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People living with HIV (PLWH) are at increased risk of pneumococcal infections compared with the general population. The objective of this study was to investigate the immunogenicity of the combined pneumococcal vaccination schedule in PLWH. In this prospective cohort study, adult PLWH on antiretroviral therapy and HIV-negative controls received the 13-valent pneumococcal conjugate vaccine (PCV13) at baseline followed by the 23-valent pneumococcal polysaccharide vaccine (PPSV23) at Month 2. Serotype-specific IgG levels of 24 vaccine serotypes were measured at Months 0, 2, 4, 6 and 12. The primary outcome was seroprotection at Month 4, defined as the proportion of patients with a post-immunisation IgG concentration of ≥1.3 μg/mL for ≥70% (17/24) of vaccine serotypes. Samples of 120 patients were analysed. Seroprotection at Month 4 was 49% (39/80) for PLWH and 82% (28/34) in controls. At Month 12, seroprotection had decreased to 23% (18/79) and 63% (22/35), respectively. Nadir CD4 count ≥200 cells/mm3, preserved kidney function and co-administration of the diphtheria–tetanus–polio (DTP) vaccine were associated with better seroprotection among PLWH. IgG levels both of PLWH and controls (all 24 vaccine serotypes) were significantly higher compared with baseline at all timepoints. Although IgG levels of all 24 vaccine serotypes increased significantly both in PLWH and controls, only a minority of PLWH achieved seroprotection after PCV13 followed by PPSV23. In addition, protective immunity waned rapidly. Further research into alternative vaccinations strategies for PLWH is needed, such as vaccination schedules with higher-valent pneumococcal vaccines. The DTP vaccine may augment pneumococcal vaccination responses.

Dear Editors, Nocardiosis is a rare but potentially severe bacterial opportunistic infection that may occur after solid organ transplantation (SOT), typically among thoracic transplant recipients and/or in recipients with a high degree of immunosuppression due to anti-rejection therapy [1]. However, nocardiosis may also occur late after transplantation among minimally immunosuppressed patients, suggesting that additional risk factors exist [1]. Recently, autoantibodies against granulocyte macrophage colony-stimulating factor (GM-CSF) have been identified among five previously healthy patients with disseminated nocardiosis [2]. These autoantibodies likely promote nocardiosis by reducing neutrophil and macrophage activation, phagocytosis, and bactericidal activity [2]. We hypothesized that anti-GM-CSF autoantibodies might be involved in post-SOT nocardiosis, especially in patients who apparently have a relatively low degree of immunosuppression. [...]

Much has changed in the medical treatment of COVID-19 after the first patient with an infection with SARS-CoV-2 in the Netherlands was diagnosed in February 2020. On the basis of limited data, at first only off-label use of (hydroxy)chloroquine seemed to be a treatment option. However, now based on the findings of several randomized studies, other medicines have been included in the Dutch guidelines about the treatment of COVID-19. In this article, we will briefly discuss the current state of affairs with regard to the drugs (hydroxy) chloroquine, remdesivir and corticosteroids. Again, it appears that only well-executed randomized clinical trials can determine the status of various supposedly effective drugs.

Introduction Toxoplasma gondii (T. gondii) is an obligate intracellular parasite that is estimated to be carried by one-third of the world population. Latent T. gondii infection has been linked to several neuropsychiatric mood disorders and behaviors. The aim of the present study was to examine whether T. gondii seropositivity is associated with affective disorders, as well as with aggression reactivity and suicidal thoughts. Methods In the Netherlands Study of Depression and Anxiety (NESDA), T. gondii antibodies were assessed in patients with current depressive (n ​= ​133), anxiety (n ​= ​188), comorbid depressive and anxiety (n ​= ​148), and remitted disorders (n ​= ​889), as well as in healthy controls (n ​= ​373) based on DSM-IV criteria. Seropositivity was analyzed in relation to disorder status, aggression reactivity and suicidal thoughts using multivariate analyses of covariance and regression analyses. Results Participants were on average 51.2 years (SD ​= ​13.2), and 64.4% were female. Seropositivity was found in 673 participants (38.9%). A strong positive association between T. gondii seropositivity and age was observed. No significant associations were found between T. gondii seropositivity and disorder status, aggression reactivity and suicidal thoughts. The adjusted odds ratio (OR) for any remitted disorder versus controls was 1.13 (95% CI: 0.87-1.49), and for any current disorder versus controls was 0.94 (95% CI: 0.69-1.28). Conclusions No evidence was found for a relationship between affective disorders and T. gondii infection in the current sample., Highlights • Increasing age is strongly associated with a higher seroprevalence of T. gondii. • No relationship was found between affective disorders and T. gondii infection. • Affective symptom severity measures were not associated with T. gondii infection. • Aggressive and suicidal thoughts were not associated with T. gondii infection.

