Seroconversion and seroprevalence of TORCH infections in a pregnant women cohort study, Mombasa, Kenya, 2017-2019.

Women infected during pregnancy with TORCH (Toxoplasmosis, Other, Rubella, Cytomegalovirus, and Herpes simplex viruses) pathogens have a higher risk of adverse birth outcomes including stillbirth / miscarriage because of mother-to-child transmission. To investigate these risks in pregnant women in Kenya, we analyzed serum specimens from a pregnancy cohort study at three healthcare facilities. A sample of 481 participants was selected for TORCH pathogen antibody testing to determine seroprevalence. A random selection of 285 from the 481 participants was selected to measure seroconversion. These sera were tested using an IgG enzyme-linked immunosorbent assay against 10 TORCH pathogens. We found that the seroprevalence of all but three of the 10 TORCH pathogens at enrollment was >30%, except for Bordetella pertussis (3.8%), Treponema pallidum (11.4%), and varicella zoster virus (0.5%). Conversely, very few participants seroconverted during their pregnancy and were herpes simplex virus type 2 (n = 24, 11.2%), parvovirus B19 (n = 14, 6.2%), and rubella (n = 12, 5.1%). For birth outcomes, 88% of the participant had live births and 12% had stillbirths or miscarriage. Cytomegalovirus positivity at enrolment had a statistically significant positive association with a live birth outcome (p = 0.0394). Of the 10 TORCH pathogens tested, none had an association with adverse pregnancy outcome.

Prevalence of microcephaly and Zika virus infection in a pregnancy cohort in Kenya, 2017-2019.

BACKGROUND: Zika virus (ZIKV), first discovered in Uganda in 1947, re-emerged globally in 2013 and was later associated with microcephaly and other birth defects. We determined the incidence of ZIKV infection and its association with adverse pregnancy and fetal outcomes in a pregnancy cohort in Kenya. METHODS: From October 2017 to July 2019, we recruited and followed up women aged ≥ 15 years and ≤ 28 weeks pregnant in three hospitals in coastal Mombasa. Monthly follow-up included risk factor questions and a blood sample collected for ZIKV serology. We collected anthropometric measures (including head circumference), cord blood, venous blood from newborns, and any evidence of birth defects. Microcephaly was defined as a head circumference (HC) < 2 standard deviations (SD) for sex and gestational age. Severe microcephaly was defined as HC < 3 SD for sex and age. We tested sera for anti-ZIKV IgM antibodies using capture enzyme-linked immunosorbent assay (ELISA) and confirmed positives using the plaque reduction neutralization test (PRNT90) for ZIKV and for dengue (DENV) on the samples that were ZIKV neutralizing antibody positive. We collected blood and urine from participants reporting fever or rash for ZIKV testing. RESULTS: Of 2889 pregnant women screened for eligibility, 2312 (80%) were enrolled. Of 1916 recorded deliveries, 1816 (94.6%) were live births and 100 (5.2%) were either stillbirths or spontaneous abortions (< 22 weeks of gestation). Among 1236 newborns with complete anthropometric measures, 11 (0.9%) had microcephaly and 3 (0.2%) had severe microcephaly. A total of 166 (7.2%) participants were positive for anti-ZIKV IgM, 136 of whom became seropositive during follow-up. Among the 166 anti-ZIKV IgM positive, 3 and 18 participants were further seropositive for ZIKV and DENV neutralizing antibodies, respectively. Of these 3 and 18 pregnant women, one and 13 (72.2%) seroconverted with antibodies to ZIKV and DENV, respectively. All 308 samples (serum and urine samples collected during sick visits and samples that were anti-ZIKV IgM positive) tested by RT-PCR were negative for ZIKV. No adverse pregnancy or neonatal outcomes were reported among the three participants with confirmed ZIKV exposure. Among newborns from pregnant women with DENV exposure, four (22.2%) were small for gestational age and one (5.6%) had microcephaly. CONCLUSIONS: The prevalence of severe microcephaly among newborns in coastal Kenya was high relative to published estimates from facility-based studies in Europe and Latin America, but little evidence of ZIKV transmission. There is a need for improved surveillance for microcephaly and other congenital malformations in Kenya.

