Last data update: Apr 29, 2024. (Total: 46658 publications since 2009)
Records 1-13 (of 13 Records) |
Query Trace: Chipeta Z [original query] |
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Causes of severe pneumonia requiring hospital admission in children without HIV infection from Africa and Asia: the PERCH multi-country case-control study
Pneumonia Etiology Research for Child Health Study Group , O'Brien Katherine L , Levine Orin S , Knoll Maria Deloria , Feikin Daniel R , DeLuca Andrea N , Driscoll Amanda J , Fancourt Nicholas , Fu Wei , Haddix Meredith , Hammitt Laura L , Higdon Melissa M , Kagucia E Wangeci , Karron Ruth A , Li Mengying , Park Daniel E , Prosperi Christine , Shi Qiyuan , Wu Zhenke , Zeger Scott L , Watson Nora L , Crawley Jane , Murdoch David R , Brooks W Abdullah , Endtz Hubert P , Zaman Khalequ , Goswami Doli , Hossain Lokman , Jahan Yasmin , Chisti Mohammod Jobayer , Howie Stephen R C , Ebruke Bernard E , Antonio Martin , McLellan Jessica L , Machuka Eunice M , Shamsul Arifin , Zaman Syed M A , Mackenzie Grant , Scott J Anthony G , Awori Juliet O , Morpeth Susan C , Kamau Alice , Kazungu Sidi , Ominde Micah Silaba , Kotloff Karen L , Tapia Milagritos D , Sow Samba O , Sylla Mamadou , Tamboura Boubou , Onwuchekwa Uma , Kourouma Nana , Toure Aliou , Sissoko Seydou , Madhi Shabir A , Moore David P , Adrian Peter V , Baillie Vicky L , Kuwanda Locadiah , Mudau Azwifarwi , Groome Michelle J , Mahomed Nasreen , Simões Eric A F , Baggett Henry C , Thamthitiwat Somsak , Maloney Susan A , Bunthi Charatdao , Rhodes Julia , Sawatwong Pongpun , Akarasewi Pasakorn , Thea Donald M , Mwananyanda Lawrence , Chipeta James , Seidenberg Phil , Mwansa James , Somwe Somwe Wa , Kwenda Geoffrey , Anderson Trevor P , Mitchell Joanne L . Lancet 2019 394 (10200) 757-779 BACKGROUND: Pneumonia is the leading cause of death among children younger than 5 years. In this study, we estimated causes of pneumonia in young African and Asian children, using novel analytical methods applied to clinical and microbiological findings. METHODS: We did a multi-site, international case-control study in nine study sites in seven countries: Bangladesh, The Gambia, Kenya, Mali, South Africa, Thailand, and Zambia. All sites enrolled in the study for 24 months. Cases were children aged 1-59 months admitted to hospital with severe pneumonia. Controls were age-group-matched children randomly selected from communities surrounding study sites. Nasopharyngeal and oropharyngeal (NP-OP), urine, blood, induced sputum, lung aspirate, pleural fluid, and gastric aspirates were tested with cultures, multiplex PCR, or both. Primary analyses were restricted to cases without HIV infection and with abnormal chest x-rays and to controls without HIV infection. We applied a Bayesian, partial latent class analysis to estimate probabilities of aetiological agents at the individual and population level, incorporating case and control data. FINDINGS: Between Aug 15, 2011, and Jan 30, 2014, we enrolled 4232 cases and 5119 community controls. The primary analysis group was comprised of 1769 (41·8% of 4232) cases without HIV infection and with positive chest x-rays and 5102 (99·7% of 5119) community controls without HIV infection. Wheezing was present in 555 (31·7%) of 1752 cases (range by site 10·6-97·3%). 30-day case-fatality ratio was 6·4% (114 of 1769 cases). Blood cultures were positive in 56 (3·2%) of 1749 cases, and Streptococcus pneumoniae was the most common bacteria isolated (19 [33·9%] of 56). Almost all cases (98·9%) and controls (98·0%) had at least one pathogen detected by PCR in the NP-OP specimen. The detection of respiratory syncytial virus (RSV), parainfluenza virus, human metapneumovirus, influenza virus, S pneumoniae, Haemophilus influenzae type b (Hib), H influenzae non-type b, and Pneumocystis jirovecii in NP-OP specimens was associated with case status. The aetiology analysis estimated that viruses accounted for 61·4% (95% credible interval [CrI] 57·3-65·6) of causes, whereas bacteria accounted for 27·3% (23·3-31·6) and Mycobacterium tuberculosis for 5·9% (3·9-8·3). Viruses were less common (54·5%, 95% CrI 47·4-61·5 vs 68·0%, 62·7-72·7) and bacteria more common (33·7%, 27·2-40·8 vs 22·8%, 18·3-27·6) in very severe pneumonia cases than in severe cases. RSV had the greatest aetiological fraction (31·1%, 95% CrI 28·4-34·2) of all pathogens. Human rhinovirus, human metapneumovirus A or B, human parainfluenza virus, S pneumoniae, M tuberculosis, and H influenzae each accounted for 5% or more of the aetiological distribution. We observed differences in aetiological fraction by age for Bordetella pertussis, parainfluenza types 1 and 3, parechovirus-enterovirus, P jirovecii, RSV, rhinovirus, Staphylococcus aureus, and S pneumoniae, and differences by severity for RSV, S aureus, S pneumoniae, and parainfluenza type 3. The leading ten pathogens of each site accounted for 79% or more of the site's aetiological fraction. INTERPRETATION: In our study, a small set of pathogens accounted for most cases of pneumonia requiring hospital admission. Preventing and treating a subset of pathogens could substantially affect childhood pneumonia outcomes. FUNDING: Bill & Melinda Gates Foundation. |
Resistance levels to non-nucleoside reverse transcriptase inhibitors among pregnant women with recent HIV infection in Malawi.
