Heterogenous transmission and seroprevalence of SARS-CoV-2 in two demographically diverse populations with low vaccination uptake in Kenya, March and June 2021.

Background: SARS-CoV-2 has extensively spread in cities and rural communities, and studies are needed to quantify exposure in the population. We report seroprevalence of SARS-CoV-2 in two well-characterized populations in Kenya at two time points. These data inform the design and delivery of public health mitigation measures. Methods: Leveraging on existing population based infectious disease surveillance (PBIDS) in two demographically diverse settings, a rural site in western Kenya in Asembo, Siaya County, and an urban informal settlement in Kibera, Nairobi County, we set up a longitudinal cohort of randomly selected households with serial sampling of all consenting household members in March and June/July 2021. Both sites included 1,794 and 1,638 participants in the March and June/July 2021, respectively. Individual seroprevalence of SARS-CoV-2 antibodies was expressed as a percentage of the seropositive among the individuals tested, accounting for household clustering and weighted by the PBIDS age and sex distribution. Results: Overall weighted individual seroprevalence increased from 56.2% (95%CI: 52.1, 60.2%) in March 2021 to 63.9% (95%CI: 59.5, 68.0%) in June 2021 in Kibera. For Asembo, the seroprevalence almost doubled from 26.0% (95%CI: 22.4, 30.0%) in March 2021 to 48.7% (95%CI: 44.3, 53.2%) in July 2021. Seroprevalence was highly heterogeneous by age and geography in these populations-higher seroprevalence was observed in the urban informal settlement (compared to the rural setting), and children aged <10 years had the lowest seroprevalence in both sites. Only 1.2% and 1.6% of the study participants reported receipt of at least one dose of the COVID-19 vaccine by the second round of serosurvey-none by the first round. Conclusions: In these two populations, SARS-CoV-2 seroprevalence increased in the first 16 months of the COVID-19 pandemic in Kenya. It is important to prioritize additional mitigation measures, such as vaccine distribution, in crowded and low socioeconomic settings.

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.

Diagnostic accuracy of the Panbio COVID-19 antigen rapid test device for SARS-CoV-2 detection in Kenya, 2021: A field evaluation.

BACKGROUND: Accurate and timely diagnosis is essential in limiting the spread of SARS-CoV-2 infection. The reference standard, rRT-PCR, requires specialized laboratories, costly reagents, and a long turnaround time. Antigen RDTs provide a feasible alternative to rRT-PCR since they are quick, relatively inexpensive, and do not require a laboratory. The WHO requires that Ag RDTs have a sensitivity ≥80% and specificity ≥97%. METHODS: This evaluation was conducted at 11 health facilities in Kenya between March and July 2021. We enrolled persons of any age with respiratory symptoms and asymptomatic contacts of confirmed COVID-19 cases. We collected demographic and clinical information and two nasopharyngeal specimens from each participant for Ag RDT testing and rRT-PCR. We calculated the diagnostic performance of the Panbio™ Ag RDT against the US Centers for Disease Control and Prevention's (CDC) rRT-PCR test. RESULTS: We evaluated the Ag RDT in 2,245 individuals where 551 (24.5%, 95% CI: 22.8-26.3%) tested positive by rRT-PCR. Overall sensitivity of the Ag RDT was 46.6% (95% CI: 42.4-50.9%), specificity 98.5% (95% CI: 97.8-99.0%), PPV 90.8% (95% CI: 86.8-93.9%) and NPV 85.0% (95% CI: 83.4-86.6%). Among symptomatic individuals, sensitivity was 60.6% (95% CI: 54.3-66.7%) and specificity was 98.1% (95% CI: 96.7-99.0%). Among asymptomatic individuals, sensitivity was 34.7% (95% CI 29.3-40.4%) and specificity was 98.7% (95% CI: 97.8-99.3%). In persons with onset of symptoms <5 days (594/876, 67.8%), sensitivity was 67.1% (95% CI: 59.2-74.3%), and 53.3% (95% CI: 40.0-66.3%) among those with onset of symptoms >7 days (157/876, 17.9%). The highest sensitivity was 87.0% (95% CI: 80.9-91.8%) in symptomatic individuals with cycle threshold (Ct) values ≤30. CONCLUSION: The overall sensitivity and NPV of the Panbio™ Ag RDT were much lower than expected. The specificity of the Ag RDT was high and satisfactory; therefore, a positive result may not require confirmation by rRT-PCR. The kit may be useful as a rapid screening tool only for symptomatic patients in high-risk settings with limited access to rRT-PCR. A negative result should be interpreted based on clinical and epidemiological information and may require retesting by rRT-PCR.

