Molecular surveillance of anti-malarial drug resistance in Democratic Republic of Congo: high variability of chloroquinoresistance and lack of amodiaquinoresistance.

BACKGROUND: The loss of chloroquine (CQ) effectiveness has led to its withdrawal from national policies as a first-line treatment for uncomplicated malaria in several endemic countries, such as the Democratic Republic of Congo (DRC). The K76T mutation on the pfcrt gene has been identified as a marker of CQ resistance and the SVMNT haplotype in codons 72-76 on the same gene has been associated with resistance to amodiaquine (AQ). In the DRC, the prevalence of K76T has decreased from 100% in 2000 to 63.9% in 2014. The purpose of this study was to determine the prevalence of K76T mutations in circulating strains of Plasmodium falciparum, 16 years after CQ withdrawal in the DRC and to investigate the presence of the SVMNT haplotype. METHODS: In 2017, ten geographical sites across the DRC were selected. Dried blood samples were collected from patients attending health centres. Malaria was first detected by a rapid diagnostic test (RDT) available on site (SD Bioline Malaria Ag Pf or CareStart Malaria Pf) or thick blood smear and then confirmed by a P. falciparum species-specific real-time PCR assay. A pfcrt gene segment containing a fragment that encodes amino acids at positions 72-76 was amplified by conventional PCR before sequencing. RESULTS: A total of 1070 patients were enrolled. Of the 806 PCR-confirmed P. falciparum positive samples, 764 were successfully sequenced. The K76T mutation was detected in 218 samples (28.5%; 95% CI 25.4%-31.9%), mainly (96%) with the CVIET haplotype. Prevalence of CQ resistance marker was unequally distributed across the country, ranging from 1.5% in Fungurume to 89.5% in Katana. The SVMNT haplotype, related to AQ resistance, was not detected. CONCLUSION: Overall, the frequency of the P. falciparum CQ resistance marker has decreased significantly and no resistance marker to AQ was detected in the DRC in 2017. However, the between regions variability of CQ resistance remains high in the country. Further studies are needed for continuous monitoring of the CQ resistance level for its prospective re-use in malaria management. The absence of the AQ resistance marker is in line with the use of this drug in the current DRC malaria treatment policy.

Breastfeeding Support Offered at Delivery is Associated with Higher Prevalence of Exclusive Breastfeeding at 6 Weeks Postpartum Among HIV Exposed Infants: A Cross-Sectional Analysis.

Objective HIV-exposed uninfected infants are almost twice as likely to die compared to infants born to HIV-uninfected women. HIV-exposed uninfected children whose mothers are on ART and who are breastfed have the lowest risk of dying by 24 months of age. Interventions to improve breastfeeding among HIV-infected mothers are needed. We aimed to assess the association between support/counseling provided by healthcare workers following delivery and the rate of exclusive breastfeeding (EBF) at 6-week postpartum. Methods This is a secondary analysis of data collected as part of a trial to evaluate the effect of conditional cash transfers on retention in and uptake of PMTCT services. Between April 2013 and August 2014, newly diagnosed HIV-infected women, ≤ 32 weeks pregnant, registering for antenatal care (ANC), in 89 clinics in Kinshasa, Democratic Republic of Congo, were recruited and followed through 6 weeks postpartum. At 6-week, participants were asked if they had given anything other than breastmilk to their infant in the 24 h preceding the interview (No = EBF) and whether a nurse or a doctor talked to them about breastfeeding after they gave birth (YES = received breastfeeding support/counseling). Logistic regression was used to estimate the odds ratios (OR) and 95% confidence intervals (CI) measuring the strength of the association between EBF and receiving breastfeeding support/counseling by a healthcare provider following delivery. Results Of 433 women enrolled, 328 attended a 6-week postpartum visit including 320 (97%) with complete information on EBF. Of those 320, 202 (63%) reported giving nothing other than breastmilk to their infant in the previous 24 h; 252 (79%) reported that a healthcare provider came to talk to them about breastfeeding following delivery. Mothers who reported receiveing breastfeeding support/counseling from a healthcare provider were more likely to exclusively breastfeed compared to those who did not (69% vs. 38%, OR 3.74; 95% CI 2.14-6.54). Adjustment for baseline sociodemographic characteristics did not change the association substantially, (adjusted OR 3.72; 95% CI 2.06-6.71). Conclusion for Practice Receipt of breastfeeding support/counseling from a healthcare provider after delivery among HIV-infected mothers in care at 6-weeks postpartum in Kinshasa almost quadrupled the odds of EBF.

