RESUMO
Mozambique is one of the four African countries which account for over half of all malaria deaths worldwide, yet little is known about the parasite genetic structure in that country. We performed P. falciparum amplicon and whole genome sequencing on 2251 malaria-infected blood samples collected in 2015 and 2018 in seven provinces of Mozambique to genotype antimalarial resistance markers and interrogate parasite population structure using genome-wide microhaplotyes. Here we show that the only resistance-associated markers observed at frequencies above 5% were pfmdr1-184F (59%), pfdhfr-51I/59 R/108 N (99%) and pfdhps-437G/540E (89%). The frequency of pfdhfr/pfdhps quintuple mutants associated with sulfadoxine-pyrimethamine resistance increased from 80% in 2015 to 89% in 2018 (p < 0.001), with a lower expected heterozygosity and higher relatedness of microhaplotypes surrounding pfdhps mutants than wild-type parasites suggestive of recent selection. pfdhfr/pfdhps quintuple mutants also increased from 72% in the north to 95% in the south (2018; p < 0.001). This resistance gradient was accompanied by a concentration of mutations at pfdhps-436 (17%) in the north, a south-to-north increase in the genetic complexity of P. falciparum infections (p = 0.001) and a microhaplotype signature of regional differentiation. The parasite population structure identified here offers insights to guide antimalarial interventions and epidemiological surveys.
Assuntos
Humanos , Malária Falciparum/prevenção & controle , Malária/patologia , Antimaláricos/farmacologia , Humanos , Resistência a Medicamentos/genética , Malária Falciparum/terapiaRESUMO
Rotavirus vaccines have been adopted in African countries since 2009, including Mozambique (2015). Disease burden data are needed to evaluate the impact of rotavirus vaccine. We report the burden of rotavirus-associated diarrhea in Mozambique from the Global Enteric Multicenter Study (GEMS) before vaccine introduction. Methods: A case-control study (GEMS), was conducted in Manhiça district, recruiting children aged 0-59 months with moderate-to-severe diarrhea (MSD) and less-severe-diarrhea (LSD) between December 2007 and November 2012; including 1-3 matched (age, sex and neighborhood) healthy community controls. Clinical and epidemiological data and stool samples (for laboratory investigation) were collected. Association of rotavirus with MSD or LSD was determined by conditional logistic regression and adjusted attributable fractions (AF) calculated, and risk factors for rotavirus diarrhea assessed. Results: Overall 915 cases and 1,977 controls for MSD, and 431 cases and 430 controls for LSD were enrolled. Rotavirus positivity was 44% (217/495) for cases and 15% (160/1046) of controls, with AF = 34.9% (95% CI: 32.85-37.06) and adjusted Odds Ratio (aOR) of 6.4 p< 0.0001 in infants with MSD compared to 30% (46/155) in cases and 14% (22/154) in controls yielding AF = 18.7%, (95% CI: 12.02-25.39) and aOR = 2.8, p = 0.0011 in infants with LSD. The proportion of children with rotavirus was 32% (21/66) among HIV-positive children and 23% (128/566) among HIV-negative ones for MSD. Presence of animals in the compound (OR = 1.9; p = 0.0151) and giving stored water to the child (OR = 2.0, p = 0.0483) were risk factors for MSD; while animals in the compound (OR = 2.37, p = 0.007); not having routine access to water on a daily basis (OR = 1.53, p = 0.015) and washing hands before cooking (OR = 1.76, p = 0.0197) were risk factors for LSD. Conclusion: The implementation of vaccination against rotavirus may likely result in a significant reduction of rotavirus-associated diarrhea, suggesting the need for monitoring of vaccine impact.