Outbreak of Middle East Respiratory Syndrome Coronavirus in Camels and Probable Spillover Infection to Humans in Kenya.

The majority of Kenya's > 3 million camels have antibodies against Middle East respiratory syndrome coronavirus (MERS-CoV), although human infection in Africa is rare. We enrolled 243 camels aged 0−24 months from 33 homesteads in Northern Kenya and followed them between April 2018 to March 2020. We collected and tested camel nasal swabs for MERS-CoV RNA by RT-PCR followed by virus isolation and whole genome sequencing of positive samples. We also documented illnesses (respiratory or other) among the camels. Human camel handlers were also swabbed, screened for respiratory signs, and samples were tested for MERS-CoV by RT-PCR. We recorded 68 illnesses among 58 camels, of which 76.5% (52/68) were respiratory signs and the majority of illnesses (73.5% or 50/68) were recorded in 2019. Overall, 124/4692 (2.6%) camel swabs collected from 83 (34.2%) calves in 15 (45.5%) homesteads between April−September 2019 screened positive, while 22 calves (26.5%) recorded reinfections (second positive swab following ≥ 2 consecutive negative tests). Sequencing revealed a distinct Clade C2 virus that lacked the signature ORF4b deletions of other Clade C viruses. Three previously reported human PCR positive cases clustered with the camel infections in time and place, strongly suggesting sporadic transmission to humans during intense camel outbreaks in Northern Kenya.

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.

Genome Sequence of Escherichia coli Isolated from an Adult in Kibera, an Urban Informal Settlement in Nairobi, Kenya.

An Escherichia coli strain (sequence type 636) was isolated from an adult residing in an urban informal settlement in Nairobi, Kenya, and was sequenced using the Illumina MiSeq platform. The draft genome was 5,075,726 bp, with a Col(BS512) plasmid plus aph(6)-Id, blaTEM-1B, and dfrA7 genes, which encode kanamycin, ampicillin, and trimethoprim resistance proteins, respectively.

Seroprevalence and risk factors of SARS-CoV-2 infection in an urban informal settlement in Nairobi, Kenya, December 2020.

Introduction: Urban informal settlements may be disproportionately affected by the COVID-19 pandemic due to overcrowding and other socioeconomic challenges that make adoption and implementation of public health mitigation measures difficult. We conducted a seroprevalence survey in the Kibera informal settlement, Nairobi, Kenya, to determine the extent of SARS-CoV-2 infection. Methods: Members of randomly selected households from an existing population-based infectious disease surveillance (PBIDS) provided blood specimens between 27 th November and 5 th December 2020. The specimens were tested for antibodies to the SARS-CoV-2 spike protein. Seroprevalence estimates were weighted by age and sex distribution of the PBIDS population and accounted for household clustering. Multivariable logistic regression was used to identify risk factors for individual seropositivity.   Results: Consent was obtained from 523 individuals in 175 households, yielding 511 serum specimens that were tested. The overall weighted seroprevalence was 43.3% (95% CI, 37.4 - 49.5%) and did not vary by sex. Of the sampled households, 122(69.7%) had at least one seropositive individual. The individual seroprevalence increased by age from 7.6% (95% CI, 2.4 - 21.3%) among children (<5 years), 32.7% (95% CI, 22.9 - 44.4%) among children 5 - 9 years, 41.8% (95% CI, 33.0 - 51.1%) for those 10-19 years, and 54.9%(46.2 - 63.3%) for adults (≥20 years). Relative to those from medium-sized households (3 and 4 individuals), participants from large (≥5 persons) households had significantly increased odds of being seropositive, aOR, 1.98(95% CI, 1.17 - 1.58), while those from small-sized households (≤2 individuals) had increased odds but not statistically significant, aOR, 2.31 (95% CI, 0.93 - 5.74).  Conclusion: In densely populated urban settings, close to half of the individuals had an infection to SARS-CoV-2 after eight months of the COVID-19 pandemic in Kenya. This highlights the importance to prioritize mitigation measures, including COVID-19 vaccine distribution, in the crowded, low socioeconomic settings.

