RESUMEN

BACKGROUND: Of the 2 million children living with HIV globally, 90% live in sub-Saharan Africa. Despite antiretroviral therapy, longstanding HIV infection is associated with several chronic complications in children including growth failure, particularly stunting and delayed puberty. Vitamin D deficiency, which is highly prevalent among children living with HIV in sub-Saharan Africa, has further adverse impact on bone health. This trial aims to establish whether supplementation with vitamin D3 and calcium carbonate improves musculoskeletal health among peripubertal children living with HIV. This paper is an update to an already existing protocol that was previously published in Trials in 2022 and details changes in the trial outcomes. METHODS/DESIGN: We will conduct an individually randomised, double-blinded, placebo-controlled trial of weekly high-dose vitamin D3 (20,000 IU) plus daily calcium carbonate (500 mg) supplementation for 48 weeks. Eight hundred and forty children living with HIV aged 11-19 years taking ART for ≥ 6 months will be enrolled and followed up for 96 weeks. The primary outcome is DXA-measured total body less-head bone mineral density Z-score (TBLH-BMD) at 48 weeks and is an update to the previous primary outcome total body less-head bone mineral content adjusted for lean mass (TBLH-BMCLBM) Z-score. The primary outcome was updated to address the substantial differences in distributions of TBLH-BMCLBM Z-score between the two sites as a result of software differences of the DXA machines. Secondary outcomes are DXA-measured TBLH-BMD Z-score adjusted for height at 48 weeks a new secondary outcome, lumbar spine bone mineral apparent density Z-score, number of respiratory infections, lean muscle mass and grip-strength at 48 and 96 weeks, and TBLH-BMD Z-score at 96 weeks. Sub-studies will investigate the effect of the intervention on vitamin D3 pathway metabolites and markers of bone turnover, intestinal microbiota, and innate and acquired immune function. DISCUSSION: This is the largest trial to date of vitamin D supplementation in children living with HIV. Intervening to address deficits in bone accrual through childhood is critical for optimising adolescent and early adult bone health, and prevention of later adult osteoporotic fractures. Trial results will draw attention to the need to screen for and treat long-term comorbidities in children living with HIV in resource-limited settings. TRIAL REGISTRATION: Pan African Clinical Trials Registry PACTR20200989766029. Registered on September 3, 2020. URL of trial registry record: https://pactr.samrc.ac.za TRIAL STATUS: Participant follow-up completed; data analysis ongoing.

Asunto(s)

Densidad Ósea , Carbonato de Calcio , Colecalciferol , Suplementos Dietéticos , Infecciones por VIH , Ensayos Clínicos Controlados Aleatorios como Asunto , Humanos , Colecalciferol/administración & dosificación , Adolescente , Infecciones por VIH/tratamiento farmacológico , Densidad Ósea/efectos de los fármacos , Niño , Carbonato de Calcio/administración & dosificación , Carbonato de Calcio/uso terapéutico , Método Doble Ciego , Masculino , Femenino , Resultado del Tratamiento , Deficiencia de Vitamina D/tratamiento farmacológico , Adulto Joven , Factores de Tiempo , Factores de Edad

RESUMEN

Macronutrient and micronutrient deficiencies are associated with tuberculosis (TB) incidence. However, evidence is limited on the impact of micronutrient (vitamins and minerals) supplementation among underweight individuals. We conducted a secondary data analysis of a randomised controlled trial of lipid nutritional supplements with and without high-dose vitamin and mineral supplementation (LNS-VM vs LNS) for underweight (Body Mass Index [BMI] <18.5 kg/m2) adults with human immunodeficiency virus (HIV) initiating antiretroviral therapy (ART) in Tanzania and Zambia (2011-2013). Incident TB disease diagnoses were extracted from trial records. We used multivariable Cox regression to estimate hazard ratios (HR) for the impact of receiving LNS-VM on TB incidence, and the dose-response relationship between baseline BMI and TB incidence. Overall, 263 (17%) of 1506 participants developed TB disease. After adjusting for age, sex, CD4 count, haemoglobin, and C-reactive protein, receiving LNS-VM was not associated with TB incidence (aHR [95%CI] = 0.93 [0.72-1.20]; p = 0.57) compared to LNS alone. There was strong evidence for an association between lower BMI and incident TB (aHR [95%CI]: 16-16.9kg/m2 = 1.15 [0.82-1.62] and <16kg/m2 = 1.70 [1.26-2.30] compared to 17-18.5kg/m2; linear trend p<0.01). There was strong evidence that the rate of developing TB was lower after initiating ART (p<0.01). In conclusion, the addition of micronutrient supplementation to LNS was not associated with lower TB incidence in this underweight ART-naive population.

