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Implementation effectiveness of revised (post-2010) World Health Organization guidelines on prevention of mother-to-child transmission of HIV using routinely collected data in sub-Saharan Africa: A systematic literature review.
Medicine. 2017 Oct; 96(40):e8055.BACKGROUND: To synthesize and evaluate the impact of implementing post-2010 World Health Organization (WHO) prevention of mother-to-child transmission (PMTCT) guidelines on attainment of PMTCT targets. METHODS: Retrospective and prospective cohort study designs that utilized routinely collected data with a focus on provision and utilization of the cascade of PMTCT services were included. The outcomes included the proportion of pregnant women who were tested during their antenatal clinic (ANC) visits; mother-to-child transmission (MTCT) rate; adherence; retention rate; and loss to follow-up (LTFU). RESULTS: Of the 1210 references screened, 45 met the inclusion criteria. The studies originated from 14 countries in sub-Saharan Africa. The highest number of studies originated from Malawi (10) followed by Nigeria and South Africa with 7 studies each. More than half of the studies were on option A while the majority of option B+ studies were conducted in Malawi. These studies indicated a high uptake of human immunodeficiency virus (HIV) testing ranging from 75% in Nigeria to over 96% in Zimbabwe and South Africa. High proportions of CD4 count testing were reported in studies only from South Africa despite that in most of the countries CD4 testing was a prerequisite to access treatment. MTCT rate ranged from 1.1% to 15.1% and it was higher in studies where data were collected in the early days of the WHO 2010 PMTCT guidelines. During the postpartum period, adherence and retention rate decreased, and LTFU increased for both HIV-positive mothers and exposed infants. CONCLUSION: Irrespective of which option was followed, uptake of antenatal HIV testing was high but there was a large drop off along later points in the PMTCT cascade. More research is needed on how to improve later components of the PMTCT cascade, especially of option B+ which is now the norm throughout sub-Saharan Africa.
Performance of the new WHO diagnostic algorithm for smear-negative pulmonary tuberculosis in HIV prevalent settings: a multisite study in Uganda.
Tropical Medicine and International Health. 2012 Jul; 17(7):884-95.OBJECTIVE: To compare the performance of the new WHO (2007) diagnostic algorithm for pulmonary tuberculosis (PTB) in high HIV prevalent settings (WHO07) to the WHO 2003 guidelines used by the Ugandan National Tuberculosis Program (UgWHO03). METHODS: A prospective observational cohort design was used at Reach Out Mbuya Parish HIV/AIDS Initiative, an urban slum community-based AIDS Service Organisation (ASO) and Kayunga Rural District Government Hospital. Newly diagnosed and enrolled HIV-infected patients were assessed for PTB. Research staff interviewed patients and staff and observed operational constraints. RESULTS: WHO07 reduced the time to diagnosis of smear-negative PTB with increased sensitivity compared with the UgWHO03 at both sites. Time to diagnosis of smear-negative PTB was significantly shorter at the urban ASO than at the rural ASO (12.4 vs. 28.5 days, P = 0.003). Diagnostic specificity and sensitivity [95% confidence intervals (CIs)] for smear-negative PTB were higher at the rural hospital compared with the urban ASO: [98% (93-100%) vs. 86% (77-92%), P = 0.001] and [95% (72-100%) vs. 90% (54-99%), P > 0.05], respectively. Common barriers to implementation of algorithms included failure by patients to attend follow-up appointments and poor adherence by healthcare workers to algorithms. CONCLUSION: At both sites, WHO07 expedited diagnosis of smear-negative PTB with increased diagnostic accuracy compared with the UgWHO03. The WHO07 expedited diagnosis more at the urban ASO but with more diagnostic accuracy at the rural hospital. Barriers to implementation should be taken into account when operationalising these guidelines for TB diagnosis in resource-limited settings. (c) 2012 Blackwell Publishing Ltd.
Validation of 2006 WHO prediction scores for true HIV infection in children less than 18 months with a positive serological HIV test.