Assuntos
Humanos , Masculino , Feminino , Criança , Infecções por Rotavirus/imunologia , Infecções por Rotavirus/epidemiologia , Rotavirus/imunologia , Vacinas contra Rotavirus/imunologia , Moçambique , Modelos LogísticosRESUMO
Background Mass drug administration (MDA) can rapidly reduce the burden of Plasmodium falciparum (Pf). However, concerns remain about its contribution to select for antimalarial drug resistance. Methods We used Sanger sequencing and real-time PCR to determine the proportion of molecular markers associated with antimalarial resistance (k13, pfpm2, pfmdr1 and pfcrt) in Pf isolates collected before (n = 99) and after (n = 112) the implementation of two monthly MDA rounds with dihydroartemisininpiperaquine (DHAp) for two consecutive years in Magude district of Southern Mozambique. Results None of the k13 polymorphisms associated with artemisinin resistance were observed in the Pf isolates analyzed. The proportion of Pf isolates with multiple copies of pfpm2, an amplification associated with piperaquine resistance, was similar in pre- (4.9%) and post-MDA groups (3.4%; p = 1.000). No statistically significant differences were observed between pre- and post-MDA groups in the proportion of Pf isolates neither with mutations in pfcrt and pfmdr1 genes, nor with the carriage of pfmdr1 multiple copies (p>0.05). Conclusions This study does not show any evidence of increased frequency of molecular makers of antimalarial resistance after MDA with DHAp in southern Mozambique where markers of antimalarial resistance were absent or low at the beginning of the intervention.
Assuntos
Humanos , Masculino , Feminino , Plasmodium falciparum/imunologia , Quinolinas/farmacologia , Resistência a Medicamentos/genética , Artemisininas/farmacologia , Malária/prevenção & controle , Antimaláricos/farmacologia , Plasmodium falciparum/genética , Plasmodium falciparum/patogenicidade , Polimorfismo Genético , Quinolinas/administração & dosagem , Quinolinas/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica , Proteínas de Protozoários/genética , Proteínas de Protozoários/metabolismo , Artemisininas/administração & dosagem , Artemisininas/uso terapêutico , Malária/parasitologia , Moçambique , Antimaláricos/administração & dosagem , Antimaláricos/uso terapêuticoRESUMO
Multidrug-resistant Escherichia coli ST131 fimH30 responsible for extra-intestinal pathogenic (ExPEC) infections is globally distributed. However, the occurrence of a subclone fimH27 of ST131 harboring both ExPEC and enteroaggregative E. coli (EAEC) related genes and belonging to commonly reported O25:H4 and other serotypes causing bacteremia in African children remain unknown. We characterized 325 E. coli isolates causing bacteremia in Mozambican children between 2001 and 2014 by conventional multiplex polymerase chain reaction and whole genome sequencing. Incidence rate of EAEC bacteremia was calculated among cases from the demographic surveillance study area. Approximately 17.5% (57/325) of isolates were EAEC, yielding an incidence rate of 45.3 episodes/105 children-years-at-risk among infants; and 44 of isolates were sequenced. 72.7% (32/44) of sequenced strains contained simultaneously genes associated with ExPEC (iutA, fyuA and traT); 88.6% (39/44) harbored the aggregative adherence fimbriae type V variant (AAF/V). Sequence type ST-131 accounted for 84.1% (37/44), predominantly belonging to serotype O25:H4 (59% of the 37); 95.6% (35/44) harbored fimH27. Approximately 15% (6/41) of the children died, and five of the six yielded ST131 strains (83.3%) mostly (60%; 3/5) due to serotypes other than O25:H4. We report the emergence of a new subclone of ST-131 E. coli strains belonging to O25:H4 and other serotypes harboring both ExPEC and EAEC virulence genes, including agg5A, associated with poor outcome in bacteremic Mozambican children, suggesting the need for prompt recognition for appropriate management.
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Humanos , Bacteriemia/epidemiologia , Escherichia coli/classificação , Criança , Moçambique/epidemiologiaRESUMO
Background Clinico-pathological discrepancies are more frequent in settings in which limited diagnostic techniques are available, but there is little information on their actual impact. Aim We assessed the accuracy of the clinical diagnoses in a tertiary referral hospital in sub-Saharan Africa by comparison with post-mortem findings. We also identified potential risk factors for misdiagnoses. Methods One hundred and twelve complete autopsy procedures were performed at the Maputo Central Hospital (Mozambique), from November 2013 to March 2015. We reviewed the clinical records. Major clinico-pathological discrepancies were assessed using a modified version of the Goldman and Battle classification. Results Major diagnostic discrepancies were detected in 65/112 cases (58%) and were particularly frequent in infection-related deaths (56/80 [70%] major discrepancies). The sensitivity of the clinical diagnosis for toxoplasmosis was 0% (95% CI: 037), 18% (95% CI: 252) for invasive fungal infections, 25% (95% CI: 557) for bacterial sepsis, 34% (95% CI: 1657), for tuberculosis, and 46% (95% CI: 1975) for bacterial pneumonia. Major discrepancies were more frequent in HIV-positive than in HIV-negative patients (48/73 [66%] vs. 17/39 [44%]; p = 0.0236). Conclusions Major clinico-pathological discrepancies are still frequent in resource constrained settings. Increasing the level of suspicion for infectious diseases and expanding the availability of diagnostic tests could significantly improve the recognition of common life-threatening infections, and thereby reduce the mortality associated with these diseases. The high frequency of clinico-pathological discrepancies questions the validity of mortality reports based on clinical data or verbal autopsy.
