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1.  Prevalence of seroconversion symptoms and relationship to set point viral load: Findings from a subtype C epidemic, 1995–2009 
AIDS (London, England)  2012;26(2):175-184.
Objective
To describe symptoms, physical exam findings, and set point viral load associated with acute HIV seroconversion in a heterosexual cohort of discordant couples in Zambia.
Design
We followed HIV serodiscordant couples in Lusaka, Zambia from 1995–2009 with HIV testing of negative partners and symptom inventories 3-monthly, and physical examinations annually.
Methods
We compared prevalence of self-reported or treated symptoms (malaria syndrome, chronic diarrhea, asthenia, night sweats, and oral candidiasis) and annual physical exam [PE] findings (unilateral or bilateral neck, axillary, or inguinal adenopathy; and dermatosis) in seroconverting versus HIV-negative or HIV-positive intervals, controlling for repeated observations, age, and sex. A composite score comprised of significant symptoms and PE findings predictive of seroconversion versus HIV-negative intervals was constructed. We modeled the relationship between number of symptoms and PE findings at seroconversion and log set-point viral load [VL] using linear regression.
Results
2,388 HIV-negative partners were followed for a median of 18 months; 429 seroconversions occurred. Neither symptoms nor PE findings were reported for most seroconverters. Seroconversion was significantly associated with malaria syndrome among non-diarrheic patients (adjusted odds ratio [aOR]=4.0) night sweats (aOR=1.4), and bilateral axillary (aOR = 1.6), inguinal (aOR=2.2), and neck (aOR=2.2) adenopathy relative to HIV-negative intervals. Median number of symptoms was positively associated with set-point VL (p<0.001).
Conclusions
Though most acute and early infections were asymptomatic, malaria syndrome was more common and more severe during seroconversion compared with HIV-negative and HIV-positive intervals. When present, symptoms and physical exam findings were non-specific and associated with higher set point viremia.
doi:10.1097/QAD.0b013e32834ed8c8
PMCID: PMC3589587  PMID: 22089380
HIV; seroconversion syndrome; set point HIV viral load
2.  Newborn Care Training and Perinatal Mortality in Communities in Developing Countries 
The New England journal of medicine  2010;362(7):614-623.
Background
Ninety-eight percent of the 3.7 million neonatal deaths and 3.3 million stillbirths per year occur in developing countries, and evaluation of community-based interventions is needed.
Methods
Using a train-the-trainer model, local instructors trained birth attendants from rural communities in six countries (Argentina, Democratic Republic of Congo, Guatemala, India, Pakistan, and Zambia) in the World Health Organization Essential Newborn Care course (routine neonatal care, resuscitation, thermoregulation, breastfeeding, kangaroo care, care of the small baby, and common illnesses), and in a modified version of the American Academy of Pediatrics Neonatal Resuscitation Program (in depth basic resuscitation), except in Argentina.
The Essential Newborn Care intervention was assessed with a before and after design (N=57, 643). The Neonatal Resuscitation Program intervention was assessed as a cluster randomized controlled trial (N=62,366). The primary outcome was 7-day neonatal mortality.
Results
The 7-day follow-up rate was 99.2%. Following Essential Newborn Care training, there was no significant reduction from baseline in all-cause 7-day neonatal (RR 0.99; CI 0.81, 1.22) or perinatal mortality; there was a significant reduction in the stillbirth rate (RR 0.69; CI 0.54, 0.88; p<0.01). Seven-day neonatal mortality, stillbirth, and perinatal mortality were not reduced in clusters randomized to Neonatal Resuscitation Program training as compared with control clusters.
Conclusions
Seven-day neonatal mortality did not decrease following the introduction of Essential Newborn Care training of community-based birth attendants, although the rate of stillbirths was reduced following this intervention. Subsequent training in the Neonatal Resuscitation Program did not significantly reduce the mortality rates. (clinicaltrials.gov number, NCT00136708).
doi:10.1056/NEJMsa0806033
PMCID: PMC3565382  PMID: 20164485
neonatal mortality; perinatal mortality; developing countries; health systems; effectiveness
3.  Local Residents Trained As ‘Influence Agents’ Most Effective In Persuading African Couples On HIV Counseling and Testing 
Health affairs (Project Hope)  2011;30(8):1488-1497.
Couples in sub-Saharan Africa are the largest group in the world at risk for HIV infection. Couples counseling and testing programs have been shown to reduce HIV transmission, but such programs remain rare in Africa. Before couples counseling and testing can become the norm, it is essential to increase demand for the services. We evaluated the effectiveness of several promotional strategies during a two -year program in Kitwe and Ndola, Zambia. The program attracted more than 7,600 couples through the use of radio broadcasts, billboards, and other strategies. The most effective recruiting technique was the use of local residents trained as “influence agents” to reach out to friends, neighbors, and others in their sphere of influence. Of the estimated 2.5 million new cases of HIV in adults and children in 2009, more than two-thirds occurred in sub-Saharan Africa.1 In Zambia, the prevalence of HIV among adults in urban and rural areas is estimated at 19 and 10 percent, respectively.2 Most HIV transmission in sub-Saharan Africa is heterosexual and occurs between cohabiting partners with discordant HIV test results3–5—that is, only one partner is HIV-positive. Thus, most new cases of HIV occur when someone infects his or her heterosexual partner. Sub-Saharan African couples with discordant HIV test results are the world’s largest risk group for HIV.6 Approximately 20 percent of Zambian couples have discordant HIV results, a rate consistent with estimates from Uganda, Rwanda, Tanzania, and Kenya.7–14
doi:10.1377/hlthaff.2009.0994
PMCID: PMC3503238  PMID: 21821565
4.  The cost of implementing a nationwide program to decrease the epilepsy treatment gap in a high gap country 
Neurology International  2012;4(3):e14.
