RESUMO
BACKGROUND: Blood cultures remain the gold standard investigation for the diagnosis of bloodstream infections. In many locations, quality-assured processing of positive blood cultures is not possible. One solution is to incubate blood cultures locally, and then transport bottles that flag positive to a central reference laboratory for organism identification and antimicrobial susceptibility testing. However, the impact of delay between the bottle flagging positive and subsequent sub-culture on the viability of the isolate has received little attention. METHODS: This study evaluated the impact of delays to sub-culture (22 h to seven days) in three different temperature conditions (2-8 °C, 22-27 °C and 35 ± 2 °C) for bottles that had flagged positive in automated detection systems using a mixture of spiked and routine clinical specimens. Ninety spiked samples for five common bacterial causes of sepsis (Escherichia coli, Haemophilus influenzae, Staphylococcus aureus, Streptococcus agalactiae and Streptococcus pneumoniae) and 125 consecutive positive clinical blood cultures were evaluated at four laboratories located in Cambodia, Lao PDR and Thailand. In addition, the utility of transport swabs for preserving organism viability was investigated. RESULTS: All organisms were recoverable from all sub-cultures in all temperature conditions with the exception of S. pneumoniae, which was less likely to be recoverable after longer delays (> 46-50 h), when stored in hotter temperatures (35 °C), and from BacT/ALERT when compared with BACTEC blood culture bottles. Storage of positive blood culture bottles in cooler temperatures (22-27 °C or below) and the use of Amies bacterial transport swabs helped preserve viability of S. pneumoniae. CONCLUSIONS: These results have practical implications for the optimal workflow for blood culture bottles that have flagged positive in automated detection systems located remotely from a central processing laboratory, particularly in tropical resource-constrained contexts.
Assuntos
Bacteriemia , Hemocultura , Bacteriemia/diagnóstico , Bacteriemia/microbiologia , Bactérias , Técnicas Bacteriológicas/métodos , Meios de Cultura , Escherichia coli , Humanos , Estudos ProspectivosRESUMO
OBJECTIVE: To assess the role of point-of-care (PoC) assessment of C-reactive protein (CRP) and white blood cell (WBC) count to identify bacterial illness in Tanzanian children with non-severe non-malarial fever. METHODS: From the outpatient department of a district hospital in Tanzania, 428 patients between 3 months and 5 years of age who presented with fever and a negative malaria test were enrolled. All had a physical examination and bacterial cultures from blood and urine. Haemoglobin, CRP and WBC were measured by PoC devices. RESULTS: Positive blood cultures were detected in 6/428 (1.4%) children and urine cultures were positive in 24/401 (6.0%). Mean WBC was similar in children with or without bacterial illness (14.0 × 109 , 95% CI 12.0-16.0 × 109 vs. 12.0 × 109 , 95% CI 11.4-12.7 × 109), while mean CRP was higher in children with bacterial illness (41.0 mg/l, 95% CI 28.3-53.6 vs. 23.8 mg/l, 95% CI 17.8-27.8). In ROC analysis, the optimum cut-off value for CRP to identify bacterial illness was 19 mg/l but with an area under the curve of only 0.62. Negative predictive values exceeded 80%, while positive predictive values were under 40%. CONCLUSION: WBC and CRP levels had limited value in identifying children with bacterial infections. The positive predictive values for both tests were too low to be used as single tools for treatment decisions.
Assuntos
Bactérias , Infecções Bacterianas/diagnóstico , Proteína C-Reativa/metabolismo , Febre/diagnóstico , Contagem de Leucócitos , Leucócitos/metabolismo , Sistemas Automatizados de Assistência Junto ao Leito , Infecções Bacterianas/sangue , Infecções Bacterianas/complicações , Infecções Bacterianas/microbiologia , Pré-Escolar , Feminino , Febre/sangue , Febre/etiologia , Febre/microbiologia , Humanos , Lactente , Malária , Masculino , Pediatria , Curva ROC , Valores de Referência , TanzâniaRESUMO
OBJECTIVE: In sub-Saharan Africa, the use of malaria rapid diagnostic tests (mRDT) has raised awareness of alternative fever causes in children but few studies have included adults. To address this gap, we conducted a study of mRDT-negative fever aetiologies among children and adults in Tanzania. METHODS: A total of 1028 patients aged 3 months to 50 years with a febrile illness and negative mRDT were enrolled from a Tanzanian hospital outpatient department. All had a physical examination and cultures from blood, nasopharynx/throat and urine. Patients were followed on Days 7 and 14 and children meeting WHO criteria for pneumonia were followed on Day 2 with chest radiology. RESULTS: Respiratory symptoms were the most frequent presenting complaint, reported by 20.3% of adults and 64.0% (339/530) of children. Of 38 X-rayed children meeting WHO pneumonia criteria, 47.4% had a normal X-ray. Overall, only 1.3% of 1028 blood cultures were positive. Salmonella typhi was the most prevalent pathogen isolated (7/13, 53.8%) and S. typhi patients reported fever for a median of 7 days (range 2-14). Children with bacteraemia did not present with WHO symptoms requiring antibiotic treatment. Young children and adults had similar prevalences of positive urine cultures (24/428 and 29/498, respectively). CONCLUSION: Few outpatient fevers are caused by blood stream bacterial infection, and most adult bacteraemia would be identified by current clinical guidelines although paediatric bacteraemia may be more difficult to diagnose. While pneumonia may be overdiagnosed, urinary tract infection was relatively common. Our results emphasise the difficulty in identifying African children in need of antibiotics among the majority who do not.
