Browsing by Author "Guffey MB"

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A Preliminary Assessment of Rotavirus Vaccine Effectiveness in Zambia.
(2016-May-01) Beres LK; Tate JE; Njobvu L; Chibwe B; Rudd C; Guffey MB; Stringer JS; Parashar UD; Chilengi R; Division of Viral Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia.; Centre for Infectious Disease Research in Zambia, Lusaka Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland.; Centre for Infectious Disease Research in Zambia, Lusaka.; University of North Carolina School of Medicine, Chapel Hill.; CIDRZ; Centre for Infectious Disease Research in Zambia (CIDRZ)
BACKGROUND: Diarrhea is the third leading cause of child death in Zambia. Up to one-third of diarrhea cases resulting in hospitalization and/or death are caused by vaccine-preventable rotavirus. In January 2012, Zambia initiated a pilot introduction of the Rotarix live, oral rotavirus vaccine in all public health facilities in Lusaka Province. METHODS: Between July 2012 and October 2013, we conducted a case-control study at 6 public sector sites to estimate rotavirus vaccine effectiveness (VE) in age-eligible children presenting with diarrhea. We computed the odds of having received at least 1 dose of Rotarix among children whose stool was positive for rotavirus antigen (cases) and children whose stool was negative (controls). We adjusted the resulting odds ratio (OR) for patient age, calendar month of presentation, and clinical site, and expressed VE as (1 - adjusted OR) × 100. RESULTS: A total of 91 rotavirus-positive cases and 298 rotavirus-negative controls who had under-5 card-confirmed vaccination status and were ≥6 months of age were included in the case-control analysis. Among rotavirus-positive children who were age-eligible to be vaccinated, 20% were hospitalized. Against rotavirus diarrhea of all severity, the adjusted 2-dose VE was 26% (95% confidence interval [CI], -30% to 58%) among children ≥6 months of age. VE against hospitalized children ≥6 months of age was 56% (95% CI, -34% to 86%). CONCLUSIONS: We observed a higher point estimate for VE against increased severity of illness compared with milder disease, but were not powered to detect a low level of VE against milder disease.
Causes of morbidity among HIV-infected children on antiretroviral therapy in primary care facilities in Lusaka, Zambia.
(2009-Oct) Mubiana-Mbewe M; Bolton-Moore C; Banda Y; Chintu N; Nalubamba-Phiri M; Giganti M; Guffey MB; Sambo P; Stringer EM; Stringer JS; Chi BH; Centre for Infectious Disease Research in Zambia, Lusaka, Zambia.; CIDRZ; Centre for Infectious Disease Research in Zambia (CIDRZ)
OBJECTIVES: To describe the pattern of incident illness in children after initiation of antiretroviral therapy (ART) in a large public health sector programme in Lusaka, Zambia. METHODS: Systematic chart review to retrospectively extract data from medical records of children (i.e. <15 years) initiating ART in the Lusaka, Zambia public sector. Incident conditions were listed separately and then grouped according to broad categories. Predictors for incident diagnoses were determined using univariate and multivariable analysis. RESULTS: Between May 2004 and June 2006, 1705 HIV-infected children initiated ART. Of these, 1235 (72%) had their medical records reviewed. Median age at ART initiation was 77 months and 554 (45%) were females. Eight hundred and forty-one (68%) children had an incident condition during this period, with a median time of occurrence of 64 days from ART initiation. Twenty-eight incident conditions were documented. When categorized, the most common were mucocutaneous conditions [incidence rate (IR): 70.6 per 100 child-years, 95% CI: 64.5-77.2] and upper respiratory tract infection (IR: 70.1 per 100 child-years; 95% CI: 64.0-76.7). Children with severe immunosuppression (i.e. CD4 < 10%) were more likely to develop lower respiratory tract infection (16.3%vs. 10.2%; P = 0.003) and mucocutaneous conditions (43.9% vs. 35.3%; P = 0.005) than those with CD4 > or = 10%. CONCLUSION: There is a high incidence of new illness after ART initiation, emphasizing the importance of close monitoring during this period. Early initiation of ART and use of antimicrobial prophylaxis may also help to reduce the occurrence of such co-morbidities.
Causes of stillbirth, neonatal death and early childhood death in rural Zambia by verbal autopsy assessments.