Bello G , Kagoli M , Chipeta S , Auld A , Chang JC , DeVos JR , Kim E , Mkungudza J , Payne D , Eliya M , Nyirenda R , Jahn A , Mzumara T , Mvula B , Dadabhai S , Namakhoma I , Babaye Y , Giron A , Jordan MR , Bertagnolio S , O'Malley G , Wadonda-Kabondo N . Antivir Ther 2022 27 (4) 13596535221121225 BACKGROUND: Information on HIV drug resistance (HIVDR) prevalence in people newly diagnosed with HIV is limited. We implemented a cross-sectional study to estimate HIVDR prevalence among pregnant women recently infected with HIV in Malawi. METHODS: The HIVDR study was nested within a routine antenatal clinic (ANC) sentinel surveillance survey. Dried blood spot samples were tested for recent infection using a limiting antigen antibody assay together with HIV viral load testing. HIV-1 protease and reverse transcriptase were sequenced using Sanger sequencing. Drug susceptibility was predicted using Stanford HIVdb algorithm (version 8.9). Weighted analysis was performed in Stata 15.1. RESULTS: Of the 21,642 pregnant women enrolled in the ANC survey, 8.4% (1826/21,642) tested HIV positive. Of these, 5.0% (92/1826) had recent HIV infection, and 90.2% (83/92) were tested by PCR. The amplification and sequencing success rate was 57.8% (48/83). The prevalence of any HIVDR was 14.6% (5/45) (95% CI: 4.7-36.8%), all of which indicated HIVDR to nonnucleoside reverse transcriptase inhibitors (NNRTIs). HIVDR to nucleoside reverse transcriptase inhibitors was 7.9% (2/45) (95% CI: 1.4-34.6%). Resistance to protease inhibitors currently in use in Malawi was not observed. CONCLUSIONS: Despite the low number of cases with presumed TDR, our study hints that resistance to NNRTIs was high, above the 10% target for regimen change. Further investigation is needed to establish the exact magnitude of presumed TDR among women recently infected with HIV. These findings support the transition to an integrase inhibitor-based first-line regimen for patients initiating or on ART. |
Leveraging gains from African Center for Integrated Laboratory Training to combat HIV epidemic in sub-Saharan Africa.
Shrivastava R , Poxon R , Rottinghaus E , Essop L , Sanon V , Chipeta Z , van-Schalkwyk E , Sekwadi P , Murangandi P , Nguyen S , Devos J , Nesby-Odell S , Stevens T , Umaru F , Cox A , Kim A , Yang C , Parsons LM , Malope-Kgokong B , Nkengasong JN . BMC Health Serv Res 2021 21 (1) 22 BACKGROUND: In sub-Saharan Africa, there is dearth of trained laboratorians and strengthened laboratory systems to provide adequate and quality laboratory services for enhanced HIV control. In response to this challenge, in 2007, the African Centre for Integrated Laboratory Training (ACILT) was established in South Africa with a mission to train staffs from countries with high burdens of diseases in skills needed to strengthen sustainable laboratory systems. This study was undertaken to assess the transference of newly gained knowledge and skills to other laboratory staff, and to identify enabling and obstructive factors to their implementation. METHODS: We used Kirkpatrick model to determine training effectiveness by assessing the transference of newly gained knowledge and skills to participant's work environment, along with measuring enabling and obstructive factors. In addition to regular course evaluations at ACILT (pre and post training), in 2015 we sent e-questionnaires to 867 participants in 43 countries for course participation between 2008 and 2014. Diagnostics courses included Viral Load, and systems strengthening included strategic planning and Biosafety and Biosecurity. SAS v9.44 and Excel were used to analyze retrospective de-identified data collected at six months pre and post-training. RESULTS: Of the 867 participants, 203 (23.4%) responded and reported average improvements in accuracy and timeliness in Viral Load programs and to systems strengthening. For Viral Load testing, frequency of corrective action for unsatisfactory proficiency scores improved from 57 to 91%, testing error rates reduced from 12.9% to 4.9%; 88% responders contributed to the first national strategic plan development and 91% developed strategies to mitigate biosafety risks in their institutions. Key enabling factors were team and management support, and key obstructive factors included insufficient resources and staff's resistance to change. CONCLUSIONS: Training at ACILT had a documented positive impact on strengthening the laboratory capacity and laboratory workforce and substantial cost savings. ACILT's investment produced a multiplier effect whereby national laboratory systems, personnel and leadership reaped training benefits. This laboratory training centre with a global clientele contributed to improve existing laboratory services, systems and networks for the HIV epidemic and is now being leveraged for COVID-19 testing that has infected 41,332,899 people globally. |