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COVID-19 , Niños Huérfanos , Certificado de Defunción , Niño , Humanos , COVID-19/mortalidad , Modelos Estadísticos , Causas de Muerte

RESUMEN

OBJECTIVE: Zambia has embarked on improving the diagnostic capacity by setting up high throughput and accurate machines in the testing process and introduction of dried blood spot (DBS) as a sample type. This was a cross sectional study to verify dried blood spot as a sample type for HIV viral load and early infant diagnosis (EID) on Hologic Panther platform and Evaluate the analytical performance (precision, linearity and measurement of uncertainty) of the Hologic Panther. RESULTS: The specificity and sensitivity of EID performance of Aptima Quant Dx assay on Hologic panther machine against the gold standard machine COBAS Taqman (CAP/CTM) was 100% with an overall agreement of 100%. The quantitative HIV Viral Load (VL) accuracy had a positive correlation of (0.96) obtained against the gold standard (plasma samples) run on COBAS4800 platform. Analytical performance of the Hologic panther machine was evaluated; Precision low positive repeatability 3.50154 and within lab 2.268915 at mean 2.88 concentration and precision high positive repeatability 1.116955 and within lab 2.010677 at mean 5.09 concentration were obtained confirming manufacturers claims. Uncertainty of measurement for this study was found to be ± 71 copies/ml. Linearity studies were determined and all points were within acceptable limits. We therefore recommend DBS as a sample type alternative to plasma for the estimation of HIV-1 viral load and EID diagnosis on the Hologic panther machine.

Asunto(s)

Infecciones por VIH , Humanos , Lactante , Carga Viral , Zambia , Estudios Transversales , Sensibilidad y Especificidad , ARN Viral

RESUMEN

Early life exposures and growth patterns may affect long-term risk of chronic non-communicable diseases (NCD). We followed up in adolescence two Zambian cohorts (n 322) recruited in infancy to investigate how two early exposures - maternal HIV exposure without HIV infection (HEU) and early growth profile - were associated with later anthropometry, body composition, blood lipids, Hb and HbA1c, blood pressure and grip strength. Although in analyses controlled for age and sex, HEU children were thinner, but not shorter, than HIV-unexposed, uninfected (HUU) children, with further control for socio-demographic factors, these differences were not significant. HEU children had higher HDL-cholesterol than HUU children and marginally lower HbA1c but no other biochemical or clinical differences. We identified three early growth profiles - adequate growth, declining and malnourished - which tracked into adolescence when differences in anthropometry and body fat were still seen. In adolescence, the early malnourished group, compared with the adequate group, had lower blood TAG and higher HDL, lower grip strength (difference: -1·87 kg, 95 % CI -3·47, -0·27; P = 0·02) and higher HbA1c (difference: 0·5 %, 95 % CI 0·2, 0·9; P = 0·005). Lower grip strength and higher HbA1c suggest the early malnourished children could be at increased risk of NCD in later life. Including early growth profile in analyses of HIV exposure reduced the associations between HIV and outcomes. The results suggest that perinatal HIV exposure may have no long-term effects unless accompanied by poor early growth. Reducing the risk of young child malnutrition may lessen children's risk of later NCD.

RESUMEN

BACKGROUND: Of the 2 million children living with HIV globally, 90% live in sub-Saharan Africa. Despite antiretroviral therapy, longstanding HIV infection is associated with several chronic complications in children including growth failure, particularly stunting and delayed puberty. Vitamin D deficiency, which is highly prevalent among children living with HIV in sub-Saharan Africa, has a further adverse impact on bone health. This trial aims to establish whether supplementation with vitamin D3 and calcium carbonate improves musculoskeletal health among peripubertal children living with HIV. METHODS/DESIGN: We will conduct an individually randomised, double-blinded, placebo-controlled trial of weekly high-dose vitamin D3 (20,000 IU) plus daily calcium carbonate (500mg) supplementation for 48 weeks. Eight hundred and forty children living with HIV aged 11-19 years taking ART for ≥6 months will be enrolled and followed up for 96 weeks. The primary outcome is total body less-head bone mineral content for lean mass adjusted for height (TBLH-BMCLBM) Z-score at 48 weeks, measured by dual-energy X-ray absorptiometry (DEXA). Secondary outcomes are DEXA-measured lumbar spine bone mineral apparent density Z-score, number of respiratory infections, lean muscle mass and grip strength at 48 and 96 weeks and TBLH-BMCLBM Z-scores at 96 weeks. Sub-studies will investigate the effect of the intervention on vitamin D3 pathway metabolites and markers of bone turnover, intestinal microbiota, and innate and acquired immune function. DISCUSSION: This is the largest trial to date of vitamin D supplementation in children living with HIV. Intervening to address deficits in bone accrual in childhood is critical for optimising adolescent and early adult bone health and prevention of later adult osteoporotic fractures. Trial results will draw attention to the need to screen for and treat long-term comorbidities in children living with HIV in resource-limited settings. TRIAL REGISTRATION: Pan African Clinical Trials Registry PACTR20200989766029 . Registered on 3 September 2020.

