Insufficient measles antibody protection in 6-month-old Malawian infants: Reconsider vaccination schedule?

Measles vaccination is currently recommended at 9 months, since maternal antibodies are supposed to protect infants until that age. In this study of 6-month-old Malawian infants 98.3% (58/59) had non-protective IgG levels against measles, irrespective of HIV exposure. Anticipating the first dose at 6 months could be considered.

Immunoglobulin G passive transfer from mothers to infants: total IgG, IgG subclasses and specific antipneumococcal IgG in 6-week Malawian infants exposed or unexposed to HIV.

BACKGROUND: The impaired transplacental passage of IgG from mothers living with HIV to their infants could be one of the causes of the high vulnerability to infections of HIV-exposed uninfected (HEU) infants, but controversial results have been obtained in different settings. The aim of this study was to assess in 6-week old HEU and HIV-unexposed, uninfected (HUU) Malawian infants the total IgG levels, the subclasses profile and the concentrations of global anti-pneumococcal capsular polysaccharide (anti-PCP) IgG and IgG2. METHODS: Dried blood spots were collected from 80 infants (40 HEU, 40 HUU) and antibodies concentrations determined by nephelometric method (total IgG and subclasses), or using ELISA (anti-PCP total IgG and IgG2). Results are expressed as median levels with IQR, while the proportions of each subclass out of the total IgG are used to describe the subclasses profile. RESULTS: At 6 weeks HEU infants had higher median levels of total IgG and IgG1 and a significantly lower level of IgG2 [0.376 (0.344-0.523) g/l vs 0.485 (0.374-0.781) g/l, p = 0.037] compared to the HUU counterparts. The IgG subclasses distribution confirmed the underrepresentation of IgG2 (IgG2 represented 5.82% of total IgG in HEU and 8.87% in HUU). The anti-PCP IgG and IgG2 levels were significantly lower in HEU infants [8.9 (5.4-15.1) mg/l vs 16.2 (9.61-25.8) mg/l in HUU, p < 0.001, and 2.69 (1.90-4.29) mg/l vs 4.47 (2.96-5.71) mg/l in HUU, p = 0.001, respectively]. CONCLUSION: Compared to HUU infants, HEU infants have IgG abnormalities mainly represented by low IgG2 levels, suggesting that despite maternal antiretroviral therapy, the mechanisms of IgG transplacental passage continue to be impaired in women living with HIV. HEU infants also showed a significantly lower level of specific anti-PCP IgG, possibly favouring a high vulnerability to S. pneumoniae infection at an age when protection is mostly depending on maternal IgG.

HIV-exposed infants with EBV infection have a reduced persistence of the immune response to the HBV vaccine.

BACKGROUND: In sub-Saharan African countries Epstein Barr virus (EBV) infection occurs in early childhood. We aim to investigate the factors associated with EBV acquisition and the impact of EBV infection on the humoral response to HBV vaccination in infants born from HIV-positive, antiretroviral-treated mothers in Malawi. METHODS: A total of 149 HIV-exposed infants were included in this longitudinal study. EBV anti-VCA IgG were measured using an ELISA assay. The EBV seroconversion was correlated with the maternal viro-immunological conditions, with infant growth and immunological vulnerability, and with the humoral response to the HBV vaccine. RESULTS: No infant was EBV-positive at 6 months (n. 52 tested). More than a third of infants (49/115 or 42.6 %) on study beyond 6 months seroconverted at 12 months. At 24 months, out of 66 tested infants, only 13 remained EBV-uninfected, while 53 (80.3 %) acquired EBV infection, rising the total proportion of EBV seroconversion to 88.7 % (102/115 infants). EBV seroconversion was significantly associated with a low maternal educational status but had no impact on infant growth or vulnerability to infections. Reduced HBsAb levels and accelerated waning of antibodies were associated with early EBV seroconversion. CONCLUSIONS: We found a heterogeneous timing of acquisition of EBV with the majority of infants born from HIV + mothers acquiring infection after 6 months. Anti-HBs levels were lower and appeared to wane faster in infants acquiring EBV infection.

Dynamics of immunoglobulin G subclasses during the first two years of life in Malawian infants born to HIV-positive mothers.

