Outbreaks of unexplained neurologic illness - Muzaffarpur, India, 2013-2014.

Outbreaks of an unexplained acute neurologic illness affecting young children and associated with high case-fatality rates have been reported in the Muzaffarpur district of Bihar state in India since 1995. The outbreaks generally peak in June and decline weeks later with the onset of monsoon rains. There have been multiple epidemiologic and laboratory investigations of this syndrome, leading to a wide spectrum of proposed causes for the illness, including infectious encephalitis and exposure to pesticides. An association between illness and litchi fruit has been postulated because Muzaffarpur is a litchi fruit-producing region. To better characterize clinical and epidemiologic features of the illness that might suggest its cause and how it can be prevented, the Indian National Centre for Disease Control (NCDC) and CDC investigated outbreaks in 2013 and 2014. Clinical and laboratory findings in 2013 suggested a noninflammatory encephalopathy, possibly caused by a toxin. A common laboratory finding was low blood glucose (<70 mg/dL) on admission, a finding associated with a poorer outcome; 44% of all cases were fatal. An ongoing 2014 investigation has found no evidence of any infectious etiology and supports the possibility that exposure to a toxin might be the cause. The outbreak period coincides with the month-long litchi harvesting season in Muzaffarpur. Although a specific etiology has not yet been determined, the 2014 investigation has identified the illness as a hypoglycemic encephalopathy and confirmed the importance of ongoing laboratory evaluation of environmental toxins to identify a potential causative agent, including markers for methylenecyclopropylglycine (MCPG), a compound found in litchi seeds known to cause hypoglycemia in animal studies. Current public health recommendations are focused on reducing mortality by urging affected families to seek prompt medical care, and ensuring rapid assessment and correction of hypoglycemia in ill children.

Microevolution of highly pathogenic avian influenza A(H5N1) viruses isolated from humans, Egypt, 2007-2011.

We analyzed highly pathogenic avian influenza A(H5N1) viruses isolated from humans infected in Egypt during 2007-2011. All analyzed viruses evolved from the lineage of subtype H5N1 viruses introduced into Egypt in 2006; we found minimal evidence of reassortment and no exotic introductions. The hemagglutinin genes of the viruses from 2011 formed a monophyletic group within clade 2.2.1 that also included human viruses from 2009 and 2010 and contemporary viruses from poultry; this finding is consistent with zoonotic transmission. Although molecular markers suggestive of decreased susceptibility to antiviral drugs were detected sporadically in the neuraminidase and matrix 2 proteins, functional neuraminidase inhibition assays did not identify resistant viruses. No other mutations suggesting a change in the threat to public health were detected in the viral proteomes. However, a comparison of representative subtype H5N1 viruses from 2011 with older subtype H5N1 viruses from Egypt revealed substantial antigenic drift.

Pandemic (H1N1) 2009 and Hajj Pilgrims who received Predeparture Vaccination, Egypt.

In Egypt, vaccination against pandemic (H1N1) 2009 virus was required of pilgrims departing for the 2009 Hajj. A survey of 551 pilgrims as they returned to Egypt found 542 (98.1% [weighted]) reported receiving the vaccine; 6 (1.0% [weighted]) were infected with influenza virus A (H3N2) but none with pandemic (H1N1) 2009 virus.

Capacity-building efforts by the AFHSC-GEIS program.

Capacity-building initiatives related to public health are defined as developing laboratory infrastructure, strengthening host-country disease surveillance initiatives, transferring technical expertise and training personnel. These initiatives represented a major piece of the Armed Forces Health Surveillance Center, Division of Global Emerging Infections Surveillance and Response System (AFHSC-GEIS) contributions to worldwide emerging infectious disease (EID) surveillance and response. Capacity-building initiatives were undertaken with over 80 local and regional Ministries of Health, Agriculture and Defense, as well as other government entities and institutions worldwide. The efforts supported at least 52 national influenza centers and other country-specific influenza, regional and U.S.-based EID reference laboratories (44 civilian, eight military) in 46 countries worldwide. Equally important, reference testing, laboratory infrastructure and equipment support was provided to over 500 field sites in 74 countries worldwide from October 2008 to September 2009. These activities allowed countries to better meet the milestones of implementation of the 2005 International Health Regulations and complemented many initiatives undertaken by other U.S. government agencies, such as the U.S. Department of Health and Human Services, the U.S. Agency for International Development and the U.S. Department of State.

Zoonotic transmission of avian influenza virus (H5N1), Egypt, 2006-2009.

