Clustering of subpatent infections in households with asymptomatic rapid diagnostic test-positive cases in Bioko Island, Equatorial Guinea independent of travel to regions of higher malaria endemicity: a cross-sectional study.

BACKGROUND: Prevalence of falciparum malaria on Bioko Island remains high despite sustained, intensive control. Progress may be hindered by high proportions of subpatent infections that are not detected by rapid diagnostic tests (RDT) but contribute to onward transmission, and by imported infections. Better understanding of the relationship between subpatent infections and RDT-detected infections, and whether this relationship is different from imported versus locally acquired infections, is imperative to better understand the sources of infection and mechanisms of transmission to tailor more effective interventions. METHODS: Quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) was performed on a sub-set of samples from the 2015 Malaria Indicator Survey to identify subpatent infections. Households with RDT(+) individuals were matched 1:4 with households with no RDT(+) individuals. The association between living in a household with an RDT(+) individual and having a subpatent infection was evaluated using multivariate hierarchical logistic regression models with inverse probability weights for selection. To evaluate possible modification of the association by potential importation of the RDT(+) case, the analysis was repeated among strata of matched sets based on the reported eight-week travel history of the RDT(+) individual(s). RESULTS: There were 142 subpatent infections detected in 1,400 individuals (10.0%). The prevalence of subpatent infections was higher in households with versus without an RDT(+) individual (15.0 vs 9.1%). The adjusted prevalence odds of subpatent infection were 2.59-fold greater (95% CI: 1.31, 5.09) for those in a household with an RDT(+) individual compared to individuals in a household without RDT(+) individuals. When stratifying by travel history of the RDT(+) individual, the association between subpatent infections and RDT(+) infections was stronger in the strata in which the RDT(+) individual(s) had not recently travelled (adjusted prevalence odds ratio (aPOR) 2.95; 95% CI:1.17, 7.41), and attenuated in the strata in which recent travel was reported (aPOR 1.76; 95% CI: 0.54, 5.67). CONCLUSIONS: There is clustering of subpatent infections around RDT(+) individual(s) when both imported and local infection are suspected. Future control strategies that aim to treat whole households in which an RDT(+) individual is found may target a substantial portion of infections that would otherwise not be detected.

Explaining progress towards Millennium Development Goal 4 for child survival in Tanzania.

BACKGROUND: During the Millennium Development Goal (MDG) era (1990-2015) the government in Mainland Tanzania and partners launched numerous initiatives to advance child survival including the comprehensive One Plan for Maternal Newborn and Child Health in 2008-2015 and a "sharpened" One Plan strategy in early 2014. Moving into the Sustainable Development Goal era, the government needs to learn from successes and challenges of striving towards MDG 4. METHODS: We expand previous work by presenting data for the full MDG period and sub-national results. We used data from six nationally-representative household surveys conducted between 1999 and 2015 to examine trends in coverage of 22 lifesaving maternal, newborn, child health and nutrition (MNCH&N) interventions, nutritional status (stunting; wasting) and breastfeeding practice across Mainland Tanzania and sub-nationally in seven standardized geographic zones. We used the Lives Saved Tool (LiST) to model the relative contribution of included interventions which saved under 5 lives during the period from 2000-2015 compared to 1999 on a national level and within the seven zones. FINDINGS: Child survival and nutritional status improved across Mainland Tanzania and in each of the seven zones across the 15-year period. MNCH&N intervention coverage varied widely and across zones with several key interventions declining across Mainland Tanzania or in specific geographical zones during all or part the period. According to our national LiST model, scale-up of 22 MNCH&N interventions - together with improvements in breastfeeding practice, stunting and wasting - saved 838 460 child lives nationally between 2000 and 2015. CONCLUSIONS: Mainland Tanzania has made significant progress in child survival and nutritional outcomes but progress cannot be completely explained by changes in intervention coverage alone. Further examination of the implementation and contextual factors shaping these trends is important to accelerate progress in the SDG era.

