The etiology of Nodding Syndrome remains unclear, and comprehensive genotyping and phenotyping data from patients remain sparse. Our objectives were to characterize the phenotype of patients with Nodding Syndrome, investigate potential contributors to disease etiology, and evaluate response to immunotherapy. This cohort study investigated members of a single-family unit from Lamwo District, Uganda. The participants for this study were selected by the Ugandan Ministry of Health as representative for Nodding Syndrome and with a conducive family structure for genomic analyses. Of the eight family members who participated in the study at the National Institutes of Health (NIH) Clinical Center, three had Nodding Syndrome. The three affected patients were extensively evaluated with metagenomic sequencing for infectious pathogens, exome sequencing, spinal fluid immune analyses, neurometabolic and toxicology testing, continuous electroencephalography, and neuroimaging. Five unaffected family members underwent a subset of testing for comparison. A distinctive interictal pattern of sleep-activated bursts of generalized and multifocal epileptiform discharges and slowing was observed in two patients. Brain imaging showed two patients had mild generalized cerebral atrophy, and both patients and unaffected family members had excessive metal deposition in the basal ganglia. Trace metal biochemical evaluation was normal. Cerebrospinal fluid (CSF) was non-inflammatory, and one patient had CSF-restricted oligoclonal bands. Onchocerca volvulus specific antibodies were present in all patients and skin snips were negative for active onchocerciasis. Metagenomic sequencing of serum and CSF revealed hepatitis B virus in the serum of one patient. Vitamin B6 metabolites were borderline low in all family members, and CSF pyridoxine metabolites were normal. Mitochondrial DNA testing was normal. Exome sequencing did not identify potentially causal candidate gene variants. Nodding Syndrome is characterized by a distinctive pattern of sleep-activated epileptiform activity. The associated growth stunting may be due to hypothalamic dysfunction. Extensive testing years after disease onset did not clarify a causal etiology. A trial of immunomodulation (plasmapheresis in two patients and intravenous immunoglobulin in one patient) was given without short-term effect, but longer-term follow-up was not possible to fully assess any benefit of this intervention.

The COVID-19 pandemic has exposed weaknesses in disease surveillance in nearly all countries. Early identification of COVID-19 cases and clusters for rapid containment was hampered by inadequate diagnostic capacity, insufficient contact tracing, fragmented data systems, incomplete data insights for public health responders, and suboptimal governance of all these elements. Once SARS-CoV-2 became widespread, interventions to control community transmission were undermined by weak surveillance of cases and insufficient national capacity to integrate data for timely adjustment of public health measures.1, 2 Although some countries had little or no reliable data, others did not share data consistently with their own populations and with WHO and other multilateral agencies. The emergence of SARS-CoV-2 variants has highlighted inadequate national pathogen genomic sequencing capacities in many countries and led to calls for expanded virus sequencing. However, sequencing without epidemiological and clinical surveillance data is insufficient to show whether new SARS-CoV-2 variants are more transmissible, more lethal, or more capable of evading immunity, including vaccine-induced immunity.3, 4

