Infectious and Parasitic Diseases
Rationale; Division addresses infectious diseases and the neglected diseases particularly diarrheal diseases, Leishmaniasis and other emerging diseases.
Infectious and parasitic diseases are not only a matter that threatens the lives of individuals in developing countries but also pose a serious impediment to the social and economic development of these countries. Infectious and parasitic diseases take a particularly heavy toll on the poor. The risk of infection in developing countries is heightened by the high rate of population growth, poverty, gender disparities, fragile healthcare and medical systems, inadequate preventive, care and treatment services, lack of safe water supply, malnutrition, etc. Poor health in turn aggravates poverty. There is therefore a pressing need to break such vicious cycle of poor health and poverty. Fighting Infectious and parasitic diseases should be a central part of the development programs of developing countries, particularly in the efforts of poverty reduction.
- Undertake research and surveillance of HIV/AIDS, Malaria and other infective agents
- Develop tools for diagnosis and screening of infectious diseases.
- Conduct clinical trials on drugs and tools for the disease
- Test solutions for management of HIV/AIDS and Malaria through implementation science
- Undertake drug response and surveillance
- Support development of policies for control of HIV, Malaria and other agents
Dr. Benson Singa
Dr. Bernard Oguttu
Dr. Nelly Mugo
Dr. Janet Oyieko
Dr. Allan Otieno
Dr. Benson Singa
PROFESSIONAL/WORK /RESEARCH EXPERIENCE:
Benson Singa is a research scientist at the Kenya Medical Research Institute’s, Centre for Clinical Research, Reproductive Health Research Unit. He has been a close collaborator on several studies of helminth, malaria, STI and HIV co-infection over the past years including programmatic evaluation.
Dr. Singa has served as a Principal Investigator (PI), a co-investigator and a medical coordinator on these studies. Singa’s background interest is in Public Health especially Sexual Reproductive Adolescent and Child Health (SRACH). These interest encompass both preventive, promotive and curative services. Additionally, Benson has interests in tropical medicine especially immune modulation and interaction between tropical diseases and HIV with having been involved in studies on current emerging issues and progress in this field especially given the continuing concern of barely contained tropical diseases and HIV infection around the globe. Currently, Benson is involved in evaluating ongoing programs especially PMTCT program and HIV in children and adolescents in a bid to improve the preventive programs being implemented in the healthcare set up. Additionally, Dr. Singa has been involved in multi-Country, multi-site research studies (including clinical trials) in the area of Diarrhoea and Childhood Acute Illness and Nutrition.
Research Grants/Current/Previous last three (3) years:
- zithromycin to prevent post-discharge morbidity and mortality in Kenyan children: A protocol for a randomized, double-blind, placebo-controlled trial.(Co-PI)
An estimated 3.5 million deaths occur annually in children less than five years of age in Sub-Saharan Africa, approximately 70% of which are due to infectious causes. One-year mortality rates as high as 15% have been documented following hospital discharge in sub-Saharan Africa, a rate that is 8-fold higher than non-hospitalized children.[7-9] Children being discharged from hospital in Africa may represent an accessible high-risk population in which to target interventions to reduce mortality.
A recent trial of mass drug administration of azithromycin reduced childhood mortality by half among children in Ethiopia in communities receiving the intervention.[10, 11] However, concerns about the potential for the emergence of antimicrobial resistance, possible toxicity, and the feasibility of delivery are all barriers to community-wide distribution of antibiotics.
Targeted chemotherapeutic interventions, including the use of cotrimoxazole among HIV-infected children and the use of amoxicillin or cefdinir among malnourished children, have been shown to reduce mortality in these specific vulnerable populations.[12-15] Children who have been recently hospitalized
are a high-risk population in which a similar targeted approach to azithromycin distribution may optimize benefit while reducing both individual and population level risks.
