Spreading of SARS-CoV-2 in West Africa and assessment of risk factors.

Although the African continent is, for the moment, less impacted than the rest of the world, it still faces the risk of a spread of COVID-19. In this study, we have conducted a systematic review of the information available in the literature in order to provide an overview of the epidemiological and clinical features of COVID-19 pandemic in West Africa and of the impact of risk factors such as comorbidities, climatic conditions and demography on the pandemic. Burkina Faso is used as a case study to better describe the situation in West Africa. The epidemiological situation of COVID-19 in West Africa is marked by a continuous increase in the numbers of confirmed cases. This geographic area had on 29 July 2020, 131 049 confirmed cases by polymerase chain reaction, 88 305 recoveries and 2102 deaths. Several factors may influence the SARS-CoV-2 circulation in Africa: (i) comorbidities: diabetes mellitus and high blood pressure could lead to an increase in the number of severe cases of SARS-CoV-2; (ii) climatic factors: the high temperatures could be a factor contributing to slow the spread of the virus and (iii) demography: the West Africa population is very young and this could be a factor limiting the occurrence of severe forms of SARS-CoV-2 infection. Although the spread of the SARS-CoV-2 epidemic in West Africa is relatively slow compared to European countries, vigilance must remain. Difficulties in access to diagnostic tests, lack of hospital equipment, but also the large number of people working in the informal sector (such as trading, businesses, transport and restoration) makes it difficult to apply preventive measures, namely physical distancing and containment.

Usutu virus: A new threat?

Usutu virus (USUV) is an emerging arbovirus that was first isolated in South Africa in 1959. This Flavivirus is maintained in the environment through a typical enzootic cycle involving mosquitoes and birds. USUV has spread to a large part of the European continent over the two decades mainly leading to substantial avian mortalities with a significant recrudescence of bird infections recorded throughout Europe within the few last years. USUV infection in humans is considered to be most often asymptomatic or to cause mild clinical signs. Nonetheless, a few cases of neurological complications such as encephalitis or meningoencephalitis have been reported. USUV and West Nile virus (WNV) share many features, like a close phylogenetic relatedness and a similar ecology, with co-circulation frequently observed in nature. However, USUV has been much less studied and in-depth comparisons of the biology of these viruses are yet rare. In this review, we discuss the main body of knowledge regarding USUV and compare it with the literature on WNV, addressing in particular virological and clinical aspects, and pointing data gaps.

Developmental determinants in non-communicable chronic diseases and ageing.

Prenatal and peri-natal events play a fundamental role in health, development of diseases and ageing (Developmental Origins of Health and Disease (DOHaD)). Research on the determinants of active and healthy ageing is a priority to: (i) inform strategies for reducing societal and individual costs of an ageing population and (ii) develop effective novel prevention strategies. It is important to compare the trajectories of respiratory diseases with those of other chronic diseases.

[Determinants of low birth weight among newborns to HIV-infected mothers not eligible for antiretroviral treatment in Africa]. / Déterminants du faible poids de naissance chez des enfants nés de mères séropositives pour le VIH, non éligibles au traitement antirétroviral, en Afrique.

BACKGROUND: Low birth weight (LBW) increases the risk of infant death, but little is known about its rate and determinants among babies born to HIV-infected mothers in sub-Saharan Africa. METHODS: This study was conducted in South Africa, Burkina Faso, Uganda and Zambia, during the recruitment process of the PROMISE-PEP (ANRS 12174) clinical trial. The study sample included 1196 subjects screened between August 2009 and December 2011, respectively 254 in South Africa, 221 in Burkina Faso, 197 in Uganda and 524 in Zambia, all ineligible for antiretroviral therapy. Data were collected during ANRS12174 clinical trial antenatal and postnatal screening visits, and during an inclusion visit for completion of an electronic case report form (eCRF). RESULTS: The mean (±SD) age of mothers was 27±5years and their mean CD4 count was 576±195cells/µL. Most mothers lived in a couple (78.7%), had no employment (72.3%) and had a good level of education (74% had gone to school). Male newborns predominated (51.7%). The mean birth weight was 3043g±435g, and 7.8% ([95%CI: 6.3%-9.3%]) of newborns weighed less than 2500g. In univariate analyses, being married or cohabiting, body mass index, WHO HIV disease stage II, female newborn and low gestational age were associated with risk of LBW. In multivariate regression model, low gestational age (aOR=3.74, P<0.0001) and female newborn (aOR=1.63, P=0.04) were significantly associated with LBW. CONCLUSION: The risk factors for LBW found in HIV-infected women ineligible for antiretroviral therapy were the same as in the general population. There was no evidence of additional risk factors associated with HIV infection.

