Surveillance To Track Progress Toward Polio Eradication - Worldwide, 2022-2023.

The reliable and timely detection of poliovirus cases through surveillance for acute flaccid paralysis (AFP), supplemented by environmental surveillance of sewage samples, is a critical component of the polio eradication program. Since 1988, the number of polio cases caused by wild poliovirus (WPV) has declined by >99.9%, and eradication of WPV serotypes 2 and 3 has been certified; only serotype 1 (WPV1) continues to circulate, and transmission remains endemic in Afghanistan and Pakistan. This surveillance update evaluated indicators from AFP surveillance, environmental surveillance for polioviruses, and Global Polio Laboratory Network performance data provided by 28 priority countries for the program during 2022-2023. No WPV1 cases have been detected outside of Afghanistan and Pakistan since August 2022, when an importation into Malawi and Mozambique resulted in an outbreak during 2021-2022. During 2022-2023, among 28 priority countries, 20 (71.4%) met national AFP surveillance indicator targets, and the number of environmental surveillance sites increased. However, low national rates of reported AFP cases in priority countries in 2023 might have resulted from surveillance reporting lags; substantial national and subnational AFP surveillance gaps persist. Maintaining high-quality surveillance is critical to achieving the goal of global polio eradication. Monitoring surveillance indicators is important to identifying gaps and guiding surveillance-strengthening activities, particularly in countries at high risk for poliovirus circulation.

Surveillance To Track Progress Toward Poliomyelitis Eradication - Worldwide, 2021-2022.

Since the Global Polio Eradication Initiative (GPEI) was established in 1988, the number of wild poliovirus (WPV) cases has declined by >99.9%, and WPV serotypes 2 and 3 have been declared eradicated (1). By the end of 2022, WPV type 1 (WPV1) transmission remained endemic only in Afghanistan and Pakistan (2,3). However, during 2021-2022, Malawi and Mozambique reported nine WPV1 cases that were genetically linked to Pakistan (4,5), and circulating vaccine-derived poliovirus (cVDPV) outbreaks were detected in 42 countries (6). cVDPVs are oral poliovirus vaccine-derived viruses that can emerge after prolonged circulation in populations with low immunity allowing reversion to neurovirulence and can cause paralysis. Polioviruses are detected primarily through surveillance for acute flaccid paralysis (AFP), and poliovirus is confirmed through stool specimen testing. Environmental surveillance, the systematic sampling of sewage and testing for the presence of poliovirus, supplements AFP surveillance. Both surveillance systems were affected by the COVID-19 pandemic's effects on public health activities during 2020 (7,8) but improved in 2021 (9). This report updates previous reports (7,9) to describe surveillance performance during 2021-2022 in 34 priority countries.* In 2022, a total of 26 (76.5%) priority countries met the two key AFP surveillance performance indicator targets nationally compared with 24 (70.6%) countries in 2021; however, substantial gaps remain in subnational areas. Environmental surveillance expanded to 725 sites in priority countries, a 31.1% increase from the 553 sites reported in 2021. High-quality surveillance is critical to rapidly detect poliovirus transmission and enable prompt poliovirus outbreak response to stop circulation. Frequent monitoring of surveillance guides improvements to achieve progress toward polio eradication.

Vaccine-derived poliovirus serotype 2 outbreaks and response in the Democratic Republic of the Congo, 2017-2021.