Assuntos
Humanos , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Idoso , Doenças Transmissíveis/mortalidade , Causas de Morte , Erros de Diagnóstico/estatística & dados numéricos , Doenças Transmissíveis/diagnóstico , Centros de Atenção Terciária/estatística & dados numéricosRESUMO
BACKGROUND: Enterotoxigenic Escherichia coli (ETEC) encoding heat-stable enterotoxin (ST) alone or with heat-labile enterotoxin (LT) cause moderate-to-severe diarrhea (MSD) in developing country children. The Global Enteric Multicenter Study (GEMS) identified ETEC encoding ST among the top four enteropathogens. Since the GEMS objective was to provide evidence to guide development and implementation of enteric vaccines and other interventions to diminish diarrheal disease morbidity and mortality, we examined colonization factor (CF) prevalence among ETEC isolates from children age <5 years with MSD and from matched controls in four African and three Asian sites. We also assessed strength of association of specific CFs with MSD. METHODOLOGY/PRINCIPAL FINDINGS: MSD cases enrolled at healthcare facilities over three years and matched controls were tested in a standardized manner for many enteropathogens. To identify ETEC, three E. coli colonies per child were tested by polymerase chain reaction (PCR) to detect genes encoding LT, ST; confirmed ETEC were examined by PCR for major CFs (Colonization Factor Antigen I [CFA/I] or Coli Surface [CS] antigens CS1-CS6) and minor CFs (CS7, CS12, CS13, CS14, CS17, CS18, CS19, CS20, CS21, CS30). ETEC from 806 cases had a single toxin/CF profile in three tested strains per child. Major CFs, components of multiple ETEC vaccine candidates, were detected in 66.0% of LT/ST and ST-only cases and were associated with MSD versus matched controls by conditional logistic regression (p≤0.006); major CFs detected in only 25.0% of LT-only cases weren't associated with MSD. ETEC encoding exclusively CS14, identified among 19.9% of 291 ST-only and 1.5% of 259 LT/ST strains, were associated with MSD (p = 0.0011). No other minor CF exhibited prevalence ≥5% and significant association with MSD. CONCLUSIONS/SIGNIFICANCE: Major CF-based efficacious ETEC vaccines could potentially prevent up to 66% of pediatric MSD cases due to ST-encoding ETEC in developing countries; adding CS14 extends coverage to ~77%.
Assuntos
Escherichia coli Enterotoxigênica/genética , Escherichia coli Enterotoxigênica/isolamento & purificação , Infecções por Escherichia coli/epidemiologia , Infecções por Escherichia coli/microbiologia , Proteínas de Fímbrias/genética , Fatores de Virulência/genética , África/epidemiologia , Ásia/epidemiologia , Estudos de Casos e Controles , Pré-Escolar , Feminino , Genótipo , Humanos , Lactente , Recém-Nascido , Masculino , Reação em Cadeia da Polimerase , PrevalênciaRESUMO
: Invasive pneumococcal disease (IPD) is a major cause of illness and death among children worldwide. 10-valent pneumococcal conjugate vaccine (PCV10) was introduced as part of the Mozambican routine immunization program in April 2013. We characterized the IPD burden in a rural area of Mozambique before PCV introduction and estimated the potential impact of this intervention. Methods: We conducted population-based surveillance for IPD, defined as S. pneumoniae isolated from blood or cerebrospinal fluid, among children <5 years old admitted to Manhiça District Hospital, a referral hospital in a rural area with high prevalence of human immunodiciency virus infection. S. pneumoniae was identified using standard microbiologic methods and serotyped using sequential multiplex PCR or Quellung. IPD incidence was calculated among cases from a defined catchment area. Results: From January 2001 through December 2012, we isolated 768 cases of IPD, 498 (65%) of which were bacteraemic pneumonia episodes. A total of 391 (51%) were from the catchment area, yielding IPD incidence rates of 479, 390 and 107 episodes per 100,000 children-years at risk among children <12, 12-23 and 24-<60 months old, respectively. The overall IPD incidence fluctuated and showed a downward trend over time. In these same age groups, in-hospital death occurred in 48 (17%), 26 (12%), and 21 (13%) of all IPD cases, respectively. Overall 90% (543/603) of IPD isolates were available for serotyping; of those, 65% were covered by PCV10 and 83% by PCV13. Among 77 hospital deaths associated with serotyped IPD, 49% and 69% were caused by isolates included in the PCV10 and PCV13, respectively. Conclusions: We describe very high rates of IPD among children in rural Mozambique that were declining before PCV introduction. Children <1 year old have the greatest incidence and case fatality; although the rates remain high among older groups as well. Most IPD episodes and many deaths among children <5 years old will likely be prevented through PCV10 introduction in Mozambique.