Digital auscultation in PERCH: Associations with chest radiography and pneumonia mortality in children
McCollum ED , Park DE , Watson NL , Fancourt NSS , Focht C , Baggett HC , Abdullah Brooks W , Howie SRC , Kotloff KL , Levine OS , Madhi SA , Murdoch DR , Scott JAG , Thea DM , Awori JO , Chipeta J , Chuananon S , DeLuca AN , Driscoll AJ , Ebruke BE , Elhilal M , Emmanouilidou D , Githua LP , Higdon MM , Hossain L , Jahan Y , Karron RA , Kyalo J , Moore DP , Mulindwa JM , Naorat S , Prosperi C , Verwey C , West JE , Knoll MD , Brien KLO , Feikin DR , Hammitt LL . Pediatr Pulmonol 2020 55 (11) 3197-3208 BACKGROUND: Whether digitally recorded lung sounds are associated with radiographic pneumonia or clinical outcomes among children in low-income and middle-income countries is unknown. We sought to address these knowledge gaps. METHODS: We enrolled 1-59 month old children hospitalized with pneumonia at eight African and Asian Pneumonia Etiology Research for Child Health sites in six countries, recorded digital stethoscope lung sounds, obtained chest radiographs, and collected clinical outcomes. Recordings were processed and reclassified into binary categories positive or negative for adventitial lung sounds. Listening and reading panels classified recordings and radiographs. Recording classification associations with chest radiographs with World Health Organization (WHO)-defined primary endpoint pneumonia (radiographic pneumonia) or mortality were evaluated. We also examined case fatality among risk strata. RESULTS: Among children without WHO danger signs, wheezing (without crackles) had a lower adjusted odds ratio (aOR) for radiographic pneumonia (0.35, 95% confidence interval (CI) 0.15, 0.82), compared to children with normal recordings. Neither crackle only (no wheeze) (aOR 2.13, 95%CI 0.91, 4.96) or any wheeze (with or without crackle) (aOR 0.63, 95%CI 0.34, 1.15) were associated with radiographic pneumonia. Among children with WHO danger signs no lung recording classification was independently associated with radiographic pneumonia, although trends towards greater odds of radiographic pneumonia were observed among children classified with crackle only (no wheeze) or any wheeze (with or without crackle). Among children without WHO danger signs, those with recorded wheezing had a lower case fatality than those without wheezing (3.8% vs 9.1%, p=0.03). CONCLUSIONS: Among lower risk children without WHO danger signs digitally recorded wheezing is associated with a lower odds for radiographic pneumonia and with lower mortality. Although further research is needed, these data indicate that with further development digital auscultation may eventually contribute to child pneumonia care. This article is protected by copyright. All rights reserved. |
Community-based HIV prevalence in KwaZulu-Natal, South Africa: results of a cross-sectional household survey
Kharsany ABM , Cawood C , Khanyile D , Lewis L , Grobler A , Puren A , Govender K , George G , Beckett S , Samsunder N , Madurai S , Toledo C , Chipeta Z , Glenshaw M , Hersey S , Abdool Karim Q . Lancet HIV 2018 5 (8) e427-e437 BACKGROUND: In high HIV burden settings, maximising the coverage of prevention strategies is crucial to achieving epidemic control. However, little is known about the reach and effect of these strategies in some communities. METHODS: We did a cross-sectional community survey in the adjacent Greater Edendale and Vulindlela areas in the uMgungundlovu district, KwaZulu-Natal, South Africa. Using a multistage cluster sampling method, we randomly selected enumeration areas, households, and individuals. One household member (aged 15-49 years) selected at random was invited for survey participation. After obtaining consent, questionnaires were administered to obtain sociodemographic, psychosocial, and behavioural information, and exposure to HIV prevention and treatment programmes. Clinical samples were collected for laboratory measurements. Statistical analyses were done accounting for multilevel sampling and weighted to represent the population. A multivariable logistic regression model assessed factors associated with HIV infection. FINDINGS: Between June 11, 2014, and June 22, 2015, we enrolled 9812 individuals. The population-weighted HIV prevalence was 36.3% (95% CI 34.8-37.8, 3969 of 9812); 44.1% (42.3-45.9, 2955 of 6265) in women and 28.0% (25.9-30.1, 1014 of 3547) in men (p<0.0001). HIV prevalence in women aged 15-24 years was 22.3% (20.2-24.4, 567 of 2224) compared with 7.6% (6.0-9.3, 124 of 1472; p<0.0001) in men of the same age. Prevalence peaked at 66.4% (61.7-71.2, 517 of 760) in women aged 35-39 years and 59.6% (53.0-66.3, 183 of 320) in men aged 40-44 years. Consistent condom use in the last 12 months was 26.5% (24.1-28.8, 