The mechanisms by which azithromycin may impact morbidity and mortality have not been well described. Among high-risk pediatric populations with history of recent illness, azithromycin may act by treating residual disease not eliminated during inpatient therapy, by providing prophylaxis from future infectious exposures during a time of immune suppression and vulnerability following illness, by treating underlying enteric dysfunction and associated mucosal immune/gut barrier disruption and inflammation, and/or by clearing asymptomatic carriage of potentially pathogenic organisms.
We propose a randomized, double-blind, placebo-controlled trial of a 5-day course of azithromycin in children age 1 to 59 months discharged from Kisii Teaching and Homabay county Referral hospitals in Western Kenya to reduce post-discharge re-hospitalizations and mortality, to explore possible mechanisms by which azithromycin has benefit and risk, and to identify correlates and intermediate markers of re-hospitalization and death in the post-discharge period.
The proposed Toto Bora study will examine a pragmatic post-discharge intervention that could be used in low resource settings to lower mortality and re-hospitalization rates in high-risk children. In addition the trial will also explore a number of scientific questions including the effect of antibiotics on enteric and nasopharyngeal infections
inflammation, and the causes of post-discharge mortality. Kisii and Homabay counties are the ideal areas in Western Kenya to test this intervention because the child mortality rate is high in Nyanza province yet the health facilities in which this Toto Bora study will be conducted have established pediatric research infrastructure.
- The Childhood Acute Illness & Nutrition Network: Building the evidence base for care of acutely ill, undernourished children in limited resource settings – cohort study (Site PI)
Summary: Undernutrition is the most important overall risk factor for childhood death in developing countries, underlying 45% of all childhood deaths worldwide.1 Undernutrition has a strong relationship with acute illness and death from common infectious diseases, such as pneumonia and diarrhoea. Despite implementation of national and international guidelines, undernourished young children with acute illness continue to have a markedly increased risk of death during hospital admission that persists following discharge. In recent reviews of the evidence that underlies current guidelines, it is clear that much of current practice is based on ‘low-quality’ evidence or no evidence at all.2 To move forward, a better understanding of the problem is needed.
This protocol concerns the three Kenyan sites contributing to an international prospective observational study across a network of sites in Africa and South Asia that aims to gain a better understanding of risk factors and mechanisms that could be targeted by interventions to lower mortality. Factors may be biological (e.g. related to infection, immunity and metabolism), nutritional (e.g. breast-feeding or diet), environmental (water and sanitation, crowding), related to the health system (e.g. access, care provision) or social (e.g. economic, childcare and health seeking behaviour). A harmonised set of data and samples will be collected across all sites.
Each site will enrol 500 acutely ill children aged 2 months to 23 months across a spectrum of nutritional status at admission to hospital and follow them up through discharge from hospital, then for a further six months. In addition, 100 children in the community who are not acutely ill will be recruited at a single time-point in order to establish community norms for demographic and biological factors. These community norms will be used to define recovery from acute illness and will help the study establish why acutely ill children remain at risk of death after apparent recovery defined by current clinical tools.
The primary endpoint will be status after six months, classified as: i) death in hospital; ii) death post-discharge; iii) readmission to hospital; iv) moderate or severe acute malnutrition; or v) a good recovery (none of the above). The frequency of these endpoints will be described along with their risk factors. Secondary analysis, including laboratory parameters examining nutrition, metabolism, infection and immunity that are measured later, will be undertaken using a nested case-control design. Children with the outcomes noted above will be compared to children who are admitted with acute illness and who experience good recovery in order to determine underlying mechanisms associated with increased risk. The extent to which children who experience poor outcomes differ from non-acutely ill children in the community, and whether these children recover post-discharge to become similar to community peers, will also be investigated.
To examine social and behavioural factors in more depth, and to support responsive ethical practice across all of the research activities, qualitative work in the Kilifi and Mbagathi hospital sites will be undertaken. Interviews will be held in each site with health providers, research staff, community representatives and parents of children. Observations will also be conducted of a range of parents’ encounters with the health system, focusing on admission, ward rounds, and discharge.