Background The objective of this systematic review and meta-analysis was to summarise the literature regarding the immunogenicity of pneumococcal conjugate vaccines (PCV) and pneumococcal polysaccharide vaccines (PPSV) in adult people living with HIV (PLWH) in the era of advanced combination antiretroviral therapy (cART). Methods The systematic review protocol was published online (PROSPERO ID: CRD 42020153137). We searched Medline (Ovid), EMBASE (Ovid), and the Global Health Library for publications from 2000 to June 11, 2020. We included all studies in adult PLWH that reported vaccine immunogenicity outcomes. The primary outcome was seroconversion rate (SCR) after PCV, PPSV and PCV/PPSV combined. For random-effects meta-analysis, we included studies defining SCR as a ≥ 2-fold increase in IgG from baseline, and reporting SCR for serotypes 6B, 14, or overall SCR, 1–3 months after vaccination. Findings Our search identified 1597 unique studies, of which 115 were eligible for full-text assessment. Of these, 39 met the inclusion criteria (11 RCTs; 28 cohort studies). A high degree of heterogeneity was observed. Nineteen studies were included in the meta-analysis. Pooled overall SCRs were 42% (95% CI 30–56%), 44% (95% CI 33–55%) and 57% (95% CI 50–63%) for PLWH who received PPSV, PCV or a combination of PCV/PPSV, respectively. Compared to PPSV alone, a combination of PCV/PPSV yielded higher SCRs (OR 2.24 95% CI 1.41- 3.58), whereas we did not observe a significant difference in SCR between PCV and PPSV23 alone. There were no statistically significant differences in geometric mean post-vaccination antibody concentrations between vaccination schedules. Vaccination at higher CD4 cell counts improved immunogenicity in 8/21 studies, especially when PCV was administered. No studies assessed the long-term immunogenicity of PCV followed by PPSV23. Quality of evidence ranged from poor (n = 19) to good quality (n = 7). A limited number of pneumococcal serotypes was assessed in the majority of studies. Interpretation We show that the recommended immunisation schedule consisting of a combination of PCV13/PPSV23, is immunogenic in PLWH in the era of advanced cART. However, the durability of this vaccination schedule remains unknown and must be addressed in future research. Vaccination with PCV should be delayed until immunological recovery (CD4>200) in recently diagnosed PLWH for optimal immunogenicity. The evidence gathered here supports wide implementation of the combination of PCV/PPSV23 for all PLWH. We recommend reassessment of this strategy once higher-valent PCVs become available. Funding HMGG is funded by a public research grant of ZonMw (project number 522004005).

Immunocompromised individuals are at increased risk of infectious diseases and their complications. The main examples of these are pneumococcal disease and influenza, infections that are both vaccine-preventable. However, responses to vaccination are often impaired in immunocompromised patients. In addition, live-attenuated vaccines, including the measles-mumps-rubella and yellow fever vaccine, cannot be administered to these patients for safety reasons. In view of the decreasing herd immunity caused by a drop in global vaccination coverage, immunocompromised individuals are at increased risk of infections such as measles, especially during travel abroad. Despite these developments, the improved quality of life resulting from novel treatment options means that immunocompromised patients are travelling more and further than ever. It is the responsibility of the treating physician of the immunocompromised individual to ensure that all the required vaccines are provided in time. To this end, the physician may also refer the patient to the general practitioner or travel clinic for the actual vaccination.