RESUMO
BACKGROUND: The epidemiology of Salmonella Typhi and invasive nontyphoidal Salmonella (NTS) differs, and prevalence of these pathogens among children in sub-Saharan Africa may vary in relation to malaria transmission intensity. METHODS: We compared the prevalence of bacteremia among febrile pediatric inpatients aged 2 months to 13 years recruited at sites of high and low malaria endemicity in Tanzania. Enrollment at Teule Hospital, the high malaria transmission site, was from June 2006 through May 2007, and at Kilimanjaro Christian Medical Centre (KCMC), the low malaria transmission site, from September 2007 through August 2008. Automated blood culture, malaria microscopy with Giemsa-stained blood films, and human immunodeficiency virus testing were performed. RESULTS: At Teule, 3639 children were enrolled compared to 467 at KCMC. Smear-positive malaria was detected in 2195 of 3639 (60.3%) children at Teule and 11 of 460 (2.4%) at KCMC (P < .001). Bacteremia was present in 336 of 3639 (9.2%) children at Teule and 20 of 463 (4.3%) at KCMC (P < .001). NTS was isolated in 162 of 3639 (4.5%) children at Teule and 1 of 463 (0.2%) at KCMC (P < .001). Salmonella Typhi was isolated from 11 (0.3%) children at Teule and 6 (1.3%) at KCMC (P = .008). With NTS excluded, the prevalence of bacteremia at Teule was 5.0% and at KCMC 4.1% (P = .391). CONCLUSIONS: Where malaria transmission was intense, invasive NTS was common and Salmonella Typhi was uncommon, whereas the inverse was observed at a low malaria transmission site. The relationship between these pathogens, the environment, and the host is a compelling area for further research.
Assuntos
Bacteriemia/epidemiologia , Infecções por Salmonella/epidemiologia , Salmonella/isolamento & purificação , Adolescente , Criança , Pré-Escolar , Coinfecção/epidemiologia , Feminino , Humanos , Lactente , Malária/epidemiologia , Masculino , Prevalência , Salmonella/classificação , Tanzânia/epidemiologiaRESUMO
BACKGROUND: In malaria-endemic settings, asymptomatic parasitemia complicates the diagnosis of malaria. Histidine-rich protein 2 (HRP2) is produced by Plasmodium falciparum, and its plasma concentration reflects the total body parasite burden. We aimed to define the malaria-attributable fraction of severe febrile illness, using the distributions of plasma P. falciparum HRP2 (PfHRP2) concentrations from parasitemic children with different clinical presentations. METHODS: Plasma samples were collected from and peripheral blood slides prepared for 1435 children aged 6-60 months in communities and a nearby hospital in northeastern Tanzania. The study population included children with severe or uncomplicated malaria, asymptomatic carriers, and healthy control subjects who had negative results of rapid diagnostic tests. The distributions of plasma PfHRP2 concentrations among the different groups were used to model severe malaria-attributable disease. RESULTS: The plasma PfHRP2 concentration showed a close correlation with the severity of infection. PfHRP2 concentrations of >1000 ng/mL denoted a malaria-attributable fraction of severe disease of 99% (95% credible interval [CI], 96%-100%), with a sensitivity of 74% (95% CI, 72%-77%), whereas a concentration of <200 ng/mL denoted severe febrile illness of an alternative diagnosis in >10% (95% CI, 3%-27%) of patients. Bacteremia was more common among patients in the lowest and highest PfHRP2 concentration quintiles. CONCLUSIONS: The plasma PfHRP2 concentration defines malaria-attributable disease and distinguishes severe malaria from coincidental parasitemia in African children in a moderate-to-high transmission setting.
