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The CIDRZ Research Repository serves as an open-access archive for peer-reviewed publications, conference papers, and other scholarly outputs from CIDRZ researchers. Our goal is to promote the dissemination of knowledge and support evidence-based public health initiatives.
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Item Lessons learnt from the first controlled human malaria infection study conducted in Nairobi, Kenya.(2015-Apr-28) Hodgson, Susanne H.; Juma, Elizabeth; Salim, Amina; Magiri, Charles; Njenga, Daniel; Molyneux, Sassy; Njuguna, Patricia; Awuondo, Ken; Lowe, Brett; Billingsley, Peter F.; Cole, Andrew O.; Ogwang, Caroline; Osier, Faith; Chilengi, Roma; Hoffman, Stephen L.; Draper, Simon J.; Ogutu, Bernhards; Marsh, KevinBACKGROUND: Controlled human malaria infection (CHMI) studies, in which healthy volunteers are infected with Plasmodium falciparum to assess the efficacy of novel malaria vaccines and drugs, have become a vital tool to accelerate vaccine and drug development. CHMI studies provide a cost-effective and expeditious way to circumvent the use of large-scale field efficacy studies to deselect intervention candidates. However, to date few modern CHMI studies have been performed in malaria-endemic countries. METHODS: An open-label, randomized pilot CHMI study was conducted using aseptic, purified, cryopreserved, infectious P. falciparum sporozoites (SPZ) (Sanaria® PfSPZ Challenge) administered intramuscularly (IM) to healthy Kenyan adults (n = 28) with varying degrees of prior exposure to P. falciparum. The purpose of the study was to establish the PfSPZ Challenge CHMI model in a Kenyan setting with the aim of increasing the international capacity for efficacy testing of malaria vaccines and drugs, and allowing earlier assessment of efficacy in a population for which interventions are being developed. This was part of the EDCTP-funded capacity development of the CHMI platform in Africa. DISCUSSION: This paper discusses in detail lessons learnt from conducting the first CHMI study in Kenya. Issues pertinent to the African setting, including community sensitization, consent and recruitment are considered. Detailed reasoning regarding the study design (for example, dose and route of administration of PfSPZ Challenge, criteria for grouping volunteers according to prior exposure to malaria and duration of follow-up post CHMI) are given and changes other centres may want to consider for future studies are suggested. CONCLUSIONS: Performing CHMI studies in an African setting presents unique but surmountable challenges and offers great opportunity for acceleration of malaria vaccine and drug development. The reflections in this paper aim to aid other centres and partners intending to use the CHMI model in Africa.Item Prevalence of hypertension and its treatment among adults presenting to primary health clinics in rural Zambia: analysis of an observational database.(2015-Sep-21) Yan, Lily D.; Chi, Benjamin H.; Sindano, Ntazana; Bosomprah, Samuel; Stringer, Jeffrey S.; Chilengi, RomaBACKGROUND: Hypertension constitutes a growing burden of illness in developing countries like Zambia. Adequately screening and treating hypertension could greatly reduce the complications of stroke and coronary disease. Our objective was to determine the prevalence of hypertension and identify current treatment practices among adult patients presenting for routine care to rural health facilities in the Better Health Outcomes through Mentoring and Assessments (BHOMA) project. METHODS: We conducted a retrospective analysis of routinely collected clinical data from 46 rural government clinics in Zambia. Our analysis cohort comprised patients ≥ 25 years with recorded blood pressure measurements, who sought care at primary health centers. Consistent with prior research, in our primary analysis, we only included data from first visits. Hypertension was defined as a systolic blood pressure ≥140 mmHg, or diastolic blood pressure ≥90 mmHg, or reported use of antihypertensive medication. A sensitivity analysis was performed using median blood pressure for individuals with multiple visits. RESULTS AND DISCUSSION: From January 2011 to December 2014, 116,130 first visits by adult patients met eligibility criteria. The crude prevalence of