Asunto(s)

Carbonato de Calcio , Colecalciferol , Infecciones por VIH , Adolescente , Densidad Ósea , Carbonato de Calcio/uso terapéutico , Niño , Colecalciferol/uso terapéutico , Suplementos Dietéticos , Método Doble Ciego , Infecciones por VIH/diagnóstico , Infecciones por VIH/tratamiento farmacológico , Humanos , Morbilidad , Ensayos Clínicos Controlados Aleatorios como Asunto , Vitamina D , Adulto Joven

RESUMEN

There is limited information as to whether people who experience severe acute malnutrition (SAM) as young children are at increased risk of overweight, high body fat and associated chronic diseases in later life. We followed up, when aged 7-12 years, 100 Zambian children who were hospitalised for SAM before age 2 years and eighty-five neighbourhood controls who had never experienced SAM. We conducted detailed anthropometry, body composition assessment by bioelectrical impedance and deuterium dilution (D2O) and measured blood lipids, Hb and HbA1c. Groups were compared by linear regression following multiple imputation for missing variables. Children with prior SAM were slightly smaller than controls, but differences, controlling for age, sex, socio-economic status and HIV exposure or infection, were significant only for hip circumference, suprailiac skinfold and fat-free mass index by D2O. Blood lipids and HbA1c did not differ between groups, but Hb was lower by 7·8 (95 % CI 0·8, 14·7) g/l and systolic blood pressure was 3·4 (95 % CI 0·4, 6·4) mmHg higher among the prior SAM group. Both anaemia and high HbA1c were common among both groups, indicating a population at risk for the double burden of over- and undernutrition and associated infectious and chronic diseases. The prior SAM children may have been at slightly greater risk than the controls; this was of little clinical significance at this young age, but the children should be followed when older and chronic diseases manifest.

Asunto(s)

Desnutrición , Desnutrición Proteico-Calórica , Desnutrición Aguda Severa , Humanos , Niño , Preescolar , Zambia , Hemoglobina Glucada , Composición Corporal , Antropometría , Enfermedad Crónica , Factores de Riesgo

RESUMEN

BackgroundThe obstetric fistula is a chronic maternal morbidity of global public health concern. The condition is preventable and, in most cases, treatable. Surgicalrepairis themainstay of treatment with varying degrees of success. The aim of this study was to determine the characteristics, surgical outcomes and factors influencing surgical outcomes of women presenting with obstetric fistulas at a Teaching Hospital in Lusaka, Zambia. Methods: Aretrospective review of medical records for all women who underwent obstetric fistula repair surgeryat Women and Newborn Hospital from 2017 to 2019. Descriptive analysis was done. Fischer's exact test was used to measure association between surgical outcomes and variables in the model.: ResultsIn total,18 out of 29 records of patients who underwentfistularepairwereretrievedandanalyzed. Ages ranged from 15 to 47 years, mean age 29years.Overtwothirds(72.23%)weremultiparous, and over 3/4ths (77.8%) underwent caesarean section in the antecedent pregnancy. Success rate for fistula repair was 83%at 2 weeks post-operative.Study findings were inadequate to show a significant association between successful repair and factors in the model. Conclusion: Majority of women presenting with obstetric fistula were multiparous with a history of prolonged labour, delivery by caesarean section and poor birth outcomes. Success rate for obstetric fistula repair at Women and Newborn Hospital was 83% at 2weeks postoperative. Further studies are needed to assess long-term outcomes and factors influencing surgical outcomes.:

Asunto(s)

Humanos , Cesárea , Fístula del Seno Cavernoso de la Carótida , Cirugía General , Enfermedades Vaginales , Anestesia Obstétrica

RESUMEN

Background: Unintended pregnancy is a major public health concern due to its impact on maternal morbidity and mortality. Contraceptive failure is one of the causes of unintended pregnancy. Data on factors associated with contraceptive method failure is scarce. This study therefore aimed to explore factors associated with contraceptive failure. Methodology: Unmatched case-control study was conducted at five Level One Hospitals in Lusaka. Convenience sampling was used to enrol 108 cases for whom pregnancy occurred while on a modern contraceptive method and 108 hospital-based controls who were on a modern contraceptive method and not pregnant. Binary and multiple logistic regressions were utilized for assessment of factors associated with failed contraception. Results: Among the 108 cases, 46 (42.6%), 40 (37%), 17 (15.7%) and 1 (0.9%) were on the oral contraceptive pill, injectable, implant and intrauterine device contraception methods respectively while 2 (1.9%) were on barrier and emergency contraceptive methods respectively. The odds of contraceptive failure when using the oral contraceptive pill was more than 7 times (AOR 7.790, 95% CI 1.210-50.161, p=0.031). Those who had contraception failure were more than 3 times more likely to be younger than 30 years old compared to those whose contraceptive method did not fail (AOR 3.559, 95% CI 1.100-11.521, p=0.034 and AOR 3.596, 95% CI 1.354-9.550, p=0.010 respectively for age groups 18-24 years and 24-30 years old). Other factors associated with higher odds of contraceptive failure were duration of marriage greater than one year, with the highest odds in those married for more than 10 years (AOR 9.744, 95% CI 2.232-42.537, p=0.002), higher social support (AOR 2.402, 95% CI 1.085-5.321, p=0.031), multiparity (AOR 15.299, 95% CI 3.034- 77.151, p=0.001), and duration of use of antecedent contraception method of more than 2-3 years (AOR 4.913, 95% CI 1.662-14.526, p=0.004). Conclusion: The oral contraceptive pill, younger age, marriage duration of more than one year and contraceptive use more than three years were associated with contraceptive failure. Good messaging and counseling on usage of the oral contraceptive pill are recommended.