Healthcare systems in many low income countries have evolved to provide services for acute, infections and are poorly structured for the provision of chronic, non-communicable diseases which are increasingly common. Epilepsy is a common chronic neurologic condition and antiepileptic drugs are affordable, but the epilepsy treatment gap remains >90% in most African countries. The World Health Organization has recently released evidence-based guidelines for epilepsy care provision at the primary care level. Based upon these guidelines, we estimated all direct costs associated with epilepsy care provision as well as the cost of healthcare worker training and social marketing. We developed a model for epilepsy care delivery primarily by primary healthcare workers. We then used a variety of sources to develop cost estimates for the actual implementation and maintenance of this program being as comprehensive as possible to include all costs incurred within the health sector. Key sensitivity analyses were completed to better understand how changes in costs for individual aspects of care impact the overall cost of care delivery. Even after including the costs of healthcare worker retraining, social marketing and capital expenditures, epilepsy care can be provided at less than $25.00 per person with epilepsy per year. This is substantially less than for drugs alone for other common chronic conditions. Implementation of epilepsy care guidelines for patients receiving care at the primary care level is a cost effective approach to decreasing the epilepsy treatment gap in high gap, low income countries.
doi:10.4081/ni.2012.e14
PMCID: PMC3555216  PMID: 23355927
epilepsy; treatment gap; cost; Africa.
5.  HIV-1 subtype C superinfected individuals mount low autologous neutralizing antibody responses prior to intrasubtype superinfection 
Retrovirology  2012;9:76.
Background
The potential role of antibodies in protection against intra-subtype HIV-1 superinfection remains to be understood. We compared the early neutralizing antibody (NAb) responses in three individuals, who were superinfected within one year of primary infection, to ten matched non-superinfected controls from a Zambian cohort of subtype C transmission cases. Sequence analysis of single genome amplified full-length envs from a previous study showed limited diversification in the individuals who became superinfected with the same HIV-1 subtype within year one post-seroconversion. We hypothesized that this reflected a blunted NAb response, which may have made these individuals more susceptible to superinfection.
Results
Neutralization assays showed that autologous plasma NAb responses to the earliest, and in some cases transmitted/founder, virus were delayed and had low to undetectable titers in all three superinfected individuals prior to superinfection. In contrast, NAbs with a median IC50 titer of 1896 were detected as early as three months post-seroconversion in non-superinfected controls. Early plasma NAbs in all subjects showed limited but variable levels of heterologous neutralization breadth. Superinfected individuals also exhibited a trend toward lower levels of gp120- and V1V2-specific IgG binding antibodies but higher gp120-specific plasma IgA binding antibodies.
Conclusions
These data suggest that the lack of development of IgG antibodies, as reflected in autologous NAbs as well as gp120 and V1V2 binding antibodies to the primary infection virus, combined with potentially competing, non-protective IgA antibodies, may increase susceptibility to superinfection in the context of settings where a single HIV-1 subtype predominates.
doi:10.1186/1742-4690-9-76
PMCID: PMC3477039  PMID: 22995123
HIV-1 superinfection; Subtype C; Neutralizing antibodies; HIV-1 transmission; HIV-1 dual infection
6.  Antenatal corticosteroids trial in preterm births to increase neonatal survival in developing countries: study protocol 
Reproductive Health  2012;9:22.
Background
Preterm birth is a major cause of neonatal mortality, responsible for 28% of neonatal deaths overall. The administration of antenatal corticosteroids to women at high risk of preterm birth is a powerful perinatal intervention to reduce neonatal mortality in resource rich environments. The effect of antenatal steroids to reduce mortality and morbidity among preterm infants in hospital settings in developed countries with high utilization is well established, yet they are not routinely used in developing countries. The impact of increasing antenatal steroid use in hospital or community settings with low utilization rates and high infant mortality among premature infants due to lack of specialized services has not been well researched. There is currently no clear evidence about the safety of antenatal corticosteroid use for community-level births.
Methods
We hypothesize that a multi country, two-arm, parallel cluster randomized controlled trial to evaluate whether a multifaceted intervention to increase the use of antenatal corticosteroids, including components to improve the identification of pregnancies at high risk of preterm birth and providing and facilitating the appropriate use of steroids, will reduce neonatal mortality at 28 days of life in preterm newborns, compared with the standard delivery of care in selected populations of six countries. 102 clusters in Argentina, Guatemala, Kenya, India, Pakistan, and Zambia will be randomized, and around 60,000 women and newborns will be enrolled. Kits containing vials of dexamethasone, syringes, gloves, and instructions for administration will be distributed. Improving the identification of women at high risk of preterm birth will be done by (1) diffusing recommendations for antenatal corticosteroids use to health providers, (2) training health providers on identification of women at high risk of preterm birth, (3) providing reminders to health providers on the use of the kits, and (4) using a color-coded tape to measure uterine height to estimate gestational age in women with unknown gestational age. In both intervention and control clusters, health providers will be trained in essential newborn care for low birth weight babies. The primary outcome is neonatal mortality at 28 days of life in preterm infants.
Trial registration
ClinicalTrials.gov. Identifier: NCT01084096
doi:10.1186/1742-4755-9-22
PMCID: PMC3477119  PMID: 22992312
Neonatal mortality; Antenatal corticosteroids; Implementation research; Preterm birth
7.  Promotion of couples’ voluntary HIV counselling and testing in Lusaka, Zambia by influence network leaders and agents 
BMJ Open  2012;2(5):e001171.