Assuntos
Humanos , Masculino , Feminino , Pré-Escolar , Criança , Streptococcus pneumoniae/imunologia , Pré-Escolar , Infecções Pneumocócicas/epidemiologia , Recém-Nascido , Moçambique/epidemiologiaRESUMO
Non-tuberculous mycobacteria (NTM) can cause disease which can be clinically and radiologically undistinguishable from tuberculosis (TB), posing a diagnostic and therapeutic challenge in high TB settings. We aim to describe the prevalence of NTM isolation and its clinical characteristics in children from rural Mozambique. This study was part of a community TB incidence study in children <3 years of age. Gastric aspirate and induced sputum sampling were performed in all presumptive TB cases and processed for smear testing using fluorochrome staining and LED Microscopy, liquid and solid culture, and molecular identification by GenoType® Mycobacterium CM/AS assays. NTM were isolated in 26.3% (204/775) of children. The most prevalent NTM species was M. intracellulare (N = 128), followed by M. scrofulaceum (N = 35) and M. fortuitum (N = 9). Children with NTM were significantly less symptomatic and less likely to present with an abnormal chest radiograph than those with M. tuberculosis. NTM were present in 21.6% of follow-up samples and 25 children had the same species isolated from ≥2 separate samples. All were considered clinically insignificant and none received specific treatment. Children with NTM isolates had equal all cause mortality and likelihood of TB treatment as those with negative culture although they were less likely to have TB ruled out.NTM isolation is frequent in presumptive TB cases but was not clinically significant in this patient cohort. However, it can contribute to TB misdiagnosis. Further studies are needed to understand the epidemiology and the clinical significance of NTM in children.
Assuntos
Humanos , Masculino , Feminino , Criança , Tuberculose , Criança , Moçambique/epidemiologiaRESUMO
Monitoring the HIV epidemic in a defined population is critical for planning treatment and preventive strategies. This is especially important in sub-Saharan Africa, which harbours the highest burden of the disease. Objective: To estimate HIV incidence in adults aged 18-47 years old and to investigate spatial variations of HIV prevalence in Manhiça, a semi-rural area of southern Mozambique. Methods: Two cross-sectional community-based surveys were conducted in 2010 and 2012 to determine HIV prevalence. Individual participants were randomly selected from the demographic surveillance system in place in the area and voluntary HIV counselling and testing was offered at the household level. HIV incidence was calculated using prevalence estimates from the two sero-surveys. Each participant's household was geocoded using a global information system. The Spatial Scan Statistics programme was used to identify areas with disproportionate excess in HIV prevalence. Results: A total of 1511 adults were tested. The estimated HIV prevalence in the community was 39.9% in 2010 and 39.7% in 2012. The overall HIV incidence was 3.6 new infections per 100 person-years at risk (PYAR) [95CI 1.56; 7.88], assuming stable epidemic conditions, and tended to be higher in women (4.9/100 PYAR [95CI 1.74; 11.85]) than in men (3.2/PYAR [95CI 1.36; 9.92]). One cluster with significant excess HIV prevalence was identified at the same geographic location in both surveys. This cluster had an HIV prevalence of 79.0% in 2010 and 52.3% in 2012. Conclusions: The findings of these first individually-randomised community-HIV sero-surveys conducted in Mozambique reinforce the need to combine HIV incidence estimates and research on micro geographical infection patterns to guide and consolidate effective prevention strategies.