BACKGROUND: Maternal antibodies are key components of the protective responses of infants who are unable to produce their own IgG until 6 months of life. There is evidence that HIV-exposed uninfected children (HEU) have IgG levels abnormalities, that can be partially responsible for the higher vulnerability to infections in the first 2 years of the life of this population. This retrospective study aimed to characterize the dynamics in plasma levels of total IgG and their isotypes during the first 2 years of life in HEU infants exclusively breastfed through 6 months of age. METHODS: Total IgG, IgG1, IgG2, IgG3 and IgG4 isotypes, and IgM and IgA plasma concentrations were determined by nephelometric methods in 30 Malawian infants born to HIV-positive women at month 1, 6 and 24 of life. RESULTS: At 1-month infants had a median concentration of total IgG of 8.48 g/l, (IQR 7.57-9.15), with an overrepresentation of the IgG1 isotype (89.0% of total) and low levels of IgG2 (0.52 g/l, IQR, 0.46-0.65). Total IgG and IgG1 concentrations were lower at 6 months (- 2.1 and - 1.12 g/dl, respectively) reflecting disappearance of maternal antibodies, but at 24 months their levels were higher with respect to the reported reference values for age-matched pairs. Abnormal isotype distribution was still present at 24 months with IgG2 remaining strongly underrepresented (0.87 g/l, 7.5% of total IgG). CONCLUSION: HIV exposure during pregnancy and breastfeeding seems to influence the IgG maturation and isotype distribution that persist in 2-year old infants.

Accumulation of HIV-1 drug resistance in patients on a standard thymidine analogue-based first line antiretroviral therapy after virological failure: implications for the activity of next-line regimens from a longitudinal study in Mozambique.

BACKGROUND: We describe the accumulation of HIV-1 drug resistance and its effect on the activity of next-line components in patients with virological failure (HIV-1 RNA >1000 copies/mL) after 1 year (t1) of first-line antiretroviral therapy (ART) not switching to second-line drugs for one additional year (t2) in low-middle income countries (LMIC). METHODS AND RESULTS: We selected 48 patients from the DREAM cohort (Maputo, Mozambique); their median pre-ART CD4+ cell count was 165 cells/µl. At t1 patients were receiving ART since a median of 12.2 months (mainly zidovudine/lamivudine/nevirapine), their median HIV RNA was 3.8 log10 copies/mL, 43 (89.6%) presented at least one resistance-associated mutation (RAM), most frequently for lamivudine/emtricitabine, nevirapine and efavirenz. Resistance to tenofovir, was 10% at 1 year and higher than 20% at 2 years, while projection at 3 years was >30%. At t2, 42 (89.4%) had a predicted low-level or higher resistance to at least 1 s-line drug. At t1, the frequency of RAM in patients with a lower adherence to pharmacy appointments (<95%) was significantly lower (12/20, 60% for NRTI and 14/20, 70% for NNRTI) than in those with a better adherence (26/28, 92.8% for NRTI and 25/28, 89.3% for NNRTI) (OR 0.12, 95% CI 0.02-0.63, p = 0.012 and OR 0.28, 95% CI 0.06-1.29, p = 0.103, respectively). Overall thymidine analogue mutations (TAMs) accumulation rate was 0.32/year, 0.50/year in the subgroup with HIV RNA >10,000 copies/mL; NNRTI RAM accumulation rate was 0.15/year, 0.40/year in the subgroup with HIV RNA >10,000 copies/mL. CONCLUSIONS: While the activity of NNRTIs is compromised early during failure, tenofovir and zidovudine activity are reduced more frequently after 1 year of documented virological failure of thymidine analogue-based first-line ART, with RAMs accumulating faster in patients with higher viral loads. The present observation may help informing decisions on when to switch to a second line ART in patients on virological failure in LMIC.

Concentrations of tenofovir, lamivudine and efavirenz in mothers and children enrolled under the Option B-Plus approach in Malawi.

