , Ratos Sprague-DawleyRESUMO
The authors compared the viability and infectivity of Cryptosporidium parvum oocysts in chlorinated tap water at various storage durations (i.e., 2 wk, 4 wk, 6 wk, or 8 wk) and at 2 cool temperatures (i.e., 10 degrees C and 4 degrees C), using in vitro (excystation) and in vivo (suckling mouse) methods. After 8 wk, mean oocyst excystation decreased to 33.4% and 26.7% at 10 degrees C and 4 degrees C, respectively. Suckling mice infectivity was higher after storage at 10 degrees C than after storage at 4 degrees C. These data suggest that Cryptosporidium parvum oocysts can survive and remain infectious for 8 wk in cool chlorinated tap water.
Assuntos
Cryptosporidium parvum/patogenicidade , Abastecimento de Água , Animais , Animais Recém-Nascidos , Bioensaio , Cryptosporidium parvum/fisiologia , Camundongos , Oocistos , Sobrevida , Temperatura , Fatores de TempoRESUMO
The physico-chemical behavior of Cryptosporidium oocysts was investigated during their transfer through an alluvial formation from Les Cayes (Haiti) via batch tests. Five approximately 3 kg soil samples were collected and combined prior to batch tests from the alluvial formations. The experiments were carried out at soil pH by equilibrating different ranges of pure oocysts concentrations and soil samples with 3mM CaCl2 and 1mM NaBr as electrolyte. We used the Debye-Hückel equation describing ion activity in a solution for a given ionic strength. The equilibrium adsorption mechanism is used to enumerate the oocysts in the soil. The results suggest that the oocysts behavior in porous media depends on soil characteristics such as soil pH, the nature of the mineral and organic constituents of the soil and the ionic strength and activities in solution. These results show that a total transfer in batch containing NaBr solutions against a partial one in batch containing CaCl2 solutions depends on the oocysts media concentration. To confirm the oocysts number retained in soil, confocal microscopy was successfully used and the images demonstrate that the majority of oocysts were retained at the range of concentrations tested. The findings from this study demonstrated that the retention of C. Parvum in soils may be influenced by chemical conditions and soils characteristics, which are important for groundwater risk assessment.
Assuntos
Cryptosporidium parvum/crescimento & desenvolvimento , Oocistos/crescimento & desenvolvimento , Solo/química , Solo/parasitologia , Animais , Concentração Osmolar , PorosidadeRESUMO
A series of new 4-alkapolyenylpyrrolo[1,2-a]quinoxaline derivatives, original and structural analogues of alkaloid chimanine B and of previously described 4-alkenylpyrrolo[1,2-a]quinoxalines, was synthesized in good yields using efficient palladium-catalyzed Suzuki-Miyaura cross-coupling reactions. These new compounds were tested for in vitro antiparasitic activity upon three Leishmania spp. strains. Biological results showed activity against the promastigote forms of L. major, L. mexicana and L. donovani with IC50 ranging from 1.2 to 14.7 µM. In attempting to investigate if our pyrrolo[1,2-a]quinoxaline derivatives are broad-spectrum antiprotozoal compounds activities toward one Trypanosoma brucei brucei strain and the W2 and 3D7 Plasmodium falciparum strains were also investigated. In parallel, the in vitro cytotoxicity of these molecules was assessed on the murine J774 and human HepG2 cell lines. Structure-activity relationships of these new synthetic compounds are here discussed.
Assuntos
Desenho de Fármacos , Leishmania/efeitos dos fármacos , Plasmodium falciparum/efeitos dos fármacos , Quinoxalinas/farmacologia , Tripanossomicidas/farmacologia , Trypanosoma brucei brucei/efeitos dos fármacos , Tripanossomíase Africana/tratamento farmacológico , Animais , Proliferação de Células/efeitos dos fármacos , Relação Dose-Resposta a Droga , Feminino , Células Hep G2 , Humanos , Macrófagos/efeitos dos fármacos , Camundongos , Estrutura Molecular , Testes de Sensibilidade Parasitária , Quinoxalinas/síntese química , Quinoxalinas/química , Relação Estrutura-Atividade , Tripanossomicidas/administração & dosagem , Tripanossomicidas/síntese química , Tripanossomíase Africana/parasitologia , Tripanossomíase Africana/veterináriaRESUMO
Mefloquine (MQ), an antimalarial drug, is used as a racemate of (-)- and (+)-enantiomers, which display biological differences. The question concerning their exact configuration remains a matter of debate. The absolute configuration of the two MQ enantiomers as well as their biological activity has been established, thus confirming the importance of the stereochemistry in the design of MQ analogues that have fewer adverse side effects.
