Henry Njuguna

Population-based incidence of typhoid fever in an urban informal settlement and a rural area in Kenya: Implications for typhoid vaccine use in Africa

Background High rates of typhoid fever in children in urban settings in Asia have led to focus on childhood immunization in Asian cities, but not in Africa, where data, mostly from rural areas, have shown low disease incidence. We set out to compare incidence of typhoid fever in a densely populated urban slum and a rural community in Kenya, hypothesizing higher rates in the urban area, given crowding and suboptimal access to safe water, sanitation and hygiene. Methods During 2007-9, we conducted population-based surveillance in Kibera, an urban informal settlement in Nairobi, and in Lwak, a rural area in western Kenya. Participants had free access to study clinics; field workers visited their homes biweekly to collect information about acute illnesses. In clinic, blood cultures were processed from patients with fever or pneumonia. Crude and adjusted incidence rates were calculated. Results In the urban site, the overall crude incidence of Salmonella enterica serovar Typhi (S. Typhi) bacteremia was 247 cases per 100,000 person-years of observation (pyo) with highest rates in children 5–9 years old (596 per 100,000 pyo) and 2–4 years old (521 per 100,000 pyo). Crude overall incidence in Lwak was 29 cases per 100,000 pyo with low rates in children 2–4 and 5–9 years old (28 and 18 cases per 100,000 pyo, respectively). Adjusted incidence rates were highest in 2–4 year old urban children (2,243 per 100,000 pyo) which were >15-fold higher than rates in the rural site for the same age group. Nearly 75% of S. Typhi isolates were multi-drug resistant. Conclusions This systematic urban slum and rural comparison showed dramatically higher typhoid incidence among urban children <10 years old with rates similar to those from Asian urban slums. The findings have potential policy implications for use of typhoid vaccines in increasingly urban Africa.

Influenza Surveillance in 15 Countries in Africa, 2006-2010

BACKGROUND In response to the potential threat of an influenza pandemic, several international institutions and governments, in partnership with African countries, invested in the development of epidemiologic and laboratory influenza surveillance capacity in Africa and the African Network of Influenza Surveillance and Epidemiology (ANISE) was formed. METHODS We used a standardized form to collect information on influenza surveillance system characteristics, the number and percent of influenza-positive patients with influenza-like illness (ILI), or severe acute respiratory infection (SARI) and virologic data from countries participating in ANISE. RESULTS Between 2006 and 2010, the number of ILI and SARI sites in 15 African countries increased from 21 to 127 and from 2 to 98, respectively. Children 0-4 years accounted for 48% of all ILI and SARI cases of which 22% and 10%, respectively, were positive for influenza. Influenza peaks were generally discernible in North and South Africa. Substantial cocirculation of influenza A and B occurred most years. CONCLUSIONS Influenza is a major cause of respiratory illness in Africa, especially in children. Further strengthening influenza surveillance, along with conducting special studies on influenza burden, cost of illness, and role of other respiratory pathogens will help detect novel influenza viruses and inform and develop targeted influenza prevention policy decisions in the region.

Epidemiology, seasonality, and burden of influenza and influenza-like illness in Urban and Rural Kenya, 2007-2010

BACKGROUND The epidemiology and burden of influenza remain poorly defined in sub-Saharan Africa. Since 2005, the Kenya Medical Research Institute and Centers for Disease Control and Prevention-Kenya have conducted population-based infectious disease surveillance in Kibera, an urban informal settlement in Nairobi, and in Lwak, a rural community in western Kenya. METHODS Nasopharyngeal and oropharyngeal swab specimens were obtained from patients who attended the study clinic and had acute lower respiratory tract (LRT) illness. Specimens were tested for influenza virus by real-time reverse-transcription polymerase chain reaction. We adjusted the incidence of influenza-associated acute LRT illness to account for patients with acute LRT illness who attended the clinic but were not sampled. RESULTS From March 2007 through February 2010, 4140 cases of acute LRT illness were evaluated in Kibera, and specimens were collected from 1197 (27%); 319 (27%) were positive for influenza virus. In Lwak, there were 6733 cases of acute LRT illness, and specimens were collected from 1641 (24%); 359 (22%) were positive for influenza virus. The crude and adjusted rates of medically attended influenza-associated acute LRT illness were 6.9 and 13.6 cases per 1000 person-years, respectively, in Kibera, and 5.6 and 23.0 cases per 1000 person-years, respectively, in Lwak. In both sites, rates of influenza-associated acute LRT illness were highest among children <2 years old and lowest among adults ≥50 years old. CONCLUSION In Kenya, the incidence of influenza-associated acute LRT illness was high in both rural and urban settings, particularly among the most vulnerable age groups.