hypertension by onsite measurement or reported use of antihypertensive medication was 23.1% [95% CI: 22.8-23.3] (23.6% in females, 22.3% in males). The age standardized prevalence of hypertension across participating sites was 28.0 [95% CI: 27.7-28.3] (29.7% in females, 25.8% in males). Sensitivity analysis revealed a similar prevalence using data from all visits. Only 5.6% of patients had a diagnosis of hypertension documented in their medical record. Among patients with hypertension, only 18.0% had any antihypertensive drug prescribed, with nifedipine (8.9%), furosemide (8.3%), and propranolol (2.4%) as the most common. CONCLUSIONS: Age standardized prevalence of hypertension in rural primary health clinics in Zambia was high compared to other studies in rural Africa; however, we diagnosed hypertension with only one measurement and this may have biased our findings. Future efforts to improve hypertension control should focus on population preventive care and primary healthcare provider education on individual management.Item Premature adult mortality in urban Zambia: a repeated population-based cross-sectional study.(2016-Mar-03) Rathod, Sujit D.; Timæus, Ian M.; Banda, Richard; Thankian, Kusanthan; Chilengi, Roma; Banda, Andrew; Lemba, Musonda; Stringer, Jeffrey S.; Chi, Benjamin H.OBJECTIVES: To measure the sex-specific and community-specific mortality rates for adults in Lusaka, Zambia, and to identify potential individual-level, household-level and community-level correlates of premature mortality. We conducted 12 survey rounds of a population-based cross-sectional study between 2004 and 2011, and collected data via a structured interview with a household head. SETTING: Households in Lusaka District, Zambia, 2004-2011. PARTICIPANTS: 43,064 household heads (88% female) who enumerated 123,807 adult household members aged between 15 and 60 years. PRIMARY OUTCOME: Premature adult mortality. RESULTS: The overall mortality rate was 16.2/1000 person-years for men and 12.3/1000 person-years for women. The conditional probability of dying between age 15 and 60 (45q15) was 0.626 for men and 0.537 for women. The top three causes of death for men and women were infectious in origin (ie, tuberculosis, HIV and malaria). We observed an over twofold variation of mortality rates between communities. The mortality rate was 1.98 times higher (95% CI 1.57 to 2.51) in households where a family member required nursing care, 1.44 times higher (95% CI 1.22 to 1.71) during the cool dry season, and 1.28 times higher (95% CI 1.06 to 1.54) in communities with low-cost housing. CONCLUSIONS: To meet Zambia's development goals, further investigation is needed into the factors associated with adult mortality. Mortality can potentially be reduced through focus on high-need households and communities, and improved infectious disease prevention and treatment services.Item Theory-based formative research on oral rehydration salts and zinc use in Lusaka, Zambia.(2016-Apr-12) Greenland, Katie; Chipungu, Jenala; Chilengi, Roma; Curtis, ValerieBACKGROUND: A theoretically grounded formative research study was carried out to investigate behaviour related to the use of Oral Rehydration Salts (ORS) and zinc tablets. The purpose was to inform the design of the behaviour change component of the Programme for Awareness and Elimination of Diarrhoea in Lusaka Province, Zambia, which aims to reduce childhood morbidity and mortality from diarrhoeal disease. METHODS: Fourteen behaviour trials were conducted among caregivers of children under-five with diarrhoea. Caregivers were recruited from two clinics situated in rural and peri-urban Lusaka. Trials took ten days and data were captured using video, observation and repeated interviews. Additional data were collected through focus group discussions with mothers, observations in clinics and pharmacies and interviews with clinic and pharmacy staff. Findings were organised according to categories of behavioural determinants from Evo-Eco theory. RESULTS: Participants were all familiar with ORS and most knew its purpose. ORS use was motivated by symptoms of dehydration, rather than the start of a diarrhoea episode, and was stopped when the child had visibly recovered energy. Only four of 14 behaviour trial participants were observed to correctly prepare ORS. Errors were