OBJECTIVES: To evaluate antiretroviral drug concentrations in mothers and infants enrolled under the Option B-Plus approach for the prevention of HIV mother-to-child transmission in Malawi and to assess the maternal virological response after 1 year of treatment. PATIENTS AND METHODS: Forty-seven women and 25 children were studied. Mothers were administered during pregnancy a combination of tenofovir, lamivudine and efavirenz and continued it during breastfeeding (up to 2 years) and thereafter. Drug concentrations were evaluated in mothers (plasma and breast milk) at 1 and 12 months post-partum and in infants (plasma) at 6 and 12 months of age. Drug concentrations were determined using an LC-MS/MS validated methodology. RESULTS: In breast milk, tenofovir concentrations were very low (breast milk/maternal plasma ratio = 0.08), while lamivudine was concentrated (breast milk/plasma ratio = 3) and efavirenz levels were 80% of those found in plasma. In infants, median levels at 6 months were 24 ng/mL tenofovir, 2.5 ng/mL lamivudine and 86.4 ng/mL efavirenz. At month 12, median levels were below the limit of quantification for the three drugs. No correlation was found between drug concentrations and laboratory parameters or indices of growth. HIV-RNA >1000 copies/mL was seen at month 1 in 15% of the women and at month 12 in 8.5%. Resistance was found in half of the women with detectable viral load. CONCLUSIONS: Breastfeeding infants under Option B-Plus are exposed to low concentrations of antiretroviral drugs. With this strategy, mothers had a good virological response 1 year after delivery.

Drug resistance mutations 18 months after discontinuation of nevirapine-based ART for prevention of mother-to-child transmission of HIV in Malawi.

OBJECTIVES: The objective of this study was to determine the prevalence of drug resistance mutations among HIV-positive women in Malawi 18 months after discontinuing nevirapine-based ART for the prevention of mother-to-child transmission. PATIENTS AND METHODS: HIV-infected antiretroviral-naive (except for single-dose nevirapine) pregnant Malawian women receiving a nevirapine-based triple antiretroviral regimen from Week 25 of gestation until 6 months of breastfeeding were included in this analysis. Drug resistance was assessed in HIV-DNA 24 months post-partum and at baseline (before the initiation of treatment). In patients with resistance, the presence of mutations was also evaluated in the corresponding plasma samples. RESULTS: Seven out of 42 (16.7%) women studied had archived drug resistance at Month 24 [six cases had NNRTI-associated mutations and two cases the M184I mutation]. In four cases, resistance mutations were already present at baseline (all NNRTI mutations). In three cases, there was an emergence of 'new' resistance (also present in the plasma in one case). Of the 35 women without resistance mutations at Month 24, only one subject had resistance mutations at baseline. Baseline resistance was significantly more common among women with mutations at 24 months compared with those harbouring a WT virus (4/7 versus 1/35, P < 0.001). CONCLUSIONS: Among women who had discontinued drugs 6 months post-partum, only 3/42 (7.1%) had accumulated new resistance mutations in HIV-DNA 2 years after delivery. These findings are reassuring in terms of the safety of the Option B strategy for the prevention of HIV mother-to-child transmission.

Viro-immunological response and emergence of resistance in HIV-infected women receiving combination antiretroviral regimens for the prevention of mother-to-child transmission in Malawi.

OBJECTIVES: To identify factors associated with detectable viral load and the emergence of drug resistance in a cohort of HIV-infected pregnant women in Malawi receiving antiretroviral combination regimens for the prevention of mother-to-infant transmission. METHODS: The study included 260 treatment-naive women who had received a three-drug nevirapine-based regimen from week 25 of gestational age until 6 months after delivery. HIV RNA was determined at month 6 and drug resistance was assessed if viral load was >50 copies/mL. Attendance at the scheduled follow-up visits was used as an indirect measure of treatment adherence. RESULTS: The rate of detectable HIV RNA at 6 months was 9.6% (25/260). The only significant predictor of this occurrence was the presence of ≥1 missed visit during follow-up (P = 0.012). Resistance was assessed in 19 of these women: 7 (37%) had a wild-type virus and the other 12 (63%) had resistance-associated mutations (nucleoside reverse transcriptase inhibitor, 7/12; non-nucleoside reverse transcriptase inhibitor, 11/12). Three of 12 cases (25%) in which mutations were detected had a viral load <1000 copies/mL. The emergence of resistance was not correlated with the presence of baseline mutations in either plasma or archived DNA. CONCLUSIONS: In this cohort of women, detectable HIV RNA 6 months post-partum was infrequent and associated with low adherence to the treatment programme. Mutations were present in 63% of the women with detectable viral load at 6 months who had samples available for resistance testing. The impact of resistance on treatment re-initiation in women discontinuing drugs after the risk of transmission has ceased can be limited.

