Quality and turnaround times of viral load monitoring under prevention of mother-to-child transmission of HIV Option B+ in six South African districts with a high antenatal HIV burden.

BACKGROUND: Barriers to monitoring maternal HIV viral load (VL) and achieving 90% viral suppression during pregnancy and breastfeeding still need to be understood in South Africa (SA). OBJECTIVES: To measure quality of VL care and turnaround times (TATs) for returning VL results to women enrolled in the prevention of mother-to-child transmission of HIV (PMTCT) programme in primary healthcare facilities. METHODS: Data were obtained from a 2018 cross-sectional evaluation of the PMTCT Option B+ programme in six SA districts with high antenatal and infant HIV prevalence. Quality of VL care was measured as the proportion of clients reporting that results were explained to them. TATs for VL results were calculated using dates abstracted from four to five randomly selected facility-based client records to report overall facility 'short TAT' (≥80% of records with TAT ≤7 days). Logistical regression and logit-based risk difference statistics were used. RESULTS: Achieving overall short TAT was uncommon. Only 50% of facilities in one rural district, zero in one urban metro district and 9 - 38% in other districts had short TAT. The significant difference between districts was influenced by the duration of keeping results in facilities after receipt from the laboratory. Expected quality of VL care received ranged between 66% and 85%. Client-related factors significantly associated with low quality of care, observed in two urban districts and one rural district, included lower education, recent initiation of antiretroviral treatment and experiencing barriers to clinic visits. Experiencing clinic visit barriers was also negatively associated with short TATs. CONCLUSIONS: We demonstrate above-average quality of care and delayed return of results to PMTCT clients. Context-specific interventions are needed to shorten TATs.

Uptake of antenatal care in high HIV-prevalence settings: Results from three population-based surveys in South Africa.

BACKGROUND: Despite substantial progress in reducing pregnancy-related preventable morbidity and mortality, these remain unacceptably high in developing countries. In 2016, the World Health Organization (WHO) revised recommendations for antenatal care (ANC) from a 4-visit model to a minimum of 8 ANC contacts to reduce perinatal mortality further and improve women's experience of care. The guidelines also recommend that the first ANC visit (ANC-1) should occur during the first trimester. OBJECTIVES: To describe the uptake of routine ANC and its associated factors in South Africa (SA) prior to the 2016 WHO recommendations, when the country recommended 4 ANC visits, to bring to light potential challenges in achieving the current recommendations. METHODS: Secondary data analyses were performed from 3 facility-based, cross-sectional national surveys, conducted to measure 6-week mother-to-child transmission of HIV and coverage of related interventions in SA. These surveys recruited mother-infant pairs attending selected public primary healthcare facilities for their infants' 6-week immunisation in 2010, 2011 -2012 and 2012 -2013. Quantitative questionnaires were used to gather sociodemographic and antenatal-to-peripartum information from Road to Health cards and maternal recall. The inclusion criteria for this secondary assessment were at least 1 ANC visit, the primary outcome being uptake of ≥4 ANC visits. A multivariable logistic regression model was used to: (i) identify maternal factors associated with ANC visits; and (ii) establish whether receiving selected ANC activities was associated with frequency or timing of ANC-1. RESULTS: Of the 9 470, 9 646 and 8 763 women who attended at least 1 ANC visit, only 47.5% (95% confidence interval (CI) 45.4 -49.6), 55.6% (95% CI 53.2 -58.0) and 56.7% (95% CI 54.3 -59.1) adhered to ≥4 ANC visits, while 36.0% (95% CI 34.5 -37.5), 43.5% (95% CI 42.0 -45.1) and 50.8% (95% CI 49.3 -52.2) attended ANC-1 early (before 20 weeks' gestation) in 2010, 2011 -2012 and 2012 -2013, respectively. Multiparity and lower socioeconomic status were significantly associated with non-adherence to the 4-visit ANC recommendation, while a later survey year, higher education, being married, >19 years old, HIV-positive, planned pregnancy and knowing how HIV is transmitted vertically were strongly related to ≥4 ANC visits. The number of women who received selected ANC activities increased significantly with survey year and ≥4 ANC visits, but was not associated with timing of ANC-1. CONCLUSIONS: Despite increases in the uptake of ≥4 ANC visits and early ANC-1 rates between 2010 and 2013, these practices remain suboptimal. Adhering to ≥4 ANC visits improved coverage of selected ANC activities, implying that strengthening efforts to increase the uptake of ANC from at least 4 to 8, could improve overall outcomes.

A rapid review of the effectiveness of screening practices at airports, land borders and ports to reduce the transmission of respiratory infectious diseases such as COVID-19.