Asunto(s)

Humanos , Anticoncepción , Efectividad Anticonceptiva , Escuelas de Párvulos , Embarazo no Planeado

RESUMEN

Expedited diagnostic processes for all suspected cervical cancer cases remain essential in the effort to improve clinical outcomes of the disease. However, in some developing countries like Zambia, there is paucity of data that assesses factors influencing diagnostic and treatment turnaround time (TAT) and other metrics vital for quality cancer care. We conducted a retrospective hospital-based study at the Cancer Diseases Hospital (CDH) for cervical cancer cases presenting to the facility between January 2014 and December 2018. Descriptive statistics were used to summarize demographic characteristics while a generalized linear model of the negative binomial was used to assess determinants of overall TAT. Our study included 2121 patient case files. The median age was 49 years (IQR: ±17) and most patients (n = 634, 31%) were aged between 41 and 50 years. The International Federation of Gynaecology and Obstetrics (FIGO) Cancer stage II (n = 941, 48%) was the most prevalent while stage IV (n = 103, 5.2%) was the least. The average diagnostic TAT in public laboratories was 1.48 (95%CI: 1.21-1.81) times longer than in private laboratories. Furthermore, referral delay was 55 days (IQR: 24-152) and the overall TAT (oTAT) was 110 days (IQR: 62-204). The age of the patient, HIV status, stage of cancer and histological subtype did not influence oTAT while marital status influenced oTAT. The observed longer oTAT may increase irreversible adverse health outcomes among cervical cancer patients. There is a need to improve cancer care in Zambia through improved health expenditure especially in public health facilities.

RESUMEN

Cervical cancer is the fourth most common cancer diagnosed among women globally. Effective screening routines and early detection are vital in reducing its disease burden and mortality. Several factors can influence the timely detection and treatment of cervical cancer, especially in low middle-income countries where the burden of this disease is highest. The data presented in this paper relates to the research article "Cervical cancer diagnosis and treatment delays in the developing world: Evidence from a hospital-based study in Zambia". The raw and analysed data include the studied patients' social demographic factors, clinical data concerning the stage and histological subtype of cancer, dates at which the various activities within the cancer treatment pathway occurred and delays to definitive treatment of cervical cancer at Zambia's only cancer treatment facility. Detailing delays to the treatment of cervical cancer allows recognition of specific points in the cancer treatment pathway requiring intervention to effectively improve cancer care and reduce the morbidity and mortality associated with the disease.

RESUMEN

Lipid-based nutrient supplements (LNS) may be beneficial for malnourished HIV-infected patients starting antiretroviral therapy (ART). We assessed the effect of adding vitamins and minerals to LNS on body composition and handgrip strength during ART initiation. ART-eligible HIV-infected patients with BMI <18·5 kg/m2 were randomised to LNS or LNS with added high-dose vitamins and minerals (LNS-VM) from referral for ART to 6 weeks post-ART and followed up until 12 weeks. Body composition by bioelectrical impedance analysis (BIA), deuterium (2H) diluted water (D2O) and air displacement plethysmography (ADP), and handgrip strength were determined at baseline and at 6 and 12 weeks post-ART, and effects of LNS-VM v. LNS at 6 and 12 weeks investigated. BIA data were available for 1461, D2O data for 479, ADP data for 498 and handgrip strength data for 1752 patients. Fat mass tended to be lower, and fat-free mass correspondingly higher, by BIA than by ADP or D2O. At 6 weeks post-ART, LNS-VM led to a higher regain of BIA-assessed fat mass (0·4 (95 % CI 0·05, 0·8) kg), but not fat-free mass, and a borderline significant increase in handgrip strength (0·72 (95 % CI -0·03, 1·5) kg). These effects were not sustained at 12 weeks. Similar effects as for BIA were seen using ADP or D2O but no differences reached statistical significance. In conclusion, LNS-VM led to a higher regain of fat mass at 6 weeks and to a borderline significant beneficial effect on handgrip strength. Further research is needed to determine appropriate timing and supplement composition to optimise nutritional interventions in malnourished HIV patients.

