Sammy Khagayi

HIV/AIDS-related mortality in Africa and Asia: evidence from INDEPTH health and demographic surveillance system sites.

Background As the HIV/AIDS pandemic has evolved over recent decades, Africa has been the most affected region, even though a large proportion of HIV/AIDS deaths have not been documented at the individual level. Systematic application of verbal autopsy (VA) methods in defined populations provides an opportunity to assess the mortality burden of the pandemic from individual data. Objective To present standardised comparisons of HIV/AIDS-related mortality at sites across Africa and Asia, including closely related causes of death such as pulmonary tuberculosis (PTB) and pneumonia. Design Deaths related to HIV/AIDS were extracted from individual demographic and VA data from 22 INDEPTH sites across Africa and Asia. VA data were standardised to WHO 2012 standard causes of death assigned using the InterVA-4 model. Between-site comparisons of mortality rates were standardised using the INDEPTH 2013 standard population. Results The dataset covered a total of 10,773 deaths attributed to HIV/AIDS, observed over 12,204,043 person-years. HIV/AIDS-related mortality fractions and mortality rates varied widely across Africa and Asia, with highest burdens in eastern and southern Africa, and lowest burdens in Asia. There was evidence of rapidly declining rates at the sites with the heaviest burdens. HIV/AIDS mortality was also strongly related to PTB mortality. On a country basis, there were strong similarities between HIV/AIDS mortality rates at INDEPTH sites and those derived from modelled estimates. Conclusions Measuring HIV/AIDS-related mortality continues to be a challenging issue, all the more so as anti-retroviral treatment programmes alleviate mortality risks. The congruence between these results and other estimates adds plausibility to both approaches. These data, covering some of the highest mortality observed during the pandemic, will be an important baseline for understanding the future decline of HIV/AIDS.Background As the HIV/AIDS pandemic has evolved over recent decades, Africa has been the most affected region, even though a large proportion of HIV/AIDS deaths have not been documented at the individual level. Systematic application of verbal autopsy (VA) methods in defined populations provides an opportunity to assess the mortality burden of the pandemic from individual data. Objective To present standardised comparisons of HIV/AIDS-related mortality at sites across Africa and Asia, including closely related causes of death such as pulmonary tuberculosis (PTB) and pneumonia. Design Deaths related to HIV/AIDS were extracted from individual demographic and VA data from 22 INDEPTH sites across Africa and Asia. VA data were standardised to WHO 2012 standard causes of death assigned using the InterVA-4 model. Between-site comparisons of mortality rates were standardised using the INDEPTH 2013 standard population. Results The dataset covered a total of 10,773 deaths attributed to HIV/AIDS, observed over 12,204,043 person-years. HIV/AIDS-related mortality fractions and mortality rates varied widely across Africa and Asia, with highest burdens in eastern and southern Africa, and lowest burdens in Asia. There was evidence of rapidly declining rates at the sites with the heaviest burdens. HIV/AIDS mortality was also strongly related to PTB mortality. On a country basis, there were strong similarities between HIV/AIDS mortality rates at INDEPTH sites and those derived from modelled estimates. Conclusions Measuring HIV/AIDS-related mortality continues to be a challenging issue, all the more so as anti-retroviral treatment programmes alleviate mortality risks. The congruence between these results and other estimates adds plausibility to both approaches. These data, covering some of the highest mortality observed during the pandemic, will be an important baseline for understanding the future decline of HIV/AIDS.

Age-specific malaria mortality rates in the KEMRI/CDC health and demographic surveillance system in western Kenya, 2003-2010.

Recent global malaria burden modeling efforts have produced significantly different estimates, particularly in adult malaria mortality. To measure malaria control progress, accurate malaria burden estimates across age groups are necessary. We determined age-specific malaria mortality rates in western Kenya to compare with recent global estimates. We collected data from 148,000 persons in a health and demographic surveillance system from 2003–2010. Standardized verbal autopsies were conducted for all deaths; probable cause of death was assigned using the InterVA-4 model. Annual malaria mortality rates per 1,000 person-years were generated by age group. Trends were analyzed using Poisson regression. From 2003–2010, in children <5 years the malaria mortality rate decreased from 13.2 to 3.7 per 1,000 person-years; the declines were greatest in the first three years of life. In children 5–14 years, the malaria mortality rate remained stable at 0.5 per 1,000 person-years. In persons ≥15 years, the malaria mortality rate decreased from 1.5 to 0.4 per 1,000 person-years. The malaria mortality rates in young children and persons aged ≥15 years decreased dramatically from 2003–2010 in western Kenya, but rates in older children have not declined. Sharp declines in some age groups likely reflect the national scale up of malaria control interventions and rapid expansion of HIV prevention services. These data highlight the importance of age-specific malaria mortality ascertainment and support current strategies to include all age groups in malaria control interventions.