(2011-Jul) Turnbull E; Lembalemba MK; Guffey MB; Bolton-Moore C; Mubiana-Mbewe M; Chintu N; Giganti MJ; Nalubamba-Phiri M; Stringer EM; Stringer JS; Chi BH; Centre for Infectious Disease Research in Zambia, Lusaka, Zambia.; CIDRZ; Centre for Infectious Disease Research in Zambia (CIDRZ)
OBJECTIVES: To describe specific causes of the high rates of stillbirth, neonatal death and early child childhood death in Zambia. METHODS: We conducted a household-based survey in rural Zambia. Socio-demographic and delivery characteristics were recorded, alongside a maternal HIV test. Verbal autopsy questionnaires were administered to elicit mortality-related information and independently reviewed by three experienced paediatricians who assigned a cause and contributing factor to death. For this secondary analysis, deaths were categorized into: stillbirths (foetal death ≥28 weeks of gestation), neonatal deaths (≤28 days) and early childhood deaths (>28 days to <2 years). RESULTS: Among 1679 households, information was collected on 148 deaths: 34% stillbirths, 26% neonatal and 40% early childhood deaths. Leading identifiable causes of stillbirth were intrauterine infection (26%) and birth asphyxia (18%). Of 32 neonatal deaths, 38 (84%) occurred within the first week of life, primarily because of infections (37%) and prematurity (34%). The majority of early childhood deaths were caused by suspected bacterial infections (82%). HIV prevalence was significantly higher in mothers who reported an early childhood death (44%) than mothers who did not (17%; P < 0.01). Factors significantly associated with mortality were lower socio-economic status (P < 0.01), inadequate water or sanitation facilities (P < 0.01), home delivery (P = 0.04) and absence of a trained delivery attendant (P < 0.01). CONCLUSION: We provide community-level data about the causes of death among children under 2 years of age. Infectious etiologies for mortality ranked highest. At a public health level, such information may have an important role in guiding prevention and treatment strategies to address perinatal and early childhood mortality.
HPTN 035 phase II/IIb randomised safety and effectiveness study of the vaginal microbicides BufferGel and 0.5% PRO 2000 for the prevention of sexually transmitted infections in women.
(2014-Aug) Guffey MB; Richardson B; Husnik M; Makanani B; Chilongozi D; Yu E; Ramjee G; Mgodi N; Gomez K; Hillier SL; Karim SA; Fred Hutchinson Cancer Research Center, Seattle, Washington, USA Department of Biostatistics, University of Washington, Seattle, Washington, USA.; University of North Carolina Project, Lilongwe, Malawi.; Fred Hutchinson Cancer Research Center, Seattle, Washington, USA.; Department of Obstetrics and Gynaecology, University of Malawi College of Medicine, Blantyre, Malawi.; Department of Psychiatry, University of Pennsylvania, Philadelphia, Pensylvania, USA.; University of KwaZulu-Natal, CAPRISA, Durban, KwaZulu-Natal, South Africa.; Department of Obstetrics and Gynaecology, University of Zimbabwe-University of California San Francisco Collaborative Research Programme, Belgravia, Harare, Zimbabwe.; FHI 360, Science Facilitation, Research Triangle Park, North Carolina, USA.; Department of Obstetrics, Gynecology and Reproductive Sciences, Magee-Womens Research Institute, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.; HIV Prevention Research Unit, South African Medical Research Council, Durban, KwaZulu-Natal, South Africa.; Departments of Medicine and Pediatrics, University of Alabama at Birmingham, Birmingham, Alabama, USA Centre for Infectious Disease Research in Zambia, Lusaka, Zambia.; CIDRZ; Centre for Infectious Disease Research in Zambia (CIDRZ)
OBJECTIVES: To estimate the effectiveness of candidate microbicides BufferGel and 0.5% PRO 2000 Gel (P) (PRO 2000) for prevention of non-ulcerative sexually transmitted infections (STIs). METHODS: Between 2005 and 2007, 3099 women were enrolled in HIV Prevention Trials Network (HPTN) protocol 035, a phase II/IIb evaluation of the safety and effectiveness of BufferGel and PRO 2000 for prevention of STIs, including Neisseria gonorrhoeae (NG), Chlamydia trachomatis (CT) and Trichomonas vaginalis (TV). Incidences of STIs were determined by study arm, and HRs of BufferGel and PRO 2000 versus placebo gel or no gel control groups were computed using discrete time Andersen-Gill proportional hazards model. RESULTS: The overall incidence rates were 1.6/100 person-years at risk (PYAR) for NG, 3.9/100 PYAR for CT and 15.3/100 PYAR for TV. For BufferGel versus placebo gel, HRs were 0.99 (95% CI 0.49 to 2.00), 1.00 (95% CI 0.64 to 1.57) and 0.95 (95% CI 0.71 to 1.25) for prevention of NG, CT and TV, respectively. For PRO 2000, HRs were 1.66 (95% CI 0.90 to 3.06), 1.16 (95% CI 0.76 to 1.79) and 1.18 (95% CI 0.90 to 1.53) for prevention of NG, CT and TV, respectively. CONCLUSIONS: The incidence of STIs was high during HIV Prevention Trials Network 035 despite provision of free condoms and comprehensive risk-reduction counselling, highlighting the need for effective STI prevention programmes in this population. Unfortunately, candidate microbicides BufferGel and PRO2000 had no protective effect against gonorrhoea, chlamydia or trichomoniasis. TRIAL REGISTRATION NUMBER: NCT00074425.