Effect of Time Since Death on Multipathogen Molecular Test Results of Postmortem Specimens Collected Using Minimally Invasive Tissue Sampling Techniques.

BACKGROUND: We used postmortem minimally invasive tissue sampling (MITS) to assess the effect of time since death on molecular detection of pathogens among respiratory illness-associated deaths. METHODS: Samples were collected from 20 deceased children (aged 1-59 months) hospitalized with respiratory illness from May 2018 through February 2019. Serial lung and/or liver and blood samples were collected using MITS starting soon after death and every 6 hours thereafter for up to 72 hours. Bodies were stored in the mortuary refrigerator for the duration of the study. All specimens were analyzed using customized multipathogen TaqMan® array cards (TACs). RESULTS: We identified a median of 3 pathogens in each child's lung tissue (range, 1-8; n = 20), 3 pathogens in each child's liver tissue (range, 1-4; n = 5), and 2 pathogens in each child's blood specimen (range, 0-4; n = 5). Pathogens were not consistently detected across all collection time points; there was no association between postmortem interval and the number of pathogens detected (P = .43) and no change in TAC cycle threshold value over time for pathogens detected in lung tissue. Human ribonucleoprotein values indicated that specimens collected were suitable for testing throughout the study period. CONCLUSIONS: Results suggest that lung, liver, and blood specimens can be collected using MITS procedures up to 4 days after death in adequately preserved bodies. However, inconsistent pathogen detection in samples needs careful consideration before drawing definitive conclusions on the etiologic causes of death.

Zika Virus Detection with 2013 Serosurvey, Mombasa, Kenya.

Acute Zika virus (ZIKV) infection has not been confirmed in Kenya. In 2018, we used specimens collected in a 2013 dengue serosurvey study in Mombasa to test for ZIKV IgM. We confirmed specific ZIKV IgM positivity in 5 persons. These results suggest recent ZIKV transmission in the coastal region of Kenya.

Building laboratory capacity to detect and characterize pathogens of public and global health security concern in Kenya.

Since 1979, multiple CDC Kenya programs have supported the development of diagnostic expertise and laboratory capacity in Kenya. In 2004, CDC's Global Disease Detection (GDD) program within the Division of Global Health Protection in Kenya (DGHP-Kenya) initiated close collaboration with Kenya Medical Research Institute (KEMRI) and developed a laboratory partnership called the Diagnostic and Laboratory Systems Program (DLSP). DLSP built onto previous efforts by malaria, human immunodeficiency virus (HIV) and tuberculosis (TB) programs and supported the expansion of the diagnostic expertise and capacity in KEMRI and the Ministry of Health. First, DLSP developed laboratory capacity for surveillance of diarrheal, respiratory, zoonotic and febrile illnesses to understand the etiology burden of these common illnesses and support evidenced-based decisions on vaccine introductions and recommendations in Kenya. Second, we have evaluated and implemented new diagnostic technologies such as TaqMan Array Cards (TAC) to detect emerging or reemerging pathogens and have recently added a next generation sequencer (NGS). Third, DLSP provided rapid laboratory diagnostic support for outbreak investigation to Kenya and regional countries. Fourth, DLSP has been assisting the Kenya National Public Health laboratory-National Influenza Center and microbiology reference laboratory to obtain World Health Organization (WHO) certification and ISO15189 accreditation respectively. Fifth, we have supported biosafety and biosecurity curriculum development to help Kenyan laboratories safely and appropriately manage infectious pathogens. These achievements, highlight how in collaboration with existing CDC programs working on HIV, tuberculosis and malaria, the Global Health Security Agenda can have significantly improve public health in Kenya and the region. Moreover, Kenya provides an example as to how laboratory science can help countries detect and control of infectious disease outbreaks and other public health threats more rapidly, thus enhancing global health security.

The contribution of respiratory pathogens to fatal and non-fatal respiratory hospitalizations: a pilot study of Taqman Array Cards (TAC) in Kenya.