Asunto(s)

Antirretrovirales/efectos adversos , Composición Corporal/efectos de los fármacos , Suplementos Dietéticos , Infecciones por VIH/complicaciones , Fuerza de la Mano , Adolescente , Adulto , Anciano , Antirretrovirales/uso terapéutico , Índice de Masa Corporal , Recuento de Linfocito CD4 , Deuterio , Impedancia Eléctrica , Femenino , Infecciones por VIH/tratamiento farmacológico , Humanos , Lípidos/administración & dosificación , Lípidos/uso terapéutico , Masculino , Desnutrición/complicaciones , Desnutrición/dietoterapia , Persona de Mediana Edad , Minerales/administración & dosificación , Minerales/uso terapéutico , Pletismografía , Tanzanía , Resultado del Tratamiento , Vitaminas/administración & dosificación , Vitaminas/uso terapéutico , Adulto Joven , Zambia

RESUMEN

Malnourished HIV-infected patients starting antiretroviral therapy (ART) are at high risk of early mortality, some of which may be attributed to altered electrolyte metabolism. We used data from a randomised controlled trial of electrolyte-enriched lipid-based nutritional supplements to assess the association of baseline and time-varying serum phosphate and K concentrations with mortality within the first 12 weeks after starting ART. Baseline phosphate results were available from 1764 patients and there were 9096 subsequent serum phosphate measurements, a median of 6 per patient. For serum K there were 1701 baseline and 8773 subsequent measures, a median of 6 per patient. Abnormally high or low serum phosphate was more common than high or low serum K. Controlling for other factors found to affect mortality in this cohort, low phosphate which had not changed from the previous time interval was associated with increased mortality; the same was not true for high phosphate or for high or low K. Both increases and decreases in serum electrolytes from the previous time interval were generally associated with increased mortality, particularly in the electrolyte-supplemented group. The results suggest that changes in serum electrolytes, largely irrespective of the starting point and the direction of change, were more strongly associated with mortality than were absolute electrolyte levels. Although K and phosphate are required for tissue deposition during recovery from malnutrition, further studies are needed to determine whether specific supplements exacerbate physiologically adverse shifts in electrolyte levels during nutritional rehabilitation of ill malnourished HIV patients.

Asunto(s)

Suplementos Dietéticos , Infecciones por VIH/mortalidad , Desnutrición/dietoterapia , Minerales/uso terapéutico , Fósforo/sangre , Potasio/sangre , Vitaminas/uso terapéutico , Adulto , África , Fármacos Anti-VIH/uso terapéutico , Electrólitos/sangre , Femenino , Alimentos Formulados , Infecciones por VIH/sangre , Infecciones por VIH/complicaciones , Infecciones por VIH/tratamiento farmacológico , Humanos , Lípidos , Masculino , Desnutrición/sangre , Desnutrición/complicaciones , Minerales/sangre , Fosfatos/sangre , Equilibrio Hidroelectrolítico

RESUMEN

INTRODUCTION: To evaluate the diagnostic performances of an in-house loop-mediated isothermal amplification (LAMP) kit and the Xpert MTB/RIF test for the diagnosis of pulmonary tuberculosis in a resource-limited setting, this study was performed at the University Teaching Hospital, Ministry of Health, the Republic of Zambia. METHODOLOGY: Two hundred sputum specimens obtained from new tuberculosis (TB) suspects were used for the evaluation of the diagnostic performance of an in-house LAMP kit in comparison with the Xpert MTB/RIF kit. RESULTS: The sensitivity of in-house LAMP and Xpert MTB/RIF was 96.9% and 95.4% in smear-positive samples, 96.8% and 100% in smear-positive/culture-positive samples, and 39.1% and 73.9% in smear-negative/culture-positive samples, respectively. The specificity of in-house LAMP and MTB/RIF kits with culture was 96.5% and 94.5%, respectively. This indicated the superiority of the Xpert MTB/RIF kit; however, mechanical errors during sample processing and the insufficient quantity of samples by Xpert MTB/RIF kit occurred at 2.0% and 19.7%, respectively, comparing to the 100% accessibility of in-house LAMP. CONCLUSIONS: Considering the results obtained in this study together with the easy setup with much simpler equipment, such as an aluminum heat block or water bath, in in-house LAMP compared with real-time polymerase chain reaction equipment in Xpert MTB/RIF kit, the applicability of in-house LAMP for the screening of tuberculosis directly from sputum in resource-limited setting seemed to be high.

