[Show abstract][Hide abstract] ABSTRACT: Rapid diagnostic tests (RDTs) detecting histidine-rich protein 2 (PfHRP2) antigen are used to identify individuals with Plasmodium falciparum infection even in low transmission settings seeking to achieve elimination. However, these RDTs lack sensitivity to detect low-density infections, produce false negatives for P. falciparum strains lacking pfhrp2 gene and do not detect species other than P. falciparum.
Results of a PfHRP2-based RDT and Plasmodium nested PCR were compared in a region of declining malaria transmission in southern Zambia using samples from community-based, cross-sectional surveys from 2008 to 2012. Participants were tested with a PfHRP2-based RDT and a finger prick blood sample was spotted onto filter paper for PCR analysis and used to prepare blood smears for microscopy. Species-specific, real-time, quantitative PCR (q-PCR) was performed on samples that tested positive either by microscopy, RDT or nested PCR.
Of 3,292 total participants enrolled, 12 (0.4%) tested positive by microscopy and 42 (1.3%) by RDT. Of 3,213 (98%) samples tested by nested PCR, 57 (1.8%) were positive, resulting in 87 participants positive by at least one of the three tests. Of these, 61 tested positive for P. falciparum by q-PCR with copy numbers ≤ 2 x 10(3) copies/μL, 5 were positive for both P. falciparum and Plasmodium malariae and 2 were positive for P. malariae alone. RDT detected 32 (53%) of P. falciparum positives, failing to detect three of the dual infections with P. malariae. Among 2,975 participants enrolled during a low transmission period between 2009 and 2012, sensitivity of the PfHRP2-based RDT compared to nested PCR was only 17%, with specificity of >99%. The pfhrp gene was detected in 80% of P. falciparum positives; however, comparison of copy number between RDT negative and RDT positive samples suggested that RDT negatives resulted from low parasitaemia and not pfhrp2 gene deletion.
Low-density P. falciparum infections not identified by currently used PfHRP2-based RDTs and the inability to detect non-falciparum malaria will hinder progress to further reduce malaria in low transmission settings of Zambia. More sensitive and specific diagnostic tests will likely be necessary to identify parasite reservoirs and achieve malaria elimination.
[Show abstract][Hide abstract] ABSTRACT: Measles cases may cluster in densely populated urban centers in sub-Saharan Africa as susceptible individuals share spatially dependent risk factors and may cluster among human immunodeficiency virus (HIV)-infected children despite high vaccination coverage.
Children hospitalized with measles at the University Teaching Hospital (UTH) in Lusaka, Zambia were enrolled in the study. The township of residence was recorded on the questionnaire and mapped; SaTScan software was used for cluster detection. A spatial-temporal scan statistic was used to investigate clustering of measles in children hospitalized during an endemic period (1998 to 2002) and during the 2010 measles outbreak in Lusaka, Zambia.
Three sequential and spatially contiguous clusters of measles cases were identified during the 2010 outbreak but no clustering among HIV-infected children was identified. In contrast, a space-time cluster among HIV-infected children was identified during the endemic period. This cluster occurred prior to the introduction of intensive measles control efforts and during a period between seasonal peaks in measles incidence.
Prediction and early identification of spatial clusters of measles will be critical to achieving measles elimination. HIV infection may contribute to spatial clustering of measles cases in some epidemiological settings.
[Show abstract][Hide abstract] ABSTRACT: In Choma District, southern Zambia, the neonatal mortality rate is approximately 40 per 1000 live births and, although the rate is decreasing, many deliveries take place outside of formal facilities. Understanding local practices during the postnatal period is essential for optimizing newborn care programs.
We conducted 36 in-depth interviews, five focus groups and eight observational sessions with recently-delivered women, traditional birth attendants, and clinic and hospital staff from three sites, focusing on skin, thermal and cord care practices for newborns in the home.
Newborns were generally kept warm by application of hats and layers of clothing. While thermal protection is provided for preterm and small newborns, the practice of nighttime bathing with cold water was common. The vernix was considered important for the preterm newborn but dangerous for HIV-exposed infants. Mothers applied various substances to the skin and umbilical cord, with special practices for preterm infants. Applied substances included petroleum jelly, commercial baby lotion, cooking oil and breastmilk. The most common substances applied to the umbilical cord were powders made of roots, burnt gourds or ash. To ward off malevolent spirits, similar powders were reportedly placed directly into dermal incisions, especially in ill children.