The Clinical Presentation of Culture-positive and Culture-negative, Quantitative Polymerase Chain Reaction (qPCR)-Attributable Shigellosis in the Global Enteric Multicenter Study and Derivation of a Shigella Severity Score: Implications for Pediatric Shigella Vaccine Trials.

BACKGROUND: Shigella is a leading cause of childhood diarrhea and target for vaccine development. Microbiologic and clinical case definitions are needed for pediatric field vaccine efficacy trials. METHODS: We compared characteristics of moderate to severe diarrhea (MSD) cases in the Global Enteric Multicenter Study (GEMS) between children with culture positive Shigella to those with culture-negative, quantitative polymerase chain reaction (qPCR)-attributable Shigella (defined by an ipaH gene cycle threshold <27.9). Among Shigella MSD cases, we determined risk factors for death and derived a clinical severity score. RESULTS: Compared to culture-positive Shigella MSD cases (n = 745), culture-negative/qPCR-attributable Shigella cases (n = 852) were more likely to be under 12 months, stunted, have a longer duration of diarrhea, and less likely to have high stool frequency or a fever. There was no difference in dehydration, hospitalization, or severe classification from a modified Vesikari score. Twenty-two (1.8%) Shigella MSD cases died within the 14-days after presentation to health facilities, and 59.1% of these deaths were in culture-negative cases. Age <12 months, diarrhea duration prior to presentation, vomiting, stunting, wasting, and hospitalization were associated with mortality. A model-derived score assigned points for dehydration, hospital admission, and longer diarrhea duration but was not significantly better at predicting 14-day mortality than a modified Vesikari score. CONCLUSIONS: A composite severity score consistent with severe disease or dysentery may be a pragmatic clinical endpoint for severe shigellosis in vaccine trials. Reliance on culture for microbiologic confirmation may miss a substantial number of Shigella cases but is currently required to measure serotype specific immunity.

Disease burden and risk factors of diarrhoea in children under five years: Evidence from Kenya's demographic health survey 2014.

OBJECTIVE: This study aimed at examining the socio-demographic, environmental and behavioural determinants of diarrhoea in children under five years in Kenya. METHODS: The study entailed an analysis of secondary data from the Kenya Demographic Health Survey (DHS) 2014 using STATA Corp 2010. A total of 19,889 children <5 years were in the study, out of whom 2,906 had diarrhoea in the last two weeks prior to the survey. Descriptive analysis of independent variables and logistic regression model was used to analyse risk factors associated with diarrhoea in children <5 years. RESULTS: The most significant risk factors (p < 0.05) associated with diarrhoea morbidity in children <5 years were child age (AOR 2.26 95% CI 1.64, 3.11), low level of caregiver's education (AOR 1.45 95% CI 1.11, 1.90) and unsafe disposal of children's faeces (AOR 1.29 95% CI 1.03, 1.61). Wealthier households (AOR 0.83 95% CI 0.68, 1) were protective for diarrhoea in children <5 years. CONCLUSION: Increasing caregiver education, wealthier households and promoting hygienic behaviours in poor households were associated with reducing diarrhoea. Programmes aimed at reducing diarrhoea may achieve better results in targeting caregivers with children in high risk age cohorts of 6-23 months.

Cost-effectiveness of conditional cash transfers to retain women in the continuum of care during pregnancy, birth and the postnatal period: protocol for an economic evaluation of the Afya trial in Kenya.

INTRODUCTION: A wealth of evidence from a range of country settings indicates that antenatal care, facility delivery and postnatal care can reduce maternal and child mortality and morbidity in high-burden settings. However, the utilisation of these services by pregnant women, particularly in low/middle-income country settings, is well below that recommended by the WHO. The Afya trial aims to assess the impact, cost-effectiveness and scalability of conditional cash transfers to promote increased utilisation of these services in rural Kenya and thus retain women in the continuum of care during pregnancy, birth and the postnatal period. This protocol describes the planned economic evaluation of the Afya trial. METHODS AND ANALYSIS: The economic evaluation will be conducted from the provider perspective as a within-trial analysis to evaluate the incremental costs and health outcomes of the cash transfer programme compared with the status quo. Incremental cost-effectiveness ratios will be presented along with a cost-consequence analysis where the incremental costs and all statistically significant outcomes will be listed separately. Sensitivity analyses will be undertaken to explore uncertainty and to ensure that results are robust. A fiscal space assessment will explore the affordability of the intervention. In addition, an analysis of equity impact of the intervention will be conducted. ETHICS AND DISSEMINATION: The study has received ethics approval from the Maseno University Ethics Review Committee, REF MSU/DRPI/MUERC/00294/16. The results of the economic evaluation will be disseminated in a peer-reviewed journal and presented at a relevant international conference. TRIAL REGISTRATION NUMBER: NCT03021070.