Assuntos
Antígenos de Protozoários/sangue , Febre/etiologia , Malária Falciparum/epidemiologia , Malária Falciparum/fisiopatologia , Malária Falciparum/transmissão , Parasitemia/parasitologia , Plasmodium falciparum/patogenicidade , Proteínas de Protozoários/sangue , Índice de Gravidade de Doença , Pré-Escolar , Feminino , Febre/epidemiologia , Febre/parasitologia , Humanos , Lactente , Malária Falciparum/parasitologia , Masculino , Parasitemia/epidemiologia , Tanzânia/epidemiologiaRESUMO
BACKGROUND: In African children, distinguishing severe falciparum malaria from other severe febrile illnesses with coincidental Plasmodium falciparum parasitaemia is a major challenge. P. falciparum histidine-rich protein 2 (PfHRP2) is released by mature sequestered parasites and can be used to estimate the total parasite burden. We investigated the prognostic significance of plasma PfHRP2 and used it to estimate the malaria-attributable fraction in African children diagnosed with severe malaria. METHODS AND FINDINGS: Admission plasma PfHRP2 was measured prospectively in African children (from Mozambique, The Gambia, Kenya, Tanzania, Uganda, Rwanda, and the Democratic Republic of the Congo) aged 1 month to 15 years with severe febrile illness and a positive P. falciparum lactate dehydrogenase (pLDH)-based rapid test in a clinical trial comparing parenteral artesunate versus quinine (the AQUAMAT trial, ISRCTN 50258054). In 3,826 severely ill children, Plasmadium falciparum PfHRP2 was higher in patients with coma (p = 0.0209), acidosis (p<0.0001), and severe anaemia (p<0.0001). Admission geometric mean (95%CI) plasma PfHRP2 was 1,611 (1,350-1,922) ng/mL in fatal cases (n = 381) versus 1,046 (991-1,104) ng/mL in survivors (n = 3,445, p<0.0001), without differences in parasitaemia as assessed by microscopy. There was a U-shaped association between log(10) plasma PfHRP2 and risk of death. Mortality increased 20% per log(10) increase in PfHRP2 above 174 ng/mL (adjusted odds ratio [AOR] 1.21, 95%CI 1.05-1.39, p = 0.009). A mechanistic model assuming a PfHRP2-independent risk of death in non-malaria illness closely fitted the observed data and showed malaria-attributable mortality less than 50% with plasma PfHRP2≤174 ng/mL. The odds ratio (OR) for death in artesunate versus quinine-treated patients was 0.61 (95%CI 0.44-0.83, p = 0.0018) in the highest PfHRP2 tertile, whereas there was no difference in the lowest tertile (OR 1.05; 95%CI 0.69-1.61; p = 0.82). A limitation of the study is that some conclusions are drawn from a mechanistic model, which is inherently dependent on certain assumptions. However, a sensitivity analysis of the model indicated that the results were robust to a plausible range of parameter estimates. Further studies are needed to validate our findings. CONCLUSIONS: Plasma PfHRP2 has prognostic significance in African children with severe falciparum malaria and provides a tool to stratify the risk of "true" severe malaria-attributable disease as opposed to other severe illnesses in parasitaemic African children.
Assuntos
Antígenos de Protozoários/sangue , Malária Falciparum/sangue , Malária Falciparum/diagnóstico , Parasitemia/sangue , Parasitemia/diagnóstico , Proteínas de Protozoários/sangue , Índice de Gravidade de Doença , Adolescente , África/epidemiologia , Artemisininas/uso terapêutico , Artesunato , Criança , Pré-Escolar , Demografia , Feminino , Humanos , Lactente , Malária Falciparum/mortalidade , Malária Falciparum/parasitologia , Masculino , Modelos Biológicos , Razão de Chances , Parasitemia/complicações , Estudos Prospectivos , Quinina/uso terapêutico , Fatores de RiscoRESUMO
BACKGROUND: Lactic acidosis is a consistent predictor of mortality owing to severe infectious disease, but its detection in low-income settings is limited to the clinical sign of "deep breathing" because of the lack of accessible technology for its measurement. We evaluated the use of a point-of-care (POC) diagnostic device for blood lactate measurement to assess the severity of illness in children admitted to a district hospital in Tanzania. METHODS: Children between the ages of 2 months and 13 years with a history of fever were enrolled in the study during a period of 1 year. A full clinical history and examination were undertaken, and blood was collected for culture, microscopy, complete blood cell count, and POC measurement of blood lactate and glucose. RESULTS: The study included 3248 children, of whom 164 (5.0%) died; 45 (27.4%) of these had raised levels of blood lactate (>5 mmol/L) but no deep breathing. Compared with mortality in children with lactate levels of ≤ 3 mmol/L, the unadjusted odds of dying were 1.6 (95% confidence interval [CI].8-3.0), 3.4 (95% CI, 1.5-7.5), and 8.9 (95% CI, 4.7-16.8) in children with blood lactate levels of 3.1-5.0, 5.1-8.0, or >8.0 mmol/L, respectively. The prevalence of raised lactate levels (>5 mmol/L) was greater in children with malaria than in children with nonmalarial febrile illness (P < .001) although the associated mortality was greater in slide-negative children. CONCLUSIONS: POC lactate measurement can contribute to the assessment of children admitted to hospital with febrile illness and can also create an opportunity for more hospitals in resource-poor settings to participate in clinical trials of interventions to reduce mortality associated with hyperlactatemia.
