Characterizing mobility patterns of forest goers in southern Lao PDR using GPS loggers.

BACKGROUND: In the Greater Mekong Subregion (GMS), forest-going populations are considered high-risk populations for malaria and are increasingly targeted by national control programmes' elimination efforts. A better understanding of forest-going populations' mobility patterns and risk associated with specific types of forest-going trips is necessary for countries in the GMS to achieve their objective of eliminating malaria by 2030. METHODS: Between March and November 2018, as part of a focal test and treat intervention (FTAT), 2,904 forest-goers were recruited in southern Lao PDR. A subset of forest-goers carried an "i-Got-U" GPS logger for roughly 2 months, configured to collect GPS coordinates every 15 to 30 min. The utilization distribution (UD) surface around each GPS trajectory was used to extract trips to the forest and forest-fringes. Trips with shared mobility characteristics in terms of duration, timing and forest penetration were identified by a hierarchical clustering algorithm. Then, clusters of trips with increased exposure to dominant malaria vectors in the region were further classified as high-risk. Finally, gradient boosting trees were used to assess which of the forest-goers' socio-demographic and behavioural characteristics best predicted their likelihood to engage in such high-risk trips. RESULTS: A total of 122 forest-goers accepted carrying a GPS logger resulting in the collection of 803 trips to the forest or forest-fringes. Six clusters of trips emerged, helping to classify 385 (48%) trips with increased exposure to malaria vectors based on high forest penetration and whether the trip happened overnight. Age, outdoor sleeping structures and number of children were the best predictors of forest-goers' probability of engaging in high-risk trips. The probability of engaging in high-risk trips was high (~ 33%) in all strata of the forest-going population. CONCLUSION: This study characterized the heterogeneity within the mobility patterns of forest-goers and attempted to further segment their role in malaria transmission in southern Lao People's Democratic Republic (PDR). National control programmes across the region can leverage these results to tailor their interventions and messaging to high-risk populations and accelerate malaria elimination.

Characterizing the spatial distribution of multiple malaria diagnostic endpoints in a low-transmission setting in Lao PDR.

The epidemiology of malaria changes as prevalence falls in low-transmission settings, with remaining infections becoming more difficult to detect and diagnose. At this stage active surveillance is critical to detect residual hotspots of transmission. However, diagnostic tools used in active surveillance generally only detect concurrent infections, and surveys may benefit from sensitive tools such as serological assays. Serology can be used to interrogate and characterize individuals' previous exposure to malaria over longer durations, providing information essential to the detection of remaining foci of infection. We ran blood samples collected from a 2016 population-based survey in the low-transmission setting of northern Lao PDR on a multiplexed bead assay to characterize historic and recent exposures to Plasmodium falciparum and vivax. Using geostatistical methods and remote-sensing data we assessed the environmental and spatial associations with exposure, and created predictive maps of exposure within the study sites. We additionally linked the active surveillance PCR and serology data with passively collected surveillance data from health facility records. We aimed to highlight the added information which can be gained from serology as a tool in active surveillance surveys in low-transmission settings, and to identify priority areas for national surveillance programmes where malaria risk is higher. We also discuss the issues faced when linking malaria data from multiple sources using multiple diagnostic endpoints.

Performance of five pulse oximeters to detect hypoxaemia as an indicator of severe illness in children under five by frontline health workers in low resource settings - A prospective, multicentre, single-blinded, trial in Cambodia, Ethiopia, South Sudan, and Uganda.