Continuous quality improvement interventions to improve long-term outcomes of antiretroviral therapy in women who initiated therapy during pregnancy or breastfeeding in the Democratic Republic of Congo: design of an open-label, parallel, group randomized trial.

BACKGROUND: Despite the rapid adoption of the World Health Organization's 2013 guidelines, children continue to be infected with HIV perinatally because of sub-optimal adherence to the continuum of HIV care in maternal and child health (MCH) clinics. To achieve the UNAIDS goal of eliminating mother-to-child HIV transmission, multiple, adaptive interventions need to be implemented to improve adherence to the HIV continuum. METHODS: The aim of this open label, parallel, group randomized trial is to evaluate the effectiveness of Continuous Quality Improvement (CQI) interventions implemented at facility and health district levels to improve retention in care and virological suppression through 24 months postpartum among pregnant and breastfeeding women receiving ART in MCH clinics in Kinshasa, Democratic Republic of Congo. Prior to randomization, the current monitoring and evaluation system will be strengthened to enable collection of high quality individual patient-level data necessary for timely indicators production and program outcomes monitoring to inform CQI interventions. Following randomization, in health districts randomized to CQI, quality improvement (QI) teams will be established at the district level and at MCH clinics level. For 18 months, QI teams will be brought together quarterly to identify key bottlenecks in the care delivery system using data from the monitoring system, develop an action plan to address those bottlenecks, and implement the action plan at the level of their district or clinics. DISCUSSION: If proven to be effective, CQI as designed here, could be scaled up rapidly in resource-scarce settings to accelerate progress towards the goal of an AIDS free generation. TRIAL REGISTRATION: The protocol was retrospectively registered on February 7, 2017. ClinicalTrials.gov Identifier: NCT03048669 .

Serological responses to the MVA-based JYNNEOS monkeypox vaccine in a cohort of participants from the Democratic Republic of Congo.

The current worldwide monkepox outbreak has reaffirmed the continued threat monkeypox virus (MPXV) poses to public health. JYNNEOS, a Modified Vaccinia Ankara (MVA)-based live, non-replicating vaccine, was recently approved for monkeypox prevention for adults at high risk of MPXV infection in the United States. Although the safety and immunogenicity of JYNNEOS have been examined previously, the clinical cohorts studied largely derive from regions where MPXV does not typically circulate. In this study, we assess the quality and longevity of serological responses to two doses of JYNNEOS vaccine in a large cohort of healthcare workers from the Democratic Republic of Congo (DRC). We show that JYNNEOS elicits a strong orthopoxvirus (OPXV)-specific antibody response in participants that peaks around day 42, or 2 weeks after the second vaccine dose. Participants with no prior history of smallpox vaccination or exposure have lower baseline antibody levels, but experience a similar fold-rise in antibody titers by day 42 as those with a prior history of vaccination. Both previously naïve and vaccinated participants generate vaccinia virus and MPXV-neutralizing antibody in response to JYNNEOS vaccination. Finally, even though total OPXV-specific IgG titers and neutralizing antibody titers declined from their peak and returned close to baseline levels by the 2-year mark, most participants remain IgG seropositive at the 2-year timepoint. Taken together, our data demonstrates that JYNNEOS vaccination triggers potent OPXV neutralizing antibody responses in a cohort of healthcare workers in DRC, a monkeypox-endemic region. MPXV vaccination with JYNNEOS may help ameliorate the disease and economic burden associated with monkeypox and combat potential outbreaks in areas with active virus circulation.

Monkeypox Rash Severity and Animal Exposures in the Democratic Republic of the Congo.

Experimental studies have suggested a larger inoculum of monkeypox virus may be associated with increased rash severity; however, little data are available on the relationship between specific animal exposures and rash severity in endemic regions. Using cross-sectional data from an active surveillance program conducted between 2005 and 2007 in the Sankuru Province of the Democratic Republic of the Congo, we explored the possible relationship between rash severity and exposures to rodents and non-human primates among confirmed MPX cases. Among the 223 PCR-confirmed MPX cases identified during active surveillance, the majority of cases (n = 149) presented with mild rash (5-100 lesions) and 33% had a more serious presentation (> 100 lesions). No association between exposure to rodents and rash severity was found in the multivariable analysis. Those that self-reported hunting NHP 3 weeks prior to onset of MPX symptoms had 2.78 times the odds of severe rash than those that did not report such exposure (95% CI: 1.18, 6.58). This study provides a preliminary step in understanding the association between animal exposure and rash severity and demonstrates correlation with exposure to NHPs and human MPX presentation. Additional research exploring the relationship between rash severity and NHPs is warranted.

