[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: Malaria risk maps may be used to guide policy decisions on whether vector control interventions should be targeted and, if so, where. Active surveillance for malaria was conducted through household surveys in Nchelenge District, Zambia from April 2012 through December 2014. Households were enumerated based on satellite imagery and randomly selected for study enrollment. At each visit, participants were administered a questionnaire and a malaria rapid diagnostic test (RDT). Logistic regression models were used to construct spatial prediction risk maps and maps of risk uncertainty. A total of 461 households were visited, comprising 1,725 participants, of whom 48% were RDT positive. Several environmental features were associated with increased household malaria risk in a multivariable logistic regression model with seasonal variation. The model was validated using both internal and external evaluation measures to generate and assess root mean square error, as well as sensitivity and specificity for predicted risk. The final, validated model was used to predict and map malaria risk including a measure of risk uncertainty. Malaria risk in a high, perennial transmission setting is widespread but heterogeneous at a local scale, with seasonal variation. Targeting malaria control interventions may not be appropriate in this epidemiological setting.
The American journal of tropical medicine and hygiene 09/2015; DOI:10.4269/ajtmh.15-0283 · 2.70 Impact Factor
[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: High-resolution satellite imagery can be used to establish a sampling frame for epidemiologic research and to describe patterns of household distribution and movement. Assessing the frequency and geographic distribution of household movement by comparing satellite images taken over time may suggest a time period for satellite image accuracy and utility for epidemiological research. All households in a 575 km2 region of southern Zambia were enumerated based on satellite images taken in 2007 and in 2011. Movement of households in the study area was assessed by comparing the images to calculate the percentage of households that were built, removed or stayed the same. We created a spatial intensity map to identify geographic areas of household movement, and to describe the spatial variation in household movement. There were a total of 3,287 household enumerated in 2007 and 3,721 in 2011. 970 households were newly observed in 2011 and 536 were no longer present. Reporting a net change of 434 households occurring over the four year period does not adequately describe the population movement within this region. Spatial variation around key features, such as around the new sealed road, points to non-uniform dynamics in population movement. These population dynamics may have implications for field studies working in this area over this time period.
American Society of Tropical Medicine and Hygiene, New Orleans; 11/2014
[Show abstract][Hide abstract] ABSTRACT: While malaria transmission has declined substantially throughout parts
of Zambia, some areas continue to experience high transmission levels despite deployment of malaria control efforts. Understanding factors associated with continued malaria transmission in these areas may inform control efforts. Household malaria surveys were conducted in Nchelenge District, Luapula Province, Zambia. Households were enumerated based on satellite imagery, 5 x 5 km grid cells were overlaid, and households were randomly chosen within selected grid cells. Households were enrolled into cross-sectional (one visit) or longitudinal (visits every other month) cohorts; analyses were restricted to cross-sectional and the first visit to longitudinal households. During study visits, adults and caretakers of children were administered a questionnaire and a blood sample was collected for a malaria rapid diagnostic test (RDT). Individual and household level factors associated with RDT positivity were analyzed using logistic regression models. A total of 1,201 individuals from 339 households were enrolled. Over the study period, 43% of participants were RDT positive. Over half
of RDT positive individuals were between the ages of 5 and 17 years, and half of RDT positive individuals had visited a health center or health post for malaria in the past 6 months. In the multi-variable logistic regression analysis, RDT positive individuals were over twice as likely to be between the ages of 5 and 17 years as compared to children younger than 5 years (OR=2.06; 95% CI: 1.23, 3.44), over half as likely to report a fever within the past two weeks (OR=1.57; 95% CI: 1.04, 2.37), and 73% more
likely to live in a household using an open well as the main water source (OR=1.73; 95% CI: 1.15, 2.6). RDT positivity was highest among children and adolescents between the ages of 5 and 17 years. RDT positives were likely to experience symptoms and have sought care. Open wells may be a breeding site for mosquito vectors, potentially contributing to malaria transmission.
American Society of Tropical Medicine and Hygiene; 11/2014
[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 · 5.23 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