593 of 2356) in men and 22.7% (20.9-24.4, 994 of 4350) in women (p=0.0033); 35.7% (33.4-37.9, 1695 of 5447) of women's male partners and 31.9% (29.5-34.3, 1102 of 3547) of men were medically circumcised (p<0.0001), and 45.6% (42.9-48.2, 1251 of 2955) of women and 36.7% (32.3-41.2, 341 of 1014) of men reported antiretroviral therapy (ART) use (p=0.0003). HIV viral suppression was achieved in 54.8% (52.0-57.5, 1574 of 2955) of women and 41.9% (37.1-46.7, 401 of 1014) of men (p<0.0001), and 87.2% (84.6-89.8, 1086 of 1251) of women and 83.9% (78.5-89.3, 284 of 341; p=0.3670) of men on ART. Age, incomplete secondary schooling, being single, having more than one lifetime sex partner (women), sexually transmitted infections, and not being medically circumcised were associated with HIV-positive status. INTERPRETATION: The HIV burden in specific age groups, the suboptimal differential coverage, and uptake of HIV prevention strategies justifies a location-based approach to surveillance with finer disaggregation by age and sex. Intensified and customised approaches to seek, identify, and link individuals to HIV services are crucial to achieving epidemic control in this community. FUNDING: The President's Emergency Plan for AIDS Relief through the Centers for Disease Control and Prevention. |
Misdiagnosis of HIV infection during a South African community-based survey: implications for rapid HIV testing
Kufa T , Kharsany AB , Cawood C , Khanyile D , Lewis L , Grobler A , Chipeta Z , Bere A , Glenshaw M , Puren A . J Int AIDS Soc 2017 20 35-43 INTRODUCTION: We describe the overall accuracy and performance of a serial rapid HIV testing algorithm used in community-based HIV testing in the context of a population-based household survey conducted in two sub-districts of uMgungundlovu district, KwaZulu-Natal, South Africa, against reference fourth-generation HIV-1/2 antibody and p24 antigen combination immunoassays. We discuss implications of the findings on rapid HIV testing programmes. METHODS: Cross-sectional design: Following enrolment into the survey, questionnaires were administered to eligible and consenting participants in order to obtain demographic and HIV-related data. Peripheral blood samples were collected for HIV-related testing. Participants were offered community-based HIV testing in the home by trained field workers using a serial algorithm with two rapid diagnostic tests (RDTs) in series. In the laboratory, reference HIV testing was conducted using two fourth-generation immunoassays with all positives in the confirmatory test considered true positives. Accuracy, sensitivity, specificity, positive predictive value, negative predictive value and false-positive and false-negative rates were determined. RESULTS: Of 10,236 individuals enrolled in the survey, 3740 were tested in the home (median age 24 years (interquartile range 19-31 years), 42.1% males and HIV positivity on RDT algorithm 8.0%). From those tested, 3729 (99.7%) had a definitive RDT result as well as a laboratory immunoassay result. The overall accuracy of the RDT when compared to the fourth-generation immunoassays was 98.8% (95% confidence interval (CI) 98.5-99.2). The sensitivity, specificity, positive predictive value and negative predictive value were 91.1% (95% CI 87.5-93.7), 99.9% (95% CI 99.8-100), 99.3% (95% CI 97.4-99.8) and 99.1% (95% CI 98.8-99.4) respectively. The false-positive and false-negative rates were 0.06% (95% CI 0.01-0.24) and 8.9% (95% CI 6.3-12.53). Compared to true positives, false negatives were more likely to be recently infected on limited antigen avidity assay and to report antiretroviral therapy (ART) use. CONCLUSIONS: The overall accuracy of the RDT algorithm was high. However, there were few false positives, and the sensitivity was lower than expected with high false negatives, despite implementation of quality assurance measures. False negatives were associated with recent (early) infection and ART exposure. The RDT algorithm was able to correctly identify the majority of HIV infections in community-based HIV testing. Messaging on the potential for false positives and false negatives should be included in these programmes. |
Global, regional, and national disease burden estimates of acute lower respiratory infections due to respiratory syncytial virus in young children in 2015: a systematic review and modelling study