Long-term hepatitis B virus surface antigen decay in HIV-1/hepatitis B virus-coinfected adults initiating a tenofovir-containing regimen.

Hepatitis B virus (HBV) surface antigen (HBsAg) decay was explored in HIV-1- and HBV-coinfected patients beginning antiretroviral (ARV) therapy containing tenofovir disoproxil fumarate (TDF). The mean HBsAg decay was 0.38 log(10) IU/ml/year (95% confidence interval [CI], 0.71 to 0.05) in 18 patients with sustained plasma HIV-1 RNA suppression and 0.15 log(10) IU/ml/year (0.21 to 0.09) in 12 patients experiencing HIV-1 virologic failure due to suboptimal adherence to ARV (P = 0.17). We estimated that six of these 18 patients will attain HBsAg values below 10 IU/ml after 10 years of treatment.

Intrafamilial cluster of pulmonary tuberculosis due to Mycobacterium bovis of the African 1 clonal complex.

A new clonal complex of Mycobacterium bovis present at high frequency in cattle from west central African countries has been described as the African 1 (Af1) clonal complex. Here, the first intrafamilial cluster of human tuberculosis cases due to M. bovis Af1 clonal complex strains is reported. We discuss hypotheses regarding modes of transmission.

Detection of SARS-CoV-2 antibodies using commercial assays and seroconversion patterns in hospitalized patients.

OBJECTIVES: SARS-CoV-2 antibody assays are needed for serological surveys and as a complement to molecular tests to confirm COVID-19. However, the kinetics of the humoral response against SARS-CoV-2 remains poorly described and relies on the performance of the different serological tests. METHODS: In this study, we evaluated the performance of six CE-marked point-of-care tests (POC) and three ELISA assays for the diagnosis of COVID-19 by exploring seroconversions in hospitalized patients who tested positive for SARS-CoV-2 RNA. RESULTS: Both the ELISA and POC tests were able to detect SARS-CoV-2 antibodies in at least half of the samples collected seven days or more after the onset of symptoms. After 15 days, the rate of detection rose to over 80% but without reaching 100%, irrespective of the test used. More than 90% of the samples collected after 15 days tested positive using the iSIA and Accu-Tell® POC tests and the ID.Vet IgG ELISA assay. Seroconversion was observed 5 to 12 days after the onset of symptoms. Three assays suffer from a specificity below 90% (EUROIMMUN IgG and IgA, UNscience, Zhuhai Livzon). CONCLUSIONS: The second week of COVID-19 seems to be the best period for assessing the sensitivity of commercial serological assays. To achieve an early diagnosis of COVID-19 based on antibody detection, a dual challenge must be met: the immunodiagnostic window period must be shortened and an optimal specificity must be conserved.

Detection of Mycobacterium tuberculosis in paucibacillary sputum: performances of the Xpert MTB/RIF ultra compared to the Xpert MTB/RIF, and IS6110 PCR.

The Xpert MTB/RIF Ultra assay has recently been launched to improve the detection of smear negative disease. This retrospective study compares the sensitivity of Xpert MTB/RIF Ultra with that of Xpert MTB/RIF tests and IS6110 real-time PCR in sputum. Diagnostic performance of three molecular tests was evaluated using 48 culture-positive clinical respiratory specimens diluted to obtain paucibacillary sputum specimens. Xpert MTB/RIF Ultra had the highest sensitivity of 100% compared to 42% (P < 0.001) for Xpert MTB/RIF and 64.5% (P = 0.02) for IS6110-PCR. All "very low" or "low" positive specimens using Xpert MTB/RIF Ultra were tested positive using IS6110-PCR, but 35.4% were found negative using Xpert MTB/RIF. Xpert MTB/RIF Ultra is more sensitive than the two other tests for sputum with a low bacterial load. Adding detection of IS6110 and IS1081 to rpoB, is a key evolution of the assay and improves the detection of Mycobacterium tuberculosis' DNA in paucibacillary sputum.