The project will provide a better understanding in order to the identify and prioritize interventions to improve survival in this high risk population. Through this process, we seek to identify potential interventions to take forward into clinical trials that will form the basis of future protocols. The network will serve as a platform for such multi-centre trials, with appropriately trained staff, adequate data and sample collection systems and optimal reporting mechanisms. The ultimate goal of this work is improved evidence for the care of undernourished children to improve survival and healthy growth and development.
- Program evaluation of a novel standardized national package of services for adolescents living with HIV in Kenya (Co-PI)
The Adolescent package of Services (APS) includes an adolescent care booklet developed by the Kenyan MOH (2013), health provider training in adolescent HIV care, disclosure and sexual and reproductive health education guidelines, provision of adolescent reproductive health services, and a standardized adolescent checklist regarding follow up activities. APS will be introduced to 20 HIV clinics in four regions (Central, Western, Nyanza, North and South Rift) in Kenya using a stepped wedge cluster randomized design. The primary objective of this evaluation is to implement and evaluate the Adolescent Package of Services (APS) in selected clinics. The primary outcome is adolescent HIV disclosure. Secondary outcomes include adolescent sexual risk behavior, pregnancy, sexual and reproductive health education (SRHE), screening of sexually transmitted infections (STIs), partner and family HIV testing ART adherence, viral suppression, and transition to HIV adult clinic. APS will be evaluated quantitatively (includes surveys) and qualitatively (focus group discussions) to assess the impact of APS. The study duration will span 30 months. This evaluation will inform the national program on adolescent health outcomes, successes and challenges with implementation of APS in Kenya and will identify the gaps that need to be addressed moving forward. Appendix 1 provides an overview of APS implementation and evaluation.
- Maternal Administered Malnutrition Monitoring System (MAMMS) Trial (Co-PI)
Acute malnutrition affects 52 million children, costs $2.1 trillion globally, and contributes to 45% of deaths among children under five years of age. Affordable home-based treatments can prevent many of these deaths, with success rates >97.5% if malnutrition is identified early. If identified late, treatment failure rates increase to 16%. Malnutrition programs currently rely on community health volunteers to screen children, which can lead to high costs, low screening coverage, and late identification.
MUAC is the preferred community malnutrition screening tool. Evidence has shown that mothers can accurately measure their child’s MUAC and identify malnutrition. Yet, there is no method of linking these mothers to the nutritional care that malnourished children require. Training mothers to use MUAC tapes to monitor their child’s nutritional status through a short message service (SMS) mobile health system could increase screening coverage and facilitate rapid engagement with nutritional services where necessary.
We propose to test the “Maternal Administered Malnutrition Monitoring System” (MAMMS) in a randomized controlled trial in Kenya. Mothers will be taught to measure their child’s MUAC at 6 or 9-month immunization visits and during 6-month follow up they will receive a weekly SMS prompting them to measure and send their child’s MUAC to a computer system which will alert a health worker when a child with malnutrition is identified. This scalable system could enable nutrition programs to optimize screening coverage, leading to early identification of malnutrition, lower costs and a reduction in under-five mortality.
Recruitment is anticipated to take 2 years following receipt of ethical approvals from the University of Washington and Kenya Medical Research Institute. Data will be managed in accordance with Good Clinical Practice and Health Insurance Portability and Accountability Act requirements. Results will be shared with the clinic and community at local and international meetings. The primary manuscripts will be published within 2-years of study completion.
- Nnedu ON, John-Stewart GC, Singa BO, Piper B, Otieno PA, Guidry A, Richardson BA, Walson J, 2012. Prevalence and correlates of insecticide-treated bednet use among HIV-1-infected adults in Kenya. AIDS Care 24: 1559-64.
- Walson J, Singa B, Sangare L, Naulikha J, Piper B, Richardson B, Otieno PA, Mbogo LW, Berkley JA, John-Stewart G, 2012. Empiric deworming to delay HIV disease progression in adults with HIV who are ineligible for initiation of antiretroviral treatment (the HEAT study): a multi-site, randomised trial. Lancet Infect Dis 12: 925-32.