Estimation of the National Disease Burden of Influenza- Associated Severe Acute Respiratory Illness in Kenya and Guatemala: A Novel Methodology

Background Knowing the national disease burden of severe influenza in low-income countries can inform policy decisions around influenza treatment and prevention. We present a novel methodology using locally generated data for estimating this burden. Methods and Findings This method begins with calculating the hospitalized severe acute respiratory illness (SARI) incidence for children <5 years old and persons ≥5 years old from population-based surveillance in one province. This base rate of SARI is then adjusted for each province based on the prevalence of risk factors and healthcare-seeking behavior. The percentage of SARI with influenza virus detected is determined from provincial-level sentinel surveillance and applied to the adjusted provincial rates of hospitalized SARI. Healthcare-seeking data from healthcare utilization surveys is used to estimate non-hospitalized influenza-associated SARI. Rates of hospitalized and non-hospitalized influenza-associated SARI are applied to census data to calculate the national number of cases. The method was field-tested in Kenya, and validated in Guatemala, using data from August 2009–July 2011. In Kenya (2009 population 38.6 million persons), the annual number of hospitalized influenza-associated SARI cases ranged from 17,129–27,659 for children <5 years old (2.9–4.7 per 1,000 persons) and 6,882–7,836 for persons ≥5 years old (0.21–0.24 per 1,000 persons), depending on year and base rate used. In Guatemala (2011 population 14.7 million persons), the annual number of hospitalized cases of influenza-associated pneumonia ranged from 1,065–2,259 (0.5–1.0 per 1,000 persons) among children <5 years old and 779–2,252 cases (0.1–0.2 per 1,000 persons) for persons ≥5 years old, depending on year and base rate used. In both countries, the number of non-hospitalized influenza-associated cases was several-fold higher than the hospitalized cases. Conclusions Influenza virus was associated with a substantial amount of severe disease in Kenya and Guatemala. This method can be performed in most low and lower-middle income countries.

Childhood cause-specific mortality in rural Western Kenya: application of the InterVA-4 model

Background Assessing the progress in achieving the United Nations Millennium Development Goals in terms of population health requires consistent and reliable information on cause-specific mortality, which is often rare in resource-constrained countries. Health and demographic surveillance systems (HDSS) have largely used medical personnel to review and assign likely causes of death based on the information gathered from standardized verbal autopsy (VA) forms. However, this approach is expensive and time consuming, and it may lead to biased results based on the knowledge and experience of individual clinicians. We assessed the cause-specific mortality for children under 5 years old (under-5 deaths) in Siaya County, obtained from a computer-based probabilistic model (InterVA-4). Design Successfully completed VA interviews for under-5 deaths conducted between January 2003 and December 2010 in the Kenya Medical Research Institute/US Centers for Disease Control and Prevention HDSS were extracted from the VA database and processed using the InterVA-4 (version 4.02) model for interpretation. Cause-specific mortality fractions were then generated from the causes of death produced by the model. Results A total of 84.33% (6,621) childhood deaths had completed VA data during the study period. Children aged 1–4 years constituted 48.53% of all cases, and 42.50% were from infants. A single cause of death was assigned to 89.18% (5,940) of cases, 8.35% (556) of cases were assigned two causes, and 2.10% (140) were assigned ‘indeterminate’ as cause of death by the InterVA-4 model. Overall, malaria (28.20%) was the leading cause of death, followed by acute respiratory infection including pneumonia (25.10%), in under-5 children over the study period. But in the first 5 years of the study period, acute respiratory infection including pneumonia was the main cause of death, followed by malaria. Similar trends were also reported in infants (29 days–11 months) and children aged 1–4 years. Conclusions Under-5 cause-specific mortality obtained using the InterVA-4 model is consistent with existing knowledge on the burden of childhood diseases in rural western Kenya.