BACKGROUND: Respiratory diseases cause substantial morbidity and mortality worldwide, with sub-Saharan Africa bearing the greatest burden. Identifying etiologies of respiratory disease is important to inform cost effective treatment, prevention and control strategies. Testing for all of the different pathogens that are potentially associated with respiratory illnesses is challenging. We piloted the use of a multi-pathogen respiratory Taqman Array Cards (TAC) to identify pathogens in respiratory samples collected from non-fatal and fatal cases and their matched asymptomatic controls. METHODS: This is a case control study comparing viral and bacterial pathogens detected among non-fatal and fatal cases to those detected among age and time matched asymptomatic controls. We used McNemar's test to compare proportions of pathogens detected among cases (non-fatal and fatal) to their matched asymptomatic controls. We used Mann-Whitney test to compare the distribution of median Cycle threshold (Ct) values among non-fatal and fatal cases to their corresponding asymptomatic controls. RESULTS: There were 72 fatal and 72 non-fatal cases matched to 72 controls. We identified at least one pathogen in 109/144 (76%) cases and 59/72 (82%) controls. For most pathogens, the median Ct values were lower among cases (fatal and non-fatal) compared to asymptomatic controls. CONCLUSIONS: Similar rates of pathogen detection among cases and controls make interpretation of results challenging. Ct-values might be helpful in interpreting clinical relevance of detected pathogens using multi-pathogen diagnostic tools.

Ebola Laboratory Response at the Eternal Love Winning Africa Campus, Monrovia, Liberia, 2014-2015.

West Africa experienced the first epidemic of Ebola virus infection, with by far the greatest number of cases in Guinea, Sierra Leone, and Liberia. The unprecedented epidemic triggered an unparalleled response, including the deployment of multiple Ebola treatment units and mobile/field diagnostic laboratories. The National Institute of Allergy and Infectious Diseases and the Centers for Disease Control and Prevention deployed a joint laboratory to Monrovia, Liberia, in August 2014 to support the newly founded Ebola treatment unit at the Eternal Love Winning Africa (ELWA) campus. The laboratory operated initially out of a tent structure but quickly moved into a fixed-wall building owing to severe weather conditions, the need for increased security, and the high sample volume. Until May 2015, when the laboratory closed, the site handled close to 6000 clinical specimens for Ebola virus diagnosis and supported the medical staff in case patient management. Laboratory operation and safety, as well as Ebola virus diagnostic assays, are described and discussed; in addition, lessons learned for future deployments are reviewed.

Plasmodium Parasitemia Associated With Increased Survival in Ebola Virus-Infected Patients.

BACKGROUND: The ongoing Ebola outbreak in West Africa has resulted in 28 646 suspected, probable, and confirmed Ebola virus infections. Nevertheless, malaria remains a large public health burden in the region affected by the outbreak. A joint Centers for Disease Control and Prevention/National Institutes of Health diagnostic laboratory was established in Monrovia, Liberia, in August 2014, to provide laboratory diagnostics for Ebola virus. METHODS: All blood samples from suspected Ebola virus-infected patients admitted to the Médecins Sans Frontières ELWA3 Ebola treatment unit in Monrovia were tested by quantitative real-time polymerase chain reaction for the presence of Ebola virus and Plasmodium species RNA. Clinical outcome in laboratory-confirmed Ebola virus-infected patients was analyzed as a function of age, sex, Ebola viremia, and Plasmodium species parasitemia. RESULTS: The case fatality rate of 1182 patients with laboratory-confirmed Ebola virus infections was 52%. The probability of surviving decreased with increasing age and decreased with increasing Ebola viral load. Ebola virus-infected patients were 20% more likely to survive when Plasmodium species parasitemia was detected, even after controlling for Ebola viral load and age; those with the highest levels of parasitemia had a survival rate of 83%. This effect was independent of treatment with antimalarials, as this was provided to all patients. Moreover, treatment with antimalarials did not affect survival in the Ebola virus mouse model. CONCLUSIONS: Plasmodium species parasitemia is associated with an increase in the probability of surviving Ebola virus infection. More research is needed to understand the molecular mechanism underlying this remarkable phenomenon and translate it into treatment options for Ebola virus infection.

The Merits of Malaria Diagnostics during an Ebola Virus Disease Outbreak.