The impact of HBV or HCV infection in a cohort of HIV-infected pregnant women receiving a nevirapine-based antiretroviral regimen in Malawi.

BACKGROUND: Coinfection with the hepatitis viruses is common in the HIV population in sub-Saharan Africa. The aim of this study was to assess, in a cohort of HIV-infected pregnant women receiving antiretroviral drugs (ARVs), the prevalence of HBV and HCV infections and to determine the impact of these infections on the occurrence of liver toxicity and on the viro-immunological response. METHODS: Women were screened for HBsAg and HCV-RNA before starting, at week 25 of gestational age, an antiretroviral regimen consisting of lamivudine and nevirapine plus either stavudine or zidovudine. Women with CD4+ < 350/mm3 continued ARVs indefinitely, while the other women interrupted treatment 6 months postpartum (end of breastfeeding period). Both groups were followed for 2 years after delivery. Liver function was monitored by alanine aminotransferase (ALT) measurement. The Cox proportional hazards model was used to identify factors associated with the emergence of liver toxicity. RESULTS: A total of 28 women out of the 309 enrolled in the study (9.1%) were coinfected with HBV (n. 27), or HCV (n. 1). During follow-up 125 women (40.4%) developed a grade ≥ 1 ALT elevation, 28 (9.1%) a grade ≥ 2 and 6 (1.9%) an elevation defining grade 3 toxicity. In a multivariate model including age, baseline CD4+ count and hemoglobin level, the presence of either HBV or HCV infection was significantly associated with the development of an ALT increase of any grade (P = 0.035). Moderate or severe liver laboratory toxicity (grade ≥ 2) was more frequent among women with baseline CD4+ > 250/mm3 (P = 0.030). In HBV-infected women a baseline HBV-DNA level above 10,000 IU/ml was significantly associated to the development of liver toxicity of grade ≥ 1 (P = 0.040). Coinfections had no impact on the immunological and virological response to antiretroviral drugs up to 2 years after delivery. CONCLUSIONS: In this cohort of nevirapine-treated women the presence of HBV or HCV was associated only to the development of mild liver toxicity, while the occurrence of moderate or severe hepatoxicity was correlated to a baseline CD4+ count > 250/mm3. No statistically significant effect of the coinfections was observed on the efficacy of antiretroviral therapy.

Implementing facility-based kangaroo mother care services: lessons from a multi-country study in Africa.

BACKGROUND: Some countries have undertaken programs that included scaling up kangaroo mother care. The aim of this study was to systematically evaluate the implementation status of facility-based kangaroo mother care services in four African countries: Malawi, Mali, Rwanda and Uganda. METHODS: A cross-sectional, mixed-method research design was used. Stakeholders provided background information at national meetings and in individual interviews. Facilities were assessed by means of a standardized tool previously applied in other settings, employing semi-structured key-informant interviews and observations in 39 health care facilities in the four countries. Each facility received a score out of a total of 30 according to six stages of implementation progress. RESULTS: Across the four countries 95 per cent of health facilities assessed demonstrated some evidence of kangaroo mother care practice. Institutions that fared better had a longer history of kangaroo mother care implementation or had been developed as centres of excellence or had strong leaders championing the implementation process. Variation existed in the quality of implementation between facilities and across countries. Important factors identified in implementation are: training and orientation; supportive supervision; integrating kangaroo mother care into quality improvement; continuity of care; high-level buy in and support for kangaroo mother care implementation; and client-oriented care. CONCLUSION: The integration of kangaroo mother care into routine newborn care services should be part of all maternal and newborn care initiatives and packages. Engaging ministries of health and other implementing partners from the outset may promote buy in and assist with the mobilization of resources for scaling up kangaroo mother care services. Mechanisms for monitoring these services should be integrated into existing health management information systems.