BACKGROUND: Cancer patients are at a higher risk for developing influenza (flu)– related complications. It is unclear if the flu vaccine exacerbates immune events in patients treated with immune checkpoint inhibitors (ICIs). METHODS: We conducted an institutional review board–IRB-approved retrospective review of advanced cancer patients on ICIs who received the flu vaccine during three 3 consecutive seasons: 2014–2015, 2015–2016, and 2016–2017. The primary outcome assessed was any “new onset” immune-related adverse event (IRAE). A subset analysis of vaccinated patients newly treated with anti–programmed cell death protein 1 (PD-1) agents (nivolumab or pembrolizumab) was conducted to assess overall IRAE rates for comparison with published clinical trials. RESULTS: During the three 3 seasons, 370 patients met criteria for ICI and vaccination within ~ twoapproximately 2 months (65 days). The most common underlying cancers were lung (46%) and melanoma (19%); 61% of patients received an anti–PD-1 agent only. In the entire cohort, 20% experienced an IRAE (any grade); incidence of grade 3 or 4 toxicity was 8%. No grade 5 events occurred. In the subset of 170 patients newly treated with anti–PD-1 agents, the overall IRAE rate was 18% and, grade 3/4 events occurred in 7.6%. Influenza was diagnosed in 2 patients. CONCLUSIONS: No increase in incidence or severity of IRAEs was detected in patients on ICIs who received the inactivated influenza vaccine within ~ approximately 2 months of ICI. For newly treated patients on anti–PDI-1 agents, IRAE rates were comparable to those from published clinical trials and did not vary with order of administration. Routine seasonal flu vaccination is encouraged in patients on ICIs.

Revision of the rabies policy in the Netherlands The WHO aims to eliminate dog-transmitted rabies deaths in humans by 2030 ('zero by 30'). The Dutch rabies policy advisory board has revised its national rabies guidelines on the basis of the WHO guidelines revised in 2018. In the revised Dutch guidelines, there is increased focus on the importance of instant wound care after potential exposure to the rabies virus. Pre-exposure prophylaxis (PrEP) is limited to two vaccines given on days 0 and 7, rather than the previous regime of three vaccines. Post-exposure prophylaxis (PEP) no longer consists of five vaccines for unvaccinated individuals; instead it is four vaccines on days 0, 3, 7, and 14-28. For type III wounds, when indicated, rabies immunoglobulin (RIG) is only injected into and around the wound bed; residual volumes are no longer administered intramuscularly. RIG no longer needs to be administered in cases of potential mucosal contact exposure to the rabies virus where there is no injury. The vaccination scheme for PrEP (3) and PEP (5) does not change for immunocompromised patients, and RIG is administered regardless of the vaccination status of the affected individual.

Background Although people living with human immunodeficiency virus (PLWH) are at increased risk of invasive pneumococcal disease (IPD) and community-acquired pneumonia (CAP), it is unclear whether this remains the case in the setting of early initiation of combination antiretroviral therapy (cART), at high CD4 cell counts. This is important, as pneumococcal vaccination coverage in PLWH is low in Europe and the United States, despite longstanding international recommendations. Methods We identified all CAP and IPD cases between 2008 and 2017 in a cohort of PLWH in a Dutch HIV referral center. We calculated incidence rates stratified by CD4 count and cART status and conducted a case-control study to identify risk factors for CAP in PLWH receiving cART. Results Incidence rates of IPD and CAP in PLWH were 111 and 1529 per 100 000 patient-years of follow-up (PYFU). Although IPD and CAP occurred more frequently in patients with CD4 counts 500 cells/μL remained higher compared with the general population (946 vs 188 per 100 000 PYFU). All IPD isolates were vaccine serotypes. Risk factors for CAP were older age, CD4 counts Conclusions The incidence of IPD and CAP among PLWH remains higher compared with the general population, even in those who are virally suppressed and have high CD4 counts. With all serotyped IPD isolates covered by pneumococcal vaccines, our study provides additional argumentation against the poor current adherence to international recommendations to vaccinate PLWH.

