Multi-country cross-sectional study of colonization with multidrug-resistant organisms: protocol and methods for the Antibiotic Resistance in Communities and Hospitals (ARCH) studies.

BACKGROUND: Antimicrobial resistance is a global health emergency. Persons colonized with multidrug-resistant organisms (MDROs) are at risk for developing subsequent multidrug-resistant infections, as colonization represents an important precursor to invasive infection. Despite reports documenting the worldwide dissemination of MDROs, fundamental questions remain regarding the burden of resistance, metrics to measure prevalence, and determinants of spread. We describe a multi-site colonization survey protocol that aims to quantify the population-based prevalence and associated risk factors for colonization with high-threat MDROs among community dwelling participants and patients admitted to hospitals within a defined population-catchment area. METHODS: Researchers in five countries (Bangladesh, Chile, Guatemala, Kenya, and India) will conduct a cross-sectional, population-based prevalence survey consisting of a risk factor questionnaire and collection of specimens to evaluate colonization with three high-threat MDROs: extended-spectrum cephalosporin-resistant Enterobacteriaceae (ESCrE), carbapenem-resistant Enterobacteriaceae (CRE), and methicillin-resistant Staphylococcus aureus (MRSA). Healthy adults residing in a household within the sampling area will be enrolled in addition to eligible hospitalized adults. Colonizing isolates of these MDROs will be compared by multilocus sequence typing (MLST) to routinely collected invasive clinical isolates, where available, to determine potential pathogenicity. A colonizing MDRO isolate will be categorized as potentially pathogenic if the MLST pattern of the colonizing isolate matches the MLST pattern of an invasive clinical isolate. The outcomes of this study will be estimates of the population-based prevalence of colonization with ESCrE, CRE, and MRSA; determination of the proportion of colonizing ESCrE, CRE, and MRSA with pathogenic characteristics based on MLST; identification of factors independently associated with ESCrE, CRE, and MRSA colonization; and creation an archive of ESCrE, CRE, and MRSA isolates for future study. DISCUSSION: This is the first study to use a common protocol to evaluate population-based prevalence and risk factors associated with MDRO colonization among community-dwelling and hospitalized adults in multiple countries with diverse epidemiological conditions, including low- and middle-income settings. The results will be used to better describe the global epidemiology of MDROs and guide the development of mitigation strategies in both community and healthcare settings. These standardized baseline surveys can also inform future studies seeking to further characterize MDRO epidemiology globally.

Adaptive Immune Responses in Humans During Nipah Virus Acute and Convalescent Phases of Infection.

BACKGROUND: Nipah virus (NiV) is 1 of 10 potential causes of imminent public health emergencies of international concern. We investigated the NiV outbreak that occurred in May 2018 in Kerala, India. Here we describe the longitudinal characteristics of cell-mediated and humoral immune responses to NiV infection during the acute and convalescent phases in 2 human survivors. METHODS: Serial blood samples were obtained from the only 2 survivors of the NiV outbreak in Kerala. We used flow cytometry to determine the absolute T-lymphocyte and B-lymphocyte counts and the phenotypes of both T and B cells. We also detected and quantitated the humoral immune response to NiV by virus-specific immunoglobulin M (IgM) and immunoglobulin G (IgG) enzyme-linked immunosorbent assay. RESULTS: Absolute numbers of T lymphocytes remained within normal limits throughout the period of illness studied in both survivors. However, a marked elevation of activated CD8 T cells was observed in both cases. More than 30% of total CD8 T cells expressed Ki67, indicating active proliferation. Proliferating (Ki-67+) CD8 T cells expressed high levels of granzyme B and PD-1, consistent with the profile of acute effector cells. Total B-lymphocyte, activated B-cell, and plasmablast counts were also elevated in NiV survivors. These individuals developed detectable NiV-specific IgM and IgG antibodies within a week of disease onset. Clearance of NiV RNA from blood preceded the appearance of virus-specific IgG and coincided with the peak of activated CD8 T cells. CONCLUSIONS: We describe for the first time longitudinal kinetic data on the activation status of human B- and T-cell populations during acute NiV infection. While marked CD8 T-cell activation was observed with effector characteristics, activated CD4 T cells were less prominent.

Estimating the annual risk of infection with Mycobacterium tuberculosis among adolescents in Western Kenya in preparation for TB vaccine trials.

