Naval Medical Research Unit EURAFCENT

The 2013–2016 West African epidemic caused by the Ebola virus was of unprecedented magnitude, duration and impact. Here we reconstruct the dispersal, proliferation and decline of Ebola virus throughout the region by analysing 1,610 Ebola virus genomes, which represent over 5% of the known cases. We test the association of geography, climate and demography with viral movement among administrative regions, inferring a classic ‘gravity’ model, with intense dispersal between larger and closer populations. Despite attenuation of international dispersal after border closures, cross-border transmission had already sown the seeds for an international epidemic, rendering these measures ineffective at curbing the epidemic. We address why the epidemic did not spread into neighbouring countries, showing that these countries were susceptible to substantial outbreaks but at lower risk of introductions. Finally, we reveal that this large epidemic was a heterogeneous and spatially dissociated collection of transmission clusters of varying size, duration and connectivity. These insights will help to inform interventions in future epidemics. Frequent dispersal and short-lived local transmission clusters fuelled the 2013–2016 Ebola virus epidemic in Guinea, Liberia and Sierra Leone. Understanding how and why viruses spread during epidemics is crucial for planning how to prevent and respond to future threats. Andrew Rambaut and colleagues provide an overview of the genetic epidemiology of the 2013–2016 epidemic caused by Ebola virus in West Africa. By analysing more than 1,600 Ebola virus genomes, the authors determine the factors that were important in the spread of the epidemic and also explain why the virus did not spread into neighbouring countries.

Acute and chronic hepatitis B virus (HBV) infection is a leading cause of liver disease worldwide. It is estimated that approximately 350 million people worldwide have chronic HBV infection and that 1 million persons die each year from HBV-related chronic liver disease. In the past decade, significant progress in the understanding of the molecular virology and pathogenesis of HBV infection has been made. In addition, effective treatment modalities have been developed for persons with chronic infection. Worldwide, prevention of HBV transmission has become a high priority. In 1992, the Global Advisory Group to the World Health Organization recommended that all countries integrate hepatitis B vaccine into national immunization programs by 1997. Currently, 80 countries have done so and several others are planning to. Many countries have reported dramatic reductions in the prevalence of chronic HBV infection among children born since the hepatitis B vaccine was introduced into infant immunization schedules. Recent reports from Taiwan indicate a reduction in the incidence of liver cancer among children as a result of widespread hepatitis B vaccination programs.

A suspected case of sexual transmission from a male survivor of Ebola virus disease (EVD) to his female partner (the patient in this report) occurred in Liberia in March 2015. Ebola virus (EBOV) genomes assembled from blood samples from the patient and a semen sample from the survivor were consistent with direct transmission. The genomes shared three substitutions that were absent from all other Western African EBOV sequences and that were distinct from the last documented transmission chain in Liberia before this case. Combined with epidemiologic data, the genomic analysis provides evidence of sexual transmission of EBOV and evidence of the persistence of infective EBOV in semen for 179 days or more after the onset of EVD. (Funded by the Defense Threat Reduction Agency and others.).

From October to December 1977, an extensive epizootic occurred in Egypt resulting in abortions and increased mortality in domestic animals, and severe clinical disease with fatalities in man. Rift Valley Fever (RVF) virus was isolated and identified as the causative agent. In humans, acute febrile, encephalitic, ocular and fatal haemorrhagic diseases were documented as resulting from RVF virus infection. A retrospective serological survey indicated RVF was recently introduced into the area. The 1977 epizootic extensively involved five Governorates. In the summer and autumn of 1978, epizootic RVF reappeared in Egypt and spread to previously uninfected areas. Virological, serological and epidemiological studies, and factors related to the spread of RVF are discussed.

Journal Article Epidemic Rift Valley fever in Egypt: observations of the spectrum of human illness Get access Larry W. Laughlin, Larry W. Laughlin 1U.S. Naval Medical Research Unit No. 3, Cairo, Arab Republic of Egypt Search for other works by this author on: Oxford Academic PubMed Google Scholar James M. Meegan, James M. Meegan 1U.S. Naval Medical Research Unit No. 3, Cairo, Arab Republic of Egypt Search for other works by this author on: Oxford Academic PubMed Google Scholar Larry J. Strausbaugh, Larry J. Strausbaugh 1U.S. Naval Medical Research Unit No. 3, Cairo, Arab Republic of Egypt Search for other works by this author on: Oxford Academic PubMed Google Scholar David M. Morens, David M. Morens 2Viral Disease Division, Bureau of Epidemiology, Center for Disease Control, Atlanta, Georgia, USA Search for other works by this author on: Oxford Academic PubMed Google Scholar Raymond H. Watten Raymond H. Watten 1U.S. Naval Medical Research Unit No. 3, Cairo, Arab Republic of Egypt Search for other works by this author on: Oxford Academic PubMed Google Scholar Transactions of The Royal Society of Tropical Medicine and Hygiene, Volume 73, Issue 6, 1979, Pages 630–633, https://doi.org/10.1016/0035-9203(79)90006-3 Published: 01 January 1979