RESUMO
The protozoan parasite Cryptosporidium sp. has emerged as one of the most important water contaminants, causing waterborne outbreaks of diarrhoeal diseases worldwide. In Haiti, cryptosporidiosis is a frequent cause of diarrhoea in children under the age of five years, HIV-infected individuals, and people living in low socioeconomic conditions, mainly due to the consumption of water or food polluted by Cryptosporidium oocysts. The aim of this study was to detect and identify Cryptosporidium oocysts present in 12 water samples collected in Port-au-Prince and 4 water samples collected in Cap Haïtien. Initial detection consisted of immunomagnetic separation - immunofluorescence assay (IMS-IFA), which was confirmed by nested PCR, targeting the most polymorphic region of the 18S rRNA gene in 15/16 samples. Genotyping was performed by PCR-restriction fragment length polymorphism (RFLP) analysis and DNA sequencing. Under our working conditions, neither nested PCR-RFLP nor direct DNA sequencing revealed the expected species diversity, as only Cryptosporidium parvum was identified in the water samples studied. This study highlights the difficulty of detecting mixed populations of Cryptosporidium species in environmental samples.
Assuntos
Criptosporidiose/parasitologia , Cryptosporidium/isolamento & purificação , Água/parasitologia , Animais , Estudos Transversais , Cryptosporidium/classificação , Cryptosporidium/genética , DNA de Protozoário/química , DNA de Protozoário/isolamento & purificação , Variação Genética , Haiti , Humanos , Oocistos/classificação , Reação em Cadeia da Polimerase , Polimorfismo de Fragmento de Restrição , Mapeamento por Restrição , Análise de Sequência de DNA , Abastecimento de ÁguaRESUMO
Cryptosporidiosis is one of the most frequent causes of diarrhea in Haiti. Transmission in children less than five years-old, HIV-infected individuals, and people living in low socio-economic conditions is frequently due to consumption of water or food contaminated by Cryptosporidium oocysts. This study examined the circulation of Cryptosporidium oocysts in surface waters and in public water supplies in the district of Port-au-Prince. Data were gathered from December 2000 to June 2002 in 37 sites. In the district of Port-au-Prince, 24/37 samples of water collected (65%) were contaminated by Cryptosporidium oocysts and 10/11 (91%) of those collected in reservoirs used by people living in peripheral areas. The rate of contamination was 7/13 (54%) in water from public standpipes provided by the public company of water distribution. All surface water (4/4) collected was highly contaminated.
Assuntos
Cryptosporidium/isolamento & purificação , Água Doce/microbiologia , Microbiologia da Água , Abastecimento de Água/análise , Haiti/epidemiologia , Humanos , Oócitos/microbiologiaRESUMO
Travel-related diarrhea is common among tourists to developing countries. We report two cases of diarrhea due to Cryptosporidium hominis and Isospora belli, respectively, in a child and an adult returning from Africa, without other associated microorganisms. We emphasize the need to detect underdiagnosed coccidiosis in diarrheic travelers with specific methods.
Assuntos
Criptosporidiose/diagnóstico , Cryptosporidium/isolamento & purificação , Diarreia/parasitologia , Isospora/isolamento & purificação , Isosporíase/diagnóstico , Viagem , Criptosporidiose/terapia , Humanos , Lactente , Isosporíase/terapia , Masculino , Pessoa de Meia-IdadeRESUMO
BACKGROUND: Former studies have pointed to a monocyte-dependent effect of antibodies in protection against malaria and thereby to cytophilic antibodies IgG1 and IgG3, which trigger monocyte receptors. Field investigations have further documented that a switch from non-cytophilic to cytophilic classes of antimalarial antibodies was associated with protection. The hypothesis that the non-cytophilic isotype imbalance could be related to concomittant helminthic infections was supported by several interventions and case-control studies. METHODS AND FINDINGS: We investigated here the hypothesis that the delayed acquisition of immunity to malaria could be related to a worm-induced Th2 drive on antimalarial immune responses. IgG1 to IgG4 responses against 6 different parasite-derived antigens were analyzed in sera from 203 Senegalese children, half carrying intestinal worms, presenting 421 clinical malaria attacks over 51 months. Results show a significant correlation between the occurrence of malaria attacks, worm carriage (particularly that of hookworms) and a decrease in cytophilic IgG1 and IgG3 responses and an increase in non-cytophilic IgG4 response to the merozoite stage protein 3 (MSP3) vaccine candidate. CONCLUSION: The results confirm the association with protection of anti-MSP3 cytophilic responses, confirm in one additional setting that worms increase malaria morbidity and show a Th2 worm-driven pattern of anti-malarial immune responses. They document why large anthelminthic mass treatments may be worth being assessed as malaria control policies.