Assuntos
Humanos , Infecções por HIV/prevenção & controle , Moçambique/epidemiologiaRESUMO
In recent years, a renewed interest in malaria elimination and eradication has emerged and seems to be rooting in the minds of the scientific community, public health specialists, funding bodies, policy makers and politicians. Malaria eradication will certainly benefit from improved and innovative tools; notwithstanding novel knowledge in fields ranging from basic science to mathematical modelling and health systems research. However, the elimination of malaria also encompasses a broad range of essential aspects that countries and other actors need to consider when thinking of embarking on such an adventure, including the implementation of innovative strategies, the ability to incorporate the most up-to-date evidence into policy, the integration of malaria into the broader health agenda, the strengthening of surveillance and health systems, capacity building, funding, advocacy and, very importantly, research. While in some cases this enthusiasm is clearly justified, some countries are still a long way from realistically advancing towards elimination. This paper attempts to provide guidance on all the necessary issues that should be considered when initiating a malaria elimination program.
Assuntos
Erradicação de Doenças/métodos , Malária/prevenção & controle , Vigilância da População , Saúde Global , HumanosRESUMO
OBJECTIVE: Haemophilus influenzae type b (Hib) conjugate vaccine has dramatically reduced invasive Hib disease worldwide. Yet, data on protection against pneumonia and among children with HIV are limited. We evaluated the impact of Hib conjugate vaccine introduction in 2009 in a rural, high-HIV prevalence area in Mozambique. STUDY DESIGN: From 2006-2011, we conducted hospital-based surveillance for invasive Hib disease and clinical pneumonia (classified as severe and very severe) among children <5 years of age. Incidences calculated using population denominators were compared between baseline (2006-2008) and post-Hib conjugate vaccine (2010-2011) periods. Surveillance data for radiologically-confirmed pneumonia among children <2 years of age in 2011 were compared with baseline data from 2004-2006. RESULTS: Among 50 cases of invasive Hib disease, 5 occurred after Hib conjugate vaccine introduction; 1 case-patient was age-eligible for Hib conjugate vaccine (and had received 3 doses). Four post-Hib conjugate vaccine case-patients (including Hib conjugate vaccine failure) had HIV. Among children <1 and <5 years of age, significant reductions occurred in rates of invasive Hib disease (91% and 85%, respectively) and very severe pneumonia (29% and 34%, respectively). Radiologically-confirmed pneumonia incidence fell significantly (33%) in children <2 years of age. Severe pneumonia incidence did not decline. CONCLUSIONS: We demonstrate important reductions in invasive disease and pneumonia following Hib conjugate vaccine introduction in a high-HIV area. Continued surveillance is needed to monitor long-term Hib conjugate vaccine effects, particularly among children with HIV.
Assuntos
Infecções por Haemophilus/epidemiologia , Infecções por Haemophilus/prevenção & controle , Vacinas Anti-Haemophilus/administração & dosagem , Haemophilus influenzae tipo b/imunologia , Pneumonia Bacteriana/epidemiologia , Pneumonia Bacteriana/prevenção & controle , Cápsulas Bacterianas/imunologia , Pré-Escolar , Infecções por HIV/imunologia , Infecções por Haemophilus/imunologia , Vacinas Anti-Haemophilus/imunologia , Humanos , Programas de Imunização , Lactente , Moçambique/epidemiologia , Pneumonia Bacteriana/imunologia , Vigilância da População , Prevalência , População RuralRESUMO
BACKGROUND: Studies on vector behaviour should be conducted in order to evaluate the effectiveness of vector control measures on malaria protection in endemic areas of Latin America, where P. vivax predominates. This work aims to investigate the fauna of anopheline mosquitoes and verify the impact of integrated vector management in two colonization projects in the Careiro Municipality, Western Brazilian Amazon. METHODS: Four mosquitoes' captures were carried out from August 2008 to March 2010, with an interval of six months between each collection. Since September 2009 a large programme to reduce the burden of malaria has started in the two communities by distribution of insecticide-treated bed nets (ITN) and intensification of indoor residual spraying (IRS). Human biting rates (HBRs), entomological inoculation rates (EIRs), malaria incidence rate (MIR) and Plasmodium carrier's prevalence were used as outcomes to estimate the impact of the control measures. RESULTS: A total of 3,189 anophelines were collected, belonging to 13 species. Anopheles darlingi was the predominant species in the period (42.6%), followed by Anopheles albitarsis (38.4%). An. darlingi HBRs showed a notable decreasing trend from the start to the end of the study. Conversely, An. albitarsis increased its contribution to overall HBRs throughout the study. For An. darlingi there was a significant positive correlation between HBRs and MIR (p = 0.002). Anopheles albitarsis HBRs showed a significant negative correlation with the corresponding MIR (p = 0.045). EIR from total anophelines and from An. darlingi and An. albitarsis presented decreasing patterns in the successive collections. Four species of anophelines (An. darlingi, An. albitarsis, Anopheles braziliensis and Anopheles nuneztovari) were naturally infected with Plasmodium, albeit at very low infection rates. There were a decrease in the MIR for both vivax and falciparum malaria and in the prevalence of Plasmodium vivax and Plasmodium falciparum carriers during the period of study. CONCLUSIONS: There is strong evidence of association between the density of An. darlingi and the incidence of malaria in the studies sites, further highlighting the importance of this vector in malaria transmission in this region. An. darlingi susceptibility to control using ITN and IRS is likely to be high in the rural settlements studied.