BACKGROUND: Low blood oxygen saturation (SpO2), or hypoxaemia, is an indicator of severe illness in children. Pulse oximetry is a globally accepted, non-invasive method to identify hypoxaemia, but rarely available outside higher-level facilities in resource-constrained countries. This study aims to evaluate the performance of different types of pulse oximeters amongst frontline health workers in Cambodia, Ethiopia, South Sudan, and Uganda. METHODS: Five pulse oximeters (POx) which passed laboratory testing, out of an initial 32 potential pulse oximeters, were evaluated by frontline health workers for performance, defined as agreement between the SpO2 measurements of the test device and the reference standard. The study protocol is registered with the Australia New Zealand Clinical Trials Registry (Ref: ACTRrn12615000348550). FINDINGS: Two finger-tip pulse oximeters (Contec and Devon), two handheld pulse oximeters (Lifebox and Utech), and one phone pulse oximeter (Masimo) passed the laboratory testing. They were evaluated for performance on 1,313 children under five years old by 207 frontline health workers between February and May 2015. Phone and handheld pulse oximeters had greater overall agreement with the reference standard (56%; 95% CI 0.52 - 0.60 to 68%; 95% CI 0.65 - 0.71) than the finger-tip POx (31%; 95% CI 0.26 to 0.36 and 47%; 95% CI 0.42 to 0.52). Fingertip POx performance was substantially lower in the 0-2 month olds; having just 17% and 25% agreement. The finger-tip devices more often underreported SpO2 readings (mean difference -7.9%; 95%CI -8.6,-7.2 and -3.9%; 95%CI -4.4,-3.4), and therefore over diagnosed hypoxaemia in the children assessed. INTERPRETATION: While the Masimo phone pulse oximeter performed best, all handheld POx with age-specific probes performed well in the hands of frontline health workers, further highlighting their suitability as a screening tool of severe illness. The poor performance of the fingertip POx suggests they should not be used in children under five by frontline health workers. It is essential that POx are performance tested on children in routine settings (in vivo), not only in laboratories or controlled settings (in vitro), before being introduced at scale. FUNDING: Bill & Melinda Gates Foundation [OPP1054367].

Population size estimation of seasonal forest-going populations in southern Lao PDR.

Forest-going populations are key to malaria transmission in the Greater Mekong Sub-region (GMS) and are therefore targeted for elimination efforts. Estimating the size of this population is essential for programs to assess, track and achieve their elimination goals. Leveraging data from three cross-sectional household surveys and one survey among forest-goers, the size of this high-risk population in a southern province of Lao PDR between December 2017 and November 2018 was estimated by two methods: population-based household surveys and capture-recapture. During the first month of the dry season, the first month of the rainy season, and the last month of the rainy season, respectively, 16.2% [14.7; 17.7], 9.3% [7.2; 11.3], and 5.3% [4.4; 6.1] of the adult population were estimated to have engaged in forest-going activities. The capture-recapture method estimated a total population size of 18,426 [16,529; 20,669] forest-goers, meaning 61.0% [54.2; 67.9] of the adult population had engaged in forest-going activities over the 12-month study period. This study demonstrates two methods for population size estimation to inform malaria research and programming. The seasonality and turnover within this forest-going population provide unique opportunities and challenges for control programs across the GMS as they work towards malaria elimination.

Spatio-temporal associations between deforestation and malaria incidence in Lao PDR.

As countries in the Greater Mekong Sub-region (GMS) increasingly focus their malaria control and elimination efforts on reducing forest-related transmission, greater understanding of the relationship between deforestation and malaria incidence will be essential for programs to assess and meet their 2030 elimination goals. Leveraging village-level health facility surveillance data and forest cover data in a spatio-temporal modeling framework, we found evidence that deforestation is associated with short-term increases, but long-term decreases confirmed malaria case incidence in Lao People's Democratic Republic (Lao PDR). We identified strong associations with deforestation measured within 30 km of villages but not with deforestation in the near (10 km) and immediate (1 km) vicinity. Results appear driven by deforestation in densely forested areas and were more pronounced for infections with Plasmodium falciparum (P. falciparum) than for Plasmodium vivax (P. vivax). These findings highlight the influence of forest activities on malaria transmission in the GMS.