BACKGROUND: Adolescents are a prime target group for tuberculosis (TB) vaccine trials that include prevention of infection (POI). The BCG vaccine is given at birth and does not prevent TB infection. TB infection, a critical endpoint for POI vaccine trials would need to be documented to estimate sample sizes in target populations. METHODS: Adolescents aged 12-18 years of age were enrolled in an area under continuous demographic surveillance. A tuberculin skin test (TST) survey was conducted as part of a study on TB prevalence and incidence. All adolescents got TSTs at enrolment and returned after 72 h for reading. A TST of ≥10 mm if HIV negative or ≥ 5 mm if HIV positive, was considered positive. RESULTS: Of 4808 adolescents returning for TST readings (96% of those enrolled), mean age was 14.4 (SD 1.9), 4518(94%) were enrolled in school and 21(0.4%) gave a previous history of tuberculosis. Among adolescents with TST reactivity, the mean TST induration was 13.2 mm (SD 5.4). The overall prevalence of latent TB infection was 1544/4808 (32.1, 95% CI 29.2-35.1) with a corresponding annual risk of TB infection (ARTI) of 2.6% (95% CI 2.2-3.1). Risk factors for a positive TST included being male (OR 1.3, 95% CI 1.2,1.5), history of having a household TB contact (OR 1.5, 95% CI 1.2,1.8), having a BCG scar (OR 1.5,95% CI 1.2,1.8), living in a rural area (OR 1.4, 95% CI 1.1,1.9), and being out of school (OR 1.8, 95% CI 1.4,2.3). CONCLUSION: We conclude that the high TB transmission rates we found in this study, suggest that adolescents in this region may be an appropriate target group for TB vaccine trials including TB vaccine trials aiming to prevent infection.

Jaundice outbreak likely caused by HEV in Amritsar, Punjab, India, 2013.

BACKGROUND: Hepatitis-E Virus (HEV) infection is endemic in Punjab, India. On 4th April 2013, public officials of Labour Colony, Amritsar reported > 20 jaundice cases occurring within several days. METHODS: We performed a case-control study to identify the cause and prevent additional cases of jaundice cases in Amritsar, Punjab, India in 2013. RESULTS: A total of 159 cases (attack rate 3.6%) and 1 death were identified in Labour and 5 adjoining colonies from January 1 to June 5, 2013. Persons with jaundice were more likely to report foul-smelling piped water (adjusted odds ratio [AOR], 4.0, 95% confidence interval [CI], 2.2-7.2) and used piped water for drinking (AOR, 5.1; 95% CI, 2.2-11.4) than persons without jaundice. Among 14 cases tested, all had anti-hepatitis E virus IgM, and none had anti-hepatitis A virus IgM. Additionally, 21/23 tap water samples from affected households had detectable fecal coliforms. An environmental investigation found that water pipelines were damaged during sewer construction and likely led to contamination of drinking water with hepatitis E virus. CONCLUSIONS: Hepatitis E outbreaks are common in India, to curb future outbreaks of hepatitis E; measures to ensure safe drinking water are urgently needed.

A cutaneous Anthrax outbreak in Koraput District of Odisha-India 2015.

BACKGROUND: Cutaneous anthrax in humans is associated with exposure to infected animals or animal products and has a case fatality rate of up to 20% if untreated. During May to June 2015, an outbreak of cutaneous anthrax was reported in Koraput district of Odisha, India, an area endemic for anthrax. We investigated the outbreak to identify risk factors and recommend control measures. METHOD: We defined a cutaneous anthrax case as skin lesions (e.g., papule, vesicle or eschar) in a person residing in Koraput district with illness onset between February 1 and July 15, 2015. We established active surveillance through a house to house survey to ascertain additional cases and conducted a 1:2 unmatched case control study to identify modifiable risk factors. In case control study, we included cases with illness onset between May 1 and July 15, 2015. We defined controls as neighbours of case without skin lesions since last 3 months. Ulcer exudates and rolled over swabs from wounds were processed in Gram stain in the Koraput district headquarter hospital laboratory. RESULT: We identified 81 cases (89% male; median age 38 years [range 5-75 years]) including 3 deaths (case fatality rate = 4%). Among 37 cases and 74 controls, illness was significantly associated with eating meat of ill cattle (OR: 14.5, 95% CI: 1.4-85.7) and with close handling of carcasses of ill animals such as burying, skinning, or chopping (OR: 342, 95% CI: 40.5-1901.8). Among 20 wound specimens collected, seven showed spore-forming, gram positive bacilli, with bamboo stick appearance suggestive of Bacillus anthracis. CONCLUSION: Our investigation revealed significant associations between eating and handling of ill animals and presence of anthrax-like organisms in lesions. We immediately initiated livestock vaccination in the area, educated the community on safe handling practices and recommended continued regular anthrax animal vaccinations to prevent future outbreaks.

Integrated point-of-care testing (POCT) for HIV, syphilis, malaria and anaemia at antenatal facilities in western Kenya: a qualitative study exploring end-users' perspectives of appropriateness, acceptability and feasibility.