Assuntos
Anopheles/efeitos dos fármacos , Anopheles/crescimento & desenvolvimento , Malária/epidemiologia , Malária/prevenção & controle , Controle de Mosquitos/métodos , Animais , Anopheles/classificação , Brasil/epidemiologia , Portador Sadio/epidemiologia , Portador Sadio/prevenção & controle , Pesquisa sobre Serviços de Saúde , Humanos , Incidência , Mosquiteiros Tratados com Inseticida/estatística & dados numéricos , Inseticidas/farmacologia , População RuralRESUMO
BACKGROUND: Severe disease attributable to Plasmodium vivax infection is already well described worldwide; however, autopsies in these patients are scarce. METHODS: From 1996 to 2010, 19 patient deaths with a clinical diagnosis of P. vivax infection occurred in a tertiary care center in the Brazilian Amazon. Seventeen of these 19 deaths were fully autopsied. Clinical charts, macroscopic autopsy reports, and stored paraffinized tissue blocks were retrieved. Nested polymerase chain reaction was performed in paraffinized samples of spleen and lung to confirm P. vivax monoinfection. Immunohistofluorescence was used to detect P. vivax parasitized red blood cells (RBCs). RESULTS: Of 17 autopsies, 13 revealed that death could be attributed to P. vivax infection; in the remaining 4, acute diseases other than malaria were found to be the cause of death. The primary complication in patients in which malaria contributed to death was acute respiratory distress syndrome (ARDS) and pulmonary edema associated with the accumulation of neutrophils in the interalveolar space (6 cases). Spleen rupture (3 cases) and multiorgan dysfunction syndrome (3 cases) were the second most common complications. One child evolving with coma was also characterized, but no parasite was detected in the brain tissue. In one patient who developed ARDS and presented negative peripheral parasitemia by the time of death, scattered parasitized red blood cells were seen inside pulmonary capillaries, suggesting some sequestration in the lung. CONCLUSIONS: In 13 of 17 deceased patients, P. vivax infection was the plausible cause of death. However, more studies are needed to understand pathogenesis related to severe disease.
Assuntos
Malária Vivax/patologia , Plasmodium vivax/isolamento & purificação , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Autopsia , Criança , Feminino , Histocitoquímica , Humanos , Lactente , Malária Vivax/diagnóstico , Masculino , Pessoa de Meia-Idade , Edema Pulmonar/parasitologia , Síndrome do Desconforto Respiratório/parasitologia , Estudos RetrospectivosRESUMO
Partial protective efficacy lasting up to 43 months after vaccination with the RTS,S malaria vaccine has been reported in one cohort (C1) of a Phase IIb trial in Mozambique, but waning efficacy was observed in a smaller contemporaneous cohort (C2). We hypothesized that low dose exposure to asexual stage parasites resulting from partial pre-erythrocytic protection afforded by RTS,S may contribute to long-term vaccine efficacy to clinical disease, which was not observed in C2 due to intense active detection of infection and treatment....