Biting mosquitos spread the malaria parasite to humans. Along the Mekong River in Southeast Asia, spending time in the surrounding forest increases a person's risk of malaria. This has led to a debate about whether deforestation in this area, which is called the Greater Mekong Sub-region (GMS), will increase or decrease malaria transmission. The answer to the debate is not clear because some malaria-transmitting mosquitos thrive in heavily forested areas, in particular in the GMS, while others prefer less forested areas. Scientists studying malaria in the Amazon in South America suspect that malaria transmission increases shortly after deforestation but decreases six to eight years later. Some studies have tested this 'frontier malaria' theory but the results have been conflicting. Fewer studies have tested this theory in Southeast Asia. But deforestation has been blamed for recent malaria outbreaks in the GMS. Using data on malaria testing and forest cover in the GMS, Rerolle et al. show that deforestation around villages increases malaria transmission in the first two years and decreases malaria rates later. This trend was driven mostly by a type of malaria called Plasmodium falciparum and was less strong for Plasmodium vivax. The location of deforested areas also mattered. Deforestation within one to 10 kilometer of villages did not affect malaria rates. Deforestation further away in about a 30 kilometer radius did affect malaria transmission. Rerolle et al. suggest this may be because villagers have to spend longer times trekking through forests to hunt or harvest wood when the wider area is deforested. Currently, National Malaria Control Programs in the GMS focus their efforts on reducing forest-related transmission. This study strengthens the evidence supporting this approach. The results also suggest that different malaria elimination strategies may be necessary for different types of malaria parasite. Using this new information could help malaria control programs better target resources or educate villagers on how to protect themselves. The innovative methods used by Rerolle et al. reveal a more complex role of deforestation in malaria transmission and may inspire other scientists to think more carefully about environmental drivers of malaria.

Tools to accelerate falciparum malaria elimination in Cambodia: a meeting report.

Cambodia targets malaria elimination by 2025. Rapid elimination will depend on successfully identifying and clearing malaria foci linked to forests. Expanding and maintaining universal access to early diagnosis and effective treatment remains the key to malaria control and ultimately malaria elimination in the Greater Mekong Subregion (GMS) in the foreseeable future. Mass Drug Administration (MDA) holds some promise in the rapid reduction of Plasmodium falciparum infections, but requires considerable investment of resources and time to mobilize the target communities. Furthermore, the most practical drug regimen for MDA in the GMS-three rounds of DHA/piperaquine-has lost some of its efficacy. Mass screening and treatment benefits asymptomatic P. falciparum carriers by clearing chronic infections, but in its current form holds little promise for malaria elimination. Hopes that "highly sensitive" diagnostic tests would provide substantial advances in screen and treat programmes have been shown to be misplaced. To reduce the burden on P. falciparum and Plasmodium vivax infections in people working in forested areas novel approaches to the use of malaria prophylaxis in forest workers should be explored. During an October 2019 workshop in Phnom Penh researchers and policymakers reviewed evidence of acceptability, feasibility and effectiveness of interventions to target malaria foci and interrupt P. falciparum transmission and discussed operational requirements and conditions for programmatic implementation.

Performance of Four Respiratory Rate Counters to Support Community Health Workers to Detect the Symptoms of Pneumonia in Children in Low Resource Settings: A Prospective, Multicentre, Hospital-Based, Single-Blinded, Comparative Trial.

BACKGROUND: Pneumonia is one of the leading causes of death in children under-five globally. The current diagnostic criteria for pneumonia are based on increased respiratory rate (RR) or chest in-drawing in children with cough and/or difficulty breathing. Accurately counting RR is difficult for community health workers (CHWs). Current RR counting devices are frequently inadequate or unavailable. This study analysed the performance of improved RR timers for detection of pneumonia symptoms in low-resource settings. METHODS: Four RR timers were evaluated on 454 children, aged from 0 to 59 months with cough and/or difficulty breathing, over three months, by CHWs in hospital settings in Cambodia, Ethiopia, South Sudan and Uganda. The devices were the Mark Two ARI timer (MK2 ARI), counting beads with ARI timer, Rrate Android phone and the Respirometer feature phone applications. Performance was evaluated for agreement with an automated RR reference standard (Masimo Root patient monitoring and connectivity platform with ISA CO2 capnography). This study is registered with ANZCTR [ACTRN12615000348550]. FINDINGS: While most CHWs managed to achieve a RR count with the four devices, the agreement was low for all; the mean difference of RR measurements from the reference standard for the four devices ranged from 0.5 (95% C.I. - 2.2 to 1.2) for the respirometer to 5.5 (95% C.I. 3.2 to 7.8) for Rrate. Performance was consistently lower for young infants (0 to < 2 months) than for older children (2 to ≤ 59 months). Agreement of RR classification into fast and normal breathing was moderate across all four devices, with Cohen's Kappa statistics ranging from 0.41 (SE 0.04) to 0.49 (SE 0.05). INTERPRETATION: None of the four devices evaluated performed well based on agreement with the reference standard. The ARI timer currently recommended for use by CHWs should only be replaced by more expensive, equally performing, automated RR devices when aspects such as usability and duration of the device significantly improve the patient-provider experience. FUNDING: Bill & Melinda Gates Foundation [OPP1054367].