mainly associated with measurement, resulting in a solution that was too concentrated. ORS was not observed to be given to children at clinics. Although zinc was unknown in this population, it was positively received by mothers keen to learn whether zinc would work better than alternative treatments to stop diarrhoea. CONCLUSIONS: ORS was sub-optimally prepared and used at home. It was not used while waiting to be seen at a clinic. In homes, the behaviour change intervention should promote early and continued use of correctly prepared ORS. In the longer-term, these behaviours may best be encouraged by changing the product design or sachet size. Despite its unfamiliarity, this population was well disposed to the use of zinc as a treatment for diarrhoea; when zinc is new to a population, promoting zinc as a solution to stopping diarrhoea, which mothers seek, may drive initial trial. Ensuring the availability of zinc in public clinics and private pharmacies prior to commencement of any promotion activities is crucial.Item Phase 1 randomized controlled trial to evaluate the safety and immunogenicity of recombinant Pichia pastoris-expressed Plasmodium falciparum apical membrane antigen 1 (PfAMA1-FVO [25-545]) in healthy Malian adults in Bandiagara.(2016-Aug-30) Thera, Mahamadou A.; Coulibaly, Drissa; Kone, Abdoulaye K.; Guindo, Ando B.; Traore, Karim; Sall, Abdourhamane H.; Diarra, Issa; Daou, Modibo; Traore, Idrissa M.; Tolo, Youssouf; Sissoko, Mady; Niangaly, Amadou; Arama, Charles; Baby, Mounirou; Kouriba, Bourema; Sissoko, Mahamadou S.; Sagara, Issaka; Toure, Ousmane B.; Dolo, Amagana; Diallo, Dapa A.; Remarque, Edmond ; Chilengi, Roma; Noor, Ramadhani; Sesay, Sanie; Thomas, Alan; Kocken, Clemens H.; Faber, Bart W.; Imoukhuede, Egeruan B.; Leroy, Odile; Doumbo, Ogobara K.BACKGROUND: The safety and immunogenicity of PfAMA1, adjuvanted with Alhydrogel(®) was assessed in malaria-experienced Malian adults. The malaria vaccine, PfAMA1-FVO [25-545] is a recombinant protein Pichia pastoris-expressed AMA-1 from Plasmodium falciparum FVO clone adsorbed to Alhydrogel(®), the control vaccine was tetanus toxoid produced from formaldehyde detoxified and purified tetanus toxin. METHODS: A double blind randomized controlled phase 1 study enrolled and followed 40 healthy adults aged 18-55 years in Bandiagara, Mali, West Africa, a rural setting with intense seasonal transmission of P. falciparum malaria. Volunteers were randomized to receive either 50 µg of malaria vaccine or the control vaccine. Three doses of vaccine were given on Days 0, 28 and 56, and participants were followed for 1 year. Solicited symptoms were assessed for seven days and unsolicited symptoms for 28 days after each vaccination. Serious adverse events were assessed throughout the study. The titres of anti-AMA-1 antibodies were measured by ELISA and P. falciparum growth inhibition assays were performed. RESULTS: Commonest local solicited adverse events were the injection site pain and swelling more frequent in the PfAMA1 group. No vaccine related serious adverse events were reported. A significant 3.5-fold increase of anti-AMA-1 IgG antibodies was observed in malaria vaccine recipients four weeks after the third immunization compared to the control group. CONCLUSION: The PfAMA1 showed a good safety profile. Most adverse events reported were of mild to moderate intensity. In addition, the vaccine induced a significant though short-lived increase in the anti-AMA1 IgG titres. Registered on www.clinicaltrials.gov with the number NCT00431808.Item Norovirus infections in young children in Lusaka Province, Zambia: clinical characteristics and molecular epidemiology.(2017-Jan-23) Howard, Leigh M.; Mwape, Innocent; Siwingwa, Mpanji ; Simuyandi, Michelo; Guffey, Brad M.; Stringer, Jeffrey S.; Chi, Benjamin H.; Edwards, Kathryn M.; Chilengi, RomaBACKGROUND: The burden, clinical features, and molecular epidemiology of norovirus infection in young children in southern Africa are not well defined. METHODS: Using data from a health facility-based surveillance study of children <5 years in Lusaka Province, Zambia presenting with diarrhea, we assessed the burden of norovirus infection. A convenience sample of 454 stool specimens was tested for norovirus using reverse-transcriptase polymerase chain reaction (RT-PCR). RT-PCR positive samples