Shi T , McAllister DA , O'Brien KL , Simoes EAF , Madhi SA , Gessner BD , Polack FP , Balsells E , Acacio S , Aguayo C , Alassani I , Ali A , Antonio M , Awasthi S , Awori JO , Azziz-Baumgartner E , Baggett HC , Baillie VL , Balmaseda A , Barahona A , Basnet S , Bassat Q , Basualdo W , Bigogo G , Bont L , Breiman RF , Brooks WA , Broor S , Bruce N , Bruden D , Buchy P , Campbell S , Carosone-Link P , Chadha M , Chipeta J , Chou M , Clara W , Cohen C , de Cuellar E , Dang DA , Dash-Yandag B , Deloria-Knoll M , Dherani M , Eap T , Ebruke BE , Echavarria M , de Freitas Lazaro Emediato CC , Fasce RA , Feikin DR , Feng L , Gentile A , Gordon A , Goswami D , Goyet S , Groome M , Halasa N , Hirve S , Homaira N , Howie SRC , Jara J , Jroundi I , Kartasasmita CB , Khuri-Bulos N , Kotloff KL , Krishnan A , Libster R , Lopez O , Lucero MG , Lucion F , Lupisan SP , Marcone DN , McCracken JP , Mejia M , Moisi JC , Montgomery JM , Moore DP , Moraleda C , Moyes J , Munywoki P , Mutyara K , Nicol MP , Nokes DJ , Nymadawa P , da Costa Oliveira MT , Oshitani H , Pandey N , Paranhos-Baccala G , Phillips LN , Picot VS , Rahman M , Rakoto-Andrianarivelo M , Rasmussen ZA , Rath BA , Robinson A , Romero C , Russomando G , Salimi V , Sawatwong P , Scheltema N , Schweiger B , Scott JAG , Seidenberg P , Shen K , Singleton R , Sotomayor V , Strand TA , Sutanto A , Sylla M , Tapia MD , Thamthitiwat S , Thomas ED , Tokarz R , Turner C , Venter M , Waicharoen S , Wang J , Watthanaworawit W , Yoshida LM , Yu H , Zar HJ , Campbell H , Nair H . Lancet 2017 390 (10098) 946-958 BACKGROUND: We have previously estimated that respiratory syncytial virus (RSV) was associated with 22% of all episodes of (severe) acute lower respiratory infection (ALRI) resulting in 55 000 to 199 000 deaths in children younger than 5 years in 2005. In the past 5 years, major research activity on RSV has yielded substantial new data from developing countries. With a considerably expanded dataset from a large international collaboration, we aimed to estimate the global incidence, hospital admission rate, and mortality from RSV-ALRI episodes in young children in 2015. METHODS: We estimated the incidence and hospital admission rate of RSV-associated ALRI (RSV-ALRI) in children younger than 5 years stratified by age and World Bank income regions from a systematic review of studies published between Jan 1, 1995, and Dec 31, 2016, and unpublished data from 76 high quality population-based studies. We estimated the RSV-ALRI incidence for 132 developing countries using a risk factor-based model and 2015 population estimates. We estimated the in-hospital RSV-ALRI mortality by combining in-hospital case fatality ratios with hospital admission estimates from hospital-based (published and unpublished) studies. We also estimated overall RSV-ALRI mortality by identifying studies reporting monthly data for ALRI mortality in the community and RSV activity. FINDINGS: We estimated that globally in 2015, 33.1 million (uncertainty range [UR] 21.6-50.3) episodes of RSV-ALRI, resulted in about 3.2 million (2.7-3.8) hospital admissions, and 59 600 (48 000-74 500) in-hospital deaths in children younger than 5 years. In children younger than 6 months, 1.4 million (UR 1.2-1.7) hospital admissions, and 27 300 (UR 20 700-36 200) in-hospital deaths were due to RSV-ALRI. We also estimated that the overall RSV-ALRI mortality could be as high as 118 200 (UR 94 600-149 400). Incidence and mortality varied substantially from year to year in any given population. INTERPRETATION: Globally, RSV is a common cause of childhood ALRI and a major cause of hospital admissions in young children, resulting in a substantial burden on health-care services. About 45% of hospital admissions and in-hospital deaths due to RSV-ALRI occur in children younger than 6 months. An effective maternal RSV vaccine or monoclonal antibody could have a substantial effect on disease burden in this age group. FUNDING: The Bill & Melinda Gates Foundation. |
The accuracy of HIV rapid testing in integrated bio-behavioral surveys of men who have sex with men across 5 provinces in South Africa
Kufa T , Lane T , Manyuchi A , Singh B , Isdahl Z , Osmand T , Grasso M , Struthers H , McIntyre J , Chipeta Z , Puren A . Medicine (Baltimore) 2017 96 (28) e7391 We describe the accuracy of serial rapid HIV testing among men who have sex with men (MSM) in South Africa and discuss the implications for HIV testing and prevention.This was a cross-sectional survey conducted at five stand-alone facilities from five provinces.Demographic, behavioral, and clinical data were collected. Dried blood spots were obtained for HIV-related testing. Participants were offered rapid HIV testing using 2 rapid diagnostic tests (RDTs) in series. In the laboratory, reference HIV testing was conducted using a third-generation enzyme immunoassay (EIA) and a fourth-generation EIA as confirmatory. Accuracy, sensitivity, specificity, positive predictive value, negative predictive value, false-positive, and false-negative rates were determined.Between August 2015 and July 2016, 2503 participants were enrolled. Of these, 2343 were tested by RDT on site with a further 2137 (91.2%) having definitive results on both RDT and EIA. Sensitivity, specificity, positive predictive value, negative predictive value, false-positive rates, and false-negative rates were 92.6% [95% confidence interval (95% CI) 89.6-94.8], 99.4% (95% CI 98.9-99.7), 97.4% (95% CI 95.2-98.6), 98.3% (95% CI 97.6-98.8), 0.6% (95% CI 0.3-1.1), and 7.4% (95% CI 5.2-10.4), respectively. False negatives were similar to true positives with respect to virological profiles.Overall accuracy of the RDT algorithm was high, but sensitivity was lower than expected. Post-HIV test counseling should include discussions of possible false-negative results and the need for retesting among HIV negatives. |