RESUMEN

BACKGROUND: In the monitoring of infant and young child feeding, dietary diversity is used as an indicator of micronutrient adequacy; however, their relation may have weakened with the increasing use of fortified complementary foods. OBJECTIVE: The objectives were to assess the relation between dietary diversity and micronutrient adequacy in an urban infant population with a high consumption of fortified foods and to investigate whether dietary diversity and micronutrient adequacy were independently associated with subsequent growth. METHODS: We used longitudinal data on 811 infants in the Chilenje Infant Growth, Nutrition, and Infection Study conducted in Lusaka, Zambia. The relation between mean micronutrient adequacies and dietary diversity scores derived from 24-h diet recalls at 6 mo of age was investigated with the use of Spearman rank correlation. Multiple linear regression was used to assess the association between micronutrient adequacy, dietary diversity, and subsequent growth to 18 mo of age. RESULTS: Overall mean micronutrient density adequacy (MMDA) and MMDA of "problem micronutrients," defined as those micronutrients (calcium, iron, zinc) with mean density adequacies less than half of estimated needs, were correlated with dietary diversity scores (ρ = 0.36 and 0.30, respectively, both P < 0.0001). Consumption of "sentinel foods" (iron rich, fortified, animal source, dairy) showed better correlation with MMDA than with dietary diversity (ρ = 0.58-0.69, all P < 0.0001). In fully adjusted analyses, MMDA calcium, iron, zinc, and dietary diversity, but not overall MMDA, were associated with linear growth to 18 mo (both P ≤ 0.028). CONCLUSIONS: Micronutrient adequacy in infants consuming fortified foods may be more accurately assessed using locally specific sentinel food indicators rather than dietary diversity scores. Nonetheless, dietary diversity has a positive effect on subsequent linear growth apart from that of micronutrient adequacy, warranting its continued monitoring and further investigation into the mechanisms underlying this finding. This trial was registered at www.controlled-trials.com as ISRCTN37460449.

Asunto(s)

Dieta , Alimentos Fortificados , Alimentos Infantiles/análisis , Fenómenos Fisiológicos Nutricionales del Lactante , Micronutrientes/administración & dosificación , Micronutrientes/sangre , Calcio de la Dieta/administración & dosificación , Calcio de la Dieta/sangre , Humanos , Lactante , Hierro de la Dieta/administración & dosificación , Hierro de la Dieta/sangre , Modelos Lineales , Estudios Longitudinales , Evaluación Nutricional , Factores Socioeconómicos , Población Urbana , Zambia , Zinc/administración & dosificación , Zinc/sangre

RESUMEN

BACKGROUND: Breastfeeding imparts beneficial immune protection and nutrition to infants for healthy growth, but it is also a route for human immunodeficiency virus (HIV) and human cytomegalovirus (HCMV) infection. In previous studies, we showed that HCMV adversely affects infant development in Africa, particularly with maternal HIV exposure. In this study, we analyzed infants risks for acquisition of HCMV infection from breastfeeding and compared HIV-positive and HIV-negative mothers. METHODS: Two cohorts were studied in Zambia. (1) Two hundred sixty-one HIV-infected and HIV-uninfected mothers were compared for HCMV deoxyribonucleic acid (DNA) loads and genotypes (glycoprotein gO) in milk from birth to 4 months postpartum. (2) Maternally HIV-exposed and HIV-unexposed infants were compared for HCMV infection risk factors. The second cohort of 460 infants, from a trial of micronutrient-fortified complementary-food to breastfeeding, were studied between 6 and 18 months of age. Human cytomegalovirus seroprevalence was assayed, and logistic regression was used to calculate risk factors for HCMV infection, including maternal HIV exposure and breastfeeding duration. RESULTS: Human cytomegalovirus was detected in breast milk from 3 days to 4 months postpartum, with significantly raised levels in HIV-positive women and independent of genotype. In infants, HCMV antibody seroprevalence was 83% by 18 months age. Longer breastfeeding duration increased infection risk in maternally HIV-unexposed (odds ratio [OR] = 2.69 for 18 months vs <12 months; 95% confidence interval [CI], 0.84-8.59; P = .03) and HIV-exposed infants (OR = 20.37 for >6 months vs never; 95% CI, 3.71-111.70; P < .001). CONCLUSIONS: Prolonged breastfeeding, which is common in Africa, increased risk of HCMV infection in infants. Both HIV-positive and HIV-negative women had extended milk HCMV secretion. Women who were HIV-positive secreted higher HCMV levels, and for longer duration, with their children at increased infection risk. Human cytomegalovirus control is required to maintain health benefits of breastfeeding.