BACKGROUND & AIMS: In 2015, a national Egyptian health issue survey was conducted to describe the prevalence of hepatitis C virus (HCV) infection. In this paper, we describe the HCV burden in 2015, compare the results with the national survey conducted in 2008, and discuss the implications of the new findings on prevention of HCV in Egypt. METHODS: A multistage probability sampling approach was used, similar to the national demographic survey conducted in 2008. More than 90% of sampled individuals complied with the interview and provided blood samples. RESULTS: In the 15-59-year age groups, the prevalence of HCV antibody was found to be 10.0% (95% CI 9.5-10.5) and that of HCV RNA to be 7.0% (95% CI 6.6-7.4). In children, 1-14 years old, the prevalence of HCV antibody and HCV RNA were 0.4% (95% CI 0.3-0.5) and 0.2% (95% CI 0.1-0.3) respectively. Approximately, 3.7 million persons have chronic HCV infection in the age group 15-59 in 2015. An estimated 29% reduction in HCV RNA prevalence has been seen since 2008, which is largely attributable to the ageing of the group infected 40-50 years ago during the mass schistosomiasis treatment campaigns. Prevention efforts may have also contributed to this decline, with an estimated 75% (95% CI 6-45) decrease in HCV incidence in the 0-19 year age groups over the past 20 years. CONCLUSIONS: These findings can be used to shape future HCV prevention policies in Egypt.

Four hundred twenty-nine patients with bacterial meningitis were assigned on a nonselective alternating basis into one of two therapeutic regimens. Patients in Group I received dexamethasone in addition to standard antibacterial chemotherapy of ampicillin and chloramphenicol whereas those in Group II received antibacterial chemotherapy alone. Dexamethasone was given intramuscularly (8 mg to children younger than 12 years and 12 mg to adults every 12 hours for 3 days). Both treatment groups were comparable with regard to age, sex, duration of symptoms and state of consciousness at the time of hospitalization. A significant reduction in the case fatality rate (P less than 0.01) was observed in patients with pneumococcal meningitis receiving dexamethasone; only 7 of 52 patients died compared with 22 of 54 patients not receiving dexamethasone. A reduction in the overall neurologic sequelae (hearing impairment and paresis) was observed in patients receiving dexamethasone. This reduction was significant only in patients with Streptococcus pneumoniae meningitis; none of the 45 surviving patients receiving steroids had hearing loss whereas 4 of 32 patients not receiving dexamethasone had severe hearing loss (P less than 0.05). No significant difference was observed between the two groups with regard to time for patients to become afebrile or to regain consciousness or in the mean admission and 24- to 36-hour cerebrospinal fluid leukocyte count, glucose or protein content.

BACKGROUND: Under combat conditions infectious disease can become a major threat to military forces. During Operation Desert Shield, there were numerous outbreaks of diarrhea among the U.S. forces. To evaluate the causes of and risk factors for diarrheal disease, we collected clinical and epidemiologic data from U.S. troops stationed in northeastern Saudi Arabia. METHODS: Between September and December 1990, stool cultures for enteric pathogens were obtained from 432 military personnel who presented with diarrhea, cramps, vomiting, or hematochezia. In addition, a questionnaire was administered to 2022 soldiers in U.S. military units located in various regions of Saudi Arabia. RESULTS: A bacterial enteric pathogen was identified in 49.5 percent of the troops with gastroenteritis. Enterotoxigenic Escherichia coli and Shigella sonnei were the most common bacterial pathogens. Of 125 E. coli infections, 39 percent were resistant to trimethoprim-sulfamethoxazole, 63 percent to tetracycline, and 48 percent to ampicillin. Of 113 shigella infections, 85 percent were resistant to trimethoprim-sulfamethoxazole, 68 percent to tetracycline, and 21 percent to ampicillin. All bacterial isolates were sensitive to norfloxacin and ciprofloxacin. After an average of two months in Saudi Arabia, 57 percent of the surveyed troops had at least one episode of diarrhea, and 20 percent reported that they were temporarily unable to carry out their duties because of diarrheal symptoms. Vomiting was infrequently reported as a primary symptom, but of 11 military personnel in whom vomiting was a major symptom, 9 (82 percent) had serologic evidence of infection with the Norwalk virus. CONCLUSIONS: Gastroenteritis caused by enterotoxigenic E. coli and shigella resistant to a number of drugs was a major problem that frequently interfered with the duties of U.S. troops during Operation Desert Shield.