Thermal care for newborns is commonly practiced but co-exists with harmful practices. Locally appropriate behavior change interventions should aim to promote chlorhexidine in place of commonly-reported application of harmful substances to the skin and umbilical cord, reduce bathing of newborns at night, and address the immediate bathing of HIV-infected newborns.
[Show abstract][Hide abstract] ABSTRACT: This report summarizes 2 children misdiagnosed with HIV infection in a clinic in rural Zambia and discusses the implications of false-positive HIV DNA tests in HIV-exposed infants, including the potential magnitude of the problem. Recommendations are needed to address the management of children receiving antiretroviral therapy who are suspected of being uninfected.
[Show abstract][Hide abstract] ABSTRACT: Although malaria is preventable and treatable, it still claims 660,000 lives every year globally with children under five years of age having the highest burden. In Zambia, malaria rapid diagnostic tests (RDTs) that only detect Plasmodium falciparum are the main confirmatory means for malaria diagnosis in most health facilities without microscopy services. As a consequence of this P. falciparum species diagnostic approach, non-falciparum malaria is not only under-diagnosed but entirely missed, thereby making the exact disease burden unknown. We thus investigated the prevalence of various Plasmodium spp. and associated burden of infection in selected communities in Zambia.
Data from two malaria hyper-endemic provinces (Eastern and Luapula) of the 2012 National Malaria Indicator Survey (MIS), conducted between April and May 2012, were used. The MIS is a nationally representative, two-stage cluster survey conducted to coincide with the end of the malaria transmission season. Social, behavioural and background information were collected from households as part of the survey. Thick blood smears, RDTs and dried blood spots (DBS) were collected from children below six years of age. Slides were stained using Giemsa and examined by microscopy while polymerase chain reaction (PCR) was used to analyse the DBS for malaria Plasmodium spp. Multivariate logistic regression was employed to examine the association between background factors and malaria.
Overall, 873 children younger than six years of age were surveyed. The overall prevalence of Plasmodium spp. by PCR was 54.3% (95% CI 51-57.6%). Of the total Plasmodium isolates, 88% were P. falciparum, 10.6% were mixed infections and 1.4% were non-falciparum mono infections. Among the mixed infections, the majority were a combination of P. falciparum and P. malariae (6.5% of all mixed infections). Children two years and older (2-5 years) had three-fold higher risk of mixed malaria infections (aOR 2.8 CI 1.31-5.69) than children younger than two years of age.
The high prevalence of mixed Plasmodium spp. infections in this population stresses review of the current malaria RDT diagnostic approaches. The observed less incidence of mixed infections in children under two years of age compared to their older two-to-five-year-old counterparts is probably due to the protective maternal passive immunity, among other factors, in that age group.
[Show abstract][Hide abstract] ABSTRACT: Background
Travel time and distance are barriers to care for HIV-infected children in rural sub-Saharan Africa. Decentralization of care is one strategy to scale-up access to antiretroviral therapy (ART), but few programs have been evaluated. We compared outcomes for children receiving care in mobile and hospital-affiliated HIV clinics in rural Zambia.
Outcomes were measured within an ongoing cohort study of HIV-infected children seeking care at Macha Hospital, Zambia from 2007 to 2012. Children in the outreach clinic group received care from the Macha HIV clinic and transferred to one of three outreach clinics. Children in the hospital-affiliated clinic group received care at Macha HIV clinic and reported Macha Hospital as the nearest healthcare facility.
Seventy-seven children transferred to the outreach clinics and were included in the analysis. Travel time to the outreach clinics was significantly shorter and fewer caretakers used public transportation, resulting in lower transportation costs and fewer obstacles accessing the clinic. Some caretakers and health care providers reported inferior quality of service provision at the outreach clinics. Sixty-eight children received ART at the outreach clinics and were compared to 41 children in the hospital-affiliated clinic group. At ART initiation, median age, weight-for-age z-scores (WAZ) and CD4+ T-cell percentages were similar for children in the hospital-affiliated and outreach clinic groups. Children in both groups experienced similar increases in WAZ and CD4+ T-cell percentages.