Assuntos
Febre/sangue , Ácido Láctico/sangue , Sistemas Automatizados de Assistência Junto ao Leito , Adolescente , Anemia/sangue , Infecções Bacterianas/sangue , Criança , Pré-Escolar , Estudos de Coortes , Feminino , Hospitais/estatística & dados numéricos , Humanos , Lactente , Modelos Logísticos , Malária Falciparum/sangue , Masculino , Mortalidade , Curva ROC , Fatores de Risco , TanzâniaRESUMO
OBJECTIVE: To compare the performance of the Paracheck™ rapid diagnostic test (RDT) with microscopy for diagnosing malaria in hospitalised children. METHODS: Children aged between 2 months and 13 years with fever were enrolled in the study over 1 year. A standard clinical history and examination were recorded and blood drawn for culture, complete blood count, Paracheck™ RDT and double-read blood slide. RESULTS: Of 3639 children enrolled, 2195 (60.3%) were slide positive. The sensitivity and specificity of Paracheck were 97.5% (95% CI 96.9-98.0) and 65.3% (95% CI 63.8-66.9), respectively. There was an inverse relationship between age-specific prevalence of parasitaemia and Paracheck specificity. In logistic regression model, false-positive Paracheck results were significantly associated with pre-admission use of antimalarial drug (OR 1.44, 95% CI 1.16-1.78), absence of current fever (OR 0.64, 95% CI 0.52-0.79) and non-typhi Salmonella bacteraemia (OR 3.89. 95% CI 2.27-6.63). In spite of high sensitivity, 56/2195 (2.6%) of true infections were Paracheck negative and 8/56 (14.3%) were in patients with >50,000 parasites/µl. CONCLUSIONS: Paracheck had poor specificity in diagnosing malaria in severely ill children; this was likely to be due to HRP2 persistence following recent parasite clearance. The combination of positive Paracheck and negative blood slide results identified a group of children at high risk of non-typhi Salmonella infection. While Paracheck was highly sensitive, some high-density infections were missed. For children with severe febrile illness, at least two reliable negative parasitological test results should be available to justify withholding antimalarial treatment; the optimal choice of these has yet to be identified.
Assuntos
Antígenos de Protozoários/sangue , Malária Falciparum/diagnóstico , Proteínas de Protozoários/sangue , Adolescente , Distribuição por Idade , Animais , Criança , Pré-Escolar , Doenças Endêmicas , Métodos Epidemiológicos , Reações Falso-Positivas , Feminino , Febre/parasitologia , Hospitalização , Hospitais de Distrito , Humanos , Lactente , Malária Falciparum/epidemiologia , Malária Falciparum/parasitologia , Masculino , Plasmodium falciparum/imunologia , Plasmodium falciparum/isolamento & purificação , Kit de Reagentes para Diagnóstico , Saúde da População Rural/estatística & dados numéricos , Tanzânia/epidemiologiaRESUMO
BACKGROUND: The annual incidence and temporal trend of severe malaria and community-acquired bacteraemia during a four-year period in Muheza, Tanzania was assessed. METHODS: Data on severely ill febrile children aged 2 months to 14 years from three prospective studies conducted at Muheza District Hospital from 2006 to 2010 was pooled and analysed. On admission, each enrolled child had a thin and thick blood film and at least one rapid diagnostic test for falciparum malaria, as well as a blood culture. The annual incidence of bacteraemia and severe malaria among children coming from Muheza was calculated and their temporal trend was assessed. RESULTS: Overall, 1, 898 severe falciparum malaria and 684 bacteraemia cases were included. Of these, 1, 356 (71%) and 482 (71%), respectively, were from the referral population of Muheza. The incidence of falciparum malaria and all-cause bacteraemia in Muheza decreased five-fold and three-fold, respectively, from the first to the fourth year of surveillance (p < 0.0001). During this period, the median ages of children from Muheza admitted with severe malaria increased from 1.7 to 2.5 years (p < 0.0001). The reduction in all-cause bacteraemia was mainly driven by the 11-fold decline in the incidence of non-typhoidal salmonellosis. The annual incidences of Haemophilus influenzae and pneumococcal invasive bacterial infections decreased as well but were much fewer in number. CONCLUSIONS: These results add to the growing evidence of the decline in malaria associated with a decrease in non-typhoidal salmonellosis and possibly other bacteraemias. Malarial prevention and control strategies may provide a greater benefit than the mere reduction of malaria alone.
Assuntos
Bacteriemia/epidemiologia , Infecções Comunitárias Adquiridas/epidemiologia , Malária/epidemiologia , Adolescente , Criança , Criança Hospitalizada , Pré-Escolar , Feminino , Infecções por Haemophilus/epidemiologia , Humanos , Incidência , Lactente , Masculino , Infecções Pneumocócicas/epidemiologia , Estudos Prospectivos , Infecções por Salmonella/epidemiologia , Tanzânia/epidemiologia , Febre Tifoide/epidemiologiaRESUMO
BACKGROUND: WHO guidelines for the treatment of young children with suspected malaria have recently changed from presumptive treatment to anti-malarial treatment guided by a blood slide or malaria rapid diagnostic test (RDT). However, there is limited evidence of the safety of this policy in routine outpatient settings in Africa. METHODS: Children 3-59 months of age with a non-severe febrile illness and no obvious cause were enrolled over a period of one year in a malaria endemic area of Tanzania. Treatment was determined by the results of a clinical examination and RDT result, and blood culture and serum lactate were also collected. RDT-negative children were followed up over 14 days. RESULTS: Over the course of one year, 965 children were enrolled; 158 (16.4%) were RDT-positive and treated with artemether-lumefantrine and 807 (83.4%) were RDT-negative and treated with non-anti-malarial medicines. Compared with RDT-positives, RDT-negative children were on average younger with a lower axillary temperature and more likely to have a history of cough or difficulty in breathing. Six (0.6%) children became RDT-positive after enrollment, all of whom were PCR-negative for Plasmodium falciparum DNA at enrollment. In addition, 12 (1.2%) children were admitted to hospital, one with possible malaria, none of whom died. A bacterial pathogen was identified in 9/965 (0.9%) children, eight of whom were RDT-negative and one was RDT-positive, but slide-negative. Excluding three children with Salmonella typhi, all of the children with bacteraemia were ≤ 12 months of age. Compared to double-read research slide results RDTs had a sensitivity of 97.8% (95% CI 96.9-98.7) and specificity of 96.3% (95% CI 96.3-98.4). CONCLUSIONS: Use of RDTs to direct the use of anti-malarial drugs in young children did not result in any missed diagnoses of malaria although new infections soon after a consultation with a negative RDT result may undermine confidence in results. Invasive bacterial disease is uncommon in children with non-severe illness and most cases occurred in infants with a current fever.