Vaccine-derived polioviruses (VDPVs) can emerge from Sabin strain poliovirus serotypes 1, 2, and 3 contained in oral poliovirus vaccine (OPV) after prolonged person-to-person transmission where population vaccination immunity against polioviruses is suboptimal. VDPVs can cause paralysis indistinguishable from wild polioviruses and outbreaks when community circulation ensues. VDPV serotype 2 outbreaks (cVDPV2) have been documented in The Democratic Republic of the Congo (DRC) since 2005. The nine cVDPV2 outbreaks detected during 2005-2012 were geographically-limited and resulted in 73 paralysis cases. No outbreaks were detected during 2013-2016. During January 1, 2017-December 31, 2021, 19 cVDPV2 outbreaks were detected in DRC. Seventeen of the 19 (including two first detected in Angola) resulted in 235 paralysis cases notified in 84 health zones in 18 of DRC's 26 provinces; no notified paralysis cases were associated with the remaining two outbreaks. The DRC-KAS-3 cVDPV2 outbreak that circulated during 2019-2021, and resulted in 101 paralysis cases in 10 provinces, was the largest recorded in DRC during the reporting period in terms of numbers of paralysis cases and geographic expanse. The 15 outbreaks occurring during 2017-early 2021 were successfully controlled with numerous supplemental immunization activities (SIAs) using monovalent OPV Sabin-strain serotype 2 (mOPV2); however, suboptimal mOPV2 vaccination coverage appears to have seeded the cVDPV2 emergences detected during semester 2, 2018 through 2021. Use of the novel OPV serotype 2 (nOPV2), designed to have greater genetic stability than mOPV2, should help DRC's efforts in controlling the more recent cVDPV2 outbreaks with a much lower risk of further seeding VDPV2 emergence. Improving nOPV2 SIA coverage should decrease the number of SIAs needed to interrupt transmission. DRC needs the support of polio eradication and Essential Immunization (EI) partners to accelerate the country's ongoing initiatives for EI strengthening, introduction of a second dose of inactivated poliovirus vaccine (IPV) to increase protection against paralysis, and improving nOPV2 SIA coverage.

The impact of the COVID-19 pandemic on measles surveillance in the World Health Organisation African Region, 2020.

INTRODUCTION: following the declaration of the COVID-19 pandemic, many countries imposed restrictions on public gatherings, health workers were repurposed for COVID-19 response, and public demand for preventive health services declined due to fear of getting COVID-19 in health care settings. These factors led to the disruption in health service delivery, including childhood immunization, in the first months of the pandemic. Measles surveillance supported with laboratory confirmation, is implemented in the African Region as part of the strategies towards attaining measles elimination. World Health Organisation developed guidelines to assist countries to continue to safely provide essential health services including immunization and the surveillance of vaccine preventable diseases during the pandemic. METHODS: we analysed the measles case-based surveillance and laboratory databases for the years 2014 to 2020, to determine the impact of the COVID-19 pandemic on measles surveillance, comparing the performance in 2020 against the preceding years. RESULTS: the weekly reporting of suspected measles cases declined starting in April 2020. Twelve countries had more than 50% decline in both the number of reported cases as well as in the number of specimens collected in 2020, as compared to the mean for the years 2014-2018. In 2020, only 30% of the specimens from suspected measles cases arrived at the national laboratory within 3 days of collection. At Regional level, 86% of the districts reported suspected measles cases in 2020, while the non-measles febrile rash illness rate was 2.1 per 100,000 population, which was the lowest rate documented since 2014. Only 11 countries met the targets for the two principal surveillance performance indicators in 2020 as compared to an average of 21 countries in the years 2014-2019. CONCLUSION: the overall quality of measles surveillance has declined during the COVID pandemic in many countries. Countries should implement immediate and proactive measures to revitalise active surveillance for measles and monitor the quality of surveillance. We recommend that countries consider implementing specimen collection and testing methods that can facilitate timely confirmation of suspected measles cases in remote communities and areas with transportation challenges.

Long-term outcomes of early initiated antiretroviral therapy in sub-Saharan children: a Cameroonian cohort study (ANRS-12140 Pediacam study, 2008-2013, Cameroon).

BACKGROUND: In most studies, the virological response is assessed during the first two years of antiretroviral treatment initiated in HIV-infected infants. However, early initiation of antiretroviral therapy exposes infants to very long-lasting treatment. Moreover, maintaining viral suppression in children is difficult. We aimed to assess the virologic response and mortality in HIV-infected children after five years of early initiated antiretroviral treatment (ART) and identify factors associated with virologic success in Cameroon. METHODS: In the ANRS-12140 Pediacam cohort study, 2008-2013, Cameroon, we included all the 149 children who were still alive after two years of early ART. Virologic response was assessed after 5 years of treatment. The probability of maintaining virologic success between two and five years of ART was estimated using Kaplan-Meier curve. The immune status and mortality were also studied at five years after ART initiation. Factors associated with a viral load < 400 copies/mL in children still alive at five years of ART were studied using logistic regressions. RESULTS: The viral load after five years of early ART was suppressed in 66.8% (60.1-73.5) of the 144 children still alive and in care. Among the children with viral suppression after two years of ART, the probability of maintaining viral suppression after five years of ART was 64.0% (54.0-74.0). The only factor associated with viral suppression after five years of ART was achievement of confirmed virological success within the first two years of ART (OR = 2.7 (1.1-6.8); p = 0.033). CONCLUSIONS: The probability of maintaining viral suppression between two and five years of early initiated ART which was quite low highlights the difficulty of parents to administer drugs daily to their children in sub-Saharan Africa. It also stressed the importance of initial viral suppression for achieving and maintaining virologic success in the long-term. Further studies should focus on identifying strategies that would enhance better retention in care and improved adherence to treatment within the first two years of ART early initiated in Sub-Saharan HIV-infected children.