BACKGROUND: HIV, syphilis, malaria and anaemia are leading preventable causes of adverse pregnancy outcomes in sub-Saharan Africa yet testing coverage for conditions other than HIV is low. Availing point-of-care tests (POCTs) at rural antenatal health facilities (dispensaries) has the potential to improve access and timely treatment. Fundamental to the adoption of and adherence to new diagnostic approaches are healthcare workers' and pregnant women's (end-users) buy-in. A qualitative approach was used to capture end-users' experiences of using POCTs for HIV, syphilis, malaria and anaemia to assess the appropriateness, acceptability and feasibility of integrated testing for ANC. METHODS: Seven dispensaries were purposively selected to implement integrated point-of-care testing for eight months in western Kenya. Semi-structured interviews were conducted with 18 healthcare workers (14 nurses, one clinical officer, two HIV testing counsellors, and one laboratory technician) who were trained, had experience doing integrated point-of-care testing, and were still working at the facilities 8-12 months after the intervention began. The interviews explored acceptability and relevance of POCTs to ANC, challenges with testing, training and supervision, and healthcare workers' perspectives of client experiences. Twelve focus group discussions with 118 pregnant women who had attended a first ANC visit at the study facilities during the intervention were conducted to explore their knowledge of HIV, syphilis, malaria, and anaemia, experience of ANC point-of-care testing services, treatments received, relationships with healthcare workers, and experience of talking to partners about HIV and syphilis results. RESULTS: Healthcare workers reported that they enjoyed gaining new skills, were enthusiastic about using POCTs, and found them easy to use and appropriate to their practice. Initial concerns that performing additional testing would increase their workload in an already strained environment were resolved with experience and proficiency with the testing procedures. However, despite having the diagnostic tools, general health system challenges such as high client to healthcare worker volume ratio, stock-outs and poor working conditions challenged the delivery of adequate counselling and management of the four conditions. Pregnant women appreciated POCTs, but reported poor healthcare worker attitudes, drug stock-outs, and fear of HIV disclosure to their partners as shortcomings to their ANC experience in general. CONCLUSION: This study provides insights on the acceptability, appropriateness, and feasibility of integrating POCTs into ANC services among end-users. While the innovation was desired and perceived as beneficial, future scale-up efforts would need to address health system weaknesses if integrated testing and subsequent effective management of the four conditions are to be achieved.

Risk Factors for Acquiring Scrub Typhus among Children in Deoria and Gorakhpur Districts, Uttar Pradesh, India, 2017.

Scrub typhus is associated with outbreaks of acute encephalitis syndrome in Uttar Pradesh, India. A case-control study indicated that children residing, playing, or visiting fields; living with firewood stored indoors; handling cattle fodder; and practicing open defecation were at increased risk for scrub typhus. Communication messages should focus on changing these behaviors.

Infant and child mortality in relation to malaria transmission in KEMRI/CDC HDSS, Western Kenya: validation of verbal autopsy.

BACKGROUND: Malaria transmission reduction is a goal of many malaria control programmes. Little is known of how much mortality can be reduced by specific reductions in transmission. Verbal autopsy (VA) is widely used for estimating malaria specific mortality rates, but does not reliably distinguish malaria from other febrile illnesses. Overall malaria attributable mortality includes both direct and indirect deaths. It is unclear what proportion of the deaths averted by reducing malaria transmission are classified as malaria in VA. METHODS: Both all-cause, and cause-specific mortality reported by VA for children under 5 years of age, were assembled from the KEMRI/CDC health and demographic surveillance system in Siaya county, rural Western Kenya for the years 2002-2004. These were linked to household-specific estimates of the Plasmodium falciparum entomological inoculation rate (EIR) based on high resolution spatio-temporal geostatistical modelling of entomological data. All-cause and malaria specific mortality (by VA), were analysed in relation to EIR, insecticide-treated net use (ITN), socioeconomic status (SES) and parameters describing space-time correlation. Time at risk for each child was analysed using Bayesian geostatistical Cox proportional hazard models, with time-dependent covariates. The outputs were used to estimate the diagnostic performance of VA in measuring mortality that can be attributed to malaria exposure. RESULTS: The overall under-five mortality rate was 80 per 1000 person-years during the study period. Eighty-one percent of the total deaths were assigned causes of death by VA, with malaria assigned as the main cause of death except in the neonatal period. Although no trend was observed in malaria-specific mortality assessed by VA, ITN use was associated with reduced all-cause mortality in infants (hazard ratio 0.15, 95% CI 0.02, 0.63) and the EIR was strongly associated with both all-cause and malaria-specific mortality. 48.2% of the deaths could be attributed to malaria by analysing the exposure-response relationship, though only 20.5% of VAs assigned malaria as the cause and the sensitivity of VAs was estimated to be only 26%. Although VAs assigned some deaths to malaria even in areas where there was estimated to be no exposure, the specificity of the VAs was estimated to be 85%. CONCLUSION: Interventions that reduce P. falciparum transmission intensity will not only significantly reduce malaria-diagnosed mortality, but also mortality assigned to other causes in under-5 year old children in endemic areas. In this setting, the VA tool based on clinician review substantially underestimates the number of deaths that could be averted by reducing malaria exposure in childhood, but has a reasonably high specificity. This suggests that malaria transmission-reducing interventions such as ITNs can potentially reduce overall child mortality by as much as twice the total direct malaria burden estimated from VAs.