To evaluate the effectiveness of an intensive hand hygiene campaign on reducing absenteeism caused by influenza-like illness (ILI), diarrhea, conjunctivitis, and laboratory-confirmed influenza, we conducted a randomized control trial in 60 elementary schools in Cairo, Egypt. Children in the intervention schools were required to wash hands twice each day, and health messages were provided through entertainment activities. Data were collected on student absenteeism and reasons for illness. School nurses collected nasal swabs from students with ILI, which were tested by using a qualitative diagnostic test for influenza A and B. Compared with results for the control group, in the intervention group, overall absences caused by ILI, diarrhea, conjunctivitis, and laboratory-confirmed influenza were reduced by 40%, 30%, 67%, and 50%, respectively (p<0.0001 for each illness). An intensive hand hygiene campaign was effective in reducing absenteeism caused by these illnesses.

Complement-fixation test reactions to eight viruses of the family Togaviridae were studied in 372 serum samples (157 rodents, 172 domestic animals, 43 humans) from Pakistan. Antibodies to each tested virus were detected. The highest over-all prevalence rates were for West Nile (WN) (7.8%), Japanese encephalitis (JE) (3.2%) and Zika (ZIKA) (2.4%) viruses, followed by Sindbis (SIN), Chikungunya (CHIK), Uganda S (UGS) and Royal Farm (RF) viruses (1.6 to 1.3%). One human serum (male, age 58 years) reacted with Dengue-1 (DEN) virus antigen (titre 1:32). Antibodies to each virus except RF were detected in human sera; antibodies to RF virus were detected only in rodent and domestic animal sera. The roles of rodents in the epidemiology of WN, JE and ZIKA viruses should be investigated. At least six of these eight viruses cause fevers in humans (fevers of unknown origin comprise about one third of the febrile episodes recorded in Pakistan).

Antibodies specific for human T-cell leukemia-lymphoma virus type I (HTLV-I) were demonstrated in serum samples from various groups of people in South Africa, Uganda, Ghana, Nigeria, Tunisia, and Egypt. The samples had been collected for other purposes and were presumably selected without bias toward clinical conditions associated with HTLV infections. Regional differences in antibody positivity were observed, indicating widely distributed loci of occurrence of HTLV on the African continent in people of both black and white ancestry. Two patients with high titers of antibody to HTLV-I had some signs of adult T-cell leukemia-lymphoma. In several groups a high frequency of false positive serum reactions was indicated when specific confirmation steps were included in the assay. Further characterization of these sera revealed highly elevated immunoglobulin levels, possibly due to polyclonal activation of immunoglobulin synthesis in these subjects. The possibility that related cross-reactive human retroviruses coexist in the same groups was not eliminated.

In Brief Objective: To describe risks for, and microbiology and antimicrobial resistance patterns of, war trauma associated infections from Operation Iraqi Freedom. Background: The invasion of Iraq resulted in casualties from high-velocity gunshot, shrapnel, and blunt trauma injuries as well as burns. Infectious complications of these unique war trauma injuries have not been described since the 1970s. Methods: Retrospective record review of all trauma casualties 5 to 65 years of age evacuated from the Iraqi theatre to U.S. Navy hospital ship, USNS Comfort March to May 2003.War trauma-associated infection was defined by positive culture from a wound or sterile body fluid (ie, blood, cerebrospinal fluid) and at least two of the following infection-associated signs/symptoms: fever, dehiscence, foul smell, peri-wound erythema, hypotension, and leukocytosis. A comparison of mechanisms of injury, demographics, and clinical variables was done using multivariate analysis. Results: Of 211 patients, 56 met criteria for infection. Infections were more common in blast injuries, soft tissue injuries, >3 wound sites, loss of limb, abdominal trauma, and higher Injury Severity Score (ISS). Wound infections accounted for 84% of cases, followed by bloodstream infections (38%). Infected were more likely to have had fever prior to arrival, and had higher probability of ICU admission and more surgical procedures. Acinetobacter species (36%) were the predominant organisms followed by Escherichia coli and Pseudomonas species (14% each). Conclusions: Similar to the Vietnam War experience, gram-negative rods, particularly Acinetobacter species, accounted for the majority of wound infections cared for on USNS Comfort during Operation Iraqi Freedom. Multidrug resistance was common, with the exception of the carbapenem class, limiting antibiotic therapy options. We reviewed 211 war-wounded patients from Iraq. Infections were more common in blast injuries, soft tissue injuries, >3 wound sites, loss of limb, abdominal trauma, and higher Injury Severity Score (ISS). Gram-negatives accounted for the majority of wound infections. Multidrug resistance was common, except for the carbapenem class, limiting antibiotic therapy options.