Epidemiology of Respiratory Syncytial Virus Infection in Rural and Urban Kenya

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

Severe Acute Respiratory Illness Deaths in Sub-Saharan Africa and the Role of Influenza: A Case Series From 8 Countries

Abstract Background. Data on causes of death due to respiratory illness in Africa are limited. Methods. From January to April 2013, 28 African countries were invited to participate in a review of severe acute respiratory illness (SARI)–associated deaths identified from influenza surveillance during 2009–2012. Results. Twenty-three countries (82%) responded, 11 (48%) collect mortality data, and 8 provided data. Data were collected from 37 714 SARI cases, and 3091 (8.2%; range by country, 5.1%–25.9%) tested positive for influenza virus. There were 1073 deaths (2.8%; range by country, 0.1%–5.3%) reported, among which influenza virus was detected in 57 (5.3%). Case-fatality proportion (CFP) was higher among countries with systematic death reporting than among those with sporadic reporting. The influenza-associated CFP was 1.8% (57 of 3091), compared with 2.9% (1016 of 34 623) for influenza virus–negative cases (P < .001). Among 834 deaths (77.7%) tested for other respiratory pathogens, rhinovirus (107 [12.8%]), adenovirus (64 [6.0%]), respiratory syncytial virus (60 [5.6%]), and Streptococcus pneumoniae (57 [5.3%]) were most commonly identified. Among 1073 deaths, 402 (37.5%) involved people aged 0–4 years, 462 (43.1%) involved people aged 5–49 years, and 209 (19.5%) involved people aged ≥50 years. Conclusions. Few African countries systematically collect data on outcomes of people hospitalized with respiratory illness. Stronger surveillance for deaths due to respiratory illness may identify risk groups for targeted vaccine use and other prevention strategies.

Results From the First Six Years of National Sentinel Surveillance for Influenza in Kenya, July 2007–June 2013

Background Recent studies have shown that influenza is associated with significant disease burden in many countries in the tropics, but until recently national surveillance for influenza was not conducted in most countries in Africa. Methods In 2007, the Kenyan Ministry of Health with technical support from the CDC-Kenya established a national sentinel surveillance system for influenza. At 11 hospitals, for every hospitalized patient with severe acute respiratory illness (SARI), and for the first three outpatients with influenza-like illness (ILI) per day, we collected both nasopharyngeal and oropharyngeal swabs. Beginning in 2008, we conducted in-hospital follow-up for SARI patients to determine outcome. Specimens were tested by real time RT-PCR for influenza A and B. Influenza A-positive specimens were subtyped for H1, H3, H5, and (beginning in May 2009) A(H1N1)pdm09. Results From July 1, 2007 through June 30, 2013, we collected specimens from 24,762 SARI and 14,013 ILI patients. For SARI and ILI case-patients, the median ages were 12 months and 16 months, respectively, and 44% and 47% were female. In all, 2,378 (9.6%) SARI cases and 2,041 (14.6%) ILI cases were positive for influenza viruses. Most influenza-associated SARI cases (58.6%) were in children <2 years old. Of all influenza-positive specimens, 78% were influenza A, 21% were influenza B, and 1% were influenza A/B coinfections. Influenza circulated in every month. In four of the six years influenza activity peaked during July–November. Of 9,419 SARI patients, 2.7% died; the median length of hospitalization was 4 days. Conclusions During six years of surveillance in Kenya, influenza was associated with nearly 10 percent of hospitalized SARI cases and one-sixth of outpatient ILI cases. Most influenza-associated SARI and ILI cases were in children <2 years old; interventions to reduce the burden of influenza, such as vaccine, could consider young children as a priority group.

Use of Population-based Surveillance to Define the High Incidence of Shigellosis in an Urban Slum in Nairobi, Kenya