Study protocol for a cluster-randomized split-plot design trial to assess the effectiveness of targeted active malaria case detection among high-risk populations in Southern Lao PDR (the AcME-Lao study).

Introduction: Novel interventions are needed to accelerate malaria elimination, especially in areas where asymptomatic parasitemia is common, and where transmission generally occurs outside of village-based settings. Testing of community members linked to a person with clinical illness (reactive case detection, RACD) has not shown effectiveness in prior studies due to the limited sensitivity of current point-of-care tests. This study aims to assess the effectiveness of active case finding in village-based and forested-based settings using novel high-sensitivity rapid diagnostic tests in Lao People's Democratic Republic (Lao PDR). Methods and analysis: This study is a cluster-randomized split-plot design trial. The interventions include village-based mass test and treat (MTAT), focal test and treat in high-risk populations (FTAT), and the combination of these approaches, using high-sensitivity rapid diagnostic tests (HS-RDTs) to asses P. falciparum infection status. Within four districts in Champasak province, Lao PDR fourteen health center-catchment areas will be randomized to either FTAT or control; and within these HCCAs, 56 villages will be randomized to either MTAT or control. In intervention areas, FTAT will be conducted by community-based peer navigators on a routine basis, and three separate rounds of MTAT are planned. The primary study outcome will be PCR-based Plasmodium falciparum prevalence after one year of implementation. Secondary outcomes include malaria incidence; interventional coverage; operational feasibility and acceptability; and cost and cost- effectiveness. Ethics and dissemination: Findings will be reported on clinicaltrials.gov, in peer-reviewed publications and through stakeholder meetings with Ministry of Health and community leaders in Lao PDR and throughout the Greater Mekong Subregion. Trial registration: clinicaltrials.gov NCT03783299 (21/12/2018).

Prevalence and risk factors for asymptomatic malaria and genotyping of glucose 6-phosphate (G6PD) deficiencies in a vivax-predominant setting, Lao PDR: implications for sub-national elimination goals.

BACKGROUND: Lao People Democratic Republic (PDR; Laos), a landlocked country in Southeast Asia, has made important progress in reducing malaria morbidity and mortality in the past 5-6 years, and the northern provinces have very low reported incidence. To support national progress towards elimination, it is critical to verify and understand these changes in disease burden. METHODS: A two-stage cluster cross-sectional survey was conducted in four districts within four northern provinces (Khua, Phongsaly Province; Paktha, Bokeo Province; Nambak, Luang Prabang, and Muang Et, Huaphanh Province). During September and October 2016, demographics and malaria risk factors were collected from a total of 1492 households. A total of 5085 persons consented to collection of blood samples for testing, by rapid diagnostic test (RDT) and polymerase chain reaction (PCR)-based testing. Risk factors for infection were examined using logistic regression; and a randomized subset of males was tested for glucose-6-phosphate dehydrogenase (G6PD) deficiencies using a combined PCR and sequencing approach. RESULTS: There were zero positives by RDT, and PCR detected Plasmodium infections in 39 (0.77%; 95% CI 0.40-1.47%) of 5082 analysable samples. The species distribution was Plasmodium vivax (28 total); Plasmodium falciparum/P. vivax (5); P. falciparum (3), Plasmodium malariae (2), and P. vivax/P. malariae (1). In multivariable analysis, the main risk factors included having any other cases within the household [aOR 12.83 (95% CI 4.40 to 37.38), p < 0.001]; and lack of bed net ownership within the household [aOR 10.91 (95% 5.42-21.94), p < 0.001]; age, sex and forest-travel were not associated with parasitaemia. A total of 910 males were tested for the six most common G6PDd in SE Asia; and 30 (3.3%; 95% CI 2.1-5.1%) had a G6PD variant allele associated with G6PD deficiency, with the majority being the Union (14) and Viangchan (11) polymorphisms, with smaller numbers of Canton and Mahidol. CONCLUSION: This is the first rigorous PCR-based population survey for malaria infection in Northern Lao PDR, and found a very low prevalence of asymptomatic Plasmodium infections by standard PCR methods, with P. vivax predominating in the surveyed districts. Clustering of cases within households, and lack of a bed nets suggest reactive case detection, and scale-up of coverage should be prioritized. The predominance of infections with P. vivax, combined with moderate levels of serious G6PD deficiencies highlight the need for careful rollout of primaquine towards elimination goals.