Malaria is a major public health concern in the countries affected by the Ebola virus disease epidemic in West Africa. We determined the feasibility of using molecular malaria diagnostics during an Ebola virus disease outbreak and report the incidence of Plasmodium spp. parasitemia in persons with suspected Ebola virus infection.

Epidemiology of respiratory syncytial virus infection in rural and urban Kenya.

BACKGROUND: Information on the epidemiology of respiratory syncytial virus (RSV) infection in Africa is limited for crowded urban areas and for rural areas where the prevalence of malaria is high. METHODS: At referral facilities in rural western Kenya and a Nairobi slum, we collected nasopharyngeal/oropharyngeal (NP/OP) swab specimens from patients with influenza-like illness (ILI) or severe acute respiratory illness (SARI) and from asymptomatic controls. Polymerase chain reaction assays were used for detection of viral pathogens. We calculated age-specific ratios of the odds of RSV detection among patients versus the odds among controls. Incidence was expressed as the number of episodes per 1000 person-years of observation. RESULTS: Between March 2007 and February 2011, RSV was detected in 501 of 4012 NP/OP swab specimens (12.5%) from children and adults in the rural site and in 321 of 2744 NP/OP swab specimens (11.7%) from those in the urban site. Among children aged <5 years, RSV was detected more commonly among rural children with SARI (odds ratio [OR], 2.0; 95% confidence interval [CI], 1.2-3.3), urban children with SARI (OR, 8.5; 95% CI, 3.1-23.6), and urban children with ILI (OR, 3.4; 95% CI, 1.2-9.6), compared with controls. The incidence of RSV disease was highest among infants with SARI aged <1 year (86.9 and 62.8 episodes per 1000 person-years of observation in rural and urban sites, respectively). CONCLUSIONS: An effective RSV vaccine would likely substantially reduce the burden of respiratory illness among children in rural and urban areas in Africa.

Dynamic Incidence of Typhoid Fever over a 10-Year Period (2010-2019) in Kibera, an Urban Informal Settlement in Nairobi, Kenya.

Typhoid fever burden can vary over time. Long-term data can inform prevention strategies; however, such data are lacking in many African settings. We reexamined typhoid fever incidence and antimicrobial resistance (AMR) over a 10-year period in Kibera, a densely populated urban informal settlement where a high burden has been previously described. We used data from the Population Based Infectious Diseases Surveillance platform to estimate crude and adjusted incidence rates and prevalence of AMR in nearly 26,000 individuals of all ages. Demographic and healthcare-seeking information was collected through household visits. Blood cultures were processed for patients with acute fever or lower respiratory infection. Between 2010 and 2019, 16,437 participants were eligible for blood culture and 11,848 (72.1%) had a culture performed. Among 11,417 noncontaminated cultures (96.4%), 237 grew Salmonella enterica serovar Typhi (2.1%). Overall crude and adjusted incidences were 95 and 188 cases per 100,000 person-years of observation (pyo), respectively. Annual crude incidence varied from 144 to 233 between 2010 and 2012 and from 9 to 55 between 2013 and 2018 and reached 130 per 100,000 pyo in 2019. Children 5-9 years old had the highest overall incidence (crude, 208; adjusted, 359 per 100,000 pyo). Among isolates tested, 156 of 217 were multidrug resistant (resistant to chloramphenicol, ampicillin, and trimethoprim/sulfamethoxazole [71.9%]) and 6 of 223 were resistant to ciprofloxacin (2.7%). Typhoid fever incidence resurged in 2019 after a prolonged period of low rates, with the highest incidence among children. Typhoid fever control measures, including vaccines, could reduce morbidity in this setting.

Molecular characterization of circulating Salmonella Typhi strains in an urban informal settlement in Kenya.