Objectives
Hypothesising that couples’ voluntary counselling and testing (CVCT) promotions can increase CVCT uptake, this study identified predictors of successful CVCT promotion in Lusaka, Zambia.
Design
Cohort study.
Setting
Lusaka, Zambia.
Participants
68 influential network leaders (INLs) identified 320 agents (INAs) who delivered 29 119 CVCT invitations to heterosexual couples.
Intervention
The CVCT promotional model used INLs who identified INAs, who in turn conducted community-based promotion and distribution of CVCT invitations in two neighbourhoods over 18 months, with a mobile unit in one neighbourhood crossing over to the other mid-way through.
Primary outcome
The primary outcome of interest was couple testing (yes/no) after receipt of a CVCT invitation. INA, couple and invitation characteristics predictive of couples’ testing were evaluated accounting for two-level clustering.
Results
INAs delivered invitations resulting in 1727 couples testing (6% success rate). In multivariate analyses, INA characteristics significantly predictive of CVCT uptake included promoting in community-based (adjusted OR (aOR)=1.3; 95% CI 1.0 to 1.8) or health (aOR=1.5; 95% CI 1.2 to 2.0) networks versus private networks; being employed in the sales/service industry (aOR=1.5; 95% CI 1.0 to 2.1) versus unskilled manual labour; owning a home (aOR=0.7; 95% CI 0.6 to 0.9) versus not; and having tested for HIV with a partner (aOR=1.4; 95% CI 1.1 to 1.7) or alone (aOR=1.3; 95% CI 1.0 to 1.6) versus never having tested. Cohabiting couples were more likely to test (aOR=1.4; 95% CI 1.2 to 1.6) than non-cohabiting couples. Context characteristics predictive of CVCT uptake included inviting couples (aOR=1.2; 95% CI 1.0 to 1.4) versus individuals; the woman (aOR=1.6; 95% CI 1.2 to 2.2) or couple (aOR=1.4; 95% CI 1.0 to 1.8) initiating contact versus the INA; the couple being socially acquainted with the INA (aOR=1.6; 95% CI 1.4 to 1.9) versus having just met; home invitation delivery (aOR=1.3; 95% CI 1.1 to 1.5) versus elsewhere; and easy invitation delivery (aOR=1.8; 95% CI 1.4 to 2.2) versus difficult as reported by the INA.
Conclusions
This study demonstrated the ability of influential people to promote CVCT and identified agent, couple and context-level factors associated with CVCT uptake in Lusaka, Zambia. We encourage the development of CVCT promotions in other sub-Saharan African countries to support sustained CVCT dissemination.
doi:10.1136/bmjopen-2012-001171
PMCID: PMC3467632  PMID: 22956641
8.  Epidemiology of stillbirth in low-middle income countries: A Global Network Study 
Objective
To determine population-based stillbirth rates and to determine whether the timing and maturity of the stillbirths suggest a high proportion of potentially preventable deaths.
Design
Prospective observational study.
Setting
Communities in six low-income countries (Democratic Republic of Congo, Kenya, Zambia, Guatemala, India, and Pakistan) and one site in a mid-income country (Argentina).
Population
Pregnant women residing in the study communities.
Methods
Over a five-year period, in selected catchment areas, using multiple methodologies, trained study staff obtained pregnancy outcomes on each delivery in their area.
Main outcome measures
Pregnancy outcome, stillbirth characteristics.
Results
Outcomes of 195 400 deliveries were included. Stillbirth rates ranged from 32 per 1 000 in Pakistan to 8 per 1 000 births in Argentina. Three-fourths (76%) of stillbirth off-spring were not macerated, 63% were ≥37 weeks and 48% weighed 2 500g or more. Across all sites, women with no education, of high and low parity, of older age, and without access to antenatal care were at significantly greater risk for stillbirth (p<0.001). Compared to those delivered by a physician, women delivered by nurses and traditional birth attendants had a lower risk of stillbirth.
Conclusions
In these low-middle income countries, most stillbirth offspring were not macerated, were reported as ≥37 weeks’ gestation, and almost half weighed at least 2 500g. With access to better medical care, especially in the intrapartum period, many of these stillbirths could likely be prevented.
doi:10.1111/j.1600-0412.2011.01275.x
PMCID: PMC3412613  PMID: 21916854
Developing countries; intrapartum stillbirth; stillbirth
9.  Home birth attendants in low income countries: who are they and what do they do? 
Background
Nearly half the world’s babies are born at home. We sought to evaluate the training, knowledge, skills, and access to medical equipment and testing for home birth attendants across 7 international sites.
Methods
Face-to-face interviews were done by trained interviewers to assess level of training, knowledge and practices regarding care during the antenatal, intrapartum and postpartum periods. The survey was administered to a sample of birth attendants conducting home or out-of-facility deliveries in 7 sites in 6 countries (India, Pakistan, Guatemala, Democratic Republic of the Congo, Kenya and Zambia).
Results
A total of 1226 home birth attendants were surveyed. Less than half the birth attendants were literate. Eighty percent had one month or less of formal training. Most home birth attendants did not have basic equipment (e.g., blood pressure apparatus, stethoscope, infant bag and mask manual resuscitator). Reporting of births and maternal and neonatal deaths to government agencies was low. Indian auxilliary nurse midwives, who perform some home but mainly clinic births, were far better trained and differed in many characteristics from the birth attendants who only performed deliveries at home.