Micronutrient and Nutritional Status of HIV-Exposed and HIV-Unexposed Malawian Infants in the First Year of Life: Assessment of Ferritin, Vitamin A, and D Status and Its Association with Growth.

Breastfed Malawian infants from Human Immunodeficiency Virus (HIV)-uninfected and HIV-infected women who received antiretroviral therapy were followed until 12 months of age, allowing us to evaluate plasma levels of ferritin, vitamin A (as retinol-binding protein, RBP), and vitamin D (25(OH)D) at six months, as well as nutritional status and growth between six and 12 months. Ferritin and RBP levels were adjusted for inflammation. The study included 88 infants, 63 of whom were part of a recent cohort (2019-2021) that included 49 HIV-exposed but uninfected (HEU) and 14 HIV-unexposed and uninfected (HUU) infants, as well as 25 infants (all HEU) from an earlier cohort (2008-2011). No differences were observed between HEU and HUU infants regarding micronutrient levels, anthropometric indexes, growth, and rates of stunting, being underweight, or wasting. HEU infants from the earlier cohort, when compared to more recent HEU infants, had significantly worse anthropometric measures at six months and inferior growth between six and twelve months. Overall, ferritin deficiency involved 68.6% of infants, while vitamin A and vitamin D deficiency involved 8% and 1.2% of infants, respectively. Micronutrient deficiencies were not associated with HIV exposure, cohort, stunting, being underweight, or wasting. At six months, stunting, being underweight, and wasting involved 25.0%, 2.7% and 2.8% of infants, respectively, with no differences related to HIV exposure. Ferritin deficiency at six months was associated with inferior subsequent growth. In this small observational study conducted in Malawian infants, no major nutritional gap was observed between HIV-exposed and HIV-unexposed infants, though the study highlighted specific nutritional deficiencies that deserve attention. High rates of stunting and ferritin deficiency were observed in the first year of life in Malawian infants, irrespective of maternal HIV status; a significant association between ferritin deficiency and worse subsequent growth was found. Vitamin A and vitamin D deficiencies were much less frequent. Based on the data observed, nutritional interventions should give priority to the correction of ferritin deficiency and chronic undernutrition.

Cytomegalovirus viremia in HIV-exposed and HIV-unexposed infants in Malawi.

In sub-Saharan Africa the great majority of infants acquire Cytomegalovirus (CMV) infection within the first year of life. Maternal long-term antiretroviral therapy (ART) has been suggested to reduce the rate of CMV acquisition in HIV-exposed infants. In the present study serum samples collected at 6 months of age from HIV-exposed and HIV-unexposed infants were analyzed for the presence of CMV DNA (with CMV positivity defined by levels of CMV DNA > 1000 UI/ml). Twenty out of 58 (34.5%) infants had CMV DNA > 1000 UI/ml. There was no difference in the prevalence of CMV viremia between HIV-exposed and -unexposed infants [33.3% (15/45) vs 38.5% (5/13), respectively, P = 0.488]. In the HIV-exposed group, mothers of CMV-negative infants had received a longer antiretroviral treatment before delivery in comparison to mothers of CMV-positive infants (28 vs 3 months, P = 0.187). No differences in weights and lengths at birth, and at 1, 6 and 12 months were observed between CMV-positive and CMV-negative infants. In this study, the prevalence of CMV viremia at six months of age was high in infants born to HIV-positive mothers receiving long-term ART, similar to that of HIV-unexposed infants. Considering the possible relevant impact of CMV on infant health, strategies for containment of the infection should be explored.

Rates of Seroprotection against Vaccine-Preventable Infectious Diseases in HIV-Exposed and -Unexposed Malawian Infants.