A shortened verbal autopsy instrument for use in routine mortality surveillance systems.

BACKGROUND: Verbal autopsy (VA) is recognized as the only feasible alternative to comprehensive medical certification of deaths in settings with no or unreliable vital registration systems. However, a barrier to its use by national registration systems has been the amount of time and cost needed for data collection. Therefore, a short VA instrument (VAI) is needed. In this paper we describe a shortened version of the VAI developed for the Population Health Metrics Research Consortium (PHMRC) Gold Standard Verbal Autopsy Validation Study using a systematic approach. METHODS: We used data from the PHMRC validation study. Using the Tariff 2.0 method, we first established a rank order of individual questions in the PHMRC VAI according to their importance in predicting causes of death. Second, we reduced the size of the instrument by dropping questions in reverse order of their importance. We assessed the predictive performance of the instrument as questions were removed at the individual level by calculating chance-corrected concordance and at the population level with cause-specific mortality fraction (CSMF) accuracy. Finally, the optimum size of the shortened instrument was determined using a first derivative analysis of the decline in performance as the size of the VA instrument decreased for adults, children, and neonates. RESULTS: The full PHMRC VAI had 183, 127, and 149 questions for adult, child, and neonatal deaths, respectively. The shortened instrument developed had 109, 69, and 67 questions, respectively, representing a decrease in the total number of questions of 40-55%. The shortened instrument, with text, showed non-significant declines in CSMF accuracy from the full instrument with text of 0.4%, 0.0%, and 0.6% for the adult, child, and neonatal modules, respectively. CONCLUSIONS: We developed a shortened VAI using a systematic approach, and assessed its performance when administered using hand-held electronic tablets and analyzed using Tariff 2.0. The length of a VA questionnaire was shortened by almost 50% without a significant drop in performance. The shortened VAI developed reduces the burden of time and resources required for data collection and analysis of cause of death data in civil registration systems.

Improving performance of the Tariff Method for assigning causes of death to verbal autopsies.

BACKGROUND: Reliable data on the distribution of causes of death (COD) in a population are fundamental to good public health practice. In the absence of comprehensive medical certification of deaths, the only feasible way to collect essential mortality data is verbal autopsy (VA). The Tariff Method was developed by the Population Health Metrics Research Consortium (PHMRC) to ascertain COD from VA information. Given its potential for improving information about COD, there is interest in refining the method. We describe the further development of the Tariff Method. METHODS: This study uses data from the PHMRC and the National Health and Medical Research Council (NHMRC) of Australia studies. Gold standard clinical diagnostic criteria for hospital deaths were specified for a target cause list. VAs were collected from families using the PHMRC verbal autopsy instrument including health care experience (HCE). The original Tariff Method (Tariff 1.0) was trained using the validated PHMRC database for which VAs had been collected for deaths with hospital records fulfilling the gold standard criteria (validated VAs). In this study, the performance of Tariff 1.0 was tested using VAs from household surveys (community VAs) collected for the PHMRC and NHMRC studies. We then corrected the model to account for the previous observed biases of the model, and Tariff 2.0 was developed. The performance of Tariff 2.0 was measured at individual and population levels using the validated PHMRC database. RESULTS: For median chance-corrected concordance (CCC) and mean cause-specific mortality fraction (CSMF) accuracy, and for each of three modules with and without HCE, Tariff 2.0 performs significantly better than the Tariff 1.0, especially in children and neonates. Improvement in CSMF accuracy with HCE was 2.5%, 7.4%, and 14.9% for adults, children, and neonates, respectively, and for median CCC with HCE it was 6.0%, 13.5%, and 21.2%, respectively. Similar levels of improvement are seen in analyses without HCE. CONCLUSIONS: Tariff 2.0 addresses the main shortcomings of the application of the Tariff Method to analyze data from VAs in community settings. It provides an estimation of COD from VAs with better performance at the individual and population level than the previous version of this method, and it is publicly available for use.