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Humanos , Malária Falciparum/parasitologia , Malária Falciparum/patologia , Malária Falciparum/epidemiologiaRESUMO
Encouraged by the early success of using dichloro-diphenyl-trichloroethane (DDT) against malaria, the World Health Organization (WHO) embarked on the Global Malaria Eradication Program (GMEP) in 1955. Fourteen years later, the campaign was discontinued when it was recognised that eradication was not achievable with the available means in many areas, although the long-term goal remained unchanged. During the GMEP, malaria was permanently eliminated from many regions. In other areas, however, substantial gains were lost in resurgences, sometimes of epidemic proportions. During the 1970s and 1980s, because of economic and financial crises, international support for malaria control declined rapidly, but in the past decade, following increasing demands from endemic countries and promising results from scaling up of control activities, interest in malaria elimination and the long-term goal of eradication has received international political and financial support. In 2007, there was a renewed call for malaria eradication and a consultative process to define a research and development agenda for malaria eradication (malERA) was established. Lessons learned from the GMEP (1955-1969) highlight the fact that no single strategy can be applicable everywhere and that a long-term commitment with a flexible strategy that includes community involvement, integration with health systems, and the development of agile surveillance systems is needed.
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Malária/prevenção & controle , Organização Mundial da Saúde , África/epidemiologia , Animais , Anopheles/parasitologia , Ásia/epidemiologia , Participação da Comunidade , DDT , Atenção à Saúde/organização & administração , Doenças Endêmicas , Previsões , Saúde Global , Política de Saúde , Humanos , Insetos Vetores/parasitologia , Inseticidas , Comunicação Interdisciplinar , Malária/epidemiologia , Malária/transmissão , Controle de Mosquitos/organização & administração , Controle de Mosquitos/tendências , Plasmodium/fisiologia , Política , Vigilância da População , Avaliação de Programas e Projetos de Saúde , Pesquisa/tendências , América do Sul/epidemiologia , Organização Mundial da Saúde/organização & administraçãoRESUMO
Background: Pneumonia is the major cause of mortality and morbidity in children worldwide. Procalcitonin (PCT) and Creactive protein (CRP) are used in developed countries to differentiate between viral and bacterial causes of pneumonia. Validity of these markers needs to be further explored in Africa. Methodology and Principal Findings: We assessed the utility of PCT and CRP to differentiate viral from invasive bacterial pneumonia in children ,5 years hospitalized with clinical severe pneumonia (CSP) in rural Mozambique, a malaria-endemic area with high HIV prevalence. Prognostic capacity of these markers was also evaluated. Out of 835 children with CSP, 87 fulfilled definition of viral pneumonia and 89 of invasive bacterial pneumonia. In absence of malaria parasites, levels of PCT and CRP were lower in the viral group when compared to the invasive bacterial one (PCT: median = 0.21 versus 8.31 ng/ml, p,0.001; CRP: 18.3 vs. 185.35 mg/l, p,0.001). However, in presence of malaria parasites distribution between clinical groups overlapped (PCT: median = 23.1 vs. 21.75 ng/ml, p = 0.825; CRP: median = 96.8 vs. 217.4 mg/l, p = 0.052). None of the two markers could predict mortality. Conclusions: Presence of malaria parasites should be taken into consideration, either for clinical or epidemiological purposes, if using PCT or CRP to differentiate viral from invasive bacterial pneumonia in malaria-endemic areas.
Assuntos
Pré-Escolar , Pneumonia , Prevenção de Doenças , Antibacterianos , Estudos Epidemiológicos , Mortalidade Infantil , Técnicas de Laboratório Clínico , Diagnóstico , Pró-Calcitonina , MoçambiqueRESUMO
BACKGROUND: Progress towards the development of a malaria vaccine against Plasmodium vivax, the most widely distributed human malaria parasite, will require a better understanding of the immune responses that confer clinical protection to patients in regions where malaria is endemic. METHODS: Glutathione S-transferase (GST) and GST-fusion proteins representing the N- terminus of the merozoite surface protein 1 of P. vivax, PvMSP1-N, and the C-terminus, PvMSP1-C, were covalently coupled to BioPlex carboxylated beads. Recombinant proteins and coupled beads were used, respectively, in ELISA and Bioplex assays using immune sera of P. vivax patients from Brazil and PNG to determine IgG and subclass responses. Concordances between the two methods in the seropositivity responses were evaluated using the Kappa statistic and the Spearman's rank correlation. RESULTS: The results using this methodology were compared with the classical microtitre enzyme-linked immnosorbent assay (ELISA), showing that the assay was sensitive, reproducible and had good concordance with ELISA; yet, further research into different statistical analyses seems desirable before claiming conclusive results exclusively based on multiplex assays. As expected, results demonstrated that PvMSP1 was immunogenic in natural infections of patients from different endemic regions of Brazil and Papua New Guinea (PNG), and that age correlated only with antibodies against the C-terminus part of the molecule. Furthermore, the IgG subclass profiles were different in these endemic regions having IgG3 predominantly recognizing PvMSP1 in Brazil and IgG1 predominantly recognizing PvMSP1 in PNG. CONCLUSIONS: This study validates the use of the multiplex assay to measure naturally-acquired IgG antibodies against the merozoite surface protein 1 of P. vivax.