PloS One. 2009; 4(4):e5312.INTRODUCTION: All infants born to HIV-positive mothers have maternal HIV antibodies, sometimes persistent for 18 months. When Polymerase Chain Reaction (PCR) is not available, August 2006 World Health Organization (WHO) recommendations suggest that clinical criteria may be used for starting antiretroviral treatment (ART) in HIV seropositive children <18 months. Predictors are at least two out of sepsis, severe pneumonia and thrush, or any stage 4 defining clinical finding according to the WHO staging system. METHODS AND RESULTS: From January 2005 to October 2006, we conducted a prospective study on 236 hospitalized children <18 months old with a positive HIV serological test at the national reference hospital in Kigali. The following data were collected: PCR, clinical signs and CD4 cell count. Current proposed clinical criteria were present in 148 of 236 children (62.7%) and in 95 of 124 infected children, resulting in 76.6% sensitivity and 52.7% specificity. For 87 children (59.0%), clinical diagnosis was made based on severe unexplained malnutrition (stage 4 clinical WHO classification), of whom only 44 (50.5%) were PCR positive. Low CD4 count had a sensitivity of 55.6% and a specificity of 78.5%. CONCLUSION: As PCR is not yet widely available, clinical diagnosis is often necessary, but these criteria have poor specificity and therefore have limited use for HIV diagnosis. Unexplained malnutrition is not clearly enough defined in WHO recommendations. Extra pulmonary tuberculosis (TB), almost impossible to prove in young children, may often be the cause of malnutrition, especially in HIV-affected families more often exposed to TB. Food supplementation and TB treatment should be initiated before starting ART in children who are staged based only on severe malnutrition.
Safety of switching to nevirapine-based highly active antiretroviral therapy at elevated CD4 cell counts in a resource-constrained setting [letter]
Journal of Acquired Immune Deficiency Syndromes. 2007 Aug 15; 45(5):598-600.The World Health Organization recommends the use of generic nevirapine (NVP)/efavirenz (EFV)-based highly active antiretroviral therapy (HAART) regimens as first-line therapy in the management of HIV in resource-limited settings. Initiating NVP-based HAART at elevated CD4 cell counts can lead to liver toxicity. Short-term risk of liver toxicity has been reported in men with CD4 counts greater than 400 cells/mL and in women with CD4 counts greater than 250 cells/mL. Hence, clinicians are advised to monitor the results of liver chemistry tests closely in the first 18 weeks of therapy because of the potential to develop life-threatening hepatic events. Mocroft et al showed that initiating NVP therapy at elevated CD4 levels may be safe for use in antiretroviral-experienced patients. Little is known about short-term adverse consequences and clinical outcome at elevated CD4 cell counts in a resource-limited setting. (author's)
The prognostic value of the World Health Organisation staging system for HIV infection and disease in rural Uganda.
AIDS. 1999; 13(18):2555-62.The objective was to assess whether the WHO staging classification for HIV provides prognostically valuable and applicable information in rural Uganda. Data were obtained from a population-based cohort of 232 HIV-infected individuals. Clinical information was obtained using a detailed questionnaire and ascertained by physical examination. Participants were seen routinely every 3 months and when they were sick. A computer algorithm based on clinical history, examination and laboratory findings was used to stage HIV-positive participants at each routine visit. Kaplan-Meier survival estimates and the Cox proportional hazard model were used to assess the prognostic strength of the clinical and laboratory categories of the system. An attendance rate of 81% and 799 person-years of follow-up were achieved. Survival probability estimates at 6 years from being seen in clinical stages 1, 2, 3, and 4 were 63%, 46%, 24%, and 6%, respectively. When staging was revised to incorporate lymphocyte categories, the survival probabilities were 73%, 62%, 39%, and 6%, respectively. Unexplained prolonged fever and severe bacterial infection had survival probabilities closer to stage 2 conditions, mucocutaneous herpes simplex virus infection for more than 1 month and cryptosporidiosis with diarrhea for more than 1 month closer to stage 3 and oral candidiasis closer to stage 4 conditions. Even without the laboratory markers, the clinical category of the WHO staging system is useful for predicting survival in individuals with HIV disease. This is important for areas with limited access to laboratory markers. A simple rearrangement of a few clinical conditions could improve the prognostic significance of the WHO system. (author's)
Classification of HIV infection and disease in women from Rwanda. Evaluation of the World Health Organization HIV staging system and recommended modifications.