To better understand the ecology and epidemiology of the highly pathogenic avian influenza virus in its transcontinental spread, we sequenced and analyzed the complete genomes of 36 recent influenza A (H5N1) viruses collected from birds in Europe, northern Africa, and southeastern Asia. These sequences, among the first complete genomes of influenza (H5N1) viruses outside Asia, clearly depict the lineages now infecting wild and domestic birds in Europe and Africa and show the relationships among these isolates and other strains affecting both birds and humans. The isolates fall into 3 distinct lineages, 1 of which contains all known non-Asian isolates. This new Euro-African lineage, which was the cause of several recent (2006) fatal human infections in Egypt and Iraq, has been introduced at least 3 times into the European-African region and has split into 3 distinct, independently evolving sublineages. One isolate provides evidence that 2 of these sublineages have recently reassorted.

During a 5-year period, 280 of 2010 patients admitted to the meningitis ward of a referral hospital in Cairo, Egypt, were clinically diagnosed as having tuberculous meningitis and were treated with either antituberculous chemotherapy and dexamethasone or antituberculous chemotherapy alone. Fatality rates and neurologic sequelae were compared for the 2 treatment groups in the 160 patients who had cerebrospinal fluid cultures positive for Mycobacterium tuberculosis. The overall mortality rate of 51% reflects the delay in receiving appropriate therapy (79% with symptoms for more than 2 weeks) and the severity of illness on admission (56% in coma, 39% drowsy). The fatality rate was significantly lower in the group receiving dexamethasone (43% vs. 59%, P less than 0.05), particularly in the drowsy patients (15% vs. 40% P less than 0.04), and in patients surviving long enough to receive at least 10 days of treatment (14% vs. 33%, P less than 0.02). Development of neurologic complications after initiation of therapy (4 vs. 10) and permanent sequelae (6 vs. 13) were significantly lower in the dexamethasone-treated group (P less than 0.02).

A review the various patterns of tick-host relationships are discussed in detail in order to answer the following questions : &lt;br&gt; 1. How, when and where did host specificity of each parasite group evolve ? &lt;br&gt; 2. How strict is specificity in each case ? &lt;br&gt; 3. Why and under what circumstances does specificity break down ? &lt;br&gt; The authors present several definitions which characterize the various degrees of parasitic specificity existing today between ticks and their hosts. &lt;br&gt; Tick-host relationships are presented in relation to life-cycle patterns and also to their appearance in the evolution of the various classes of terrestrial vertebrates. Special attention is paid to the ticks of mammals. A family tree has been set up to display the families, subfamilies and genera of ticks.

Epidemiological factors related to the introduction, spread and maintenance of Rift Valley fever (RVF) virus were studied during the 1977–1978 epizootic in Egypt. Culex pipiens is the most ubiquitous and prevalent mosquito species in the Nile Valley and Delta. Isolation of RVF virus from unengorged C. pipiens, and demonstration of laboratory transmission of the virus by this species, strongly implicate it as the chief vector in Egypt. Virus transmission to man also occurs by contamination when handling infected meat and by inhaling natural virus aerosols. Wild rodents apparently do not serve as RVF virus reservoirs. Domestic sheep, cattle, buffaloes, camels, goats, donkeys and dogs act as amplifying hosts. Over 30% of the camels sampled at the southern border of Egypt were serologically positive for antibodies to RVF virus and it appears likely that the virus was introduced into Egypt, either by these animals or by other vehicles from the south.

To measure the incidence of typhoid fever and other febrile illnesses in Bilbeis District, Egypt, we conducted a household survey to determine patterns of health seeking among persons with fever. Then we established surveillance for 4 months among a representative sample of health providers who saw febrile patients. Health providers collected epidemiologic information and blood (for culture and serologic testing) from eligible patients. After adjusting for the provider sampling scheme, test sensitivity, and seasonality, we estimated that the incidence of typhoid fever was 13/100,000 persons per year, and the incidence of brucellosis was 18/100,000 persons per year in the district. This surveillance tool could have wide applications for surveillance for febrile illness in developing countries.