The Epidemiology and Burden of Influenza B/Victoria and B/Yamagata Lineages in Kenya, 2012-2016.

BACKGROUND: The impact of influenza B virus circulation in Sub-Saharan Africa is not well described. METHODS: We analyzed data from acute respiratory illness (ARI) in Kenya. We assessed clinical features and age-specific hospitalization and outpatient visit rates by person-years for influenza B/Victoria and B/Yamagata and the extent to which circulating influenza B lineages in Kenya matched the vaccine strain component of the corresponding season (based on Northern Hemisphere [October-March] and Southern Hemisphere [April-September] vaccine availability). RESULTS: From 2012 to 2016, influenza B represented 31% of all influenza-associated ARIs detected (annual range, 13-61%). Rates of influenza B hospitalization and outpatient visits were higher for <5 vs ≥5 years. Among <5 years, B/Victoria was associated with pneumonia hospitalization (64% vs 44%; P = .010) and in-hospital mortality (6% vs 0%; P = .042) compared with B/Yamagata, although the mean annual hospitalization rate for B/Victoria was comparable to that estimated for B/Yamagata. The 2 lineages co-circulated, and there were mismatches with available trivalent influenza vaccines in 2/9 seasons assessed. CONCLUSIONS: Influenza B causes substantial burden in Kenya, particularly among children aged <5 years, in whom B/Victoria may be associated with increased severity. Our findings suggest a benefit from including both lineages when considering influenza vaccination in Kenya.

Barriers to formal health care seeking during pregnancy, childbirth and postnatal period: a qualitative study in Siaya County in rural Kenya.

BACKGROUND: There is broad agreement that antenatal care (ANC) interventions, skilled attendance at birth and management of complications arising after delivery are key strategies that can tackle the high burden of maternal mortality in sub-Saharan Africa. In Kenya, utilisation rate of these services has remained low despite a government policy on free maternal care. The present study sought to understand what factors are leading to the low healthcare seeking during pregnancy, child birth and postnatal period in Siaya County in Kenya. METHODS: Six Focus Group Discussions were conducted with 50 women attending ANC in 6 public primary healthcare facilities. Participants were drawn from a sample of 200 women who were eligible participants in a Conditional Cash Transfer project aimed at increasing utilization of healthcare services during pregnancy and postnatal period. Interviews were conducted at the health facilities, recorded, transcribed and analysed using thematic analysis. RESULTS: Multiple factors beyond the commonly reported distance to health facility and lack of transportation and finances explained the low utilization of services. Emergent themes included a lack of understanding of the role of ANC beyond the treatment of regular ailments. Women with no complicated pregnancies therefore missed or went in late for the visits. A missed health visit contributed to future missed visits, not just for ANC but also for facility delivery and postnatal care. The underlying cause of this relationship was a fear of reprimand from the health staff and denial of care. The negative attitude of the health workers explained the pervasive fear expressed by the participants, as well as being on its own a reason for not making the visits. The effect was not just on the woman with the negative experience, but spiraled and affected the decision of other women and their social networks. CONCLUSIONS: The complexity of the barriers to healthcare visits implies that narrow focused solutions are unlikely to succeed. Instead, there should broad-based solutions that focus on the entire continuum of maternal care with a special focus on ANC. There is an urgent need to shift the negative attitude of healthcare workers towards their clients.

Conditional cash transfers to retain rural Kenyan women in the continuum of care during pregnancy, birth and the postnatal period: protocol for a cluster randomized controlled trial.