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Antimaláricos/administração & dosagem , Testes Diagnósticos de Rotina/métodos , Monitoramento de Medicamentos/métodos , Malária Falciparum/diagnóstico , Malária Falciparum/tratamento farmacológico , Bacteriemia/diagnóstico , Sangue/microbiologia , Sangue/parasitologia , Pré-Escolar , Feminino , Humanos , Lactente , Lactatos/sangue , Masculino , Sensibilidade e Especificidade , TanzâniaRESUMO
BACKGROUND: Typhoid fever remains a significant health problem in many developing countries. A rapid test with a performance comparable to that of blood culture would be highly useful. A rapid diagnostic test for typhoid fever, Tubex®, is commercially available that uses particle separation to detect immunoglobulin M directed towards Salmonella Typhi O9 lipopolysaccharide in sera. METHODS: We assessed the sensitivity and specificity of the Tubex test among Tanzanian children hospitalized with febrile illness using blood culture as gold standard. Evaluation was done considering blood culture confirmed S. Typhi with non-typhi salmonella (NTS) and non - salmonella isolates as controls as well as with non-salmonella isolates only. RESULTS: Of 139 samples tested with Tubex, 33 were positive for S. Typhi in blood culture, 49 were culture-confirmed NTS infections, and 57 were other non-salmonella infections. Thirteen hemolyzed samples were excluded. Using all non - S. Typhi isolates as controls, we showed a sensitivity of 79% and a specificity of 89%. When the analysis was repeated excluding NTS from the pool of controls we showed a sensitivity of 79% and a specificity of 97%. There was no significant difference in the test performance using the two different control groups (p > 0.05). CONCLUSION: This first evaluation of the Tubex test in an African setting showed a similar performance to those seen in some Asian settings. Comparison with the earlier results of a Widal test using the same samples showed no significant difference (p > 0.05) for any of the performance indicators, irrespective of the applied control group.
Assuntos
Testes Diagnósticos de Rotina/métodos , Febre Tifoide/diagnóstico , Anticorpos Antibacterianos/sangue , Anticorpos Antibacterianos/imunologia , Criança , Criança Hospitalizada/estatística & dados numéricos , Pré-Escolar , Testes Diagnósticos de Rotina/instrumentação , Humanos , Masculino , População Rural/estatística & dados numéricos , Salmonella typhi/imunologia , Salmonella typhi/isolamento & purificação , Tanzânia , Febre Tifoide/sangue , Febre Tifoide/imunologia , Febre Tifoide/microbiologiaRESUMO
In every year, up to one million children die due to pneumococcal disease. Children infected with Human Immunodeficiency Virus (HIV) are mostly affected, as they appear to have higher rates of pneumococcal carriage and invasive disease. Successful immunity is dependent on mounting a sufficient immune response to the vaccine. We conducted a double blinded crossover randomised controlled trial to determine the serum antibody response (≥4-fold and geometric mean concentration) to pneumococcal vaccine (PCV13) serotypes at 3 months after second vaccination. We also determined the number and proportion of children carrying new (not present at baseline) vaccine serotypes of S. pneumoniae isolated from nasopharynx at 6 months post initial vaccination in recipients of Prevenar13® compared with those given Haemophilus influenzae-type b (Hib) vaccine (control). The study was conducted at St Augustine's also known as Teule Hospital in Muheza, Tanga Tanzania. 225 HIV infected children aged 1-14 years were enrolled from Jan 2013 to Nov 2013 and randomised to Prevenar13® or Hib vaccines each given at baseline and 2-3 months later. Nasopharyngeal and serum samples were collected at baseline and 4-6 months later. Serotyping was done by Quellung Reaction using Staten antisera. Serum antibodies were ELISA quantified. The study revealed a non-significant reduction in the acquisition of new vaccine serotypes of S. pneumoniae in the recipients of PCV13 by nearly a third compared to those who received Hib vaccine. The vaccine efficacy was 30.5% (95% confidence interval [CI] -6.4-54.6%, P = 0.100)]. The antibody response was not enough to induce a 4-fold rise in GMC in 7 of the 13 vaccine serotypes. When combining the effects of preventing new acquisition and clearing existing vaccine type carriage, the overall efficacy was 31.5% (95% CI 1.5-52.4%, P = 0.045). In the PCV13 group, the proportion of participants carrying vaccine serotype was significantly lower after 2 doses of PCV13 (30%; 32/107), compared with the baseline proportion (48%; 51/107). The introduction of PCV13 targeting HIV-positive children in a setting similar to Tanzania is likely to be associated with appreciable decrease in the acquisition and carriage of pneumococci, which is an important marker of the likely effect of the vaccine on pneumococcal disease. Clinical Trial Registration: https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=335579, identifier ACTRN12610000999033.