underwent additional nucleotide sequencing for genogroup and genotype identification. Clinical features and severity of diarrheal illnesses were compared between norovirus-positive and -negative subjects using Chi-squared and t-tests. RESULTS: Norovirus was detected in 52/454 (11.5%) specimens tested. Abdominal pain, fever, and vomiting were the most common presenting features in norovirus-associated illnesses. However, there were no significant differences in the clinical features of norovirus-positive compared to norovirus-negative illnesses. Of 43 isolates that were available for sequencing, 31 (72.1%) were genogroup II (GII) and 12 (27.9%) were genogroup I (GI). The distribution of genotypes was diverse. CONCLUSIONS: Noroviruses were detected in approximately 10% of young children with diarrhea in the Lusaka Province of Zambia, with GII representing the majority of infections. These findings support the role of norovirus in symptomatic diarrhea disease in Africa. Further studies are needed to confirm these observations and to evaluate prevention strategies.Item Exploring community participation in project design: application of the community conversation approach to improve maternal and newborn health in Zambia.(2017-Mar-23) Mutale, Wilbroad; Masoso, Chisala; Mwanza, Bisalom; Chirwa, Cindy; Mwaba, Lasidah; Siwale, Zumbe ; Lamisa, Barbara; Musatwe, Dennis; Chilengi, RomaBACKGROUND: The United Nations Development Programme (UNDP) has adopted an approach entitled Community Conversation (CC) to improve community engagement in addressing health challenges. CCs are based on Paulo Freire's transformative communication approach, in which communities pose problems and critically examine their everyday life experiences through discussion. We adopted this approach to engage communities in maternal and newborn health discussions in three rural districts of Zambia, with the aim of developing community-generated interventions. METHODS: Sixty (60) CCs were held in three target districts, covering a total of 20 health facilities. Communities were purposively selected in each district to capture a range of rural and peri-urban areas at varying distances from health facilities. Conversations were held four times in each community between May and September 2014. All conversations were digitally recorded and later transcribed. NVivo version 10 was used for data analysis. RESULTS AND DISCUSSION: The major barriers to accessing maternal health services included geography, limited infrastructure, lack of knowledge, shortage of human resources and essential commodities, and insufficient involvement of male partners. From the demand side, a lack of information and misconceptions, and, from the supply side, inadequately trained health workers with poor attitudes, negatively affected access to maternal health services in target districts either directly or indirectly. At least 17 of 20 communities suggested solutions to these challenges, including targeted community sensitisation on the importance of safe motherhood, family planning and prevention of teenage pregnancy. Community members and key stakeholders committed time and resources to address these challenges with minimal external support. CONCLUSION: We successfully applied the CC approach to explore maternal health challenges in three rural districts of Zambia. CCs functioned as an advocacy platform to facilitate direct engagement with key decision makers within the community and to align priorities while incorporating community views. There was a general lack of knowledge about safe motherhood and family planning in all three districts. However, other problems were unique to health facilities, demonstrating the need for tailored interventions.Item Use of Lot quality assurance sampling surveys to evaluate community health worker performance in rural Zambia: a case of Luangwa district.