BACKGROUND: Sub-Saharan Africa and south Asia contributed 81% of 5.9 million under-5 deaths and 77% of 2.6 million stillbirths worldwide in 2015. Vital registration and verbal autopsy data are mainstays for the estimation of leading causes of death, but both are non-specific and focus on a single underlying cause. We aimed to provide granular data on the contributory causes of death in stillborn fetuses and in deceased neonates and children younger than 5 years, to inform child mortality prevention efforts. METHODS: The Child Health and Mortality Prevention Surveillance (CHAMPS) Network was established at sites in seven countries (Baliakandi, Bangladesh; Harar and Kersa, Ethiopia; Siaya and Kisumu, Kenya; Bamako, Mali; Manhica, Mozambique; Bombali, Sierra Leone; and Soweto, South Africa) to collect standardised, population-based, longitudinal data on under-5 mortality and stillbirths in sub-Saharan Africa and south Asia, to improve the accuracy of determining causes of death. Here, we analysed data obtained in the first 2 years after the implementation of CHAMPS at the first five operational sites, during which surveillance and post-mortem diagnostics, including minimally invasive tissue sampling (MITS), were used. Data were abstracted from all available clinical records of deceased children, and relevant maternal health records were also extracted for stillbirths and neonatal deaths, to incorporate reported pregnancy or delivery complications. Expert panels followed standardised procedures to characterise causal chains leading to death, including underlying, intermediate (comorbid or antecedent causes), and immediate causes of death for stillbirths, neonatal deaths, and child (age 1-59 months) deaths. FINDINGS: Between Dec 10, 2016, and Dec 31, 2018, MITS procedures were implemented at five sites in Mozambique, South Africa, Kenya, Mali, and Bangladesh. We screened 2385 death notifications for inclusion eligibility, following which 1295 families were approached for consent; consent was provided for MITS by 963 (74%) of 1295 eligible cases approached. At least one cause of death was identified in 912 (98%) of 933 cases (180 stillbirths, 449 neonatal deaths, and 304 child deaths); two or more conditions were identified in the causal chain for 585 (63%) of 933 cases. The most common underlying causes of stillbirth were perinatal asphyxia or hypoxia (130 [72%] of 180 stillbirths) and congenital infection or sepsis (27 [15%]). The most common underlying causes of neonatal death were preterm birth complications (187 [42%] of 449 neonatal deaths), perinatal asphyxia or hypoxia (98 [22%]), and neonatal sepsis (50 [11%]). The most common underlying causes of child deaths were congenital birth defects (39 [13%] of 304 deaths), lower respiratory infection (37 [12%]), and HIV (35 [12%]). In 503 (54%) of 933 cases, at least one contributory pathogen was identified. Cytomegalovirus, Escherichia coli, group B Streptococcus, and other infections contributed to 30 (17%) of 180 stillbirths. Among neonatal deaths with underlying prematurity, 60% were precipitated by other infectious causes. Of the 275 child deaths with infectious causes, the most common contributory pathogens were Klebsiella pneumoniae (86 [31%]), Streptococcus pneumoniae (54 [20%]), HIV (40 [15%]), and cytomegalovirus (34 [12%]), and multiple infections were common. Lower respiratory tract infection contributed to 174 (57%) of 304 child deaths. INTERPRETATION: Cause of death determination using MITS enabled detailed characterisation of contributing conditions. Global estimates of child mortality aetiologies, which are currently based on a single syndromic cause for each death, will be strengthened by findings from CHAMPS. This approach adds specificity and provides a more complete overview of the chain of events leading to death, highlighting multiple potential interventions to prevent under-5 mortality and stillbirths. FUNDING: Bill & Melinda Gates Foundation.

Nodding syndrome is an epileptic disorder of unknown etiology that occurs in children in East Africa. There is an epidemiological association with Onchocerca volvulus, the parasitic worm that causes onchocerciasis (river blindness), but there is limited evidence that the parasite itself is neuroinvasive. We hypothesized that nodding syndrome may be an autoimmune-mediated disease. Using protein chip methodology, we detected autoantibodies to leiomodin-1 more abundantly in patients with nodding syndrome compared to unaffected controls from the same village. Leiomodin-1 autoantibodies were found in both the sera and cerebrospinal fluid of patients with nodding syndrome. Leiomodin-1 was found to be expressed in mature and developing human neurons in vitro and was localized in mouse brain to the CA3 region of the hippocampus, Purkinje cells in the cerebellum, and cortical neurons, structures that also appear to be affected in patients with nodding syndrome. Antibodies targeting leiomodin-1 were neurotoxic in vitro, and leiomodin-1 antibodies purified from patients with nodding syndrome were cross-reactive with O. volvulus antigens. This study provides initial evidence supporting the hypothesis that nodding syndrome is an autoimmune epileptic disorder caused by molecular mimicry with O. volvulus antigens and suggests that patients may benefit from immunomodulatory therapies.

We estimated the seroprevalence and determined the frequency of acute infections with Neorickettsia sennetsu, spotted fever group rickettsiae, Rickettsia typhi, and Orientia tsutsugamushi among 2,225 febrile patients presenting to community hospitals in three rural Thailand provinces during 2002-2005. The seroprevalence was 0.2% for sennetsu neorickettsiosis (SN), 0.8% for spotted fever group (SFG) rickettsiae, 4.2% for murine typhus (MT), and 4.2% for scrub typhus (ST). The frequency of acute infections was 0.1% for SN, 0.6% for SFG, 2.2% for MT, and 1.5% for ST. Additional studies to confirm the distribution of these pathogens and to identify animal reservoirs and transmission cycles are needed to understand the risk of infection.