Comparative Immunovirological and Clinical Responses to Antiretroviral Therapy Between HIV-1 Group O and HIV-1 Group M Infected Patients.

BACKGROUND: Little is known about impact of genetic divergence of human immunodeficiency virus type 1 group O (HIV-1/O) relative to HIV-1 group M (HIV-1/M) on therapeutic outcomes. We aimed to determine if responses to standardized combination antiretroviral therapy (cART) were similar between groups despite strain divergence. METHODS: We performed an open nonrandomized study comparing the immunological, virological, and clinical responses to cART based on 2 nucleoside reverse transcriptase inhibitors plus 1 ritonavir-boosted protease inhibitor, in naive and paired HIV-1/O vs HIV-1/M infected (+) patients (ratio 1:2), matched on several criteria. The primary endpoint was the proportion of patients with undetectable plasma viral load (pVL, threshold 60 copies/mL) at week (W) 48. Secondary endpoints were the proportion of patients with undetectable pVL at W24 and W96 and CD4 evolution between baseline and W24, W48, and W96. RESULTS: Forty-seven HIV-1/O+ and 94 HIV-1/M+ patients were included. Mean pVL at baseline was significantly lower by 1 log for HIV-1/O+ vs HIV-1/M+ patients. At W48, no significant difference was observed between populations with undetectable pVL and differences at W24 and W96 were not significant. A difference in CD4 gain was observed in favor of HIV-1/M at W48 and W96, but this was not significant when adjusted on both matched criteria and pVL at baseline. CONCLUSIONS: Our data demonstrate similar immunovirological and clinical response between HIV-1/O+ and HIV-1/M+ patients. They also reveal significantly lower baseline replication for HIV-1/O variants, suggesting specific virological properties and physiopathology that now need to be addressed. CLINICAL TRIALS REGISTRATION: NCT00658346.

Low rate of early vertical transmission of HIV supports the feasibility of effective implementation of the national PMTCT guidelines in routine practice of referral hospitals in Cameroon.

Background: Vertical (VT) transmission of HIV remains a public health concern in sub-Saharan Africa. Objective: To investigate the VT rate and factors associated with transmission in routine practice in three referral hospitals in Cameroon. Methods: All HIV-infected mothers who delivered in maternity wards or sought paediatric services during the first postnatal week from November 2007 to October 2010 were invited to participate in the ANRS-Pediacam cohort. Their infants were followed at 6, 10 and 14 weeks of life and HIV status was determined from the 6th week of life using real-time PCR. For those who were breastfed and negative at the first PCR, a second test was performed 6 weeks after breast-feeding was stopped. Logistic regression was performed to identify the independent risk factors of VT. Results: Overall, 2053 HIV-exposed infants were enrolled. Of these, 1827 were tested for HIV including 1777 before the age of 3 months, and 59 were HIV-infected, resulting in an overall early VT rate of 3.3% (CI 2.5-4.3). The VT rate was significantly associated with the type of maternal exposure to ART (0.5%, 2/439, p<0.001, CI 0.0-1.6) in mothers who commenced HAART before pregnancy, 1.9% (6/321, CI 0.7-4.0) in mothers who commenced HAART during pregnancy, 4.1% (34/837, CI 2.8-5.6) in those on short-course ART and 11.1% (17/153, CI 6.6-17.2) in mothers not receiving ART. On multivariate analysis, the type of exposure to ART remained significantly associated with being small for gestational age (aOR 5.0, CI 2.4-10.3, p < 0.001) and female gender (aOR 2.1, CI 1.2-3.8, p = 0.01). Conclusion: The successfully low rate of VT transmission of HIV in mothers who commenced HAART in early pregnancy strongly supports the need to improve access to diagnosis and early treatment of all women of childbearing age with HIV through the national PMTCT programme. Abbreviations: ANRS: French National Agency for Research on AIDS and Viral Hepatitis; ART: antiretroviral therapy; ARV: antiretroviral; AUDIPOG: Association des Utilisateurs de Dossiers Informatisés en Pédiatrie, Obstétrique et Gynécologie; CHM/MCC-CBF: The Central Hospital Maternity/Mother and Child Centre of the Chantal Biya Foundation; EHC: Essos Hospital Centre; EPI: Expanded Programme on Immunization; HAART: highly active antiretroviral therapy; HBV: hepatitis B virus; IQR: interquartile range; LH: Laquintinie Hospital; MTCT: mother-to-child transmission; NVP: nevirapine; Pediacam: Pediatrie Cameroun; PMTCT: prevention of mother-to-child transmission; SGAG: small for gestational age and gender; UNAIDS: Joint United Nations Program on HIV/AIDS; WHO: World Health Organization; ZDV: zidovudine; 3TC: lamivudine.