BACKGROUND: The evaluation of seroprotection rates against vaccine-preventable infectious diseases allows for the identification of risk populations. HIV-exposed infants, even if not infected with HIV, have higher morbidity and mortality in comparison to unexposed counterparts. The aim of this study was to compare the specific IgG levels against Haemophilus influenzae type-B (HiB), Hepatitis-B (HBV), and Streptococcus pneumoniae (Spn) in two groups of infants (HIV-exposed and HIV-unexposed) living in Malawi. METHODS: Blood samples from 62 infants, 49 HIV-exposed, uninfected (HEU), and born to women living with HIV and 13 HIV-unexposed and uninfected (HUU), were collected at 6 months, and specific IgG levels were determined using ELISA tests. RESULTS: The antibody levels against HiB, HBV, and Spn were similar in the two groups. At six months, all HUU infants and 81.6% of HEU infants showed seroprotective levels against HiB, while a percentage of protection varying from 80.6 to 84.6% was observed for HBV and Spn regardless of HIV exposure. Only 59.2% of HEU and 69.2% of HUU infants showed antibody protection against all three pathogens. CONCLUSIONS: These results indicate similar rates of seroprotection among HEU and HUU infants but also suggest that a consistent fraction of infants received incomplete vaccinations. Strategies to enforce participation in immunization programs in Malawi should be a health priority.

Emergence of lamivudine resistance hepatitis B virus mutations in pregnant women infected with HBV and HIV receiving antiretroviral prophylaxis for the prevention of mother-to-infant transmission in Malawi.

HIV/HBV co-infection is highly prevalent in sub-Saharan Africa. The aim of this study was to determine if the use of triple combination lamivudine-containing prophylaxis for the prevention of mother-to-infant HIV transmission was associated with the emergence of lamivudine HBV mutations. The study included 21 pregnant co-infected women in Malawi who received either zidovudine or stavudine plus lamivudine and nevirapine from week 25 of gestation until 6 months after delivery or indefinitely if they met the criteria for treatment (CD4+ <350/mm(3)). HBV-DNA was determined using the Roche COBAS assay. Resistance mutations were assessed by the Trugene assay (Siemens Diagnostics). At baseline 33% of the women were HBeAg positive and had HBV-DNA > 10(4) IU/ml. Median CD4 count was 237 cells/mm(3) and median HIV-RNA was 3.8 log(10) copies/ml. After a median of 259 days of treatment, HBV-DNA was detectable in 9 out of 21 patients (42.8%). In three cases the HBV-DNA level was >10(4) IU/ml. Resistance mutations (M204I in five cases and L180M + M204I/V in one case) were present in 6 (28.6%) patients. Women with a resistant virus had significantly higher baseline HBV-DNA levels than those not developing resistance (1.1 × 10(7) IU/ml vs. 20.8 IU/ml, P = 0.022). Levels of ALT and AST were higher in women with resistant viruses compared to those retaining a wild-type virus. A high rate of lamivudine resistance was seen in this cohort of pregnant women. Follow-up of these patients will clarify if the presence of resistance has a significant impact on liver disease.

Seroprevalence of Brucella Infection in a Cohort of HIV-Positive Malawian Pregnant Women Living in Urban Areas.

Background: The seroprevalence of Brucella infection in sub-Saharan regions is high, and no recent data are available for Malawi, a country in which >60% of the population is involved in agropastoral activity. Aim: To evaluated the seroprevalence of Brucella in a cohort of HIV-positive pregnant women, living in an urban setting in Malawi. Methods: Sera of 201 pregnant women were tested for Brucella IgG. The Rose Bengal Plate Test and Serum Agglutination Tube test were used to determine antibody titer. Results: Five out of 201 (2.48%) women show positivity to Brucella, consistent with a past exposition to the infection. All five women delivered healthy infants, but two of them reported previous abortion/stillbirths, with a higher rate than those of the rest of the cohort (40% vs. 21.5%). Conclusions: This is one of the first reports of exposure of pregnant women to Brucella infection in Malawi, providing evidence of Brucella occurrence in an urban setting. Control programs should be introduced to reduce its impact on animal and human health.

Dynamics of SARS-CoV-2 exposure in Malawian infants between February 2020 and May 2021.