What are the most sensitive and specific sign and symptom combinations for influenza in patients hospitalized with acute respiratory illness? Results from western Kenya, January 2007–July 2010

Influenza causes severe illness and deaths, and global surveillance systems use different clinical case definitions to identify patients for diagnostic testing. We used data collected during January 2007-July 2010 at hospital-based influenza surveillance sites in western Kenya to calculate sensitivity, specificity, positive predictive value, and negative predictive value for eight clinical sign/symptom combinations in hospitalized patients with acute respiratory illnesses, including severe acute respiratory illness (SARI) (persons aged 2-59 months: cough or difficulty breathing with an elevated respiratory rate or a danger sign; persons aged ≥5 years: temperature ≥38 °C, difficulty breathing, and cough or sore throat) and influenza-like illness (ILI) (all ages: temperature ≥38 °C and cough or sore throat). Overall, 4800 persons aged ≥2 months were tested for influenza; 416 (9%) had laboratory-confirmed influenza infections. The symptom combination of cough with fever (subjective or measured ≥38 °C) had high sensitivity [87·0%, 95% confidence interval (CI) 83·3-88·9], and ILI had high specificity (70·0%, 95% CI 68·6-71·3). The case definition combining cough and any fever is a simple, sensitive case definition for influenza in hospitalized persons of all age groups, whereas the ILI case definition is the most specific. The SARI case definition did not maximize sensitivity or specificity.

Influenza and Malaria Coinfection Among Young Children in Western Kenya, 2009–2011

BACKGROUND Although children <5 years old in sub-Saharan Africa are vulnerable to both malaria and influenza, little is known about coinfection. METHODS This retrospective, cross-sectional study in rural western Kenya examined outpatient visits and hospitalizations associated with febrile acute respiratory illness (ARI) during a 2-year period (July 2009-June 2011) in children <5 years old. RESULTS Across sites, 45% (149/331) of influenza-positive patients were coinfected with malaria, whereas only 6% (149/2408) of malaria-positive patients were coinfected with influenza. Depending on age, coinfection was present in 4%-8% of outpatient visits and 1%-3% of inpatient admissions for febrile ARI. Children with influenza were less likely than those without to have malaria (risk ratio [RR], 0.57-0.76 across sites and ages), and children with malaria were less likely than those without to have influenza (RR, 0.36-0.63). Among coinfected children aged 24-59 months, hospital length of stay was 2.7 and 2.8 days longer than influenza-only-infected children at the 2 sites, and 1.3 and 3.1 days longer than those with malaria only (all P < .01). CONCLUSIONS Coinfection with malaria and influenza was uncommon but associated with longer hospitalization than single infections among children 24-59 months of age.

High burden of rotavirus gastroenteritis in young children in rural western Kenya, 2010-2011.

Background: Diarrhea is a leading cause of hospitalization and death in children <5 years of age. Objectives: To facilitate evaluation of the impact of rotavirus vaccine introduction in western Kenya, we estimated baseline rates of rotavirus-associated hospitalization and mortality among children <5 years of age. Methods: From January 2010 to December 2011, we collected demographic, clinical and laboratory data for children <5 years of age seeking care at the district hospital and 2 outpatient facilities within a Health and Demographic Surveillance System (HDSS). Children with acute gastroenteritis (AGE), defined as ≥3 loose stools and/or ≥1 episode of unexplained vomiting followed by loose stool within a 24-hour period, were asked to provide a stool sample for rotavirus ELISA testing. Rates of rotavirus-associated hospitalization and mortality were estimated using time of residence in the HDSS to calculate person-years of observation. To estimate the rotavirus-associated mortality rate, we applied the percentage positive for rotavirus among AGE hospitalizations to verbal autopsy estimates of diarrhea deaths in the HDSS. Results: There were 4991 hospitalizations of children <5 years of age; 1134 (23%) were for AGE and stool specimens were obtained from 790 (70%). Rotavirus was detected in 211 (27%) specimens. Among 4951 <5 outpatient sick visits, 608 (12%) were for AGE; 320 (51%) provided specimens and 62 (20%) were positive for rotavirus. Rotavirus AGE accounted for 501 <5 hospitalizations per 100,000 person-years of observation. Rotavirus-associated <5 mortality was 136 deaths per 100,000 person-years of observation. Conclusions: Continued surveillance of rotavirus AGE will provide timely data on the population-level impact of rotavirus vaccine following its likely introduction in 2014.