During March 2006-March 2009, a total of 6,355 suspected cases of avian influenza (H5N1) were reported to the Ministry of Health in Egypt. Sixty-three (1%) patients had confirmed infections; 24 (38%) died. Risk factors for death included female sex, age > or = 15 years, and receiving the first dose of oseltamivir >2 days after illness onset. All but 2 case-patients reported exposure to domestic poultry probably infected with avian influenza virus (H5N1). No cases of human-to-human transmission were found. Greatest risks for infection and death were reported among women > or = 15 years of age, who accounted for 38% of infections and 83% of deaths. The lower case-fatality rate in Egypt could be caused by a less virulent virus clade. However, the lower mortality rate seems to be caused by the large number of infected children who were identified early, received prompt treatment, and had less severe clinical disease.

Effects of duration of injection drug use and age at first injection on HCV among IDU in Kabul, Afghanistan.

BACKGROUND: Hepatitis C virus (HCV) prevalence is high among injection drug users (IDUs) in Afghanistan. Duration of injection and young age at first injection are common risk factors for HCV in IDU populations. The association of HCV with these time factors was analyzed. METHODS: Socio-demographic and drug use behavior information were collected. Participants had rapid testing for HCV with recombinant immunoblot assay confirmation. Modeling of non-linear associations was performed using fractional polynomial logistic regression. RESULTS: Among 459 male IDUs, age at first injection had a constant HCV risk (odds ratio (OR): 1.01 per year; 95% confidence interval (CI): 0.98-1.03), while each additional year of injection drug use had a significantly increased risk (OR: 4.72 per year, 95% CI: 2.92-7.66). HCV risk increased significantly with each additional year of injecting drug use by groups of injectors: young (< or =22 years, OR: 1.97; 95% CI: 1.27-3.07), middle (23-28 years, OR: 1.76; 95% CI: 1.28-2.43) and older (> or =29 years, OR: 7.56; 95% CI: 3.15-18.14). CONCLUSION: The probability of HCV infection increased markedly by duration of injection drug use and varied according to age at first injection. Drug counseling and educational efforts should be directed to older drug users who have not yet initiated injecting and to young IDUs to avert infection and reduce risky drug use behaviors.

Antigenic and genetic diversity of highly pathogenic avian influenza A (H5N1) viruses isolated in Egypt.

Highly pathogenic avian influenza A virus (H5N1) has diverged antigenically and genetically since its initial detection in Asia in 1997. Viruses belonging to clade 2.2 in particular have been reported in numerous countries with the majority occurring in Egypt. Previous reports identified antigenic similarities between viruses belonging to clade 2.2. However, poultry and human viruses isolated in northern Egypt during 2007 and 2008 were found to be antigenically distinct from other clade 2.2 viruses from this country. Genetic analysis of the hemagglutinin revealed a high degree of nucleotide and amino acid divergence. The antigenic changes in Egyptian viruses isolated during 2007-08 necessitated that two of these strains be considered as potential H5N1 pre-pandemic vaccine candidates.

A cross-sectional assessment of utilization of addiction treatment among injection drug users in Kabul, Afghanistan.

The purpose of this study was to describe prior use of detoxification and addiction-treatment programs among injection drug users (IDUs) in Kabul, Afghanistan. From 2005-2006, IDUs (n = 464) recruited into this cross-sectional study completed an interviewer-administered questionnaire and whole blood rapid testing with fingerstick samples for HIV, syphilis, and hepatitis C antibody and B surface antigen testing. Participants were predominantly male (99.8%), Afghan (98.9%), and had little formal education. Correlates of detoxification and addiction treatment were identified with logistic regression. The majority (94.0%, n = 435) felt great/urgent need for treatment, of whom 56.3% (n = 245) reported inability to access treatment. Prior detoxification was associated with new needle use with each injection (AOR = 1.91, 95% CI: 1.12-3.26) and prior incarceration (AOR = 1.81, 95% CI: 1.04-3.13). The study's limitations are noted. Rapid scale-up and subsidy of needle and syringe programs and opioid agonist treatment is urgently needed in Kabul.

Isolation of cryptococcus, Candida, Aspergillus, Rhodotorula and nocardia from meningitis patients in egypt.