Patients with solid tumours receiving chemotherapy are at risk for influenza complications. Yearly influenza vaccination is recommended to patients treated with chemotherapy. However, adherence to vaccination is low, most likely due to lack of data on efficacy, optimal timing and safety of vaccination. There is scarce evidence for the effectiveness of the influenza vaccine in adult patients with solid tumours and chemotherapy on reduction of pneumonia, decreased mortality and fewer interruptions of oncological treatment. A review of 20 non-randomised serological studies in adult patients with different cancer types and chemotherapy provides insight in general trends of response to vaccination. Overall, the magnitude of the antibody response after influenza vaccination (i.e. seroconversion) can be lower than in healthy controls, but the majority of patients with solid tumours is able to mount a timely, protective immunological response (i.e. seroprotection) regardless of chemotherapy schedule, similar to healthy controls. Small sample sizes, patient heterogeneity and lack of comparable study designs limit more specific recommendations related to cancer type and optimal timing of vaccination. The inactivated influenza vaccine is safe to administer to immunosuppressed patients; side-effects are similar to those in healthy individuals. Although vaccination before start of chemotherapy is preferred to ensure optimal protection in adults with solid tumours, also vaccination during chemotherapy can reduce influenza-related complications considering the overall trends in serological response. Given the increased morbidity and mortality of influenza, influenza vaccination should be advocated as an inexpensive and safe preventive measure in patients with solid tumours receiving chemotherapy.

BACKGROUND: Influenza vaccination is recommended in patients with cancer to reduce influenza-related complications. Recently, more immune-related adverse events (irAEs) were demonstrated in patients with lung cancer who were vaccinated with the trivalent seasonal influenza vaccine during anti-programmed death receptor 1 (PD-1) immunotherapy. Confirmation of these findings is essential before recommendations on influenza vaccination may be revoked.METHODS: In this cohort study in patients with lung cancer receiving nivolumab 3 mg/kg every 2 weeks during two influenza seasons (2015/16-2016/17), irAEs have been monitored. Incidence, timing and severity of irAEs were compared between vaccinated patients and non-vaccinated patients.FINDINGS: In a compassionate use programme, 127 patients with lung cancer had been treated with at least one dose of nivolumab during two national influenza vaccination campaigns from September until December of 2015 and 2016. Forty-two patients had received the influenza vaccine, and 85 patients were not vaccinated. Median follow-up period was 118 days (interquartile range 106-119). Mean age was 64 years (range 46-83). In vaccinated and non-vaccinated patients, the incidence of irAEs was 26% and 22%, respectively, rate ratio 1.20 (95% confidence interval [CI] 0.51-2.65). The incidence of serious irAEs was 7% and 4%, respectively, rate ratio 2.07 (95% CI 0.28-15.43). Influenza vaccination while receiving nivolumab did not result in significant differences in the rates of discontinuation, death, clinical deterioration or tumour response between the groups.INTERPRETATION: Influenza vaccination in patients with lung cancer receiving anti-PD-1 immunotherapy does not induce irAEs in our cohort. With this result, influenza vaccination should not be deterred from this group of patients.

Background There is a lack of severity assessment tools to identify adults presenting with febrile urinary tract infection (FUTI) at risk for complicated outcome and guide admission policy. We aimed to validate the Prediction Rule for Admission policy in Complicated urinary Tract InfeCtion LEiden (PRACTICE), a modified form of the pneumonia severity index, and to subsequentially assess its use in clinical practice. Methods A prospective observational multicenter study for model validation (2004–2009), followed by a multicenter controlled clinical trial with stepped wedge cluster-randomization for impact assessment (2010–2014), with a follow up of 3 months. Paricipants were 1157 consecutive patients with a presumptive diagnosis of acute febrile UTI (787 in validation cohort and 370 in the randomized trial), enrolled at emergency departments of 7 hospitals and 35 primary care centers in the Netherlands. The clinical prediction rule contained 12 predictors of complicated course. In the randomized trial the PRACTICE included guidance on hospitalization for high risk (>100 points) and home discharge for low risk patients (