Uptake of skilled attendance along the continuum of care in rural Western Kenya: selected analysis from Global Health initiative survey-2012.

BACKGROUND: Examining skilled attendance throughout pregnancy, delivery and immediate postnatal period is proxy indicator on the progress towards reduction of maternal and neonatal mortality in developing countries. METHODS: We conducted a cross-sectional baseline survey of households of mothers with at least 1 child under-5 years in 2012 within the KEMRI/CDC health and demographic surveillance system (HDSS) area in rural western Kenya. RESULTS: Out of 8260 mother-child pairs, data on antenatal care (ANC) in the most recent pregnancy was obtained for 89% (n = 8260); 97% (n = 7387) reported attendance. Data on number of ANC visits was available for 89% (n = 7140); 52% (n = 6335) of mothers reported ≥4 ANC visits. Data on gestation month at first ANC was available for 94% (n = 7140) of mothers; 14% (n = 6690) reported first visit was in1sttrimester (0-12 weeks), 73% in 2nd trimester (14-28 weeks) and remaining 13% in third trimester. Forty nine percent (n = 8259) of mothers delivered in a Health Facility (HF), 48% at home and 3% en route to HF. Forty percent (n = 7140) and 63% (n = 4028) of mothers reporting ANC attendance and HF delivery respectively also reported receiving postnatal care (PNC). About 36% (n = 8259) of mothers reported newborn assessment (NBA). Sixty eight percent (n = 3966) of mothers that delivered at home reported taking newborn for HF check-up, with only 5% (n = 2693) doing so within 48 h of delivery. Being ≤34 years (OR 1.8; 95% CI 1.4-2.4) and at least primary education (OR 5.3; 95% CI 1.8-15.3) were significantly associated with ANC attendance. Being ≤34 years (OR 1.7; 95% CI 1.5-2.0), post-secondary vs primary education (OR 10; 95% CI 4.4-23.4), ANC attendance (OR 4.5; 95% CI 3.2-6.1), completing ≥4 ANC visits (OR 2.0; 95% CI 1.8-2.2), were strongly associated with HF delivery. The continuum of care was such that 97% (n = 7387) mothers reported ANC attendance, 49% reported both ANC and HF delivery attendance, 34% reported ANC, HF delivery and PNC attendance and only 18% reported ANC, HF delivery, PNC and NBA attendance. CONCLUSION: Uptake of services drastically declined from antenatal to postnatal period, along the continuum of care. Age and education were key determinants of uptake.

Use of menstrual cups among school girls: longitudinal observations nested in a randomised controlled feasibility study in rural western Kenya.

BACKGROUND: A menstrual cup can be a good solution for menstrual hygiene management in economically challenged settings. As part of a pilot study we assessed uptake and maintenance of cup use among young school girls in Kenya. METHODS: A total of 192 girls between 14 to 16 years were enrolled in 10 schools in Nyanza Province, Western Kenya; these schools were assigned menstrual cups as part of the cluster-randomized pilot study. Girls were provided with menstrual cups in addition to training and guidance on use, puberty education, and instructions for menstrual hygiene. During repeated individual visits with nurses, girls reported use of the menstrual cup and nurses recorded colour change of the cup. RESULTS: Girls were able to keep their cups in good condition, with only 12 cups (6.3%) lost (dropped in toilet, lost or destroyed). Verbally reported cup use increased from 84% in the first 3 months (n = 143) to 96% after 9 months (n = 74). Colour change of the cup, as 'uptake' indicator of use, was detected in 70.8% of 192 participants, with a median time of 5 months (range 1-14 months). Uptake differed by school and was significantly higher among girls who experienced menarche within the past year (adjusted risk ratio 1.29, 95% CI 1.04-1.60), and was faster among girls enrolled in the second study year (hazard ratio 3.93, 95% CI 2.09-7.38). The kappa score comparing self-report and cup colour observation was 0.044 (p = 0.028), indicating that agreement was only slightly higher than by random chance. CONCLUSIONS: Objective evidence through cup colour change suggests school girls in rural Africa can use menstrual cups, with uptake improving with peer group education and over time. TRIAL REGISTRATION: ISRCTN17486946 . Retrospectively registered 09 December 2014.

Pneumococcal carriage and antibiotic susceptibility patterns from two cross-sectional colonization surveys among children aged <5 years prior to the introduction of 10-valent pneumococcal conjugate vaccine - Kenya, 2009-2010.