Intimate partner violence and prevention of mother to child transmission of HIV: Evidence from Kinshasa, Democratic Republic of Congo.

Intimate partner violence (IPV) is a risk factor for non-adherence to HIV treatment for women, however the evidence on the impact of IPV on uptake of the prevention of mother to child transmission of HIV (PMTCT) cascade is inconclusive. We examined data from 433 HIV positive pregnant women in Kinshasa, Democratic Republic of Congo, enrolled between April 2013 and August 2014 and followed-up through 6 weeks postpartum. Participants were asked about their IPV experiences in a face-to-face interview at enrollment. Measures of PMTCT cascade included: uptake of clinical appointments and services, viral suppression, and adherence to antiretrovirals (ARV). Approximately half of the sample (51%) had experienced some form of IPV; 35% had experienced emotional abuse, 29% physical abuse, and 19% sexual abuse. There were no statistically significant associations between experiencing any form of IPV and uptake of clinical appointments and services (Adjusted Prevalence Ratio [aPR] = 1.02; 95% [CI]: 0.89-1.17), viral load suppression (aPR = 1.07, 95% CI:0.96-1.19) and ARV adherence (aPR = 1.01, 95% CI: 0.87-1.18). Findings from this study indicate that, among HIV-infected pregnant women enrolled in PMTCT care, experiencing IPV does not reduce adherence to clinic visits and services, adherence to ARV. The high prevalence of IPV in this population suggests that IPV screening and intervention should be included as part of standard care for PMTCT.

Human Exposure to Wild Animals in the Sankuru Province of the Democratic Republic of the Congo.

Due to the high level of biological diversity in the Congo Basin and human population dependence on bushmeat, the DRC represents an ideal location for expanding knowledge on wild animal exposures and thus the potential for transmission of zoonotic pathogens. However, limited information exists on patterns and extent of contact with wildlife in such communities. Using a cross-sectional study, 14 villages in the Sankuru Province of the DRC were surveyed between August and September 2007. Villagers ≥ 1 year of age and at home of the time of the survey were eligible and enrolled to describe and assess factors associated with animal exposures (both activity and type of animal). Among respondents, 91% reported exposure to rodents, 89% to duikers, 78% to non-human primates (NHPs), and 32% reported contact with bats in the month prior to the survey. The most frequently reported activities included eating (95%), cooking (70%), and butchering or skinning of animals (55%). The activities and animals to which subjects had contact varied by sex and age. Moreover, we observed a high correlation of the same activities across animal types. In this and other populations that rely on bushmeat, there is a high frequency of exposure to multiple animal species through various modalities. In the event of future zoonotic disease outbreaks, effective public health interventions and campaigns that mitigate the risk of animal contact during outbreaks need to be broad to include various modes of contact and should be directed to both men and women across all age groups. As available information is limited, further studies are necessary to better understand the complex relationships and exposures individuals have with animals.

Conditional Cash Transfers Improve Retention in PMTCT Services by Mitigating the Negative Effect of Not Having Money to Come to the Clinic.

OBJECTIVE: To elucidate the mechanisms by which a cash incentive intervention increases retention in prevention of mother-to-child transmission services. METHODS: We used data from a randomized controlled trial in Kinshasa, Democratic Republic of Congo. Perceptual factors associated with loss to follow-up (LTFU) through 6 weeks postpartum were first identified. Then, binomial models were used to assess interactions between LTFU and identified factors, and the cash incentive intervention. RESULTS: Participants were less likely to be LTFU if they perceived HIV as a "very serious" health problem for their baby vs. not [risk difference (RD), -0.13; 95% confidence interval (CI): -0.30 to 0.04], if they believed it would be "very likely" to pass HIV to their baby if they did not take any HIV drug vs. not (RD, -0.15; 95% CI: -0.32 to 0.02), and if they anticipated that not having money would make it difficult for them to come to the clinic vs. not (RD, 0.12; 95% CI: -0.07 to 0.30). The effect of each of the 3 factors on LTFU was antagonistic to that of receiving the cash incentive intervention. The excess risk due to interaction between the cash incentive intervention and the anticipated difficulty of "not having money" to come to the clinic was exactly equal to the effect of removing this perceived barrier (excess risk due to interaction, -0.12; 95% CI: -0.35 to 0.10). CONCLUSIONS: Our analyses show that cash transfers improve retention in prevention of mother-to-child transmission services mainly by mitigating the negative effect of not having money to come to the clinic.