Asunto(s)

Lactancia Materna , Infecciones por Citomegalovirus/transmisión , Infecciones por VIH/complicaciones , Transmisión Vertical de Enfermedad Infecciosa , África del Sur del Sahara , Estudios de Cohortes , Citomegalovirus/aislamiento & purificación , Femenino , Humanos , Lactante , Leche Humana/virología , Madres , Ensayos Clínicos Controlados Aleatorios como Asunto , Factores de Riesgo , Estudios Seroepidemiológicos , Carga Viral

RESUMEN

BACKGROUND: Early growth and health of HIV-exposed, uninfected (HEU) children is poorer than that of their HIV-unexposed, uninfected (HUU) counterparts but there is little information about longer term effects of early HIV exposure. We previously recruited two cohorts of HEU and HUU Zambian infants and documented the poorer infant growth and health of the HEU compared to the HUU children. We followed up HEU and HUU children from these cohorts when they were school-aged and compared their growth, health, biochemical markers of acute or chronic disease, and school grades. METHODS: We recruited 111 HEU and 279 HUU children aged 6-12 years. We measured anthropometry, determined health by questionnaire and clinical examination, viewed the child's most recent school report, and measured blood pressure, haemoglobin (Hb), HbA1c, glucose, cholesterol, and C-reactive protein (CRP). RESULTS: Anthropometric measures were lower among HEU than HUU children, significantly so for hip circumference (age- and sex-adjusted difference -1.74 cm; 95% confidence interval (CI) -3.24, -0.24; P = 0.023) and mid-upper-arm circumference (adjusted difference -0.63 cm, 95% CI -1.23, -0.04; P = 0.037) and with borderline effects for body mass index, thigh circumference and subscapular skinfolds. HEU children had significantly lower total, trunk, and limb fat percentages. All anthropometric and body composition differences became non-significant after adjustment for sociodemographic variables which differed between HEU and HUU children. More HEU than HUU children reported minor illnesses and were prescribed medication at the time of visit. There were no differences in biochemical markers between groups. HEU children had lower math grades than HUU children even after adjustment for socioeconomic variables. CONCLUSIONS: Although HEU children were smaller and had lower percent fat than HUU children, this appeared to be due mainly to their poorer socioeconomic status. Reasons for lower school grades require further research.

Asunto(s)

Desarrollo Infantil , Infecciones por VIH , Estado de Salud , Complicaciones Infecciosas del Embarazo , Efectos Tardíos de la Exposición Prenatal , Logro , Antropometría , Biomarcadores , Composición Corporal , Niño , Estudios Transversales , Femenino , Estudios de Seguimiento , Humanos , Masculino , Embarazo , Factores Socioeconómicos , Zambia

RESUMEN

BACKGROUND: Malnourished HIV-infected African adults are at high risk of early mortality after starting antiretroviral therapy (ART). We hypothesized that short-course, high-dose vitamin and mineral supplementation in lipid nutritional supplements would decrease mortality. METHODS: The study was an individually-randomised phase III trial conducted in ART clinics in Mwanza, Tanzania, and Lusaka, Zambia. Participants were 1,815 ART-naïve non-pregnant adults with body mass index (BMI) <18.5 kg/m² who were referred for ART based on CD4 count <350 cells/µL or WHO stage 3 or 4 disease. The intervention was a lipid-based nutritional supplement either without (LNS) or with additional vitamins and minerals (LNS-VM), beginning prior to ART initiation; supplement amounts were 30 g/day (150 kcal) from recruitment until 2 weeks after starting ART and 250 g/day (1,400 kcal) from weeks 2 to 6 after starting ART. The primary outcome was mortality between recruitment and 12 weeks of ART. Secondary outcomes were serious adverse events (SAEs) and abnormal electrolytes throughout, and BMI and CD4 count at 12 weeks ART. RESULTS: Follow-up for the primary outcome was 91%. Median adherence was 66%. There were 181 deaths in the LNS group (83.7/100 person-years) and 184 (82.6/100 person-years) in the LNS-VM group (rate ratio (RR), 0.99; 95% CI, 0.80-1.21; P = 0.89). The intervention did not affect SAEs or BMI, but decreased the incidence of low serum phosphate (RR, 0.73; 95% CI, 0.55-0.97; P = 0.03) and increased the incidence of high serum potassium (RR, 1.60; 95% CI, 1.19-2.15; P = 0.002) and phosphate (RR, 1.23; 95% CI, 1.10-1.37; P <0.001). Mean CD4 count at 12 weeks post-ART was 25 cells/µL (95% CI, 4-46) higher in the LNS-VM compared to the LNS arm (P = 0.02). CONCLUSIONS: High-dose vitamin and mineral supplementation in LNS, compared to LNS alone, did not decrease mortality or clinical SAEs in malnourished African adults initiating ART, but improved CD4 count. The higher frequency of elevated serum potassium and phosphate levels suggests high-level electrolyte supplementation for all patients is inadvisable but the addition of micronutrient supplements to ART may provide clinical benefits in these patients. TRIAL REGISTRATION: PACTR201106000300631, registered on 1st June 2011.