BACKGROUND: Travel screening for infectious diseases is often implemented to delay or prevent the entry of infected persons to a country/area. OBJECTIVES: To evaluate the effectiveness of different point-of-entry screening strategies in achieving a reduction in imported COVID-19 transmission. METHODS: A rapid evidence review was conducted, systematically searching PubMed and Google Scholar and grey literature on 27 March 2020. RESULTS: We screened 1 194 records. Nine potential full-text articles were assessed for eligibility and included. Three articles investigated the effectiveness of entry-based thermal and body temperature scanning. Entry-based infrared thermal or body temperature scanning for COVID-19 was unlikely to be effective. Two systematic reviews found no additional benefit of travel restrictions/screening. In a COVID-19 modelling study, airport screening was not effective, with exit and entry thermal scanning identifying half and missing almost half of infected travellers. Two other modelling studies found that entry-based travel screening would achieve only modest delays in community transmission, while international travel quarantine could reduce case importations by 80%. CONCLUSIONS: There is insufficient evidence to support entry and exit screening at points of entry, as these strategies detect just over half of the infected cases, missing almost half at entry points. The benefits of airport screening therefore need to be context specific and weighed against the resources and cost of implementation, the contribution of imported cases to total cases, and the benefits of identifying 50% of cases in the South African context with the country's high HIV and tuberculosis prevalence and limited resources to deal with a pandemic of this nature.

A rapid review of the effectiveness of screening practices at airports, land borders and ports to reduce the transmission of respiratory infectious diseases such as COVID-19

Background. Travel screening for infectious diseases is often implemented to delay or prevent the entry of infected persons to a country/area.Objectives. To evaluate the effectiveness of different point-of-entry screening strategies in achieving a reduction in imported COVID-19 transmission.Methods. A rapid evidence review was conducted, systematically searching PubMed and Google Scholar and grey literature on 27 March 2020.Results. We screened 1 194 records. Nine potential full-text articles were assessed for eligibility and included. Three articles investigated the effectiveness of entry-based thermal and body temperature scanning. Entry-based infrared thermal or body temperature scanning for COVID-19 was unlikely to be effective. Two systematic reviews found no additional benefit of travel restrictions/screening. In a COVID-19 modelling study, airport screening was not effective, with exit and entry thermal scanning identifying half and missing almost half of infected travellers. Two other modelling studies found that entry-based travel screening would achieve only modest delays in community transmission, while international travel quarantine could reduce case importations by 80%.Conclusions. There is insufficient evidence to support entry and exit screening at points of entry, as these strategies detect just over half of the infected cases, missing almost half at entry points. The benefits of airport screening therefore need to be context specific and weighed against the resources and cost of implementation, the contribution of imported cases to total cases, and the benefits of identifying 50% of cases in the South African context with the country's high HIV and tuberculosis prevalence and limited resources to deal with a pandemic of this nature

A study of vaccine-induced immune pressure on breakthrough infections in the Phambili phase 2b HIV-1 vaccine efficacy trial.

INTRODUCTION: The Merck Adenovirus-5 Gag/Pol/Nef HIV-1 subtype-B vaccine evaluated in predominately subtype B epidemic regions (Step Study), while not preventing infection, exerted vaccine-induced immune pressure on HIV-1 breakthrough infections. Here we investigated if the same vaccine exerted immune pressure when tested in the Phambili Phase 2b study in a subtype C epidemic. MATERIALS AND METHODS: A sieve analysis, which compares breakthrough viruses from placebo and vaccine arms, was performed on 277 near full-length genomes generated from 23 vaccine and 20 placebo recipients. Vaccine coverage was estimated by computing the percentage of 9-mers that were exact matches to the vaccine insert. RESULTS: There was significantly greater protein distances from the vaccine immunogen sequence in Gag (p=0.045) and Nef (p=0.021) in viruses infecting vaccine recipients compared to placebo recipients. Twenty-seven putative sites of vaccine-induced pressure were identified (p<0.05) in Gag (n=10), Pol (n=7) and Nef (n=10), although they did not remain significant after adjustment for multiple comparisons. We found the epitope sieve effect in Step was driven by HLA A∗02:01; an allele which was found in low frequency in Phambili participants compared to Step participants. Furthermore, the coverage of the vaccine against subtype C Phambili viruses was 31%, 46% and 14% for Gag, Pol and Nef, respectively, compared to subtype B Step virus coverage of 56%, 61% and 26%, respectively. DISCUSSION: This study presents evidence of sieve effects in Gag and Nef; however could not confirm effects on specific amino acid sites. We propose that this weaker signal of vaccine immune pressure detected in the Phambili study compared to the Step study may have been influenced by differences in host genetics (HLA allele frequency) and reduced impact of vaccine-induced immune responses due to mismatch between the viral subtype in the vaccine and infecting subtypes.

Temporal association of HLA-B*81:01- and HLA-B*39:10-mediated HIV-1 p24 sequence evolution with disease progression.