Conclusions
Home birth attendants in low-income countries were often illiterate, could not read numbers and had little formal training. Most had few of the skills or access to tests, medications and equipment that are necessary to reduce maternal, fetal or neonatal mortality.
doi:10.1186/1471-2393-12-34
PMCID: PMC3493311  PMID: 22583622
Home births; Traditional birth attendants; Perinatal mortality
10.  Cost-effectiveness of Essential Newborn Care Training in Urban First-Level Facilities 
Pediatrics  2011;127(5):e1176-e1181.
OBJECTIVE:
To determine the cost-effectiveness of the World Health Organization (WHO) Essential Newborn Care (ENC) training of health care providers in first-level facilities in the 2 largest cities in Zambia.
METHODS:
Data were extracted from a study in which the effectiveness of the ENC training was evaluated (including universal precautions and cleanliness, routine neonatal care, resuscitation, thermoregulation, breastfeeding, skin-to-skin care, care of the small infant, danger signs, and common illnesses). The costs to train an ENC instructor for each first-level delivery facility and the costs of salary/benefits for 2 coordinators responsible for maintenance of the program were recorded in 2005 US dollars. The incremental costs per life gained and per disability-adjusted life-year averted were calculated.
SETTING:
A 5-day ENC training-of-trainers was conducted in Lusaka, Zambia, to certify 18 college-trained midwives as ENC instructors. The instructors trained all clinic midwives working in their first-level facilities as part of a before-and-after study of the effect of ENC training on early neonatal mortality conducted from Oct 2004 to Nov 2006.
RESULTS:
All-cause 7-day (early) neonatal mortality decreased from 11.5 per 1000 to 6.8 per 1000 live births after ENC training of the clinic midwives (relative risk: 0.59; 95% confidence interval: 0.48–0.77; P < .001; 40 615 births). The intervention costs were $208 per life saved and $5.24 per disability-adjusted life-year averted.
CONCLUSIONS:
ENC training of clinic midwives who provide care in low-risk facilities is a low-cost intervention that can reduce early neonatal mortality in these settings.
doi:10.1542/peds.2010-2158
PMCID: PMC3387868  PMID: 21502223
developing countries; low-middle income countries; neonatal mortality; perinatal mortality; midwives
11.  A Randomized Controlled Trial to Promote Long-Term Contraceptive Use Among HIV-Serodiscordant and Concordant Positive Couples in Zambia 
Journal of Women's Health  2011;20(4):567-574.
Abstract
Background
Countries facing high HIV prevalence often also experience high levels of fertility and low contraceptive use, suggesting high levels of unmet need for contraceptive services. In particular, the unique needs of couples with one or both partners HIV positive are largely missing from many current family planning efforts, which focus on the prevention of pregnancies in the absence of reduction of the risk of HIV and other sexually transmitted infections (STIs).
Methods
This article presents an examination of contraceptive method uptake among a cohort of HIV serodiscordant and concordant positive study participants in Zambia.
Results
Baseline contraceptive use was low; however, exposure to a video-based intervention that provided information on contraceptive methods and modeled desirable future planning behaviors dramatically increased the uptake of modern contraceptive methods.
Conclusions
Including information on family planning in voluntary counseling and testing (VCT) services in addition to tailoring the delivery of family planning information to meet the needs and concerns of HIV-positive women or those with HIV-positive partners is an essential step in the delivery of services and prevention efforts to reduce the transmission of HIV. Family planning and HIV prevention programs should integrate counseling on dual method use, combining condoms for HIV/STI prevention with a long-acting contraceptive for added protection against unplanned pregnancy.
doi:10.1089/jwh.2010.2113
PMCID: PMC3115412  PMID: 21410332
12.  Timing and source of subtype-C HIV-1 superinfection in the newly infected partner of Zambian couples with disparate viruses 
Retrovirology  2012;9:22.
Background
HIV-1 superinfection occurs at varying frequencies in different at risk populations. Though seroincidence is decreased, in the negative partner of HIV-discordant couples after joint testing and counseling in the Zambia Emory HIV Research Project (ZEHRP) cohort, the annual infection rate remains relatively high at 7-8%. Based on sequencing within the gp41 region of each partner's virus, 24% of new infections between 2004 and 2008 were the result of transmission from a non-spousal partner. Since these seroconvertors and their spouses have disparate epidemiologically-unlinked viruses, there is a risk of superinfection within the marriage. We have, therefore, investigated the incidence and viral origin of superinfection in these couples.
Results
Superinfection was detected by heteroduplex mobility assay (HMA), degenerate base counting of the gp41 sequence, or by phylogenetic analysis of the longitudinal sequences. It was confirmed by full-length env single genome amplification and phylogenetic analysis. In 22 couples (44 individuals), followed for up to five years, three of the newly infected (initially HIV uninfected) partners became superinfected. In each case superinfection occurred during the first 12 months following initial infection of the negative partner, and in each case the superinfecting virus was derived from a non-spousal partner. In addition, one probable case of intra-couple HIV-1 superinfection was observed in a chronically infected partner at the time of his seroconverting spouse's initial viremia. Extensive recombination within the env gene was observed following superinfection.