First report of the genomic characterization of rubella viruses circulating in Cameroon.

Rubella is an acute and contagious viral infection whose gravidity resides in infection during pregnancy, which can result in miscarriage, fetal death, stillbirth, or infants with congenital malformations. This study aimed to describe the genome of rubella viruses (RUBVs) circulating in Cameroon. Throat swabs were collected from health districts as part of the measles surveillance program from 2010 to 2016 and sent to the Centre Pasteur of Cameroon. Samples were amplified by genotyping reverse transcription polymerase chain reaction (RT-PCR) in the search of two overlapping fragments of the gene that encodes the E1 envelope glycoprotein of RUBV. PCR products were sequenced and phylogenetic analysis was performed with MEGA 6 software. Overall, 9 of 43 samples (20.93%) were successfully amplified and sequenced but only eight sequences could be exploited for phylogenetic analysis with respect to the required fragment length of 739 nucleotides. Analysis of viral sequences from Cameroon with other epidemiologically relevant sequences from around the world showed that all RUBVs belonged to lineage L1 of genotype 1G. Cameroon sequences clustered with viruses from West Africa including Nigeria, Ivory Coast, and Ghana with a percentage similarity of 95.4% to 99.2%. This study will enable an update on the molecular epidemiology of RUBV in Cameroon and help in monitoring circulating RUBV for a better implementation of elimination strategies.

Short Communication: Characterization of a New HIV-1 Group N Isolate Originating from a Cameroonian Patient.

HIV-1 group N (HIV-1/N) remains rare and mainly restricted to Cameroon. In this study, we report a new HIV-1/N infected case identified during routine HIV screening activities in Yaounde. The genetic characterization of the near full-length genome of this virus strain revealed that it is genetically distinct to all HIV-1/N described to date. However, the Vpu protein responsible for tetherin antagonism displayed the same amino acid substitutions (E15A, V19A, I25L, and V26L) as other HIV-1/N from Cameroon.

Virologic Response to Early Antiretroviral Therapy in HIV-infected Infants: Evaluation After 2 Years of Treatment in the Pediacam Study, Cameroon.

INTRODUCTION: Little is known about virologic responses to early antiretroviral therapy (ART) in HIV-infected infants in resource-limited settings. We estimated the probability of achieving viral suppression within 2 years of ART initiation and investigated the factors associated with success. METHODS: We analyzed all 190 infants from the Cameroon Pediacam who initiated ART by 12 months of age. The main outcome measure was viral suppression (<1000 copies/mL) on at least 1 occasion; the other outcome measures considered were viral suppression (<400 copies/mL) on at least 1 occasion and confirmed viral suppression (both thresholds) on 2 consecutive occasions. We used competing-risks regression for a time-to-event analysis to estimate the cumulative incidence of outcomes and univariate and multivariate models to identify risk factors. RESULTS: During the first 24 months of ART, 20.0% (38) of the infants died, giving a mortality rate of 11.9 deaths per 100 infant-years (95% confidence interval: 8.1-15.7). The probability of achieving a viral load below 1000 or 400 copies/mL was 80.0% (69.0-81.0) and 78.0% (66.0-79.0), respectively. The probability of virologic suppression (with these 2 thresholds) on 2 consecutive occasions was 67.0% (56.0-70.0) and 60.0% (49.0-64.0), respectively. Virologic success was associated with not having missed any doses of treatment before the visit, but not with socioeconomic and living conditions. CONCLUSION: Many early treated children failed to achieve virologic suppression, likely due to a combination of adherence difficulties, drug dosing and viral resistance, which highlights the need for routine viral load monitoring. The high infant mortality despite early ART initiation needs to be addressed in sub-Saharan countries.