HLA-B*81:01 and HLA-B*39:10 alleles have been associated with viremic control in HIV-1 subtype C infection. Both alleles restrict the TL9 epitope in p24 Gag, and cytotoxic-T-lymphocyte (CTL)-mediated escape mutations in this epitope have been associated with an in vitro fitness cost to the virus. We investigated the timing and impact of mutations in the TL9 epitope on disease progression in five B*81:01- and two B*39:10-positive subtype C-infected individuals. Whereas both B*39:10 participants sampled at 2 months postinfection had viruses with mutations in the TL9 epitope, in three of the five (3/5) B*81:01 participants, TL9 escape mutations were only detected 10 months after infection, taking an additional 10 to 15 months to reach fixation. In the two remaining B*81:01 individuals, one carried a TL9 escape variant at 2 weeks postinfection, whereas no escape mutations were detected in the virus from the other participant for up to 33 months postinfection, despite CTL targeting of the epitope. In all participants, escape mutations in TL9 were linked to coevolving residues in the region of Gag known to be associated with host tropism. Late escape in TL9, together with coevolution of putative compensatory mutations, coincided with a spontaneous increase in viral loads in two individuals who were otherwise controlling the infection. These results provide in vivo evidence of the detrimental impact of B*81:01-mediated viral evolution, in a single Gag p24 epitope, on the control of viremia.

Clinical and epidemiological features of HIV infection at a referral clinic in Zambia.

Among 1,350 patients with serologically confirmed HIV-1 infection evaluated at the Dermatovenerealogy Clinic, University Teaching Hospital. Lusaka, through March 1987, 125 (9.3%) had AIDS, 1,178 (87.3%) had AIDS-related complex, and 46 (3.5%) were asymptomatic. The male to female ratio of cases was 1.5:1 and women were younger (mean age of 26.2 years) than were men (mean age of 31.2 years). HIV-infected persons had significantly more lifetime sex partners than uninfected persons; other risk factors were a prior history of venereal disease, blood transfusion, travel abroad, and a positive syphilis serology. Clinical features in decreasing order of frequency were weight loss, persistent generalized lymphadenopathy, chronic cough, multidermatomal herpes zoster, diarrhea, recurrent fevers, tuberculosis, and oropharyngeal candidiasis. The WHO clinical case definition for the diagnosis of AIDS had a low positive predictive value for the 125 Zambians with AIDS, but among all those infected with HIV, the positive predictive value was 76.4%. Thirty (35.3%) of 85 patients who were HIV seronegative when first examined acquired HIV infections during a 12- to 39-month (means = 21.8 months) period of observation. Heterosexual intercourse unrelated to prostitution appears to be the major mode of HIV transmission in Lusaka.

PIP: The clinical and epidemiologic characteristics of the 1st 1350 individuals diagnosed at Zambia's Dermatovenerealogy Clinic in Lusaka between August 1985-December 1986 as a positive for human immunodeficiency virus (HIV) infection were evaluated. 125 (9.3%) of these seropositive individuals presented with aggressive Kaposi's sarcoma or an opportunistic infection and were thus diagnosed with acquired immunodeficiency syndrome (AIDS), 1178 (87.3%) had AIDS-related complex (ARC), and a further 47 (3.5%) were asymptomatic. The male to female ratio of HIV-positive cases was 1.5 to 1. Female patients were younger (mean age 26.1 years) than male patients (mean age, 31.2 years). The only sexual practice acknowledged by the vast majority of cases was heterosexual vaginal intercourse, although infected men and women had significantly more lifetime sexual partners than uninfected controls. Other significant risk factors for HIV seropositivity were (for men) blood transfusion, travel outside of Zambia, and a history of syphilis; for women, these risk factors were blood transfusion and a history of venereal disease. The most common clinical features in AIDS and ARC patients were, in decreasing order of frequency, weight loss greater than 10%, generalized lymphadenopathy, chronic cough, multidermatomal herpes zoster, recurrent diarrhea, recurrent fever, tuberculosis, and oropharyngeal candidiasis. The provisional WHO clinical case definition of AIDS in Africa has a positive predictive value of 82.1 for the sample as a whole, but only 46.3 for the 125 patients diagnosed with AIDS. 17 of the HIV-positive patients had died by the 18-month follow-up.

A clinical sickness score for the critically ill in Central Africa.

Scoring systems provide a means for comparing results, ensuring consistent standards and evaluating changes in therapy. The APACHE II system depends partly on the results of laboratory tests which are not normally available in Central Africa. The aim of this study was to develop a scoring system based only on clinical observations. Six hundred and twenty-four consecutive admissions to the intensive care unit (ICU) were allocated a clinical sickness score (CSS) according to pulse rate, blood pressure, respiration rate, urine output, Glasgow Coma Scale, temperature and age. CSS was significantly associated with outcome, there being no significant difference between actual and predicted outcomes calculated by logistic regression analysis. There was a significant difference between mean scores for survivors and non-survivors in all diagnostic groups except diabetes. The proportional change in score from admission was also significantly associated with outcome on each subsequent day in ICU. The CSS provides an objective measure of illness severity for critically ill patients in Africa.