Conclusions
In this subtype-C discordant couple cohort, superinfection, during the first year after HIV-1 infection of the previously negative partner, occurred at a rate similar to primary infection (13.6% [95% CI 5.2-34.8] vs 7.8% [7.1-8.6]). While limited intra-couple superinfection may in part reflect continued condom usage within couples, this and our lack of detecting newly superinfected individuals after one year of primary infection raise the possibility that immunological resistance to intra-subtype superinfection may develop over time in subtype C infected individuals.
doi:10.1186/1742-4690-9-22
PMCID: PMC3349552  PMID: 22433432
13.  Epilepsy-Associated Stigma in Zambia: What factors predict greater felt stigma in a highly stigmatized population? 
Epilepsy & behavior : E&B  2010;19(3):414-418.
Epilepsy-associated stigma in Africa has been largely described in terms of enacted stigma or discrimination. We conducted a study of 169 adults with epilepsy attending epilepsy clinics in Zambia’s Lusaka or Southern province using a 3-item instrument (maximum score 3). Potential determinants of felt stigma including age, gender, education, wealth, disclosure status (meaning whether or how their community members knew of their condition), seizure type (generalized vs. partial), seizure frequency, the presence of visible epilepsy-associated stigmata, personal contagion beliefs and community contagion beliefs were also assessed. The median stigma score was 2.5, suggesting some ceiling effect in the instrument. People with epilepsy who believed their condition to be contagious, who thought their community believed epilepsy to be contagious and whose condition had been revealed to their community against their wishes reported more felt stigma. Community and clinic-based educational campaigns to dispel contagion beliefs are needed.
doi:10.1016/j.yebeh.2010.08.017
PMCID: PMC3005974  PMID: 20851056
contagion beliefs; disclosure; stigmata; felt stigma; epilepsy
14.  Diagnosis of latent tuberculosis infection among HIV discordant partners using interferon gamma release assays 
BMC Infectious Diseases  2011;11:264.
Background
There is limited data on the effect of HIV status and CD4 counts on performance of Interferon-g Release assays (IGRAs) for diagnosis of latent tuberculosis infection (LTBI).
Methods
A cross sectional study was conducted to assess the prevalence of and risk factors for a positive diagnostic test for LTBI, using tuberculin skin test (TST) and IGRAs among HIV-discordant couples in Zambia.
Results
A total of 596 subjects (298 couples) were enrolled. Median CD4 count among HIV positive persons was 388 cells/μl, (range 51-1330). HIV negative persons were more likely than their HIV positive partner, to have a positive diagnostic test for LTBI with TST (203 vs 128), QFT (171 vs 109) and TSPOT (156 vs. 109). On multivariate analysis, HIV negative status was an independent predictor for a positive QFT (OR = 2.22, 95% CI 1.42- 3.46) and TSPOT (OR = 1.79, 95% CI 1.16-2.77). Among HIV positive subjects a CD4 count ≥ 388 cells/μl was associated with a positive TST (OR = 1.76 95% CI 1.10-2.82) and QFT (OR = 1.71 95% CI 1.06-2.77) but not TSPOT (OR = 1.20 95% CI 0.74-1.94).
Conclusions
Persons with HIV had significantly fewer positive diagnostic tests for LTBI with TST, QFT and TSPOT. Persons with a CD4 count < 388 cells/μl were less likely to have a positive TST or QFT, but not less likely to have a positive TSPOT. TSPOT may perform better than TST or QFT in HIV positive individuals.
doi:10.1186/1471-2334-11-264
PMCID: PMC3198954  PMID: 21962029
15.  Validation of the UCLA Child Post traumatic stress disorder-reaction index in Zambia 
Background
Sexual violence against children is a major global health and human rights problem. In order to address this issue there needs to be a better understanding of the issue and the consequences. One major challenge in accomplishing this goal has been a lack of validated child mental health assessments in low-resource countries where the prevalence of sexual violence is high. This paper presents results from a validation study of a trauma-focused mental health assessment tool - the UCLA Post-traumatic Stress Disorder - Reaction Index (PTSD-RI) in Zambia.
Methods
The PTSD-RI was adapted through the addition of locally relevant items and validated using local responses to three cross-cultural criterion validity questions. Reliability of the symptoms scale was assessed using Cronbach alpha analyses. Discriminant validity was assessed comparing mean scale scores of cases and non-cases. Concurrent validity was assessed comparing mean scale scores to a traumatic experience index. Sensitivity and specificity analyses were run using receiver operating curves.
Results
Analysis of data from 352 youth attending a clinic specializing in sexual abuse showed that this adapted PTSD-RI demonstrated good reliability, with Cronbach alpha scores greater than .90 on all the evaluated scales. The symptom scales were able to statistically significantly discriminate between locally identified cases and non-cases, and higher symptom scale scores were associated with increased numbers of trauma exposures which is an indication of concurrent validity. Sensitivity and specificity analyses resulted in an adequate area under the curve, indicating that this tool was appropriate for case definition.
Conclusions
This study has shown that validating mental health assessment tools in a low-resource country is feasible, and that by taking the time to adapt a measure to the local context, a useful and valid Zambian version of the PTSD-RI was developed to detect traumatic stress among youth. This valid tool can now be used to appropriately measure treatment effectiveness, and more effectively and efficiently triage youth to appropriate services.
