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.

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.

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.

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.

Risks of miscarriage and inadvertent exposure to artemisinin derivatives in the first trimester of pregnancy: a prospective cohort study in western Kenya.

BACKGROUND: The artemisinin anti-malarials are widely deployed as artemisinin-based combination therapy (ACT). However, they are not recommended for uncomplicated malaria during the first trimester because safety data from humans are scarce. METHODS: This was a prospective cohort study of women of child-bearing age carried out in 2011-2013, evaluating the relationship between inadvertent ACT exposure during first trimester and miscarriage. Community-based surveillance was used to identify 1134 early pregnancies. Cox proportional hazard models with left truncation were used. RESULTS: The risk of miscarriage among pregnancies exposed to ACT (confirmed + unconfirmed) in the first trimester, or during the embryo-sensitive period (≥6 to <13 weeks gestation) was higher than among pregnancies unexposed to anti-malarials in the first trimester: hazard ratio (HR) = 1.70, 95 % CI (1.08-2.68) and HR = 1.61 (0.96-2.70). For confirmed ACT-exposures (primary analysis) the corresponding values were: HR = 1.24 (0.56-2.74) and HR = 0.73 (0.19-2.82) relative to unexposed women, and HR = 0.99 (0.12-8.33) and HR = 0.32 (0.03-3.61) relative to quinine exposure, but the numbers of quinine exposures were very small. CONCLUSION: ACT exposure in early pregnancy was more common than quinine exposure. Confirmed inadvertent artemisinin exposure during the potential embryo-sensitive period was not associated with increased risk of miscarriage. Confirmatory studies are needed to rule out a smaller than three-fold increase in risk.

The impact of home-based HIV counseling and testing on care-seeking and incidence of common infectious disease syndromes in rural western Kenya.

BACKGROUND: In much of Africa, most individuals living with HIV do not know their status. Home-based counseling and testing (HBCT) leads to more HIV-infected people learning their HIV status. However, there is little data on whether knowing one's HIV-positive status necessarily leads to uptake of HIV care, which could in turn, lead to a reduction in the prevalence of common infectious disease syndromes. METHODS: In 2008, Kenya Medical Research Institute (KEMRI) in collaboration with the Centers for Disease Control and Prevention (CDC) offered HBCT to individuals (aged ≥13 years) under active surveillance for infectious disease syndromes in Lwak in rural western Kenya. HIV test results were linked to morbidity and healthcare-seeking data collected by field workers through bi-weekly home visits. We analyzed changes in healthcare seeking behaviors using proportions, and incidence (expressed as episodes per person-year) of acute respiratory illness (ARI), severe acute respiratory illness (SARI), acute febrile illness (AFI) and diarrhea among first-time HIV testers in the year before and after HBCT, stratified by their test result and if HIV-positive, whether they sought care at HIV Patient Support Centers (PSCs). RESULTS: Of 9,613 individuals offered HBCT, 6,366 (66%) were first-time testers, 698 (11%) of whom were HIV-infected. One year after HBCT, 50% of HIV-infected persons had enrolled at PSCs - 92% of whom had started cotrimoxazole and 37% of those eligible for antiretroviral treatment had initiated therapy. Among HIV-infected persons enrolled in PSCs, AFI and diarrhea incidence decreased in the year after HBCT (rate ratio [RR] 0.84; 95% confidence interval [CI] 0.77 - 0.91 and RR 0.84, 95% CI 0.73 - 0.98, respectively). Among HIV-infected persons not attending PSCs and among HIV-uninfected persons, decreases in incidence were significantly lower. While decreases also occurred in rates of respiratory illnesses among HIV-positive persons in care, there were similar decreases in the other two groups. CONCLUSIONS: Large scale HBCT enabled a large number of newly diagnosed HIV-infected persons to know their HIV status, leading to a change in care seeking behavior and ultimately a decrease in incidence of common infectious disease syndromes through appropriate treatment and care.

Preparing for human papillomavirus vaccine introduction in Kenya: implications from focus-group and interview discussions with caregivers and opinion leaders in Western Kenya.

