Could China's journey of malaria elimination extend to Africa?

World Health Organization (WHO) certified China malaria-free on June 30, 2021, which brightens the goal of global malaria elimination efforts. China contributed its unique innovations to the global community: Artemisinin, discovered by Tu Youyou, has saved millions of lives globally; the "1-3-7" norm developed in 2012, has been adapted in the local contexts of countries in the Southeast Asia and Africa. How to the targets of Global Technical Strategy for Malaria (GTS) 2016-2030. By looking into the malaria control phase, towards elimination phase from 1960 to 2011 in sub-Saharan Africa and China, we found that the gap in malaria burden will widen unless the interventions in Africa are enhanced. It is imperative to identify the key China-Africa cooperation areas on malaria control and elimination, so that synergized efforts could be pooled together to help African countries achieve the elimination goal. The practices from China malaria control and elimination efforts could be leveraged to fast-track malaria elimination efforts in Africa, which makes it possible that the China's journey of malaria elimination extends to Africa.

Longitudinal Comparison of Antibiotic Resistance in Diarrheagenic and Non-pathogenic Escherichia coli from Young Tanzanian Children.

Enteroaggregative, enteropathogenic, and enterotoxigenic Escherichia coli contribute significantly to the burden of diarrheal infections particularly in developing countries. Antibiotic resistance is increasingly common among bacterial pathogens including pathogenic E. coli. We assessed the relationship between pathogenic E. coli carriage and resistance to six antibiotics in E. coli isolated from young children in rural Tanzania. We surveyed temporal stability in antibiotic resistance in 2492 E. coli isolated from fecal samples obtained from young children in rural Tanzania collected over a 6 months period. Approximately half of the 377 children sampled were exposed to an azithromycin mass treatment program for trachoma control and half resided in control villages. Children were sampled at baseline, 1-, 3-, and 6 months following azithromycin treatment. We compared resistance to six antibiotics in pathogenic and non-pathogenic strains at the population level, within fecal specimens, and within individuals over time using chi-square tests, paired odds ratios, and logistic regression, respectively. Resistance to ampicillin and trimethoprim/sulfamethoxazole was highly prevalent (>65%). Resistance to 5 of 6 antibiotics tested and multi-drug resistance occurred more frequently in pathogenic isolates (p ≤ 0.001) within fecal specimens and overall. Azithromycin mass treatment exposure was significantly associated with increased odds of carriage of isolates resistant to erythromycin (OR 3.64, p < 0.001) and trimethoprim/sulfamethoxazole (OR 1.60, p < 0.05). Pathogenic isolates were approximately twice as likely to be resistant to erythromycin, ampicillin, or trimethoprim/sulfamethoxazole compared to non-pathogenic isolates from the same fecal specimen. The potential linkage between resistance and virulence in E. coli suggests hygiene and sanitation interventions aimed at reducing disease burden could play a role in controlling transmission of antibiotic resistance.

Community mass treatment with azithromycin for trachoma: Factors associated with change in participation of children from the first to the second round.

BACKGROUND: Mass drug administration (MDA) with azithromycin is an important part of trachoma control programs. Maintaining high participation among children is challenging. AIM: We assessed factors identifying households with a child who changed participation from the first MDA to the second MDA compared to households where all children participated at both MDAs. METHODS: Two case-control comparisons were conducted in 11 Tanzanian communities, which underwent MDA in 2008 and 2009. The first case group (n=165) was a random sample of households with a child who changed from a 2008 non-participant to a 2009 participant (delayed participant). The second case group (n=165) was a random sample of households with a child who went from a 2008 participant to a 2009 non-participant (change to non-participant). Controls (n=330) were a random sample of households where all children participated in both rounds. Risk factors were assessed using questionnaires asked of children's guardians. Logistic models with a random-intercept were used to estimate odds ratios and 95% confidence intervals. RESULTS: Households with delayed participation were more likely to be in communities with fewer treatment days (OR=2.98, 95% CI=1.80-4.92) and assigned to Community Treatment Assistants (CTA) with a wide area to cover (OR=1.88, 95% CI=1.09-3.23). Households with change to non-participation were more likely to live further from the distribution site (OR=3.17, 95% CI=1.19-8.46), have the guardian born outside the village with short-term residency (OR=2.64, 95% CI=1.32-5.31), and be assigned to a male CTA (OR=1.75, 95% CI=1.08-2.83). CONCLUSIONS: Factors related to program accessibility were associated with delayed participation and maintaining participation.