ANNALS OF INTERNAL MEDICINE. 1995 Feb 15; 122(4):262-70.In Rwanda, health workers followed 412 HIV infected women attending prenatal and pediatric outpatient clinics in Kigali for 4 years. Researchers used these findings to evaluate WHO's HIV Staging System and predictors of mortality and to produce an HIV staging system for sub-Saharan Africa. The 36-month cumulative mortality was 9% for women originally in stage I, 15% for those in stage II, and 25% for those in stage III, and 27% for those in stage IV (p = 0.001). Significant predictors of mortality at 36 months were oral candidiasis, a low body mass index (=or< 19 kg/sq. m), a history of oral or genital ulcers (especially chronic ulcers), a low hematocrit (<0.38), and a high erythrocyte sedimentation rate (>65 mm/h) (p < 0.001). 12 of the 96 women who died by 36 months had developed pulmonary or extrapulmonary tuberculosis (TB). The researchers revised the WHO system by adding oral candidiasis, chronic oral or genital ulcers, and pulmonary TB to clinical stage IV (severe HIV disease). In the laboratory axis of the system, they replaced lymphocyte count with hematocrit and erythrocyte sedimentation rate. Using the modified laboratory axis, the 36-month mortality rate was 10% for women with normal laboratory results (stage A) and 33% for those with low hematocrit and a high erythrocyte sedimentation rate (stage B). Based on the proposed single staging system, the 36-month mortality rate was 7% for women in stage I, 10% for those in stage II, 29% for those in stage III, and 62% for those in stage IV (p < 0.001). The researchers used these results to propose a staging system that is relevant for sub-Saharan Africa, considers the extent of HIV-related outcomes, requires only inexpensive and available laboratory tests, and has clear prognostic significance. Both clinicians and researchers can use this modified staging system.
Validation of the proposed World Health Organization staging system for HIV disease and infection in a cohort of intravenous drug users.
AIDS. 1994 Aug; 8(8):1129-33.In Maryland, researchers aimed to determine whether clinical staging using the World Health Organization (WHO) proposed system would predict progression from HIV seropositivity to AIDS. They used product-limit estimates with right censoring to compare time of progression to AIDS among 694 intravenous drug users (IVDUs) in Baltimore who were HIV-positive by January, 1992, from each of the WHO proposed system's 1st 3 clinical stages. The researchers used Cox proportional hazard methods to examine the effect of race, sex, age, and baseline injection status on the risk of progression by clinical stage. Most of the participants were Black (95%), poor (legal income of <$5000/year, 78%), and male (75.8%). Many (35%) were homeless. At the time of the index visit, the proportion of IVDUs at WHO stages 1, 2, and 3 were 49%, 10%, and 41%, respectively. At the end of the study period, 67 (9.7%) of all IVDUs had progressed to AIDS. The product-limit estimates for progression to AIDS over a 3-year period indicate that the risk of progression to AIDS increases as the stages advance (6.5% for stage 1, 10.4% for stage 2, and 17.1% for stage 3; logrank p = .003). Age, race, sex, and baseline injection status did not affect the association between initial clinical stage and progression. The hazard for progression to AIDS relative to stage 1 was 1.51 for stage 2 and 2.39 for stage 3. These findings suggest that WHO'S proposed staging system for HIV infection and AIDS may predict progression from HIV seropositivity to AIDS using clinical criteria alone. This system would be most useful in areas with limited routine access to laboratory markers (e.g., CD4 counts), such as in many developing countries.