A systematic review and meta-analysis reveal that Campylobacter spp. and antibiotic resistance are widespread in humans in sub-Saharan Africa.

INTRODUCTION: Campylobacter spp. are zoonotic bacteria that cause gastroenteritis in humans worldwide, whose main symptom is diarrhea. In certain cases, extra intestinal manifestations may occur, such as Guillain Barré syndrome. The bacteria cause severe diarrhea mostly in children and in immunocompromised individuals. This review aims to address the prevalence of Campylobacter spp. in humans in sub-Saharan Africa. It also aims to understand the impact of HIV in the prevalence, as well as to report data on antibiotic resistance and propose research priorities. METHODS: We followed PRISMA guidelines to find studies on the occurrence of Campylobacter spp. in humans in all countries from sub-Saharan Africa. Studies published between 2000 and 2020 were searched in PubMed, Cochrane Library, CINAHL, African Index Medicus, African Journals Online, Google Scholar and Science Direct. We have conducted a random-effect meta-analysis and calculated the proportion of resistant isolates to different antibiotics. RESULTS AND DISCUSSION: We found 77 studies that described such occurrence in humans in 20 out of 53 sub-Saharan African countries. Campylobacter jejuni was the most prevalent species. Pooled prevalence was 9.9% (CI: 8.4%-11.6%). No major variations within the different sub-regions were found. Most studies reported Campylobacter spp. as the cause of diarrhea, mainly in children. Some studies reported the bacteria as a possible etiologic agent of acute flaccid paralysis and urinary tract infection. Campylobacter spp. presented a higher pooled prevalence in HIV infected patients, although not statistically significant. High proportions of resistant strains were reported for many antibiotics, including erythromycin and tetracycline. CONCLUSION: Campylobacter spp. occur in sub-Saharan Africa, although information is scarce or inexistent for many countries. Research priorities should include investigation of the understudied species; extra intestinal manifestations; the impact of HIV infection and associated risk factors. Control strategies should be reinforced to contain the spread of this pathogen and drug resistance.

Genetic Variants in the IL-4/IL-13 Pathway Influence Measles Vaccine Responses and Vaccine Failure in Children from Mozambique.

Despite effective measles vaccines, measles still causes severe morbidity and mortality worldwide, particularly in developing countries. The Th2 pathway involving interleukin (IL)-4 and IL-13 cytokines, and their receptor IL-4Rα, play important roles in the Th1/Th2 balance and antibody production. A Th2 skewing of the cytokine milieu may affect vaccine responses. We investigated IL-4, IL-13, and IL-4Rα polymorphisms and their impact on measles IgG responses and measles vaccine failure, in two separate cohorts: 12-month-old Australian children immunized with measles-mumps-rubella vaccine (n = 137) and a case/control cohort of children aged 6 months-14 years from Mozambique, Africa (n = 89), some of whom were vaccinated, but still contracted measles (vaccine failure). We found that IL-4Rα haplotypes for Val75Ile, Ser503Pro, and Arg576Gln were associated with measles IgG in Mozambican children (p = 0.016 and p = 0.032 for Val.Pro.Arg and Val.Ser.Arg, respectively), but not Australian children. IL-4Rα 503Pro was more prevalent in Mozambique vaccine failure cases compared with controls (p = 0.008). We showed that the impact of Th2 genes on measles vaccine responses differs between ethnicities and IL-4Rα polymorphisms may work in combination to affect measles antibody responses and vaccine failure in Mozambican children. Studies in this area are particularly important in developing countries like Mozambique where measles is still a major health issue.

Polymorphisms in key innate immune genes and their effects on measles vaccine responses and vaccine failure in children from Mozambique.

Despite an effective vaccine, measles remains a major health problem globally, particularly in developing countries. More than 30% of children show primary vaccine failure and therefore remain vulnerable to measles. Genetic variation in key innate pathogen recognition receptors, such as the measles cell entry receptors CD46 and SLAM, measles attachment receptor DC-SIGN, the antiviral toll-like receptors (TLR)3, TLR7 and TLR8, and the cytosolic antiviral receptor RIG-I, may significantly affect measles IgG antibody responses. Measles is still highly prevalent in developing countries such as those in Africa however there is no previous data on the effect of these innate immune genes in a resident African population. Polymorphisms (n=29) in the candidate genes were genotyped in a cohort of vaccinated children (n=238) aged 6 months-14 years from Mozambique, Africa who either had vaccine failure and contracted measles (cases; n=66) or controls (n=172). Contrasting previous associations with measles responses in Caucasians and/or strong evidence for candidacy, we found little indication that these key innate immune genes affect measles IgG responses in our cohort of Mozambican children. We did however identify that CD46 and TLR8 variants may be involved in the occurrence of measles vaccine failure. This study highlights the importance of genetic studies in resident, non-Caucasian populations, from areas where determining the factors that may affect measles control is of a high priority.

Measles-specific neutralizing antibodies in rural Mozambique: seroprevalence and presence in breast milk.

In Mozambique, as in many sub-Saharan countries, measles remains a public health problem. We conducted cross-sectional surveys in which we assessed measles-specific antibodies in serum and breast milk by plaque reduction neutralization (PRN) assay and measles secretory IgA in breast milk by enzyme-linked immunosorbent assay. A total of 151 persons < 1 month to 23 years of age were surveyed; 81 (53.6%) of 151 had PRN titers equal to or above the protective level (>/= 200 mIU/mL). We found many serosusceptible persons, including 20.5% in whom no PRN antibody was detected. Almost all (96%) infants 6-8 months of age had non-protective PRN titers. Overall, 20.7% (6 of 29) of persons known to have received measles vaccine had non-protective titers. The geometric mean titer (GMT) of breast milk PRN antibodies was 41.6 mIU/mL (95% confidence interval [CI] = 34.0-51.0 mIU/mL) and the secretory IgA GMT was 227.6 (EU/mL) (95% CI = 179.1-289.1 EU/mL). The PRN titers of breast milk tended to increase with age. A notable proportion of the population in Manhiça, Mozambique apparently remains susceptible to clinical measles despite recent mass vaccination campaigns.

Etiology of diarrhea in children younger than 5 years of age admitted in a rural hospital of southern Mozambique.

Diarrhea is one of the main causes of morbidity and mortality among children in sub-Saharan Africa and one of the main causes of hospital admissions in rural areas. Stool samples were collected from 529 children admitted with diarrhea to the Manhiça District Hospital (September 2000 to September 2001) and processed to detect bacterial enteropathogens, parasites, and virus. Diarrheagenic Escherichia coli, isolated from 120 samples (22.6%; enteroaggregative [corrected] [9.6%], enterotoxigenic [6.8%], enteropathogenic [corrected] [4.3%], and verotoxigenic [1.9%]) was the most frequently isolated pathogen, followed by Ascaris lumbricoides (9.3%). Others detected included Salmonella spp. and Giardia lamblia (2.5% each) and Campylobacter spp. (1.7%). A. lumbricoides (92% versus 8%; P<0.001) and Strongyloides stercolaris (100% versus 0%; P=0.008) were most frequently isolated in children older than 12 months of age. Resistance to trimethoprim-sulphametoxazole and ampicillin was high. Etiologic data on diarrheal diseases and susceptibility patterns of diarrheal pathogens are important tools for clinical management and control strategic planning.