BACKGROUND: Cervical cancer claims the lives of 275,000 women each year; most of these deaths occur in low-or middle-income countries. In Kenya, cervical cancer is the leading cause of cancer-related mortality among women of reproductive age. Kenya's Ministry of Public Health and Sanitation has developed a comprehensive strategy to prevent cervical cancer, which includes plans for vaccinating preteen girls against human papillomavirus (HPV) by 2015. To identify HPV vaccine communication and mobilization needs, this research sought to understand HPV vaccine-related perceptions and concerns of male and female caregivers and community leaders in four rural communities of western Kenya. METHODS: We conducted five focus groups with caregivers (n = 56) and 12 key-informant interviews with opinion leaders to explore cervical cancer-related knowledge, attitudes and beliefs, as well as acceptability of HPV vaccination for 9-12 year-old girls. Four researchers independently reviewed the data and developed codes based on questions in interview guides and topics that emerged organically, before comparing and reconciling results through a group consensus process. RESULTS: Cervical cancer was not commonly recognized, though it was understood generally in terms of its symptoms. By association with cancer and genital/reproductive organs, cervical cancer was feared and stigmatized. Overall acceptability of a vaccine that prevents cervical cancer was high, so long as it was endorsed by trusted agencies and communities were sensitized first. Some concerns emerged related to vaccine safety (e.g., impact on fertility), program intent, and health equity. CONCLUSION: For successful vaccine introduction in Kenya, there is a need for communication and mobilization efforts to raise cervical cancer awareness; prompt demand for vaccination; address health equity concerns and stigma; and minimize potential resistance. Visible endorsement by government leaders and community influencers can provide reassurance of the vaccine's safety, efficacy and benefits for girls and communities. Involvement of community leadership, parents and champions may also be critical for combatting stigma and making cervical cancer relevant to Kenyan communities. These findings underscore the need for adequate planning and resources for information, education and communication prior to vaccine introduction. Specific recommendations for communication and social-marketing strategies are made.

Perspectives of men on antenatal and delivery care service utilisation in rural western Kenya: a qualitative study.

BACKGROUND: Poor utilisation of facility-based antenatal and delivery care services in Kenya hampers reduction of maternal mortality. Studies suggest that the participation of men in antenatal and delivery care is associated with better health care seeking behaviour, yet many reproductive health programs do not facilitate their involvement. This qualitative study conducted in rural Western Kenya, explored men's perceptions of antenatal and delivery care services and identified factors that facilitated or constrained their involvement. METHODS: Eight focus group discussions were conducted with 68 married men between 20-65 years of age in May 2011. Participants were of the Luo ethnic group residing in Asembo, western Kenya. The area has a high HIV-prevalence and polygamy is common. A topic guide was used to guide the discussions and a thematic framework approach for data analysis. RESULTS: Overall, men were positive in their views of antenatal and delivery care, as decision makers they often encouraged, some even 'forced', their wives to attend for antenatal or delivery care. Many reasons why it was beneficial to accompany their wives were provided, yet few did this in practice unless there was a clinical complication. The three main barriers relating to cultural norms identified were: 1) pregnancy support was considered a female role; and the male role that of provider; 2) negative health care worker attitudes towards men's participation, and 3) couple unfriendly antenatal and delivery unit infrastructure. CONCLUSION: Although men reported to facilitate their wives' utilisation of antenatal and delivery care services, this does not translate to practice as adherence to antenatal-care schedules and facility based delivery is generally poor. Equally, reasons proffered why they should accompany their wives are not carried through into practice, with barriers outweighing facilitators. Recommendations to improve men involvement and potentially increase services utilisation include awareness campaigns targeting men, exploring promotion of joint HIV testing and counselling, staff training, and design of couple friendly antenatal and delivery units.

Moving toward tuberculosis elimination: implementation of statewide targeted tuberculin testing in Tennessee.

RATIONALE: From 1993 to 2010, annual U.S. tuberculosis (TB) rates declined by 58%. However, this decline has slowed and disproportionately occurred among U.S.-born (78%) versus foreign-born persons (47%). Addressing the high burden of latent TB infection (LTBI) must be prioritized. OBJECTIVES: Only Tennessee has implemented a statewide program for finding and treating people with LTBI. The program was designed to address high statewide TB rates and growing burden among the foreign-born. We sought to assess the feasibility and yield of Tennessee's program. METHODS: Analyzing data from the 4.8-year period from program inception in March 2002 through December 2006, we quantified patients screened using a TB risk assessment tool, tuberculin skin tests (TST) placed and read, TST results, and patients initiating and completing LTBI treatment. We then estimated the number needed to screen to find and treat one person with LTBI and to prevent one case of TB. MEASUREMENTS AND MAIN RESULTS: Of 168,517 persons screened, 102,709 had a TST placed and read. Among 9,090 (9%) with a positive TST result, 53% initiated treatment, 54% of whom completed treatment. An estimated 195 TB cases were prevented over the 4.8 years analyzed, and program performance measures improved annually. The number of TSTs placed to prevent one TB case ranged from 150 for foreign-born persons to 9,834 for persons without TB risk. CONCLUSIONS: Targeted tuberculin testing and LTBI treatment is feasible and likely to reduce TB rates over time. Yield and cost-effectiveness are maximized by prioritizing foreign-born persons, a large population with high TB risk.