A new human coronavirus (CoV), subsequently named Middle East respiratory syndrome (MERS)-CoV, was first reported in Saudi Arabia in September 2012. In response, we developed two real-time reverse transcription-PCR (rRT-PCR) assays targeting the MERS-CoV nucleocapsid (N) gene and evaluated these assays as a panel with a previously published assay targeting the region upstream of the MERS-CoV envelope gene (upE) for the detection and confirmation of MERS-CoV infection. All assays detected ≤10 copies/reaction of quantified RNA transcripts, with a linear dynamic range of 8 log units and 1.3 × 10(-3) 50% tissue culture infective doses (TCID50)/ml of cultured MERS-CoV per reaction. All assays performed comparably with respiratory, serum, and stool specimens spiked with cultured virus. No false-positive amplifications were obtained with other human coronaviruses or common respiratory viral pathogens or with 336 diverse clinical specimens from non-MERS-CoV cases; specimens from two confirmed MERS-CoV cases were positive with all assay signatures. In June 2012, the U.S. Food and Drug Administration authorized emergency use of the rRT-PCR assay panel as an in vitro diagnostic test for MERS-CoV. A kit consisting of the three assay signatures and a positive control was assembled and distributed to public health laboratories in the United States and internationally to support MERS-CoV surveillance and public health responses.

We studied the malaria transmission dynamics in Kassena Nankana district (KND), a site in northern Ghana proposed for testing malaria vaccines. Intensive mosquito sampling for 1 year using human landing catches in three micro-ecological sites (irrigated, lowland and rocky highland) yielded 18 228 mosquitoes. Anopheles gambiae s.l. and Anopheles funestus constituted 94.3% of the total collection with 76.8% captured from the irrigated communities. Other species collected but in relatively few numbers were Anopheles pharoensis (5.4%) and Anopheles rufipes (0.3%). Molecular analysis of 728 An. gambiae.s.l. identified Anopheles gambiae s.s. as the most dominant sibling species (97.7%) of the An. gambiae complex from the three ecological sites. Biting rates of the vectors (36.7 bites per man per night) were significantly higher (P<0.05) in the irrigated area than in the non-irrigated lowland (5.2) and rocky highlands (5.9). Plasmodium falciparum sporozoite rates of 7.2% (295/4075) and 7.1% (269/3773) were estimated for An. gambiae s.s. and An. funestus, respectively. Transmission was highly seasonal, and the heaviest transmission occurred from June to October. The intensity of transmission was higher for people in the irrigated communities than the non-irrigated ones. An overall annual entomological inoculation rate (EIR) of 418 infective bites was estimated in KND. There were micro-ecological variations in the EIRs, with values of 228 infective bites in the rocky highlands, 360 in the lowlands and 630 in the irrigated area. Approximately 60% of malaria transmission in KND occurred indoors during the second half of the night, peaking at daybreak between 04.00 and 06.00 hours. Vaccine trials could be conducted in this district, with timing dependent on the seasonal patterns and intensity of transmission taking into consideration the micro-geographical differences and vaccine trial objectives.

Serologic surveys in Egypt have documented human and animal exposure to vector-borne bacterial pathogens, but the presence and distribution of these agents in arthropods has not been determined. Between July 2002 and July 2003, fleas were collected from 221 mammals trapped in 17 cities throughout Egypt. A total of 987 fleas were collected, representing four species (Ctenocephalides felis, Echidnophaga gallinacea, Leptopsylla segnis, and Xenopsylla cheopis); 899 of these fleas were X. cheopis from rats (Rattus spp.). Fleas were tested for DNA from Anaplasma spp., Bartonella spp., Coxiella burnetii, Ehrlichia spp., Rickettsia spp., and Yersinia pestis. Rickettsia typhi, the agent of murine typhus, was detected in X. cheopis and L. segnis from rats from nine cities. A spotted-fever group Rickettsia sp. similar to "RF2125" was detected in E. gallinacea, and two unidentified spotted fever group Rickettsia were detected in two X. cheopis. Novel Bartonella genotypes were detected in X. cheopis and L. segnis from three cities. Coxiella burnetii was detected in two fleas. Anaplasma, Ehrlichia, and Y. pestis were not detected.