Prevalence of Hypertension and Its Associated Risk Factors among 34,111 HAART Naïve HIV-Infected Adults in Dar es Salaam, Tanzania.

Background. Elevated blood pressure has been reported among treatment naïve HIV-infected patients. We investigated prevalence of hypertension and its associated risk factors in a HAART naïve HIV-infected population in Dar es Salaam, Tanzania. Methods. A cross-sectional analysis was conducted among HAART naïve HIV-infected patients. Hypertension was defined as systolic blood pressure (SBP) ≥ 140 mmHg and/or diastolic blood pressure (DBP) ≥ 90 mmHg. Overweight and obesity were defined as body mass index (BMI) between 25.0-29.9 kg/m2 and ≥30 kg/m2, respectively. We used relative risks to examine factors associated with hypertension. Results. Prevalence of hypertension was found to be 12.5%. After adjusting for possible confounders, risk of hypertension was 10% more in male than female patients. Patients aged ≥50 years had more than 2-fold increased risk for hypertension compared to 30-39-years-old patients. Overweight and obesity were associated with 51% and 94% increased risk for hypertension compared to normal weight patients. Low CD4+ T-cell count, advanced WHO clinical disease stage, and history of TB were associated with 10%, 42%, and 14% decreased risk for hypertension. Conclusions. Older age, male gender, and overweight/obesity were associated with hypertension. Immune suppression and history of TB were associated with lower risk for hypertension. HIV treatment programs should screen and manage hypertension even in HAART naïve individuals.

Mortality and treatment failure among HIV-infected adults in Dar Es Salaam, Tanzania.

OBJECTIVES: Monitoring antiretroviral treatment (ART) outcomes is essential for assessing the success of HIV care and treatment programs in resource-limited settings (RLS). METHODS: Longitudinal analyses of clinical and immunologic parameters in HIV-infected adults initiated on ART between November 2004 and June 2008 at Management and Development for Health (MDH)-Presidents Emergency Plan For AIDS Relief PEPFAR supported HIV care and treatment clinics in Tanzania. RESULTS: A total of 12 842 patients were analyzed (65.9% female, median baseline CD4 count, 106 cells/mm(3)). Significant improvements in immunologic status were observed with an increase in CD4 count to 298 (interquartile range [IQR] 199-416), 372 (256-490) and 427 (314-580) cells/mm(3), at 1, 2, and 3 years, respectively. Overall mortality was 13.1% (1682 of 12 842). Male sex, World Health Organization (WHO) stage III/IV, CD4 <200 cells/mm(3), hemoglobin (Hgb) <8.5 g/dL, and stavudine (d4T)-containing regimens were independently associated with early and overall mortality. CONCLUSIONS: Closer monitoring of males and patients with advanced HIV disease following ART initiation may improve clinical and immunologic outcomes in these individuals.

Nutritional status and mortality among HIV-infected patients receiving antiretroviral therapy in Tanzania.

BACKGROUND: Poor nutritional status is associated with immunologic impairment and adverse health outcomes among adults infected with human immunodeficiency virus (HIV). METHODS: We investigated body mass index (BMI), middle upper arm circumference (MUAC), and hemoglobin (Hgb) concentrations at initiation of antiretroviral therapy (ART) in 18,271 HIV-infected Tanzanian adults and their changes in the first 3 months of ART, in relation to the subsequent risk of death. RESULTS: Lower BMI, MUAC, and Hgb concentrations at ART initiation were strongly associated with a higher risk of death within 3 months. Among patients who survived >3 months after ART initiation, those with a decrease in weight, MUAC, or Hgb concentrations by 3 months had a higher risk of death during the first year. After 1 year, only a decrease in MUAC by 3 months after ART initiation was associated with a higher risk of death. Weight loss was associated with a higher risk of death across all levels of baseline BMI, with the highest risk observed among patients with BMI <17 kg/m(2) (relative risk, 7.9; 95% confidence interval, 4.4-14.4). CONCLUSIONS: Poor nutritional status at ART initiation and decreased nutritional status in the first 3 months of ART were strong independent predictors of mortality. The role of nutritional interventions as adjunct therapies to ART merits further investigation.