Effect of HIV-1 and antiretroviral therapy on herpes simplex virus type 2: a prospective study in African women.

OBJECTIVES: To document the natural history of herpes simplex virus type 2 (HSV-2) in relation to HIV and highly active antiretroviral therapy (HAART) in Africa, a longitudinal study was conducted of women in the placebo arms of two randomised controlled trials of HSV-suppressive therapy in Burkina Faso. METHODS: 22 HIV-uninfected women (group 1), 30 HIV-1-infected women taking HAART (group 2), and 68 HIV-1-infected women not eligible for HAART (group 3) were followed over 24 weeks. HSV-2 DNA was detected on alternate weeks using real-time PCR from cervicovaginal lavages. Plasma HIV-1 RNA was measured every month. CD4 cell counts were measured at enrollment. RESULTS: Ulcers occurred on 1.9%, 3.1% and 7.2% of visits in groups 1, 2 and 3 (p = 0.02). Cervicovaginal HSV-2 DNA was detected in 45.5%, 63.3% and 67.6% of women (p = 0.11), and on 4.3%, 9.7% and 15.5% of visits in the three groups (p<0.001). Among HIV-infected women, cervicovaginal HSV-2 DNA was detected more frequently during ulcer episodes (adjusted risk ratio (aRR) 2.79, 95% CI 2.01 to 3.86) and less frequently among women practising vaginal douching (aRR 0.60, 95% CI 0.40 to 0.91). Compared with women not taking HAART and with CD4 cell counts of 500 cells/microl or greater, women on HAART had a similar risk of HSV-2 shedding (aRR 0.95, 95% CI 0.52 to 1.73), whereas women with CD4 cell counts of 200-500 cells/microl were more likely to shed HSV-2 (aRR 1.71, 95% CI 1.02 to 2.86). CONCLUSIONS: HSV-2 reactivations occur more frequently among HIV-infected women, particularly those with low CD4 cell counts, and are only partly reduced by HAART. HSV therapy may benefit HIV-infected individuals during HAART.

Longitudinal effect following initiation of highly active antiretroviral therapy on plasma and cervico-vaginal HIV-1 RNA among women in Burkina Faso.

BACKGROUND: Highly active antiretroviral therapy (HAART) could decrease HIV-1 transmissibility by reducing genital and plasma HIV-1 RNA. METHODS: We evaluated the effect of HAART on genital and plasma HIV-1 RNA in a cohort of 39 antiretroviral-naïve women in Burkina Faso. Cervico-vaginal lavages were collected before HAART initiation and at six visits over 28 weeks while on HAART. Blood samples were collected at baseline and at three and four visits for CD4 and plasma HIV-1 RNA measurements, respectively. RESULTS: Before HAART, 72% of women had detectable genital HIV-1 RNA. After 18 weeks on HAART, only one woman (2.5%) had detectable plasma HIV-1 RNA and two women (5.1%) had detectable genital HIV-1 RNA. Similar results were observed at each follow-up visit. However, 16/34 (47%) women with consistently undetectable plasma HIV-1 RNA shed HIV-1 at least once between weeks 18 and 28. In samples with detectable genital HIV-1, the mean quantity of HIV-1 RNA decreased from 3.87 prior to HAART to 3.04 log(10) copies/mL at last visit (median 29 weeks; a 6.8-fold decrease in absolute number of copies/mL) (p = 0.04). A significant median CD4 lymphocyte cell gain of 121 cells/muL (interquartile range 59 to 204) was measured between pre-HAART and last visit. CONCLUSION: These findings suggest that HAART could play a role in reducing HIV transmission in Africa; however, they underscore the need to emphasise safe sex practices with patients taking HAART.

Comprehensive proteomic analysis of the human milk proteome: contribution of protein fractionation.