A high burden of Salmonella enterica subspecies enterica serovar Typhi (S. Typhi) bacteremia has been reported from urban informal settlements in sub-Saharan Africa, yet little is known about the introduction of these strains to the region. Understanding regional differences in the predominant strains of S. Typhi can provide insight into the genomic epidemiology. We genetically characterized 310 S. Typhi isolates from typhoid fever surveillance conducted over a 12-year period (2007-2019) in Kibera, an urban informal settlement in Nairobi, Kenya, to assess the circulating strains, their antimicrobial resistance attributes, and how they relate to global S. Typhi isolates. Whole genome multi-locus sequence typing (wgMLST) identified 4 clades, with up to 303 pairwise allelic differences. The identified genotypes correlated with wgMLST clades. The predominant clade contained 290 (93.5%) isolates with a median of 14 allele differences (range 0-52) and consisted entirely of genotypes 4.3.1.1 and 4.3.1.2. Resistance determinants were identified exclusively in the predominant clade. Determinants associated with resistance to aminoglycosides were observed in 245 isolates (79.0%), sulphonamide in 243 isolates (78.4%), trimethoprim in 247 isolates (79.7%), tetracycline in 224 isolates (72.3%), chloramphenicol in 247 isolates (79.6%), ß-lactams in 239 isolates (77.1%) and quinolones in 62 isolates (20.0%). Multidrug resistance (MDR) determinants (defined as determinants conferring resistance to ampicillin, chloramphenicol and cotrimoxazole) were found in 235 (75.8%) isolates. The prevalence of MDR associated genes was similar throughout the study period (2007-2012: 203, 76.3% vs 2013-2019: 32, 72.7%; Fisher's Exact Test: P = 0.5478, while the proportion of isolates harboring quinolone resistance determinants increased (2007-2012: 42, 15.8% and 2013-2019: 20, 45.5%; Fisher's Exact Test: P<0.0001) following a decline in S. Typhi in Kibera. Some isolates (49, 15.8%) harbored both MDR and quinolone resistance determinants. There were no determinants associated with resistance to cephalosporins or azithromycin detected among the isolates sequenced in this study. Plasmid markers were only identified in the main clade including IncHI1A and IncHI1B(R27) in 226 (72.9%) isolates, and IncQ1 in 238 (76.8%) isolates. Molecular clock analysis of global typhoid isolates and isolates from Kibera suggests that genotype 4.3.1 has been introduced multiple times in Kibera. Several genomes from Kibera formed a clade with genomes from Kenya, Malawi, South Africa, and Tanzania. The most recent common ancestor (MRCA) for these isolates was from around 1997. Another isolate from Kibera grouped with several isolates from Uganda, sharing a common ancestor from around 2009. In summary, S. Typhi in Kibera belong to four wgMLST clades one of which is frequently associated with MDR genes and this poses a challenge in treatment and control.

Impact Evaluation of the Kenya Frontline Field Epidemiology Training Program: Repeated-Measures Study.

BACKGROUND: In 2014, Kenya's Field Epidemiology and Laboratory Training Program (FELTP) initiated a 3-month field-based frontline training, Field Epidemiology Training Program (FETP-F), for local public health workers. OBJECTIVE: This study aimed to measure the effect of FETP-F on participant workplace practices regarding quality and consistency of public health data, critical interaction with public health data, and improvements in on-time reporting (OTR). METHODS: Between February and April 2017, FELTP conducted a mixed methods evaluation via online survey to examine outcomes achieved among all 215 graduates from 2014 and 2015. Data quality assessment (DQA) and data consistency assessment (DCA) scores, OTR percentages, and ratings of the training experience were the quantitative measures tracked from baseline and then at 6-month intervals up to 18 months postcompletion of the training. The qualitative component consisted of semistructured face-to-face interviews and observations. Quantitative data were analyzed using descriptive statistics and one-way analysis of variance (ANOVA). Qualitative data were transcribed and analyzed to identify key themes and dimensions. RESULTS: In total, 103 (47%) graduates responded to the survey. Quantitative analyses showed that the training significantly increased the mean DQA and OTR scores but there was a nonsignificant increase in mean DCA scores. Qualitative analyses found that 68% of respondents acquired new skills, 83% applied those skills to their day-to-day work, and 91% improved work methods. CONCLUSIONS: FETP-F improved overall data quality and OTR at the agency level but had minimal impact on data consistency between local, county, and national public health agencies. Participants reported that they acquired practical skills that improved data collation and analysis and OTR.

Factors associated with malnutrition in children < 5 years in western Kenya: a hospital-based unmatched case control study.