A cheap and open HIV viral load technique applicable in routine analysis in a resource limited setting with a wide HIV genetic diversity.

BACKGROUND: HIV infection in Cameroon is characterized by a great viral diversity with all HIV-1 groups (M, N, O, and P) and HIV-2 in circulation. HIV group determination is very important if tailored viral load analysis and treatments are to be applied. In our laboratory, HIV viral load is carried out using two platforms; Biocentric and Abbott depending on the HIV group identified. Biocentric which quantifies HIV-1 group M is a cheap and open system useful in resource limited settings. The objective of this study was to compare the viral load analyses of serologically group-indeterminate HIV samples using the two platforms with the view of reducing cost. METHODS: Consecutive samples received between March and May 2014, and between August and September 2014 in our laboratory for HIV viral load analysis were included. All these samples were analyzed for their HIV groups using an in-house ELISA serotyping test. All HIV-1 group M samples were quantified using the Biocentric test while all other known atypical samples (HIV-1 groups N, O and P) were analyzed using the Abbott technique. HIV group-indeterminate samples (by serotyping) were quantified with both techniques. RESULTS: Among the 6355 plasma samples received, HIV-1 group M was identified in 6026 (94.82%) cases; HIV-1 group O, in 20 (0.31%); HIV-1 group M + O, in 3 (0.05%) and HIV-2, in 3 (0.05%) case. HIV-group indeterminate samples represented about 4.76% (303/6355) and only 231 of them were available for analysis by Abbott Real-Time HIV-1 and Generic HIV Viral Load techniques. Results showed that 188 (81.39%) samples had undetectable viral load in both techniques. All the detectable samples showed high viral load, with a mean of 4.5 log copies/ml (range 2.1-6.5) for Abbott Real-Time and 4.5 log copies/ml (range 2-6.4) for Generic HIV Viral Load. The mean viral load difference between the two techniques was 0.03 log10 copies/ml and a good correlation was obtained (r 2 = 0.89; P < 0.001). CONCLUSION: Our results suggest that cheaper and open techniques such as Biocentric could be useful alternatives for HIV viral load follow-up quantification in resource limited settings like Cameroon; even with its high viral diversity.

HIV Drug Resistance Testing in a Resource Limited Setting with High Viral Diversity: The First Twenty Eight Months Experience.

BACKGROUND: First line antiretroviral therapy in a resource-limited setting consists of nucleotide and non-nucleotide reverse transcriptase inhibitors. Protease inhibitors are the hub of second line therapy. The decision to change antiretroviral therapy for a patient is frequently presumptive because of the lack of genotypic resistance tests in routine follow-up. We describe here the resistance profiles observed in patients with varying terms of antiretroviral therapy in Cameroon after implementation of HIV genotypic resistance testing in routine practice. METHODS: HIV genotypic resistance testing was carried out on consecutive samples received between August 2013 and November 2015. Protease (Prot) and reverse transcriptase (Rt) genes of the HIV genome were amplified, sequenced and analyzed for drug resistance mutations following the algorithm set up by the French National Agency for research on HIV/AIDS and viral hepatitis. RESULTS: Specimens from a total of 167 patients infected with non-B HIV subtypes were received during the study period. Overall 61.7% patients had viral loads of more than 3log copies/ml, suggesting treatment failure. Among the 72 patients on first line, 56 (77.8%) were resistant to Lamivudine, 57 (79.1%) to Efavirenz and 58 (80.6%) to Nevirapine. Overall, more patients (75.0%) on first line antiretroviral therapy harbored multi-drug resistance compared to their counterparts on second line (25.8%). CONCLUSION: This study revealed that a group of patients with antiretroviral therapy failure harbored multi-drug resistance mutations related to the majority of drugs in the first line regimen. Therefore, HIV resistance testing could be a useful tool to improve HIV care in resource limited settings like Cameroon where treatment options are limited.