In-depth analysis of the milk proteome by mass spectrometry is challenged by the presence of few high-abundance proteins that interfere with the detection of lower-abundance proteins. Here, we evaluated the proteomic analysis of milk samples following a strong anion exchange fractionation procedure using denaturating conditions ensuring the disruption of protein-protein interactions. Crude whey or skim milk and their different resulting fractions were analyzed by protein chip array mass spectrometry. Using protein chip array mass spectrometry, several high-abundance proteins were localized in distinct fractions increasing the total number of unique peptides and proteins detected. This total number increased by about 20-30% by combining different chromatographic surface arrays used for capture. Reproducible results were obtained in human skim milk and whey; however this approach was not successful with milk fat globule membrane and required refinement. Hence, milk profiling by anion exchange fractionation combined to protein chip array mass spectrometry represents a promising tool to detect unknown low-abundance milk proteins that may ultimately prove useful as biomarkers of diseases transmitted by breastfeeding.

Association between breast milk fatty acids and HIV-1 transmission through breastfeeding.

A residual mother-to-child transmission of HIV through breastfeeding persists despite prophylaxis. We identified breast milk fatty acids (FA) associated with postnatal HIV transmission through breastfeeding in a case-control study. Cases (n=23) were HIV-infected women with an infant who acquired HIV after 6 weeks of age. Controls (n=23) were matched on infant׳s age at sample collection. Adjusting for maternal antenatal plasma CD4 T cell count, cis-vaccenic acid (18:1n-7) and eicosatrienoic acid (20:3n-3) were associated with HIV transmission in opposite dose-response manner: OR (tertile 3 versus tertile 1): 10.8 and 0.16, p for trend=0.02 and 0.03, respectively. These fatty acids correlated with HIV RNA load, T helper-1 related cytokines, IL15, IP10, and ß2 microglobulin, positively for cis-vaccenic acid, negatively for eicosatrienoic acid. These results suggested a change in FA synthesis by mammary gland cells leading to increased cis-vaccenic acid in milk of mothers who transmitted HIV to their infant during breastfeeding.

The epidemiology of HIV infection and AIDS in Africa.

Only 10 years after it was first recognized in Africa, HIV infection is already the leading cause of adult death in many cities of the continent and has increased childhood mortality. This article reviews critical aspects of the dynamics of this epidemic, including routes of transmission, factors influencing the rate of transmission and strategies to combat this disaster.

PIP: HIV infection is the leading cause of adult mortality in many African cities and has increased the level of child mortality. The author reviews critical aspects of the dynamics of the epidemic, including routes of transmission, factors influencing the rate of transmission, and strategies to combat the disaster. The impoverishment of the population, women's economic dependence, deteriorating educational systems, and overloading of health services have contributed dramatically to the spread of HIV. Moreover, the political and social trauma endured by certain African populations may contribute to the HIV/AIDS epidemic. Prevention will continue to be extremely important and should be reinforced by promotion of the use of condoms, STD control programs, prophylaxis of mother-to-child transmission, and vaccine development. Efforts also need to be taken to improve the quality of life of HIV-infected individuals in Africa. The management of HIV-induced disease should be an HIV/AIDS research priority on the continent. Much depends upon the commitment of African political decision makers, the public sector, international agencies, pharmaceutical companies, and local communities.

Adult and paediatric AIDS patients lacking HIV antibodies detected by enzyme immunoassay in central Africa: further serological studies.

We describe HIV antigen and HIV-1, HIV-2 and human T-cell leukaemia virus type I (HTLV-I) Western blot (WB) results in 20 adults and 12 children with AIDS who were shown to be HIV-1 seronegative by two commercial enzyme immunoassays (EIA), in Kigali, Rwanda, central Africa. These patients represented 3% of adults and 7.4% of children with AIDS observed in Kigali during the study period. Thirteen of the adults and five of the children were HIV-1 WB positive. All patients were HTLV-I WB negative. One adult AIDS patient had a reactive HIV-2 WB; he is the first HIV-2-infected individual to be diagnosed in Rwanda. HIV antigenaemia was demonstrated in only one adult and one child, suggesting that HIV antigenaemia is not frequent in African AIDS patients, even in the case of weak immunologic responses to HIV core proteins. Three adults and four children had none of the serological markers detected. This study showed that HIV EIA negativity occurs infrequently in African patients with AIDS. In such a situation, an attempt to detect HIV antibodies by a more sensitive technique, such as WB, is necessary.

The latex condom, an efficient barrier against sexual transmission of AIDS-related viruses.