Short-term malaria reduction by single-dose azithromycin during mass drug administration for trachoma, Tanzania.

Single-dose mass drug administration of azithromycin (AZT) is underway to eliminate trachoma worldwide. Studies in Ethiopia showed a reduction in all-cause childhood deaths after administration. To examine the effect of single-dose AZ MDA on prevalent malaria infections in a large prospective cohort of children and parents in Dodoma Province, Tanzania, we quantified the temporal prevalence of malaria parasitemia by real-time PCR for 6 months after single-dose AZT. In the first month after treatment but not in subsequent months, Plasmodium falciparum infections were reduced by 73% (95% CI 43%-89%) in treatment versus control villages and differences remained significant (p = 0.00497) in multivariate models with village-level random effects. Genetic sequencing of P. falciparum ribosomal L4 protein showed no mutations associated with AZT resistance. AZT mass drug administration caused a transient, 1-month antimalarial effect without selecting for P. falciparum ribosomal L4 resistance mutations in a region with a 10-year history of treating trachoma with this drug.

Increased carriage of macrolide-resistant fecal E. coli following mass distribution of azithromycin for trachoma control.

BACKGROUND: Mass drug treatment with azithromycin (MDA) is part of the WHO-endorsed 'SAFE' strategy for trachoma control in endemic communities. MDA has been associated with reduced trachoma prevalence and short-term reductions in other bacterial infections, but can also lead to increased circulation of macrolide-resistant bacteria. METHODS: We prospectively monitored macrolide resistance in fecal E. coli collected from young children participating in the PRET+ Study in rural Tanzania. MDA was administered in four villages with >10% trachoma prevalence. Four nearby communities with lower trachoma prevalence served as controls. Rectal swabs were collected during cross-sectional surveys performed at baseline, 1, 3 and 6 months after MDA. Fecal E. coli isolates were screened for macrolide susceptibility using disc diffusion and minimum inhibitory concentration methods. Cross-sectional and longitudinal differences in resistance prevalence by MDA exposure were compared using t-tests and logistic regression. RESULTS: There was no difference in the proportion of individuals carrying azithromycin-resistant E. coli at baseline (0.21 vs. 0.16, P > 0.05). Azithromycin resistance carriage prevalence remained stable over follow-up in non-MDA villages but increased sharply in MDA villages (0.61 at 1 month, 0.42 at 3 months and 0.31 at 6 months). MDA exposure was highly associated with azithromycin resistance carriage at 1 month post-MDA (OR 15.27, P < 0.001) and subsequent surveys. Younger age and recent diarrhoea were also associated with increased odds of resistance (P < 0.01). CONCLUSIONS: MDA resulted in significantly increased prevalence of macrolide resistance in E. coli. Although MDA is effective for trachoma elimination, it has costs; it is essential to monitor antimicrobial resistance following MDA.

Mass distribution of azithromycin for trachoma control is associated with increased risk of azithromycin-resistant Streptococcus pneumoniae carriage in young children 6 months after treatment.

BACKGROUND: Emerging evidence suggests that the mass distribution of azithromycin for trachoma control (MDA) may increase circulation of macrolide resistance in bacteria associated with severe pediatric infections in treated communities. METHODS: We examined the effect of MDA on nasopharyngeal carriage of antibiotic-resistant Streptococcus pneumoniae among 1015 young children living in rural Tanzania. MDA with a single dose of oral azithromycin was provided in 4 of 8 communities where trachoma prevalence was ≥10%. Isolates were tested for susceptibility to azithromycin (AZM) and commonly used antibiotics by disk diffusion and Etest. We calculated the proportion of antibiotic-resistant S. pneumoniae carriage at baseline and again 1, 3, and 6 months after treatment, and at comparable intervals in the untreated villages. RESULTS: The proportion of AZM-resistant isolates was similar between groups at baseline (MDA: 35.8% vs non-MDA: 35.4%), however, this proportion was greater in the MDA group in all subsequent surveys. At 6 months, the percentage of AZM-resistant isolates was significantly higher in the MDA group (81.9% vs 46.9%, P < .001). The odds of AZM-resistant carriage was 5-fold greater in the MDA group (odds ratio, 4.95 [95% confidence interval, 3.23-7.61]). The proportion of isolates clinically resistant to AZM (minimum inhibitory concentration ≥16 µg/mL) was also significantly greater in the MDA group at 6 months (35.3% vs 12.4%, P < .006). CONCLUSIONS: Mass distribution of a single dose of oral azithromycin for trachoma was associated with increased circulation of macrolide-resistant S. pneumoniae carriage among young children in the 6 months following treatment. It is crucial that changes in antibiotic resistance patterns and their clinical significance in the treatment of severe pediatric infections be assessed in future MDA trials.