Countries around the world face a perfect storm of converging threats that might substantially increase the risk from infectious disease epidemics, despite improvements in technologies, communication, and some health systems. New pathogens emerge each year, some of which have high mortality and the potential for efficient transmission—eg, severe acute respiratory syndrome (SARS),1 Middle East respiratory syndrome coronavirus,2 and avian influenza A H7N9.3 Existing pathogens are becoming resistant to available antibiotics and several are now resistant to virtually all available treatment.4 There is also the potential threat of intentional release of biological agents, which can be developed or synthesised biologically and disseminated at low cost and with little scientific expertise. Moreover, the accelerated pace of globalisation amplifies these risks: a disease is just a plane trip away, and an outbreak anywhere is a threat everywhere. | One of the primary responsibilities of any government is to protect the health and safety of its people. There are three key elements of health security: prevention wherever possible, early detection, and timely and effective response. Although many countries are now better able to manage infectious disease threats than in the past, these improvements have often been small in scale and limited in scope. The International Health Regulations (IHR), revised by WHO in 2005 to more directly address new and emerging epidemic threats,5 require all 194 signatory countries to improve capacity in these and other areas as part of their commitment to protecting health.6 Yet, at least 80% of countries did not report full IHR compliance by the 2012 deadline.7

Over the past decade, Vietnam has successfully responded to global health security (GHS) challenges, including domestic elimination of severe acute respiratory syndrome (SARS) and rapid public health responses to human infections with influenza A(H5N1) virus. However, new threats such as Middle East respiratory syndrome coronavirus (MERS-CoV) and influenza A(H7N9) present continued challenges, reinforcing the need to improve the global capacity to prevent, detect, and respond to public health threats. In June 2012, Vietnam, along with many other nations, obtained a 2-year extension for meeting core surveillance and response requirements of the 2005 International Health Regulations (IHR). During March-September 2013, CDC and the Vietnamese Ministry of Health (MoH) collaborated on a GHS demonstration project to improve public health emergency detection and response capacity. The project aimed to demonstrate, in a short period, that enhancements to Vietnam's health system in surveillance and early detection of and response to diseases and outbreaks could contribute to meeting the IHR core capacities, consistent with the Asia Pacific Strategy for Emerging Diseases. Work focused on enhancements to three interrelated priority areas and included achievements in 1) establishing an emergency operations center (EOC) at the General Department of Preventive Medicine with training of personnel for public health emergency management; 2) improving the nationwide laboratory system, including enhanced testing capability for several priority pathogens (i.e., those in Vietnam most likely to contribute to public health emergencies of international concern); and 3) creating an emergency response information systems platform, including a demonstration of real-time reporting capability. Lessons learned included awareness that integrated functions within the health system for GHS require careful planning, stakeholder buy-in, and intradepartmental and interdepartmental coordination and communication.

Increasingly, the need to strengthen global capacity to prevent, detect, and respond to public health threats around the globe is being recognized. CDC, in partnership with the World Health Organization (WHO), has committed to building capacity by assisting member states with strengthening their national capacity for integrated disease surveillance and response as required by International Health Regulations (IHR). CDC and other U.S. agencies have reinforced their pledge through creation of global health security (GHS) demonstration projects. One such project was conducted during March-September 2013, when the Uganda Ministry of Health (MoH) and CDC implemented upgrades in three areas: 1) strengthening the public health laboratory system by increasing the capacity of diagnostic and specimen referral networks, 2) enhancing the existing communications and information systems for outbreak response, and 3) developing a public health emergency operations center (EOC) (Figure 1). The GHS demonstration project outcomes included development of an outbreak response module that allowed reporting of suspected cases of illness caused by priority pathogens via short messaging service (SMS; i.e., text messaging) to the Uganda District Health Information System (DHIS-2) and expansion of the biologic specimen transport and laboratory reporting system supported by the President's Emergency Plan for AIDS Relief (PEPFAR). Other enhancements included strengthening laboratory management, establishing and equipping the EOC, and evaluating these enhancements during an outbreak exercise. In 6 months, the project demonstrated that targeted enhancements resulted in substantial improvements to the ability of Uganda's public health system to detect and respond to health threats.