Influence of HLA class I and HLA-KIR compound genotypes on HIV-2 infection and markers of disease progression in a Manjako community in West Africa.

Overall, the time to AIDS after HIV-2 infection is longer than with HIV-1, and many individuals infected with HIV-2 virus remain healthy throughout their lives. Multiple HLA and KIR gene products have been implicated in the control of HIV-1, but the effect of variation at these loci on HIV-2 disease is unknown. We show here for the first time that HLA-B*1503 is associated significantly with poor prognosis after HIV-2 infection and that HLA-B*0801 is associated with susceptibility to infection. Interestingly, previous data indicate that HLA-B*1503 is associated with low viral loads in HIV-1 clade B infection but has no significant effect on viral load in clade C infection. In general, alleles strongly associated with HIV-1 disease showed no effect in HIV-2 disease. These data emphasize the unique nature of the effects of HLA and HLA/KIR combinations on HIV-2 immune responses relative to HIV-1, which could be related to their distinct clinical course.

Risk factors for and clinical outcome of congenital cytomegalovirus infection in a peri-urban West-African birth cohort.

BACKGROUND: Congenital cytomegalovirus (CMV) infection is the most prevalent congenital infection worldwide. Epidemiology and clinical outcomes are known to vary with socio-economic background, but few data are available from developing countries, where the overall burden of infectious diseases is frequently high. METHODOLOGY/PRINCIPAL FINDINGS: As part of an ongoing birth cohort study in The Gambia among term infants, urine samples were collected at birth and tested by PCR for the presence of CMV DNA. Risk factors for transmission and clinical outcome were assessed, including placental malaria infection. Babies were followed up at home monthly for morbidity and anthropometry, and at one year of age a clinical evaluation was performed. The prevalence of congenital CMV infection was 5.4% (40/741). A higher prevalence of hepatomegaly was the only significant clinical difference at birth. Congenitally infected children were more often first born babies (adjusted odds ratio (OR) 5.3, 95% confidence interval (CI) 2.0-13.7), more frequently born in crowded compounds (adjusted OR 2.9, 95%CI 1.0-8.3) and active placental malaria was more prevalent (adjusted OR 2.9, 95%CI 1.0-8.4). These associations were corrected for maternal age, bed net use and season of birth. During the first year of follow up, mothers of congenitally infected children reported more health complaints for their child. CONCLUSIONS/SIGNIFICANCE: In this study, the prevalence of congenital CMV among healthy neonates was much higher than previously reported in industrialised countries, and was associated with active placental malaria infection. There were no obvious clinical implications during the first year of life. The effect of early life CMV on the developing infant in the Gambia could be mitigated by environmental factors, such as the high burden of other infections.

Incidence of tuberculosis and survival after its diagnosis in patients infected with HIV-1 and HIV-2.

BACKGROUND: In sub-Saharan Africa, tuberculosis (TB) is the most frequently diagnosed opportunistic infection and cause of death among HIV-infected patients. HIV-2 has been associated with less immune suppression, slower disease progression and longer survival. OBJECTIVE: To examine whether the incidence of TB and survival after TB are associated with CD4 cell count rather than HIV type. METHODS: Clinical and immunological data were retrospectively evaluated among an open clinic-based cohort of HIV-1- and HIV-2-infected patients to determine incidence of TB (first diagnosis > 28 days after HIV diagnosis) and subsequent mortality. Patients were grouped by CD4 cell count into those with < 200, 200-500 and > 500 x 10 cells/l. RESULTS: Incident TB was diagnosed among 159 of 2012 patients, with 4973 person-years of observation time. In 105/159 (66.0%), the diagnosis was confirmed by direct microscopy or culture. Incidence of TB was highest in the group with < 200 x 10 cells/l (9.1/100 and 8.8/100 person-years in HIV-1 and HIV-2, respectively). Adjusted for CD4 cell count, there was no significant difference in incidence or mortality following TB between HIV-1- and HIV-2-infected patients. Mortality rate was higher in those with incident TB and HIV infection, most markedly in the group with the highest CD4 cell count (hazard ratio, 10.0; 95% confidence interval, 5.1-19.7). CONCLUSION: Adjusted for CD4 cell count, incidence of TB was similar among HIV-1- and HIV-2-infected patients. Mortality rates after TB diagnosis were similar in both groups and high compared with those without TB.