Background Worldwide, Shigella causes an estimated 160 million infections and >1 million deaths annually. However, limited incidence data are available from African urban slums. We investigated the epidemiology of shigellosis and drug susceptibility patterns within a densely populated urban settlement in Nairobi, Kenya through population-based surveillance. Methods Surveillance participants were interviewed in their homes every 2 weeks by community interviewers. Participants also had free access to a designated study clinic in the surveillance area where stool specimens were collected from patients with diarrhea (≥3 loose stools within 24 hours) or dysentery (≥1 stool with visible blood during previous 24 hours). We adjusted crude incidence rates for participants meeting stool collection criteria at household visits who reported visiting another clinic. Results Shigella species were isolated from 224 (23%) of 976 stool specimens. The overall adjusted incidence rate was 408/100,000 person years of observation (PYO) with highest rates among adults 34–49 years old (1,575/100,000 PYO). Isolates were: Shigella flexneri (64%), S. dysenteriae (11%), S. sonnei (9%), and S. boydii (5%). Over 90% of all Shigella isolates were resistant to trimethoprim-sulfamethoxazole and sulfisoxazole. Additional resistance included nalidixic acid (3%), ciprofloxacin (1%) and ceftriaxone (1%). Conclusion More than 1 of every 200 persons experience shigellosis each year in this Kenyan urban slum, yielding rates similar to those in some Asian countries. Provision of safe drinking water, improved sanitation, and hygiene in urban slums are needed to reduce disease burden, in addition to development of effective Shigella vaccines.

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.

Viral Shedding in Patients Infected with Pandemic Influenza A (H1N1) Virus in Kenya, 2009

Background Understanding shedding patterns of 2009 pandemic influenza A (H1N1) (pH1N1) can inform recommendations about infection control measures. We evaluated the duration of pH1N1 virus shedding in patients in Nairobi, Kenya. Methods Nasopharyngeal (NP) and oropharyngeal (OP) specimens were collected from consenting laboratory-confirmed pH1N1 cases every 2 days during October 14–November 25, 2009, and tested at the Centers for Diseases Control and Prevention-Kenya by real time reverse transcriptase polymerase chain reaction (rRT-PCR). A subset of rRT-PCR-positive samples was cultured. Results Of 285 NP/OP specimens from patients with acute respiratory illness, 140 (49%) tested positive for pH1N1 by rRT-PCR; 106 (76%) patients consented and were enrolled. The median age was 6 years (Range: 4 months–41 years); only two patients, both asthmatic, received oseltamivir. The median duration of pH1N1 detection after illness onset was 8 days (95% CI: 7–10 days) for rRT-PCR and 3 days (Range: 0–13 days) for viral isolation. Viable pH1N1 virus was isolated from 132/162 (81%) of rRT-PCR-positive specimens, which included 118/125 (94%) rRT-PCR-positive specimens collected on day 0–7 after symptoms onset. Viral RNA was detectable in 18 (17%) and virus isolated in 7/18 (39%) of specimens collected from patients after all their symptoms had resolved. Conclusions In this cohort, pH1N1 was detected by rRT-PCR for a median of 8 days. There was a strong correlation between rRT-PCR results and virus isolation in the first week of illness. In some patients, pH1N1 virus was detectable after all their symptoms had resolved.

Secondary Household Transmission of 2009 Pandemic Influenza A (H1N1) Virus among an Urban and Rural Population in Kenya, 2009–2010

Background In Kenya, >1,200 laboratory-confirmed 2009 pandemic influenza A (H1N1) (pH1N1) cases occurred since June 2009. We used population-based infectious disease surveillance (PBIDS) data to assess household transmission of pH1N1 in urban Nairobi (Kibera) and rural Lwak. Methods We defined a pH1N1 patient as laboratory-confirmed pH1N1 infection among PBIDS participants during August 1, 2009–February 5, 2010, in Kibera, or August 1, 2009–January 20, 2010, in Lwak, and a case household as a household with a laboratory-confirmed pH1N1 patient. Community interviewers visited PBIDS-participating households to inquire about illnesses among household members. We randomly selected 4 comparison households per case household matched by number of children aged <5. Comparison households had a household visit 10 days before or after the matched patient symptom onset date. We defined influenza-like illnesses (ILI) as self-reported cough or sore throat, and a self-reported fever ≤8 days after the pH1N1 patients symptom onset in case households and ≤8 days before selected household visit in comparison households. We used the Cochran-Mantel-Haenszel test to compare proportions of ILIs among case and comparison households, and log binomial-model to compare that of Kibera and Lwak. Results Among household contacts of patients with confirmed pH1N1 in Kibera, 4.6% had ILI compared with 8.2% in Lwak (risk ratio [RR], 0.5; 95% confidence interval [CI], 0.3–0.9). Household contacts of patients were more likely to have ILIs than comparison-household members in both Kibera (RR, 1.8; 95% CI, 1.1–2.8) and Lwak (RR, 2.6; 95% CI, 1.6–4.3). Overall, ILI was not associated with patient age. However, ILI rates among household contacts were higher among children aged <5 years than persons aged ≥5 years in Lwak, but not Kibera. Conclusions Substantial pH1N1 household transmission occurred in urban and rural Kenya. Household transmission rates were higher in the rural area.