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Anticorpos Antibacterianos/sangue , Infecções por HIV , Infecções Pneumocócicas/microbiologia , Infecções Pneumocócicas/prevenção & controle , Vacinas Pneumocócicas/imunologia , Síndrome da Imunodeficiência Adquirida/complicações , Adolescente , Anticorpos Antibacterianos/efeitos dos fármacos , Portador Sadio/imunologia , Criança , Pré-Escolar , Estudos Cross-Over , Método Duplo-Cego , Feminino , Infecções por HIV/complicações , Humanos , Lactente , Masculino , Infecções Pneumocócicas/imunologia , Vacinas Pneumocócicas/uso terapêutico , Sorogrupo , Streptococcus pneumoniae , Tanzânia , Vacinas Conjugadas/imunologiaRESUMO
BACKGROUND: The diagnosis of typhoid fever is confirmed by culture of Salmonella enterica serotype Typhi (S. typhi). However, a more rapid, simpler, and cheaper diagnostic method would be very useful especially in developing countries. The Widal test is widely used in Africa but little information exists about its reliability. METHODS: We assessed the performance of the Widal tube agglutination test among febrile hospitalized Tanzanian children. We calculated the sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of various anti-TH and -TO titers using culture-confirmed typhoid fever cases as the "true positives" and all other febrile children with blood culture negative for S. typhi as the "true negatives." RESULTS: We found that 16 (1%) of 1,680 children had culture-proven typhoid fever. A single anti-TH titer of 1:80 and higher was the optimal indicator of typhoid fever. This had a sensitivity of 75%, specificity of 98%, NPV of 100%, but PPV was only 26%. We compared our main findings with those from previous studies. CONCLUSION: Among febrile hospitalized Tanzanian children with a low prevalence of typhoid fever, a Widal titer of > or = 1:80 performed well in terms of sensitivity, specificity, and NPV. However a test with improved PPV that is similarly easy to apply and cost-efficient is desirable.
Assuntos
Testes de Aglutinação/métodos , Técnicas Bacteriológicas/métodos , Salmonella typhi/imunologia , Febre Tifoide/diagnóstico , Adolescente , Criança , Pré-Escolar , Países em Desenvolvimento , Hospitais , Humanos , Lactente , Valor Preditivo dos Testes , População Rural , Sensibilidade e Especificidade , TanzâniaRESUMO
In a region with high rates of mortality among children aged <5 years, the underfunded health care systems of sub-Saharan Africa have few resources available to perform surveillance activities that can help determine the causes of morbidity and mortality in the region. At present, there are few examples of attempts to promote public health care surveillance that might inform current debates about how to expand and improve surveillance, particularly for bacterial diseases. Driven by this gap in knowledge, we attempted to explore the successes and failures of the Network for Surveillance of Pneumococcal Disease in the East African Region and to share the experiences of what are essentially nonresearch public-sector hospitals in East Africa, with the hopes that surveillance systems for other diseases, especially those that require complex diagnostic support, may be informed by these experiences. The state of services essential for surveillance and the measures taken to overcome any shortcomings are described, as is the progress made in improving clinical diagnosis, laboratory processing, and data management. For surveillance to play a role in public health care, ministries of health and associated institutions must own and push forward the surveillance agenda, with support from global partners, and take advantage of the developments that have been achieved within the institutions.
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Redes Comunitárias/organização & administração , Infecções Pneumocócicas/epidemiologia , Vigilância da População/métodos , África Oriental/epidemiologia , Pré-Escolar , Humanos , LactenteRESUMO
BACKGROUND: Acute febrile illness is the most common cause of outpatient attendance and mortality for children in Africa. Malaria and bacterial disease are difficult to differentiate with limited diagnostic facilities. Combinations of antibiotics and antimalarials are potentially attractive for treatment of the syndrome. Azithromycin plus artesunate (AT+AS) is an effective antimalarial combination for adults in Asia. METHODS: We performed an individually randomized, open-label trial of AZ+AS versus artemether-lumefantrine (AL) involving children (age, 6-59 months) with uncomplicated malaria in Muheza, Tanzania. The primary outcome was parasitological failure by day 28. Parasitological failure by day 42 and failure corrected for reinfection were major secondary outcomes. RESULTS: Of 2497 children screened, 261 were eligible; 129 were randomized to the AZ+AS arm, and 132 were randomized to the AL arm; 92% and 91%, respectively, underwent follow-up to 28 days. Planned interim analysis was performed after 200 patients reached day 28 follow-up and led the Data and Safety Monitoring Board to halt further recruitment. All children had a complete initial response to treatment, but 69 (58%) of 119 children in the AZ+AS arm and 24 (20%) of 120 in the AL arm had asexual parasites at or by day 28 (adjusted odds ratio for failure with AZ+AS treatment, 6.1; 95% confidence interval, 3.3-11.4; P < .001). When analysis was restricted to children with recrudescence, the parasitological failure rate was 32% in the AZ+AS arm and 9% in the AL arm. This difference was maintained at day 42. CONCLUSIONS: This trial does not support the use of AZ+AS as treatment for malaria or acute febrile illness in children in areas of Africa with high levels of existing antimalarial drug resistance. CLINICAL TRIALS REGISTRATION: ClinicalTrials.gov NCT00694694.