Chest radiograph findings in childhood pneumonia cases from the multisite PERCH Study
Fancourt N , Deloria Knoll M , Baggett HC , Brooks WA , Feikin DR , Hammitt LL , Howie SRC , Kotloff KL , Levine OS , Madhi SA , Murdoch DR , Scott JAG , Thea DM , Awori JO , Barger-Kamate B , Chipeta J , DeLuca AN , Diallo M , Driscoll AJ , Ebruke BE , Higdon MM , Jahan Y , Karron RA , Mahomed N , Moore DP , Nahar K , Naorat S , Ominde MS , Park DE , Prosperi C , Wa Somwe S , Thamthitiwat S , Zaman SMA , Zeger SL , O'Brien KL . Clin Infect Dis 2017 64 S262-s270 Background: Chest radiographs (CXRs) are frequently used to assess pneumonia cases. Variations in CXR appearances between epidemiological settings and their correlation with clinical signs are not well documented. Methods: The Pneumonia Etiology Research for Child Health project enrolled 4232 cases of hospitalized World Health Organization (WHO)-defined severe and very severe pneumonia from 9 sites in 7 countries (Bangladesh, the Gambia, Kenya, Mali, South Africa, Thailand, and Zambia). At admission, each case underwent a standardized assessment of clinical signs and pneumonia risk factors by trained health personnel, and a CXR was taken that was interpreted using the standardized WHO methodology. CXRs were categorized as abnormal (consolidation and/or other infiltrate), normal, or uninterpretable. Results: CXRs were interpretable in 3587 (85%) cases, of which 1935 (54%) were abnormal (site range, 35%-64%). Cases with abnormal CXRs were more likely than those with normal CXRs to have hypoxemia (45% vs 26%), crackles (69% vs 62%), tachypnea (85% vs 80%), or fever (20% vs 16%) and less likely to have wheeze (30% vs 38%; all P < .05). CXR consolidation was associated with a higher case fatality ratio at 30-day follow-up (13.5%) compared to other infiltrate (4.7%) or normal (4.9%) CXRs. Conclusions: Clinically diagnosed pneumonia cases with abnormal CXRs were more likely to have signs typically associated with pneumonia. However, CXR-normal cases were common, and clinical signs considered indicative of pneumonia were present in substantial proportions of these cases. CXR-consolidation cases represent a group with an increased likelihood of death at 30 days post-discharge. |
Evaluation of Pneumococcal Load in Blood by Polymerase Chain Reaction for the Diagnosis of Pneumococcal Pneumonia in Young Children in the PERCH Study.
Deloria Knoll M , Morpeth SC , Scott JAG , Watson NL , Park DE , Baggett HC , Brooks WA , Feikin DR , Hammitt LL , Howie SRC , Kotloff KL , Levine OS , O'Brien KL , Thea DM , Ahmed D , Antonio M , Awori JO , Baillie VL , Chipeta J , Deluca AN , Dione M , Driscoll AJ , Higdon MM , Jatapai A , Karron RA , Mazumder R , Moore DP , Mwansa J , Nyongesa S , Prosperi C , Seidenberg P , Siludjai D , Sow SO , Tamboura B , Zeger SL , Murdoch DR , Madhi SA . Clin Infect Dis 2017 64 S357-s367 Background.: Detection of pneumococcus by lytA polymerase chain reaction (PCR) in blood had poor diagnostic accuracy for diagnosing pneumococcal pneumonia in children in 9 African and Asian sites. We assessed the value of blood lytA quantification in diagnosing pneumococcal pneumonia. Methods.: The Pneumonia Etiology Research for Child Health (PERCH) case-control study tested whole blood by PCR for pneumococcus in children aged 1-59 months hospitalized with signs of pneumonia and in age-frequency matched community controls. The distribution of load among PCR-positive participants was compared between microbiologically confirmed pneumococcal pneumonia (MCPP) cases, cases confirmed for nonpneumococcal pathogens, nonconfirmed cases, and controls. Receiver operating characteristic analyses determined the "optimal threshold" that distinguished MCPP cases from controls. Results.: Load was available for 290 of 291 cases with pneumococcal PCR detected in blood and 273 of 273 controls. Load was higher in MCPP cases than controls (median, 4.0 x 103 vs 0.19 x 103 copies/mL), but overlapped substantially (range, 0.16-989.9 x 103 copies/mL and 0.01-551.9 x 103 copies/mL, respectively). The proportion with high load (≥2.2 log10 copies/mL) was 62.5% among MCPP cases, 4.3% among nonconfirmed cases, 9.3% among cases confirmed for a nonpneumococcal pathogen, and 3.1% among controls. Pneumococcal load in blood was not associated with respiratory tract illness in controls (P = .32). High blood pneumococcal load was associated with alveolar consolidation on chest radiograph in nonconfirmed cases, and with high (>6.9 log10 copies/mL) nasopharyngeal/oropharyngeal load and C-reactive protein ≥40 mg/L (both P < .01) in nonconfirmed cases but not controls. Conclusions.: Quantitative pneumococcal PCR in blood has limited diagnostic utility for identifying pneumococcal pneumonia in individual children, but may be informative in epidemiological studies. |