BACKGROUND: When assessing health status, physicians may focus on objective symptoms and diagnoses, whereas individuals may focus more on subjective symptoms, functional limitations and quality of life. METHODS: In the Zutphen Elderly Study, 710 community-living men (aged 64-84 years) were followed until death for 15 years. Self-rated health was assessed through a single-item question. Physician-rated health was estimated on a Likert scale by physicians after medical history assessment and physical examination. Both health ratings were categorised into three groups. All-cause, cardiovascular and cancer mortality rates were analysed in Cox proportional-hazards models. RESULTS: There were 352 (49.6%) men who felt healthy and 225 (31.7%) men with a good physician-rated health. During 15 years of follow-up 503 of 710 men (70.8%) died, of whom 229 (45.5%) from cardiovascular causes and 144 (28.6%) from cancer. Self-rated and physician-rated health both predicted independently all-cause mortality (hazard ratios [HR] for worst vs. best health category: 1.72; 95% confidence interval [CI]: 1.26-2.33, and 1.77; 95% CI: 1.36-2.29; respectively; P-values of

The extravasation of DNA-binding vesicant drugs, such as epirubicin, is a feared complication of chemotherapy and can lead to extensive damage at injury sites. We describe a 56-year-old woman with breast cancer who received adjuvant chemotherapy after a breast-preserving surgical procedure. Due to catheter tip misplacement, epirubicin, 5-fluouracil, and cyclophosphamide were administered intrapleurally. To minimize long-term sequelae, flushing of the cavities and systemic administration of steroids were performed. Besides this treatment, empirically, 3-day therapy with dexrazoxane was added to prevent tissue damage and the risk of cardiac damage. Because of the potential benefits of dexrazoxane and its relatively mild side effects, its use should be considered in cases of the intrapleural extravasation of anthracyclines. We do emphasis the need for stringent surgical and oncological nursing procedures when using central venous access catheters in oncology.

In Jakarta, Indonesia, over 80% of patients with typhoid fever or paratyphoid fever are treated in outpatient settings. In a community-based prospective passive surveillance study, we identified 59 typhoid, 23 paratyphoid fever and 259 non-enteric fever outpatients, all blood culture-confirmed. We compared their symptoms with the aim of developing a clinical prediction rule that may help direct empirical antibiotic treatment to cases with suspected (para)typhoid fever, rather than all febrile patients, or refer patients for additional diagnostic tests. Paratyphoid fever (Salmonella paratyphi A) could not be distinguished clinically from typhoid fever. Decisions on empirical antibiotic treatment and advice on hygiene measures in patients with suspected (para)typhoid fever should take into account chills and absence of cough in the first week of fever and delirium in the second week of illness. This prediction rule increases the likelihood of (para)typhoid fever from 1:10 in the first week to, at most, 2:3 in the second week of a febrile illness. However, we were not able to propose a robust clinical prediction rule that could be used as absolute screening method for decisions on additional diagnostic tests, because of the low sensitivity of presenting symptoms in (para)typhoid fever.

A total of 370 patients were included, 237 in the control period and 133 in the intervention period. Use of PRACTICE significantly reduced the primary hospitalization rate (from 92%, in the control group to 72%, in the intervention group, p

Diabetes is considered a risk factor for acquisition of febrile urinary tract infection (UTI) (1,2), but there is a lack of information on the association of diabetes with the subsequent course of disease and its outcome. We performed a prospective observational multicenter cohort study including consecutive adults with community-onset febrile UTI presenting at 7 emergency departments and 35 primary care centers. The effect of preexisting diabetes on presentation and microbiological and clinical outcome was assessed and multivariable logistic regression performed to establish whether diabetes was an independent risk factor for a complicated course. View this table: Table 1 Baseline characteristics of 858 patients presenting with febrile UTI Of 858 patients, 140 had diabetes (93% type 2 diabetes), of whom 41 (30%) used insulin, 19 (14%) were managed by diet only, and the remaining were managed by a combination of metformin, insulin, and diet. Patients with diabetes were older (median age 73 years [interquartile range {IQR} 46–78] vs. 64 [IQR 42–77], P < 0.001), were more frequently male (48 vs. 35%, P = 0.006), and had a higher …