Disease outbreaks of international public health importance continue to occur regularly; detecting and tracking significant new public health threats in countries that cannot or might not report such events to the global health community is a challenge. The Centers for Disease Control and Prevention's (CDC) Global Disease Detection (GDD) Operations Center, established in early 2007, monitors infectious and non-infectious public health events to identify new or unexplained global public health threats and better position CDC to respond, if public health assistance is requested or required. At any one time, the GDD Operations Center actively monitors approximately 30-40 such public health threats; here we provide our perspective on five of the top global infectious disease threats that we were watching in 2012: 1 avian influenza A (H5N1), 2 cholera, 3 wild poliovirus, 4 enterovirus-71, and 5 extensively drug-resistant tuberculosis.

INTRODUCTION: Nodding Syndrome (NS), an unexplained illness characterized by spells of head bobbing, has been reported in Sudan and Tanzania, perhaps as early as 1962. Hypothesized causes include sorghum consumption, measles, and onchocerciasis infection. In 2009, a couple thousand cases were reportedly in Northern Uganda. METHODS: In December 2009, we identified cases in Kitgum District. The case definition included persons who were previously developmentally normal who had nodding. Cases, further defined as 5- to 15-years-old with an additional neurological deficit, were matched to village controls to assess risk factors and test biological specimens. Logistic regression models were used to evaluate associations. RESULTS: Surveillance identified 224 cases; most (95%) were 5-15-years-old (range = 2-27). Cases were reported in Uganda since 1997. The overall prevalence was 12 cases per 1,000 (range by parish = 0.6-46). The case-control investigation (n = 49 case/village control pairs) showed no association between NS and previously reported measles; sorghum was consumed by most subjects. Positive onchocerciasis serology [age-adjusted odds ratio (AOR1) = 14.4 (2.7, 78.3)], exposure to munitions [AOR1 = 13.9 (1.4, 135.3)], and consumption of crushed roots [AOR1 = 5.4 (1.3, 22.1)] were more likely in cases. Vitamin B6 deficiency was present in the majority of cases (84%) and controls (75%). CONCLUSION: NS appears to be increasing in Uganda since 2000 with 2009 parish prevalence as high as 46 cases per 1,000 5- to 15-year old children. Our results found no supporting evidence for many proposed NS risk factors, revealed association with onchocerciasis, which for the first time was examined with serologic testing, and raised nutritional deficiencies and toxic exposures as possible etiologies.

Ten years have elapsed since the World Health Organization issued its first global alert for an unexplained illness named severe acute respiratory syndrome (SARS). The anniversary provides an opportunity to reflect on the international response to this new global microbial threat. While global surveillance and response capacity for public health threats have been strengthened, critical gaps remain. Of 194 World Health Organization member states that signed on to the International Health Regulations (2005), <20% had achieved compliance with the core capacities required by the deadline in June 2012. Lessons learned from the global SARS outbreak highlight the need to avoid complacency, strengthen efforts to improve global capacity to address the next pandemic using all available 21st century tools, and support research to develop new treatment options, countermeasures, and insights while striving to address the global inequities that are the root cause of many of these challenges.

For many decades, Haiti has had poor health-service statistics and some of the highest rates of disease in the Americas region. Before 2010, only 17% of the Haitian population had access to appropriate sanitation, measles vaccine coverage was just 47%, HIV prevalence was 1·9%, and lymphatic filariasis affected 7% of the population.1, 2, 3, 4 | On Jan 12, 2010, a 7·0 magnitude earthquake struck Haiti, resulting in the deaths of more than 200 000 people, destruction of infrastructure, and further weakening of an already fragile health system.5 Although no-one doubted the resilience of the Haitian people, both international and domestic public health organisations recognised the vulnerability that this national disaster had created. International aid arrived quickly after the earthquake to provide for basic needs, but there was a growing feeling that the disaster should prompt the transformation of Haiti's health-care system. However, the Haitian Government had only just begun efforts to coordinate this process and to define medium-term goals5 when the inadvertent introduction of Vibrio cholerae in October, 2010 resulted in the worst cholera epidemic experienced by a single country in more than a century.6 | As the Haitian health system began to recover from the cholera epidemic, the Ministry of Public Health and Population (MSPP) started to look beyond emergency responses and towards improvement of longer-term health care for the population. In a collaborative process led by MSPP, the US Centers for Disease Control and Prevention (CDC) and other organisations identified seven public health impact goals (panel) that support national health priorities to improve health service delivery and disease outcomes in the years ahead.