Trends in weekly reported net use by children during and after rainy season in central Tanzania.

BACKGROUND: The use of long-lasting insecticidal nets (LLINs) is one of the principal interventions to prevent malaria in young children, reducing episodes of malaria by 50% and child deaths by one fifth. Prioritizing young children for net use is important to achieve mortality reductions, particularly during transmission seasons. METHODS: Households were followed up weekly from January through June 2009 to track net use among children under seven under as well as caretakers. Net use rates for children and caretakers in net-owning households were calculated by dividing the number of person-weeks of net use by the number of person-weeks of follow-up. Use was stratified by age of the child or caretaker status. Determinants of ownership and of use were assessed using multivariate models. RESULTS: Overall, 60.1% of the households reported owning a bed net at least once during the study period. Among net owners, use rates remained high during and after the rainy season. Rates of use per person-week decreased as the age of the child rose from 0 to six years old; at ages 0-23 months and 24-35 months use rates per person-week were 0.93 and 0.92 respectively during the study period, while for children ages 3 and 4 use rates per person-week were 0.86 and 0.80. For children ages 5-6 person-week ratios dropped to 0.55. This represents an incidence rate ratio of 1.67 for children ages 0-23 months compared to children aged 5-6. Caretakers had use rates similar to those of children age 0-35 months. Having fewer children under age seven in the household also appeared to positively impact net use rates for individual children. CONCLUSIONS: In this area of Tanzania, net use is very high among net-owning households, with no variability either at the beginning or end of the rainy season high transmission period. The youngest children are prioritized for sleeping under the net and caretakers also have high rates of use. Given the high use rates, increasing the number of nets available in the household is likely to boost use rates by older children.

Azithromycin mass treatment for trachoma control: risk factors for non-participation of children in two treatment rounds.

BACKGROUND: Persistent non-participation of children in mass drug administration (MDAs) for trachoma may reduce program impact. Risk factors that identify families where participation is a problem or program characteristics that foster non-participation are poorly understood. We examined risk factors for households with at least one child who did not participate in two MDAs compared to households where all children participated in both MDAs. METHODS/PRINCIPAL FINDINGS: We conducted a case control study in 28 Tanzanian communities. Cases included all 152 households with at least one child who did not participate in the 2008 and 2009 MDAs with azithromycin. Controls consisted of a random sample of 460 households where all children participated in both MDAs. A questionnaire was asked of all families. Random-intercept logistic regression models were used to estimate odds ratios (ORs) and 95% confidence intervals (CIs), control for clustering, and adjust for community size. In total, 140 case households and 452 control households were included in the analyses. Compared to controls, guardians in case households had higher odds of reporting excellent health (OR 4.12 (CI 95% 1.57-10.86)), reporting a burden due to family health (OR 3.15 (95% CI 1.35-7.35)), reduced ability to rely on others for assistance (OR 1.66 (95% CI 1.01-2.75)), being in a two (versus five) days distribution program (OR 3.31 (95% CI 1.68-6.50)) and living in a community with < 2 community treatment assistants (CTAs)/1000 residents (OR 2.07 (95% CI 1.04-4.12). Furthermore, case households were more likely to have more children, younger guardians, unfamiliarity with CTAs, and CTAs with more travel time to their assigned households (p-values < 0.05). CONCLUSIONS/SIGNIFICANCE: Compared to full participation households, households with persistent non-participation had a higher burden of familial responsibility and seemed less connected in the community. Additional distribution days and lessening CTAs' travel time to their furthest assigned households may prevent non-participation.