Meningitis occurs throughout Egypt and is largely attributed to bacterial pathogens, but there is little information on fungal etiologies of meningitis. We, therefore, investigated fungal infections among Egyptian patients with acute and subacute meningitis who tested negative for bacterial and viral agents. A total of 1000 cerebrospinal fluid (CSF) samples collected from nine governorates of Egypt during 1998-2002 were initially stained with Gram's, India ink, and lacto-phenol cotton-blue stains, and examined under light microscope to detect fungal elements. All CSF samples were cultured on brain heart infusion, Wickerham and Staib agar media for fungus isolation. CSF with suspected Cryptococcus neoformans infections were also tested by latex agglutination test for antigen detection. Species identification of selected isolates was carried out at the Mycotic Diseases Branch, CDC, Atlanta, Georgia, USA. Fungal agents were detected microscopically and by culture in 17 of 1000 (1.7%) CSF samples tested. Ten of 17 were identified as C. neoformans var grubii (serotype A), 4 as Candida albicans, and one each of Aspergillus candidus, Rhodotorula mucilaginosa (rubra) and Nocardia spp (actinomycetes). Out of the 17 cases with fungal CSF infection, 8 died (Cryptococcus-3, Candida-2, Aspergillus, Rhodotorula and Nocardia) and 2 suffered neurological sequelae. Of the 10 cryptococcal meningitis patients, 4 were HIV positive and one was diagnosed with lymphoma. To our knowledge, this is the first study on isolation of fungi other than Cryptococcus from CSF of Egyptian patients with acute/subacute meningitis. Consideration must now be given to cryptococcosis and candidiasis as potential etiologies of meningitis in Egypt.

Outbreak of Q fever among US military in western Iraq, June-July 2005.

An outbreak of Q fever occurred in 22 (58%) of 38 Marines deployed to Iraq in 2005. Fever (in 100% of patients), respiratory symptoms (76%), and gastrointestinal symptoms (53%) were common. Possible risk factors included dust and exposure to animals and ticks.

Brucellosis as a cause of acute febrile illness in Egypt.

To develop better estimates of brucellosis incidence, we conducted population-based surveillance for acute febrile illness (AFI) in Fayoum governorate (population 2347249), Egypt during two summer periods (2002 and 2003). All hospitals and a representative sample of community healthcare providers were included. AFI patients without obvious etiology were tested for brucellosis by culture and serology. Incidence estimates were calculated adjusting for sampling methodology and study period. Of 4490 AFI patients enrolled, 321 (7%) met the brucellosis case definition. The estimated annual incidence of brucellosis per 100000 population was 64 and 70 in 2002 and 2003, respectively. The median age of brucellosis patients was 26 years and 70% were male; 53% were initially diagnosed as typhoid fever. Close contact with animals and consumption of unpasteurized milk products were associated with brucellosis. The high incidence of brucellosis in Fayoum highlights its public health importance, and the need to implement prevention strategies in humans and animals.

Association of acute toxic encephalopathy with litchi consumption in an outbreak in Muzaffarpur, India, 2014: a case-control study.

BACKGROUND: Outbreaks of unexplained illness frequently remain under-investigated. In India, outbreaks of an acute neurological illness with high mortality among children occur annually in Muzaffarpur, the country's largest litchi cultivation region. In 2014, we aimed to investigate the cause and risk factors for this illness. METHODS: In this hospital-based surveillance and nested age-matched case-control study, we did laboratory investigations to assess potential infectious and non-infectious causes of this acute neurological illness. Cases were children aged 15 years or younger who were admitted to two hospitals in Muzaffarpur with new-onset seizures or altered sensorium. Age-matched controls were residents of Muzaffarpur who were admitted to the same two hospitals for a non-neurologic illness within seven days of the date of admission of the case. Clinical specimens (blood, cerebrospinal fluid, and urine) and environmental specimens (litchis) were tested for evidence of infectious pathogens, pesticides, toxic metals, and other non-infectious causes, including presence of hypoglycin A or methylenecyclopropylglycine (MCPG), naturally-occurring fruit-based toxins that cause hypoglycaemia and metabolic derangement. Matched and unmatched (controlling for age) bivariate analyses were done and risk factors for illness were expressed as matched odds ratios and odds ratios (unmatched analyses). FINDINGS: Between May 26, and July 17, 2014, 390 patients meeting the case definition were admitted to the two referral hospitals in Muzaffarpur, of whom 122 (31%) died. On admission, 204 (62%) of 327 had blood glucose concentration of 70 mg/dL or less. 104 cases were compared with 104 age-matched hospital controls. Litchi consumption (matched odds ratio [mOR] 9·6 [95% CI 3·6 - 24]) and absence of an evening meal (2·2 [1·2-4·3]) in the 24 h preceding illness onset were associated with illness. The absence of an evening meal significantly modified the effect of eating litchis on illness (odds ratio [OR] 7·8 [95% CI 3·3-18·8], without evening meal; OR 3·6 [1·1-11·1] with an evening meal). Tests for infectious agents and pesticides were negative. Metabolites of hypoglycin A, MCPG, or both were detected in 48 [66%] of 73 urine specimens from case-patients and none from 15 controls; 72 (90%) of 80 case-patient specimens had abnormal plasma acylcarnitine profiles, consistent with severe disruption of fatty acid metabolism. In 36 litchi arils tested from Muzaffarpur, hypoglycin A concentrations ranged from 12·4 µg/g to 152·0 µg/g and MCPG ranged from 44·9 µg/g to 220·0 µg/g. INTERPRETATION: Our investigation suggests an outbreak of acute encephalopathy in Muzaffarpur associated with both hypoglycin A and MCPG toxicity. To prevent illness and reduce mortality in the region, we recommended minimising litchi consumption, ensuring receipt of an evening meal and implementing rapid glucose correction for suspected illness. A comprehensive investigative approach in Muzaffarpur led to timely public health recommendations, underscoring the importance of using systematic methods in other unexplained illness outbreaks. FUNDING: US Centers for Disease Control and Prevention.