HIV care and treatment can be effectively delivered to HIV-infected children at rural health centers through mobile ART teams, removing potential barriers to uptake and retention. Outreach teams should be supported to increase access to HIV care and treatment in rural areas.
PLoS ONE 08/2014; 9(8):e104884. DOI:10.1371/journal.pone.0104884 · 3.23 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Malaria control interventions have been scaled-up in Zambia in conjunction with a malaria surveillance system. Although substantial progress has been achieved in reducing morbidity and mortality, national and local information demonstrated marked heterogeneity in the impact of malaria control across the country. This study reports the high burden of malaria in Nchelenge District, Luapula Province, Zambia from 2006 to 2012 after seven years of control measures.
Yearly aggregated information on cases of malaria, malaria deaths, use of malaria diagnostics, and malaria control interventions from 2006 to 2012 were obtained from the Nchelenge District Health Office. Trends in the number of malaria cases, methods of diagnosis, malaria positivity rate among pregnant women, and intervention coverage were analysed using descriptive statistics.
Malaria prevalence remained high, increasing from 38% in 2006 to 53% in 2012. Increasing numbers of cases of severe malaria were reported until 2010. Intense seasonal malaria transmission was observed with seasonal declines in the number of cases between April and August, although malaria transmission continued throughout the year. Clinical diagnosis without accompanying confirmation declined from 95% in 2006 to 35% in 2012. Intervention coverage with long-lasting insecticide-treated nets and indoor residual spraying increased from 2006 to 2012.
Despite high coverage with vector control interventions, the burden of malaria in Nchelenge District, Zambia remained high. The high parasite prevalence could accurately reflect the true burden, perhaps in part as a consequence of population movement, or improved access to care and case reporting. Quality information at fine spatial scales will be critical for targeting effective interventions and measurement of progress.
[Show abstract][Hide abstract] ABSTRACT: The timing of a child's first acute lower respiratory infection (ALRI) is important, because the younger a child is when he or she experiences ALRI, the greater the risk of death. Indoor exposure to particulate matter less than or equal to 2.5 µm in diameter (PM2.5) has been associated with increased frequency of ALRI, but little is known about how it may affect the timing of a child's first ALRI. In this study, we aimed to estimate the association between a child's age at first ALRI and indoor exposure to PM2.5 in a low-income community in Dhaka, Bangladesh. We followed 257 children from birth through age 2 years to record their age at first ALRI. Between May 2009 and April 2010, we also measured indoor concentrations of PM2.5 in children's homes. We used generalized gamma distribution models to estimate the relative age at first ALRI associated with the mean number of hours in which PM2.5 concentrations exceeded 100 µg/m(3). Each hour in which PM2.5 levels exceeded 100 µg/m(3) was independently associated with a 12% decrease (95% confidence interval: 2, 21; P = 0.021) in age at first ALRI. Interventions to reduce indoor exposure to PM2.5 could increase the ages at which children experience their first ALRI in this urban community.
American journal of epidemiology 03/2014; 179(8). DOI:10.1093/aje/kwu002 · 4.98 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Early infant HIV diagnosis is challenging in sub-Saharan Africa, particularly in rural areas where laboratory capacity is limited. Specimens must be transported to central laboratories for testing, leading to delays in diagnosis and initiation of antiretroviral therapy. This study was undertaken in rural Zambia to measure the turnaround time for confirmation of HIV infection and identify delays in diagnosis.
Chart reviews were conducted from 2010-2012 for children undergoing early infant HIV diagnosis at Macha Hospital in Zambia. Relevant dates, receipt of drugs by mother and child for the prevention of mother-to-child transmission (PMTCT), and test results were abstracted.