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Antimaláricos/uso terapêutico , Artemisininas/uso terapêutico , Azitromicina/uso terapêutico , Etanolaminas/uso terapêutico , Febre de Causa Desconhecida/tratamento farmacológico , Fluorenos/uso terapêutico , Malária/tratamento farmacológico , Animais , Artemeter , Artesunato , Pré-Escolar , Quimioterapia Combinada , Feminino , Humanos , Lactente , Lumefantrina , Masculino , Tanzânia , Resultado do TratamentoRESUMO
Interferon-gamma (IFN-γ) release assays (IGRAs) are used to detect cellular immune recognition of Mycobacterium tuberculosis The chemokine IFN-γ-inducible protein 10 (IP-10) is an alternative diagnostic biomarker to IFN-γ. Several conditions interfere with IGRA test performance. We aimed to assess the possible influence of Plasmodium falciparum infection on the IGRA test QuantiFERON-TB GOLD® In-Tube (QFT) test and an in-house IP-10 release assay. In total, 241 Tanzanian adults were included; 184 patients with uncomplicated malaria (88 human immunodeficiency virus [HIV] coinfected) and 57 HIV-infected patients without malaria infection. Malaria was treated with artemether-lumefantrine (Coartem®). QFT testing was performed before initiation of malaria treatment and at days 7 and 42. In total, 172 patients completed follow-up. IFN-γ and IP-10 was measured in QFT supernatants. We found that during malaria infection IFN-γ and IP-10 levels in the unstimulated samples were elevated, mitogen responsiveness was impaired, and CD4 cell counts were decreased. These alterations reverted after malaria treatment. Concurrent malaria infection did not affect QFT test results, whereas there were more indeterminate IP-10 results during acute malaria infection. We suggest that IGRA and IP-10 release assay results of malaria patients should be interpreted with caution and that testing preferably should be postponed until after malaria treatment.
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Testes de Liberação de Interferon-gama , Tuberculose Latente/diagnóstico , Malária Falciparum/complicações , Adolescente , Adulto , Contagem de Linfócito CD4 , Estudos de Casos e Controles , Quimiocina CXCL10/sangue , Coinfecção , Reações Falso-Negativas , Feminino , Infecções por HIV/complicações , Humanos , Interferon gama/sangue , Testes de Liberação de Interferon-gama/normas , Tuberculose Latente/complicações , Masculino , Pessoa de Meia-Idade , Tanzânia/epidemiologia , Adulto JovemRESUMO
BACKGROUND: The burden of typhoid in sub-Saharan African (SSA) countries has been difficult to estimate, in part, due to suboptimal laboratory diagnostics. However, surveillance blood cultures at two sites in Nigeria have identified typhoid associated with Salmonella enterica serovar Typhi (S. Typhi) as an important cause of bacteremia in children. METHODS: A total of 128 S. Typhi isolates from these studies in Nigeria were whole-genome sequenced, and the resulting data was used to place these Nigerian isolates into a worldwide context based on their phylogeny and carriage of molecular determinants of antibiotic resistance. RESULTS: Several distinct S. Typhi genotypes were identified in Nigeria that were related to other clusters of S. Typhi isolates from north, west and central regions of Africa. The rapidly expanding S. Typhi clade 4.3.1 (H58) previously associated with multiple antimicrobial resistances in Asia and in east, central and southern Africa, was not detected in this study. However, antimicrobial resistance was common amongst the Nigerian isolates and was associated with several plasmids, including the IncHI1 plasmid commonly associated with S. Typhi. CONCLUSIONS: These data indicate that typhoid in Nigeria was established through multiple independent introductions into the country, with evidence of regional spread. MDR typhoid appears to be evolving independently of the haplotype H58 found in other typhoid endemic countries. This study highlights an urgent need for routine surveillance to monitor the epidemiology of typhoid and evolution of antimicrobial resistance within the bacterial population as a means to facilitate public health interventions to reduce the substantial morbidity and mortality of typhoid.