BACKGROUND: Antenatal care (ANC), facility delivery and postnatal care (PNC) are proven to reduce maternal and child mortality and morbidity in high-burden settings. However, few pregnant rural women use these services sufficiently. This study aims to assess the impact, cost-effectiveness and scalability of conditional cash transfers to promote increased contact between pregnant women or women who have recently given birth and the formal healthcare system in Kenya. METHODS: The intervention tested is a conditional cash transfer to women for ANC health visits, a facility birth and PNC visits until their newborn baby reaches 1 year of age. The study is a cluster randomized controlled trial in Siaya County, Kenya. The trial clusters are 48 randomly selected public primary health facilities, 24 of which are in the intervention arm of the study and 24 in the control arm. The unit of randomization is the health facility. A target sample of 7200 study participants comprises pregnant women identified and recruited at their first ANC visit over a 12-month recruitment period and their subsequent newborns. All pregnant women attending one of the selected trial facilities for their first ANC visit during the recruitment period are eligible for the trial and invited to participate. Enrolled mothers are followed up at all health visits during their pregnancy, at facility delivery and for a number of visits after delivery. They are also contacted at three additional time points after enrolling in the study: 5-10days after enrolment, 6 months after the expected delivery date and 12 27 months after birth. If they have not delivered in a facility, there is an additional follow-up 2 wees after the expected due date. The impact of the conditional cash transfers on maternal healthcare services and utilization will be measured by the trial's primary outcomes: the proportion of all eligible ANC visits made during pregnancy, delivery at a health facility, the proportion of all eligible PNC visits attended, the proportion of referrals attended during the pregnancy and the postnatal period, and the proportion of eligible child immunization appointments attended. Secondary outcomes include; health screening and infection control, live birth, maternal and child survival 48 h after delivery, exclusive breastfeeding, post-partum contraceptive use and maternal and newborn morbidity. Data sources for the measurement of outcomes include routine health records, an electronic card-reader system and telephone surveys and focus group discussions. A full economic evaluation will be conducted to assess the cost of delivery and cost effectiveness of the intervention and the benefit incidence and equity impact of trial activities and outcomes. DISCUSSION: This trial will contribute to evidence on the effectiveness and cost-effectiveness of conditional cash transfers in facilitating health visits and promoting maternal and child health in rural Kenya and in other comparable contexts. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03021070 . Registered on 13 January 2017.

Survey of local impacts of biofuel crop production and adoption of ethanol stoves in southern Africa.

The two datasets outlined in this paper contain information related to (a) the local impacts of biofuel feedstock production, and (b) the factors that influence the adoption and/or sustained use of ethanol stoves in southern Africa. The first dataset was generated through extensive household surveys around four operational jatropha and sugarcane production sites in Malawi, Mozambique, and Swaziland. This project aimed to examine the local impacts of the most prominent modes of existing or intended biofuel feedstock production in southern Africa. The resulting dataset contains information about impacts on rural livelihoods, ecosystem services, food security and poverty alleviation. The second dataset is the outcome of research into factors that influence the adoption and sustained use of ethanol stoves. This dataset was collected through a household survey in Maputo city where the only large-scale ethanol stove dissemination programme in Africa has been implemented.

A Combined Syndromic Approach to Examine Viral, Bacterial, and Parasitic Agents among Febrile Patients: A Pilot Study in Kilombero, Tanzania.

The use of fever syndromic surveillance in sub-Saharan Africa is an effective approach to determine the prevalence of both malarial and nonmalarial infectious agents. We collected both blood and naso/oro-pharyngeal (NP/OP) swabs from consecutive consenting patients ≥ 1 year of age, with an axillary temperature ≥ 37.5°C, and symptom onset of ≤ 5 days. Specimens were analyzed using both acute febrile illness (AFI) and respiratory TaqMan array cards (Resp TAC) for multiagent detection of 56 different bloodstream and respiratory agents. In addition, we collected epidemiologic data to further characterize our patient population. We enrolled 205 febrile patients, including 70 children (1 < 15 years of age; 34%) and 135 adults (≥ 15 years of age; 66%). AFI TAC and Resp TAC were performed on 191 whole blood specimens and 115 NP/OP specimens, respectively. We detected nucleic acid for Plasmodium (57%), Leptospira (2%), and dengue virus (1%) among blood specimens. In addition, we detected 17 different respiratory agents, most notably, Haemophilus influenzae (64%), Streptococcus pneumonia (56%), Moraxella catarrhalis (39%), and respiratory syncytial virus (11%) among NP/OP specimens. Overall median cycle threshold was measured at 26.5. This study provides a proof-of-concept for the use of a multiagent diagnostic approach for exploratory research on febrile illness and underscores the utility of quantitative molecular diagnostics in complex epidemiologic settings of sub-Saharan Africa.

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.

Effectiveness of interventions to reduce household air pollution and/or improve health in homes using solid fuel in low-and-middle income countries: A systematic review and meta-analysis.