Assuntos
Helmintíase/imunologia , Helmintos/imunologia , Malária Falciparum/imunologia , Plasmodium falciparum/imunologia , Adolescente , Animais , Anticorpos Antiprotozoários/sangue , Anticorpos Antiprotozoários/imunologia , Antígenos de Protozoários/imunologia , Criança , Pré-Escolar , Comorbidade , Feminino , Helmintíase/epidemiologia , Helmintos/fisiologia , Interações Hospedeiro-Parasita/imunologia , Humanos , Imunoglobulina G/sangue , Imunoglobulina G/imunologia , Lactente , Malária Falciparum/sangue , Malária Falciparum/epidemiologia , Masculino , Plasmodium falciparum/fisiologia , Estudos Prospectivos , Proteínas de Protozoários/imunologia , Senegal/epidemiologia , Células Th2/imunologiaRESUMO
This study investigated the presence of Enterocytozoon bieneusi as a possible cause of chronic diarrhea in Haitian patients attending the GHESKIO AIDS clinic in Port-au-Prince, Haiti. Coccidian oocysts were found by polymerase chain reaction (PCR) in the stools of 58/74 patients with chronic diarrhea and included the following agents: 45 (60%) Cryptosporidium spp., 27 (34%) Cyclospora cayetanensis, and 11 (15%) Isospora belli. Four patients (5.5%) were co-infected with E. bieneusi and one (1.4%) had E. bieneusi alone. The PCR-restriction fragment length polymorphism (RFLP) method made it possible to document the presence in human feces of E. bieneusi in Haiti. As in sub-Saharan Africa, the association of E. bieneusi with coccidian parasites found in Haitian patients with diarrhea is probably caused by the high level of fecal contamination of soils and surface waters usually associated with countries with low hygienic standards.
Assuntos
Coccidiose/microbiologia , Diarreia/microbiologia , Enterocytozoon/isolamento & purificação , Soropositividade para HIV/microbiologia , Enteropatias Parasitárias/microbiologia , Adolescente , Adulto , Criança , Pré-Escolar , Doença Crônica , Feminino , Humanos , Lactente , Masculino , Pessoa de Meia-IdadeRESUMO
Contamination by water-born infectious diseases is closely linked to urban slums conditions such as overcrowding and high level of faecal pollution by animal and human excreta. In this environment, cryptosporidiosis is a major cause of acute diarrhoea in children and chronic persistent diarrhoea in AIDS patients, resulting in increased morbidity and mortality in both populations. The aims of this study conducted in Port-au-Prince, Haiti were to: (i) determine the frequency of Cryptosporidium infection in two populations of patients with diarrhoea, children and AIDS patients, and the existence of Cryptosporidium carriage in healthy adults living in close contact with them; (ii) identify by molecular genotyping the Cryptosporidium species involved; and (iii) evaluate the viability of Cryptosporidium oocysts isolated from human stools. From January 2000 to January 2001, 158 of 1529 diarrhoea stool samples collected from 93 patients with diarrhoea, 57 adults followed at Centres GHESKIO and 36 children admitted at the University Hospital in Port-au-Prince contained Cryptosporidium oocysts (10.3%). The majority of adult patients (98%) were HIV-infected whereas the majority of children (81%) tested negative for HIV. Cryptosporidium was documented in only 1/102 healthy persons living in contact with Cryptosporidium infected patients and infection was with the same genotype as that of the contact patient. Among the 69 Cryptosporidium isolates studied for genotyping, three species were identified: C. hominis (59%), C. parvum (38%) and C. felis (3%). The two C. felis cases are the first reported from AIDS patients in the Caribbean. Most of the children regardless of their HIV status were infected with C. hominis (72%), whereas AIDS patients were more likely to be infected by either human or animal genotypes. These data confirm that immunocompromised individuals are susceptible to a wide range of Cryptosporidium spp. Viability of Cryptosporidium oocysts were determined in an experimental mouse model for 17/18 specimen studied including in 12/13 C. hominis, 4/4 C. parvum and 1/1 C. felis. Infectivity in newborn mice was found to be dose-dependent and more effective with C. parvum than the other two genotypes. Cryptosporidiosis remains a frequent hazard for both AIDS patients and young children in Haiti because of poor hygiene, particularly contaminated water and overcrowded conditions associated with urban slums.