BACKGROUND: Pneumococci are spread by persons with nasopharyngeal colonization, a necessary precursor to invasive disease. Pneumococcal conjugate vaccines can prevent colonization with vaccine serotype strains. In 2011, Kenya became one of the first African countries to introduce the 10-valent pneumococcal conjugate vaccine (PCV10) into its national immunization program. Serial cross-sectional colonization surveys were conducted to assess baseline pneumococcal colonization, antibiotic resistance patterns, and factors associated with resistance. METHODS: Annual surveys were conducted in one urban and one rural site during 2009 and 2010 among children aged <5 years. To reflect differences in vaccine target population, recruitment was age-stratified in Kibera, whereas a simple random sample of children was drawn in Lwak. Nasopharyngeal swabs were collected from eligible children. Pneumococci were isolated and serotyped. Antibiotic susceptibility testing was performed using the 2009 isolates. Antibiotic nonsusceptibility was defined as intermediate susceptibility or resistance to ≥1 antibiotics (i.e., penicillin, chloramphenicol, levofloxacin, erythromycin, tetracycline, cotrimoxazole, and clindamycin); multidrug resistance (MDR) was defined as nonsusceptibility to ≥3 antibiotics. Weighted analysis was conducted when appropriate. Modified Poisson regression was used to calculate factors associated with antibiotic nonsusceptibility. RESULTS: Of 1,087 enrolled (Kibera: 740, Lwak: 347), 90.0% of these were colonized with pneumococci, and 37.3% were colonized with PCV10 serotypes. There were no differences by survey site or year. Of 657 (of 730; 90%) isolates tested for antibiotic susceptibility, nonsusceptibility to cotrimoxazole and penicillin was found in 98.6 and 81.9% of isolates, respectively. MDR was found in 15.9% of isolates and most often involved nonsusceptibility to cotrimoxazole and penicillin; 40.4% of MDR isolates were PCV10 serotypes. In the multivariable model, PCV10 serotypes were independently associated with penicillin nonsusceptibility (Prevalence Ratio: 1.2, 95% CI 1.1-1.3), but not with MDR. CONCLUSIONS: Before PCV10 introduction, nearly all Kenyan children aged <5 years were colonized with pneumococci, and PCV10 serotype colonization was common. PCV10 serotypes were associated with penicillin nonsusceptibility. Given that colonization with PCV10 serotypes is associated with greater risk for invasive disease than colonization with other serotypes, successful PCV10 introduction in Kenya is likely to have a substantial impact in reducing vaccine-type pneumococcal disease and drug-resistant pneumococcal infection.

'We do not know': a qualitative study exploring boys perceptions of menstruation in India.

BACKGROUND: In low-middle income countries and other areas of poverty, menstrual hygiene management (MHM) can be problematic for women and girls. Issues include lack of knowledge about menstruation and MHM, and stigma around menstruation, also access to affordable and absorbent materials; privacy to change; adequate washing, cleaning and drying facilities; as well as appropriate and accessible disposal facilities. In order to effect change and tackle these issues, particularly in patriarchal societies, males may need to become advocates for MHM alongside women. However, little is known about their knowledge and attitudes towards menstruation, which may need addressing before they can assist in acting as advocates for change. The present study was undertaken to explore knowledge and attitudes about menstruation among adolescent boys across India, in order to gauge their potential to support their 'sisters'. METHODS: The study was undertaken across three states in India, chosen a priori to represent the cultural and socio-economic diversity. Qualitative data using focus group discussions with 85 boys aged 13-17 years, from 8 schools, was gathered. Data were analysed using thematic analysis. RESULTS: The results were organised into three main themes, reflecting the key research questions: boys' knowledge of menstruation, source of knowledge, and attitudes towards menstruation and menstruating girls. Knowledge comprised three aspects; biological function which were generally poorly understood; cultural rites which were recognized by all; and girls' behaviour and demeanour, which were noted to be withdrawn. Some boys learnt about puberty and menstruation as part of the curriculum but had concerns this was not in-depth, or was missed out altogether. Most gathered knowledge from informal sources, from overhearing conversations or observing cultural rituals. Few boys openly displayed a negative attitude, although a minority voiced the idea that menstruation is a 'disease'. Boys were mostly sympathetic to their menstruating sisters and wanted to support them. CONCLUSIONS: These findings provide some optimism that males can become advocates in moving forward the MHM agenda. The reasons for this are twofold: boys were keen for knowledge about menstruation, searching information out despite societal norms being for them to remain ignorant, they were also largely sympathetic to their menstruating sisters and fellow classmates and understanding of the issues surrounding the need for good MHM.

The World Health Organization Measles Programmatic Risk Assessment Tool-Pilot Testing in India, 2014.