Cytomegalovirus infection in HIV-infected versus non-infected infants and HIV disease progression in Cytomegalovirus infected versus non infected infants early treated with cART in the ANRS 12140-Pediacam study in Cameroon.

BACKGROUND: The outcome of CMV/HIV co-infection in infants treated early with combined antiretroviral therapy (cART) in resource-limited settings has not been described. We aimed to estimate the prevalence and identify factors associated with early CMV infection in HIV-infected and non-infected infants included in a study in Cameroon, and to compare HIV disease progression and survival after 1 year of early cART, following infants' CMV status. METHODS: HIV-infected infants followed from birth or from HIV diagnosis before 7 months old and HIV-uninfected infants born to HIV-infected or uninfected mothers were tested for CMV at a median age of 4.0 months [Interquartile range (IQR): 3.4-4.9]. Multivariable logistic regression was performed to identify factors associated with CMV infection. Early cART was offered to HIV-infected infants: mortality, immunological and virological outcomes were assessed. RESULTS: Three hundred and sixty-nine infants were tested. The proportion of infants infected with CMV at baseline was significantly higher in HIV-infected than in HIV-uninfected groups (58.9% (86/146) vs 30.0% (67/223), p < 0.001). At baseline, median CMV viral load was higher in HIV-infected (3.7 log copies/ml [IQR; 3.1-4.3]) than in HIV-uninfected infants (2.8 log copies [IQR; 2.1-3.4], p < 0.001). cART was initiated in 90% of HIV-infected infants (132/146) at a median age of 4.0 months (IQR; 3.2-5.9); in this sub-group CMV infection was independently associated with being followed from the time of HIV diagnosis rather than from birth (aOR = 3.1, 95%CI [1.2-8.0]), born to a non-single mother (aOR = 3.4[1.4-8.1]), and breastfeeding (aOR = 7.3 [2.7-19.4]). HIV-infected infants were retested after a median of 7.1 months [4.8-9.5]: CMV was undetectable in 37 of the 61 (60.7%) initially CMV-infected cases and became detectable in 8 of the 38 (21.1%) initially CMV-negative cases. After 1 year of cART, the probability of death (0.185 vs 0.203; p = 0.75), the proportion of cases with HIV RNA viral load <400 copies/ml (75.5% vs 61.5%; p = 0.17) and the mean CD4 percentage increase (10.97% vs 6.88%; p = 0.15) did not differ between CMV+ and CMV- infants. CONCLUSIONS: We observed a high prevalence of CMV infection among HIV-infected infants. Early initiation of cART may have limited the negative impact of CMV even in the absence of specific anti-CMV treatment.

First evidence of transmission of an HIV-1 M/O intergroup recombinant virus.

OBJECTIVE: Despite the genetic divergence between HIV-1 groups M and O, HIV-1  M/O intergroup recombinants were reported. Actually, there is no data on the transmissibility of such recombinant forms. During a surveillance of HIV genetic diversity in Cameroon, we investigated the possible direct transmission of an HIV-1  M/O recombinant virus in an HIV-infected couple. METHODS: Consecutive samples obtained from the couple were analysed for detection of dual HIV-1 groups M and O infections, and HIV-1  M/O recombinant forms. Analyses were performed using a serological and molecular algorithm based on HIV serotyping and group-specific PCRs targeting the polymerase and envelope genes. Pattern characterization of the strains found in both patients was based on complete genome sequencing. Phylogenetic and similarity profile analyses were performed to investigate the genetic relationship between viruses from both spouses and the previously described recombinant forms. RESULTS: The sero-molecular algorithm data showed a group O serotype confirmed by molecular analysis in the envelope regions, whereas molecular tests identified HIV-1 group M in the polymerase. Phylogenetic analyses and similarity profiles of the full-length genome sequences showed that both spouses were infected with a unique recombinant virus having two recombination breakpoints in the vpr gene and LTR region. No phylogenetic link was found with the previous M/O recombinants. CONCLUSION: We provide, for the first time, molecular evidence of direct transmission of an HIV-1  M/O recombinant, highlighting the potential spread of these divergent viruses. The importance of HIV-1 recombination on genetic evolution and public health when implying divergent strains as group O has to be carefully considered.