doi:10.1186/1752-4458-5-24
PMCID: PMC3205018  PMID: 21943178
PTSD; assessment validation; children; low resource country; mental health
16.  The Current Availability of Antiepileptic Drugs in Zambia: Implications for the ILAE/WHO “Out of the Shadows” Campaign 
Recent concerns regarding antiepileptic drug (AED) availability in Zambia led us to conduct a study in the Lusaka and Southern Provinces to quantify the availability and cost of AEDs and assess determinants. Among 111 pharmacies, almost one-half did not carry AEDs (N = 54; 49.1%). Available AEDs were phenobarbitone (21; 18.9%), carbamazepine (27; 24.3%), valproic acid (4; 3.6%), and phenytoin (3; 2.7%). Adult out-of-pocket monthly costs ranged from US $7 to $30. Pediatric syrups were universally unavailable. Interviews revealed several barriers to AED provision, including that handling phenobarbitone (historically the most affordable AED) has become increasingly difficult because of newly enforced regulatory requirements. Personal communications with epilepsy-care providers in other low income countries suggest that this problem may be widespread. Improved enforcement of existing drug regulations may be contributing to the AED shortage. Social programs aimed at encouraging people with epilepsy to come “out of the shadows” must be preceded by improved AED access.
doi:10.4269/ajtmh.2010.10-0100
PMCID: PMC2929053  PMID: 20810822
17.  Classifying perinatal mortality using verbal autopsy: is there a role for nonphysicians? 
Background
Because of a physician shortage in many low-income countries, the use of nonphysicians to classify perinatal mortality (stillbirth and early neonatal death) using verbal autopsy could be useful.
Objective
To determine the extent to which underlying perinatal causes of deaths assigned by nonphysicians in Guatemala, Pakistan, Zambia, and the Democratic Republic of the Congo using a verbal autopsy method are concordant with underlying perinatal cause of death assigned by physician panels.
Methods
Using a train-the-trainer model, 13 physicians and 40 nonphysicians were trained to determine cause of death using a standardized verbal autopsy training program. Subsequently, panels of two physicians and individual nonphysicians from this trained cohort independently reviewed verbal autopsy data from a sample of 118 early neonatal deaths and 134 stillbirths. With the cause of death assigned by the physician panel as the reference standard, sensitivity, specificity, positive and negative predictive values, and cause-specific mortality fractions were calculated to assess nonphysicians' coding responses. Robustness criteria to assess how well nonphysicians performed were used.
Results
Causes of early neonatal death and stillbirth assigned by nonphysicians were concordant with physician-assigned causes 47% and 57% of the time, respectively. Tetanus filled robustness criteria for early neonatal death, and cord prolapse filled robustness criteria for stillbirth.
Conclusions
There are significant differences in underlying cause of death as determined by physicians and nonphysicians even when they receive similar training in cause of death determination. Currently, it does not appear that nonphysicians can be used reliably to assign underlying cause of perinatal death using verbal autopsy.
doi:10.1186/1478-7954-9-42
PMCID: PMC3160935  PMID: 21819582
18.  Knowledge and Perceptions of Couples' Voluntary Counseling and Testing in Urban Rwanda and Zambia: A Cross-Sectional Household Survey 
PLoS ONE  2011;6(5):e19573.
Background
Most incident HIV infections in sub-Saharan Africa occur between cohabiting, discordant, heterosexual couples. Though couples' voluntary HIV counseling and testing (CVCT) is an effective, well-studied intervention in Africa, <1% of couples have been jointly tested.
Methods
We conducted cross-sectional household surveys in Kigali, Rwanda (n = 600) and Lusaka, Zambia (n = 603) to ascertain knowledge, perceptions, and barriers to use of CVCT.
Results
Compared to Lusaka, Kigali respondents were significantly more aware of HIV testing sites (79% vs. 56%); had greater knowledge of HIV serodiscordance between couples (83% vs. 43%); believed CVCT is good (96% vs. 72%); and were willing to test jointly (91% vs. 47%). Stigma, fear of partner reaction, and distance/cost/logistics were CVCT barriers.
Conclusions
Though most respondents had positive attitudes toward CVCT, the majority were unaware that serodiscordance between cohabiting couples is possible. Future messages should target gaps in knowledge about serodiscordance, provide logistical information about CVCT services, and aim to reduce stigma and fear.
doi:10.1371/journal.pone.0019573
PMCID: PMC3090401  PMID: 21573068
19.  Indeterminate and discrepant rapid HIV test results in couples' HIV testing and counselling centres in Africa 
Background
Many HIV voluntary testing and counselling centres in Africa use rapid antibody tests, in parallel or in sequence, to establish same-day HIV status. The interpretation of indeterminate or discrepant results between different rapid tests on one sample poses a challenge. We investigated the use of an algorithm using three serial rapid HIV tests in cohabiting couples to resolve unclear serostatuses.
Methods
Heterosexual couples visited the Rwanda Zambia HIV Research Group testing centres in Kigali, Rwanda, and Lusaka, Zambia, to assess HIV infection status. Individuals with unclear HIV rapid antibody test results (indeterminate) or discrepant results were asked to return for repeat testing to resolve HIV status. If either partner of a couple tested positive or indeterminate with the screening test, both partners were tested with a confirmatory test. Individuals with indeterminate or discrepant results were further tested with a tie-breaker and monthly retesting. HIV-RNA viral load was determined when HIV status was not resolved by follow-up rapid testing. Individuals were classified based on two of three initial tests as "Positive", "Negative" or "Other". Follow-up testing and/or HIV-RNA viral load testing determined them as "Infected", "Uninfected" or "Unresolved".
Results
Of 45,820 individuals tested as couples, 2.3% (4.1% of couples) had at least one discrepant or indeterminate rapid result. A total of 65% of those individuals had follow-up testing and of those individuals initially classified as "Negative" by three initial rapid tests, less than 1% were resolved as "Infected". In contrast, of those individuals with at least one discrepant or indeterminate result who were initially classified as "Positive", only 46% were resolved as "Infected", while the remainder was resolved as "Uninfected" (46%) or "Unresolved" (8%). A positive HIV serostatus of one of the partners was a strong predictor of infection in the other partner as 48% of individuals who resolved as "Infected" had an HIV-infected spouse.