Measles is a leading cause of child mortality, and reduction of child mortality is a key Millennium Development Goal. In 2014, the World Health Organization and the U.S. Centers for Disease Control and Prevention developed a measles programmatic risk assessment tool to support country measles elimination efforts. The tool was pilot tested in the State of Uttarakhand in August 2014 to assess its utility in India. The tool assessed measles risk for the 13 districts of Uttarakhand as a function of indicator scores in four categories: population immunity, surveillance quality, program delivery performance, and threat. The highest potential overall score was 100. Scores from each category were totaled to assign an overall risk score for each district. From this risk score, districts were categorized as low, medium, high, or very high risk. Of the 13 districts in Uttarakhand in 2014, the tool classified one district (Haridwar) as very high risk and three districts (Almora, Champawat, and Pauri Garhwal) as high risk. The measles risk in these four districts was largely due to low population immunity from high MCV1-MCV2 drop-out rates, low MCV1 and MCV2 coverage, and the lack of a supplementary immunization activity (SIA) within the past three years. This tool can be used to support measles elimination in India by identifying districts that might be at risk for measles outbreaks, and to guide risk mitigation efforts, including strengthening routine immunization services and implementing SIAs.

Risk factors for death during a resurgence of influenza-A (H1N1) pdm09 in Punjab State in 2013.

BACKGROUND: In 2013, high mortality from influenza-A (H1N1) pdm09 (pH1N1) was observed in Punjab, India. OBJECTIVES: To describe cases and deaths of 2013 pH1N1 positives, to evaluate the high case fatality ratio and risk factors for pH1N1-associated mortality among the hospitalized cases in Punjab for 2013. METHODS: A case-control study was conducted and compared those who died from confirmed pH1N1 with those who survived in the hospital between January 1, 2013, and April 30, 2013. Sociodemographic and clinical details were extracted from hospital records and from telephone interviews with controls and next of kin of cases using pretested questionnaires. Logistic regression analysis was performed. RESULTS: A total of 182 laboratory-confirmed pH1N1 cases (99 males and 83 females) were hospitalized in 30 hospitals in Punjab; 42 (23%) patients died. Those who died were significantly more likely to be younger than 50 years of age (adjusted odds ratio [AOR] =10.6, 95% confidence interval [CI] =1.8-21.1), be obese (AOR = 16.7, 95% CI = 1.6-170.7), and have visited more than two health-care facilities before laboratory confirmation (AOR = 25.8, 95% CI = 5.4-121.6). CONCLUSIONS: The health-care community should have a high index of suspicion for influenza, and general community should be sensitized about risk factors and to seek medical advice early in the illness.

Intermittent screening and treatment or intermittent preventive treatment with dihydroartemisinin-piperaquine versus intermittent preventive treatment with sulfadoxine-pyrimethamine for the control of malaria during pregnancy in western Kenya: an open-label, three-group, randomised controlled superiority trial.

BACKGROUND: Every year, more than 32 million pregnancies in sub-Saharan Africa are at risk of malaria infection and its adverse consequences. The effectiveness of the intermittent preventive treatment with sulfadoxine-pyrimethamine strategy recommended by WHO is threatened by high levels of parasite resistance. We aimed to assess the efficacy and safety of two alternative strategies: intermittent screening with malaria rapid diagnostic tests and treatment of women who test positive with dihydroartemisinin-piperaquine, and intermittent preventive treatment with dihydroartemisinin-piperaquine. METHODS: We did this open-label, three-group, randomised controlled superiority trial at four sites in western Kenya with high malaria transmission and sulfadoxine-pyrimethamine resistance. HIV-negative pregnant women between 16 and 32 weeks' gestation were randomly assigned (1:1:1), via computer-generated permuted-block randomisation (block sizes of three, six, and nine), to receive intermittent screening and treatment with dihydroartemisinin-piperaquine, intermittent preventive treatment with dihydroartemisinin-piperaquine, or intermittent preventive treatment with sulfadoxine-pyrimethamine. Study participants, study clinic nurses, and the study coordinator were aware of treatment allocation, but allocation was concealed from study investigators, delivery unit nurses, and laboratory staff. The primary outcome was malaria infection at delivery, defined as a composite of peripheral or placental parasitaemia detected by placental histology, microscopy, or rapid diagnostic test. The primary analysis was by modified intention to treat. This study is registered with ClinicalTrials.gov, number NCT01669941. FINDINGS: Between Aug 21, 2012, and June 19, 2014, we randomly assigned 1546 women to receive intermittent screening and treatment with dihydroartemisinin-piperaquine (n=515), intermittent preventive treatment with dihydroartemisinin-piperaquine (n=516), or intermittent preventive treatment with sulfadoxine-pyrimethamine (n=515); 1368 (88%) women comprised the intention-to-treat population for the primary endpoint. Prevalence of malaria infection at delivery was lower in the intermittent preventive treatment with dihydroartemisinin-piperaquine group than in the intermittent preventive treatment with sulfadoxine-pyrimethamine group (15 [3%] of 457 women vs 47 [10%] of 459 women; relative risk 0·32, 95% CI 0·18-0·56; p<0·0001), but not in the intermittent screening and treatment with dihydroartemisinin-piperaquine group (57 [13%] of 452 women; 1·23, 0·86-1·77; p=0·26). Compared with intermittent preventive treatment with sulfadoxine-pyrimethamine, intermittent preventive treatment with dihydroartemisinin-piperaquine was associated with a lower incidence of malaria infection during pregnancy (192·0 vs 54·4 events per 100 person-years; incidence rate ratio [IRR] 0·28, 95% CI 0·22-0·36; p<0·0001) and clinical malaria during pregnancy (37·9 vs 6·1 events; 0·16, 0·08-0·33; p<0·0001), whereas intermittent screening and treatment with dihydroartemisinin-piperaquine was associated with a higher incidence of malaria infection (232·0 events; 1·21, 1·03-1·41; p=0·0177) and clinical malaria (53·4 events; 1·41, 1·00-1·98; p=0·0475). We recorded 303 maternal and infant serious adverse events, which were least frequent in the intermittent preventive treatment with dihydroartemisinin-piperaquine group. INTERPRETATION: At current levels of rapid diagnostic test sensitivity, intermittent screening and treatment is not a suitable alternative to intermittent preventive treatment with sulfadoxine-pyrimethamine in the context of high sulfadoxine-pyrimethamine resistance and malaria transmission. However, dihydroartemisinin-piperaquine is a promising alternative drug to replace sulfadoxine-pyrimethamine for intermittent preventive treatment. Future studies should investigate the efficacy, safety, operational feasibility, and cost-effectiveness of intermittent preventive treatment with dihydroartemisinin-piperaquine. FUNDING: The Malaria in Pregnancy Consortium, which is funded through a grant from the Bill & Melinda Gates Foundation to the Liverpool School of Tropical Medicine.