Body mass index at time of HIV diagnosis: a strong and independent predictor of survival.

BACKGROUND: Identification of basic prognostic indicators of HIV infection is essential before widespread antiretroviral therapy can be implemented in low-technology settings. This study assessed how well body mass index (BMI:kg/m2) predicts survival. METHODS: BMI within 3 months of HIV diagnosis was obtained from 1657 patients aged > or = 15 years, recruited in a seroprevalent clinical cohort in The Gambia since 1992 and followed up at least once. Baseline CD4+ counts and clinical assessment at time of diagnosis were done. RESULTS: The mortality hazard ratio (HR) of those with a baseline BMI <18 compared with those with a baseline BMI > or = 18 was 3.4 (95% CI, 3.0-3.9). The median survival time of those presenting with a BMI <16 was 0.8 years, in contrast to a median survival of 8.9 years for those with a baseline BMI > or = 22. Baseline BMI <18 remained a highly significant independent predictor of mortality after adjustment for age, sex, co-trimoxazole prophylaxis, tuberculosis, reported wasting at diagnosis, and baseline CD4+ cell count (adjusted HR = 2.5, 95% CI 2.0-3.0). Sensitivity and specificity of baseline BMI <18 was comparable to that of a CD4+ count <200 in predicting mortality within 6 months of diagnosis. DISCUSSION: BMI at diagnosis is a strong, independent predictor of survival in HIV-infected patients in West Africa. In the absence of sophisticated clinical and laboratory support, BMI may also prove a useful guide for deciding when to initiate antiretroviral therapy.

Mortality of HIV-1, HIV-2 and HIV-1/HIV-2 dually infected patients in a clinic-based cohort in The Gambia.

OBJECTIVE: To assess and compare the mortality rates of patients with HIV-1, HIV-2 or both infections (HIV-D) in the same population. DESIGN: Clinic-based cohort study. METHODS: HIV-seropositive patients aged 15 years and older who attended the Medical Research Council clinics in Fajara between May 1986 and September 1997 were recruited. Clinical assessment using the Karnofsky score, CDC cell staging, WHO staging, and CD4 cell counts was performed at baseline. Patients attended clinic every 3 months; if they did not attend, they were visited at home by field workers to ascertain survival status. No patient was on antiretroviral therapy during the study period. RESULTS: Data from 1519 HIV-positive adult patients were analysed. A total of 746 patients had HIV-1, 666 HIV-2, and 107 patients had HIV-D. A total of 828 patients (55%) died, and 161 (11%) were lost to follow-up. The median follow-up was 12 months (range 0-128). CD4 cell counts were available for 894 patients. Compared with HIV-1, the adjusted hazards ratio for mortality in the CD4 cell count category 500 cells/microl or greater was 0.50 for HIV-2 (95% CI 0.28-0.88) and 1.27 (95% CI 0.51-3.7) for HIV-D. Among those with CD4 cell counts less than 500 cells/microl the mortality rates in HIV-2 and HIV-D were similar to those in HIV-1. DISCUSSION: HIV-2-infected patients with CD4 cell counts of 500 cells/microl and greater had a significantly lower mortality rate than HIV-1-infected patients. HIV-2-infected patients with advanced disease had the same poor prognosis as patients with HIV-1. Dually infected patients had mortality rates similar to HIV-1.