Conclusions
In more than 45,000 individuals counselled and tested as couples, only 5% of individuals with indeterminate or discrepant rapid HIV test results were HIV infected. This represented only 0.1% of all individuals tested. Thus, algorithms using screening, confirmatory and tie-breaker rapid tests are reliable with two of three tests negative, but not when two of three tests are positive. False positive antibody tests may persist. HIV-positive partner serostatus should prompt repeat testing.
doi:10.1186/1758-2652-14-18
PMCID: PMC3086828  PMID: 21477317
20.  The influence of informed consent content on study participants’ contraceptive knowledge and concerns 
Studies in family planning  2010;41(3):217-224.
Objectives
Little is known about how the information presented in the informed consent process influences study outcomes among participants. This paper examines how the content of the informed consent document may influence baseline levels of knowledge among study participants.
Methods
We examined the influence of the content of informed consent documents on reported contraceptive knowledge and concerns among two groups of sero-discordant and HIV concordant positive couples enrolled in research projects at an HIV research center in Lusaka, Zambia.
Results
We found significant differences in the reporting of both contraceptive knowledge and concerns between couples viewing consent forms that included detailed information on contraception and those viewing consent forms without the detailed information.
Conclusions
The protection of human subjects is vital. The future challenge, however, lies in creating informed consent documents that can find the balance between ensuring that participants give truly informed consent, and educating participants in ways that compromise the assessment of the impact of behavioral interventions.
doi:10.1111/j.1728-4465.2010.00245.x
PMCID: PMC3039305  PMID: 21331352
21.  Complementary feeding: a Global Network cluster randomized controlled trial 
BMC Pediatrics  2011;11:4.
Background
Inadequate and inappropriate complementary feeding are major factors contributing to excess morbidity and mortality in young children in low resource settings. Animal source foods in particular are cited as essential to achieve micronutrient requirements. The efficacy of the recommendation for regular meat consumption, however, has not been systematically evaluated.
Methods/Design
A cluster randomized efficacy trial was designed to test the hypothesis that 12 months of daily intake of beef added as a complementary food would result in greater linear growth velocity than a micronutrient fortified equi-caloric rice-soy cereal supplement. The study is being conducted in 4 sites of the Global Network for Women's and Children's Health Research located in Guatemala, Pakistan, Democratic Republic of the Congo (DRC) and Zambia in communities with toddler stunting rates of at least 20%. Five clusters per country were randomized to each of the food arms, with 30 infants in each cluster. The daily meat or cereal supplement was delivered to the home by community coordinators, starting when the infants were 6 months of age and continuing through 18 months. All participating mothers received nutrition education messages to enhance complementary feeding practices delivered by study coordinators and through posters at the local health center. Outcome measures, obtained at 6, 9, 12, and 18 months by a separate assessment team, included anthropometry; dietary variety and diversity scores; biomarkers of iron, zinc and Vitamin B12 status (18 months); neurocognitive development (12 and 18 months); and incidence of infectious morbidity throughout the trial. The trial was supervised by a trial steering committee, and an independent data monitoring committee provided oversight for the safety and conduct of the trial.
Discussion
Findings from this trial will test the efficacy of daily intake of meat commencing at age 6 months and, if beneficial, will provide a strong rationale for global efforts to enhance local supplies of meat as a complementary food for young children.
Trial registration
NCT01084109
doi:10.1186/1471-2431-11-4
PMCID: PMC3032692  PMID: 21232139
22.  Communities, birth attendants and health facilities: a continuum of emergency maternal and newborn care (the global network's EmONC trial) 
Background
Maternal and newborn mortality rates remain unacceptably high, especially where the majority of births occur in home settings or in facilities with inadequate resources. The introduction of emergency obstetric and newborn care services has been proposed by several organizations in order to improve pregnancy outcomes. However, the effectiveness of emergency obstetric and neonatal care services has never been proven. Also unproven is the effectiveness of community mobilization and community birth attendant training to improve pregnancy outcomes.
Methods/Design
We have developed a cluster-randomized controlled trial to evaluate the impact of a comprehensive intervention of community mobilization, birth attendant training and improvement of quality of care in health facilities on perinatal mortality in low and middle-income countries where the majority of births take place in homes or first level care facilities. This trial will take place in 106 clusters (300-500 deliveries per year each) across 7 sites of the Global Network for Women's and Children's Health Research in Argentina, Guatemala, India, Kenya, Pakistan and Zambia. The trial intervention has three key elements, community mobilization, home-based life saving skills for communities and birth attendants, and training of providers at obstetric facilities to improve quality of care. The primary outcome of the trial is perinatal mortality. Secondary outcomes include rates of stillbirth, 7-day neonatal mortality, maternal death or severe morbidity (including obstetric fistula, eclampsia and obstetrical sepsis) and 28-day neonatal mortality.
Discussion
In this trial, we are evaluating a combination of interventions including community mobilization and facility training in an attempt to improve pregnancy outcomes. If successful, the results of this trial will provide important information for policy makers and clinicians as they attempt to improve delivery services for pregnant women and newborns in low-income countries.
Trial Registration
ClinicalTrials.gov NCT01073488
doi:10.1186/1471-2393-10-82
PMCID: PMC3017016  PMID: 21156060
23.  The social and economic impact of epilepsy in Zambia: a cross-sectional study 
Lancet neurology  2007;6(1):39-44.