Early diagnosis of HIV infection in infants - one Caribbean and six sub-Saharan African countries, 2011-2015
Diallo K , Kim AA , Lecher S , Ellenberger D , Beard RS , Dale H , Hurlston M , Rivadeneira M , Fonjungo PN , Broyles LN , Zhang G , Sleeman K , Nguyen S , Jadczak S , Abiola N , Ewetola R , Muwonga J , Fwamba F , Mwangi C , Naluguza M , Kiyaga C , Ssewanyana I , Varough D , Wysler D , Lowrance D , Louis FJ , Desinor O , Buteau J , Kesner F , Rouzier V , Segaren N , Lewis T , Sarr A , Chipungu G , Gupta S , Singer D , Mwenda R , Kapoteza H , Chipeta Z , Knight N , Carmona S , MacLeod W , Sherman G , Pillay Y , Ndongmo CB , Mugisa B , Mwila A , McAuley J , Chipimo PJ , Kaonga W , Nsofwa D , Nsama D , Mwamba FZ , Moyo C , Phiri C , Borget MY , Ya-Kouadio L , Kouame A , Adje-Toure CA , Nkengasong J . MMWR Morb Mortal Wkly Rep 2016 65 (46) 1285-1290 Pediatric human immunodeficiency virus (HIV) infection remains an important public health issue in resource-limited settings. In 2015, 1.4 million children aged <15 years were estimated to be living with HIV (including 170,000 infants born in 2015), with the vast majority living in sub-Saharan Africa. In 2014, 150,000 children died from HIV-related causes worldwide. Access to timely HIV diagnosis and treatment for HIV-infected infants reduces HIV-associated mortality, which is approximately 50% by age 2 years without treatment. Since 2011, the annual number of HIV-infected children has declined by 50%. Despite this gain, in 2014, only 42% of HIV-exposed infants received a diagnostic test for HIV, and in 2015, only 51% of children living with HIV received antiretroviral therapy (1). Access to services for early infant diagnosis of HIV (which includes access to testing for HIV-exposed infants and clinical diagnosis of HIV-infected infants) is critical for reducing HIV-associated mortality in children aged <15 years. Using data collected from seven countries supported by the U.S. President's Emergency Plan for AIDS Relief (PEPFAR), progress in the provision of HIV testing services for early infant diagnosis was assessed. During 2011-2015, the total number of HIV diagnostic tests performed among HIV-exposed infants within 6 weeks after birth (tests for early infant diagnosis of HIV), as recommended by the World Health Organization (WHO) increased in all seven countries (Cote d'Ivoire, the Democratic Republic of the Congo, Haiti, Malawi, South Africa, Uganda, and Zambia); however, in 2015, the rate of testing for early infant diagnosis among HIV-exposed infants was <50% in five countries. HIV positivity among those tested declined in all seven countries, with three countries (Cote d'Ivoire, the Democratic Republic of the Congo, and Uganda) reporting >50% decline. The most common challenges for access to testing for early infant diagnosis included difficulties in specimen transport, long turnaround time between specimen collection and receipt of results, and limitations in supply chain management. Further reductions in HIV mortality in children can be achieved through continued expansion and improvement of services for early infant diagnosis in PEPFAR-supported countries, including initiatives targeted to reach HIV-exposed infants, ensure access to programs for early infant diagnosis of HIV, and facilitate prompt linkage to treatment for children diagnosed with HIV infection. |
Pertussis-associated pneumonia in infants and children from low- and middle-income countries participating in the PERCH Study