BACKGROUND: Cookstove intervention programs have been increasing over the past two (2) decades in Low and Middle Income Countries (LMICs) across the globe. However, there remains uncertainty regarding the effects of these interventions on household air pollution concentrations, personal exposure concentrations and health outcomes. OBJECTIVES: The primary objective was to determine if household air pollution (HAP) interventions were associated with improved indoor air quality (IAQ) in households in LMICs. Given the potential impact of HAP interventions on health, a secondary objective was to evaluate the effectiveness of HAP interventions to improve health in populations receiving these interventions. DATA SOURCES: OVID Medline, Ovid Embase, SCOPUS and PubMED were searched from their inception until December 2015 with no restrictions on study design. The WHO Global database of household air pollution measurements and Members' archives were also reviewed together with the reference lists of identified reviews and relevant articles. STUDY ELIGIBILITY CRITERIA, PARTICIPANTS AND INTERVENTION: We considered randomized controlled trials, or non-randomized control trials, or before-and-after studies; original studies; studies conducted in a LMIC (based on the United Nations Human Development Report released in March 2013 (World Bank, 2013); interventions that were explicitly aimed at improving IAQ and/or health from solid fuel use; studies published in a peer-reviewed journal or student theses or reports; studies that reported on outcomes which was indicative of IAQ or/and health. There was no restriction on the type of comparator (e.g. household receiving plancha vs. household using traditional cookstove) used in the intervention study. STUDY APPRAISAL AND SYNTHESIS METHODS: Five review authors independently used pre-designed data collection forms to extract information from the original studies and assessed risk of bias using the Effective Public Health Practice Project (EPHPP). We computed standardized weighted mean difference (SMD) using random-effects models. Heterogeneity was computed using the Q and I2-statistics. We examined the influence of various characteristics on the study-specific effect estimates by stratifying the analysis by population type, study design, intervention type, and duration of exposure monitoring. The trim and fill method was used to assess the potential impact of missing studies. RESULTS: Fifty-five studies met our a priori inclusion criteria and were included in the systematic review. Fifteen studies provided 43 effect estimates for our meta-analysis. The largest improvement in HAP was observed for average particulate matter (PM) (SMD=1.57) concentrations in household kitchens (1.03), followed by daily personal average concentrations of PM (1.18), and carbon monoxide (CO) concentrations in kitchens. With respect to personal PM, significant improvement was observed in studies of children (1.26) and studies monitoring PM for ≥24h (1.32). This observation was also noted in terms of studies of kitchen concentrations of CO. A significant improvement was also observed for kitchen levels of PM in both adult populations (1.56) and in RCT/cohort designs (1.59) involving replacing cookstoves without chimneys. Our findings on health outcomes were inconclusive. LIMITATIONS, CONCLUSIONS AND IMPLICATIONS OF KEY FINDINGS: We observed high statistical between study variability in the study-specific estimate. Thus, care should be taken in concluding that HAP interventions - as currently designed and implemented - support reductions in the average kitchen and personal levels of PM and CO. Further, there is limited evidence that current stand-alone HAP interventions yield any health benefits. Post-intervention levels of pollutants were generally still greatly in excess of the relevant WHO guideline and thus a need to promote cleaner fuels in LMICs to reduce HAP levels below the WHO guidelines. SYSTEMATIC REVIEW REGISTRATION NUMBER: The review has been registered with PROSPERO (registration number CRD42014009768).

Household air pollution following replacement of traditional open fire with an improved rocket type cookstove.

Cooking with biomass fuel is an important source of household air pollution (HAP) in developing countries, and a leading risk factor for ill-health. Although various designs of "improved cookstoves" (ICS) have been promoted as HAP interventions in these settings, few of them have undergone in-field evaluation, partly due to the challenge of conducting field measurements in remote settings. In this study we assessed the change in carbon monoxide (CO) exposure following the replacement of the traditional three-stone stove with a popular ICS in 49 homes in Western Kenya. We also assessed the suitability of using kitchen CO as a proxy for kitchen PM2.5. Reduction in 48h mean kitchen CO was 3.1ppm (95% CI: -8.1, 1.8) and in personal CO was 0.9ppm (95% CI: -4.3, 2.6) following stove replacements. Overall, 48-h kitchen and personal CO exposures were lower after stove replacement (28% and 12%, respectively) but with wide confidence intervals that also suggested possible increases in exposure. There were statistically significant reductions in peak kitchen and personal CO concentrations represented by the 8-h 95th percentile: reductions of 26.1ppm (95% CI: -44.6, -7.6) and 8.0ppm (95% CI: -12.2, -3.8), respectively. This is equivalent to 53% reduction in kitchen CO and 39% reduction in personal CO. We found good correlation between kitchen CO and PM2.5 concentrations overall (r=0.73, n=33 over averaging periods approximating 1day), which varied by time of day and exposure setting. These variations limit the applicability of CO as a proxy measure for PM2.5 concentrations. A combination of interventions, including better designed stoves, improved ventilation and cleaner fuels, may be needed to reduce HAP to levels that are likely to improve health.