Norovirus infections in young children in Lusaka Province, Zambia: clinical characteristics and molecular epidemiology.
(2017-Jan-23) Howard LM; Mwape I; Siwingwa M; Simuyandi M; Guffey MB; Stringer JS; Chi BH; Edwards KM; Chilengi R; Department of Pediatrics, Division of Pediatric Infectious Diseases, Vanderbilt University Medical Center, D-7228 MCN; 1161 21st Ave S, Nashville, TN, 37232, USA. leigh.howard@vanderbilt.edu.; Centre for Infectious Disease Research in Zambia (CIDRZ), P.O. Box 34681, Lusaka, 10101, Zambia.; Division of Global Women's Health, University of North Carolina (UNC) - Chapel Hill, 130 Mason Farm Rd., 2nd Floor, Campus Box #7030, 27599-7030, Chapel Hill, NC, USA. Roma.Chilengi@cidrz.org.; Division of Global Women's Health, University of North Carolina (UNC) - Chapel Hill, 130 Mason Farm Rd., 2nd Floor, Campus Box #7030, 27599-7030, Chapel Hill, NC, USA.; Centre for Infectious Disease Research in Zambia (CIDRZ), P.O. Box 34681, Lusaka, 10101, Zambia. Roma.Chilengi@cidrz.org.; Department of Pediatrics, Division of Pediatric Infectious Diseases, Vanderbilt University Medical Center, D-7228 MCN; 1161 21st Ave S, Nashville, TN, 37232, USA.
BACKGROUND: 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.
Single genome amplification of proviral HIV-1 DNA from dried blood spot specimens collected during early infant screening programs in Lusaka, Zambia.
(2014-Jul) Seu L; Mwape I; Guffey MB; University of Alabama at Birmingham, Division of Infectious Diseases, 1900 University Boulevard, THT 215E, Birmingham, AL 35294, United States. Electronic address: Innocent.Mwape@cidrz.org.; Centre for Infectious Disease Research Zambia, 5032 Great North Road, P.O. Box 34681, Lusaka, Zambia; University of Alabama at Birmingham, Division of Infectious Diseases, 1900 University Boulevard, THT 215E, Birmingham, AL 35294, United States. Electronic address: ls2026@uab.edu.; Centre for Infectious Disease Research Zambia, 5032 Great North Road, P.O. Box 34681, Lusaka, Zambia; University of Alabama at Birmingham, Division of Infectious Diseases, 1900 University Boulevard, THT 215E, Birmingham, AL 35294, United States. Electronic address: guffey@uab.edu.; CIDRZ; Centre for Infectious Disease Research in Zambia (CIDRZ)
The ability to evaluate individual HIV-1 virions from the quasispecies of vertically infected infants was evaluated in a field setting at the Centre for Infectious Disease Research in Zambia. Infant heel-prick blood specimens were spotted onto dried blood spot (DBS) filter paper cards at government health clinics. Nucleic acid was extracted and used as a template for HIV-1 proviral DNA detection by a commercial Amplicor HIV-1 PCR test (Roche, version 1.5). On samples that tested positive by commercial diagnostic assay, amplification of DNA was performed using an in-house assay of the 5' and 3' region of the HIV-1 genome. Additionally, fragments covering 1200 nucleotides within pol (full length protease and partial reverse transcriptase) and 1400 nucleotides within env (variable 1-variable 5 region) were further analyzed by single genome amplification (SGA). In summary, we have demonstrated an in-house assay for amplifying the 5' and 3' proviral HIV-1 DNA as well as pol and env proviral DNA fragments from DBS cards collected and analyzed entirely in Zambia. In conclusion, this study shows the feasibility of utilizing DBS cards to amplify the whole proviral HIV-1 genome as well as perform SGA on key HIV-1 genes.
Six-month hemoglobin concentration and its association with subsequent mortality among adults on antiretroviral therapy in Lusaka, Zambia.
(2012-Sep-01) Giganti MJ; Limbada M; Mwango A; Moyo C; Mulenga LB; Guffey MB; Mulenga PL; Bolton-Moore C; Stringer JS; Chi BH; Centre for Infectious Disease Research in Zambia, Lusaka, Zambia. giganticidrz@gmail.com; CIDRZ; Centre for Infectious Disease Research in Zambia (CIDRZ)
Little is known about changes in hemoglobin concentration early in the course of antiretroviral therapy and its subsequent relation to survival. We analyzed data for 40,410 HIV-infected adults on antiretroviral therapy in Lusaka, Zambia. Our main exposure of interest was 6-month hemoglobin, but we stratified our analysis by baseline hemoglobin to allow for potential effect modification. Patients with a 6-month hemoglobin <8.5 g/dL, regardless of baseline, had the highest hazard for death after 6 months (hazard ratio: 4.5; 95% confidence interval: 3.3 to 6.3). Future work should look to identify causes of anemia in settings such as ours and evaluate strategies for more timely diagnosis and treatment.