Deaths ascribed to non-communicable diseases among rural Kenyan adults are proportionately increasing: evidence from a health and demographic surveillance system, 2003-2010

Background Non-communicable diseases (NCDs) result in more deaths globally than other causes. Monitoring systems require strengthening to attribute the NCD burden and deaths in low and middle-income countries (LMICs). Data from health and demographic surveillance systems (HDSS) can contribute towards this goal. Methods and Findings Between 2003 and 2010, 15,228 deaths in adults aged 15 years (y) and older were identified retrospectively using the HDSS census and verbal autopsy in rural western Kenya, attributed into broad categories using InterVA-4 computer algorithms; 37% were ascribed to NCDs, 60% to communicable diseases (CDs), 3% to injuries, and <1% maternal causes. Median age at death for NCDs was 66y and 71y for females and males, respectively, with 43% (39% male, 48% female) of NCD deaths occurring prematurely among adults aged below 65y. NCD deaths were mainly attributed to cancers (35%) and cardio-vascular diseases (CVDs; 29%). The proportionate mortality from NCDs rose from 35% in 2003 to 45% in 2010 (χ2 linear trend 93.4; p<0.001). While overall annual mortality rates (MRs) for NCDs fell, cancer-specific MRs rose from 200 to 262 per 100,000 population, mainly due to increasing deaths in adults aged 65y and older, and to respiratory neoplasms in all age groups. The substantial fall in CD MRs resulted in similar MRs for CDs and NCDs among all adult females by 2010. NCD MRs for adults aged 15y to <65y fell from 409 to 183 per 100,000 among females and from 517 to 283 per 100,000 population among males. NCD MRs were higher among males than females aged both below, and at or above, 65y. Conclusions NCDs constitute a significant proportion of deaths in rural western Kenya. Evidence of the increasing contribution of NCDs to overall mortality supports international recommendations to introduce or enhance prevention, screening, diagnosis and treatment programmes in LMICs.

Comparison of severe acute respiratory illness (sari) and clinical pneumonia case definitions for the detection of influenza virus infections among hospitalized patients, western Kenya, 2009‐2013

Although the severe acute respiratory illness (SARI) case definition is increasingly used for inpatient influenza surveillance, pneumonia is a more familiar term to clinicians and policymakers. We evaluated WHO case definitions for severe acute respiratory illness (SARI) and pneumonia (Integrated Management of Childhood Illnesses (IMCI) for children aged <5 years and Integrated Management of Adolescent and Adult Illnesses (IMAI) for patients aged ≥13 years) for detecting laboratory‐confirmed influenza among hospitalized ARI patients. Sensitivities were 84% for SARI and 69% for IMCI pneumonia in children aged <5 years and 60% for SARI and 57% for IMAI pneumonia in patients aged ≥13 years. Clinical pneumonia case definitions may be a useful complement to SARI for inpatient influenza surveillance.

Risk of Injection-Site Abscess among Infants Receiving a Preservative-Free, Two-Dose Vial Formulation of Pneumococcal Conjugate Vaccine in Kenya

There is a theoretical risk of adverse events following immunization with a preservative-free, 2-dose vial formulation of 10-valent-pneumococcal conjugate vaccine (PCV10). We set out to measure this risk. Four population-based surveillance sites in Kenya (total annual birth cohort of 11,500 infants) were used to conduct a 2-year post-introduction vaccine safety study of PCV10. Injection-site abscesses occurring within 7 days following vaccine administration were clinically diagnosed in all study sites (passive facility-based surveillance) and, also, detected by caregiver-reported symptoms of swelling plus discharge in two sites (active household-based surveillance). Abscess risk was expressed as the number of abscesses per 100,000 injections and was compared for the second vs first vial dose of PCV10 and for PCV10 vs pentavalent vaccine (comparator). A total of 58,288 PCV10 injections were recorded, including 24,054 and 19,702 identified as first and second vial doses, respectively (14,532 unknown vial dose). The risk ratio for abscess following injection with the second (41 per 100,000) vs first (33 per 100,000) vial dose of PCV10 was 1.22 (95% confidence interval [CI] 0.37–4.06). The comparator vaccine was changed from a 2-dose to 10-dose presentation midway through the study. The matched odds ratios for abscess following PCV10 were 1.00 (95% CI 0.12–8.56) and 0.27 (95% CI 0.14–0.54) when compared to the 2-dose and 10-dose pentavalent vaccine presentations, respectively. In Kenya immunization with PCV10 was not associated with an increased risk of injection site abscess, providing confidence that the vaccine may be safely used in Africa. The relatively higher risk of abscess following the 10-dose presentation of pentavalent vaccine merits further study.