Prevalence of reproductive tract infections and the predictive value of girls' symptom-based reporting: findings from a cross-sectional survey in rural western Kenya.

OBJECTIVES: Reproductive tract infections (RTIs), including sexually acquired, among adolescent girls is a public health concern, but few studies have measured prevalence in low-middle-income countries. The objective of this study was to examine prevalence in rural schoolgirls in Kenya against their reported symptoms. METHODS: In 2013, a survey was conducted in 542 adolescent schoolgirls aged 14-17 years who were enrolled in a menstrual feasibility study. Vaginal self-swabbing was conducted after girls were interviewed face-to-face by trained nurses on symptoms. The prevalence of girls with symptoms and laboratory-confirmed infections, and the sensitivity, specificity, positive and negative predictive values of symptoms compared with laboratory results, were calculated. RESULTS: Of 515 girls agreeing to self-swab, 510 answered symptom questions. A quarter (24%) reported one or more symptoms; most commonly vaginal discharge (11%), pain (9%) or itching (4%). Laboratory tests confirmed 28% of girls had one or more RTI. Prevalence rose with age; among girls aged 16-17 years, 33% had infections. Bacterial vaginosis was the most common (18%), followed by Candida albicans (9%), Chlamydia trachomatis (3%), Trichomonas vaginalis (3%) and Neisseria gonorrhoeae (1%). Reported symptoms had a low sensitivity and positive predictive value. Three-quarters of girls with bacterial vaginosis and C. albicans, and 50% with T. vaginalis were asymptomatic. CONCLUSIONS: There is a high prevalence of adolescent schoolgirls with RTI in rural Kenya. Public efforts are required to identify and treat infections among girls to reduce longer-term sequelae but poor reliability of symptom reporting minimises utility of symptom-based diagnosis in this population. TRIAL REGISTRATION NUMBER: ISRCTN17486946.

High Streptococcus pneumoniae colonization prevalence among HIV-infected Kenyan parents in the year before pneumococcal conjugate vaccine introduction.

BACKGROUND: Streptococcus pneumoniae is a leading cause of pneumonia, meningitis and sepsis in developing countries, particularly among children and HIV-infected persons. Pneumococcal oropharyngeal (OP) or nasopharyngeal (NP) colonization is a precursor to development of invasive disease. New conjugate vaccines hold promise for reducing colonization and disease. METHODS: Prior to introduction of 10-valent pneumococcal conjugate vaccine (PCV10), we conducted a cross-sectional survey among HIV-infected parents of children <5 years old in rural Kenya. Other parents living with an HIV-infected adult were also enrolled. After broth enrichment, NP and OP swabs were cultured for pneumococcus. Serotypes were identified by Quellung. Antimicrobial susceptibility was performed using broth microdilution. RESULTS: We enrolled 973 parents; 549 (56.4%) were HIV-infected, 153 (15.7%) were HIV-uninfected and 271 (27.9%) had unknown HIV status. Among HIV-infected parents, the median age was 32 years (range 15-74) and 374/549 (68%) were mothers. Pneumococci were isolated from 237/549 (43.2%) HIV-infected parents and 41/153 (26.8%) HIV-non-infected parents (p = 0.0003). Colonization with PCV10 serotypes was not significantly more frequent in HIV-infected (12.9%) than HIV-uninfected parents (11.8%; p = 0.70). Among HIV-infected parents, cooking site separate from sleeping area and CD4 count >250 were protective (OR = 0.6; 95% CI 0.4, 0.9 and OR = 0.5; 95% CI 0.2, 0.9, respectively); other associations were not identified. Among 309 isolates tested from all parents, 255 (80.4%) were penicillin non-susceptible (MIC ≥0.12 µg/ml). CONCLUSIONS: Prevalence of pneumococcal colonization is high among HIV-infected parents in rural Kenya. If young children are the pneumococcal reservoir for this population, PCV10 introduction may reduce vaccine-type colonization and disease among HIV-infected parents through indirect protection.