BACKGROUND: Nodding syndrome is an unexplained illness characterised by head-bobbing spells. The clinical and epidemiological features are incompletely described, and the explanation for the nodding and the underlying cause of nodding syndrome are unknown. We aimed to describe the clinical and neurological diagnostic features of this illness. METHODS: In December, 2009, we did a multifaceted investigation to assess epidemiological and clinical illness features in 13 parishes in Kitgum District, Uganda. We defined a case as a previously healthy child aged 5-15 years with reported nodding and at least one other neurological deficit. Children from a systematic sample of a case-control investigation were enrolled in a clinical case series which included history, physical assessment, and neurological examinations; a subset had electroencephalography (EEG), electromyography, brain MRI, CSF analysis, or a combination of these analyses. We reassessed the available children 8 months later. FINDINGS: We enrolled 23 children (median age 12 years, range 7-15 years) in the case-series investigation, all of whom reported at least daily head nodding. 14 children had reported seizures. Seven (30%) children had gross cognitive impairment, and children with nodding did worse on cognitive tasks than did age-matched controls, with significantly lower scores on tests of short-term recall and attention, semantic fluency and fund of knowledge, and motor praxis. We obtained CSF samples from 16 children, all of which had normal glucose and protein concentrations. EEG of 12 children with nodding syndrome showed disorganised, slow background (n=10), and interictal generalised 2.5-3.0 Hz spike and slow waves (n=10). Two children had nodding episodes during EEG, which showed generalised electrodecrement and paraspinal electromyography dropout consistent with atonic seizures. MRI in four of five children showed generalised cerebral and cerebellar atrophy. Reassessment of 12 children found that six worsened in their clinical condition between the first evaluation and the follow-up evaluation interval, as indicated by more frequent head nodding or seizure episodes, and none had cessation or decrease in frequency of these episodes. INTERPRETATION: Nodding syndrome is an epidemic epilepsy associated with encephalopathy, with head nodding caused by atonic seizures. The natural history, cause, and management of the disorder remain to be determined. FUNDING: Division of Global Disease Detection and Emergency Response, US Centers for Disease Control and Prevention.

The global spread of severe acute respiratory syndrome highlighted the need to detect and control disease outbreaks at their source, as envisioned by the 2005 revised International Health Regulations (IHR). June 2012 marked the initial deadline by which all 194 World Health Organization (WHO) member states agreed to have IHR core capacities fully implemented for limiting the spread of public health emergencies of international concern. Many countries fell short of these implementation goals and requested a 2-year extension. The degree to which achieving IHR compliance will result in global health security is not clear, but what is clear is that progress against the threat of epidemic disease requires a focused approach that can be monitored and measured efficiently. We developed concrete goals and metrics for 4 of the 8 core capacities with other US government partners in consultation with WHO and national collaborators worldwide. The intent is to offer an example of an approach to implementing and monitoring IHR for consideration or adaptation by countries that complements other frameworks and goals of IHR. Without concrete metrics, IHR may waste its considerable promise as an instrument for global health security against public health emergencies.

Annual peaks in incidence are almost universal features of infectious disease epidemiology, yet a consistent explanation for this phenomenon remains elusive. The article by Murray and colleagues [Reference Murray1] adds rigorously collected and analysed data and proposes household crowding as an explanation, but there are internal inconsistencies in this study as there are throughout the infectious disease seasonality literature. What exists are models that explain only a subset of the data, or proposed drivers for seasonality that correlate with the seasonal variation for one pathogen in one geographical area, but break down for the same pathogen in another location, or correlate well for several years and then fail to do so consistently over time. And yet a regular annual variation in the incidence of acute respiratory infections is among the most undeniable patterns in infectious disease epidemiology, almost begging for a simple explanation. | The study by Murray and colleagues begins by acknowledging a contradiction. The authors note that a recent laboratory study identified cold, dry air as more conducive to the aerosol transmission of influenza viruses in guinea pigs [Reference Lowen2], but that such an explanation could not be the reason for the seasonal increase in Bangladesh, because that peak occurs during the hottest, wettest time of the year. They go on to describe an elegant study exploring the hypothesis that household crowding during the rainy season is the explanation. Indeed, during a single 3-month period respiratory infections were significantly more likely to be associated with rainy days than were control periods. Their explanation that people were crowded indoors during the rains, increasing the transmission of influenza and other respiratory viruses, appears to have been substantiated by a stronger association for homes with >3 inhabitants.