Barger-Kamate B , Deloria Knoll M , Kagucia EW , Prosperi C , Baggett HC , Brooks WA , Feikin DR , Hammitt LL , Howie SR , Levine OS , Madhi SA , Scott JA , Thea DM , Amornintapichet T , Anderson TP , Awori JO , Baillie VL , Chipeta J , DeLuca AN , Driscoll AJ , Goswami D , Higdon MM , Hossain L , Karron RA , Maloney S , Moore DP , Morpeth SC , Mwananyanda L , Ofordile O , Olutunde E , Park DE , Sow SO , Tapia MD , Murdoch DR , O'Brien KL , Kotloff KL . Clin Infect Dis 2016 63 S187-s196 BACKGROUND: Few data exist describing pertussis epidemiology among infants and children in low- and middle-income countries to guide preventive strategies. METHODS: Children 1-59 months of age hospitalized with World Health Organization-defined severe or very severe pneumonia in 7 African and Asian countries and similarly aged community controls were enrolled in the Pneumonia Etiology Research for Child Health study. They underwent a standardized clinical evaluation and provided nasopharyngeal and oropharyngeal swabs and induced sputum (cases only) for Bordetella pertussis polymerase chain reaction. Risk factors and pertussis-associated clinical findings were identified. RESULTS: Bordetella pertussis was detected in 53 of 4200 (1.3%) cases and 11 of 5196 (0.2%) controls. In the age stratum 1-5 months, 40 (2.3% of 1721) cases were positive, all from African sites, as were 8 (0.5% of 1617) controls. Pertussis-positive African cases 1-5 months old, compared to controls, were more often human immunodeficiency virus (HIV) uninfected-exposed (adjusted odds ratio [aOR], 2.2), unvaccinated (aOR, 3.7), underweight (aOR, 6.3), and too young to be immunized (aOR, 16.1) (all P ≤ .05). Compared with pertussis-negative African cases in this age group, pertussis-positive cases were younger, more likely to vomit (aOR, 2.6), to cough ≥14 days (aOR, 6.3), to have leukocyte counts >20 000 cells/microL (aOR, 4.6), and to have lymphocyte counts >10 000 cells/microL (aOR, 7.2) (all P ≤ .05). The case fatality ratio of pertussis-infected pneumonia cases 1-5 months of age was 12.5% (95% confidence interval, 4.2%-26.8%; 5/40); pertussis was identified in 3.7% of 137 in-hospital deaths among African cases in this age group. CONCLUSIONS: In the postneonatal period, pertussis causes a small fraction of hospitalized pneumonia cases and deaths; however, case fatality is substantial. The propensity to infect unvaccinated infants and those at risk for insufficient immunity (too young to be vaccinated, premature, HIV-infected/exposed) suggests that the role for maternal vaccination should be considered along with efforts to reduce exposure to risk factors and to optimize childhood pertussis vaccination coverage. |
Strengthening HIV surveillance in the antiretroviral therapy era: rationale and design of a longitudinal study to monitor HIV prevalence and incidence in the uMgungundlovu district, KwaZulu-Natal, South Africa
Kharsany AB , Cawood C , Khanyile D , Grobler A , McKinnon LR , Samsunder N , Frohlich JA , Abdool Karim Q , Puren A , Welte A , George G , Govender K , Toledo C , Chipeta Z , Zembe L , Glenshaw MT , Madurai L , Deyde V M , Bere A . BMC Public Health 2015 15 (1) 1149 BACKGROUND: South Africa has over 6,000,000 HIV infected individuals and the province of KwaZulu-Natal (KZN) is the most severely affected. As public health initiatives to better control the HIV epidemic are implemented, timely, detailed and robust surveillance data are needed to monitor, evaluate and inform the programmatic interventions and policies over time. We describe the rationale and design of the HIV Incidence Provincial Surveillance System (HIPSS) to monitor HIV prevalence and incidence. METHODS/DESIGN: The household-based survey will include a sample of men and women from two sub-districts of the uMgungundlovu municipality (Vulindlela and the Greater Edendale) of KZN, South Africa. The study is designed as two sequential cross-sectional surveys of 10,000 randomly selected individuals aged 15-49 years to be conducted one year apart. From the cross sectional surveys, two sequential cohorts of HIV negative individuals aged 15-35 years will be followed-up one year later to measure the primary outcome of HIV incidence. Secondary outcomes include the laboratory measurements for pulmonary tuberculosis, sexually transmitted infections and evaluating tests for estimating population-level HIV incidence. Antiretroviral therapy (ART) access, HIV-1 RNA viral load, and CD4 cell counts in HIV positive individuals will assess the effectiveness of the HIV treatment cascade. Household and individual-level socio-demographic characteristics, exposure to HIV programmatic interventions and risk behaviours will be assessed as predictors of HIV incidence. The incidence rate ratio of the two cohorts will be calculated to quantify the change in HIV incidence between consecutive samples. In anticipation of better availability of population-level HIV prevention and treatment programmes leading to decreases in HIV incidence, the sample size provides 84 % power to detect a reduction of 30 % in the HIV incidence rate between surveys. DISCUSSION: The results from HIPSS will provide critical data regarding HIV prevalence and incidence in this community and will establish whether HIV prevention and treatment efforts in a "real world", non-trial setting have an impact on HIV incidence at a population level. Importantly, the study design and methods will inform future methods for HIV surveillance. |
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