Background: Very limited information is available on SARS-CoV-2 seroprevalence in infants in sub-Saharan countries. Objective: In this study, we aimed to determine the rate and the temporal evolution of SARS CoV-2 seropositivity in breastfed Malawian infants. Study design: Blood samples (n = 250) from 158 infants, born to HIV-negative women and women living with HIV, collected from February 2020 to May 2021, were first tested using an Anti-IgG/A/M SARS CoV 2 ELISA assay against trimeric spike protein, and then, if positive, confirmed using a second ELISA assay detecting IgG against Receptor Binding Domain. Results: The confirmed prevalence of anti-SARS CoV-2 antibodies was 31.0% (95% CI: 23.7%-38.3%) with no significant difference between HIV-exposed and HIV-unexposed infants (29.3% and 37.1% respectively, P = 0.410). The presence of anti-SARS-CoV-2 IgG was not associated with maternal socioeconomic or demographic indices. Conclusions: Our data underline the wide spread of the SARS-CoV-2 infection in the pediatric population in sub-Saharan Africa. Design of more specific serological tests for African samples and improvements in serosurveillance programs are needed for more rigorous monitoring of the dynamics of SARS-CoV-2 infection in Africa.

Dried blood spots for the quantitative evaluation of IgG isotypes and correlation with serum samples in HIV-exposed uninfected (HEU) infants.

BACKGROUND: The determination of IgG levels and their subclasses can provide clinically relevant information on the status of the immune system. Here we determined the sensitivity and reproducibility of the quantification of IgG subclasses from Dried Blood Spots (DBS) in Malawian uninfected infants exposed to HIV (HEU). METHODS: Sixty paired samples of serum and DBS from HEU infants were used. Samples were collected from 1, 6, and 24-month old infants. IgGs concentrations from both serum and DBS were analyzed by BN ProSpec Siemens assay, using a different setting for sample dilutions. The reproducibility of the DBS method was tested on 10 samples run twice, starting from the DBS extraction process. To assess the systematic, proportional, and random differences, we computed the Passing-Bablok regression, and the Bland-Altman analysis to estimate the total mean bias between the two tests. RESULTS: The IgG isotypes concentrations from serum and DBS showed significant differences in all the comparisons. Generally, the DBS method underestimated IgG subclasses' values showing a recovery range between 51.2% and 77.6%. Passing Bablok regression on age-based groups showed agreement for IgG, IgG1, and IgG2, but not for IgG3 and IgG4. The mean bias obtained with the Bland Altman test varied largely depending on IgG isotypes (-0.02-2.21 g/l) Coefficient of variation <7.0% was found in the repeated tests for IgG, IgG1, IgG3, and IgG4, while it was 12.4% for IgG2. CONCLUSIONS: Varying degrees of differences were seen in the IgGs measurement in the two different matrices. In IgGs analysis, the DBS method offers promise for population-based research, but the results should be carefully evaluated and considered as a relative value since they are not equivalent to the serum concentrations.

Improving Skin-to-Skin Practice for babies in Kangaroo Mother Care in Malawi through the use of a customized baby wrap: A randomized control trial.

BACKGROUND: Complications of prematurity are a leading cause of newborn death in Malawi. Despite early adoption of Kangaroo mother care (KMC), coverage remains low and women have expressed challenges in using the traditional wrapper-chitenje. In 2016, a study was conducted to evaluate the acceptability and effectiveness of a customized KMC wrap in improving adherence to KMC practices among mothers. METHODS: Mother-baby dyads (301) were randomized to receive either a customized CarePlus Wrap developed by Lærdal Global Health or a traditional chitenje. Enrolled mother-baby dyads were assessed in the KMC ward at 2-3 days after of admission, and then again at 7-15 days post-discharge. Topics covered included skin-to-skin practices, breastfeeding, perceptions of the wrap, and family/community support. Chi square tests were used to assess associations between wrap type and KMC practices. The study received ethics approval. RESULTS: This study found that a customized KMC wrap is highly acceptable to women and improved skin-to-skin practices in facility-based KMC: 44% of mothers using a customized wrap reported 20 or more hours per day, compared to 33% of mothers using the traditional chitenje. Women using the customized wrap reported being comfortable in keeping the baby in skin-to-skin position more often than women using the chitenje (96% vs. 71%), and they were able to tie on the wrap themselves (86% vs. 10%). At the time of discharge from KMC, more women who used the customized wrap were satisfied with the wrap than those who used the traditional chitenje (94% vs. 56%). The customized wrap did not appear to impact other newborn practices, such as breastfeeding. CONCLUSIONS: This study provides evidence that a customized KMC wrap is highly acceptable to mothers, and it can contribute to better skin-to-skin practices. Use of a customized wrap may be one mechanism to support mothers in practicing KMC and skin-to-skin contact in addition to other interventions.