BACKGROUND: Globally, under-nutrition accounts for > 3 million deaths annually among children < 5 years, with Kenya having ~ 35,000 deaths. This study aimed to identify factors associated with malnutrition in children aged < 5 years in western Kenya. METHODS: We conducted a hospital-based unmatched case-control study between May and June 2017. Cases were defined as children aged 6-59 months with either z-score for weight-for-height ≤ -2SD or ≥ +2SD; weight-for-age ≤ -2SD or ≥ +2SD; or height-for-age ≤ -2SD. Controls were children aged 6-59 months with age-appropriate anthropometric measurements. Cases were consecutively recruited while systematic random sampling was used to select controls. Data from interviews and clinical records were collected and entered into Epi-Info, which was used to run unconditional logistic regression analyses. RESULTS: A total of 94 cases and 281 controls were recruited. Of the cases, 84% (79/94) were under-nourished. Mother not having attended ante-natal clinic (OR = 7.9; 95% CI: 1.5-41.2), deworming (OR = 0.8; 95% CI: 0.4-1.2), and pre-lacteal feeding (OR = 1.8; 95% CI: 1.1-3.0) were associated with under-nutrition. Delayed developmental milestones (AOR = 13.9; 95% CI: 2.8-68.6); low birth weight (AOR = 3.3; 95% CI: 1.4-7.6), and paternal lack of formal education (AOR = 4.9; 95% CI: 1.3-18.9) were independently associated with under-nutrition. CONCLUSION: Proper pre-natal care, child feeding practices and deworming programs should be enhanced to reduce pediatric malnutrition.

Prevalence and risk factors associated with asymptomatic Plasmodium falciparum infection and anemia among pregnant women at the first antenatal care visit: A hospital based cross-sectional study in Kwale County, Kenya.

BACKGROUND: Prevalence of Prevalence of malaria in pregnancy (MiP) in Kenya ranges from 9% to 18%. We estimated the prevalence and factors associated with MiP and anemia in pregnancy (AiP) among asymptomatic women attending antenatal care (ANC) visits. METHODS: We performed a cross-sectional study among pregnant women attending ANC at Msambweni Hospital, between September 2018 and February 2019. Data was collected and analyzed in Epi Info 7. Descriptive statistics were calculated and we compared MiP and AiP in asymptomatic cases to those without either condition. Adjusted prevalence Odds odds ratios (aPOR) and 95% confidence intervals (CI) were calculated to identify factors associated with asymptomatic MiP and AiP. RESULTS: We interviewed 308 study participants; their mean age was 26.6 years (± 5.8 years), mean gestational age was 21.8 weeks (± 6.0 weeks), 173 (56.2%) were in the second trimester of pregnancy, 12.9% (40/308) had MiP and 62.7% had AiP. Women who were aged ≤ 20 years had three times likelihood of developing MiP (aPOR = 3.1 Cl: 1.3-7.35) compared to those aged >20 years old. The likelihood of AiP was higher among women with gestational age ≥ 16 weeks (aPOR = 3.9, CI: 1.96-7.75), those with parasitemia (aPOR = 3.3, 95% CI: 1.31-8.18), those in third trimester of pregnancy (aPOR = 2.6, 95% CI:1.40-4.96) and those who reported eating soil as a craving during pregnancy (aPOR = 1.9, 95%CI:1.15-3.29). CONCLUSIONS: Majority of the women had asymptomatic MiP and AiP. MiP was observed in one tenth of all study participants. Asymptomatic MiP was associated with younger age while AiP was associated with gestational age parasitemia, and soil consumption as a craving during pregnancy.

Using a field quantitative real-time PCR test to rapidly identify highly viremic rift valley fever cases.