(2017-Apr-17) Mwanza, Moses; Zulu, Japhet; Topp, Stephanie M.; Musonda, Patrick; Mutale, Wilbroad; Chilengi, RomaBACKGROUND: The Better Health Outcomes through Mentoring and Assessment (BHOMA) project is a cluster randomized controlled trial aimed at reducing age-standardized mortality rates in three rural districts through involvement of Community Health Workers (CHWs), Traditional Birth Attendants (TBAs), and Neighborhood Health Committees (NHCs). CHWs conduct quarterly surveys on all households using a questionnaire that captures key health events occurring within their catchment population. In order to validate contact with households, we utilize the Lot Quality Assurance Sampling (LQAS) methodology. In this study, we report experiences of applying the LQAS approach to monitor performance of CHWs in Luangwa District. METHODS: Between April 2011 and December 2013, seven health facilities in Luangwa district were enrolled into the BHOMA project. The health facility catchment areas were divided into 33 geographic zones. Quality assurance was performed each quarter by randomly selecting zones representing about 90% of enrolled catchment areas from which 19 households per zone where also randomly identified. The surveys were conducted by CHW supervisors who had been trained on using the LQAS questionnaire. Information collected included household identity number (ID), whether the CHW visited the household, duration of the most recent visit, and what health information was discussed during the CHW visit. The threshold for success was set at 75% household outreach by CHWs in each zone. RESULTS: There are 4,616 total households in the 33 zones. This yielded a target of 32,212 household visits by community health workers during the 7 survey rounds. Based on the set cutoff point for passing the surveys (at least 75% households confirmed as visited), only one team of CHWs at Luangwa high school failed to reach the target during round 1 of the surveys; all the teams otherwise registered successful visits in all the surveys. CONCLUSIONS: We have employed the LQAS methodology for assurance that quarterly surveys were successfully done. This methodology proved helpful in identifying poorly performing CHWs and could be useful for evaluating CHW performance in other areas. TRIAL REGISTRATION: Identifier: NCT01942278 . Date of Registration: September 2013.Item Disentangling the effects of a multiple behaviour change intervention for diarrhoea control in Zambia: a theory-based process evaluation.(2017-Oct-17) Greenland, Katie; Chipungu, Jenala; Chilekwa, Joyce; Chilengi, Roma; Curtis, ValBACKGROUND: Diarrhoea is a leading cause of child death in Zambia. As elsewhere, the disease burden could be greatly reduced through caregiver uptake of existing prevention and treatment strategies. We recently reported the results of the Komboni Housewives intervention which tested a novel strategy employing motives including affiliation and disgust to improve caregiver practice of four diarrhoea control behaviours: exclusive breastfeeding; handwashing with soap; and correct preparation and use of oral rehydration salts (ORS) and zinc. The intervention was delivered via community events (women's forums and road shows), at health clinics (group session) and via radio. A cluster randomised trial revealed that the intervention resulted in a small improvement in exclusive breastfeeding practices, but was only associated with small changes in the other behaviours in areas with greater intervention exposure. This paper reports the findings of the process evaluation that was conducted alongside the trial to investigate how factors associated with intervention delivery and receipt influenced caregiver uptake of the target behaviours. METHODS: Process data were collected from the eight peri-urban and rural intervention areas throughout the six-month implementation period and in all 16 clusters 4-6 weeks afterwards. Intervention implementation (fidelity, reach, dose delivered and recruitment strategies) and receipt (participant engagement and responses, and mediators) were explored through review of intervention activity logs, unannounced observation of intervention events, semi-structured interviews, focus groups with implementers and intervention recipients, and household surveys. Evaluation methods and analyses were guided by the intervention's theory of change and the evaluation framework of Linnan and Steckler. RESULTS: Intervention reach was lower than intended: 39% of the surveyed population reported attending one or more face-to-face intervention event, of whom only 11% attended two or more intervention events. The intervention was not equally feasible to deliver in all settings: fewer events took place in remote rural areas, and the intervention did not adequately