Could caregiver reporting adherence help detect virological failure in Cameroonian early treated HIV-infected infants?

BACKGROUND: Viral load is still the marker of choice for monitoring adherence to combined antiretroviral therapy (cART) and confirming the success of HIV treatment. Unfortunately it is difficult to access in many resource-poor settings. We aimed to measure the performance of caregiver reporting adherence for detecting virological failure in routine practice during the first 2 years after cART initiation in infants. METHODS: PEDIACAM is an ongoing prospective cohort study including HIV1-infected infants diagnosed before 7 months of age between November 2007 and October 2011 in Cameroon. Adherence was assessed using a questionnaire administered every 3 months from cART initiation; the HIV-RNA viral load was determined at the same visits. Virological failure was defined as having a viral load ≥ 1000 cp/mL at 3 and 12 months after cART initiation or having a viral load ≥ 400 cp/mL at 24 months after cART initiation. The performance of each current missed and cumulative missed dose defined according to adherence as reported by caregiver was assessed using the viral load as the gold standard. RESULTS: cART was initiated at a median age of 4 months (IQR: 3-6) in the 167 infants included. The cumulative missed dose showed the best overall performance for detecting virological failure after 12 months of cART (AUC test, p = 0.005, LR + =4.4 and LR- = 0.4). Whatever the adherence reporting criterion, the negative predictive value was high (NPV ≥ 75%) 12 and 24 months after cART initiation, whereas the positive predictive value was low (PPV ≤ 50%). CONCLUSIONS: The adherence questionnaire administered by the health care provider to the infants' caregivers is not reliable for detecting virological failure in routine practice: its positive predictive value is low. However, the cumulative missed dose measurement may be a reliable predictor of virological success, particularly after 12 months of cART, given its high negative predictive value.

The Two-Phase Emergence of Non Pandemic HIV-1 Group O in Cameroon.

Unlike the pandemic form of HIV-1 (group M), group O viruses are endemic in west central Africa, especially in Cameroon. However, little is known about group O's genetic evolution, and why this highly divergent lineage has not become pandemic. Using a unique and large set of group O sequences from samples collected from 1987 to 2012, we find that this lineage has evolved in successive slow and fast phases of diversification, with a most recent common ancestor estimated to have existed around 1930 (1914-1944). The most rapid periods of diversification occurred in the 1950s and in the 1980s, and could be linked to favourable epidemiological contexts in Cameroon. Group O genetic diversity reflects this two-phase evolution, with two distinct populations potentially having different viral properties. The currently predominant viral population emerged in the 1980s, from an ancient population which had first developed in the 1950s, and is characterized by higher growth and evolutionary rates, and the natural presence of the Y181C resistance mutation, thought to confer a phenotypic advantage. Our findings show that although this evolutionary pattern is specific to HIV-1 group O, it paralleled the early spread of HIV-1 group M in the Democratic Republic of Congo. Both viral lineages are likely to have benefited from similar epidemiological contexts. The relative role of virological and social factors in the distinct epidemic histories of HIV-1 group O and M needs to be reassessed.

Feasibility of Routinely Offering Early Combined Antiretroviral Therapy to HIV-infected Infants in a Resource-limited Country: The ANRS-PediaCAM Study in Cameroon.

BACKGROUND: Early diagnosis of HIV is increasingly available for infants in resource-limited settings. We assessed the timing of events until combined antiretroviral therapy (cART) initiation in infants diagnosed before 7 months of age in Cameroon. METHODS: The ANRS-PediaCAM cohort included HIV-infected infants followed from birth associated with prevention of mother-to-child transmission activities (group 1) or diagnosed for any other reason before 7 months of age (group 2). All infants were offered free cART early after diagnosis. Frequency and factors associated with no or delayed cART initiation, were studied using univariable and multivariable logistic regressions. RESULTS: Between 2007 and 2011, 210 HIV-infected infants (group 1: 69; group 2: 141) were included. Fewer group 1 (14.3%) than group 2 (59.1%) infants were symptomatic (World Health Organization stage 3 or 4). Overall, 5.7% (n = 12) died before receiving any cART. Of the remaining 198 infants, 3.0% (n = 6) were not treated. The median age at initiating cART was 4.1 months [interquartile range (IQR): 3.2-5.6]. The median time until cART initiation after HIV testing was 6.2 weeks (IQR: 4.4-9.4) in group 1 and 5.1 weeks (IQR: 2.9-9.4) in group 2. No or delayed cART, observed for 37.9% (75 of 198) of the infants, was associated with clinical site [adjusted odds ratio (aOR): 4.8; 95% confidence interval: (2.1-11.2)], late diagnosis [aOR: 2.0 (0.9-4.1)], and delayed pretherapeutic biological assessment [aOR: 3.7 (1.4-10.0)]. CONCLUSIONS: Although most children included were treated before age 7 months, the initiation of therapy was delayed for more than 1 in 3. The period around HIV diagnosis is critical and should be better managed to reduce delays before cART initiation.