Approximately 8% of Rift Valley fever (RVF) cases develop severe disease, leading to hemorrhage, hepatitis, and/or encephalitis and resulting in up to 50% of deaths. A major obstacle in the management of RVF and other viral hemorrhagic fever cases in outbreaks that occur in rural settings is the inability to rapidly identify such cases, with poor prognosis early enough to allow for more-aggressive therapies. During an RVF outbreak in Kenya in 2006 to 2007, we evaluated whether quantitative real-time reverse transcription-PCR (qRT-PCR) could be used in the field to rapidly identify viremic RVF cases with risk of death. In 52 of 430 RVF cases analyzed by qRT-PCR and virus culture, 18 died (case fatality rate [CFR] = 34.6%). Levels of viremia in fatal cases were significantly higher than those in nonfatal cases (mean of 10(5.2) versus 10(2.9) per ml; P < 0.005). A negative correlation between the levels of infectious virus particles and the qRT-PCR crossover threshold (C(T)) values allowed the use of qRT-PCR to assess prognosis. The CFR was 50.0% among cases with C(T) values of <27.0 (corresponding to 2.1 x 10(4) viral RNA particles/ml of serum) and 4.5% among cases with C(T) values of >or=27.0. This cutoff yielded 93.8% sensitivity and a 95.5% negative predictive value; the specificity and positive predictive value were 58% and 50%, respectively. This study shows a correlation between high viremia and fatality and indicates that qRT-PCR testing can identify nearly all fatal RVF cases.

A diagnostic and epidemiologic investigation of acute febrile illness (AFI) in Kilombero, Tanzania.

INTRODUCTION: In low-resource settings, empiric case management of febrile illness is routine as a result of limited access to laboratory diagnostics. The use of comprehensive fever syndromic surveillance, with enhanced clinical microbiology, advanced diagnostics and more robust epidemiologic investigation, could enable healthcare providers to offer a differential diagnosis of fever syndrome and more appropriate care and treatment. METHODS: We conducted a year-long exploratory study of fever syndrome among patients ≥ 1 year if age, presenting to clinical settings with an axillary temperature of ≥37.5°C and symptomatic onset of ≤5 days. Blood and naso-pharyngeal/oral-pharyngeal (NP/OP) specimens were collected and analyzed, respectively, using AFI and respiratory TaqMan Array Cards (TAC) for multi-pathogen detection of 57 potential causative agents. Furthermore, we examined numerous epidemiologic correlates of febrile illness, and conducted demographic, clinical, and behavioral domain-specific multivariate regression to statistically establish associations with agent detection. RESULTS: From 15 September 2014-13 September 2015, 1007 febrile patients were enrolled, and 997 contributed an epidemiologic survey, including: 14% (n = 139) 1<5yrs, 19% (n = 186) 5-14yrs, and 67% (n = 672) ≥15yrs. AFI TAC and respiratory TAC were performed on 842 whole blood specimens and 385 NP/OP specimens, respectively. Of the 57 agents surveyed, Plasmodium was the most common agent detected. AFI TAC detected nucleic acid for one or more of seven microbial agents in 49% of AFI blood samples, including: Plasmodium (47%), Leptospira (3%), Bartonella (1%), Salmonella enterica (1%), Coxiella burnetii (1%), Rickettsia (1%), and West Nile virus (1%). Respiratory TAC detected nucleic acid for 24 different microbial agents, including 12 viruses and 12 bacteria. The most common agents detected among our surveyed population were: Haemophilus influenzae (67%), Streptococcus pneumoniae (55%), Moraxella catarrhalis (39%), Staphylococcus aureus (37%), Pseudomonas aeruginosa (36%), Human Rhinovirus (25%), influenza A (24%), Klebsiella pneumoniae (14%), Enterovirus (15%) and group A Streptococcus (12%). Our epidemiologic investigation demonstrated both age and symptomatic presentation to be associated with a number of detected agents, including, but not limited to, influenza A and Plasmodium. Linear regression of fully-adjusted mean cycle threshold (Ct) values for Plasmodium also identified statistically significant lower mean Ct values for older children (20.8), patients presenting with severe fever (21.1) and headache (21.5), as well as patients admitted for in-patient care and treatment (22.4). CONCLUSIONS: This study is the first to employ two syndromic TaqMan Array Cards for the simultaneous survey of 57 different organisms to better characterize the type and prevalence of detected agents among febrile patients. Additionally, we provide an analysis of the association between adjusted mean Ct values for Plasmodium and key clinical and demographic variables, which may further inform clinical decision-making based upon intensity of infection, as observed across endemic settings of sub-Saharan Africa.

Serologic Evidence of the Geographic Distribution of Bacterial Zoonotic Agents in Kenya, 2007.