Using verbal autopsy to measure causes of death: the comparative performance of existing methods.

BACKGROUND: Monitoring progress with disease and injury reduction in many populations will require widespread use of verbal autopsy (VA). Multiple methods have been developed for assigning cause of death from a VA but their application is restricted by uncertainty about their reliability. METHODS: We investigated the validity of five automated VA methods for assigning cause of death: InterVA-4, Random Forest (RF), Simplified Symptom Pattern (SSP), Tariff method (Tariff), and King-Lu (KL), in addition to physician review of VA forms (PCVA), based on 12,535 cases from diverse populations for which the true cause of death had been reliably established. For adults, children, neonates and stillbirths, performance was assessed separately for individuals using sensitivity, specificity, Kappa, and chance-corrected concordance (CCC) and for populations using cause specific mortality fraction (CSMF) accuracy, with and without additional diagnostic information from prior contact with health services. A total of 500 train-test splits were used to ensure that results are robust to variation in the underlying cause of death distribution. RESULTS: Three automated diagnostic methods, Tariff, SSP, and RF, but not InterVA-4, performed better than physician review in all age groups, study sites, and for the majority of causes of death studied. For adults, CSMF accuracy ranged from 0.764 to 0.770, compared with 0.680 for PCVA and 0.625 for InterVA; CCC varied from 49.2% to 54.1%, compared with 42.2% for PCVA, and 23.8% for InterVA. For children, CSMF accuracy was 0.783 for Tariff, 0.678 for PCVA, and 0.520 for InterVA; CCC was 52.5% for Tariff, 44.5% for PCVA, and 30.3% for InterVA. For neonates, CSMF accuracy was 0.817 for Tariff, 0.719 for PCVA, and 0.629 for InterVA; CCC varied from 47.3% to 50.3% for the three automated methods, 29.3% for PCVA, and 19.4% for InterVA. The method with the highest sensitivity for a specific cause varied by cause. CONCLUSIONS: Physician review of verbal autopsy questionnaires is less accurate than automated methods in determining both individual and population causes of death. Overall, Tariff performs as well or better than other methods and should be widely applied in routine mortality surveillance systems with poor cause of death certification practices.

Barriers and promoters of home-based pasteurization of breastmilk among HIV-infected mothers in greater Dar es Salaam, Tanzania.

BACKGROUND: For the past decade, heat-treating breastmilk has been an infant feeding option recommended by the World Health Organization as a strategy to reduce vertical transmission. However, little is known about field experiences with it. Our primary objective was to explore the barriers and promoters of the implementation of breastmilk pasteurization, "flash-heating" (FH), in the real-world setting of Dar es Salaam, Tanzania. SUBJECTS AND METHODS: Nineteen in-depth interviews were conducted with participants in a home-based infant feeding counseling intervention in which FH was promoted after 6 months of exclusive breastfeeding. Additionally, three focus group discussions were conducted with peer counselors. Interviews were transcribed, translated, and coded independently using NVivo 8 software (QSR International). Data were analyzed using the socioecological framework. RESULTS: Information and support provided by peer counselors were the most important promoters of initiation and continuation of FH; this impacted individual-, interpersonal-, and institutional-level promoters of success. Other promoters included perceived successful breastmilk expression, infant health after initiation of FH, and the inability to pay for replacement milks. Stigma was the most important barrier and cut across all levels of the framework. Other barriers included doubt about the safety or importance of pasteurized breastmilk, difficulties with expressing milk (often attributed to poor diet), and competing responsibilities. The most common suggestion for improving the uptake and duration of FH was community education. CONCLUSIONS: Given the acknowledged role of breastmilk pasteurization in the prevention of vertical transmission, further implementation research is needed. A multilevel intervention addressing barriers to FH would likely improve uptake.