Assuntos
Anticorpos Antiprotozoários/imunologia , Glutationa Transferase/imunologia , Imunoglobulina G/sangue , Proteína 1 de Superfície de Merozoito/imunologia , Plasmodium vivax/imunologia , Animais , Anticorpos Antiprotozoários/sangue , Formação de Anticorpos , Brasil/epidemiologia , Ensaio de Imunoadsorção Enzimática , Glutationa Transferase/análise , Humanos , Imunoglobulina G/classificação , Malária Vivax/epidemiologia , Malária Vivax/imunologia , Malária Vivax/prevenção & controle , Proteína 1 de Superfície de Merozoito/análise , Papua Nova Guiné/epidemiologia , Plasmodium vivax/isolamento & purificação , Proteínas Recombinantes/imunologiaRESUMO
Background: Malaria remains a leading global health problem that requires the improved use of existing interventions and the accelerated development of new control methods. We aimed to assess the safety, immunogenicity, and initial efficacy of the malaria vaccine RTS,S/AS02D in infants in Africa. Methods: We did a phase I/IIb double-blind randomised trial of 214 infants in Mozambique. Infants were randomly assigned to receive three doses either of RTS,S/AS02D or the hepatitis B vaccine Engerix-B at ages 10 weeks, 14 weeks, and 18 weeks of age, as well as routine immunisation vaccines given at 8, 12, and 16 weeks of age. The primary endpoint was safety of the RTS,S/AS02D during the first 6 months of the study, and analysis was by intention to treat. Secondary endpoints included immunogenicity and analysis of new Plasmodium falciparum infections during a 3-month follow up after the third dose. Time to new infections in the per-protocol cohort were compared between groups using Cox regression models. This study is registered with ClinicalTrials.gov, number NCT00197028. Findings: There were 17 children (15.9%; 95% CI 9.5-24.2) with serious adverse events in each group. In the follow-up which ended on March 6, 2007, there were 31 serious adverse events in the RTS,S/AS02D group and 30 serious adverse events in the Engerix-B group, none of which were reported as related to vaccination. There were four deaths during this same follow-up period; all of them after the active detection of infection period had finished at study month 6 (two in RTSS/AS02D group and two in the Engerix-B group). RTS,S/AS02D induced high titres of anti-circumsporozoite antibodies. 68 first or only P falciparum infections were documented: 22 in the RTS,S/AS02D group and 46 in the control group. The adjusted vaccine efficacy was 65.9% (95% CI 42.6-79.8%, p<0.0001). Interpretation: The RTS,S/AS02D malaria vaccine was safe, well tolerated, and immunogenic in young infants. These findings set the stage for expanded phase III efficacy studies to confirm vaccine efficacy against clinical malaria disease
Assuntos
Humanos , Masculino , Feminino , Criança , Vacinas Antimaláricas/administração & dosagem , Vacinas Antimaláricas/efeitos adversos , Malária/prevenção & controle , Plasmodium falciparum/imunologia , Anticorpos Antiprotozoários/sangue , MoçambiqueRESUMO
The molecular epidemiology, antimicrobial susceptibility, and mechanisms of resistance of 34 Salmonella spp. strains causing acute gastroenteritis, isolated from different provinces in Cuba, were determined. Sixty-four percent of the strains showed multiresistance. Salmonella typhimurium was the most frequent with 15 strains (44%), 13 of which belonged to phagotype 104 and presented similar genetic profiles of pulsed field gel electrophoresis. High levels of resistance to tetracycline (53%), spectinomycin (50%), ampicillin (44%), and chloramphenicol (41%) were found. Resistance to tetracycline was associated with the tet G and tet A genes. Resistance to ampicillin was caused by the presence of beta-lactamases, mainly the CARB type. The floR gene was the main mechanism of resistance to chloramphenicol. Our results showed an antimicrobial susceptible clone of Salmonella enterica serotype Agona in two separate regions. This is the first report of the widespread dissemination of a multiresistant clone of S. enterica serotype Typhimurium definitive phage type 104 in Cuba.