With more than 250,000 cases and 4,000 deaths in the first 6 months, the cholera epidemic in Haiti has been one of the most explosive and deadly in recent history. It is also one of the best documented, with detailed surveillance information available from the beginning of the epidemic, which allowed its spread to all parts of the country to be traced. Piarroux et al. make good use of this information, along with their own careful field investigations, to trace the epidemic to its beginning and propose an explanation for its origins (1).

We estimated the prevalence of anti-Bartonella antibodies among febrile and non-febrile patients presenting to community hospitals in rural Thailand from February 2002 through March 2003. Single serum specimens were tested for IgG titers to four Bartonella species, B. henselae, B. quintana, B. elizabethae and B. vinsonii subsp vinsonii using an indirect immunofluorescent assay. A titer 21:256 was considered positive. Forty-two febrile patients (9.9%) and 19 non-febrile patients (19%) had positive serology titers to at least one Bartonella species. Age-standardized Bartonella seroprevalence differed significantly between febrile (10%) and non-febrile patients (18%, p=0.047), but did not differ by gender. Among all 521 patients, IgG titers 21:256 to B. henselae were found in 20 participants (3.8%), while 17 (3.3%) had seropositivity to B. quintana, 51 (9.8%) to B. elizabethae, and 19 (3.6%) to B. vinsonii subsp vinsonii. These results suggest exposure to Bartonella species is more common in rural Thailand than previously suspected.

It has been a year since the earthquake of January 12, 2010, devastated the poorest country in the Western Hemisphere. Piles of rubble remaining throughout the Haitian capital and a devastating cholera epidemic provide stark reminders of the challenges that arise in the absence of the infrastructure and institutions that most of us take for granted. Strong public health systems are essential for maintaining and improving health and well-being. Fortunately, progress has been made in public health during the past year, which should encourage those who hoped that tackling the challenges of an unprecedented disaster could lead to long-term improvements in the health of the Haitian people.

To the Editor: Pandemic (H1N1) 2009 highlighted challenges faced by disease surveillance systems. New approaches to complement traditional surveillance are needed, and new technologies provide new opportunities. We evaluated cell phone technology for surveillance of influenza outbreaks during the outbreak of pandemic (H1N1) 2009 in Mexico.

BACKGROUND: Japanese encephalitis virus (JEV) is endemic in Thailand and prevention strategies include vaccination, vector control, and health education. METHODS: Between July 2003 and August 2005, we conducted hospital-based surveillance for encephalitis at seven hospitals in Bangkok and Hat Yai. Serum and cerebrospinal (CSF) specimens were tested for evidence of recent JEV infection by immunoglobulin M (IgM) enzyme-linked immunosorbent assay (ELISA) and a plaque reduction neutralization test (PRNT). RESULTS: Of the 147 patients enrolled and tested, 24 (16%) had evidence of acute flavivirus infection: 22 (15%) with JEV and two (1%) with dengue virus. Of the 22 Japanese encephalitis (JE) cases, 10 (46%) were aged ≤15 years. The median length of hospital stay was 13 days; one 13-year-old child died. Ten percent of encephalitis patients enrolled in Bangkok hospitals were found to have JEV infection compared to 28% of patients enrolled in hospitals in southern Thailand (p<0.01). Four (40%) of the 10 children with JE were reported as being vaccinated. CONCLUSIONS: JEV remains an important cause of encephalitis among hospitalized patients in Thailand. The high proportion of JE among encephalitis cases is concerning and additional public health prevention efforts or expanded vaccination may be needed.