Population Health Metrics Research Consortium gold standard verbal autopsy validation study: design, implementation, and development of analysis datasets.

BACKGROUND: Verbal autopsy methods are critically important for evaluating the leading causes of death in populations without adequate vital registration systems. With a myriad of analytical and data collection approaches, it is essential to create a high quality validation dataset from different populations to evaluate comparative method performance and make recommendations for future verbal autopsy implementation. This study was undertaken to compile a set of strictly defined gold standard deaths for which verbal autopsies were collected to validate the accuracy of different methods of verbal autopsy cause of death assignment. METHODS: Data collection was implemented in six sites in four countries: Andhra Pradesh, India; Bohol, Philippines; Dar es Salaam, Tanzania; Mexico City, Mexico; Pemba Island, Tanzania; and Uttar Pradesh, India. The Population Health Metrics Research Consortium (PHMRC) developed stringent diagnostic criteria including laboratory, pathology, and medical imaging findings to identify gold standard deaths in health facilities as well as an enhanced verbal autopsy instrument based on World Health Organization (WHO) standards. A cause list was constructed based on the WHO Global Burden of Disease estimates of the leading causes of death, potential to identify unique signs and symptoms, and the likely existence of sufficient medical technology to ascertain gold standard cases. Blinded verbal autopsies were collected on all gold standard deaths. RESULTS: Over 12,000 verbal autopsies on deaths with gold standard diagnoses were collected (7,836 adults, 2,075 children, 1,629 neonates, and 1,002 stillbirths). Difficulties in finding sufficient cases to meet gold standard criteria as well as problems with misclassification for certain causes meant that the target list of causes for analysis was reduced to 34 for adults, 21 for children, and 10 for neonates, excluding stillbirths. To ensure strict independence for the validation of methods and assessment of comparative performance, 500 test-train datasets were created from the universe of cases, covering a range of cause-specific compositions. CONCLUSIONS: This unique, robust validation dataset will allow scholars to evaluate the performance of different verbal autopsy analytic methods as well as instrument design. This dataset can be used to inform the implementation of verbal autopsies to more reliably ascertain cause of death in national health information systems.

Infant feeding practices among HIV-positive women in Dar es Salaam, Tanzania, indicate a need for more intensive infant feeding counselling.

OBJECTIVE: To assess feeding practices of infants born to HIV-positive women in Dar es Salaam, Tanzania. These data then served as a proxy to evaluate the adequacy of current infant feeding counselling. DESIGN: A cross-sectional survey of infant feeding behaviours. SETTING: Four clinics in greater Dar es Salaam in early 2008. SUBJECTS: A total of 196 HIV-positive mothers of children aged 6-10 months recruited from HIV clinics. RESULTS: Initiation of breast-feeding was reported by 95·4 % of survey participants. In the entire sample, 80·1 %, 34·2 % and 13·3 % of women reported exclusive breast-feeding (EBF) up to 2, 4 and 6 months, respectively. Median duration of EBF among women who ever breast-fed was 3 (interquartile range (IQR): 2·1, 4·0) months. Most non-breast-milk foods fed to infants were low in nutrient density. Complete cessation of breast-feeding occurred within 14 d of the introduction of non-breast-milk foods among 138 of the 187 children (73·8 %) who had ever received any breast milk. Of the 187 infants in the study who ever received breast milk, 19·4 % received neither human milk nor any replacement milks for 1 week or more (median duration of no milk was 14 (IQR: 7, 152) d). CONCLUSIONS: Infant feeding practices among these HIV-positive mothers resulted in infants receiving far less breast milk and more mixed complementary feeds than recommended, thus placing them at greater risk of both malnutrition and HIV infection. An environment that better enables mothers to follow national guidelines is urgently needed. More intensive infant feeding counselling programmes would very likely increase rates of optimal infant feeding.