IgG abnormalities in HIV-positive Malawian women initiating antiretroviral therapy during pregnancy persist after 24 months of treatment.

OBJECTIVES: Hypergammaglobulinemia and anomalies in the IgG subclass distribution are common in HIV-infected individuals and persist even after many years of antiretroviral therapy (ART). The aim of this study was to investigate the IgG profile and dynamics in pregnant HIV-infected Malawian women in the Option B era. METHODS: Thirty-seven treatment-naive women received ART from the third trimester of pregnancy to 6 months post delivery (end of the breastfeeding period). ART continuation (group C) or interruption (group I) was then decided on the basis of the CD4+ cell count at enrolment (>350 or ≤350/µl). Total IgG and IgG subclasses were determined in maternal serum using a nephelometric assay at baseline and at 6 and 24 months postpartum. RESULTS: At enrolment, 36/37 women had IgG levels >15g/l and there was a predominance of the IgG1 isotype (more than 90%) in parallel with underrepresentation of IgG2 (5.0%). After 6 months of ART, both groups showed a significant median decrease in total IgG (-3.1g/l in group I, -3.5g/l in group C) and in IgG1 (-4.0g/l and -3.6g/l, respectively), but only a modest recovery in IgG2 levels (+0.16 in group I, +0.14g/l in group C). At month 24, hypergammaglobulinemia was still present in 73.7% of women in group C, although a significant reduction was observed in total IgG level and in IgG1 and IgG3 subclasses (p<0.0001 in all cases). IgG2 levels did not show any significant change. In group I at 24 months, total IgG and IgG subclasses had returned to levels comparable to those at baseline. CONCLUSIONS: The beneficial effects of 24 months of ART appear to be limited in the B-cell compartment, with an incomplete reduction of total IgG levels and no recovery of IgG2 depletion. A short ART period did not have significant effects on IgG abnormalities in women who interrupted treatment.

Readiness of hospitals to provide Kangaroo Mother Care (KMC) and documentation of KMC service delivery: Analysis of Malawi 2014 Emergency Obstetric and Newborn Care (EmONC) survey data.

BACKGROUND: Malawi introduced Kangaroo Mother Care (KMC) in 1999 as part of its efforts to address newborn morbidity and mortality and has continued to expand KMC services across the country. Yet, data on availability of KMC services and routine service provision are limited. METHODS: Data from the 2014 Emergency Obstetric Newborn Care (EmONC) survey, which was a census of all 87 hospitals in Malawi, were analyzed. The WHO service availability and readiness domains were used to generate indicators for KMC service readiness and an additional domain for documentation of KMC services was included. Levels of KMC service delivery were quantified using data extracted from a 12-month register review and a KMC initiation rate was calculated for each facility by dividing the reported number of babies initiated on KMC by the number of live births at facility. We defined three levels of KMC readiness and two levels of KMC operational status. RESULTS: 79% of hospitals (69/87) reported providing inpatient KMC services. More than half of the hospitals (62%; 54/87) met the most basic definition of readiness (staff, space for KMC and functional weighing scale) and 35% (30/87) met an expanded definition of readiness (guidelines, staff, space, scale and register in use). Only 15% (13/87) of hospitals had all KMC tracer items. Less than half of the hospitals (43%; 37/87) met criteria for KMC operational status at minimum levels (≥1/100 live births), and just 16% (14/87) met criteria for KMC operational status at routine levels (≥5/100 live births). CONCLUSIONS: Our study found large differences between reported levels of KMC services and documented levels of KMC readiness and service provision among hospitals in Malawi. It is recommended that facility assessments of services such as KMC include record reviews to better estimate service availability and delivery. Further efforts to strengthen the capacity of Malawian hospitals to deliver KMC are needed.