403 infants provided 476 samples for early infant diagnosis. The median age at the "6-week" and "6-month" assessments was 8.1 weeks and 7.0 months, respectively. The majority of mothers (80%) and infants (67%) received PMTCT. The median time between sample collection and arrival at the central laboratory in Lusaka was 17 days (IQR: 10, 28); arrival at the central laboratory to testing was 6 days (IQR: 5, 11); testing to return of results to the clinic was 29 days (IQR: 17, 36); arrival of results at the clinic to return of results to the caregiver was 45 days (IQR: 24, 79). The total median time from sample collection to return of results to the caregiver was 92 days (IQR: 84, 145). The proportion of HIV PCR positive samples was 12%. The total median turnaround time was shorter for HIV PCR positive as compared to negative or invalid samples (85 vs. 92 days; p = 0.08).
Delays in processing and communicating test results were identified, particularly in returning results from the central laboratory to the clinic and from the clinic to the caregiver. A more efficient process is needed so that caregivers can be provided test results more rapidly, potentially resulting in earlier treatment initiation and better outcomes for HIV-infected infants.
PLoS ONE 01/2014; 9(1):e87028. DOI:10.1371/journal.pone.0087028 · 3.23 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Recent outbreaks of measles and polio in low-income countries illustrate that conventional methods for estimating vaccination coverage do not adequately identify susceptible children. Immune markers of protection against vaccine-preventable diseases in oral fluid (OF) or blood may generate more accurate measures of effective vaccination history, but questions remain about whether antibody surveys are feasible and informative tools for monitoring immunization program performance compared to conventional vaccination coverage indicators. This study compares six indicators of measles vaccination status, including immune markers in oral fluid and blood, from children in rural Bangladesh and evaluates the implications of using each indicator to estimate measles vaccination coverage.
A cross-sectional population-based study of children ages 12-16 months in Mirzapur, Bangladesh, ascertained measles vaccination (MCV1) history from conventional indicators: maternal report, vaccination card records, 'card + history' and EPI clinic records. Oral fluid from all participants (n = 1226) and blood from a subset (n = 342) were tested for measles IgG antibodies as indicators of MCV1 history and compared to conventional MCV1 coverage indicators.
Maternal report yielded the highest MCV1 coverage estimates (90.8%), followed by EPI records (88.6%), and card + history (84.2%). Seroprotection against measles by OF (57.3%) was significantly lower than other indicators, even after adjusting for incomplete seroconversion and assay performance (71.5%). Among children with blood results, 88.6% were seroprotected, which was significantly higher than coverage by card + history and OF serostatus but consistent with coverage by maternal report and EPI records. Children with vaccination cards or EPI records were more likely to have a history of receiving MCV1 than those without cards or records. Despite similar MCV1 coverage estimates across most indicators, within-child agreement was poor for all indicators.
Measles IgG antibodies in OF was not a suitable immune marker for monitoring measles vaccination coverage in this setting. Because agreement between conventional MCV1 indicators was mediocre, immune marker surveillance with blood samples could be used to validate conventional MCV1 indicators and generate adjusted results that can be compared across indicators.
BMC Public Health 12/2013; 13(1):1211. DOI:10.1186/1471-2458-13-1211 · 2.32 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Malaria control was strengthened in Zambia over the past decade. The two primary interventions for vector control are indoor residual spraying (IRS) and long-lasting insecticide-treated nets (LLINs). Using passive malaria surveillance data collected from 2006 to 2011 through the Zambian District Health Information System, the associations between increased coverage with LLINs and IRS and the burden of malaria in Zambia was evaluated.
National passive malaria surveillance data from 2006 to 2011 were analysed. A district-level, random-effects model with Poisson regression was used to explore the association between malaria cases and coverage with LLINs and IRS. Malaria cases and LLINs and IRS coverage were mapped to visualize spatiotemporal variation in malaria for each year.
From 2006--2011, 24.6 million LLINs were distributed and 6.4 million houses were sprayed with insecticide. Coverage with LLINs was not uniformly distributed over the study period and IRS was targeted to central and southern districts where malaria transmission was low. LLIN coverage was associated with a reduction in malaria cases, although an increase in the number of malaria cases was reported in some districts over the study period. A high burden of malaria persisted in north-eastern Zambia, whereas a reduction in the number of reported malaria cases was observed in western and southern Zambia.
Enhanced and targeted interventions in north-eastern Zambia where the burden of malaria remains high, as well as efforts to sustain low malaria transmission in the south-west, will be necessary for Zambia to achieve the national goal of being malaria free by 2030.