Host genetic factors are thought to contribute to susceptibility and outcome in infectious diseases. A polymorphism in a proinflammatory gene, tumor necrosis factor-alpha (TNFA - 308), was recently found to be associated with susceptibility to typhoid fever. As the observation was made in hospitalized patients, a potential confounder could be that the TNFA polymorphism is associated with the severity of established illness resulting in hospital admission rather than susceptibility to disease. We tested whether the association with TNFA - 308 is present also in typhoid fever patients enrolled in a community-based case-control study in an endemic area in Indonesia. Common polymorphisms in other proinflammatory genes were assayed as well. Samples of patients with blood culture-confirmed typhoid fever (n = 90) and paratyphoid fever (n = 26) and fever controls (n = 337) were compared with those of community controls (n = 322). In these groups, we analyzed polymorphisms in TNFA by PCR and RFLP, polymorphisms of IFNG, IL1A, IL1B, IL1R1, TNFRSF1A, CASP1, and CRP by Sequenom MassArray (San Diego, CA), and polymorphisms in IL12B and IFNGR1 by fragment length analysis. The IL1R1 polymorphisms were nearly absent in the Indonesian population. The TNFA - 308 polymorphism was not associated with typhoid fever (OR 0.35, 95% CI 0.1-1.0) in this population. The polymorphisms at TNFA - 238 or in IFNG, IL1A, IL1B, IL12B, TNFRSF1A, IFNGR1, CASP1, and CRP were also not associated with typhoid or paratyphoid fever. We conclude that polymorphisms in proinflammatory genes do not contribute to susceptibility to typhoid fever and, in view of earlier findings, suggest that the TNFA - 308 polymorphism is likely related to severity of established disease rather than to susceptibility per se.

Background Typhoid fever, caused by the Gram-negative bacterium Salmonella enterica serovar Typhi, is a major cause of community-acquired bacteremia and death worldwide. S100A8 (MRP8) and S100A9 (MRP14) form bioactive antimicrobial heterodimers (calprotectin) that can activate Toll-like receptor 4, promoting lethal, endotoxin-induced shock and multi-organ failure. We aimed to characterize the expression and function of S100A8/A9 in patients with typhoid fever and in a murine invasive Salmonella model. Methods and principal findings S100A8/A9 protein levels were determined in acute phase plasma or feces from 28 Bangladeshi patients, and convalescent phase plasma from 60 Indonesian patients with blood culture or PCR-confirmed typhoid fever, and compared to 98 healthy control subjects. To functionally characterize the role of S100A8/A9, we challenged wildtype (WT) and S100A9-/- mice with S. Typhimurium and determined bacterial loads and inflammation 2- and 5- days post infection. We further assessed the antimicrobial function of recombinant S100A8/A9 on S. Typhimurium and S. Typhi replication in vitro. Typhoid fever patients demonstrated a marked increase of S100A8/A9 in acute phase plasma and feces and this increases correlated with duration of fever prior to admission. S100A8/A9 directly inhibited the growth of S. Typhimurium and S. Typhi in vitro in a dose and time dependent fashion. WT mice inoculated with S. Typhimurium showed increased levels of S100A8/A9 in both the liver and the systemic compartment but S100A9-/- mice were indistinguishable from WT mice with respect to bacterial growth, survival, and inflammatory responses, as determined by cytokine release, histopathology and organ injury. Conclusion S100A8/A9 is markedly elevated in human typhoid, correlates with duration of fever prior to admission and directly inhibits the growth of S. Typhimurium and S. Typhi in vitro. Despite elevated levels in the murine invasive Salmonella model, S100A8/A9 does not contribute to an effective host response against S. Typhimurium in mice., Author Summary Bacterial pathogens are recognized by the host upon infection through interactions between their virulence factors and host cell receptors leading to the activation and recruitment of innate immune cells. Salmonella Typhi, the etiologic agent for typhoid fever, however harbors a number of factors, such as a polysaccharide capsule, which prevent the detection of these virulence factors, and thereby dampens the innate host response. Besides bacterial virulence factors, the host can detect endogenous danger molecules which are released upon tissue damage. S100A8/A9, an extracellular protein complex, is such a danger signal that is able to further amplify the systemic inflammatory response upon infection. In the present study we investigated the role of S100A8/A9 during invasive Salmonella infection and observed a marked increase of this protein in patients with typhoid fever, which correlates with disease stage and severity. Furthermore we found that S100A8/A9 directly inhibited the growth of Salmonella species in vitro thereby functioning as an antimicrobial. When mice were infected with Salmonella, the levels of S100A8/A9 were also elevated but mice lacking this protein did not have an altered host response to infection. The role and importance of the elevated levels of S100A8/A9 in human typhoid fever requires further study.