RESUMO
Data from a prospective study of 3,319 children ages 2 months to 5 years admitted with febrile illness to a Tanzanian district hospital were analyzed to determine the relationship of blood glucose and mortality. Hypoglycemia (blood sugar < 2.5 mmol/L and < 45 mg/dL) was found in 105 of 3,319 (3.2%) children at admission, and low-normal blood glucose (2.5-5 mmol/L and 45-90 mg/dL) was found in 773 of 3,319 (23.3%) children. Mortality was inversely related to admission blood sugar; compared with children with an admission blood glucose of > 5 mmol/L, the adjusted odds of dying were 3.3 (95% confidence interval = 2.1-5.2) and 9.8 (95% confidence interval = 5.1-19.0) among children with admission blood glucose 2.5-5 and < 2.5 mmol/L, respectively. Receiver operating characteristic (ROC) analysis suggested an optimal cutoff for admission blood sugar of < 5 mmol/L in predicting mortality (sensitivity = 57.7%, specificity = 75.2%). A cutoff for admission blood glucose of < 5 mmol/L represents a simple and clinically useful predictor of mortality in children admitted with severe febrile illness to hospital in resource-poor settings.
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Glicemia , Febre/sangue , Hipoglicemia/complicações , Malária Falciparum/sangue , Malária Falciparum/mortalidade , Pré-Escolar , Feminino , Humanos , Hipoglicemia/sangue , Hipoglicemia/epidemiologia , Lactente , Malária Falciparum/epidemiologia , Masculino , Estudos Prospectivos , Curva ROC , Tanzânia/epidemiologiaRESUMO
Severe febrile illness is a major cause of adult hospital admission in Africa. Studies of non-malarial fever come largely from children or from high HIV prevalence settings. This prospective study of adult admissions with severe febrile illness in a malaria-endemic area with moderate/low HIV prevalence investigated admission diagnosis as well as final diagnosis based on results of investigations. Severe malaria was the admission diagnosis in 148/198 (74.7%) cases. Plasmodium falciparum was identified in 38/188 (20.2%) admissions and 26/198 (13.1%) were bacteraemic, with 13/25 (52%) prescribed empirical antibiotics. HIV was equally common among those with (16/37; 43.2%) and without P. falciparum (50/138; 36.2%) (p=0.44). In 6/22 (27.3%) deaths, blood cultures were positive for a pathogen, with Streptococcus pneumoniae, Escherichia coli and non-Typhi Salmonella predominating. Chest radiography was suspicious for bacterial/mycobacterial disease in 5/22 additional deaths. Systemic inflammatory response syndrome criteria were more sensitive but less specific than WHO severe malaria criteria for predicting mortality. Malaria is overdiagnosed in adults with severe febrile illness and was not associated with mortality in the absence of co-infection in this high-incidence setting. Adults with severe febrile illness should be tested for malaria and HIV using rapid, sensitive tests. Early antibiotic use should be promoted. Improved diagnostics for invasive bacterial disease are needed.
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Infecções Oportunistas Relacionadas com a AIDS/epidemiologia , Síndrome da Imunodeficiência Adquirida/epidemiologia , Bacteriemia/diagnóstico , Bacteriemia/epidemiologia , Febre/epidemiologia , Febre/microbiologia , Hospitalização/estatística & dados numéricos , Malária/epidemiologia , Infecções Oportunistas Relacionadas com a AIDS/imunologia , Infecções Oportunistas Relacionadas com a AIDS/microbiologia , Síndrome da Imunodeficiência Adquirida/imunologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Bacteriemia/complicações , Bacteriemia/microbiologia , Contagem de Linfócito CD4 , Coinfecção , Feminino , Febre/imunologia , Mortalidade Hospitalar , Humanos , Malária/imunologia , Malária/microbiologia , Masculino , Pessoa de Meia-Idade , Prevalência , Estudos Prospectivos , Tanzânia/epidemiologiaRESUMO
BACKGROUND: Excluding HIV infection among infants and young children in resource-poor settings where nucleic acid amplification tests (NAAT) are not routinely available remains a considerable challenge. OBJECTIVES: To assess the performance of two rapid HIV antibody tests (RT) used alone and in parallel for excluding HIV infection among acutely ill infants and children <18 months in comparison to NAAT in a region where maternal HIV prevalence was approximately 7%. STUDY DESIGN: Infants and children ≥2<18 months admitted to hospital with an acute febrile illness had two rapid antibody tests in parallel, with single and parallel results subsequently compared against NAAT. RESULTS: HIV prevalence among 1602 enrolled infants was 3.4%. All 1526 infants with 2 negative RT were HIV negative by NAAT. All 46 infants with 2 positive RT were HIV positive by NAAT. The overall specificity of two rapid tests for excluding HIV infection was 99.5%. Sensitivity and specificity were ≥99% and >98%, respectively, across all age brackets ≥2<18 months. Overall sensitivity and specificity for a single RT was 98.2% and 99%, respectively, for Determine, and 85.5% and 99.6%, respectively, for Capillus. CONCLUSIONS: In a setting with a maternal HIV prevalence rate of <10%, a single negative RT had excellent specificity and two negative RT performed in parallel had a perfect negative predictive value for HIV infection among acutely ill patients <18 months of age. In this and similar settings, RT could assist with excluding HIV infection with much lower complexity and cost than NAAT.