Molecular epidemiology of HIV Type 1 in Ukraine: birthplace of an epidemic.

During the 1990s, HIV-1 spread rapidly through drug networks in Ukraine and from there throughout the former Soviet Union. To examine the origins of this epidemic, the genetics of HIV-1 in Ukraine were studied. Proviral DNA from PBMC was extracted and PCR amplified. Part of pol and nearly full genomes of HIV-1 were sequenced and characterized. The predominant genetic form in 163 strains was subtype A (66%), followed by subtypes B (30%), C (2%), D (1%), and a new AB recombinant form (1%). HIV strains from Kiev were diverse having subtypes A, B, C, and D. In Crimea, Donetsk, Poltava, and Odessa, however, the strains were overwhelmingly subtype A, while in Nikolaev subtype B predominated. After the near simultaneous introduction of subtypes A and B in Ukraine, subtype B remained where it was introduced while subtype A spread widely, creating the fastest growing epidemic in the world.

Genetic forms of HIV Type 1 in the former Soviet Union dominate the epidemic in Azerbaijan.

A total of 125 strains collected in Azerbaijan between 1999 and 2002 from HIV seropositives were genetically classified. Of 84 strains classified using HMA, 91.6% were subtype A, 1.2% subtype B, and 7.1% untypeable. Of 41 strains analyzed using partial pol gene sequences, 90.2% were subtype A, 7.3% subtype B, and 2.4% CRF03_AB. Most sequenced A strains clustered with those circulating in countries of the former Soviet Union (FSU). Two of three sequenced B strains were from individuals who traveled to FSU clustering tightly with B strains from Nikolayev, Ukraine. CRF03_AB, characteristic of the 1996 epidemic in Kaliningrad, Russia, was sequenced from an individual who lived in Russia from 1995 until 2001. The HIV epidemic in Azerbaijan is concentrated in IDU and is closely connected to other such epidemics to the east based on genetics. Of the 41 sequenced strains, 95% were close genetic relatives of HIV strains in IDU networks in the FSU.

Short report: HIV infection among commercial sex workers and injecting drug users in the Czech Republic.

Since the first HIV case was diagnosed in the Czech Republic in 1985, there is a lack of information regarding the epidemiology of HIV infection in most high-risk groups. To determine the prevalence of, and risk factors for, HIV among female and male commercial sex workers (FCSW and MCSW, respectively) and injecting drug users (IDUs), cross-sectional studies were conducted in the cities of Cheb, Usti nad Labem, Ostrava, and Prague of the Czech Republic. A total of 1,277 subjects were enrolled, which included 585 FCSWs, 230 MCSWs, and 462 IDUs. The HIV prevalences were 0.7% (95% CI: 0.2-1.7%), 0.9% (95% CI: 0.1-3.1%), and 0.2% (95% CI: 0.005-1.2%) among FCSWs, MCSWs, and IDUs, respectively. Although low HIV prevalences were found, ongoing sentinel surveillance studies, which address modifiable behavioral and biologic risk factors among high-risk groups, are necessary to guide strategies to stem the tide of the epidemic in this country.

High HIV prevalence and risk factors among injection drug users in Tashkent, Uzbekistan, 2003-2004.