penetrate communities in several peri-urban sites where the population density was high, the population was slightly higher socio-economic status, recruitment was challenging, and numerous alternative sources of entertainment existed. Adaptations made by the implementers affected the fidelity of implementation of messages for all target behaviours. Incorrect messages were consequently recalled by intervention recipients. Participants were most receptive to the novel disgust and skills-based interactive demonstrations targeting exclusive breastfeeding and ORS preparation respectively. However, initial disgust elicitation was not followed by a change in associated psychological mediators, and social norms were not measurably changed. CONCLUSIONS: The lack of measured behaviour change was likely due to issues with both the intervention's content and its delivery. Achieving high reach and intensity in community interventions delivered in diverse settings is challenging. Achieving high fidelity is also challenging when multiple behaviours are targeted for change. Further work using improved tools is needed to explore the use of subconscious motives in behaviour change interventions. To better uncover how and why interventions achieve their measured effects, process evaluations of complex interventions should develop and employ frameworks for investigation and interpretation that are structured around the intervention's theory of change and the local context. TRIAL REGISTRATION: The study was registered as part of the larger trial on 5 March 2014 with ClinicalTrials.gov: NCT02081521 .Item Immunogenicity of rotavirus vaccine (RotarixTM) in infants with environmental enteric dysfunction.(2017) Mwape, Innocent; Bosomprah, Samuel; Mwaba, John; Mwila-Kazimbaya, Katayi; Laban, Natasha M.; Chisenga, Caroline C.; Sijumbila, Gibson; Simuyandi, Michelo; Chilengi, RomaINTRODUCTION: Deployment of rotavirus vaccines has contributed to significant declines in diarrheal morbidity and mortality globally. Unfortunately, vaccine performance in low-middle income countries (LMICs) is generally lower than in developed countries. The cause for this has been associated with several host and maternal factors including poor water sanitation and hygiene (WASH) status, which are predominant in LMICs. More recently, environmental enteric dysfunction (EED) has specifically been hypothesized to contribute to poor vaccine uptake and response. The aim of this study was to examine the association between serological biomarkers of EED and seroconversion to rotavirus vaccine in Zambian infants. METHODS: This was a retrospective cohort study of 142 infants who had been fully immunized with Rotarix™, and had known seroconversion status. Seroconversion was defined as 4-fold or more increase in rotavirus-specific IgA titres between pre-vaccination and one month post-dose two vaccination. We performed ELISA assays to assess soluble CD14 (sCD14), Endotoxin Core IgG Antibodies (EndoCAb), intestinal fatty acid binding protein (i-FABP) and Zonulin according to the manufacturers protocols. Generalised linear model with family-poisson, link-log and robust standard error was used to estimate the independent effects of biomarkers on seroconversion adjusting for important cofounders. RESULTS: The median concentration of Zonulin, Soluble CD14, EndoCaB, and IFABP were 209.3 (IQR = 39.7, 395.1), 21.5 (IQR = 21.5, 21.5), 0.3 (IQR = 0.3, 0.3), and 107.7 (IQR = 6.4, 1141.4) respectively. In multivariable analyses adjusting for the independent effect of other biomarkers and confounders (i.e. age of child at vaccination, breast-milk anti-rotavirus IgA, infant serum anti-rotavirus IgG, and IgA seropositivity at baseline), there was strong evidence of about 24% increase in seroconversion due to doubling Zonulin concentration (Adjusted risk ratio (aRR) = 1.24; 95% CI = 1.12 to1.37; p<0.0001). Similarly, we found about 7% increase in seroconversion due to doubling IFABP concentration (aRR = 1.07; 95% CI = 1.02 to 1.13; p = 0.006). CONCLUSION: We found that high levels of zonulin and IFABP played a role in seroconversion. It is plausible that increased gut permeability in EED allows greater uptake of the live virus within the vaccine, but later consequences result in deleterious local structural distortions and malabsorption syndromes.