No studies have quantified the impact of pre-culture antibiotic use on the recovery of individual blood-borne pathogens or on population-level incidence estimates for Streptococcus pneumoniae. We conducted bloodstream infection surveillance in Thailand during November 2005-June 2008. Pre-culture antibiotic use was assessed by reported use and by serum antimicrobial activity. Of 35,639 patient blood cultures, 27% had reported pre-culture antibiotic use and 24% (of 24,538 tested) had serum antimicrobial activity. Pathogen isolation was half as common in patients with versus without antibiotic use; S. pneumoniae isolation was 4- to 9-fold less common (0.09% versus 0.37% by reported antibiotic use; 0.05% versus 0.45% by serum antimicrobial activity, P < 0.01). Pre-culture antibiotic use by serum antimicrobial activity reduced pneumococcal bacteremia incidence by 32% overall and 39% in children < 5 years of age. Our findings highlight the limitations of culture-based detection methods to estimate invasive pneumococcal disease incidence in settings where pre-culture antibiotic use is common.

To determine the role of Bartonella species as causes of acute febrile illness in humans from Thailand, we used a novel strategy of co-cultivation of blood with eukaryotic cells and subsequent phylogenetic analysis of Bartonella-specific DNA products. Bartonella species were identified in 14 blood clots from febrile patients. Sequence analysis showed that more than one-half of the genotypes identified in human patients were similar or identical to homologous sequences identified in rodents from Asia and were closely related to B. elizabethae, B. rattimassiliensis, and B. tribocorum. The remaining genotypes belonged to B. henselae, B. vinsonii, and B. tamiae. Among the positive febrile patients, animal exposure was common: 36% reported owning either dogs or cats and 71% reported rat exposure during the 2 weeks before illness onset. The findings suggest that rodents are likely reservoirs for a substantial portion of cases of human Bartonella infections in Thailand.

Although pneumonia is a leading cause of death from infectious disease worldwide, comprehensive information about its causes and incidence in low- and middle-income countries is lacking. Active surveillance of hospitalized patients with pneumonia is ongoing in Thailand. Consenting patients are tested for seven bacterial and 14 viral respiratory pathogens by PCR and viral culture on nasopharyngeal swab specimens, serology on acute/convalescent sera, sputum smears and antigen detection tests on urine. Between September 2003 and December 2005, there were 1730 episodes of radiographically confirmed pneumonia (34.6% in children aged <5 years); 66 patients (3.8%) died. A recognized pathogen was identified in 42.5% of episodes. Respiratory syncytial virus (RSV) infection was associated with 16.7% of all pneumonias, 41.2% in children. The viral pathogen with the highest incidence in children aged <5 years was RSV (417.1/100 000 per year) and in persons aged 50 years, influenza virus A (38.8/100 000 per year). These data can help guide health policy towards effective prevention strategies.

BACKGROUND: Animal models and data from influenza pandemics suggest that influenza infection predisposes individuals to pneumococcal pneumonia. Influenza may contribute to high winter rates of pneumococcal pneumonia during non-pandemic periods, but the magnitude of this effect is unknown. With use of United States surveillance data during 1995-2006, we estimated the association between influenza circulation and invasive pneumococcal pneumonia rates. METHODS: Weekly invasive pneumococcal pneumonia incidence, defined by isolation of pneumococci from normally sterile sites in persons with clinical or radiographic pneumonia, was estimated from active population-based surveillance in 3 regions of the United States. We used influenza virus data collected by World Health Organization collaborating laboratories in the same 3 regions in seasonally adjusted negative binomial regression models to estimate the influenza-associated fraction of pneumococcal pneumonia. RESULTS: During approximately 185 million person-years of surveillance, we observed 21,239 episodes of invasive pneumococcal pneumonia; 485,691 specimens were tested for influenza. Influenza circulation was associated with 11%-14% of pneumococcal pneumonia during periods of influenza circulation and 5%-6% overall. In 2 of 3 regions, the association was strongest when influenza circulation data were lagged by 1 week. CONCLUSIONS: During recent seasonal influenza epidemics in the United States, a modest but potentially preventable fraction of invasive pneumococcal pneumonia was associated with influenza circulation.

Rates of invasive pneumococcal disease in the United States increase dramatically, or “spike,” during winter holidays.1 We analyzed population-based surveillance data to determine whether spikes may be caused by increased transmission from children to older adults. | Pneumococci spread through upper respiratory secretions, especially those of young children.2 Certain serotypes disproportionately colonize young children.3 The introduction of the pediatric heptavalent pneumococcal conjugate vaccine (PCV7; Prevnar, Wyeth) in 2000 led to a decrease in invasive pneumococcal disease among vaccinated children and reduced transmission to unvaccinated persons.2,4