Using a mechanical model, we studied human immunodeficiency virus (HIV) leakage through six different trademark condoms. The presence of the recovered virus was determined after passage to MT-2 cells and to cultured mitogen-stimulated normal human peripheral blood mononuclear cells (PMC). Only the natural membrane condom showed virus leakage after inside pressure. In addition, the kinetics of virus inactivation at 37 degrees C were followed inside and outside the condom. The virus was partially inactivated after 10 min at 37 degrees C inside the condom, but the degree of inactivation seemed higher in some of the trademark condoms.

PIP: 6 trademark condoms, 5 made of latex (Durex Coral, Ortho Shields, Prime, KLV, and Man-To-Man) and 1 lubricated natural membrane condom (Kling-Tite Naturalamb) were tested mechanically to determine whether they were effective barriers to leakage of the human immunodeficiency virus (HIV). A 3 ml suspension of HIV concentrate was put into each condom and the condom placed over the plunger of a disposable syringe. The plunger was vigorously pumped as many as 50 times for each condom. No virus crossed the membrane of any of the latex condoms, but a significant passage of retroviral antigen through a leak in the natural membrane condom occurred after only 10 pumping movements. In addition some of the latex condoms were treated with spermicide, and these showed varying degrees of virus inactivation inside the condom. Further studies should be done on the use of spermicide-treated condoms. In any case, the use of condoms should be promoted among groups at high risk for AIDS such as prostitutes in Central Africa where condom use remains unpopular.

Estimating the incubation period of paediatric AIDS in Rwanda.

OBJECTIVE: To estimate the distribution of the incubation period of paediatric AIDS in Rwanda. DESIGN: Data were collected between February 1984 and December 1990 at the Centre Hospitalier de Kigali (CHK), the capital city of Rwanda, Central Africa. PATIENTS: We used a sample of 685 AIDS cases registered consecutively in the Department of Paediatrics of the CHK, in which the proportion of perinatally acquired HIV-1 infection was estimated to be 98.6%. METHODS: We performed both non-parametric and parametric analyses. The methods of estimation were adapted to truncated data, using essentially the same methods as Auger et al. in their analysis of data from the New York City and the New York State AIDS case registries in 1988. RESULTS: We found that a double Weibull model fitted the data very well and that the risk of developing AIDS was high for subjects under 18 months of age, but lower for older subjects. CONCLUSIONS: Our results were qualitatively similar to those of Auger et al.. There were quantitative differences between the two studies, but it was not possible to compare median survival periods. Parameters such as median or mean survival times cannot be validly estimated using only data from registers because these data exclude infected subjects who have not yet developed AIDS.

PIP: The authors used nonparametric and parametric methods and data on 685 AIDS cases at the Centre Hospitalier de Kigali, collected between February 1984 and December 1990, to estimate the distribution of pediatric AIDS in Kigali, Rwanda. 98.6% of the cases probably acquired AIDS via vertical transmission. A combination of the 2 Weibul distributions (parametric method) resulted in a good fit, suggesting that the sample population consisted of a subpopulation with a short incubation period and an other with a longer incubation period. The researchers could not deduce proof of heterogeneity from the shape of the distribution, however. The probability of developing AIDS during the first year of life was 0.29, which corresponded with that of the European Collaborative Study (0.26). The risk of developing pediatric AIDS increased considerably for children less than 18 months old but fell and became constant for older children. The qualitative findings matched those of a study in New York City. Even though quantitative differences between this study and the other study existed, the researchers could not compare median survival times. Since data from registers did not include HIV-infected children who had not yet developed AIDS, the researchers were not able to estimate median and mean survival periods. A possible source of bias was that the data were from a surveillance system based on cases at just 1 hospital, which probably did not see all pediatric AIDS cases. In conclusion, truncated data determined rather well the distribution of incubation periods, but could not provide much information about the scale parameters of the model.

Risk factors for HIV seropositivity in selected urban-based Rwandese adults.

In January 1987, HIV antibodies were detected by means of an immunoenzymatic assay, indirect immunofluorescence and Western blot in 52 out of 302 male urban-based professionals and in 28 out of 150 health workers in Kigali, Rwanda. Univariate analysis showed an association between HIV seropositivity and a history of sexually transmitted diseases (STD), blood transfusion, medical injections for treatment of STD, and medical injections for treatment of febrile illnesses. However, injection related to treatment of other conditions were not associated with HIV seropositivity. Among health workers, no association between HIV seropositivity and professional or accidental exposure to HIV-infected patients or to their body fluids was identified. Discriminant analysis showed that HIV seropositivity was associated only with a history of STD and with a history of blood transfusion. In central Africa, a history of STD and a history of blood transfusion should be considered as risk factors for HIV seropositivity. Medical or accidental injections do not seem to play a major role in the transmission of HIV among adults in central Africa.