Dengue and Chikungunya Virus Infections among Young Febrile Adults Evaluated for Acute HIV-1 Infection in Coastal Kenya.

BACKGROUND: Fever is common among patients seeking care in sub-Saharan Africa (sSA), but causes other than malaria are rarely diagnosed. We assessed dengue and chikungunya virus infections among young febrile adults evaluated for acute HIV infection (AHI) and malaria in coastal Kenya. METHODS: We tested plasma samples obtained in a cross-sectional study from febrile adult patients aged 18-35 years evaluated for AHI and malaria at urgent care seeking at seven health facilities in coastal Kenya in 2014-2015. Dengue virus (DENV) and chikungunya virus (CHIKV) were amplified using quantitative real-time reverse-transcription polymerase chain reaction. We conducted logistic regression analyses to determine independent predictors of dengue virus infection. RESULTS: 489 samples that were negative for both AHI and malaria were tested, of which 43 (8.8%, 95% confidence interval [CI]: 6.4-11.7) were positive for DENV infection. No participant was positive for CHIKV infection. DENV infections were associated with clinic visits in the rainy season (adjusted odds ratio (AOR) = 3.0, 95% CI: 1.3-6.5) and evaluation at a private health facility (AOR 5.2, 95% CI: 2.0-13.1) or research health facility (AOR = 25.6, 95% CI: 8.9-73.2) instead of a public health facility. CONCLUSION: A high prevalence of DENV infections was found in febrile young adult patients evaluated for AHI. Our data suggests that DENV, along with AHI and malaria, should be considered in the differential diagnosis of the adult patient seeking care for fever in coastal Kenya.

Use of quantitative molecular diagnostic methods to identify causes of diarrhoea in children: a reanalysis of the GEMS case-control study.

BACKGROUND: Diarrhoea is the second leading cause of mortality in children worldwide, but establishing the cause can be complicated by diverse diagnostic approaches and varying test characteristics. We used quantitative molecular diagnostic methods to reassess causes of diarrhoea in the Global Enteric Multicenter Study (GEMS). METHODS: GEMS was a study of moderate to severe diarrhoea in children younger than 5 years in Africa and Asia. We used quantitative real-time PCR (qPCR) to test for 32 enteropathogens in stool samples from cases and matched asymptomatic controls from GEMS, and compared pathogen-specific attributable incidences with those found with the original GEMS microbiological methods, including culture, EIA, and reverse-transcriptase PCR. We calculated revised pathogen-specific burdens of disease and assessed causes in individual children. FINDINGS: We analysed 5304 sample pairs. For most pathogens, incidence was greater with qPCR than with the original methods, particularly for adenovirus 40/41 (around five times), Shigella spp or enteroinvasive Escherichia coli (EIEC) and Campylobactor jejuni o C coli (around two times), and heat-stable enterotoxin-producing E coli ([ST-ETEC] around 1·5 times). The six most attributable pathogens became, in descending order, Shigella spp, rotavirus, adenovirus 40/41, ST-ETEC, Cryptosporidium spp, and Campylobacter spp. Pathogen-attributable diarrhoeal burden was 89·3% (95% CI 83·2-96·0) at the population level, compared with 51·5% (48·0-55·0) in the original GEMS analysis. The top six pathogens accounted for 77·8% (74·6-80·9) of all attributable diarrhoea. With use of model-derived quantitative cutoffs to assess individual diarrhoeal cases, 2254 (42·5%) of 5304 cases had one diarrhoea-associated pathogen detected and 2063 (38·9%) had two or more, with Shigella spp and rotavirus being the pathogens most strongly associated with diarrhoea in children with mixed infections. INTERPRETATION: A quantitative molecular diagnostic approach improved population-level and case-level characterisation of the causes of diarrhoea and indicated a high burden of disease associated with six pathogens, for which targeted treatment should be prioritised. FUNDING: Bill & Melinda Gates Foundation.