Diseases of zoonotic origin contribute to the burden of febrile illnesses in developing countries. We evaluated serologic evidence of exposure to Bacillus anthracis, Brucella spp., spotted fever group rickettsioses (SFGR), and typhus group rickettsioses (TGR) from samples of persons aged 15-64 years collected during a nationwide human immunodeficiency virus (HIV) serosurvey conducted in 2007 in Kenya. The seropositivity observed for pathogens was B. anthracis 11.3%, Brucella spp. 3.0%, SFGR 23.3%, and TGR 0.6%. On univariate analysis, seropositivity for each pathogen was significantly associated with the following risk factors: B. anthracis with province of residence; Brucella spp. with sex, education level, and wealth; SFGR with age, education level, wealth, and province of residence; and TGR with province of residence. On multivariate analysis, seropositivity remained significantly associated with wealth and province for B. anthracis; with sex and age for Brucella spp; and with sex, education level, and province of residence for SFGR whereas TGR had no significance. High IgG seropositivity to these zoonotic pathogens (especially, B. anthracis and SFGR) suggests substantial exposure. These pathogens should be considered in the differential diagnosis of febrile illness in Kenya.

An outbreak of acute febrile illness caused by Sandfly Fever Sicilian Virus in the Afar region of Ethiopia, 2011.

In malaria-endemic regions, many medical facilities have limited capacity to diagnose non-malarial etiologies of acute febrile illness (AFI). As a result, the etiology of AFI is seldom determined, although AFI remains a major cause of morbidity in developing countries. An outbreak of AFI was reported in the Afar region of Ethiopia in August of 2011. Retrospectively, 12,816 suspected AFI cases were identified by review of medical records. Symptoms were mild and self-limiting within 3 days after the date of onset; no fatalities were identified. All initial test results of AFI patient specimens were negative for selected pathogens using standard microbiological and molecular techniques. High-throughput sequencing of nucleic acid extracts of serum specimens from 29 AFI cases identified 17 (59%) of 29 samples as positive for Sandfly Fever Sicilian Virus (SFSV). These results were further confirmed by specific reverse transcription polymerase chain reaction. This is the first study implicating SFSV as an etiological agent for AFI in Ethiopia.

Outbreak of beriberi among African Union troops in Mogadishu, Somalia.

CONTEXT AND OBJECTIVES: In July 2009, WHO and partners were notified of a large outbreak of unknown illness, including deaths, among African Union (AU) soldiers in Mogadishu. Illnesses were characterized by peripheral edema, dyspnea, palpitations, and fever. Our objectives were to determine the cause of the outbreak, and to design and recommend control strategies. DESIGN, SETTING, AND PARTICIPANTS: The illness was defined as acute onset of lower limb edema, with dyspnea, chest pain, palpitations, nausea, vomiting, abdominal pain, or headache. Investigations in Nairobi and Mogadishu included clinical, epidemiologic, environmental, and laboratory studies. A case-control study was performed to identify risk factors for illness. RESULTS: From April 26, 2009 to May 1, 2010, 241 AU soldiers had lower limb edema and at least one additional symptom; four patients died. At least 52 soldiers were airlifted to hospitals in Kenya and Uganda. Four of 31 hospitalized patients in Kenya had right-sided heart failure with pulmonary hypertension. Initial laboratory investigations did not reveal hematologic, metabolic, infectious or toxicological abnormalities. Illness was associated with exclusive consumption of food provided to troops (not eating locally acquired foods) and a high level of insecurity (e.g., being exposed to enemy fire on a daily basis). Because the syndrome was clinically compatible with wet beriberi, thiamine was administered to ill soldiers, resulting in rapid and dramatic resolution. Blood samples taken from 16 cases prior to treatment showed increased levels of erythrocyte transketolase activation coefficient, consistent with thiamine deficiency. With mass thiamine supplementation for healthy troops, the number of subsequent beriberi cases decreased with no further deaths reported. CONCLUSIONS: An outbreak of wet beriberi caused by thiamine deficiency due to restricted diet occurred among soldiers in a modern, well-equipped army. Vigilance to ensure adequate micronutrient intake must be a priority in populations completely dependent upon nutritional support from external sources.