- Arndt MB, John-Stewart G, Richardson BA, Singa B, van Lieshout L, Verweij JJ, Sangare LR, Mbogo LW, Naulikha JM, Walson JL, 2013. Impact of helminth diagnostic test performance on estimation of risk factors and outcomes in HIV-positive adults. PLoS One 8: e81915.
- Singa B, Glick SN, Bock N, Walson J, Chaba L, Odek J, McClelland RS, Djomand G, Gao H, John-Stewart G, 2013. Sexually transmitted infections among HIV-infected adults in HIV care programs in Kenya: a national sample of HIV clinics. Sex Transm Dis 40: 148-53.
- Walson JL, Sangare LR, Singa BO, Naulikha JM, Piper BK, Yuhas K, Onchiri FM, Otieno PA, Mermin J, Zeh C, Richardson BA, John-Stewart G, 2013. Evaluation of impact of long-lasting insecticide-treated bed nets and point-of-use water filters on HIV-1 disease progression in Kenya. AIDS 27: 1493-501.
- Gerns Storey HL, Richardson BA, Singa B, Naulikha J, Prindle VC, Diaz-Ochoa VE, Felgner PL, Camerini D, Horton H, John-Stewart G, Walson JL, 2014. Use of principal components analysis and protein microarray to explore the association of HIV-1-specific IgG responses with disease progression. AIDS Res Hum Retroviruses 30: 37-44.
- Pavlinac PB, John-Stewart GC, Naulikha JM, Onchiri FM, Denno DM, Odundo EA, Singa BO, Richardson AB, Walson JL, 2014. High-risk enteric pathogens associated with HIV infection and HIV exposure in Kenyan children with acute diarrhoea. AIDS.
- Pavlinac PB, Naulikha JM, Chaba L, Kimani N, Sangare LR, Yuhas K, Singa BO, John-Stewart G, Walson JL, 2014. Water Filter Provision and Home-Based Filter Reinforcement Reduce Diarrhea in Kenyan HIV-Infected Adults and Their Household Members. Am J Trop Med Hyg 91: 273-80
- Onchiri FM, Pavlinac PB, Singa BO, Naulikha JM, Odundo EA, Farquhar C, Farquhar, C, Richardson BA, John-Stewart G, Walson, JL. Bacteremia Among Febrile Children in Areas of Differing Malaria Transmission in Rural Kenya: A Prospective Cross-sectional study. Journal of the Pediatric Infectious Disease Society (JPIDS). (In press)
- Pavlinac PB, Naulikha JM, John-Stewart GC, Onchiri FM, Okumu AO, Sitati RN, Cranmer LM, Lokken EM, Singa BO, Walson JL. Mycobacterium tuberculosis bacteremia among acutely febrile children in Western Kenya. American Journal of Tropical Medicine & Hygiene (AJTMH). (In press)
- Pavlinac PB, Denno DM, John-Stewart GC, Onchiri FM, Naulikha JM, Odundo EA, Hulseberg CE, Singa BO, Manhart LE, Walson JL. Failure of syndrome-based diarrhea management guidelines to detect Shigella infections in Kenyan children. Journal of the Pediatric Infectious Disease Society (JPIDS). (In press)
- Onchiri FM, Pavlinac PB, Singa BO, Naulikha JM, Odundo EA, Farquhar C, Farquhar, C, Richardson BA, John-Stewart G, Walson, JL. Frequency and correlates of malaria over-treatment in areas of differing malaria transmission: a cross-sectional study in rural Western Kenya. Malaria Journal 2015,14:97; PMC4349314
- Pavlinac PB, John-Stewart GC, Naulikha JM, Onchiri FM, Denno DM, Odundo EA, Singa BO, Richardson AB, Walson JL. High-risk enteric pathogens associated with HIV infection and HIV exposure in Kenyan children with acute diarrhoea. AIDS 2014; 28: 2287-2296; PMC4346243
- Onchiri, Frankline M.; Pavlinac, Patricia B.; Singa, Benson O.; Naulikha, Jacqueline M.; Odundo, Elizabeth A.; Farquhar, Carey; Richardson, Barbra A.; John-Stewart, Grace; Walson, Judd L.: Low Bacteremia Prevalence Among Febrile Children in Areas of Differing Malaria Transmission in Rural Kenya: A Cross-Sectional Study. Journal of the Pediatric Infectious Diseases Society; Dec2016, Vol. 5 Issue 4, p385-394.