[Show abstract][Hide abstract] ABSTRACT: Exposure to particulate matter (PM2.5 ) from the burning of biomass is associated with increased risk of respiratory disease. In Dhaka, Bangladesh, households that do not burn biomass often still experience high concentrations of PM2.5 but the sources remain unexplained. We characterized the diurnal variation in the concentrations of PM2.5 in 257 households and compared the risk of experiencing high PM2.5 concentrations in biomass and non-biomass users. Indoor PM2.5 concentrations were estimated every minute over 24 hours once a month from April 2009 through April 2010. We found that households that used gas or electricity experienced PM2.5 concentrations exceeding 1000 μg/m(3) for a mean of 35 minutes within a 24-hour period compared to 66 minutes in biomass burning households. In both households that used biomass and those that had no obvious source of particulate matter, the probability of PM2.5 exceeding 1000 μg/m(3) were highest during distinct morning, afternoon and evening periods. In such densely populated settings, indoor pollution in clean fuel households may be determined by biomass used by neighbors, with the highest risk of exposure occurring during cooking periods. Community interventions to reduce biomass use may reduce exposure to high concentrations of PM2.5 in both biomass and non-biomass using households. This article is protected by copyright. All rights reserved.
Indoor Air 08/2013; DOI:10.1111/ina.12065 · 4.20 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Case detection and treatment are critical to malaria control and elimination as infected individuals who do not seek medical care can serve as persistent reservoirs for transmission.
Household malaria surveys were conducted in two study areas within Southern Province, Zambia in 2007 and 2008. Cross-sectional surveys were conducted approximately five times throughout the year in each of the two study areas. During study visits, adults and caretakers of children were administered a questionnaire and a blood sample was obtained for a rapid diagnostic test (RDT) for malaria. These data were used to estimate the proportions of individuals with malaria potentially identified through passive case detection at health care facilities and those potentially identified through reactive case finding. Simulations were performed to extrapolate data from sampled to non-sampled households. Radii of increasing size surrounding households with an index case were examined to determine the proportion of households with an infected individual that would be identified through reactive case detection.
In the 2007 high transmission setting, with a parasite prevalence of 23%, screening neighboring households within 500 meters of an index case could have identified 89% of all households with an RDT positive resident and 90% of all RDT positive individuals. In the 2008 low transmission setting, with a parasite prevalence of 8%, screening neighboring households within 500 meters of a household with an index case could have identified 77% of all households with an RDT positive resident and 76% of all RDT positive individuals.
Testing and treating individuals residing within a defined radius from an index case has the potential to be an effective strategy to identify and treat a large proportion of infected individuals who do not seek medical care, although the efficiency of this strategy is likely to decrease with declining parasite prevalence.
PLoS ONE 08/2013; 8(8):e70972. DOI:10.1371/journal.pone.0070972 · 3.23 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Background. In 2010, Zambia had a large measles outbreak providing an opportunity to measure changes in measles serostatus following highly active antiretroviral therapy (HAART), exposure to measles virus and revaccination among children infected with human immunodeficiency virus (HIV).Methods. A prospective cohort study of 169 HIV-infected Zambian children 9 to 60 months of age with a history of measles vaccination was conducted to characterize the effects of HAART and revaccination on measles IgG serostatus by enzyme immunoassay.Results. Prior to the measles outbreak, only 23% of HIV-infected children were measles IgG seropositive at HAART initiation. After adjusting for 6-month changes in baseline age and 5% changes in nadir CD4(+) T cell percentage, HAART was not associated with measles IgG seroconversion. However, 18 of 19 children seroconverted after revaccination. Eight children seroconverted during the outbreak without revaccination and were likely exposed to wild-type measles virus but none were reported to have had clinical measles.Conclusions. Immune reconstitution after HAART initiation did not restore protective levels of measles IgG antibodies but almost all children developed protective antibody levels after revaccination. Some previously vaccinated HIV-infected children had serological evidence of exposure to wild-type measles virus without a reported history of measles.
The Journal of Infectious Diseases 08/2013; 208(11). DOI:10.1093/infdis/jit404 · 5.78 Impact Factor