Different factors associated with loss to follow-up of infants born to HIV-infected or uninfected mothers: observations from the ANRS 12140-PEDIACAM study in Cameroon.

BACKGROUND: Loss to follow-up (LTFU) is a cause of potential bias in clinical studies. Differing LTFU between study groups may affect internal validity and generalizability of the results. Understanding reasons for LTFU could help improve follow-up in clinical studies and thereby contribute to goals for prevention, treatment, or research being achieved. We explored factors associated with LTFU of mother-child pairs after inclusion in the ANRS 12140-Pediacam study. METHODS: From November 2007 to October 2010, 4104 infants including 2053 born to HIV-infected mothers and 2051 born to HIV-uninfected mothers matched individually on gender and study site were enrolled during the first week of life in three referral hospitals in Cameroon and scheduled for visits at 6, 10 and 14 weeks of age. Visits were designated 1, 2 and 3, in chronological order, irrespective of the child's age at the time of the visit. Mother-child pairs were considered lost to follow-up if they never returned for a clinical visit within the first six months after inclusion. Uni- and multivariable logistic regression were adjusted on matching variables to identify factors associated with LTFU according to maternal HIV status. RESULTS: LTFU among HIV-unexposed infants was four times higher than among HIV-exposed infants (36.7% vs 9.8%, p < 0.001). Emergency caesarean section (adjusted Odds Ratio (aOR) = 2.46 95% Confidence Interval (CI) [1.47-4.13]), young maternal age (aOR = 2.29, 95% CI [1.18-4.46]), and absence of antiretroviral treatment for prophylaxis (aOR = 3.45, 95% CI [2.30-5.19]) were independently associated with LTFU among HIV-exposed infants. Factors associated with LTFU among HIV-unexposed infants included young maternal age (aOR = 1.96, 95% CI [1.36-2.81]), low maternal education level (aOR = 2.77, 95% CI [1.95-3.95]) and housewife/unemployed mothers (aOR = 1.56, 95% CI [1.16-2.11]). CONCLUSION: Failure to return for at least one scheduled clinical visit is a problem especially among HIV-unexposed infants included in studies involving HIV-exposed infants. Factors associated with this type of LTFU included maternal characteristics, socio-economic status, quality of antenatal care and obstetrical context of delivery. Enhanced counselling in antenatal and intrapartum services is required for mothers at high risk of failure to return for follow-up visits.

Molecular characterization of a new mosaic Simian Immunodeficiency Virus in a naturally infected tantalus monkey (Chlorocebus tantalus) from Cameroon: a challenge to the virus-host co-evolution of SIVagm in African green monkeys.

African green monkeys (AGMs) represent the most widely distributed non-human primates species in Africa. SIVagm naturally infects four of the 6 AGMs species at high prevalence in a species-specific manner. To date, only limited information is available on molecular characteristics of SIVagm infecting Chlorocebus tantalus. Here, we characterized the full-length genome of a virus infecting a naturally infected captive C. tantalus from Cameroon by amplifying and sequencing sub-genomic PCR fragments. The isolate (SIVagmTAN-CM545) is 9923bp long and contained all canonical genes of a functional SIV. SIVagmTAN-CM545 showed a mosaic structure, with gag, pol, nef and accessory genes closely related to SIVagmSAB infecting Chlorocebus sabaeus monkeys from west Africa, and the env gene, closely related to SIVagmTAN infecting tantalus monkeys from Central Africa. Thus SIVagmTAN-CM545 is SIVagmSAB/SIVagmTAN recombinant. These unexpected findings suggest that the evolution of SIVagm is more complex than previously thought and warrant further studies.