Summary
Background
Among the 40 million people with epilepsy worldwide, 80% reside in low-income regions where human and technological resources for care are extremely limited. Qualitative and experiential reports indicate that people with epilepsy in Africa are also disadvantaged socially and economically, but few quantitative systematic data are available. We sought to assess the social and economic effect of living with epilepsy in sub-Saharan Africa.
Methods
We did a cross-sectional study of people with epilepsy concurrently matched for age, sex, and site of care to individuals with a non-stigmatised chronic medical condition. Verbally administered questionnaires provided comparison data for demographic characteristics, education, employment status, housing and environment quality, food security, healthcare use, personal safety, and perceived stigma.
Findings
People with epilepsy had higher mean perceived stigma scores (1·8 vs 0·4; p<0·0001), poorer employment status (p=0·0001), and less education (7·1 vs 9·4 years; p<0·0001) than did the comparison group. People with epilepsy also had less education than their nearest-age same sex sibling (7·1 vs 9·1 years; p<0·0001), whereas the comparison group did not (9·4 vs 9·6 years; p=0·42). Housing and environmental quality were poorer for people with epilepsy, who had little access to water, were unlikely to have electricity in their home (19% vs 51%; p<0·0001), and who had greater food insecurity than did the control group. During pregnancy, women with epilepsy were more likely to deliver at home rather than in a hospital or clinic (40% vs 15%; p=0·0007). Personal safety for people with epilepsy was also more problematic; rape rates were 20% among women with epilepsy vs 3% in the control group (p=0·004).
Interpretation
People with epilepsy in Zambia have substantially poorer social and economic status than do their peers with non-stigmatised chronic medical conditions. Suboptimum housing quality differentially exposes these individuals to the risk of burns and drowning during a seizure. Vulnerability to physical violence is extreme, especially for women with epilepsy.
doi:10.1016/S1474-4422(06)70629-9
PMCID: PMC2938018  PMID: 17166800
24.  Zambian health care workers’ knowledge, attitudes, beliefs, and practices regarding epilepsy 
Epilepsy & behavior : E&B  2006;10(1):111-119.
Objective
Zambia suffers from a physician shortage, leaving the provision of care for those with epilepsy to nonphysician health care workers who may not be adequately trained for this task. These individuals are also important community opinion leaders. Our goal in this study was to determine the knowledge, attitudes, beliefs, and practices of these health care workers with respect to epilepsy.
Methods
Health care workers in urban and rural districts of Zambia completed a self-administered, 48-item questionnaire containing items addressing demographics, personal experience with epilepsy, social tolerance, willingness to provide care, epilepsy care knowledge, and estimates of others’ attitudes. Analyses were conducted to assess characteristics associated with more epilepsy care knowledge and social tolerance.
Results
The response rate was 92% (n = 276). Those who had received both didactic and bedside training (P = 0.02) and more recent graduates (P = 0.007) had greater knowledge. Greater knowledge was associated with more social tolerance (P = 0.005), but having a family member with epilepsy was not (P = 0.61). Health care workers were generally willing to provide care to this patient population, but ~25% would not allow their child to marry someone with epilepsy and 20% thought people with epilepsy should not marry or hold employment. Respondents reported that people with epilepsy are feared and/or rejected by both their families (75%) and their community (88.8%).
Conclusions
Knowledge gaps exist particularly in acute management and recognition of partial epilepsy. More recent graduates were more knowledgeable, suggesting that curriculum changes instituted in 2000 may be improving care. Health care workers expressed both personal and professional reservations about people with epilepsy marrying. In addition to improving diagnosis and treatment skills, educational programs must address underlying attitudes that may worsen existing stigmatizing trends.
doi:10.1016/j.yebeh.2006.08.012
PMCID: PMC2938019  PMID: 17055341
Stigma; Quality of care; Person with epilepsy; Tolerance; Knowledge
25.  Knowledge, Use, and Concerns about Contraceptive Methods among Sero-Discordant Couples in Rwanda and Zambia 
Journal of Women's Health  2009;18(9):1449-1456.
Abstract
Objective
The unique needs of sero-discordant couples are largely missing from many current family planning efforts, which focus on the prevention of pregnancies in absence of the reduction of the risk of human immunodeficiency virus (HIV) and other sexually transmitted infections (STIs). Conversely, HIV testing and programs focus exclusively on condom use without discussion of more effective contraceptive methods. In order to provide information to inform the development of family planning services tailored to the unique needs of sero-discordant couples, this study examined the contraceptive knowledge, use, and concerns among sero-discordant couples in urban Rwanda and Zambia.
Methods
This article presents a comparison of family planning knowledge, use, and concerns about contraception among two cohorts of HIV sero-discordant study participants in Rwanda and Zambia.
Results
The results reveal an interesting profile of contraceptive knowledge and use among sero-discordant couples; in both settings, despite high levels of knowledge of contraception, use of contraceptive methods remains relatively low. There is a clear gender difference in both the reporting of knowledge and use of contraceptive methods, and there is evidence of clandestine contraceptive use by women.
Conclusions
Including information on family planning in voluntary counseling and testing (VCT) services in addition to tailoring the delivery of family planning information to meet to needs and concerns of HIV-positive women or those with HIV positive partners is an essential step in the delivery of services and prevention efforts to reduce the transmission of HIV. Family planning and HIV prevention programs should integrate counseling on “dual method use,” combining condoms for HIV/STI prevention with a long-acting contraceptive for added protection against unplanned pregnancy.
doi:10.1089/jwh.2008.1160
PMCID: PMC2825682  PMID: 19708802

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