Mass distribution of azithromycin for trachoma control is associated with short-term reduction in risk of acute lower respiratory infection in young children.

BACKGROUND: We evaluated the effect of a single mass distribution of azithromycin for trachoma on the risk of acute lower respiratory infection (ALRI) during a 6-month period among young children living in 8 communities in rural Tanzania. METHODS: In 8 communities, a cohort of randomly selected children (n = 1036) was followed for incidence of ALRI episodes. Mass treatment for trachoma using a single dose of oral azithromycin was provided in 4 of the 8 communities where trachoma prevalence was .10%. All children were followed with biweekly surveillance at home for 6 months. Incidence of ALRI episodes was calculated for 0 to 1 month, 1 to 3 months, and 3 to 6 months posttreatment and in comparable time points in the nontreated villages. RESULTS: In the multivariate analysis, living in a MDA village was associated with a 38% (rate ratio 5 0.62, 95% confidence interval [CI] = 0.43-0.91) decreased risk of ALRI in the 0- to 1-month follow-up period as compared with those in the untreated communities after adjusting for covariates and clustering. There were no significant differences in ALRI incidence by exposure status in the 1- to 3-month (rate ratio = 0.91, 95% CI = 0.69-1.20) and in the 3- to 6-month (rate ratio = 1.00, 95% CI = 0.76-1.30) follow-up periods. CONCLUSIONS: Mass distribution of a single dose of oral azithromycin for trachoma is associated with a significant short-term reduction in ALRI morbidity among young children.

Association of mass treatment with azithromycin in trachoma-endemic communities with short-term reduced risk of diarrhea in young children.

A cohort study was designed to assess the impact of mass distribution of azithromycin (MDA) for trachoma control on incidence over six months of pediatric diarrhea in eight communities in rural Tanzania. A single dose of azithromycin was offered to all residents in four communities, where trachoma prevalence was ≥ 10%. Four geographically matched communities had trachoma prevalences < 10% and did not receive MDA. All randomly selected children (n = 1036) were followed-up for six months post-MDA with bi-weekly surveillance at home. In the 0-1-month and 1-3-month periods, MDA exposure was associated with a 39% (rate ratio = 0.61, 95% confidence interval = 0.39-0.95) and 24% (rate ratio = 0.76, 95% confidence interval = 0.54-1.07) lower risk of diarrhea, respectively, compared with those unexposed, after adjustment for clustering and covariates. By the 3-6-month period, diarrhea incidence was comparable between groups. Thus, MDA was associated with a short-term reduction in diarrheal morbidity in children.

Prevalence and density-related concordance of three diagnostic tests for malaria in a region of Tanzania with hypoendemic malaria.

Accurate malaria diagnosis has dual roles in identification of symptomatic persons for effective malaria treatment and also enumeration of asymptomatic persons who contribute to the epidemiologic determinants of transmission. Three currently used diagnostic tests, microscopy, rapid diagnostic tests (RDTs), and real-time PCR, all have different sensitivities and specificities, which are parasite density dependent. Here, we compare their concordance among 451 febrile episodes in a cohort of 2,058 children and adults followed over 6 months in a region in central Tanzania with hypoendemic malaria. Microscopy, a histidine-rich protein-based RDT, and two different real-time PCR gene probes detected Plasmodium falciparum in 20, 54, 41, and 78 episodes of fever, respectively. They had complete concordance in only 9 episodes. Real-time PCR with an 18S probe was more sensitive than with a mitochondrial probe for cytochrome b despite higher copy numbers of mitochondrial DNA. Both PCR yields were increased 4-fold by glycogen/acetate precipitation with low-speed centrifugation. Duplicate PCR increases low-density malaria detection. RDT had the highest number of unique positives, presumably from persistent antigen despite the absence of parasites, although RDT did not detect 3 parasitemias with over 1,000 parasites/µl. In a latent class analysis, real-time PCR had significantly higher sensitivity than did microscopy or RDT. Agreement between real-time PCR, RDT, and microscopy was highest in March and April, when both the P. falciparum parasite rate and parasite densities are highest. Real-time PCR is more sensitive and specific than RDT and microscopy in low-prevalence, low-parasite-density settings.