We assessed the water supply, water quality and human waste disposal and their association with diarrheal illness in Jatinegara, East-Jakarta, where part of the area has been involved in the Kampung Improvement Program (KIP). Three hundred seventy-eight households, randomly selected in the study area, were visited and questioned about water source, sanitation and diarrheal illness during the previous 3 months. Microbiological quality of drinking water was assessed. The water sources were boreholes (243; 64%), the water mains (77; 20%), bottled water (45; 12%), and vendors or dug wells (243; 4%). Fecal coliforms were isolated in 56% of the samples [median 23 (IQR 6-240) /100 ml in the contaminated samples]. Only 2 (3%) of the water mains' samples contained100 fecal coliforms/100 ml, compared to 57 (24%) groundwater samples. Most residents used private toilets with drainage into on-site septic tanks, yet in over one quarter of households human excreta was disposed of into rivers or gutters. KIP areas lagged behind in environmental hygiene. Diarrheal episodes, reported in one third of the households, were significantly associated with water contaminated with100 fecal coliforms/100 ml [OR 2.4 (95% CI: 1.4-4.2)], but no association with water source or environmental contamination was found. Significantly, all individuals reported boiling water before consumption.

SUMMARYWe evaluated the association between typhoid fever andHelicobacter pyloriinfection, as the latter microorganism may influence gastric acid secretion and consequently increase susceptibility toSalmonella typhiinfection. Anti-H. pyloriIgG and IgA antibody titres (ELISA) and gastrin concentration (RIA) were determined in the plasma of 87 blood culture-confirmed typhoid fever cases (collected after clinical recovery) and 232 random healthy controls without a history of typhoid fever, in the Jatinegara district, Jakarta. Patients with typhoid fever more often than controls were seropositive forH. pyloriIgG (67%vs. 50%,PH. pyloriIgA seropositivity was not associated with typhoid fever. Plasma gastrin concentrations indicative of hypochlorhydria (i.e. gastrin ⩾25 or ⩾100 ng/l) were not significantly elevated in typhoid fever cases compared to controls (P=0·54 andP=0·27 respectively). In a multivariate analysis, typhoid fever was independently associated with young age (H. pyloriIgG seropositivity (OR 1·93, 95% CI 1·10–3·40). Typhoid fever was independently associated withH. pyloriIgG seropositivity, but not with elevated gastrin concentration. Therefore, the association suggests a common risk of environmental exposure to both bacteria, e.g. poor hygiene, rather than a causal relationship via reduced gastric acid production.

The cystic fibrosis transmembrane conductance regulator (CFTR) is the affected protein in cystic fibrosis (CF). The high rate of CF carriers has led to speculation that there must be, similar to the sickle cell haemoglobin advantage in malaria, a selective advantage for heterozygotes. Such a selective advantage may be conferred through reduced attachment of Salmonella typhi to intestinal mucosa, thus providing resistance to typhoid fever. We tested this hypothesis by genotyping patients and controls in a typhoid endemic area in Indonesia for two highly polymorphic markers in CFTR and the most common CF mutation. We found an association between genotypes in CFTR and susceptibility to typhoid fever (OR=2.6). These analyses suggest that the role CFTR plays in vitro in S. typhi infection is also important for infection in the human population.