HIV antibodies in a remote rural area in Rwanda, Central Africa: an analysis of potential risk factors for HIV seropositivity.

Detection of HIV antibodies by means of an immunoenzymatic assay, an indirect immunofluorescence technique and Western blot was attempted on 375 serum samples collected in the Murunda area, a remote rural area situated in Rwanda, central Africa. Two out of 147 (1.4%) adults from a strict rural area, five out of 59 (8.5%) adults from an adjacent market place, and 49 out of 169 (30%) STD clinic attenders from the same area were HIV seropositive. In the first two groups, HIV seropositivity was associated with a history of sexually transmitted disease (STD) in the previous 2 years (P less than 0.001) and with a history of travel to a Rwandese urban centre in the previous 5 years (P less than 0.05). This study suggests that HIV seroprevalence is low in rural central Africa compared with urban centres. Risk factors for HIV seropositivity are similar in rural and urban-based adults in Rwanda, i.e. heterosexual promiscuity and STDs. Many HIV seropositive rural subjects from this study are likely to have acquired HIV infection through sexual contacts in Rwandese cities.

PIP: 375 serum samples collected from youth and adults in Murunda, a remote rural area in Rwanda, were analyzed for antibodies to human immunodeficiency virus (HIV). Study subjects were drawn from 3 selected populations: those from the village of Rulimba, a strictly rural area; adults from Gisiza, an adjacent rural market place that is connected by roads to 2 other cities; and patients from the same district who attended the Murunda health center for treatment of a sexually transmitted disease during the study period. The prevalence of HIV seropositivity was 2/147 (1.4%) in the strictly rural group, 5/59 (8.5%) in the market place area, and 49/169 (30%) among patients receiving treatment for sexually transmitted diseases. No significant differences existed between male and female subjects in terms of HIV seropositivity. HIV seropositivity was also associated with a history of venereal diseases in the market place sample. These results suggest that Rwanda's rural population (93%) is at lower risk of HIV infection that the urban population. Where HIV infection does exist in rural areas, it is transmitted mainly by heterosexual contact with persons from urban centers. The relatively high rate of HIV infection observed in adults living in a rural market place accessible from most of the Rwandan main cities, together with the association between HIV seropositivity and past residency or travel in urban centers, indicates that most of the rural-based seropositive adults identified in this study were infected elsewhere. These findings also contradict the popular assumption that HIV was present in an unrecognized form for many years in rural Central Africa.

Acceptability of voluntary HIV testing by pregnant women in developing countries: an international survey. Ghent International Working Group on Mother-to-Child Transmission of HIV.

OBJECTIVE: To evaluate acceptability of voluntary HIV counselling and testing (VCT) by pregnant women in the context of clinical trials assessing interventions to reduce mother-to-child transmission (MCT) of HIV in developing countries. METHODS: During September-October 1997, 13 studies located in West (Abidjan, Bobo Dioulasso), East (Nairobi, Mombasa, Dar Es Salaam, Blantyre, Lusaka, Harare) and South Africa (Soweto, Durban), and Thailand (Bangkok) were included in a cross-sectional mailing survey about the acceptability of VCT in antenatal clinics. Acceptance rate, return rate, overall acceptability of VCT (acceptance of both pre- and post-VCT sessions) were obtained using a standardized questionnaire. RESULTS: The median overall acceptability of VCT was 69% (range, 33-95%). Overall acceptability of VCT most frequently depended on return rates because acceptance rates were generally high. Where several studies were conducted in parallel in the same city or the same country, overall acceptability rates of HIV testing were generally comparable even if the intervention programmes differed. Overall acceptability rates of VCT were high in antenatal clinics where a particular effort in implementing VCT programmes had been made. CONCLUSIONS: This international survey shows that despite many obstacles, VCT is feasible and acceptable for pregnant women aiming to reduce their risk of transmitting HIV to their children.