Conditional Cash Transfers to Increase Retention in PMTCT Care, Antiretroviral Adherence, and Postpartum Virological Suppression: A Randomized Controlled Trial.

BACKGROUND: Novel strategies are needed to increase retention in prevention of mother-to-child HIV transmission (PMTCT) services. We have recently shown that small, incremental cash transfers conditional on attending clinic resulted in increased retention along the PMTCT cascade. However, whether women who receive incentives to attend clinic visits are as adherent to antiretrovirals (ARV) as those who do not was unknown. OBJECTIVE: To determine whether HIV-infected women who received incentives to remain in care were as adherent to antiretroviral treatment and achieved the same level of viral suppression at 6 weeks postpartum as those who did not receive incentives but also remained in care. METHODS: Newly diagnosed HIV-infected women at ≤32 weeks gestational age were recruited at antenatal care clinics in Kinshasa, Democratic Republic of Congo. Women were randomized in a 1:1 ratio to an intervention or control group. The intervention group received compensation ($5, plus $1 increment at each subsequent visit) conditional on attending scheduled clinic visits and accepting offered PMTCT services, whereas the control group received usual care. The proportion of participants who remained in care, were fully adherent (took all their pills at each visit) or with undetectable viral load at 6 weeks postpartum were compared across group. RESULTS: Among 433 women randomized (216 in intervention group and 217 in control group), 332 (76.7%) remained in care at 6 weeks postpartum, including 174 (80.6%) in the intervention group and 158 (72.8%) in the control group, (P = 0.04). Data on pill count were available for 297 participants (89.5%), including 156 (89.7%) and 141 (89.2%) in the intervention and control groups, respectively; 69.9% (109/156) and 68.1% (96/141) in the intervention and control groups had perfect adherence [risk difference, 0.02; 95% CI: -0.06 to 0.09]. Viral load results were available for 171 (98.3%) and 155 (98.7%) women in the intervention and control groups, respectively; 66.1% (113/171) in the intervention group and 69.7% (108/155) in the control group had an undetectable viral load (risk difference, -0.04; 95% CI: -0.14 to 0.07). Results were similar after adjusting for marital status, age, education, baseline CD4 count, viral load, gestational age, and initial ARV regimen. CONCLUSIONS: Although the provision of cash incentives to HIV-infected pregnant women led to higher retention in care at 6 weeks postpartum, among those retained in care, adherence to ARVs and virologic suppression did not differ by study group.

Conditional cash transfers and uptake of and retention in prevention of mother-to-child HIV transmission care: a randomised controlled trial.

BACKGROUND: Novel strategies are needed to increase retention in and uptake of prevention of mother-to-child HIV transmission (PMTCT) services in sub-Saharan Africa. We aimed to determine whether small, increasing cash payments, which were conditional on attendance at scheduled clinic visits and receipt of proposed services can increase the proportions of HIV-infected pregnant women who accept available PMTCT services and remain in care. METHODS: In this randomised controlled trial, we recruited newly diagnosed HIV-infected women, who were 32 or less weeks pregnant, from 89 antenatal care clinics in Kinshasa, Democratic Republic of Congo, and randomly assigned (1:1) them to either the intervention group or the control group using computer-based randomisation with varying block sizes of four, six, and eight. The intervention group received compensation on the condition that they attended scheduled clinic visits and accepted offered PMTCT services (US$5, plus US$1 increment at every subsequent visit), whereas the control group received usual care. Outcomes assessed included retention in care at 6 weeks' post partum and uptake of PMTCT services, measured by attendance of all scheduled clinic visits and acceptance of proposed services up to 6 weeks' post partum. Analyses were by intention to treat. This trial is registered with ClinicalTrials.org, number NCT01838005. FINDINGS: Between April 18, 2013, and Aug 30, 2014, 612 potential participants were identified, 545 were screened, and 433 were enrolled and randomly assigned; 217 to the control group and 216 to the intervention group. At 6 weeks' post partum, 174 participants in the intervention group (81%) and 157 in the control group (72%) were retained in care (risk ratio [RR] 1·11; 95% CI 1·00-1·24). 146 participants in the intervention group (68%) and 116 in the control group (54%) attended all clinic visits and accepted proposed services (RR 1·26; 95% CI 1·08-1·48). Results were similar after adjustment for marital status, age, and education. INTERPRETATION: Among women with newly diagnosed HIV, small, incremental cash incentives resulted in increased retention along the PMTCT cascade and uptake of available services. The cost-effectiveness of these incentives and their effect on HIV-free survival warrant further investigation. FUNDING: President's Emergency Plan for AIDS Relief and the National Institute of Health and Child Development.