Asunto(s)

Antirretrovirales/uso terapéutico , Suplementos Dietéticos , Infecciones por VIH/mortalidad , Desnutrición/dietoterapia , Vitaminas/administración & dosificación , Adulto , Índice de Masa Corporal , Recuento de Linfocito CD4 , Electrólitos/sangre , Femenino , Infecciones por VIH/complicaciones , Infecciones por VIH/tratamiento farmacológico , Humanos , Masculino , Desnutrición/complicaciones , Persona de Mediana Edad , Tanzanía , Zambia

RESUMEN

BACKGROUND: Loop-mediated isothermal amplification (LAMP) is a novel strategy which amplifies DNA with high sensitivity and rapidity under isothermal conditions. In the present study, the performance of the repetitive insertion mobile element (RIME)-LAMP and human serum resistance-associated gene (SRA)-LAMP assays were evaluated using clinical specimens obtained from four male patients from Luangwa and Zambezi valleys in Zambia and Zimbabwe, respectively. FINDINGS: The cases reported in this preliminary communication were all first diagnosed by microscopy, through passive surveillance, and confirmed by both RIME-LAMP and SRA-LAMP. A good correlation between microscopy and LAMP was observed and contributed to staging and successful treatment of patient. RIME-LAMP and SRA-LAMP complimented each other well in all the cases. CONCLUSIONS: Both RIME-LAMP and SRA-LAMP were able to detect Trypanosoma brucei rhodesiense DNA in patient blood and CSF and hence confirmed HAT in the parasitaemic patients. Our study indicates that the LAMP technique is a potential tool for HAT diagnosis, staging and may be useful for making therapeutic decisions. However, no statistically significant conclusion may be drawn due to the limited sample size used in the present study. It is thus imperative to conduct a detailed study to further evaluate the potential of LAMP as a bedside diagnostic test for HAT.

Asunto(s)

Técnicas de Amplificación de Ácido Nucleico/métodos , Tripanosomiasis Africana/diagnóstico , Tripanosomiasis Africana/epidemiología , Adulto , Enfermedades Transmisibles Emergentes , Humanos , Masculino , Factores de Tiempo , Zambia/epidemiología , Zimbabwe/epidemiología

RESUMEN

The present randomised trial investigated the effects of feeding Zambian infants from 6 to 18 months old either a richly or basal micronutrient-fortified complementary/replacement food on gut integrity and systemic inflammation. Blood samples were obtained from all infants (n 743) at 6 and 18 months for the assessment of serum C-reactive protein (CRP) and α1-acid glycoprotein (AGP). A subsample of 502 infants, selected from the main cohort to include a larger proportion of infants with HIV-positive mothers, was assigned to lactulose/mannitol gut permeability tests. Lactulose:mannitol (L:M) ratio analyses were adjusted for baseline urinary L:M ratio, socio-economic status, mother's education, season of birth and baseline stunting, and stratified by maternal antenatal HIV status, child's sex, concurrent breast-feeding status and anaemia at baseline. There was no significant difference in geometric mean L:M ratio between the richly fortified and basal-fortified porridge arms at 12 months (0·47 (95 % CI 0·41, 0·55) v. 0·41 (95 % CI 0·34, 0·49); P = 0·16 adjusted). At 18 months, the richly fortified porridge group had a significantly higher geometric mean L:M ratio than the basal-fortified group (0·23 (95 % CI 0·19, 0·28) v. 0·15 (95 % CI 0·12, 0·19); P = 0·02 adjusted). This effect was evident for all stratifications, significantly among boys (P = 0·04), among the infants of HIV-negative mothers (P = 0·01), among the infants of HIV-negative mothers not concurrently breast-fed (P = 0·01) and among those who were not anaemic at baseline (P = 0·03). CRP, but not AGP, was positively associated with L:M ratio, but there were no significant effects of the diet on either CRP or AGP. In conclusion, a richly fortified complementary/replacement food did not benefit and may have worsened intestinal permeability.

Asunto(s)

Proteína C-Reactiva/análisis , Alimentos Fortificados , Seropositividad para VIH/fisiopatología , Alimentos Infantiles , Absorción Intestinal , Síndromes de Malabsorción/dietoterapia , Micronutrientes/uso terapéutico , Anemia/complicaciones , Estudios de Cohortes , Femenino , Alimentos Fortificados/análisis , Seropositividad para VIH/congénito , Seropositividad para VIH/inmunología , Humanos , Lactante , Alimentos Infantiles/análisis , Intestinos/inmunología , Intestinos/fisiopatología , Lactulosa/metabolismo , Lactulosa/orina , Perdida de Seguimiento , Síndromes de Malabsorción/complicaciones , Síndromes de Malabsorción/etiología , Síndromes de Malabsorción/fisiopatología , Masculino , Manitol/metabolismo , Manitol/orina , Permeabilidad , Caracteres Sexuales , Zambia