- Ronen, Keshet; McGrath, Christine J.; Langat, Agnes C.; Kinuthia, John; Omolo, Danvers; Singa, Benson; Katana, Abraham K.; Ng’Ang’A, Lucy W.; John- Stewart, Grace. Gaps in Adolescent Engagement in Antenatal Care and Prevention of Mother-to-Child HIV Transmission Services in Kenya. JAIDS: Journal of Acquired Immune Deficiency Syndromes; 1/1/2017, Vol. 74 Issue 1, p30-37.
- Pavlinac, Patricia B.; Singa, Benson O.; John-Stewart, Grace C.; Richardson, Barbra A.; Brander, Rebecca L.; McGrath, Christine J.; Tickell, Kirkby D.; Amondi, Mary; Rwigi, Doreen; Babigumira, Joseph B.; Kariuki, Sam; Nduati, Ruth; Walson, Judd L. Azithromycin to prevent post-discharge morbidity and mortality in Kenyan children: a protocol for a randomised, double-blind, placebo-controlled trial (the Toto Bora trial). BMJ Open; Dec2017, Vol. 7 Issue 12, p1-11.
- Tickell, Kirkby D.; Pavlinac, Patricia B.; John-Stewart, Grace C.; Denno, Donna M.; Richardson, Barbra A.; Naulikha, Jaqueline M.; Kirera, Ronald K.; Swierczewski, Brett E.; Singa, Benson O.; Walson, Judd L. Impact of Childhood Nutritional Status on Pathogen Prevalence and Severity of Acute Diarrhea. American Journal of Tropical Medicine & Hygiene; Nov2017, Vol. 97 Issue 5, p1337-1344
- Pintye, Jillian; Langat, Agnes; Singa, Benson; Kinuthia, John; Odeny, Beryne; Katana, Abraham; Nganga, Lucy; John-Stewart, Grace; McGrath, Christine J. Maternal tenofovir disoproxil fumarate use in pregnancy and growth outcomes among HIV-exposed uninfected infants in Kenya. Infectious Diseases in Obstetrics and Gynecology. Annual, 2016
- Kinuthia, John; Singa, Benson; McGrath, Christine J.; Odeny, Beryne; Langat, Agnes; Katana, Abraham; Ng’ang’a, Lucy; Pintye, Jillian; John-Stewart, Grace. Prevalence and correlates of non-disclosure of maternal HIV status to male partners: a national survey in Kenya. BMC Public Health. May 30, 2018, Vol. 18 Issue 1
- Polyak, Christina S.; Yuhas, Krista; Singa, Benson; Khaemba, Monica; Walson, Judd; Richardson, Barbra A.; John-Stewart, Grace. Cotrimoxazole Prophylaxis Discontinuation among Antiretroviral-Treated HIV-1-Infected Adults in Kenya: A Randomized Non-inferiority Trial. PLoS Medicine (PLOS MED), 1/5/2016; 13(1): 1-16.
- Ottichilo, Ronald K.; Polyak, Christina S.; Guyah, Bernard; Singa, Benson; Nyataya, Josphat; Yuhas, Krista; John-Stewart, Grace; Waitumbi, John N. Malaria Parasitemia and Parasite Density in Antiretroviral-Treated HIV-Infected Adults Following Discontinuation of Cotrimoxazole Prophylaxis. Journal of Infectious Diseases (J INFECT DIS), Jan2017; 215(1): 88-94