Contains fulltext : 58946.pdf (Publisher’s version ) (Closed access) CONTEXT: The proportion of paratyphoid fever cases to typhoid fever cases may change due to urbanization and increased dependency on food purchased from street vendors. For containment of paratyphoid a different strategy may be needed than for typhoid, because risk factors for disease may not coincide and current typhoid vaccines do not protect against paratyphoid fever. OBJECTIVE: To determine risk factors for typhoid and paratyphoid fever in an endemic area. DESIGN, SETTING, AND PARTICIPANTS: Community-based case-control study conducted from June 2001 to February 2003 in hospitals and outpatient health centers in Jatinegara district, Jakarta, Indonesia. Enrolled participants were 1019 consecutive patients with fever lasting 3 or more days, from which 69 blood culture-confirmed typhoid cases, 24 confirmed paratyphoid cases, and 289 control patients with fever but without Salmonella bacteremia were interviewed, plus 378 randomly selected community controls. MAIN OUTCOME MEASURES: Blood culture-confirmed typhoid or paratyphoid fever; risk factors for both diseases. RESULTS: In 1019 fever patients we identified 88 (9%) Salmonella typhi and 26 (3%) Salmonella paratyphi A infections. Paratyphoid fever among cases was independently associated with consumption of food from street vendors (comparison with community controls: odds ratio [OR], 3.34; 95% confidence interval [CI], 1.41-7.91; with fever controls: OR, 5.17; 95% CI, 2.12-12.60) and flooding (comparison with community controls: OR, 4.52; 95% CI, 1.90-10.73; with fever controls: OR, 3.25; 95% CI, 1.31-8.02). By contrast, independent risk factors for typhoid fever using the community control group were mostly related to the household, ie, to recent typhoid fever in the household (OR, 2.38; 95% CI, 1.03-5.48); no use of soap for handwashing (OR, 1.91; 95% CI, 1.06-3.46); sharing food from the same plate (OR, 1.93; 95% CI, 1.10-3.37), and no toilet in the household (OR, 2.20; 95% CI, 1.06-4.55). Also, typhoid fever was associated with young age in years (OR, 0.96; 95% CI, 0.94-0.98). In comparison with fever controls, risk factors for typhoid fever were use of ice cubes (OR, 2.27; 95% CI, 1.31-3.93) and female sex (OR, 1.79; 95% CI, 1.04-3.06). Fecal contamination of drinking water was not associated with typhoid or paratyphoid fever. We did not detect fecal carriers among food handlers in the households. CONCLUSIONS: In Jakarta, typhoid and paratyphoid fever are associated with distinct routes of transmission, with the risk factors for disease either mainly within the household (typhoid) or outside the household (paratyphoid).

In adults with febrile urinary tract infection (fUTI), data on optimal treatment duration in patients other than non-pregnant women without comorbidities are lacking. A randomized placebo-controlled, double-blind, non-inferiority trial among 35 primary care centers and 7 emergency departments of regional hospitals in the Netherlands. Women and men aged ≥ 18 years with a diagnosis of fUTI were randomly assigned to receive antibiotic treatment for 7 or 14 days (the second week being ciprofloxacin 500 mg or placebo orally twice daily). Patients indicated to receive antimicrobial treatment for at least 14 days were excluded from randomization. The primary endpoint was the clinical cure rate through the 10- to 18-day post-treatment visit with preset subgroup analysis including sex. Secondary endpoints were bacteriologic cure rate at 10–18 days post-treatment and clinical cure at 70–84 days post-treatment. Of 357 patients included, 200 were eligible for randomization; 97 patients were randomly assigned to 7 days and 103 patients to 14 days of treatment. Overall, short-term clinical cure occurred in 85 (90%) patients treated for 7 days and in 94 (95%) of those treated for 14 days (difference –4.5%; 90% CI, –10.7 to 1.7; P non-inferiority = 0.072, non-inferiority not confirmed). In women, clinical cure was 94% and 93% in those treated for 7 and 14 days, respectively (difference 0.9; 90% CI, –6.9 to 8.7, P non-inferiority = 0.011, non-inferiority confirmed) and, in men, this was 86% versus 98% (difference –11.2; 90% CI –20.6 to –1.8, P superiority = 0.025, inferiority confirmed). The bacteriologic cure rate was 93% versus 97% (difference –4.3%; 90% CI, –9.7 to 1.2, P non-inferiority = 0.041) and the long-term clinical cure rate was 92% versus 91% (difference 1.6%; 90% CI, –5.3 to 8.4; P non-inferiority = 0.005) for 7 days versus 14 days of treatment, respectively. In the subgroups of men and women, long-term clinical cure rates met the criteria for non-inferiority, indicating there was no difference in the need for antibiotic retreatment for UTI during 70–84 days follow-up post-treatment. Women with fUTI can be treated successfully with antibiotics for 7 days. In men, 7 days of antibiotic treatment for fUTI is inferior to 14 days during short-term follow-up but it is non-inferior when looking at longer follow-up. The study was registered at ClinicalTrials.gov [ NCT00809913 ; December 16, 2008] and trialregister.nl [ NTR1583 ; December 19, 2008].