Kyasanur Forest disease outbreak and vaccination strategy,Shimoga District, India, 2013-2014.

We investigated a Kyasanur Forest disease outbreak in Karnataka, India during December 2013-April 2014. Surveillance and retrospective study indicated low vaccine coverage, low vaccine effectiveness, and spread of disease to areas beyond those selected for vaccination and to age groups not targeted for vaccination. To control disease, vaccination strategies need to be reviewed.

A phase 3 trial of RTS,S/AS01 malaria vaccine in African infants.

BACKGROUND: The candidate malaria vaccine RTS,S/AS01 reduced episodes of both clinical and severe malaria in children 5 to 17 months of age by approximately 50% in an ongoing phase 3 trial. We studied infants 6 to 12 weeks of age recruited for the same trial. METHODS: We administered RTS,S/AS01 or a comparator vaccine to 6537 infants who were 6 to 12 weeks of age at the time of the first vaccination in conjunction with Expanded Program on Immunization (EPI) vaccines in a three-dose monthly schedule. Vaccine efficacy against the first or only episode of clinical malaria during the 12 months after vaccination, a coprimary end point, was analyzed with the use of Cox regression. Vaccine efficacy against all malaria episodes, vaccine efficacy against severe malaria, safety, and immunogenicity were also assessed. RESULTS: The incidence of the first or only episode of clinical malaria in the intention-to-treat population during the 14 months after the first dose of vaccine was 0.31 per person-year in the RTS,S/AS01 group and 0.40 per person-year in the control group, for a vaccine efficacy of 30.1% (95% confidence interval [CI], 23.6 to 36.1). Vaccine efficacy in the per-protocol population was 31.3% (97.5% CI, 23.6 to 38.3). Vaccine efficacy against severe malaria was 26.0% (95% CI, -7.4 to 48.6) in the intention-to-treat population and 36.6% (95% CI, 4.6 to 57.7) in the per-protocol population. Serious adverse events occurred with a similar frequency in the two study groups. One month after administration of the third dose of RTS,S/AS01, 99.7% of children were positive for anti-circumsporozoite antibodies, with a geometric mean titer of 209 EU per milliliter (95% CI, 197 to 222). CONCLUSIONS: The RTS,S/AS01 vaccine coadministered with EPI vaccines provided modest protection against both clinical and severe malaria in young infants. (Funded by GlaxoSmithKline Biologicals and the PATH Malaria Vaccine Initiative; RTS,S ClinicalTrials.gov number, NCT00866619.).

Viral Hepatitis Surveillance--India, 2011-2013.

The burden of viral hepatitis in India is not well characterized. In 2009, the national Integrated Disease Surveillance Programme (IDSP) began conducting surveillance across all Indian states for epidemic-prone diseases, including foodborne and waterborne forms of viral hepatitis (e.g., hepatitis A and E). Information on outbreaks of all forms of viral hepatitis, including A, B, C, and E, also is collected. This report summarizes viral hepatitis surveillance and outbreak data reported to IDSP during 2011-2013. During this period, 804,782 hepatitis cases and 291 outbreaks were reported; the virus type was unspecified in 92% of cases. Among 599,605 cases tested for hepatitis A, 44,663 (7.4%) were positive, and among 187,040 tested for hepatitis E, 19,508 (10.4%) were positive. At least one hepatitis outbreak report was received from 23 (66%) of 35 Indian states. Two-thirds of outbreaks were reported from rural areas. Among 163 (56%) outbreaks with known etiology, 78 (48%) were caused by hepatitis E, 54 (33%) by hepatitis A, 19 (12%) by both hepatitis A and E, and 12 (7%) by hepatitis B or hepatitis C. Contaminated drinking water was the source of most outbreaks. Improvements in water quality and sanitation as well as inclusion of hepatitis A vaccine in childhood immunization programs should be considered to reduce the public health burden of hepatitis in India. Efforts to decrease the proportion of cases for which the etiology is unspecified, including expanding the IDSP to support hepatitis B and C testing, might help further elucidate the epidemiology of these diseases.