OBJECTIVES: To determine HIV prevalence and potential associations with sociodemographic and behavioral factors among injection drug users (IDUs) in Tashkent, Uzbekistan. METHODS: Subjects in this cross-sectional study provided sociodemographic and risk behavior data and were tested for HIV antibody with a saliva-based enzyme-linked immunosorbent assay (ELISA), followed by saliva-based Western blot confirmation. RESULTS: Among the 701 IDU subjects enrolled, 209 (29.8%) were diagnosed with HIV infection, HIV infection was more likely among those unemployed (adjusted odds ratio [AOR]=1.47); whose first drug of abuse was heroin (AOR=2.21) or opium poppy extract (AOR=1.61); with a prior history of hepatitis (AOR=1.39); and those who reported never using condoms (AOR=1.65). Independent risk factors associated with HIV infection were heroin as the first illicit drug of abuse, prior hepatitis, lack of condom use, and unemployment. CONCLUSIONS: Heroin use, sexual transmission, and high unemployment seem to play important roles in HIV transmission. Implementation of effective harm reduction strategies is critical to control the expansion of the HIV epidemic in this country as well as in this region.

Utilization of contraception and abortion and its relationship to HIV infection among female sex workers in Tashkent, Uzbekistan.

OBJECTIVE: This study aimed to describe reported contraceptive and abortion utilization and their relationship to human immunodeficiency virus (HIV) infection among female sex workers (FSW) in Tashkent, Uzbekistan. METHODS: For this cross-sectional study, women were recruited through outreach workers affiliated with Istiqbolli Avlod. Participants completed a self-administered questionnaire and underwent HIV testing. RESULTS: Of 448 participants, the majority (86.2%, n=386) used contraception; 39.6% reported inconsistent use. Methods most frequently utilized were condoms (50.9%) and intrauterine devices (16.1%). One fourth (24.3%, n=109) reported multiple (>or=3) prior abortions. Inconsistent contraceptive users were more likely to be infected with HIV (AOR=2.72, 95% CI=1.19-6.22), but such infection was not related to a specific contraceptive method, including condoms, or utilization of abortion. CONCLUSIONS: Inconsistent contraceptive use is common and may be a predictor of HIV infection among Tashkent FSW. Factors preventing consistent contraceptive use may be related to HIV risk and require further study in this population.

HIV type 1 strains common in Europe, Africa, and Asia cocirculate in Yemen.

To determine the HIV-1 genetic diversity in Yemen, 19 strains collected from men and women were sequenced in pol and six of those were full genome sequenced; all were phylogenetically analyzed. Using the pol sequence data, nine (47.3%) were subtype B, six (31.6%) subtype C, two (10.5%) subtype D, one strain (5.3%) subtype A, and another (5.3%) a unique recombinant form (URF). Concordant phylogenies were also obtained for the six strains full genome sequenced. Most of the strains were from the capitol, Sana'a (n=16). Five of the C strains clustered with African Cs, and one clustered with the Indian C strains. Of the two subtype D strains, one clustered with Ugandan strains and one with Cameroon. The subtype A strain was similar to a Cameroon variant of subtype A and the URF strain was a recombinant between CRF11, CRF13, and subtype B. The HIV epidemic in Yemen is extremely complex, with strains of HIV-1 that have originated in East and West Africa, Europe, and India.

Endemic infectious diseases of Afghanistan.

The current crisis in Afghanistan has resulted in an influx of Western military personnel, peacekeepers, humanitarian workers, and journalists. At the same time, unprecedented numbers of internally displaced persons and refugees have overwhelmed much of the already fragile infrastructure, setting the stage for outbreaks of infectious diseases among both foreigners and local populations. This review surveys the literature concerning the infectious diseases of Afghanistan and south-central Asia, with particular emphasis on diseases not typically seen in the Western world.

Safety and immunogenicity of an inactivated hepatitis A vaccine among HIV-infected subjects.

BACKGROUND: Hepatitis A is a major health risk for many human immunodeficiency virus (HIV)-infected individuals. Vaccination is a potentially attractive measure to reduce the incidence of hepatitis A among this population, but data on its safety and immunogenicity are incomplete. METHODS: Ninety HIV-uninfected adults received an inactivated hepatitis A vaccine (VAQTA; Merck), and 90 HIV-infected subjects were randomized, in double-blind fashion, to receive either the vaccine or placebo. The HIV-infected subjects were stratified by CD4 cell count, with 45 subjects having CD4 cell counts of > or =300 cells/mm3 and 45 subjects having CD4 cell counts of <300 cells/mm3. Vaccine was given at weeks 0 and 24 of the study.Results. Seroconversion rates at week 28 of the study were 94% among the HIV-infected subjects and 100% among the HIV-uninfected control subjects. HIV-infected subjects with CD4 cell counts of <300 cells/mm3 had a seroconversion rate of 87%, and HIV-infected subjects with CD4 cell counts of > or =300 cells/mm3 had a seroconversion rate of 100%. The vaccine was generally well tolerated, and no adverse effect on either HIV load or CD4 cell count was found. CONCLUSION: Hepatitis A vaccine was both immunogenic and safe among HIV-infected subjects.